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{o»tk»/ttU) (tidtvinB) Bird Fuh Mammal 
 
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 3. Cover-glass preparation of spinal cord of ox, 
 {Stained vjiih methylene blue). 
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 250. 
 
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 d, cartilage cells (yellow) (Macalluni). 
 
 Fronhspieee 
 
A 
 
 MANUAL OF PHYSIOLOGY 
 
 HlHitb practical lEvcrcisce 
 
 BY 
 
 G. N. STEWART, M.A , D.Sc, M.D. Edin., D.P.H. Camb. 
 
 PKOPESSOR OF EXPERIMENTAL MEDICINE IN WESTERN RESERVE UNIVERSITY, CLINICAL 
 
 'I'HVSIOLOGIST TO LAKFSIDE HOSPITAL, CLEVELAND ; FORMERLV PROFESSOR OK 
 
 l-HVSIOLOOV IN THE UNIVEKSITV OF CHICAGO ; PROFESSOR OF PHVSIOI.nnY IN 
 
 THR Wl-STEKN RESERVE UNIVERSITY; GEORGE HEN'RY LEWES STUDENT; 
 
 EXAMINER IN PHYSIOLOGY IN THE UNIVERSITY OF ABERDI KN ; 
 
 SENIOR DEMONSTRATOR OF PHYSIOLOGY IN THE OWENS 
 
 COLLEGE, VICTORIA UNIVERSITY, ETC. 
 
 WITH COLOURED PLATE AND 492 OTHER ILLUSTRATIONS 
 
 EIGHTH EDITION 
 
 UNIVERSITY SERIES 
 
 NEW YORK 
 
 WILLIAM WOOD AND COMPANY 
 
 MDCCCCXVIII 
 All rights reserved 
 
// 
 
 Printed in Great Britain 
 
 
PREFACE TO THE EIGHTH EDITION 
 
 In tlio midst of arms the laboratories are silent, and if the book has 
 not been quite so extensively revised in this as in the previous 
 edition tliere is only too valid an excuse in the withering influence 
 of the war upon the output of new work. Nevertheless, consider- 
 able changes and additions have been made, especially in the 
 portions dealing with the chemical phenomena of respiration, the 
 functions of the endocrine organs and metabolism. Some of the 
 newer calorimetric work has been more adequately taken account 
 of. The tiltration-reabsorption theory of urine formation, as 
 recently formulated by Professor Cushny, is discussed, although 
 necessarily in less detail than its importance merits. Some of the 
 more recent results of the examination of the mechanics of the 
 circulation by optical methods of recording have been noticed. 
 Several of the old illustrations have been omitted and a considerable 
 number of new ones added. In deference to the opinion of a 
 number of teachers a bibliography has been inserted in the form of 
 an appendix. Most of the references are to papers written in 
 English, as these will necessarily be of the most general use, and in 
 an}' case will usually contain references to the most important paper;-, 
 in other languages. An exception is made in favour of monographs 
 which are themselves provided with extensive bibliographies. 
 Recent communications are often cited in preference to older ones 
 on the same subject, not because the new work is necessarily 
 better or more important than the old, but because recent papers 
 will, as a matter of course, refer to previous publications. 
 
 Despite suggestions made from time to time by critical friends 
 and friendly critics (it is curious how little there is of cross division 
 here), the Practical Exercises have been retained in their original 
 place at the end of the related chapters. The author has been 
 asked more than once whether it would not be better to collect 
 them into a separate small volume, for greater convenience of use 
 in the laboratory. Apart from the fact that this would entail a not 
 inconsiderable duplication of material, including illustrations, the 
 exercises in their present form and position being supplemented freely 
 by cress-references to the text, the suggested change would run 
 counter to all the ideas of the author as to the relation between text- 
 book and practical work in the study of a science like physiology. 
 But for the exigencies of curricula, which necessarily, having to reckon 
 
 V l> 
 
vi PREFACE TO THE EIGHTH EDITIOS 
 
 v\"ith the brcxity of life, tend to sunder thin|<s which should be joined, 
 and in the stuh- measure, the law of action and reaction holding^ 
 own in scheduK-s and time tables, to join tiling's whicli were better 
 apart, it would have seemed to the author even more appropriate 
 to place the exercises at the beginning of the chapters, or best of 
 all to interweave them with the text till the ' phase boundaries ' 
 between the two disappeared as far as might be — a process which 
 might perhaps often be applied with adxaiitage to the phase 
 boundaries (of lath and plaster, still more of mental attitude) 
 between lecture - room and laboratory. The book would then 
 become, if the design could be adequately carried out, a text-book 
 of physiology, in the perusal of which the student was not permitted 
 to forget for a moment that the value of the so - called ' facts ' 
 described was in the last analysis dependent wholly upon the 
 accuracy of innumerable observations carried out in the laborator\' 
 by methods and apparatus with which he had gained, or was gaining, 
 some first-hand acquaintance in his practical work. When a 
 statement in the text is followed by a page reference to the Practical 
 Exercises this is for the precise purpose of reminding the student 
 that the laboratory is the seed-bed of the whole science. Lest he 
 forget this the exercises are not even placed all at the end of the 
 book, still less in a separate volume. 
 
 The question has been sometimes asked whether the methods, 
 and especiallv the apparatus described in the exercises, will exactly 
 suit most laboratories. They will not, and they ought not to be 
 expected to do so. This is also necessarily true of all laboratory- 
 guides. All must be adapted in some measure not only to the 
 material equipment of any particular laboratory in which they are 
 being used, but quite as much to the ideas and, what is by no means 
 unimportant, to the habits of the teacher. To a certain extent in 
 America a standardization of physiological apparatus for students^ 
 has been realized, and this has Ix^en of considerable benefit to the 
 teaching of physiology. Individual teachers and laboratories have 
 nevertheless gone on developing their own ideas with marked 
 advantage, and nothing would be less desirable than the unifomiity 
 of machine-made physiological teaching, could this be achieved, 
 which luckilv. in the nature of things, it cannot be. 
 
 Cleveland, 
 
 April, 191S. 
 
EXTRACT FROM THE PREFACE TO 
 THE FIRST EDITION 
 
 In this book an attempt has been made to iutenveave formal ex- 
 position with practical work, according to a programme which I 
 have followed for some time past in teaching Physiology to medical 
 students on the other side of the Atlantic, and which has, it is 
 believed, proved to be well adapted to their needs and opportunities. 
 It ought, however, to be explained that, for various reasons, a 
 somewhat wider range of experiment is open to the student in 
 America than in this countr}-. But as nobody will use this book 
 except in a regular laboratory and under responsible guidance, it 
 has not been thought necessary' to mark in any special manner the 
 parts of the exercises which the English student must do by proxy 
 (that is, learn from demonstrations), and the parts he ought to 
 perform for himself. 
 
 An arrangement of the exercises with reference to the systematic 
 course has this advantage — that by a little care it is possible to 
 secure that practical work on a given subject shall actually be going 
 on at the time it is being expounded in the lectures. Cross-refer- 
 ence from lecture-room to laboratory, and from laboratory to 
 iecture-room, from the detailed discussion of the relations of a 
 phenomenon to the living fact itself, is thus rendered easy, natural, 
 and fruitful. 
 
 As some teachers may wish to know how a course such as that 
 described in the Practical Exercises maj- be conducted for a fairly 
 large class, a few words on the method we have followed may not 
 be out of place. It is obvious that many of the exercises require 
 more than one person for their performance; and it may be said 
 
viii EXTRACT FROM THE PREFACE TO THE FIRST EDITION 
 
 that, except in the case of the simpler experiments and the chemical 
 work as a whole, which each student does for himself, it has been 
 found convenient to divide the class into groups of four, each group 
 remaining together throughout the session. It is possible that some 
 may find a group of four too large a unit, and it is certain that three, 
 or perhaps even two, would be better; but in a large school so 
 minute a subdivision is hardly possible, without entailing excessive 
 labour on the teachers. 
 
 The systematic portion of the book is so arranged that it can 
 equally well be used independently of the practical work, and aims 
 at being in itself a complete exposition of the subject, adapted to 
 the requirements of the student of medicine. 
 
 As to the matter of the text, it is hardly necessary to say that 
 this book does not aspire to the dubious distinction of originality; 
 and it is literally impossible to acknowledge all the sources from 
 which information has been derived. In many cases names have 
 been quoted, but names no less worthy of mention have often been 
 of necessity omitted. 
 
 G. N. STEWART. 
 
 Cambridge, 
 
 September, 1895. 
 
 ERRATA 
 
 On p. G17, line 5 from bottom, for ' McCollom ' read ' McCollum ' 
 
 ,, p. C32, line 28. for ' McGollom ' read ' McCollum.' 
 
 ,, p. 647, line 13. for ' are' rend ' is.' 
 
 ,, p. 648. line II, for ' and ' rend ' the.' 
 
 ,, pp. 667 and 669 (headline), /(>/■ ' adrenals ' read ' pituitary.' 
 
 ,, p. 671 (headline), /o/- 'adrenals' read ' pineal gland.' 
 
 • • P- f'73 (headline), /oy ' adreii-ils' read 'spleen,' 
 
CONTENTS 
 
 CHAPTER I. 
 INTRODUCTION. 
 
 PAca 
 
 Chemical composition of living matter - - - - i 
 
 Proteins --------i 
 
 Carbo-hydrates .-..-.- 3 
 Fats .... ^ ... 3 
 
 Structure of living matter ------ 4 
 
 l-unctions of living matter - - - - - 6 
 
 CHAPTER II. 
 
 THE CIRCULATING LIQUIDS OF THE BODY. 
 
 Section I. — Morphology of the Blood - - * '4 
 
 Blood-corpuscles - - - . . _ le 
 
 Life-history of the corpuscles - - - - 20 
 
 Section II. — General Physical and Chemical Properties of 
 
 THE Blood - - - - . - 23 
 
 Viscosity of blood - - - . - -23 
 
 Reaction of blood - - - - . - 24 
 
 Specific gravity of blood - - - - - 26 
 
 Electrical conductivity of blood - - - - 26 
 
 Relative volume of corpuscles and plasma - - - 27 
 
 Haemolysis - - - - - . - 28 
 
 Agglutination - - - - - . - 30 
 
 Precipitins - - - - - - -31 
 
 Anaphylaxis - - • - - . - 32 
 
 Coagulation of blood - - - - - - 33 
 
 Vaso-constrictor property of shed blood - - -45 
 
 Section III. — The Chemical Composition of Blood - - 47 
 
 Haemoglobin and its derivatives - - - - 50 
 
 Section IV. — Quantity and Distribution of the Bi god - 55 
 Quantity of blood - - - - - -cc 
 
 Distribution of blood ------ ^ 
 
X CONTENTS 
 
 PACK 
 
 Section V. — J '^mph and Chyle - - - - 57 
 
 Lymph ------- 57 
 
 Chyle - 58 
 
 Section VI. — Functions of Blood and Lymph - - 59 
 
 Phagocytosis - - - - - - - 59 
 
 Diapedesis -- - - - - -61 
 
 CHAPTER III. 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH. 
 
 Section I. — Preliminary Anatomical and Physical Data - 80 
 
 Physiological anatomy of the vascular system - - 81 
 
 Flow of a liquid through tubes - - - - 83 
 
 Section II. — The Beat of the Heart in its Physical or 
 
 Mechanical Relations - - - - - 85 
 
 Events in the cardiac cycle - - - - - 85 
 
 The sounds of the heart - - - - - 88 
 
 The cardiac impulse - - - - - - 90 
 
 Endocardiac pressure - - - - - 92 
 
 The ventricular pressure-curve - - - - 94 
 
 The auricular and venous pressure-curve - - - 98 
 
 Section III. — Physical or Mechanical Phenomena of the 
 
 Circulation in the Bloodvessels . - . loi 
 
 The arterial pulse ..---- loi 
 
 Arterial blood -pressure . . . . _ 109 
 
 Measurement of the blood-pressure in man - - - 113 
 Velocity of the blood - - - - - -117 
 
 Measurement of velocity of blood - - - - 120 
 
 The volume-pulse - - - - - -127 
 
 The circulation in the capillaries - - - - 129 
 
 The circulation in the veins - - - - - 132 
 
 The circulation -time - - - - - - ^35 
 
 Work and output of heart - - - - - ^39 
 
 Section IV. — The Heart-Beat in its Physiological Rela- 
 tions ..-.--- 140 
 Intrinsic nerves of the heart - - - - -141 
 Cause of the heart-beat ..... 141 
 Conduction and co-ordination in heart ... 146 
 Auriculo- ventricular bundle - - - - - ^47 
 Fibrillary contractions - - - - -151 
 Chemical conditions of heart-beat ... - 152 
 Resuscitation of the heart - - - - - ^53 
 Refractory period of heart - - - - - '55 
 
coxTi:yTS xi 
 
 PACK 
 
 Section V. — The Nervous Regulation of the Heart (Ex- 
 trinsic Nervous Mechanism of the Heart) - - 156 
 Action of poisons on the heart - - - - 166 
 Normal excitation of cardiac nervous mechanism - - 168 
 
 Section VI. — The Nervous Regulation of the Bloodvessels 
 
 (Vaso-Motor Nerves) - - - - - 173 
 
 The chief vaso-motor nerves - - - - - 175 
 
 Vaso-dilator fibres - - - - - - 179 
 
 Course of the vaso-motor nerves - - - - 181 
 
 Vaso-motor centres - - - - - - 1S2 
 
 Vaso-motor reflexes - - - - - - 185 
 
 Influence of gravity on the circulation - - - iqo 
 
 Section VII. — The Lymphatic Circulation - - - 192 
 
 CH.\PTER TV. 
 
 RESPIRATION. 
 
 Section I. — Pret.iminarv Anatomical Data ... 22> 
 
 Physiological anatomy of the respiratory apparatus - - 223 
 
 Blood-supply of the lungs ----- 223 
 
 Section II. — Mechanical Phenomena or External Respira- 
 tion --..--. 225 
 Types of respiration - - - - - -229 
 
 .Artificial respiration - - - - - - 230 
 
 Respiratory sovmds - - - - - -231 
 
 Frequency of respiration - - - - - 2 3.f 
 
 Vital capacity ------- 236 
 
 The dead space - - - - - - 236 
 
 Intrathoracic pressure . - - - . 236 
 
 Respiratory pressure -.---- 238 
 
 Section III. — The Chemistry of External Respiration - 239 
 
 Inspired and expired air - - - - - 239 
 
 .\lveolar air - - - - - - - -41 
 
 Respiratory quotient - - - - - - -41 
 
 Ventilation ------- 242 
 
 The quantity of carbon dioxide given off and of oxygen 
 
 absorbed ------- 243 
 
 Section IV. — The Gases of the Blood . - - - 245 
 
 Physical introduction ------ 245 
 
 Quantity of the blood -gases - - - - - ^50 
 
 Distribution and condition of oxygen in the blood - - 252 
 
 Distribution and condition of carbon dioxide in the blood - 255 
 
 The tension of the blood-gases ... - 2^8 
 
 Mechanism of the gaseous exchar.ge in the lungs - - 263 
 
xii CONTEXTS 
 
 lACB 
 
 Section \'. — Intiunai. or Tissuf. Rt-spiration - - - 265 
 
 Seats of oxidation ---... 265 
 
 Passage of oxy<^en fioTu the blood into the tissues - - 266 
 
 Respiration of muscle - - - . . 269 
 
 Nature of the oxidati\e process - - - - 271 
 
 Passage of carbon dioxide from the tissues intn the blood - 2jz 
 
 SfXTION VI. — RliLATIOX OI- RESPIRATION TO THE N'ERVOIS 
 
 System ---.... 274 
 
 The respiratory centre and its connections - - - 274 
 
 Regulation of respiration through the vagus - - - 276 
 
 Action of other afferent fibres on the respiration • - 280 
 
 The chemical regulation of the respiration - - - 281 
 
 Apnoea ....... 283. 
 
 Automaticity of the respiratory centre ... 284 
 
 Special moditications of the respiratory movements - - 287 
 
 Section \'II. — The Influence of Respiration on the Blood- 
 Pressure ---.-.. 2St> 
 
 Section VIII. — The Effects of breathing CondensI'D and 
 
 Rarefied .\ir ---... 295 
 
 Section IX. — Cutaneous Respiration - . . . 299 
 
 CHAPTER V. 
 
 VOICE AND SPEECH. 
 
 Voice --.-.... 307 
 
 Speech - - - - - - - -312 
 
 CHAPTER VI. 
 
 DIGESTION. 
 
 Section I. — Preliminary Anatomical and Chemical Data - 318 
 
 Anatomy of alimentary canal - - - - 319 
 
 Section II. — Mechanical Phenomena of Digestion - - 321 
 
 Mastication ... .... 321 
 
 Deglntition ----... ^^22 
 
 Movements of stomach - - - - - 326 
 
 Movements of intestines - - - - . t;28 
 
 Influence of central nervous system on gastro-intestina! 
 movements - " \ - - - - - -331 
 
 Defeecation - - - - - - - 33-2 
 
 Vomiting ....... ^^^ 
 
 Section III. — Chemistry of the Digestive Juices — Ferments 336 
 
 Saliva ..-----. ^.^^ 
 
 Gastric juice ------- ^^c^ 
 
 Antiseptic functions of gastric jiiice ... - ^.^5 
 
co.vrt.vrs xiu 
 
 Sr.cTiON III. {continued) — pa<* 
 
 Pancreatic juice ...... 358 
 
 Bile - - - - - - - - :^^'3 
 
 Succus entericus -..-.- 370 
 
 Section IV. — Secretion of the Digestive Juices — Micro- 
 scopical Ch.\xges in the Glan'd Cells - - - 374 
 Changes in pancreas and parotid during secretion - - 375 
 Changes in gastric glands during secretion ... 377 
 Changes in mucous glands during secretion - - - 381 
 Mode of formation of the digestive juices - - - 383 
 Why are the tissues of digestion not affected by the digestive 
 ferments ?- - - - - - - 38S 
 
 Section V. — Influence of the Xervous System on the 
 
 Digestive Glands - - - - - - 39' 
 
 Influence of nervous system on salivary glands - -391 
 
 Influence of nervous system on gastric glands - - 40 
 
 Influence of nervous 5\-stem on the pancreas - - 405 
 
 Secretin .-....- 407 
 
 Influence of nervous system on secretion of bile - - 411 
 Influence of nervous system on the secretion of intestinal 
 
 juice ....... ^i^ 
 
 Secretion of the digestive juices (summary) . - - 415 
 
 Section VI. — Survey of Digestion as a Whole - - 416 
 
 Reaction of intestinal contents - . - - 419 
 
 Bacterial digestion ..,..- 422 
 
 Faeces .---.--- 423 
 
 CHAPTER VII. 
 
 ABSORPTION. 
 
 Section I. — Preliminary Physico-Chemical Data • - 426 
 
 Imbibition, diffusion, and osmosis .... 426 
 
 Electrolytes - - - - - - - 428 
 
 Surface tension - - - . . - 429 
 
 Adsorption - - - - - ■ - 430 
 
 Section II. — Mechanism of Absorption - • -431 
 
 Theories of absorption . . . . . ^33 
 
 Permeability of intestinal epithelium - - - 437 
 
 Absorption from the peritoneal cavity - - - 439 
 
 Section III. — Absorption of the Various Food Substances - 441 
 
 .\bsorption of fat - - - . - - 44 • 
 
 Absorption of carbo-hydrates - . . - 4^3 
 
 Absorption of water and salts .... ^^u 
 
 Ab-orption of proteins .... - 4^7 
 
CONTESTS 
 
 CHAPTER VIII. 
 FORMATION OF LYMPH. 
 
 PAGK 
 
 Difieren kinds of lymph -----. 466 
 
 Fa :tors concerned in lymph formation - . . . ^57 
 
 The contribution of the tissue-cells to the lymph - - - 472 
 
 CHATTER IX. 
 
 EXCRETION. 
 
 Section I. — Excretion by ihe Kionevs — The Chemistry of 
 
 THE Urine - - - - - - -4 76 
 
 The urine in disease .---.. ^83 
 
 Section II. — The Secretion of the Urine ... ^g^ 
 
 Bloodvessels and tubules of the kidney - . - 489 
 
 Theories of renal secretion - - - - . ^gj 
 
 Excretion of pigments by the Icidney . - . _ ^g^ 
 
 Influence of the circulation on the secretion of urine - 506 
 
 Section III. — Expulsion of the Urine - - - - 510 
 
 Section IV. — Excretion by tmf. Skin - . - - 511 
 
 CHAPTER X. 
 METABOLISM, NUTRITION AND DIETETICS. 
 
 Section I. — Met.^bolism of Carbo-Hvdr.'vtes — Glycogen - 533 
 
 Glycogen-formsrs .-..-. 3^5 
 
 Function and fate of the glycogen - - . . 339 
 
 Fate of the sugar — glycob'sis .... ^^q 
 
 Intermediary metabolism of carbo-hydrates . - - 5-}- 
 
 The experimental glycosurias .... 3^5 
 
 Diabetes m?llitus - - - - - - 552 
 
 Section II. — Metabolism of Fat .... ^^^ 
 
 Form ition of fat from carbo-hydrates - - - 500 
 
 Formation of fat from protein .... 3^2 
 
 Intermediary metabohsm of fat .... ^(j^ 
 
 Non-nutritive functions of fat - - - - 50b 
 
 Obesity ..-..-. 308 
 
 Metabolism of sterins - ' - - - -570 
 
 Metabolism of phosphatides ... - - 371 
 
 Section HI. — Metabolism of Proteins - - - . 372 
 
 Living and dead proteins - - - - '57^ 
 
 Formition of amino-acids from tissue-proteins . . 378 
 
 Formation of hippuric acid . - - . . 380 
 
 Fate of amino-aci'.ls in the boJy .... 382 
 
CONTENTS XV 
 
 Section III. (continued) — pace 
 
 Formation of urea .---.- 583 
 
 Formation of uric acid ..... 590 
 
 Metabolism of nucleic acids and purin bases - - - 592 
 
 Creatin and creatinin ------ 597 
 
 Autolysis ------- 599 
 
 Section IV. — Statistics of Nutrition — Income and Expendi- 
 ture OF the Body in Terms of Matter - - - 601 
 The nitrogen balance-sheet — nitrogenous equilibrium - 602 
 Relation of nitrogenous metabolism to muscular work - 610 
 Relative value of different proteins in nutrition - - 612 
 The carbon balance-sheet - - - - - 618 
 
 The oxygen deficit ------ 620 
 
 Inorganic salts in nutrition - ... - 620 
 
 Section V. — Dietetics ------ 622 
 
 Stimulants - - - - - - - 630 
 
 Vitamines -..-.-- 632 
 
 CHAPTER XL 
 
 INTERNAL SECRETION— ENDOCRINE GLANDS. 
 
 Pancreas -------- C3O 
 
 Sexual organs ..----. 5^0 
 
 Thymus .-.--.-- 643 
 
 Thyroid and parathyroid ------ 645 
 
 Adrenals -------- 5^3 
 
 Pituitary ---.---- 666 
 
 Spleen -------- 672 
 
 CHAPTER XTI. 
 ANIMAL HEAT. 
 
 Section I. — Thermometry and Calorimktry - - . 674 
 
 Body-temperature .--... 580 
 
 Section II. — Income and Expenditure of the Body in Terms 
 
 OF Energy - - - - - - -681 
 
 Heat-loss - - - - - - - 681 
 
 Heat-production --.... 5S3 
 
 Basal metabolism -.-... 5S6 
 Seats of heat-production . . - . . 585 
 
 Section III. — Thermotaxis . - - . . 5qo 
 
 Relations between heat-production, surface and blood -flow - 696 
 
 The nervous system and thermotaxis ... yoo 
 
 Fever -------- 703 
 
 Section IV. — Temperature Topography - - - 709 
 
 Normal variations in body temperature - - - 712 
 
XVI COSTLXTS '■ 
 
 CHAPTER XIII. 
 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES. 
 
 I'ACB 
 
 Section I. — Prf.limin.\ry OBsiiRVATioxs — Phv.sical and Tkch- 
 
 NiCAL Data ...... 723 
 
 Cilia --.-.-.- 733 
 
 Section II. — Physical Properties and Stimulation of 
 
 Muscle .--.... 735 
 
 Elasticity of muscle --..-- 735 
 
 Stimulation of muscle ..... 737 
 
 Direct excitability of muscle - ... - 738 
 
 SrxTiON III. — Physical and Mechanical Phenomena of the 
 
 Muscular Contraction .... - 742 
 
 Optical phenomena — structure of muscle - - - 742 
 
 Mechanical phenomena ..... 745 
 
 Mu.scular fatigue ...... 749 
 
 Electrical tetanus ...... 756 
 
 Voluntary contraction ..... 760 
 
 Thermal phenfimena and transformation of energy irt mus- 
 cular contraction ...... 762 
 
 Relation between mechanical energy and heat-production in 
 
 active muscle ...... 76^ 
 
 Section IV. — Chemical Phenomena of Muscular Contraction 767 
 
 Formation of lactic acid ..... 759 
 
 The substances metabolized in muscular contraction - 771 
 
 Rigor -----... 774 
 
 CHAPTER XIV. 
 
 NERVE. 
 
 Section I. — The Nerve-Impulse or Propagated Disturb- 
 ance: its Initiation and Conduction - - . 7S1 
 Stimulation of nerve ----.. 783 
 Excitability of nerve ---... 784 
 Electrotonus .---.-. 785 
 Conduction in nerve ----.. 790 
 Velocity of the nerve-impulse .... 79^ 
 
 Section II. — Chemistry, Degeneration, and Regeneration 
 
 OF Nerve .----.. 794 
 
 Chemistry of nerve ...... 794 
 
 Degeneration of nerve ..... 79^ 
 
 Regeneration of nerve ..... 798 
 
 Trophic nerves ...... 805 
 
 Classification of nerves ..... 807 
 
CONTENTS xvji 
 
 CHATTER XV. 
 ELECTRO-PHYSIOLOGY. 
 
 PACI 
 
 Currents of rest and action ..... 82^ 
 
 Relation between action current and functional activity - - ^-^7 
 
 Polarization of muscle and nerve .... - 829 
 
 F.lectrotonic currents .-...- 830 
 
 Heart-currents _.---•- 833 
 
 Human electro-cardiogram ..... 835 
 
 Glandular currents ...... 838 
 
 Eye-currents ....... 839 
 
 Electric fishes .... . . 840 
 
 CH.\PTER XVT. 
 THE CENTRAL NERVOUS SYSTEM. 
 
 Section I. — Structure — Histological Elements - - 847 
 
 Development - ...... 849 
 
 Histological elements ------ 850 
 
 Nutrition of the neuron - - - - - 858 
 
 Section II. — Gener.\l Arr.'^ngement of the Grey and White 
 
 Matter in the Central Nervous System - - 861 
 
 Section III. — Arrangement of Grey and White Matter in 
 
 Spinal Cord ...... 863 
 
 Tracts of the cord ...... 866 
 
 Section IV. — .\rrangement of Grey and White Matter in 
 
 THE Upper Portion of the Cerebro-Spinal Axis - 869 
 
 Section V. — Connections of the Long Paths of the Cord - 870 
 
 Section VI. — Paths from and to the Cortex - - - 878 
 
 Section VII. — Connections of Brain Ste.m with Cord — 
 
 Connections of Cerebellum . . . . S84 
 
 Section VIII. — Functions of the Central Nervous System 
 
 — the Spinal Cord ..... 887 
 
 Decussation of the sensory paths .... gg^ 
 
 Refle.x action - - - - - - -897 
 
 Principle of the common path .... 899 
 
 Role of the receptor in reflex action - . - - 900 
 
 Characteristic properties of the reflex arc - - - 902 
 
 Irradiation of refle.x action ... . 905 
 
 Co-ordination of refle.xes - . . . . 908 
 
 Influence of the brain on spinal reflexes ... qi© 
 
 Automatism of the spinal cord .... 916 
 
 Muscular tonus — postural reflexes - - - - 917 
 
xviii CONTENTS 
 
 I'ACC 
 
 Section IX. — The Cranial Xf.rvhs .... 920 
 
 Section X. — Functions of thi. Uhain . - - - 931 
 
 Functions of the cerebellum ----- 933 
 
 Equilibration and orientation .... 936 
 
 Forced movements .-..-. 944 
 
 Functions of the cerebral c(;rte.\ ... - 947 
 
 Motor areas - - - - - • - 951 
 
 Histological differentiation of the cortex - - - 958 
 
 Sensory areas .-.---- 965 
 
 Aphasia ....--. 969 
 
 Localization of function in central nervous sj'stem - - 975 
 
 Influence of anastomosis of nerves on function • - 976 
 
 Co-ordmation of voluntary movements - - - 981 
 
 Reaction time ...--- 982 
 
 Section XL— Fatigue and Sleep— Hypnosis - - - 983 
 
 Section XI f. — Size of Brain and Intelligence — Cerebral 
 Circulation — Chemistry of Nervous Activity — Cere- 
 BRo-spiNAL Fluid ------ 988 
 
 (•iiapti:r xvil 
 the autonomic nervous systeim - - 1003 
 
 chapter xvi il 
 the senses. 
 
 The Senses in General ------ 1006 
 
 Section I. — Vision .-..-- 1008 
 
 Physical introduction . . - . - 1008 
 
 Structure of the eye - - - - - - 10 14 
 
 Chemistry of the refractive media - - - - ioi(» 
 
 Refraction in the eye ------ 10x7 
 
 Accommodation ..---- 1020 
 
 Functions of the iris ------ 1026 
 
 Defects of the eye ..---- 1027 
 
 Ophthalmoscope - - - - - - 1031 
 
 Skiascopy ------- 1034 
 
 Diplopia .--..-- 1037 
 
 Steroscopic vision ------ 1039 
 
 Visual judgments and illusions ... - 1040 
 
 Purkinje's figures ------ 1042 
 
 Blind spot ------- 1044 
 
 Rods and cones in vision - - . - - 1045 
 
 Talbot "s law - - - - - - - 1050 
 
 Colour vision - - - - - - - 1051 
 
 Contrast - - - - - - - 1056 
 
 Perimetrv - - - • - ' ' " '°58 
 
COM i:nts xt% 
 
 Section I. [contiinwd) — ta-.b 
 
 Culoiir-blindncss -...-- 1059 
 
 Movements of the eyes ..... loUi 
 
 Section II. — Hearing -...-- 10O4 
 Section III. — Smell and Taste ----- loj^ 
 
 Section IV. — Cutaneous and Inter.val Sensations - - 1078 
 
 Tactile senses ------- 1078 
 
 Sensations of warmth and cold . . - - 1081 
 
 Pain -------- 1083 
 
 Phenomena after section of cutaneous nerves - - 1085 
 
 Muscular sense ...-.- 1094 
 
 Sensations of hunger and thirst - . . - 109O 
 
 CHAPTER -XIX. 
 REPRODUCTION. 
 Regeneration of tissues - - - . 
 
 Reproduction in the higher animals 
 Menstruation - - - 
 
 Development of the ovum ... 
 
 Parthenogenesis - - - . - 
 
 Formation of the embryo - 
 
 Development of the connections - - - 
 
 Exchange of materials in the placenta 
 MetaboUsm of the embryo . - 
 
 Par?urition - . - - . 
 
 Milk ------ 
 
 Cultivation of tissues outside of the body - 
 Transplantation of tissues . - - 
 
 Parabiosis ------ 
 
 Appendix A. — Comparison of Metrical with 
 Measures - . - - . 
 
 Appendix B. — Bibliography - - - 
 
 Index ------ 
 
 PRACTICAL EXERCISES. 
 
 CHAPTER I. 
 
 General reactions of proteins - - - - - 7 
 
 Colour reactions of proteins - - - - - 8 
 
 Precipitation reactions of proteins - - - - 8 
 
 Special reactions of groups of proteir.s - - . - g 
 
 ReaTtions of I'erivalives of pr.-teins - - . . ^ 
 
 Carbo-hydrates - - - - - - -i» 
 
 Fats - - - - - -- -II 
 
 Scheme for testing for proteins and carbo-hydratas - - 13 
 
 • 
 
 - 
 
 III7 
 
 - 
 
 - 
 
 II18 
 
 - 
 
 - 
 
 1 1 20 
 
 - 
 
 - 
 
 II22 
 
 - 
 
 - 
 
 1 123 
 
 - 
 
 - 
 
 II24 
 
 - 
 
 - 
 
 II26 
 
 - 
 
 - 
 
 II 29 
 
 - 
 
 - 
 
 I 133 
 
 - 
 
 - 
 
 II37 
 
 - 
 
 - 
 
 II39 
 
 - 
 
 - 
 
 II42 
 
 - 
 
 - 
 
 II42 
 
 - 
 
 - 
 
 II46 
 
 Engli; 
 
 H 
 
 
 - 
 
 - 
 
 II5I 
 
 - 
 
 - 
 
 II5-J 
 
 . 
 
 . 
 
 1216 
 
2X C0^ TENTS 
 
 CHAPTER II. 
 
 1. Reaction of blood - - - - - - 02 
 
 2. Sjjecific gravity of blood - - - - - 62 
 
 3. Coagulation of blood - - - - - - 62 
 
 4. Preparation of fibrin-ferment - - - - - '^5 
 
 5. Preparation of extracts containing thrombokinase - - 05 
 
 6. Serum - - - - - - - - '\5 
 
 7. Action of serum on artery rings ... - 00 
 
 8. Comparison of action of serum and epinephrin on artery rings 66 
 
 9. Comparison of action of serum and plasma on artery rings - 66 
 10. Enumeration of the blood-corpuscles - - - - ''7 
 \ I . Hacmatocrite .... .-.08 
 \2. Electrical conductivity of blood - - - - 68 
 
 13. Opacity of blood - - - - - - 70 
 
 14. Laking of blood - - - • - - 70 
 
 15. Hitmolysis and agglutination - - - - •71 
 
 16. Osmotic resistance of coloured corpuscles - - - 73 
 
 17. Blood-pigment - - - - - - 73 
 
 (i) Preparation of haemoglobin crystals - - - 73 
 {2) Spectroscopic examination of haemoglobin and its 
 
 derivatives - - - - "74 
 
 (3) Guaiacum test for blood - - - - 7^ 
 
 (4) Quantitative estimation of haemoglobin - - 76 
 
 (5) Haemin test for blood -pigment - - • 7^ 
 
 CHAPTER HI. 
 
 1. Microscopic examination of the circulating blood - - 193 
 
 2. Anatomy of the frog's heart - - - - - i94 
 
 3. Beat of the heart - - - - - - 194 
 
 4. Apex of the heart - - - - - - 194 
 
 5. Heart tracings - - - - - - 194 
 
 6. Dissection of vagus and cardiac sympathetic in frog - - 1 96 
 
 7. Stimulation of the vagus in the frog - - - - 198 
 
 8. Stimulation of the junction of the sinus and auricles - - 198 
 
 9. Action of muscarine and atropine on the heart - - 199 
 
 10. Stannius' experiment - - - - - - i99 
 
 11. Stimulation of cardiac sympathetic in frog - - - i99 
 
 12. Action of inorganic salts on heart-muscle - - - 200 
 
 13. Action of the mammalian heart - - - - 201 
 
 14. Perfusion of the isolated mammalian heart - - - 205 
 
 15. Action of the valves of the heart .... 206 
 
 16. Sounds of the heart .----- 207 
 
 17. Cardiogram -.---•- 207 
 
CONTENTS 
 
 xxi 
 
 PACK 
 
 1 8. Sphygmographic tracings ..... 208 
 
 19. Venous pulse tracing from jugular .... 209 
 
 20. Polygraph tracings --.... 209 
 
 21. Plethysmographic tracings - - - - - 210 
 
 22. Pulse-rate - - - - - - -210 
 
 23. Blood-pressure tracing . . _ . - 210 
 
 24. Estimation of arterial pressure in man ... 213 
 
 25. Influence of position of the body oti blood-pressure - - 213 
 
 26. Effects of haemorrhage and transfusion on blood-pressure - 214 
 
 27. Influence of proteoses on blood-pressure - - - 215 
 
 28. Effect of suprarenal extract on blood-pressure - - 216 
 
 29. Action of epinephrin on artery rings - . - - 216 
 
 30. Determination of the circulation-time ... 217 
 
 31. Measurement of the blood-flow in the hands . . - 219 
 
 32. Vaso-motor reflexes - - - - • -221 
 
 I. 
 2. 
 3- 
 4- 
 5- 
 6. 
 
 7- 
 8. 
 
 9- 
 10. 
 II. 
 
 CHAPTER IV. 
 
 Tracing of the respiratory movements in man 
 Production of apnoea and periodic breathing in man - 
 Tracing of the respiratory movements in animals 
 Heat dyspnoea -----.- 
 Measurement of volume of air inspired and expired - 
 Cardio-pneumatic movements - - - . - 
 
 Auscultation of the lungs . _ - . . 
 
 Measurement of the respiratory pressure - . - 
 
 Estimation of carbon dioxide and water given off by an animal 
 Muscular contraction in the absence of free oxygen - 
 Oxidizinsr ferments ------ 
 
 300 
 300 
 300 
 302 
 303 
 303 
 304 
 304 
 305 
 306 
 306 
 
 CHAPTERS VI. AND VII. 
 
 1. Contraction of isolated intestines in Ringer's solution - 452 
 
 2. Effect of serum, on the contractions of intestinal segments - 453 
 
 3. Action of epinephrin on intestinal segments - - - 433 
 
 4. Quantitative estimation of ferment action - - - 433 
 
 5. Chemistry and digestive action of saliva - . . ^^^ 
 
 6. Stimulation of the chorda tympani - - - . 436 
 
 7. Effect of drugs on the secretion of saliva ... 437 
 
 8. Digestive action of gastric juice .... 438 
 
 9. To obtain chyme and gastric juice .... 439 
 
 10. Digestive action of pancreatic juice - - - - 460 
 
 11. Chemistry of bile .--... 462 
 
 12. Microscopical examination of fa?ces - - - - 463 
 
CONTENTS 
 
 rAGR 
 
 13. Absorption of fat -.---- 463 
 
 14. Time required for digestion and absorption of food sub- 
 
 stances ------- 464 
 
 15. Quantity of cane-sugar inverted and absorbed in a given 
 
 time ------- 464 
 
 16. Auto-digestion of the stomach .... 465 
 
 CHAPTER IX. 
 
 1. Specific gravity of urine - - - - -515 
 
 2. Reaction of urine - - - - - -515 
 
 3. Chlorides in urine - - • - - - 515 
 
 4. Phosphates in urine - - - - - -516 
 
 5. Sulphates in urine ------ 517 
 
 6. Indoxyl in urine - - - - - -517 
 
 7. Urea -.---.-- 518 
 
 8. Ammonia in urine - - - - - -521 
 
 9. Total nitrogen in urine - - - - -521 
 
 10. Uric acid ------- 523 
 
 11. Creatinin ------- 323 
 
 12. Hippuric acid ------- 524 
 
 13. Proteins in urine ------ 524 
 
 14. Sugar in urine ...... 325 
 
 15. Pentoses in urine ------ 528 
 
 16. Acetone in urine ------ 529 
 
 17. Determination of the freezing-point of urine - - - 529 
 
 18. Examination of urine - - - - - "531 
 
 19. Urinary sediments - - - - - -531 
 
 CHAPTERS X., XL, AND XII. 
 
 1. Glycogen - - - - - - - 715 
 
 2. Catheterism ------- 716 
 
 J. Experimental glycosuria - - - - - 716 
 
 (i) Injection of sugar into the blood - - - 716 
 
 (2) Phlorhizin glycosuria - - - * 717 
 
 (3) Alimentary glycosuria - - - - 717 
 
 (4) Estimation of the sugar in blood - - - 717 
 
 4. Milk -------- 718 
 
 5. Cheese -------- 719 
 
 6. Flour -------- 719 
 
 7. Bread -------- 720 
 
 8. Excretion of urea (and total nitrogen) and proteins in food - 720 
 
 9. Action of epinephrin ------ 720 
 
 10. Measurement of the heat given off in respiration - - 721 
 
CONTENTS 
 
 CHAPTERS XIII. AND XIV. 
 
 Difference of make and break induction shocks 
 
 Stimulation by the voltaic current - - - - 
 
 CiHary motion ...--- 
 
 Direct excitability of muscle — curara - - - - 
 
 Graphic record of ' twitch ' - 
 
 Influence of temperature on the muscle-curve 
 
 Influence of load on the muscle-curve . - - 
 
 Influence of fatigue on the muscle-curve . . - 
 
 Seat of exhaustion in fatigue of the muscle-nerve preparation 
 
 Influence of veratrine on muscular contraction 
 
 Measurement of the latent period of muscular contraction 
 
 Summation of stimuli ------ 
 
 Superposition of contractions - - - - - 
 
 Composition of tetanus _ . - - - 
 
 Contraction of smooth muscles . . - - 
 
 Velocity of the nerve-impulse - - - - - 
 
 Chemistry of muscle ------ 
 
 Reaction of muscle in rest, activity, and rigor 
 
 CHAPTER XV. 
 
 Galvani's experiment ------ 
 
 Contraction without metals - - - - - 
 
 Secondary contraction . - - - - 
 
 Demarcation and action currents with capillary electrometer 
 Action current of the heart - - - - - 
 
 Electrotonus ------- 
 
 Paradoxical contraction . . . - - 
 
 Alterations in excitability and conductivity produced in nerve 
 by a voltaic current . . - - - 
 
 9. Formula of contraction . - - - - 
 
 10. Formula of contraction for (human) nerves in situ 
 
 11. Ritter's tetanus ------ 
 
 I. 
 2. 
 3- 
 
 4- 
 5- 
 o. 
 
 7- 
 8. 
 
 9- 
 10. 
 II. 
 
 12. 
 
 13- 
 14. 
 
 15- 
 16. 
 
 17- 
 
 18. 
 
 PAGE 
 807 
 810 
 811 
 811 
 811 
 813 
 
 813 
 813 
 8I4 
 
 815 
 81O 
 816 
 816 
 817 
 818 
 819 
 820 
 
 842 
 842 
 842 
 842 
 844 
 844 
 844 
 
 844 
 
 845 
 846 
 846 
 
 CHAPTER XVI. 
 
 1 . Section and stimulation of nerve-roots 
 
 2. Reflex action in the ' spinal ' frog 
 
 3. Reflex time - - - - 
 
 4. Inhibition of the reflexes 
 
 5. Spinal cord and muscular tonus 
 
 6. Spinal cord and tonus of the bloodvesseh 
 
 7. Action of strychnine - - - 
 
 8. Mammalian spinal preparation 
 
 9. Decerebrate cat preparation - 
 
 10. Swallowing reflex _ - - 
 
 - 994 
 
 - 995 
 
 - 995 
 
 - 996 
 
 - 996 
 
 - 996 
 
 - 996 
 
 - 996 
 
 - 998 
 
 - 1000 
 
CONTENTS 
 
 PACP 
 
 11. Reflex postural tonus ..... ioo( 
 
 12. Reflexes in man ...... looo 
 
 13. Excision of cerebral hemispheres in the frog - - - 1000 
 
 14. Excision of cerebral hemispheres in the pigeon - looi 
 
 15. Stimulation of the motor areas in the dog - - - looi 
 
 CHAPTER XVIII. 
 
 T. Dissection of the eye ------ iioi 
 
 2. I'ormation of inverted image on the retina - - 1102 
 
 3. Helmholtz's phakoscope ..... 1102 
 
 4. Scheiner's experiment - - - - - 1103 
 
 5. Kiihne's artificial eye ------ 1104 
 
 6. Astigmatism (ophthalmometer) - - - - 1105 
 
 7. Spherical aberration ------ 1106 
 
 8. Chromatic aberration - - - - - -11 06 
 
 9. Measurement of the field of vision - - - - iioo 
 ;o. Mapping the blind spot - . . . . noy 
 [I. The yellow spot --.... 1107 
 
 12. Ophthalmoscope - - - - - -11 08 
 
 13. Retinoscopy ---.._. nog 
 
 14. Pupillo-dilator and constrictor fibres - - - -mo 
 13. Colour-mixing - - - - - - -iiii 
 
 16. After-images - - - - - - -mi 
 
 17. Retinal fatigue- - - - - - -im 
 
 18. Visual acuity - - - - - - -iiii 
 
 19. Colour-blindness - - - - - -1112 
 
 20. Talbot's law - - - - - - -1113 
 
 21. Purkinje's figures - - - - - - 1113 
 
 22. Relation of pitch and vibration frequency - - - 1113 
 
 23. Beats - - - - - - - -III 3 
 
 24. Sympathetic vibration - - - - - m ^ 
 
 25. Galton's whistle - - - - - -iii^ 
 
 26. Cranial conduction of sound - - - - -1113 
 
 27. Taste - - - - - - - -1113 
 
 28. Smell - - - - - - - -1114 
 
 29. Touch and pressure - - - - - -1114 
 
 30. Temperature sensations - - - - -1115 
 
 31. Pciin - - - - - - - -mo 
 
 CHAPTER XIX. 
 
 1. Contractions of isolated uterine rings - - - . 1147 
 
 2. Comparison of changes of tone produced in uterus segments by 
 
 ditlerent concentrations of adrenalin - - - 1149 
 
 3. Partition of adrenalin between serum and corpuscles - 11 49 
 
A MANUAL OF PHYSIOLOGY 
 
 CHAPTER I 
 INTRODUCTION 
 
 Living matter, whether it is studied in plants or in animals, has 
 certain peculiarities of chemical composition and structure, but 
 especially certain peculiarities of action or function, which mark it 
 off from the unorganized material of the dead world around it. 
 
 Chemical Composition of Living Matter. — ^Although we cannot 
 analyze the living substance as such, we can to a certain, but 
 limited, extent reconstruct it, so to speak, from its ruins. When 
 subjected to anal)i:ical processes, which necessarily kill it, living 
 matter in\'ariably yields bodies of the class of proteins, exceeding^ 
 complex substances, which have approximately the following com- 
 position: Carbon, 51-5 to 54-5 per cent.; oxygen, 20-9 to 23-5 per 
 cent.; nitrogen, 15-2 to 17 per cent.; hydrogen, 6-9 to 7-3 per cent., 
 with small quantities of sulphur. Nucleo-proteins , which are com- 
 pounds of ordinar}^ proteins with nucleic acids, a series of sulphur- 
 free organic acids rich in phosphorus, are constantly met with. 
 Certain carbo-hydrates, composed of carbon, hydrogen, and oxygen 
 (the last two in the proportions necessary to form water), of which 
 glycogen (CgHioOjln may be taken as a type, appear to be always 
 present. Fats, which consist of carbon, hydrogen, and oxygen, and 
 of which tristeaiin, a compound of stearic acid with glycerin, of 
 the formula C3H5,3(Ci8H3502), may be given as an example, are 
 often, and certain lipoids, e.g., lecithin (p. 4), are always, found. 
 Finally, water and certain inorganic salts, such as the chlorides and 
 phosphates of sodium, potassium, and calcium, are constantly present. 
 
 The Proteins. — The constitution of the protein molecule is still un- 
 known ; but when proteins are broken down by the action of ferments, 
 such as exist in gastric and in pancreatic juice, or by chemical methods 
 — for example, by boiling with dilute acids — the most important of 
 the cleavage products are various amino-acids (p. 360). It has there- 
 fore been suggested that proteins arc built up by the linking together of 
 amino-acids, the different proteins ditfering quantitatively or quali- 
 tatively as regards the amino-acids present (E. Fischer). Thus serum- 
 albumin and egg-albumin yield no glycin or glycocoll (amino-acetic 
 acid, CH2.NH2.COOH), while glycin is constantly found among the 
 cleavage products of serum-globulin. And while leucin («-amino- 
 
 I 
 
2 INTRODUCTION 
 
 isobutylacL-tic acid) is present to the extent of about 205 per cent, in 
 the cleavage products of (horse's) serum-albumin, (hen's) egg-albumin 
 yields only j' i per cent. 
 
 On the other hand, egg-albumin yields 8'i per cent, of alanin (amino- 
 propionic acid, C2H4.NH2.COOH), while serum-albumin yields only 
 2' 7 per cent. Of the aromatic amino-acids — that is, amino-acids united 
 to the benzene ring — phenyl-alanin (amino-propionic acid in which one 
 atom of H is replaced by phenyl, CeHg) is obtained to the extent of 
 44 per cent, from egg-albumin, and a little over 3 per cent, from .serum- 
 albumin. Tj'rosin or oxyphenyl-alanin (amino-propionic acid in which 
 a H atom is replaced by oxyplienyl, QH4.OH) appears to the amount 
 of I' 5 per cent, among the cleavage products of egg-albumin, and to 
 the amount of 2"i per cent, among tho.se of serum-albumin. It is an 
 interesting point in this connection that gelatin, which jdelds 165 per 
 cent, of glycin, yields no tyrosin at all; tryptophane, an aromatic 
 amino-acid still more complex than tj-rosin, is also absent. These facts 
 afford an explanation of certain colour reactions of proteins long known 
 empirically, but only recently understood (p. 8). The process by which 
 the protein molecule is thus decomposed is called hydrolysis — that is, 
 the molecule takes up water, and then splits into smaller molecules. 
 The hydrolysis occurs in various stages, bodies like acid- or alkali- 
 albumin (meta- or infra-proteins) being first formed, then proteoses, 
 then peptones. The peptones are further split into bodies containing 
 a relatively small number of amino-acids linked together. These bodies 
 are called polypeptides, which finally are decomposed so as to yield the 
 individual amino-acids, also called in this connection the peptides or 
 monopeptides, the " building-stones " out of which the protein molecule 
 is constructed. The inverse process can al.so be carried on to a certain 
 extent, and Fischer has taken an important step towards the eventual 
 synthesis of proteins by showing how polypeptides of increasing com- 
 plexity can be built up by linking amino-acids together. When two 
 amino-acids are so united, the resulting compound is called a dipeptide ; 
 with three amino-acids we get tripeptidcs, etc. Still more complicated 
 polypeptides may thus be formed in the laborator\', which give some of 
 the characteristic reactions of peptones. 
 
 The numerous substances included in the group of proteins may be 
 classified as follows, beginning with the simplest: 
 
 1. Protamins, such as the bodies called salmin and sturin present in 
 fish-sperm. 
 
 2. Histones, bodies separated from blood-corpuscles. Globin, the 
 protein constituent of haemoglobin, is one of them. Unlike the other 
 groups of proteins, they arc precipitated by ammonia. 
 
 3. Albumins. 
 
 4. Globulins. 
 
 5. Sclcro-proteins or albuminoids, such as gelatin and keratin. 
 
 6. Phospho-protcins, including such substances as vitellin, a body 
 obtainable from egg-yolk, and caseinogen, the chief protein of milk. 
 They are rich in phosphorus, but are to be distinguished from nucleo- 
 proteins, which also contain a relatively large amount of phosphorus, 
 by the fact that they do not yield tho purin bases, the characteristic 
 products of the decomposition of nucleo-proteins. 
 
 7. Conjugated proteins, substances in which the protein molecule is 
 united to another constituent, usually spoken of as a ' prosthetic ' group. 
 Thus the nucleo-proteins consist of protein united with nucleic acid, 
 the chromo-proteins {e.g., hremoglobin) of protein united with a pig- 
 ment, and the gluco-protcins {e.g , mucin) of protein united with a 
 carbo-hydrate group. 
 
CHEMICAL COMPOSITION OF LIVING MATTER 3 
 
 Among the derivatives of proteins, the most important are those 
 already mentioned as being produced in protein-hydrolysis, viz.: 
 
 (a) Meta-protcins. 
 
 (6) Proteoses, including albumose, the proteose derived from albu- 
 min; globulose, that derived from globulin; gclatose, thiit derived from 
 gelatin, etc. The proteoses may be further subdivided, according to 
 the order in which they are formed in digestion into proto-proteoses, 
 hetero-protcoses, and deutero-proteoses. 
 
 (c) Peptones. 
 
 (d) Polypeptides. The majority of these are artificial products, 
 formed by the synthesis of amino-acids, although some can be obtained 
 from proteins by hydrolysis. Only a few of those hitherto prepared 
 give the biuret test. 
 
 However formidable the above list may appear to the student, it 
 gives an inadequate idea of the extreme complexity of the protein class 
 and its richness in individuals. For, apart from the fact that the list 
 has been purposely left incomplete, especially as regards the numerous 
 vegetable proteins, there is the best evidence that proteins of the same 
 name from different animal species have certain properties which dis- 
 tinguish them from each other. The serum-albumins can be crystal- 
 lized much more easily in some animals than in others. The same is 
 conspicuously true of the haemoglobins, which differ also in certain 
 animals in the relative proportion of sulphur and iron in the molecule, 
 as well as in the crystalline form. Even when no chemical or physical 
 differences have as yet been made out, proteins of the same name from 
 the blood or organs of different species show notable ' specific ' differ- 
 ences when subjected to certain biological tests (see, e.g., the paragraph 
 on Precipitins, p. 31 ; and that on Anaphylaxis, p. 32). 
 
 Carbo-Hydrates. — The most important carbo-hydrates in their physio- 
 logical relations are dextrose, levulose, galactose, lactose, maltose, 
 sucrose (cane-sugar), starch, and glycogen. As regards their chemical 
 constitution, the simplest carbo-hydrates are aldehydes or ketones — 
 that is, the first oxidation products of primary and secondary alcohols 
 respectively. Thus dextrose is the aldehyde of sorbite, a hexatomic 
 alcohol (an alcohol containing six OH groups), while levulose is the 
 ketone of the isomeric alcohol called mannite, and galactose the alde- 
 hyde of the isomeric alcohol called dulcite. The sugars containing six 
 carbon atoms are termed hexoses. They include dextrose, levulose, 
 and galactose. The empirical formula of these three simple sugars (or 
 monosaccharides) is the same (CgHj^Og), but, owing to the different 
 arrangement of the atoms or groups of atoms, they have each their 
 characteristic properties by which they can be easily distinguished. 
 For example, dextrose rotates the plane of polarization to the right, 
 levulose to the left. By the union or ' condensation ' of two molecules 
 of a monosaccharide, with loss of a molecule of water, a disaccharide is 
 formed. Cane-sugar, maltose, and lactose, all with the same empirical 
 formula, (CJ2H22O11), are disaccharides. Cane-sugar yields on hydro- 
 lysis a mixture of equal parts of dextrose and levulose; lactose, a mix- 
 ture of dextrose and galactose ; while maltose is converted into dextrose. 
 By the condensation of more than two molecules of monosaccharide 
 polysaccharides are formed, such as starch, dextrin, and glycogen. The 
 exact molecular weights of these substances are unknown. Their 
 general formula can be written (CgHjoOs)*, where n represents the 
 number of monosaccharide molecules condensed to form the poly- 
 saccharide, in the case of starch probably some hundreds. 
 
 Fats and Lipoids. — The fats are compounds of higher fatty acids 
 with glycerin (glycerin esters). The ordinary body-fat consists of a 
 
4 INTRODUCTION 
 
 mixture of three neutral fats (palmitin, stearin, and olein) which differ 
 both chemically and physically from each other — e.g.. in melting-point 
 and in the so-called iodine value, the number which represents the 
 amount of iodine taken up from a standard solution. Olein melts at 
 -5° C, palmitin at 45° C, and stearin at a still higher temperature. 
 It is, therefore, the presence of olein which keeps the body-fat liquid 
 at the temperature of the body. The fats are soluble in ether, in hot 
 alcohol, and in many other liquids, but insoluble in water. Besides 
 the ordinary fats, the tissues and liquids of the bod}- contain phospha- 
 tides, a group of compounds wliich stand in close relation to the fats, 
 but differ in containing phosphoric acid and nitrogenous bases. The 
 most important representative of this group is lecithin (C42Hg4NP09), 
 a fat-like compound which yields on decomposition, in addition to 
 gljxerin and a fatty acid, phosphoric acid and a nitrogen-containing 
 substance called cholin (p. 366). Lecithin, though foimd in all cells, is 
 especially abundant in nervous tissues. It is associated with choles- 
 terin and with other substances which, like lecithin and cholesterin, 
 are soluble in ether and similar solvents of fat. For this reason these 
 substances are often grouped together as lipoids, although some of 
 them are chemically different from fat. Cholesterin, for instance, is an 
 alcohol. Although usually present only in small amount, the lipoids 
 play a very important part in the structure and in the economy of the 
 cell. 
 
 Structure of Living Matter — The Cell.* — Bioplasm is the name 
 given to the living matter of cells. The portion of the bioplasm 
 differentiated as the nucleus is distinguished by the term karyo- 
 plasm, and the portion outside the nucleus bv the term protoplasm 
 or cytoplasm. Protoplasm, when examined in its most primitive 
 undifferentiated condition in such cells as the amoeba or the white 
 blood-corpuscles, appears on tirst view a homogeneous, structureless 
 mass, except for certain granules embedded in it, and consisting 
 either of products formed by its activity or of food materials. But 
 even here more careful study reveals a certain complexity of struc- 
 ture. At the very least, an external layer, or ectoplasm, can be dis- 
 tinguished from the interior mass, or endoplasm. There is reason 
 to believe that even where no histological demonstration of an 
 ectoplasmic layer or a definite envelope is possible, the surface of 
 the cell is physiologically different from its interior. In many cells 
 the protoplasm presents the appearance of a honeycomb or net- 
 work, with granules usually situated at the nodes, and holding in 
 its vesicles or meshes a fluid, perhaps containing pabulum, from 
 which the waste of the living framework is made good, or material 
 upon which it works, and which it is its business to transform. 
 Some observers, however, maintain that the network is an artificial 
 appearance produced by the precipitation of the colloid constituents 
 of the protoplasm by the fixing reagent, or even by the coagulative 
 processes associated with the act of dying, and that the unaltered 
 living substance is a homogeneous fluid or jelly. It is known that 
 
 * Space permits only the slightest sketch of this subject here. For de- 
 tailed information the student is referred to textbooks of histology. 
 
STRUCTURE OF LIVING MATTER 5 
 
 changes of reaction occur when the living substance dies, and slight 
 chanpes of reaction, i.e., changes in the relative concentration of 
 hydrogen ions (H + ) and hydroxyl ions (0H-), can bring about 
 similar precipitates in colloid solutions. Nevertheless in some cells 
 a certain differentiation in the structure of the protoplasm can be 
 seen during life and before the addition of any reagent, and in such 
 cases there can be no doubt that the structural details pre-exist 
 and arc not arte-facts. In certain respects protoplasm behaves 
 like a liquid, and in others like a solid, a peculiarity which is un- 
 doubtedly associated with the fact that its chief constituents exist 
 in the colloid state, as experiments with such substances as gelatin 
 and agar have shown. In building up our typical cell we start with 
 a piece of protoplasm. Somewhere in the midst of this we find a 
 body which, if not absolutely different in kind from the protoplasm 
 of the rest of the cell or cytoplasm, is yet marked off from it by very 
 definite morphological and chemical characters. 
 
 This is the nucleus, generally of round or oval shape, and bounded 
 by an envelope. Within the envelope lies a second network of 
 fine threads, which do not themselves stain with nuclear dyes such 
 as hematoxylin. But in or on these ' achromatic ' filaments lie 
 small, highly refractive particles, staining readily and deeply with 
 dyes, and therefore described as consisting of chromatin. This chro- 
 matin is either made up of nucleins (conjugated proteins particu- 
 larly rich in nucleic acid, and therefore in phosphorus), or yields 
 nucleins by its decomposition; and it seems to owe its affinity for 
 certain staining substances to the presence of nucleic acid. The 
 meshes of the nuclear reticulum contain a semi-fluid material, 
 which does not readily stain. The nucleus is distinguished from 
 the cytoplasm, even as regards its inorganic constituents, by the 
 absence of potassium.* Besides the nucleus, another much smaller 
 structure, the centrosome, is differentiated from the protoplasm 
 of many cells. This is a minute dot staining deeply with such dyes 
 as hematoxylin, and generally situated near the nucleus. Sur- 
 rounding it is a clear area, the attraction sphere, in and beyond 
 which fine fibrils radiate out into the cytoplasm. Both the attrac • 
 tion sphere and the nucleus play an important part in division of 
 the cell by the process known as karyokinesis, or mitosis, or in- 
 direct division, which is by far the most common mode. 
 
 When the nucleus is about to divide, the chromatin granules 
 arrange themselves into one or more coiled filaments or skeins, 
 which then break up into a number of separate portions called 
 
 * This has been shown microchemically. The potassium is precipitated 
 by a solution of hexanitrite of sodium and cobalt as orange-yellow crystals of 
 the triple salt, hexanitrite of potassium, sodium, and cobalt. Where very 
 minute traces of potassium are present, ammonium sulphide must be added, 
 after washing out the excess of the cobalt reagent. Black cobalt sulphide is 
 thus formed from the triple salt (Macallum, Frontispiece). 
 
6 INTRODUCTION 
 
 chromosomes. These undergo a remarkable series of transforma- 
 tions, leading eventually to the segregation of the nuclear chromatin 
 in two separate daughter nuclei, each surrounded by a portion of 
 the original cytoplasm. Apart from its role in the division, and 
 therefore in the multiplication, of the cell, the nucleus is now known 
 to exert an influence perhaps not less important upon those chemical 
 changes in the cytoplasm which are necessary for its normal nutri- 
 tion and function.* It is doubtful whether any portion of proto- 
 plasm can permanently survive the loss of its nuclear material. It 
 must be remembered, however, that nuclear material may some- 
 times be present in diffuse form in cells which do not show a nucleus 
 in the histological sense. 
 
 When we carry back the analysis of an organized body as far as 
 we can, we find that every organ of it is made up of cells, which 
 upon the whole conform to the type we have been describing, 
 although there are many differences in details. Some organisms 
 there are, low down in the scale, w^ose whole activity is confined 
 within the narrow limits of a single cell. The amceba sets up in life 
 as a cell split off from its parent. It divides in its turn, and each 
 half is a complete amoeba. When we come a little higher than the 
 amoeba, we find organisms which consist of several cells, and 
 ' specialization of function ' begins to appear. Thus the hydra, the 
 ' common fresh-water polyp ' of our ponds and marshes, has an outer 
 set of cells, the ectoderm, and an inner set, the endoderm. Through 
 the superficial portions of the former it learns what is going on in 
 the- world; by the contraction of their deeply placed processes it 
 shapes its life to its environment. As we mount in the animal 
 scale, specialization of structure and of function are found con- 
 tinually advancing, and the various kinds of cells are grouped 
 together into colonies or organs. In some organs and tissues the 
 bond of union is simple juxtaposition and similarity of function of 
 the constituent cells. But in others the union is protoplasmic, pro- 
 cesses of the cytoplasm actually passing from cell to cell. This is 
 seen in certain epithelial tissues, and conspicuously in the cardiac 
 muscle. 
 
 The Functions of Living Matter. — The pecnUnv functions of living 
 matter as exhibited in the animal body will form the subject of the 
 main portion of this book ; and we need only say here: (i) That in all 
 living organisms certain chemical changes go on, the sum total of 
 which constitutes the metabolism of the body. These may be 
 divided into {a) integrative or anabolic changes, by which complex 
 substances (including the living matter itself) are built up from 
 
 ♦ According to Hertwig, a precursor of chromatin, ' prochromatin,' a sub- 
 stance without characteristic staining reaction, is formed in the cytoplasm, 
 taken up by the nucleus, and there elaborated into chromatin. From the 
 nucleus chromatin and its derivatives return to the cytoplasm to be used in 
 its function. 
 
FUNCTIONS Of LIVING MATTER 7 
 
 simpler materials; and (b) disintegrative or kataholic changes, in 
 which complex bodies (including the living substance) are broken 
 down into comparatively simple products. In plants, upon the 
 whole, it is integration which predominates; from substances so 
 simple as the carbon dioxide of the air and the nitrates of the soil 
 the plant builds up its carbo-hydrates and its proteins. In animals 
 the main drift of the metabolic current is from the complex to the 
 simple; no animal can construct its own protoplasm from the 
 inorganic materials that lie around it; it must have ready-made 
 f >rotcin in its food. But in all plants there is some disintegration ; 
 in all animals there is some synthesis. The progress of biochemistry 
 in recent years has indeed shown that the synthetic powers of 
 animal cells have been greatly underestimated. (2) The living sub- 
 stance is excitable — that is, it responds to certain external im- 
 pressions, or stimuli, by actions peculiar to each kind of cell. 
 (3) The living substance reproduces itself. All the manifold activities 
 included under these three heads have but one source, the trans- 
 formation of the energy of the food. It is not, however, upon the 
 whole, peculiarities in food, but in molecular structure, that underlie 
 the peculiarities of function of different living cells. A locomotive 
 is fed with coal; a steam-pump is fed with coal. The one carries 
 the mail, and the other keeps a mine from being flooded. Wherein 
 lies the difference of action ? Clearly in the build, the structure of 
 the mechanism, which determines the manner in which energy shall 
 be transformed within it, not in any difference in the source of the 
 energy. So one animal cell, wh( a it is stimulated, shortens or con- 
 tracts; another, fed perhaps with the same food, selects certain 
 constituents from the blood or lymph, and passes them through its 
 substance, changing them, it may be, on the way; and a third sets 
 up impulses which, when transmitted to the other two, initiate the 
 contraction or secretion. In the living body the cell is the machine; 
 the transformation of the energy of the food is the process which 
 ' runs ' it. The structure and arrangement of cells and the steps 
 by which energy is transformed within them sum up the whole of 
 biology. 
 
 PRACTICAL EXERCISES ON CHAPTER I. 
 
 Reactions of Proteins. 
 
 I. General Reactions of Proteins. — Egg-alburain may be taken as a 
 type. Prepare a sohition of it by adding water to white of egg, which 
 consists mainly of egg-albumin with a little globulin. In breaking the 
 egg, take care that none of the yolk gets mixed with the white. Snip 
 the white up witli scissors in a large capsule, then add ten or fifteen 
 times its volume of distilled water. The solution becomes turbid from 
 the precipitation of traces of globulin, since globulins a,re insoluble in 
 distilled water. Stir thoroughly, strain through several layers of muslin, 
 and then filter through paper. 
 
8 INTRODUCTION 
 
 Colour Reactions. 
 
 (i) Add to a little of the solution in a test-tube a few drops of strong 
 nitric acid. A precipitate is tlirown down, wliich becomes yellow on 
 boiling. Cool, and add strong ammonia; the colour changes to orange 
 [xantho-proteic reaction). The reaction depends upon tlic presence of 
 aromatic groups in the protein (in phenylalanin, tyrosin, tryptophane, 
 oxj-tryptophane), which are converted into nitro-compounds. 
 
 (2) To a third portion add a drop or two of very dilute cupric sulphate 
 and excess of sodium or potassium hydroxide; a violet colour appears 
 {Piotrow ski's test). Peptones and proteoses (albumoses) give a pink 
 [biuret reaction).* See p. 458. 
 
 (3) To another portion add Millon's reagent ;t a white precipitate 
 comes down, which is turned reddish on boiling. If only traces of 
 protein are present, no precipitate is caused, but the liquid takes on a 
 red tinge. The reaction is due to tyrosin. It is given by all aromatic 
 substances which contain tiie group CgHg with at least one H replaced 
 by OH, i.e., the hydroxyphenyl group CaH40H. 
 
 (4) Adamkiewicz's Reaction {Hopkins's modification). — To a small 
 quantity of the albumin solution add the same bulk of dilute glyoxylic 
 acid. J Mix, and to the mixture add an equal volume of strong pure 
 sulphuric acid. A purple colour is obtained. The substance in the 
 protein molecule which gives tlie reaction is tryptophane (p. 360). 
 
 (5) The Formaldehyde Reaction. — Add to the albumin solution a few- 
 drops of a very dilute solution of formaldehyde (i : 2,500), and then 
 allow some strong (commercial) sulphuric acid to run from a pipette 
 into the bottom of the test-tube. A purple ring appears at the surface 
 of contact. This reaction depends on the presence of tryptophane in 
 the protein. 
 
 Precipitation Reactions, 
 
 (6) Acidify another portion strongly with acetic acid, and add a few 
 drops of a solution of potassium ferrocyanide. A white precipitate is 
 obtained. Peptones do not give this reaction. 
 
 (7) Heat a portion to 30° C. on a water-bath. Saturate with crystals 
 of ammonium sulphate; the albumin is precipitated. Filter, and test 
 the filtrate for proteins by (2). None, or only slight traces, wUl be 
 found. The sodium hydroxide must be added in more than sufficient 
 quantity to decompose all the ammonium sulphate. It will be best to 
 add a piece of the solid hydroxide. Peptones are not precipitated by 
 ammonium sulphate, but all other proteins are. 
 
 (8) Add alcohol to a small quantity of the solution. The protein is 
 
 • The reaction is also given, although more faintly, with the hydroxides of 
 lithium, strontium, and barium. It is given by all substances containing at 
 lea^t two CONH2 groups attached to one another (as in oxamide), or to the 
 nitrogen atom (as in biuret) , or to the same carbon atom. 
 
 f Millon's reagent consists of a mixture of the nitrates of mercury with 
 nitric acid in excess, and some nitrous acid. To make it. dissolve mercury in 
 its own weight of strong nitric acid, and add to the solution thus obtained 
 twice its volume of water. Let it stand for a short time, and then decant the 
 clear liquid, which is the reagent. 
 
 X A solution containing glyoxylic acid in the requisite strength can be 
 prepared by treating half a litre of a saturated solution of oxalic acid with 
 40 grammes of 2 per cent, sodium amalgam in a tall cylinder. When all the 
 hydrogen has been evolved, the solution is filtered, and diluted with twice its 
 volume of water. Oxalic acid and sodium binoxalate are also present in the 
 solution. 
 
PRACTICAL EXERCISES g 
 
 precipitated. It can be redissolvcd at first, but rapidly becomes in- 
 soluble. 
 
 .;. Special Reactions of Certain Proteins — (i) Heat-Coagulable Pro- 
 teins : (u) Albumins. — (a) Heat a little ot the solution of egg-albumin in 
 a Ust-tubc; it coagulates. With another sample determine the tem- 
 perature of coagulation, first very slightly acidulating with a 2 per cent, 
 solution of acetic acid. 
 
 To determine the Temperature of Coagulation. — Support a beaker by 
 a ring which just grips it at the rim. Nearly fill the beaker with water, 
 and slide the ring on the stand till the lower part of the beaker is im- 
 mersed in a small water-bath (a tin can will do quite well). In this 
 beaker place a test-tube, and in the test-tube a thermometer, both sup- 
 ported by rings or clamps attached to the same stand. Put into the 
 test-tube at least enough of the albumin solution to completely cover 
 the bulb of the thermometer, and heat the bath, stirring the water in 
 the beaker occasionally with a feather or a splinter of wood, or a glass 
 rod, the end of which is guarded with a piece of indiarubber tubing. 
 Note the temperature at which the solution becomes turbid, and then 
 the temperature at which a distinct coagulum or precipitate is formed. 
 Repeat with the unacidulated albumin solution. 
 
 (/3) A similar experiment may be performed with serum-albumin 
 obtained as on p. 65. 
 
 {b) Globulins. — Use serum-globulin (p. 65), or myosinogen (p. 819). 
 Fibrinogen is also a globulin, but cannot easily be obtained in quantity. 
 Verify the following properties of globulins: 
 (a) They coagulate on heating. 
 0) They are insoluble in distilled water (p. 65). 
 (7) They are precipitated by saturation with magnesium sulphate or 
 sodium chloride (p. 65). 
 
 They give the general protein tests (i) to (8). 
 
 Both the heat-coagulated proteins and such protein-s as the solid 
 fibrin which is formed from fibrinogen in the clotting of blood give such 
 of the general protein tests, (i), (2), (3) (p. 8), as with suitable modifica- 
 tions can be instituted on solid substances. Thus, in performing (2), a 
 flake of fibrin or a small piece of the boiled egg-white should be soaked 
 for a few minutes in a dilute solution of cupric sulphate. Then the 
 excess of the cupric sulphate should be poured off, and sodium hydroxide 
 added, when the coagulated protein will become violet. Heat-coagu- 
 lated proteins are insoluble in water, weak acids and alkalies, and salxne 
 solutions ; fibrin is slightly soluble in the latter. 
 
 (2) Gelatin. — Add some pieces of gelatin to cold water in a test-tube. 
 It does not dissolve. Immerse the tube in a boiling water-bath till the 
 gelatin goes into solution. Then cool the test-tube under the tap; the 
 solution sets into a jelly. On heating it redissolves. 
 
 Try the general protein reactions (p. 8) on a dilute solution. In 
 Piotrowski's test a violet colour is obtained. The tests which depend 
 on the presence of tyrosin or tryptophane are not given by a solution 
 of pure gelatin, since these amino-acids are absent from the gelatin 
 molecule. Commercial gelatin may give a slight reaction due to 
 traces of other proteins. 
 
 3. Reactions of Certain Derivatives of Native Proteins — (i) Meta- 
 Proteins : {a) Acid- Albumin.— 'Yo a solution of egg-albumin add a little 
 04 per cent, hydrochloric acid, and heat to about body temperature — 
 say 40° C. — for a few minutes. Acid-albumin is formed. It can be 
 produced from all albumins and globulins by the action of dilute acid. 
 Make the following tests : 
 
 (a) Add to a portion of the solution in a test-tube a few drops of a 
 
lo INTRODUCTION 
 
 solution of litmus; the colour becomes red. Now add drop by drop 
 sodium carbonate or dilute sodium hydroxide solution till the tint just 
 begins to change to blue. A precipitate of acid-albumin is thrown 
 down . Add a little more of the alkali, and the precipitate is redissolved. 
 It can be again brought down by neutralizing with acid. 
 
 (fi) Heat a portion of the solution to boiling; no precipitate is formed. 
 (y) Add strong nitric acid; a precipitate appears, which dissolves on 
 heating, and the liquid becomes yellow. 
 
 (6) Alkali-albumin. — To a solution of egg-albumin add a little sodium 
 hydroxide, and heat gently for a few minutes. Alkali-albumin is 
 produced. It can be derived by similar treatment from any albumin 
 or globulin. 
 
 (a) Neutralize, after colouring with litmus solution, by the addition 
 of dilute hydrochloric or acetic acid. Alkali-albumin is precipitated 
 when neutralization has been reached. It is redissolved in excess of 
 the acid. 
 
 (3) To another portion of the solution of alkali-albumin add a few 
 drops of sodium phosphate solution, then litmus, and then dilute acid 
 till the alkali-albumin is precipitated. More of the, dilute acid should 
 now be required to precipitate the alkali-albumin, since the sodium 
 phosphate must first be changed into acid sodium phosphate. 
 
 (y) On heating the solution of alkali-albumin there is no coagulation. 
 (2) Proteoses. — For preparation and reactions, see p. 458. They 
 differ from albumins and globulins in not being coagulated by heat, and 
 from meta-proteins in not being precipitated by neutralization. They 
 are soluble (with the exception of hetero-albumose) in distilled water, 
 and are not precipitated by saturation of their solutions with mag- 
 nesium sulphate or sodium chloride. Saturation with ammonium sul- 
 phate precipitates them. With a solution of ' commercial peptone,' 
 which consists chiefly of albumoses, and contains only a little true 
 peptone, perform the following tests: 
 
 (a) Boil the slightly acidulated solution; there is no coagulation. 
 ()9) Biuret reaction, p. 8. 
 
 (y) To a portion oif the solution add its own volume of saturated 
 ammonium sulphate solution. The primary albumoses (proto- and 
 hetero-albumose) are precipitated. Filter. Add a drop of sulphuric 
 acid to the filtrate and saturate it with ammonium sulphate crystals. 
 The secondary' or deutero-albumoses are precipitated. Filter. The 
 filtrate still contains peptones. Use it for (3). 
 
 (3) Peptones. — For preparation and tests, see p. 459. They differ 
 from heat-coagulable proteins and meta-proteins in the same way as 
 proteoses, and they differ from proteoses in not being precipitated by 
 ammonium sulphate. On the filtrate from (2) perform the biuret test, 
 as described in (7), p. 8; and note that the pink colour is the same as 
 that given by proteoses. 
 
 Carbo-Hydrates. 
 
 1. Glucose or Dextrose. — Make a solution of dextrose in water, and 
 applv to it Trommer 's test for reducing sugar. Put some of the dextrose 
 solution in a test-tube, tlicn a few drops of cupric sulphate, and then 
 excess of sodium or potassium hydroxide. The blue precipitate of 
 cupric hydroxide which is first thrown down is immediately dissolved 
 in the presence of dextrose and many other organic substances. Now 
 boil the blue liquid, and a yellow or red precipitate (cuprous hydroxide 
 or oxide) is formed. 
 
PRACTICAL EXERCISES ii 
 
 2. Cane-Sugar. — Perform Truium'^r's test witli a .sample of a solution. 
 A blue liquid is obtained, which is not changed on boiling. Now put 
 the rest of the .solution in a flask. Add s'^th of its bulk of strong hydro- 
 chloric acid, and boil for a quarter of an hour. Again perform Trom- 
 mer's test. Remember that excess of alkali must be present after the 
 acid is neutralized. The test now shows much reducing sugar. The 
 cane-sugar has been ' inverted ' — i.e., changed into a mixture of 
 dextrose and levulose. 
 
 3. Starch. — (i) Cut a slice from a well-washed potato ; take a scraping 
 from it with a knife, and examine with the microscope. Note the starcii 
 granules with their concentric markings, using a small diaphragm. 
 Run a drop of dilute iodine solution under the cover-slip, and observe 
 that the granules become bluish. Examine also with a polarization 
 microscope. (2) Rub up a little starch in a mortar with cold water, 
 then add boiling water and stir thoroughly. Decant into a capsule or 
 beaker, and boil for a few minutes. After the liquid has cooled, perform 
 the following experiments: 
 
 (a) Add a few drops of iodine solution to a little of the thin starch 
 mucilage in a test-tube. A blue colour is produced, which disappears 
 on heating, returns on cooling, is bleached by the addition of a little 
 sodium hydroxide, and restored by dilute acid. 
 
 (6) Test the starch solution for reducing sugar by Trammer's test. 
 If none is found, boil some of the mucilage with a little dilute sulphuric 
 acid in a flask for twenty minutes, and again perform Trommer's test. 
 Abundance of reducing sugar will now be present. 
 
 4. Dextrin. — Dissolve some dextrin in boiling water. Cool. Add 
 iodine solution to a portion; a reddish-brown (port-wine) colour results, 
 which disappears on heating. As a control, the same amount of iodine 
 should be added to an equal quantity of water in another test-tube. 
 The colour returns on cooling. The colour is also bleached by alkali, 
 restored by acid. Excess of iodine should be added for the bleaching 
 experiment {i.e., more than enough to give the maximum depth of tint). 
 If too little iodine has been added, there may be no restoration of the 
 colour by the acid. The addition of a little more iodine to the acid 
 solution will then cause the port- wine colour to return, and this may 
 be again bleached by alkali, and will now be restored by acid. 
 
 5. Glycogen. — See p. 715. 
 
 6. Molisch 's Test for Carbo-Hydrates. — This is a general test for carbo- 
 hydrates. It is also given by proteins which contain a carbo-hydrate 
 group. Put a drop of dextrose solution in a test-tube. Add a drop 
 of a 10 per cent, solution of a-naphthol in methyl alcohol, and then 
 o'5 c.c. of water. Then cautiously allow i c.c. of pure concentrated 
 sulphuric acid to run under the mixture, and shake gently. A violet or 
 reddish colour appears. 
 
 Fats. 
 
 1. Take a little lard or olive-oil, and observe that fat is soluble in 
 ether or warm alcohol, but not in water. Put a drop of the ethereal 
 solution of fat on a piece of paper, and note that it leaves a greasy stain. 
 
 2. Put a little alcohol in a test-tube, and then a drop of phenol- 
 phthalein solution and a drop or two of dilute sodium hydroxide to give 
 the solution a red colour. Add a few drops of an ethereal solution of 
 the lard or olive-oil. If the red colour persists, the fat is neutral; if it 
 disappears, the fat contains free fatty acids. 
 
 3. Saponification. — Melt some lard in a porcelain dish, and pour it 
 
12 INTRODUCTION 
 
 into an alcoholic solution of potassium hydroxide previously heated on 
 a water-bath nearly to boiling. Mix well, and keep the mixture gently 
 boiling on the bath till saponification is complete. This only takes a 
 short time. Remove a little of the soap solution, and drop it into dis- 
 tilled water in a test-tube. If unsaponificd fat is present, it will rise to 
 the top as drops of oil. In this case boiling should be continued. If 
 all the fat has been saponified, the soap solution will mix with the 
 water and no oil-drops will separate. 
 
 4. Fatty Acids. — Heat some 20 per cent, sulphuric acid in a small 
 flask nearly to boiling, and drop into it some of the soap obtained in 3. 
 The fatty acids separate out and rise to the top as an oily layer. Cool, 
 skim off the fatty acid, and wash it with distilled water till the wash- 
 water is no longer acid. 
 
 (a) Dissolve a little of the washed fatty acid in ether. Add a few 
 drops of an alkaline solution of phenolphthalein to a few c.c. of water 
 in a test-tube . Drop into this the ethereal solution of fatty acid. The 
 red colour is discharged. 
 
 (b) Put a small portion of the fatty acid on a glass slide resting on a 
 piece of white paper. Place on it a drop or two of a i per cent, solution 
 of osmic acid (osmium tetroxide). The osmic acid is reduced to a lower 
 oxide (which is black) by the action of oleic acid present in the fatty 
 acid raixture, which abstracts some of the oxygen. Any fat which 
 contains olein or oleic acid, as body-fat does, is therefore blackened by 
 osmic acid. 
 
 (c) Add to a portion of the fatty acid some sodium hydroxide solution, 
 and warm. Sodium soap is formed. Add warm water and shake up. 
 A lather is produced. Keep the soap solution for 6. Keep a little of 
 the fatty acid for 5 (b) and 6 (b). 
 
 5. Glycerin. — (a) Add to a little glycerin in a dry test-tube a few 
 crystals of potassium bisulphate (KHSO4), and heat over the free flame. 
 Acrolein is given off, which is recognized by its pungent odour, and by 
 blackening a piece of filter-paper moistened with ammoniacal silver 
 nitrate solution, and held over the mouth of the test-tube. The paper 
 is blackened owing to the reducing action of the vapour on the silver 
 nitrate. 
 
 (6) Repeat this test with lard, and with a portion of the fatty acid 
 from 4. Acrolein will be given off by the lard because glycerin is con- 
 tained in neutral fat, but not by the fatty acid if it has been properly 
 separated from the glycerin. 
 
 6. Emulsification. — (a) Take three test-tubes and label them A, B, 
 and C. Put a few c.c. of water in A, a solution of soap in B, and a 
 dilute solution of sodium carbonate or sodium hydroxide in C. To each 
 add a few drops of fresh olive-oil and shake . An emulsion will be formed 
 in B, but not in A. Probably there will be some emulsification in C also, 
 owing to the presence in the oil of some fatty acid, which forms soap 
 with the alkali. But if the oil is free from fatty acid, no emulsion will 
 be formed. 
 
 (6) Repeat (a) with rancid olive-oil, which contains much fatty acid, 
 or with fresh olive-oil to which some of the fatty acid obtained in 4 has 
 been added. A good emulsion will be produced in C as well as in B. 
 
 7. MeUing-Point of Fat. — Put into a very narrow test-tube or a short 
 piece of narrow glass tubing some finely divided mutton fat, freed, as 
 far as possible, from connective tissue. Fasten the test-tube on to the 
 bulb of a thermometer with a rubber band, and immerse the ther- 
 mometer and tube in a beaker filled with water and standing on a water- 
 bath, which is gradually heated. Observe the temperature at which 
 the fat melts. Repeat the experiment with hog's lard and dog's fat. 
 
PRACTICAL EXERCISES 13 
 
 SCHEME FOR TESTING A SOLUTION FOR THE MORE COMMON 
 PROTEINS AND PROTEIN-DERIVATIVES, AND FOR CARBO- 
 HYDRATES 
 
 1. Note the reaction, and whether the Hquid is coloured or colourless, clear 
 or opalescent. A reddish c olour suggests blood ; opalescence suggests glyco- 
 gen or starch. Try one or more of the general protein tests {e.g., the xantho- 
 proteic or biuret). If the result is positive, proceed as in 2; if negative, pass 
 to 3. 
 
 2. Test for Proteins. — (i) If the reaction is acid or alkaline, neutralize with 
 very dilute sodium carbonate or sulphuric acid. A precipitate =acid- or 
 alkali-albumin, according as the original reaction is acid or alkaline. If the 
 original reaction is neutral, no acid- or alkali-albumin can be present in 
 solution. Filter off the precipitate, if any. 
 
 (2) Boil some of the filtrate from (i) (or some of the original solution if 
 it is neutral), acidulating slightly with dilute acetic acid. A precipitate = 
 albumin or globulin. Filter, and keep the filtrate. 
 
 (3) If a precipitate has been obtained in (2), [a) saturate some of the original 
 solution with magnesium sulphate, or half saturate it with ammonium sulphate 
 {i.e., add to it an equal volume of saturated ammonium sulphate solution). 
 If there is no precipitate, globulin is absent, and therefore the precipitate 
 obtained in (2) must be albumin. A precipitate ^globulin. But albumin 
 may also be present in the solution. To see whether this is so, filter off the 
 globulin and boil the filtrate after acidulation with acetic acid. A precipitate 
 = albumin. 
 
 {b) Half saturate the filtrate from (2) with ammonium sulphate {i.e., add its 
 own volume of a saturated solution of the salt). A precipitate = primary 
 proteoses. Filter. 
 
 (c) Satura^-e the filtrate from {b) with ammonium sulphate crystals. A 
 precipitate = secondary proteoses. Filter. 
 
 {d) To the filtrate from (c) add excess of solid sodium hydroxide in small 
 pieces at a time. Much ammonia is given off. Allow the test-tube to stand 
 fifteen minutes, shaking it at intervals. Then add dilute cupric sulphate, 
 and if much of the sodium sulphate formed remains undissolved, add water 
 to dissolve it. A well-marked rose colour = peptone. 
 
 (4) If no precipitate has been obtained in (2), the solution contains neither 
 albumin nor globulin. To test whether primary or secondary proteose or 
 peptone is present, apply (3) {b), (c), and {d). 
 
 3. Test for Carbo-Hydrates. — Use the original solution, freed from coagu- 
 lable proteins, if such have been found, by acidulation and boiling. 
 
 (i) Add iodine. If the solution is alkaline neutralize it before adding the 
 iodine. A blue colour = starch. Confirm by boiling with dilute sulphuric 
 acid and testing for reducing sugar. A reddish-brown colour with iodine = 
 glycogen or dextrin. 
 
 Glycogen gives an opalescent, dextrin a clear, solution. Glycogen is pre- 
 cipitated by basic lead acetate, dextrin is not (p. 715). Both are changed 
 into reducing sugar by boiling with dilute acid. 
 
 (2) Add to some of the original solution cupric sulphate and excess of 
 sodium hydroxide, and boil. Yellow or red precipitate = reducing sugar. 
 
 (3) If (i) and (2) are negative, boil some of the liquid with one-twentieth 
 of its volume of strong hydrochloric acid for fifteen minutes, and test as in (2). 
 A red or yellow precipitate indicates that a disaccharide like cane-sugar was 
 originally present, and has been inverted. 
 
CHAPTER II 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 In the living cells of the animal body chemical changes are con- 
 stantly going on; energy, on the whole, is running down; complex 
 substances are being broken up into simpler combinations. So long 
 as life lasts, food must be brought to the tissues, and waste products 
 carried away from them. In lowly forms like the amoeba these 
 functions are performed by interchange at the surface of the 
 animal without any special mechanism; but in all complex organ- 
 isms they are the business of special liquids, which circulate in 
 finely branching channels, and are brought into close relation at 
 various parts of their course with absorbing organs, with eliminating 
 organs, and with the tissue elements in general. 
 
 In the higher animals three circulating liquids have been dis- 
 tinguished: blood, lymph, and chyle. But it is to be remarked 
 that chyle is only lymph derived from the walls of the alimentar\- 
 canal, and therefore, during digestion, containing certain freshly- 
 absorbed constituents of the food ; while both ordinary lymph and 
 chyle ultimately find their way into the blood, and are in their turn 
 recruited from it. The blood contains at one time or another 
 everything which is about to become part of the tissues, and every- 
 thing which has ceased to belong to them. It is at once the 
 scavenger and the food-provider of the cell. But no bloodvessel 
 enters any cell;* and if we could unravel the complex mass of 
 tissue elements which essentially constitute what we call an organ, 
 we should see a sheet of cells, with capillaries in very close relation 
 to them, but everywhere separated from them by a thin layer of 
 Ivmph. And to describe in a word the circulation of the food 
 substances we may say that the blood feeds the lymph, and the lymph 
 feeds the cell. 
 
 Section I. — Morphology of the Blood. 
 
 The blood consists essentially of a Hquid part, the plasma, in 
 which are suspended cellular elements, the corpuscles. When the 
 circulation in a frog's web or lung or in the tail of a tadpole is 
 
 * Fine intracellular canaliculi, communicating with the blood-capillaiits, 
 and probably performing a nutritive function, since they seem to contain 
 bloocl-plasma have been described by Schafer and others in the liver cells. 
 
 14 
 
THE BLOOD-CORPUSCLES 
 
 15 
 
 examined under tlie microscope, the bloodvessels are seen to be 
 crowded with oval bodies — of a yellowish tinge in a thin layer, but 
 in thick layers crimson — which move with varying velocity, now 
 in single file, now jostling each other two or three abreast, as they 
 are borne along in the axis of an apparently scanty stream of 
 transparent liquid. Nearer the walls of the vessels, sometimes 
 clinging to them for a little and then being washed away again, 
 may be seen, especially as the blood-flow slackens, a few com- 
 paratively small, round, colourless cells. The oval bodies are the 
 red or coloured corpuscles, or erythrocytes; the colourless elements 
 are the white blood-corpuscles, or leucocytes; the liquid in which 
 they float is the plasma (Practical Exercises, p. 193). 
 
 The Red Blood-Corpuscles, or Erythrocytes, differ in shape and 
 size and in other respects in different animal groups. In amphib- 
 ians, such as the frog and the newt, they are flattened ellipsoids 
 containing a nucleus, and the same 
 
 is true of nearly all the other ver- Elephant 00^4. 
 
 tebrates, except mammals. In /'^l^^^^zHr -^'^ ""V 
 
 mammals they are discs, hollowed f f//<^^:^\^..Sheep. -ooso 
 out on both the flat surfaces, or [([{C)mTT-'%°''^i j T*' 
 biconcave, and possess no nucleus. \ \S>=^^/ 
 But the red corpuscles of the llama ^-^^Zll^^^^ 
 and the camel, although non- 
 
 1,1 IT J 1 • u Fig- I- — Diagram showing Relative 
 
 nucleated, are ellipsoidal in shape, %^^^ ^f r/^ Corpuscles of Various 
 
 like those of the lower vertebrates. Animals. 
 
 As to size, the average diameter 
 
 in man is between 7 and 8 /u* In the frog the long diameter is 
 
 about 22 f^, while in Proteus it is as much as 60 ju, and in Amphiuma, 
 
 the corpuscles of which can be seen with the naked eye, nearly 
 
 80 /J, [Frontispiece) . 
 
 As regards the structure of the red corpuscles, the most prob- 
 able view is that they are solid bodies, with a spongy and elastic 
 structureless framework, denser at the surface of the corpuscle than 
 in its centre, but continuous throughout its whole mass (Rollett). 
 The denser peripheral layer constitutes a physiological envelope 
 which permits the passage of certain substances into or out of the 
 corpuscles, and hinders the passage of others. In the large oval 
 corpuscles of Necturus (see Frontispiece) the envelope can be clearly 
 demonstrated as a detachable membrane comparable to the mem- 
 brane surrounding the nucleus. 
 
 Envelope and spongework are sometimes spoken of as the stroma 
 of the corpuscle, in contradistinction to its most important con- 
 stituent, a highly complex pigment, the haemoglobin. This pigment 
 is not in solution as such, for its solubility is not nearly great 
 enough to permit this, but either in solution as a compound with 
 * A micro-millimetre, represented by symbol fi, is ttjVtt millimetre. 
 
i6 77//: CIRCULATING LIQUIDS OF THE BODY 
 
 some otluT nnUnown substance, or more probably bound in some 
 solid or semi-solid combination to the stroma, and filling up the 
 space within the enxelope in the interstices of the spongework. 
 Since there is good reason to believe that the haemoglobin as 
 obtained artificiall}^ from the corpuscles is not quite the same sub- 
 stance as the native blood-pigment within them, the latter is some- 
 times distinguished by a separate name — haemochrome. To the 
 physical properties of the stroma it is usual to attribute the great 
 elasticity of the corpuscles -that is, the power of recovering their 
 original shape after distortion — for their elasticity is in no wise 
 impaired by the removal of the haemoglobin. 
 
 Rouleaux Formation. — When blood with disc-shaped corpuscles is 
 shed, there is a great tendency for the corpuscles to run together into 
 groups resembling rouleaux, or piles of coin. No satisfactory explana- 
 tion of this curious fact has yet been given. 
 
 Crenation of the corpuscles, a condition in which they become 
 studded with fine projections, is caused by the addition of moderately 
 strong salt solution, by the passage of shocks of electricity at high 
 potential, as from a Leyden jar, or by simple exposure to the air. Con- 
 centrated saline solutions, which abstract water from the corpuscles 
 and cause them to shrink, make the colour of blood a brighter red, 
 because more light is now reflected from the crumpled surfaces. On 
 the other hand, the addition of water renders the corpuscles spherical; 
 more of the light passes through them, less is reflected, and the colour 
 becomes dark crimson [Frontispiece). 
 
 The White Blood-Corpuscles, or Leucocytes. — The red corpuscles 
 are peculiar to blood. The white corpuscles may be looked upon 
 as peripatetic portions of the mesoderm (see Chap. XIX.), and some 
 of them ought not in strictness to be called blood-corpuscles. They 
 are more truly body corpuscles. Similar cells are found in many 
 
 situations, and wan- 
 der everywhere in the 
 spaces of the connec- 
 tive tissue. They pass 
 into the bloodvessels 
 with the lymph, and 
 may pass out of them 
 again in virtue of 
 their amoeboid power. 
 They consist of proto- 
 
 Fig. 3.— Amoeboid Movement. A, B, C. D. succes- P^''^sm, lesS differ- 
 sive changes in the form of an amoeba. entiated than that 
 
 of any other cells in 
 the body, and under the microscope appear as granular, colour- 
 less, transparent bodies, spherical in form when at rest, and 
 containing a nucleus, often tri- or multi-lobed. Many of the leuco 
 cytes of frog's blood at the ordinary temperature, and of mam- 
 malian blood when artificially heated on the warm stage, may be 
 
THE BLOOD-CORPUSCLES 
 
 n 
 
 seen to undergo slow changes of form. Processes called pseudo- 
 podia are pushed out at one portion of the surface, retracted at 
 another, and thus the corpuscle gradually moves or ' flows ' from 
 place to place, and envelopes or cats up substances, such as grains 
 of carmine, which come in its way. This kind of motion was first 
 observed in the amoeba, and is therefore called amcjeboid. It is 
 perhaps due to local alterations of surface tension; at any rate, 
 similar phenomena can be thus produced artificially. The leuco- 
 cytes of human blood are not all of the same size, and differ also in 
 other respects. They may be classified according to the presence 
 or absence of granules in their protoplasm, and the fineness or 
 coarseness of the granules ; according to the chemical nature of the 
 dyes with which the granules most readily stain, and according to 
 the form of the nucleus. Five or six varieties of leucocytes may 
 -thus be distinguished in normal blood [Frontispiece) : 
 
 1. Polymoyphonudear Neutrophile Cells. — The nucleus assumes a 
 great variety of forms, often contorted or deeply lobed, the lobes being 
 united by fine strands of chromatin. The cytoplasm contains numerous 
 fine refractive granules, which stain best neither with simple acid dyes 
 like eosin nor with simple basic dyes like methylene blue, but with 
 mixtures which must be assumed to contain ' neutral ' stains, like 
 Ehrlich's so-called triacid stain.* These cells make up 65 to 75 per 
 cent, of the total number of leucocytes. Their diameter is 10 to 
 12 /i. 
 
 2. Eosinophile Cells (12 to 15 ^ in diameter), much less numerous in 
 normal blood than the neutrophiles (less than 5 per cent, of the whole), 
 but found in considerable numbers in the serous cavities, the connec- 
 tive tissue, and the bone-marrow. The granules in the cytoplasm are 
 coarser than the neutrophile granules, and stain much more deeply 
 with eosin. The nucleus may be simple, lobed, or even divided into 
 fragments between which no connection can be traced. It is less rich 
 in chromatin, and stains less easily with basic dyes, like methylene blue, 
 than the nucleus of the first variety. 
 
 3. Large Mononuclear (also called Transitional) Leucocytes, with a 
 diameter of 12 to 15 /x. They possess a large simple or slightly lobed 
 nucleus, poor in chromatin, surrounded by a relatively great amount 
 of cytoplasm, with faint neutrophile granules — i.e., granules which stain 
 with neutral dyes. They constitute 3 to 5 per cent, of the total number 
 of leucocytes. 
 
 4. Lymphocytes of Two Varieties — {a) Small Lymphocytes. — Smaller 
 cells than any of the preceding (diameter 6 fi), possessing a single large 
 nucleus, surrounded by a comparatively small amount of non-granular 
 cytoplasm; 20 to 25 per cent, of the leucocytes of the blood belong to 
 this group. The lymphocytes are markedly deficient in the power of 
 amoeboid motion in comparison with the other varieties of colourless 
 corpuscles. 
 
 (b) Large Lymphocytes. — The largest of all the white cells of the blood, 
 and at least twice as large as the small lymphocytes. They possess 
 a relatively great proportion of cytoplasm, which is devoid of (;ranules. 
 They constitute no more than i per cent, of the total number of the 
 colourless corpuscles. 
 
 * A mixture of orange G., acid fuchsin, and methyl green. 
 
 2 
 
l8 THE CIRCULATING LIQUIDS OF THE bOD\ 
 
 5. ' Mast Cells,' or ' Basophiles,' the least numerous variety (05 per 
 cent, of the total number). Wry few arc to be found in the normal 
 blood of adults, but more in cliildren. They are somewhat smaller 
 than the neutrophils (average diameter about 10 fi). The nucleus is 
 irregularly trilobed. The protoplasm shows coarse granules, which do 
 not glitter like the granules of the eosinophile cells, and are therefore 
 less conspicuous in the unstained condition. Unlike the eosinophile 
 granules, they stain with basic dyes, such as methylene blue. 
 
 Blood-Plates, or Thromboqrtes. — When blood is examined im- 
 mediately after being shed, small colourless bodies (i to 3 // in 
 diameter) of various shapes, but usually round or oval, may be seen. 
 These are the blood-plates or platelets, also called thrombocytes, 
 on account of their function in the coagulation of blood. If the 
 blood is not at once subjected to some procedure which prevents 
 clotting, the platelets swell and then break up. There is reason to 
 believe that in most of the methods of preventing coagulation the 
 essential action is to hinder the break-up of the platelets (p. 37). 
 They can be isolated by receiving a drop of blood from the finger 
 upon a well-cleaned cover-slip, which is then laid, supported by two 
 thin glass fibres, on a carefully cleaned slide. The plasma with the 
 coloured corpuscles and leucocytes are washed away by irrigating 
 the space between slide and sUp with a suitable solution, e.g., a 
 salt solution containing a certain proportion of manganese sulphate, 
 which prevents disintegration of the platelets. The platelets stick 
 to the cover-shp (Deetjen). They can then be fixed and stained. 
 The blood-plates can even, like leucocytes, be kept alive on 
 the warm stage in an appropriate medium (agar, to which certain 
 salts have been added), and then show lively amoeboid movements 
 (Deetjen). They have been described as nucleated cells, although 
 the nucleus is not easy to stain, and with the ultra-microscope, a 
 delicate mesins of testing whether such an object as a platelet is 
 optically homogeneous, no evidence of the presence of a nucleus 
 has been obtained. The origin of the platelets has been a matter of 
 lively controversy. They are not produced by the breaking up of 
 other elements of the shed blood, for they have been observed 
 within the freshly excised, and therefore still living, capillaries — 
 in the mesentery of the guinea-pig and rat (Osier). According to 
 the best evidence, they are derivatives neither of the erythro- 
 C5rtes nor of the leucocytes of the blood, but are de\eloped from 
 special elements (so-called megakar\'ocytes) of the blood-forming 
 organs (bone-marrow) (J. H. Wright). 
 
 Enumeration of the Blood-Corpuscles.— This is done by taking a 
 measured quantitv of l)l()od. diluting it to a knowTi extent with a 
 liquid which does not destroy the corpuscles, and counting the 
 number in a given volume of the diluted blood (p. 67). 
 
 The average number of red corpuscles in a cubic millimetre of 
 blood is about 5,000,000 in a healthy man, and about 4,500,000 in 
 
THE BLOOD-CORPUSCLES 
 
 19 
 
 a healthy vvuiiian, but a variation of 1,000,000 up or down can hardly 
 he considered abnormal. In persons suffering from profound anaemia 
 the number may sink to 1,000,000 per cubic millimetre, or even 
 less. In one case of pernicious anaemia, only 143,000 corpuscles 
 
 per cubic millimetre were present, the 
 lowest number recorded. In new-born 
 children the average is over 6,000,000, 
 and in the inhabitants of high plateaus 
 or mountnins it may rise to 7,000,000 or 
 Fig.s-CurveshowingtheNumber ^ven more. In the latter instance a 
 of Red Corpuscles at Different residence of a fortnight m the rarefied 
 Ages (after Sorensen's Estima- ^ir is Sufficient to bring about the in- 
 tions). The figures along the ^ Subsequent residence of a 
 
 horizontal axis are vears ot age, ^'^^'^ ^' ""'^ a. kj^u ^ 1 •, * 
 
 those along the vertical axis fortnight m the lowlands to annul it.'^ 
 millions of corpuscles per cubic In certain pathological conditions a 
 millimetre of blood. ^^^^^ increase in the relative number of 
 
 corpuscles (polycythemia) is found. Over 13,000,000 erythrocyte*^ 
 to the cubic millimetre have been counted in a case of cyanosis (im- 
 perfect oxygenation of the blood, with blueness of the lips, etc.), due 
 to congenital disease of the heart. An interesting form of experi- 
 mental polycythaemia is caused by injection of adrenahn. 
 
 The nimiber of white blood-corpuscles is on the average about 
 10,000 per cubic millimetre of blood, or 
 one leucocyte for every 500 red blood- 
 corpuscles. But if the count is made 
 when digestion is relatively inactive, 
 four to five hours after a meal, it gives 
 no more than 7,000 to the cubic milli- 
 metre. In new-born children the 
 average number is over 18,000 per 
 cubic millimetre. The total leucocyte 
 count, and still more the so-called dif- 
 ferential count, i.e., the determination 
 of the relative number of the different 
 kinds of leucocytes, is often resorted to 
 in the study of pathological conditions. 
 A distinct increase in the number is 
 designated leucocytosis. In leukaemia 
 the number of white corpuscles is 
 enormously increased — on the average 
 to about 300,000, but in extreme cases 
 to 600,000 per cubic miUimetre — while at the same time the number 
 
 * In 113 apparently healthy students (male) the average number of red 
 corpuscles was 5,190,000 per cubic millimetre. In 104 of these, the number 
 ranged from 4,000,000 to 6,400,000; in 71 (or 63 per cent, of the whole), from 
 4.400,000 to 5,500,000; in 3, from 3,500,000 to 3,900,000; in 5, from 6,500,000 
 to 7,000,000. In one observation the number reached 7,300,000. 
 
 i:m 
 
 I 
 
 K m 
 
 Fig. 4. — Curve showing Propor 
 tion of White Corpuscles to Red 
 at Different Times of the Day 
 (after the Results of Hirt). At 
 I the morning meal was taken ; 
 at II the midday meal; at III 
 the evening meal. During 
 active digestion the number of 
 lymphocytes in the blood is 
 greatly increased, both abso- 
 lutely and relatively to the 
 number of the other leucocytes. 
 
20 THE CIRCULATING LIQUIDS OP THE BODl 
 
 of the red corpuscles is diminished; and the ratio of white to red 
 may approach 1:4. As the anaemia rapidly advances towards the 
 fatal termination of an acute case, and the erytlirocyte count falls to 
 1,000,000, or even less, the ratio may come still nearer to unity. An 
 increase in the number of leucocytes has also been observed in cer 
 tain infective diseases as part of the inflammatory' reaction. There 
 are also physiological variations, even within short periods of time; 
 for example, the number of lymphocytes is increased when digestion 
 is going on (digestive lymphocytosis). The normal number of 
 blood-plates varies from a quarter to half a million to the cubic 
 millimetre, but may be greater in disease and at high levels 
 (Kemp). 
 
 Life-History of the Corpuscles. — The corpuscles of the blood, like 
 the body itself, fulhl the allotted round of life, and then die. They 
 arise, perform their functions for a time, and disappear. But 
 although the place and mode of their origin, the seat of their destruc- 
 tion or decay, and the average length of their life, have been the 
 subject of active research and still more active discussion for many 
 years, much yet remains unsettled. 
 
 Origin of the Erythrocytes. — In the embryo the red corpuscles, even 
 of those forms (mammals) whicli have non-nucleated corpuscles in 
 adult life, are at first possessed of nuclei, and approximately spherical 
 in form. In the human foetus, at the fourth week all the red corpuscles 
 are nucleated. Later on the nucleated corpuscles gradually diminish 
 in number, and at birth they have almost or altogether disappeared, 
 some of them, at least, having been converted by a shrivelling of the 
 nucleus into the ordinary non-nucleated form. In the newly bom rat, 
 which comes into the world in a comparatively immature state, many 
 of the red corpuscles may be seen to be still nucleated. The first cor- 
 puscles formed in embryonic life are developed outside of the embryo 
 altogether. Even before the heart has as yet begun to beat, certain 
 cells of the mesoderm (see Chapter XIX.) in a zone (' vascular area ') 
 around the growing embryo begin to sprout into long, anastomosing 
 processes, which afterwards become hollowed out to form capillary 
 bloodvessels. At the same time clumps of nuclei, formed by division 
 of the original nuclei of the cells, gather at the nodes of the network. 
 Around each nucleus clings a little lump of protoplasm, which soon 
 develops haemoglobin in its substance ; and the new-made corpuscles 
 float away within the new-made vessels, where they rapidly multiply 
 by mitosis. In later cmbrj'onic life the nucleated corpuscles continue 
 in part to be developed within the bloodvessels in the liver, allantois, 
 spleen, and red bone-marrow, and in certain localities in the connective 
 tissue, by mitotic division of previously existing nucleated corpuscles, 
 in part to be formed endogenously within special cells in the liver and 
 perhaps other organs. Still later the nucleated corpuscles give place in 
 the blood of the mammal to non-nucleated erythrocytes. Many of 
 these are doubtless derived from the nucleated corpuscles, but some 
 appear to be produced in the interior of certain cells of the connective 
 tissue, and are non-nucleated from the start. 
 
 In the mammal in extra-uterine life the chief seat of formation 
 of the red blood-corpuscles, or haematopoiesis, is the red marrow of 
 
THE BLOOD-CORPUSCLES ai 
 
 the bones of the skull and trunk, and of the ends of the long bones 
 of tile limbs. Special nucleated cells in the marrow, originally 
 colourless, multiply by karyokinesis, take up hsemoglobin or, what 
 is much more likely, form it within their j)rotoplasm, and are 
 transformed by various stages into the ordinary non-nucleated red 
 corpuscles, which then pass into the blood-stream. These blood- 
 fomiing cells have received the name of erythroblasts or h.'emato- 
 blasts. According to their size, erythroblasts have been distinguished 
 as normoblasts, megaloblasts, and microblasts. The normo- 
 blasts are most numerous, and have about the same diameter as 
 the full-formed erythrocytes, into which they are believed to 
 develop. The megaloblasts are larger, and the microblasts smaller, 
 and they are thought to be the precursors of those aberrant forms 
 of erythrocytes sometimes found in the blood in certain diseases. 
 After haemorrhage rapid regeneration of the blood takes place, so 
 that in a few weeks the loss of even as much as a third of the total 
 blood is made good. The plasma is much sooner restored to its 
 normal amount than the corpuscles. Microscopical examination 
 shows in the red marrow the tokens of increased production of 
 coloured corpuscles, and nucleated erythrocytes appear in the 
 blood, the normoblasts being, as it were, hurried into the circula- 
 tion before the transformation which normally results in the dis- 
 appearance of the nucleus is complete. The same is true in 
 severe pathological ansemias, e.g., pernicious ansemia. It is a 
 matter of interest that other organs also, which in embr^'onic 
 life perform a haematopoietic function, particularly the spleen, 
 may, in such emergencies, again take on the office of forming 
 blood-corpuscles. 
 
 A constant destruction of red blood-corpuscles must go on, for 
 the bile-pigment and the pigments of the urine are derived from 
 blood-pigment. The bile-pigment is formed in the liver. It con- 
 tains no iron ; but the liver cells are rich in iron, and on treatment 
 with hydrochloric acid and potassium ferrocyanide, a section of 
 liver is coloured by Prussian blue. Iron must therefore be 
 removed by the liver from the blood-pigment or from one of its 
 derivatives; and there is other evidence that the liver is either one 
 of the places in which red corpuscles are actually destroyed, or 
 receives blood charged with the products of their destruction. 
 Although it cannot be doubted that in all animals whose blood 
 contains haemoglobin the iron found in the liver bears an important 
 relation to the building up or breaking down of the blood-pigment, 
 the injection of haemoglobin or haemin, indeed, increasing markedly 
 the amount of iron in the liver, as well as in the spleen, bone-marrow 
 and other tissues, this does not seem to be the only function of the 
 hepatic iron, for the liver of the crayfish and the lobster, which 
 have no haemoglobin in their blood, is rich in iron. Destruction of 
 
22 THE CIRCULATING LIQUIDS OF THE BODY 
 
 erythrocytes may also take place in the spleen and bone-marrow. 
 Although the statement that free blood-pigment exists in demon- 
 strable amount in the plasma of the splenic \ein is incorrect, red 
 corpuscles have been seen in various stages of decomposition within 
 large amceboid cells in the splenic pulp; and deposits containing 
 iron ha\e been found there and in tlie red l:)one-marrow in certain 
 pathological conditions. But there is no good foundation for the 
 statement sometimes rather fancifully made that the spleen is in 
 any special sense the ' graveyard of the red corpuscles.' Some of 
 the coloured corpuscles may break up in the blood itself, forming 
 granules of pigment, which may then be taken up by the liver, spleen, 
 and lymph glands. Indeed, it is probable that a large proportion 
 of the woni-out erythrocytes are finally destroyed in the blood- 
 stream. The portal circulation may be more than other vascular 
 tracts a seat of this natural decay, perhaps in virtue of the presence 
 of substances with a hemolytic action (p. 28) absorbed from the 
 alimentary- canal. 
 
 It has been argued that the erythrocytes must be short-lived, 
 since they are devoid of nuclei (p. 6). and attempts have been 
 made to calculate the average time for which they survive in the 
 circulation from the amount of haemoglobin (or of its derivative, 
 haematin) required to furnish the daily excretion of bile-pigment. 
 The results arrived at, however, are not sufficiently trustworthv to 
 warrant their citation. 
 
 Origin and Fate of the Leucocytes. — There has been much dis- 
 cussion as to the origin of the white blood-corpuscles. The 
 numerous theories fall into two groups, which have been designated 
 somewhat pompously the monistic and the dualistic. According 
 to the first, all the colourless corpuscles arise from a single type 
 of parent cell, namely, the lymphocyte type, in its small or large 
 variety. According to the dualistic school, a fundamental distinc- 
 tion exists between the lymphocytes, or cells peculiar to lymphoid 
 tissues, and to the blood on the one hand, and the remaining varieties 
 of leucocytes on the other. The former are supposed to be derived 
 from the lymphoUasts of lymphoid tissue, and the latter from the 
 myeloblasts, the forerunners of the myelocytes of bone-marrow. 
 The question has recently been studied by Foot by a new method, 
 namely, by cultivating chicken marrow outside of the body, and 
 watching the transformation of certain of its cells. He concludes 
 in favour of the development of the polymorphonuclear leucocyte 
 from a lymphoid type of cell existing in the marrow, a conclusion 
 in harmonv with the monistic view. As regards their immediate 
 source, the small lymphocytes of the blood are undoubtedly derived 
 from the lymph, and are identical with the lymph-corpuscles. 
 That they are formed largely in the l^nnphatic glands is shown 
 by the fact that the lymph coming to the glands is much poorer 
 
THE BLOOD-CORPUSCLES 23 
 
 in corpuscles than that which leaves them. The lymphatic glands, 
 however, although the principal, are not the only seat of formation 
 of lymphocytes, for lymph contains some corpuscles before it has 
 passed through any gland; and although a certain number of these 
 may have found their way by diapedesis from the blood, others are 
 developed in the diffuse adenoid tissue, or in special collections of it, 
 such as the thymus, the tonsils, the Payer's patches and solitary 
 follicles of the intestine, and the splenic corpuscles. To a very 
 small extent white blood-corpuscles may multiply by karyokinesis 
 or indirect division in the blood. 
 
 The fate of the leucoc5rtes is even less known than that of the 
 red corpuscles, for they contain no characteristic substance, like 
 the blood-pigment, by which their destruction may be traced. That 
 they are constantly disappearing is certain, for they are constantly 
 being produced. Not a few of them actually escape from the 
 mucous membranes of the respiratory, digestive, and urinary 
 tracts. The remnants of broken-down leucocytes have been found 
 in the spleen and lymph glands. It must be assumed that many 
 break up in the blood-plasma itself. 
 
 Section II. — General Physical and Chemical Properties of 
 
 THE Blood. 
 
 Fresh blood varies in colour, from scarlet in the arteries to 
 purple-red in the veins. It is a somewhat viscid liquid, with a 
 saline taste and a peculiar odour. 
 
 Viscosity of Blood. — The viscosity of normal dog's blood is about 
 six times greater than that of distilled water at body temperature. 
 It can be determined by allowing the blood to flow through a capil- 
 lary tube of known dimensions under a definite pressure, and 
 measuring the amount which escapes in a given time. In general 
 the viscosity and specific gravity of the blood vary in the same 
 direction, although there is not an exact proportionality^ between 
 them. Thus, sweating, which causes a diminution of the water of 
 the blood, causes also an increase in its viscosity. With increasing 
 temperature the viscosity of the blood diminishes, as is the case 
 with other liquids (Burton-Opitz). 
 
 In polycythasmia, where the number of ervthrocytes in propor- 
 tion to plasma is greatly increased, the viscosity of the blood in- 
 creases in an equal degree. In one case of polj^cythsemia, with a 
 blood-count of 8,300,000, the viscosit}'' was 9-4 times that of water; 
 in a case of marked chlorosis it was only 2-14. But the importance 
 of this factor in causing an abnormal blood-pressure by increasing 
 or diminishing the resistance to the blood-flow has been exaggerated. 
 Although it has been shown that in the living vessels, so long as 
 
24 THE CIRCULATING LIQUIDS OF THE BODY 
 
 their calibre remains constant, the flow is affected by changes in 
 the viscosity of the blood, just as in ghiss tubes, compensation by 
 adjustment of the vascular calibre is so ample and so easy tha: 
 even the greatest alterations of viscosity produce little effect on 
 the mean blood-pressure. 
 
 Reaction of Blood. — In the sense in which the term is used in 
 physical chemistry, the reaction of a solution depends on the pro- 
 portion between its content of hydrogen (H + ) and hvdroxyl 
 (OH — ) ions, an excess of hydrogen ions corresponding to an acid 
 and an excess of hydroxyl ions to an alkaline reaction. It has been 
 sho\Mi by a physical method (the determination of the electro- 
 motive force of a cell containing blood or serum as one liquid) that 
 hydroxyl ions are present only in small excess, and that blood is 
 really but a little more alkaline than distilled water. Practically, 
 it may be regarded as a neutral liquid. Under a great variety of 
 conditions, physiological and pathological, its reaction remains 
 almost unchanged. Yet it is known that acids (carbon dioxide, 
 lactic, phosphoric, and sulphuric acids) are constantly being pro- 
 duced in the normal metabolism of the tissues. The administra- 
 tion of large quantities of acid or alkali causes a surprisingly small 
 effect. In diabetes, even when it can be proved that an abnormal 
 production of acid substances is taking place, the blood shows little, 
 if any, diminution in the proportion of hydroxyl ions; it remains 
 to all intents and purposes a neutral liquid. In diabetic coma, 
 where the blood may in extreme cases turn blue litmus red, the 
 true reaction is only slightly altered. 
 
 The manner in which the reaction of the blood, the tissue liquids, 
 and probably the protoplasm itself, is regulated within sucli narrow 
 limits is a subject of great interest. For there is reason to believe 
 that it is of the utmost moment that the equilibrium should be 
 maintained not only in order that the functions of the tissues may 
 be properly perfonned, but that danger to life may be averted. 
 To be sure, the excretor\' organs, the lungs and the kidneys, provide 
 the means by which the excess of acid (or of alkali) is finallv, under 
 normal circumstances, eliminated. Other regulative mechanisms 
 also exist. For example, it has been shown that when an excessive 
 production of acids (acidosis) occurs in conditions of disordered 
 metabolism, or when acids are purposely administered in large 
 amount, a greater quantity of ammonia, split off from the pro- 
 teins, is mobilized to aid in neutralizing the acids. But very 
 simple experiments on blood in vitro are sufficient to show that 
 the blood itself has a great capacity, as compared with water, to 
 resist a change in its reaction even when large amounts of acid or 
 alkali are added to it. The secret of the reaction-regulating power 
 lies, therefore, to a large extent in the blood itself. Two factors 
 have been shown to be of importance: (i) The power of the proteins^ 
 
GENERAL PHYSICAL A SD CHEMICAL PROPERTIES 25 
 
 in virtue of their amphoteric character, to combine either with 
 acids or with bases, so that, when excess of base is added to blood, 
 the proteins act as acids, and neutraHze the base; when excess of 
 acid is added, the proteins act as bases, and neutralize the acid. 
 (2) The equilibrium of certain of the inorganic constituents of the 
 blood (carbon dioxide, the carbonates, and the phosphates) is such 
 that even great variations in the concentration of any of these, 
 such as may nomially occur, produce scarcely any effect upon the 
 concentrations of the hydrogen and hydroxyl ions. 
 
 Thus, when phosphoric acid and sodiuin hydroxide are added to 
 water in certain proportions, and the sohition placed under a certain 
 tension of carbon dioxide (which is kept constant), we get a more or 
 less accurate imitation of blood as regiirds tlie inorganic substances 
 concerned in the regulation of its reaction, sodium bicarbonate 
 (NaHCOg) and disodium phosphate (Na2HP04) being present in the 
 solution as in blood. It is found that when the quantities are so chosen 
 that the H + concentration lies within the limits of variation of the 
 normal blood reaction, relatively large quantities of alkalies can be 
 added or withdrawn without causing much change in the H + concen- 
 tration. It can be shown both theoretical!}' and experimentally that 
 precisely those weak acids present in blood (CO2, XaH2P04) require the 
 largest addition of alkali to alter the reaction to a given extent, and 
 are therefore particularly suited to give stability to the reaction. 
 Thus carbon dioxide requires twenty-four times, and monosodium 
 phosphate thirty-tliree times, as much alkali as an equivalent solution 
 of acetic acid to cause a g^ven alteration of colour in rosolic acid 
 (E. Henderson). 
 
 The so-called ' titratable ' alkalinity of blood or serum, measured by 
 the amount of standard acid which must be added before the colour of 
 the indicator used changes from alkaline to acid, bears no necessary or 
 fixed proportion to the actual alkalinity. When blood, for instance, 
 is titrated with hydrochloric acid, with methyl orange as indicator, at 
 the point where the red colour appears all the disodium phosphate and 
 sodium bicarbonate will have been changed into monosodium phos- 
 phate and carbon dioxide, all the alkali removed from combination 
 with proteins, a certain amount of acid-protein compounds formed, 
 and other minor reactions produced (Henderson). It is difficult to 
 correlate the quantity deduced from such a titration with any physio- 
 logical condition, although undoubtedly it bears some relation to the 
 acid-neutralizing power of the blood, and some relation to its real 
 reaction. Still, by titration information of value can be obtained 
 which is not j-ielded by the physico-chemical method in regard to the 
 potential ' acid capacity ' of the blood and its power of resistance against 
 acid-poisoning. 
 
 What is estimated here is the quantity of acid required to satisfy the 
 proteins and to react with the carbonates and phosphates before that 
 concentration of hydrogen and hydroxyl ions just necessary to cause 
 the change of colour is established. This is not the same for different 
 indicators, since there is a certain minimum ratio in the concentration 
 of these ions at which each indicator turns in one or the other direction, 
 none turning precisely at the neutral point. Thus sermn appears to be 
 acid when tested with phenolphthalein, and alkali must be added to 
 the serum before the pink colour indicating alkalinity is produced. 
 On the other hand, with litmus or methyl orange it gives the alkaline 
 
26 THE CIRCULATING LIQUIDS OF THE BODY 
 
 reaction, and a considerable amount of acid must be added before the 
 colour of the indicator which denotes acidity appears. The true re- 
 action of the serum is not, of course, at one and tlic same time both 
 alkaline and acid ; but it is so near neutrality that it falls just below the 
 degree of alkalinity necessary to give the pink colour with phenol- 
 phthalcin, and just below tlie degree of acidity wliich gives the pink 
 colour corresponding to an acid reaction with metliyl orange. Certain 
 indicators — for example, rosolic acid — turn so as to give sharp cok)ur 
 reactions at about the concentration of hydrogen and hydroxyl ions 
 in the blood, and these may possibly be of use in determining the 
 changes in the true reaction for clinical purposes (Adler). 
 
 More closely related to the true alkalinity of the blood than the 
 titratable alkalinity is the carbon dioxide content. The estimation 
 of the total carbon dioxide in a sample of blood throws light upon 
 the capacity of the blood to perform one of its most important 
 functions — the transportation of carbon dioxide — and to preserve 
 one of its essential properties— an almost neutral reaction — in the 
 presence of an excessive intake or production of acid substances. 
 In herbivorous animals the carbon dioxide content of the blood is 
 easily lessened by the administration of acids, but in carnivora 
 and in man it is much more difficult to bring about such a decided 
 effect, for the reason already mentioned, the acid being neutralized 
 by ammonia. In many diseases, however, and particularly in those 
 accompanied by fever, this protective mechanism breaks down. 
 
 Specific Gravity of Blood. — ^The average specific gravity of blood 
 is about 1066 at birth. It falls during infancy to about 1050 in 
 the third year, then rises till puberty is reached to about 1058 in 
 males (at the seventeenth year), and 1055 in females (at the four- 
 teenth year). It remains at this level during middle life in males, 
 but falls somewhat in females. In chlorotic anaemia of young 
 women it may be as low as 1030 or 1035. It rises in starvation. 
 Sleep and regular exercise increase it (Lloyd Jones).* The specific 
 gravity of the serum or plasma varies from 1026 to 1032. 
 
 The Electrical Conductivity of Blood.— The liquid portion of the 
 blood conducts the current entirely by means of the electrolytes 
 dissolved in it, the most important of these being the inorganic 
 salts; and the conductivity of the serum varies, in different speci- 
 mens of blood, within a comparatively narrow range. The con- 
 ductivity of entire (defibrinated) blood, on the contrary, varies 
 within wide limits. For instance, in a case of pernicious anaemia 
 the conductivity of the blood was found to be almost double that 
 of normal human blood, while the conductivity of the serum was 
 normal. The most influential factor which governs this variation 
 
 * In 165 students (male) the average specific gravity of the blood, as deter- 
 mined by Hammerschlag's method (p. 02) was 1054-4. In 149 of these the 
 variation was from 1050 to 1065; in 94 (or 57 per cent, of the whole), from 
 1054 to 1060; in 4, from 1046 to 1049; in 9, from 1066 to 1070. In 3 the 
 specific gravity was only 1040 to 1042. 
 
GENERAL PHYSICAL AND CHEMICAL PROPERTIES 27 
 
 is the relative volume of the corpuscles and serum. When the 
 blood is relatively rich in corpuscles and poor in serum, its con- 
 ductivity is low; when it is poor in corpuscles and rich in serum, 
 its conductivity is high. The explanation is that the corpuscle 
 refuses passage to the ions of the dissociated molecules, which, in 
 virtue of their electrical charges, render a liquid like blood a con- 
 ductor (p. 428), or permits them only to pass very slowly, so that 
 the intact red corpuscles have an electrical conductivity so man}- 
 times less than that of serum, that they may, in comparison, be 
 looked upon as non-conductors (Practical Exercises, p. 69). 
 
 The Relative Volume of Corpuscles and Plasma in Unclotted 
 Blood, or, what can be converted into this by a small correction, 
 the relative volume of corpuscles and serum in defibrinated blood, 
 can be easily determined, with approximate accuracy, by com- 
 paring the electrical conductivity of entire blood with that of its 
 serum.* Another method, more suitable for clinical work, though 
 not so accurate, is the so-called hgematocrite method. A small 
 quantity of blood is centrifugalized in a graduated glass tube of 
 narrow bore until the corpuscles have been collected into a solid 
 ' thread ' at the outer extremity of the tube. Their volume and 
 that of the clear plasma which has been separated from them are 
 then read off on the scale. The hsematocrite must rotate at such a 
 high speed (10,000 turns a minute) that separation of the corpuscles 
 from the plasma is accomplished before clotting has occurred. 
 Dilution of the blood with liquids which prevent clotting is not 
 permissible for exact work (Practical Exercises, p. 68). By these 
 and other methods too elaborate for description here, it has been 
 shown that the plasma or serum usually makes up rather less than 
 two-thirds, and the corpuscles rather more than one-third, of the 
 blood. But this proportion is, of course, liable to the same varia- 
 tions as the number of corpuscles in a cubic millimetre of blood. 
 It depends, further, the number of corpuscles being given, on the 
 average volume of each corpuscle. For instance, when the mole- 
 cular concentration, and therefore the osmotic pressure (p. 427), 
 of the plasma is reduced, as by the addition of water or the abstrac- 
 tion of salts, water passes into the corpuscles and they swell ; when 
 the molecular concentration of the plasma is increased, by the 
 abstraction of water or the addition of salts, water passes out of 
 the corpuscles, and they shrink. In human serum the average 
 
 ♦ The formula p = jr -^ (174 - K(b)), where p is the number of c.c. of serum 
 
 in 100 c.c. of blood; K{b), K{s), the specific conductivities respectively of the 
 blood and serum (both measured at or reduced to 5° C, and, to obtain whole 
 numbers, multipHed by 10*), may be used in the calculation. K is the specific 
 conductivity of the liquid — i.e., the conductivity of a cube of the liquid of 
 I centimetre side. The conductivity of a similar cube of mercury is 10,630. 
 
28 THE CIRCULATING LIQUIDS OF THE BODY 
 
 depression of tlie freezing-point below that of distilled water, which 
 is a measure of the molecular concentration and of the osmotic 
 pressure, is about o-^fr C. (Practical Exercises, p. 73). For clinical 
 purposes, the determination of the relative volume of corpuscles and 
 plasma is most useful in cases where the average size of the erythro- 
 cytes departs from the normal, and where, accordingly, the enumera- 
 tion of the corpuscles would give an erroneous idea of thf^ir total mass. 
 
 Laking of Blood, or Haemolysis.- — Even in thin layers blood is 
 opaque, owing to reflection of tlie light by the red corpuscles. It 
 becomes transparent or ' laky ' when by any means the pigment 
 is brought out of the corpuscles and goes into true solution. Re- 
 peated freezing and thawing of the blood, the addition of water, 
 the passage of electricaJ currents, constant and induced,* putre- 
 faction, heating the blood to 60° C., and many chemical agents (as 
 bile-salts, ether, saponin), cause this change. Certain complex 
 poisons of animal origin, such as snake- venoms, bee-poison, spider- 
 poison or arachnolysin, and certain toxins produced by pathogenic 
 bacteria — -for instance, tetanolysin, formed by the tetanus bacillus 
 — also possess decided hsemol\i;ic power. The blood-serum of 
 certain animals acts on the coloured corpuscles of others, and sets 
 free their pigment — for example, the serum of the dog or ox causes 
 haemolysis of rabbit's corpuscles; the serum of the ox, goat, dog, 
 or rabbit lakes guinea-pig's corpuscles. But rabbit's serum does 
 not lake dog's corpuscles, and guinea-pig's serum is inactive towards 
 the corpuscles both of the rabbit and the dog. It has been shown 
 that in haemoh^sis bv foreign serum two bodies are concerned: one, 
 which is easilv destroyed by heating to about 56° C, the so-called 
 complement, and another, the intermediary body or amboceptor, 
 which is not affected by being heated to this temperature. Thus 
 if dog's serum be heated to 56° C. for twenty minutes, no amount 
 of it will lake rabbit's washed corpuscles— that is, rabbit's corpuscles 
 freed from their own serum by repeated washing with salt solution 
 and centrifugalization. If, however, serum which is not itself 
 haemol^-tic for rabbit's blood {e.g., rabbit's or guinea-pig's serum) 
 be added to the washed rabbit's corpuscles, they will be laked by 
 the heated dog's serum. Unheated dog's serum will lake rabbit's 
 corpuscles, whether they have been washed free from their own 
 serum or not (Practical Exercises, p. 71). 
 
 The hypothesis which best explains these facts and many similar 
 ones is that dog's serum contains both of the bodies necessary for 
 haemolysis of rabbit's corpuscles. When the complement has been 
 rendered inactive by heating, the amboceptor cannot cause laking 
 
 • The laking action of induced currents is due simply to the heating of the 
 blood. Condenser discharges, which cause liberation of the haemoglobin 
 without raising the temperature of the blood as a whole to the point at which 
 heat-laking occurs, possibly act in the same way by causing local heating of 
 the corpuscles owing to their high resistance. 
 
GENERAL PHYSICAL AND CHEMICAL PROPERTIES 29 
 
 by itself. Rabbit's serum contains complement, but not the 
 specific amboceptor necessary for the laking of rabbit's corpuscles. 
 Accordingly, the addition of fresh rabbit's serum to heated dog's 
 scrum restores complement to the latter, and thus it is again ren- 
 dered active for rabbit's corpuscles. The amboceptor is supposed 
 to unite on the one hand with certain groups in the corpuscle and 
 on the other with the complement, which is thus enabled to develop 
 its hi€mol}d;ic action upon the envelope or the stroma. The com- 
 plement is incapable of acting, even in the presence of amboceptor, 
 if the temperature is reduced to 0° C. Nevertheless, the corpuscles 
 take up amboceptor at this temperature, and on this fact is based 
 a method of freeing serum from amboceptor. For example, if 
 dog's serum and excess of rabbit's washed corpuscles, both pre- 
 viously cooled to 0° C, be mixed and placed at 0° C for some hours, 
 and the serum then removed, it will be found that it has lost the 
 power of laking rabbit's corpuscles, washed or unwashed, at air or 
 body temperature, although it will still do so on the addition of 
 dog's serum in which the complement has been destroyed by 
 heating it to 56° C The real nature and mode of action of com- 
 plements and amboceptors are not yet satisfactorily determined. 
 The laws of chemical equivalents and definite proportions do not 
 seem to be observed in the reactions into which they enter. It has 
 therefore been suspected that the bodies in question belong to the 
 group of ferments, or are closely related thereto, and there is some 
 evidence that a fat-splitting enzyme, or lipase, is concerned in the 
 complement action (Jobling). 
 
 As to the manner in which hasmolytic agents cause the hberation of 
 the blood-pigment, the fact that in so many forms of laking the cor- 
 puscles swell up before the heemoglobin escapes indicates that the 
 entrance of water is an important step. The entrance of water is 
 favoured by changes produced in the chemical and physical condition 
 of certain constituents of the superficial layer (envelope) of the cor- 
 puscle, as well as by changes in its interior. Saponin and ether, for 
 example, are known to be solvents of cholesterin and lecithin, and 
 cholesterin and lecithin are important constituents of the stroma and 
 envelope of the erjirhrocyte. It is easy to understand that if a portion 
 of one or both of these substances is dissolved, or altered without being 
 actually dissolved, profound changes may be produced in the permea- 
 bility of the corpuscle to water and to the salts dissolved in the liquid 
 in which the erythrocytes are suspended. In addition to this change 
 of permeability, many laking agents, perhaps all, exert also a more direct 
 influence on the normal relations of the native blood-pigment to tlu 
 stroma. Ether and saponin, for instance, seem to act in two ways — 
 bv disorganizing the envelope through solution of its lipoids, and thus 
 increasing its permeability to water; and by helping to dissociate the 
 blood-pigment-stroma complex by exerting a pull on the lipoids of the 
 stroma, while the water simultaneously exerts a pull on the pigment. 
 
 The conclusion follows from this view of haemolysis, that the erythro- 
 cytes, normally so perfectly adapted to the plasma in which they float, 
 may. when the conditions on which their equihbrivun with it depends 
 
30 THE CIRCULATING LIQUIDS OF THE BODY 
 
 are altered, be rapidly and inevitably destroyed by that very plasma 
 itself. It is, indeed, the very fact of the exquisite adaptation of liquid 
 and cell for a strictly regulated exchange of material which constitutes 
 the danger when the regulation is upset. A liquid like mercury, which 
 is not adapted either to give anything to erythrocytes in contact with 
 it or to take anything from them, would not cause hajmolysis, even if 
 the permeability of the corpuscles for water or sodium chloride were 
 increased to any extent. The continued survival of the erythrocytes in 
 an aqueous solution of salts and proteins like the plasma — nay, more, 
 the protection of the corpuscles up to a certain point by the plasma 
 against the attack of extraneous haemolytic agents — are facts we are 
 prone to take so much for granted as to forget that they depend entirely 
 upon a most delicate adjustment of the permeability of the corpuscles 
 for essential constituents of the plasma. Disturb these relations to a 
 sufficient degree, and the plasma becomes a poison to tlie erythrocytes 
 not much less deadly than distilled water. 
 
 When we add to blood a hemolytic substance, and see that presently 
 the blood-pigment has left the corpuscles, we are apt to attribute the 
 whole effect to the foreign material added, and to say that the saponin, 
 the ether, the alien serum, has laked the blood. In a certain sense this 
 is true, but it is not the whole truth. In reality the h^emolytic agent 
 has acted in an essential degree, although not exclusively, by overthrow- 
 ing the equilibrium between the corpuscles and the aqueous solution 
 of certain substances in which they are suspended. To say that the 
 foreign substance alone causes the hemolysis is no more accurate than 
 it would be to say that a man swimming strongly in a rough sea, who 
 sinks when hit and stunned by a piece of wreckage, was drowned by 
 the blow, and not by the sea. No doubt it is true that, but for the 
 blow, he would have continued to swim; yet, in reality, he loses his life 
 because he is environed by a medium deadly to him as soon as his power 
 of adjustment to it has been too much diminished. On land, the blow 
 would have stunned, but would not have killed him. In like manner, 
 to glance at one phase of the natural decay of the corpuscles within the 
 body, an erythrocyte may float secure in its watery environment 
 through many rounds of the circulation. But its security is not static, 
 like that of a log floating on the water. It is dynamic, a triumph of 
 perfect physico-chemical poise, as the security of the swimmer, still 
 more of the tight-rope dancer, is dynamic, a triumph of perfect neuro- 
 muscular poise. The time, however, arrives when, either through 
 changes in the corpuscle itself (the changes of cellular senility, as we 
 may call them), or through changes in the environing medium, or 
 through a combination of the two, the adjustment is upset, and the 
 erythrocyte is now destroyed by the plasma in which it has so long 
 lived . 
 
 In general haemolysis by foreign serum is preceded by agglutina- 
 tion or aggregation of the corpuscles into groups. Agglutination 
 may be obtained without haemolysis by heating the haimolytic 
 serum to the temperature at which the complement is destroyed, 
 since the agglutinating agents, or agglulinins, are relatively resistant 
 to heat. Besides the amboceptors naturally present in the blood 
 of certain animals, and capable, in conjunction with complement, of 
 hsemolyzing the corpuscles of certain other animals, amboceptors 
 may be produced in much greater strength by artificial means. 
 
CEXERAL PHYSICAL AMD CHhMlCAL PROPERIII-.S 31 
 
 When the corpuscles of one animal are injected intraperitoneally 
 or subcutaneously into an animal of a different kind, the serum of 
 the latter acquires the property of agglutinating and laking the 
 corpuscles of an animal of the same kind as that whose corpuscles 
 have been injected. This is especiall}' marked if the injection is 
 several times repeated at intervals of a few days. If, for instance, 
 dog's corpuscles are injected into a rabbit, the rabbit's serum after 
 a time becomes strongly hgemolytic for dog's corpuscles. It also 
 agglutinates them. This is due to the appearance in the rabbit's 
 serum of an amboceptor and an agglutinin which have a specific 
 action on dog's corpuscles. Such a serum is often termed an 
 immune serum, and the animal which has received the injections 
 is spoken of as immunized in regard to this particular kind of 
 corpuscles. For the reaction involved in the production of the 
 amboceptor and agglutinin is a particular case of the peculiar and 
 specific response which the body makes to the presence of foreign 
 juices or cells, including bacteria, and which constitutes an attempt 
 to render itself ' immune ' to them. 
 
 Many other animal cells besides the coloured blood- corpuscles give 
 rise, when injected, to similar specific substances (cytolysins), which 
 cause destruction of cells of the same kind — e.g., leucocytes and 
 spermatozoa.* The process of haemolysis is more easily followed 
 than the cytol3^sis of ordinary cells. Yet in its main features it is 
 essentially similar. 
 
 In each case the specific antibody seems to be produced in response 
 to the presence of some particular constituent of the foreign cell. The 
 substances which on injection give rise to antibodies are spoken of as 
 antigens. In tlie case of the ery-throcj^tes there is evidence that the 
 antigens (both the haemolj-sinogen, which causes the production of 
 specific amboceptor, and the agglutininogen, the substance which gives 
 rise to specific agglutinin) are lipoids, or are so closely associated with 
 the lipoids of the corpuscles that they are extracted by the same solvents. 
 Thus ethereal extracts of erythrocytes cause the production of hasmol- 
 ysin and agglutinin, just as the entire corpuscles do. The group of 
 antibodies known as precipitins is of special interest. 
 
 Precipitins.- — When the serum of one animal is injected into 
 another of a different group, the serum of the latter acquires the 
 property of causing a precipitate in the normal serum of animals 
 of the same group as that whose serum was injected, but not 
 
 * Recent studies have tended to modify the view that the cytotoxins 
 formed after the introduction of different foreign tissues into animals are 
 quite specific for each tissue. Thus Lambert, using tissues cultivated on 
 media outside of the body for testing the toxic action, finds that the plasma 
 of guinea-pigs which have received injections of either chick embryo heart or 
 intestine becomes toxic for both of these tissues. In like manner the plasma 
 of guinea-pigs treated by injection of rat sarcoma, a tumour which can be 
 propagated by inoculation in rats, acquires a toxic action on cultures of both 
 rat sarcoma and the skin of embryo rats. And the plasma of guinea-pigs 
 treated with rat embryo skin is also toxic for cells of both types. 
 
32 THE CIRCULATING LIQUIDS OF THE BODY 
 
 in the serum of any other kind of animal. Thus, if human blood 
 or serum is repeatedly injected at short intervals int(j a rabbit, tiie 
 serum of the rabbit will cause a precipitate in diluted human blood 
 or serum, but not in the blood or serum of other animals, except 
 that of monkeys, where a slight reaction may be obtained. The 
 specific bodies which cause the precipitation are termed precipitins. 
 The phenomenon has been made the basis of a method of dis- 
 tinguishing human blood for forensic purposes. Other animal 
 tiuids and solutions containing tissue proteins likewise give rise to 
 the production of precipitins. Thus, when cow's milk is injected 
 into a rabbit, the rabbit's serum acquires the power of precipitating 
 the caseinogen of cow's milk. Indeed, the response of the animal 
 body to the presence of foreign proteins is so catholic, and at the 
 same time so approximately specific, that many artificially isolated 
 proteins, even those of vegetable origin, after as careful purifica- 
 tion as possible, occasion, when injected, the production of anti- 
 bodies which will precipitate from a solution only the variety of 
 protein injected, or sometimes also, though in slighter degree, pro- 
 teins nearly related to it. 
 
 Anaphylaxis. — Under certain conditions the injection of a toxin, a 
 serum, or a protein solution, instead of chciting an immunity reaction 
 which tends to combat the eft'ects of a subsequent injection of the same 
 material, produces the opposite result — namely, a sensitization of the 
 animal which renders the second dose far more harmful than the first. 
 Thus, Kichet found that animals into which eel serum, or the poison 
 contained in the tentacles of Actinaria, was subcutaneously introduced 
 became much more sensitive to the toxic action of a second injection. 
 This phenomenon he designated anaphylaxis, as being the opposite of 
 the prophylaxis or protection afforded by previous treatment with the 
 toxins hitherto studied. Later on it was discovered that tlie sub- 
 cutaneous injection of a great variety of proteins alien to the animal 
 into which they are introduced causes anaphylaxis. Only very minute 
 amounts are necessary for the first or sensitizing dose, and an interval 
 considerably greater than that employed in the production of an 
 immune serum (p. 31) is allowed to elapse before the second injection 
 is made. The symptoms induced in the .sensitized animal by a subse- 
 quent dose of the same material used in sensitization differ somewhat 
 in different animals, but may be designated in general terms as those 
 of collapse or shock (anaphylactic shock). They have been especiallv 
 studied in the rabbit and guinea-pig, the heart being particularly affected 
 in the former, and the lungs in the latter. Tiie symptoms are very 
 severe, and manifest themselves within a very short time (a few minutes) 
 ol the injection. A large proportion of the animals die. If an animal 
 recovers, it does so suddenly, and for some time afterwards it is in- 
 sensitive to the particular protein. While the real nature of protein 
 sensitization or anaphylaxis is not as yet understood, it affords a new 
 and delicate test for the detection and discrimination of proteins, and 
 has already been utiHzed in a number ol practical applications. For 
 instance, the sophistication of sausages with other than the orthodox 
 ingredients — e.g., witli lionseflcsh — can be thus exposed, since an animal 
 sensitized by horseflesh will exhibit anaphylaxis to horseflesh, but not 
 to beef or pork. In like manner, the anaphylactic reaction may be 
 
GENERAL PHYSICAf. AXD CHEMICAL PROPERTIES 33 
 
 iiseJ lor the klciitific.ition of human blood. It is probable that an- 
 aphylaxis plays an important role in certain pathological reactions. It 
 is well known, for example, that some persons are so susceptible to 
 particular foods that the slightest indulgence in them brings on an 
 attack of urticaria or nettlerash. it has been suggested that these 
 persons have become sensitized to certain foreign proteins — such as 
 those existing in eggs, veal, pork, strawberries, shellfish, or whatever 
 the peccant article of diet may be — possibly by absorption at some 
 previous time, owing to gastro-intestinal disturbance, of small quan- 
 tities of the proteins which have escaped complete digestion. 
 
 It is only when proteins arc introduced parenterally (i.e., by some 
 other route than the alimentary canal, such as the subcutaneous tissue, 
 the blood, or the serous cavities) that the immunity reactions already 
 described and the phenomenon of anaphylaxis can be experimcntallj'' 
 produced. For in digestion the protein molecule is decomposed, and 
 although, as will be seen later on, the decomposition products are not 
 the same for each kind of protein, the factor on which the specificity 
 of the molecule depends does not survive the hydrolysis. 
 
 Coagulation of the Blood. 
 
 Since changes begin in the blood as soon as it is shed, having 
 for their outcome clotting or coagulation, we have to gather from 
 the composition of the stable factors of clotted blood, or of blood 
 which has been artificially prevented from clotting, some notion of 
 the composition of the unalteied fluid as it circulates within the 
 vessels. The first step, therefore, in the study of the chemistry 
 of blood is the study of coagulation. 
 
 When blood is shed, its viscidity soon begins to increase, and 
 after an interval, varying with the kind of blood, the temperature 
 of the air, and other conditions, but in man seldom exceeding ten, 
 or falling below three, minutes, it sets into a firm jelly. This jelly 
 gradually shrinks and squeezes out a straw-coloured liquid, the 
 serum. Under the microscope the serum is seen to contain few or 
 no red corpuscles; these are nearly all in the clot, entangled in the 
 meshes of a kind of network of fine fibrils composed of fibrin. In 
 uncoagulated blood no such fibrils are present ; they have accordingH' 
 been formed by a change in some constituent or constituents of 
 the normal blood. Now, it has been shown that there exists in the 
 plasma — nhe liquid portion of unclotted blood — -a substance from 
 which fibrin can be derived, while no such substance is present in 
 the corpuscles. In various ways coagulation can be prevented or 
 delayed, and the plasma separated from the corpuscles. For 
 example, the blood of the horse clots very slowly, and a low tem- 
 perature lessens the rapidity of coagulation of every kind of blood. 
 If horse's blood is run into a vessel surrounded by ice and allowed 
 to stand, the corpuscles, being of greater specific gravity than the 
 plasma, gradually sink to the bottom, and the clear straw-yellow 
 plasma can be pipetted off. Or the addition of neutral salts to 
 
 3 
 
34 THE CIRCULATING LIQUIDS OF THE BODY 
 
 blood may be used to delay coagulation, the blood being run direct 
 from the animal into, say, a third of its volume of saturated mag- 
 nesium sulphate solution. The plasma may then be conveniently 
 separated from the corpuscles by means of a centrifugal machine. 
 Again, two ligatures may be placed on a large bloodvessel, so that 
 a portion of it can be excised full of blood and suspended vertically 
 (the so-called experiment of the ' living test-tube ') ; coagulation 
 is long delayed, and the corpuscles sink to the lower end. In these 
 and man}- other ways plasma free from corpuscles can be got ; and 
 it is found that when the conditions which restrain coagulation are 
 removed— when, for instance, the temperature of the horse's plasma 
 is allowed to rise or the magnesium sulphate plasma is diluted with 
 several times its bulk of water— clotting takes place, with forma- 
 tion of fibrin in all respects similar to that of ordinary blood-clot. 
 The corpuscles themselves cannot form a clot.* From this we con- 
 clude that the essential process in coagulation of the blood is the 
 formation of fibrin from some constituent of the plasma, and that 
 the presence of corpuscles in ordinary blood-clot is accidental. 
 In accordance with this conclusion, we find that l>-mph entirely 
 free from red corpuscles clots spontaneously, with formation of 
 fibrin ; and when fibrin is removed from newly shed blood by whip- 
 ping it with a bundle of twigs or a piece of wood, it will no longer 
 coagulate, although all the corpuscles are still there. 
 
 What, now, is the substance in the plasma which is changed into 
 fibrin when blood coagulates ? If plasma, obtained in any of the 
 ways described, be saturated with sodium chloride, a precipitate is 
 thrown down. The filtrate separated from this precipitate does not 
 coagulate on dilution with water; but the precipitate itself — the 
 so-called plasmine of Denis — on being dissolved in a little water, 
 does form a clot. Fibrin is therefore derived from something in 
 this precipitate. Now, ' plasmine ' contains two protein bodies — 
 fibrinogen, which coagulates by heat at about 56° C, and serum- 
 globulin, which coagulates at about 75° C, and it was at one time 
 believed that both of these entered into the formation of fibrin 
 (Schmidt). Hammersten, however, has sho\\Ti that fibrinogen alone 
 is a precursor of fibrin; pure serum-globulin neither helps nor 
 hinders its formation. This obser\-er isolated fibrinogen from blood- 
 plasma by adding sodium chloride till about 13 per cent, was 
 present. With this amount the fibrinogen is precipitated, while 
 serum-globulin is not precipitated till 20 per cent, of salt is reached. 
 After precipitation of the fibrinogen, the plasma no longer coagu- 
 lates; and a solution of pure fibrinogen can be made to clot and 
 to form fibrin, while a solution of serum-globulin cannot. Blood- 
 
 * Bird's corpuscles, however, washed free from plasma, will form a clot 
 when laked in various ways, as by addition of water or by freezing and 
 thawing. 
 
COAGULATION 35 
 
 serum, too, which contains abundance of serum-globuHn, but no 
 fibrinogen, will not coagulate. 
 
 So far, then, we have reached the conclusion that fibrin is formed 
 by a change in a subsfance, fibrinogen, which can be obtained by 
 certain methods from blood-plasma. It may be added that there 
 is evidence that fibrinogen exists as such in the circulating blood; 
 for if unclotted blood be suddenly heated to about 56° C, the tem- 
 perature of heat-coagulation of fibrinogen, the blood for ever loses 
 its power of clotting. The liver seems to be an important place of 
 origin of fibrinogen, which may also be formed in the bone-marrow. 
 That the liver is intimatel}' concerned in the production of fibrinogen 
 is indicated by a number of facts. In phosphoras poisoning, and 
 notably in poisoning by chloroform, which causes necrosis, especially 
 of the central portions of the hepatic lobules, the amount of 
 fibrinogen in the blood is quickly diminished. The diminution is 
 proportional to the extent of the injury to the liver, and the blood 
 loses more or less completely its power of clotting. If the injury 
 is repaired, the fibrinogen is rapidly regenerated (Whipple). If the 
 blood is allowed to circulate for a time in the head and thorax of 
 an animal without passing into the rest of the animal's body, it 
 becomes incoagulable, and the fibrinogen is found to be markedly 
 deficient in amount. When the blood of an animal is defibrinated 
 by whipping, and reinjected, regeneration of the fibrinogen does 
 not occur if the liver has been eliminated, whereas it takes place 
 rapidly if the liver is intact (Meek) . 
 
 Since fibrinogen is readily soluble in dilute saline solutions, and 
 fibrin only soluble with great diflficult^^ we may say that in coagu- 
 lation of the blood a substance soluble in the plasma passes into an 
 insoluble form. How is this change determined when blood is 
 shed ? We have said that a solution of pure fibrinogen can be 
 made to coagulate, but it does not coagulate of itself. The addition 
 of another substance in minute quantity is necessary. This sub- 
 stance, to which the name thrombin has been applied, can be 
 obtained in various ways, although not in a state of purity; for 
 example, by precipitating blood-serum, or defibrinated blood, with 
 fifteen to twenty times its bulk of alcohol, letting the whole stand 
 for a month or more, and then extracting the precipitate with 
 water. All the ordinary proteins of the blood having been ren- 
 dered insoluble by the alcohol, the thrombin passes into solution 
 in the water, and the addition of a trace of the extract to a solution 
 of fibrinogen causes coagulation. When purified as well as possible, 
 thrombin still gives protein reactions, but it is not known whether 
 it is really a protein. 
 
 The action of thrombin on fibrinogen helps to explain many 
 experiments in coagulation. Thus, transudations like hydrocele 
 fluid do not clot spontaneously, although they contain fibrinogen, 
 
36 THE CIRCULATING LIQUIDS OF THE BODY 
 
 which can be precipitated from them by a stream of carbon dioxide 
 or by sodium chloride. But the addition of a httle thrombin 
 causes hydrocele fluid to coagulate. So does the addition of serum, 
 not because of the serum-globulin which it contains, as was once 
 believed, but because of the thrombin in it. The addition of blood- 
 clot, either before or after the corpuscles have been washed away, 
 or of serum-globuUn obtained from serum, also causes coagulation 
 of hydrocele fluid, and for a similar reason, the thrombin having a 
 tendency to cling to everything derived from a liquid containing 
 it. On the other hand, serum which, although thrombin is present 
 in it, does not of itself clot, because the fibrinogen has all been 
 changed into fibrin during coagulation of the blood, can be made 
 to coagulate by the addition of hydrocele fluid, which contains 
 fibrinogen. We have thus arrived a step farther in our attempt to ex- 
 plain the coagulation of the blood : it is essentially due to the formation 
 of fibrin front the fibrinogen of the plasma under the infitience of 
 thrombin. Up to this point there is agreement between physiologists. 
 Some difference of opinion exists, however, as to the manner in 
 which thrombin is formed or activated when blood is shed, aud a? 
 to the nature of its action upon fibrinogen once it is fully formed. 
 
 The Formation of Thrombin from its Precursors. — There is good 
 reason to believe that thrombin is formed by the interaction of three 
 factors: (i) A substance which, since it is a precursor of thrombin, 
 is called thrombogen, or prothrombin. It is already present in the 
 circulating plasma. (2) A substance liberated from the formed ele- 
 ments of the shed blood, but which can be obtained also from the 
 cells of all tissues. Since it has been supposed to act upon throm- 
 bogen, changing it into fully formed thrombin, much in the same 
 way as enterokinase (p. 37c) acts upon trypsinogen, changing it 
 into fully formed trypsin, it is called thrombokinase (Morawitz). 
 (3) Calcium ions. The following experiments illustrate the role of 
 these three factors: 
 
 The plasma obtained by drawing off bird's blood — e.g., the blood of a 
 fowl or goose — through a perfectly clean cannula into a perfectly clean 
 vessel, without contact with the tissues, and tlicn rapidlj' centrifugal- 
 izing off the formed elements, can be kept unclotted for days and even 
 weeks. The addition of a small amount of tissue extract (procured by 
 rubbing up blood-free liver, thymus, muscle, or other organs with sand, 
 and extracting for several hours with salt solution) to the bird's plasma 
 causes rapid coagulation. The plasma contains thrombogen and 
 calcium salts, but is lacking in thrombokinase, which is supplied by the 
 tissue extract. A solution of fibrinogen containing calcium will clot 
 if serum, in which fibrin-ferment is always present, be added. It will 
 not clot on addition of tissue-extract alone, nor on addition of bird's 
 plasma alone (obtained as above), but will readily coagulate if both 
 tissue extract and bird's plasma be added. Therefore, something in 
 the bird's plasma (thrombogen), plus something in the tissue extract 
 (thrombokinase), produce in the presence of calcium the same effect as 
 the thrombin of serum. It can be shown that calcium is only necessary 
 
COAGULATION 37 
 
 for the formation of the tlirombin, but not for its action on fibrinogen. 
 For instance, a calcium-free sohition of fibrinogen can be made to clot 
 by serum from which the calcium has been removed. 
 
 If a soluble oxalate (potassium or ammonium oxalate) is mixed with 
 freshly drawn dog's blood to the amount of o"2 or 03 percent., the blood 
 remains unclotted. The plasma separated from this oxalatcd blood 
 contains both thrombogen and thrombokinasc, but it docs not coagu- 
 late, because the calcium has been precipitated out in the form of in- 
 soluble calcium oxalate. In the absence of calcium the reaction of the 
 thrombogen and thrombokinase which leads to the formation of 
 thrombin does not take place. All that is necessary to bring about 
 coagulation is to add calcium chloride in somewhat greater quantity 
 than is required to combine with any excess of oxalate present. If more 
 than a certain amount of calcium be added, clotting is hindered instead 
 of being helped, so that it is only within certain limits of concentration 
 that calcium favours coagulation. From oxalate plasma a nucleo- 
 protein or a mixture of nucleo-proteins can be separated which contains 
 thrombogen and thrombokinase, but little or no calcium, and does not 
 cause clotting, but which on treatment with a calcium salt acquires the 
 properties of thrombin. 
 
 When sodium fluoride is added to freshly drawn blood to the amount 
 of o'3 per cent., coagulation is also prevented. But there is this differ- 
 ence between oxalate and fluoride plasma — that, although the calcium 
 has been precipitated in both, the addition of calcium chloride to fluoride 
 plasma is not sufficient to induce clotting. Tissue extract containing 
 thrombokinase must be supplied as well. In some way or other sodium 
 fluoride interferes with the liberation of thrombokinase from the formed 
 elements of the blood, although in the concentration mentioned it does 
 not hinder the action of fully formed thrombin, as is shown by the fact 
 that fluoride plasma coagulates on the addition of a little serum, which 
 supplies thrombin. The fluoride blood clots readily if it is diluted with 
 water, and at the same time mixed with calcium chloride solution, for 
 the water damages the formed elements, and thus favours the liberation 
 of thrombokinase. 
 
 Sodium citrate solution prevents the coagulation of blood run into 
 it, although there is no precipitation of the calcium. The addition of 
 calcium chloride to citrate plasma induces clotting, and the action of 
 the citrate is assumed to be due to the formation of a compound with 
 the calcium of the blood, which does not dissociate so as to yield calcium 
 ions. It ought to be remarked, however, that in all so-called decalci- 
 fied plasmas, as ordinarily obtained, blood-platelets are present, and 
 that platelets disintegrate under the influence of calcium salts. It 
 has been shown, indeed, that many of the reagents and procedures 
 which hinder the clotting of shed blood also prevent the breaking up of 
 the platelets. Thus, the cooling of the blood, the addition of hirudin, 
 sodium oxalate, sodium citrate, manganese salts, etc., which are 
 classical methods used in obtaining platelets for microscopical study, 
 are also classical methods of hindering coagulation. These facts have 
 not hitherto been sufficiently taken account of in interpreting experi- 
 ments on decalcified blood. They indicate that the decalcifying agents 
 may hinder clotting by interfering with the liberation of essential sub- 
 stances from the platelets, and that this may be the decisive factor, and 
 not merely the withdrawal of the calcium from the field where the 
 already liberated thrombokinase and thrombogen would otherwise 
 react to form thrombin. 
 
 When proteoses (or peptones) are injected into the circulation of a 
 dog or goose, the blood is deprived of the power of coagulation. The 
 
38 THE CIRCULATING LIQUIDS OF THE BODY 
 
 peptone plasma must be assumed to contain both thrombogcn and 
 thronibokinasc, since it can be made to clot in various ways {e.g.. by dilu- 
 tion with water or by slight acidulation with acetic acid) without the 
 addition of anything which could supply either of these factors. Yet 
 a little tissue extract causes it to clot much more rapidly than simple 
 dilution or acidulation, and more rapidly than the addition of serum. 
 So that either the thrombokinase already present in peptone plasma is 
 present in an unavailable form, or in some way the formation of throm- 
 bin from its precursors is hindered. .But this is not the only cause of 
 the incoagulability of peptone plasma. It may be shown to contain 
 an aiitithrombin, a body which antagonizes the action of fully formed 
 thrombin, and wliich does not seem to be a ferment, since it acts quan- 
 titatively in proportion to the amount present. This is the reason why, 
 although peptone plasma can always be made to clot by the addition 
 of fibrin ferment, in serum, for instance, relatively large quantities of 
 it must be supplied (Practical Excixises, pp. 64, 65). 
 
 Fig. 5. — Fibrin Formation in Horse's Plasma (Ultramicroscope) (Stiibel). Several 
 clmnps of disintegrated platelets from which the fibrin filaments radiate. 
 
 An extract of the head of the medicinal leech in salt solution prevents 
 the clotting of blood both in the test-tube and when injected into the 
 circulation. The plasma obtained differs from peptone plasma in 
 refusing to coagulate unless tissue extract is added. It is therefore 
 deficient in thrombokinase, or, rather, as has been shown, the kinase 
 present is unable to act, because neutralized by antikinase present in the 
 leech extract. Leech extract also contains an antithrombin, which can 
 be neutralized by a sufficient amount of thrombin. In the small 
 wound from which the leech sucks blood this sufficient amount is not 
 present, and the blood-remains unclotted, as it also docs in the alimen- 
 tary canal of the leech. The anticoagulant substance, hirudin, has 
 been isolated, and gives the reactions of an alburaose. 
 
 Sources of Thrombogen and Thrombokinase.— It has already been 
 stated that thrombogen exists in the circulating plasma. This is 
 shown by the fact that fluoride plasma obtained from blood drawn 
 directly through a wide cannula into sodium fluoride solution, with 
 
COAGULATION 
 
 39 
 
 all precautions to prevent alteration of the blood, and immediately 
 separated from the formed elements by the centrifuge, will clot 
 on the addition of tissue extract. The source of the thrombogen 
 has been thought to be the blood-plates, but this has not been 
 proved. Throm])okinase is not present in the circulating plasma. 
 In shed and clotting blood which has not been allowed to come into 
 contact with cut tissues, the only possible sources of thrombokinase, 
 so far as we know, are the corpuscles and the blood-plates. The 
 red corpuscles we ma3^ at once dismiss, for although the stromata, 
 especiallv of nucleated corpuscles, contain thrombokinase, or can 
 under artificial conditions be made to develop that action on 
 coagulation by which we recognize its presence, not only do they 
 remain intact under ordinary circumstances during coagulation, 
 but there is strong evidence, as 
 has already been pointed out, 
 that they do not make any essen- 
 tial contribution to the process. 
 We have left over the leucocytes 
 and the platelets, and it is highly 
 probable that from the platelets 
 thrombokinase is liberated in the 
 first moments after blood is 
 drawn, and, acting on the throm- 
 bogen already present in the plas- 
 ma, changes it into actual throm- 
 bin. This surmise is strengthened 
 by the fact that in freshly shed 
 mammalian blood extensive de- 
 struction of blood-plates takes 
 place. Viewed with the ultra- 
 microscope, the blood-platelets, 
 in a drop of clotting plasma, 
 
 which are at first homogeneous in appearance (optically empty), 
 become granular. Then the platelets begin to agglutinate and 
 swell up, and the agglutinated platelets are transformed into clumps 
 of granules, from which needles of fibrin shoot out. Other needles 
 and filaments of fibrin form in contact with the glass or free in 
 the plasma, and soon the field is occupied by a felt-work of 
 fibrin. The leucocytes have not been observed to be related to the 
 process, at least, in the blood of mammals (Stiibel). It is true that 
 the white layer or ' buffy coat ' which tops the tardily formed clot 
 of horse's blood, and consists of the hghter, and therefore more 
 slowly sinking colourless cells, causes clotting in otherwise in- 
 coagulable liquids like hydrocele fluid much more readily than the 
 red portion of the clot, and yields far more thrombin on treatment 
 with alcohol. It can also be easily verified that in mammalian 
 
 Fig . 6. — Fibrin Formation in Plasma from 
 a Case of Haemophilia (Ultramicro- 
 scope) (Stiibel). The needles of fibrin 
 cire slowly formed, and very large. 
 
|o THE CIRCULATING LIQUIDS OF THE BODY 
 
 blood collected in paraffined vessels, so as to delay clotting, and 
 immediately centrifugalized, coagulation begins in and around the 
 layer of white elements, and then spreads upwards in the stratum 
 of plasma and downwards in the stratum of erythrocytes. But in 
 this white upper layer platelets are always intermingled with leuco- 
 cytes. It has been shown, however, that the blood of the cray- 
 fish, which coagulates with extreme rapidity, contains certain 
 colourless corpuscles, which immediately it is withdrawn, break 
 up with explosive suddenness, and that substances which hinder 
 the breaking up of these corpuscles restrain coagulation (Hardy). 
 In the blood of another crustacean Limnlus, the kingcrab, coagula- 
 tion is preceded by an agglutination of the leucocytes which exhibit 
 amoeboid movements. They become entangled by the interlacing 
 of the pseudopodia which they protrude (L. Loeb). 
 
 Thedisintegrationof the platelets in shed blood has been attributed 
 by Deetjen to an increase in the alkalinity of the blood, by escape 
 of carbon dioxide, it may be. \\'hen blood is placed on a quartz 
 slide and covered with a quartz cover-slip, the platelets, according 
 to this observer, do not break up ; but if they are brought into con- 
 tact with a medium whose OH — concentration is raised ten times 
 or more above that of freshly drawn blood (still only a weak alka- 
 line reaction), disintegration ensues. He supposes that the contact 
 of glass acts harmfully on account of the alkali in it. It is im- 
 possible to say at present whether this observation has any bearing 
 on normal coagulation. 
 
 Thrombokinase has been shown to exist not only in the leuco- 
 cj^tes, the platelets, and the stromata of the coloured corpuscles, but, 
 as already stated, in all tissues hitherto examined. Under ordinary 
 circumstances it appears that a larger amount of thrombogen is 
 liberated or is already present in shed blood than can be changed 
 into thrombin by the thrombokinase set free, since serum contains 
 a surplus of thrombogen in addition to the fully formed ferment. 
 This is shown by the fact that the activity of a given quantity of 
 serum in causing the coagulation of a plasma not spontaneously 
 coagulable or of a fibrinogen solution is increased by the addition 
 of tissue extract (containing thrombokinase). 
 
 The thrombin of any particular kind of vertebrate blood has no 
 marked specific action— that is, will cause coagulation in solutions of 
 fibrinogen or plasma of very different origin. For example, the 
 sera of all vertebrates hitherto investigated induce clotting in 
 goose's plasma. On the other hand, it appears that a greater degree 
 of specificity exists in the case of the thrombokinase and throm- 
 bogen, the specificity being absolute in some cases, relative in others. 
 That is to say, the thrombokinase of one animal may activate the 
 thrombogen of an animal of another group, while it may fail to 
 activate the thrombogen of an animal belonging to a third group. 
 
COAGULATION 41 
 
 But it will always activate the thrombogen of an animal of the 
 same kind. 
 
 To sum up, we may say that when blood is shed, thrombin is rapidly 
 formed by the action of thrombokinase, liberated from the leucocytes, 
 the blood-plates, and possibly to some extent from the erythrocytes, 
 upon thrombogen, already present in the circulating plasma. Further 
 —and this is of great practical importance — since no vessel is opened 
 under ordinary circumstances except through a wound in the overly- 
 ing structures, the cut tissues supply a store of thrombokinase at 
 the point tohere it is required to aid in the stanching of the wound. 
 Calcium is essential to the reaction by which thrombogen and thrombo- 
 kinase form thrombin, but is not necessary for that action of thrombin 
 on Jlbrinoges by which fibrin is produced (Practical Exercises, 
 pp. 62-65). 
 
 The Nature of the Action of Thrombin on Fibrinogen. — The usual 
 view, first advanced by Schmidt many years ago, is that thrombin 
 acts as an enzyme. Hence it is often spoken of as hbrin-ferment. 
 In support of this theory it has been stated that the thrombin 
 does not itself seem to be used up in the process, nor to enter bodilx' 
 into the fibrin formed; that a small quantity of it can cause an 
 indefinitely large amount of fibrinogen to clot; and that its power 
 is abolished by boiling (p. 333). There has been a disposition 
 among more recent observers to question this evidence. Accord- 
 ing to Rettger, the quantity of fibrin formed when a small amount of 
 thrombin is added to a fibrinogen solution tends to a fixed maxi- 
 mum, which does not increase with the time of action.* Under 
 certain conditions, also, it is said that thrombin is not destroyed at 
 the temperature of boiling water. Whatever the precise nature of 
 the reaction which leads to the precipitation of the fibrinogen in the 
 form of fibrils, thrombin is very loosely combined if combined at 
 all in the fibrin, since it is readily extracted by an 8 per cent, 
 solution of sodium chloride. This, indeed, is one of the best ways 
 of obtaining an active thrombin solution. 
 
 The view which we have followed above, in accordance with 
 Morawitz, that the substances in tissue extracts which favour 
 coagulation do so by activating prothrombin to fully formed 
 thrombin, has also been opposed by a number of the more recent 
 workers. Some consider that they exert a direct action upon 
 fibrinogen similar to, although not necessarily identical with, that 
 of thrombin, and speak of them as coagulins (L. Loeb). Howell 
 holds that these substances, which he prefers to term thromboplastic 
 substances, since this makes no assumption as to their mode of 
 action, play a quite different, role, namely, that of neutralizing anti- 
 thrombin. His observations have led him to the conclusion that 
 
 * The inquiry is complicated by the fact that fibrin, once formed, tends to 
 adsorb the remaining thrombin and so to interfere with its further action. 
 
42 THE CIRCULATING LIQUIDS OF THE BODY 
 
 the effective thromboplastic substance in the tissues is a plios- 
 phatide, probably kephalin, united with protein. 
 
 Intravascular Coagulation Regulation of the Clotting Process, 
 or Thrombotaxis. — So far we have been considering the problem 
 of coagulation as if all the data for its solution could be 
 obtained by a study of the blood itself. In other words, our main 
 business up to this point has been the explanation of coagulation 
 in the shed blood; it has been only incidentally, and with the object 
 of casting light on the question of extravascular clotting, that we 
 have touched on the coagulation of the blood within the living 
 vessels. It is not possible here to adequately discuss, nor even to 
 define, the differences between the two problems. All we can do 
 is to warn the student, and to emphasize the warning by one or 
 two illustrations, that valuable as is the knowledge derived from 
 experiments on extravascular coagulation, it would be totally mis- 
 leading if applied without modification to the circulating blood. 
 For instance, we have recognized in the blood-plates an important 
 source of the thrombokinase which plays so great a part in the 
 clotting of shed blood; but wc may be sure that blood-plates are 
 constantly breaking down in the lymph and the blood, and we have 
 to inquire how it is that coagulation does not occur, except in 
 disease, within the vessels. Calcium is not wanting to the circu- 
 lating plasma, fibrinogen is not wanting, and it has already been 
 mentioned that thrombogen exists in perfectly fresh and, as we 
 may say, still living blood. Why, then, docs it not coagulate ? 
 Some have said that coagulation is ' restrained ' by the contact of 
 the living walls of the bloodvessels; but although it is certain that 
 the contact of foreign matter — and all dead matter is foreign to 
 living cells — does hasten the destruction of blood-plates or that 
 alteration in them on which the liberation of the precursors of the 
 ferment depends, it is evident that it is just this ' restraining ' in- 
 fluence of the vessels, if it is due to anything more than the mere 
 smoothness of their endothelial lining, which has to be explained. 
 The best answer which can be given to the question is: First, that 
 the quantity of thrombokinase free in the plasma at any given time 
 must be small, since no evidence of its presence in fluoride plasma 
 can be obtained. If thrombokinase is liberated in the circulating 
 blood, we may assume that it is changed into some inactive sub- 
 stance, or quickly eliminated. And it appears that, unlike the true 
 ferments, thrombokinase acts quantitatively — i.e., in proportion to 
 its amount — upon thrombogen. Second, an antithrombin exists 
 in the circulating ])lasma, and even if fully formed fibrin-ferment 
 were present, it could not cause coagulation until the antithrombin 
 had been neutralized. This antithrombin is probably not manu- 
 factured in the blood, or at least not exclusively in the blood, but 
 in the tissues, and there is no reason to deny the vessels themselves 
 
COAGULATION 43 
 
 a share in its production, even if its presence has not hitherto been 
 demonstrated in the internal coat (L. Loeb). So that living blood 
 within the living vessels may be said to be acted upon by two sets 
 of influences, one tending to favour coagulation, the other to oppose 
 it. In the clotting of extra,vascular plasma, free from corpuscles, 
 we may indeed see the continuation, under modified conditions, of 
 a normal process always going on within the bloodvessels. Under 
 normal conditions, the processes that make for coagulation never 
 obtain the upper hand. 
 
 Indeed the margin of safety within which what may be called 
 the thrombo-regulative mechanism works seems to be surprisingly 
 wide, and the equilibrium in the circulating blood far more stable 
 than observations on clotting outside of the body might lead us to 
 suppose. Very considerable quantities of thrombin or of de- 
 fibrinated blood or serum containing thrombin can be injected into 
 the blood-stream without ill effect. According to Howell, the 
 presence of the abnoiTnally great amount of thrombin causes the 
 formation of sufficient antithrombin to neutralize it, probably by a 
 protective reflex secretion. In like manner the injection of tissue 
 extracts or a solution of thrombo plastic substance (thrombokinase) 
 prepared from them by precipitation doss not necessarily induce 
 coagulation in the vessels. On the contrary, when injected slowly 
 or in small amount into the veins of an animal, it abolishes for a 
 time the power of coagulation of the blood; and when this ' nega- 
 tive phase,' as it is called, has been once established, even a very 
 large and rapid injection produces no further effect, possibly because 
 an antibody which neutralizes the action of thrombokinase has 
 been produced. In both cases the limits of safety can be over- 
 stepped, and intravascular clotting induced by the injection either 
 of thrombin or of thrombokinase. When a considerable quantity 
 of the active substance in tissue extract is introduced at the first 
 injection, extensive coagulation in the vessels instantly ensues; the 
 animal dies in a few minutes; and the right side of the heart, the 
 venae cavse, the portal vein, and perhaps the pulmonary arteries, 
 may be found choked with thrombi. Here the injected thrombo- 
 kinase is responsible for the clotting, thrombogen and calcium being 
 alreadv present. Curiously enough, intravascular coagulation fails 
 to be produced in a certain proportion of cases when albino animals 
 are injected with material from pigmented animals, while there is 
 no absolute failure of coagulation when albinos are injected with 
 material from albinos, and no failure when pigmented animals are 
 injected with material either from other pigmented animals or from 
 albinos. Intravascular coagulation on injection of tissue extracts 
 is especially striking in birds. 
 
 To a certain extent the action of tissue extracts in coagulation 
 can be imitated by other substances of animal origin, such as the 
 
44 THE CIRCULATING LIQUIDS OF THE BODY 
 
 venoms of some vipers (Martin). It is not known whether these 
 substances act on the blood-plates, leucocytes, or other cells, and 
 thus cause an increased production or an increased liberation of 
 one or more of the precursors of thrombin, or whether they take 
 part directly in its formation. But there is some evidence that 
 the venoms which favour coagulation do so in virtue of their con- 
 taining a kinase. On tlie other hand, cobra-venom prevents coagula- 
 tion by means of an antikinase — that is, a substance which antago- 
 nizes the action of kinase, and so hinders the formation of thrombin. 
 It does not contain an antithrombin — that is, a body which will 
 prevent the action of thrombin already formed (Mellanby). 
 
 Relation of the Liver to Coagulation.^ — ^It is not known with any 
 degree of certainty whether the thrombo-regulative processes are 
 especially associated with any particular organ. But there are 
 facts which suggest that the relations of the liver to the coagulation 
 of the blood are peculiarly close. Not only, as previously shown, 
 does it take an important share in the formation of fibrinogen, but 
 there is some evidence that it is closely related to the formation 
 of antithrombin. We have already mentioned that the injection 
 of commercial peptone, which consists chiefly of proteoses, into 
 the blood of dogs causes it to lose its coagulability. The effect 
 gradually passes away, till after some hours the original power of 
 coagulation is restored (p. 63). The liver is known to be intimately 
 concerned in the production of this remarkable result, for if the 
 circulation through it be interrupted, the injection of proteose is 
 ineffective. Further, if a solution of proteose is artificially 
 circulated through an excised liver, a substance (perhaps an anti- 
 thrombin) is formed which is capable of suspending the coagula- 
 tion of blood outside of the body, a property which proteoses them- 
 selves do not possess, or possess only in slight degree. It is not 
 believed that the proteose is actually changed into this anticoagu- 
 lant substance, but rather that the liver cells produce it as a 
 ' reaction ' to the presence of the foreign substance, being perhaps 
 stimulated in some way by the circulating proteose. In part the 
 abnormally great alkalinity of the peptone blood, due to the excess 
 of alkali secreted by the liver, is responsible for its slow coagulation. 
 Under certain conditions, some of which are known and others not, 
 the injection even of one or other of the purified proteoses causes 
 not retardation, but hastening, of coagulation ; and if this has been 
 the result of a first injection, a second is equally unsuccessful. It 
 is possible that by an effort of the organism to restore the normal 
 coagulability of the blood, on which its very existence depends, 
 substances which favour coagulation are produced, and that the 
 result of an injection of proteose is determined by the relative 
 amount of coagulant and anticoagulant secreted in a given time. 
 Protamins (products obtained from the ripe milt of certain fishes, 
 
COAGULATION 45 
 
 and believed to be the simplest proteins) exert, when injected 
 intravenously, a retarding influence on coagulation, and lower the 
 blood-pressure, just as albumoses do (Thompson). Even serum- 
 albumin and serum-globulin possess this property in some degree. 
 All these substances also cause a diminution in the number of 
 leucocytes in the blood owing, in the case of albumose at any rate, 
 to their accumulation in the abdominal vessels, and not to any 
 actual destruction of them. 
 
 It has been lately announced that the adrenal glands have a relation 
 to the coagulation of the blood. Stimulation of the splanchnic nerve, 
 which supphcs sccretorj^' fibres to the adrenal, greatly hastens coagula- 
 tion, but has no such effect if the adrenal on the corresponding side 
 has been previously removed (Cannon). It is possible that this effect 
 is exerted through the liver, since it is known that one important 
 function of the liver, the regulation of the sugar content of the blood, 
 is intimately dependent upon the adrenal, and is affected by excitation 
 of its splanchnic nerve-supply. 
 
 In certain pathological conditions the normal balance of the factors 
 that make for clotting and prevent it may be upset, and the scales may 
 tip in either direction. In patients suffering from the formation of 
 spontaneous clots in the veins (thrombosis) it is stated that the anti- 
 thrombin in the blood is diminished, the amount of prothrombin being 
 normal. The mere slowing of the blood-stream in conditions where 
 the circulatory mechanism is enfeebled may favour thrombosis. For 
 anything which cripples the circulation, and consequently limits the 
 free interchange between blood and tissues, interferes with the elimina- 
 tion or neutralization of the precursors of thrombin, and with the 
 entrance of the substances that render the fully formed thrombin in- 
 active. This, as well as the injury caused by the ligature, which may 
 favour the passage of thromboplastic substances into the lumen of the 
 occluded vessel, is a possible factor in the formation of the clot 
 on which the surgeon relies for the permanent sealing of ligated 
 vessels. 
 
 In haemophilia, a disease in which the coagulation of the blood is 
 charactcristicall}^ slow, and in which even slight wounds may occasion 
 severe or fatal haemorrhage, the thrombogen (prothrombin) has been 
 found deficient in amount, and the injection of normal serum or the 
 transfusion of normal blood has been used with temporary advantage 
 in the treatment of the condition. In certain cases of purpura, how- 
 ever, where haemorrhage also occurs with abnormal ease, no variation 
 from the normal could be detected in the content of either antithrombin 
 or prothrombin (Howell) . Some have supposed that in such conditions 
 the fault is an unnatural fragility of the small vessels rather than a 
 deficiency in the power of the blood to clot, but of this also no actual 
 evidence has been adduced. Another factor on which the promptness 
 and completeness of the sealing of wounded vessels may depend has been 
 recently brought into notice, namely — 
 
 The Vaso-Qonstrictor Property of Shed Blood.— It has been shown 
 that when blood is shed and no precautions are taken to prevent 
 clotting, it very quickly develops the power of causing marked 
 constriction of bloodvessels. This can be demonstrated by allow- 
 ing the serum to act on rings cut from arteries (Practical Exercises, 
 
46 THE CIRCULATING LIQUIDS OF THE BODY 
 
 p. 66), or by perfusing the liind-legs of frogs with a sahnc solu- 
 tion containing serum. Plasma derived from blood in which the 
 platelets have been prevented from breaking down, and which 
 therefore remains imclotted, has no such effect, or a much slighter 
 
 Pig y — Sheep Artery Rings. At 14 and i5 Ringer's solution was replaced by citrate 
 plasma (two different specimens). At 15 and 17 the plasmas were replaced by 
 the corresponding sera. At 18 and 19 the sera replaced Ringer's solution directly. 
 Time-trace, half-minutes. Tracings reduced to }. 
 
 effect. But when the platelets are separated from the plasma 
 and then decomposed, the resulting extracts of platelets are rich 
 in vaso-constrictor material. In the sealing of wounded vessels 
 the platelets would therefore appear to play a double role, yielding 
 
 Fig 8. — Frog Perfusion Experiment with Serum. The drops of liquid flowing through 
 the preparation are recorded. At 11 citrate plasma was injected; at 13 the 
 corresponding citrate serum. The tracing is to be read from left to right. 
 Time is marked in half-minutes 
 
 a substance which causes constriction of the vessel in the neigh- 
 bourhood of the wound while a plug of clot is being formed, thanks 
 to other substances liberated from the platelets, whicli take an 
 essential part in coagulation. The vaso-constriction may perhaps 
 
VASO COXSTJUCTOR PROPIIRTY OF SllIiD BLOOD 
 
 47 
 
 be looked upon as a form of ' first aid ' to diminish the hiemor- 
 rhage, and also to make it less easy for the beginning clot to be 
 washed away. It is obvious that the two processes would be 
 mutually advantageous in dealing with those injuries of the vascular 
 system on the prompt repair of which tlu; very existence of the 
 
 
 
 A -- 
 
 -\r 
 
 ?\/" 
 
 f 1 -, '^ 
 
 
 1/ 
 
 
 
 V r 
 
 
 
 
 
 -v^ 
 
 
 Jcc Strum*^ciCraCt 
 
 /cc P/asma 
 
 /cc Plasma 
 
 /Ci SerurrfC Urate 
 
 Fig. 9. — Frog Perfusion Experiment with Serum. Curves showing the flow. The 
 number of drops per half-minute is laid off along the vertical axis, and the time 
 {in half-minutes) along the horizontal axis; 38 drops correspond to i cc. 
 
 organism at all times depends, and it is not without interest to 
 find that special formed elements in the blood, the platelets, are 
 pre-eminently associated with both processes. 
 
 Section III. — ^The Chemical Composition of Blood. 
 
 The serum of coagulated blood represents the plasma minus 
 fibrinogen; the clot represents the corpuscles plus fibrin. Thus: 
 
 Plasma - Fibrin (ogen) = Serum. 
 
 Corpuscles + Fibrin = Clot. 
 
 Plasma -f Corpuscles = Scrum -f Clot = Blood. 
 
 Bulky as the clot is, the quantity of fibrin is trifling (0-2 to 0-4 per 
 cent, in human blood). The plasma contains about 10 per cent. 
 of solids, the red corpuscles about 40 per cent., the entire blood 
 about 20 per cent. 
 
 Serum contains 7 to 8 per cent, of proteins, about o-8 per cent, 
 of inorganic salts, and small quantities of neutral fats, soaps, 
 cholesterin esters, lecithin, dextrose, urea, lactic acid, glycuronic 
 
 acid, amino - acids. 
 
 Solids 
 
 \fMV9r 
 
 Corpuscles 
 Flasma 
 
 and other sub- 
 
 Fig. 
 
 10. — Diagram showing Relative Quantity of Solids 
 and Water in Red Corpuscles and Plasma. 
 
 stances, 
 proteins 
 albumin 
 globulin. 
 bit the 
 
 The chief 
 
 are serum- 
 
 and serum- 
 
 In the rab- 
 
 former, in 
 
 the horse the latter, is the more abundant; in man they exist in not 
 far from equal amount. A small quantity of nucleo-protein and of 
 fibrino-globulin (which some consider a soluble product formed from 
 
48 
 
 THE CIRCULATING LIQUIDS 01' THE BODY 
 
 librinogen in clotting) is also present. Ferments which cause 
 hydrolysis of proteins and carbohydrates, a ferment (lipase) which 
 acts upon fats, and certain oxidizing ferments (oxydases), have also 
 been demonstrated. The chemical nature of the bodies which 
 confer on serum or plasma its specific ha^molytic, agglutinating, 
 precipitating, and bactericidal properties has not been definitely 
 determined. 
 
 The quantitative composition of serum, especially as regards the 
 inorganic salts, is remarkably con.staut in animals of the same species, 
 and even in animals of dilfercnt species belonging to tlie same, or to 
 not very widely separated, natural groups. In cold-blooded animals 
 the serum-albumin is scantier tlian in mammals, the globulin relatively 
 more plentiful. 
 
 Serum-albumin belongs to the class of native albumins. It has 
 been obtained in a crystalline form from the serum of horse's blood. It 
 
 Fig. II. — Perspective View of Vivi-Diflusion Apparatus (Abel). This form of the 
 apparatus contains sixteen tubes. A, arterial cannula; B, venous cannula: 
 C, side tube for introduction of hirudin; D, inflow tube; E, outlet tube for the 
 blood ; F, G, supporting rod attached at H and K to branched V-tubes; L, burette 
 for hirudin; M, N, tube for filling and emptying liquid in outer jacket; O, air 
 outlet; P, dichotomous branching-point of inflow tube; Q and R, quadruple 
 branching-points of the same ; S, S, wooden supports; T, thermometer. At 
 each of the points H and K the blood is collected from four tubes into one, 
 bending round to the back, and there redividing into four return flow tubes. 
 Arrows show the direction of the flow. 
 
 is soluble in distilled water, and is not precipitated by saturating its 
 solutions with certain neutral salts. Heated in neutral or sliglitly 
 acid solution, it coagulates first at 73°, then at 77°, then at 84° C. 
 Altliough this is not of itself sufficient proof, there is other evidence 
 that it consists of a mixture of proteins. 
 
 Serum-globulin, also called paraglobulin, belongs to the globulin 
 group of proteins. When heated, it coagulates at about 75° C. (p. (j). 
 It is insoluble in distilled water, and is precipitated by saturation with 
 such neutral salts as magnesium sulphate, or by half-saturation with 
 ammonium sulpliatc. It appears tliat, as thus obtained, it is not a 
 single substance, but a mixture of at least two proteins — en-globulin, 
 
CHEMICAL COMPOSITION OF BLOOD 
 
 49 
 
 which can be precipitated from its saline solution by dialyzing off the 
 salts, and pseudo-globulin, which cannot be so precipitated. 
 
 In addition to the nitrogen represented as protein, serum (or plasma) 
 contains non-protein nitrogen, the amount of which varies with the 
 nature of the food and the stage of digestion. Part of this fraction is 
 attributal.)le to urea and other metabolites on their way to be excreted, 
 but another portion, and an important one, is due to amino-acids 
 absorbed from the intestine during the digestion of proteins and on 
 their way to be utilized in the tissues. 
 
 Of tlie inorganic salts of serum, the most important are sodium 
 chloride and sodium bicarbonate. Small amounts of potassium, 
 calcium, and magnesium, united with phosphoric acid or chlorine, and 
 a trace of fluoride, are also present. A portion of the salts is loosely 
 combined with the proteins. 
 
 Our loiowlcdge of the chemistry of the circulating plasma is likely 
 to be notably augmented by the method of vivi-diffiision recently intro- 
 duced by Abel. An arteiy of an anaesthetized animal is connected by 
 a cannula to a system of celloidin tubes immersed in a saline solution. 
 Blood passes from the artery through the tubes, where it exchanges 
 diffusible constituents with the solution, and is then returned to the 
 animal's body by another cannula attached to a vein. Coagulation 
 of the blood in the apparatus is prevented by hirudin, and under 
 aseptic conditions the circulation may proceed through the tubes for a 
 long time. The saline solution can then be analyzed for substances which 
 have entered it from the blood — amino-acids, for example (Fig. ii). 
 
 The following tables give some details of the composition of blood : 
 
 1,000 Grammes of Pig's Blood (Corpuscles, 435'09; Serum, 56491) 
 
 contained 
 
 
 Corpuscles. 
 
 Serum. 
 
 
 Corpuscles. 
 
 Serum. 
 
 Water 
 
 272-20 
 
 518-36 
 
 P2O5 as nuclein 
 
 0-0455 
 
 0-0123 
 
 Solids 
 
 162-89 
 
 46-54 
 
 Na.,b .. 
 
 * 
 
 2-401 
 
 Haemoglobin 
 
 142-20 
 
 
 KoO . . 
 
 2-157 
 
 0-152 
 
 Protein 
 
 8-35 
 
 38-26 
 
 Fe.,03.. 
 
 0-696 
 
 
 Sugar 
 
 
 0-684 
 
 CaO . . 
 
 
 
 0-0689 
 
 Cholesterin 
 
 0-213 
 
 0-231 
 
 MgO .. 
 
 0-0656 
 
 0-0233 
 
 Lecithin 
 
 1-504 
 
 0-805 
 
 CI 
 
 0-642 
 
 2-048 
 
 Fat . . 
 
 
 I-I04 
 
 P2O.5 .. 
 
 0-895 
 
 O-III 
 
 Fatty acids 
 
 0-027 
 
 0-448 
 
 Inorganic P2O5 
 
 0-719 
 
 0-296 
 
 Proteins of Plasma in 1,000 Grammes. 
 
 
 Albumin. 
 
 Globulin. 
 
 Fibrinogen. 
 
 Total. 
 
 Man 
 
 40-1 
 
 28.3 
 
 4-2 
 
 72-6 
 
 Dog 
 
 31-7 
 
 22-6 
 
 6-0 
 
 60-3 
 
 Sheep . . 
 
 38-3 
 
 30-0 
 
 4-6 
 
 72-9 
 
 Horse 
 
 28-0 
 
 47-9 
 
 4-5 
 
 80-4 
 
 Pig .. 
 
 44-2 
 
 29-8 
 
 6-5 
 
 80-5 
 
 * The pig's erythrocytes are peculiar in that the sodium appears to be 
 entirely confined to the plasma. 
 
5.. THE CIRCULATING LIQUIDS OF THE BODY 
 
 The Coloured Corpuscles consist of rather less than 60 per cent, of 
 water and ratlicr more than 40 per cent, of solids. Of the solids the 
 pigment haemoglobin makes up about 90 per cent. ; the ])roteins and 
 nucleo-protein of the stroma about 7 percent.; lecithin and choles- 
 terin 2 to 3 per cent.; inorganic salts (which vary greatly in their 
 relative proportions in different animals, but in man consist chiefly 
 of phosphates and chloride of potassium, with a much smaller 
 amount of sodium chloride) about i per cent. Potassium has been 
 demonstrated microchemically in frog's erythrocytes (Macallum) 
 {Frontispiece). There is evidence that a portion of the salts is more 
 firmly combined than the rest, so that, even after the action of the 
 most energetic laking agents, this fraction remains attached to the 
 stroma. The erythrocytes of some animals — e.g., the dog — contain 
 dextrose. When dextrose is added to human blood it rapidly dis- 
 tributes itself over corpuscles and plasma (Rona), although not 
 exactly in proportion to their respective volumes (Masing). Hither- 
 to the dextrose in blood has been reckoned as if it all belonged to the 
 plasma. 
 
 Hcemoglohin. — Of all the solid constituents of the blood, haemoglobin 
 is present in greatest amount, constituting as it does no less than 
 13 per cent., by weight, of that liquid. It is an exceedingly complex 
 
 body, containing car- 
 D On bon, hydrogen, nitro- 
 
 Wa gen, and oxygen in 
 H much the same pro- 
 
 portions in which they 
 exist in ordinary pro- 
 teins (p. i). Iron is 
 also present to the ex- 
 Fig. 12.— Diagram of Spectroscope. A, source of light ; *^"* of almost exactly 
 B, lave." of bluod; C. collimator for rendering rays one-third of I percent., 
 parallel; D, prism; E, telescope. ^"'1 there is alsoahttle 
 
 sxilpliur. Hai'moglobin 
 is made up of a protein element whicli contains all the sulphur and a 
 pigment which contains all the iron, the protein constituting by far 
 the larger portion of the gigantic molecule, whose weight has been 
 estimated at more than 16,000 times that of a molecule of hydrogen. 
 Since its percentage composition is still undetermined with absolute 
 precision, it is impossible to give an empirical formula that is more 
 than approximately correct. For dog's haemoglobin Jaquet gives 
 ^758^^ 1203*^ 195^:1'"'^^ ^-'iH' which would make the molecular weight 16,669. 
 Direct determinations of the molecular weight gave 13,115 for 
 oxyhaMUoglobin of the horse, and 16,321 for that of the ox (Hiifner and 
 (iansser). Whilcthe.se numbers need not be taken as more than a rough 
 approximation, they at least show that the hsmoglobin molecule is an 
 exceedingly large one. 
 
 The most remarkable property of h.Tmoglobin is its power of 
 combining loosely with oxygen when exposed to an atmosphere con- 
 taining it, and of again giving it up in the presence of oxidizable 
 substances or in an atmosphere in which the partial pressure of 
 oxygen (pp. 248-253) has been reduced below a certain limit. It 
 
CLEMICAL C0Ml'06iiiUN Oh' CLOOD 
 
 51 
 
 D 
 
 E b 
 
 BW 630 620 m 600 590 580 570 560 5^0 5¥) 53fll j2o| 510 500 490\ m 
 
 \i<n\,„X ■ \i"\. ..li'lJiMlli.iil.iilr.iJiiiilii.llii 
 
 TO bOU iW beu 6/U ibU i)M OW JJ(^ Ja/j oiu JW ¥J(/j '*ot 
 I ,:l,J,..,l„.J|,.il,J,.„l„J, .1,1.,!.:.! .i:,.|i,.L., I ■■-.I iihiiilM,i„'iliii;l;i„ l i ,| ;' .i 
 
 7(9 // I i2 13 I 74- 
 
 I ■ ■ ■ ■! , , ,1 ....1 1 , ,1 .1,. I ,1 I . ^ I i ■ I ll M M I 
 
 . 
 
 1 
 
 
 >!?^'" 
 
 1?;^^ 
 
 ^ 
 
 1 
 
 » 
 
 Fig. 13.— Table of Spectra of H.-emoglobin and its Derivatives (Ziemka and Miiller). 
 I, Osyha;moglobin ; 2, reduced ha:moglobin 3, met hemoglobin: 4. a- d l^matin; 
 5. alkaline ha;matin; 6, haemochromogen ; 7. acid hcxmatoporphyrin ; S, alkaliae 
 haematoporphyrin ; 9, cairbon monoxide haemoglobin. 
 
52 
 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 is this property that enables haemoglobin to perform the part of an 
 oxygen-carrier to the tissues, a function of the first importance, 
 which will be more minutely considered when we come to deal with 
 respiration. 
 
 The bright red colour of blood drawn from an artery or of venous 
 blood after free exposure to air is due to the fact that the haemo- 
 globin is in the oxidized state 
 — in the state of oxyhaemo- 
 globin, as it is called. The 
 anumnt of oxygen with which 
 haemoglobin combines to form 
 oxyliaimoglobin is such that 
 one atom of iron corresponds to 
 two atoms of oxygen. If the 
 formula for haemoglobin given 
 on p. 50 be represented by 
 the sj'^mbol Hb, a molecule of 
 oxy haemoglobin would be re- 
 presented as HbOj. If the 
 oxygen is removed by means of 
 reducing agents, such as am- 
 monium sulphide, or by ex- 
 posure to the vacuum of an air- 
 pump, the colour darkens, the 
 blood-pigment being now in the 
 form of reduced haemoglobin. 
 In ordinary venous blood a 
 large proportion of the pigment 
 is in this condition, but there is 
 always oxyhaemoglobin present 
 as well. In asphyxia (p. 281), 
 however, nearly the whole of 
 the oxyhaemoglobin may dis- 
 appear. 
 
 Crystallization of II aemoglobin. — In the circulating blood the haemo- 
 globin is related in such a way to the .stroma of the corpuscles that, 
 although the latter are suspended in a liquid readily capable of dissolv- 
 ing the pigment, it yet remains under ordinary circumstances strictly 
 within them. In a few invertebrates, however, it is normally in solution 
 in the circulating liquid. As a rare occurrence haenioglobin may form 
 crystals inside the corpuscles (p. 71). When it is in any way brought 
 into solution outside the body, it shows in many animals,' but "not in the 
 same degree in all, a tendency to crystallization ;' and the ease with which 
 crystallization can be induced is in inverse proportion to the solubility 
 of the haemoglobin. Thus, it is far more difficult to obtain crystals of 
 haemoglobin from human blood than from the blood of the rat, guinea- 
 pig, or dog, whose blood-pigment is less soluble than that of man, and 
 for a like reason the oxyhaemoglobin of the bird, the rabbit, or the frog 
 crystallizes still less readily than that of human blood. 
 
 J'ig. 14. — Oxyharnoglobin Crystals (Frey). 
 a,h, from man; c, from cat; d, from guinea- 
 pig; e, from hamster;/, frotn squirrel. 
 
CHEMICAL COMPOSITION OF BLOOD 53 
 
 As to the form of the crystals, in the vast majority of aniiiials they 
 are rhombic prisms or needles, but in the guinea-pig they are sphenoids 
 belonging to the rhombic system, and in the squirrel six-sided plates of 
 the hexagonal system (Fig. 14). Careful study of the crystallography of 
 ' hemoglobin from a large number of animals has established differences 
 and resemblances so constant and so clear-cut that they may be used for 
 the purposes of classification and for the identification of the source of 
 a specimen of blood (Rcichert and Brown). 
 
 Reduced ha-moglobin can also be caused to crystallize, though with 
 more difficulty than oxyhaemoglobin, since it is more soluble. Crystals 
 of reduced haemoglobin were first prepared from human blood by Hiifner, 
 who allowed it to putrefy in sealed tubes for several weeks. 
 
 When a solution of oxyhaemoglobin of moderate strength is ex- 
 amined with the spectroscope, two well-marked absorption bands 
 are seen, one a little to the right of Fraunhofer's line D, and the other 
 a little to the left of E. A third band exists in the extreme violet 
 between G and H. It cannot be detected with an ordinary spectro- 
 scope, but has been studied by the aid of a fluorescent eyepiece, by 
 projecting the spectrum on a fluorescent screen, and by photograph- 
 ing the spectrum. The addition of a reducing agent, such as 
 ammonium sulphide, causes the bands in the visible spectrum to 
 disappear, and they are replaced by a less sharply defined band, of 
 which the centre is about equidistant from D and E. This is the 
 characteristic band of reduced haemoglobin. The spectrum of 
 ordinary venous blood shows the bands of oxyhsemoglobin. 
 
 Carbonic oxide hcBmoglobin is a representative of a class of haemo- 
 globin compounds analogous to oxyhaemoglobin, in which the loosely- 
 combined oxygen has been replaced by other gases (carbon monoxide, 
 nitric oxide) in firmer union. Its spectrum shows two bands very like 
 those of oxyhaemoglobin, but a little nearer the violet end. Carbonic 
 oxide haemoglobin is formed in poisoning with coal-gas. Owing to the 
 great stability of the compound, the haemoglobin can no longer be 
 oxidized in the lungs, and death may take place from asphyxia. It 
 is, however, gradually broken up, and therefore artificial respiration 
 may be of use in such cases. Inhalation of oxygen and especially 
 transfusion of blood are also of great value. 
 
 Methcsmoglobin is a derivative of oxyhaemoglobin which can be 
 formed from it in various ways — e.g., by the addition of ferricyanide of 
 potassium or nitrite of amyl (Gamgee), by electrolysis (in the neigh- 
 bourhood of the anode), or by the action of the oxidizing ferment 
 ' echidnase ' in the poison of the viper (Phisalix) . It very often appears 
 in an oxyhaemoglobin solution which is exposed to the air. It has been 
 found in the urine in cases of haemoglobinuria, in the fluid of ovarian 
 cysts, and in haematoceles. The strongest band in its spectrum is 
 in the red, between C and D, but nearer C, nearly in the same position 
 as the band of acid-haematin. Reducing agents, such as ammonium 
 sulphide, change methaemoglobin first into oxyhaemoglobin and then 
 into reduced haemoglobin. It has by some been regarded as a more 
 highly oxidized haemoglobin than oxyhaemoglobin. Rebutting evidence 
 has, however, been offered to the effect that the same quantity of 
 oxygen is required to saturate both pigments, and this evidence appears 
 to be sound. The difference lies rather in the manner in which the 
 oxygen is united to the haemoglobin in the methaemoglobin molecule 
 than in the quantity of oxygen which it contains. For methacmo- 
 
54 
 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 globin, unlike oxyluinioglobin, parts with no oxygen to the vacuum, 
 while, on the other hand, in the presence of reducing agents it yields up its 
 oxygen even more readily than oxyhaemoglobin does (Haldahe) (p. 248). 
 F5y the action of acids or alkalies oxyhai^moglobin is split into a pig- 
 ment, haematin, and a protein, globin, belonging to the histon group. 
 It is easily precipitated from solution by ammoma. On hydrolysis, it 
 
 r-i 
 
 uc^^ 
 
 Hh 
 
 
 Tu/ff 
 banJf 
 
 n 
 
 ^'^ 
 
 0x1/ ^b 
 
 Carljcntc OyCideffh 
 
 Ha emc ch to mo tfi tt I 
 
 Haematijiicrphijrtn (actdj\ 
 
 Mcthaemci^lohirt \ 
 
 field Haematm I '^"^ 
 
 Alkaline Haemal m \t'^^j 
 
 Reduced hk. J^''"^ 
 
 rig 15. — Diagram to show the Chief Characteristics by which Haemoglobin and 
 some of Its Derivatives may be recognized Spectroscopically. The position of 
 the middle of each band is indicated rougiily by a vertical line. 
 
 yields a large amount of histidin, to which its basic properties are chiefly 
 due From 100 grammes of oxyhaemoglobin about 4 grammes of hae- 
 matin arc obtained. As to the pigment moietv, when haemoglobin is 
 acted on by acids in the absence of oxvgen, hcemochromogen is first 
 formed, which then gradually loses its iron and is changed into haemato- 
 , porphyrin. If oxy- 
 
 TTvicks 29-2 
 
 OreaT' ve.i»»ls,ke<irT\ lungs 22'7 
 
 Bones 8z 
 
 hlealinesY qeniM organs 63 
 
 ^kizL 21 
 
 Kidneys 16 
 
 Nerve cenTlres 12. 
 
 Spleen '2. 
 
 Fig. i6. — Diagram to illustrate the Distribution of the 
 Blood in the Various Organs of a Rabbit (after Ranke's 
 Measurements). The numbers are percentages of the 
 total blood. 
 
 gen be present, h«E- 
 matin is the final 
 product. Ha;matin 
 may be considered 
 as the compound 
 which haemocliro- 
 mogen forms with 
 oxygen. By the 
 action of alkalies re- 
 duced haemoglobin 
 yields ha?mochro- 
 mogen, which is stable in alkaline solution, and gives a beautiful 
 spectrum with two bands, bearing some resemblance to those of oxy- 
 haemoglobin, but placed nearer the violet end. The band next the red 
 end is much sharper than the other (p. 76). Hirmochromogen binds 
 exactly the same amount of oxygen as the hamoglobin from which it is 
 derived, and it is flue to the haemochronK>gcn in its molecule that the 
 blood-pigment fulfils its function of taking up and transporting oxygen. 
 H (D>natin (C:j.)H;,.,()4X4.Fe()H 1, the most frequent result of the splitting 
 up of haemoglobin, is gcnerallv obtained as an amorphous substance 
 with a bluish-black colour and a metallic lustre, insoluble in water, 
 but soluble in dilute alkalies and acids, or in alcohol containing them. 
 In addition to the iron of the haemoglobin, lucmatin contains the four 
 chief elements of proteins — carbon, hydrogen, nitrogen, and oxgyen 
 (Practical Exercises, p. 75). 
 
 H cBtnatoporphyrin (C33H3gOflN4), or iron-free hsematin, may' be ob- 
 tained from blood or hsemoglobin by the action of strong sulphuric 
 acid, from haematin or ha;min by the action of hydrobromic acid. It 
 
QUANTITY AND DISTRIBUTION 01- liLOOl) 55 
 
 is distinguished from tliese pigments by the fact that it contains no 
 iron. When strong sulphuric acid is allowed to act on blood or haemo- 
 globin solution, ha'matoporphyrin is also pnxluced, as may be easily 
 shown by the spectroscope. Its spectrum in acid solution shows two 
 bands, one just to the left of D, the other about midway between D 
 and E. Like oxyha?mogl(jbin, reduced haemoglobin, carbonic oxide 
 haemoglobin, methaemoglobin, and other derivatives of haemoglobin, 
 it also has a band in the ultra-violet. 
 
 H(pmi>i (C.j.,FI;j.,()4N4.FeCl) is readily obtained from hsmatin and 
 also from luemoglobin by heating with dilute hydrochloric acid, and also 
 directly from blood, as described in the Practical Exercises, p. 78. It 
 crystallizes in the form of small rhombic plates, of a brownish or 
 brownish-black colour (Fig. 24, p. 78). They are insoluble in water, 
 but readily soluble in dilute alkalies (Practical Exercises, p. 79). 
 
 Chemistry of the White Blood-Corpuscles. — The composition of pus- 
 cells and the leucocytes of lymphatic glands has alone been investigated. 
 The chief constituents of the latter are a globulin coagulating by heat 
 at 48° to 50° C. ; a nucleo-protein coagulating in 5 per cent, magnesium 
 sulphate solution at 75° C., and causing coagulation of the blood on 
 injection into the veins of rabbits; an albumin coagulating at 73° C. ; 
 and a ferment with powers like the pepsin of the gastric juice. In pus- 
 cells glycogen has been found, and it can be demonstrated micro- 
 chemically in the leucocytes of blood by the iodine reaction in various 
 conditions. Fats, cholesterol, and lecithin are also present, as well 
 as the so-called protagon. The ordinary inorganic constituents have 
 been demonstrated — namely, potassium, sodium, calcium, magnesium, 
 and iron, united with chlorine and phosphoric acid. The total solids 
 amount to 11 to 12 per cent. 
 
 Section IV. — Quantity and Distribution of the Blood. 
 
 The Quantity of Blood. — The quantity of blood in an animal is 
 most accurately determined by the method of Welcker. The animal 
 is bled from the carotid into a weighed flask. When blood has 
 ceased to flow the vessels are washed out with water or physiological 
 saline solution, and the last traces of blood are removed by chopping 
 up the body, after the intestinal contents have been cleared away, 
 and extracting it with water. The extract and washings are mixed 
 and weighed; a given quantity of the mixture is placed in a haema- 
 tinometer (a glass trough with parallel sides, e.g.), and a weighed 
 quantity of the unmixed blood diluted in a similar vessel till the tint 
 is the same in both. From the amount of dilution required, the 
 quantity of blood in the watery solution can be calculated. This is 
 added to the amount of unmixed blood directly determined. Since 
 haemorrhage is immediately followed by the entrance of liquid into 
 the bloodvessels from the lymph and tissue fluids, somewhat too 
 high a result will be obtained if the bleeding is at all prolonged. It 
 is well, therefore, to take only a moderate amount of blood for direct 
 estimation, and to compute the balance by the colorimetric method. 
 
 Many other methods have been devised on the principle of in- 
 jecting a known quantity of some substance into the circulating 
 blood, and then, after an interval has been allowed for mixture, 
 determining the change produced in a sample. Thus, the specific 
 
56 THE CIRCULATING LIQUIDS OF THE BODY 
 
 gravity of a drop of blood having been measured, a certain quantity 
 of a solution of sodium chloride isotonic with the plasma may be 
 injected into a vein, and the specific gravity again determined. Or 
 the electrical resistance of a small sam])le of blood may be measured 
 before and after injection of a given quantity of isotonic salt solution. 
 
 The total mass of blood in a living man has been estimated by caus- 
 ing the person to inhale a mixture of carbon monoxide with oxygen 
 or air. The amount of carbon monoxide taken up is determined and 
 also, in a sample of blood taken from the finger the percentage 
 amount to which the haemoglobin has become saturated with carbon 
 monoxide. All that remains is to estimate the volume of carbon 
 monoxide (or, what is precisely the same thing, the volume of 
 oxygen) which lOO c.c. of blood will take up. This latter quantity 
 is called the percentage oxygen capacity. From these data the 
 total volume of the blood can be calculated. If the volume is 
 multiplied by the specific gravity the mass is obtained. Notwith- 
 standing the elegance of this method in principle, it is by no means 
 easy to obtain accurate results with it in practice. It unques- 
 tionably gives values for the total quantity of blood which are too 
 low. A better method is to inject into a vein a measured quantity 
 of a solution of a pigment (" vital red "), which is only slowly elimin- 
 ated and is not taken up to a sensible degree by the erythrocytes. 
 Samples of blood are drawn before and a short time after the injec- 
 tion and the plasma separated from each by the centrifuge. The 
 amount of pigment is then determined which must be added to the 
 first sample of plasma to make its tint the same as that of the 
 second. The total quantity of plasma can thus be calculated and 
 from it, by determining the relative proportion of corpuscles and 
 plasma in the blood, the total quantity of blood (Rowntree, etc.). 
 
 The quantity of blood in the body was greatly over-estimated by 
 the ancient physicians. Avicenna put it at 25 lb., and many loose 
 statements are on record of as much as 20 lb. being lost by a patient 
 without causing death. By Welcker's method the proportion of 
 blood to body-weight has been found to be in the dog i : 13, cat i : 14, 
 horse 1:15, frog 1:17, rabbit 1:19, fowl 1:20. In new-born 
 children the proportion was i : ig, in adult human beings (executed 
 criminals) i : 13. By the ' vital red ' method, the amount of 
 plasma was found to be one-twentieth and that of blood one- 
 eleventh to one-twelfth of the body-weight. 
 
 According to Dreyer, the blood vohinic is a function of the surface 
 of the body, so that the smaller and lighter animals in any given species 
 have a relatively greater blood volume than the larger and heavier 
 individuals. Accordingly, he considers that the practice of expressing 
 the volume of blood as a percentage of the body-weight should be 
 abandoned. 
 
 Fig. 16 (p. 54) illustrates the distribution of the blood in the 
 various organs of a rabbit. The liver and skeletal muscles each con- 
 tain rather more than one-fourth; the heart, lungs, and great vessels 
 
LYMPH AND CHYLE 
 
 57 
 
 rather loss than one- fourth; and the rest of the body about one-lifth, 
 of the total blood. The kidney and spleen of the rabbit each contain 
 one-eighth of their own weight of blood, the liver between one-third 
 and one-fourth of its weight, the muscles only one-twentieth of their 
 weight. 
 
 Section V. — ^Lymph and Chyle. 
 
 Lymph has been defined as blood without its red corpuscles 
 (Johannes Miiller) ; it resembles, in fact, a dilute blood-plasma, 
 containing leucocytes, some of which (lymphocytes) are common to 
 lymph and blood, others (coarsely granular basophile cells, present 
 only in small numbers) are absent from the blood. I-ymph also 
 contains thrombocytes. The reason of this similarity appears when 
 it is recognized that the plasma of tissue-lymph (p. 460) is derived, 
 in large part at any rate, from the plasma of blood by a process of 
 physiological filtration (or secretion) through the walls of the 
 capillaries into the lymph-spaces that everywhere occupy the inter- 
 stices of areolar tissue, while the lymph of the lymphatic vessels is 
 in turn derived from the tissue fluid. But in addition to the con- 
 stituents of the plasma, lymph contains substances produced in the 
 metabolism of the tissues which pass into it directly. As collected 
 from one of the large lymphatic vessels of the Hmbs, or from the 
 thoracic duct of a fasting animal, lymph is a colourless or some- 
 times yellowish or slightly reddish liquid of alkaline reaction. Its 
 specific gravity is much less than that of the blood (1015 to 1030). 
 It coagulates spontaneously, but the clot is always less firm and less 
 bulky than that of blood. The plasma contains fibrinogen, from 
 which the fibrin of the clot is derived. Serum-albumin and serum- 
 globulin are present in much the same relative proportion as in blood, 
 although in smaller absolute amount. Neutral fats, urea, and sugar 
 are also found in small quantities. The inorganic salts are the same 
 as those of the blood-serum, and exist in about the same amount, 
 sodium preponderating among the bases, as it does in serum. The 
 following table shows the results of analyses of lymph from man and 
 the horse (Munk) : 
 
 
 Man. 
 
 Horse. 
 
 Water .... 
 
 /"Fibrin . - - 
 
 Other proteins - 
 
 Solids < Fat - - - - 
 
 Extractives* 
 
 I^Salts - - - - 
 
 95 -0 per cent. 
 
 O-I ^ 
 
 4-1 
 
 trace 5-0 
 
 0-3 
 
 0-5 ) 
 
 95-8 per cent. 
 
 O'l \ 
 2-9 
 
 trace - 4*2 
 
 O-I 
 
 i-i j 
 
 1 
 
 • The term ' extractives ' is somewhat loosely applied to organic substances 
 which exist in so small an amount, or have such indefinite chemical characters, 
 that they cannot be separately estimated, and are extracted together from the 
 residue by various solvents. 
 
58 
 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 Chyle is merely the name given to the lymph coming from the 
 alimentary canal. The fat of the food is absorbed by the lym- 
 phatics, and during digestion the chyle is crowded with fine fatty 
 globules, which give it a milky appearance. There may also be in 
 chyle a few red blood-corpuscles, carried into the thoracic duct by a 
 back-flow from the veins into which it opens. Chyle clots like 
 ordinary lymph, the size of the clot varying according to the quantity 
 of fat present and enmeshed by the fibrin. Wounds of the thoracic 
 duct or of lymphatics opening into it are occasionally produced in 
 operations on the neck, and when these remain open chyle may be 
 readily collected. In samples obtained from a patient onlj' a week 
 after the section of a branch of the duct during an operation for the 
 removal of tubercular glands, water constituted 928-90 parts in 
 1,000, total solids 71-10, inorganic solids 6-04, organic solids 65-06, 
 proteins 18-52, ether extract (fatty substances) 19-30 (Sollmann). 
 The following is the composition of a sample analyzed by Paton, and 
 obtained from a fistula of the thoracic duct in a man: 
 
 Water - . _ . 953-4 
 
 Solids - - - . ^5.5 
 
 Inorganic - - - - 6-5 
 
 Organic - - - . ^o-i 
 
 Proteins - - - iS"? 
 
 Fats . - - - 24-06 
 
 Cholesterin - - - 0-6 
 
 Lecithin - . _ 0*36 
 
 The quantity of chyle flowing from the fistula was estimated at as 
 much as 3 to 4 kilos per twenty-four hours, or nearly as much as the 
 whole of the blood. The flow has been calculated in various animals 
 at one-eighteenth to one-seventh of the body-weight in the twenty- 
 four hours. The quantity of lymph in the body is unknown, but it 
 must be very great — perhaps two or three times that of the blood. 
 
 Allied to tissue-lymph, but not identical with it, are the fluids 
 present in health in very small amount in such serous ca\nties as the 
 pericardium. The synovial fluid of the joints differs from lymph 
 especially in containing a small amount of a mucin-like substance. 
 
 The aqueous humour, and still more the cerebro-spinal fluid, arc 
 characterized by a marked deficiency in solids, especially protein. 
 In the following table (from Spiro) the differences in the composition 
 of lymph and alHed fluids from different parts of the body are illus- 
 trated. 
 
 
 Man : Ly:nph from 
 Fistisa in Thigh. 
 
 Horse : T>yinph 
 
 from Nr-ik during 
 
 Mastication. 
 
 Aqueous 
 Humour. 
 
 Cerebro-Spinal 
 Fluid. 
 
 99 to 99-2 
 
 0-02 to 0-16 
 
 Water - - 
 Salts - - 
 Fat - - 
 Protein - 
 
 oG-4 to 94-3 
 0-7 ,, 0-87 
 0'06 ., 0-22I 
 2-8 ,. 4-8 / 
 
 95 
 075 
 
 37 
 
 98-7 
 
 0-5 to 0-8 
 
 0-72 
 
FUNCTIONS OF BLOOD AND LYMPH 59 
 
 The gases of the blood and lyinpli will be treated of in 
 Chapter IV., the formation of lymph in Chapter VIII., its circulation 
 in Chapter III. 
 
 Section VI. — The Funxtions of Blood and Lymph, 
 
 We have already said that these liquids provide the tissues with 
 the materials they require, and carry away from them materials 
 which have served their turn and are done with. These materials 
 are gaseous, liquid, and solid. Oxygen is brought to the tissues in 
 the red corpuscles ; carbon dioxide is carried away from them partly 
 in the erythrocytes, but chiefly in the plasma of the blood and 
 lymph. The water and solids which the cells of the body take in 
 and give out are also, at one time or another, constituents of the 
 plasma. The heat produced in the tissues, too, is, to a large extent, 
 conducted into the blood and distributed by it throughout the body. 
 The leucocytes, as will be seen farther on, aid in some measure in the 
 absorption of certain of the food substances from the intestine. It is 
 not known whether, apart from this, they play any role in the normal 
 nutrition of other cells, although it is probable that they exercise an 
 influence on the plasma in which they live. But they have impor- 
 tant functions of another kind, to which it is necessary to refer briefly 
 here. 
 
 Phagocytosis. — Certain of the amoeboid cells of blood and lymph, 
 and the cells of the splenic pulp, are able to include or ' eat up ' 
 foreign bodies with which they come in contact, in the same way as 
 the amoeba takes in its food. Such cells are called phagocytes; and 
 it is to be remarked that this term neither comprises all leucocytes 
 nor excludes all other cells, for some fixed cells, such as those of the 
 endothelial Hning of bloodvessels, are phagocytes in \-irtue of their 
 power of sending out protoplasmic processes, while the small, 
 relatively immobile lymphocyte is not a phagocyte. 
 
 Although it is not at present possible to assign a physiological 
 value to all the phenomena of phagocjrtosis, either as regards the 
 phagocytes themselves or as regards the organism of which they 
 form a part, there seems little doubt that under certain circumstances 
 the process is connected with the removal of structures which in the 
 ■course of development have become obsolete, or wath the neutral- 
 ization or elimination of harmful substances introduced from with- 
 out, or formed by the activity of bacteria within the tissues. During 
 the metamorphosis of some larvae, groups of cilia and muscle-fibres 
 may be absorbed and eaten up by the leucocytes. In the metamor- 
 phosis of maggots, for example, the muscular fibres of the abdominal 
 wall, which are used in creeping, and are therefore not required in 
 the adult, degenerate, and are devoured by swarms of leucocytes 
 "which migrate into them. In the human subject an example of 
 
6o THE CIRCULATING LIQUIDS OF THE BODY 
 
 absorption of tissue by the aid of leucocytes is the removal of the 
 necrosed decidua reflexa, the fold of uterine mucous membrane 
 which envelops the ovum (Minot). 
 
 The behaviour of phagocytes towards pathogenic micro-organisms 
 is of even greater interest and importance. Metchnikoff laid the 
 foundation of our knowledge of this subject by his researches on 
 Daphnia, a small crustacean with transparent tissues, which can be 
 observed under the microscope. When this creature is fed with a 
 fungus, Monospora, the spores of the latter find their way into the 
 body-cavity. Here they are at once attacked by the leucoc3H:es, 
 ingested, and destroyed. But after a time so many spores get 
 through that the leucocj^es are unable to deal with them all; some 
 of them develop into the first or ' conidium ' stage of the fungus; the 
 conidia poison the leucocytes, instead of being destroyed by them, 
 and the animal generally dies. Occasionally, however, the leuco- 
 cytes are able to destroy all the spores, and the life of the Daphnia is 
 preserved. This battle, ending sometimes in victory, sometimes in 
 defeat, is believed by Metchnikoff to be tj^'pical of the struggle which 
 the phagocytes of higher animals and of man seem to engage in 
 when the germs of disease are introduced into the organism. He 
 supposes that the immunity to certain diseases possessed naturally 
 by some animals, and which may be conferred on others by vaccina- 
 tion with various protective substances, is, to a large extent, due to 
 the early and complete success of the phagocytes in the fight with 
 the bacteria; and that in rapidly- fatal diseases — such as chicken- 
 cholera in birds and rabbits, and anthrax in mice — the absence of 
 any effective phagocytosis is the factor which determines the result. 
 Others have laid stress on the action of protective substances sup- 
 posed to exist in the plasma itself. It is possible that such sub- 
 stances are manufactured by the leucocytes, and either given off by 
 them to the plasma by a process of ' excretion,' or liberated by their 
 complete solution. 
 
 The most recent investigations go to show that Metchnikoff's 
 phagocytic theory of immunity requires modification, at any rate in 
 the case of the higher animals and man, although the brilliant 
 biological observations on which it was originally built retain all 
 their value. He supposed that in the immunizing process the 
 leucocytes underwent certain changes, acquired, so to speak, a sort 
 of ' education ' that enabled them to cope with bacteria against 
 which they were previously powerless. It seems more probable 
 that in the presence of the substances that confer imnumity, not only 
 the leucocytes, but other cells, are stimulated to produce bodies 
 which cut short the life, or inhibit the growth, of the bacteria 
 (alexins), or prepare them for being taken up by the phagocytes 
 (opsonins). It has been shown that bacteria which have been in 
 contact with serum containing the appropriate opsonins are taken 
 
FUNCTIONS OF BLOOD AND LYMPH 6i 
 
 up readily by leucocytes washed free from serum constituents by 
 physiological salt solution, whereas the washed leucocytes either do 
 not ingest bacteria which have not been acted on by serum, or take 
 them up in much smaller numbers. There is some evidence that in 
 certain bacterial infections — for example, chronic furunculosis, a 
 condition in which crops of boils continue to appear — the grip of the 
 bacteria on the body is perpetuated by a deficiency in the amount or 
 in the activity of opsonins capable of acting specifically upon the 
 micro-organisms in question. A numerical expression, which in 
 certain cases, perhaps, gives a measure of the patient's resistance to 
 the infection, has been worked out by Wright under the name 
 ' opsonic index.' This index is the ratio between the average 
 number of bacteria taken up, under certain fixed conditions, by each 
 polymorphonuclear leucocyte in an emulsion made with the patient's 
 serum, and the average number taken up by similar leucocytes in an 
 emulsion made with normal serum. The significance of this index 
 and even the practicability of the methods used to ascertain it, are 
 still the subject of discussion. 
 
 Diapedesis. — The fact that leucocytes can pass out of the blood- 
 vessels into the tissues has a very important bearing on the subject 
 of phagocytosis. The phenomenon is called diapedesis, and is best 
 seen when a transparent part, such as the mesentery of the frog, is 
 irritated. The first effect of irritation is an increase in the flow of 
 blood through the affected region. If the irritation continues, or if 
 it was originally severe, the current soon begins to slacken, the 
 corpuscles stagnate in the vessels, and inflammatory stasis is pro- 
 duced. The leucocj^es adhere in large numbers to the walls of the 
 capillaries, and particularly of the small veins, and then begin to pass 
 slowl}^ through them by amoeboid movements, the passage taking 
 place at the junctions between, or it may be through the substance of, 
 the endothelial cells. Plasma is also poured out into the tissues, 
 the whole forming an inflammatory exudation. Even red blood- 
 corpuscles may pass out of the vessels in small numbers. The 
 exudation may be gradually reabsorbed, or destruction of tissue 
 may ensue, and a collection of pus be formed. The cells of pus are 
 emigrated leucocytes (Practical Exercises, Chap. III., p. 193). 
 
 Their emigration is connected \\dth the defence of the organism 
 against the entrance of certain forms of bacteria at the seat of 
 injury, and with the repair of the injured tissue, but the nature of 
 the summons which gathers them there is not yet clearly under- 
 stood. It is probably some sort of chemical attraction (chemio- 
 taxis) between constituents of the bacteria or decomposition prod- 
 ucts of the injured tissue on the one hand, and constituents of the 
 leucocytes on the other. 
 
 As for the blood-plates, it will suffice to say by way of summary 
 that their important function in the sealing of wounded vessels (p. 46) 
 
6i THE CIRCULATING LIQUIDS OF THE BODY 
 
 is the sole office which at present can be attributed to them. And 
 if it is permissible to consider the leucocytes as a patrol for the 
 defence of the tissues in general against invading micro-organisms, it 
 may perhaps not be too far-fetched an idea to look upon the blood- 
 plates as essentially a patrol in the interests of the anatomical 
 integrity of the vascular system itself. This does not exclude the 
 possibility that the clo'^ting of extravasated plasma may furnish a 
 more favourable medium for the processes of repair in all injured 
 tissues. 
 
 PRACTICAL EXERCISES ON CHAPTER II. 
 
 N.B. — In the following exercises all experiments on animals which 
 would cat^e the slightest pain are to be done under complete ancesthesia. 
 
 1. Reaction of Blood. — (i) Put a drop of fresh dog's or ox blood on 
 a piece of glazed neutral litmus paper (the litmus paper can be glazed 
 by dipping it into a neutral solution of gelatin and allowing it to dry). 
 Wash the blood ofiE in lo to 30 seconds with distilled water. A bluish 
 stain will be left, showing that fresh blood is alkaline. (2) Repeat with 
 dog's or ox serum. It is not necessarv' to wash the serum off, as it 
 does not obscure the change of colour. (3) Repeat (i) with human 
 blood. With a clean suture-needle or a good-sized sewing-needle 
 which has been sterilized in the flame of a Bunsen burner, prick one of 
 the fingers behind the nail. Bandaging the finger with a handkerchief 
 from above downwards, so as to render its tip congested, will often 
 facilitate the getting of a good-sized drop, but for quantitative experi- 
 ments, like 2. 10, and i 7 (4). this should not be done. 
 
 2. Specific Gravity of Blood — Hammerschlag's Method. — (i) Put a 
 mixture of chloroform and benzol of specific gravity i-o6o into a small 
 glass cylinder. Put a drop of dog's or o.x defibrinated blood into the 
 mixture by means of a small pipette. If the drop sinks add chloroform, 
 if it rises add benzol, till it just remains suspended when the liquid has 
 been well stirred. Then with a small hydrometer measure the specific 
 gravity of the mixture, which is now equal to that of the blood. Filter 
 the liquid to free it from blood, and put it back into the stock-bottle. 
 (2) Obtain a drop of human blood as in i, and repeat the measurement 
 of the specific gravity. 
 
 3. Coagulation of Blood.* — (i) Take three tumblers or beakers, label 
 them a. ;i. and 7. and measure into each 100 c.c. of water. Mark the 
 level of the water by strips of gummed paper, and pour it out. (If a 
 sufficient number of graduated cylinders is available, they may of 
 course be used, and this measurement avoided.) Into a put 25 c.c 
 of a saturated solution of magnesium sulphate, into ^ 25 c.c. of a i per 
 cent, solution of potassium or ammonium oxalate in 0-9 per cent, 
 solution of sodium chloride, and into y 25 c.c. of a i'2 per cent, solution 
 of sodium fluoride in 0-9 per cent, salt solution If the dog provided 
 is a large one, these quantities may be all doubled ; for a small dog they 
 may be all halved. 
 
 • This experiment requires two laboratory periods, the various blood mix- 
 tures being obtained during the first and worked up during the second. 
 
PRACTICAL EXERCISES 63 
 
 (2) Insert a cannula into the central end of the carotid artery of a 
 dog anaesthetized with morphine* and ether, or A.C.E. mixture. f 
 
 To put a Cannula into an Artery. — Select a glass cannula of suitable 
 size, feel for the artery, make an incision in its course through the 
 skin, then isolate about an inch of it with forceps or a blunt needle, 
 carefully clearing away the fascia or connective tissue. Next pass a 
 small pair of forceps under the arterj\ and draw two ligatures 
 through below it. If the cannula is to be inserted into the central 
 end of the artery, tie the ligature which is farthest from the heart, 
 and cut one end short. Then between the heart and the other 
 ligature compress the artery with a small clamp (often spoken of as 
 ' bulldog ' forceps). Now lift the arter^^ by the distal ligature, make a 
 transverse slit in it with a pair of fine scissors, insert the cannula, and 
 tie the ligature over its neck. Cut the ends of the ligature short. If 
 the cannula is to be put into the distal end of the ^.ttevy, both ligatures 
 must be between the clamp and the heart, and the bulldog must be put 
 on before the first ligature (the one nearest the heart) is tied, so that 
 the piece of bloodvessel between it and the ligature may be full of 
 blood, as this facilitates the opening of the artery. 
 
 (3) Run into a, /3, and y enough blood to fill them to the mark. 
 Shake the vessels, or stir up once or twice with a glass rod, to mix the 
 blood and solution. 
 
 (4) Take a small thin copper or brass vessel, and place it in a freezing 
 mixture of ice and salt. Run into it some of the blood from the artery. 
 It soon freezes to a hard mass. Now take the vessel out of the 
 freezing mixture and allow the blood to thaw. It will be seen that it 
 remains liquid for a short time and then clots. 
 
 (5) Run some of the blood into a porcelain capsule, stirring it 
 vigorously with a glass rod. The fibrin collects on the rod; the blood 
 is defibrinated and will no longer clot. 
 
 (6) Now let some blood run into a small beaker or jar. Notice that 
 the blood begins to clot in a few minutes, and that soon the vessel 
 can be tilted without spilling it. Note the time required for clotting 
 to occur. Set the coagulated blood aside, and observe next day that 
 clear yellow serum has separated from the clot. 
 
 (7) Weigh out a quantit}' of Witte's ' peptone ' equivalent to 
 0'5 gramme for every kilo of bodj^- weight of the dog. Dissolve the 
 peptone in about twenty times its weight of 0-9 per cent, salt solution. 
 Put a cannula into the central end of a crural vein (p. 212). Fill the 
 cannula with the peptone solution and connect it with a burette. Put 
 15 drops of the peptone solution into a test-tube labelled ' Peptone A.' 
 Put the rest into the burette, and see that the connecting tube is filled 
 with the solution and free from air. Run into the test-tube about 
 5 c.c. of blood from the cannula in the carotid. Now let the peptone 
 solution flow from the burette into the vein. Feel the pulse o\'er the 
 heart as the solution is running in. If the heart becomes very weak, 
 stop the injection ; otherwise the animal may die from the great lower- 
 ing of blood-pressure (p. 214). As soon as the injection is finished, 
 draw off a sample of 5 c.c. of blood into a test-tube labelled ' Pep- 
 tone B,' and let it stand. In ten minutes collect five further samples 
 of 5 c.c. (' Peptone C, D, E, F, G '), and a large one, H; in half an hour 
 
 * One to 2 centigrammes of morphine hydrochlorate per kilogramme of 
 body-weight should be injected subcutaneously about half an hour before 
 the operation. Ten c.c. of a 2 per cent, solution is sufficient for a dog of 
 good size. Note that diarrhoea and salivation are caused by such a dose. 
 For directions for fastening the dog on the holder, see footnote on p. 199. 
 
 t A mixture of i part of alcohol, 2 of ether, and 3 of chloroform. 
 
64 
 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 another set of five small samples, and at as long an interval as possible 
 thereafter five more. Now letting the dog bleed to death, observe that 
 the flow of blood is temporarilj' increased by pres.sure on the abdominal 
 walls, which squeezes it towards the heart, by passive movements of 
 the hind-legs, and also during the convulsions of asphyxia, which soon 
 appear. Add to the peptone blood D 5 c.c. of serum, to H a little 
 sodium chloride extract of liver, to F a little extract of muscle, and to 
 G 15 drops of a 2 per cent, solution of calcium chloride, and put C, D, 
 E. F, and G into a water-bath at 40° C. Treat the other sets of small 
 
 samples in the same way. Note 
 liow long each specimen takes to 
 clot, and report your results.* 
 
 (8) Observe that the blood in a, 
 8, and y has not coagulated. Label 
 four test-tubes ' Oxalate A, B, C, 
 D.' and put into each about 5 c.c. 
 of the oxalated blood. Add to A 
 and B 5 or 6 drops of a 2 per cent, 
 solution of calcium chloride, to C 12 
 drops, and to D as much as there 
 is of the blood. Leave A at the 
 ordinary temperature, put the other 
 test-tubes in a water-bath at 40" C, 
 and note when clotting occurs. 
 
 (9) To 10 c.c. of the fluoride blood 
 add a little more CaCl2 than is re- 
 quired to combine with the excess 
 of fluoride present. Label four test- 
 tubes ' Fluoride A, B, C, D,' and 
 into each put about 2 c.c. of this 
 ' recalcified ' fluoride blood. To B 
 add I c.c. liver extract to C 1 c.c. 
 muscle extract, and to D 4 c.c. 
 water. Label two more test-tubes 
 ' Fluoride E and F.' Into each put 
 2 c.c. of the fluoride blood without 
 CaCl2. Add also to E i c.c. liver 
 extract and to F i c.c. serum. Put 
 all the tubes in a bath at about 
 40° C, and observe in which and in 
 what time coagulation takes place. 
 
 (10) By means of a centrifuge 
 (Fig. 1 7) separate the plasma from 
 the corpuscles in a, ji, and y, and 
 also from the peptone blood. 
 
 With the oxalate plasma from /3, 
 and the fluoride plasma from y, repeat the observations in (8) and 
 (9), using smaller quantities of the plasma, if necessarj', in small test- 
 tubes. With the plasma from a perform the following experiments: 
 Put a small quantity of the plasma (i c.c.) into four test-tubes, labelling 
 
 • Sometimes the injection of peptone hastens coagulation instead of hinder- 
 ing it. It has been asserted that this is only the case when small doses are 
 used (less than 0-02 gramme per kilo of body-weight). But in 2 dogs out of 
 ri a dose of 0*5 gramme per kilo has been seen to hasten coagulation, and in 
 I out of 12 to leave it unaffected; in the other 9 coagulation was markedly 
 retarded 
 
 Fig. I/. — Centrifuge (Jung). The four 
 cylinders shown at the top of the 
 figure are so swung that they become 
 horizontal as soon as speed is up. 
 
PRACTICAL EXERCISES 65 
 
 them ' Magnesium Sulphate A, B, C, D.' Dilute B with four times, C 
 with eight times, and D with twenty times as much distilled water as 
 was taken of the plasma. Observe in which, if any, coagulation occurs, 
 and the time of its occurrence, and report the result. 
 
 (11) With peptone plasma from H and from the peptone blood 
 obtained later repeat the experiments done in (7). In addition tlilute 
 I c.c. of the plasma with three volumes of water and i c.c. of it with 
 ten volumes of water, and put in the bath at 40° C. Observe whether 
 clotting occurs. 
 
 Instead of dog's blood, the blood of an ox or pig may be obtained at 
 the slauglitcr-housc. 
 
 4. Preparation of Fibrin-Ferment. — Precipitate blood-serum with 
 ten times its volume oi ;ilcohol. Let it stand for several weeks, then 
 extract the precipitate with water. The water dissolves out the fibrin- 
 ferment, but not tlie coagulated serum proteins. 
 
 3. Preparation of Tissue Extracts containing Thrombokinase. — In a 
 dog or rabbit killed by bleeding insert a cannula into the lower end of 
 the thoracic aorta. Fill the cannula with 0-9 per cent, salt solution, 
 and connect it with a bottle also containing salt solution. Wash 
 out the vessels of the lower portion of the body, making an opening 
 in the inferior vena cava above the diaphragm to allow the liquid 
 to escape. For the sake of cleanliness, a cannula armed with a 
 piece of rubber tubing should be inserted for this purpose into the 
 inferior vena cava. Continue the injection till the liquid issues colour- 
 less. Then remove portions of liver and muscle. Mince each separately. 
 Rub up with sand in a mortar. Add o-g per cent, sodium chloride 
 solution and rub up again. Put into bottles and keep in the ice-chest. 
 For use take off some of the liquid from the top with a pipette, or strain 
 through cheese-cloth. 
 
 6. Serum. — Test the reaction, and determine, both by the hydrom- 
 eter and the pycnometer, or specific gravity bottle, the specific 
 gravity of the serum provided, or of the serum obtained in experi- 
 ment 3. 
 
 Serum Proteins. — (i) Saturate serum with magnesium sulphate 
 crv'stals at 30° C. The serum-globulin is precipitated. Filter off. 
 Wash the precipitate on the filter with a saturated solution of mag- 
 nesium sulphate. Dissolve the precipitate by the addition of a little 
 distilled water, and perform the following tests for globulins : (a) Satu- 
 rate with magnesium sulphate. A precipitate is obtained. (6) Drop 
 into a large quantity of water, and a flocculent precipitate falls down, 
 (c) Heat. Q>agulation occurs. Determine the temperature of coagfu- 
 lation (p. 9). 
 
 (2) To a portion of the filtrate from (i) add sodium sulphate to 
 saturation. The serum-albumin is precipitated. (Neither magnesium 
 sulphate nor sodium sulphate precipitates serum-albumin alone, but 
 the double salt sodio-magnesium sulphate precipitates it, and this is 
 formed when sodium sulphate is added to magnesium sulphate.) 
 
 (3) Dilute another portion of the filtrate from (i) with its own bulk 
 of water. Very slightly acidulate with dilute acetic acid, and de- 
 termine the temperature of heat coagulation. 
 
 (4) Precipitate the serum-globulin from another portion of scrum by 
 adding to it an equal volume of saturated solution of ammonium 
 sulphate. Filter. Precipitate the serum-albumin from the filtrate by 
 saturating with ammonium sulphate cr\-stals. 
 
 (5) Dilute serum with ten to twenty times its volume of distilled 
 water, and pass through it a stream of carbon dioxide. The serum- 
 globulin is partially precipitated. 
 
 5 
 
66 THE CIRCULATING LIQUIDS OF THE BODY 
 
 (6) Acidulate some scrum with dilute acetic acid and boil. Filtei 
 off the coagulum. and to the filtrate add silver nitrate. A non-protein 
 precipitate insoluble in nitric acid, but soluble in ammonia, indicates 
 the presence of clilorides. 
 
 7. Action of Serum on Artery Rings. — Cut a number of rings about 
 li millimetres wide from a fresh carotid artery of the sheep, obtained 
 from the slaughter-house. Keep the rings in a dish in Ringer's solu- 
 tion.* They should be as nearly as possible of uniform width. A small 
 cylindrical glass vessel is supported on a stand in such a way that it 
 can be easily lowered into a bath of water kept at a temperature of 
 about 39° to 40". A stock of Ringer's solution is kept in a beaker 
 or bottle immersed in the bath. A ring of the artery is put into the 
 small cylinder, where it is held between two aluminium hooks, one 
 fastened to the bottom of the cylinder, the other (the upper one) con- 
 nected with the short arm of a lever, the long arm of which is arranged 
 to write on a slowly revolving drum. A time-trace, say in half- 
 minutes, is recorded below. The small cylinder is now filled with 
 warm Ringer's solution and lowered into the bath. Oxygen is bubbled 
 through the solution by means of a side-tube near the bottom of the 
 cylindrical vessel. The artery- ring is now stretched for five minutes 
 by a weight of 10 grammes attached to the long arm of the lever at the 
 same distance from the axis as that at which the ring is attached. 
 After the stretching period the weight is removed, and a little time 
 allowed to elapse till the writing-point traces a horizontal line on the 
 drum. Then a bent pipette is filled with serum already heated to bath 
 temperature in a vessel immersed in the bath. The pipette is intro- 
 duced into the small cylinder so tliat its point is at the bottom, without 
 disturbing the ring, and tlie serum is allowed to run in till the Ringer 
 solution is displaced. The ring shortens under the influence of the con- 
 strictor substance in the serum, and the tracing is continued till the 
 shortening has reached its maximum and the trace is again horizontal 
 (Fig. 3, p. 46). 
 
 ^ arious dilutions of the serum are now made with Ringer's solution, 
 and the greatest dilution in which the serum will still cause a percep- 
 tible constriction of the rings is determined. This affords a measure 
 of comparison with other sera of the strength of the constrictor action. 
 For each dilution of serum a separate ring must be used. It must be 
 remembered that comparisons of this kind can only be made with 
 arteries of the same sensitiveness, and different arteries vary much in 
 this regard. 
 
 8. Comparison of the Action of Serum and Adrenalin (Epinephrin) on 
 Artery Rings. — Tracings showing the effect of \ arious dilutions of 
 adrenalin chloride on artery rings may now be taken for comparison 
 with the serum effects. The adrenalin dilutions should be made just 
 before use, as adrenalin is rapidly oxidized. Or a separate experiment 
 on the action of adrenalin may be made under ' Circulation,' as on 
 p. 216. 
 
 9. Comparison of the Action of Serum and Plasma on Artery Rings. — 
 Citrate ])lasma is obtained as follows: A cannula and attached rubber 
 tube are boiled, oiled inside with fresh olive-oil, and filled with a citrate 
 
 * This is the name given to a solution containing the most important of 
 the inorganic constituents of blood-serum in approximately the normal pro- 
 portions. The various ' Ringer's solutions ' used by different workers have 
 varied slightly. That recommended by Locke (for perfusion of the isolated 
 heart) contains NaCl, 0-9 per cent.; KCl, 0*042 per cent.; CaCl2. 0-024 P^r cent.; 
 NaHC03, o-oi to 0-03 per cent.; with in addition o'l per cent, of dextrose, 
 which can be omitted lor such experiments as 7. 
 
PRACTICAL EXERCISES 
 
 f>7 
 
 solution made by dissolving sodium citrate in Ringer's solution to the 
 extent of 2 per cent. The solution is prevented from escaping by a 
 clip on the tube. The cannula is inserted into the carotid of a dog, 
 the end of the rubber tube dipped below a quantity of citrate- 
 Ringer solution in a beaker and a volume of blood equal to that of the 
 solution run in. Then the blood and solution are at once stirred gently, 
 but sufficiently to insure proper admixture. 
 
 Some blood is now run into another vessel, defibrinated, and 
 measured. An equal volume of the citrate-Ringer solution is added to 
 it while the mass of fibrin is still floating in the blood, .\fter mixing, 
 the fibrin is removed. Plasma is then separated by the centrifuge from 
 the first specimen of blood, and serum from the second, and comparison 
 experiments are made with each on artery rings. If the plasma has 
 been properly obtained, it will have little constrictor effect on the 
 rings in comparison with the serum. In making the comparison, 
 arteries which give a decided effect with serum should be employed. 
 The defibrinated blood and the unclotted citrate blood may also be 
 used for tlie comparison. 
 
 Fig. I&. — Thoma-Zeiss Ha-mocytometer. M, mouthpiece of lube G, by which 
 blood is sucked into S; E, bead for mixing; a, view of slide from above; b, in 
 section; c, squares in middle of B, as seen under microscope. 
 
 10. Enumeration of the Blood - Corpuscles. — Use the Thoma-Zeiss 
 apparatus (Fig. 18). (i) Suck a drop of ox or dog's blood up into 
 the capillary tube 5 to the mark i. Wipe off any blood which 
 may adhere to the end of the tube. Then fill it with 3 per 
 cent, sodium chloride to the mark loi. This represents a dilution of 
 100 times. Mix the blood and solution thoroughly, then blow out a 
 drop or two of the liquid to remove all the solution which remains in 
 the capillary- tube. Now fill the shallow cell B with the blood mixture. 
 Put the cover-glass on, taking care that it does not float on the liquid, 
 but that the cell is exactly filled. Put the slide under the microscope 
 (say Leitz's oc. III., obj. 5), and count the number of red corpuscles 
 in not less -tlitei' ten 'to twenty squares. Sixteen squares is a good 
 routine number. The greater the number of squares counted, the 
 nearer will be the approximation to the truth. Now take the average 
 number in a square. The depth of the cell is ^'^ mm., the area of each 
 square j^^ sq. mm. The volume of the column of liquid standing 
 upon a square is ^oVht cub. mm. One cub. mm- of the diluted blood 
 would therefore contain 4,000 times as many corpuscles as one square. 
 But the blood has been diluted 100 times, therefore i cub. mm. of the 
 
68 
 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 undiluted blood would contain 400,000 times the number of corpuscles 
 in one square. Suppose the average for a square is found to be 13. 
 This would correspond to 5,200,000 corpuscles in i cub. mm. of blood. 
 Compare your result with the true number supplied by the demon- 
 strator. (2) Prick the finger to obtain a drop of blood, and repeat 
 the crunt as in (i).* 
 
 To Count the White Corpuscles. — Add to i part of blood 9 parts of 
 \ per cent, acetic acid, in order to lake the coloured corpuscles and 
 render it easy to see the leucocytes. 
 
 II. Relative Volume of Corpuscles and Plasma by Haematocrite. — 
 (i) For pructice, fill the two graduated glass tubes with the defibrinated 
 blood of an animal. The rubber tube with mouthpiece supplied with 
 the apparatus is to be attached to the glass tube, and the blood sucked 
 up. Press the tip of the index-finger against the pointed end, and care- 
 fully remove the rubber tube. Place the tube in the haematocrite frame, 
 blunt end outwards — that is, farthest from the axis of rotation — and 
 then slip the pointed end down into position against the spring. Instead 
 of the rubber tube, a special suction pipette for automatically filling 
 the graduated tubes may be employed (Daland). Attach the haemato- 
 crite frame to the centrifuge, and rotate till the volume of sediment 
 
 Fig. 19. 
 
 3 
 
 -Hfpmatocrite. A, haematocrite attachment with graduated tubes; B, auto- 
 matic pipette for filling the tubes (Daland). 
 
 (corpuscles) ceases to diminish. The graduations are best read with a 
 hand lens. The leucocytes will be seen to form a thin whitish line 
 proximal to the column of red corpuscles. 
 
 (2) Prick the finger or the lobe of the ear, fill the tubes as in (i), and 
 centrifugalize. Evciything must be done as rapidly as possible, so 
 that the blood may not clot till the separation of plasma and corpuscles 
 is completed. The centrifuge must rotate very rapidly (about 10,000 
 revolutions a minute) for two or three minutes. For clmical purposes 
 it is best to rotate the centrifuge always at the same speed for the 
 same length of time rather than to aim at reaching a constant length 
 of the column of corpuscles. In this way useful comparative results 
 can be obtained. It is well, to avoid the risk of accident, to rotate the 
 centrifuge imder a guard. 
 
 12. Electrical Conductivity of Blood. — (i) Fill a small U-tube with 
 blood up to a mark. In each limb insert a platinum electrodef con- 
 
 * If the tube has not been properly filled, blow the blood out immediately. 
 On no account permit it to clot in the capillary tube. 
 
 t If the platmum electrodes are of good size and the resistance of the tube 
 of liquid considerable, it is not necessau-y to platinize them — i.e.. to cover them 
 by electrolysis of a solution of platinic chloride with a layer of platinum-black. 
 
PRACTICAL EXERCISES 69 
 
 nected with a holder, which insures that the electrode shall always dip 
 to the same depth into the tube. Arrange the U-tube so that it is 
 immersed at least to the mark in water of constant temperature. Water 
 running freely from the cold-water tap into and out of a large vessel 
 will have a sufficiently constant temperature for the purpose. A ther- 
 mometer must be fixed in the water with its bulb in contact with the 
 U-tube. Connect the electrodes with a resistance-box in the Wheat- 
 stone's bridge arrangement (Fig. 231, p. 726), so that the U-tube 
 occupies the position of the unknown resistance CD. Instead of the 
 battery F, connect the poles of the secondary of a small induction-coil, 
 arranged for an interrupted current, with A and C, and instead of tlie 
 galvanometer G insert a telephone. The resistances AB and AD will 
 be obtained by taking out two plugs from the appropriate part of the 
 resistanoe-box. Whether AB and AD should be equal (say, 10 : 10, 
 100 : 100, or 1,000 : 1,000 ohms) or unequal (say, 10 : 100, or 
 100 : 1,000, or 10 : 1,000 ohms) will depend upon the resistance of 
 the tube of liquid to be measured. Take out from the part of the box 
 corresponding to BC a plug representing a resistance something like 
 that which the tube of blood is expected to have. Close the primary 
 circuit of the induction-coil, and apply the telephone to the ear. A 
 buzzing sound will be heard, which will be louder the farther from the 
 true resistance of the tube the resistance taken out of the box is. Go 
 on altering the resistance in the box by taking out or putting in plugs 
 till the sound disappears, or is reduced to a minimum. The tempera- 
 ture of the water should now be read off. The resistance of the tube of 
 blood for this temperature can easily be calculated from the formula 
 on p. 726. It increases about 2 per cent, for each degree Centigrade of 
 diminution of temperature. The conductivity is the reciprocal of the 
 resistance. By determining once for all the resistance of the tube 
 when filled with a standard solution of a salt whose conductivity is 
 known, the specific conductivity of the blood can be expressed in 
 definite units, but this is not necessary for the purposes of the student. 
 Compare the resistances of defibrinated blood, serum, o-q per cent, 
 sodium chloride solution, and a sediment of blood-corpuscles separated 
 by centrifugalization. 
 
 (2) Instead of the resistance-box a wire mounted on a scale may be 
 used for the resistances AB, AD, the ends of the wire being connected 
 at B and D. A slider with an insulated handle moving along the 
 graduated wire is joined by a flexible wire with one pole of the secondary 
 coil, the other pole being connected at C. The resistance BC is consti- 
 tuted by a rheostat from which a fixed resistance can be taken out. 
 Instead of obtaining the minimum sound in the telephone by varying 
 the resistance BC in the box, the measurement is made by varydng the 
 position of the slider; in other words, by changing the ratio AB: AD. 
 
 (3) If no rheostat is available instructive comparative measurements 
 may still be made with the graduated wire by substituting for the 
 resistance BC a U-tube of another liquid. 
 
 If the tubes are of the same dimensions, and the liquids with which 
 they are filled are approximately at the same initial temperature, it 
 is not necessary to immerse them in water at constant temperature. It 
 is sufficient to place them side by side in the air. Perform the following 
 experiments in this way: 
 
 (a) Label the tubes A and B. Fill them both to the mark with 
 0-9 per cent. NaCl solution. Connect as in the figure, and move the 
 slider along the wire till the sound is a minimum. Probably the two 
 tubes are not exactly of the same dimensions, and therefore the slider 
 will not be exactly in the middle of the wire. Suppose it is at 49-0 
 
TO THE CIRCULATING LIQUIDS OF THE BODY 
 
 the total length of the wire being loo. Then resistance of A : resistance 
 
 49 
 of B:: 4Q'0 : si-o, i.e., resistance of A = -- resistance of B. 
 
 [b) Fill A with defibrinated blood, keeping B filled with NaCl solu- 
 tion, and repeat the measurement. The slider must now be moved 
 much farther away from the zero of the scale. Suppose the minimum 
 sound is obtained with the slider at 70-0. Then resistance of blood = 
 
 3 CI 
 
 X -^ resistance of the NaCl solution. 
 7 49 
 
 (c) Compare in the same waji- the resistance of scrum with that of 
 the NaCl solution. It will be found much less tlian that of the blood. 
 
 {d) Centrifugalize some of the blood for as long as is convenient, and 
 compare the resistance of tlie blood from the top of the tubes and from 
 the bottom of the tubes with that of the NaCl solution. The resistance 
 of the blood from the bottom of the tubes will be found much greater 
 than that of the blood from the top. 
 
 13. Opacity of Blood. — Smear a little fresh blood on a glass slide, and 
 hold the slide above some i)rinted matter. It will not be possible to 
 read it, because the light is reflected from the corpuscles in all directions, 
 and little of it passes tlirough. 
 
 14. Laking of Blood by Chemical and Physical Agents. — (i) Put a 
 little fresh blood into three test-lubes, A, B, and C. Dilute A with an 
 equal volume, B with two volumes, and C with three volumes, of dis- 
 tilled water, and repeat experiment 9. The print can now be read 
 probably through a layer of A, but certainly through B and C, since 
 the haemoglobin is dissolved out of the corpuscles by the water and 
 goes into solution, the blood becoming transparent or laked. That the 
 difference is not due merely to dilution can be shown by putting an 
 equal quantity of blood in two test-tubes, and gradually diluting one 
 with distilled water and the other with a 0'9 per cent, solution of 
 sodium chloride, which does not dissolve out the haemoglobin. Print 
 can be read through the first with a smaller degree of dilution than 
 through the second. Examine the laked blood with the microscope 
 for the ' ghosts,' or shadows of the red corpuscles. The addition of a 
 drop or two of methylene blue will render them somewhat more distinct. 
 
 (2) Heat a little dog's or ox blood in a test-tube immersed in a water- 
 bath. Put a thermometer in the test-tube, taking care that there is 
 enough blood to cover the bulb. Keep the temperature about 60° C. 
 In a few minutes the blood becomes dark and laking occurs. 
 
 (3) [a) Put a little blood into each of four test-tubes. To one add a 
 little ether, to another a little chloroform, to the third dilute acetic 
 acid in 0-9 per cent. NaCl, and to the fourth a dilute solution of bile 
 salts (or of sodium taurocholatc) in 0-9 per cent. NaCl solution. Laking 
 occurs in all. 
 
 [b) To 5 c.c. of blood add 0-5 c.c. of a 3 per cent, solution of saponin 
 in 0'9 per cent. NaCl solution, and put the mixture at 40° C. Laking 
 soon occurs. 
 
 (c) Using a 10 per cent, dilution of blood (blood to which nine volumes 
 of NaCl solution have been added) or a 5 per cent, suspension of washed 
 corpuscles in NaCl solution {i.e.. a suspension of corpuscles which have 
 been washed free from serum by being repeatedly mixed with NaCl 
 solution and centrifugalized), determine the minimum dose of 0-3 per 
 cent, saponin solution which will just cause complete laking. Keep the 
 tubes at about 40° C, and observe them from time to time. Now add 
 to some of the 10 per cent, dilution or the 5 per cent, suspension of blood 
 an equal volume of scrum from the same kind of blood, and repeat the 
 determination of the minimum dose of saponin necessary for laking. 
 
PRACTICAL EXERCISES 71 
 
 It will be found that more is now required. The cholestcrin in the 
 serum neutralizes the action of some of the saponin. 
 
 (4) {a) Put I c.c. of blood into each of two tost-tubcs. To one add 
 I c.c. of 2 per cent, aqueous solution of urea, and to the other 3 c.c. 
 Laking will take place in the second, whether this has been the case in 
 the first or not. 
 
 {b) Repeat the experiment with a 2 per cent, solution of urea in 
 0'9 per cent. NaCl sohition. Laking docs not occur. 'Ihis shows that 
 the urea in the first experiment did not act as a haemolytic agent. 
 Laking occurred because urea penetrates the corpuscles easily, and 
 therefore, although the freezing-point of the urea solution is not verj- 
 different from that of the NaCl solution, its actual osmotic pressure, 
 in relation to the envelopes of the corpuscles, is very much less, and the 
 laking is really water-laking. 
 
 (5) Put some blood into a flask or test-tube, cork up, and let it stand 
 till it begins to putrefy. It becomes laked. The same occurs when 
 the blood is collected aseptically in a sterile tube and sealed up, although 
 it takes a longer time for the laking to become complete. 
 
 (6) With blood containing nucleated corpuscles (necturus, frog or 
 chicken) diluted with isotonic salt solution, perform the following 
 experiments imder the microscope : 
 
 (a) With a glass rod drawn to a fine point put a small drop of blood 
 on a slide, and near it a drop of distilled water. Carefully lower the 
 cover-slip and observe the interface with the microscope, first with the 
 low and then with the high power. Then mix and see complete laking. 
 Add a little methylene blue. Note that the nuclei still stain. 
 
 (6) Place a small drop of a 3 per cent, solution of saponin in isotonic 
 salt solution on a slide, and near it a small drop of blood. Observe as 
 in (a). Repeat with a 2 per cent, solution of sodium taurocholate in 
 salt solution. If necturus corpuscles, which are splendid objects for 
 such experiments on account of their great size, have been used, 
 intracorpuscular crystallization of the haemoglobin may be observed. 
 
 (c) Repeat (a) and [b) with mammalian blood. Note that the cor- 
 puscles swell before being laked by the saponin. If any of the corpuscles 
 are crenated, it may be seen that before being laked by the saponin 
 the crenations disappear, the corpuscles becoming round, while in the 
 taurocholate solution they may remain crenated till laking has occurred. 
 This indicates that the permeability of the envelopes is not affected in 
 the same way by the two laking agents. 
 
 15. Haemolysis and Agglutination by Foreign Serum. — (i) To a small 
 quantity of rabbit's blood add an equal volume of dog's serum. Mix 
 and let stand at 40° C. The colour of tlie blood is soon darker than 
 before, and it can be seen to be laked. Examine microscopically. 
 
 (2) Place a small drop of rabbit's blood and a somewhat larger drop 
 of the dog's serum on a slide, near, but not quite in contact with, each 
 other. Now put on a cover-slip, so that the drops just come together, 
 and examine at once with the microscope with a moderately high power. 
 Where the two drops mingle, the red corpuscles will be seen first to 
 become agglutinated into groups, and then to fade out, leaving only 
 their ' ghosts.' A few of the corpuscles which come into contact witn 
 the, as yet, undiluted serum may be entirely dissolved. 
 
 (3) Heat some of the dog's serum to 60° C. for ten minutes, and 
 repeat (i) and (2). No laking will now be produced in the rabbit's 
 corpuscles, but agglutination may be observed as before. 
 
 (4) Repeat (i) and (2) with dog's blood and rabbit's serum. The 
 blood will not be laked. although sometimes the dog's corpuscles may 
 become crenated. There will be no agglutination. 
 
72 THE CIRCULATING LIQUIDS OF THE BODY 
 
 (5) With a 5 per cent, suspension of rabbit's washed corpuscles 
 perform the following experiments:* 
 
 Put into each of six small test-tubes i c.c. of the suspension. Label 
 the tubes A, A', B, B', C, C 
 
 (a) To A and A' add respectively o-i c.c. and 0'5 c.c. ox serum. 
 
 (b) To B and B' add respectively O'l c.c. and 0'5 c.c. dog's serum. 
 
 (c) To C and C add respectively ci c.c. and 0-5 c.c. of 0-9 per cent, 
 sodium chloride solution. 
 
 Put all the tubes in a bath at 40° C. Compare the amount of laking 
 and agglutination in the various tubes at intervals of two minutes or 
 less. Repeat (a), (&), and (c) with guinea-pig's washed corpuscles and 
 serum of ox and dog. Determine which of these sera has the strongest 
 haemolytic power.| 
 
 (6) Heat I c.c. o:( ox and dog's serum respectively to 56° C, keeping 
 it at tiiat temperature, or not more than a couple of degrees above it, 
 for tenj minutes, and repeat experiment (5), labelling the tubes D, D', 
 E, E', F, F'. Save the rest of the heated sera for (8). There is no 
 laking in any of the tubes, but probably agglutination in D, D', and 
 E, E'. (The complement is destroyed, but not the intermediary body 
 or amboceptor, or the agglutinin — p. 28.) 
 
 (7) Put half of the contents of tubes D, D', E, E', into four separate 
 test-tubes, and add to each 0-2 c.c. of rabbit's serum. If there is laking 
 now it is because the rabbit's serum contains complement. Save the 
 balance of D, D', E and E' for (8). 
 
 (8) Allow 0'5 c.c. of ox serum to act at o* C. on the rabbit's washed 
 corpuscles contained in 5 c.c. of the 5 per cent, suspension after removal 
 of the sodium chloride solution. The ox serum and rabbit's corpuscles 
 are separately cooled to 0° C. before being mixed, and the mixture is 
 then kept at 0° C. for one hour. Centrifugalize the serum off rapidly. 
 Label it ' Serum S.' To 0-2 c.c. of the original 5 per cent, suspension 
 of rabbit's washed corpuscles add o-i c.c. of this serum (labelling the 
 tube G), and put at 40° C. with a control-tube containing the same 
 amount of suspension plus salt solution instead of serum. Add the 
 rest of the serum S, cooled to 0° C, to the same cooled rabbit's cor- 
 puscles, and leave for a further period at 0° C. Then centrifugalize 
 rapidly, and to 0*2 c.c. of the original suspension of washed rabbit's 
 corpuscles add o-i c.c. of serum S (labelling the tube H), and put at 
 40° C. with a sodium chloride tube as control. There may be no 
 
 • The material obtained from one medium-sized dog. two rabbits, and one 
 guinea-pig is enough for fifty or sixty students, working together in sets of 
 two, to perform experiments (5) to (8). In order to obtain a serum more 
 strongly haemolytic for rabbit's corpuscles than normal dog's serum, a dog 
 may be ' immunized ' by previous injection of all the washed corpuscles 
 obtainable from a rabbit. The injection should be made under the skin or, 
 better, into the peritoneal cavity — of course, with aseptic precautions. It 
 should be repeated not less than twice, with an interval of ten days between 
 the successive injections, and the dog's blood should be drawn off about ten 
 days after the last injection. 
 
 f To determine the amount of laking at any given moment, drop the small 
 test-tubes into the metallic centrifuge cups after shaking them up, cind centrif- 
 ugalize. A ver>' short time is sufficient to separate a clear supernatant 
 liquid, from the tint of which the extent of the haemolysis can be deduced. 
 Before replacing the tubes in the thermostat, they should, of course, be shaken 
 up. Small test-tubes of about 8 mm. internal diameter and short enough to 
 go conveniently into the centrifuge cups are the most serviceable. 
 
 I For exact work a longer time is recommended. But for the student the 
 time is made as short as possible, and it is only in exceptional cases that ten 
 minutes is not enough. 
 
PRACTICAL EXERCISES 7j 
 
 laking in either G or H, or if there is laking it may be greater in G than 
 in H. The amboceptor has been removed from serum S by the rabbit's 
 corpuscles. Add o-i c.c. of this ' inactivated ' serum to the balance 
 of D, D', and E, E' (left from 6). Laking will occur because the serum S 
 contains complement, and the heated serum added in (6) to these tubes 
 contains amboceptor. Wash the rabbit's corpuscles which have been 
 treated with ox scrum at o° C. with cooled sodium chloride solution. 
 Add to them some of serum S (that from the top of tube H will do if 
 no more is left), and put at 40° C. Laking will occur, showing that the 
 amboceptor was fixed by the rabbit's corj)uscles at 0° C. To a further 
 portion of the washed rabbit's corpuscles which were treated with ox 
 serum at 0° C. add normal rabbit's serum, and put at 40° C. If laking 
 occurs it is because the rabbit's serum contains complement. 
 
 Dog's serum may be used instead of ox serum for experiment (8). 
 
 16. Osmotic Resistance of the Coloured Corpuscles. — Fill a burette 
 with a I per cent, solution of sodium chloride and another with dis- 
 tilled water. Take a series of ten test-tubes and run into the first 
 6 c.c. of the NaCl solution, into the second 5 -8 c.c, into the third 
 5-6 c.c, and so on, always making a difference of 0-2 c.c. between 
 successive test-tubes. From the other burette run in enough distilled 
 water to make up 10 c.c. of solution in each tube — that is, 4 c.c. of dis- 
 tilled water for the first tube, 4-2 c.c. for the second, and so on. Shake 
 up. The tubes now contain a series of solutions of salt differing in 
 strength by 0-02 per cent, in successive tubes, the strongest being o*6 
 per cent., and the weakest 0-42 per cent. Number the tubes i to 10, 
 beginning with the strongest solution. Put into each tube one drop of 
 perfectly fresh blood. Shake moderately so as to mix the blood and 
 salt solution, and allow the tubes to stand for ten to thirty minutes. 
 Observe the colour of the clear liquid above the sediment of corpuscles. 
 Determine in which tube the first tinge of haemoglobin appears. The 
 next higher concentration of the salt solution is that in which all the 
 corpuscles are just able to retain their haemoglobin, and is a measure of 
 the minimum osmotic resistance of the corpuscles, or the resistance 
 of the weakest corpuscles. Repeat with blood which has stood at room 
 temperature for twelve to twenty-four hours. For clinical purposes 
 tubes, each containing 5 c.c of salt solution, may be used. A single 
 drop of blood can then be distributed between the tubes with a fme 
 pipette or a glass rod, beginning with the most concentrated solution, 
 and passing do%vn to the less concentrated. The blood must be dis- 
 tributed rapidly before coagulation occurs. Only such concentrations 
 of the salt solution as are known to correspond to the possible variations 
 of the osmotic resistance for any particular disease or for any particular 
 variety of blood need be employed. 
 
 17. Blood-Pigment — (i) Preparation of Haemoglobin Crystals. — [a) 
 To a little dog's blood in a narrow test-tube add its own volume or 
 twdce its volume of chloroform. Invert the tube ten or twelve times 
 so as to allow the chloroform to act on the blood, but avoid violent 
 shaking. When the tube is now allowed to stand for a few minutes 
 the laked blood all rises to the top. Remove a little of the layer of 
 blood without taking with it any of the chloroform layer, and examine 
 the oxyhaemoglobin crystals with the microscope. They form long 
 rhombic prisms and needles (Fig. 14, p. ^2). 
 
 {b) Add a little crude saponin to dog's blood in a test-tube. Shake 
 up well, and allow it to stand till the colour becomes dark. Then shake 
 vigorously, and a mass of haemoglobin crystals will be formed. 
 
 (c) Put a small drop of guinea-pig's blood on a slide. Mix with a 
 
74 THE ClRCUl.AriNG LIQUIDS OF THE liODY 
 
 drop of Canada balsam and cover. Tetrahedral crystals of oxy- 
 haemoglobin will form after a time. The slide may be kept. 
 
 (2) Spectroscopic Examination of Haemoglobin and its Derivatives. 
 — (a) With a small, direct-vision spectroscojjc look at a bright part of 
 the sky or a white cloud. Focus by pulling out or pushing in the eye- 
 piece until the numerous fine dark lines (Fraunhofcr's lines), running 
 verticallj- across the spectrum, are seen. Narrow the slit by moving 
 the milled edge till the lines are as sharp as they can be made. Note 
 especially the line D in the orange, the lines K and b in the green, 
 and F in the blue. Always hold the spectroscope so that the red is 
 at the left of the field. Now dip an iron or platinum wire with a 
 loop on the end of it into water, and then into some common salt or 
 sodium carbonate, and fasten or hold it in the flame of a fishtail burner. 
 On examining the flame with the spectroscope, a bright yellow line 
 will be seen occupying the position of the dark line D in the solar 
 spectrum. This is a convenient line of reference in the spectrum, and 
 in studying the spectra of haemoglobin and its derivatives, the position 
 of the absorption bands with regard to the D line should always be 
 noted. The dark lines in the solar spectrum are due to the absorption 
 of light of a definite range of wave-lengths by metals in a state of vapour 
 in the ?un's atmosphere, and of course no dark lines arc seen in the 
 spectrum of a gas-flame. Put some defibrinated blood into a test-tube. 
 
 B 
 Fig. 20. — Direct Vision Spectroscope ot Simple Type. A , slot in which a pin on the 
 eyepiece C slides in focussing the spectrum : B, milled head, by the rotation 
 of which the slit is narrowed or widened. 
 
 Fasten it vertically in a clamp in front of the flame and examine it 
 with the spectroscope, holding the latter in one hand with the slit close 
 to the test-tube, and focussing the eyepiece with the other. Or arrange 
 the spectroscope, test-tube and gas-flame on a stand as in Fig. 21. 
 Nothing can be seen till the blood is diluted. Pour a little of the blood 
 into another test-tube, and go on diluting till, on focussing, two bands of 
 oxyhcpmoglobin are seen in the position indicated in Fig. 13, p. 51 . Draw 
 the spectrum; then dilute still more, and observe which of the bands 
 first disappears. Now put 5 c.c. of the blood into another test-tube, 
 and dilute it with four times its volume of water. Take 5 c.c. of this 
 dilution, and again add four times as much water, and so on till the 
 solution is only faintly coloured. Note with what degree of dilution 
 the bands disappear. Then examine each of the solutions with the 
 spectroscope and draw its spectrum. 
 
 (ft) Make a solution of blood which shows the oxyhaemoglobin bands 
 sharply. Add some ammonium sulphide solution to reduce the oxy- 
 haemoglobin. Heat gently to about body temperature. A single, 
 ill-defined band now appears, occupying a position midway between 
 the oxyhaemoglobin bands, and the latter disappear. This is the 
 band 01 reduced hcrmoglobin (Fig. 13). 
 
 (c) Carbonic Oxide Hamoglobin. — Pass coal-gas through blood for 
 
PRACTICAL EXERCISES 
 
 75 
 
 Test' tub 
 
 a considerable time. Examine some of the blood (after dilution) 
 with the spectroscope. Two bands, almost in the position of the 
 oxyhncmoglobin bands, are seen ; but no change is caused by the 
 addition of ammonium sulphide, since carbonic oxide haemoglobin is 
 a more stable compound than oxy haemoglobin. 
 
 (d) Metlurmoglobin. — Put .some blood into a test-tube, add a few 
 drops of a solution of fcrricyanidc of potassiimi, and heat gently. On 
 diluting a well-marked band will be seen in the red. On addition of 
 ammonium sulphide this band disappears; the oxyliaemoglolnn bands 
 are seen for a moment, and then give place to the band of reduced 
 haemoglobin (Fig. 13. p. 51). 
 
 [e) Acid Hcrmatin. — To a little diluted blood add strong acetic acid 
 and heat gently. The colour becomes brownish. Tlie spectrum 
 sliows a band in the red between C and D, not far from the position 
 of the band of methaemoglobin. The addition of a drop or two of 
 ammonium sulphide causes no change in the spectrum, and this is a 
 means of distinguishing acid hasmatin from methaemoglobin. If more 
 ammonium sulphide be added, 
 haematin will be precipitated 
 when the acid solution has been 
 rendered neutral, and a further 
 addition of ammonium sulphide 
 or sodium hydroxide will cause 
 the haematin to be again dis- 
 solved, a solution of alkaline 
 hasmatin being formed. This 
 in its turn may be reduced by 
 an excess of ammonium sul- 
 phide, and the spectrum of 
 haemochromogen may be ob- 
 tained (Fig. 13, p. 51). 
 
 Since the watery solution 
 of acid haematin obtained as 
 above is usually somewhat tur- 
 bid, a solution in acid ether is 
 sometimes employed for spec- 
 troscopic examination. Add to 
 a little undiluted dcfibrinated 
 blood about half its volume of 
 glacial acetic acid, and then not 
 less than an equal volume of 
 ether. ]\Iix well, pour off the ethereal extract and examine it with the 
 spectroscope, diluting, if necessar3^ with ether and glacial acetic acid. 
 It shows a strong band in the red somewhat farther from the D line 
 than the methaemoglobin band. On dilution, three additional fainter 
 bands may be seen. 
 
 (/) Alkaline Htematin. — To diluted blood add strong acetic acid and 
 warm gently for a few minutes. Then, when the spectroscopic ex- 
 amination of a sample shows that acid haematin has been formed, 
 neutralize with sodium hydroxide. A brownish precipitate of haematin 
 is thrown down, which dissolves in an excess of sodium hydroxide, 
 giving a solution of alkaline haematin (or alkali haematin). 
 
 Or add sodium hydroxide to blood directlJ^ and warm for a couple of 
 minutes after the colour has changed decidedly to brownish-black. 
 The spectrum of alkaline haematin is a broad but ill-defined band just 
 overlapping the D line, and situated chiefly to the red side of it (Fig. 13). 
 The solution should be shaken up with air before being examined, as 
 
 Spectroscope 
 Solution 
 
 Fig. 21. — Spectroscopic Examination of 
 Blood -Pigment. 
 
76 THE CIRCULATING LIQUIDS OF THE BODY 
 
 some of the alkali haematin is changed into haemochromogen by re- 
 ducing substances formed by the action of the alkali on the blood. 
 
 {g) Hcemochromogen. — To a solution of alkaline haematin add a drop 
 or two of ammonium sulphide. The band near D disappears, and two 
 bands make their appearance in the green (Fig. 13, p. 31). 
 
 (A) Hamatoporphyyin. — Put some strong sulphuric acid into a test- 
 tube. Add a few drops of blood, agitate the test-tube till the blood 
 di.-solves, and examine the purple liquid, diluting it, if necessary, 
 with sulphuric acid. Its spectrum shows two well-marked bands, one 
 just to the left of D, and the other midway between D and E (Fig. 13). 
 
 (3) Guaiacum Test for Blood. — A test for blood — much used in 
 hospitals, and, indeed, a delicate one, but quite untrustworthy unless 
 certain precautions be taken — is the guaiacum test. A drop of freshly- 
 prepared tincture of guaiacum is added to the liquid to be tested, and 
 then peroxide of hydrogen. If blood be present, the guaiacum strikes 
 a blue or greenish-blue colour. The decomposition of the peroxide 
 by the blood is due mainly to the hnemoglobin of the corpuscles. Any 
 derivative of haemoglobin which still contains the iron will act, and 
 boiling does not abolish this power. On the other hand, oxydases or 
 oxidizing ferments present, not only in the formed elements of blood, 
 but elsewhere, e.g., in fresh vegetable protoplasm, milk, seminal fluid, 
 and pus, will cause the same colour (p. 271), but not if they have been 
 previously boiled.* The test has been considered chiefly of value as 
 a negative test. When the blue colour is not obtained, we have good 
 evidence that blood is absent. But, according to Buckmastcr, if the 
 precaution of first boiling the liquid suspected to contain blood be 
 adopted, it is also a good positive test. It is. however, far inferior to 
 the haemin test (p. 7«) where that can be obtained, and of course in- 
 ferior to the identification of erythrocytes with the microscope, or to 
 the spectroscopic identification of the blood-pigment where the material 
 is suitable for this. 
 
 (4) Quantitative Estimation of Haemoglobin — [a) By Haldane's Modi- 
 fication of Gowers 1 1 crnioglobinomctey . — Place in the graduated tube B 
 (Fig. 22) an amount of water less than will ultimately be required to 
 dilute the blood to the required tint. Puncture the finger or lobe of 
 the ear with one of the small lancets in F, and fill the capillary pipette D 
 to a little beyond the mark 20. Wipe the p)oint of the pipette and dab 
 it on a piece of filter-paper till the blood stands exactly at the mark. 
 Blow the blood into the water in B, and rinse the pipette with the water. 
 Attach the cap of tube G to a gas-burner. Introduce the rubber tube 
 into B nearly to the level of the water, and allow gas to pass for a few 
 seconds. Withdraw the tube while the gas is still passing. Immediately 
 close the end of B with the finger, and move the tube so that the 
 liquid passes from end to end of it at least a dozen times, to saturate 
 the haemoglobin with carbonic oxide. While this is being done, the 
 tube should be held in a cloth, otherwise it will become heated, and 
 liquid will spurt out when the finger is removed. Water is now added 
 
 * The formed elements of blood really contain no less than three ferments 
 of interest in this connection: (i) A catalase which decomposes peroxide of 
 hydrogen into water and molecular oxygen {i.e., oxygen not in the atomic 
 or nascent state). This reaction is given by both blood and pus. (2) An 
 oxydase (also spelled oxidase), which oxidizes guaiacum and similar substances 
 without the presence of hydrogen peroxide. This reaction is obtainable even 
 from aqueous extracts of leucoc3i;es. (3) A peroxydase (also spelled peroxi- 
 dase) which causes the oxidation of these substances only in the presence of 
 hydrogen peroxide, a reaction also given by leucocytes. These ferments are 
 all inactivated Iby boiling (Kastle). 
 
PRACTICAL EXERCISES 
 
 71 
 
 drop by drop with the pipette stopper of the bottle E, which is used 
 for holding the water, the tube being inverted after each addition, 
 till the tint in B is the same as tliat in A. In comparing the tubes, 
 they should be held against the light from the sky or from an opal 
 glass lamp-shade. It is necessary to transpose the tubes repeatedly. 
 The level at which the tints are equal is read off on B half a minute 
 after the addition of the last drop of water. Water is now again added 
 by drops till the tint in B is just roticeably weaker than in A, and the 
 mean of the two readings is taken. The result is the percentage actually 
 present of the average proportion of haemoglobin in the blood of healthy 
 adult males. Healthy women give an average of only 89 per cent., 
 and healthy children an average of only 87 per cent., of the proportion 
 in men. The liquid in A is a i per cent, solution of blood containing 
 the average percentage of haemoglobin found in the blood of healthy 
 
 Fig. 22. — Haldane's Modification of Gowers' HaBmoglobinometer. 
 
 adult males, and having an oxygen capacity of 18 5 per cent. — i.e.. 
 100 c.c. of the blood with which the standard was made would take 
 up in combination from air 18*5 c.c. of oxygen. The solution in A has 
 been saturated with carbonic oxide. 
 
 This method is probably more accurate than any other used in clinical 
 work, the error, in the hands of an experienced observer, not exceeding 
 I per cent. 
 
 [b) By Fleischl's HcBtnometer (Fig. 23). — Fill with distilled water that 
 compartment a' of the small cylinder (above tlie stage) which is over 
 the tinted wedge. Put a little distilled water into the other compart- 
 ment a. Now prick the finger and fill one of the small capillary tubes 
 with blood. See that none of the blood is smeared on the outside of 
 the tube. Then wash all the blood into the water in compartment a, 
 gild fill it to the brim with distilled water. By means of the milled 
 
78 
 
 THE CIRCULATING LIQUIDS OF THE BODY 
 
 head T move the tinted wedge K till the depth of colour is the same 
 
 in the two compartments. The percentage of the normal quantity 
 of haemoglobin is given by the graduated scale P. For example, if the 
 reading is 90, the blood contains 90 per cent, of the normal amount; 
 if 100, it contains the normal quantity. The ob.servations should be 
 made in a dark room, the white surface S, arranged below the compart- 
 ments a and a', being illuminated by a lamp. Or the instrument may 
 be placed in a small box, lighted by a candle. It is best that each result 
 should be the mean of two readings, one just too large and the other 
 just too small. In any case the instrument does not give readings 
 accurate to less than 5 per cent. 
 
 (c) Hoppe-Seyley's Method. — Two parallel-sided glass troughs are 
 used. In one is put a standard solution of oxy haemoglobin of known 
 strength, in the other a measured quantity of the blood to be 
 
 tested. The latter is diluted 
 with water until its tint 
 appears the same as that 
 of the standard solution, 
 when the troughs are placed 
 
 Fig. 23. — Fleisclil's Haemometer. 
 
 Crystals of Haemin 
 (Frey). 
 
 side by side on white paper. 
 From the quantity of water 
 added it is easy to calculate 
 the proportion of haemo- 
 globin in the undiluted 
 blood. Greater accuracy is obtained if the haemoglobin in the standard 
 solution and that of tlic blood are converted into carbonic oxide haemo- 
 globin by passing a stream of coal-gas through them. 
 
 {d) 1 allquisi's Method. — In this method the tint produced by a 
 drop of blood on a piece of white filter-paper is compared with a scale 
 representing 10 percentages of haemoglobin (from 10 to 100 per cent.). 
 The standard filter-paper is supplied in the form of a book with the 
 scale. To make an estimation, all that is necessary is to toucli a drop 
 of blood with a piece of the filter-paper, and allow the blood to diffuse 
 slowly through the paper, so as to give an even stain. The position 
 of the stain is then determined by the scale; e.g.. it may be deeper 
 than 90. but fainter than 100, in which case the percentage of haemo- 
 globin hes between 90 and 100. The method is by no means a very 
 accuratconc, but more accurate than it appears at first sight. 
 
 (5) Microscopic Test for Blood-Pigment. — Put a drop of blood on a 
 slide. Allow the blood to dry, or heat ii- gently over a flame, so as to 
 evaporate the water. Add a drop of glacial acetic acid ; put on a cover- 
 
PRACTICAL EXERCISES jg 
 
 glass, and again heat slowly till the liquid just begins to boil. Take 
 the slide away from the flame for a few seconds, then heat it again for 
 a moment ; and repeat this process two or three times. Now let the 
 slide cool, and examine with the microscope (high power). The small 
 black, or brownish-black, crystals of hcemin will be seen (Fig. 24, p. 78). 
 This is an important test where only a minute trace of blood is to be 
 examined, as in some medico-legal cases. If a blood-stain is old, a 
 minute crystal of sodium chloride should be added along with the 
 glacial acetic acid. Fresh blood contains enough sodium chloride. 
 
 A blood-stain on a piece of cloth may first of all be soaked in a small 
 quantity of distilled water, and the liquid examined with the spectro- 
 scope or the micro-spectroscope (a microscope in which a small spectro- 
 scope is substituted for the eyepiece). Then evaporate the liquid to 
 dryness on a water-bath, and apply the haemin test. Or perform the 
 haemin test directly on the piece of cloth. In a fresh stain the blood- 
 corpuscles might be recognized under the microscope. Very few 
 liquids, however, are available for washing out the blood, as all ordinary 
 solutions, and even serum itself, cause laking of dried corpuscles 
 (Guthrie). Absolute alcohol, or 35 per cent, potassium hydroxide, 
 may be used to soak and rub up the cloth in. 
 
CHAPTER III 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 The blood can only fulfil its functions by continual movement. 
 This movement implies a constant transformation of energy'; and in 
 the animal body the transformation of energy into mechanical work 
 is almost entirely allotted to a special form of tissue, muscle. In 
 most animals there exist one or more rhythmically contractile 
 muscular organs, or hearts, upon which the chief share of the work 
 of keeping up the circulation falls. 
 
 Section I. — Preliminary Anatomical and Physical Dat.\. 
 
 Comparative. — In Echinus a contractile tube connects the two vascu- 
 lar rings that surround the beginning and end of the alimentary canal , 
 and plays the part of a heart. In the lower Crustacea and in insects 
 the heart is simply the contractile and generally sacculated dorsal 
 bloodvessel; in the higher Crustacea, such as the lobster, it is a well- 
 defined muscular sac situated dorsally. A closed vascular system is 
 the exception among invertebrates. In most of them the blood 
 passes from the arteries into irregular spaces or lacunae in the tissues, 
 and thence finds its way back to the heart. In the primitive vertebrate 
 heart five parts can be distinguished as we proceed from the venous 
 to the arterial end: (i) The sinus venosus, into which the great veins 
 open ; (2) the auricular canal, from the dorsal wall of which is developed 
 — (3) the auricle; (4) the ventricle; (5) the bulbus arteriosus, from which 
 the chief artery starts (Fig. 25, p. 81). Amphioxus, the lowest verte- 
 brate, has a primitive lacunar vascular system; a contractile dorsal 
 bloodvessel serves as ai'tcrial or systemic heart, a contractile ventral 
 vessel as venous or respiratory heart. From the latter, vessels go to 
 the gills. Fishes possess only a respiratory heart, consisting of a venous 
 sinus, auricle, ventricle, and bulbus arteriosus. This drives the blood 
 to the gills, from which it is gathered into the aorta; it has thence to 
 find its way without further propulsion through the systemic vessels. 
 Amphibians have a venous sinus, two auricles, a single 'C"?tricle, and 
 an arterial bulb; reptiles, two auricles and two incompletely-separated 
 ventricles. In birds and mammals the respiratory and systemic 
 hearts are completely separated. The former, consisting of the right 
 auricle and ventricle, propels the blood through the lungs; the latter, 
 consisting of the left auricle and ventricle, receives it from the pul- 
 monary veins, and sends it through the systemic vessels. 
 
 The sinus venosus seems to be represented in the mammalian heart 
 by certain small portions of tissue, especially the so-called sino-auricular 
 node, a little knot of primitive fibres near the mouth of the superior 
 
 80 
 
AN.-iTOMlCAL AND PHYSICAL DATA 
 
 vena cava. The auricular canal is probably represented by the 
 auriculo-vcntricular bundle (conveniently designated as the a. -v. bundle), 
 which will again be referred to in relation to the conduction of the heart- 
 beat from auricles to ventricles (p. 147). This bundle starts from a 
 clump of primitive tissue, the auriculo-ventricular node (a. -v. node) 
 at the base of the interauricular septum on the right side, below and 
 to the right of the coronarj' sinus, and runs down the interventricular 
 septum. The sino-auricular and tlie auriculo-\-entricular nodes are 
 connected by fibres which run in tiie interauricular septum, so that it 
 may be considered that the primitive cardiac tube is still represented 
 from base to apex of the adult 
 mammalian heart, although onlj- 
 by very slender threads of tissue, 
 amidst the massive secondary 
 developments of auricular and 
 ventricular muscle (Keith and 
 Flack) . 
 
 General View of the Circulation 
 in Man. — The whole circuit of the 
 blood is divided into two portions, 
 very distinct from each other, 
 both anatomically and function- 
 ally — the respiratory or lesser 
 circulation, and the systemic or 
 greater circulation. Starting from 
 the left ventricle, the blood passes 
 along the systemic A-essels — ar- 
 teries, capillaries, veins — and, on 
 returning to the heart, is poured 
 into the right auricle, and thence 
 into the right ventricle. From 
 the latter it is driven through the 
 pulmonary artery to the lungs, 
 passes through the capillaries of 
 these organs, and returns through 
 the pulmonar}' veins to the left 
 
 ■ K J J. • 1 Tu „ _4-„i Fiff. 2%. — Diagram of Primitive Vertebrate 
 
 auricle and ventricle. The portal ^ '°; •'; t- • „ c of, ,,-„.. 4^„^a :,, +1,^ 
 
 ^ - Heart, combmmg Features tound in the 
 
 Eel, Dogfish, and Frog (Flack, after 
 
 Keith), a. Sinus venosus; b, auricular 
 
 canal; c, auricle; <i, ventricle ; e, bulbus 
 cordis; /, aorta; i-i, sino-auricular junc- 
 tion and venous valves; 2-2, junction of 
 canal and auricle; 3-3, annular part of 
 auricle; 5, bulbo-ventricular junction. 
 
 system, which gathers up the 
 blood from the intestines, forms 
 a kind of loop on the sj-stemic 
 circulation. The lymph-current 
 is also in a sense a slow and stag- 
 nant side-stream of the blood- 
 circulation; for substances are 
 constantly passing from the 
 
 bloodvessels into the lymph-spaces, and returning, although after a com- 
 paratively long interval, into the blood by the great lymphatic trunks. 
 Physiological Anatomy of the Vascular System. — The heart is to be 
 looked upon as a portion of a bloodvessel which has been modified to 
 act as a pump for driving the blood in a definite direction. IMorpho- 
 logically it is a bloodvessel; and the physiological property of auto- 
 matic rhythmical contraction which belongs to the heart in so eminent 
 a degree is, as has been mentioned (p. 80), an endowment of blood- 
 vessels in many animals that possess no localized heart. Even in 
 some mammals contractile bloodvessels occur; the veins of the bat's 
 wing, for example, beat with a regular rhythm, and perform the func- 
 tion of accessorv hearts. 
 
82 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 The whole vascular system is lined with a single layer of endothelial 
 cells. In the capillaries nothing else is present; the endothelial layer 
 forms the whole tliickness of the wall. In young animals, at any rate, 
 the endothelial cells of the capillaries are capable of contracting when 
 stimulated ; and changes in the calibre of these vessels can be brought 
 about in this way. The walls of the arteries and veins are chiefly 
 made up of two kinds of tissue, which render them distensible and 
 elastic : non-striped muscular fibres and j'cUow clastic fibres. The 
 muscular fibres are mainly arranged as a circular middle coat, which, 
 especially in the smaller arteries, is relatively thick. One conspicuous 
 layer of elastic fibres marks the boundary between the middle and 
 inner coats. In the larger arteries elastic laminae are also scattered 
 freely among the muscular fibres of the middle coat. The outer coat 
 is composed chiefly of ordinary' connective tissue. The veins differ 
 from the arteries in having thinner walls, with the layers less distinctly 
 marked, and containing a smaller proportion of non-striped muscle 
 and elastic tissue ; although in some veins, those of the pregnant uterus, 
 for instance, and the cardiac ends of the large thoracic veins, there is 
 a greater development of muscular tissue. Further, and this is of prime 
 physiological importance, valves are present in many veins. These 
 are semilunar folds of the internal coat projecting into the lumen in 
 such a direction as to favour the flow of blood towards the heart, 
 but to check its return. In some veins, as the venae cavae, the pulmonary 
 veins, the veins of most internal organs, and of bone, there are no valves ; 
 in the portal system they are rudimentary in man and the great majority 
 of mammals. The valves are especially well marked in the lower limbs, 
 where the venous circulation is uphill. When a valve ceases to perform 
 its function of supporting the column of blood between it and the 
 valve next above, the foundation of varicose veins is laid; the valve 
 immediately below the incompetent one, having to bear up too great 
 a weight of blood, tends to yield in its turn, and so the condition spreads. 
 The smallest veins, or venules, are ver\- like the smallest arteries, or 
 arterioles, but somewhat wider and less muscular. The transition 
 from the capillaries to the arterioles and venules is not abrupt, but 
 may be considered as marked bj^ the appearance of the non-striped 
 muscular fibres, at first scattered singly, but gradually becoming closer 
 and more numerous as we pass away from the capillaries, until at length 
 they form a complete layer. 
 
 In the heart the muscular element is greatly developed and differ- 
 entiated. Both histologically and physiologically the fibres seem to 
 stand between the striated skeletal muscle and the smooth muscle. In 
 the mammal the cardiac muscular fibres are generally described as 
 made up of short oblong cells, devoid of a sarcolcmma, often branched, 
 and arranged in anastomosing rows, each cell ha\ing a single nucleus 
 in the middle of it. But it has recently been shown that the muscle 
 fibrils run right through the apparent cell boundaries, and form a con- 
 tinuous sheet of tissue anastomosing in everj' direction. The fibres 
 are transversely striated, but the striae are not so distinct as in skeletal 
 muscle. A sarcolemma is not absent, although it is more delicate 
 than in skeletal muscle, and perhaps of a different nature. Many 
 fibres pass from one auricle to the other, and from one ventricle to the 
 other. 
 
 In the frog's heart the muscular fibres are spindle-shaped, like those 
 of smooth muscle, but transversely striated, like those of skeletal 
 muscle. From the sinus to the apex of the ventricle there is a con- 
 tinuous sheet of muscular tissue. 
 
ANATOMICAL AND PHYSICAL DATA 83 
 
 The problems of the circulation are partly physical, partly vital. 
 Some of the phenomena observed in the blood-stream of a living 
 animal can be reproduced on an artificial model ; and they may justly 
 be called the physical or mechanical phenomena of the circulation. 
 Others are essentially bound up with the properties of living tissues ; 
 and these may be classified as the vital or physiological phenomena of 
 the circulation. The distinction, although by no means sharp and 
 absolute, is a convenient one — at least, for purposes of description; 
 and as such we shall use it. But it must not be forgotten that the 
 physiological factors play into the sphere of the physical, and the 
 physical factors modify the physiological. Considered in its 
 physical relations, the circulation of the blood is the flow of a liquid 
 along a system of elastic tubes, the bloodvessels, under the influence 
 of an intermittent pressure produced by the action of a central 
 pump, the heart. But the branch of d}Tiamics which treats of the 
 movement of liquids, or hydrodynamics, is one of the most difficult 
 parts of physics, and even in the physical portion of our subject we 
 are forced to rely chiefly on empirical methods. It would, therefore, 
 not be profitable to enter here into mathematical theory, but it may 
 be well to recall to the mind of the reader one or two of the simplest 
 data connected with the flow of liquids through tubes: 
 
 Torricelli's Theorem. — Suppose a vessel filled with water, the level 
 of which is kept constant; the velocity with which the water will 
 escape from a hole in the side of the vessel at a vertical depth h below 
 the surface will be t;= \/2gh, where g is the acceleration produced by 
 gravity.* In other words, the velocity is that which the water would 
 have acquired in falling in vacuo through the distance h. This formula 
 was deduced experimentally by Torricelli, and holds only when the 
 resistance to the outflow is so small as to be negligible. The reason of 
 this restriction will be easily seen, if we consider that when a mass 
 tn of water has flowed out of the opening, and an equal mass m has 
 flowed in at the top to maintain the old level, everything is the same 
 as before, except that energy of position equal to that possessed by 
 a mass m at a height h has disappeared. If this has all been changed 
 into kinetic energy E, in the form of_visible motion of the escaping 
 water, then 'E = imv^=mgh, i.e., v= sj'^gh. If, however, there has been 
 any sensible resistance to the outflow, any sensible friction, some of 
 the potential energy- (energ\- of position) will have been spent in over- 
 coming this, and will have ultimately been transformed into the kinetic 
 energy of molecular motion, or heat. 
 
 Flow of a Liquid through Tubes. — Next let a horizontal tube of imi- 
 form cross-section be fitted on to the orifice. The velocity of outflow 
 will be diminished, for resistances now come into play. When the 
 liquid flowing through a tube wets it, the layer next the wall of the 
 tube is prevented by adhesion from moving on. The particles next 
 this stationary layer rub on it, so to speak, and are retarded, although 
 not stopped altogether. The next layer rubs on the comparatively 
 slowl)- moving particles outside it, and is also delayed, although not 
 so much as thiat in contact with the immovable layer on the walls of 
 
 * I.e., the amount added per second to the velocity of a falling body 
 (^ = 32 feet). 
 
THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 the tube. In this way it comes about that every particle of the liquid 
 is hindered by its friction against others — those in the axis of the tube 
 least, those near the peripliery most — and part of the energy of position 
 of the water in the reservoir is used up i.i overcoming this resistance, 
 only the remainder being transformed into the visible kinetic energy 
 of the liquid escaping from the open end of the tube. 
 
 If vertical tubes be inserted at different points of the horizontal 
 tube, it will be found that the water stands at continually decreasing 
 heights as we pass away from the reservoir towards the open end of 
 the tube. The height of the liquid in any of the vertical tubes indicates 
 the lateral pressure at the point at which it is inserted; in other words, 
 the excess of potential energy, or energy of position, which at that 
 point the liquid possesses as compared with the water at the free end, 
 wlicre the pressure is zero. If the centre of the cross-section of the 
 free end of the tube be joined to the centres of all the menisci, it will 
 be found that the line is a straight line. The lateral pressure at any 
 point of the tube is therefore proportional to its distance from the free 
 end. Since the same quantity of water must pass through each cross- 
 section of the horizontal tube in a given time as flows out at the open 
 end, the kinetic energy of the liquid at every cross-section must be 
 
 constant and equal to ^mv^, 
 where v is the mean velocity 
 (the quantity which escapes in 
 umt of dme divided by the 
 cross-section) of the water at 
 the free end. 
 
 Just inside the orifice the 
 total energy of a mass m of 
 water is mgh; just beyond it 
 at the first vertical tube, mgh' 
 + lniv'^, where h' is the lateral 
 pressure. On the assumption 
 that between the inside of the 
 orifice and the first tube no 
 energy has been transformed 
 into heat (an assumption 
 the more nearly correct tlie 
 smaller the distance between 
 it and the inside of the orifice is made), we liave mgh = mgh' + \mv'^. 
 i.e., Imv- -^ mg{h - h') . In other words, the portion of the energy of 
 position of the water in the reservoir which is transformed into the 
 kinetic cncrg\'^ of the water flowing along the horizontal tube is measured 
 by the difference between the height of the level of the reservoir and 
 the lateral pressure at the beginning of the horizontal tube — that is, 
 the height at which the straight line joining the menisci of the vertical 
 tubes intersects the column of water in the reservoir. Let H represent 
 the height corresponding to that part of the energy of position which 
 is transformed into the kinetic energy of the flowing water. H is easily 
 calculated when the mean velocity of efflux is known. For v= ^2gH 
 by TorriccUi's theorem (since none of the energy corresponding to H 
 
 IS supposed to be used up in overcoming friction), or H= . At the 
 
 second tube the lateral pressure is only h". The sum of the visible 
 kinetic and potential energy here is therefore hnv- + mgh" . A quantity 
 of energy mg{h' — h") must have been transformed into heat owing to 
 the resistance caused by fluid friction in the portion of the horizontal 
 
 (^^E 
 
 I 
 
 
 
 ' 
 
 ^^m 
 
 \ ^^ 
 
 C^ 
 
 
 
 ^^^A^: 
 
 ^ 
 
 \ ^ 
 
 ? h" ^^""^ 
 
 ^ 
 
 ^~^^~"'^"^ "- 
 
 :- 
 
 ==s= 
 
 ^ ~"- 
 
 h"" 
 
 Fig. 26. — Diagram to illustrate Flow of 
 Water along a Horizontal Tube connected 
 with a Reservoir. 
 
ANATOMICAL AND PHYSICAL DATA 85 
 
 tube between the first two vertical tubes. In general the energy of 
 position represented by the lateral pressure at any point is equal to 
 the energy used up in overcoming the resistance of the portion of the 
 path beyond tliis point. 
 
 Velocity of Outflow. — It has been found by experiment that v, the 
 mean velocity of outflow, when the tube is not of very small calibre, 
 varies directly as the diameter, and therefore the volume of outflow 
 as the cube of the diameter. In fine capillary tubes the mean velocity 
 is proportional to the square, and the volume of outflow to the fourth 
 power of the diameter (Poiscuille). If, for example, the linear velocity 
 of the blood in a capillary of 10 /x in diameter is \ mm. per sec, it will 
 be four times as great (or 2 mm. per sec.) in a capillary of 20 /x diameter, 
 and one-fourth as great (or ^ mm. per sec.) in a capillary of 5 /i diameter, 
 the pressure being supposed equal in all. The volume of outflow per 
 second is obtained by multiplying the cross-section by the linear 
 velocity. The cross-section of a circular capillary, 10 /n in diameter, 
 is TT (5XTjfjjj)2 -=, say, j^o^ sq. mm. The outflow will be i^UqX^ 
 = ogJuo cub. mm. per sec. The outflow from the capillary of .>o n 
 diameter would be sixteen times as much, from the 5 fj. capillary only 
 one-sixteenth as much. Some idea of the extremely minute scale 
 on which the blood-flow through a single capillary takes place may 
 be obtained if we consider that for the capillary of 10 ^ diameter a 
 flow of 05^00 cub. mm. per sec. would scarcely amount to i cub. mm 
 in six hours, or to i c.c. in 250 days. 
 
 When the initial energy is obtained in any other way than by means 
 of a ' head ' of water in a reservoir — say, by the descent of a piston 
 which keeps up a constant pressure in a cylinder filled with liquid — 
 the results are exactly the same. Even when the horizontal tube is 
 distensible and elastic, there is no difference when once the tube has 
 taken up its position of equilibrium for any given pressure, and that 
 pressure does not vary^ 
 
 Flow with Intermittent Pressure. — When this acts on a rigid tube, 
 everything is the same as before. When the pressure alters, the 
 flow at once comes to correspond with the new pressure. Water 
 thrown by a force-pump into a system of rigid tubes escapes at every 
 stroke of the pump in exactly the quantity in which it enters, for 
 water is practically incompressible, and the total quantity present 
 at one time in the system cannot be sensibly altered. In the intervals 
 between the strokes the flow ceases; in other words, it is intermittent. 
 It is very different with a system of distensible and elastic tubes. 
 During each stroke the tubes expand, and make room for a portion 
 of the extra liquid thrown into them, so that a smaller quantity flows 
 out than passes in. In the intervals between the strokes the distended 
 tubes, in virtue of their elasticity, tend to regain their original calibre. 
 Pressure is thus exerted upon the liquid, and it continues to be forced 
 out, so that when the strokes of the pump succeed each other with 
 sufficient rapidity, the outflow becomes continuous. This is the state 
 of affairs in the vascular system. The intermittent action of the 
 heart is toned down in the elastic vessels to a continuous steady flow. 
 
 Section II. — The Beat of the Heart in its Physical or 
 Mechanical Relations. 
 
 Events in the Cardiac Cycle. — In the frog's heart the contraction 
 can be seen to begin about the mouths of the great veins which open 
 into the sinus venosus. Thence it spreads in succession over the 
 
86 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 sinus and auricles, hesitates for a moment at the auriculo-ventric- 
 ular junction, and then with a certain suddenness invades the 
 ventricle. In the mammalian heart the contraction likewise com- 
 mences, so far as can be ascertained by inspection or the study of 
 tracings, in the region near the mouths of the veins opening into the 
 auricles. It will be seen, when the question of the origin of the 
 rhythmical beat is being discussed (p. 141), that the actual starting- 
 point is probably the sinus tissue of the right auricle (p. 142) near the 
 opening of the superior vena cava, which is richly provided with 
 muscular fibres ak n to those of the heart. But the wave advances 
 so rapidly that it is difficult to trace in its course a regular progress 
 from base to apex, although the ventricular beat undoubtedly 
 follows that of the auricle, and in a heart beating normally the 
 electrical change associated with contraction of the ventricle 
 begins at the base, then reaches the apex (p. 853), and finally passes 
 towards the orifices of the great arteries. 
 
 The most conspicuous events in the beat of the heart, in their 
 normal sequence, are: (i) the auricular contraction or systole, (2) the 
 ventricular contraction or systole, each followed by relaxation, (3) the 
 pause. The auricles, into which, and beyond which into the ven- 
 tricles, blood has been flowing during the pause from the great 
 thoracic veins, contract sharply, the right, perhaps, a little before 
 the left. The contraction begins in the muscular tissue that 
 surrounds the orifices of the veins, so that these, destitute of valves 
 as they are, are functionally, at least, if not anatomically, sealed up 
 for an instant, and regurgitation of blood into them is to a great 
 extent, if not entirely, prevented. Apparently, complete closure 
 of the inferior cava is unnecessary, the pressure of the blood in it 
 being sufficiently high to hinder any important back-flow. The 
 action of the circular fibres of the veins in closing their orifices is 
 reinforced by the contraction of a band of muscle (the tcBuia ter- 
 minalis) in the roof of the right auricle. This band compresses 
 especially the mouth of the superior vena cava. The filling of the 
 ventricles is thus completed. The actual amount of extra blood 
 injected into the ventricles by the auricular contraction is not large. 
 The ventricles are already nearly charged, but the auricles, so to 
 speak, ram the charge home. The ventricular contraction follows 
 hard on the relaxation of the auricles. The mitral and tricuspid 
 valves, whose strong but delicate curtains have during the diastole 
 been hanging down into the ventricles and swinging freely in the 
 entering current of blood, are floated up as the intraventricular 
 pressure begins to rise, so that, in the first moment of the sudden 
 and powerful ventricular systole, the free edges of their segments 
 come together, and the auriculo-ventricular orifices are completely 
 closed (Fig. 98, p. 206). In the measure in which the pressure in the 
 contracting ventricles increases, the contact of the valvular seg- 
 
MECHANICS OF THE HEART-BEAT 87 
 
 monts becomes closer and more extensive; and their tendency to 
 belly into the auricles is opposed by the pull of the chorda.* tendinea;, 
 whose slender cords, inserted into the valves from border to base, are 
 kept taut, in spite of the shortening of the ventricles by the con- 
 traction of the papillary muscles. The arrangement and connec- 
 tions of the muscular fibres of the heart are such that during the 
 auricukir systole the auriculo-ventricular groove moves towards the 
 base of the heart, while during the systole of the ventricles it moves 
 towards the apex, which constitutes a relatively fixed point on 
 account of the mutual action of the numerous fibres which converge 
 here and constitute the ' whorl.' The hnc joining the apex and 
 the origin of the aorta does not shorten when the ventricles contract, 
 but all parts of the heart are drawn towards this line. The apex is, 
 therefore, pushed forwards, while the rest of the ventricular surface 
 is being drawn inwards. During the systole, the ventricles change 
 their shape in such a way that their combined cross-section — which 
 in the relaxed state is a rough ellipse with the major axis from right 
 to left — becomes approximately circular, and they then form a right 
 circular cone. As soon as the pressure of the blood within the con- 
 tracting ventricles exceeds that in the aorta and pulmonary artery 
 respectively, the semilunar valves, which at the beginning of the 
 ventricular systole are closed, yield to the pressure, and blood is 
 driven from the ventricles into these arteries. 
 
 The ventricles are more or less completely emptied during the 
 contraction, which seems still to be maintained for a short time after 
 the blood has ceased to pass out. The contraction is followed 
 by sudden relaxation. The intraventricular pressure falls. The 
 lunules of the semilunar valves slap together under the weight of the 
 blood as it attempts to regurgitate, the corpora Arantii seal up the 
 central chink, and the aorta and pulmonary artery are thus cut off 
 from the heart. Then follows an interval during W'hich the w^hole 
 heart is at rest, namely, the interval between the end of the relaxa- 
 tion of the ventricles and the beginning of the systole of the auricles. 
 This constitutes the pause. The whole series of events is called a 
 cardiac cycle or revolution (see Practical Exercises, p. 201). 
 
 It will be easily understood that the time occupied by any one of 
 the events of the cardiac cycle is not constant, for the rate of the 
 heart is variable. If we take about 70 beats a minute as the average 
 normal rate in a man, the ventricular systole will occupy about 
 0*3 second; the diastole,* including the ventricular relaxation, about 
 
 • The term ' diastole ' is variously used, as meaning the pause, the pause 
 plus the period during which relaxation is occurring, or the period of re- 
 laxation alone. We shall employ it in the second sense. Henderson refers 
 to the period during which the ventricular muscle is at rest, from the end of 
 its relaxation to the onset of the auricular systole, as the 'diastasis' and the 
 period during which the relaxation is taking place as the 'diastole,' a termin- 
 ology which seems worthy of general adoption. 
 
88 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 0-5 second. The systole of the auricle is one-third as long as that of 
 the ventricle. 
 
 This rhythmical beat of the heart is the ground phenomenon of 
 the circulation. It reveals itself by certain tokens — sounds, surface- 
 movements or pulsations, alterations of the pressure and velocity of 
 the blood, changes of volume in parts — all periodic phenom^a, 
 continually recurring with the same period as the heart -beat, and all 
 fundamentally connected together. And if we hold fast the idea 
 that when we take a pulse-tracing, or a blood-pressure curve, or a 
 plethysmographic record, we are really investigating the same fact 
 from different sides, we shall be able, by following the cardiac rhythm 
 and its consequences as far as we can trace them, to hang upon a 
 single thread many of the most important of the phj^sical phenom- 
 ena of the circulation. 
 
 The Sounds of the Heart. — When the ear is applied to the chest, or 
 to a stethoscope placed over the cardiac region, two sounds are 
 heard with every beat of the heart. They follow each other closely, 
 and are succeeded by a period of silence. The dull booming ' first 
 sound ' is heard loudest in a region which we shall afterwards have 
 to speak of as that of the ' cardiac impulse ' (p. 90) ; the short, sharp, 
 ' second sound ' over the junction of the second right costal cartilage 
 with the sternum. 
 
 The heart-sounds can be registered by placing over the chest a 
 microphone receiver connected with a string galvanometer. The 
 magnified sounds are translated into electrical changes which cause 
 movements of the fibre of the galvanometer, and the movements are 
 photographed on a travelling plate (Eitithoven) . The record is called 
 a cardiophonogram. When this is studied, a third sound can be 
 detected, and it is probable that it is present in all persons, although it 
 is as a rule inaudible to auscultation. It occurs early in diastole very 
 shortly after the second sound. In those persons in whom it is audible 
 it is most distinct over the region of cardiac impulse. It is described 
 as softer and of lower pitch than the second sound (Thayer). 
 
 There has been much discussion as to the cause of the first sound. 
 That a sound corresponding with it in time is heard in an excised 
 bloodless heart when it contracts is certain ; and therefore the first 
 sound cannot be exclusively due, as some have asserted, to vibra- 
 tions of the auriculo-ventricular valves when they are suddenly 
 rendered tense by the contraction of the ventricles, for in a bloodless 
 heart the valves are not stretched. Part of the sound must accord- 
 ingly be associated with the muscular contraction as such. 
 
 Again, the fact that the first sound is heard during the whole, or 
 nearly the whole, of the ventricular systole is against the idea that 
 it is exclusivelv due to the vibrations of membranes like the valves, 
 which would speedily be damped by the blood and rendered in- 
 audible. But while there is good reason to believe that the vibra- 
 tion of the suddenly-contracted ventricles is the fundamental factor, 
 the shock sets up vibrations also in the blood, the chest-wall, and 
 
MECHANICS OF THE HEARl'-HEAT 8y 
 
 perhaps the resonant tissue of the lungs. Further, as we shall see 
 later on (p. 760), the sound caused by a contracting muscle readily 
 calls forth sympathetic resonance in the ear, and the peculiar boom- 
 ing character of the hrst sound may be due to the superpositi(jn of 
 these VcU"ious resonance tones upon the muscular note. But, in 
 addition, the vibration of the auriculo-ventricular valves un- 
 doubtedly contributes to the production of the sound, and some 
 observers have been able to distinguish in the first sound the valvular 
 and the muscular elements, the fomier being higher in pitch than the 
 latter, but a minor third below the second sound. In the excised 
 empty heart the deeper tone of the first sound is alone heard, while 
 the higher note is elicited when in a dead heart the auriculo-ventric- 
 ular valves are suddenly put under tension (Haycraft). When the 
 mitral valve is prevented from closing by experimental division of 
 the chordae tendineae, or by pathological lesions, the first sound of 
 the heart is altered or replaced by a ' murmur.' This evidence is 
 not only important as regards the physiological question, but of 
 great practical interest from its bearing on the diagnosis of cardiac 
 disease. It may be added that the point of the chest-wall at which 
 the first sound is most easily recognized is also the point at which a 
 changed sound or murmur connected with disease of the mitral valve 
 is most distinctly heard. The sound is, therefore, best conducted 
 from the mitral valve along the heart to the point at which it comes 
 in contact with the wall of the chest. Changes in the first sound con- 
 nected with disease of the tricuspid valve are heard best, in the com- 
 paratively rare cases where they can be distinctly recognized, in the 
 third to the fifth interspace, a Httle to the right of the sternum. 
 
 The second sound is caused by the vibrations of the semilunar 
 valves when suddenly closed, ' the recoiUng blood forcing them back, 
 as one unfurls an umbrella, and with an audible check as they 
 tighten ' (Watson). The sharpness of its note is lost, and nothing 
 but a rushing noise or bruit can be heard, when the valves are hooked 
 back and prevented from closing. It is altered, or replaced by a 
 murmur, when the valves are diseased. As there is a mitral and a 
 tricuspid factor in the first sound, so there is an aortic and a pul- 
 monary factor in the second. The place where the second sound is 
 best heard (over the junction of the second right costal cartilage and 
 sternum) is that at which any change produced by disease of the 
 aortic valves is most easily recognized. The sound is conducted up 
 from the valves along the aorta, which comes nearest to the surface 
 at this point. Changes connected with disease of the pulmonary 
 valves are most readily detected over the second left intercostal 
 space near the edge of the sternum, for here the pulmonary artery 
 most nearly approaches the chest-wall. The first sound is ' systolic ' 
 — that is, it occurs during the ventricular systole; the second is 
 ' diastolic,' beginning at the commencement of the diastole 
 
90 
 
 THE CIRCULATION OF THE BLOOD A\D LYMPH 
 
 Various explanations of the third sound have been given, but, as 
 the authors who have studied it are not even agreed as to whether it 
 is produced at the auriculo-ventricular orifices or at the aortic and 
 puhnonary orifices, it would not be useful to discuss them at present. 
 The Cardiac Impulse. — A surface-movement is seen, or an impulse 
 felt, at every cardiac contraction in various situations where the 
 heart or arteries approach the surface. The pulsation, or impulse, 
 of the heart, often stj'led the apex-beat, is usually most distinct to 
 sight and touch in a small area lying in the fifth left intercostal 
 space, between the mammary and the parasternal line,* and gener- 
 .alh', in an adult, about an inch and a half to the sternal side of the 
 former. It is due to the systolic hardening of the ventricles, which 
 are here in contact with the chest-wall, the contact being at the 
 same time rendered closer by their change of shape, and by a slight 
 
 movement of rotation of 
 the heart from left to right 
 during the contraction 
 (Practical Exercises, 
 p. 207). When the left 
 ventricle is in contact with 
 the chest at the position of 
 the apex-beat, as is usually 
 the case, an important 
 element in the impulse is 
 the actual forward thrust 
 of the apex. WTien the 
 apex-beat corresponds in 
 position wnih the right 
 ventricle, there is no 
 actual forward movement, 
 although the hardening of 
 the ventricle may be felt as a tlirust by the finger. Even in health 
 the position of the impulse varies somewhat with the position of 
 the body and the respirator^' movements. In children it is usually 
 situated in the fourth intercostal space. In disease its displacement 
 is an important diagnostic sign, and may be very marked, especially 
 in cases of effusion of fluid into the pleural cavity. It is sometimes, 
 though not invariably, a little lower in the standing than in the 
 sitting position, and shifts an inch or two to the left or right when 
 the person hes on the corresponding side. 
 
 Various instruments, called cardiographs, have been devised for 
 magnifying and recording the movements produced by the cardiac 
 impulse. Marey's cardiograph (Fig. 27) consists essentially of a small 
 
 * The mammary line is an imaginary vertical line supposed to be drawn 
 on the chest through the middle point of the clavicle. It usually, but not 
 necessarily, parses through the nipple. The parasternal line is the vertical 
 line lying midway between the mammary line and the corresponding border 
 of the sternum. 
 
 27. — Diagram of Marey's Cardiograph. 
 
MECHANICS OF THE HEART- BEAT 
 
 91 
 
 chamber, or tambour, filled with air, and closed at one end by a flexible 
 membrane carrying a button, which can be adjusted to the wall of the 
 chest. This receiving tambour is connected by a tube with a recording 
 tambour, the flexible plate of which acts upon a lever writing on a 
 travelling surface — a uniformly-rotating drum, for example — covered 
 with smoked paper. Any movement communicated to the button 
 forces in the end of the tambour to which it is attached, and thus 
 raises the pressure of the air in it and in the recording tambour; the 
 flexible plate of the latter moves in response, and the lever transfers 
 the movement to the paper. The tracing, or cardiogram, obtained in 
 this way shows a small elevation corresponding to the auricular systole, 
 succeeded by a large abrupt rise corresponding to the beginning of 
 the first sound, and caused by the ventricular systole. This ventricular 
 elevation is the essential portion of the curve; it is alone felt by the 
 palpatmg hand, and the auricular elevation is often absent from the 
 cardiogram in man. The rise is maintained, with small secondary 
 oscillations, for about o-;; of a second in a tracing from a normal man, 
 then gives way to a sudden de- 
 scent, that marks the relaxation 
 of the ventricles, the beginning 
 of the second sound, and the 
 closure of the semilunar valves. 
 An interval of about 0-5 second 
 elapses before the curve begins 
 again to rise at the next auricular 
 contraction. 
 
 Such was the interpretation 
 which Chauveau and Marey put 
 upon their tracings. Although 
 neither their resiilts nor their 
 deductions from them have 
 escaped the criticism of succeed- 
 ing investigators, it is doubtful 
 whether any adequate reason 
 has been brought forward for 
 discarding them, and Chauveau has furnished further proofs of their 
 accuracy. The difficulties that beset the subject are great, for the 
 cardiogram is a record of a complex series of events. The very rapid 
 variation of pressure within the ventricles, the change of volume and 
 of shape of the heart, the slight change of position of its apex, must 
 all leave their mark upon the curve, which is besides distorted by the 
 resistance of the elastic chest-wall, the inertia of the recording lever, 
 and the compression of the air in the connecting tubes. It is only by 
 comparing in animals the cardiographic record with the changes of 
 blood-pressure in the heart and arteries that our present degree of 
 knowledge of the human cardiogram has been attained. Could we 
 register directly the fluctuations of pressure in the interior of the human 
 heart, the cardiographic method would be rarely employed. For 
 cl.nical purposes the receiving tambour can be advantageously replaced 
 by a small glass funnel or a small metal cup, the open end of which is 
 applied without a membrane over the cardiac impulse, the stem being 
 connected with the recording tambour. In cases in which the right 
 ventricle is in contact with the chest-wall at the position of the apex- 
 beat the cardiogram is ' inverted ' — that is to say, the chest-wall is 
 drawn in during systole and protruded during diastole of the ventricles. 
 Inversion of the cardiogram is, therefore, not an infallible sign of the 
 pathological condition known as adherent pericardium (Mackenzie). 
 
 Fig. 28. — Cardiogram taken with Marey"~ 
 Cardiograph. A, auricular systole ; 
 V, ventricular systole ; D, diastole. 
 The arrow shows the direction in which 
 the tracing is to be read. 
 
92 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 Endocardiac Pressure. — The function of the heart is to maintain 
 an excess of pressure in the aorta and puhnonary artery sufficient to 
 overcome the friction of the whole vascular channel, and to keep up 
 the flow of blood. So long as the semilunar valves are closed, most 
 of the work of the contracting ventricles is expended in raising the 
 pressure of the blood within them. At the moment when blood 
 begins to pass into the arteries, nearly all the energy of this blood is 
 potential; it is the energy of a liquid under pressure. During a 
 cardiac cycle the pressure in the cavities of the heart, or the endo- 
 cardiac pressure, varies from moment to moment, and its variations 
 
 afford important 
 (lata for the study 
 of the mechanics of 
 the circulation. 
 
 Manometers. — For 
 the study of the endo- 
 cardiac pressure, the 
 ordinary mercurial 
 manometer (p. no) 
 is unsuitable, since, 
 owing to the rela- 
 tively great amount 
 of work required to 
 produce a given dis- 
 placement of the mer- 
 cury, it does not 
 readily follow rapid 
 changes of pressure, 
 and the mercurial 
 column, once dis- 
 placed, continues for 
 a time to execute 
 vibrations of its own, 
 which are compoun- 
 ded with the true oscillations of blood-pressure. But by introducing 
 in the connection between the manometer and the heart a valve so 
 arranged as to oppose the passage of blood towards the heart, while it 
 favours its passage towards the manometer, the maximum pressure 
 attained in the cardiac cavities during the cycle may be measured with 
 considerable accuracy. When the valve is reversed the apparatus 
 becomes a minimum manometer. In this way it has been found that 
 in large dogs the pressure in the left ventricle may rise as high as 230 
 to 240 mm. of mercury, and sink as low as - 30 to - 50 mm. ; while in 
 the right ventricle it may be as much as 70 mm., and as little as 
 — 25 mm. In the right auricle a maximum pressure of 20 mm. of 
 mercury has been recorded, and a minimum pressure of - 10 mm. or 
 even less. But these results were obtained under somewhat exceptional 
 experimental conditions, and the normal maximum pressures in the 
 heart cavities in man are probably not so high, especially in the right 
 auricle and ventricle. 
 
 Our knowledge of the maximum and minimum pressure attained 
 in the cavities of the heart, even if it were far more precise than it 
 actually is, would only carry us a little way in the study of the endo- 
 cardiac pressure-curve, for it would merely tell us how far above the 
 
 Fig. 29. — Curves of Enducardiac Pressure takeu with 
 Cardiac Sounds. Aur., auricular curve; Vent., ven- 
 tricular curve; AS, period of auricular systole, in- 
 cluding relaxation; VS, of ventricular systole, including 
 relaxation; D, pause. 
 
MECHANICS OF THE HEART-BEAT 
 
 93 
 
 J, -^ 
 
 pjg 30. — Diagram of Hurthle's Elastic Mano- 
 meter. T, small chamber covered by mem- 
 brane; t, tube communicating with interior 
 of heart; L, compound lever to magnify the 
 movements of the membrane. 
 
 base-line of atmospheric pressure the curve ascends, and how far below 
 the base-line it sinks. To exhaust the problem, we require to have 
 tracings of the exact form of the curve for each of the cavities of the 
 heart, and to know the time-relations of the curves so as to be able to 
 compare them with each other, and with tlie pressure-curves of the great 
 arteries and great veins. To obtain satisfactory tracings of the swiftly- 
 changing cndocardiac pressure 
 is a task of the highest techni- 
 cal difliculty, and it is only in 
 very recent years that it has 
 been accomplished, with an y ap- 
 proach to accuracy by the use 
 of clastic manometers, in which 
 the blood-pressure is counter- 
 balanced, not by the weight of 
 a column of liquid, as in the 
 mercurial manometer, but by 
 the resistance to compression 
 of a small column of air or the 
 tension of an elastic disc or of 
 a spring. Modifications in the 
 
 nature and dimensions of the clastic resistance of the recordmg apparatus 
 and of the size of the cavity have produced successive improvements, as, 
 e.g., in the manometers of Hiirthle (Fig 30). 
 
 The penetrating analysis of the principles of manometer construction 
 by Frank has recently stimulated renewed investigation of the whole 
 subject with the aid of instruments whose movements are optically re- 
 
 pjg 3i_ — Diagram of Optical Manometer (Wiggers). 
 A is a vertical glass tube surmounted by a hollow 
 brass cylinder, B, which contains a stopcock, C 
 whose lumen comes into apposition with a plate, 
 a, having a small opening in it. By opening the 
 stopcock more or less, the pulsations will be ' damped ' 
 to a smaller or greater extent. Above a the cylinder 
 ends in a segment capsule b [i.e., a capsule cut away 
 at one side) 3 mm. in diameter, covered with rubber 
 dam. Upon this a small piece of celluloid carr>'ing 
 a little mirror, c, is fastened, so that it pivots on the 
 chord side of the capsule. Over the capsule and its 
 recording mirror is mounted a support bearing an 
 inclined reflecting mirror, E, adjustable about a 
 horizontal axis by a screw, so that the image of the 
 lecording mirror appears within it. Upon this 
 image a strong light is focussed. The incident rays 
 are doubly reflected, as shown in the figure, and the 
 movements of the capsule are thus greatly magnified. 
 The beam of light is photographed on a moving 
 plate. 
 
 corded on a photographic plate, so as to eliminate all unnecessary fric- 
 tion. Fig. 31 is a diagram of the manometer devised by Wiggers on 
 this principle. , -.li 
 
 Hiirthle's spring manometer consists of a small drum covered with 
 an indiarubber membrane, loosely arranged so as not to vibrate with 
 a period of its own. The drum is connected with the heart or with 
 a vessel, and the blood-pressure is transmitted to a steel spring by 
 means of a light metal disc fastened on the membrane. The spring 
 
94 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 acts on a writing lever. The instrument is so constructed that for a 
 given change of pressure the quantity of liquid displaced is as small 
 as possible, and it is on this that its capacity to follow sudden varia- 
 tions of pressure chiefly depends. The manometer is connected with 
 the cavity of the heart by an appropriately curved cannula of metal 
 or glass, which, after being filled with some liquid that prevents co- 
 agulation (Practical Exercises, p. 211), is pushed through the jugular 
 vein into the right auricle or ventricle, or through the carotid artery 
 and aorta into the left ventricle. Some observers fill only the cannula 
 with fluid, and leave the capsule of the elastic niimomcter and as much 
 of the connections as possible full of air. Others fill the whole system 
 with liquid. And around the question of the relative merits of ' trans- 
 mission ' by liquid and by air has raged a controversy which, however, 
 now shows signs of coming to an end. For there is reason to suppose 
 that the character of the curves obtained is modified among other 
 circumstances by the manner in which the pressure is transmitted, as 
 it is certainly modified by the dimensions and mass of the moving parts 
 and the method of recording. As Wiggers has pointed out, the differ- 
 ences in the records obtained by different observers, even with the latest 
 methods of optical registration, are determined largely by the sensitive- 
 ness and degree of damping of the manometer. 
 
 The Ventricular Pressure-Curve. — Thus, the pressure-curve of the 
 ventricle, according to most of those who have employed mano- 
 meters with hquid transmission and small inertia of the moving 
 parts (Fig. 33), remains after the first abrupt rise, which undoubtedly 
 corresponds to the ventricular systole, well above the abscissa line 
 for a considerable time, and then descends somewhat less suddenly 
 than it rose. This systohc ' plateau,' although usually broken by 
 minor heights and hollows, which may be partly due to inertia oscilla- 
 tions of the liquid or the recording apparatus, would indicate that 
 the ventricular pressure, after its first swift rise, maintained itself at 
 a considerable height throughout the greater part of the systole. 
 The tracings yielded by most of the manometers with air trans- 
 mission show the same suddenness in the first part of the upstroke 
 and the last part of the descent — that is, the same abruptness 
 in the beginning of the contraction and the end of the relaxa- 
 tion. But they differ totally in the intermediate portion of the 
 curve, which, climbing ever more gradually as it nears its apex, 
 remains but a moment at the maximum, then immediately descend- 
 ing forms a ' peak,' and not a plateau. It ought to be distinctly 
 understood, however, that the use of the term ' plateau ' must not be 
 taken to imply that the pressure remains constant and the curve 
 parallel to the abscissa during this interval. 
 
 Wiggers, using the optical method of recording the pressure- 
 curve in the right ventricle (p. 93), finds that when the auricular 
 pressure and the pressure in the pulmonary artery are normal the 
 curve of intraventricular pressure may be divided into (i) an auric- 
 ular period; (2) a period of rising pressure while the ventricle is 
 contracting and its cavity is closed by the auriculo- ventricular and 
 semilunar valves; (3) an ejection period during which the pressure 
 
MECHANICS OF THE HEART-BEAT 
 
 95 
 
 still rises, reaches a summit, and then slowly falls; and (4) a relaxa- 
 tion period (Fig. 32). 
 
 Without entering further into a technical discussion, we may say 
 
 CiirotifJ 
 
 e 
 
 ■ r 
 
 d' , 
 <i ; , 
 
 
 ! 1 
 
 \ 
 
 Fig. 32. — Intraventricular Pressure Curves with Optical Recording (Wiggers). Three 
 types of normal curves are reproduced, taken with manometers of different 
 degrees of sensitiveness. The second at the left-hand side was taken with the 
 least sensitive, a — b, auricular systolic; b — d, isometric period, during which 
 the auriculo-ventricular and the semilunar vaU'es are both closed; d — f, ejection 
 period; after/, diastole. 
 
 the bulk of the evidence goes to show that the plateau is not, as the 
 advocates of the peak have claimed, an artificial phenomenon, but 
 does in reality correspond to that continuation of the systole of the 
 
 Fig. 33. — Simultaneous Record of Pressure in Left Ventricle (V) and Aorta (A). 
 (Hiirthle.) The tracings were fallen with elastic manometers; indicates a 
 point just before the closure of the mitral valve; i, the opening of the semilunar 
 valve; 2, beginning of the relaxation of the ventricle; 3, the closure of the semi- 
 lunar valve; 4, the opening of the mitral valve. The ventricular curve shows 
 a * plateau.' 
 
 ventricle, that dogged grip, if we may so phrase it, which it seems to 
 maintain upon the blood after the greater portion of it has been 
 expelled. 
 
qg the circulation of the blood and lymph 
 
 This conclusion is essentially in accordance with the results of 
 Chauveau and Marej', obtained long ago by means of their ' cardiac 
 sound,' which was in principle an elastic manometer. 
 
 It consisted of an ampulla of indiarubbcr, supported on a frame- 
 work, and communicating with a long lube, which was connected with 
 a recording tambour. The ampulla was introduced into the heart (ot 
 a horse) through the jugular vein or carotid arter\' in the way already 
 described. Sometimes a double sound was employed, armed witli 
 two ampullae, placed at such a distance from each other that when 
 one was in the right ventricle the other was in the auricle of the same 
 side. Each ampulla communicated by a separate tube in the common 
 stem of the instrument with a recording tambour, and the writing 
 points of the two tambours were arranged in the same vertical line. 
 When any change in the blood-pressure takes place, the degree of 
 compression of the ampullae is altered, and the change is transmitted 
 along the air-tight connections to the recording tambours. 
 
 On most of the endocardiac pressure tracings taken with modern 
 manometers, whether the curves belong to the tj^pe of the peak or of 
 the plateau, no sudden change of curvature, no nick, or crease, or 
 undulation reveals the moment of opening or closure of any valve. 
 This has been considered by some writers a striking tribute to the 
 smooth working of the cardiac pump. There is reason to think, 
 however, that the smoothness of the curve is still in some degree 
 artificial, and on some of the records obtained by optical methods 
 (Fig. 32) indications of changes of curvature, associated with the 
 action of the valves, may be observed. But even in the absence of 
 such indications, by experimentally graduating a pair of elastic 
 manometers, and obtaining with them simultaneous records of the 
 pressure in auricle and ventricle, or by using a ' differential ' mano- 
 meter, in which the pressures in two ca\nties are opposed to each 
 other, so that the movement of the membrane corresponds to their 
 difference, we can calculate at what points of the ventricular curve 
 the pressure is just greater than and just less than the pressure in the 
 auricle. The first point, it is evident, will correspond to the instant 
 at which the mitral or tricuspid valve, as the case may be, is closed, 
 and the second to the instant at which it is opened. And in like 
 manner, by comparing the pressure-curve of the aorta with that of 
 tht.; left ventricle, the moment of opening and closure of the semi- 
 lunar valves may be determined (Figs. 33 and 34). According to the 
 best observations, the closure of the semilunar valves takes place at 
 a time corresponding to a point on the upper portion of the descend- 
 ing limb of the intraventricular curve. 
 
 On the blood-pressure curve of the aorta, simultaneously registered, 
 the corresponding point is near the bottom of the so-called ' aortic ' 
 notch (p. 105) which precedes the dicrotic elevation. For clinical 
 purposes, in man the moment of closure of the semilunar valves 
 (denoted by the abbreviation S.C. point) may be taken as 0-03 second 
 before the bottom of the aortic notch in sphygniographic tracings 
 from the carotid, this being approximately the a\erage time occupied 
 
MECHANICS OF THE HEART-BEAT 97 
 
 by the pulse-wave in travelling from the aorta to the carotid. The 
 S.C. point, the A.O. point, or moment of opening of the auriculo- 
 ventricular valves, and the Leginnhig of the ventricular systole, are 
 three important points of reference in the measurement and inter- 
 pretation of pulse -tracings in clinical work. The A.O. point in man 
 may be taken as a point ' 0-03 second in advance of the summit of 
 the dicrotic wave ' on the carotid pulse-tracing (Lewis). But this is 
 the most difficult of the three standard points to determine clinically 
 with anything like accuracy. 
 
 The study of tlie curves of endocardiac pressure enables us to add 
 precision in certain points to the description of the events of the 
 cardiac cycle which we have already given, and, as regards the 
 ventricles, to divide the cycle into four periods: 
 
 (i) A period during which the pressure is lower in the ventricles than 
 either in the auricles or the arteries, and the auricido -ventricular valves 
 are consequently open, and the semilunar valves closed. This is the 
 period of ' filling ' of the heart, or the pause. 
 
 (2) A period, beginning with the ventricular systole, during which the 
 pressure is increasing abruptly in the ventricles, while they are as yet 
 completely cut off from the auricles on the one hand and the arteries on 
 the other by the closure of both sets of valves. This is the period of 
 ' rising pressure,' during which the ventricles are, so to say, ' getting up 
 steam.' The interval between the beginning of the ventricular systole 
 and the opening of the semilunar valves is termed the ' presphygmic ' 
 interval. 
 
 (3) A period during which the pressure in the ventricles overtops that 
 in the arteries, and the semilunar valves are open, while the auriculo- 
 ventricular valves remain shut. This is the period of ' discharge ' or 
 * sphygmic ' period. 
 
 (4) A period during which the pressure in the ventricles is again less 
 than the arterial, while it still exceeds the auricular pressure, and both 
 sets of valves are closed. This is the period of rapid relaxation. The 
 interval between the closure of the semilunar and the opening of the 
 auric ulo-ventricular valves is sometimes called the ' post-sphygmic ' 
 interval. 
 
 Of the four periods, the second and fourth are exceedingly brief. 
 The third is relatively long and constant, being but slightly depen- 
 dent on either the pulse-rate or the pressure in the arteries. The 
 duration of the first period varies inversely as the frequency of the 
 heart ; with the ordinary pulse-rate it is the longest of all. 
 
 From records taken in a person with a defect in the chest-wall which 
 rendered the heart accessible the following results were obtained as 
 to the duration of the various events of the cardiac cycle : First and 
 fourth periods together, 0-445; third period, 0*254; second period (pre- 
 sphygmic interval), 0'05i second, the pulse-rate being 80 a minute 
 (Tigerstedt). In another case with a similar defect the first period 
 lasted 0-32, the fourth period (post-sphygmic interval) 0'o6, the second 
 and third periods together 0-4, and the auricular systole 0*1 second, 
 the pulse-rate being 66. 
 
 7 
 
98 
 
 Tlin CIRCULATION OF THE BLUOD ASD LYMPH 
 
 The Auricular (and Venous) Pressure-Curve. — The fluctuations of 
 pressure in the aurieUs, allhou^'h cfjn fined witliin narrower hmits 
 tlian in the ventricles, are of equal interest. They have been studied 
 in considerable detail both in animals and by indirect methods in 
 man. No fewer than three distinct elevations or ' positive waves,' 
 separated or followed by three depressions or ' negative waves,' 
 have been described on the curve of intra-auricular pressure. 
 
 The first elevation corresponds to the systole of the auricle. The 
 second coincides with the onset of the ventricular systole, and is 
 
 Fig. 34. — Schematic Comparison of Pressure Curves in the Auricle (or Superior 
 Vena Cava), the Ventricle and the .\orta in the 1 )og (Fredericq). In the auricular 
 curve are to be distinguished ab, the first positive or pres>-stolic wave, corre- 
 sponding to the auricular systole (o wave); 6ft' or be, second positive wave or 
 fcrst systolic wave, which corresponds with the beginning of the ventricular 
 systole (c wave); b'cd, the steep negative wave of which the beginning corre- 
 sponds to the opening of the semilunar valves; def. the third positive wave 
 (v wave), more or less serrated, ending at /. the point of opening of the auriculo- 
 ventricular valves: fg, a negative wave corresponding to the relaxation of the 
 ventricle. The time is indicated along the abscissa in tenths of a second, the 
 pressure along the vertical axis at the left in mm. of mercury. 
 
 probably due to the sudden bulging of the auriculo- ventricular valve 
 into the auricle, or even to a slight regurgitation of blood from the 
 ventricle through the valve before it has completely closed. The 
 cause of the third elevation, which occurs during the period occupied 
 in the ventricular pressure-curve by the plateau, is less clearly made 
 out. In man, the events taking place in the right auricle during its 
 
MECHANICS OF THE HEART-BEAT 
 
 99 
 
 ?.ystole can be followed to some extent by recording the venous pulse 
 in the jugular veins, especially the internal jugular, at the root of the 
 the neck (Fig. 36). Successful tracings can be obtained, not only in 
 certain pathological conditions, but in many normal individuals, and 
 it is probably only a matter of improved technique to obtain them 
 in all. The jugular venous pulse-tracing, like the intra-auricular 
 pressure-curve, shows in general three well-marked elevations and 
 three depressions, and there is good evidence that, broadly speaking, 
 these features of the jugular curve corre- 
 spond as regards their origin with the 
 changes of pressure in the auricle. 
 
 Identical features are observed on records 
 of the normal venous pulse taken from veins 
 of dogs near the heart, and on records of tlie 
 pulse taken by a sound in the oesophagus. 
 The oesophagus pulse is related to the pul- 
 sation of the left auricle, the venous pulse to 
 the changes of pressure in the right auricle. 
 The first elevation, called the a (auricular) 
 or p (presystolic) wave, begins with, and is 
 the result of, the auricular systole. It is 
 probably produced by stasis in the veins due 
 to the contraction of the auricle, as well as 
 to the effect of the impact of the auricular 
 systole. The downstroke on the curve which 
 succeeds this first elevation corresponds to 
 the first negative wave or presystolic fall, 
 which is due to the auricular relaxation . This 
 
 Fig. 35. — Schema of Events in the Cardiac Cyclt, 
 in Relation to the Venous Pulse (Ewing). i. Tracing 
 from Vena Cava, showing presystolic rise and fall, 
 PR. PF (a wave) ; SR. systolic rise and fall 
 (c wave); O', first onflow wave and, DR, diastolic 
 rise and fall (t; wave); O*, second onflow wave; 
 2. auricular myogram (tracing of contraction of 
 auricle); 3, ventricular myogram (tracing of con- 
 traction of ventricle); 4, record of the movement 
 of the aurictilo-ventricular septum; 5, ventricular 
 volume curve (plethysmographic curve of dis- 
 charge of the ventricles ) ; 6, curve of aortic pressure ; 
 7, intraventricular pressure -curve. 
 
 fall of pressure is terminated by a rise — the second positive wave — which 
 begins at the same moment as the ventricular systole, and is the ex- 
 pression on the venous pulse-curve of that second elevation of the 
 intra-auricular pressure whose probable cause has already been found 
 in the sharp protrusion of the auriculo-ventricular valve into the 
 auricular cavity under the stress of the ventricular systole while the 
 semilunar valve are still closed. In addition to the actual bulgmg of 
 the auriculo-ventricular valves, the impact of the sudden contraction 
 of the ventricle on its contents transmitted through the valve to 
 the contents of the auricle may aid in producing the rise of venous 
 pressure. The second elevation has been termed the c wave by certain 
 
too THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 writers, who studRci it on jugular tracings, because they supposed it 
 to be simply transmitted from the pulse in the acijacent carotid artery. 
 This, however, has been shown to be erroneous, although it is true 
 enough that pulsations transmitted from the great arteries of the 
 thorax and neck may augment or distort the second elevaticjn of the 
 venous pulse. It has been proposed tiiat the second positive wave 
 should be called the s (systolic) wave. It lasts practicallv throughout 
 the presphygmic period of the ventricular systole; the opening of the 
 semilunar valves, as indicated by the appearance of the pulse in the 
 innominate artery, occurs just before the end of the second elevation 
 (Porter, Ewing, etc.). The rapid discharge of the ventricle through the 
 open semilunar valves, and its consequent diminution in size, especially 
 in its longitudinal diameter, is associated with a dilatation of the 
 auricular cavity and a fall of intra-auricular pressure which is expressed 
 on the venous pul^-^ -curve as the downstroke succeeding the second 
 positive wave. Thi:i second negative wave gives place to the third 
 positive wave, due to the steady inflow of blood into the auricle 
 from the veins. According to Ewing, the third positive wave, the v 
 
 V£_Yvix^^ Pulse »" ^^ M^^ 
 
 Fig. 36. — Normal .\p(X and Vonous Pulses, Photographically Recorded (reduced 
 nine-tenths) (Niles and Wipgers). P, presystolic (or a) wave ; S, systolic (or c) 
 wave ; Dj, first diastolic (v) wave. In this venous record a second diastolic 
 wave, D2, is present. S*, vibrations corresponding to first sound ; S^, to second 
 sound. 
 
 wave of Mackenzie, really consists of t%vo waves, the " first onflow 
 wave " and the " diastolic rise " or rf wave. This last is terminated by 
 the third negative wa\e or diastolic fall of venous pressure coincident 
 with the opening of the auriculo- ventricular valves. The re-examina- 
 tion of the venous pulse with apparatus of which the moving parts 
 have an exceedinglv small mass and optical methods of recording (see 
 p. 93) has confirmed the existence on the phlebogram of three essential 
 waves. A fourth is sometimes added when the cardiac cycle is long. 
 The first wave is clearly presystolic, the second systolic, as agreed by 
 all observers who have used polygraph tracings. The third wave, 
 however, is diastolic, as is, of course, the fourth when it exists. The 
 position of these waves can be definitely fixed by simultaneous heart 
 apex tracings, since on such optically recorded cardiograms the heart- 
 sounds are represented by distinct vibrations, except where the chest 
 wall is too thick or the heart overlaid by emphysematous lung Some- 
 times heart-sound vibrations may be present also on the record of the 
 venous pulse (Wiggers). 
 
MECHANICS OF THE CIRCULATION I\ THE VESSELS loi 
 
 The jugular curve, when properly interpnted, affords valuable 
 information as to the action of the auricle, information of the same 
 kind as that afforded by the arterial pulse-tracing and the cardiogram 
 as to the action of the ventricle. In the interpretation of the venous 
 piilse-tracings, a simultaneous record of tlie radial or. better, the 
 carotid pulse or of the apex-beat is always important, and often 
 indispensable, for it enables the time of onset of the ventricular 
 systole to be marked upon the phlebogram (the venous trace), and 
 this facihtates the identification of the a wave, which must immedi- 
 ately precede, and the c or s wave, which should coincide with the 
 beginning of the contraction of the ventricle. The student must, 
 however, be warned that the proper interpretation of such tracings 
 in the study of cardiac disease is often difficult and requires special 
 knowledge and training.* 
 
 Suction Action of the Ventricle. — We have alrea<1y said that a 
 negative pressure may be detected in the cardiac cavities by means of 
 a special form of mercurial manometer. This is confirmed by an 
 examination of the tracings written by good elastic manometers, for 
 the curves of both ventricles may often descend below the line of 
 atmospheric pressure. The cause of this negative pressure has been 
 much discussed. In part it may be ascribed to the aspiration of the 
 thoracic cage when it expands during inspiration (p. 226). But since 
 the pressure in a vigorously-beating heart may still become negative, 
 when the thorax has been opened, and the influence of the respiratory 
 movements eliminated, we must conclude that the recoil of the some- 
 what narrowed, or at least distorted, auriculo-ventricular rings, and of 
 elastic structures in the walls of the ventricles, exerts of itself a certain 
 suction upon the blood. This, however, is not an important factor in 
 the maintenance of the circulation. 
 
 Section III. — Physical or Mechanical Phenomena of the 
 Circulation in the Bloodvessels. 
 
 The Arterial Pulse. — At each contracton of the heart a quantity of 
 blood, probably varjang within rather wide limits (p. 139), is forced 
 into the already full aorta. If the walls of the bloodvessels were 
 rigid, it is evident (p. 85) that exactly the same quantity would pass 
 at once from the veins into the right auricle. The work of the 
 ventricle would all be spent within the time of the systole, and only 
 while blood was being pumped out of the heart would any enter it. 
 Since, however, the vessels are extensible, some of the blood forced 
 into the aorta during the systole is heaped up in the arteries, beyond 
 which, in the narrow arterioles and in the capillary tract, with its 
 relatively great surface, the chief resistance lies. The arteries are 
 accordingly distended to a greater extent than before the systole, 
 and, being elastic, they keep contracting upon their contents until 
 the next systole over-distends them again. In this way, during the 
 pause, the walls of the arteries are executing a kind of elastic sj^stole, 
 
 * The necessary details must be sought in such works as Mackenzie'* 
 ' Diseases of the Heart.' 
 
I02 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 and driving the bhxjd on into the capillaries. The W(jrk done by the 
 ventricle is, in fact, i)artly stored up as potential energy in tiie tense 
 arterial wall, and this energy is being continually transformed into 
 work upon the blood during the pause, the heart continuing, as it 
 were, to contract by proxy during its diastole. Thus, the blood 
 progresses along the arteries in a series of waves, to which the name 
 of ' blood-waves ' or ' pulse-waves ' may be given. Wherever the 
 pulse-wave spreads it manifests itself in various ways — by an increase 
 of blood-pressure, an increase in the mean velocity of the blood-flow, 
 an increase in the volume of organs, and by the visible and palpable 
 signs to which the name of pulse is commonly given in a restricted 
 sense. The intermittence in the flow with which the pulse-wave is 
 necessarily associated is at its height at the beginning of the aorta. 
 In middle-sized arteries, such as the radial, it is still well marked, but 
 it dies away as the capillaries are reached, and only under special 
 conditions passes on into the veins, where, however, as has just been 
 mentioned, pulsatory phenomena of a different origin maybe detected. 
 
 The pulse was well known to the Greek physicians, and used by 
 them to a certain extent as an indication in practical medicine. 
 Harvey demonstrated with some clearness the relation of the pulse 
 to the contraction of the heart, but Thomas Young was the fir.st to 
 form a proper conception of it as the outward token of a wave prop- 
 agated from heart to periphery. 
 
 When the finger is placed over a superficial artery like the carotid, 
 the radial, or the temporal, a throb or beat is felt, which, without 
 measurement, seems to be exactly coincident with the cardiac 
 impulse. In certain situations the pulse can be seen as a distinct 
 rhythmical rise and fall of the skin over the vessel. The throbbing 
 of the carotid, especially after exertion, is familiar to everyone, and 
 the beat of the ulnar artery can be easily rendered \'isible by extend- 
 ing the hand sharply on the wrist. When the pulse is felt by the 
 finger, it is not the expansion, but the hardening of the wall of the 
 vessel, due to the increase of arterial pressure, that is perceived ; and 
 even a superficial artery, when embedded in soft tissues so that it 
 cannot be compressed, gives no token of its presence to the sense of 
 touch. Sometimes an artery is longitudinally extended by the 
 pulse- wave, and this extension may be far more conspicuous than 
 the lateral dilatation. This is particularly seen when one point of 
 the vessel is fixed and a more distal point offers some obstruction to 
 the blood-flow, as at a bifurcation or in an artery which has been 
 ligatured and divided. 
 
 By means of the sphygmograph, the lateral movements of the 
 arterial wall, or, rather, in man, the movements of the skin and other 
 tissues lying over the bloodvessel, can be magnified and recorded. 
 
 It would be very unprofitable to enumerate all the sphygmographs 
 which ingenuity has invented and found names for. The first attempt 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 
 
 if^3 
 
 Fig- 37- — Scheme of Marey's Sphygmo- 
 graph. A, toothed wheel connected with 
 axle H. and gearing into toothed upright 
 B; C. ivory pad which rests over blood- 
 vessel and is pressed on it by moving G. 
 a screw passing through the sprin'g J ; 
 E, writing-lever attached to axle H, and 
 moved by its rotation. E writes on D, a 
 travelling surface moved bv clockwork F. 
 
 to magnify the movements of the pulse was made by loosely attaching 
 
 a thin fibre of glass or wax to the skin with a little Jard, in order to 
 
 demonstrate the venous pulse which appears under certain conditions. 
 
 In all modem sphygmographs there is a part, usually button-shaped, 
 
 which is pressed over the artery by means of a spring, as in Marey's 
 
 and Dudgeon's sphygmographs, 
 
 or by a weight, or by a column of 
 
 liquid. In Marey's instrument, 
 
 the button acts upon a toothed 
 
 rod gearing into a toothed wheel, 
 
 to which a lever, or a system of 
 
 levers, is attached. The lever has 
 
 a writing-point which records the 
 
 movement on a smoked plate, or 
 
 a plate covered with smoked 
 
 paper, drawn uniformly along by 
 
 clockwork (Figs. 37, loo). Special 
 
 forms of sphygmographs (poly- 
 graphs) have been devised, which. 
 
 by the addition of one or more 
 
 recording tambours, permit the 
 
 simultaneous record of movements from two or more points of the 
 
 vascular system — for example, the radial artery and the jugular vein, 
 
 or the radial or carotid artery, jugular vein, and the apex of the heart. 
 
 In rare cases, with de- 
 fect of the chest wall, 
 a tracing may be ob- 
 tained even from the 
 aorta (Fig. 40). 
 
 In a normal arterial 
 pulse-tracing (Fig. 38) 
 the ascent or ana- 
 crotic limb is abrupt 
 and unbroken; the 
 descent or katacrotic 
 limb is more gradual, 
 and is interrupted by 
 one, two, or even 
 three or more, second- 
 SiTy wavelets. The 
 most important and 
 constant of these is 
 the one marked 3, 
 which has received the 
 name of the dicrotic 
 wave. Usually less 
 marked, and some- 
 
 Fig. 38. — Pulse-Tracings, i, primary elevation ; 2, predi- 
 crotic or first tidal wave ; 3, dicrotic wave. The 
 depression between 2 and 3 is the dicrotic or aortic 
 notch; 3 is better marked in B than in A. C, dicrotic 
 pulse with low arterial pressure; D, pulse with high 
 arterial pressure — summit of primary elevation in the 
 form of an ascending plateau. E, systolic anacrotic 
 pulse; the secondary wavelet a occurs during the 
 upstroke corresponding to the ventricular systole. 
 F, presystolic anacrotic pulse; a occurs just before 
 the systole of the ventricle. In this rarer form of 
 anacrotism, a may sometimes be due to the auricular 
 systole when the aortic valves are incompetent. 
 
 times absent, is the 
 wavelet 2 between the dicrotic elevation and the apex of the curve. 
 It is generally termed the predicrotic wave. Oscillations, due to 
 vibrations of the recording apparatus, appear on many pulse- 
 
I04 TUi: CIRCULATIOS Ul- THE liLOOD AND LYMFH 
 
 tracings, and it is important to rt'cognizc their cause, so that no 
 weight may be given to them. 
 
 In the explanation of the pulse-tracing, a fundamental fact to be 
 borne in iniiul is the elasticity of the vessels. When an incompres- 
 sible fluid like water is injected bj- an intermittent pump into one end 
 ol an elastic tube a wave is set up, which is transmitted to the other 
 end of the tube. It is a jw.sitive wave — tliat 
 is, it causes an increase of pressure and an 
 expansion of the tube wherever it arrives; 
 and if a series of levers be placed in contact 
 with the tube, they will rise and sink in 
 succession as the wave passes them. After 
 the passage of this primary wave the walls of 
 the tube, instead of coming instantly to rest 
 in their original position, regain it by a series 
 of oscillations, first shrinking too much, then 
 expanding too much, but at each movement 
 coming nearer to the position of equilibrium. 
 Each vibration of the elastic wall is of course 
 accompanied by a change of pressure in the 
 contents of the tube. This change of pressure 
 runs along the tube as a wave; and such 
 waves, succeeding the primarj' one, may be 
 1 ig. ■( - Pulse - Tracmgs t;a-llcd secondary waves of oscillation. These 
 from ^ Different Arteries secondary waves will be set up in an elastic 
 (V. Frey). T, temporal; sj^stem whether the distal end of the system 
 i?, radial : P, artery of foot, be closed or open. But if it is closed, or 
 sufficiently obstructed without being actu- 
 ally closed, secondary waves of another kind may also be generated, 
 the primar)-^ waNC on arri^•ing at the distal end being reflected there. 
 The reflected wave running back towards the central end may there 
 again undergo reflexion, and pass out once more towards the distal end 
 as a centrifugal, twice-reflected wave. When the liquid ceases to enter 
 the tube at the end of the stroke, a wave of diminished pressure^a 
 negative wave — is generated at the central 
 end, and is propagated to the distal end, 
 where it may be reflected just like the posi- 
 tive wave. 
 
 AlthouG^li under certain conditions the 
 dicrotic wave is so marked tliat the double 
 beat of the pulse was discovered and 
 named by physicians long before the in- 
 vention of any sphygmograph, perhaps 
 no physiological question has been more 
 discussed or is less understood than the F»g- 40. — Puise-Curve from 
 mechanism of its production. Two ^^*° "^""^^ (^^^" '^'8«''- 
 points, however, seem to be clear : (i) That 
 
 it is a centrifugal, and not a centripetal, wave — that is to say, it 
 travels away from, and not towards, the heart ; (2) that the aortic 
 semilunar valves have something to do with its origin. 
 
 It is not a centripetal wave, for in tracings taken at all parts of the 
 arterial path, no matter what the distance from the heart and the 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 105 
 
 capillaries {e.g., the origin of the carotid and the radial at the wrist), 
 the dicrotic wave is separated by the same interval from the begin- 
 ning of the primary elevation. This can only be explained by 
 supposing that it has the same point of origin, and travels with the 
 same velocity and in the same direction as the primary wave. It is 
 not, then, a wave reflected directly from the peripheral distribution 
 of the artery from which the pulse-tracing is taken. 
 
 Some writers have contended that it is a centrifugal twice -re fleeted 
 wave, and, indeed, traces of such waves may be detected in the vessels 
 of newly-killed animals when changes of pressure of the same order 
 of magnitude as the arterial pulse are artificially produced by a pump 
 and recorded by elastic manometers connected with the interior of 
 an artery. It has been supposed that these secondary waves are 
 reflected first from peripheral points at which the blood-flow is particu- 
 larly obstructed (the bifurcations of the larger arteries, and the small 
 arteries and capillaries in general), and that, running towards the heart, 
 they are again reflected outwards from the semilunar valves. It has 
 been urged in support of this view that in very small animals (guinea- 
 pigs) no dicrotic elevation occurs on the pulse-tracing, since the path 
 which the reflected wave has to follow is so short that it arrives at the 
 root of the aorta before the primary elevation is over. But this 
 argument is by no means conclusive, and, indeed, the great difference 
 in the distance from the heart of the numerous points at which reflection 
 must take place is one of the chief difficulties of the hypothesis. For 
 it is not easy to understand how the reflected fragments of the primary 
 wave, arriving at different intervals at the heart, can be integrated into 
 the single considerable dicrotic elevation. 
 
 The explanation that best takes account of the facts and renders 
 most clear the role of the semilunar valves is somewhat as follows: 
 When the systole abruptly comes to an end and the outflow from the 
 ventricle ceases, the column of blood in the aorta tends still to move 
 on in virtue of its inertia, and a diminution of pressure, accom- 
 panied by a corresponding contraction of the aorta, takes place 
 behind it, just as a negative wave is set up in the central end of the 
 elastic tube when the stroke of the pump is over. At the same 
 moment, and while the semilunar valves are still for an instant in- 
 completely closed, the diminution of pressure in the beginning of the 
 aorta is intensified by the aspiration of the relaxing ventricle, which 
 sucks the blood back against the valves, and draws them a little way 
 into its cavity. A negative wave, therefore — a wave of diminished 
 pressure, represented in the pulse-curve by the ' aortic notch ' — 
 travels out towards the periphery. The diminution of pressure is 
 quickly followed by a rebound, as always happens in an elastic 
 system. The recoiUng blood meets the closed semilunar valves. 
 The aorta expands again, and the expansion is propagated once more 
 along the arteries as the dicrotic elevation. It is possible that this 
 elevation may be reinforced by a reflected wave produced in the 
 manner described. 
 
lo6 THE Clh'CULATJON OF THE BLOOD ASD LYMPH 
 
 When the semilunar valve beromes incompL-tcnt in disease, or is 
 rendered insulin it nt in animals by tlie artilit ial rupture of one or 
 more of its segments, the dicrotic wave, as will be readily understood 
 from the manner in which it is produced, eitlier disappears altogether 
 or is markedly enfeebled. But apart from any anatomical lesion or 
 functional defect in the aortic valves, the prominence of the wave 
 varies with a great number of circumstances, some of which are in a 
 measure understood, while others remain obscure. It varies in par- 
 ticular with the abruptness of discharge of the ventricle and the ex- 
 tensibility of the arteries. The conditions are usually favourable when 
 the arterial pressure is low, for the blood then passes quickly from the 
 ventricle into the arteries, which, already only moderately tense, are 
 easily dilated by the primary wave, then sharply collapse, and are again 
 abruptly distended when the dicrotic wave arrives. And, in fact, an 
 exaggeration of the dicrotic wavelet may be artificially produced by 
 nitrite of amyl (Fig. lo j, p. 209), a drug which lessens the blood-pressure 
 by dilating the small arteries. Muscular exercise (Fig. loi, p. 209), 
 running or bicycling, for instance, has a similar effect on the sphygmo- 
 gram, although the explanation can scarcely be the same, since the blood- 
 pressure mounts rapidly when moderate exercise begins, and only 
 gradually falls during its continuance, with an abrupt decline to normal 
 or below it on cessation of work (Bowen). The increase in the pulse- 
 rate may have something to do in this case with the exaggeration of the 
 dicrotism, which is very frequently, although by no means invariably, 
 associated with a rapidly-beating heart, and therefore is often seen in 
 fever. On the other hand, in certain diseases associated with a high 
 arterial pressure, the dicrotic elevation almost disappears. Ather- 
 omatous arteries, being very inextensible, do not allow a dicrotic pulse. 
 
 Since the pulse represents a periodical increase and diminution in 
 the amount of distension of an artery at any point, the line joining 
 all the minima of the pulse-curve will vary in its height above the 
 base-line, or line of no pressure, according to the amount of permanent 
 distension, i.e., permanent blood-pressure, which the heart in any given 
 circumstances is able to maintain. Any circumstance that tends to 
 lessen the permanent distension will cause a fall of the line of minima, 
 and any circumstance tending to increase the distension will cause that 
 line to rise. If, for example, the arm be raised while a pulse-tracing 
 is being taken from the wrist, the line of minima falls because the 
 permanent pressure in the radial artery is diminished. 
 
 The form of the pulse-curve varies in the different arteries, and 
 therefore in making conipurisons the same artery should be used. 
 When the wave of blood only enters an artery slowly, the ascending 
 part of the curve will be oblique. This is normally the case in a 
 pulse-curve of a distant artery, such as the posterior tibial. The 
 heiglit of the wave is also less than in an artery nearer the heart, such 
 as the carotid, or even the axillary, where the primary elevation is 
 relatively abrupt (Fig. 39, p. 104). 
 
 Anacrotic Pulse. — As a rule, the ascent of the tracing is unbroken 
 by secondary waves, but in certain circumstances these may appear 
 on it. This condition, which, when well marked at any rate, may 
 be considered pathological, is called anacrotism (Fig. 38). It is seen 
 when the disclKirge of the left ventricle into the aorta is slow and 
 difficult — e.g., in cases where the orifice of the aorta has been 
 
MECHANICS OF THE CIRCULATION IN THE VESSEL!^ 107 
 
 narrowed from disease oi tlie semilunar valvi's (aortic stenosis). 
 Since this condition is associated with hypertrophy and dilatation 
 of the li'ft ventricle, the slow emptyiiif.^ of the ventricle is partly due 
 to the greater quantity of blood which it contains. In whatever 
 way the delay in the emptjnng of the ventricle is brought about, the 
 most probable explanation of the anacrotic pulse is that the delay 
 affords time for one or more secondary waves to be developed in the 
 arterial system before the summit of the curve has been reached, and 
 that these are superposed upon the long-drawn primary elevation. 
 In aortic insuHiciency, where the left side of the heart is never cut off 
 entirely from the aorta, the auricular impulse is sometimes marked 
 on the pulse-curve as a distinct elevation; and this gives rise to a 
 peculiar kind of anacrotic pulse, especially in the arteries nearest the 
 heart (Fig. 38, F, p. 103). 
 
 Frequency of the Pulse. — In health, the working of the cardiac 
 pump is so smooth and apparently so self-directed that it needs a 
 certain degree of attention to perceive that the rate of the stroke is 
 not absolutely constant. It is, in reahty, affected by many internal 
 conditions and external influences. 
 
 At the end of foetal hfe the rate is given as 144 to 133; from birth 
 till the end of the first year, 140 to 123 ; from 10 to 15 years, 91 to 76; 
 from 20 to 25 years, 73 to 69. It remains at this till 60 years, and 
 increases again somewhat in old age.* At all ages the pulse is some- 
 what quicker in the female than in the male, the excess amounting to 
 about 8 beats a minute. So that if we take the average rate for a 
 man (in the sitting position) as 72, the average for a woman will be 
 80. The difference is partly due to the fact that the average man 
 is taller than the average woman; and it is known that in persons of 
 the same sex and age the pulse-rate has an inverse relation to the 
 stature. But there may be, in addition, a real sexual difference. 
 It must not be forgotten that a certain number of perfectly healthy 
 persons, who may even be noted for their powers of physical en- 
 durance, have an habitually slow pulse, not above 50 in the minute. 
 The position of the body exercises a slight, but relatively constant, 
 influence on the rate, which is greater in the standing than in the 
 sitting posture, and greater in the latter than in the recumbent 
 position. And this is true even when muscular action is as far as 
 possible ehminated by fastening the person to a board. The pulse 
 
 * It must be remembered that these numbers are merely averages. Some 
 healthy individuals have a much lower pulse-rate than 72 per minute, and 
 some a rate considerably greater. Thus, while the average pulse-rate (taken 
 in the sitting position) of 87 healthy (male) students, whose ages ranged from 
 18 to 36 years, was 73, the extreme variation was from 54 to 89. In the 
 standing position the average was 80, and the variations 64 to 105. In 
 the supine position, average 69, and variations 48 to 98. After a short spell 
 of muscular exercise (generally running up and down some flights of stairs) 
 the average in the standing position was 119, the variations 75 to 164, and 
 the average increase 32. 
 
lo8 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 is further affected by tho respiratory movements, especially when 
 they are exaggerated in forced breathing, being accelerated during 
 each inspiration (p. 293). It is also increased by the taking of food, 
 and especially of alcoholic stimulants, by muscular i-xercise, in fever 
 and many other pathological conditions, and by a high external 
 temperature. A warm bath, for example, causes a very distinct 
 acceleration of the heart; and Delaroche found that in air at the 
 temperature of 65° C his pulse went up to 160. A cold bath may 
 depress the pulse-rate to 60, or even less. During sleep it may fall 
 to 50. It is greatly influenced by psychical events, and that in the 
 direction either of an increase or a decrease. Finally, it ought to be 
 remembered as of some practical importance that the pulse-rate in 
 women and children, but particularly in the latter, is less steady 
 than in men, and more apt to be affected by trivial causes. And it 
 is a good general rule to let a short interval elapse after the finger is 
 laid on the artery before beginning to count the pulse, so that the 
 acceleration due to the agitation of the patient may have time to 
 subside. 
 
 Rate of Propagation of the Pulse-Wave. — When pulse-tracings are 
 taken simultaneously at two points of the arterial system unequally 
 distant from the heart, by two sphygmographs whose writing-points 
 move in the same vertical straight line, it is found that the ascent 
 of the curve begins later at the more distant than at the nearer point. 
 Since waves hke the pulse-wave travel with approximately the same 
 velocity in different parts of an elastic system like the arterial ' tree,' 
 this ' delay ' must be due to the difference in the length of the two 
 paths. The difference in length can be measured; the time- value of 
 the ' delay ' can be deduced from the rate of movement of the re- 
 cording surface; dividing the length by the time, we arrive at the 
 rate of propagation of the pulse-wave. The average rate has been 
 found to be about 7 metres per second in man in the arteries of the 
 upper limb, and 8 metres in those of the lower limb, the difference 
 being due to the smaller distensibihty of the latter. In sleep the 
 velocity diminishes almost a metre a second. It increases in arterio- 
 sclerosis, where the distensibihty of the arteries is diminished, and 
 in chronic nc^phritis with hypertrophy of the heart, in which the 
 blood-pressure is increased. The mean velocity of the pulse- wave 
 is about the same as the speed of a moderately fast steamship (say, 
 17 miles an hour), but less than that of a wave of the sea in a strong 
 gale. The velocity of the pulse-wave must not be confounded with 
 that of the blood-stream itself, which is not one-thirtieth as great. 
 A ripple passes over the surface of a river at its own rate — a rate 
 that is independent of the velocity of the current. The passage of 
 the ripple is not a bodily transference of the particles of water of 
 which at any given moment the wave is composed, but the propaga- 
 tion of a change of relative position of the particles. The mere fact 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 105 
 
 that the ripple can pass upstream as well as down is sufficient to 
 illustrate this. The pulse-wave does not, however, correspond in 
 every respect to a ripple on a stream, for the bodily transfer of the 
 blood depends upon the series of blood- waves which the heart sets 
 travelling along the arteries. Every particle of blood is advanced, 
 on the whole, by a certain distance with every pulse- wave in which 
 for the time it takes its place. But no particle continues in the 
 front of the pulse- wave from beginning to end of the arterial system. 
 The ' delay ' or ' retardation ' of the pulse (the interval, say, between 
 the beginning of the ascent of the carotid and radial curves) is 
 practically constant in the same individual, not only in health, but 
 also in most diseases. But the retardation is markedly increased 
 when the pulse-wave has to pass through a portion of an artery 
 whose lumen is either greatly widened (in aneurism) or greatly 
 constricted (in endarteritis obliterans). 
 
 The Blood- Pressure Pulse in the Arteries.— In man it is only 
 possible to trace the pulse-wave along the arteries by movements of 
 the walls of the vessels transmitted through the overlying tissues. 
 In animals the changes of pressure that occu- in the blood itself can 
 be directly registered, and these changes may be spoken of as the 
 blood-pressure pulse. At bottom, as already pointed out, the 
 phenomenon is exactly the same as that we have been dealing with 
 in our study of the external pulse. We are only now to follow, by 
 a more direct, and in some respects a more perfect method, the same 
 wave of blood along the same channel. 
 
 Measurement of the Arterial Blood-Pressure. — Hales was the first to 
 measure the blood-pressure. This he did by connecting a tall glass 
 tube with the crural artery of a horse. The height to which the blood 
 rose in the tube indicated the pressure in the vessel. Poise uille, nearly 
 half a century later, applied the mercury manometer, which had already 
 been used in physics, to the measurement of blood-pressure. Ludwig 
 and others improved this method by making the manometer self- 
 registering by means of a float in the open limb, supporting a style 
 which writes on a revolving drum, or kymograph. (For the method 
 of taking a blood-pressure tracing, see p. 210.) 
 
 For reasons already mentioned, the mercurial manometer is better 
 suited for measuring the mean blood-pressure, or for recording changes 
 in the pressure which last for some time, than for following the rapid 
 variations of the pulse-wave. For the latter purpose, one of the class 
 of elastic manometers is required (p. 93). 
 
 A blood-pressure tracing taken from an artery with a manonieter 
 of this sort yields the truest picture of the pulse-wave which it is 
 possible to obtain, because the reproduction of it is the most direct. 
 The fact that such a tracing shows a close agreement with the trace 
 of a good sphygmograph properly applied to the corresponding artery 
 on the other side is a striking proof of the general accuracy of the 
 sphygmographic method for physiological purposes, and enables us to 
 guide ourselves in transferring to man, in whom, of course, the sphyg- 
 mograph can alone be used, the information derived from direct 
 manometric observations in animals. 
 
no THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 For the same reason it is unnecessary to discuss the nianometric 
 tracings, as regards the pulsatory phenomena, in all their details. 
 It will be sufficient to say that, while the form of the blood- pressure 
 pulse-curve varies with the mean blood-pressure, th'- dicrotic wave 
 is always marked on it, preceded by one or more oscillations falling 
 within the period of the systole, and followid by one or more within 
 the period of the diastole. When the blooil-pn-ssure is low, the tirst 
 or primary elevation is the highest of the whole curve (Fig. 42). When 
 the blood-pressure is high, the maximum falls later coinciding with 
 
 one of the secondary 
 systolic waves, but 
 always preceding the 
 dicrotic wave; and the 
 
 ^==^ 
 
 curve assumes an 
 erotic character. 
 
 ana- 
 
 That all the secondary 
 oscillations, including the 
 dicrotic wavelet, arc cen- 
 trifugal, and not centrip- 
 etal, may be shown, just 
 as in the sphygmographic 
 method, by recording the 
 blood -pressure simultane- 
 ously at two points of the 
 arterial sj-stcm at differ- 
 ent distances from the 
 heart — e.g.. in the crural 
 and carotid arteries. The 
 secondary waves are 
 found, by measuring the 
 tracings, to reach the 
 more distal point later 
 than the more central. 
 
 The increase of pres- 
 sure during the systole, 
 as indicated by the height 
 of the primary elevation, 
 is always very large , much 
 larger than it appears in a 
 tracing taken with a mer- 
 cury manometer. In the 
 rabbit this pulsatory variation is one-third to one -fourth of the minimum 
 pressure. In the dog it is still greater, owing to the slower rate of the 
 heart, and often amounts to 50 mm. of mercury, while under favourable 
 conditions (low minimum pressure and slowly - beating heart) the 
 systolic increase of pressure may be actually more than double the 
 minimum (Hiirthlc). Pick found also, by means of his spring man- 
 ometer, that the pulsatory variations of blood-pressure were greater 
 than the respiratory variiltions (p. 2Su). although in the records of 
 the mercury manometer the reverse appears often to be the case. 
 Landois, too, in the course of experiments in which a divided artery 
 was allowed to spout against a moving surface, and to trace on it a 
 sort of pulse-curve painted in blood (a hieniautogram as it is called). 
 
 Fig. 41. — .\rrangement for taking a Blood-Pressure 
 Tracing. M, manometer; Hg, niercun-; F, float 
 armed with writing-point; A. thread attached to 
 a wire projecting from the drum and supporting 
 a small weight. The thread keeps the writing- 
 point in contact with the smoked paper on the 
 drum. B is a strong rubber tube connecting the 
 manometer with the artery; C a pinchcock on 
 the rubber tube, which is taken off when a tracing 
 is to be obtained. 
 
MECHANICS OF THE CIRCULATION IN THE VI-SSELS in 
 
 observed that the rate of escape of the blood was nearly 50 per cent, 
 greater during the systole than during the pause of the heart. The 
 existence of the dicrotic wave on this tracing was long looked on as the 
 best proof that it was not an artificial phenomenon. 
 
 The wave of increased pres- 
 sure, as it runs along the arterial 
 system, carries with it wherever 
 it arrives an increase of potential 
 energy. But this excess of po- 
 tential energy is continually being 
 worn down, owing to the friction 
 of the vascular bed; and although 
 in the comparatively large arteries 
 the loss of energy is not great, it 
 rapidly increases as the arteries 
 approach their termination, and 
 begin to break up into the narrow 
 arterioles which feed the capillary 
 network. For not only is the ratio 
 of the total surface to the total 
 cross-section, and therefore the 
 friction, increased with every 
 bifurcation, but the mere change 
 of direction and division of the 
 wave cannot take place without 
 loss of energy. For this reason 
 the fluctuations of blood-pres- 
 sure are greater in the large arteries near the heart than in arteries 
 smaller and more remote. In the wide and much-branched capillary 
 bed the pulse-wave disappears altogether, and the blood-pressure 
 becomes relatively constant or permanent. And it is for some 
 
 purposes convenient to look upon 
 the blood -pressure in the arteries as 
 made up of a permanent element, 
 with pulsatory oscillations super- 
 posed on it. Since no portion of the 
 arterial system is more than partially 
 emptied in the interval between two 
 blood-waves, the minimum or per- 
 manent pressure is always positive 
 —i.e., always above that of the atmosphere, the beats of the heart 
 succeeding each other so rapidly that the successive waves over- 
 lap or ' interfere,' and are only separated at their crests. 
 
 If the heart is stopped while a blood-pressure tracing is being 
 taken — and we shall see later on how this can be done (p. 157) — the 
 minimum Hne of the tracing goes on falhng towards the zero-line. 
 
 Fig. 42. — Curves of Blood-l*ressure taken 
 with a Spring Manometer from the 
 Carotid Artery of a Dog (Hiirthle). 
 When I was taken the blood-pressure 
 was high; 2 corresponds to a medium, 
 3 to a low, and 4 to a very low, blood- 
 pressure; p is the primary elevation 
 — this and the succeeding elevations 
 between p and a are called systolic 
 waves; the systolic waves are followed 
 by a marked elevation d, which corre- 
 sponds to the dicrotic wave. 
 
 v'VWWV'^ 
 
 Fig. 43. — Blood - Pressure Tracing. 
 The horizontal straight line inter- 
 secting the curves is the line of 
 mean pressure. 
 
112 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 When the heart begins beating again, the pressure-curve rises, not 
 by a continuous ascent, but by successive leaps, each corresponding 
 to a beat of the heart, and each overtopping its predecessor, tiU the 
 old line of minimum or of mean pressure is again reached. 
 
 The mean arterial blood -pressure is the permanent pressure plus 
 one-half of the average pulsatory oscillation. In a blood-pressure 
 tracing the line of permanent pressure joins all the minima; the line 
 of maximum pressure joins all the maxima ; the line of mean pressure 
 is drawn between them in such a way that, of the area included 
 between it and the blood- pressure curve, as much lies above as below 
 it (Fig. 43). As has been said, a tracing taken with a mercury man- 
 ometer gives approximate!}' the mean blood-pressure. Each beat of 
 the heart is represented on it by a single elevation of variable size, 
 sometimes not amounting to more than one-twentieth of the height 
 of the curve above the line of zero or atmospheric pressure, but some- 
 times much larger. The oscillations due to the heart-beat are 
 superposed upon much longer, and often, as registered in this way, 
 larger waves, caused by the movements of respiration. So much 
 having been said by way of definition, we have now to consider the 
 amount of the mean arterial pressure, the variations which it under- 
 goes, and the factors on which its maintenance depends. 
 
 As to its amount, it will be sufficiently accurate to say that in the 
 systemic arteries of warm-blooded animals in general (including 
 birds), and of man in particular, the mean pressure does not, under 
 ordinary conditions, descend much below 100 mm. of mercury, nor 
 rise much above 200 mm. ; while in cold-blooded animals it seldom 
 exceeds 50 mm., and may fall as low as 20 mm. 
 
 It does not seem possible, at least with our present data, to further 
 subdivide these two great groups; nor do we know precisely whether 
 the distinction depends mainly on morphological or mainly on physio- 
 logical dififerences, whether, that is to say, the warm-blooded animal 
 has a higher blood-pressure than the cold-blooded chiefly because its 
 vascular system (and especially its heart) is anatomically more perfect, 
 or because its heart beats faster and works harder. It may be that 
 it is for both of these reasons that the birds, which in certain other 
 respects are more nearly related to the reptiles than to the mammals, 
 mount, as regards the pressure of the blood, into the mammalian class, 
 and that a manometer in the carotid of a goose will rise as high, or 
 almost as high, as in the carotid of a horse, a sheep, or a dog, while the 
 pressure in the aorta of a tortoise is no higher than in the aorta of a frog. 
 But we know that the mere average rate of the heart has of itself com- 
 paratively little influence on the blood-pressure within either group, 
 for the heart of a rabbit beats, on the average, very much faster than 
 the heart of a dog. and yet the arterial pressure in the dog is certainly 
 at least as great as in the rabbit. Nor docs the size of the body seem 
 to have any definite relation to the mean pressure, even in animals 
 of the same species; and there is no reason to suppose that the pressure 
 is materially less in the radial artery of a dwarf than in the radial artery 
 of a giant. 
 
MFCflAXICS OF Tin-: CIRCULATION IN THE VESSELS 
 
 "3 
 
 Measurement of the Blood-Pressure in Man .—In man the blood- 
 pressuiv has been estiinatid hy adjusting over an artery an instru- 
 ment known as a sj^liygmomanometer or sphygmometer, which, in 
 its most modern form, consists essentially of a hollow rubber pad or 
 bag containing air, and connected with a metallic pressure gauge or 
 a mercurial manometer. 
 
 The simplest method is that devised by Riva-Rocci (Fig. 44). An 
 armlet in the form of a broad rubber bag, supported externally by 
 canvas or leatlicr, is adjusted round the upper arm. The interior of the 
 bag is connected with a mercury manometer, and also with a strong 
 rubber bulb provided with a valve. By rhythmical compression of 
 the bidb the pressure can be raised. Between the pressure bulb and 
 the rest of the system is a thin rubber balloon, which by its distension 
 renders the changes of pressure more gradual. The finger of the 
 observer is placed (>\er the radial artery, and the 
 pressure is raised luitil the pulse disappears. Then 
 the pressure is allowed to fall gradually, and the 
 manometer reading at the moment when the pidse 
 first reappears in the radial gives the maximum or 
 systolic pressure in the brachial artery. 
 
 Instead of palpating the radial artery, a stetho- 
 scope may be placed over the brachial just below 
 the edge of the armlet, according to the method of 
 Korotkoff, by which, in addition to the systolic, the 
 minimimi or diastolic pressure may be 
 determined. This is much the best of 
 all the methods of measuring the arterial 
 pressures in man. The pressure is 
 raised somewhat above that necessary 
 to obliterate the pulse, and then allowed 
 to fall slowly. At the moment when 
 pulsations first begin to break through 
 below the armlet, a succession of sharp 
 taps, synchronous with the pulse, is 
 heard. The tapping sound grows rapidly 
 louder as the artery opens up more and 
 more, then abruptly diminishes and 
 changes its character, and gradually dis- 
 appears. Several pha.ses have been distinguished after the first maxi- 
 mum. Everybody agrees that the pressure shown by the manometer 
 when the sound is first heard is the sj^stolic pressure. This corresponds 
 closely with the systolic pressure as determined by palpating the radial ; 
 and it can be shown experimentally that at pressures in the armlet 
 exceeding this the lumen of the brachial artery is actually obliterated 
 and not merely narrowed to such a degree as to prevent the passage of 
 the pulse wave, while still permitting the passage of some blood (see 
 Practical Exercises, p. 213). 
 
 The diastolic pressure is the pressure at which a sudden weakening 
 and dulling of the sound occurs (beginning of the fourth phase), and not 
 the pressure at which the sound becomes altogether inaudible (Mac- 
 William, etc.). The sound seems t(j be due to vibrations set up in the 
 walls of the artery and the structures in contact with it when it is 
 suddenly opened by the pul.se waves. According to Erlanger, the essen- 
 tial thing is the ' water hammer ' action of the blood when, moving 
 through the artery under compression in the armlet, it strikes the stag- 
 nant blood in the uncompressed artery below and distends it. 
 
 Fig. 44. — Riva-Rocci Apparatus. 
 a, armlet; b, manometer tube; 
 c, bottle containing mercury, 
 into which b dips ; d, thin 
 rubber bulb ; e, thick rubber 
 bulb for getting up pressure. 
 
114 
 
 THE CIRCULATIOX <>I- THE BLOOD AND LYMPH 
 
 Various instnimenls have been dcvisecl for dctcnniuiiig the blood 
 pressure from tlie changes in the oscillations communicated to the arm- 
 let by the artery as the pressure in the armlet is allowed to fall or caused 
 to rise. The sphygmomanometer of Erlanger (Fig. 45) is arranged to 
 
 obtain graphic records of the pulse 
 from which both the maximum 
 and the minimum blood-pressures 
 may be deduced. The mean pres- 
 sure cannot be directly measured, 
 but must lie much nearer to the 
 minimuin than to the maximum, 
 since the line of mean pressure bi- 
 sects the area enclosed by the 
 pulse curve, and this area is broad 
 at the base and narrow at the apex. 
 The rubber bag is applied in the 
 form of a cuff or armlet to the arm 
 above the elbow over the brachial 
 artery. It communicates with a 
 mercury manometer, which gives 
 the pressure exerted upon the arm. 
 It is also connected with a rubber 
 bulb, B, enclosed in 
 a glass bulb, G, and 
 through a stopcock 
 with a syringe bulb, 
 V, provided with a 
 ^ valve. The space 
 between B and G 
 communicates (1) 
 with the tambour; 
 (2) with the exterior 
 through the stopcock 
 by the tube E, and 
 also through a pin- 
 point opening in the 
 membrane of the 
 tambour. While the 
 armlet is 
 being ad- 
 justed the 
 sto]K-ock is 
 turned so 
 that the rubber bag is 
 in communication with 
 the external air through 
 1". The same is true of 
 the space TS in the 
 glass bulb. The tam- 
 bour is thus protected 
 against undue strain during adjustment. The stopcock is now rotated 
 so as to cut off the armlet from the exterior and to permit the entrance 
 of air through I*" from V, which is used as a pump to raise the pressure, 
 the space TS and the tambour being still in communication with the 
 exterior. When the desired pressure has been reached, the stopcock 
 is turned into an intermediate position, which cuts off both the armlet 
 and the space TS from the exterior, and the pulse is then transmitted to 
 the tambour and recorded on the drum. By certain adjustments of the 
 
 Fig. 45. — Sphygmomanometer of Erlanger. 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 115 
 
 stopcock air can be allowcil to escape more or less rapidly from the 
 armlet. 
 
 To determine the maximum or systolic blood-pressure, the air- 
 pressure in the armlet is raised considerably (about 50 mm. Ilg) above 
 what it is expected to be. While the lever is writing on the drum 
 the small oscillations due to the impact on the bag of the pulse-waves 
 in the central portion of the obliterated artery, the pressure is gradually 
 diminished by allowing air to escape. At the moment when the 
 pressure upon the arm falls below the maximum blood-pressure, and 
 the pulse-wave is first able to break through the brachial artery, the 
 oscillations of the lever will more or less abruptly increase in amplitude. 
 The pressure shown by the manometer at this point is the systolic 
 blood-pressure. To obtain the minimum or diastolic pressure, the air- 
 pressure in the armlet is raised somewhat (to to 15 mm. Hg) above the 
 pressure expected. The pressure is diminished by 5 mm. Hg at a time, 
 records of the oscillations being taken on the drum. The manometer 
 reading at the point at which the oscillations, after reaching the maxi- 
 mum, begin abruptly to diminish, corresponds to the minimum blood- 
 pressure. 
 
 According to Brooks and Luckhardt, the criteria which are supposed 
 to fix the systolic and diastolic pressures in these and similar methods 
 yield results which are too high. The personal equation also seems to 
 introduce a considerable error in the selection of the points on the trac- 
 ings at which the characteristic changes are supposed to occur (Kilgore). 
 
 In using the sphygmometer of Hill and Barnard (Fig. 46), the bag 
 is inflated till the pulsation indicated by the gauge reaches a maxi- 
 mum. The mean 
 pressure shown 
 at this point is 
 assumed to be 
 equal to,or some- 
 what greater 
 than, the dia- 
 stolic pressure. 
 
 The effect of 
 muscular exer- 
 cise upon the 
 pressure is in- 
 fluenced by the 
 nature of the 
 work. Such an 
 effort as the lift- 
 ing of a heavy 
 weight causes 
 a sudden and 
 great increase, 
 which is very 
 transient. Thus, 
 
 the average arterial pressure in a number of men was 11 1 before, 
 180 during, and no two to three minutes after the lift (McCurdy). The 
 rise of pressure in this case is dvie largely to the marked diminution of 
 the calibre of the bloodvessels mechanically produced by the strong 
 and sustained contraction of the muscles. This increases the resistance 
 to the passage of the blood along the arteries, while the veins are emptied 
 by the pressure, and more blood thus reaches the right side of the heart. 
 It is obvious that the heart and vessels may easily be exposed to an 
 injurious strain during such eftorts. In such an exercise as running, 
 while the pressure mounts to some extent at first, as already mentioned, 
 
 Fig. 46. — Sphygmometer of Hill and Barnard. It consists of 
 a broad armlet, A, connected by a T-tube, B, with a pressure 
 gauge, C, and a small compressing air-pump, D, fitted with 
 a valve. 
 
ii6 THE CIRCULATION OF THE BLOOD AXD LYMPH 
 
 the rise is not mainlaineil. owing to the dilatation of the cutaneous 
 vessels. In the antcrif)r tibial artcrj- of a boy whose leg was to Ix: 
 amputated, the blood-pressure, measured by means of a manometer 
 connected directly with the artery, was found to vary from loo to 
 i6o mm., according to the position of the body and other circum- 
 stances. In a woman sixty years old, in good health, the following 
 readings were obtained with a sphygmomanometer: 
 
 June 28 . _ - . - 126^130 mm. of mercury. 
 
 ,, 29 - - - - - 126 — 136 
 Aug. 3 132—144 
 
 ,.7 134—140 
 
 ,.12 136 — 144 
 
 Such mcasurcMiients on man show that the mean blood-pressure 
 under similar conditions in one and the same artery, and in one and 
 the same indivndual, may vary for a considerable time only within 
 comparatively narrow limits. 
 
 This relative constancy of the general arterial pressure is the 
 result of a dehcate adjustment between the work of the heart, the 
 resistance of the vessels, and the volume of the circulating liquid. 
 The quantity of the blood is tolerably steady in health, and con- 
 siderable changes may be artificially produced in it (p. 191) without 
 affecting the pressure in any great degree. On the other hand, the 
 work of the heart and the peripheral resistance are highly variable 
 and vastly influential. A narrowing of the arterioles throughout 
 the bod\^ or in some extensive vascular tract increases the peripheral 
 resistance; and if the heart continues to beat as before, the pressure 
 must rise. If the arterioles are widened, while the heart's action 
 remains unchanged, the pressure must fall. In like manner an 
 increase or a decrease in the activity of the heart, in the absence of any 
 change in the peripheral resistance, will cause a rise or a fall in the 
 blood-pressure. But if a slowing of the heart is accompanied by an 
 increase in the peripheral resistance, or a dilatation of the arterioles 
 by an increase in the activity of the heart, the one change may be 
 partially or completely balanced by the other, and the pressure may 
 vary within narrow hmits or not at all. 
 
 Not only is the mean pressure, as measured in a large artery, 
 tolerably constant, but if recorded simultaneously in two arteries at 
 different distances from the heart, it is seen to decrease very gradu- 
 ally so long as the arteries remain large enough to hold a cannula. 
 It is nearly as high, for instance, in the crural artery of a dog as in 
 the carotid. It is easy to see that this must be so, for the resistance 
 of the arteries between the point where the arterioles are given off 
 and the heart is only a small fraction of the total resistance of the 
 vascular path; and we have said (p. 84) that the lateral pressure at 
 any cross-section of a system of tubes through which liquid is flow- 
 ing is proportional to the resistance still to be overcome. This is 
 also the reason why the pressure is always much lower in the pul- 
 monary artery and right ventricle than in the aorta and left ventricle 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 117 
 
 (only one -fifth to one-sixth as great), for the total resistance of the 
 vascular path through the lungs is much less than that of the 
 systemic circuit. In dogs with natural respiration the pressure in 
 the pulmonary artery was found to vary between 14 and 26 mm. of 
 mercury, averaging about 20 mm. 
 
 The Velocity-Pulse. — We have seen that the blood is propelled 
 through the arteries in a series of waves that travel from the heart 
 towards the periphery. The particles in the front of the pulse-wave 
 are constantly changing, but since every section of the arterial tree 
 is successively distended, every section contains more blood while 
 the pulse-wave is passing over it than it contained immediately 
 before. And since there is always a fairly free passage for this blood 
 towards the periphery, there is a bodily transfer on the whole of a 
 certain quantity with every wave. 
 
 The translation of the blood, instead of being entirely intermittent, 
 as it would be in a rigid tube or in an elastic system with a slow 
 action of the central pump, is to some extent constantly going on ; 
 for a portion of a blood-wave is always passing through every section 
 of the arterial channel. Thus, we arrive at the same distinction as 
 to the onward movement of the blood itself as we previously reached 
 in regard to the blood-pressure, the distinction between the constant 
 or permanent factor of the velocity and the periodic factor, which 
 we may call the velocity-pulse. 
 
 The Velocity of the Blood. — By the velocity or rate of flow of a river 
 we should mean, if the flow were uniform throughout the whole cross- 
 section, the rate of movement of any given portion or particle of the 
 water. If we could identify a portion of the water, we could determine 
 the velocity by measuring the distance travelled over by that portion 
 in a given time. If the velocity was uniform over the channel, we could 
 predict the actual time which would be required to traverse any 
 fractional part of the measured distance. If, however, the velocity 
 of the current changed from point to point, then we could only deduce 
 from our observation the mean rate of the river for the measured dis- 
 tance. To determine the actual rate for any given portion of this 
 distance over which the rate was uniform, we should have to make a 
 separate observation for this portion alone. 
 
 But as soon as we pass from an ideal frictionless river to an actual 
 stream, in which the water at the bottom and near the banks flows 
 more slowly than that in the middle and on the surface, we are in every 
 case restricted to the notion of mean velocity. We may distinguish 
 between the velocity of different parts of the current, between that of 
 the mid-stream and the side current, the bottom and the surface layers; 
 but when we consider the river as a whole, we take cognizance only 
 of the mean or average velocity. And at any cross-section this may 
 be defined as the volume of water passing per hour, or whatever the 
 unit of time may be, divided by the cross-section of the current. It is 
 evident that this does not enable us to determine the actual velocity 
 of any given particle of the water at any given moment within a 
 measured interval ; nor does it tell us whether or not the average velocity 
 of the current has itself undergone variations within the period of 
 observation. 
 
Ii8 THF. CIRCULATION OF THE BLOOD AND LYMPH 
 
 Wc lia\(! dwelt upon this point because the measurement of the 
 velocity of the blood, to which we must now turn, involves the same 
 considerations. Within the smaller arteries, as the microscope 
 shows us, and as we should in any case expect from what we know 
 of fluid motion, the blood-current, apart from the periodical varia- 
 tions in its velocity, due to the action" of the heart, varies in speed 
 . from point to point of the same cross-section. The layer next the 
 periphery of the vessel, the so-called peripheral plasma-layer or 
 Poiseuille's space, moves more slowly than the central portion, the 
 axial stream. In fact, we must suppose that in the large as well as 
 in the small vessels the layer just in contact with the vessel-wall is 
 at rest, while the stratum internal to this slides on it and has its 
 velocity diminished by the friction. The next layer again slides on 
 the last, but since this is already in motion, its velocity is not so 
 much diminished, and so on. The velocity' must therefore increase 
 as we pass towards the axis of the bloodvessel, and reach its maxi- 
 mum there (p. 193). 
 
 Again, the velocity must be altered wherever an alteration occurs 
 in the width of the bed, that is, in the total cross-section of the 
 vascular system ; for since as much blood comes back in a given time 
 to the right side of the heart as leaves the left side, the same quantity 
 must pass in a given time through every cross-section of the circula- 
 tion. Wherever the total section of the vascular tree increases, the 
 blood-current must slacken; wherever it diminishes, the current 
 must become more rapid. Now, the total section, increasing some- 
 what as we pass from the heart along the branching arteries, under- 
 goes an abrupt augmentation, and reaches its maximum in the 
 capillary region. It suddenly diminishes again at the venous end 
 of the capillar}^ tract, and then more gradually as we pass heart - 
 wards along the veins, but never becomes so small as in the arterial 
 tract. We must, therefore, expect the mean velocity to be greatest 
 in the large arteries, less in the veins, and least in the arterioles, 
 capillaries, and venules. It must, of course, be remembered that the 
 total section varies from time to time at any given distance from the 
 heart. The capillary tract is especially variable in its area, and 
 capillaries full of blood at one moment may be collapsed and empty 
 at another, according to the changes of calibre and pressure in the 
 arteries which feed and the veins which drain them. 
 
 Although in strictness we are only at present concerned with the 
 arteries, it will be well to consider here what a change of velocity at 
 any part of the vascular channel really implies. To say that when 
 the channel widens the velocity diminishes is not to explain the 
 meaning of this diminution. A diminution of velocity implies a 
 diminution of kinetic energy, and it is necessary to know what becomes 
 of the energy that disappears. The stock of energy imparted by the 
 contraction of the heart to a given mass of blood constantly diminishes 
 as it passes round from the aorta to the right side of the heart, for 
 friction is constantly being overcome and heat generated. Tliis energy, 
 
Mechanics of the circulation in the vessels iir> 
 
 as \vc have seen, exists in a moving liquid in two forms, potential and 
 kinetic, the former being measured by the lateral pressure, the latter 
 var^-ing directly as the square of the velocity. Whenever the velocit}', 
 and therefore the kinetic energy, of a given mass of the blood is 
 diminished without a corresponding increase in the potential energy, 
 some of the total stock of energy must have been used up to overcome 
 resistance (p. 84). 
 
 In a uniform, rigid, horizontal tube, as has been already remarked, 
 the velocity (and consequently the kinetic energy) is the same at 
 ever^' cross-section of the tube, while the potential energy, represented 
 by the lateral pressure, diminishes regularly along the tube. When 
 the calibre of the tube varies, it is different. Suppose, for instance, 
 that the liquid passes from a narrower to a wider part, the velocity 
 must diminish in the latter. The kinetic energy of visible motion 
 which has disappeared must liave left something in its room. Here 
 there are three possibilities: (i) The kinetic energy that has disappeared 
 may be just enough to overcome the extra friction in the wider part of 
 the tube due to eddies and consequent change of direction of the lines 
 of flow; in this case the potential energy of a given mass of the liquid 
 will be the same at the beginning of the wider part as in the narrower 
 part. The lost kinetic energy will have been transformed into heat. 
 (2) The kinetic energv' which has disappeared may be greater than is 
 enough to overcome the extra resistance ; a portion of it must, therefore, 
 have gone to increase the potential energy, and the lateral pressure will 
 be greater in the wide than in the narrow part. (3) The lost kinetic 
 energ}' may be less than enough to overcome the extra resistance ; in 
 this case both the lateral pressure and the velocity will be less in the 
 wide than in the narrow part. It has been experimentally shown that 
 when a narrow portion of a tube is succeeded by a considerably wider 
 portion, and this again by a narrow part, case (2) holds; and the liquid 
 may, under these conditions, actually flow from a place of lower to a 
 place of higher lateral pressure. 
 
 In the vascular s\-stein the conditions are not the same. The 
 widening of t le bed which takes place as we proceed in the direction 
 of the arterial current is not due to the widening of a single trunk, 
 but to the branching of the channel into smaller and smaller tubes. 
 In the larger arteries the increase of resistance is so gradual that both 
 the potential and the kinetic energy diminish only slowly, and the 
 lateral pressure and velocity are not much less in the femoral artery 
 than in the aorta or carotid. But in the arterioles the friction 
 increases so greatly that although the velocity, and therefore the 
 kinetic energy, in the capillary region is much less than in the 
 arteries, the amount of kinetic energy lost is not upon the whole 
 equivalent to the energy consumed in overcoming the extra resis- 
 tance; the potential energy of the blood is also drawn upon, and the 
 lateral pressure falls sharply in the capillary region, as well as the 
 velocity. Where the capillaries open into the veins, the lateral pres- 
 sure again sinks abruptly, while the velocity begins to increase, tiU in 
 the largest veins it is probably about half as great as in the aorta. 
 Where does the extra kinetic energy of the blood in the veins come 
 from ? To say that the vascular channel again contracts as the 
 blood passes from the capillaries into the veins, and that, since the 
 
120 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 same quantitj' must How tlirough every cross-section of the channel, 
 the velocity must necessarily be greater in the narrower than in the 
 wider part, docs not answer the question. The greater portion of 
 tlie kinetic energy of the arterial blood is, as we have seen, destroyed, 
 or, rather, changed into an unavailable form, into heat, in the capil- 
 lary region. The mean velocity of the blood in the capillaries is not 
 more than -5^-^ to 77^ of the velocity in the aorta; the kinetic energy 
 of a given mass of blood in the capillaries cannot therefore be more 
 than („ J^)2, or 4-5 075-0 o^ ^^^ kinetic energy in the aorta. In the veins, 
 taking the velocity at half the arterial velocity, the kinetic energy 
 of the mass would be one-fourth of that in the aorta, or at least 
 10,000 times as great as in the capillary region. This extra kinetic 
 energy comes partly from the transformation of some of the poten- 
 tial energy of the blood. The resistance in the veins is very small 
 compared with that in the capillaries; less of the potential energy 
 represented by the lateral pressure at the end of the capillary tract 
 is required to overcome this resistance, and some of it is converted 
 into the kinetic energy of visible motion, the lateral pressure at the 
 same time falling somewhat abruptly. Contributory sources of 
 kinetic energy in the veins are the aspiration caused by the respira- 
 tory movements and the pressure caused by muscular contraction 
 in general, which, thanks to the valves, always aids the flow towards 
 the heart. From these two sources new energy is supplied, to rein- 
 force the remnant due to the cardiac systole (p. 133). 
 
 Measurement of the Velocity of the Blood — i. Direct Observation. — 
 (a) This method can be applied to transparent parts by observing the 
 rate of flow of the corpuscles under the microscope. But it is only 
 where the blood moves slowly, as in the capillaries, that the method 
 is of use . (b) Part of the path of the blood through a large vessel may 
 be artificially rendered transparent by the introduction of a glass tube, 
 of approximately the same bore as the vessel (Volkmann). The tube 
 is filled with salt solution, and the blood admitted by means of a stoji- 
 cock at the moment of observation. The time which the blood takes 
 to pass from one end of the tube to the other is noted, and the length 
 divided by the time gives the velocity of the blood in the tube. If the 
 calibre of the tube is the same as that of the artery, tliis is also the 
 velocity in the vessel; but if the calibre is different, a correction would 
 have to be made. The method is not a good one, for the reason, among 
 others, that the long tube introduces an extra resi.stance. 
 
 2. Ludwig's Stromuhr. — This instrument measures the quantity of 
 blood which passes in a given time through the vessel at the cross- 
 section where it is inserted. It consists of a U-shaped tube, with the 
 limbs widened into bulbs, but narrow at the free ends, which are con- 
 nected with a metal disc. By rotating the instrument, these ends 
 can be placed alternately in communication with a cannula in the 
 central, and another in the peripheral, portion of a divided artery; 
 or they can be placed so that none of the blood passes through the bulbs, 
 but all goes by a short-cut. One limb of the instrument is filled with 
 oil, and the other with defibrinated blood. The limb containing the 
 oil is first put into communication with the central end. and that con- 
 taining the blood witli the peripheral end, of the artery. The blood 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 121 
 
 from the artery rushes in and displaces the oil into the other limb, tlie 
 defibrinated blood passing on into the circuhition. As soon as the bloofl 
 has reached a certain height, indicated by a mark, the instrument is 
 reversed and the oil is again displaced into the limb it originally 
 occupied. This process is repeated again and again, the time from 
 
 beginning to end of an experiment being 
 carefully noted. The number of times 
 the blood has filled a bulb in that 
 period, the capacity of the bulb and the 
 cross-section of the vessel being known, 
 all the data required for calculating the 
 velocity of the blood in the vessel have 
 been obtained. 
 
 Suppose, for example, that the cap- 
 acity of the bulb up to the mark is 5 c.c, 
 and that it is filled twelve times in a 
 minute, the quantity flowing through 
 the cross-section of the artery is i c.c, 
 or 1,000 cub. mm., per second. Let the 
 diameter of the vessel be 3 mm., then its 
 /'3y_ 3-i4X9 , 
 
 sectional area is tt x 
 
 -=J lir~^ 
 
 Fig. 47. — Stromuhr of Ludwig and 
 Dogiel. A, B, glass bulbs; a, a 
 metal disc, to which A and G 
 are attached, and which can be 
 rotated on the disc b; E, F, can- 
 nula attached to b, and con- 
 nected with the peripheral and 
 central ends of a divided blood- 
 vessel. .\t the beginning of the 
 experiment, A and the junction 
 between A and B are filled with 
 oil; B is filled with physiological 
 salt solution or defibrinated 
 blood: a being turned into the 
 position shown in the figure, the 
 blood passes through F and D 
 into A , and the oil is forced into 
 B. As soon as the blood has 
 reached the mark m, the disc a, 
 with the bulbs, is rapidly ro- 
 tated, so that C is now opposite 
 jF. The blood now passes into 
 B, and the oil is again driven 
 into A. When the oil has 
 reached D, reversal is again 
 made, and so on. 
 
 = 7-06 
 
 sq. mm. The velocity is — ;-^ = 141 mm 
 
 per second. 
 
 Various improvements in this method 
 have been made, such as a graphic regis- 
 tration of the reversals of the stromuhr. 
 
 3. A tube or box, in which swings a 
 small pendulum, is inserted in the course 
 
 Fig. 48.— Pitot'l-Tubes. 
 
 of the vessel. The pendulum is deflected 
 by the blood, and the amount of the 
 deflection bears a relation to the ve- 
 locity of the stream (Vierordt's hcsmatachometer ; Chauveau and Lortet's 
 much more perfect dromograph) (Fig. 49). 
 
 4. Pilot's Tubes.— li two vertical tubes, a and b, of the form sho\vn in 
 Fig. 48, be inserted into a horizontal tube in which liquid is flowing in 
 the direction of the arrow, the level will be higher in a than would be 
 the case in an ordinary side-tube without an elbow ; in 6 it will be lower. 
 For the moving liquid will exert a push on the column in a, and a pull 
 
nil-: CIRCULATION 0I< THE BLOOD AND LYMPH 
 
 tfffjL'Tj'j.^'g 
 
 on that in h. The amount of this push and pull will vary with the 
 velocity, so that a change in the latt r will correspond to an alteration 
 in the difference of level in the two tubes. Instruments on this prin- 
 ciple have been constructed by Marey and Cybulski, the former regis- 
 tering the movements of the two columns of blood by connecting the 
 tubes to tambours provided with writing levers, the latter by photo- 
 graphy (Fig. 50). 
 
 5. 7 he electrical method, described on p. 135, 
 for the measurement of the circulation time, can 
 also be applied to the estimation of the mean 
 velocity of the blood between two cross-sections 
 of the arterial path which are separated by a 
 sufficient distance. For example, salt solution 
 can be injected into the left ventricle or the be- 
 ginning of the aorta, and the interval which it 
 takes to reach a pair of electrodes in contact with, 
 say, the femoral artery determined. Kjiowing 
 the distance between the point of injection and 
 the electrodes, we can then calculate the mean 
 velocity. 
 
 6. In the calorimetric method of measuring the 
 quantity of blood which passes through such 
 parts as the hands (or feet) in man, the flow is 
 deduced from the quantity of heat given off by 
 the part in a given time, and the difference be- 
 tween the temperatures of the blood entering and 
 leaving the part. The hands are immersed in a 
 large bath of water (a few degrees below arterial 
 blood temperature) for a sufficient time to permit 
 any change of temperature of the parts due to 
 the difference in temperature between them and 
 the water to be estabhshed. The hands are then 
 rapidly transferred to calorimeters previously 
 filled with water at the same temperature as that 
 of the bath. All the heat henceforth given off 
 can be assumed to be due to the cooling of the 
 blood passing through the hands, since the small 
 amount of heat produced in the resting hands is 
 negligible for this purpose. The temperature of 
 the arterial blood at the wrist is taken as 0*5° C. 
 below that of the rectum, this beuig the relation 
 actually found in a normal man.* The tempera- 
 ture of the venous blood leaving the hand is taken 
 as that of the calorimeter, since it has been found 
 that blood withdrawn from the hand veins by 
 puncture, and collected with suitable precautions 
 to prevent loss of heat as far as possible and to 
 permit the calculation of the unavoidable loss, 
 has a temperature only a negligible fraction 
 
 of a degree above that of the bath in which the hand is im- 
 mersed. The flow in grammes per minute is obtained from the formula 
 
 H I 
 
 Q= /-. 'YTy "' where Q is the quantity of blood, H the number 
 
 * The temperature of the arterial blootl at the wrist was assumed to be the 
 calorimeter temperature at which the calorimeter neither loses heat to tlie hand 
 nor gTJns heat from it. If the heat production in the resting hand is negligible, 
 this must correspond to the temperature of the entering blood. 
 
 Fig. 49. — Chauveau's 
 Dromograph. A, tube 
 connected with blood- 
 vessel; B, metal cylin- 
 der in communica- 
 tion with A. The upper 
 end of B has a hole in 
 the centre, which is 
 covered by a mem- 
 brane, m, through 
 which a lever, C, 
 passes; C has a small 
 disc, p, at its end, 
 which projects into the 
 lumen of A, and is de- 
 flected in the direction 
 of the blood - stream 
 through A. The de- 
 flection is registered by 
 a recording tambour in 
 communication by the 
 tube E with a tambour 
 D, the flexible mem- 
 brane of which is con- 
 nected with the lever 
 or pendulum C. 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 
 
 123 
 
 of small calorics (gramme-calories) given off in m minutes, T the tem- 
 perature of the blood entering the hand, T^ the temperature of the 
 blood leaving the hand, and s the specific heat of blood (o-g). For 
 purposes of comparison the volume of the hands is measured, and the 
 blood-flow expressed in grammes per 100 c.c. of hand per minute. 
 Further details are given in the Practical Exercises (p. 219). Fig. 51 
 shows one of the calorimeters on its adjustable stand. The collar of 
 thick felt which fits closely around the wrist, and prevents loss of heat 
 from the orifice through which the hand is 
 inserted, is shown standing on the top of 
 the calorimeter, as also the thermometer 
 with the small sliding lens, or ' reader.' In 
 Fig. 108, p. .220. the position of the subject 
 with haads in the calorimeters is shown. 
 
 Fig- 50. — Cybulski's Arrangement for recording 
 Variations in the Velocity of the Blood. A, tube 
 connected with central, B with peripheral, end 
 of divided bloodvessel. The blood stands higher 
 in the tube C than in D. A beam of light passing 
 through the meniscus in both tubes is focussed by 
 the lens L on the travelling photographic plate E. 
 The velocity at any moment is deduced from the 
 height of the meniscus in the two tubes C and D. 
 
 Fig. 51. — Calorimeter with 
 stand for measuring 
 blood-flow in hand. 
 
 Of these methods, 3 and 4 are alone suited for the study of the 
 velocity-pulse, that is, the change of velocity occurring with every 
 beat of the heart. The curves obtanied by Chauveau's dromo- 
 graph show a general agreement with blood-pressure tracings taken 
 by a spring manometer, and with records of the external pulse 
 obtained by a sphygmograph. There is a primary increase of 
 velocity corresponding with the ventricular systole, and a secondary 
 increase corresponding wdth the dicrotic wave (Fig. 54). Like all 
 the other pulsatory phenomena, the velocity-pulse disappears in the 
 capillaries, and is only present under exceptional circumstances in 
 the veins. 
 
124 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 Fick, from a comparison of sphygmographic and plethysmographic 
 tracings (p. 128). taken simultaneously from the radial artery and 
 the hand, has demonstrated that in man the vcItm it\ pnlsc exhibits 
 
 tig. 52. Fig. 53. 
 
 Fig. 52. — The highest of the three curves is a plethysmographic record taken from 
 the hand; the second curve is a sphygmogram taken simultaneously from the 
 corresponding radial artery; the lowest (interrupted) curve is the curve of velocity 
 deduced from a comparison of the first two (Fick). 
 
 Fig- 53- — Simultaneous plethysmographic and sphygmographic tracings. 
 
 the same general characters as in animals (Figs. 52 and 53). And 
 V. Kries has confirmed Fick's conclusions by actual records of the 
 velocity-pulse obtained by means of an arrangement called a gas 
 tachograph (Fig. 55). 
 
 Fig. 54. — Simultaneous Tracings of the Velocity (Upper Curs'c) and I'rcssure (Lower 
 Curve) (Lortet). The tracings were taken from the carotid artery of a hersc. 
 The curve of velocity was obtained by the dromograph. The dicrotic wave is 
 marked on it. The slightly curved ordinates drawn through the cur\'es indicate 
 corresponding points. 
 
 This consist.s of a plethysmograph connected with the tube of a gas- 
 burner. Wlicn the part enclosed in the plethysmograph expands, air 
 issues from the connecting tube, and causes an increase in the height of 
 the flame. When the part shrinks, air is dra\vn in from the flame, 
 which is depressed. Since the speed of the blood in the veins may be 
 considered constant during the time of an experiment, the rate at which 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 125 
 
 the volume of tlie part alters at any moment is a measure of the pulsa- 
 tory clumge of velocity in the arteries of the part. And by photo- 
 graphing the movements of the flame on a travelling sensitive surface, 
 the velocity-pulse is directly recorded. 
 
 The mean velocity, like the mean blood-pressure, is more variable 
 in the large arteries near the heart than in the smaller and more 
 di stant arteries. 
 Dogiel found in 
 measurements 
 taken with the 
 stromuhr (a good 
 instrument for the 
 estimation of mean 
 speed), within a 
 period of two 
 minutes, velocities 
 ranging from over 
 200 mm. to under 
 100 mm. per second 
 in the carotid of the 
 rabbit, and from over 500 mm. to less than 250 mm. in the carotid of 
 the dog. Chauveau, with the dromograph, found the velocity in the 
 carotid of a horse to be 520 mm. per second during systole, 150 mm. 
 during the pause, 220 mm. during the period of the dicrotic wave. 
 
 It is probable, however, that, if these numbers are at all accurate 
 for bloodvessels in the immediate neighbourhood of the heart, there 
 must be a rapid diminution in the velocity even while the arteries 
 are still of considerable calibre. For it has been found by the 
 electrical method that, in anaesthetized dogs at any rate, as is shown 
 in the following table, the mean velocity between the origin of the 
 aorta and the crural artery in the middle of the thigh is usually less 
 than 100 mm. per second. 
 
 Fig- 55- — Photographic Record of the Velocity-Pulse ob- 
 tained by the Gas Tachograph (v. Kries). The upper 
 curve is the photographic representation of the move- 
 ments of the flame, and corresponds to the curve of 
 velocity. 
 
 
 
 Distance 
 
 Average Time be- 
 
 
 Average 
 Velocity 
 
 Average 
 
 No. of 
 
 Body- 
 
 between Point 
 
 tween Injection 
 
 Average 
 
 Distance 
 
 traversed per 
 
 Heart-beat, 
 
 in Milli- 
 
 Experi- 
 
 weight 
 
 of Injection and 
 
 and Arrival of the 
 
 Pulse-rate 
 
 per 
 Secoi d, 
 in Milli- 
 
 ment. 
 
 in Kilos. 
 
 Electrodes, 
 in Millimetres. 
 
 Salt Solution, in 
 
 per Minute. 
 
 
 
 
 
 
 metres. 
 
 metres. 
 
 I. 
 
 34-55 
 
 420 
 
 4-62 
 
 105 
 
 90-9 
 
 51-9 
 
 II. 
 
 17-5 
 
 495 
 
 5-7 
 
 69 
 
 86-8 
 
 75-4 
 
 III. 
 
 14-99 
 
 400 
 
 5-0 
 
 102 
 
 8o-o 
 
 47-0 
 
 IV. 
 
 10-32 
 
 470 
 
 7-12 
 
 74-5 
 
 72.9 
 
 587 
 
 V. 
 
 7-165 
 
 330 
 
 7-83 
 
 46-3 
 (weak beat) 
 
 42-1 
 
 54-5 
 
 In I. the injecting cannula was in the descending part of the thoracic 
 aorta, in V. at the very origin of the aorta, and in II., III., and IV. 
 in the left ventricle. 
 
126 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 As to the speed of the blood in the arteries of man, our data are 
 insufficient for more than a loose estimate. But it does not seem 
 likely that the mean velocity of a particle of blood in moving from 
 the heart to the femoral artery can exceed 150 mm. per second for 
 the whole of its path. This would correspond to rather more than 
 a third of a mile per hour. In the arch of the aorta the average 
 speed may be twice as great. ' The rivers of the blood ' are, even 
 at their fastest, no more rapid than a sluggish stream. A red cor- 
 puscle, even if it continued to move with the velocity with which it 
 set out through the aorta, would only cover about 15 miles in twenty- 
 four hours, and would require five years to go round the world. 
 
 The average flow through the hands of a healthy young man, as 
 determined in eighteen experiments on different dates ranging over 
 two years, at room temperatures varying from 19° to 27° C, was 
 12-8 grammes per 100 c.c. of hand per minute for the right hand, and 
 12*3 grammes for the left. Ten of the observations on tliis man are con- 
 densed in the table. 
 
 Date. 
 
 Temperature of — 
 
 Blood-flow in Grammes 
 
 per 100 c.c. of Hand 
 
 per Minute. 
 
 Room. 
 
 Arterial 
 Blood. 
 
 Calorim. 
 
 Right. 
 
 Left. 
 
 November 30, 19 10 - 
 
 December 22, 1910 - 
 February i, 191 1 
 March 17, 191 1 
 May 24, 191 1 - 
 November 3, 191 1 - 
 November 9, 1911 - 
 November 15, 191 1 - 
 December 11, 1911 - 
 March 26, 1913 
 
 20*2 
 2I'I 
 22-8 
 2I-I 
 27-0 
 25-1 
 24-1 
 25-2 
 24-5 
 24-5 
 
 36-6 
 36-8 
 
 36-9 
 36-6 
 36-8 
 367 
 36-7 
 36-8 
 36-6 
 36-6 
 
 28-0 
 29.7 
 
 30-3 
 29-9 
 
 30 -9 
 30-0 
 30-8 
 
 30-8 
 3I-I 
 31-5 
 
 lO-I 
 
 137 
 12-6 
 
 II-8 
 18-5 
 
 I2-I 
 
 13-7 
 14-0 
 12-4 
 
 147 
 
 9-4 
 
 12-5 
 12-7 
 
 II-3 
 
 17-5 
 
 II-7 
 
 1^-5 
 13-8 
 
 I2'0 
 
 I5-I 
 
 Since the great function of the circulation in the skin is the regulation 
 of the temperature of the body (see Chapter XII. ), the blood-flow in 
 the hands is, of course, much influenced by the external temperature. 
 Thus, by far the greatest flow in the above table corresponds to the 
 high room temperature of 27° C. With a given external temperature, 
 the degree of humidity of the air also affects the flow. Under similar 
 conditions of external temperature and daily routine, including diet, 
 the hand flow in one and the same individual does not ^■ary greatly 
 when measured at about the same hour on different days. Different 
 individuals, when tested under apparently similar conditions, show a 
 greater range in the blood-flow. Some normal persons know and say 
 that their hands are habitually cool or cold; others, like the man on 
 whom the above results were obtained, that their hands are habitually 
 warm. The former may be expected to show a relatively small, and 
 the latter a relatively large, flow of blood through the liands. It is 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 127 
 
 possible that such habitual differences are associated with differences 
 in the total heat value of the food consumed or in the proportions of 
 the various food substances, especially of proteins (sec p 605), 
 for it is well known that even persons engaged in the same work, and 
 living under similar external conditions, may differ greatly in their 
 dietetic habits, both as to (juantity and quality of the food. And since 
 the cutaneous circulation is by far the most important factor in the 
 loss of heat from the body, the hearty eaters, other things being equal, 
 may be expected to have the largest blood-flow through parts like the 
 hands. The importance of the flow through the skin in the total hand 
 flow is illustrated by the fact that the flow per unit of volume through 
 the distal half of the hand, which, of course, has a large surface in 
 proportion to its volume, is considerably greater than through the hand 
 as a whole. For the forearm the flow per 100 c.c. is, in its turn, much 
 less than in the hand (ilewlett) . In the foot the blood-flow, as estimated 
 by the calorimetric method, is smaller per unit of volume of the part 
 than in the hand, the ratio of foot flow to hand flow per 100 c.c. of the 
 part usually lying in normal persons between i to 3 and i to 2. This 
 is largely due to the proportionally greater proportion of skin in the 
 hand, as well as to the smaller proportion of bone, which has not an 
 active circulation. In the sitting position the following results were 
 obtained for the flow in the feet on the person whose hand flows have 
 been given above : 
 
 Dat«. 
 
 Temperature of-^ 
 
 Blood-flow in Grammet 
 
 per loo c.c. of Foot 
 
 per Minute. 
 
 Room. 
 
 Arterial 
 Blood. 
 
 Calorim.! 
 
 Right. 
 
 Left 
 
 May 2, 191 1 - - - 
 May 18, 1911 - - - 
 June 17,1911 - - - 
 March 26, 1913 
 
 25-2 
 26'4 
 21-8 
 
 24-5 
 
 36-8 
 36-9 
 
 37-0 
 36-5 
 
 30-4 
 
 31-4 
 30-6 
 
 31-4 
 
 3-5 
 3-5 
 
 4-9 
 3-9 
 
 4-2 
 
 4-1 
 
 The great variations in the vascularity of different organs and parts, 
 as revealed by the examination of injected specimens or by inspection 
 of the organs during life, indicate that there must be great differences 
 in the blood-flow. Observations with the stromuhr in animals have 
 shown that this is the case. The following list gives the number of 
 c.c. of blood passing per minute through 100 grammes of organ, according 
 to the results of Burton-Opitz, Tigerstedt, and other observers : 
 
 Posterior extremity. 
 
 5 
 
 Liver (venous) 
 
 59 
 
 Skeletal muscle 
 
 .... 12 
 
 Liver (total) . . 
 
 84 
 
 Head 
 
 .. 20 
 
 Brain . . 
 
 .. 136 
 
 Stomach 
 
 . . 21 
 
 Kidney 
 
 .. 150 
 
 Liver (arterial) 
 
 ... 25 
 
 Adrenal 
 
 500 
 
 Intestines 
 
 .. 31 
 
 Thyroid gland 
 
 .. 560 
 
 Spleen 
 
 .. 58 
 
 
 
 The Volume-Pulse. — When the pulse- wave reaches a part it dis- 
 tends its arteries, increases its volume, and gives rise to what may 
 be called the volume-pulse. 
 
128 
 
 THE CIRCULATION^ OF THE BLOOD AND LYMPH 
 
 This may be readily recorded by means of a plethysmograpli , an 
 instrument consisting essentially of a chamber with rigid walls which 
 enclose the organ, the intervening space being filled up with liquid 
 (Fig. 56). The movements of the liquid are transmitted either through 
 a tube filled with air to a recording tambour, or directly to a piston or 
 float acting upon a writing lever. Special names have been given to 
 plethysmographs adapted to particular organs; for example, Roy's 
 oncometer for the kidney. The method has been successfully applied 
 to the investigation of circulatory changes in man, a finger, a hand or 
 an entire limb being enclosed in the plethysmograpli. With a fairly 
 sensitive arrangement, every beat of the heart is represented on the 
 tracing l>y a primary elevation and a dicrotic wave (Fig. 57). 
 
 The general appearance of the 
 curve is very similar to that of an 
 ordinary pulse-tracing, though 
 there are some differences of detail, 
 especially in the time relations. A 
 volume-pulse has been actually ob- 
 served not only in limbs and por- 
 tions of hmbs, but also (in animals) 
 in the spleen, kidney and brain 
 and other organs, and in the orbit. 
 
 Fig. 56. — Plethysiujgraph (MossOJ. M, balanced test-tube, in communication with 
 the glass vessel, D, which contains the arm, escape of water being prevented by 
 the rubber cufi, A. When water passes from vessel D to M. or from M to D. 
 M moves down or up, and its movements are recorded by the writing-point .V. 
 M is steadied by the liquid in P, into which it dips. 
 
 The so-called cardio-pneumatic movements also constitute a 
 volume-pulse, although of complex origin. This name is given to 
 the rhvthmical changes of pressure accompanying the beat of the 
 heart, which can be detected in the air of the respiratory passages 
 when one nostril is connected with a recording tambour, or water 
 manometer, the other nostril and the mouth being closed, and the 
 respiration suspended in inspiration, with the glottis open. Or the 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 129 
 
 mouth may be connected with the recording apparatus, the nostrils 
 being closed. One factor in the production of these movements may 
 be the change of lilood- volume in the soft tissues of the mouth, naso- 
 pharynx, and perhaps also in the lower respiratory passages accom- 
 panying the heart-beat. Another factor, and a more influential one, 
 is the rhythmical alteration of pressure caused directly by the alter- 
 nate systole and diastole of the heart in the air contained in the 
 lung-tissue surrounding it, which acts as a kind of air plethysmo- 
 graph. One interesting way in which the cardio-pneumatic move- 
 ments may reveal themselves is by a variation with each beat of the 
 heart in the intensity of a note prolonged in singing, especially after 
 fatigue has set in. Upon the whole, the air-pressure falls during 
 systole, owing to the expulsion of blood from the chest, and rises 
 during diastole. The main cardio-pneumatic movement is, there- 
 fore, a systolic inspiration and a diastolic expiration (Practical 
 Exercises, p. 303). 
 
 Doubtless the weight of an organ would also show a pulse correspond- 
 ing to the beat of the heart, and so would the temperature — at least, 
 of the superficial parts. For the amount of heat given off by the blood 
 
 J'ig- 57- — Plethysmograph Tracing troia Ann. The tracing was taken by means oi 
 a tambour connected with the plethysmograph. The dicrotic wave is distinctly 
 marked. 
 
 to the skin increases with its mean velocity, and, therefore, although 
 the difference may not in general be measurable, more heat is pre- 
 sumably given off during the systolic increase of velocity than during 
 the diastolic slackening. And this, along with other considerations, 
 suggests that, at any rate in certain situations and under certain con- 
 ditions, there may even be a pulse of chemical change ; that is, a slight 
 and as yet doubtless inappreciable ebb and flow of metabolism corre- 
 sponding to the rhythm of the heart. 
 
 The Circulation in the Capillaries. — From the arteries the blood 
 passes into a network of narrow and thin-walled vessels, the capil- 
 laries, which in their turn are connected with the finest rootlets of 
 the veins. Physiologically-, the arterioles and venules must for 
 many purposes be included in the capillary tract, but the great 
 anatomical difference — the presence of circularly-arranged muscular 
 fibres in the arterioles, their absence in the capillaries — has its 
 
 9 
 
130 THE ClJiCULATION OF THE BLOOD AND LYMPH 
 
 ph\'siological correlative. The calibre of the arterioles can be 
 altered by contraction of these fibres under nervous influences; the 
 calibre of the capillaries, although it varies passively with the blood- 
 pressure, and is possibly to some extent affected by active con- 
 traction of the endothelial cells, cannot be under the control of vaso- 
 motor nerves acting on muscular fibres (but see p. 173). 
 
 Harvey had deduced from his observations the existence of 
 channels between the arteries and the veins. Malpighi was the first 
 to observe the capillary blood-stream with the microscope, and thus 
 to give ocular demonstration of the truth of Harvey's brilliant 
 reasoning. He used the lungs, mesentery and bladder of the frog. 
 The web of the frog, the tail of the tadpole, the wing of the bat, the 
 mesentery of the rabbit and rat. and other transparent parts, have 
 also been frequently employed for such investigations. From the 
 apparent velocity of the corpuscles and the degree of magnification, 
 
 Fig. 58. — Diagram to Illustrate the Slope of Pressure along the Vascular S\-stem. 
 A, arterial; C, capillary; V, venous tract. The interrupted line represents the 
 line of mean pressure in the arteries, the \vav>' line indicating that the pressure 
 varies with each heart-beat. The line passes below the abscissa axis (line of 
 zero or atmospheric pressure) in the veins, indicating that at the end of the venous 
 system the pressure becomes negative. 
 
 it is easy to calculate the velocity of the capillary blood-stream. 
 It has been estimated at from 02 to 08 mm. per second in different 
 parts and different animals. 
 
 The comparative slowness of the current and the disappearance 
 of the pulse are the chief characteristics of the capillary circulation. 
 The explanation we have already found in the great resistance of 
 the narrow arterioles and the much-branched capillary vessels. 
 Although the average diameter of a capillary is only about 10 fi 
 (5 to 20 yu in different parts of the body), the number of branches 
 is so prodigious that the total cross-section of the sj'stemic capillary 
 tract has been estimated at 500 to 700 times that of the aorta. 
 Such estimates are, of course, by no means exact. 
 
 The total cross-section of the vascular channel gradually widens 
 as it passes away from the left ventricle. In the capillary region 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 131 
 
 it undergoes a great and sudden increase. A part of this increase 
 K to be attributed to the arterioles, which, although individually 
 very narrow, have a total bed considerably greater than that of the 
 arteries from which they spring. Where the arterioles pass into 
 the capillaries proper, a further and a still greater and more abrupt 
 increase in the bed occurs. At the venous end of this region the 
 cross-section is again somewhat abruptly contracted, and then 
 gradually lessens as the right side of the heart is approached; but 
 the united sectional area of the large thoracic veins is greater than 
 that of the aorta. 
 
 Attempts have been made to measure the blood-pressure in the 
 capillaries by weighting a small plate of glass laid on the back of one of 
 the fingers behind the nail, until the capillaries are just emptied, as 
 shown by the paling of ihe skin (v, Kries), or by observing the height of 
 a column of liquid that 
 just stops the circula- 
 tion in a transparent 
 part (Roy and Graham 
 Brown). The last- 
 named observers found 
 that a pressure of 100 
 to 150 mm. of water 
 (about 7 to II mm. 
 of Hg) was needed to 
 bring the blood to a 
 standstill in the capil- 
 laries and veins of the 
 frog's web; that is, 
 about a third of the 
 blood-pressure in the 
 frog's aorta. The pres- 
 sure in the capillaries 
 at the root of the nail 
 in man varies from 
 
 30 to 50 mm. of mercury, as estimated by the method of v. Kries. But 
 the method is exposed to serious errors. The method of measuring the 
 venous pressure described on p. 132 can also be applied to the capillaries, 
 and is somewhat more satisfactory. 
 
 Under certain conditions the pulse-wave may pass into the 
 capillaries and appear beyond them as a venous pulse. Thus, we 
 shall see that when the small arteries of the submaxillary gland are 
 widened, and the vascular resistance lessened, by the stimulation of 
 the chorda tympani nerve, the pulse passes through to the veins. 
 And, normally, a pulse may be seen in the wide capillaries of the 
 nail-bed — especially when they are partially emptied by pressure — 
 as a flicker of pink that comes and goes with every beat of the heart. 
 
 We have seen that the lateral pressure at any point of a uniform 
 rigid tube through which water is flowing is proportional to the amount 
 of resistance in the portion of the tube between this point and the outlet. 
 In any system of tubes the sum of the potential and kinetic energy 
 must diminish in the direction of the flow; and although the problem 
 
 Fig. 59. — Relation of Blood- Pressure, Velocity, and 
 Cross-Section. The cur\es P, V, and S represent the 
 blood -pressure, velocity of the blood, and total cross- 
 section respectively in the arteries A, capillaries C, 
 and veins V. 
 
132 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 is complicated in the vascular system by the branching of the channel 
 and the variation in the total cross-section, yet theory and experiment 
 agree that in the larger arteries the lateral pressure diminishes but 
 slowly from the heart to the periphery', the resistance being small com- 
 pared with the resistance of the whole circuit. In the capillary region 
 the vascular resistance abruptly increases; the velocity (and therefore 
 the kinetic energy) abruptly diminishes, and the lateral pressure falls 
 much more steeply between the beginning and the end of this region 
 than between the heart and its commencement. In the veins onTj- a 
 small remnant of resistance remains to be overcome, and the lateral 
 pressure must sink again rather suddenly about the end of the capillary 
 tract. Fig. 59 shows by a rough diagram the manner in which the 
 pressure, velocity and cross-section probably change from part to part 
 of the vascular system. 
 
 The Circulation i.i the Veins. — The slope of pressure, as we have 
 just explained, must fall rather suddenly near the beginning and 
 near the end of the capillary tract. It continues falling as we pass 
 along the veins, till the heart is again reached. In the right heart, 
 and in the thoracic portions of the great veins which enter it, the 
 pressure may be negative — that is, less than the atmospheric 
 pressure. And since nowhere in the venous system is the pressure 
 more than a small fraction of that in the arteries, its measurement 
 in the veins is correspondingly difficult, because any obstruction 
 to the normal flow is apt to artificially raise the pressure. A man- 
 ometer containing some lighter liquid than mercury, such as water 
 or a solution of sodium citrate or magnesium sulphate, is usually 
 employed, so that the difference of level may be as great as possible. 
 In the sheep the pressure was found to be 3 mm. of mercury in the 
 brachial, and about 11 mm. in the crural vein. Burton-Opitz 
 obtained the following pressures in dogs (of about 15 kilos) : left 
 facial vein, 51; right external jugular, -011; central end of superior 
 vena cava, — 2*8 ; femoral vein, 5-4; renal vein, lo-g; portal vein, 
 8-9 mm. of mercury. 
 
 Estimation of Venous Pressure in Man. — The venous pressure in man 
 has been estimated by several observers with more or less satisfactory 
 results. The best-known method is that of v. Recklinghausen. A 
 circular rubber bag. with a central opening, is laid over tlie course of 
 a vein, so that the vein can be observed through the opening, as in 
 Fig. 60. The bag is smeared with glycerin. A glass plate is laid over 
 the opening and held firmly, so that the vein and the surrounding skin 
 are in a closed chamber. The bag is provided with a side-tube, which 
 connects it with a pump and a water manometer. By means of the 
 pump air is forced into the bag till the vein is just seen to collapse. 
 The pressure indicated on the manometer at this moment is taken as 
 the pressure in the vein. 
 
 By means of a modification in this method, Eyster and Hooker have 
 found that the pressure in the small veins of the arm or hand generally 
 varies between 3 and 10 cm. of water. In conditions of congestion of 
 the venous system the pressure may rise to 20 cm. of water (say 15 mm. 
 of mercury^) or more. 
 
 In making this meatsurement it is necessary to take account of the 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 133 
 
 position of the vein, since the hydrostatic factor (p. iQo) in the venous 
 pressure is so important. Thus it is obvious that the pressure in the 
 veins of the hand will be greater when it is hanging down than when 
 it is raised to level of the heart or above it. Accordingly, the actual 
 readings of the manometer must always be corrected for the vertical 
 distance between the vein and the heart, the height of a column of 
 blood equal to this distance being deducted from or added to the 
 manometer reading, according to whether the vein is below or above 
 the heart level. For practical purposes the heart level is supposed to 
 correspond to the lower end of the sternum (costal angle). 
 
 For the measurement of the pressure in the right auricle, the follow- 
 ing simple and elegant method has been given by Gaertner, following 
 a suggestion of Frey: He raises the arm of the sitting patient, and 
 observes a small vein on the back of the hand. At the moment when the 
 vein collapses the elevation of the arm is stopped, and the vertical 
 distance between the vein and the heart measured. This expressed in 
 millimetres of blood {i.e.. approximately of water) is the pressure in 
 the auricle, since the veins of the arm constitute manometer tubes 
 connected with the auricle. 
 
 The venous pressure being so low, or, in other words, the potential 
 energy which the systole of the heart imparts to the blood being so 
 greatly exhausted 
 
 before it reaches Q J^ 
 
 the veins, other in- r B>^-n_^ ^"^^^^^^^^^ 
 
 fluences begin here 
 appreciably to 
 affect the blood- 
 stream : 
 
 1. Contraction of Fig. 60. — Diagram of Measurement of Venous Pressure 
 
 a^ M',j<:rJfl<: This (V.Recklinghausen). H, back of hand, with V, a vein ; 
 
 me mui>ue,^. 1 las ^ ^^^ rubber bag with central opening; T, tube leading 
 
 COmpreseSS the from bag to manometer and pump; G, glass plate, 
 
 neighbouring veins, 
 
 and since the blood is compelled by the valves, if it moves at 
 all, to move towards the heart, the venous circulation is in this 
 way helped. 
 
 2. Aspiration of the Thorax. — In inspiration the intrathoracic 
 pressure, and therefore the pressure in the great thoracic veins, is 
 diminished, and blood is drawn from the more peripheral parts of 
 the venous system into the right heart (p. 226). 
 
 3. Aspiration of the Heart.— When the heart after its contraction 
 suddenly relaxes, the endocardiac pressure becomes negative, and 
 blood is sucked into it, just as when the indiarubber ball of a syringe 
 is compressed and then allowed to expand. But we cannot attribute 
 any great importance to this ; and, of course, it is only the relaxa- 
 tion of the right ventricle which could directly affect the venous 
 circulation. 
 
 4. Every change of position of the Umbs, as in walking, aids the 
 venous circulation (Braune), and this independently of the muscular 
 contraction. When the thigh of a dead body is rotated outwards, and 
 
134 ^^^ CIRCULATION OF THE BLOOD AND LYMPH 
 
 at the same time extended, a manometer connected with the femoral 
 vein shows a negative pressure of 5 to 10 mm. of water. When the 
 opposite movements are made, the pressure becomes positive. 
 
 It follows from the number of casually-acting influences which 
 affect the blood-flow in the veins that it cannot be very regular or 
 constant. We have seen that in the great arteries there is a con- 
 siderable variation of velocity and of pressure with every discharge 
 of the ventricle, and although this variation is absent from the 
 veins, since normally the pulse, due to the ventricular discharge, 
 does not penetrate into them, the venous flow is, nevertheless, as a 
 matter of fact, more irregular than the arterial. So that if it is 
 difficult to give a useful definition of the term ' velocity of the 
 blood ' in the case of the arteries, it is still more difficult to do so in 
 the case of the veins. Where voluntary movement is prevented, 
 one potent cause of variation in the venous flow is eliminated; and 
 In curarized animals certain observers have found but little differ- 
 ence between the mean velocity in the veins and in the corre- 
 sponding arteries. Others have found the velocity in the veins 
 considerably less, which is indeed what we should expect from the 
 fact that the average cross-section of the venous system is greater 
 than that of the arterial system. Burton-Opitz, by means of a 
 stromuhr, obtained a mean velocity of 147 mm. per second in the 
 external jugular vein of a 13-kilo dog. 
 
 To sum up, we may conclude that, upon the whole, the blood 
 passes with gradually-diminishing velocity from the left ventricle 
 along the arteries ; it is greatly and somewhat suddenly slowed in the 
 broad and branching capillary bed; but the stream gathers force 
 again as it becomes more and more narrowed in the venous channel, 
 although it never acquires the speed which it has in the aorta. 
 
 Venous Pulse. — To complete the account of the circulation in the 
 veins, it may be recalled that, in addition to the venous pulse 
 described on p. 131, which, as an occasional phenomenon, may 
 travel through widened arterioles and capillaries from the arteries 
 into the veins, and therefore in the direction of the blood-stream, 
 a so-called venous pulse, travelling from the heart against the blood- 
 stream and depending on variations of pressure in the right auricle, 
 may be detected in the jugular veins in healthy persons, and more 
 distinctly in certain disorders of the circulation, where indeed it 
 may be evident at a greater distance from the heart — for example, 
 over the liver as the so-called li\er pulse. In animals a venous 
 pulse of this nature has been demonstrated in the vence cavae, the 
 jugular vein, and with a delicate manometer even in the large veins 
 of the Umbs. It moves with a speed of i to 3 metres a second 
 (Morrow). It is most easily observed in the jugular veins in man, 
 because of their proximity to the heart. We have already pointed 
 out the significance of the study of this venous pulse for the analysis 
 
MECHANICS OF THE CIRCULATION IN THE VESSELS 135 
 
 of cardiac events (p. 100). A jugular venous pulse of a perfectly 
 different origin is seen in cases of incompetence of the tricuspid 
 valve. Here the chief elevation is synchronous with the ventricular 
 systole, and is caused by the regurgitation of blood from the right 
 ventricle through the auricle into the veins. The so-called ' com- 
 municated venous pulse ' is simply due to the proximity of some 
 large artery, especially when enclosed in a common sheath, whose 
 pulsations are directly transmitted to the vein. The changes of 
 pressure in the great veins accompanying the respiratory move- 
 ments (p. 290) are also sometimes spoken of as a venous pulse, but 
 they are produced in a different way — namely, by the rhythmical 
 alteration in the intrathoracic pressure, which alternately favours 
 and hinders the venous return to the heart. 
 
 The Circulation-Time. — Hering was the first who attempted to 
 measure the time required by the blood, or by a blood-corpuscle, to 
 complete the circuit of the vascular system. He injected a solution of 
 potassium ferrocyanide into a vein (generally the jugular), and collected 
 blood at intervals from the corresponding vein of the opposite side. 
 After the blood had clotted, he tested for the ferrocyanide by addition 
 of ferric chloride to the serum. The first of the samples that gave the 
 Prussian blue reaction corresponded to the time when the injected salt 
 had just completed the circulation. This method was improved by 
 Vierordt, who arranged a number of cups on a revolving disc below the 
 \ein from which the blood was to be taken. In these cups samples of 
 the blood were received, and the rate of rotation of the disc being known, 
 it was possible to measure the interval between the injection and appear- 
 ance of the salt with considerable accuracy. Hermann made a further 
 advance by allowing the blood to play upon a revolving drum covered 
 with paper soaked in ferric chloride, and by using the less poisonous 
 sodium ferrocyanide for injection. 
 
 Even as thus modified, the method laboured under serious defects. 
 It was not possible to make more than a single observation on one 
 animal, at least without allowing a considerable interval for the elimina- 
 tion of the ferrocyanide, and, further, the method was unsuited for the 
 estimation of the circulation-time in individual organs. In both of 
 these respects the more recently introduced electrical method presents 
 considerable advantages; for by its aid we can not only obtain satis- 
 factory measurements of the circulation-time in such organs as the 
 lungs, liver, kidney, etc., but we can repeat them an indefinite number 
 of times on the same animal. 
 
 A cannula, connected with a burette (or a Mariotte's bottle, or a 
 syringe), containing a solution of sodium chloride (usually a i'5 to 
 2 per cent, solution), is tied into a vessel — say the jugular vein. Sup- 
 pose that the time of the circulation from the jugular to the carotid is 
 required — that is, practically the time of the lesser or pulmonary circu- 
 lation. A small portion of one carotid artery is isolated, and laid on 
 a pair of hook-shaped platinum electrodes,* covered, except on the 
 concave side of the hook, with a layer of insulating varnish. To 
 further secure insulation, a bit of very thin sheet-indiarubber is slipped 
 between the artery and the tissues. By means of the electrodes the 
 
 * The electrodes can easily be made by beating out one end of a piece of 
 thick platinum wire to a breadth of 5 or 6 mm., and then bending the flattened 
 part into a hook, or by bending pieces of stout platinum foil. 
 
136 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 piece of artery lying bttwccn them, with the blood that flows in it, is 
 connected up as one of the resistiinccs in a Whcatstonc's bridge (p. 726). 
 The secondary coil of a small inductorium, arranged for giving an inter- 
 rupted current, and with a single Daniell or dry cell in its primary, is 
 substituted for the batter^', and a telephone for the galvanometer, 
 according to Kohlrausch's well-kno\"m method for the measurement of 
 the resistance of electrol>i:es. It is well to have the induction machine 
 set up in a separate room and connected to the resistance-box by long 
 wires, so that the noise of the Necf's hammer may be inaudible. The 
 bridge is balanced by adjusting the resistances until the sound heard 
 in the telephone is at its minimum intensity, the secondary coil being 
 placed at such a distance from the primary that there is' no sign of 
 stimulation of muscles or ner\'es in the neighbourhood of the electrodes 
 
 f \u,r»KC"^-||'^*'' 
 
 Fig. 61. 
 
 -Measurement of the Pulmonary Circulation-Time in Rabbit by Injection 
 of Methvlene Blue. 
 
 when the current is closed. A definite, small quantity of the salt solu- 
 tion is now allowed to run into the vein by turning the stop-cock of the 
 burette. It moves on with the velocity of the blood, and reaching the 
 arter\' on the electrodes causes a diminution of its electrical resistance 
 (p. 26). This disturbs the balance of the bridge, and the sound in the 
 telephone becomes louder. The time from the beginning of the injec- 
 tion to the alteration in the sound is the circulation - time between 
 jugular and carotid. It can be read off by a stop-watch, or more 
 accurately by an electric time-maker writing on a revolving drum 
 (Fig. 62). Instead of the telephone a galvanometer may be used, the 
 equal and oppositely directed induction shocks being replaced by a 
 weak voltaic current, and the platinum by unpolarizable electrodes 
 (p. 731). But this is less convenient. 
 
■ ' '. I. 11/, i: ; 
 MECHANICS OF THE CIRCULATION IN THE VESSELS 137 
 
 The circulation-time of an organ like the kidney can be measured by 
 adjusting a pair of clcctrodts under the renal artery and anotlier under 
 the renal vein, and reading off the interval required by the salt solution 
 to pass from the point of injection first to the artery and then to the 
 vein. The difference is the circulation-time through the kidney. 
 
 For certain purposes, and particularly for measurements on small 
 animals like the rabbit, or on organs whose vessels are too delicate to 
 be placed on electrodes without the risk of serious interference with 
 the circulation, anotlier method may be employed with advantage. It 
 depends on the injection of a pigment, like methylene blue, which at 
 first overpowers the colour of the blood and shows through the walls of 
 the bloodvessels, but is soon reduced to a colourless substance (Fig. 61). 
 The details of the method are given in the Practical Exercises (p. 217.) 
 
 It may be said in general terms that in one and the same animal 
 the time of the lesser circulation is short as compared with the total 
 circulation-time, relatively constant, and but little affected by changes 
 of temperature. In animals of the same species it increases with the 
 size, but more slowly, and rather in proportion to the increase of 
 surface than to the increase of weight. 
 
 Thus a dog weighing 2 kilogrammes had an average pulmonary 
 circulation-time of 4'05 seconds, while that of a dog weighing 11 8 kilos 
 was 8'7 seconds, and that of a dog with a body-weight of i8"2 kilos only 
 io*4 seconds. It is probable that in a man the pulmonary circulation- 
 time is not usually much less than 12 seconds, nor much more than 
 15 seconds. 
 
 The circulation-time in the kidney, spleen and liver is relatively 
 long and much more variable than that of the lungs, being easily 
 affected by exposure and changes of temperature (increased by 
 cold, diminished by warmth). 
 
 In a dog of 13-3 kilos weight the average circulation-time of the 
 spleen was 10 -95 seconds; kidney, 13-3 seconds; lungs, 8-4 seconds. 
 The circulation-time of the stomach and intestines is (in the rabbit) 
 comparatively short, not exceeding very greatly that of the lungs, 
 but it is lengthened by exposure. The circulation-time of the 
 retina and that of the heart (coronary circulation) are the shortest 
 of all. 
 
 The total circulation-time is properly the time required for the whole 
 of the blood to complete the round of the pulmonary and systemic 
 circulation. But there are many routes open to any given particle of 
 blood in making its systemic circuit. If it passes from the aorta through 
 the coronary- circulation it takes an exceedingly short route. If it passes 
 through the intestines and liver, or through the kidney, or through the 
 lower limbs, it takes a long route. So that to determine the total cir- 
 culation-time by direct measurement we must know (i) the quantity 
 of blood that passes on the average by each path in a given time, and 
 (2) the average circulation-time of each path. If the average weight of 
 blood in each^jrgan be represented by wi, w^, w^, etc.; and the average 
 circulation-times by 1^, t^, t^, etc. ; and / be the total systemic circulation- 
 
 t t t 
 
 tmie; then iffy, w^-: , "'37. etc., will represent the quantity of blood 
 
 *1 *2 '3 
 
 passing through each organ in t seconds, since in the average circula- 
 
i3« 
 
 THE CIRCULATION OF THE BLOOD AXD LYMPH 
 
 tion-timc of an organ the whole of the blood in it at the beginning of 
 the period of observation will have been exchanged for fresh blood. 
 But the whole of the blood in the body, which we may call VV, passes 
 once round the systemic circulation in t seconds. Therefore, 
 
 w.r +tt'oT +w^-, etc.,=W. In this equation everj-thing can be de. 
 
 /i 
 
 ''t. 
 
 n 
 
 JLJLJLJLJLJLJLJIJULJLJIJUUULJLJLX 
 
 127 
 
 tcrmined by experiment except /. and therefore / can be calculated. 
 .A.dding t to the pulmonary circulation -time, we arrive at the tota 
 circulation-time. 
 
 Although our experimental data are as yet too meagre to make the 
 calculation more than a rough approximation, it apjjcars probable that 
 in certain animals the total circulation-time is five or six times as great 
 as the pulmonary circulation -time. If the same ratio holds good in 
 man. the total circulation-time is unlikely to be much less than a minute 
 
 or much greater than a 
 
 ' J L_ minute and a quarter. 
 
 We shall see directly 
 that this estimate is 
 confirmed by data de- 
 rived from a different 
 source. In the mean- 
 time, we may use it 
 {provisionally to calcu- 
 ate the work done by 
 the heart. Let us take 
 for simplicity the total 
 circulation - time as i 
 minute in a 70 - kilo 
 man, the quantity of 
 blood as 4^ kilos,* and 
 the mean pressure in 
 the aorta as 150 mm. 
 of mercury. Up to the 
 time when the semi- 
 lunarvalves areopened, 
 the work done by the 
 left ventricle is spent 
 in raising the intraven- 
 tricular pressure till it 
 is sufficient to over- 
 come the pressure in 
 the aorta. If a vertical 
 tube were connected 
 with the left ventricle, 
 the blood would rise till 
 the column was of the same weight as a column of mercury of equal section 
 and 150 mm. high. This column of blood would be about 192 metres in 
 height. If a reservoir were placed in communication with the tube at 
 this height, a quantity of blood equal to that ejected from the ventricle 
 would at each systole pass into the reservoir; and the work which the 
 blood thus collected would be capable of doing, if it were allowed to 
 fall to the level of the heart, v.ould be equal to the work expended by 
 the heart in forcing it up. Thus, in i minute the work of the left ven- 
 tricle would be equal to that done in raising 4^ kilos of blood to a height 
 
 * The mean of the 5^ kilos given by most writers, and of the 3J kilos ob- 
 tained by Haldane and Smith (p. 56). 
 
 _JLJl_a_JLJLJl_Jl-JlJUn_n_JLJLJLJLJLJLJlJL 
 
 Fig. 62. — Time of the Lesser Circulation. Cat anaes- 
 thetized with Ether. Time-trace, seconds. The line 
 above the time-trace was written by an electro- 
 magnetic signal, the circuit of which was closed at 
 the moment when injection of methylene blue into 
 the jugular vein was begun, and opened at the 
 moment when the change of colour in the carotid 
 was observed. I. normal circulation-time; II, cir- 
 culation-time after section of both vagi (much 
 diminished); HI, circulation-time during stimulation 
 of the peripheral end of one vagtis (much increased). 
 
MLCflAMCS OF THE CI HCIJLATION IN THE VESSELS 139 
 
 of I 92 metres — that is, about S()4 kilogramme-metres; in 24 hours it 
 would be, say, 12,450 kilogrammt-mctrcs. 'Jaking the mean pressure 
 in the puhnonary artery at one-third of the aortic pressure, we get for 
 the daily work of the right ventricle about 4,150 kilogramme-metres. 
 The work ol the two ventricles is thus about 16,600 kilogramme-metres,* 
 which is enough to raise a weight of nearly 4 pounds from the bottom 
 of the deepest mine in the world to the top of its highest mountain, or 
 to raise the man himself to ij^ times the height of the spire of Strasburg 
 Cathedral, or twice the height of the loftiest ' skyscraper ' in New York. 
 By friction in the bloodvessels this work is almost all changed into its 
 equivalent of heat, nearly 40,000 gramme-calories (p. 688) . Further, since 
 the contraction of the heart is always maximal (p. 154), and there is 
 reason to believe that the quantity of blood ejected at a single systole 
 by the left ventricle (being dependent upon the inflow from the pulmon- 
 ary veins, and therefore upon the inflow into the right side of the heart 
 from the systemic veins) varies widely, some of the mechanical effect 
 of the contraction must be wasted when the quantity is less than the 
 ventricle is capable of expelling. 
 
 Output of the Heart. — If 4J kilos of blood pass through the heart in 
 I minute with the average pulse-rate of 72 per minute, the quantity 
 
 ejected by either ventricle with every systole will be — — = 62*5 grm., 
 
 or a little less than 60 c.c. The output may be expressed in grammes 
 or cubic centimetres per minute (the minute volume), or per second, or 
 per beat. It has been measured in animals in several ways — e.g., by 
 inserting a stromuhr (p. 121) on the course of the aorta, or by recording 
 the variations in the volume of the heart, or, better, of the ventricles, 
 by means of a plethysmograph (cardiometer of Henderson), in which 
 the organ is enclosed. Another method, which does not entail the 
 opening of the chest, is to allow a salt solution to riin slowly, for a de- 
 finite number of seconds, into the left ventricle through a tube passed 
 into it from the carotid artery. A sample of the mixture of blood and 
 salt solution is collected from a branch of the femoral artery, where its 
 arrival is detected by the change of electrical resistance (p. 135). From 
 the amount of salt solution which must be added to a normal sample 
 of blood drawn before the injection to make its conductivity the same 
 as that of the sample taken during the passage of the mixture, the 
 quantity of blood with which the solution was mixed in the ventricle 
 during the injection can be approximately determined. By this method 
 it has been shown in a series of experiments on more than twenty dogs, 
 ranging in weight from 5 to nearly 35 kilos, that the output of the 
 left ventricle per kilo of body-weight per second diminishes as the size 
 of the animal increases ; and the relation between body-weight and out- 
 put is such that in a man weighing 70 kilos we can hardly suppose that 
 the ventricle discharges, during bodily rest, more than 105 grm. of 
 blood per second, or 87 grm. (80 c.c.) per heart-beat with a pulse-rate 
 of 72. Putting this result along with that deduced from the circulation- 
 time, we can pretty safely conclude that the average amount of blood 
 thrown out by each ventricle at each beat is not more than 70 or 80 c.c. 
 Zuntz, from the quantity of oxygen absorbed by the blood in the lungs 
 in a definite short time, and the difference between the oxygen content 
 of samples of the arterial and venous blood, has estimated the output 
 per beat at 60 c.c. But according to him this may be doubled during 
 
 • Since the blood on expulsion is moving with a certain velocity, an addi- 
 tion might be made for its kinetic energy. But this would only increase the 
 total work by a small fraction (about i per cent.). 
 
140 77//; CJRCULATIOS Ol- THE BLOOD AND LYMPH 
 
 severe muscular work, wlicn, as a matter of fact, by the aid of the 
 Rontgcn-rays or by percussion of the chest, the volume of the heart 
 may be shown to be considerably increased. Tigcrstedt, on the basis 
 of stromuhr measurements in animals, puts the ventricular output per 
 beat in man at 50 to 100 c.c; Plesch, on the basis of gasometric ob- 
 servations on man, at 59 c.c. Recently Krogh, using a gasometric 
 method based on the absorption of nitrous oxide gas in the lungs, found 
 that the minute volume during rest may vary between wide limits 
 (2-8 to 87 litres of blood per minute, corresponding, with a pulse-rate 
 of 70, to 40 c.c. to 120 c.c. per beat). During muscular work there is 
 a great and immediate increase, up to, it may be, 21-6 litres per minute. 
 These great variations in the output of the ventricle depend primarily 
 upon variations in the rate of return of the blood to the heart by the 
 veins. According to Henderson, however, such great variations in the 
 output per beat as are postulated by the majority of physiologists who 
 have worked at the subject do not occur, and the fundamental variable 
 is the rate of the beat. 
 
 In healthy persons in whom the pulse-rate is permanently much 
 below the normal (p. 107) the output of the ventricle per beat must, of 
 course, be correspondingly increased. In a man with a pulse -rate 
 always below 40 during rest in the sitting position, the flow in the hands 
 was found to be normal in amount, and all the signs of a normal delivery 
 of blood from the left ventricle were present. Here the output per 
 beat must have been twice the usual amount during rest. 
 
 Section IV. — The Heart-Beat in its Physiolog cal 
 Relations. 
 
 So far we have been considering the circulation as a purely 
 physical problem. We have spoken of the action of the heart as 
 that of a force-pump, and perhaps to a small extent that of a suction- 
 pump too. We have spoken of the bloodvessels as a system of more 
 or less elastic tubes through which the blood is propelled. We have 
 spoken of the resistance which the blood experiences and the pressure 
 which it exerts in this system of tubes, and we have considered the 
 causes of this resistance, the interpretation of this pressure, and the 
 physical changes in the vascular system that may lead to variations 
 of both. But so far we have not at all, or only incidentally and very 
 briefly, dealt with the physiological mechanism through which the 
 physical changes are brought about. We have now to see that, 
 although the heart is a pump, it is a living pump; that, although the 
 vascular system is an arrangement of tubes, these tubes are alive; 
 and that both heart and vessels are kept constantly in the most 
 delicate poise and balance by impulses passing from the central 
 nervous system along the nerves. 
 
 In many respects, and notably as regards the influence of nerves 
 on it, we may look upon the heart as an expanded, thickened and 
 rhythmically-contractile bloodvessel, so that an account of its 
 innervation may fitly precede the description of vaso-motor action 
 in general. 
 
THE HEART-BEAT IN ITS PHYSIOLOGICAL RELATIONS 141 
 
 The Relation of the Heart to the Nervous System. — A very simple 
 experiment is suthcient to prove that the beat of the heart does not 
 depend on its connection with tlie central nervous system, for an 
 excised frog's heart may, under favourable conditions, of which the 
 most important are a moderately low temperature, the presence of 
 oxygen, and the prevention of evaporation, continue to beat for days. 
 The mammalian heart also, after removal from the body, beats for 
 a time, and indeed, if defibrinated blood be artificially circulated 
 through the coronary vessels, for several or even many hours. But 
 although this proves that the heart can beat when separated from 
 the central nervous system, it does not prove that nervous influence 
 is not essential to its action, for in the cardiac substance nervous 
 elements, both cells and fibres, are to be found. 
 
 The Intrinsic Nerves of the Heart. — In the heart of the frog 
 numerous nerve-cells occur in the sinus venosus, especially near its 
 junction with the right auricle (Remak's ganghon). A branch 
 from each vagus, or rather from each vago-sympathetic nerve (for 
 in the frog the vagus is joined a Httle below its exit from the skull 
 by the sympathetic), enters the heart along the superior vena cava 
 (pp. 157, 198). 
 
 Running through the sinus, with whose ganglion-cells the true vagus 
 fibres, or some ol them, are believed to make physiological junction 
 (p. 163), the nerves pursue their course to the auricular septum. Here 
 they form an intricate plexus, studded with ganglion-cells. From the 
 plexus nerve-fibres issue in two main bundles, which pass down the 
 anterior and posterior borders of the septum to end in two clumps of 
 nerve-cells (Bidder's ganglia), situated at the auriculo- ventricular 
 groove. These ganglia in turn give off fine nerve-bundles to the ven- 
 tricle, which form three plexuses — one under the pericardium, another 
 under the endocardium, and a third in the muscular wall itself, or myo- 
 cardium. From the last of these plexuses numerous non-raedullated 
 fibres run in among the muscular fibres and end in close relation with 
 them. Similar plexuses of nerve-fibres exist in the mammalian ventricle. 
 But while scattered ganglion-cells are found in the upper part of the 
 ventricular wall, most observers have been unable to demonstrate any 
 either in the mammal or the frog in the apical half. In the rat's heart, 
 according to the careful obser\'ations of Schwartz, true gangUon-cells 
 are confined to an area on the posterior surface of the auricles, lying 
 always under the visceral pericardium. Other writers, however, have 
 stated that ganglion-cells do exist in the apex both of the cat's and of 
 the frog's heart. In connection with the whole question it must be 
 home in mind that in other organs improved histological methods have 
 brought typical nerve-cells to light in situations where they were not 
 suspected or were denied to exist, and, further, that all investigators 
 are not agreed upon the histological criteria by which ganglion-cells are 
 to be distinguished. 
 
 Cause of the Rhythmical Beat of the Heart. — Scarcely any physio- 
 logical question has excited greater interest for many years than the 
 mechanism of the heart-beat. Several properties of the cardiac 
 tissue ought to be distinguished in discussing this question: (i) Its 
 
I42 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 automatism — i.e., its power of beating in the absence of external 
 stimuli; (2) its rhythmicity — i.e., its power of responding to con- 
 tinuous stimulation by a series of rhythmically repeated contrac- 
 tions; (3) its conductivity — i.e., its power of conducting the contrac- 
 tion wave or the impulse to contraction once it has been set up; and 
 (4) the power of co-ordination, in virtue of which the various parts 
 of the heart beat in a regular sequence. 
 
 The excitability of the cardiac tissue — that is, its power of appro- 
 priate response (namely, by contraction) to a suitable stimulus — 
 does not particularly concern us here, since it is in no wise a property 
 special to the heart. Only, as we shall see in the sequel, the time- 
 relations of this excitability are of interest, for the existence of a 
 refractory period — that is, an interval during which the cardiac 
 muscle refuses to respond to excitation — throws light upon the 
 rhythmicity of the heart-beat. The tonicity of the heart — i.e., its 
 power of remaining contracted to a certain extent in the intervals 
 between successive beats — is another property of great importance 
 in certain aspects, but which only needs to bo mentioned at present. 
 
 Automatism of the Heart-Beat — Neurogenic and Myogenic Hypo- 
 theses. — That the heart-beat is automatic is sufficiently shown by 
 the fact that, as already mentioned, an excised and empty heart 
 will go on beating for a time, for many hours or even for days in the 
 case of cold-blooded animals. When blood, or even a suitable 
 solution of such inorganic salts as exist in serum, is caused to circu- 
 late through the coronary vessels of the excised heart of a warm- 
 blooded animal, it also continues to contract for a long time. In 
 trying to understand the real significance of the automatic beat of 
 the heart, physiologists have endeavoured, first, to compare different 
 portions of the heart as regards the degree in which they possess this 
 property of automaticity; and, second, to associate, if possible, one 
 or other of the active tissues that compose the organ, muscle, and 
 nervous tissue, with this characteristic property. It cannot be 
 pretended that a final answer to this question is possible at present. 
 Nor is the historical controversy which it has occasioned perhaps as 
 important in itself as the space usually devoted to it in textbooks 
 might imply. Yet it is probable that the series of fundamental 
 facts in the physiology of the heart elicited in the long discussion can 
 be best presented, even for the purposes of the elementary student, 
 as they were originally brought forward in the form of pros and 
 cons, of arguments for and against the neurogenic or the myogenic 
 hypothesis. There is good evidence that as in the amphibian 
 heart the contraction starts in the sinus venosus, so in the mam- 
 malian heart it starts in the sinus tissue of the right auricle in the 
 region of the sino-auricular node. Attempts have been made to 
 demonstrate that the origination of the impulses which are after- 
 wards conducted to all parts of the heart is normally confined to 
 
THE HLART-BhAT IN ITS PHYSIOLOGICAL RELATIONS 143 
 
 the node itself, and the sino-auricular node is by some authors 
 denominated the pace-maker of the heart, the tissue which sets the 
 pace for the rest of the organ and gives the time to auricles and 
 ventricles alike. The experimental results, however, are by no 
 means harmonious, some observers finding that destruction of the 
 region of the node causes no change in the rate of the heart-beat, 
 others that the beat is permanently slowed. But even were we in 
 a position to sharply delimit a given region of the heart as the point 
 at which the strong tendency to contraction inherent in the cardiac 
 tissue as a whole first breaks into an actual beat, this would scarcely 
 enable us to decide offhand where the cause of the automatism 
 resides, in the muscular tissue or in the intrinsic nervous apparatus, 
 because in nearly all animals hitherto investigated the muscular 
 tissue, ganglion-cells, and nerve-fibres are inseparably intermingled. 
 In Limulus, however, the horseshoe or king crab, the cardiac 
 ganglion-cells are collected in a nerve-cord running longitudinally in 
 the median line along the dorsal surface of the segmented heart, and 
 
 z^^,::C:>^:^::^2:^^, 
 
 Fig. 63. — -The Heart ana che Heart Nerves of Limulus: Dorsal View (Carlson). (The 
 heart is figured one-half the natural size of a large specimen.) aa. Anterior 
 artery; la, lateral arteries; In, lateral nerves; mnc, median nerve-cord; os, ostia. 
 
 sending off at intervals branches to two lateral cords, and also 
 branches which enter the heart muscle directly (Fig. 63). When 
 the median nerve-cord is removed, as can be done without injuring 
 the muscle, the heart ceases for ever to beat spontaneously. It 
 still contracts when directly stimulated, mechanically or electrically, 
 but the contraction never outlasts the stimulation. The automatic 
 power therefore resides in the nerve-cord alone, and not in the 
 muscle. The same is true of the rhjrthmical power, for excitation 
 of the nerves that pass from the median cord to the muscle produces, 
 ' not a rhythmical series of beats in the resting, and an acceleration 
 of the rhythm in the pulsating heart, but a tetanus closely resembling 
 that produced in skeletal muscle on stimulation of a motor nerve ' 
 (Carlson). Conduction and co-ordination are also effected in this 
 heart through the nervous mechanism, and essentially through the 
 median nerve-cord; for section of the longitudinal nerves in any 
 segment of the heart abohshes the co-ordination of the two ends of 
 the heart on either side of the lesion, while division of the muscle 
 in any segment does not affect the co-ordination. It is not per- 
 missible to transfer these results wholesale to higher hearts, and 
 
144 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 especially the conclusions as to rhythm, conduction, and co-ordina- 
 tion. Nevertlu>less the Limulus heart affords one absolutely un 
 ambiguous example of a heart whose rhythmical beat is sustained 
 by nervous impulses. And in the case of the higher animals also 
 facts may be adduced in favour of the neurogenic origin of the beat. 
 The isolated auricular appendices of the mammalian heart, in which 
 no ganglion-cells have been found, refuse to beat spontaneously. 
 If in the frog we divide the sinus, which is conspicuously rich in 
 ganglion-cells, from the lower portion of the heart, it continues to 
 pulsate. A fragment from the base of the ventricle will go on 
 contracting if it includes Bidder's ganghon, but not otherwise. We 
 cut off the lower two-thirds of the frog's ventricle, the so-called 
 apex preparation, which either contains no ganglion-cells or is 
 relatively poor in them, and it remains obstinately at rest. Further, 
 if, without actually cutting off the apex, we dissever it physiologically 
 from the heart by crushing a narrow zone of tissue midway between 
 it and the auriculo- ventricular groove, we abolish for ever its power 
 of spontaneous rh^'-thmical contraction. The frog may hve for 
 many weeks, but in general the apex remains in permanent diastole. 
 It can be caused to contract by an artificial stimulus, but it neither 
 takes part in the spontaneous contraction of the rest of the heart, 
 nor does it start an independent beat of its own. 
 
 What can be simpler than to assume that the sinus beats because 
 it has numerous ganglion-cells in its walls, and that the apex refuses 
 to beat because it has comparatively few or none ? Could we pick 
 out the nerve-cells from the sinus, without injuring the muscular 
 tissue, as easily as we can extirpate the median nerve-cord in 
 Limulus, we may well suppose that it would lose its power of auto- 
 matic contraction. And although, if we pursue our investigations 
 -a little farther, facts may emerge which seem to contradict the 
 neurogenic hypothesis, the contradiction is usually only apparent. 
 Let us inquire, for instance, what happens to the auricles and ven- 
 tricle of the frog's heart when the sinus is cut off. The answer is 
 that as a rule, while the sinus goes on beating, the rest of the heart 
 comes to a standstill, in spite of the numerous ganglion-cells in the 
 auricular septum and the auriculo-ventricular groove. Not only 
 so, but if the ventricle be now severed from the auricles by a section 
 carried through the groove, it is the former, poor in nerve-cells 
 though it be, which will usually first begin to beat. We shall again 
 have to discuss this experiment (p. i6b). It, at any rate, cannot be 
 interpreted as proving that the automaticity of the heart does not 
 depend upon the presence of ganglion-cells. For although a portion 
 of the heart rich in ganglion-cells may, under the circumstances 
 mentioned, refuse for a time to beat, there is good evidence that 
 this is due either to a peculiar condition called inhibition into which 
 the muscular tissue or the nerve-cells of the lower portions of the 
 
THE HEART-BEAT IN ITS PHYSIOLOGICAL liELATf()\S 145 
 
 heart have been thrown by the first section, or more probably to 
 the loss of the accustomed impulses from the sinus which normally 
 give the signal for the auricular contraction. A stronger argument 
 in favour of the myogenic theory is the fact that the embryonic 
 heart beats with a regular rhythm at a time when as yet no ganglion- 
 cells have settled in its walls. But it may well be that this primitive 
 automatic power of the cardiac muscle, absolutely necessary at iirst, 
 since the early establishment of the circulation is essential for the 
 development of the tissues in general and of the nervous system in 
 particular, falls into abeyance when the intrinsic cardiac nervous 
 mechanism is completed, or at least becomes subordinated to the 
 latter. The advocates of the myogenic theory further state that 
 the isolated bulbus aortse of the frog, and even tiny fragments of it, 
 will pulsate spontaneously, and that the same is true of small 
 portions of the great veins which open into the sinus. The rhyth- 
 mical contraction of the veins of the bat's wing has also been con- 
 sidered an argument in favour of myogenic automatism. In none 
 of these cases, however, can the complete absence of ganghon-cells 
 be considered satisfactorily demonstrated. The statement that a 
 portion of the apex of the dog's ventricle continues for a considerable 
 time to beat with a rhythm of its own when connected with the rest 
 of the heart by nothing but its bloodvessels and the narrow isthmus 
 of visceral pericardium and connective tissue in which they lie has 
 not been confirmed by all observers. But even if it be accepted, it 
 can hardly be used as a decisive argument against the neurogenic 
 theory so long as the absence of ganglion-cells from such a ventricular 
 strip has not been demonstrated. 
 
 The fact that under the influence of a constant stimulus portions 
 of the heart can be made to beat rhythmically has been sometimes, 
 though erroneously, brought forward as evidence of myogenic 
 automatism. Thus the supposedly ganglion-free apex of the frog's 
 heart, lifeless as it seems when left to itself, can be caused to execute 
 a long and faultless series of pulsations when its cavity is distended 
 with defibrinated blood or serum, or certain artificial nutritive 
 fluids, or even physiological salt solution. The passage of a constant 
 current through the preparation may also start a regular rhythm. 
 But apart from the question whether nervous elements would not 
 be subjected to the constant stimulus impartially with the muscular 
 elements (and nerve-fibres, at any rate, are acknowledged to be 
 present), the beat here produced ought not to be considered as an 
 automatic beat, but as a contraction evoked by an external stimulus. 
 Such experiments, in fact, throw no light upon the automatism of 
 the heart, but prove clearly its rhythmicity — i.e., its power of 
 responding to a continuous stimulus by regularly recurring con- 
 tractions. While we are hardly at present in a position to dis- 
 criminate sharply between the influence of constant stimulation 
 
146 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 upon the nervous and upon the muscular elements of the heart, and 
 certainly not in a position to deny to the nervous elements the 
 power of responding to such stimulation by rhythmical discharges, 
 it cannot be doubted that tin cardiac muscle itself possesses rhythmi- 
 cal power. One of the best proofs of this is deri\-ed from observa- 
 tions on the growth of tissue cultures containing fragments of heart 
 muscle. A group of heart muscle cells which had become entirely 
 separated from the rest of the culture continued to beat rhythmically 
 although with a different rhythm from that of the original piece. 
 No ganglion cells or nerve fibres could be seen in it. Rhythmical 
 contraction was observed even in a single isolated heart muscle cell 
 (Burrows). The power of rhythmical contraction is a property 
 which also belongs to the smooth muscle of such tubes as the ureter, 
 whose rhythmical contraction is affected by distension much as that 
 of the heart is, and in a smaller degree even to ordinary skeletal 
 muscle, which can contract with a kind of rhythm under the stimulus 
 of a certain tension and in certain saline solutions. But just as the 
 primitive automatism of the cardiac muscle may have become sub- 
 ordinated in the course of development to the automatism of the 
 nervous elements, so the primitive rhythmical power of the muscle 
 may under ordinary conditions remain in abeyance and yet be 
 capable of asserting itself in favourable circumstances, and when the 
 normal rhythmical impulses from the nervous apparatus are with- 
 drawn. In any case, in the normally beating heart the opportunity 
 for the exercise of the rhythmical power of the muscle does not 
 arise, at least in the case of the lower portions of the heart. For the 
 impulses which (in the frog's heart), descending from the sinus, 
 liberate the contraction of the auricles, and the impulses which, 
 descending from the auricles, liberate the contraction of the ventricle, 
 appear to be discrete, and not continuous; in other words, the lower 
 portions of the heart do not receive from the upper portions a con- 
 tinuous stream of stimuli to which they respond by rhythmical con- 
 tractions, but a series of rhythmically repeated impulses, each of 
 which evokes a single contraction. One of the best proofs of this 
 is that if the sinus is heated the ventricle beats much more rapidly in 
 unison with the rapidly beating sinus and auricles, while if the 
 ventricle itself is heated no change takes place in its rhythm. Now, 
 if the ventricle responds to a constant stimulus by rhythmical beats, 
 the condition of the ventricular tissue ought to affect the rate of its 
 beat. In the mammalian heart, too, an alteration in the tempera- 
 ture of a definite area of the wall of the right auricle lying between 
 the mouths of the venae cavae produces a change in the rate of the 
 whole heart, while no effect is caused by altering the temperature 
 of any other portion of the heart. It has already been stated that 
 tlie impulses from the nerve-cord which maintain the rhythm in the 
 Limulus heart are also discontinuous. 
 Conduction and Co-ordination. — -The question of the conduction 
 
THi: III \RT liF.AT IK ITS PHVSIoiJU.IC AL NI'.LATIOXS 
 
 H7 
 
 of Iho excitation over the heart and the co-ordination of its ])arts 
 is in tlie same position as the question of the automatism and 
 rhythmicity. In tlic horseshoe crab, as already remarked, the 
 mechanism appears to be a nervous one. In higher hearts, on the 
 other hand, facts have been discovered whicii favour each of the 
 rival hypotheses. In the frog's heart the probability that the con- 
 traction wave is propagated from fibre to fibre of the muscle without 
 the intervention of nerves has been much insisted upon, since the 
 muscular tissue, although presenting certain variations in its 
 character in the different divisions of the heart and at their junctions, 
 forms a practically continuous sheet over the whole organ from 
 base to apex. In support of this view has been brought forward 
 the observation that the delay of the wave at the auriculo- ventricu- 
 lar groove is much greater than it ought to be if the excitation were 
 transmitted by nerves, since the velocity of the nerve-impulse is 
 exceedingly great (p. 793) ; and the further observation that, when 
 the ventricle is caused to contract by artificial stimulation of the 
 auricle, this delay is appreciably greater when the stimulus is appHed 
 as far from the ventricle as possible than when it is applied as near 
 to it as possible. The delay has been attributed to the ' embryonic ' 
 character of the muscular tissue at the junction of the sinus with the 
 auricles and of the auricles with the ventricles. But it has never 
 been demonstrated that muscular fibres with the histological char- 
 acters described do, as a matter of fact, conduct the contraction 
 wave so much more slowly than the other cardiac muscular fibres 
 It is just as probable, and indeed more so, that, whether the con- 
 traction travels in any particular division of the heart directly from 
 muscle-fibre to muscle-fibre or not, the impulse to contraction is 
 transferred from each division of the heart to the next by a nervous 
 mechanism whose action is timed with the very object of securing 
 a certain interval between the systoles of successive divisions. In 
 any case, since we know that the velocity of the nerve-impulse is 
 very different in different varieties of nerves, the question cannot be 
 decided by general arguments of this kind. In Limulus, as a matter 
 of fact, the velocity in the intrinsic heart nerves is only one-tenth as 
 great as in the ordinary motor (hmb) nerves of the animal (Carlson). 
 In the mammalian heart the alleged absence of muscular con- 
 nection between the auricles and ventricles was long the foundation 
 of the general belief that the link was a nervous one. Certainly 
 there is no dearth of nerves which might serve as such a bridge. 
 But it has been shown (Kent, His, etc.) that in the mammahan 
 heart, too, a slender band of muscular fibres, arising at a definite 
 point (the auriculo- ventricular node) near the coronary sinus on the 
 right side of the interauricular septum below the fossa ovaUs, passes 
 forwards and downwards through the fibrous ring between the 
 auricles and ventricles under the septal cusp of the tricuspid valve. 
 It then divides into two branches, one for each ventricle, which run 
 
148 THE CIRCULATIOS OF THE BLOOD A\D LYMPH 
 
 down till' iuU'ivcntricular st'j)tum towards the apex, spreading out 
 as tlic Purkinje fibres or their equivalent, to blend at last with the 
 ordinary muscle of the ventricles, and particularly of the inter- 
 ventricukir septum. The fibres of the bundle are narrower than the 
 other fibres of the auricles, very rich in nuclei, and only slightly 
 differentiated into fibrillae. They seem to represent the remains ol 
 the primitive cardiac tube, which by the development of certain 
 pouches and twists becomes transformed into a multi-chambered 
 heart. Their resemblance to embryonic fibres suggests that they 
 may have retained the primitive capacity of the mesodermic tissue 
 of the embryonic heart to conduct, and even to originate, the 
 
 Fig, 64. — Right Auricle and Ventricle of Calf, to show Auriculo-Ventricular Band 
 (Keitli). I, central cartilage; 2, main auriculo-ventricular bundle; 3, auriculo- 
 ventriculcU' (A-V) node; 4, right septal division of the bundle; 5, moderator band; 
 6, msdial or septal cusp of tricuspid valve; 8, coronary sinus. 
 
 rhythmical contraction. But while there is no decisive evidence 
 that they constitute an automatic cardio- motor centre, as some 
 authors have supposed, they, or at least the narrow bridge of tissue 
 in which they he, do play an important part in the conduction of 
 the contraction from the auricles to the ventricles. For compres- 
 sion of the band produces a block, just as the pressure of a clamp 
 in the auriculo-ventricular groove does in the frog's heart (Kent). 
 With a certain degree of pressure the ventricle beats only once for 
 two beats of the auricle, with greater pressure only once for three 
 or more auricular beats. With a still greater pressure or after 
 crushing or section of the bundle conduction is abolished, and the 
 ventricle either remains at rest for a time, as in the frog's heart, or 
 
THi: HEART-BJiAT IN ITS PHYSIOLOGICAL RILLATlUSS 149 
 
 what is much mure common, imnicdiati'ly slaits btatiiif,' with an 
 indepondent rliythm, which is slower than that of the auricles 
 (Erlanger). It can be considered certain that in these obser\'ations 
 ncr\es may have been involved in the block as well as the muscle of 
 the auriculo-ventricular band, since this band is richly provided 
 
 rt ft 0* ^ a a a 
 
 Fig. 65.— Jugular (Upper) and Carotid (Lower) Pulse -Tracing from a Case of Arterio- 
 sclerosis, showing Partial Failure of Conduction in the Auriculo-Ventricular 
 Bundle (Cushny and Grosh). The ventricle only beats once to two beats of the 
 auricle. Time-trace, fifths of a second. 
 
 with nerve-fibres as well as ganglion-cells (Wilson). Yet it is 
 unlikely tliat all the nerves capable of conducting the impulses to 
 contraction should be' gathered into such a narrow compass, and 
 therefore the experiment supports the view that the conduction, is 
 carried out in the muscular tissue. And if the conduction of the 
 
 Fig 66.— Tracing of Jugular (Upper) and Radial (Lower) Pulse from a Maii with 
 Heart-Block (Le^^ris and Macnalty). In the cycles marked 34. 35. and 36 the 
 ventricular contraction, although less frequent than the auricular, was initiated 
 from the auricle. In the last two cycles (37 and 38) and the pause of 36 complete 
 heart -block was present. On the' jugular trace the a-c interval (representing 
 the interval between the onset of the auricular and ventricular contractions) is 
 given, and on the radial trace the duration of a cardiac cycle, both in fifths of a 
 second. 
 
 excitation from auricles to ventricles is accomplished by a muscular 
 connection, it is natvual to suppose that the co-ordination of sym- 
 metrical portions of the heart on either side of the longitudinal axis, 
 the co-ordination in virtue of which the two auricles contract 
 together and the two ventricles together, is also achieved by the 
 passage of impulses through the muscular tissue. In accordance 
 
150 THE CIRCULATION OP THE BLOOD A WD LYMPH 
 
 with this, it has been shown that the wntriclts in the d'»g and cat 
 continue to boat in unison, after the attempt has been made to 
 sever any nerves connecting them by extensive zigzag incisions, so 
 long as they are united by a narrow bridge of muscle (Porter). 
 
 In disease, interference with the conduction of the stimulus from 
 auricles to ventricles along the atrio-ventricular bundle is a not un- 
 common phenomenon. According to the degree of interference, the 
 ventricular contraction may be simply delayed, or only a certain pro- 
 portion of the auricular contractions (every second, every third, or 
 every fourth) may be conducted to the ventricle, or, finally, the block 
 may be complete, and the ventricle then contracts quite independently 
 of the auricle, the stimulus to contraction originating, perhaps, in the 
 uninjured portion of the bundle below the seat of the block. These 
 conditions are most easily recognized by comparing tracings simul- 
 taneously obtained from the jugular vein and the radial artery or apex- 
 beat (p. 90). When the block is complete the rate of the ventricle is 
 very slow (about 30 in the minute, or less), the time of the ventricular 
 beat is clearly unrelated to that of the auricular, and the stability of 
 the ventricular rhythm is abnormally great, such circumstances as 
 usually cause a marked increase in tlie pulse-rate — mental excitement, 
 for instance — affecting it little or not at all. This is the condition in 
 
 Fig. 67. — Polygraph Tracing £r .in a Case of True Bradycardia (Carter). The lower 
 trace is the radial, the upper the jugular. Time-trace, fifths of a second. 
 
 the so-called Stokes-Adams disease. In some of these cases pathological 
 (syphilitic) changes in the A-V bundle have actually been discovered 
 at necropsy. In others there is some reason to belie\'e that abnormal 
 excitation of the cardio-inhibitory nerves may be responsible even for 
 long-continued block, especially when the conductivity of the bimdle 
 has been already permanently diminished. 
 
 Cases of slow heart are also known in which there is no block in 
 the conduction system, but the original rh>i:hm of the auricle is slow 
 (so-called true br.idycardia. Fig. 67). 
 
 Kent ha^ pointed out that the muscular connection between the 
 auricles and ventricles is not single and confii.cd to the A-V bundle, 
 but multiple, and that the co-ordinated action of the chambers of the 
 heart is to some extent dependent upon the integrity of muscular 
 connections other than that which exists in the A-V bundle. One of 
 these he describes as the ' right lateral connection.' at the junction of 
 the right auricle, the right ventricle, and the tricuspid valve, at the 
 right-hand margin of the heart. The existence of this additional con- 
 nection, the importance of which relatively to that of the A-V bundle 
 need not be the same in every heart, may explain otherwise puzzling 
 
THi: HEART-BEAT /.V ITS PHYSfnEnClCAL RIU.ATIOXS 151 
 
 results Ixith cliniral and cxptMimental c.^., lliat sometimes co-ordina- 
 tion between the ventricles and auricles has continued after destruction 
 of the A-V bundle, while sometimes co-ordination has been upset by 
 lesions not affecting the bundle. 
 
 Fibrillary Contraction. — In the case of the warm-blooded Iicart a 
 coniph^tc breakdown of co-ordination occurs under certain cinnnn- 
 stanccs, producing the phenomenon known as fibrillary contraction, 
 or delirium cordis, a condition in which each minute portion, perhaps 
 each fibre, of the whole heart, or of a portion of it, goes on contract- 
 ing in a disorderly manner, quite independently of the rest. The 
 condition is often seen in a heart that has been exposed for some 
 time, particularly in the ventricle, and can be induced by stimulating 
 it with strong induction shocks or by ligation of the coronary 
 arteries. According to the best evidence, the condition is due to 
 the fact that the conductivity of the fibrillating muscle is interfered 
 with so that the contraction wave is prevented from running its 
 usual course. The consequence of this ' blocking ' is that the 
 normal co-ordinated action of the musculature gives place to the 
 confused movement characteristic of fibrillation (Porter, Garrey). 
 There is no reason to believe that fibrillary contraction is connected 
 with the loss of impulses from any special co-ordinating centre, for 
 it is not peculiar to the heart, but is typically seen in the tongue 
 when the circulation after a long interruption is restored. The 
 peculiar ' boiling ' movement is exactly similar to that observed in 
 the heart, probably because the tongue also contains fibres running 
 in, several directions. 
 
 The confused fibrillary contractions are quite ineffective for driving 
 on the contents of the heart. Fibrillation of the ventricle is therefore 
 incompatible with life. On the other hand, auricular fibrillation, far 
 from being immediately fatal, is one of the most common of the chronic 
 cardiac disorders in man. It is characterized by extreme irregularity 
 of the pulse, due to the fact that the ventricles are played upon by an 
 irregular stream of impulses from the fibrillating auricles to which they 
 respond as they best can. The auricular wave {a. Figs. 65-67) is absent 
 from the jugular pulse-tracing and the P wave (p. 836), corresponding 
 to the electrical change produced by the normally contracting auricles, 
 is absent from the electrocardiogram. Auricular flutter is a condition 
 which must be distinguished from auricular fibrillation. When a weak 
 stimulus is applied to the auricle of a dog or cat, the auricular beats are 
 grcii.tly increased in frequency up to 300 or 400 a minute. Although 
 the beats are so rapid, they are otherwise normal beats. When the 
 strength of the stimulus is increased, this condition of flutter 
 (Mac William) passes into fibrillation. Auricular flutter is also recog- 
 nized clinically. In the majority of cases the ventricle does not respond 
 to each beat of the auricle, and the arterial pulse is irregular; but each 
 auricular contraction produces its appropriate effect upon the electro- 
 cardiogram and often also upon the jugular tracing (Mackenzie). 
 
 Without entering further into a discussion of the rival hypotheses, 
 we may sum up by saying that for one heart {that of Limulus) the 
 automatism and the rhythmical power have been clearly shown to reside 
 
15^: rni: cinci'latjox of the blood axd lymph 
 
 in the local nervous apparalus ; for the hearts of other animals full and 
 formal proof of the neurogenic theory, so far as those tico properties of 
 the cardiac tissue are concerned, has not been given. As regards the 
 conduction and co-ordination of the contraction, the hulk of the evidence 
 (leaving the Limulus heart out of account) points to the muscular tissue 
 as the channel throw^h which the effective impulses pass. The normal 
 order or sequence in which the different parts of the heart contract depends 
 upon the fact that the automatism of the upper portions is more pro- 
 nounced than that of the loiver, so that under strictly physiological con- 
 ditions the contraction is only propagated, and not originated, by the 
 loicer parts of the heart. When, however, the signal to contraction 
 normalh' given b\' the basal region is prevented from reaching the 
 lower parts, an independent automatic rhythm of the latter may be 
 developed, as in the case of the mammalian ventricle mentioned 
 above. Here we may suppose that the automatic mechanism of the 
 lower portions of the heart discharges itself as soon as a sufficient 
 accumulation of energy has taken place in it, although it requires 
 a longer time to reach the point of discharge than the automatic 
 mechanism of higher parts, and therefore is normally discharged 
 from above. Under certain conditions the normal sequence can be 
 reversed. In the heart of the skate it is eas}-, by stimulating the 
 bulbus arteriosus, to cause a contraction passing from bulbus to 
 sinus. The power of propagating the contraction may also be 
 artificially altered. As already mentioned, it may be diminished or 
 abolished by pressure. The same effect may be produced by fatigue 
 or cold, while heating a portion of the heart in general increases its 
 power of conducting the contraction. 
 
 Chemical Conditions of the Beat. When we have localized the 
 essential mechanism of the rhythmical beat in the nervous or in the 
 muscular elements, the question may still be asked what the 
 chemical and physical conditions are which are necessary to its 
 maintenance. While it is known that a supply of arterial blood at 
 or near body-temperature, and under a sufficient pressure, is required 
 for permanent cardiac contraction, much simpler solutions will 
 suffice to maintain the activity even of the isolated mammalian heart 
 for a considerable time. One of the best of these is a solution contain- 
 ing sodium chloride, potassium chloride, calcium chloride, and sodium 
 bicarbonate in the proportions in which they exist in blood-serum, 
 with the addition of a small quantity of dextrose (Locke, p. 66). 
 When this solution, properly oxygenated and warmed, is circulated 
 through the coronary vessels of an excised rabbit's or cat's heart, 
 strong and regular beats may be observed for many hours. Some 
 investigators have claimed for sodium chloride, and even for sodium 
 ions, others for calcium salts or calcium ions, a special role in the 
 origination or maintenance of the rhvtlmiical beat. There is no 
 doubt that strips from the ventricle of the tortoise or turtle, which 
 
THE 111: ART-BEAT IN ITS PHYSIOLOGICAL RELATIOSS 153 
 
 after isolation have ceased beating, and if left to themselves in a 
 moist chamber do not develop rhythmical contractions, begin after 
 a while to beat when immersed in or irrigated with a solution of 
 sodium chloride or a solution of cane-sugar containing a little of that 
 salt. They refuse to beat in any solution which does not contain 
 sodium chloride (Lingle). The addition of calcium chloride to the 
 sodium chloride solution, or preliminary treatment of the strip with 
 a solution of a calcium salt before its immersion in the sodium 
 chloride solution, hastens the onset of the contractions, and increases 
 the length of time for which they are kept up (Erlanger). It is 
 unquestionable that for the normal beat of the heart the presence 
 of both salts is one of the necessary conditions, but there is at 
 present no sufficient foundation for the view that either the one or 
 the other acts as a special chemical excitant of the automatic 
 contraction. Still less necessary is it to make this assumption for 
 potassium. Certain potassium salts are, of course, beneficial to 
 the heart as to other tissues. This might be assumed from their 
 presence in blood and lymph, and it has been shown experi- 
 mentally. But a terrapin's heart will continue beating, and beating 
 well for a considerable time when irrigated with a solution con- 
 taining sodium and calcium salts alone and free from potassium. 
 That the reaction of the perfusive fluid is of great importance in 
 connection with the origination of rhythm is well established, and 
 it is an interesting fact that the limits of H ion concentration 
 within which the development of spontaneous beats is possible 
 differs for the hearts of different kinds of animals (Mines), and even 
 for the different portions of the frog's heart (Dale and Thacker). 
 While these facts illustrate the importance of the inorganic com- 
 position of the nutritive Hquids for the action of the heart, they 
 leave the old question of the existence and the nature of an inner 
 stimulus to the rhythmic contraction very much where it was. 
 
 Resuscitation of the Heart. — Not only can the beat of the freshly- 
 excised mammaUan heart be long maintained by artificial circulation, 
 but many hours or even some days after somatic death pulsation 
 may be restored by the perfusion of such a solution of inorganic 
 salts as Locke's through the coronary vessels. Kuliabko in this 
 way was able to restore a rabbit's heart which had been kept forty- 
 four hom-s in the ice-chest. Even after an interval of three to five 
 days from the death of the animal, in other experiments, pulsation 
 returned in certain parts of the heart, while twenty hours after 
 death from double pneumonia the heart of a boy three months 
 old was restored, and went on beating for over an hour. He obtained 
 also more or less complete restoration of the beat in the hearts of 
 persons dead from bronchitis combined with peritonitis or menin- 
 gitis, and from cholera infantum, but was unsuccessful in cases of 
 diphtheria complicated with septicaemia or erysipelas, and in cases 
 
154 THE circulation: Oh' THE BLOOD ASD LYMl'JI 
 
 of pleurisy witli elfusioii. It is to be remarked, howevt-r, that 
 althougli beats of a kind can be obtained a long time after death, 
 they are either confined to tlic auricles or to jiortions of them, or, 
 if they involve the ventricles too, they are only shallow and local 
 contractions, especially seen in the neighbourhood of the larger 
 coronary vessels, and are utterly inadequate to the maintenance 
 of an eflicient circulation. The heart can also be resuscitated in situ 
 for some time after complete stoppage without the injection of any 
 solution by clamping the aorta in the thorax and practising direct 
 cardiac massage, the lower end of the animal at the same time being 
 elevated to allow blood to pass out of the engorged abdominal veins 
 to the right auricle. The clamping of the aorta permits a sufficient 
 pressure to be attained for the filling of the coronary arteries. The 
 injection of adrenalin into the blood has also been recommended as 
 a means of raising the blood- pressure by constricting the small 
 arteries, and stimulating the action of the cardiac muscle. The 
 possibility of restoration of the mammahan heart many hours after 
 somatic death has been considered by some a strong argument for 
 the myogenic theory of cardiac automatism, since, they say, it is 
 improbable that ganglion-cells, elsewhere such physiologically 
 fragile structures, should in the heart retain their vitality for so 
 long a time. But it is easy to overdo this argument, and we must 
 not assume without proof that ganglion-cells in all parts of the body 
 have an equal capacity of survival. Indeed, we know that there 
 are great differences, the nerv^ous mechanism concerned in respira- 
 tion, eg., being capable of restoration when the circulation is re- 
 newed after total anamia of the brain and cervical cord lasting for 
 as much as an hour (in cats), while the nervous mechanism con- 
 cerned in voluntary movements cannot be completely restored even 
 after a much shorter interval. It is very probable that the cardiac 
 ganglia, if the all-important automatic function of the heart depends 
 upon them, are, like the cardiac muscle, endowed with exceptional 
 powers of resistance to those changes which constitute death. 
 The possibility also must not be overlooked that the contractions 
 obtained after such long intervals are not truly automatic, but 
 similar rather to the rhythmical beats developed under the influence 
 of pressure in the frog's apex preparation or by immersion in salt 
 solutions of tortoise ventricle strips. 
 
 In addition to its marked power of rhythmical contraction, the 
 cardiac muscle is distinguished from ordinary skeletal muscle by 
 other peculiarities. It used to be considered the most striking of 
 these peculiarities that ' it is everything or nothing with the heart '; 
 in other words, that the heart muscle, when it contracts, makes the 
 best effort of which it is capable at the time; a weak stimulus, if 
 it can just produce a beat, causing as great a contraction as a strong 
 stimulus. Recent work, however, has indicated that this property 
 
THE HEART-BEAT IN ITS PHYSIOLOCJCAL RELATIONS 155 
 
 is also possessed by the skeletal muscle-fibre. When a whole skeletal 
 muscle is excited either directly or through its motor nerve, it is 
 true that throughout a considerable range increase of stimulus is 
 accompanied by an apparent increase in the strength of contraction. 
 But there is reason to believe that this is because a larger and larger 
 number of fibres become involved in the excitation as the stimulus 
 is increased, and not because each fibre responds more and more 
 strongly (Lucas). In skeletal muscle the fibres are completely 
 isolated from each other, and the excitation does not spread from 
 fibre to fibre, as happens in the heart. 
 
 Refractory Period and Extra Contraction of Hear! Muscle. — A 
 more characteristic property of the cardiac muscle than the ' all or 
 nothing ' law is that a true tetanus of the heart cannot be obtained 
 at all, or only under very special conditions. When the ventricle 
 of a normally beating frog's heart is stimulated by a rapid series of 
 induction shocks, its rate is generally increased, but there is no 
 definite relation between the number of stimuli and the number of 
 beats. Many of the stimuli are ineffective. In the same way a 
 portion of the heart, such as the apex of the ventricle, when stimu- 
 lated in the quiescent condition by an interrupted current, responds 
 by a rhythmical series of beats, and not by a tetanus. It is evident 
 that the cardiac muscle, like ordinary striped muscle, is for some 
 time after excitation incapable of responding to a fresh stimulus — 
 i.e., there is a refractory period. But this is immensely longer in 
 cardiac than in skeletal muscle. When the phenomenon is analyzed, 
 it is found that a stimulus falling into the heart muscle between the 
 moment at which the contraction begins and the moment at which 
 it reaches its maximum produces no effect — is, so to speak, ignored. 
 When the stimulus is thrown in at any point between the maximum 
 of the systole and the beginning of the next contraction, it causes 
 what is called an extra contraction. The extra contraction is 
 followed by a longer pause than usual — a so-called compensatory 
 pause — which just restores the rhythm, so that the succeeding 
 systole falls in the curve where it would have fallen had there been 
 no extra contraction (Fig. 68) . 
 
 In man, extra systoles followed by compensatory pauses may occur 
 under pathological conditions, giving rise to an important group of 
 cardiac irregularities. These extra systoles may be cither auricular or 
 ventricular, the auricle or the ventricle contracting prematurely without 
 wailing for the signal of the sinus rhythm. The analysis of pulse - 
 tracings showing these irregularities has led to results of great physio- 
 logical and clinical interest (Cushny, Mackenzie, etc.), but cannot be 
 dwelt on here. When every second beat is an extra systole, generally 
 weaker than the preceding and the succeeding normal beat, the condi- 
 tion is called pulsus higeminus. The weaker beat is always followed 
 by a compensatory pause of greater duration than that preceding it. 
 From the pulsus bigeminus must be distinguished that form of alterna- 
 ting pulse termed pulsus alternans, in which every second beat is dimin- 
 shed in size, but the intervals separating the beats are of uniform length. 
 
156 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 The refractory period is shorter for strong than for weak stimuli, 
 and is markedly diminished by raising the temperature of the heart. 
 So that stimulation of the heated heart with a series of strong 
 induction shocks may cause a tetaniforni condition, if not a typical 
 
 tetanus. The con- 
 traction of the 
 normally beating 
 heart is really a 
 simple contrac- 
 tion, and not a 
 tetanus. The 
 electrical changes 
 correspond to a 
 single contraction 
 (P-833) ; and when 
 the nerve of a 
 nerve-muscle pre- 
 paration is laid 
 on the heart, the 
 muscle responds 
 to each beat by a 
 simple twitch, 
 and not by tet- 
 anus (p. 20.^). 
 That the cardiac 
 muscle itself, apart from the intrinsic nervous mechanism, shows 
 the phenomenon of ' refractory state ' has been shown in the 
 Limulus heart after extirpation of the ganglion (Carlson). 
 
 Like ordinary skeletal muscle, the cardiac muscle is at first bene- 
 fited by contraction, perhaps by an ' augmenting ' action of fatigue- 
 l^roducts such as carbon dioxide (Lee), so that when the apex is 
 stimulated at regular intervals each contraction is somewhat 
 stronger than the preceding one. To this phenomenon the name of 
 the staircase or ' treppe ' has been given, from the appearance of the 
 tracings (p. 749). 
 
 l"ig. 68. — Refractory Period and Compensatory Pause 
 (Marey). A frog's lieart was stimulated at a point corre- 
 sponding to the nick in the horizontal line below each 
 curve. In i and 2 there was no response ; in 3 and 4 there 
 was an extra contraction, succeeded by a compensatory 
 pause. 
 
 Section V. — The Nervous Regulation of the Heart 
 (Extrinsic Nervous Mechanism of the Heart). 
 
 While, as we have seen, the essential cause of the rhythmical beat 
 of the heart resides in the tissue of the heart itself, it is constantly 
 affected by impulses that reach it from the central nervous system. 
 These impulses are of two kinds, or, rather, produce two distinct 
 effects: inhibition, shown by a diminution in the rate or force of the 
 heart-beat, or in the ease with which the contraction is conducted 
 over the heart-wall; and augmentation, or increase in the rate or 
 
THE NliliVOUS REGULATION OF THE HEART 
 
 157 
 
 force of the beat or in the conductivity. Both the inhibitory and 
 th ' augmentor impulses arise in the medulla oblongata, and perhaps 
 a narrow zone of the neighbouring portion of the cord; and they can 
 be artificially excited by stimulation in this region. They pursue 
 their course to the heart by fibres which may in certain animals be 
 mingled together, but are anatomically distinct. We may, there- 
 fore, divide the extrinsic or external nervous mechanisnr of the 
 heart into a cardio-inhibitory centre with its efferent inhibitory 
 nerve-fibres and a cardio-augmentor centre with its efferent acceler- 
 ator or augmentor fibres. Both of those centres, as we shall see, 
 have, in addition, extensive relations 
 with afferent nerve- fibres from all parts 
 of the body, including the heart itself. 
 
 It was in the vagus of the frog that 
 inhibitory nerves were first discovered 
 by the brothers Weber seventy years 
 ago, and even now our knowledge of the 
 cardiac nervous mechanism is more com- 
 plete in this animal than in any other. 
 We shall, therefore, first describe the 
 phenomena of inhibition and augmen- 
 tation as we see them in the heart of the 
 frog, and then pass on to the mammal. 
 
 In the frog the inhibitory fibres leave 
 the medulla oblongata in tlie vagus nerve. 
 Tlie augmentor fibres come off from the 
 upper part of the spinal cord by a branch 
 from the third nerve to the third sympa- 
 thetic gangUon, and thence find their way 
 along the sympathetic cord to its junction 
 with the vagus, in which they run, mingled 
 with the inhibitory fibres, down to the heart. 
 
 When the vago-sympathetic in the 
 frog or toad is cut, and its peripheral 
 end stimulated, the heart in the vast 
 majority of cases is stopped or slowed, 
 or its beat is distinctly weakened without, it may be, any marked 
 slowing. In other w^ords, the rate at which the heart was 
 working before the stimulation is greatly diminished, or reduced 
 to zero. Such an effect, a diminution of the rate of working, 
 we call Inhibition. What precise form the inhibition shall take, 
 whether the stoppage shall be complete or partial, and if partial 
 whether the beats shall be simply weakened without being slowed 
 or both slowed and weakened, appears to depend partly upon the 
 strength of the stimulus used and partly upon the state of the 
 heart itself. Some hearts it may be impossible to stop with weak 
 stimulation, although other signs of inhibition may be distinct; 
 
 Fig. 69. — Diagram of Extrinsic 
 Nerves of Frog's Heart (after 
 Foster). Ill, 3rd spinal 
 nerve; AV, annulus of Vieus- 
 sens; X, roots of vagus; IX, 
 glosso-pharyngeal nerve; VS, 
 combined vagus and sympa- 
 thetic; I, 2, and 3, the ist. 
 2nd, and 3rd sympathetic 
 ganglia. The dark line indi- 
 cates the course of the sym- 
 pathetic fibres. The arrows 
 show the direction of the aug- 
 mentor impulses. 
 
158 THE CIRCULATIOS OF THE BLOOD AND LYMPH 
 
 while they are readily stopped by stronger stimulation. In other 
 cases the strongest stimulation may not produce complete standstill. 
 Again, the inhibitory effect produced on a heated heart by a given 
 strength of stimulation of the vagus may be greater than that caused 
 in a heart at the ordinary temperature or a cooled heart. This is 
 especially e\ndent on the auricular tracings when these are recorded 
 separately from those of the ventricle. Even on the verge of heat 
 standstill of the heart inhibition is easily obtained (Fig. 71). Some 
 writers have assumed that the different inhibitory effects produced 
 by the vagus are due to the existence in it of separate groups of fibres, 
 somr affecting only the rate of the contraction, others its strength. 
 
 Fig. 70. — Tracing from Frog's Heart. A, auricular, V, ventricular tracing. Sinus 
 stimulated (primary coil 70 mm. from secondary). Heart at temperature 
 ii"2° C. Complete standstill. The time-tracing between the curves marks 
 intervals of two seconds. 
 
 others still the conductivity of the muscular tissue and its excita- 
 bility. This theory has ennched the vocabulary of physiology 
 with a number of sonorous terms derived from the Greek, but has 
 not otherwise established itself, although it has been useful in 
 emphasizing the fact that the inhibitory nerves can influence the 
 heart-beat in several distinct ways. 
 
 But there are other points of importance to be noted in regard to 
 this inhibition : (i) It does not begin for a little time after stimulation 
 has begun. In other words, there is a distinct latent period; and 
 the length of this latent period is related to the phase of the heart's 
 
THE KERV0U6 REC.ULATION OE THE HEART 
 
 150 
 
 contraction at whicli the stimulus is thrown in, and to the rate at 
 which the heart is beating. As a general rule, the heart makes at 
 least one beat before it stops. 
 
 (2) The inhibition does not continue indefinitely, even if stimula- 
 tion of the nerve is kept up. Sooner or later, and usually, in fact, 
 after an interval of a few seconds, the heart begins again to beat if it 
 has been completely stopped, or to quicken its beat if it has only been 
 slowed, or to strengthen it if the inhibition has only weakened the 
 contraction, and it soon regains its old rate of working. Not only 
 so, but very often there follows a longer or shorter period during 
 which the heart work.^ at a gi-eater rate than it did before the inhibi- 
 tion, and this greater rate of working may be manifested by increased 
 
 Fig. 71. — Activity of Vagus on Verge of Heat Standstill. Auricular and ventricular 
 contractions of toad's heart recorded. Heart at 34'5* C, v 50, stimulation of 
 vagus (distance of coils 50 mm.). The ventricle was already in heat standstill; 
 the auricle was at once inhibited. Then follows secondary augmentation (due 
 to the sympathetic fibres), during which the ventricle also resumes beating. 
 An interval of a minute elapsed between the first and second parts of the 
 tracing, during which the heart remained at 34'5° C. The auricle was almost 
 in standstill (contractions can still be seen on the curve with a lens), when the 
 vagus was again stimulated at v 50 with the same distance between the coils. 
 Complete inhibition followed by secondary augmentation. 
 
 frequency of beat, or increased strength of beat, or by both. When 
 the temperature of the heart is low, increased frequency ; when it is 
 high, increased strength, is generally seen during this period of 
 secondary augmentation* The cause of this secondary augmentation, 
 and of the primary augmentation sometimes seen in fresh prepara- 
 tions and often in hearts that have been long exposed (Fig. 73), 
 excited much speculation before it was known that sympathetic 
 fibres existed in the vagus. There is no longer any doubt that it is 
 due to the stimulation of these accelerator or, as it is better to call 
 
 * Augmentation is termed ' secondary ' when it is preceded by inhibition, 
 primary ' when it is not so preceded 
 
i6o THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 them (since mere acceleration is not the only consequence of their 
 stimulation), augmentor fibres in the mixed nerve. For (i) excita- 
 tion of the roots of the vagus proper within the skull, and therefore 
 above the junction of the sympathetic fibres, causes no secondary 
 augmentation, or very little, and the inhibition lasts far longer than 
 when tlie mixed trunk is stimulated. (2) Excitation of the upper 
 or cephalic end of the sympathetic cord before it has joined the 
 vagus causes, after a relatively long latent period, marked augmenta- 
 tion. And if the contractions of the heart are registered, the 
 tracing bears a close resemblance to the curve of secondary augmen- 
 tation following excitation of the mixed nerve on the other side 
 with an equally strong stimulus and for an equal time. (3) When 
 tlie vago-sympathetic is stimulated weakly there is little or no 
 
 Fig. 72. — Frog's Heart: Vagus stimulated. Temperature of heart 8° C; 78 mm. 
 between the coils. Diminution in force of auricle and ventricle, but not com- 
 plete standstill. Time-tracing shows two-second inter\-als. 
 
 secondary augmentation. Now, it is known that the augment or 
 fibres require a comparatively strong stimulus to cause any eftect 
 when they are separately excited, whereas a weak stimulus will 
 excite the inhibitory fibres. 
 
 The question arises at this point, why it is that, when the inhibitory 
 and augmentor fibres are stimulated together in the mixed nerve (and 
 the same is true when the sympathetic on one side and the vagus on 
 the other are stimulated at the same time), the inhibitory effect always 
 comes first, when there is any inhibitory- effect, while the augmentation 
 always has to follow. The answer has sometimes been given, that the 
 latent period of the augmentor fibres is longer than that of the inhibitory 
 fibres. But although this is certainly the case, the answer is insuffi- 
 cient. For the period of postponement may be much greater than the 
 
Till'. ST.RVOUS REGULATION OF THE HEART 
 
 161 
 
 latent prriod of tlie sympatlittic fibres when stimulated by themselves. 
 The inhibition apparently runs its course without being affected by the 
 simultaneous augmentor effect, which, lying latent until the end of the 
 inhibition, then bursts out and completes its own curve. It is not like 
 the passing of two waves through each other, but rather like the stopping 
 of one wave until the other has passed by. It seems as if augmentation 
 cannot develop itself in the presence of inhibition — at least, until the 
 latter is nearly spent. Like a musical-box devised to play a series of 
 melodies in a fixed order, and from which a particular tune cannot be 
 obtained till those preceding it have been run through, the heart, in 
 some way or other, is arranged, in the presence of competing impulses 
 from its extrinsic iRT\es, to play the tune of inhibition before the tune 
 
 Fig. 7317. — Frog'a Heart. A, auricular, V, ventricular tracing. Ventricle beating very 
 feebly. Vagus stimulated (60 mm. between coils). Marked augmentation of 
 ventricular beat. 
 
 of augmentation. In the frog, at any rate, the two processes can hardly 
 be considered as antagonistic, in the sense that a definite amount of 
 aiigmcntor excitation can overcome a definite amount of inhibitorv 
 excitation. Nor is it the case that, when tlic heart is played upon at 
 the same time by impulses of both kinds, it pits them against each other 
 and strikes the balance accurately between them. It is possible, how- 
 ei'er, that when the inhibitory fibres are ver\' weakly, and the augmentor 
 fibres ver^' strongly stimulated, the amount of inhibition may be some- 
 what diminished. In mammals, on the otiicr hand, a true antagonism 
 seems to exist; and stimulation of the inlii'.^itory nerves is less effective 
 when the augmentors are excited at the s.'.me time. The cardiac nerves 
 affect not only the rate and force of tlie contraction, but also the con- 
 
l62 
 
 THE {'IRCrLATlOS OF THE BI.nOD A\D I.YMPH 
 
 ductivity of the heart. Thus in the frog's heart (hiring stimulation of 
 the vaf-iis, the contraction passes more slowly, and during stinnilation 
 of the symiKithetic more quickly, from auricles to ventricle. 
 
 In mammals (anil m what follows wc shall restrict ourselves chiefly 
 to the dog. cat, and rabbit, as it is in these animals that the subject 
 has been most carefidly studied) the inhibitory fibres run down the 
 vagus in the neck and reach the heart by its cardiac branches. They 
 are derived from the bulbar roots ol the spinal accessory, whose inner 
 branch joins the vagus. The nugmcniny nlires leave the spinal cord in 
 the anterior roots of the second and llur>i thoracic nerves, and possibly 
 to some extent bv the fourth and fifth. Through the corresponding 
 
 Fig. 7.^6.— Miniature MyocaidioRraph factual size) 
 (Wiggers). C, light aUimiiiium segment capsule 
 covered by tightly stretched rubber dam, upon 
 wliich is cemented an aluminium plate pivoting 
 npiin tiierliord side of tlic capsule. The plate 
 carries a light arm, A, with an eyelet at its ei>d. 
 A similar arm, A^, is rigidly fastened to the body 
 of the capsule. The arms can be bent so that 
 the distance between the eyelets varies from 
 3 to 23 millimetres, and are connected by 
 stitches through the eyelets to points on the 
 auricular surface. The approximation of the 
 points causes a negative pressure in tht' cap- 
 sule, and in the recording capsule (see descrip- 
 tion of l"ig. 31, p. 03) connected with it by the 
 tube T. Hence, the down-stroke of the curve 
 represents contraction, the up-stroke relaxation. 
 The apparatus is supported by a very light 
 spring, S. 'i"his enables it to follow varying 
 degrees of distension and movement of the 
 auricle without affecting the curve of contrac- 
 tion. The small mass (less than 2 gm.) and 
 high vibration frequency of the instrument 
 insure a more faithful record of the con- 
 traction than with older forms. 
 
 white rami communicantcs they reach the sympathetic cord, and 
 running iip through the stellate ganglion (first thoracic), and the 
 annuhhi of V'icussens, which surrounds the subclavian artery, to the 
 inferior cervical ganglion, thev pass off to the heart by separate 'acce- 
 lerator ' branches, taking origin either from the anindus or from the 
 inferior cervical ganglion. Some augmentor fibres are often, if not 
 always, present in the dog's vago-svmpathctic in the neck. It is 
 especially easy to demonstrate their presence five or six days after 
 section of the nerve, when the excitability of the inhibitory fibres has 
 disappeared. 
 
 In the dog the vagus and cervical sympathetic are, in the great 
 majority of cases, contained in a strong common sheath, and pass 
 
77//; .\i livous iriA.ii.A ri(>\ oh' i iii. iii: \i<r k,, 
 
 together through the infcric)r cervical gangUon. I'pon opening this 
 sheath thcv may with care l)c separated, the fibres running in distinct 
 strands, and not mixed together as in the vago-sympathetic ot the frog. 
 For some distance below the superior cervical ganglion the cervical 
 sympathetic is not connected with the vagus, and here the nerves may 
 be separately stimulated without any artificial isolation. In the rabbit 
 and some other mammals, including man, the vagus and sympathetic 
 nm a separate course in the neck. 
 
 In the mammal, the inhibitory fibres have a smaller direct action 
 on the ventricle than in the frog. It indeed beats more slowly when 
 the auricle is slowed, but this is only because in the normally beating 
 heart the ventricle takes the time from the auricle. The strength 
 of the ventricular contractions may be not at all diminished, even 
 when the auricle is beating very feebly during inhibition. When the 
 auricle is completely stopped, which does not occur so readily as in 
 the frog, the ventricle also stops for a short time, but soon begins to 
 beat again with an independent rhythm of its own. In the frog the 
 ventricle is directly affected by stimulation of the vagus, and the 
 force of its beats is diminished independently of the inhibitory 
 effects in the auricles (Practical Exercises, pp. 198, 203). 
 
 It has been shown by delicate optical methods of recording the 
 contraction of small units of the auricular musculature (designated 
 as the ' fractionate ' contraction by Wiggers) by the method illus- 
 trated in Fig. 736, that the diminution in the size of the contrac- 
 tion produced by stimulation of the vagus is essentially due to 
 depression of the contractility of the muscle, and not, or at any rate 
 not primarily, to a diminution in its excitabilit}'. In other words, 
 the strength of stimulus needed to elicit a contraction of the muscle 
 when under the influence of vagus excitation, in the early part of 
 the inhibition at least, is not increased, whereas the size of the 
 contraction evoked by a given stimulus is diminished (Fig. 74). 
 
 It is not doubted that the excitation of the vagus does reduce the 
 excitability of the auricular muscle, but this reduction seems not to 
 occur so early as the reduction in the amplitude of the beat, and 
 cannot therefore be responsible for it. The duration of each 
 (fractionate) contraction is not altered by vagus excitation. It 
 can hkewise be shown that the depression of contractility is not 
 secondary to the depression of conductivity produced by the vagus. 
 Finally, it is not dependent upon the slowing of the rhythm which 
 accompanies the diminution in the contraction of the naturally 
 beating auricle. For when the auricle is compelled to beat with an 
 artificial rhythm by applying to it a series of regularly spaced 
 electrical stimuli at a more rapid rate than the normal rh>i:hm, 
 stimulation of the vagus still causes reduction in the amplitude of 
 the contraction without change in the rate (Fig. 74). One other 
 point is worthy of note. Excitation of the vagus causes an increase 
 in the size of the first, or occasionally of the first two subsequent 
 
i64 
 
 THE CTRCrn.AriON OF THE BLOOD AND LYMPH 
 
 contractions ol the auricular muscle when the rhythm is slowed, 
 but not otherwise. It is probable that this is due to the beneficial 
 influence of the longer period of rest associated with the diminution 
 in frequency of the beat before the inhibitory action has had time 
 to cause depression in the amplitude (Wiggers). 
 
 vs W^ 
 
 % Vruii ui it AC <t J-I I XK 
 
 WWB. ytwo. marrti. wtmu ■■ 
 
 "mpirrfw 
 
 1o 
 
 off 
 
 I'ig. 74. — -Influence of the Vagus on the Contraclioti uf ilic l>('n'~- Ki;;in Auiulr 
 The two upper curve? are simultaneous records of the contraction of very short 
 portions of the auricle (bocalled fractionate contraction) taken from two 
 regions, one near the sinus node P, and one far from it, D. The contraction 
 begins and ends slightly sooner in the proximal than in the distal region. 
 The losvest curve shows the depressant effect of the vagus excitation mani- 
 fested when an artificial rhythm (a series of electrical break shocks), which is 
 not altered by sthnulation of the vagus, is substituted for the normal rhythm 
 sustained by the ' pacemaker.* 
 
 The inhibitory fibres, then, influence the heart particularly 
 through the auricles; they are par excellence auricular nerves. On 
 the other hand, the accclernntes in all ni.mimals which have been 
 investigated not only extend to the \-entricles. but are even mainlv 
 distributed to them. They are emphatically ventricular fibres, and 
 
THE NERVOUS REGULATIOS OE THE HEART 165 
 
 in accordance with its greater mass the left ventricle receives more 
 fibres than the right. 
 
 Stimulation of the accelerator nerves in the dog causes an 
 increase in tlie force of both the auricular and ventricular con- 
 traction, and as a rule, in addition, some increase in the rate of 
 the beat. 
 
 As to the nature of the physiological linkage between the cardiac 
 nerves and the muscular tissue of the heart we know but Uttlc. 
 (ianglion-colls lie on the course of the vagus fibres after they 
 have entered the lieart, and although the view has been advocated 
 that they are simply stations where the inhibitory impulses pass 
 from medullated to non-medullatcd tibus, and where possibly other 
 
 Fig- 75- — ^ ood-Presu ■ Iracings: Rabbit. Vagus stinmlated at r. Stimulus 
 biroiigci m B tlian in A (Hiirthlc's spring manometer). 
 
 anatomical changes and rearrangements occuf, they may be inter- 
 mediate mechanisms which essentially modify the physiological 
 impulses falHng into them. It has been stated that in the dog the 
 right vagus controls chiefly the rate of the heart, and the left vagus 
 chiefly the conduction from auricles to ventricles, and the suggestion 
 has been made that this is because the right vagus has a special 
 relation to the sino-auricular node, in which impulses are supposed 
 to arise, and the left vagus a special relation to the auriculo-ven- 
 tricular node, the upper end of the A-V bundle, the main conduction 
 system (Cohn and Lewis). 
 
 The nervi accelerant es are already non-medullated before they 
 
I66 Tlir. CIRCri ATWS 01' THE BLOOD ASH I.YMPH 
 
 reach the heart. The fact tliat tlic action of the accch'rantes can 
 be rt'stortd by perfusing the heart with a nutrient sohition at a 
 much longer interval after somatic death than the action of the 
 vagus strengthens the suggestion that ganglion-cells are interposed 
 on the inhibitory though not on the augmcntor path, without, 
 however, proving of itself that such a difference exist> In one 
 experiment the heart of an anthropoid ape was revived when thicc 
 successive periods — viz., four and a half, twenty-eight and a half, 
 and fifty-three hours respectively — had elapsed after the death of 
 the animal, although during the last period the heart had been 
 twice frozen hard. The vagus was shown to be still capable 
 of causing some inhibition six hours after death, and the 
 accelerans some augmentation as late as fifty-three hours after 
 death (Hering). 
 
 In the discussions over the relation of the extrinsic to the intrinsic 
 cardiac nervous apparatus appeal has frequently been made to the 
 action of certain poisons on the heart. Thus, after vicotine stimulation 
 of the vago-sympathctic causes no inhibition of the frog's heart; it may 
 cause augmentation. But stimulation of the junction of the sinus and 
 auricle still causes inhibition. Atropine not only abolishes the inhibi- 
 tory effect of .stimulation of the vagus trunk, but also that of stimula- 
 tion of the junction of sinus and auricle. Muscarine causes diastolic 
 arrest in a heart ah-eadv poisoned with nicotine, but not in a heart 
 under the influence of atropine. And a heart brought to a standstill by 
 muscarine can be made to beat again by the application of atropine, 
 although not by nicotine. 
 
 These facts may be explained as follows: Nicotine paralyzes, not the 
 very ends of the vagus, but the ganglia through which its fibres pass. 
 Stimulation of the sinus, which is practically stimulation of the vagus 
 fibres between the ganglion-cells and the muscular fibres, is therefore 
 effective, although stimulation of the nerve-trunk is not (Langley). 
 On the other hand, the atropine group paralyzes the nervc-cndin'gs 
 themselves, or interferes with the reception of the inhibitory impulses 
 by acting on a so-called receptive substance in the muscle (p. 182), so 
 that neither stimulation of the sinus nor of the nerve-trunk can cause 
 inhibition. Muscarine, on the contrary, stimulates the vagus fibres 
 between the nerve-cells and the muscle, or the actual nerve-endings, or 
 exerts an inhibitory action on the muscle itself through the appropriate 
 receptive substance, and thus keeps the heart in a state of permanent 
 inhibition, which is removed when atropine cuts out the nerve-endings, 
 or combines with the receptive substance. It is quite in accordance 
 with this that muscarine has no effect on a heart whose vagus nerves, 
 as occasionally happens, have no inhibitory power. Pilocarpine has 
 very much the same action as muscarine. 
 
 Stannius' Experiment. — Another series of phenomena, intimately 
 related to our present subject, have excited, since they were first made 
 known by Stannius, an enormous amount of discussion. The chief 
 facts of this classical experiment we have already mentioned (p. 144), 
 and they are also described in the f^ractical Exercises (p. i<)4). They 
 are easy to verify, but difficult to interjjret. The most probable explana- 
 tion of the standstill caused by the first ligature is that the lower portion 
 
Till: M-in'ors f^'iA.ri..iri().\ oi' i iii. iii.ih'T 
 
 i"7 
 
 <il tlic lKa:l. when cut utt tiom the sinus m wliicli Ihc btat normally 
 originates, needs some lime for llie development of its automatic power 
 to the p(Mnt at which an independent rhythm can be maintained. The 
 effects following the second Stannius ligature seem to depend upon the 
 power of the ventricle to develop and maintain an independent rhythm, 
 but the contractions are supposed by some to be started by stimulation 
 of the muscular tissue in the auriculo-vcntricular groove by the ligature. 
 Nature of Inhibition and Augmentation. - So far we have been dis- 
 cussing the phenomena of iiijiibilion and augmentation as ultimate 
 facts. We have not attempted to go behind them, nor to ask what it 
 is that really happens when inhibitory impulses fall into a heart, which 
 from the first days of embryonic life has gone on beating with a regular 
 rhythm, and in the space of a second or two bring it to a standstill. 
 The question cannot fail to press itself u]on the niind of anyone who 
 has ever witnessed this most beautiful of physiological experiments; 
 
 Fig. 76. — Frog's Heart. Sympathetic stimulated (30 mm. between the coils). 
 Temperature 12°. Marked increase in force. Only auricular tracing repro- 
 duced. Time-trace, two-second intervals. 
 
 but as yet there is no answ^er except ingenious speculations. The most 
 plausible of these is the trophic theory of Gaskell, who sees in the vagus 
 a nerve which so acts upon the chemical changes going on in the heart 
 as to give them a trophic, or anaboUc, or constructive turn, and thus to 
 lessen for the time the destructive changes underlying the muscular 
 contraction. The augmentor nerves, on the other hand, are supposed 
 to exert a katabolic influence, and to favour these destructive changes. 
 And while, according to Gaskell, the natural consequence of inhibition 
 is a stage of increased efficiency and working power when the inhibition 
 has passed away, the natural complement of augmentation is a tem- 
 porary exhaustion. It is very risky, however, to rely, as Gaskell did, 
 upon a supposed change of sign in the electrical effects during vagus 
 stimulation, and the only chemical test to which the theory has been 
 subjected, the comparison of the oxygen consumption of the heart during 
 and in the absence of inhibition, is adverse to it. The amount of oxygen 
 used up relatively to the functional activity of the heart as measured by 
 the product of the frequency of the beat and the maximal increase of pres- 
 sure caused bv it, is not increased by stimulation of the vagus (Rohde). 
 
I6S 
 
 THE CI RCVL Alios OF THE BLinU) AM) I.VMPU 
 
 Whatexcr tlic exact mcclianisui of aiigmcntaliun inav Ix-, there is 
 no basis for the statement that the cardio-auKnientor nerves have 
 an action on ihc heart so fundamentally different from the action of 
 motor nerves on skeletal muscle that they cannot originate contractions 
 in a heart entirely at rest. ICxcitation of the cardio-augmentor nerves 
 can cause rhythiiucal contractions in the perfectly quiescent heart of 
 molluscs, and a sudden and prolonged outburst of beats of great 
 force in the frog's heart, which has Ix-cn brought to a standstill bv 
 cautiously heating it to 40'' to 43" C. (Practical Kxercises, p. 194) for 
 a minute or two, or t(j a considerably lower temperature, for a longer 
 time (l-'ig. 77). A similar effect can be obtained on the quiescent 
 mammalian heart b\- stimuh'tion of the ncrvi accclerantcs. 
 
 28' 5 
 S30 
 
 rTTTTm I M M 1 1 I 11 I 1 1 I I I ( 1 1 I 1 1 r I rmnni 
 
 />/•»-,- r^'^^-ry 
 
 ].jg. y-_. — Effect of Stiimilalioii of I'roj^'s Cardiac S\ iiipallictic during Lumplcte 
 Standstill of tlie Heart at 28-5" C. Upper tracing, auricle ; lower, ventricle. 
 To be read froui ri(,'lit to left. Time-trace, two-second iuter\-als. 
 
 The Normal Excitation of the Cardiac Nervous Mechanism. — 
 W'c ha\"c now to intjuirc how this elaborate nervous mechanism is 
 normally set into action. And we may say at once, that striking as 
 are the effects of experimental stimulation of the vagus trunk or the 
 ncrvi accelerantes in their course, it is only under exceptional cir- 
 cumstances that the efferent nene-fibres, at any rate before they 
 have entered the heart, can be directly excited in the intact body. 
 In certain cases the pressure of a tumour or an anouinsm on the 
 nerve-trunks, or. in the case of the accelerators the progress of a 
 jiathological change in the sympathetic ganglia through which the 
 
THE SEh'VOVS RJ.GULA'J I(h\ OF THL 11 HART ib-t 
 
 nerve-trunks, or, in the case of the accelerators, the progress of a 
 pathological change in the sympathetic ganglia through which the 
 fibres pass, has been thought to bring about by direct stimulation 
 a slowing or a quickening of the pulse. In some individuals the 
 vagus has been excited by compressing it against a bony tumour 
 in the neck; and by compressing the nerve against the vertebral 
 column it is possible to cause inhibition in many normal persons, 
 although it ought to be stated that the experiment is not free from 
 danger. But it is from the cardio-inhibitory and cardio-augmcn'ur 
 centres in the medulla oblongata that the impulses which regul'iie 
 the activity of the heart are normally discharged. Inhibitory im- 
 pulses are constantly passing out from the medulla, for section of 
 both vagi causes almost invariably an increase in the rate of the 
 heart, at least in mammals, although the increase is less conspicuous 
 in animals like the rabbit, whose normal pulse-rate is high, than in 
 animals like the dog, whose pulse-rate is comparatively \o\v. Section 
 of one vagus usually causes only a comparatively slight increase, for 
 the other is able of itself to control the heart. It is not certainly 
 known whether the augmentor centre in like manner discharges a 
 continuous stream of impulses, or is only roused to occasional activity 
 by special stimuli. For the results of section of the nervi acceler- 
 antes, or the extirpation of the inferior cervdcal and stellate gangha, 
 are dubious and conflicting. But if it does exert a tonic influence 
 on the heart, this is feebler than the tone of the inhibitory centre. 
 As to the nature of this inhibitory- tone, and the manner in which it 
 is maintained, we know but little. It may be that the chemical 
 changes in the nerve-cells of the inhibitory centre lead of themselves 
 to the discharge of impulses along the inhibitory nerves. But there 
 is some evidence that, in the complete absence of stimulation from 
 without, the activity of the centre would languish, and perhaps be 
 ultimately extinguished. For when the greater number of the 
 afferent impulses have been cut off from the medulla oblongata by 
 a transverse section carried through its lower border, division of the 
 vagi produces little effect on the rate of the heart. Also, when the 
 upper cervical cord and the brain are resuscitated after a period of 
 anaemia, the return of cardio-inhibitory tone is tardy in comparison 
 with the return of the truly automatic function of respiration, and 
 does not seem to precede the opening up of the afferent paths to the 
 cardio-inhibitory centre. Indeed, reflex inhibition may be produced 
 at a time when the inhibitory centre has regained none of its tone. 
 The suggestion is that the normal tone of the centre is largely 
 dependent upon reflex impulses. Be this as it may, we know that 
 the activity of the inhibitory centre is profoundly influenced — and 
 that both in the direction of an increase and of a diminution — by 
 impulses that fall into it through afferent nerves and by stimuli 
 directly applied to it. And wo ma^- assume that the same is true 
 of the augmentor centre. The common statement that stimulation 
 
17" 7lir. CtRCUI.ATlOS OF THE nLOOJ) AXP LYMPH 
 
 t>f thr ct-ntial end of one \agus, the otlier l;eing intact, pnjcluccf. 
 distinct inhibition docs not hold for all mammals. In dogs this is 
 Sometimes the case, but often (under anaesthesia, at any rate) there 
 IS little or no inhibition, or even augmentation. In etherized cats, 
 on the other hand, some inhibition is always seen. Of all the afferent 
 fibres of the vagus, the pulmonary fibres produce the most marke<l 
 reflex inhibition. The cardiac fibres are much less effective. 
 
 These pulmonary nerves also influence the respiratory and vaso- 
 motor centres. The respiration is temporarily arrested, and the 
 blood-pressure falls through the dilatation of the small arteries when 
 they are excited. It is of interest in connection with the subject 
 of death during the administration of anaesthetics, that the afferent 
 vagus fibres coming from the alveoli of the lungs can be chemically 
 stinuilated when irritant vapours, such as chloroform, hydrochloric 
 acid, ammonia, bromine, or formaldehyde are inhaled through a 
 tracheal cannula, causing reflex arrest of the heart and of the respira- 
 tory movements and a fall of blood-pressure tlurough vaso-dilatation 
 (Brodie). At a certain stage in chloroform anaesthesia, before it 
 has become very deep, comparatively trifling cavises may bring 
 about great and sudden changes in the pulse-rate, owing to the 
 abnormal mobility of the vagus centre (MacWilliam). 
 
 The depressor nerve, a branch of the vagus, which is easily found 
 in the rabbit as a slender nerve running close to the sympathetic 
 in the neck, and a little to its inner side, but in the dog is usually 
 blended with the vago-sympathetic, falls into the same category 
 ^vith the vagus itself as regards its reflex action on the heart, to 
 which it bears an important relation. In all mammals some of its 
 fibres end in the wall of the aorta, but some of them may run down 
 over the heart to the ventricle. Stimulation of its peripheral end 
 has no effect, for the fibres in it which influence the circulation are 
 afferent, not efferent. But excitation of its central end causes a 
 marked fall of blood-pressure (p. 185), accompanied by, but not 
 essentially due to, a distinct slowing of the heart. If the animal is 
 not anaesthetized, there may be signs of pain, and for this reason the 
 depressor has sometimes been spoken of, somewhat loosely, as the 
 sensory nerve of the heart. The abdominal sjnnpathetic (of the 
 frog) also contains afferent fibres, through which reflex inhibition of 
 the heart can be produced when the}' are excited mechanically by a 
 rapid succession of light strokes on the abdomen with the handle 
 of a scalpel. 
 
 On the other hand, when the central end of an ordinary peripheral 
 ne. ve like the sciatic or brachial is excited, the common eifect is pure 
 augmentation (Fig. 78), which sometimes develops itself with even 
 greater suddenness than when the accelerator nerves are directly 
 stimulated. Occasionally, however, the augmentation is abruptly 
 followed by a typical vagus action. Here the reflex inhibitory effect 
 seems to break in upon and cut short the reflex augmentor effect. 
 
THE KERVOUS REi.V I.ATION Ol- THE HEART 
 
 171 
 
 These examples show that certain alUrent nerves are especially 
 related to the cardio-inhibitory, and others to the cardio-aug mentor, 
 centre, or at least that the central connections of some nerves arc 
 such that inhibition is the usual effect of their reflex excitation, 
 while the opposite is the case with other nerves. But it is im- 
 probable that the effect of a stream of afferent impulses reaching 
 the cardiac centres by any given nerve is determined solely by 
 anatomical relations. The intensity and the nature of the stimulus 
 seem also to have something to do with the result. For when 
 ordinary sensory nerves are weakly stimulated, augmentation is 
 said to be more common than inhibition, and the opposite when 
 they are strongly stimulated. And while a chemical stimulus, like 
 the inhaled vapour of chloroform or ammonia, raiises in the rabbit 
 
 Fig- 78. — Myocardiographic Tracing of Cat's Ventricle. The signal line shows the 
 point at which the central end of the brachial nerve was stimulated during 
 resuscitation of the animal after a period of cerebral ansmia. Some augmenta- 
 tion of the ventricular beat is seen. The notches in the ventricular tracing are 
 dtie to the artificial respiration. Time-trace, seconds. 
 
 reflex inhibition of the heart through the fibres of the trigeminus 
 that confer common sensation on the mucous membrane of the nose, 
 the mechanical excitation of the sensory nerves of the pharynx 
 and oesophagus when water is slowly sipped causes acceleration.* 
 The stimulation of the nerves of special sense is followed sometimes 
 by the one effect and sometimes by the other. To complete the 
 catalogue of the nervous channels by which impulses may reach the 
 cardiac centres in the medulla, we may add that there must be an 
 extensive connection between them and the cerebral cortex, since 
 every passing emotion leaves its trace upon the curve of cardiac 
 action. The so-called ' reflex cardiac death,' which is an occasional 
 consequence of intense psychical influences (anxiety, fright, etc.), 
 
 • In 78 healthy students the average pulse-rate (in the .sitting position) 
 was increased fram 73 to 85 per minute by sipping water. 
 
172 THE CIRCULATIOS' OF THE BLOOD AND LYMI'H 
 
 may be due to the prolonged excitation of the cardio-inhibitory 
 centre, as well as to the disturbance of other centres in the bulb by 
 the cortical storm. It is a remarkable fact, too, and one that can 
 only be explained by such a connection, that aithouph in the vast 
 majority of individuals the will has no influence whatever on the 
 rate or force of the heart, except, perhaps, indirectly through the 
 respiration, some persons have the power, by a voluntary effort, of 
 markedly accelerating the pulse. In ont- case of this kind it was 
 noticed that perspiration broke out on the hands and other parts of 
 the body when the heart was voluntarily accelerated. A rise of 
 blood-pressure due to constriction of the vessels has also been 
 observed. The effort cannot be kept up for more than a short time, 
 and the pulse-rate quickly goes back to normal. It has been 
 recently shown that this peculiar power is more common than has 
 been supposed, and that where it is present in rudiment it can be 
 cultivated, although it is a dangerous acquisition. 
 
 As an example of the direct action on a cardiac centre of a 
 changed chemical composition of the blood, we may cite the 
 inhibition produced by injection of bile into a vein and revealed 
 in the slow pulse of many cases of jaundice ; and as an instance 
 of the direct action of a physical change, the slovsing of the heart 
 as the blood-pressure rises (p. i88) in asphyxia or on clamping the 
 aorta. The variation in the pulse-rate associated with changes 
 in the position of the body, to which we have already referred 
 (p. 107), is brought about by direct stimulation of the in- 
 hibitorv centre by the increase of blood-pressure in the medulla 
 oblongata when a person who has been standing assumes the supine, 
 or even the sitting, posture. But it is also due in part to changes in 
 the amount of muscular contraction, since muscular exercise cause* 
 acceleration of the heart either reflexly, through afferent muscular 
 nerves, or by a direct effect of waste products of the metabolism of 
 the muscles on the cardiac centres in the bulb or on the heart itself 
 (p. 280). 
 
 Theoretically, quickening of the heart might be caused either by 
 a diminution in the inhibitory tone or by an increase in the acti\nty 
 of the augmentor centre ; and slowing of the heart might be due 
 either to a diminution in the augmentor tone, if such exists, or to 
 an increase in the activity of the inhibitory centre. So that it is 
 not always easy to interpret such results as we have quoted above. 
 But it would appear that under ordinary conditions the rate of the 
 heart is mainly regulated by the inhibitory centre, which, within a 
 considerable range, can produce variations in either direction. The 
 augmentor mechanism is perhaps merely auxiliary to the inhibitory, 
 being called into action only in emergencies. 
 
THE MzinoUS UEGULAliUN Ob I HE BLOODVESSELS 17; 
 
 Section VI. — ^The Nervous Regulation of the Bloodvessels 
 (Vaso-Motor Nerves). 
 
 Just as the muscular walls of the heart are governed by two sets 
 of nerve-fibres, a set which keeps down the rate; of working and a 
 set which may increase it, the muscular walls of the vessels are under 
 the control of nerves which have the power of diminishing their 
 calibre {vaso-constrictor), and of nerves which have the power of 
 increasing it (vaso-dilator). All nerves that affect the calibre of the 
 vessels, whether vaso-constrictor or vaso-dilator, are included under 
 the general name vaso-motor. These vaso-motor nerves, like the 
 augmentor and inhibitory fibres of the heart, are connected with a 
 centre or centres, which in turn are in relation with numerous afferent 
 nerves. It is convenient to distinguish the afferent nerves which 
 cause on the whole a vaso-constriction and a consequent increase 
 of arterial pressure as pressor nerves, and those which cause on the 
 whole vaso-dilatation, with fall of pressure, as depressor nerves, 
 reserving the terms vaso-constrictor and vaso-dilator for the efferent 
 portions of the reflex arcs. It is through this reflex mechanism 
 that the bloodvessels are mainly influenced, although the endings 
 of the vaso-motor nerves in the smooth muscular fibres or the 
 muscular fibres themselves are sometimes directly affected by sub- 
 stances circulating in the blood. Proteoses, for instance, cause by 
 peripheral action dilatation of the vessels and a fall of blood-pressure 
 (p. 215); suprarenal extract, or its active principle, adrenalin, or 
 epinephrin, constriction, with a rise of pressure (pp. 216, 655). Apo- 
 codeine paralyzes the vaso-motor nerve-endings after a preliminary 
 stimulation, and now adrenalin causes no constriction. Chryso- 
 toxin, an active principle of ergot, causes a marked rise of blood- 
 pressure by stimulating the sympathetic ganglion-cells or the pre- 
 ganglionic fibres of the vaso-constrictor path, ^^aso-motor nerves 
 control chiefly the small arteries. They have no direct influence on 
 the capillaries.* Nor has the existence of an effective vaso-motor 
 regulation of the calibre of the veins, except in the portal system, 
 been proved up to this time by any clear and unambiguous experi- 
 ment, although there are grounds on which it has been surmised 
 that the nervous system does influence the ' tone ' of the whole 
 venous tract. These grounds will be mentioned in the proper place. 
 
 * It is usually taught that the capillaries, being devoid of muscular fibres 
 in their walls, are not supplied with vaso-motor fibres, and that the only kind 
 of active contraction of which they axe capable is due to a process analogous 
 to the turgescence of vegetable cells, the thickness of the wall being increased 
 at the expense of the lumen, while the total cross-section of the vessel remains 
 unchanged. It has been asserted, however, that a true contraction, in which 
 both the tdtal section and the lumen are diminished, may be caused in the 
 capillaries of the nictitating membrane of the frog either by direct stimulation 
 or by excitation of vaso-motor fibres in the sympathetic (Steinach and Kahn). 
 
174 THE CIRCULATION OF Till- BLOOD AND LYMPH 
 
 Meanwhile, before describing the distribution of the best-known 
 tracts of vaso-motor fibres and defining the position of the vaso- 
 motor centres, we must glance at the methods by which our know- 
 ledge has been attained. 
 
 (i) In translucent parts inspection is sufficient. Paling of the part 
 indicates constriction ; flusliing, dilatation of the small vessels. This 
 method has been much used, sometimes in conjunction with (2), in such 
 parts as the balls of the toes of dogs or cats, the ear of the rabbit, the 
 conjunctiva, the mucous membrane of the mouth and gums, the web of 
 the frog, the wing of the bat, the intestines, etc. 
 
 (2) Observation of changes in the temperature of parts. This method 
 has been chiefly employed in investigating the vaso-motor nerves of 
 the limbs, the thermometer bulb being fixed between the toes. In such 
 peripheral parts the temperature of the blood is normally less than that 
 of the blood in the internal organs, because the opportunities of cooling 
 are greater. The effect of a freer circulation of blood (dilatation of the 
 arteries) is to raise the temperature ; of a more restricted circulation 
 (constriction of the arteries), to lower it. 
 
 (3) Measurement of the blood-pressure. If we measure the arterial 
 blood-pressure ct one point, and find that stimulation of certain nerves 
 increases it without affecting the action of the heart, we can conclude 
 that upon the whole the tone of the small vessels has been increased. 
 But we cannot tell in what region or regions the increase has taken place ; 
 nor can we tell whether it has not been accompanied by diminution of 
 tone in other tracts. 
 
 But if we measure simultaneously the blood-pressure in the chief 
 artery and chief vein of a part such as a limb, we can tell from the 
 changes caused by section or stimulation of nerves whether, and in 
 what sense, the tone of the small vessels within this area has been altered. 
 For example, if we found that the lateral pressure in the artery was 
 diminished, while at the same time it was increased in the vein, we 
 should know that the ' resistance ' between artery and vein had been 
 lessened, and that the blood now found its way more readily from the 
 artery into the vein. If, on the other hand, the venous pressure was 
 diminished, and the arterial pressure simultaneously increased, we should 
 have to conclude that the vascular resistance in the p>art was greater 
 than before. If the pressure both in artery and vein was increased, we 
 could not come to any conclusion as to local changes of resistance with- 
 out knowing how the general blood-pressure had varied. 
 
 (4) The measurement of the velocity of the blood in the vessels of 
 the part. This may be done by the stromuhr or dromograph, or by 
 allowing the blood to escape from a small vein and measuring the 
 outflow in a given time, or, without opening the vessels, by estimating 
 the circulation-time (p. 135). When changes in the general arterial 
 pressure are eliminated, slowing of the blood-stream through a part 
 corresponds to increase of vascular resistance in it ; increase in the rate 
 of flow implies diminished vascular resistance . Sometimes the red colour 
 of the blood issuing from a cut vein, and the visible pulse in the stream, 
 indicate with certainty that the vessels of the organ have been dilated. 
 
 (5) Alterations in the volume of an organ or limb are often taken as 
 indications of changes in the calibre of the small vessels in it. We 
 have already seen how these alterations are recorded by means of a 
 plethysmograph (p. 128). The brain is enclosed in the skull as m a 
 natural plethysmograph, and changes in its volume may be registered 
 by connecting a recording apparatus with a trephine hole. 
 
THE NERVOUS REGULATIOS OF THE BLOODVESSELS 175 
 
 (6) For the separation of the effects of stimulation of vaso-constrictor 
 and vaso-dilator fibres when they are mingled together, as is the case 
 in many nerves, advantage is taken of certain differences between them. 
 For example, the vaso-constrictors lose their excitability sooner than 
 the vaso-dilators when cut off from the nerve-cells to which they belong. 
 So that if a nerve is divided, and some days allowed to elapse before 
 stimulation, only the dilators will be excited. The vaso-dilators are 
 more sensitive to weak stimuli repeated at long intervals than to strong 
 and frequent stimuli, and the opposite is true of the constrictors. WTien 
 a nerve containing both kinds of fibres is heated, the excitability of 
 the vaso-constrictors is increased in a greater degree than that of the 
 dilators: when tlie nerve is cooled, the dilators preserve their excita- 
 bility at a temperature at which the constrictors have ceased to respond 
 to stimulation (Fig. 79). 
 
 The Chief Vaso-Motor Nerves. — The first discovery of vaso-motor 
 nerves was made in the cervical sympatlietic. When this nerve is 
 
 79. — Plethysmograms: Hind-Limb ot Cat (alter Bowditch and Warren). To be 
 read from right to left. On the left hand is shown the efifect of slow stimulation 
 of the sciatic (i per second); on the right hand the effect of rapid stimulation 
 (64 per second). In the first case the limb swelled owing to excitation of the 
 vaso-dilators; in the second, it shrank tl^ough excitation of the vaso-constrictors. 
 
 cut, the corresponding side of the head, and especially the ear, 
 become greatly injected ouing to the dilatation of the vessels. This 
 experiment can be very readily performed on the rabbit, and the 
 changes are most easily followed in an albino. The ear on the side 
 of the cut nerve is redder and hotter than the other; the main 
 arteries and veins are swoUen with blood, and many vessels formerly 
 in\nsible come into view. The slow rhythmical changes of calibre, 
 which in the normal rabbit are very characteristically seen in the 
 middle artery of the ear, disappear for a time after section of the 
 sympathetic, although they ultimately again become \'isible. 
 
 Stimulation of the cephaUc end of the cut sympathetic causes a 
 marked constriction of the vessels and a fall of temperature on the 
 same side of the head. From these facts we know that the cervical 
 
176 THE CmCULATiON OF Till-: BLOOD A WD r.YMPH 
 
 synipatlietic in inanir.ials contains vaso-constrictur fibres for the 
 side of the head and ear, and that these fibres are constantly in 
 action. Certain parts of the eye, and the saHvary glands, larynx, 
 oesophagus, and th\Toid gland, are also supplied with vaso- motor 
 (constrictor) nerves from the cervical sympathetic. 
 
 It has been asserted that the cervical sympathetic contains some of 
 the vaso-constrictor fibres that supply the corrcspondin;^ half of the 
 brain and its membranes, but this lias been disputed, and some ob- 
 servers deny that the vessels of the brain have any vaso-motor nerves. 
 Non-medullated nervc-fibies, however, may be seen in and around the 
 walls of the cerebral and spinal bloodvessels, and it is difficult to believe 
 that these have not a vaso-motor function, although this has not as 
 yet been clearly demonstrated by experimental methods. 
 
 It has sometimes been argued that we ought not to expect the brain 
 to be supplied with vaso-motors. For it is enclosed in a rigid box, and 
 the quantity of blood in it can be increased or diminished only to tlie 
 slight extent to which the ccrebro-spinal liquid can be displaced into 
 the vertebral canal. Important changes in the cerebral blood-supply 
 are therefore brought about, it is said, not by a widening or narrowing 
 of the cerebral vessels, but by an alteration in the velocity of the blood 
 in them as a result of a rise or fall of the systemic arterial pressure. 
 This argument, however, leaves out of account the consideration that 
 in general the brain does not function as a whole, but that certain 
 parts of it may often become active and relatively hypera?mic, while 
 other parts are inactive and relatively anaemic, and that important 
 changes in the distribution of the blood in the encephalon may be 
 effected, although the total mass of blood in the organ undergoes little 
 or no alteration. It is, of course, true that it is not the absolute quantity 
 of blood in an organ which is a function of its activity, but the rate at 
 which it is renewed. And it is theoretically possible that an organ at 
 rest should contain as much blood as when it is acti\e, or even more. 
 But such cases, if they exist, are certainly rare. The fact that adrenalin 
 generallv constricts the vessels of a perfused brain (Wiggers) is in favour 
 of the ex stence of vaso-motors. The retina, which from the stand- 
 point of development is a portion of tlie brain, is undoubtedly supplied 
 with vaso-constrictor fibres which run in the cervical sympathetic. 
 
 That the cervical sympathetic contains some dilator fibres is 
 proved by the fact that stimulation of the cephalic end in the dog 
 causes flushing of the mucous membrane of the mouth on the same 
 side. Further, after division of the nerve on one side in the rabbit 
 it may be observed that when the animal is excited the vessels of the 
 ear whose nerve is intact may become still more dilated than those 
 whose constrictor fibres have been paralyzed. The only explana- 
 tion is that vaso- dilators are being excited from the central nervous 
 system. 
 
 " The vaso-motor fibres of the head run up in the cervical sympa- 
 thetic, and then pass into various cerebral nerves, of which the fifth 
 or trigeminus is the most important. 
 
 The trigeminus nerve contains vaso-constrictor nerves for various 
 parts of the eye (conjunctiva, sclerotic, iris), and for the mucous 
 
THE NERVOUS REGVLATIOS Of THE BLOODVESSELS ijo 
 
 membrane of the nose and gums, and section of it is followed by 
 dilatation of the vessels of these ri.j4ions. The lingual branch of 
 the trigeminus supplies vaso-motor tibres to the tongue, and ap- 
 parently l:»oth vaso-constrictor and vaso-dilator. 
 
 In some animals — the rabbit, for instance — the ear derives part 
 of its vaso-motor supply through the great auricular nerve, a branch 
 of the third 'crvical nerve, which they reach as grey rami from the 
 stellate ganglion. 
 
 Another great vaso-motor tract, the most influential in the body, 
 is contained in the splanchnic nerves, which govern the vessels of 
 many of the abdominal organs. Section of these nerves causes an 
 immediate and sharp fall of arterial pressure. The intestinal vessels 
 are dilated and overfilled with blood. As a necessary consequence 
 of their immense capacity, the rest of the vascular system is uoder- 
 filled, and the blood-pressure falls accordingly. Stimulation of the 
 peripheral end of the splanchnic nerves causes a great rise of blood- 
 pressure, owing to the constriction of vessels in the intestinal area. 
 We therefore conclude that in the splanchnics there are vaso-motor 
 fibres of the constrictor type, and that impulses are constantly 
 passing down them to maintain the normal tone of the vascular 
 tract which they command. When the splanchnic nerves are 
 stimulated, the adrenal glands are so affected that adrenahn passes 
 out by the veins into the blood-stream. It is clear that if the quan- 
 tity thus liberated were sufficiently large and its liberation suffi- 
 ciently prompt it might play a part in the rise of pressure (p. 66i) 
 which follows stimulation of the nerves, whether they are excited 
 directly or in the normal course of events reflexly. But it has not 
 been demonstrated that this is an effective factor. Dilator fibres 
 (for the intestines and the kidney, for example) have also been 
 discovered in the splanchnic nerves, although the constrictors 
 predominate, and special methods have to be employed for the 
 detection of the dilators. 
 
 The same is true of the nerves of the extremities, which certainly 
 contain vaso-dilator fibres in addition to vaso-constrictors, although 
 the difficulty of demonstrating the presence of the former is fully 
 as great as it is in the splanchnics. For the investigation is com- 
 plicated b}- the fact that such nerves as the sciatic supply with 
 vaso-motor fibres two leading tissues — skin and muscle ; and these 
 are not necessarily affected in the same direction or to the same 
 extent by stimulation of their vaso-motor fibres. The vaso-con- 
 strictors under ordinary conditions preponderate, so that section of 
 the sciatic or the brachial is generally followed by flushing of the 
 balls of the toes and rise of temperature of the feet, stimulation by 
 paling and fall of temperature. By talcing advantage, however, of 
 the unequal excitability of dilators and constrictors in a degenerating 
 nerve, and of the differences between the two kinds of fibres in their 
 
t7c THE CinCULAllOS UI- IHL BLOOD AND LYMPH 
 
 reaction to electrical stimuli (p. 175), it has been shown that vaso- 
 dilators are also present, and come to the front when the conditions are 
 rendered favourable for them and unfavourable for the constrictors. 
 
 Vaso-motor fibres for the fore-limb (dog) issue from the cord in the 
 anterior roots of the third to the eleventh dorsal nerves, and for the 
 hind-limb in the anterior roots of the eleventh dorsal to the tliird lumbar. 
 Stimulation of most of these roots causes constriction of the vessels 
 but stimulation of the eleventh dorsal may cause dilatation (Bayliss 
 and Bradford). 
 
 Ihe I'aso-Molor Nerves of Muscle. — When the motor nerve of the thin 
 mylo-hjoid muscle of the frog, which can be observed under the micro- 
 scope, is cut, and the peripheral end stimulated, the vessels are seen to 
 dilate distinctly, and this effect is not abolished when contraction of 
 the muscle is prevented by a dose of curara insufficient to paralyze the 
 vaso-motor nerves. This indicates the existence in the nerve of vaso- 
 dilator fibres. But we must be cautious in transferring this result to 
 ordinary skeletal muscle, for the mylo-hyoid is more closely allied to 
 the muscles of the tongue than, for example, to the muscles of the limbs, 
 and in the mammal the tongue muscles are known to be better supplied 
 with vaso-dilator fibres than the limb muscles. The average flow of 
 blood through a manmialian muscle is indeed increased during volun- 
 tary- contraction, and during rhythmically repeated artificial tctaniza- 
 tion of its motor nerve. The outflow of blood from the main vein of 
 the levator labii superioris, one of the muscles used in feeding in the 
 horse, was found to be in one experiment nearly eight tinics, in another 
 about seven times, and in a third three and a half times as great during 
 vohmtary work with it (in chewing) as in rest. But as no increa.se in 
 the blood-flow through the skeletal muscles of a completely curarized 
 mammal during excitation of their nerves has ever been satLsfactorily 
 demonstrated, wc must conclude that they are very scantily provided 
 with vaso-dilator fibres or not at all. It is uncertain whether they are 
 supplied with vaso-constrictors. The undoubted increase in the blood- 
 flow in contraction may therefore be connected in some way with the 
 mcichanical or chemical changes in the muscular fibres themselves. 
 
 It has been suggested that the muscular vessels are widened by the 
 direct action of the acid products of tlie active muscle, since \er)' dilute 
 acids (lactic acid, e.g.) cause general dilatation of the small vessels. 
 A similar explanation has been extended to the dilatation of the vessels 
 of the brain during cerebral activity by some of those who deny the 
 existence of vaso-motor nerves for that organ, but here the evidence 
 is by no means satisfactory-. The v;:gus has been stated to contain 
 vaso-constrictor, and the annulus of \'icussens vaso-dilator, fibres for 
 the coronary arteries of the heart. But this question Ls far from being 
 settled. Adrenalin causes dilatation and not constriction of the 
 coronary vessels. There is some reason to believe that the metabolic 
 products liberated in the heart-muscle, e.g., carbon dioxide, govern the 
 changes in the calibre of the coronary arterioles. A close relationship 
 cxi-sts between the output of carbon dioxide and the rate of flow through 
 the coronary circulation. In asphyxia the flow through the coronary 
 \esscls is notably increased; indeed, it is at its maximum just before 
 the heart fails altogether, as if an effort were being made to keep the 
 heart going to the last by maldng up to it in the quantity of the blood 
 supplied what it lacks in quality. As this increased flow is seen in the 
 isolated heart-lung preparation, it has been concluded that metabolites 
 produced in the cardiac muscle itself cause an increased coronary flow 
 when increased demands arc made on the heart, a local regulative 
 
THE NERVOUS REGULATION OF THE BLOODVESSELS x;9 
 
 mechanism being thus constituted. There is some evidence that carbon 
 dioxide is not tlic most potent ol tlicse substances. 
 
 Vaso-Moloy Xcivcs of the Lungs. — There has been much discussion as 
 to the course, and even as to the existence, of vaso-motor fibres for the 
 lungs. The problem is perhaps the most difficult in the whole range of 
 vaso-motor topography, for the pulmonar\- circulation is so related to 
 other vascular tracts, that changes produced in the \-cssels of distant 
 organs by the stimulation or section of nerves may affect the quantity 
 of blood received by tlu' right side of the heart, and therefore the 
 quantity propelled througli the lungs and the pressure in the pulmonary 
 artery. And changes in the systemic arterial pressure may favour or 
 hinder the discharge of the left ventricle, and therefore affect the pres- 
 sure in the left auricle and the pulmonary veins. Nevertheless, evidence 
 has been obtained from a number of sources that the lungs are supplied 
 with vaso-constrictor fibres. Plumicr, perfusing isolated, ' surviving ' 
 lungs with blood under constant pressure and measuring the outflow, 
 showed that adrenalin and also stimulation of the annulus of Vieussens 
 caused great diminution in the flow — that is, constriction of the vessels. 
 Wiggcrs also obtained constriction with adrenalin. Fiihner and 
 Starling, working with a preparation including the heart as well as the 
 lungs, found that adrenalin caused a rise of pressui-c in the pulmonary 
 artery coupled with a fall of pressure in the left auricle, which could 
 only be due to constriction of the vessels of the lungs. It is assumed 
 that adrenalin produces vaso-constriction only in vessels supplied with 
 \'aso-constrictor nerves (p. 653), and that in organs where this substance 
 does not cause vaso-constriction no such fibres are present. In mam- 
 mals the vaso-constrictor fibres seem to pass out from the upper half 
 of the dorsal spinal cord, and some of them can be detected nearer their 
 destination in the annulus of Vieussens. The vago -sympathetic of the 
 tortoise contains vaso-constrictors for the lung of the same side (Krogh). 
 
 Vaso-Dilator Fibres. — In most of the peripheral nerves these are 
 mingled with vaso-constrictors; but in certain situations, for an 
 anatomical reason that will be mentioned presently, nerves exist in 
 which the only vaso-motor fibres are of the dilator t5'pe. Of these, 
 the most conspicuous examples aje the chorda tympani and the 
 nervi crigentes or pelvic nerves; and, indeed, it was in the chorda 
 that vaso-dilators were first discovered by Bernard. The chorda 
 tympani contains vaso-dilator and secretory fibres for the sub- 
 maxillary and subungual salivary glands. With the secretory fibres 
 we have at present nothing to do; and the whole subject will have 
 to be retvirned to, and more fully discussed in Chapter VI. But a 
 most marked vascular change is produced by stimulation of the 
 peripheral end of the divided chorda tympani nerve. The glands 
 flush red; more blood is evidently passing through their vessels. 
 Allowed to escape from a divided vein, the blood is seen to be of a 
 bright arterial colour and shows a distinct pulse. The small arteries 
 have been dilated by the action of the vaso-motor fibres in the nerve. 
 The resistance being thus reduced, the blood passes in a fuller and 
 more rapid stream through the capillaries into the veins, and on the 
 way there is not time for it to become completely venous. These 
 vaso-dilator fibres are not in constant action, for section of the 
 
l8o THE CUiCrLATIOS OF THE ni.nOD AST) LYMPH 
 
 nerve, as a rule, produces little or no diangi-. Vaso-constrictor 
 fibres pass to the salivary glands from the cervical sympathrtic 
 along the arteries, and stimulation of that nerve causes narrowing of 
 the vessels and diminution of the blood-fiow. sometimes almost to 
 complete stoppage. 
 
 The nervi erigentes are the nerves through which erection of the 
 penis is caused. WTien they are divided there is no effect, but 
 stimulation of the peripheral end causes dilatation of the vessels of 
 the erectile tissue of the organ, which becomes overfilled with 
 blood. During stimulation of these nerves, the quantity of blood 
 flowing from the cut dorsal vein of the penis may be fifteen times 
 greater than in the absence of stimulation. It spurts out in a strong 
 stream, and is bi^^'hter than ordinary venous blof>d (Eckhard). 
 Stimulation of the peripheral end of the nervns pudendus causes 
 constriction of the vessels of the penis, so that it contains vaso- 
 constrictor fibres which are the antagonists of the nervi erigentes. 
 
 Vaso-Motor Nerves of Veins. — Like arteries, veins have plexuses 
 of nerve-fibres in their walls, and contract in response to various 
 stimuU. In some cases — e.g., in the wing of the bat — rhythmical 
 contractions of the veins are strikingly displayed, but they do not 
 depend on the central nervous system, as they persist after section 
 of the brachial nerves. The e.xistence of vaso-constrictor fibres for 
 the venules given off in the liver by the portal vein is indicated by the 
 fact that adrenalin diminishes the blood flow through the organ even 
 when the hepatic artery has been tied (Burton-Opitz; Macleod and 
 Pearce, etc.). Stimulation of the distal end of the hepatic ple.xus 
 causes similar effects. The fibres issue from the spinal cord by the 
 anterior roots of the third to the eleventh dorsal nerves, but chiefly 
 in the fifth to the ninth dorsal. The arterioles arising from the 
 hepatic artery have their own vaso-motor supply, which is more com- 
 plete than that of the portal vessels. When the liver is enclosed in 
 a plethysmograph, and the central end of an ordinarv sensory nerve, 
 like the sciatic, e.xcited, reflex vaso-constriction takes place in the 
 portal area, the volume of the organ diminishes, and the blood-pres- 
 sure rises in the portal vein (Frangois-Franck). 
 
 The vena portae and its branches are in the physiological sense 
 arteries rather than veins, since they break up into capillaries, and 
 it was to be expected that the regulation of the blood-flow in them 
 would be carried out in the same way as in ordinary arteries, namely, 
 bv means of vaso-motor nerves. But we must not. without special 
 proof, extend the results obtained in the portal system to ordinary 
 veins. A certain amount of evidence, however, exists that even 
 such veins as those of the extremities are supplied, though scantily, 
 with vaso-constrictor (veno-motor) fibres. After ligation of the 
 crural artery or aorta, stimulation of the peripheral end of the 
 sciatic has been seen to cause contraction of short portions of the 
 superficial veins of the leg. 
 
TIIF. NERVOUS REGUI.AllON OF THE tSLOODVESSELS i8i 
 
 Fiiuilly, acJrriialin (tjjint'plirin) causes constriction of rings of 
 ' surviving ' veins just as of artery rings, although in correspondence 
 with the smaller amount of muscular tissue in the former the con- 
 traction is not so strong. As adrenalin is assumed to act only upon 
 muscle supplied by sympathetic nerve-fibres (p. 655), this would 
 seem to indicate the existence of such a supply for veins. The 
 question is an important one in connection with the regulation of 
 the fiUing, and therefore of the discharge, of the heart (Henderson), 
 but the experimental data are as yet too meagre to justify further 
 discussion of the matter here. 
 
 Course of the Vaso-Motor Nerves. — In the dog the vaso -constrictors 
 pass out as fine medullatcd fibres (i'8 to 3-6 yu in diameter) in the 
 anterior roots of the second dorsal to about the second lumbar nerves. 
 They proceed by the white rami communicantes to the lateral sym- 
 pathetic ganglia, where, or in more distal ganglia such as the inferior 
 mesenteric, they lose their medulla, and their axis-cylinder processes 
 (p. 85 1) break up into fibrils that come into close relation with 
 the nerve-cells of the ganglia. These ganglion-cells in their turn send 
 off axis-cylinder processes, which, enveloped by a neurilemma, pass as 
 non-meduUatcd fibres by various routes to their final destination, the 
 unstript'd muscular fibres of the bloodvessels. Their course to the head 
 has been already described. To the limbs they are distributed in the 
 great nerves (brachial plexus, sciatic, etc.), which they reach from the 
 sympathetic ganglia by the grey rami communicantes. 
 
 The outflow of vaso-dilator fibies is not restricted to the same portion 
 of the cord from which the outflow of constrictor fibres takes place. 
 Their existence is indeed most easily demonstrated in nerves springing 
 from those regions of the cerebro-spinal axis from which vaso-constrictor 
 fibres do not arise, and where, therefore, we have not to contend with 
 the difliculty of interpreting mixed effects. Vaso-dilators for the 
 external generative organs and the mucous membrane of the lower end 
 of the rectum pass out as small medullated fibres of the anterior roots, 
 of certain of the sacral nerves (mainly the second and third in the cat) 
 into the pelvic nerve (nervus erigens). They end in relation with 
 ganglion-cells in the neighbourhood of the organs which they supply. 
 The seventh and ninth cranial nerves carry vaso-dilator fibres which 
 are distributed by way of the lingual and other branches of the fiith 
 to the salivary glands, the tongue, the mucous membrane of the floor 
 of the mouth, and part of the soft palate. Those in the lingual, passing 
 through the chorda tympani, end in gangi ion-cells near the submaxillar^' 
 and sublingual glands, and the axons of these cells continue the path 
 to the vessels of the glands. It is supposed that the vaso-dilators dis- 
 tributed in other branches of the fiith also have ganglion-cells on their 
 course. In fact, there is good evidence that everj' elferent vaso-motor 
 fibre is interrupted by one, and only by one, ganglion-cell between the 
 cord and the bloodvessels. The statement has been made that for 
 certain regions of the body, especially the skin of the limbs, the vaso- 
 dilator nerves are contained, not in the anterior, but in the posterior 
 roots. And these, it is claimed, are not aberrant efferent fibres which 
 have strayed in the course of development into the wrong roots, but true 
 posterior root-fibres whose cells of origin lie in the spinal ganglia, and 
 which conduct efferent vaso-dilator impulses in the wrong direction, so 
 to speak, from the cord to the periphery — ' antidromic ' impulses 
 (Bayliss). 
 
i82 THE CIRCULATION OF THE BLOOD AXD LYMFH 
 
 Effect of Nicotine on Nerve-Cells. — A method which has been found 
 most fruitful in studying the relations of sympathetic ganglion-cells to 
 the vaso-motor fibres, as well as to the pilo-motor* and secretory fibres 
 which in certain situations are so intricately mingled with them, must 
 here be mentioned. It depends upon the fact that when a suitable 
 dose of nicotine (lo milligrammes in a cat) is injected into a vein, or a 
 solution is painted on a ganglion with a brush, the passage of nerve- 
 mipulses through the ganglion is blocked for a time (Langley). The 
 nerve-fibres peripheral to the ganglion are not affected. The question 
 whether efferent fibres are connected with ner\e-cells between a given 
 point and their peripheral distribution can, therefore, be answered by 
 observing whether any effect of stimulation is abolished by nicotine. 
 If, for instance, the excitation of a nerve caused constriction of certain 
 bloodvessels before, and has no effect after, the application of nicotine 
 to a ganglion, its \aso-constrictor fibres, or some of them, must be con- 
 nected with nerve-cells in that ganglion. Langley has brought forward 
 evidence, that many of the bodies which are commonly supposed to act 
 upon nerve-endings (as nicotine, curara, atropine, pilocarpine, adrenalin, 
 etc.) really act upon ' receptive ' sub.stances of the cells in connection 
 with which the nerve-fibres end. These receptive substances are con- 
 ceived to be capable of being specificallj- afiected by chemical bodies 
 and by nerv'ous stimuli, and in their turn to be capable of influencing 
 the metabolism of the main cell substance on which its function depends. 
 The receptive substances thus form beyond the histological link of the 
 nerve -ending a kind of chemical link between the nerve-fibre and the 
 cell which it supplies. 
 
 We have thus traced the vaso-motor nerves from the cerebro- 
 spinal axis to the bloodvessels which they control ; it still remains 
 to define the portion of the central nervous system to which these 
 scattered threads are related, which holds them in its hand and acts 
 upon them as the needs of the organism may require. 
 
 Vaso-Motor Centres. — Now, experiment has shown that there is 
 one very definite region of the spinal bulb which has a most intimate 
 relation to the vaso-motor nerves. If while the blood-pressure in 
 the carotid is being registered, say, in a curarized rabbit, the central 
 end of a peripheral nerve like the sciatic is stimulated, the pressure 
 rises so long as the bulb is intact, this rise being largely due to the 
 reflex constriction of the vessels in the splanchnic area. If a series 
 of transverse sections be made through the brain, the rise of pressure 
 caused by stimulation of the sciatic is not affected till the upper 
 limit of the bulb is almost reached. If the slicing is still carried 
 downwards, the blood-pressure sinks, and the rise following stimu- 
 lation of the sciatic becomes less and less. When the medulla has 
 been cut away to a certain level, only an insignificant rise or none 
 at all can be obtained. The portion of the medulla the removal of 
 which exerts an influence on the blood-pressure, and its increase by 
 reflex stimulation, extends from a level 4 to 5 mm. above the point 
 of the calamus scriptorius to within i to 2 mm. of the corpora 
 quadrigemina. Stimulation of the medulla causes a rise, destruc- 
 
 * Pilo-motor nerves supply the smooth arrector pili muscles, whose contrac- 
 tion causes the hair to ' stand on end.' 
 
THE NERVOUS REGULATION 01- THE BLOODVESSELS 18.I 
 
 tion of tliis portion of it a severe fall, of general blood-pressure. 
 There is evidently in this region a nervous ' centre ' so intimately 
 related, if not to all the vaso- motor nerves, at least to such very 
 important tracts as to deserve the name of a vaso-motor centre. 
 Experiment has shown that this is much the most influential centre, 
 and it is usually called the chief or general vaso-motor centre. Some 
 writers prefer to speak of it as the vaso-constrictor centre, since it 
 is undoubtedly connected with most or all of the vaso-constrictor 
 paths, and has not been shown to be similarly connected with the 
 vaso-dilator paths. There is, indeed, not the same solid evidence 
 for the existence of a general vaso-dilator centre in the bulb as for 
 the existence of the general vaso-constrictor centre. Yet there are 
 facts which indicate that the bulbar vaso-motor centre or centres, 
 when reilexly stimulated, can, and often do, respond not merely by 
 an increase or a remission of vaso-constrictor tone, but by a simul- 
 taneous inhibition of vaso-constrictor fibres and excitation of vase- 
 dilators leading to a fall of pressure, or by a simultaneous inhibititm 
 of vaso-dilators and excitation of vaso-constrictors leading to a rise 
 of pressure. 
 
 The spinal cells of origin of the pre-ganglionic segments of the 
 vaso-constrictor paths constitute subordinate centres which either 
 normally support a certain degree of vascular tone, or come to do so 
 after the chief vaso-motor centre has been cut off. 
 
 Thus, in the frog it is possible to go on destroying more and more 
 of the cord from above downwards, and still to obtain reflex vaso- 
 motor effects, as seen in the vessels of the web, by stimulating the 
 central end of the sciatic nerve. Although these effects indeed 
 diminish in amount as the destruction of the cord proceeds, yet a 
 distinct change can be caused when onl}^ a small portion of the ccrd 
 remains intact. 
 
 Similarly, in the mammal evidence has been obtained of the 
 existence of ' centres ' at various levels of the cord, capable of acting 
 eventually, if not at once, as vaso-constrictor centres after the loss 
 of the controlling influence of the bulb. The best example of a 
 vaso-dilator centre is that situated in the lumbar cord, which controls 
 the erection of the penis. After total section of the cord at the upper 
 limit of the lumbar region, erection, which is known to be due to a 
 reflex dilatation of the arteries of the organ through the ner\'i eri- 
 gentes, can still be caused (in dogs) by mechanical stimulation of 
 the glans penis, so long as the afferent fibres of the reflex arc con- 
 tained in the ner vus pudendus are intact. Destruction of the lumbar 
 cord abolishes the effect. It is impossible to avoid the conclusion 
 that a vaso-dilator or erection centre, which is in relation on the 
 one hand with the ner\n erigentes, and on the other with the nervus 
 pudendus, exists in the lower portion of the spinal cord. \'aso- 
 motor centres for the hind-limbs have also been located in the 
 
i84 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 same region. When the brain, the bulb, and the upper portion of 
 the cord have been eliminated by hgation of all the arteries from 
 which blood can possibl}' reach them, a sufficient vascular pressure 
 persists to permit the circulation to go on in the lower portion of 
 the body for hours. And while sectipn — or freezing (Fig. 80) — of 
 the cord in the lower cervical region causes a marked fall of pressure, 
 this i'. not permanent if the animal is allowed to survive. Forty-one 
 days after total section of the cord at the seventh cervical segment 
 in a dog an arterial pressure of 130 mm. of mercury was found. A 
 mechanism for the maintenance of vascular tone exists even beyond 
 the limits of the central nervous system. For when the lower 
 portion of the cord is completely destroyed, the dilatation of the 
 vessels of the hind-limbs, which is at first so conspicuous, passes 
 away after a time, the functions of vaso-motor centres having 
 perhaps been assumed by the sympathetic ganglia (Goltz and 
 Ewald). When the lumbo-sacral sympathetic chain is extirpated, 
 
 ^^i^ii/"'^ 
 
 '^^'^^Jh^,^^^;^ 
 
 J'ig. 80. — Effect on Blojd-PiL=:jiirc ui Freezing Spinal Cord (I'ike). At i the first 
 or second dorsal segment of a dog's cord was frozen with liquid air; at 2 and 3 
 central end of sciatic stimulated without effect on pressure (respectively one and 
 a half and three minutes Jifter freezing of cord). (Four-fifths of original size.) 
 
 there is a further loss of vascular tone in the affected region. But 
 even this is not irremediable. After a time recovery again occurs, 
 although it may be more partial and tardy than before. This may 
 take place either through the intervention of still more peripheral 
 ganglia, or through the development of a certain tonus by the 
 muscular fibres of the vessels when abandoned to themselves. 
 
 As to the nature of the tone of the general vaso-motor centre, the 
 same question may be asked which has been already discussed for 
 the cardio-inhibitory centre. Is it reliex, or does it depend upon 
 direct excitation of the centre by some constituent of the blood or 
 lymph, or some substance produced in the centre itself ? The best 
 answer which can at present be made is that a constant central 
 excitation by the carbon dioxide formed in the centre or circulating 
 in the blood is a not unimportant factor in the maintenance of the 
 vaso-motor tone. A marked diminution in the carbon dioxide 
 tension of the blood, a condition which is termed ' acapnia," may 
 indeed contribute to the severe fall of blood-pressure associated with 
 
77//; .\7-:A'F^()r.s- regulatios or riu: ui.ooDVESbELs 185 
 
 surgical shock (Henderson). In addition to the direct influence of 
 carbon dioxide, and possibly of other substances, the arrival of 
 afferent impulses at the centre seems to play a part in maintaining 
 that continual discharge of efferent impulses along the vaso-motor 
 nerves which constitutes its tone. In this regard, the vaso-motor 
 centre occupies an intermediate position between the respiratory 
 centre, the most purely automatic, and the cardio-inhibitory centre, 
 the most purely reflex of the three great bulbar mechanisms. 
 
 Of the anatomical relations of the nerve-cells that make up the 
 b\ilbar and spinal vaso-motor centres, little more is knowni than may 
 be deduced from the physiological facts we have been reciting. It has 
 been surmised on histological grounds that certain cells of small size 
 scattered up and down the thoracic and upper lumbar regions of the 
 cord in the lateral horn (intermedio -lateral tract), and perhaps cropping 
 out also in the bulb, arc vaso-motor cells. There is good evidence that 
 the prc-g<mglionic sympathetic fibres, including tlic vaso-motor fibres 
 wliich we have already discovered emerging from tlie cord in the spinal 
 roots, are connected with these cells. And, indeed, there is reason to 
 believe that the connection is made without the intervention of any 
 other nerve-cells, and that the axis-cylinders of these vaso-motor fibres 
 arc the axis-cylinder processes of the \'aso-motor cells. So that the 
 simplest efferent path along which vaso-motor impulses can pass may 
 be conEidercd as built up of two neurons, one with its cell-body in the 
 cord, and the other in a sympathetic ganglion. Less is knowTi of the 
 elements which constitute the bulbar centre and of their connections. 
 But since it would appear that the spinal \'aso-motor centres are under 
 the control of the chief centre in the bulb, it is necessary to suppose 
 that the axis-cylinder processes of some of the cells of the bulbar centre 
 come into relation with the spinal vaso-motor cells, and that impulses 
 passing, let us say, from the bulb to the vessels of the leg, would have 
 to traverse three neurons (p. 852). 
 
 Vaso-Motor Reflexes. — We have already seen that the cardiac 
 centres are constantly influenced by afferent impulses, and that in 
 the direction either of augmentation or inhibition. The vaso-motor 
 centre in the bulb is equally sensitive to such impulses. They 
 reach it for the most part along the same nerves, and by increasing or 
 diminishing its tone cause sometimes constriction and sometimes 
 dilatation of the vessels, the result depending partly upon the ana- 
 tomical connection of the afferent fibres, but apparently in part also 
 upon the state of the centre. 
 
 Of the afferent nerves that cause vaso-dilatation, the most im- 
 portant is the depressor, whose reflex inhibitory action on the heart 
 has been already described. The fall in the arterial pressure is due 
 chiefl}-, not to the inhibition of the heart, but to inhibition of the 
 vaso-constrictor tone of the bulbar vaso-motor centre, combined 
 with stimulation of vaso-dilator nerves, and consequent general dila- 
 tation of the arterioles throughout the body. That the depressor 
 action involves excitation of vaso-dilators follows from the fact that 
 vaso-dilatation occurs in the limbs on stimulation of the depressor 
 after their vaso-constrictor nerves have been cut. Stimulation of the 
 central end of the depressor may also cause dilatation of the 
 
l86 Tin: CIRCl'LArWS 01- THE BLOOD ASD LYMPH 
 
 vessels of the submaxillary gland even on the opposite side, whether 
 the sympathetic has been divided or not! so long as the chorda 
 tympani is intact, and this dilatation is not accompanied by a flow 
 of saUva. Stimulation of the depressor produces its usual result after 
 section of the vagi. It has been suggested that the function of the 
 nerve is to act as an automatic clieck upon the blood-pressure in the 
 interest both of the heart and the vessels, its terminations in the 
 aorta or the ventricular wall bcine niechanirally stimulated whert the 
 pressure tends to rise towards the danger limit. In rare cases, 
 efferent inhibitory fibres for the heart have been found in the depres- 
 sor of the rabbit. 
 
 Many of the peripheral 
 nerves contain fibr( s 
 whose stimulation is fol- 
 lov.ed by dib.tation of the 
 
 Fig. 8i. — Diagram of Deprossor 
 in Rabbit. X, vagus ; Si,, 
 superior laryngeal ; D, de- 
 pressor. Arrows show course 
 of impulses. 
 
 
 
 / • 
 
 ' ^. — :.. 
 
 K 
 
 (WvV^^'A'- 
 
 '111 il 
 
 I- 
 
 
 ^HB 
 
 [\ 
 
 ■ •; 
 
 ■ws^tm 
 
 1 
 
 
 rig. 82. — ^Blood-Prosure Tracing: Rabbit. Central 
 end of depressor stimulated at i ; stimulation 
 stopped at 2. Time-trace, seconds. 
 
 bloodvessels in special regions, usually the areas to which they are 
 themselves distributed, accompanied by constriction of distant and, 
 it mav be, more extensive vascular tracts. Thus, the usual local effect 
 of stimulating the afferent hbres of the lowest three thoracic nerves, 
 in whose anterior roots run the vaso-motor fibres for the kidney, is 
 a dilatation of the renal vessels (Bradford), and the usual local effect 
 of stimulating the infra-orbital or supra-orbital nerve a dilatation 
 of the external maxillary artery. But the general effect in both 
 cases is vaso-constriction in other regions of the body, which more 
 than compensates the local dilatation, so that the arterial blood- 
 pressure rises. It is not difficult to see that both of these changes 
 render it easier for the part to obtain an increased supply of blood. 
 
 Sometirrcs the reciprocal relation between vaso-dilatation in one part 
 of the body and vaso-constriction in another is only apparent. For 
 example, sUmulatiou ul the cut end of the sciatic causes, as we have 
 already seen, extensive va.so-coustriction and a notable rise in the blood- 
 pressure. The constriction certainly involves the splanchnic area; but 
 
77//: \I-RVOUS lUlGULATION OF THE BLOODVESSELS i87 
 
 superficial parts, as the lips, may be seen to be flushed with blood. 
 In asphyxia, when the vaso-motor centres arc directly stimulated by 
 the venous blood, tliis apparent antagonism is still better marked: the 
 cutaneous vessels arc widely dilated and engorged, the face is livid, 
 but the abdominal organs arc pale and bloodless (Heidenhain). The 
 blood-pressure rises rapidly, reaches a maximum, and then gradually 
 falls as the vaso-motor centre becomes paralyzed (Figs. 84 and 85). It 
 has been shown that in both cases vaso-constriction ot the skin is really 
 produced as well as vaso-constriction of the internal organs, but the 
 increased blood-pressure mechanically overcomes the constriction of 
 the cutaneous vessels. 
 
 The kind of stimulus seems to have something to do with the 
 direction of the reflex vaso-motor change. For while electrical 
 stimulation of e\^ery muscular nerve, even of the very finest twigs 
 that can be isolated and laid on electrodes, provokes always, whether 
 the shocks follow each other rapidly or slowly, a rise of general 
 
 Fig. 83. — Pressor Effect of Stimulation of Central End of Vagus in a Cat during 
 Resuscitation after Cerebral Anaemia. The depressions in the signal line ABC 
 indicate the duration of three successive excitations of equal strength, sixty-five, 
 seventy-three, and seventy-nine minutes respectively after restoration of the 
 circulation. The pressor effect increases as resuscitation proceeds. Later on 
 the original depressor effect was again obtained. The upper tracing is that of 
 the artificial respiration. (Two-thirds original size.) 
 
 blood-pressure, mechanical stimulation of a muscle, as by kneading 
 or massage, causes a fall. The condition of the afferent fibres also 
 exerts an influence. For example, excitation of the central end of a 
 sciatic nerve that has been cooled is followed by vaso-dilatation 
 and fall of pressure, the opposite of the ordinary result. These and 
 similar facts have led to the idea that most afferent nerves contain 
 two kinds of fibres, whose stimulation can affect the actf^ty of the 
 vaso-motor centres — ' reflex vaso-constrictor,' or ' pressor ' fibres, 
 and ' reflex vaso-dilator,' or ' depressor ' fibres. The branch of the 
 vagus, however, to which the name ' depressor * has been specially 
 given is usually described as the only peripheral nerve the excitation 
 of which is in all circumstances followed by a general diminution of 
 arterial pressure. But this is not strictly correct, for at an early 
 period in the resuscitation of the brain after anaemia excitation of 
 
J 88 TUIi CIRCULATION 01- THE BLOOD ASD LYMPH 
 
 the rabbit's ' depressor ' causes a slight rise of pressure not followed 
 by any fall. This, perhaps, indicates the presence in the ' depressor ' 
 of a small number of pressor fibres, which are resuscitated sooner 
 than the depressor fibres proper. The same phenomenon, only 
 more marked, may be seen when the central end of the cat's va]L(us, 
 containing the depressor fibres, is e.xcited at interval> during resus- 
 citation (Fig. 83). Or the result may depend upon a change in tht- 
 response of the altered vaso-motor centres to impulses reaching 
 them along the depressor fibres. If specific ' depressor ' fibres exist 
 in other nerves, they are so mingled with ' pressor ' fibres that their 
 action is masked when both are stimulated together. The state of 
 the vaso-motor centre is unquestionably a factor which has some 
 importance in determining the result of reflex vaso-motor stimula- 
 tion. For instance, in an animal deeply anaesthetized with chloro- 
 form or chloral, excitation of pressor fibres (in an ordinary sensory 
 
 Fig. 84. — Rise of Blood- Pressure in Asphy.xia : Rabbit. Respiration stopped at i. 
 Interval bet^veen 2 and 3 (not reproduced) 44 seconds, during which the blood- 
 pressure steadily rose. At 4, respiration resumed. Time-trace, seconds. 
 
 nerve) causes, not a rise, but a fall of blood-pressure; while in an 
 animal fully under the influence of strychnine stimulation of the 
 depressor nerve causes not a fall, but a rise. 
 
 The vaso-motor reflexes in man can be conveniently studied by 
 the calori metric method described on p. 221. One of the most 
 important of the vaso-motor reactions is that by which the vessels 
 of the skin respond to the temperature of the environment so as 
 to regulate the loss of heat from the body (p. 699). When one 
 hand, eg. the left, is immersed in cold water (say at about 8° C), 
 the blood-flow in the right is at once reduced owing to reflex vaso- 
 constriction. Other parts of the body are also affected, but not so 
 readily as the contra-lateral hand, since the segments of the cord 
 into which the afferent fibres from a given skin area run are at the 
 same time the segments from which the efferent vaso-motor fibres 
 for the symmetrically-placed area on the opposite side of the body 
 arise. The reflex diminution in the flow persists for a time which 
 
THE NERVOUS REGUEATlOK OF THE BLOOD VESSELS i8.> 
 
 varies with the iiuHvidual, tlie external temperature, and other 
 circumstances, and then as a rule rather suddenly the vaso-con- 
 strictit)n gives way and tiie flow brgins again to increase, even whilr- 
 the left hand is still kept in the cold water. When the left hand is 
 transferred from the cold to warm water (at 43° or 44° C), the first 
 effect is a transient diminution in the blood-flow in the right hand. 
 This soon gives place to an increase (vaso-dilatation). As an ex- 
 ample, the following table gives the condensed results of three 
 experiments on two young men. Experiments II. and III. were on 
 the same man at an interval of three days. 
 
 
 Te 
 
 mperature o 
 
 f— 
 
 Duration 
 
 Flow in Grms. 
 
 
 Experi- _ 
 ment. | 
 
 
 
 
 of 
 Observation 
 
 per 100 c.c. 
 of Right Hand 
 
 Left Hand in — 
 
 
 Arterial 
 Blood. 
 
 
 
 Room. 
 
 Calorim. 
 
 in Minutes. 
 
 per Minute. 
 
 ' 
 
 , 
 
 '28-9] 
 29-0 
 
 
 r3i-i 
 
 31-7 
 
 16 
 
 12-2 
 
 
 I. - 
 
 36-6 
 
 4 
 
 6-9 
 
 Cold water. 1 
 
 29-0 
 
 31-2 
 132-3 
 
 6 
 
 9-9 
 
 Cold water still. 
 
 
 .29-iJ 
 
 
 II 
 
 II-6 
 
 Warm water. 
 
 1 
 
 '24-0^ 
 
 
 f3o-9 
 
 13 
 
 lO-I 
 
 — 
 
 
 24'2 
 
 
 31-3 
 
 13 
 
 5-0 
 
 Cold water. 
 
 II. - 
 
 23-9 '- 
 
 36-0 
 
 • 31-4 
 
 2 
 
 3-4 
 
 Warm water. 
 
 1 
 
 23-9 
 
 
 31-5 
 
 3 
 
 8-4 
 
 Warm water still. 
 
 
 l23-9J 
 
 
 l3i-7 
 
 7 
 
 15-0 
 
 Warm water still. 
 
 
 '24-81 
 
 
 ('3I-6 
 
 15 
 
 12-4 
 
 — 
 
 ■ 
 
 24-4 
 
 
 32-1 
 
 5 
 
 5-9 
 
 Cold water. 
 
 111. 
 
 24-4 ■ 
 
 36-5 
 
 - 32-2 
 
 5 
 
 10-7 
 
 Cold water still. 
 
 
 24-4 
 
 
 32-4 
 
 3 
 
 7-9 
 
 Warm water. 
 
 ' 
 
 124-5. 
 
 
 132*6 
 
 7 
 
 I7'6 
 
 Warm water still. 
 
 Such facts enable us to some extent to understand the manner in 
 which the distribution of the blood is adjusted to the requirements 
 of the different parts of the body, so that to a certain degree of 
 approximation no organ has too much, and none too little. The 
 blood-supply of the organs is always shifting with the calls upon 
 them. Now, it is the actively-digesting stomach and the activelj'- 
 secreting glands of the alimentarj' tract w-hich must be fed with a 
 full stream of blood, to supply waste and to carry away absorbed 
 nutriment. Again, it is the working muscles of the legs or of the 
 arms that need the chief blood-supply. But wherever the call may 
 be, the vaso-motor mechanism is able, in health, to answer it by 
 bringing about a widening of the small arteries of the part which 
 needs more blood, and a compensatory narrowing of the vessels 
 of other parts whose needs are not so great. 
 
 It is also through the vaso-motor system, and especially by the 
 action of that portion of it which governs the abdominal vessels, and 
 
igo THE CJRCULATIOX OF THE BLOOD ASD LYMPH 
 
 of the netves that regulate the work of the heart, that in animals 
 to which the upright position is normal (monkey) and in man the 
 influence of changes of posture on the circulation is almost com- 
 pletely compensated.* The pressure in the upper part of the 
 human brachial artery has been measured with a sphygmoman- 
 ometer, first in the horizontal and then immediately afterwards in 
 the standing posture, and in health it has been found to remain 
 practically unchanged (Hill). But if the person was overworked or 
 out of sorts, the compensation was less complete. It is well known 
 that in debilitated persons, especially if long confined to bed, the 
 sudden assumption of the upright position may cause vertigo, and 
 even syncope, the normal compensatory mechanism being deranged. 
 In such animals as the rabbit this compensation is totally inefficient. 
 When a domesticated rabbit, which has been kept in a hutch, is 
 suspended vertically with the feet down, the blood drains into the 
 abdominal vessels, syncope speedily ensues, and in a period that 
 ranges from less than a quarter to three-quarters of an hour the 
 animal dies in the convulsions of acute cerebral anaemia (Salathe, 
 Hill). The head-down position has no ill-effects. In wild rabbits, 
 whose abdominal wall is more tense and elastic, these fatal symp- 
 toms are not easily produced, and the same is true of cats and dogs. 
 But in all animals, when the compensation is destroyed, as in 
 paralysis of the vaso-motor centre by chloroform, the circulation 
 may Ise profoundly influenced by the position of the body: elevation 
 of the head may lead to cerebral auiemia, syncope, and even death ; 
 elevation of the legs, and particularly the abdomen, may restore the 
 sinking pulse by filling the heart and the vessels of the brain. If a 
 chloralized dog be fastened on a board which can be rotated about 
 a horizontal axis passing under the neck, the blood-pressure in the 
 carotid artery falls greatly when the animal is made to assume the 
 vertical position with the head up, and either rises a little or remains 
 practically unchanged when the head is made to hang down. So 
 great may the fall of pressure be in the former position that death 
 may occur if it be long maintained (Practical Exercises, p. 213). 
 
 • Two factors may be distinguished in the blood-pressure, the hydrostatic 
 and the hydrodynamic elements. The hydrostatic portion of the pressure is 
 due to the weight of the column of blood acting on the vessel; the hydro- 
 dynamic portion of the pressure is due to the work of the heart. If a dog be 
 securely fastened to a holder arranged in such a way that the animal can be 
 placed vertically, with the head up or down, and the mean blood-pressure in 
 the crural arterv be measured in the two j)ositions. there will be a considerable 
 difference. iVr when the legs arc uppermost the heart has to overcome the 
 weight of the column of blood rising above it to the crural arten*-; when the 
 head is uppermost the action of the heart is reinforced by the weight of the 
 blood. And if no change were produced in the action of the heart, or in the 
 general resistance of the vascular path, by the change of position, this differ- 
 ence would be equal to the pressure of a column of blood twice as high as the 
 straight-line distance between the cannula and the point of the arterial system 
 at wiiich the pressure is the same with head up as with head down (indifferent 
 point J. 
 
THi: SEUVOLS REGVLATIOS Of- IHIL HLOUDVESSI-LS x<)i 
 
 I'inally, it is in virtue of the ama/ing ])Ovvtr of accommodation 
 possessed by the vascular system, as controlled by the vaso-motor 
 and cardiac nerves, that so long as these are not disabled the total 
 quantity of blood may be greatly diminished or greatly increased, 
 without endangering life, or even causing more than a transient 
 alteration in the arterial pressure. It is not until at least a quarter 
 of the blood has been withdrawn that there is an\' notable effect 
 on the pressure, for the loss is quickly compensated bv an increase 
 in the activity of the heart and a constriction of the small arteries. 
 An animal may recover after losing considerably more than half its 
 blood.* Conversely, the volume of the circulating liquid may be 
 doubled by the injection of blood or physiological salt solution 
 without causing death, and increased by 50 per cent, without any 
 marked increase in the pressure. The excess is promptly stowed 
 
 ..^ 
 
 0^ 
 
 ^;00mim^,^^ 
 
 <^-« 
 
 
 F.u. S5. — Blood- Pressure Tracing from a Dog poisoned with Alcohol. 
 The respiratory centrebeing paralyzed, respiration stopped, and f he 
 ty- pical rise of blood-pressure in asphyxia took place. The pressure 
 had again fallen, and total paral\-sis of the vaso-niotor centre was 
 near at hand, when at A the animal made a single respiratory 
 movement. The quantity of oxgyen thus taken in was enough to 
 restore the vaso-inotor centre, and the blood-pressure again rose. This was 
 repeated five or six times. (Three-fourths original size.) 
 
 awa}' in the dilated vessels, especially those of the splanchnic area; 
 the water passes rapidly into the lymph, and is then more gradually 
 eliminated by the kidneys. 
 
 From these facts we can deduce the practical lesson, that blood- 
 letting, unless fairly copious, is useless as a means of lowering the 
 general arterial pressure, while it need not be feared that transfusion 
 of a considerable quantity of blood, or of salt solution, in cases of 
 severe haemorrhage, will dangerously increase the pressure. And 
 from the physiological point of view the term ' haemorrhage ' includes 
 more than it does in its ordinary sense. For as dirt to the sanir 
 tarian is ' matter in the wrong place,' haemorrhage to the physiolo- 
 gist is blood in the wrong place. Not a drop of blood may be lost 
 from the body, and yet death may occur from haemorrhage into the 
 pleural or the abdominal cavity, into the stomach or intestines. 
 Not only so, but a man may bleed to death into his own blood- 
 
 * It is not usually possible to obtain quite two-thirds of the total blood by 
 bleeding a dog from a large artery. In seven dogs bled from the carotid, 
 the ratio of the weight of the blood obtained to the bodv-weight was 
 I : 24-7. I : 21-7. I : 23-7. i : lo-d. i : iS-(). i : ib, i : i V5 In the last case, the 
 blood clotte 1 wi'.h abnormal slo vnes • and the animal died in a few minutes. 
 
IQJ Tin: CIRLVLATIOS OP Tin: TiLoOb AM) LYMPH 
 
 vessels; in surgical (also sometimes called traumatic or vascular) 
 shock, it would ai)])iar that tlu- blood wliich ought to be cinulating 
 through the brain, lieart, and lungs may stagnate in the dilated \'eins. 
 The essential nature of ' vascular ' shock, which slioujd be dis- 
 tinguished from tJie spinal shock d( .^riibed in Chapter XVI. is so 
 little understood, in spite of the large amount of work devoted to 
 the subject, that it would not be profitable to discuss it here. It may 
 be remarked, however, that there is no reason to suppose that ex- 
 haustion or loss of sensitiveness of the vaso-motor centre is concerned. 
 \Miile an undue proportion of the blood is accumulated in the great 
 \eins, the arterioles and capillaries of the splanchnic area, like those 
 of the skin, are contracted and contain less blood than normal (Lyon, 
 Janeway and Jackson, etc.). 
 
 Section VII. — The Lymph.\tic Circulation. 
 
 As has ah-eady been stated, some of the (.onstitiicnts of the blood, 
 instead of passing back to the heart from the capillaries along the veins, 
 find their wav by a much more tedious route along the lymphatics. 
 The blood capillaries are everywhere in very intimate relaticMi with 
 Ivmph capillaries, which, completely lined with epithelioid cells, lie in 
 irregular spaces in the connective-tissue that everywhere accompanies 
 and supports the bloodvessels. The constituents of the blood-plasma 
 are filtered through, or secreted by the capillary walls into these lymph 
 spaces, and mingling there with waste products discharged by the cells 
 of the tissues, form the liquid known as tissue liquid or tissue lymph. 
 From the tissue liquid the lymph capillaries take up the constituents 
 of the ' lymphatic ' lymph, which then passes into larger lymphatic 
 vessels, with lymphatic glands at intervals on their course. These fall 
 into still larger trunks, and finally the greater part of the lymj^h reaches 
 the blood again by the thoracic duct, which opens into the venous 
 system at the junction of the left subclavian and internal jugular veins. 
 The lymph from the right side of the head and neck, the right e.xtremity, 
 and the right side of the thorax, with its viscera, is collected by the 
 right lymphatic duct, which opens at the junction of the right sub- 
 clavian and internal jugular veins. The openings of both ducts are 
 guarded by semilunar valves, which prevent the reflux of blood from 
 the veins. Serous cavities like the pleural sacs, although differing 
 from ordinary lymph spaces, are connected through small opening , 
 called stomata, with lymphatic vessels. 
 
 The rate of flow of the lymph in the thoracic duct is very small com- 
 pared with that of the blood in the arteries — only about 4 mm. per 
 second, according to one observer. Xcvcrthcless, a substance injected 
 into the blood can be detected in the lymph of the duct in four to seven 
 minutes (Tschirwinsky). The factors which contribute to the main- 
 tenance of the lymph flow are : 
 
 (i) The pressure under wdiich it passes from the blood capillaries into 
 the lymph spaces and from the lymph spaces into the lymph capillaries. 
 The pressure in the thoracic duct of a horse may be as high as i z mm. 
 of mercury; in the dog it may be less than 1 mm. The difference is 
 probably due, in part at least, to a difference in the experimental con- 
 ditions, dogs being usuallv anaesthetized for such measurements, horses 
 not. The pressure in the lymph ca))illaries must, of course, be higher 
 than in the thoracic duct — how much higher we do not know. 
 
 (2) The contraction of muscles increases the pressure of the lymph 
 by compressing the channels \n which it is crmtained, and the valves 
 
THE LYMPHATIC CIRCULATION I93 
 
 with which the lymphatics are even more richly provided than the 
 veins, hinder a backward and favour an onward flow. The contractions 
 of the intestines, and especially of the villi, aitl the movement of 
 the chyle. By the contraction of the diaphraf,Mn, sub.stances may 
 be Slicked from the peritoneal cavity into the lymphatics of its 
 central tendon, throuj^h the stomata in the serous layer with which 
 its lower surface is clad. It is even possible by passive movements of 
 the diaphragm in a dead rabbit to inject its lymphatics with a coloured 
 liquid placed on its peritoneal surface. Passive movements of the 
 limbs and massage of the niuscles arc also known to hasten the sluggish 
 current of the lymph, and are sometimes employed with this object in 
 the treatment of disease. 
 
 (3) The mo\-ements of respiration aid the flow. At every inspiration 
 the pressure in the great veins near the heart becomes negative, and 
 IvTnph is sucked into them (p. 226). 
 
 (4) In some animals rhythmically - contracting muscular sacs or 
 hearts exist on the course of the lymphatic circulation. The frog has 
 two pairs, an anterior and a posterior, of these lymph hearts, which 
 pulsate, although not with any great regularity, at an average rate ol 
 sixty to seventy beats a minute, and are governed by motor and inhibi- 
 tory centres situated in the spinal cord. The beat is not directly ini- 
 tiated from the cord, but the tonic influence of the cord is necessary in 
 order that the lymph hearts may continue to beat (Tschermak). Such 
 hearts are also found in reptiles. It is possible that in animals without 
 localized lymph hearts the smooth muscle, which is so conspicuous an 
 element in the walls of the lymphatic vessels, may aid the flow by 
 rhythmical contractions. 
 
 PRACTICAL EXERCISES ON CHAPTER III. 
 
 I. Microscopic Examination of the Circulating Blood. — (i) Take a 
 tadpole and lay it on a glass slide. Cover the tail with a large cover- 
 slip, and examine it with the low power (I.eitz, oc. III., obj. 3). 
 Generalh' the tail will stick so closely to the slide, and the animal will 
 move so little, that a sufficiently good view of the circulation can be 
 obtained. If there is any troiiblc, destroy the brain with a needle. 
 Observe the current of the blood in the arteries, capillaries and veins. 
 An arteiy may be easily distinguished from a vein by looking for a 
 place at which the vessel bifurcates. In veins the blood flows in the 
 two branches of the fork towards the point of bifurcation, in afteries 
 away from it. Sketch a part of a field. 
 
 To Pith a Frog. — Wrap the animal in a towel, bend the head forwards 
 with the index-finger of one hand, feel with the other for the depression 
 at the junction of the head and backbone, and push a narrow-bladed 
 knife right down in the middle line. The spinal cord will thus be 
 divided with little bleeding. Now push into the cavity of the skull a 
 piece of pointed lucifer match. The brain will thus be destroyed. The 
 spinal cord can be destroyed by passing a blunt needle down inside the 
 vertebral canal. 
 
 (2) Take a frog and pith its brain only, inserting a match to prevent 
 bleeding. Pin the frog on a plate of cork into one end of which a 
 glass slide has been fastened with sealing-wax. Lay the web of one 
 of the hind-legs on the glass and gently separate two of the toes, if 
 necessary by threads attached to them and secured to the cork plate. 
 Put the plate on the microscope -stage and fasten by the clips (see 
 pp. 15, 118). 
 
 (3) After tlie normal circulation has been studied thoroughly put a 
 very small drop of tincture of cantharides on the p(jrtion of the web 
 
 13 
 
194 THE CIRC LLATIOX OF THE BLOOD ASD LYMPH 
 
 which is in the field of the microscope, using a fine pipette. Observe 
 the process of inflammation, including stasis and diapcdcsis (p. 6i). 
 
 2. Anatomy of the Frog's Heart.- Expose the heart of a pithed frog 
 by pinching up ilie skin over the abdomen in the middle line, dividing 
 it' with scissors up to the lower jaw, and then cutting through the 
 abdominal muscles and the bony pectoral girdle. The external ab- 
 dominal vein, which will be observed on reflecting the skin, can be 
 easily avoided. The heart will now be seen enclosed in a thin mem- 
 brane, the pericardium, which should be grasped with fine-pointed 
 forceps and freely divided. Connecting the posterior surface of the 
 heart and the pericardium is a slender band of connective tissue, the 
 fra^num. A silk ligature may be passed roun<l this with a threaded 
 curved needle, or curved fine-pointed forceps: and tied, and then the 
 frjonum may be divided posterior to the ligature. The anatomical 
 arrangement of the various parts of the heart should now be studied. 
 Xote the single ventricle with the bulbus arteriosus, the two auricles, 
 and the sinus venosus, turning the heart over to sec the latter by means 
 of the ligature. Observe the whitish crescent at the junction of the 
 sinus venosus and the right auricle (Fig. 86). 
 
 .S- The Beat of the Heart. — Xote that the auricles beat first, and 
 then the \entriclc. The ventricle becomes smaller and paler during 
 
 its systole, and blushes 
 red during diastole. 
 Count the number of 
 beats of the heart in a 
 minute. Now excise the 
 heart, lifting it by means 
 of tlie ligature, and tak- 
 ingcare tocutwide of the 
 sinus \enosus. Place the 
 heart in a small porce- 
 lain capsule on a little 
 blotting - paper moist - 
 cned with physiological 
 salt solution.* Observe 
 that it goes on beating. 
 Put a little ice or snow 
 in contact with the heart 
 and count the number of 
 beats in a minute. The 
 rate is greatly dimin- 
 ished. Now remove the ice and blotting-paper, cover the heart with 
 the salt solution, and heat, noting the temperature with a thermometer. 
 Observe that the heart beats faster and faster as the temperature rises. 
 At 40° to 43' C. it stops beating in diastole (heat standstill). Now at 
 once pour off the heated liquid, and run in some cold salt solution. The 
 heart will begin to beat again. 
 
 4. Cut off the apex of the ventricle a little below the auriculo- 
 ventricular groove. The auricles, with the attached portions of the 
 ventricle, go on beating. The apex does not contract spontaneously, 
 but can be made to beat by stimulating it mechanically (by pricking 
 it with a needle) or electrically. Divide the still contracting portion 
 of the heart by a longitudinal incision. The two halves go on beating. 
 
 5. Heart Tracings. — (1) Fasten a myograph-plate (Fig. 87) on a 
 stand. Take a long light lever, consisting of a straw or a piece of 
 
 • For frog's tissues this should be 0-7 to 0-75 per cent, sodium chloride 
 solution, for mammalian tissues a little stronger (about 0-9 per acnt.). 
 
 rig. 86. — Frog's Hfart with Stanuius' Ligatures in 
 Position (Cyon). .\ntPiior surface of heart shown 
 on the left, posterior surface on the right, a, right 
 auricle; h, left auricle; c, ventricle; </, bulbus arte- 
 riosus; e,f, aorta-; g, sinus venosus. 
 
PRACTICAL EXERCISES 
 
 195 
 
 ^ « "wjui '""^^Mlfc^ 
 
 Fia 
 
 87. — Arrangement for obtaining a 
 Heart Tracing from a Frog. 
 
 thin chip, armed at one end \vilh a writing-point of parchment-paper, 
 supported near the other end by a horizontal axis, and pierced not 
 far from the axis by a needle carrying on its point a small piece of 
 cork or a ball of sealing-wax. 
 
 A coimtcrpoise is adjusted on the short arm of the lever in the form 
 of a small leaden weight. Cover a drum with glazed paper and smoke 
 it. The paper must be i)ut on so tightly that it will not slip. 
 To smoke the drum, hold it by the spindle in both hands over 
 a fish-tail burner, depress the drum in the fiame, and rotate 
 rapidly. The speed of the drum can be varied by putting in 
 or taking out a small vane. Arrange an electro-magnetic time- 
 marker for writing seconds (Fig. 
 88). Pith a frog (brain only). 
 expose the heart, and put under 
 it a cover-slip to give it support. 
 Pin the frog on the myograph- 
 plate, and adjust the foot of the 
 lever so that it rests on the ven- 
 tricle or the auriculo-ventricular 
 junction. Bring the writing-point 
 of the lever and that of the time- 
 marker vcrticalh- under each other 
 on the surface of the drum. Set off 
 the drum at the slow speed (say, 
 a centimetre a second) . When the 
 lever rests on the auriculo-ventricular junction, the part of the tracing 
 corresponding to the contraction of the heart will be broken into two 
 
 portions, representing 
 the systole of the auri- 
 cles and ventricle re- 
 spectively. Cut the 
 paper off the drum 
 with a knife (keeping 
 the back of the knife 
 to the drum to avoid 
 scoring it) and carry 
 it to the varnishing- 
 trough, holding the 
 tracing bv the ends 
 with both hands, 
 smoked side up. Im- 
 merse the middle of it 
 in the varnish, draw 
 first one end and then 
 the other through the 
 varnish, let it drip 
 for a minute into the 
 trough, and fasten it 
 up with a pin to dn.-. 
 (2) Heart Tracing, 
 with Simultaneous Re- 
 cord of Auricular and Ventricular Contractions. — (a) For this purpose two 
 levers may be arranged, ' nc resting on the auricle, the other on the ven- 
 tricle, the writing-points being placed in the same vertical straight line 
 on the drum. A convenient form of apparatus is shown in Fig. Sq. 
 
 [b) Gaskell's Method {a modification of). — Attach a silk ligature to 
 the very apex of the ventricle. Divide the frs>num, cut the aorta 
 
 Fig. 88. — Electro - Magnetic Time - Marker connected 
 with Metronome. The pendulum of the metro- 
 nome carries a wire which closes the circuit when 
 it dips into either of the mercury cups, Hg. 
 
t96 
 
 THE CIRCULATION OF THE BLOOD ASD LYMPH 
 
 across close to the bulbiis, piiuh up a tiny portion of the auricle and 
 ligature it. Remove the intestines, liver, lungs, etc.. care being taken 
 in cutting away the liver not to injure the sinus. Then rcmo\e tlic 
 lower jaw, and cut awAy the whole of the body except the head, part 
 of the oesophagus, and the tissue connecting it with the heart. Fix 
 the head in a clamp sliding on an ordinar^'^ stand. The heart is held 
 at the auriculo-vcntricular junction in a Gaskell's clamp supported on 
 a separate btand. The thread connected with the ventricle is brought 
 round a pulley and attached to a lever above the heart. The auricle 
 is connected with another lever. The writing-points of the two levers 
 arc arranged in a vertical line on the drum. The small pulley must 
 be oiled from time to time to lessen the friction (Fig. 90). 
 
 If tortoises or turtles are available, the much larger heart of these 
 animals may be used for Experiments 5 (2) (a) and (6). The animal 
 having been killed by cutting oft its head, the ventral portion of the 
 carapace is detach<: d by the saw. The pericardium can now be slit 
 open, and the pads of the levers arranged on auricles and ventricle 
 
 Fig. 89. — Apparatus for obtaining a Simultaneous Tracing of AuricuUr and 
 Ventricular Contractions. 
 
 respectively, as in Experiment 5 (2) (a), without further disturbing 
 the heart. Or the heart may be removed, together with the upj^er 
 portion of the body, the pericardium opmcd, and the liver cut away. 
 The aortic tnmk is then divided, and the portion of it attached to 
 the heart grasped by a small forceps clamp. Fine silk ligatures are 
 attached to the apex of the ventricle and the top of the right auricle. 
 The vagus nerves are exposed in the neck, ligatcd. and divided. The 
 upper portion of the body is supported on a stand. The forceps grasp- 
 ing the aorta is fixed in an ordinary holder, and the threads are attached 
 to the levers, as in Experiment 3 (2) (b). 
 
 With the vagi. Experiment 7 may be perfonned. It must be remem- 
 bered that the actiMty of the two vagi is unequal in the tortoise, the 
 right being the more active. 
 
 6. Dissection of the Vagus and Cardiac Sympathetic Nerves in the 
 Frog. — (i) Put the tissues in the region of the neck on the stretch by 
 passing into the gullet a narrow test-tube or a thic k glass rod nioistened 
 with water, and by pinning apart the anterior limbs. Expose the heart 
 
PRACTICAL EXERCISES 
 
 ^V 
 
 UK] 
 
 by «utting througli the pectoral girdle in the way drscribcd in 2 (p. 194). 
 On eleaiiiig away a little connective tissue and ninscle witli a seeker, 
 three large nerves will come into view. The upper is the glosso- 
 pharvngeal, the lower the hypoglossal; the vagus crosses diagonally 
 between them (Fig. 91). Above the v;'gus trunk, running parallel to 
 it, and separated from it 
 by a thin muscle and a 
 bloodvessel (the carotid 
 artery), lies its lar5Tigcal 
 branch. The vagus should 
 be traced up to the gang- 
 lion situated on it near its 
 exit from the skull. 
 
 (2) Then cut away the 
 lower jaw, dividing and 
 reflecting the membrane 
 covering the roof of the 
 mouth. At the junction 
 of the skull and the back- 
 bone will be seen on each 
 side the levator anguli 
 scapulae muscle (Fig. 9^). 
 Remove this muscle care- 
 fully with fine forceps. 
 Clear away a little con- 
 nective tissue lying just 
 over tlie upper cervical 
 vertebnc, and the s^tu- 
 pathetic chain, with its 
 ganglia, will be seen. Pass 
 a fine silk thread beneath 
 the sympathetic alx)ut the 
 level of the large brachial 
 nerve, by means of a 
 sewing-needle which has 
 been slightly bent in a 
 flame and fastened in a 
 handle. Tie the ligature, 
 divide the sympathetic be- 
 low it, and isolate it care- 
 fully with fine scissors up 
 to its junction with the 
 vagus ganglion. 
 
 Batteries — To set np a 
 Daniell Cell. — Fill the por- 
 ous pot (Fig. 230, p. 724), 
 previously well soaked in 
 water, with dilute sulph- 
 uric acid (I part of com- 
 mercial acid to 10 or 15 
 parts of water) to within 
 \\ inches of the brim, and place in it the piece of amalgamated zinc. If 
 the zinc is not properly amalgamated, leave it in the pot for a minute or 
 two to clean its surface. Then lift it out, pour over it a little mcrcurv, 
 and rub the mercury thoroughly over it with a cloth. Put tlie pot 
 into the outer vessel, which contains the copper plate, and is filled 
 with a saturated solution of sulphate of copper, with some undissolved 
 
 Fig. 90.— Arrangement for recording Auricular 
 and Ventricular Contractions (and studying the 
 Influence of Temperature of the Heart). C, 
 clamp holding the heart at the auriculo-ven- 
 tricular groove; P, pulley round which a thread 
 attached to the apex of the ventricle passes to 
 the lever L'; L, lever connected with auricle. 
 (The rest of the arrangement is for studying the 
 influence of temperature on the heart and its 
 neri-es, G being a vessel filled with physiological 
 salt solution in which the heart is immersed; R. 
 an inflow tube from a reservoir containing salt 
 solution at the temperature required; O', an out- 
 flow tube by which G may be emptied into the 
 beaker B'; O, a tube passing to the beaker B to 
 prevent overflow from G; T, a thermometer.) 
 
198 THE CIRCVLATIUS Ob THE BLOOD A\D lA MFH 
 
 crj'stals to keep it saturated. After using the Daniell, it must always 
 be taken down. The outer pot is left with the copper plate and the 
 sulphate solution in it. The zinc is washed and brushed bright. The 
 sulphuric acid is poured into the stock bottle, and the porous jx)t put 
 into a large jar of water to soak. 
 
 The Bichromate Cell contains only one liquid — a mixture of i part 
 of sulphuric acid with 4 parts of a 10 per cent, solution of potassium 
 bicliromate. In this is placed one, or in some forms two. carbon 
 plates and a plate of amalgamated zinc, .\fter using the battery, take 
 the zinc out of the liquid. 
 
 The Leclanche battery consists of a porous pot filled with a mixture 
 
 of manganese dioxide and carbon packed around a carbon plate, which 
 
 forms the positive pole. The pot stands in an outer jar of glass filled 
 
 with a saturated solution of ammonium chloride, into which dips an 
 
 amalgamated zinc rod, which constitutes the negative pole. Various 
 
 forms of dry batteries can be conveniently used for running induction- 
 
 . coils or time-markers, but are not 
 
 'V '.•>.< /.-•v |i . iJH adapted for yielding constant cur- 
 
 'I'' f^H rents of long duratio'.i. 
 
 >,A ^^V ' Wi 7- Stimulation of the Vagus in 
 
 /^'y^9««^'^1^_J». the Frog.— -Make the same arrange- 
 
 \J/^^^ ^\\ ment.s as in 5 (i) (p. 195), but in 
 
 f\^ i9 M / / ^^idition set up an induction 
 
 7 .^ ^Lqfyo^eaL machine arranged for an inter- 
 
 / /^^^ \\ branch 0/ rupted current (Fig. 93), with a 
 
 (~""~'T' ^^C H ^^'^^'^ Daniell, abichromate, a Leclanche, 
 
 >!, I'' ^^^^v~-^ or a dr^' cell in the primary circuit, 
 
 /"^^J i ^^^ ^\ which should also include a simple 
 
 //^/io^«i<i/-^A^^^^^ y^ \ V key. Insert a short-circuiting key 
 
 \/ijat/^.^ — ^w'^^kX. \ ^ *^® secondary' circuit. Attach 
 
 ^^ / " //H L^B ^^^^'^X \ *^® electrodes to the short-circmt- 
 
 'If v^ )M V-- "^S key, push the secondary coil 
 
 ^ ' //f -f ^rW /J \ "P 'towards the primary imtil the 
 
 I (1 ^ ^^^\(/y I shocks are distinctly felt on the 
 
 A\ \ B H^rl y^ / \ tongue when the Neef 's hammer is 
 \J I p / set going and the short-circuiting 
 
 ■ Lv{i^ ' / key opened. Pith the brain of a 
 
 Fig. 91. -The Relations of the Vagus f^g, expose the hearl, dissect out 
 in the Frog. ^^^ vagus on one side, ligature it 
 
 as high up as possible, and divide 
 above th^ ligature. Fasten the electrodes on the cork plate by means 
 of an indiarubber band, and lay the vagus on them. Set the drum 
 off (at slow speed). After a dozen heart-beats have been recorded, 
 stimulate the vagus for two or three seconds by opening the short- 
 circuiting key. If the nerve is active, the heart will be slowed, 
 weakened, or stopped. In the last case the lever will trace an unbroken 
 straight line ; but even if the stimulation is continued the beats will 
 again begin. 
 
 8. Stimulation of the Junction of the Sinus and Auricles. — After a 
 sufficient number of the observations described in 7 have been taken 
 with varying time and strength of stimulation, lake the writing-points 
 off the drum, apply the electrodes directly to the crescent at the junc- 
 tion of the sinus venosus with the right auricle, and stimulate. The 
 heart will be affected ven,- much in the same way cis by stimulation of 
 the vagus, except that during the actual stimulation its beats may be 
 quickened and the inhibition may only begin after the electrodes have 
 been removed (Fig. 70, p. 158). 
 
PRACTICAL EXERCISES 
 
 IJfV 
 
 £AS 
 
 g. Effect of Muscarine (or Pilocarpine) and Atropine. — Paint on tlie 
 sinus venosus with a small camcl's-hair brush a very dilute solution oi 
 muscarine (or of pilocarpine). The heart will soon be seen to beat 
 more slowly, and will ultinuitdy stop in diastole. Now apply a dilute 
 solution of sulphate of atropine to the sinus. The heart will again 
 begin to beat. Stimulation of the vagus \vill now cause no inhibition 
 of the heart, because its endings have been paralyzed by atropine. 
 (Muscarine or pilocarpine has also been applied to the heart, but it 
 could be shown by a separate experiment that atropine by itself has 
 the same effect on the vagus endings — p. i6 .) 
 
 10. Stannius' Experiment. — Pith a frog. Expose the heart in the 
 way described under 2 ip. 194). Ligature the fraenum with a fine sillt 
 thread, and use the thread to manipulate the heart. With a curved 
 needle pass a moistened silk thread between the aorta and the superior 
 \ena, cava, and tie it round the 
 junction of the sinus and right 
 auricle (Fig. 86). The auricles 
 and ventricle stop beating as 
 soon as the ligature is tightened. 
 The sinus venosus goes on beat- 
 ing. Now separate the ven- 
 tricle from the rest of the heart 
 by an incision through tlie 
 auriculo-ventricular groove, or 
 tie a second ligature in the 
 groove. The ventricle begins 
 to beat again, the auricle re- 
 maining quiescent in diastole 
 (p. i6d). Occasionally both 
 auricle and ventricle, or only 
 the auricle, may begin to beat. 
 
 11. Stimulation of Cardiac 
 Sympathetic Fibres in the Frog 
 — (i) In the vagosympathetic 
 after the inhibitory fibres have 
 been cut out by atropine. — 
 Arrange ever\-tliing as in 7 
 (p. 198). Assure yourself, by 
 stimulating the vagus, that it 
 inhibits the heart, and take 
 a tracing during stimulation. 
 Then paint a dilute solution 
 of atropine on the sinus. 
 Stimulation of the vagus, which is really the vago-sxTupathetic (see 
 Fig. 92), will now cause, not inhibition, but augmentation (increase 
 in rate or force, or both), since the endings of the inhibitor^' fibres have 
 been paralyzed by atropine. The strength of the stimulating current 
 required to bring out a typical augmentor effect is greater than that 
 needed to stimulate the inhibiton,- fibres. Take a tracing to show 
 augmentation produced by stimulating the nerve. 
 
 (2) By direct stimulation of the cervical sympathetic. — Make the same 
 arrangements as in 11 (i), but, instead of isolating the vagus, dissect 
 out the s^Tnpathetic on one side in the manner described in 6 (2) (p. 197). 
 and do not apply atropine to the heart. Lay the upper (cephalic) end 
 of the sympathetic on very fine and well-insulated electrodes, and 
 stimulate (Fig. 76, p. 167). (To insulate electrodes the points may be 
 covered with melted paraffin. When the paraf&n has cooled, a narrow 
 
 Fig. 92. — Relation of the Sympathetic to 
 the Vagus in the Frog (after Gaskell). 
 Sym, sympathetic chain ; G, ganglion of 
 the vagus; VS, vago - sympathetic ; GP, 
 glosso-pharj-ngeal nerve; LAS, levator 
 anguli scapulae muscle ; SA, subclavian 
 artery; A, descending aorta; V, vertebral 
 column; OC, occipital part of skull; 1-4, 
 spinal nerves. 
 
200 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 groove, just siiffn itiit to lay l>arc tlio wires on tlic upper side, is made 
 in it, and the nerve is laid in this groove.) 
 
 Experiments 7, 11 (i) and 11 (_») will be rendered more exact by 
 connecting a second electro-magnetic signal with a Fold's commutator 
 without cross-wires (Fig. i).}), in such a way that the circuit is inter- 
 rupted at the instant when stimulation begins. 
 
 12. The Action of Inorganic Salts on Heart-Muscle. — Expose and 
 remove the heart of a tortoise or turtle (p. nj6). Cut off the apical two- 
 thirds of the ventricle by an incision parallel to the auriculo-ventricular 
 groove. By a second parallel cut remove a ring of tissue 2 or 3 milli- 
 metres wide from the upper end of this portion of the ventricle. Divide 
 the ring at opposite ends of a dianacter, so as to form two strips. Tie 
 a fine silk thread to each end of one strip. Attach one of the threads 
 to the short limb of a glass rod bent at right angles, so that it can be 
 immersed at will in a beaker. The other end of the rod is fixed in a 
 holder sliding on a stand. Attach the second thread to the short arm 
 
 Fig. js. — Arrangement of Induction Machine for Tetanus. B, battery; K, simple 
 key; P, primary coil; S. secondary coil: A, C, binding screws to be connected 
 with battery for single shocks; F. G, binding screws for tetanizing current; N, 
 Neef's hammer; D, short-circuiting key in secondary; E, electrodes. D and E 
 are drawn to a much larger scale than the rest of the figure. 
 
 of a counterpoised lever arranged to write on a slowly-moving drum. 
 If the strip is still beating, wait till the contractions have ceased ; then 
 (i) Immerse the strip in a beaker filled with 07 per cent, solution of 
 sodium chloride. After a time it begins to beat rhythmically. The 
 contractions become rapidly stronger, and then after a while diminish, 
 and gradually cease. The tone or tonus of the strip is diminished by 
 the solution. 
 
 (2) Arrange the other strip in the same way, and immerse it in a 
 solution of calcium chloride (about i per cent.) isotonic with the sodium 
 chloride solution used in (i). If the strip is contracting, the contrac- 
 tions will cease. Rhythmical contractions will not appear as in the 
 sodium cliloride solution. The tone of the strip may be increased. 
 
 (3) Remove most of the calcium chloride solution from the beaker, 
 and fill it up with 07 per cent, sodium chloride solution. The rhythmi- 
 cal contractions will appear after a longer or shorter latent period, and 
 will be stronger and last for a longer time than in the sodium chloride 
 solution alone. 
 
 (4) Immerse a fresh strip in a solution containing sodium chloride 
 
PRACTICAL F.XHRCfSES 
 
 2or 
 
 (07 por cent), calriuin i hlorido (ooiT per cent.), and potassium 
 chloride (003 per cent.) (a modified Ringer's solution). A longer 
 series of rhythmical contractions will be ol)t;uned than in either (i) 
 or (3). That this is not due to the potassium chloride acting alone 
 can be shown by immersing a strip in a solution of potassium chloride 
 (about 09 per cent.) isotonic with the sodium chloride solution used 
 in (i). No contractions will be caused. 
 
 13. The Action of the Mammalian Heart. — Inject under the skin of a 
 dog (preferably a small one) i c.c. of a 2 per cent, solution of morphine 
 hydrochlorate for e\cr\' kilo of body-weight. .\s soon as the morphine 
 has taken effect (in 15 to 30 minutes, but better after an hour), fasten 
 the animal back down on a holder (as in Fig. i35. P- 301). pushing the 
 mouth-pin behind the canine teeth and screwing the nut liome.* In 
 the meantime select a tracheal cannulaf of suitable size, and get ready 
 instruments for dissection — one or two pairs of artery-forceps, a pair 
 of artery-clamps (bulldog pattern), two or three glass cannulcc of 
 
 Pig g^_ — Arrangement for recording the Beginning and End of Stimulation. C. 
 Pohl's commutator without cross-wires; B, battery in circuit of primary coil P; 
 B', battery in circuit of electro-magnetic signal T; K, simple key in primary 
 circuit; S, secondary coil. When the bridge of the commutator is tilted into 
 the position shown in the figure, the primary circuit is closed and the circuit of 
 the signal broken. 
 
 various sizes for bloodvessels, ten strong waxed ligatures, sponges, 
 hot water, a towel or two, and a pair of bellows to be connected with 
 the tracheal cannula when the chest is opened. Arrange an induction- 
 
 * A simple but efticient and convenient holder for a dog may be easily 
 constructed as follows: Take a board of the length required (2I to 5 feet, 
 according to the size of the dog) . At one end fasten two short upright wooden 
 pins, with a clear space of 4 to 6 inches between them. These are pierced 
 from side to side with four or five holes at different heights. An iron p:a passes 
 behind the canine teeth of the animal through two corresponding holes in the 
 uprights, and the muzzle is tied over this by a cord which secures the head. 
 For a large dog an upper pair of holes is used, for a small dog a lower pair. 
 The feet are fastened by cords to saaples inserted into the sides of the board, 
 the fore-legs being drawn tailwards for all operations on the neck or head, 
 headwards for operations on the thorax. A rabbit-holder can be made in 
 exactly the same way. 
 
 t A tracheal cannula is easily made by heating a piece of glass tubing, 
 about 6 inches long, a short distance from one end, and drawing it out slightly 
 so as to form a ' neck.' The tubing is then bent about its middle to an obtuse 
 angle, and the end next the neck is ground obliquely on a stone. The diameter 
 of the cannula should be about the same as that of the trachea, into which it 
 is to be inserted by its oblique end. 
 
202 THE CIRCULATION OF THE BLOOD ASD LYMPH 
 
 coil and elcctnxlcs for a tt tanizing current (Fig. 93, p. 200). With 
 scissors curved on the flat cHj) away the hair from the front of the 
 neck. Put tlie hair carefully away, and remove all the loose hairs 
 with a wet sjKinge so that tluy may not get into the wounds. Give ether, 
 or pour into the stomach by a tube 3 c.c. of a 05 per cent, solution 
 of chloroform in 10 per cent, alcohol per kilo of body-weight, diluted 
 before administration with 3 or 4 volumes of water (Grehant's method). 
 To put a Cannula in the Trachea. — The hair having been clipped in 
 the middle line of the neck and the skin shaved, a mesial incision is 
 to be made, beginning a little below the cricoid cartilage, which can 
 be felt with the finger. The trachea is then cleared from its attach- 
 ments by forceps or a blunt needle, and two strong ligatures are passed 
 beneath it. A single loop is placed on each of these, but is not drawn 
 tight. Raiding the trachea by means of the upper ligature, the student 
 makes a longitudinal incision through two or three of llie cartilaginous 
 rings, inserts the cannula, and ties the lower ligature firmly around its 
 neck. The upper ligature can now be withdrawn. 
 
 Clip off the hair on each side of the sternum. Make an incision on 
 each side through the skin and down to the co.stal cartilages about 
 2 inches from the edge of the breast-bone, and long enough to expose 
 about four costal cartilages (say, 3rd to 6th). With a curved needle 
 pass waxed ligatures round the cartilages, and tie firmly to compress 
 the intercostal vessels. The bellows should now, or earlier if any 
 symptoms of impeded respiration have appeared, be connected with 
 one end of the horizontal limb of a glass T-piece, the other end of 
 which is similarly connected with the tracheal cannula. The stem of 
 the T-piece is provided with a short piece of rubber tubing, which, 
 when artificial respiration is being carried on, is to be alternately closed 
 and opened — closed during inflation of the lungs, and opened when 
 the air is to be allowed to escape from them. Or a screw-clamp may 
 be adjusted on the piece of tubing so that the opening is sufficiently 
 narrow to permit the lungs to be properly inflated when the bellows 
 are compressed, and yet sufficiently wide to permit easy escape of the 
 air and collapse of the lungs at the end of each inflation. Etner may, 
 when necessary, be administered, by inserting between the T-piece and 
 the tube from the bellows an ether bottle \\ ith two tubes passing through 
 the cork to within an inch or two of the ether. If the cannula has a 
 side-opening, as is usually the case v/ith metal cannulae, the T-piece 
 may be dispensed with. One student should take sole charge of the 
 artificial respiration, v.hich ought to be begun as soon as the chest has 
 been opened, and continued at the rate of about twenty inflations 
 per minute. The costal cartilages are rapidly cut through with strong 
 scissors just on the sternal side of the ligatures, the artificial respira- 
 tion being suspended for an instant, as each cut is made, to avoid 
 wounding the lungs. The sternum is divided at its lower end and 
 turned up. If there is much bleeding a ligature should be tied round 
 its upper end. With a curved needle a ligature is passed below the 
 internal mammarj' arteries as they approach the sternum. That bone 
 may now be removed, and the heart, enclosed in the pericardium, come? 
 into view. A thread is passed with a suture-needle through each side ol 
 tlie pericardium, which is then stitched to the chest-wall and opened. 
 
 {a) Note the various portions of the heart, right and left ventricles, 
 right and left auricles, with the auricular app.ndices. Feel the heait 
 with the hand, and observe that the right ventricle is softer and has 
 thinner walls than the left, and that the auricles are softer than the 
 ventricles. Note how all the parts of the heart harden in the hand 
 during systole and soften during diastole (pp. 86, 90). 
 
PRACTICAL EXERCISrS 
 
 203 
 
 (b) Dissect out the vago-sympathetic on one side in the neck of the 
 <log. The guide to the nerve is the carotid artery. These two struc- 
 tures and the internal jugu- 
 lar vein lie side by side in 
 a common sheath. Feel 
 for the artery a little ex- 
 ternal to the trachea, ci.t 
 down on it, open the sheath , 
 isolate the vago-sympa- 
 thetic for about an inch, 
 pass two ligatures under it, 
 tie them, and divide be- 
 tween the ligatures. The 
 peripheral and central ends 
 of the nerve may now 
 be successively stimulated. 
 Stimulation of the peri- 
 pheral end causes slowing 
 of the heart, or stoppage 
 in diastole. Feel that it 
 softens when it stops. It 
 soon begins to beat again. 
 Stimulation of the central 
 end of the vago-sympa- 
 thetic may or may not 
 cause inhibition . If it does, 
 expose the other vago- 
 sjTnpathetic . divide it, and 
 repeat the stimulation of 
 the central end . There will 
 now be no inhibition of the 
 heart. Incidentally it may 
 be seen that stimulation 
 of the central end of the 
 vago - sjTnpathetic causes 
 strong, though, of course, 
 withopened chest, abortive, 
 respiratory movements. 
 
 {c) Pith a frog (brain 
 and cord), dissect out the 
 sciatic nerve on one side up 
 to the sacral plexus. Cut 
 off the whole leg. Drop the 
 cut end of the nerve on the 
 heart, and hold the prep- 
 aration so that the nerve 
 touches the heart also by 
 its longitudinal surface. At 
 each cardiac beat the nerve 
 is stimulated by the action 
 current (p. 833), and the 
 muscles of the leg contract. 
 
 [d) Raise the board so 
 that the head of the animal 
 is down and the hind-feet 
 up, and note whether there 
 is any effect on the action 
 
 Fig. 95- — Myocardiograph of Adami and Roy 
 (modified by Cushny and Matthews). AB, a 
 perpendicular rod descending from a universal 
 joint, which is not shown in the figure; CD, a 
 brass sheath, moving easily on the rod, and 
 bearing on its upper end an ivory pulley, and at 
 its lower end a horizontal bar, which is inter- 
 rupted by a plate of hard rubber, I. The per 
 pendicular rod EF moves on the horizontal bai 
 by the hinge-joint, J. EF is hooked at one end 
 for attachment to the heart, and bored at the 
 other for a thread which, passing over the pulley 
 at C, passes through the universal joint and 
 moves a writing lever not shown in the figure. 
 CD is prevented from moving up AB by a ring of 
 brass, G, which is screwed to AB, but is not 
 attached to CD ; the hook F can therefore move 
 to and from AB, and can rotate round it, while 
 it cannot move up or down. The hooks F and B 
 are insulated from each other by the hard rubber. 
 I. H is a binding post through which, and 
 through another connected with A, induction 
 shocks may be sent at will into the portion 
 of the heart lying between the hooks. 
 
204 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 and filling of the lirart. Hrprat the observation witli iu-ad up and 
 
 feet clown. 
 
 {e) C(jniprcss the aoiia with the fnigcrs, and observe the effect on 
 
 tlie degiee of dilatation of the various cavities of the heart. Repeat 
 
 the experiment with the inferior vena cava, and compare the results. 
 
 ~ if) Smoke a drum. Insert the 
 
 hooks of the myocardiograph (Fig. 95) 
 into the ventricle, taking care not 
 to penetrate deeply into the wall. 
 Arrange the lever to write on the 
 drum. While a tracing is being 
 taken stimulate the peripheral end of 
 the vagus. Unhook the cardiograph. 
 {g) Stop the artificial respiration, 
 and observe the changes which take 
 place in the auricles and ventricles, 
 comparing particularly the right side 
 of the heart with the left. Before 
 the heart has stopped beating, re- 
 commence the artificial respiration. 
 
 (A) Connect a cylinder of oxygen 
 with a good-sized rubber catheter. 
 
 D .'C 
 
 Fig. 96.— Arrangement to illustrate Action of Cardiac Valves in the Heart o£ an 0\ 
 (Gad). C, glass window in left auricle; D, window in aorta; E. tube inserted 
 through apex of heart into left ventricle and connected with pump P; A. side 
 tube on E, through which wires are connected with a tiny incandescent lamp in 
 the ventricle ; W. water in bottle B ; T. T', tubes. 
 
 and pass the catheter down the tracheal cannula or through a separate 
 opening in the trachea. Allow a small stream of oxygen to flow into 
 the lungs. Artificial respiration is now unnecessary. The lungs 
 remain at rest, yet the blood is sufficiently oxygenated, and the heart 
 goes on beating. The myocardiographic tracing thus goes on undis- 
 turbed by respiratory movements. 
 
 (»■) Stop the oxygen, and resume the artificial respiration. Make a 
 
PRACTICAL EXERCISES 
 
 205 
 
 Small penetrating wound with a scalpel in the left ventricle. Observe 
 the course of the lucinorrhagc, and note especially the difference in 
 systole and diastole. 
 
 (/) Lay the electrodes on the heart, and stimulate it with a strong 
 interrupted current. The character of the contraction soon becomes 
 profoundly altered. Shallow, irregular 
 contractions flicker over the surface, with 
 a kind of simmering movement sugges- 
 tive of a boiling pot (delirium cordis, 
 fibrillar contraction). Now kill the ani- 
 mal by stopping the artificial respiration. 
 Observe how long the heart continues to 
 beat, and which of its divisions stops 
 last. 
 
 {k) Make a dissection of the cervical 
 sympathetic up to the superior cervical 
 ganglion, and (hnvn through the inferior 
 cervical ganglion to the stellate or hrst 
 thoracic ganglion. Make out the annuhis 
 of Vieusscns and the cardiac sympa- 
 thetic (accelerator) branches going off 
 from the annulus or the inferior cei'vical 
 ganglion to the cardiac plexus. 
 
 14. Perfusion of the Isolated Mam- 
 malian Heart, — -The heart of a dog em- 
 ployed for some other experiment may 
 be used. Or a rabbit may be killed by 
 a blow on the back of the head, and 
 the heart at once removed. The aorta 
 should not be cut off too short. Tie a 
 cannula into the aorta and attach it to 
 a T-picce connected by rubber tubes, 
 which must be perfectly clean, with two 
 bottles, one containing Ringer's solution 
 (pp. 66, 201), preferably that made with 
 dextrose, the other containing defibrin- 
 ated blood diluted with Ringer's solu- 
 tion. The dcfibrinated blood should be 
 strained so as to remove any small pieces 
 of fibrin. The bottles are supported on a 
 high stand, so that the level of the bottles 
 above the heart can be altered, and the 
 pressure of the perfusion liquid thus 
 varied. Perfusion may be begun with 
 Ringer, to wash out any remaining blood 
 and obviate the possible formation of 
 clots in tlie small vessels. Oxygen is 
 allowed to bubble through the Ringer's 
 solution, but this is not necessarj^ for the 
 blood, since, if shaken up, it will retain 
 far more oxygen than the Ringer's solu- 
 tion. The temperature of the liquids 
 should be at about 40° C. when nearing the heart 
 easily insured by interposing a worm immersed m a heated bath or 
 other heating arrangement between the cannula and the T-tube. and tor 
 the studv of its movements by inspection the heart itself can be placed 
 m a glass" vessel immersed in the bath. When records of the contractions 
 
 Fig. 97. — Mammalian Heart Per- 
 fusion Apparatus (Gunn). a, 
 Liebig condenser, cut off as 
 shown ; b, inlet for the warm 
 water ; d, thermometer ahnost 
 filling up the lumen of the thin 
 glass tube c ; e, cork ; /. cannula 
 for aorta fitted with a collar of 
 rubber tubing, g, in the end of 
 the tube c ; h, Y-tube connected 
 with two reservoirs, one contain- 
 ing Ringer's solution, the other 
 any other liquid which is to be 
 perfused. 
 
 This can be most 
 
THE CIRCULA'JtO^ OF THE JSLOOt) A XI) LYMPH 
 
 arc to be obtained, threads are attaclud to the auricle and to the apex 
 of the ventricl ■. The heart is suspended by fastening the cannula in a 
 holder on a stand, and the threads, after passing over pulleys to give 
 them a convenient direction, are attached to writing-levers. 
 
 As the heart cannot now be easily kept immersed in the bath, it is 
 suspended in the air, and can be kept warm by the following simple 
 arrangement: A copper pipe about 4 inches long is slit on one side, and 
 on the opposite side is screwed or riveted to a copper rod, under wliicli 
 is hung a spirit-lamp. The lamp is adjuslcd at such a point on the rod 
 that when the copper tube is placed around the heart the heat conducted 
 along the rod keeps the air around the heart at about body-temperature. 
 The perfusion liquid before it enters the heart may be heated thus: 
 A Liebig's condenser is cut through the middle, and the large end 
 closed by a paraffined cork. A glass tube is run down from the toj) 
 through this cork, and the aorta is attached directly to this, so that 
 the heart is very near the condenser. This tube is mostly filled up by 
 a thermometer, so that the perfusion liquid passes through it in a thin 
 stream which is easily heated by the water in the condenser, which 
 
 contains a second ther- 
 mometer. This water is 
 kept constantly flowing 
 through the condenser 
 from a heated bath. The 
 T-piece connecting with 
 the perfusion bottles is 
 attached to the upper 
 end of the glass tube 
 to which the heart is 
 attached (Gunn and 
 Cushnv). 
 
 15. Action of the 
 Valves of the Heart.— ^ 
 (i) Study the action ul 
 the Aalves of the o.x- 
 licart, connected with 
 the pump P and bottle B 
 in the artificial scheme, 
 as shown in Fig. 96. The 
 cavity of the heart is 
 illuminated by means of 
 a small electric lamp, the 
 wires of which pass in at 
 A. When the j)iston of the pump is })ushed down, water is forced 
 through the aorta D along the tulie 1' into the bottle, and flows back 
 again into the left auricle by tho tube T'. During each stroke of the 
 pump the auriculo-ventricular valve is seen through the glass disc 
 mserted into C" to close, and the semilunar v;ilve is seen through the 
 glass in D to open. When the piston is raised, the semilunar valve is 
 seen to be closed and the auriculo-ventricular \ai\e to be opened. 
 For comparison, a human heart with a valvular lesion might be u.sed. 
 
 {2) With the sheep's or dog's heart i)rovided, pci-form the follow^ing 
 experiments : 
 
 (a) Open the peric;udium and notice how it is reflected around the 
 great vessels at the base of the heart. Distinguish the pulmonary 
 arterj-, the aorta, the superior and inferior vena- cav.e. and the pul- 
 monar\- veins. The trachea and portions of the lungs mav also be 
 attached. If so, remove them carefully without injuring the heart. 
 
 o 
 F"ig. 98. — Diagram of Valves of the Heart. Tlie 
 valves are supposed to be viewed from above, the 
 auricles having been partially removed. A, a'»rta 
 with semilunar valve; B, pulmonary artery and 
 valve; C, tricuspid, and D, mitral valve; E, right, 
 andF, left coronary artery; (1, wall of right, and H, 
 of left auricle. I, wall')f right, andj, of 1 -ft ventricle. 
 
PRACTICAL LXLliCISES 207 
 
 {b) Take two wide glass tubes, drawn slightly into a nork at one end. 
 One of the tubes slioukl be about 10 cm. long, and tlv: other about 
 50 cni. Tic the short tube A firmly by its neck into liie superior \'ena 
 cava, the long tube B into the pulmonaiy arterJ^ Ligature the inferior 
 vena cava. Connect .A by a small piece of rubber tubing with a funnel 
 supported in a ring on a stand. Pour water into the funnel till the 
 riglit side of the heart is full. It will escape from the left azygos vein, 
 which must be tied. Put on any additional ligatures that may be 
 needed to render the heart water-tight. Support B in the vertical 
 position by a clamp. Fill the- funnel with water, and it will rise in B 
 to the same le\'cl as in the funnel. Now compress the right ventricle 
 with the hand, and the water will rise higher in B. Relax the pressure 
 and notice that the water remains at the higher level in B, being pre- 
 vented by the semilunar valves from flowing back into the ventricle. 
 By alternately compressing the ventricle and allowing it to relax, water 
 can be pumped into B till it escapes from its upper end, and if this is 
 so curved that the water falls into the funnel, a ' circukition ' which 
 imitates that of the blood tan be established. Note that during the 
 pumping the sinuses of Valsalva, behind the semilunar valves at the 
 origin of the pulmonary artery, become prominent. 
 
 (c) Take out B and tear out one of the segments of the semilunar 
 valve. Replace B, and notice that, while compression of the ventricle 
 has the same effect as before, the water no longer keeps its level on 
 relaxation, but regurgitates into tlic ventricle. This illustrates the 
 condition kno\vn as insufficiency or incompetence of the valves. But 
 if the injury is not too extensive, it is still possible, by more vigorously 
 and more rapidly compressing the heart, to pump water into the fumiel. 
 This illustrates the establishment of compensation in cases of valvular 
 lesion. 
 
 (d) Now remove both tubes. Tic the pulmonary artery. Cut away 
 the greater part of the right auricle. Pour water into the auriculo- 
 ventricular orifice, and notice that the segments of the tricuspid valve 
 are floated up so as to close the orifice. Invert the heart, and the 
 ventricle will remain full of water. Open the right ventricle carefully, 
 and study the papillary muscles and the chordae tendineie, noting that 
 the latter are inserted into the lower surface of the ■segments of the 
 tricuspid valve, as well as into their free edges. 
 
 (e) Repeat {b), [c), and {d) on the left side of the heart, tying tube B 
 into the aorta as far from th? heart as possible, and A into the left auricle. 
 
 (/) Separate the aorta from the left ventricle, cutting wide of its 
 origin so as not to injure the semilunar valves, and tie a short wide 
 tube into its distal end. Pill the tube with water, and notice that the 
 vahes support it. Cut open the aorta just between two adjacent segments 
 of the valve, and notice the pockets behind the segments, and how they 
 are related to each other, and connected to the wall of the vessel. 
 
 16. Sounds of the Heart. — (a) In a fellow-student notice the position 
 of the cardiac impulse, the chest being well exposed. Use both a 
 l:)inaural and a single-tube stethoscope. Place the chest-piece of the 
 stethoscope over the impulse, and make out the two sounds and the 
 pause, {b) With the hand over the radial or brachial artery, try to 
 determine whether the beat of the pulse is felt in the period of the 
 sounds or of the pause, (c) Listen with the stethoscope over the 
 junction of the second right costal cartilage with the sternum, and 
 compare the relative intensity of the two sounds as heard here with 
 their ;elative intensity as heard over the cardiac impulse. 
 
 17. Cardiogram. — Smoke a drum, and arrange a recording tambour 
 and a time-marker beating half or quarter seconds to write on it (Fig. 88, 
 
2oS THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 p. 195). Apply the button of a cardiograph (Fig. -'7. p. 90) over your 
 own cardiac inipuls'\ and fasten it round the body by the bands attached 
 to the instrument. Connect the cardiograph by an indiarubber tube 
 with a recording tainlx)ur (Fig. 99). Set the drum off at a fast speed, 
 take a tracing, and vaniish it. Compare with Fig. 28 (p. 91), and if 
 the tracing is sufficiently typical, as is often not the case with human 
 cardiograms, measure oiit the time-value of the various events in the 
 cardiac revolution. 
 
 ^ ■ *&- - ■'■ "■■ ■■' 
 
 Fig. 99. — Marey's Tambour. 
 
 For the cardiograph, a small glass funnel, or thistle-tube, the stem 
 of which is connected with the recording tambour, may be substituted, 
 the broad end of the funnel being pressed over the apex-beat. 
 
 18. Sphygmographic Tracings.— Attach a Marey's sphygmograph 
 (Fig. 37, p. 103) to the arm. Fasten a smoked paper on the plate D. 
 Apply the pad C of the sphygmograph to the wrist over the point 
 
 where the pulse of the radial 
 artcn,- can be most distinctly 
 felt. Adjust the pressure by 
 moving the screw G. The 
 writing-point of the lever E 
 will rise and fall with ever\- 
 pulsc-bcat. When cverjiihing 
 is sat ibfactorily arranged, set 
 off the clockwork which 
 
 Dudgeon's Sphygmograph. 
 
 moves the plate D. and a pulse tracing will be obtained. Study the 
 changes which can be produced in the pulse curve — \a) by altering the 
 position of the bodv (sitting standing, and lying down) ; (6) by exercise 
 (Fig. 101); (c) by inhalation of 1 drops of amyl nitrite poured on a hand- 
 kerchief by the demonstrator (Fig. 102); {d) by raising the arm above 
 the head and letting it hang at the side ; [e] by compression of the brachial 
 artery at the bend of the elbow; (/) by altering the pressure of the pad 
 \'amish the tracings after marking on'them the conditions under which 
 they were obtained. 
 
 A Dudgeon's sphygmograph (Fig. 100) may also be employed. In 
 this the clockwork carries the strip of blackened paper along beneath 
 
PJiA C TI CA L EXERCISES 
 
 200 
 
 /X.fV.'^^.l 
 
 'U\JiJV.!UUUUUUV 
 
 Fig. loi. — Effect of Exercise oa the 
 Pulse (Marey). Upper tracing, 
 normal; lower, cifter running. 
 
 the needle which records the movements of the artery. Or a small 
 glass funnel or thistlc-tubc connected with a recording tambour may 
 be pressed over the carotid artcr\-. The lever of the tambour writes 
 on a drum, on which at the same time lialf or quarter seconds arc 
 marked by an ele* tro-niagnctic signal. 
 i<). Venous Pulse Tracing from the 
 Jugular Vein. — Arrange a rcconlir.g 
 tambour to write on a drum. Con- 
 nect the tambour with the stem of a 
 small glass thistle-tube or funnel tor 
 with a small metal cup) by a piece of 
 narrow rubber tubing, and apply the 
 cup-shaped end of the thistlo-tubc 
 over the right jugular bulb of a 
 fellow-student. This liesabout i inch 
 external to the right stemo-clavicular 
 articulation, and a little above it. The 
 receiver may have to be moved about 
 a little until the best pulsation is 
 obtained. The ' patient ' should be 
 
 lying down, the shoulders slightly raised, the head on a pillow and turned 
 slightly to the right, in order to relax the right stemo-mastoid muscle 
 (Mackenzie). 
 
 20. Polygraph Tracings.— Arrang; the polygraph over the radial 
 artery, as with an ordinary- sphvg nograph. so that the lever will record 
 the radial pulse when the strip' of paper is set moving. If the mstru- 
 
 ment has only one tambour, con- 
 nect the tambour to a receiver 
 or thistle-tube o\-er the jugular 
 bulb. The writing-point of the 
 tambour is arranged so as to be 
 immediately below the writing- 
 point connected with the radial. 
 If the polygraph is pro\'ided 
 with clockwork to record time, 
 set oft the time-marker writing 
 fifths of a second. When it is 
 seen that the writing-points are 
 marking properly, start the 
 clockwork which moves the 
 strip of smoked paper. Repeat 
 the observation with the tam- 
 bour connected with the apex- 
 beat. Letter the cur\-es as far 
 as possible as in Figs. 65 and 
 66 (p. 149) without at present 
 attempting their exact analysis. 
 If the polygraph has two tam- 
 bours, simultaneous tracing of the radial pulse, the jugular pulse, and the 
 cardiac impulse, or of the carotid pulse, the jugular pulse, and the apex- 
 beat, may be taken, and other combinations as well. If no polygraph 
 is available, a drum may be employed, the tracings being all taken with 
 thistle-tubes connected With recording tambours. The levers of the 
 tambours must be arranged to write on the drum in the same vertical 
 straight line, or, without making the adjustment quite exact, vertical lines 
 of reference may be drawn through, each curve, with the drum at rest, 
 indicating the relative positions of the writing-points. 
 
 Fig. 102. — Effect of .\rnyl Nitrite on the 
 Pulse (Marey). Upper tracing, normal; 
 lower, after inhalation of amyl nitrite. 
 
210 TJJI-: CJRCLJ.AIIO.S Ut lllh liJ.OOD ASD J.VMPH 
 
 21. Plethysmographic Tracings.— Connect the vessel D (Fig. 36. 
 p. 128), uiiiciiy Willi ;i recording lamb(,ur by tlie lube F, omitting for 
 simp'.icily the" recording arrangimcnt in the figure. Place the arm 
 in the plcthysmogn'ph, and adjust the indiarubbcr band to make 
 a watertight connection. Support D so that the arm rests easily 
 within it. and fill it with water at body temperature. No water must get 
 into the tambour, and it is well to insert a piece of glass tubing in the 
 connection between it and the plctliysmograph. so that it may be seen 
 when the water is rising too high. A T-piece with a short piece of 
 rubber tubing on the stem should be inserted in the course of the tube 
 leading to the tambour. All adjustments are made with the T-picce 
 open, and when a tracing is to be taken the short rubber tube is closed 
 by a clip. Arrange a time-marker to wTite half or quarter seconds 
 (Fig. 88, p. n»5). Adjust the writing-point to write on a druni, and 
 close the upper tubulurc C with a cork. The quantity of blood in the 
 arm is increased with cver>' sy.stole of the left ventricle, diminished in 
 diahtole. The lever will therefore rise when the ventricle contracts, 
 and sink when it relaxes. 
 
 (i) Take tracings with the arm (a) horizontal, [b) hanging down. 
 
 (2) With the arm horizontal, take tracings to show the effect {a) of 
 closing and opening the fist inside the plethysmograph;* (fc) of apply- 
 ing a light bandago round the arm a little way above the indiarubber 
 band; (c) of inhaling 2 drops of amyl nitrite. 
 
 Instead of the arm plethysmograph, a small plethysmograph to hold 
 a finger may be employed. It consists of a glass tube drawn out at 
 one end. The wide end is provided with a rubber collar. The narrow 
 end is connected by a small rubber tube with a ver\- small and sensitive 
 recording tambour, a T-picce being inserted on the connection as b< fore. 
 With the T-piece closed fill the tuoe with water. Then, holding up the 
 wide end of the tube, the tip of the finger is put in so as just to close 
 the tube. The T-piece is then raised and opened, and the finger pushed 
 in as far as it will go. The collar must fit the finger so as to form a 
 watertight joint. Now get the proper pressure in the tambour by 
 blowing into the T-piece, and close the clamp. A time-tracing can l>e 
 taken as before. 
 
 22. Pulse-Rate. — (i) Count the radial pulse for a minute in the 
 sitting, supine, and standing positions. Use a stop-watch, setting it 
 off on a pulse-beat and counting the next beat as one. Make three 
 observations in each position. 
 
 (2) Count the pulse in a person sitting at rest, and then again in the 
 sitting position immediately after active muscular exertion. Note how 
 long it takes before the pulse-rate comes back to normal. 
 
 (3) Count the pulse in a person sitting at rest. Repeat the observa- 
 tion while water is being slowly sipped, and note any change. 
 
 (4) With one hand over the thorax of a rabbit, count its pulse. Then 
 notice the effect (a) of suddenly closing its nostrils, [b) of bringing a 
 small piece of cotton-wool sprinkled with ammonia or chloroform in 
 front of the no.se {reflex inhibition of the heart). 
 
 23. Blood-Pressure Tracing. — (a) Put a dog under morphine (p. 63). 
 Sot up an induction machine arranged for an interrupted current 
 (Fig. 93, p. 200). Fill the U-shaped manometer tube lif this has 
 not already been done) with clean mercury- to the height of 10 to 
 12 cm. in each limb. If the float tends to stick, half an inch of oil 
 may be put above the mercury- in the distal (straight) limb before 
 putting in the float. But where the mercury is clean and dr^-, and the 
 
 • Closing the fist causes a tall in the curve — i.e.. a diminution in the volume 
 ot the arm. On opening the hand, the curve regains its level. 
 
PRACTICAL EXERCISES 2ii 
 
 size of tliL' tloat proix^rly adjusted to that of the tube, this is no! neces- 
 sary, and is to L>e avoided. Then, tilting the tube < arefully, hll the 
 proximal limb (i.e., the limb which is to be connected with the blood- 
 vessel) with a saturated solution of sodium carbonate or a half-saturated 
 solution of magnesium sulphate, or, what is better for most purposes, 
 a z per cent, solution of sodium citrate. This is easily done by means 
 of a pipette furnished with a long point. Now attach a .strong rubber 
 tube to the proximal end of the manometer, and fill it also with the 
 solution. All air must be got out of the manometer and its connecting- 
 tube. Raise the end of the rubber tube and blow into it, so as to cause 
 a difference of about lo cm. in the height of the mercury in the two 
 limbs of the manometer, and, without releasing the pressure, clamp the 
 tube with a pinchcock or screw clamp (Fig. 4 , p. 1 10). 
 
 Now smoke a druni, and arrange the writing-point of the manometer- 
 float so that it will write on it. Suspend a small weight by a piece of 
 silk thread from a support attached to the stand of the drum, so that 
 it hangs down outside of the writing-po-nt of the manometer-float and 
 always keeps it in contact with the smoked surface without undue 
 friction. Or a piece of glass rod drawn out to a fine thread in the 
 blowpipe flame answers ver^' well. Below the writing-point of the 
 float, and in the same vertical line with it, adjust the writing-point 
 of a time-marker beating seconds (Fig. 88, p. 193). 
 
 Next fasten the animal on a holder, back down. Give ether and 
 insert a tracheal cannula (p. 202). (The tracheal cannula is not abso- 
 lutely required for the experiment, but it is convenient, as the animal 
 is more under control, and artificial respiration can be begun at any 
 moment, should this be necessary-.) Insert a glass cannula, armed 
 with a short piece of rubber tubing, into the central (cardiac) end of 
 the carotid artery (p. 63). Leaving the bulldog forceps on the arterv', 
 fill the cannula and tube with the sodium citrate or one of the other 
 solutions. Slip the rubber tube over a short glass connecting-tube. Fill 
 this also with the solution, and connect it with the manometer-tube, 
 seeing that both are quite full of liquid, so that no air may be enclosed. 
 
 Where a permanent working place is provided for blood-pressure 
 experiments it is convenient to connect the cannula and manometer 
 with a pressure-bottle containing the sodium citrate solution, and to 
 use a three-way cannula for the bloodvessels (Fig. 103). The cannula 
 has a bulbous enlargement, which hinders clotting. The end of the 
 cannula is connected with the tube from the pressure-bottle, which is 
 closed by a clip, and the side-tube is connected with one limb, E, of 
 the manometer showm in Fig. 104. E is itself provided with a side- 
 tube, F, armed with a short piece of rubber tubing. The cannula does 
 not require to be fiJled with liquid before being inserted into the aiter^-. 
 By opening F and releasing the clip on the tube from the pressure- 
 bottle the cannula and the tube connecting it with the manometer can 
 be filled, and any blood-clots can be easily washed out in the course of 
 an experiment. Before the bulldog forceps is taken off the artery to 
 obtain a blood-pressure tracing, F must be closed, and the clip on" the 
 tube from the pressure-bottle opened. The bottle is attached to a 
 strong cord passing over a pulley, by which it is raised to a height 
 sufficient to balance approximately the pressure in the artery. The 
 tube to the pressure-bottle is then clipped. If no manometer with 
 side-tube is available, a T-piece can be inserted in the connection 
 between the cannula and the manometer, and the cannula can be 
 washed out through this. 
 
 Now take the bulldog forceps oft the artery-, and allow the drum to 
 revolve at slow speed. The writing-point of the manometer-float will 
 
THE CIRCULATION Oh THE BLOOD ASI> LYMPH 
 
 trace a ( uvvc showing an ckvalion for ta-.h heart-beat, and 
 waves due to the movements of respiration. 
 
 (6) lst)late the vago-synipathetic nerve D 
 in the neck. Lig.iture doubly, and cut 
 between the ligatures. Stimulate the peri- 
 pheral (lower) end ; the heart will be slowed 
 or stopped, and the blood-pressure will fall. 
 Stimulate the central (upper) end; there 
 may bo inhibition of the heart or accelera- 
 tion, and the pressure may fall or ri.se 
 (p. 170). 
 
 (c) Expose and di\ide the other vago- 
 sympathetic while a tracing is being taken. 
 
 \gain stimulate the central end of the 
 nerve and observe whether there is any 
 effect. 
 
 (d) Expose the sciatic nerve in one leg, 
 as follows : The leg having been loosened 
 from the holder, the foot is seized by one 
 hand and lifted straight up, so as to put 
 
 longci 
 
 Thrce-wav Cannula. 
 
 the skin of the thigh on the stretch. An 
 incision is now made in the middle line on 
 the posterior aspect of the thigh, through 
 the skin and subcutaneous tissue. The 
 muscles are separated in the line of the 
 incision with the fingers, and the sciatic 
 nerve comes into \iew lying deeply be- 
 tween them. Place a double ligature on it, 
 and divide between the hgatures. Stimu- 
 late the upper (central end); the blood- 
 pressure proljably rises, and the heart may 
 be accelerated. Stimulate the peripheral 
 end of the nerve ; there is little change in 
 the blood-pressure and none in the rate of 
 the heart. 
 
 {e) Note, incidentally, that stimulation 
 of the central end of the sciatic or the upper 
 
 I'JK- i"J4- — Manometer with 
 Side-tube (Guthrie). A, float; 
 B, collar through which the 
 wire C of the float moves; D, 
 vertical wire fixed to mano- 
 meter-holder, which keeps the 
 writing-point on the drum; 
 E, limb of manometer con- 
 nected with cannula, with its 
 side-piece, F. 
 
 icephaUc) end of the vago-sympathctic 
 
 mav cause increase in the rate and depth of the respiratory movements^ 
 
 Dilatation of the pupil is also caused by stimulation of the upper end ol 
 
PRACTICAL EXERCISES 
 
 axj 
 
 the vago-sym pathetic through the sympathetic (pupillo-dilator) fibres 
 that supply the iris. 
 
 (/) Again stimulate the peripheral end of one vagus, or of both at 
 the same time, wliile a tracing is being taken, and see how long it is 
 possible to keep the heart from beating. Sometimes, but rarely in the 
 dog. inhibition can be kept up so long that the animal dies. 
 
 [g) Close the tracheal cannula so that air can no longer enter the 
 lungs. In a very short time the blood-pressure curve begins to rise 
 (rise of asphyxia). After some minutes the pressure falls, and finally, 
 when the circulation has stopped completely and the pressure has 
 become equalized throughout the whole vascular system, a residual 
 pressure of only a few mm. (usually about lo mm. Hg) is indicated. 
 In order to-'get the true zero pressure, disconnect the arterial cannula 
 
 oti-m'-ilbiion- of ' 
 
 c ent ral. end stopped 
 
 Peripheral er>ci yrf' 
 
 -,v/^^ 
 
 e. ■n_ol 
 .SiMTnu.lcited 
 
 Fig. 105. — Blood- Pi essuxe Tracing from a Dog: Stimulation ot Central and Peripheral 
 Ends of Vagus. The other vagus was intact. Stimulation of the peripheral end 
 caused stoppage of the heart and a marked fall of pressure. Stimulation of the 
 central end produced a great rise of pressure, with, perhaps, a slight acceleration 
 of the heart. 
 
 from the manometer, and allow the writing-point to trace a horizontal 
 straight line (line of zero pressure) on the drum (Figs. 84 and 85). 
 
 24. Estimation of the Arterial Blood-Pressure in Man. — Use the Riva- 
 Rocci apparatus, as described on p. 113. Beghi with the subject in the 
 sitting position. The observer's left hand maj- be used for palpating 
 the pulse, and the right for working the bulb. Employ the ausculta- 
 tory method as well as palpation, and determine the systohc and dias- 
 tolic pressures. Repeat the observations with the person standing up 
 and lying down. Investigate the effect of muscular exercise on the 
 blood-pressure. 
 
 25. The Influence of the Position of the Body on the Blood-Pressure. 
 — Inject into the rectum of a dog 3 to 4 grm. of chloral hydrate dis- 
 solved in a little water. See chat it does not run out again immediately 
 
214 THn CIRCULATION OF THE BLOOD AND LYMTII 
 
 after injection. In ten minutes anicbthclizc the animal fully with a 
 mixture of equal parts of alcohol, chloroform, and ether (one of the 
 so-called A.C.1£. mixtures), or with chloroform, and tic it very securely, 
 back downward, on a board, which can be rotated around a liorizontal 
 axis, corresponding in position to the point at which the cannula is to 
 be inserted.* Set up a drum and manometer as in 23 (p. 2 10), but with 
 a rubber connecting-tube of such length as will allow free rotation of 
 the board. Put a cannula in the trachea. Insert a cannula into the 
 central end of the carotid artery at a point immediately above the axis 
 of rotation of the board, and connect it with the manometer. 
 
 (a) Take a blood-pressure tracing with the board horizontal. 
 
 (b) Whilst the tracing is being taken, rotate the board so that the 
 position of the animal becomes vertical, with the feet down. Mark 
 on the tracing the moment when the change of position takes place. 
 The pressure falls. Replace the dog in the horizontal position. The 
 manometer regains its former level. Now rotate the board, till the 
 animal is again vertical, but with feet up and head down, and observe 
 tlie effect on the blood-pressure. The respiratory variations in the 
 prer^sure are usually greater with feet down than with head down. 
 Notice in both cases whether there is any change in the rate of the heart. 
 
 (c) Take the board off the stands, lay it on a table, expose the femoral 
 artery, and insert a cannula into it. Shift the axis so that it now lies 
 below this cannula. Replace the board on the stands, and repeat (a) 
 and (6). The fall of pressure will now take place in the head-down 
 position.! In the feet-down position (with the cannula in the femoral 
 artery) a rise of pressure in general takes place. But sometimes this 
 is very small, and lasts only a few seconds, being succeeded by a fall, 
 during which the heart-beats on the tracing are much weaker than 
 before, since enough blood is not reaching the heart to enable it to 
 maintain the pressure. In the feet-down position see whether the 
 corneal reflex can be got. If not, as is likely, turn the animal into the 
 head-down position. The reflex may now soon be obtained, and it 
 may again disappear on putting the animal in the feet-down position. 
 If the chloroform anaesthesia is light the reflex may not be abolished 
 in the feet-down position, although .strong respiratory movements may 
 occur, owing to an;cniia of tlie medulla oblongata. 
 
 26. Effects of Haemorrhage and Transfusion on the Blood-Pressure. 
 — Anaesthetize a dog with morphine and ether, and insert a cannula 
 into the trachea. Put a cannula into the central end of the carotid 
 artery and another into the central end of the femoral artery. Then 
 insert a cannula, which should have a piece of indiarubber tubing 2 to 
 3 inches in length on its w-ide end, into the central end of the femoral 
 vein on the opposite side. In doing this more care is necessary than 
 
 * A simple arrangement for this purpose is a board with a number of staples 
 fastened in pairs into its lower surface, so that an iron rod can be pushed 
 through any pair, and form a horizontal axis at right angles to the length of 
 the board. The dog having been tied down, the rod is pushed iluough the 
 pair of staples corresponding to the position of the cannula in the artery that 
 is to be connected with the manometer. The projecting ends of the rod rest 
 in two ordinary clamp-holders, fastened at a convenient height on two strong 
 stands, whose bases are clamped to tlic end of a table. The other end of the 
 board is supported by a jiiece of wood that rests on the floor, and can be re- 
 moved when the board is to be rotated. 
 
 •f In 16 dogs the fall of pressure in the carotid in the feet-down position 
 varied from 12 to luo mm. of mercury; average fall, 44-4 mm. In 12 out of 
 the i6 animals the rise of pressure in the head-down position varied from 
 2 to 36 mm. ; in i there was no change; in 3 there was a fall of 5 to 24 mm. 
 
PRACTICAL EXERClSliS 215 
 
 ill putting a ciinnuhi into an artery. Feel for the femoral artery, cut 
 down over it, and with forceps or a blunt needle separate the femoral 
 vein from it for about an inch. Pass two ligatures under the vein, and 
 tic a loose loop on each. Put a pair of bulldog forceps on the vein 
 between the ligatures and the heart. Now tic the lower (distal) liga- 
 ture, and cut one end short. The piece of vein between it and the 
 bulldog forceps is thus distended with blood, and this facilitates the 
 next step. With fine-pointed scissors make a snip in the wall of the 
 vein. The cannula is now pushed through the slit in the vein, and 
 the upper ligature tied firmly round its neck. By the aid of a pipette, 
 made by drawing a piece of glass tubing out to a long point, the cannula 
 and rubber tube arc then completely filled with 09 per cent, salt 
 solution. Be sure to pass the point of the piprtte right down to the 
 point of the cannula, so as to dislodge any bubble of air that may tend 
 to cling there. Then, holding up the open end of the rubber tube, 
 close it, without allowing any air to enter, by means of a screw clamp 
 or bulldog forceps, or a small piece of glass rod. Connect the cannula 
 in the carotid with a manometer, arranged to write on a drum as in 
 experiment 23 (p. iio). Take the bulldog off the carotid, and measure 
 the difteronce in the level of the mercury in the two limbs of the man- 
 ometer with a millimetre scale. 
 
 (i) («) Wliilc a tracing is being taken, draw off about 10 c.c. of blood 
 from the femoral artery, and observe whether there is any effect on 
 the tracing. Mark on the tracing the moment when the removal of 
 the blood begins and ends. 
 
 (6) Repeat (a), but run off about 100 c.c* of blood, and let this be 
 immediately delibrinatcd. Then draw off portions of 100 c.c* at short 
 intervals until a distinct fall of blood-pressure has been produced. All 
 the samples of blood should be defibrinatcd and strained through 
 cheese-cloth. 
 
 (2) (a) Now, while a tracing is being taken, inject the whole of the 
 defibrinatcd blood slowly through the cannula in the femoral vein by 
 means of a funnel supported by a stand at such a height that the blood 
 runs in easily. A pinchcock should be put on the tube connecting the 
 funnel and the cannula, and this should be closed before the funnel is 
 quite empty, so as to obviate any risk of air getting into the vein . Of 
 course, the cannula and connecting-tubes must all be freed from air 
 before injection is begun. Again measure the difference in the level 
 of the mercury and compare the pressure with that observed before 
 the first haemorrhage. 
 
 (6) Inject into the vein, while a tracing is being obtained, about 
 100 c.c* of o'9 per cent, salt solution heated to 40° C, and go on 
 injecting portions of 100 c.c. until a distinct rise of pressure has taken 
 place, keeping a record of the total amount injected, and marking the 
 time of each injection on the curve. 
 
 (c) After an interval of thirty minutes, again measure the height of 
 the mercury in the manometer. Then bleed the dog to death while a 
 tracing is being recorded. 
 
 27. The Influence of Proteoses (and Peptones) on the Blood-Pressure. 
 — Set up the apparatus for taking a blood-pressure tracing as in experi- 
 ment 23 (p. 216), but omit the induction-coil. Weigh a dog. Weigh 
 out a quantity of Witte's peptone equivalent to 05 grm. for every kilo 
 of body-weight. Dissolve the peptone in about ten times its weight 
 of- o"9 per cent, salt solution. Anaesthetize the dog with morphine and 
 ether or A.C.E. mixture. Insert a cannula into the trachea. Put 
 cannulae into the central end of one carotid and of one femoral vein 
 
 * 200 c.c. for a large dog. 
 
2I(. 
 
 Tin-: ctncui.ATioN of the blood and lymph 
 
 (p. 214). Connect the carotid with the manometer, and tlic femoral 
 vein with a bnrette or large syringe containing the peptone solution. 
 Take care that the connecting-tube and cannula are free from air. 
 Now commence to take a blood-pressure tracing and while it is going 
 on inject the peptone solution. Tlie ]iressure fails owing largely to 
 a dilatation of the small arteries through the direct action of the pep- 
 tone on llicir nius( idartissur or on 1 1ircndiiiqs of the vaso-motor nerves.* 
 28. Effect of Suprarenal Extract on the Blood-Pressure. — Make the 
 arrangements for a blood-prcssurc tracing from a dog as in 23 (p. 210). 
 Put a ramiula in the carotid and another in the femoral vein or one of 
 its branches (p. 214). Expose both vagi in the neck, and pass threads 
 loosely under them. Connect the carotid with the manometer and 
 take a tracing. Then, while the tracing is continued, inject slowly 
 into the femoral vein an amount of watery extract corresponding to 
 about o'2 grm. of suprarenal, or, wdiat is more convenient, a few c.c. 
 of a solution of adrenalin chloride of the strength of i to 50,000 in 
 o'9 per cent.'^ sodium' chloride solution, the dose depending, of course, 
 on the size of the animal. The blood-pressure risesf owing to con- 
 
 .1 PeJDtone' irijej''. ri . 
 
 .^t'^ 
 
 ..UAI^'^*^'' 
 
 Fig. 106. — Effect of Injection of l^eptone on the Blood- Pressure in a Hog. 
 (To be read from right to left.) 
 
 striction of the arterioles by direct excitation of the junction between 
 their vaso-constrictor nerves pud their muscular tissue. The heart is 
 slowed, but its beat is strengthened. At once cut both vagi while a 
 tracing is being taken; the blood-pressure ri.ses still more (p. 655). 
 The rise of pressure is sometimes so great that to prevent the mercury 
 from being forced out of the manometer the tube must be clipped. 
 The rise is not long maintained, but a second injection causes a renewed 
 increase of pressure. 
 
 29. Action of Epinephrin (Adrenalin) on Artery Rings. — The experi- 
 ment (8) described on p. (>(> in coimeclion with the constrictor action 
 of serum may equally well be performed here. 
 
 * In 12 (logs the blood-pressure always fell, the amount of the fall varying 
 from 81 to 21 mm. of mercury (average, 60 mm.). It sometimes returned to 
 normal in twenty to thirty minutes, but usually required a longer time. In 
 some dogs, after the injection of the whole of this amount of peptone, death 
 occurs before there has been any considerable recovery of the pressure. 
 
 f The amount of the initial rise of pressure is very variable, since tlie slow- 
 ing of the heart tends to diminish the pressure, while the constriction of the 
 arterioles tends to increase it. Thus, in one experiment the increase of pres- 
 sure on injection of the extract was only 6 mm. of mercury, while in another 
 it was 36 mm. On section of the vagi in this second experiment, there was 
 an additional rise of 64 nun., and after a second injection a further rise oi 
 70 mm., making an increase of 190 mm. in all above the original pressure. 
 
PR ACT IC A I. HXhliClSES 
 
 2J7 
 
 30. Determination of the Circulation-Time. — (kj bi yiu uith an arii- 
 ticial sclicnu- (I'ig. 107). l'"ill the syringe with a (r2 per cent, sohitioa 
 of methylene blue. Allow the water to flow from the bottle by loosen- 
 ing the clamp. Inject a definite quantity of the methylene-bluc solu- 
 tion, and with a stop-watch observe how long it takes to pass from 
 ■the point of injection to the end of the glass tube filled with beads 
 Make ten readings of this kind, and take the mean. Then raise the 
 bottle so as to increase the ra c of flow of the water, and repeat the 
 observations. The ' circulation-lime ' will be found to be diminished. 
 
 This corresponds to an increase of 
 blood- pressure due to increased act 
 tivity of the heart, without change 
 in the calibre of the bloodvessels. 
 Next, leaving the bottle in its present 
 position, diminish the outflow by 
 tightening (he clamp; the circulation- 
 time will be increased. This corre^- 
 })onds to an increase of blood-pressure 
 due to diminution in the calibre of 
 the small arteries. 
 
 (b) Fill the syringe* with methy- 
 lene-blue solution (o'2 per cent, in 
 
 Fig. 107. — Artificial Scheme tj illustrate a Method of measuring the Circulation- 
 Time. B, bottle Containing water, the rate of outflow of which is regulated by 
 screw-clanip a; S, syringe filled with methyleue-blue solution, connected with 
 T-piece A; M, beaker containing methylene-blue solution; b, c, screw-clamps; 
 C, T-piece, inserted in the course of the flexible tube E, and connected with the 
 glass tube T, which is filled with beads; I', outflow tube. The clamp c having 
 been closed and b opened, the syringe is filled with the methylene-blue solution; 
 b is then closed, c opened, and a definite quantity of the solution injected into the 
 system. The time from the beginning of injection till the appearance of the blue 
 at G is measured with the stop-watch. 
 
 0-9 per cent, salt solution), as in [a). Keep the solution warmed to 
 40^ C. by immersing the small beaker containing it in a water-bath, or 
 heating it over a Bunsen with a small flame. Weigh a rabbit or cat. 
 In the case of the rabbit, inject | grm. chloral hydrate into the rectum, 
 and later on give ether if nece"ssar3\ If a cat, give ether alone, or 
 urethane (1-5 grm. per kilo by stomach tube 1 to 2 hours before). 
 Fasten it on a holder, back downwards (Fig. Or, p. 136). Cover it with 
 a towel to keep it warm. Clip off the hair on the front of the neck, and 
 make an incision i J inches long in the middle line, beginning a little 
 
 * A burette, slo))ed so as to make a small angle with the horizontal, may 
 be substituted for the syringe. The burette is supported on a stand at such 
 a height (say 10-15 cm. above the level of the cannula) that the methylene- 
 blue solution runs without great force into the jugular. The danger of pro- 
 ducing an abnormal result by suddenly raising the pressure in the right side 
 of the heart is thus avoided. 
 
2iS THE CIRCULATION OF THli BLUOlJ ASU LYMPH 
 
 way below the cricoid cartilage. Relk-ct the skin and isolate the 
 external jugular vein, which is quite superficial. Carefully separate 
 about f inch of the vein from the surrounding tissue, and pass two 
 ligatures luidcr it, but do not tic thcni. Compress the vein with a pair 
 of bulldog forceps between the heart and the ligatures. Now tie the 
 uppermost of the two ligatures (that next the head), but only put a 
 single loose loop on the other. The piece of vein between the upper 
 ligature and the bulldog is now distended with blood. With fine- 
 pointed scissors make a small slit in the vein, taking great care not to 
 divide it completely, insert the cannula, and tie the loose ligature firmly 
 over its neck. Fill the cannula and the small piece of rubber tubing 
 attached to it with 09 per cent, salt solution by means of a pipette 
 with a long point. Expose the carotid on the other side, isolate it tor 
 J inch, clear it carefully from its sheath, slip under it a strip of thin 
 sheet indiarubber, and between this and the artery a little piece of white 
 glazed paper. Connect the cannula in the jugular with the T-piece 
 attached to the syringe. Care must be taken that no air remains in 
 the cannula or its connecting-tube, as a rabbit not unfrequcntly dies 
 instantaneously when a bubble of air is injected into the right heart, 
 although a considerable quantity of air can generally be injected into 
 the jugular of a dog without killing it. 
 
 Now take off the bulldog from the vein, and make a series of observa- 
 tions on the pulmonary circulation-time. The animal must be so 
 placed that a good light falls on the carotid. If necessary, the light 
 of a gas-flame may be concentrated on it by a lens. The student holds 
 the stop-watch in one hand, and injects a measured quantity of the 
 methylene-blue solution with the other. Uniformity in the quantity 
 injected is secured by fastening on the piston of the syringe a screv/- 
 clamp, which stops the piston at the desired point. The observation 
 consists in setting off the watch at the moment when injection begins 
 and stopping it when the blue appears in the carotid. After each 
 injection the screw-clamp or pinchcock on the tube connected with the 
 cannula must be tightened, the other opened, and the syringe refilled. 
 Great care must be taken never to open the two clamps at the same 
 time, as in that case blood may regurgitate through the jugular and 
 fill the syringe, or methylene blue may be sucked into the circulation. 
 As many observations as possible should be taken, and the mean 
 determined. The circulation-time observed is approximately that of 
 the lesser circulation, the time taken by the blood to pass from the 
 left ventricle to the carotid being negligible for the purposes of the 
 student. 
 
 The specific gravity of the blood may also be tested at the beginning 
 and end of the experiment by Hammcrschlag's method (p. (^2). If 
 a large number of injections have been made in quick succession, the 
 specific gra\ity will be less than normal ; but if a considerable interval 
 has been allowed to elapse after the last injection, little or no differ- 
 ence may be found, as the surplus liquid readily passes out of the 
 bloodvessels. 
 
 Necropsy. — Obserxe particularly the state of the lungs, whether the 
 bladder is distended or not, and whether any of the serous cavities or 
 the intestines contain much liquid; so as to determine, if possible, by 
 what channel the water injected into the blood may have been elimin- 
 ated. Study the distribution of the methylene blue in such organ? as 
 the kidneys and the muscles immediately after death, and notice that 
 the blue colour becomes more pronounced after exposure for a time to 
 the air. Make a longitudinal section through a kidn?y, and observe 
 that the pigment is found especially in the cortex and around the 
 
PRACTICAI. EXERi ISES 
 
 219 
 
 pelvis at the apices of the jjyrainids, or it may be only in the cortex. 
 The urine is greenish. If some methylene blue has been injected after 
 the heart ceased to beat, the lilood vessels, particularly in the mesentery, 
 may be beautifully maj^ped out by the pigment. This is not the 
 case if the last injection took place before death, since the methylene 
 blue is rapidly reduced by living tissues to a colourless substance, 
 Icuco-methylene blue. 
 
 31. Measurement of the Blood-Flow in the Hands. — Arrange the 
 calorimeters as in Fig. knS. The thermometers in the calorimeters 
 should be graduated in tenths of a degree, so that by means of the small 
 lenses or ' readers ' which slide on the stems hundredths of a degree 
 can be estimated. Where it is desirable that a number of students 
 should make observations in as short a time as possible, one calorimeter 
 can be allotted to each subject, the other hand being kept in the pocket 
 or covered with a glove if the room is cool, so as to avoid rellex vaso- 
 motor interference. A felt collar is chosen which fits the wrist closely. 
 A liorizontal pencil-mark is made at the lower edge of the styloid 
 process of the ulna, and another parallel mark at a distance above this 
 slightly greater than the thickness of the collar. When this second 
 mark is just kept in view above the collar with the hand in the 
 calorimeter, the first (lower) mark will be ju^t l)eIow the level of the 
 lid. A large bath holding 20 or 30 litres or more (a clean ' garbage ' 
 or ' offal ' can is suitable) is filled with water at about 32° C. The 
 exact temperature is not important, but it should be about the same 
 in all measurements which are to be compared. An ordinary' ther- 
 mometer graduated in degrees is all that is necessary for reading the 
 temperature of the bath. The calorimeters are now filled from the 
 bath. They are conveniently made of such a size that 3 litres of water 
 and the hand can be contained in them without any slopping over 
 when the water is stirred. Time is saved by having a metal flask 
 which just holds the quantity of water that goes into each calorimeter. 
 'J'he orifices of the calorimeters are closed by felt discs. The subject, 
 sitting in a high chair placed between the calorimeters, now immerses 
 his hands in the bath to a point between the two marks. The fingers 
 are kept spread. The bath is occasionally stirred. An ordinary ther- 
 mometer suspended at the back of the chair gives the room tempera- 
 ture. After ten minutes the hands are withdrawn from the bath, the 
 wrists rapidly dried with a towel, the hands at once introduced into the 
 calorimeters, and the felt collars adjusted round the wrists. The sub- 
 ject leans back comfortably in the chair, allowing the arms to hang 
 down without effort. The fingers are kept slightly spread. The ob- 
 server sits on a low seat behind the subject, and reads the thermometers 
 from time to time, always after stirring the water well with goose- 
 feathers passing through the stirring-holes in the lid. The readings 
 can be made at intervals of a minute, two minutes, or any interval 
 which is convenient. At the end the hands are quickly withdrawn, 
 the felt discs put over the orifices, and the water vigorously stirred for 
 ten or fifteen seconds before the thermometers are read. In this way 
 any errors due to imperfect stirring or to accidental contact of the 
 hands with the thermometers are eliminated. 
 
 The volume of each hand is now measured by immersing it exactly 
 to the lower mark in water contained in a glass douche-can connected 
 by a short rubber tube with a pipette furnished with a side-tube at its 
 lower end. The lowest graduation on the burette (50 on a 50 c.c. 
 burette) is brought level with the water before the hand is immersed. 
 While the hand is being held steadily and vertically in the water by 
 an assistant, the level of the water in the burette is read off. All that 
 
220 THE CIRCULATION OF THE BLOOD AND LYMPH 
 
 is necessary to get the volume of the hand is to pour water into the 
 can from a graduated measure after withdrawal of the hand until the 
 same level is reached. Or the value of a division of tlie burette can 
 be determined ouce for all. The burette is simply used as a transparent 
 scale. Wlien the two hands are successively measured, the small 
 amount of water removed by the first is automatically restored by 
 dipping the second into a separate vessel of water, and putting it wet 
 into tlie douche-can. The rectal i mpcrature should now be obtained. 
 The temperature of the arterial blood entering the hand is taken as 
 o'5'' C. below that of the rectum. If only the mouth temperature can 
 be got, the thermometer should be put in a second time without shaking 
 
 Fig. io8. — Calorimetric Method of measuring Blood-Flow in Hands. 
 
 down to see if it rises any more. The mouth temperature is taken as 
 equal to the arterial blood temperature. 
 
 After thorough stirring, the calorimeter temperatures can now be 
 read again. The two being noted, the amoimt of cooling of the calor- 
 imeters can be determined. This has to be added to the actually 
 obser\'ed rise of the thermometers during immersion of the hands. 
 
 Suppose an experiment yielded the following data: Rise of ther- 
 mometer in a calorimeter in twenty minutes during immersion of a hand 
 in it, io° C; temperature of calorimeter at beginning of the twenty 
 minutes. 310° C. ; at end of twenty minutes, 320° C; cooling of calor- 
 imeter in twenty minutes, 01° C; water in calorimeter, 3,000 c.c; 
 
PRACTICAL EXERCISES 221 
 
 volume of liaml, 450 c.c. ; rectal teinpLnitiire, 370° C. ; water e(|uival<.iit 
 of calorimeter, 100 c.c. 
 
 The water equivalent of the hand is 450 x 08* - 360 c.c. 
 The water equivalent of tlie calorimeter is - 100 c.c. 
 Water ------ 3,000 c.c. 
 
 Total - . . _ 3,460 c.c. 
 
 3,460 X I." I = 3,806 .small calories given oft by the hand in twenty 
 minutes. 
 
 Temperature of arterial blood (36" 5°) minus temperature of venous 
 blood Gi'o", the mean temperature of the calorimeter) =^5"o. 
 
 Flow per minute through hand = ^^^ x — ' = 42-3 grm. 
 
 Flow per loo c.c. of hand per minute ^94 grm. 
 
 The readings of the calorimeter thermometers for the first one or two 
 minutes may not be usable, owing to disturbance caused by the intro- 
 duction of the hands. As soon as they begin to rise steadily and 
 imiformly, the readings can be utilized for the calculation of the flow. 
 
 32. Vasomotor Reflexes. — Begin as in 31. Then, after the hands 
 have been in the calorimeters for a sufficient period (say ten minutes) to 
 allow satisfactory readings for the determination of the blood-flow to 
 be obtained, rapidly transfer one hand to cold water (at about 8° C), 
 while the other remains in the calorimeter. Continue reading the 
 calorimeter thermometer. Its rise will be checked by reflex vaso- 
 constriction. If the hand is kept for a few minutes in the calorimeter, 
 the reflex vaso-constriction of the hand in the calorimeter will probably 
 disappear, and the thermometer will rise faster. When a sufficient 
 number of readings have been obtained for calculating the alteration 
 in the flow, which will usually be the case in eight or ten minutes, 
 transfer the hand from the cold water to warm water (at about 43° C), 
 and continue reading the calorimeter thermometer. There is usually 
 a reflex vaso-constriction followed by vaso-dilatation. 
 
 * This factor is the product of the specific gravity and the specific heat of 
 the hand. The volume multiplied by the specific gravity gives the mass of 
 the hand, which multiplied by the specific heat, gives the water equivalent of 
 the hand . 
 
 t The reciprocal of the specific heat of blood (see formula, p. 122). 
 
CHAPTER IV 
 
 RESPIRATION 
 
 Respiration in its widest sense is the sum total of the processes by 
 which the ultimate elements of the body gain the oxygen they 
 require, and get rid of the carbon dioxide they produce. 
 
 Section I. — Preliminary Anatomical Data. 
 
 Comparative. — In a unicellular organism no special mechanism of 
 respiration is needed; the oxygen diffuses in, and the carbon dioxide 
 diffuses out, through the general surface. The simple wants of such 
 multicellular animals as the coelenterates, the group to which the sea- 
 anemone belongs, are also supplied by diffusion through the ectoderm 
 from and into the surrounding water, and through the endodcrm from 
 and into the contents of the body-cavity and its ramifications. 
 
 But in animals of more complex structure special arrangements 
 become necessary, and respiration is divided into two stages: (i) Ex- 
 ternal respiration, an interchange between the air or water and a cir- 
 culating medium or blood as it passes through richly vascular skin, 
 gills, tracheae, or lungs; and (2) internal respiration, an interchange 
 between the blood, or lymph, and the cells. 
 
 Jn the lower kinds of worms respiration goes on solely through the 
 skin, under which plexuses of bloodvessels often exist, but in some 
 higher worms there are special vascular appendages that play the part 
 of gills. The Crustacea also possess gills, while in the other arthropoda 
 respiration is carried on either by the general surface of the body (in 
 some low forms), or more commonly by means of trachea;, or branched 
 tubes surrounded by blood spaces and communicating externally with 
 the air and internally by their finest twigs with the individual cells. 
 Most of the moUusca breathe by gills, but a few only by the skin. 
 
 Among vertebrates the fishes and larval amphibians breathe by gills, 
 but most adult amphibians have lungs. The skin, too, in such animals 
 as the frog has a very important respiratory function, more of the 
 gaseous exchange taking place through it in some conditions than 
 through the lungs. 
 
 One small group of fishes, the dipnoi, has the peculiarity of possessing 
 both gills and a kind of lungs, the swim-bladder being surrounded with 
 a plexus of bloodvessels and taking on a respiratory function. 
 
 In all the higher vertebrates the respiration is carried on by lungs; 
 the trifling amount of gaseous interchange which can possibly take 
 place through the skin is not worth takiag into account. The lungs 
 arc to be regarded as developed from outgrowths of the alimentary 
 canal, beginning near the mouth. 
 
 2(23 
 
j'h'i:r.n/i.\.U\'Y AW-troMicAf. data 223 
 
 The object oi all special respiratory arrangements being, in (ho first 
 instance, to facilitate the gaseous exchange Ix'twcen the surrounding 
 medium (air or water) and the blood, a prime necessity of a respiratt^ry 
 organ, be it skin, gill, trachea, or lung, is a free supply of bi(Jod, in 
 vessels so tine and thin that diffusion readily takes place into them 
 and out of them. But a free supply of blood would be of no avail if the 
 n'edium to which tlie blood ga\c up its carbon dioxide and from which 
 it drew its oxygen was not being constantly and sufficiently renewed. 
 
 Sometimes the natural currents of the water or the air are of them- 
 selves sufficient to secure this renewal; in other cases, artificial currents 
 are set up by cilia, or special bailing organs, like the scaphognathites 
 of the lobster. In all the higher animals, active movements by which 
 air or water is brought into contact with the respiratory surfaces, are 
 necessary; and it is possible that such movements take place even in 
 (he trachea' of insects and other air-breathing arthropoda. Fishes, by 
 rhvthmical swallowing movements, take in water through the mouth 
 anfl pass it over the gills and out by the gill-slits, while the frog distends 
 its lungs by swallowing air. 
 
 Physiological Anatomy of the Respiratory Apparatus. — In man the 
 respiratory apparatus consists of a tube (the trachea) widened at its 
 upper part into the larynx, which contains the special mechanism of 
 voice, and communicates through the nose or mouth with the external 
 air. Below, the trachea divides dendritically into innumerable 
 branches, the ultimate divisions of which are called bronchioles. Each 
 bronchiole ends in several openings or vestibula, each of which in turn 
 leads into a dilatation called an atrium. I-rom each atrium are given 
 off two, or more, often funnel-shaped diverticula, the infundibula, the 
 walls of which are everywhere pitted with recesses or alcoves, called 
 alveoli. The atria are also lined with alveoli. The infundibula (with 
 the atria) constitute the essential distensible elements of the lung, by 
 the alternate stretching and relaxation of which the respiratory changes 
 in the volume of the organ are mainly brought about. The trachea and 
 bronchi are strengthened by hyaline cartilage which renders them rela- 
 tively rigid. But the fact that the cartilage does not form complete 
 rings permits small changes of calibre to take place. 
 
 In the bronchioles, no cartilage is present, but the circularly-arranged 
 muscular fibres still persist, and also form a thin layer in the infundi- 
 bula. In the air-cells, or alveoli, however, there are no muscular fibres. 
 Their walls consist essentially of a network of elastic fibres, continuous 
 with a similar layer in the infundibula and bronchioles, and covered on 
 the side next the lumen by a single layer of large, clear epithelial scales, 
 with here and there a few smaller and more granular polyhedral cells. 
 From the larynx to the bronchioles the mucous membrane is ciliated 
 on its free surface, the cilia lashing upwards so as to move the secre- 
 tion towards the larynx and mouth. In the infundibula the ciliated 
 epithelium begins to disappear, and is absent from the alveoli. Part 
 of the nasal cavity and the upper part of the pharynx are also lined with 
 ciliated epithelium. Mucous glands are present in abundance in the 
 upper portic n ; of the respiratory passages, but disappear in the smaller 
 bronchi. 
 
 Blood-Supply of the Lungs. — The quantity of blood traversing the 
 lungs bears no proportion to the amount required for their actual 
 nourishment. Small, however, as this latter quantity is, it cannot 
 apparently be derived from the vitiated blood of the right ventricle, 
 but is obtained directly from the aortic system by the bronchial arteries. 
 These are distributed with the bronchi, which they supply as well as 
 the connective tissue of the interlobular septa running through the 
 
224 RESPIHATIO^J 
 
 substance of the lung, llif pleura lining it and the walls of the large 
 bloodvessels. Most of the blood from the bronchial arteries is returned 
 by the bronchial veins into the systemic venous system, but some of it 
 finds its way by anastomoses into the pulmonary veins. 
 
 The branches of the pulmonary artery arc also distributed with the 
 bronchi, and break up into a dense capillary network around the alveoli. 
 From the capillaries veins arise which, gradually uniting, form the large 
 pulmonary veins that pour their blood into the left auricle. 
 
 The same quantity of blood must, on the whole, pass per unit of 
 time through the lesser as tlirough the greater circulation, otherwise 
 equilibrium could not exist, and blood would accumulate either in the 
 lungs or in the systemic vessels. But it does not follow that at each 
 heart-beat the output of the two ventricles is exactly equal. If, indeed, 
 the capacity of the lesser circulation were constant, the quantity- 
 driven out at one systole by the right ventricle would be the same as 
 that ejected at the next by the left ventricle. But it is known that 
 the capacity of the pulmonary vessels is altered by the movements 
 of respiration and probably in other ways, so that it is only on the 
 average of a number of beats that the output of the two ventricles can 
 be supposed equal. 
 
 The time required by a given small portion of blood — e.g., by a single 
 corpuscle — to complete the round of the lesser circulation, is, as we 
 have seen (p. 137), much less than the average time needed to complete 
 the systemic circulation. In man the ratio is probably about i : 5. 
 Since all the blood in a vascular tract must pass out of it in a period 
 equal to the circulation time, the average quantity of blood in the 
 lungs and right heart of a man would thus be about one-fifth of that in 
 the systemic vessels. That is to say, not less than 700 grm. out of the 
 4^^ kilos* of blood in a 70-kilo man would be contained in the lesser cir- 
 culation, and about 3 J kilos in the greater. This corresponds sufficiently 
 well with calculations from other data. 
 
 For example, the average weight of the lungs in three persons exe- 
 cuted by beheading, was 457 grm. (Gluge). The average weight of 
 the lungs in a great number of persons who had died a natural death 
 was 1,024 g-if^- (Juncker). The weight of the pulmonary tissue alone 
 in the first set of cases must be less than 457 grm.. for the lungs of a 
 person who has bled to death are never bloodless. In a dog killed by 
 bleeding from the carotid, one-quarter of the weight of the lungs con- 
 sisted of blood. Assuming the same proportion for the decapitated 
 individuals, we get 343 grm. as the net weight of the blood-free lungs. 
 Deducting this from 1,024 grm., we arrive at 681 grm. as the average 
 quantity of blood in the lungs. Adding to this the quantity in the 
 right side of the heart (p. 140), we get, in round numb:rs, 750 grm. 
 as the amount in the lesser circulation. It is true that in the living 
 body the conditions are not the same as after death; but it is probable 
 that in a laige number of cases taken at random the differences would 
 be approximately equalized. 
 
 It has been further calculated that the total area of the alveolar 
 surface of the lungs of a man is about 100 square metres (sixty times 
 greater than the area of the skin), of which, perhaps, 75 square metres 
 are occupied by capillaries. The average thickness of this immense 
 sheet of blood has been reckoned to be equal to the diameter of a red 
 blood-corpuscle, or, say, 8 u. This would give 600 c.c. (630 grm.) as 
 the quantity of blood in the lungs, which is probably somewhat too 
 low an estimate. 
 
 ♦ See footnote on p. 139 
 
MECHASICAI. PIIESOMENA OF EXTERXAI. RES/'/RATmX 325 
 
 ]f we take the pulmoiiiiry circuhition-liiue us 13 seconds (p. 137). 
 
 07 X 60 X 6t) 
 and the quantity of blood in the hings as 700 grni., then ~7o~ 
 
 — 194 kilos of blood will pass througli the lungs in an iiour, or 4,050 
 kilos (say, 4,400 litres) in twenty-four hours. 1 his would fill a cubical 
 tank in which the man could almost stand upright with the lid closed. 
 
 Section II. ^Mechanical Phenomena of Extkknal 
 Respiration. 
 
 The lungs are enclosed in an air-tight box, the thorax; or it may 
 be said with e(iual truth that they form part of the wall of the 
 thoracic cavit}-, and the part which has by far the greatest capacity 
 of adjustment. The alveolar surface of the lungs is in contact with 
 the air. The pleura, which covers their internal surface, is reflected 
 over the chest-walls and diaphragm, so as to form two lateral sacs, 
 the pleural cavities. In health these are almost obliterated, and the 
 visceral and parietal pleurae, separated and lubricated by a few 
 drops of lymph, glide on each other with every movement of 
 respiration. But in disease the pleural cavities may be filled and 
 their walls widely separated by exudation, as in pleurisy, or by 
 blood, as in rupture of an aneurism, or by air in the condition 
 known as pneumo-thorax. Between the two pleural sacs lies a mesial 
 space, the mediastinum, commonly divided into an anterior medias- 
 tinum in front of the heart, and a posterior mediastinum behind it. 
 The pleural and pericardial sacs and the mediastinum constitute 
 together the thoracic cavity. The external surface of the chest- 
 wall and the alveolar surface of the lungs are subjected to the 
 pressure of the atmosphere, to which the pressure in the thoracic 
 cavity (intra-thoracic pressure) w ould be exactly equal if its bound- 
 aries were perfectly ^delding. But in reality the intra-thoracic 
 pressure is always normally something less than this. For even 
 the lungs, the least rigid part of the boundary, oppose a certain 
 resistance to distension, and so hold off, as it were, from the thoracic 
 cavity a portion of the alveolar pressure; and in any given position 
 of the chest the intra-thoracic pressure is equal to the atmospheric 
 pressure minus this elastic tension of the lungs. 
 
 The object of the respiratory movements is the renewal of the air 
 in contact with the alveolar membrane — in other words, the ventila- 
 tion of the lungs. Two main methods are followed by sanitary 
 engineers in the ventilation of buildings: they force air in, or they 
 draw it in. In both cases the movement of the air depends on the 
 establishment of a slope of pressure from the inlet to the interior. 
 In the first method, this is done b}^ increasing the pressure at the 
 inlet; in the second, by diminishing the pressure at the outlet. In 
 certain animals Nature, in solving its problem of ventilation, has 
 made use of the first principle. Thus, the frog forces air into its 
 
 15 
 
226 
 
 Uh.Sl'IHATION 
 
 lungs by a swallowing movement. In aitiliciai respiration, as 
 practised in physiological experiments, the same method is usually 
 employed: air is driven into the lungs under pressure. But in the 
 vast majority of air-breathing animals, including man, the opposite 
 principle has been adopted; and the ' indraught ' of air from nose 
 and pliarynx to alveoli is not set up by increasing the pressure in 
 the former, but by diminishing it in the latter. This ' indraught,' 
 or inspiration, is brought about by certain movements of the chest- 
 wall, which increase the capacity of the 
 thoracic cage and lower the pressure in the 
 thoracic cavity. The expansion of the 
 highly-distensible lungs keeps pace with 
 the diminution of pressure in tlie pleural 
 sacs, and they follow at every point tin- 
 retreating chest - wall and diaphragm, 
 although they do not expand equally in 
 all directions. The dorsal surface in con- 
 tact with the vertebral column, the 
 mediastinal surface in contact with the 
 pericardium and the contents of the 
 mediastinum, and the surface of the apex, 
 move but little. The surfaces in contact 
 with the diaphragm, ribs, and sternum 
 have the greatest range of movement. 
 Intermediate portions of the parenchyma 
 of the hmgs expand in a degree determined 
 by their distance from the relatively 
 stationary and mobile surfaces. The pres- 
 sure of the air in the alveoli during the 
 rapid expansion of the lungs necessarily 
 sinks below that of the at;nospliere, and 
 air rushes in through the trachea and 
 bronchi till the difference is equalized. 
 Then commences the movement of ex- 
 piration. The expanded chest falls back 
 to its original limits; the pressure in the 
 thoracic cavity increases; the distended 
 lungs, in virtue of their elasticity, shrink to their former volume; 
 the pressure of the air in the al\-eoli rises above that of the atmo- 
 sphere, and with this reversal of the slope of pressure air streams 
 out of the bronchi and trachea. 
 
 In inspiration the chest dilates in all its diameters. Its vertical 
 diameter is increased by the contraction of the diaphragm, which, 
 composed of a central tendon, a peripheral ring of muscular tissue, 
 and the two muscular crura, bulges up into the thorax in the form 
 of two flattened domes, one on each side, and thus closes its lower 
 
 Fig. .109. — Scheme to illus- 
 trate the Movements of the 
 Lungs in the Chest. T is 
 a buttle from which the 
 bottom has been removed: 
 1), a flexible and elastic 
 iiienibrane tied on the 
 bottle, and capable of being 
 pulled out by the string S 
 so as to increase the ca- 
 pacity of the bottle. L is 
 a thin elastic bag repre- 
 senting the lungs. It coin- 
 municateswith the external 
 air by a glass tube fitted 
 airtight through a cork in 
 the neck of the bottle. 
 When D is drawn down, the 
 pressure of the e.xternal air 
 causes L to expand. When 
 the string is let go. L con- 
 tracts again, in virtue of 
 its elasticity. 
 
Mr.arAMc.u. phenomena or r:.\TEh\\.u. hTsri ration 227 
 
 aperture. When the diaphragm contracts, even in ordinary quiet 
 breathing, the central tendon descends distinctly (about half an 
 inch) after the manner of a piston. The acute angle which the 
 muscular ring makes during relaxation with the thoracic wall opens 
 out around its whole circumference, so as to form a groove of trian- 
 gular section. But the most peripheral portion of the ring is alwaj's 
 kept in close apposition to the chest- wall by the negative intra- 
 thoracic pressure. The lungs follow the descending diaphragm, 
 their lower borders keeping accurately in contact with it. The 
 descent of the diaphragm is not directly downwards, but downwards 
 and forwards. For it is compounded of two movements, the spinal 
 segment of the muscle (the crura) causing a vertical elongation of 
 the thorax, while the sterno-costal part (the muscular ring) pushes 
 the abdominal viscera downwards and forwards (Keith). Since 
 the diaphragm is attached to the lower ribs, there is a tendency 
 during its contraction for these to be drawn inwards and upwards; 
 but this is opposed by the pressure of the abdominal viscera, and by 
 the action of the qnadratiis litmbormn, which fixes the twelfth rib, 
 and of the serratus posticus inferior, which draws the lower four 
 ribs backward. When these and the other inspiratory muscles 
 that act especially upon the ribs are paralyzed by injuW to the 
 spinal cord, and respiration is carried on by the diaphragm alone, 
 the hne of its attachment to the ribs is distinctly marked during 
 inspiration by a shallow circular groove. 
 
 The thorax is also enlarged by the action of certain muscles that 
 act upon the ribs. Among the elevators of the ribs, as their name 
 indicates, are usually reckoned, although erroneously, the levatores 
 costanim — twelve in number on each side. They arise from the 
 transverse processes of the last cervical and first eleven dorsal 
 vertebrae, and passing obliquely downwards and outwards, are in- 
 serted between the tubercle and the angle into the first or second rib 
 below their origin. They do not elevate the ribs, but take part in 
 lateral movements of the spinal column. The scalene muscles, 
 which may in a lean person be felt to be tense during inspiration, 
 fix the first and second ribs (scalenus anticus and medius, the first ; 
 scalenus posticus, the second rib), and so aft'ord a fixed line for the 
 intercostal muscles to work from on the lower ribs. 
 
 The most important elevators of the ribs are the external inter- 
 costals. The intercartilaginous portions of the internal inter- 
 costals (the intercartilaginei muscles, as they are sometimes called) 
 also contract simultaneously with the diaphragm, and may there- 
 fore be included in the list of inspiratory muscles; but instead of 
 elevating the ribs they depress the costal cartilages, and thus help 
 to widen the angles between them and the ribs. In addition to 
 increasing the capacity of the chest, the contraction of the external 
 intercostals and the intercartilaginous muscles aids in inspiration 
 
:28 RESPIRATION 
 
 by augniLnting tlie rigidity of the intercostal spaces, and so pre- 
 venting them from being drawn in as easily as would otherwise be 
 the case when the thorax is expanded by the action of the dia- 
 phragm and the other inspiratory muscles. 
 
 Leaving out of account the floating ribs, which functionally form 
 a part of the abdominal wall, the ribs in relation to their respiratory 
 functions may be divided into the following groups: (i) The first 
 rib, which, moving itself very httle, provides a fixed line towards 
 which the next set of ribs may be raised. 
 
 (2) An. upper costal series consisting of the ribs from the second 
 to the fifth. These are raised in inspiration towards the fixed first 
 rib by the contraction of the intercostal muscles. The movement 
 of these ribs is, mainly at any rate, a rotation around a transverse 
 axis, the axes on which they move corresponding to their necks. 
 The manner in which they are articulated to the vertebrae prevents 
 any sensible rotation around an antero-posterior axis or ' bucket- 
 handle ' movement. Since these ribs slant downwards and forwards 
 to their sternal attachments, the sternum is raised when they are 
 elevated; or, rather, since the manubrium is practically immovable 
 in ordinary breathing, the body of that bone is bent on the manu- 
 brium at the manubrio-sternal joint. This causes an increase in 
 the antero-posterior diameter of the thorax. Further, since the 
 arches formed by the ribs widen in regular progression from above 
 downwards in the upper portion of the thoracic cage, so that the 
 second rib is a segment of a larger circle than the first, and the 
 third than the second, it is clear that a general elevation of the chest 
 will tend to increase the transverse diameter at any given level. 
 Such an increase is also favoured by the opening out of the angles 
 between the bony ribs and the costal cartilages under the influence 
 of the couple (or pair of oppositely directed forces) that acts on them 
 
 viz., the upward pull of the external intercostals exerted on the 
 
 ribs, and the downward pull of the intercartilaginei and the resist- 
 ance of the sternum to further displacement exerted on the carti- 
 lages. The whole arrangement is perfectly adapted to permit the 
 expansion of the roughly conical upper lobes of the lungs. 
 
 (3) The lower costal series, consisting of the ribs from the sixth 
 to the tenth. These ribs, with their muscles, form a mechanism 
 which normally acts along with the diaphragm (Keith). They are 
 so arranged that in inspiration the lateral and anterior part of 
 each moves outwards to a greater extent than the one above it. 
 There is not only a rotation around a transverse axis, by which the 
 lower end of the sternum, connected to these ribs by the combined 
 cartilages of the sixth to the ninth, is elevated, but also a rotation 
 around an antero-posterior axis. The movement of the lower ribs 
 results, therefore, in increasing both the back-to-front diameter and 
 the transverse diameter of the lower portion of the thorax. The 
 
MECHANICAL PHl.XOMKXA Ol' hXTHRSAr. PF.SPI h\lTlO\ z>., 
 
 widening of the thorax from side to side may also be in a sHght 
 degree ascribed to a twisting movement of the ribs, which tends to 
 evert their lower borders. With the diaphragm, these lower ribs 
 arranged in a vertical series of not very different curvature con- 
 stitute a mechanism for the inspiratory expansion of the roughly 
 cylindrical lower lobes of the lungs. 
 
 Expiration in perfectly tranquil breathing is brought about with 
 less aid from active muscular contraction. The sense of effort 
 disappears as soon as the chest ceases to expand. The diaphragm 
 and the elevators of the ribs relax. The structures that have been 
 stretched or twisted recoil into their original positions; the struc- 
 tures that have been raised against the force of gra\'ity fall back 
 by their weight, and in the measure in which the pressure increases 
 in the thoracic cavity the elasticity of the lungs causes them to 
 slirink. The pressure in the alveoli, which at the end of inspiration 
 was just equal to that of the atmosphere, is thus increased, and the 
 air expelled. It is probable that, even in man and in quiet respira- 
 tion, the interosseous portions of the internal intercostals help b}' 
 their contraction in depressing the ribs, and that a slight contrac- 
 tion of the abdominal muscles hastens the return of the diaphragm 
 to its position of rest. In reptiles and birds, expiration is normally 
 effected by an active muscular contraction. This is also true in 
 some mammals — the rabbit, for instance, in which the external 
 obhque muscles of the abdominal wall take an important share in 
 the expiratory act 
 
 Types of Respiration. — Differences exist also, not only between 
 different groups of animals, but even between women and men, in 
 the relative importance in inspiration of the diaphragm and the 
 muscles that raise the lower ribs on the one hand, and the muscles 
 that elevate the upper ribs on the other. When the movements of 
 the diaphragm predominate, the respiration is said to be of the 
 abdominal or diaphragmatic type ; when the movemenus of the upper 
 ribs and sternum are most conspicuous, of the costal or thoracic type. 
 In abdominal respiration, the inspiratory movement commences at 
 the diaphragm, and then involves the lower ribs and the tip of the 
 sternum. In costal respiration, the upper ribs initiate the move- 
 ment, and are followed by the abdomen. In the rabbit, during 
 quiet breathing, the respiration is purely diaphragmatic, the ribs 
 remain motionless; and herbivorous animals in general conform 
 more or less closely to this type. In the carnivora, on the contrarj', 
 the costal t\'pe prevails. Man allies himself as regards his respira- 
 tion with the rabbit and the sheep ; he uses his diaphragm more than 
 his upper ribs. Ci\'ilized woman falls into the class of the wolf and 
 the tiger; she uses her upper ribs more than her diaphragm. The 
 cause of the difference between men and women has been much 
 discussed. It is not a primitive sexual difference, for it is far from 
 
230 RESPIRATION 
 
 being universal; in the uncivilized and semi-civilized races that 
 have been investigated, the women breathe like the men. It is 
 therefore probable that the predominance of the costal type among 
 women of European race is a peculiarity developed by a mode of 
 dressing which hampers the movements of the diaphragm while 
 permitting the elevation of the ribs. This conclusion is strengthened 
 by the fact that in children no difference exists; both boys and girls 
 show the abdominal type of respiration. 
 
 All this refers to ordinary breathing. In forced respiration, when 
 the need for air becomes urgent, costal breathing always becomes 
 prominent alike in men, in women, and in animals, for by elevation 
 of the ribs the capacity of the chest can be increased to a greater 
 degree than by any contraction of the diaphragm. 
 
 In forced inspiration, indeed, all the muscles that can elevate the 
 ribs may be thrown into contraction, as well as other muscles which 
 give these fixed points to act from. During a paroxysm of asthma, 
 for example, the patient may grasp the back of a chair with his 
 hands, so as to fix the arm? and shoulders and allow the pertorals 
 and serratus magnus to raise the ribs. Similarly in forced expiration 
 all the muscles are used which can depress the ribs, or increase the 
 intra-abdominal pressure and push up the diaphragm. 
 
 Artificial Respiration. — An efficient pulmonary \entilation can be 
 obtained by various methods when the natural breathing is in abey- 
 ance. In animals the method most commonly employed for ex- 
 perimental purposes is the rhythmical inflation of the hings by a 
 pump or bellows, or by a stream of compressed air which is regularly 
 interrupted, the chest being allowed to collapse after each inflation. 
 Wlien the animal is to be kept alive after the experiment the inflation 
 is produced through a tube introduced through the glottis. If the 
 animai is not to be kept alive, the apparatus is generally connected 
 with a cannula in the trachea. When it is desired to avoid move- 
 ments of the lungs, respiration may be maintained by a stream of 
 oxygen through a catheter passed down the trachea (method of 
 insufflation). In man the exchange of air between the atmosphere 
 and the lungs may be most readily accomplished by strong rhythmi- 
 cal compression of the lower part of the chest. This forces out 
 some of the air from the lungs; on relaxing the pressure the chest 
 expands again and air is drawn in. Schafer has shown that this is 
 the most efficient method of respiration in resuscitation of the ap- 
 parently drowned. ' The patient is placed face downwards on the 
 ground, with a f(jlded coat under the lower part of the chest. The 
 operator puts himself athwart or at the side of the patient, facing his 
 head and kneeling upon one or both knees (Fig. no), and places his 
 hands on each side over the lower part of the back (lowest ribs). He 
 then slowly throws the weight of his bodv forward to bear upon his 
 own arms, and thus presses upon the thorax and forces air out of 
 the lungs. He then gradually relaxes the pressure by bringing his 
 
MIA IIAMC.IL l'lli:\(>Mh.\.l OJ- ]:.\ llhW.lL UESl'IKAl luS i^i 
 
 own body iij) a^ain tt» a more I'lcd i><»siti()ii, hut witlujut moving 
 the hands.' Air is tliu> diawn into \\\v limys. The process is 
 repeated tvehe to filleeii tiine.-^ a minute. 
 
 Certain accessory phenomena (movements and sounds) are asso- 
 ciared with tlie proper movements of respiration. The larynx rises 
 in expiration, and sinks in inspiration. The glottis (and particu- 
 larly its posterior portion, the glottis respiratoria) is widened during 
 deep inspiration and narrowed during deep expiration. The same 
 is the case with the nostrils, and, indeed, in some persons the alae 
 nasi move even in ordinary breathing. It has long been known 
 that in deep respiration changes in the calibre of the bronchi syn- 
 chronous with the respiratory movements may occur. In young 
 persons it may be directly observed with the bronchoscope, an 
 instrument used by laryngologists for exploring the larger bronchi, 
 
 that these dilate 
 in inspiration 
 and constrict in 
 expiration (In- 
 galls). In part 
 at least these 
 movements are 
 passively pro- 
 duced by the 
 changes of intra- 
 thoracic pres- 
 sure, but it has 
 not been defi- 
 nitely deter- 
 mined whether 
 they are not in 
 ])art caused by 
 
 alternate contraction and relaxation of the circular bronchial 
 muscles. To these muscles has sometimes been attributed the 
 function of regulating the flow of air into and out of the infundib- 
 ula, as the muscle of the arterioles regulates the distribution of the 
 blood in the organs. 
 
 As regards the respiratory sounds, all that is necessary to be said 
 here is that when we Ustcn over the greater portion of the kings with 
 the ear, or, much better, with a stethoscope, a soft breezy murmur, 
 that has been compared to the rustUng of the wind through distant 
 trees, is heard. This has been called the vesicular murmur. It is only 
 heard in health during inspiration and the very beginning of expira- 
 tion, and is louder in children than in adults. Around the larger 
 bronchi and the trachea a blowing sound is heard, which certainly 
 originates at the glottis, and is strengthened by the resonance of the 
 air-tubes. In health this is not recognized over the greater portion of 
 the lung. But in certain diseases in which the alveoli are devoid of 
 air, whether from compression or because they are filled up with 
 exudation, and in other conditions, this bronchial or tubular breathing 
 
 Fig. no. — Artificial Respiration in Cases of Drowning (after 
 Schafer). 
 
^Ji TiF.SPI RATION 
 
 may be I)card over tlic affected area. The bronclii themselves, how- 
 ever, must still be patent and contain air. i'hc most commonly 
 accepted explanation is tliat the laryngeal sound is better conducted 
 through the smaller bronchi towards the surface of the lungs when 
 their walls have been rendered more rigid bv the solidification of the 
 parenchyma, in spite of the fact that the consolidated tissue as such 
 does not conduct the sound so well as the air-containing alveoli. It 
 seems probable that, in addition, the columns of air in the bronchi, 
 which arc encased in solid tissue, may actually increase the intensity 
 of the transmitted laryngeal murmur by resonance. 
 
 It has been much debated whether the vesicular murmur also arises 
 at the glottis, and is modified by transmission through the pulmonary 
 tissue, or whether it arises somewhere in the terminal bronchi, the 
 infundibula or the alveoli. Both views may be supported by certain 
 arguments, and to both some objections maj' be raised. The fact 
 appears to be that tliere are two elements in the inspiratory murmur — 
 a true vesicular sound, produced about the place where the terminal 
 bronchioles give off the infundibula. and a resonance sound set up in 
 the trachea and bronchi by the glottic murnmr. This resonance sound 
 as heard over portions of the lung containing onh' snxall bronchi has 
 a different character from that heard over large bronclii, inasmuch as 
 the fundamental note, and to a still greater extent the overtones 
 Jp. 310), are much weakened in those small and easily-distensible 
 tubes. The true vesicular element is heard all over the lungs, but 
 the resonant laryngeal element in large animals, like the horse and ox, 
 dies out as an audible murmur before it reaches the reTnotest lobules, 
 and can only be distinguished over a portion of the pulmonary- area. 
 When the glottic sound is eliminated by causing an anJrmil to breathe 
 through a tracheal fistula, the vesicular murmur is still heard, and in 
 the horse is even somewhtit sharper than normal, although in the dog 
 it is softer and weaker. The expiratory' murmur does not seem to 
 contain a true vesicular element, but is exclusively due to the resonance 
 of the expiratory glottic sound (Marek). It is generally admitted, and 
 this is of great importance in practical medicine, that when the normal 
 vesicular sound is heard over any portion of the lung tissue, it may be 
 inferred that this portion is being properly distended, and that air is 
 freely entering its alveoli. 
 
 Up to this point we liave contented ourselves with a purely 
 ([ualitative description of the mechanical phenomena of respiration. 
 We have now to consider their quantitative relations, and the 
 methods by which these have been studied. 
 
 The expansion of the lungs in inspiration may be easily demonstrated 
 in man, and even a rough estimate of its amount obtained, by the clinical 
 method of percussion. For example, the resonant note tliat is elicited 
 when a finger laid on the chest at a part where it overlies the right 
 lung is smartly struck can be followed down until it is lost in the ' liver 
 duhiess.' If the lower limit of the resonant area be marked on the 
 chest-wall first in full inspiration, and then in full expiration, the mark 
 will be lower in the former than in the latter, and the difference will 
 represent the difference in the vertical length of the shrunken and dis- 
 tended lung. A similar enlargement in the transverse direction ma\ 
 bo demonstrated in the same way, the inner borders of the lungs coming 
 nearer to the middle line in inspiration, and receding from it in expira- 
 tion. The examination of the chest by the Rontgen rays has also 
 
MECMAMCAL IVlhXUMLXA Ol- /•.VV/l /I'.V.IL UILSPIRATIO^ 233 
 
 yielded results of importance in the study of nornuil respiratory con- 
 ditions, and still more important results in pulmonary disease. 
 
 For most physiological purposes, however, a faithful graphic record 
 of the respiratory movements is indispensable. This may be obtained — 
 
 (i) 13y registering the movements 
 of a single point, or the variations in 
 a single circumference, of the bound- 
 ary of the thoracic cavity. In man, 
 changes in the circumference of the 
 thorax at any level can be recorded 
 by means of a tambour adjusted to 
 the chest (Figs. 1 1 1 and 13.4), and in 
 communication with another, which 
 is provided with a writing lever 
 (Figs. 99 and 137). Or an elastic 
 tube, with a spiral spring in its 
 lumen, may be fastened around the 
 tliorax or abdomen and connected 
 with a piston-recorder (a small cylin- 
 der in which works a piston carrying 
 a writing-point) (Fitz). 
 
 (2) By recording the changes of 
 pressure produced in the air-passages 
 by the respiratory movements. This 
 can be done by connecting a cannula 
 in the trachea of an animal with a 
 recording tambour in the manner 
 described in the Practical Exercises 
 (p 300). The variations of pressure 
 may be measured by connecting a 
 manometer with the trachea, or in 
 man with the noiJtril. 
 
 (3) By writing off the changes of pressure which occur in the thoracic 
 cavity during respiration. For this purpose a trocar (Fig. 113) is intro- 
 duced through an intercostal space into one of the pleural sacs, without 
 the admission of air, or into the pericardium, and then connected with 
 a manometer or other recording apparatus. Or a tube, similar in con- 
 struction to a car- 
 diac sound (p. 96), 
 may be pushed 
 down the oesopha- 
 gus. The varia- 
 tions in the intra- 
 thorrxlc pressure 
 are transmitted to 
 the air in the elas- 
 tic bag. and thence 
 to a tambour. 
 
 (4) In the rabbit 
 the part of the dia- 
 phragm attached to the ensiform cartilage may be isolated from the 
 rest and its contractions recorded by a lever (Head) . For some purposes 
 this is the best method. 
 
 When the respiratory movements are studied in any of these ways, 
 it is found that there is practically no pause between the end of 
 
 I-'ig. III. — Scheme of Tambour for 
 recording Respiratory Movements. 
 C. a metal capsule connected airtight 
 with B, A. two caoutchouc mem- 
 branes, the chamber formed by which 
 can be inflated by means of the tube 
 and stopcock E. The tube D con- 
 nects the space H with a registering 
 tambour provided with a lever. The 
 membrane .\ is applied to the chest, 
 round which the inextensible strings 
 F are tied. At every expansion of the 
 chest the pressure in H is increased, 
 and the increase of pressure is trans- 
 mitted to the registering tambour. 
 
 Fig. 112. — ^Respiratory Tracing from Man (Marey). 
 stroke, inspiration; up stroke, expiration. 
 
 Down 
 
■!34 
 
 RESPlUAriDS 
 
 d 
 
 \_fa 
 
 Fig. US- 
 
 inspiration and till' bcj^inninf,' of expiration. Xor, although the 
 chest collapses more gradually than it expands, is there any distinct 
 interval in ordinary breathing between the end of expiration and 
 the beginning of the sucxeeding inspiration. When, however, the 
 respiration is unusually slow, an actual pause (expiratory pausej 
 may occur at this point. Expiration takes 
 somewhat longer time than inspiration, the 
 ratio varying from 7 : 6 to 3 : 2, according to 
 age, sex, and other circumstances. 
 
 The frequency of respiration is by no means 
 constant even in health. All kinds of in- 
 fluences affect it. It is dif^cult even to direct 
 the attention to the respiratory act without 
 bringing about a modification in its rhythm. 
 In the adult 15 to 20 respirations per minute 
 may be taken as about the normal. In young 
 children the frequency may be twice as great 
 (new-born child, 50 to 70; child from i to 5 
 years old, 20 to 30 per minute). It is greater 
 in a female than in a male of the same age. A 
 rise of temperature increases it; 150 respira- 
 tions per minute have been seen in a dog with 
 a high temperature. Sudden coohng of the skin, 
 exercise, and various emotional states, increase 
 the rate, and sleep diminishes it. The will can 
 alter the frequency and depth of respiration 
 for a time, and even stop it altogether, but in 
 less than a minute, in ordinary individuals, the 
 desire to breathe becomes imperative. Cato's 
 assertion that he could kill himself at any time 
 ' merely by holding his breath ' is only a proof 
 that he was a better philosopher than physi- 
 ologist. After a period of forced respiration 
 the breath can be held for a much longer time. 
 This is due to the ' washing out ' of the carbon 
 dioxide, the normal stimulus to the respiratory 
 centre (p. 281). After six minutes of forced 
 breathing the interval of voluntary inhibition can be extended be- 
 yond four minutes. A profes>ional diver has remained under water 
 in a tank for about four and three-quarter minutes. When oxygen 
 is inhaled instead of air during the last few breaths of the forced 
 respiration, the interval during which the breath can be held may 
 be much increased (up to nine or ten minutes). In animals the rate 
 of respiration can be greatly affected by drugs and by the section 
 and stimulation of certain nerves; but to this we shall return when 
 we come to consider the nervous mechanism of respiration. 
 
 Simple 
 Pleural Cannula. B. 
 a line of small spurs 
 which, after the can- 
 nula C has been 
 pushed without ad- 
 mission of air through 
 an intercostal space 
 into the pleural 
 cavity, stick in the 
 parietal pleura and 
 securely fasten the 
 cannula. Traction 
 being made on the 
 cannula, a ligature is 
 tied at L around the 
 protruding tissue for 
 greater security. S, 
 side-tube by whichthe 
 cannula is connected 
 with a manometer or 
 tambour. 
 
MIXHASICAL I'in.SDMENA Of I:.\TI:RSAL in:Sl'lh'ATIO\' 235 
 
 It cannot tail to be observed that to a great extent the rate of 
 respiration is affected by the same circumstances as the frequency 
 of the heart (p. 107), and in the same direction. And, indeed, in 
 health, these two physiological quantities, amid all their absolute 
 variations, maintain to each other a fairly constant ratio (i to 4 or 
 
 I to 5 in man). Even in many diseases 
 this proportion remains tolerably 
 stable, although in others it is dis- 
 turbed. 
 
 The total quantity of air expired, or, 
 what comes to the same thing, the 
 alteration in the capacity of the chest 
 during expiration, can be measured by 
 means of a gas-meter or of a spiro- 
 meter (Fig. 114), which consists of an 
 inverted graduated glass cyhnder dip- 
 ping by its open mouth into water 
 and balanced by weights. The vessel 
 is sunk till it is full of water, the air 
 being allowed to escape by a cock. 
 The expired air is now permitted to 
 enter it through a tube, and displaces 
 some of the water. The spirometer 
 is adjusted so that the level of the 
 water inside and outside is the same, 
 and then the volume of air contained in it is read off. This gives 
 the volume of the expired air at atmospheric pressure. Similarly, 
 by breathing air from the spirometer the amount inspired can be 
 measured (p. 303). 
 
 From 400 to 500 c.c. of air* are taken in and given out at each 
 respiration in quiet breathing. This is called tidal air. It amounts 
 to 35 pounds by weight 
 in twenty-four hours, 
 or enough to fill, at 
 atmospheric pressure, 
 a cubical box with a 
 side of 8 feet. With 
 the deepest possible in- 
 spiration room can be 
 made for 2,000 c.c. more ; this is called complemental air. By a forced 
 expiration 1,500 c.c. can be expelled besides the tidal air ; and to this 
 
 ♦ The average for 81 healthy students, with an average body-weight of 
 66 kilos, was 460 c.c, or 7 c.c. per kilo. In 4 new-born children the tidal air 
 varied from 20 to 30 c.c, and from 76 to 7' 3 c.c. per kilo, which is not very 
 different from the amount in the adult. The pulmonary ventilation must 
 therefore be far more rapid in the child, since its respiratory frequency is so 
 much greater. 
 
 Fig. 114. — Diagram of Spirometer. 
 A. vessel filled with water. B, 
 glass cylinder with scale C, 
 swung on pulleys and counter- 
 poised by weights W. D, tube 
 for breathing through. 
 
 y^tal I M///M//M Compkmntal air 
 
 . )mm. \ Rp.str7un? Oip 
 
 Fig. 115. — Diagram to illustrate the Relative Amoimt 
 of Complemental, Tidal, Supplemental, and Residual 
 Air. 
 
2j6 PKSPIRATIOK 
 
 quantity tne nami' •>{ supplemental or reserve air has ht-en given. 
 After the deepest expiratiun tlitrr always remains i.ooo to 1.200 c.c. 
 of air in the lungs (Durig), and this is railed the residual air. After 
 a normal expiration following a normal inspiration the lungs still 
 contain stationary air to the amount of about 2.500 c.c. 
 
 The term vital or respiratory capacity is ap])lied to the quantitx' 
 of air which can be expelled by the deepest expiration following the 
 deepest inspiration, and amounts in an adult of average height to 
 3,500 or 4.000 c.c. The maximum quantity of air which the lungs 
 can contain is evidently equal to vital capacity plus residual air. 
 At one time the vital capacity was thought to be capable of affording 
 valuable information in the diagnosis of chest diseases; but little 
 stress is now laid upon it, as it varies from so many causes. For 
 instance, it can be increased by practice with the spirometer. It is 
 greater in mountaineers than in the inhabitants of lowland plains. 
 
 The Dead Space. — It is clear from the figures we have given that in 
 ordinary breathing only a small proportion of the air in the lungs 
 comes in direct at each inspiration from the atmosphere, and only a 
 small proportion escapes into the atmosphere at each expiration. 
 The greater part of the air in the lungs is simply moved a little farther 
 from the upper respiratory passages, or a little nearer them; and 
 fresh oxygen reaches the alveoli, as carbon dioxide leaves them, 
 mainly by diffasion, aided by convection currents due to inequali- 
 ties of temperature, and to the churning which the alternate expan- 
 sion and shrinking of the lungs, and the pulsations of their arteries 
 must produce. But that some of the tidal air strikes right down 
 to the alveoli is evident enough. For the respiratory ' dead space ' 
 — that is, the capacity of the upper air-passages and the bronchial 
 tree down to the infundibula — -is only 140 c.c, or one-third of the 
 amount of the tidal air (Zuntz, Loewy). There is no direct way of 
 determining whether any respiratory exchange goes on through the 
 walls of the upper air-passages. But by indirect methods it has 
 been estimated that about 30 per cent, of the volume of the tidal air 
 is pure air (Haldane and Priestley). This, of course, corresponds 
 to the ' effective ' dead space. Taking the average tidal air at 
 4O0 c.c. (p. 235), it is clear that the effective corresponds very closely 
 with the anatomical dead space— that is to say, the respiratory 
 function of the air-passages above the point where the infundibula 
 are given off is negligible. Although such calculations can only b2 
 approximately correct, the agreement is of intere;ft. Some observers 
 have stated that great variations occur in the size of the dead space 
 with changes in the depth of respiration, its volume being increased 
 four or even eight times by very deep breathing. This, however, 
 is incorrect, although with maximum expansion of the lungs the 
 increase may amount to 100 c.c. (Krogh and Lindhard, Pearce). 
 
 The Amount and Variations of the Intrathoracic Pressure. — In 
 the deepi'St expiration the lung> are ncxcr con^pKlely ( <illaj)-ed: their 
 
MECHANICAL I'Ur.NOMnNA OI- EXTLRNAL hliSHl RAT l()\ j^ 
 
 clastic fibres are still stretched; and the tension of these acts in th<: 
 opposite direction to the external atmospheric pressure, and dimin 
 ishes by its amount the pressure inside the thoracic cavity. In tin 
 dead body Donders measured the value of this tension, and there- 
 fore of the negative pressure of the thorax, by tying a manometer 
 into the trachea, and then causing the lungs to collapse by opening 
 the chest. It varied from 7-5 mm. of mercury in the expiratory 
 position to 9 mm. in the inspiratory. So far as can be judged from 
 observations made on persons suffering from various diseases of the 
 respirator\' organs, the alterations during ordinary broathyig do not 
 
 Fig. 116. — Variations of Intrathoracic Pressure. Upper curve, carotid blood-pres- 
 sure (dog) lower curve, intrapleural pressure. At 4:: the trachea was closed ; 
 the blood-pressure curve shows the rise of asphyxia, and the intrapleural curve, 
 greatly exaggerated pressure variations due to the strong and slow but abortive 
 respirations. 
 
 amount to more than 3 or 4 mm. of mercury. But when an attempt 
 is made in the dead body to imitate a deep inspiration by making 
 traction on the chest walls so as to expand the lungs, the intra- 
 thoracic pressure may fall to —30 mm. of mercury; and in a living 
 rabbit, during a deep natural inspiration, a pressure of —20 mm. 
 has been seen. 
 
 The reason why the lungs collapse when the chest is opened is 
 that the pressure is now equal on the pleural and alveolar surfaces, 
 being in both cases that of the atmosphere. There is therefore 
 nothing to oppose the elasticity of the lungs, which tends to con- 
 tract them. So long as the chest is unopened, the pressure on the 
 pleural surface of the lungs is less than that on the alveolar surface 
 
238 RESPIRATION 
 
 and the elastic tension can only cause them to shrink until it just 
 balances this difference. 
 
 In intra-uterine hfe, and in stillborn cliildren who have never 
 breathed, the lungs arc completely collapsed (atelectatic), and there 
 is no negative intrathoracic pressure. They are kept in this con- 
 dition b}- adhesion of the walls of the bronchioles and alveoli. If 
 the lungs have been once inflated, this adhesion ceases to act, and 
 they never completely collapse again. 
 
 Amount and Variations of the Respiratory or Intrapulmonary 
 Pressure. — As we have already remarked, the pressure in the alveoli 
 and air-passages is less than that of the atmosphere while the in- 
 spiratory movement is going on, greater than that of the atmosphere 
 during the expiratory movement, and equal to that of the atmo- 
 sphere when the chest-walls are at rest. When the external air- 
 passages are closed— e.g., by connecting a manometer with the 
 mouth and pinching the nostrils — the greatest possible variations 
 of pressure are produced. In the deepest inspiration under these 
 conditions a negative pressure of about 75 mm. of mercury {i.e., a 
 pressure less than that of the atmosphere by this amount) has been 
 found, and in deep expiration a somewhat greater positive pressure* 
 (Practical Exercises, p. 304). 
 
 But with ordinary breathing, the variations of pressure as 
 measured by this method do not exceed 5 to 10 mm. of mercury 
 above or below the pressure of the atmosphere. 
 
 When the external openings are not obstructed, as, for example, 
 when the lateral pressure is taken in the trachea of an animal by 
 means of a cannula with a side-tube connected with a manometer, 
 still smaller, and doubtless truer, values have been found (2-3 mm. 
 of mercury as the positive expiratory pressure and i mm. as the 
 negative inspiratory pressure in dogs). But since the respiratory 
 passages are abruptly narrowed at the glottis, the variations of 
 pressure muit be greater below than above it, and in general they 
 must increase with the distance from that orifice, being greater, for 
 instance, in the alveoli than in the bronchi. 
 
 The mechanical phenomena of respiration having been described, 
 it might seem logical to consider next the nervous mechanism by 
 which the respiratory movements are controlled; but the regulation 
 of these movements through the nervous system is in so important 
 a degree a chemical regulation that it cannot be properly understood 
 without some knowledge of the chemical changes in the blood 
 associated with external and internal respiration. We therefore 
 pass to the consideration of — 
 
 * The maximum negative pressure in deepest inspiration averaged for ^g 
 students -73 mm. (highest observation - 137 mm.) of mercury; the maxi- 
 mum positive pressure in deepest expiration, -f- So mm. (highest observation 
 -f 140 mm.). 
 
Tiir. cnr.Mis] u'i or esti:u\'aj. ri.spi ration 230 
 
 Section III. — The Chemistry of External Respiration. 
 
 Our knowledge of this subject has been entirely acquired in the 
 last 200 years, and chiefly in the last century. 
 
 Boyle showed by means of the air-pump that animals die in a 
 Va;(!:uhm, and Bernouilli that fish cannot live in water from whirh 
 the air has been driven out by boiling. 
 
 Mayow, of Oxford, seems to a considerable extent to have antici- 
 pated Black, who in 1757 demonstrated the presence of carbonic 
 acid (carbon dioxide) in expired air by the turbidity which it causes 
 in lime-water. 
 
 A fundamental step was the discovery of oxygen by Priestley in 
 1771, and his proof that the venous blood could be made crimson, 
 like arterial, by being shaken up with oxygen. 
 
 Lavoisier discovered the composition of carbonic acid, and applied 
 his discovery to the explanation of the respiratory processes in 
 animals, the heat of which he showed to be generated, like that of a 
 candle, by the union of carbon and oxygen. He made many further 
 important experiments on respiration, publishing some of h:^ results 
 in 1789, when the French Revolution, in which he was to be one of 
 the most distinguished victims, was breaking out. He made the 
 mistake, however, of supposing that the oxidation of the carbon 
 takes place in the blood as it passes through the lesser circulation. 
 
 That some carbon dioxide is formed in the lungs there is no reason 
 to doubt, and the quantity may even be considerable. But that 
 they are not the chief seat of oxidation was sufficiently proved as 
 soon as it was known that the blood which comes to them from the 
 right heart is rich in carbon dioxide, while the blood which leaves 
 them through the pulmonary veins is comparatively poor. 
 
 There are two main lines on which research has gone in trying to 
 solve the chemical problems of respiration: (i) The analysis and 
 comparison of the inspired and expired air, or, in general, the in- 
 vestigation of the gaseous exchange between the blood and tlis air 
 in the lungs. (2) The analysis and comparison of the gases of 
 arterial and venous blood, of the other liquids, and of the solid 
 tissues of the body, with a view to the determination of the gaseous 
 exchange between the tissues and the blood. We shall take these 
 up as far as possible in their order. 
 
 The methods which have been used for comparing the composi- 
 tion of inspired and expired air and estimating the respiratory ex- 
 change are very various 
 
 (i) Breathing into one spirometer and out of another, the inspired 
 and expired air being directed by valves. The contents of the spiro- 
 meters are analyzed at the end of the experiment (Speck). In the 
 arrangement of Zuntz and Geppert, instead of the whole of the expired 
 air, a sample is collected for analysis during the entire duration of the 
 experiment, while the total volume expired is measured by a gas-meter. 
 This is a very convenient method for observations on man, especially 
 
2^o nr.spin.iTroN 
 
 ill (liscMMV but cacli (.xpciiment can only be airried on at most for 
 tilteen to twenty mmutcs. 
 
 (2) A small apparatus, much on the same principle, was used for 
 rabbits by Pfliigcr and his pupils. A cannula in the trachea was con- 
 nected with a balanced and self-adjusting spirometer containing oxygen, 
 and the inspired and expired air separated by potassium hydroxide 
 valves, which absorbed the carbon dioxide. The amount of oxygen 
 used could be read oft on the spirometer, and the amount of carbon 
 dioxide produced estimated in the liquid of the valves. 
 
 (3) Elaborate arrangements, such as Pettenkofer's great respiration 
 apparatus, and the still larger and more efficient modifications of it 
 constructed since his time, in which a man, or even several men, can 
 remain for an indefinite period, working, eating, and sleeping. Air is 
 drawn out of the chamber by an engine, its volume being measured 
 by a gas-meter. But as it would be far too troublesome to analyze 
 the whole of the air, a sample stream of it is constantly drawn off, which 
 also passes through a gas-meter, through drying-tubes containing 
 sulphuric acid, and through tubes filled with baryta water. The baryta 
 solution is titrated to determine the quantity of carbon dioxide ; the 
 increase in weight of the drydng tubes gives the quantity of aqueous 
 vapour. A similar sample stream of the air before it passes into the 
 chamber is treated exactly in the same way, and from the data thus got 
 the quantity of carbon dioxide and aqueous vapour given off can readily 
 be ascertained. The oxygen can be calculated, as the difference be- 
 tween the fijial body-weight and the original body-weight plus the 
 weight of the carbon dioxide and water eliminated, but may also be 
 directly estimated by special methods. 
 
 (4) Haldane and Pembrey have elaborated a gravimetric method, 
 which is very suitable for small animals. It depends upon the absorp- 
 tion of carbon dioxide by soda lime. (See Practical l-lxercises, p. 3^;.) 
 In Atwater's so-called respiration calorimeter, which will be referred to 
 again under ' Animal Heat.' and by which, not only the gaseous metab- 
 olism, but the heat production can be measured in man, the carbon 
 dioxide is estimated in the same way. 
 
 Inspired and Expired Air. — The expired air is at or near the body 
 temperature, and is saturated witli \\atcr\- \apour. In ordinary 
 breathing it contains about 4 per cent, of carbon dioxide, while the 
 inspired air only contains a trace. The expired air contains lO or 
 17 per cent, of oxygen, the inspired air about 21 per cent. There arc 
 in addition in expired air small quantities of hydrogen and marsh- 
 gas derived from the alimentary canal, either directly from eructa- 
 tion or after absorption into the blood. Sometimes a trace of 
 ammonia can be detected in the air of expiration, but this is due to 
 decomposition of proteins taking place in the mouth, especially in 
 carious +eeth, or in the air-passages and lungs in disease of these 
 organs. It has indeed been shown that the lungs are practically 
 impermeable for ammonia. Expired air is entirely free from float- 
 ing matter (dust), which is always present in the inspired air. The 
 volume of the expired air, owing to its higher temperature and ex- 
 cess of watery vapour, is somewhat greater than that of the inspired 
 air, but if it be measured at the temperature and degree of satura- 
 tion of the latter, the \olumc is somewhat less. Since the oxygen 
 of a given quantity of carbon dioxide would have exactly the same 
 
THE CHEMISTRY OE EXTERNAL EESPlR.lT lOK i.,i 
 
 volume as the carbon dioxide itself :\i a gi\en temperature and 
 pressure, it is clear that the deficienc}' is due to the fact that all th(; 
 oxygen which is taken up in the lungs is not given oft" as carbon 
 dioxide. Some of it, going to oxidize hydrogen, reappears as water. 
 
 Alveolar Air. — The percentage of carbon dioxide in the air of the 
 alveoli is of course greater and that of oxygen less than in the 
 ordinary expired air. lM)r the relatively pure air of the dead-space 
 makes up a substantial fraction of the tidal air. The mean of the 
 oxygen or carbon dioxide percentages in samples taken from the 
 last portions of the air of two deep expirations, one following an 
 ordinary inspiration and the other following an ordinary expiration, 
 corresponds fairly well with the mean percentage in the alveoli 
 during ordinary breathing. This method becomes untrustworthy 
 duiing muscular work. The average percentage of oxygen may 
 be taken as I4'5, corresponding to a partial pressure (p. 248) 
 of 109 mm, of mercury. The percentage of carbon dioxide in 
 the alveolar air with the body at rest is remarkably constant in one 
 and the same individual at constant atmospheric pressure. It 
 varies in different men from 4-6 to 6*2 (mean 5'5) per cent, of the dry 
 alveolar air. In women and in children of both sexes it is less than 
 in men. From this we conclude that in men the partial pressure 
 of carbon dioxide in the alveoli may be at least one-eighteenth of 
 an atmosphere, or 42 mm. of mercury (Fitzgerald and Haldane). 
 
 Respiratory Quotient. — The quotient of the volume of oxygen 
 given out as carbon dioxide by the volume of oxygen taken in is 
 the respiratory quotient. It shows what proportion of the oxygen 
 is used to oxidize carbon. It may approach unity on a carbo-hydrate 
 diet which contains enough oxgyen to oxidize all its own hydrogen 
 to water. With a diet rich in fat it is least of all; with a diet of 
 lean meat it is intermediate in amount. For ordinary fat contains 
 no more than one-sixth, and proteins not one-half, of the oxygen 
 needed to oxidize their hydrogen (p. 620). In man on a mixed diet 
 the respiratory quotient may be taken as 0*8 or O'Q. So long as the 
 type of respiration is not changed, the respiratory quotient may 
 remain constant for a wide range of metabolism. In hibernating 
 animals, however, the respiratory quotient may become very small 
 during winter sleep (as low as 0-25), both the output of carbon 
 dioxide and the c(jnsumption of oxygen falling enormously, but 
 the former in general more than the latter. This has been explained 
 on the assumption that oxygen is stored away in winter sleep in the 
 form of incompletely oxidized substances. On the other hand, in 
 dyspnoea accompanying muscular exertion the respiratory quotient 
 has been found as high as 1-2. It must be remembered that even 
 a voluntary increase in the respiratory movements causes an imme- 
 diate temporary increase in the respiratory quotient, owing to the 
 ' washing out ' of carbon dioxide from the blood and tissues. This 
 change has no metabolic significance. Indeed, the determination 
 
 i6 
 
-,i AV;.S7'/AM //O.V 
 
 of tlu" 'csijiratorv quotient for short periods has onl\ a limitrfl 
 \ ahic, and such ohscrvations must hv int('r])rctod with great can-. 
 Ill starvation the respiratory quotient diminislies, the production 
 of carbon dioxide falhiip; off at a greater rate than the consumption 
 of oxygen, for the starving organism hves on its own fat and pro- 
 teins, and has only a trifling carbo-hydrate stock to draw upon. 
 In a diabetic patient, fed on a diet of fat and protein alone, the 
 respinitory quotient was only o-6 to 07, just as in a starving man. 
 Total Respiratory Exchange. — The amount of oxygen absorbed in 
 a man at rest lias been determined under certain conditions as about 
 0-29 gramme per hour, and the discharge of carbon dioxide as about 
 0-33 gramme per hour per kilogramme of body- weight. In an 
 average man weighing 70 kilos the mean production of carbon 
 dioxide is about 800 grammes (400 litres) in twenty- four hours, and 
 the mean consumption of oxygen about 700 grammes (490 litres). 
 But there are very great variations depending upon the state of the 
 body as regards rest or muscular activity and on other circum- 
 stances. In hard work the production of carbon dioxide was foimd 
 to rise to nearly 1,300 grammes, and in rest to sink to less than 
 700 grammes, the consumption of oxygen in the same circumstances 
 increasing to nearly 1,100 grammes and diminishing to 600 grammes. 
 In rest, in moderate exertion, and in hard work, the production of 
 carbon dioxide was found to be nearly proportionate to the numbers 
 2, 3, and 6 respectively. When unaccustomed work is performed, 
 the increase in the carbon dioxide output (and oxygen intake) may 
 be much greater. With training it diminishes. In a case of diabetes 
 the consumption of oxygen was 50 per cent, greater than in a healthy 
 man, corresponding to the higher heat-equivalent of the food of 
 the diabetic patient. 
 
 Ventilation. — Taking 400 litres per twenty-four hours, or 17 litres 
 per hour, as the m-an production of carbon dioxide by an average male 
 adult at rest or doing only light work, we can calculate the quantity of 
 fresh air which must be supplied to a room in order to keep it properly 
 ventilated. 
 
 It has been found that when the carbon dioxide given off in respiration 
 amounts to no more than 2 parts in 10,000 in tTie air of an ordinary 
 room, the air remains sweet. When the carbon dioxide given off reaches 
 4 parts in 10,000, the room feels distinctly, and at 6 in 10,000 disagree- 
 ably, close, while at 9 parts in 10,000 it is oppressive and almost in- 
 tolerable. This is not due to the carbon dioxide as such, for pure 
 carbon dioxide added alone in similar proportions to the air of a room 
 has not the same bad effect, and the amount of this gas is onlv taken 
 as an index of the extent to which the air has been vitiated by some 
 other products or processes connected with the occupation of the 
 room. Very often the mere rise of temperature in a crowded and ill- 
 ventilated space is sufficient to induce dis.igroeablc symptoms, especially 
 as it is inevitably associated with an ijicrcase in the humidity of the 
 air, which reduces the capacity of the body to cool itself by increasing 
 the secretion of sweat. Thus it has been found that persons in a 
 respirator)' chamber feel quite comfortable with only moderate ventila- 
 tion when the carbon dioxide has risen to i per cent., if care is taken 
 
THt- Ctn:.\flSTRY OF EXThUKAL RESP]UATIOS 243 
 
 that the temperature and the proportion of water\' vapour do not rise 
 too high. In aildition, however, it has been supposed by some that a 
 volatile poison exhaled from the lungs is j>eculiarly responsible for the 
 evil effects. Certain observers, indeed, alleged that the condensed 
 vapour of the breath, when injected into rabbits, produced fatal symp- 
 toms. But this has been shown to be erroneous; and the most careful 
 experiments have failed to detect in the air expired by healthy persons 
 any trace of such a poison. It has therefore been suggested that the 
 odour and some of the other ill-effects of a close room are due to sub- 
 stances given off in the sweat and the sebum, and allowed by persons 
 of uncleanly habits to accumulate on the skin, and also to the products 
 of slow putrefactive processes constantly going on, under favourable 
 conditions, on the walls, fioor, or furniture, but only becoming per- 
 ceptible to the sense of smell when ventilation is insufficient. In a 
 small, newly-painted chamber, presumably free from such impurities, 
 it was not until the carbon dioxide reached 3 to 4 per cent., an immensely 
 greater proportion than occurs even in very badly ventilated rooms, 
 that marked discomfort, with dyspnoea, began to be felt. No close 
 odour could be detected. 
 
 Nevertheless, experience has shown that it is a good working rule for 
 ventilation to take the limit of permissible respiratory impurity at 
 2 parts of carbon dioxide per 10,000; and the 17 litres of carbon dioxide 
 given off in tke hour will require 85.000 Litres (or 3,000 cubic feet) of 
 air to dilute it to this extent. This is the average quantity required 
 for the male adult per hour. For men engaged in active labour, as in 
 factories or mines, twice this amount may not be too much. For 
 women and children less is required than for men. If a room smells 
 close, it needs ventilation, whatever be the proportion of carbon dioxide 
 in the air. It must be remembered that in permanently occupied 
 rooms mere increase in the size will not compensate for incomplete 
 renewal of the air, although it may be easier to ventilate a large room 
 than a small one ■without causing draughts and other inconveniences. 
 But as few apartments are occupied during the whole twenty-four hoiirs, 
 a large room which can be thoroughly ventilated in the absence of its 
 inmates has a distinct advantage over a small one in its great initial 
 stock of fresh air. The cubic space per head in an ordinan- dwelling- 
 house should be not less than 28 cubic metres or 1,000 cubic feet. 
 
 The quantity of carbon dioxide given off (and of oxygen consumed) 
 is not onl}' affected by muscular work, but also by everything which 
 influences the general metabolism. In males it is greater on the 
 average than in females (in the latter there is a temporary increase 
 during pregnancy), but for the same body- weight and under similar 
 external conditions there is no difference between the sexes. The 
 gaseous exchange is greater in proportion to the body-weight in the 
 child than in the adult. This depends largely on the fact that, 
 other things being equal, the metabolism is relatively to the body- 
 weight more active in a small than in a large organism, since 
 the surface (and therefore the heat loss) is relatively greater in the 
 former. But it has been shown that even in proportion to the 
 surface the metabolism is greater in youth than in adult life, and 
 greater in the vigorous adult than in the old man. So that the age 
 of the organism has an influence apart from the extent of surface. 
 The taking of food increases the gaseous exchange, partly from the 
 
244 
 
 RESPinATION 
 
 increased mechanical and chemical work performed by the aU- 
 mentary canal and the cHj^'estive glands. But that this is not the 
 sole cause of the increase is shown by the fact that it varies with 
 different kinds of food to a greater extent than can be explained 
 by differences in the ease with which they are digested. For in- 
 stance, maize produces a much greater increase than oats when 
 given in equal amount, and a protein diet a greater increase than a 
 diet of carbo-hydrate or fat. Sleep diminishes the production of 
 carbon dioxide partly because the muscles are at rest, but also to 
 .some extent because the external stimuli that in waking life excite 
 the nerves of special sense are absent or ineffective. Even a bright 
 light is said to cause an increase in the aonount of carbon dioxide 
 produced and of ox3-gen consumed; but probably only by increasing 
 muscular movements, including the movements of respiration. 
 The external temperature also has an influence. In poikilothermal 
 animals (such as the frog), the temperature of which varies with 
 that of the surrounding medium, the production of carbon dioxide, 
 on the whole, diminishes as the external temperature falls, and 
 increases as it rises. In homoiothertnal animals, that is, animals 
 with constant blood temperature, external cold increases the pro- 
 duction of carbon dioxide and the consumption of oxygen. But if 
 the connection of the nervous system with the striated muscles has 
 been cut out by curara, the warm-blooded animal behaves like the 
 cold-blooded (Pfliiger and his pupils in guinea-pig and rabbit). 
 These interesting facts will be returned to under ' Animal Heat.' 
 
 Cold-blooded animals produce far less carbon dioxide, and con- 
 sume far less oxygen, per kilo of body-weight than warm-blooded. 
 
 The following table shows the relation between the body-weight 
 and the excretion of carbon dioxide in man : 
 
 Age. 
 
 1 
 
 MI- • u. • VI COo excreted per Kilo 
 Weight in K.los. per Hour. 
 
 Male 
 
 f58 
 
 44 
 
 35 
 
 ^8 
 
 i6 
 I 9-6 
 
 84'6 0'4i gramme 
 76'5 0-48 
 65 " 0-51 
 82 0-49 
 
 577 0-59 .. 
 22 0*92 
 
 r66 
 
 Female a ^ 
 
 iio 
 
 66-9 
 
 53-9 
 557 
 23 
 
 0-39 
 0-54 
 0-45 
 083 .. 
 
 The next table illustrates the difference in the intensity of metab- 
 olism in different kinds of animals, a difference, however, largely 
 dependent upon relative size: 
 
Tin: Cin-MISTRY OF F.XTERNAL RESPIRATION 
 
 245 
 
 
 Oxygen absorbed per 
 kilo per Hour. 
 
 Carbon Dioxide given off 
 per Kilo per Hour. 
 
 
 
 Respiratory Quotient 
 
 Animal. 
 
 
 
 
 CO2 Oj (in CO2) 
 
 
 Id Grms. 
 
 In C.C. 
 
 In Grms. 
 
 In C.C. 
 
 Ol°' ~02~- 
 
 Greenfincli - 
 
 I V<JOO 
 
 9091 
 
 13-590 
 
 6909 
 
 0-76 
 
 Hen - 
 
 1-058 
 
 740 
 
 1-327 
 
 675 
 
 0-91 
 
 Dog - 
 
 1-303 
 
 911 
 
 1-325 
 
 674 
 
 074 
 
 Rabbit 
 
 o-()87 
 
 690 
 
 1-244 
 
 632 
 
 0-91 
 
 Sheep - 
 
 0-490 
 
 343 
 
 0-671 
 
 .341 
 
 0-99 
 
 Boar - 
 
 0-39I 
 
 ^73 
 
 0-443 
 
 2-25 
 
 0-82 
 
 Frog - 
 
 0-105 
 
 73-4 
 
 0-II3 
 
 57-7 
 
 0-78 
 
 Crayfish 
 
 0-054 
 
 38 
 
 0-0O4 
 
 32-7 
 
 0-86 
 
 Forced respiration, although it will temporarily increase the 
 quantity of carbon dioxide given off by the lungs, and thus raise 
 for a short time the respiratory quotient, does not sensibly affect 
 the production ; it is only the store of already formed carbon dioxide 
 in the body which is drawn upon. The amount of oxygen taken 
 up is little altered by changes in the movements of respiration. 
 Within wide limits the oxygen consumption of the organism is in- 
 dependent of the supply of oxygen offered to it. 
 
 How it is that the depth of the respiration may affect the rate at 
 which carbon dioxide is eliminated, we can only understand when 
 we have examined the process by which the gaseous interchange 
 between the blood and the air of the alveoli is accomplished; and 
 before doing this it is necessary to consider the condition of the 
 oxygen and carbon dioxide in the blood. 
 
 Section IV. — ^The Gases of the Blood. 
 
 Physical Introduction. — Matter may be assumed to be made up of 
 molecules beyond which it cannot be divided without altering its essen- 
 tial character. A molecule may consist of two or more particles of 
 matter (atoms) bound to each other by chemical links. The kinetic 
 theory of matter supposes the molecules of a substance to be in constant 
 motion, frequently colliding with each other, and thus having the direc- 
 tion of their motion changed. 
 
 In a gas the mean free path, that is, the average distance which a 
 molecule travels without striking another, is comparatively long, and 
 far more time is passed by any molecule without an encounter than is 
 taken up with collisions. Although the average velocity of the mole- 
 cules is very great, these collisions will produce all sorts of differences 
 in the actual velocity of different molecules at any given time. Some 
 will be moving at a greater, some at a slower rate, than the average; 
 while some may be for a moment at rest. If the gas is in a closed 
 vessel, the molecules will be constantly striking its sides and rebounding 
 from them. If a ver}' small opening is made in the vessel, some mole- 
 cules will occasionally hit on the opening and escape altogether. If the 
 opening is made larger, or the experiment continued for a longer time 
 
24<5 prspiRATTny < 
 
 with the small opening, all the molecules will in course of time have 
 passed out of the vessel into the air, while molecules of the oxygen, 
 nitrogen, and argon of the air will have passed in. In a gas, then, not 
 enclosed by impenetrable boundaries, there is no restriction on the path 
 which a molecule may take, no tendency for it to keep within any limits. 
 
 When two chemically indifferent gases are placed in contact with each 
 other, diffusion will go on till they are uniformly mixed. The diffusion 
 of gases may be illustrated thus. Suppose we have a perfectly level 
 and in every way uniform field di\idcd into two equal parts by a visible 
 but intangible line, the well-known whitewash line, for instance. On 
 one side of the line place 500 blind men in green, and on the other 500 
 blind men in red. At a given signal let them begin to move about in 
 the field. Some of the men in green will pass over the line to the ' red ' 
 side; some of the men in red will wander to the ' green ' side. Some 
 of the men may pass over the line and again come back to the side 
 they started from. But, upon the whole, after a given interval has 
 elapsed, as many green coats will be seen on the red side as red coats 
 on the green. And if the interval is long enough there will be at length 
 about 250 men in red and 250 in green on each side of the boundary- 
 line. WTien this state of equilibrium has once been reached, it will 
 henceforth be maintained, for, upon the whole, as many red uniforms 
 will pass across the line in one direction, as will recross it in the other. 
 
 In a liquid it is very different ; the molecule has no free path. In the 
 depth of the liquid no molecule ever gets out of the reach of other 
 molecules, although after an encounter there is no tendency to return on 
 the old path rather than to choose any other; so that any molecule 
 may wander through the whole liquid. Although the average velocity 
 of the molecules is much less in the liquid state than it would be for 
 the same substance in the state of gas or vapour (gas in presence of its 
 liquid), some of them may have velocities much above the average. 
 If any of these happen to be moving near the surface and towards it, 
 they may overcome the attraction of the neighbouring molecules and 
 escape as vapour. But if in their further wanderings they strike the 
 liquid again, they may again become bound down as liquid molecules. 
 And so a constant interchange may take place between a liquid and its 
 vapour, or between a liquid and any other gas, until the btate of equi- 
 librium is reached, in which on the average as many molecules leave the 
 liquid to become vapour as are restored by the vapour to the liquid, or as 
 many molecules of the dissolved gas escape from solution as enter into it. 
 
 For the sake of a simple illustration, let us take the case of a shallow 
 vessel of water originally gas-free, standing exposed to the air. It will 
 be found after a time that the water contains the atmospheric gases in 
 certain proportions — in round numbers, about yjjj of its volume of 
 oxygen and -^q of its volume of nitrogen (measured at 760 mm. mercury 
 and 0° C). 
 
 Now, let a similar vessel of gas-free water be placed in a large airtight 
 box filled with air at atmospheric pressure, and let the oxygen be all 
 absorbed before the water is exposed to the atmosphere of the box. 
 The latter now consists practically only of the nitrogen of the air, and 
 its pressure will be only about four-fiiths that of the external atmo- 
 sphere. Nevertheless, the quantity of nitrogen absorbed by the water 
 will be exactly the same as was absorbed from the air. If the box 
 was completely exhausted, and then a quantity of oxj'gen, equal to that 
 in it at first, introduced before the water was exposed to it, the pressure 
 would be found to be only about one-fifth that of the external atmo- 
 sphere ; but the quantity of oxygen taken up by the water would be 
 exactly equal to that taken up in the first experiment. 
 
Till'. GASFs Of Tin: isr.OOD 
 
 2.17 
 
 Two well-known physical laws are illustrated by our supposed ex- 
 periments: (i) In a mixture of gases which do not act chemically on each 
 other the pressure exerted by each gas {called the partial presstire of the 
 gas) is the same as it ivould exert if the others were absent. (2) The quan- 
 tity {mass) of a gas absorbed by a liquid which does not act chemically upon 
 it is proportional to the partial pressure of the gas. It also depends upon 
 the nature of the gas and of the liquid, anil on the temperature, increase 
 of temperature in general diminishing the quantity of gas absorbed. 
 It is to be noted that when the volume of the absorbed gas is measured 
 at a pressure equal to the partial pressure under which ii was absorbed, 
 the same volume of gas is taken up at every pressure. 
 
 The volume of a gas (reduced to 0° C. and 760 mm. pressure) physi- 
 cally' absorbed or dissolved in i c.c. of a liquid exposed to the gas at 
 760 mm. pressure is called the absorption coefficient of the gas in that 
 liquid. The following table from Bohr shows the absorption coefficients 
 of the three gases of physiological interest— oxygen, nitrogen, and 
 carbon dioxide in water, blood-plasma, whole blood and blood-corpuscles 
 at the body temperature (38° C.) : 
 
 Water 
 
 Blood-plasma 
 Blood - 
 Blood-cells - 
 
 Oxygen. 
 
 0-0237 
 0-023 
 0-022 
 0-019 
 
 Nitrogen. 
 
 0-0122 
 O-0I2 
 O-OII 
 O-OIO 
 
 Carbon Dioxide. 
 
 o'555 
 0-541 
 0-511 
 
 0-450 
 
 Suppose, now, that a vessel of water, saturated with oxygen and 
 nitrogen for the partial pressures under which these gases exist in the 
 air, is placed in a box filled with pure nitrog<-n at full atmospheric pres- 
 sure. As we have seen, there is a constant interchange going on between 
 a liquid which contains gas in solution and the atmosphere to which it 
 is exposed. Oxygen and nitrogen molecules will therefore continue to 
 leave the water; but if the box is large, few oxygen molecules will find 
 their way back to the water, and ultimately little oxygen will remain 
 in it. In other words, the quantity of oxygen absorbed by the water 
 will become again proportional to the partial pressure of oxygen, which 
 is not now much above zero. On the other hand, molecules of nitrogen 
 will at first enter the water in larger number than they escape from it, 
 for the pressure of the nitrogen is now that of the external atmosphere, 
 of which its partial pressure was formerly only four-fifths. In unit 
 volume of the gas above the water there will be 5 molecules of nitrogen 
 for every 4 molecules in the same volume of atmospheric air. There- 
 fore, on the average 5 nitrogen molecules will in a given time get en- 
 tangled by liquid molecules for every 4 which came within their sphere 
 of attraction before. On the whole, then, the water will lose oxygen 
 and gain nitrogen, while the atmosphere of the airtight box will gain 
 oxygen and lose nitrogen. 
 
 In the case of water, in which oxygon and nitrogen are absorbed 
 solely in solution, the partial pressures of these gases under which the 
 water was originally saturated could, of course, be easily calculated 
 from the amount dissolved and the ccefficient of absorption. But 
 supposing that these partial pressures were unkno^\^l, it is evident that 
 by exposing it to an atmosphere of known composition, and afterwards 
 determining the changes produced m the composition of that atmo- 
 
248 
 
 RKSPIRA TION 
 
 w^ w^ 
 
 sphere by loss to. or gain from, the gases of the water, wc could find out 
 something about the original partial pressures. If, for example, the 
 quantity of oxygen in the atmospliere or the 
 chamber was increased, we could conclude that 
 the jiartial pn ssure of oxygen under which the 
 water had been saturated was greater than 
 that in the chamber at the beginning of the 
 expcrmient. And if we found that with a 
 certain partial pressure of oxygen in the atmo- 
 sphere of the chamber there was neither gain 
 nor loss of this gas, we might be sure that the 
 partial pressure (the temperature l)cing sup- 
 posed not to vary) was the same when the 
 water was saturated. We shall see later on 
 how this principle has been applied to deter- 
 mine the partial ])ressure of oxygen or carbon 
 dioxiile which just suffices to prevent blood, or 
 any other of the liquids of the body, from 
 losing or gaining these gases when they are not 
 merely dissolved, but also combined in the 
 form of dissociable compounds. This pressure 
 is evidently equal to that exerted by the gases 
 of the licjuid at its surface, which is sometimes 
 called their ' tension ' ; for if it were greater, 
 gas would, upon the whole, pass into the blood ; 
 and if it were less, gas would escape from the 
 blood. Thus, the tension of a gas in solution in 
 a liquid is equal to the partial pressure of that 
 gas in an atmosphere to which the liquid is ex- 
 posed, which is just sufficient to prevent gain or 
 loss of the gas by the liquid (p. 258). 
 
 The following imaginary experiment may 
 further illustrate the meaning of the term ' ten- 
 sion ' of a gas in a lic[uid in this connection. 
 
 Suppose a cylinder filled with a liquid con- 
 taining a gas in solution, and closed above by 
 a piston moving airtight and without friction, 
 in contact with the surface of the liquid (Fig. 
 117). Let the weight of the pi.ston be balanced 
 by a counterpoise. The pressure at the sur- 
 face of the liquid is evidently that of the 
 atmosphere. Now, let the whole be put into 
 the receiver of an air-pump, and the air 
 gradually exhausted. Let exhaustion proceed 
 until gas begins to escape from the licpiid and 
 lies in a thin Uiycr between its surface and the 
 piston, the quantity of gas whicli has become 
 free being very small in proportion to that 
 still in solution. At this point the piston is 
 acted upon by two forces which balance each 
 other, the pressure of the air in the receiver 
 acting downwards, and the pressure of the gas 
 escaping from the liquid acting upwards. If 
 the pressure in the receiver is now slightly 
 increased, the gas is again absorbed. The pressure at which this ju.st 
 happens, and against which the pi.ston is still supported by the impacts 
 of gaseous molecules flying out of the liquid while no pressure is as yet 
 
 Fig. ii/- — Imaginary Ex- 
 periment to illustrate 
 ' Tension ' of a Gas in a 
 Liquid. P, frictionless 
 piston; L, liquid in cy- 
 linder; G, gas beginning 
 to escape from litjuid. 
 P is exactly counter- 
 poised. In addition to 
 the manner described in 
 the text, the experiment 
 may be supposed to be 
 j)ertormed thus: Let the 
 weight, \V, be deter- 
 mined which, when the 
 receiver is completely 
 exhausted, suffices just to 
 keep the pi" on in contact 
 with the litpiid. The 
 pressure of the gas is 
 then just counter- 
 I)alanced by W; and if 
 S is the area of the cross- 
 section of the piston, the 
 jiressure of the gas per 
 
 W 
 
 unit of area is j^. Or, if 
 
 the piston is hollow, and 
 mercury is poured into 
 it so as just to keep it in 
 contact with the liquid, 
 the height of the column 
 of mercury required is 
 also equal to the pressure 
 or tension of the gas. 
 
TIIF GASES or THE BI.OOD 
 
 249 
 
 exerted dirci tly Ixtwicii the liquid and the piston, is obviously equal 
 to the pressure or tension of the gas in the Uquid. 
 
 From the above principles it follows that a gas held in solution may 
 be extracted by exposure to an atmosphere in which the partial pressure 
 of the gas is niade as small as possible. Thus, oxygen can be obtained 
 from liquids in which it is simply dissolved by putting them in an 
 atmosphere of hydrogen or nitrogen, in which the partial pressure of 
 oxygen is zero, or in the vacuum 01 an air-pump, in which it is extremely 
 small. Heat also aids the expulsion of dissolved gases. Some gases 
 held in weak chemical union, like the loosely-combined oxygen of 
 oxyluemoglobin, can be obtained by dissociation of their compounds 
 
 Fig. 118.— Scheme of Gas-Pump. \. the blood 
 bulb; B. the froth chamber; C, the drying tube; 
 U. fixed mercury bulb ; E. movable mercury 
 bulb connected by a flexible tube with D; F, 
 eudiometer; G, a narrow delivery tube; i. 2, 3, 4. 
 taps, 4 being a three-way tap. A is filled with 
 blood by connecting the tap i by means of a 
 tube with a bloodvessel. Taps i and 2 are then 
 closed. The rest of the apparatus from B to D is 
 now exhausted by raising E, with tap 4 turned 
 so as to place D only in communication with G, 
 till the mercury fills D. Tap 4 is now turned so as 
 to connect C with D, and cut off G from D, and E 
 is lowered. The mercury passes out of D, and air 
 passes into it from B and C. Tap 4 is again turned 
 so as to cut off C from D and connect G and D. E 
 is raised and the mercury passes into D and forces 
 the air out through G, the end of which has not 
 hitherto been placed under F. This alternate 
 raising and lowering of E is continued till a man- 
 ometer connected between C and 4 indicates that 
 the pressure has been sufficiently reduced. The 
 tap 2 is now opened; the gases of the blood bubble up into the froth chamber, pass 
 through the drying-tube C, which is filled with pumice-stone and sulphuric acid, and 
 enter D. The end of G is placed under the eudiometer F, and by raising E. with 
 tap 4 turned so as to cut off C, the gases are forced out through G and collected 
 m F. The movements required for exhaustion can be repeated several times till 
 no more gas comes off. The escape of gas from the blood is facilitated by immersing 
 the bulb A in water at 40" to 50° C. 
 
 when the partial piessure is reduced. More stable combinations may 
 require to be broken up by chemical agents — carbonates, for instance, 
 by acids. 
 
 Extraction of the Blood-Gases. — This is best accomplished by ex- 
 posing blood to a nearly perfect vacuum. The gas-pumps which have 
 hztn most largely used in blood analysis are constructed on the principle 
 of the Torricellian vacuum. A diagram of a simple form of Pfliiger's 
 gas-pump is given in Fig. 118. The gases obtained are ultimately dried 
 and collected in a eudiometer, which is a graduated glass tube with i.^s 
 mouth dipping into mercury. The carbon dioxide is estimated by 
 introducing a little potassium hydroxide to absorb it. The diminution 
 in the volume of the gas contained in the eudiometer gives the volume 
 of the carbon dioxide. The oxygen may be estimated by putting into 
 the eudiometer more than enough hydrogen to unite with all the oxygen 
 so as to form water, and then, after reading ofif the volume, exploding 
 the mixture by means of an electric spark passed through two platinum 
 wires fused into the glass. One-third of the diminution of volume 
 represents the quantity of oxygen present. It can also be estimated 
 
250 ruspiration 
 
 by absorption \vith a solution of pyrogallic acid anil potassium hyiliox- 
 ide, or an alkaline solution of sodium hydrosulplute, which is more 
 cleanly. The remainder of the original mixture of blood-gases, after 
 deduction of the carbon dioxide and oxygen, is put down as nitrogen 
 (with, no doubt, a small proportion of argon). l"or the sake of easy 
 comparison, the observed volume of gas is always stated in terms of its 
 equivalent at a standard pressure and temperature (7()o mm., or some- 
 times on the C(jntinent i metre of mercury, and o C). 
 
 It is also possible in various ways to estimate the amount of oxygen 
 in blood without the use of the pump. Thus, since a definite volume of 
 oxygen (1338 c.c. at 0° C. and 760 mm. pressure) combines with a 
 gramme of h?cmoglobin, we can calculate the total volume of oxygen 
 present if we know how much of the blood-pigment is in the form of 
 oxyha>moglobin ; and this can be determined by means of the spectro- 
 photometer. Or potassium fcrricyanidc may be added to the blood. 
 This expels the oxygen from its combination witii the hanioglobin, 
 which then unities with an exactly equal amount of oxygen obtained 
 from the ferricyanide to form methiemoglobin (Haldane) (p. 75). 
 
 In the hands of Barcroft and his pupils this method has been highly 
 developed, so that accurate results can be obtained with small quantities 
 of blood (i c.c, and with the smaller apparatus even o-i c.c.). Bar- 
 croft's differential apparatus consists essentially of two small bottles, 
 as nearly alike as possible, connected by a manometer filled with oil (of 
 cloves). The amount of oxygen liberated in one of the bottles by 
 potassium ferricyanide from a measured amount of blood can be est-t- 
 mated from the displacement of the liquid in the manometer. Tlie 
 function of the second bottle is to automatically eliminate effects due 
 to changes in the temperature of the bath in which the apparatus is 
 immersed, etc., since bf)th bottles are affected alike. 
 
 The Quantity of the Blood-Gases. — In arterial and in venous blood 
 oxygen, carbon dioxide, nitrogen, and argon are constantly found. 
 Both the oxygen and the carbon dioxide vary considerably in 
 amount in the arterial blood, even of individuals of the same animal 
 group, and, of course, much more in the venous blood, as might 
 naturally be expected, since even to the eye it varies greatly accord- 
 ing to the vein it is obtained from, the rapidity of the circulation, 
 and the activity of the tissues whicli it has just left. In one 
 observation on blood obtained directly from a human artery, 2i'6c.c. 
 of oxygen, 40*3 c.c. of carbon dioxide, and !•() c.c of nitrogen were 
 found in 100 c.c. of blood. Tlie quantity of oxygen taken up outside 
 of the body by specimens of human blood drawn from six normal 
 persons, when shaken up with atmospheric air, varied from 1 7-6 c.c. 
 to 22-5 c.c. per 100 c.c. of blood, the variations depending mainly 
 on the hgemoglobin content. The arterial blood as it actually left 
 the lungs of those persons must have contained somewhat less oxygen 
 (about I c.c. less per 100 c.c. of blood), since the partial pressure of 
 oxygen in the alveolar air is decidedly below that in atmospheric 
 air. In dogs the amount of carbon dioxide in arterial blood has 
 been found to vary from 35 to 45 c.c. per 100 c.c. of blood, the 
 differences being due to variations in the extent of the pulmonary 
 ventilation and to other factors. 
 
TIIIl gases Ol- iHE IIUJOD 231 
 
 In a scries of observations on the venous blood of dogs the oxygen 
 content ranged from 5-5 to i6-6c.c. (average ii-gc.c), and the carbon 
 dioxide content from 38-8 c.c. to 47-5 (average 44-3 c.c.) per 100 c.c. 
 of blood (Schoffer). It will be sufficiently accurate to assume that 
 on the average, 
 
 Volumes of 
 
 O2. COi;. N2. 
 
 too volumes of arterial blood yield - - 20 40 1-2 
 
 „ ,, mixed venous blood (from 
 
 right heart) yield 10-12 45-50 1-2 
 
 (reduced to 0° C. antl -Oo mm. of mercury). 
 
 Average venous blood contains 7 or 8 per cent, by volume less 
 oxygen, and 7 or 8 per cent, more carbon dioxide, than arterial 
 blood. Thus, in the lungs the blood gains about twice as many 
 volumes of oxygen per cent, as the air loses, and the air gains about 
 half as many volumes of carbon dioxide per cent, as the blood loses. 
 It is easy to see that this must be so, for the volume of air inspired 
 in a given time is about twice as great as that of the blood which 
 passes through the pulmonary circulation (pp. 223, 236). Even 
 arterial blood is not quite saturated with oxygen; it can still take 
 up a variable small amount. The percentage saturation with 
 oxygen of the arterial blood of a normal woman from whom 
 blood was being transfused into a patient was directly determined. 
 The blood proved to be 94 per cent, saturated — i.e., it could still 
 have taken up about one-sixteenth of the quantity contained in 
 it. Nor is venous blood nearly saturated with carbon dioxide; 
 when shaken with the gas it can take up about 150 volumes per cent. 
 
 The total oxygen capacity of the blood in any individual can be 
 determined, if the volume of the blood is known (p. 56), by estimating 
 the amount of oxygen needed to saturate a sample of the blood. 
 This is most conveniently done by the ferricyanide method mth 
 Barcroft's apparatus. Suppose, for example, that i c.c. of blood, 
 after being thoroughly shaken up with air or oxygen, gives off 
 0-2 c.c. of oxygen when acted upon by ferricyanide, and that the 
 total volume of the blood has been determined to be 5 litres, then 
 the total oxygen capacity of the blood will be 1,000 c.c. This 
 quantity, it is clear, is a measure of the power of the blood to trans- 
 port oxygen. The oxygen capacity of a sample of blood is propor- 
 tional to the amount of haemoglobin in it, so that the estimation of 
 the percentage amount of haemoglobin by a properly standardized 
 hsemoglobinometer is really an estimation of the oxgyen capacity of 
 the quantity of blood used for the determination. The total oxygen 
 capacity of the body cannot, of course, be derived from such an 
 observation, any more than the total quantity of haemoglobin, unless 
 the amount of blood in the body is known. 
 
 When the gases are not removed from blood immediately after 
 
252 RESPIRATION 
 
 it is drawn, it yields more carbon dioxide and less oxygen than if it 
 is evacuated at once (Pfliigcr). From this it is concluded that 
 oxidation g(X's on in the blood for some time after it is shed. The 
 oxidizable substances are, however, confined to the corpuscles, 
 which suggests that ordinary metabolism simply continues for 
 some time in the formed elements of the shed blood, and that the 
 disappearance of oxygen is not due to the oxidation of substances 
 which have reached the blood from the tissues. It is an interesting 
 fact that the rate of oxygen consumption of nucleated (bird's) ery- 
 throcytes is much greater than that of non-nucleated mammalian 
 corpuscles. The young non-nucleated erythrocytes, which in experi- 
 mental aniemia in manmials [e.g., after hiemorrhage) find their way 
 in large numbers into the circulation, have a relatively intense 
 metabolism, and therefore consume a relatively large amount of 
 oxygen. 
 
 The Distribution and Condition of the Oxygen in the Blood. — ^The 
 oxygen is nearly all contained in the corpuscles. A little oxygen 
 can be pumped out of serum (o-2 or o«3 per cent, by volume), but this 
 follows the Henry-Dalton law of pressures — that is, it comes off in 
 proportion to the reduction of the partial pressure of the oxygen in 
 the pump, and is simply in solution. 
 
 \\lien blood at body temperature is shaken up with air at the 
 ordinary pressure, corresponding to a partial pressure of oxygen 
 of a little over one-fifth of an atmosphere (in round numbers i6o mm. 
 of mercury), the blood-pigment becomes saturated with oxygen or 
 nearly so. When the blood is now pumped out, very little oxygen 
 ( omes off till the pressure has been reduced to about half an atmo- 
 sphere, corresponding to a pressure of oxygen of about 80 mm. 
 At about 70 mm. partial pressure the dissociation is somewhat 
 greater. At a third to a quarter of an atmosphere (50 to 40 mm.'; 
 the amount of oxygen liberated is markedly increased, and the dis- 
 sociation becomes more and more rapid as the pressure falls to- 
 wards zero. This behaviour shows that the oxygen is not simply 
 absorbed, but is united, as a dissociable compound, to some con- 
 stituent of the blood. The same thing is, of course, seen when 
 defibrinated blood is saturated at body temperature with oxygen at 
 different pressures. As the partial pressure of the gas is increased 
 from z.ero the first increments of pressure correspond to a much 
 greater absorption of oxygen than further equal increments. Thus 
 as is seen in Fig. 120, with an oxygen pressure of 10 mm. 100 c.c. 
 of blood took up 6 c.c. of oxygen, or 30 per cent, of the amount 
 required to saturate it. When the pressure of oxygen was 30 mm. 
 over 16 c.c. of oxygen was absorbed, the blood being 80 per cent, 
 saturated. A further increase of the oxygen pressure to 40 mm. 
 increased the quantity of the gas taken up by only 2 c.c. (to 90 per 
 cent, saturation). TL^ uext increment of 10 mm. in the oxygen 
 
THE GASES 01' THE BLUOD 
 
 253 
 
 pressure only produced an additional absorption of i c.c, and above 
 this increasing the pressure had very little effect. 
 
 We may suppose that at the ordinary tcnipcralurc and pressiire 
 some oxygen is rontinually escaping from the bonds bv which it is tied 
 to the haemoglobin: but, on the whole, an equal number of free mole- 
 cules of oxygen, coming within the range of the haemoglobin molecules, 
 are entangled by them, an 1 thus ecpiiiibriuni is kept up. If now the 
 atmospheric pressure, ard therefore the partial pressure of oxygen 
 is reduced, the tendency 
 
 of the oxygen to break 
 off from the haemoglobin 
 will be unchanged, and as 
 many molecules on the 
 whole will escape as before ; 
 but even after a consider- 
 able reduction of pressure 
 the haemoglobin, such is its 
 avidity for oxygen, will still 
 be able to seize as much 
 oxygen as it loses. The 
 more, however, the partial 
 pressure of the oxygen is 
 diminished — that is to say, 
 the fewer oxygen molecules 
 there are in a given space 
 above the haemoglobin — • 
 the smaller will be the 
 chance of the loss being 
 made up by accidental cap- 
 tures. At a certain pressure 
 the escapes will become 
 conspicuously more numer- 
 ous than the captures ; and 
 the gas-pvimp will giv-e evi- 
 dence of this. The higher 
 the temperature of the 
 haemoglobin is, the greater 
 will be the average yelocitj' 
 of the molecules, and the 
 
 ■•e-cc'^tage of Oxvac 
 
 1 J 2 
 
 6 3 9 5 ? C 
 
 •. ; 8 9 J 10 s nt * 
 
 r 
 
 'ie'c 
 
 
 
 
 
 
 
 
 
 i — 
 
 
 
 
 
 -^ 
 
 *■ " 
 
 
 
 
 
 
 38^ 
 
 
 
 
 
 
 
 
 
 / 
 
 
 
 
 
 
 
 
 
 / 
 
 / 
 
 
 
 
 
 
 
 
 
 / 
 
 
 
 
 
 
 
 
 
 
 / 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Partial Pressure of Oxygen 
 
 Fig. 119- — Curves of Dissociation of Oxyhtemo- 
 globin freed from salts by dialysis (after Bar- 
 croft). .\long the horizontal axis are plotted 
 the partial pressures (numbers below the curve) 
 of oxvgen in air, to which a solution (jt hcemo- 
 globin was exposed. The corresponding per- 
 centages of oxygen are given above the curve. 
 Along the vertical axis is plotted the percentage 
 saturation of the haemoglobin with oxygen. 
 
 greater the chance of escape of molecules of oxygen. 
 
 It is easily proved that the substance in the corpuscles which 
 unites with oxygen is the blood-pigment. Although a solution of 
 oxyhasmoglobin crystals behaves towards oxvgen somewhat differ- 
 ently from blood containing the same proportion of the native pig- 
 ment, the maximum amount of oxygen taken up is the same for 
 each. Much labour has been spent in determining curves \yhich 
 express the relation between the partial pressure of oxygen to which 
 blood or a haemoglobin solution is exposed, and the proportion to 
 which the blood pigment becomes saturated with oxygen under 
 each pressure. The differences in the results of the various in- 
 vestigators who have worked out the curves of dissociation for 
 haemoglobin and for blood (Figs. 119. 120, 121) have been largely 
 cleared up by the researches of Barcroft and his co-workers. One 
 
^5A 
 
 IfnSPlRATION 
 
 factor wliith was overlooked ui the e;irlier uljservations is the 
 influence of salts. 
 
 The form o{ curve (a rectangular luperbohi. I'ig. i iq) which Hiifncr 
 put forward by an unjustifiable generalization, as the curve of dis- 
 sociation of oxyhacmoglobin is only found when the hscnioglobin solu- 
 tion is thoroughly freed from salts, as by prolonged dialysis. When 
 this condition is 'fulfilled it can be shown that the curve is always a 
 rectangular hyperbola, but a different one for each temperature at 
 which the observations are made. I"or ha-moglobin solutions not freed 
 from salts or for blood or dilutions ftf blood the curve is of a different 
 order altogether, a curve with a double contour (S-shaped). (Figs. 120, 
 121). If to a solution of haemoglobin freed from salts and yielding a 
 rectangular hyperbola as its dissociation curve, salts be added in the 
 quantities and uf the kiml known to exist in dog's blood, the curve of 
 
 «0r 1 1 1 r=-i ■ I iTtri 
 
 •0 
 •0 
 
 
 
 
 
 B^ 
 
 — ^ 
 
 -1 
 
 
 ^ 
 
 
 
 
 
 
 
 
 
 i 
 
 / 
 
 
 > 
 
 ^ 
 
 
 
 
 
 
 
 
 
 
 
 / 
 
 / 
 
 / 
 
 
 
 
 
 
 
 
 
 
 
 
 
 y 
 
 f 
 
 / 
 
 
 
 
 
 
 
 
 
 
 
 
 Vt 
 
 
 / 
 
 / 
 
 
 
 
 
 
 
 
 
 
 
 
 
 40 
 SO 
 ZO 
 
 to 
 
 
 1 i 
 
 f 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 '/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 jj 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 /. -- 
 
 _. 
 
 ._, 
 
 „_ 
 
 _ 
 
 __ 
 
 ._ 
 
 i. 
 
 ._ 
 
 _, 
 
 ._ 
 
 ._ 
 
 
 ,_. 
 
 18 UC 
 
 leoc 
 
 I4CjC 
 
 lacjQ 
 
 lOCC 
 
 • ce. 
 
 6CC 
 
 4CC 
 
 2 C.C 
 3CC 
 
 1-ig 
 
 10 to JO 40 t« M 70 «0 10 100 HO 120 130 140 ISO 
 
 ijo. — (JuiV'~ (jf l>i?'?')Ciation of Oxygen for Horse's Blood (Bj and L'og's Haemo- 
 globin solution (H) at 38^ C. (Boiir). The figures along the base-line are th? 
 partial pressures of oxygen to which the blood aud haemoglobin solution were 
 exposed. Those along the vertical axis on the left are the percentage saturations 
 with oxygen. The figures along the vertical at the right give the actual number 
 of C.C of oxygen chemically combined by 100 c.c. of the blood for each pressure 
 of oxygen. The interrupted line P indicates the amount of oxygen dissolved in 
 the plasma of the blood at each partial pressure on the assumption that the 
 plasma is two-thirds of the volume of the blood. Thus, at 150 mm. oxygen 
 pressure the plasma of 100 c.c. of blood took up 0-3 c.c. oxygen. 
 
 dissociation given by dog's blood is obtained. The addition of the 
 salts appropriate to human blood in the proper amounts causes the 
 hvperbolic curve of the pure haemoglobin solution to change into an 
 S-shaped curve, such as is given by human blood, and so on. 
 
 The foundation has thus been removed from the theor\' that 
 different animals possess h?emoglobins differing in their capacity 
 to take up oxy.gen. The salts are su])]^i)sed to alter the dissociation 
 curve, by changing the degree of aggregation of the hsmoglobin 
 molecules- — i.e., by causing them to adhere to each other to a greater 
 or less extent according to the quantity and kind of salts present. 
 
 Another factor which greatly influences the binding power of 
 hremoglobin for o.xygen, and therefore the dissociation curve, is 
 the reaction of the blood (p. 24). When the hydrogen-ion concen- 
 
THE GASES or THE HLoOD 
 
 t ration is incioasod. as by addition of carbon dioxitio (I'ig. 1 211 or 
 lactic acid, the effect is to increase the dissociation tension of 
 oxyhitmoglobin. or what is a different way of expressing the same 
 thing, to diminish the amount of oxygen taken up under a given 
 oxygen partial pressure. So that to obtain a given percentage 
 saturation oi the inemoglobin, a greater partial pressure of oxygen 
 mvist be employed than in the absence of the acid. 
 
 So sensitive is the dissociation curve to changes in the hvdrogen-ion 
 concentration, that a metliod (if detecting and estiinatinp; alterations in 
 the acidity of the blood has boon ba^cd upon the (Ictcrniination of the 
 percentage saturation of tlie blood 
 with oxygen, at a detinile partial 
 pressure. The influence of the 
 carbon dioxide in the patient's 
 blood is eliminated by adding to 
 the gaseous mixture with which 
 the blood is shaken up a per- 
 centage of carbon dioxide, corre- 
 sponding to the partial pressure 
 of that gas in the blood, that is 
 to say, a percentage equal to the 
 percentage of carbon dioxide in 
 his alveolar air (p. 241'!. 
 
 In blood haemoglobin, of 
 course, exists in the presence 
 of salts and of carbon dioxide 
 and other acid metabohtes, and 
 tlierefore such curves as are 
 given in Figs. 120 and 121, 
 more nearly represent the dis- 
 sociation ciu'ves of the blood 
 pigment under physiological conditions, than those reproduced in 
 Fig. 119. 
 
 The Distribution and Condition of the Carbon Dioxide in the 
 Blood. — The question is much more complicated than for the 
 oxvgen, which is practically confined to one of the morphological 
 elements of the blood (the erythroc^'tes), and exists in the form of a 
 single compound. Carbon dioxide is distributed over the entire 
 blood in important amounts, and is present in several forms. The 
 serum vields a larger percentage of carbon dioxide than the cloc, 
 but this percentage is not great enough to allow us to assume that 
 the whole of the carbon dioxide is contained in the plasma. Some- 
 what more than a third of it belongs to the corpuscles. 
 
 As regards the condition of the carbon dioxide, it is known that 
 some of it is simply dissolved in the plasma and corpuscles; but 
 although this fraction, on account of the relatively high cdefificient of 
 absorption of the gas (p. 245), is much greater than the corresponding 
 oxygen fraction, it is insignificant in comparison with the quantity 
 chemicallv combined. Carbon dioxide is united in dissociable 
 
 Fig. 
 
 'i^ 30 «0 is 00 Id eo 90 (OS 
 
 121. — Dissociation Curves of Blood, 
 with Different Tensions of CO3 (o, ;,, 
 20, 40, and 90 mm.). Ordiaates = 
 percentage saturation. Abscissa? = 
 oxygen pressure. (After Barcroft.) 
 
2S6 RESPIRATION 
 
 combinations with a number of the constituents of the blotKl, both 
 inorganic and organic, and our knowledge of these combinations, 
 especially of the compounds formed with organic substances, is far 
 Irom complete. The inquiry is complicated by the circumstance 
 that the proportion of the total combined carbon dioxide united 
 with a given constituent or bound by plasma and corpuscles respec- 
 tively is not constant, but varies with the varying tension of the gas, 
 while the total amount of carbon dioxide is itself dependent upon 
 the varying ' titratable alkalinity ' (p. 25). There is no doubt that 
 some of the carbon dioxide in blood is combined with alkali, but 
 the amount of alkali available is not nearly suthcient to unite with 
 all the carbon dioxide even in the form of bicarbonate. Some of 
 the dissociable carbon dio ide must therefore be combined with 
 organic substances. The relations, even of that portion which 
 exists as bicarbonate, are peculiar. This is sufficiently indicated by 
 the fact that from defibrinated blood the whole of the carbon 
 dioxide can in time be pumped out without the addition of an acid 
 to displace it from the bases with which it is united. On the other 
 hand, from a bicarbonate solution whose concentration corresponds 
 to that of the blood, not much more than half of the loosely bound 
 carbon dioxide (that is, the carbon dioxide which comes off accord- 
 ing to the equation 2HXaC03= Na^COg +COj + HgO) can be ob- 
 tained even when the evacuation is kept up for days. This is only 
 about one-fourth of the total carbon dioxide in the bicarbonate; 
 yet, when sodium bicarbonate is added to blood, even in consider- 
 able amount, all the carbon dioxide in it can be obtained by the 
 pump. From serum a great deal, but not the whole, of the carbon 
 dioxide can be likewise pumped out, and the liberation of the gas 
 does not stop, as in the case of the bicarbonate solution, when all 
 the bicarbonate has been cliiinged into carbonate. The- residue 
 (from 10 to 18 per cent, of the whole) is set free on the addition of 
 an acid — e.g., phosphoric acid. 
 
 The most satisfactory explanation is that in tlic serum there exist 
 substances which can act as weak acids in gradually driving out the 
 carbon dioxide, when its escape is rendered easier by tlie vacuum. 
 The quantitv of these, however, is not so large but that a jiortion of 
 the carbon dioxide remains in the scrum. Tlio proteins of the serum, 
 such as scrum-globulin, behave in certahi r.spccts like weak acids, 
 and may contribute to tlie driving out of the carbon dioxide. When 
 defibrinated blood is pumped out, the whole of the carbon dioxide can 
 be removed, apparently because substances of acid nature pass from 
 the corpuscles into the serum and help to break up the carbonates. 
 The liajmoglobin in tlie corpuscles acts as a weak acid, and as some 
 corpuscles arc ha^molyzed during the evacuation, the haemoglobin may 
 exert this action in the scrum as well as in the interior of the corpuscles. 
 
 The quantity of carbon dioxide combined with alkali (as bicar- 
 bonate) has not been exactly determined. Bohr estimated it by 
 shaking blood with atmospheric air, which was supposed to leave 
 
THE GASES OF THE BLOOD 
 
 257 
 
 the bicarbonate intact, while removing nearly all the rest of the 
 carbon dioxide, the compounds of the gas with organic constituents 
 of the blood being more easily dissociated than the bicarbonate. 
 The best known of these compounds is that which carbon dioxide 
 seems to form with haemoglobin. A solution of haemoglobin absorbs 
 more of the gas than water, and the quantity taken up is not pro- 
 portional to the pressure. There is also evidence of the existence 
 of dissociable combinations between carbon dioxide and the proteins 
 of the plasma, by which considerable amounts of the gas can be 
 bound at such carbon dioxide tensions as normalh^ exist in blood. 
 
 In the red corpuscles a portion of the carbon dioxide is in com- 
 Ignition with alkalies. We know that the corpuscles contain more 
 alkali than the serum, and the titratable alkalinity of ' laked ' 
 blood (pp. 25, 28) is greater than that of unlaked blood, unless 
 a long time is allowed in the case of the latter for the alkalies of the 
 corpuscles to reach the acid used in titration. The haemoglobin of 
 the corpuscles holds a portion of the carbon dioxide in weak com- 
 bination. 
 
 Although the student is warned not to give too much weight to 
 the actual numbers, the present position of our knowledge in regard 
 to the distribution and condition of the carbon dioxide of the blood 
 may be summed up by quoting the calculation of Loewy, that in 
 100 c.c. of arterial blood containing (with a carbon dioxide tension 
 of 30 mm. of mercury) 40 c.c. of carbon dioxide, there are — 
 
 
 In Plasma. 
 
 In Corpuscles. 
 
 1 
 
 In ]{lood. 
 
 Physically absorbed - - - 
 Combined as bicarbonate 
 In organic combinations 
 
 1-2 C.C. 
 I2-0 ,, 
 II-8 ,, 
 
 07 C.C. 
 6-8 ,, 
 7-5 .. 
 
 1-9 C.C. 
 i8-8 ,. 
 19-3 ,. 
 
 When blood is saturated with carbon dioxide and then sepai-ated into 
 serum and clot, the serum is found to yield more gas than the clot; but 
 if the serum and clot are separately saturated, the latter takes up more 
 carbon dioxide than the former. From this it is argued that a substance 
 combined with carbon dioxide must in blood saturated with the gas pass 
 out of the corpuscles into the scrum. The corpuscles at the same time 
 gain water and become larger. The molecular concentration (p. .|2'j) 
 of the serum of defibrinated blood, as measured by the lowering of the 
 freezing-point, increases when it is saturated with carbon dioxide. On 
 the other hand, when blood is saturated with oxygen, the corpuscles 
 lose water and shrink in volume, while the molecular concentration of 
 the serum is diminished. Hamburger has extended these observations 
 to the circulating blood, and has shown that the plasma of venous 
 blood has a higher percentage of alkali, protein, sugar, and fat than 
 the plasma of arterial blood, and that the corpuscles have a greater 
 volume, though not a greater diameter. He therefore supposes that in 
 the pulmonary capillaries, under the influence of oxygen, water passes 
 into the plasma from the corpuscles. In the systemic capillaries the 
 blood becomes loaded with carbon dioxide, and therefore the corpuscles 
 
 17 
 
23 S RESPIRATION 
 
 take up water from the plasma, which accordingly has a more concen- 
 trated supply of food-substances to offer to the tissues than the plasma 
 of arterial blood itself. Some writers see in this interchange an auto- 
 matic arrang.^ment by which oxidation is favoured. \Vhitcver may be 
 thought of this view — and objections to it aro not wanting— the current 
 theory, that the corpuscles are simply passive carriers of oxygen, and 
 exercise no further influence on the plasma, breaks down in face of the 
 facts. We must admit that an active and many-sided commerce exists 
 between them and the liquid in which they float. 
 
 The nitrogen of the blood is siniph' absorbed.* 
 
 The Tension of the Blood-Gases. — If the gases of the blood existed 
 in simple solution, their tension or partial pressure could be deduced 
 from the amount dissolved and the coefficient of absorption. We 
 have seen that they are mainly combined, and it is characteristic 
 of dissociable compounds of this kind that the relation between the 
 partial pressure of the gas in contact with the liquid and the quantity 
 of gas taken up is much more compHcated than in the case of pure 
 physical absorption. It is therefore necessary to determine the 
 tension directly. 
 
 This can be done by means of arrangements called aerotonometers. 
 There are various forms of aerotonometer, but the object of all is to 
 bring the blood into contact with an atmosphere or gaseous mixture 
 into which the gases of the blood can diffuse and from which gases can 
 enter the blood. When the composition of the mixture has ceased to 
 change, the gases in it are under the same partial pressure as the corre- 
 sponding gases in the blood, and all that is necessary in order to arrive 
 at the tension of the blood-gases is to determine the final composition 
 of the gaseous mixture by analysis. The speed with which equilibrium 
 is attained depends essentially upon the magnitude of the surface of 
 contact between the blood and the g<is mixture in proportion to the 
 volume of the gas space. In the earlier observations with the aerotono- 
 meter it was found tf» be very difficult to get complete equilibrium, and 
 therefore the gas space was filled at the beginning with a mixture whose 
 gases had partial pressures as nearly equal as possible to those expected 
 in the blood. In one form of the apparatus the blood is made to pass 
 directly from the vessel to glass tubes, which it traverses at the same 
 time, the stream being divided between them; it then passes out again. 
 The tubes are warmed by means of a water-jacket to the body-tem- 
 perature. Some of them are filled with gaseous mixtures having a 
 greater, and the others with mixtures having a smaller, partial pressure, 
 say of carbon dioxide, than is expected to be found in the blood. As 
 the latter runs in a thin sheet over the walls of the tubes, it loses carbon 
 dioxide to some of them and takes up carbon dioxide from others. 
 From the alteration in the proportion of the carbon dioxide in the tubes, 
 the partial pressure of that gas in the blood is calculated — that is, the 
 partial pressure which would be necessary in the tubes in order that 
 the blood might pass through them without losing or gaining carbon 
 dioxide (p. 248). 
 
 Bohr's aerotonometer, constructed and worked much in the same 
 way as a stromuhr (p. 121), permits the blood after passing through the 
 gas space to return to the circulation. A stream of blood can thus be 
 
 * But according to Buckmaster and Gardner, the volume of nitrogen in 
 blood does not foUow the ordinary physical laws of absorption with vaxyiag 
 nitroge;! pressures in the alveolar air. 
 
THE GASES OF THE BLOOD 
 
 259 
 
 kept in coiitiict with the gas for a quarter of an hour or longer, so as 
 to insure equihbrium. Finally, in Krogh's microtovomcier tlij gas space 
 
 kt 
 
 to uisure equilibrium, x-iiiaiiy, in rvrogn s microionome'er tiij gas space 
 is reduced to the smallest possible dimensions, being composed merely 
 of an air-bubble 1 mm. in diameter, which is exposed to the contact of 
 a stream of blood from an artery or vein. Equilibrium is established 
 so quickly that it is indilferent whether a bubble of air or of pure 
 nitrogen is employed. The bubble is analyzed at the end of the obser- 
 vation, and its composition gives the tension of the blood gases. 
 
 Suppose that the gaseous mixture which is in equilibrium with the 
 blood contains 10 per cent, of oxygen and 5 per cent, of carbon dioxide, 
 
 Fig. 122. — Krogh's Micro to- 
 nometer. The apparatus, 
 which is filled with salt solu- 
 tion, consists of a graduated 
 capillary tube, 3, the lower 
 part of which, with its ex- 
 panded lower end, is shown 
 on a much enlarged scale in 
 A. The rest of the capillary 
 tube, surrounded by a water- 
 jacket to control the tempera- 
 ture, is shown on a smaller 
 scale in B. 2 is a gas-bubble, 
 against which blood flowing 
 from the very narrow mouth 
 of the tube i plays, i is con- 
 nected by a rubber tube with 
 a cannula in a bloodvessel. 
 The blood forces its way up 
 above the gas-bubble, which 
 is pressed a little down by the 
 current, and kept oscillating 
 rapidly. The blood flows off 
 through the tube 5, and is 
 collected drop by drop and 
 measured. By means of the 
 screw 4, shown in B, which 
 moves in mercury, the gas- 
 bubble can be drawn into the 
 capillary for measurement. 
 The upper end of the capil- 
 lary tube also expands into a 
 funnel-shaped cavity, which 
 is closed by a stopper, and 
 is only used for cleaning the 
 apparatus. 
 
 the tension of oxvgen in the blood would be one-tenth of an atmosphere 
 [i.e., of 760 mm. of mercurj'). or 76 mm , and the tension of the carbon 
 dioxide in the blood one-twentieth of an atmosphere, or 38 mm. of 
 mercunv". 
 
 Another method hy which the tensio;i of the gases in the venous 
 blood passing from the right heart through the lungs has been estimated 
 depends upon the use of the pulmonary catheter. This consists of two 
 tubes, one within the other. The inner tube, which is a fine elastic 
 catheter, projects free from the other for a little distance at its lower 
 end. The outer tube terminates in a thin india-rufjber balloon, through 
 which the inner tube passes without communicating with the balloon. 
 
26o RESPIRA TION 
 
 The balloon can be inflated so as to block the bronchus into which it 
 is passed, and cut off the corresponding portion of the hing from com- 
 munication with the outer air. A sample of the air below the block can 
 be drawn off through the inner tube, which opens free in the bronchus. 
 
 This method has been applied both to animals and to man. In 
 observations on man the catheter was passed into the right bronchus 
 so as to occlude at will any one of the lobes of the right lung. On the 
 assumption that the ga.seous exchange in the lungs depends essentially 
 on the physical process of diffusion, the occluded alveoli will correspond 
 to the gas space of an aerotonometer. When the occlusion has lasted 
 long enough for the gases in the alveoli and the blood ga^es to come 
 completely into equilibrium — say half an hour — all that is necessary is 
 to draw off the air, and from its composition to deduce the tensions in 
 the blood. Since the respiratory function of the occluded lobe is in 
 abeyance, the blood circulating in it is all unaltered venous blood, as it 
 comes from the right ventricle, so that the gas tensions found can be 
 considered those of the mixed venous blood. 
 
 For estimating the oxygen tension in the arterial blood a method 
 was introduced by Haldane and Smith, which differs fundamentally 
 from those described above, in that it docs not depend upon the use of 
 aerotonometers. They applied it not only to animals but also to man. 
 The subject of the experiment breathes air containing a definitely 
 known verA- small percentage of carbon monoxide until the haemoglobin 
 has united with as much of that gas as it will take up for the given 
 concentration of it in the air. Then the percentage amount to which 
 the haemoglobin has become saturated with carbon monoxide is deter- 
 mined in a sample of blood taken, say, from the finger. Xow, the final 
 saturation with carbon monoxide of a haemoglobin solution brought 
 into contact with a gaseous mixture containing carbon monoxide and 
 oxygen, depends on the relative tensions of the two gases in the liquid. 
 But the tension of carbon monoxide in the blood leaving the lungs will 
 (after absorption has ceased"* be the same as that in the inspired air. 
 Knowing this tension and the degree of saturation of the haemoglobin 
 w^ith carbon monoxide, the oxygen tension in the blood leaving the 
 lungs — i.e., in the arterial blood — ii^ known. 
 
 Before proceeding to the consideration oi the results obtained by 
 these di^■cr^- methods, it may be well to point out that when a gas 
 is stated to be under such and such a tension in the blood, no direct 
 information is given as to the quantify of gas present . For instance, 
 the oxygen tension in blood exposed to atmospheric air will be the 
 same for the erythrocytes as for the serimi — namely, about ibo mm. 
 of mercury; but lOO c.c. of serum will scarcely 'ontain i c.c. of 
 oxygen, while too c.c. of corpuscles will have absorbed about 60 c.c. 
 of the gas. 
 
 \\Tien we now turn to the actual blood-gas tension.s obtained by 
 different observers and by different methods, these, as displayed in 
 such a table as appears on p. 261, seem to present, at first sight, 
 nothing but a welter of widely diverging and contradictory figiu-es. 
 
 This table, at the time it was drawn up a few \ear? ago, represented 
 the outcome of a vast amount of work by physiologists of the greatest 
 ability, and specially skilled in such studies. To-day, the absolute 
 numbers possess little value, especially in \4ew of the fact that most 
 
THE GASES OF THE BLOOD 
 
 261 
 
 of them could not be accurately compared with the corresponding 
 gas tensions in the alveolar air. The discussion of the table is 
 none the less instructive to the student who desires to learn how 
 knowledge is won, and how frequently an advance in knowledge is 
 dependent upon an advance in technique. 
 
 As regards the venous blood, we have already learnt that very 
 considerable variations in the content of oxygen and of carbon 
 dioxide are associated with the varying functional activity of the 
 tissues from wliich the blood comes. This factor, of course, is also 
 not without influence upon the gas tensions of the venors blood. 
 The carbon dioxide tension of arterial blood is affected by variations 
 in the amount of the pulmonary ventilation, which affect the partial 
 pressure of the carbon dioxide in the alveolar air and thus alter the 
 steepness of the slope of pressure between the two sides of the pul- 
 monary membrane. 
 
 
 Arterial Blood : 
 
 Venous Blood : 
 
 
 Tension in 
 
 Mm. He. 
 
 Tension in Mm. Hg. 
 
 riK.- or,^ Vl .K.™1 
 
 
 
 
 ^OSCTTOf BllQ irlCtOOQ. 
 
 Oxygen. 
 
 Carbon 
 Dioxide. 
 
 Oxygen. 
 
 Carbon 
 Dioxide. 
 
 9. 
 
 Strassburg - - - - 
 
 21-43 
 
 16-29 
 
 10-35 
 
 38-49 
 
 
 
 
 (29-6)* 
 
 (20) 
 
 (20-6) 
 
 (41) 
 
 6 
 
 Herter 
 
 39-79 
 
 17-31 
 
 — 
 
 
 c ■ 
 
 Bohr 
 
 101-144 
 
 20-32 
 
 — 
 
 
 
 
 
 Bohr (later series) 
 
 — 
 
 9-27 
 
 — 
 
 26-43 
 
 E 
 
 Fredericq - - - - 
 
 91-105 
 
 17-19 
 
 
 
 
 
 < 
 
 Falloise . - . . 
 
 ■ — 
 
 
 
 17-37 
 
 32-54 
 
 t'u 
 
 
 
 
 (42-5) 
 
 g rWolflfberg . - . . 
 
 — 
 
 
 
 (26) 
 
 18-37 
 
 JJ _ Nussbaum - - - - 
 
 — 
 
 
 
 (27) 
 
 24-33 
 
 J ^ 1 Loewy and Schrotter \ p. 
 
 ( ~ 
 
 — 
 
 (37-7) 
 
 34-59 
 
 ^ Haldane and Smith J "^^^ 
 
 U00 + 
 
 "" 
 
 — 
 
 (45) 
 
 It is chiefly the enormous differences in the recorded oxygen 
 tensions of the arterial blood which excite surprise. To some ex- 
 tent, indeed, these also may depend upon differences in the partial 
 pressure of the oxygen in the alveoli, and it has been shown experi- 
 mentally (by the aerotono meter) that with increasing oxygen tension 
 of the inspired air the oxygen tension of the arterial blood increases 
 (Fredericq). Still, the differences which can possibly have existed 
 in the partial pressure of the oxygen in the alveoh in the various 
 series of observations can onlj^ to a small extent account for the 
 differences in th^ results. The main reason for the great range of 
 values lies unquestionably in the different experimental procedures 
 • The numbers in brackets are averages. 
 
2t^2 RESPIRATION 
 
 by which they were obtained. There is no doubt that in the earHcr 
 observations with the uerotonometer (Strassburgj tiic oxygen of 
 tlie blood could not have come into equilibrium with the mixture 
 in the gas space, in which the oxygen pressure was at the beginning 
 much lower than that in the blood ; the results are therefore too low. 
 The same is true for the oxygen tension of the venous blood, but as 
 this is in any case considerably smaller than that of the arterial 
 blood, the proportional error is not so great. The later experiments 
 (of Herter), given in the second line of the table, yield much higher 
 values, owing to improved technique, but the findings are still to be 
 regarded as minimal and not average results. At the other end of 
 the scale stand the results oi Haklanc and Smith, who lound m man 
 an oxygen tension in the arterial blood of over 200 mm. of mercury 
 equal to more than 26 per cent, of an atmosphere. This exceeds 
 the partial pressure of oxygen in the external air, and is about twice 
 as great as that of the air of the alveoli. In the bird they found 
 an oxygen tension of between 300 and 400 mm., equal to 45 per 
 cent, of an atmosphere. 
 
 The chief interest of this discussion of the blood-gas tensions Hes 
 in their fundamental importance in the problem of the gaseous 
 exchange in the lungs, on the one hand, and between the blood and 
 tissues on the other. In the presence of such results Haldane and 
 Smith necessarily adopted a secretion theory of gaseous exchange 
 in the lungs. For it was manifestly impossible for oxygen to diffuse 
 from the alveoli into the blood against the slope of pressure. 
 
 Their findings, however, differed so vastly from those of all observers 
 who had used tonometric methods, and it seemed so difficult to assign 
 an adequate physiological value to the slight increase in the percentage 
 saturation of the ha?moglobin with oxygen (see Figs. 119-121), which 
 could be brought about by even a great excess of ox^'gen tension above 
 that of atmospheric air, that there was a general disposition to distrust 
 the accuracy of their method. At the same time the ordinary tono- 
 metric techiiiquc left so much to be desired that there seemed little 
 hope of bringing the matter to a decisive test. The introduction a 
 few years ago by Krogh, of better aerotonometric methods, and the 
 remarkable series of researches carried out by their aid, have changed 
 the whole aspect of the question. He showed that in tlie arterial blood 
 of rabbits the oxygen tension was in all cases somewhat (usually 2 to 
 3 per cent, of the atmospheric pressure, or 15 to 23 mm. of mercury) 
 lower than the oxygen tension in air from the bifurcation of the trachea. 
 In animals it is not possible to obtain the actual alveolar air. These 
 results agree very well with those of Fredericq, who found in dogs 
 oxygen tensions of 13 to 14 per cent, of an atmosphere- -i.e., something 
 like 100 mm. of mercury, when the animals breathed atmospheric air. 
 Krogh proved that the amount of oxygen lost by self-reduction of 
 the blood (see p. 2G1) in his aerotonometer wan negligible, even in 
 rabbits, although it is known that rabbit's blood uses up more oxygen 
 than that of higher mammals. He also pointed ou^some sources of 
 error in the Haldane-Smith method. About the same time Haldane. 
 after a careful re-examination of the question, came to the con- 
 clusion that his previous results were much too high; and that 
 
77/ L (,ASLS Ol- Till:: BLOOD 263 
 
 during rest nul when normal air is breathed the oxygen tension in 
 arterial blood never exceeds the tension in the alveolar air. He still 
 beheves, and brings forward evidence for liis belief, that even the best 
 aerotonometric methods yield with arterial blood oxygen pressures 
 lower than the true oxygen pressure in the blood leaving the pulmonary 
 capillaries. But he no longer doubts that a sufhcicnt slope of pressure 
 exists between the alveoli and the blood to explain the absorption of 
 oxygen under ordinary conditions. 
 
 To all intents and purposes, then, we may look upon the contro- 
 versy as closed, and with the happy result, too rare in physiological 
 disputes, that a practically unanimous conchision has been arri\ed 
 at. While the oxygen tension in arterial blood may jail only slightly 
 below that in alveolar air, the difference perhaps being even less than 
 that found by Krogh, the slope of pressure is always, under ordinary 
 conditions at least, from the alveoli to the blood. 
 
 Mechanism of the Gaseous Exchange in the Lungs. — Granting 
 that this is so, it must still be asked whether the diffusion of oxygen 
 from the lungs into the blood can take place rapidly enough to 
 account for the quantities actually absorbed. 
 
 Calculations made on the basis of such anatomical and physical data 
 as are available (total surface of the lungs, thickness of the membrane 
 which separates the air of the alveoli and the blood in the capillaries, 
 rate of ' invasion,' or entrance of the gases into water; velocity of 
 diffusion of oxygen and carbon dioxide), indicate that even with differ- 
 ences of oxygen tension between the blood and the alveolar air, which 
 would lie within the limits of error of our present methods of measure- 
 ment, enough oxygen covUd diffuse across the pulmonary membrane to 
 cover the whole normal intake. 
 
 For example, it has been shown from determinations of the ' invasion- 
 coefficient ' of oxygen that 300 c.c. of oxygen, the amount ordinarily 
 absorbed in a minute, in an average man, can be carried from the alveo- 
 lar air into the wet surface of the pulmonary epithelium with a difference 
 of oxygen pressure of a little over 3 mm. of mercury. If during mus- 
 cular exercise six or seven times as miich oxygen were absorbed, the 
 necessary difference of oxygen pressure would still be only about 20 mm. 
 of mercury, less than 3 per cent, of an atmosphere. 
 
 It is one thing, however, to know that the necessary oxygen can be 
 taken up into the surface of the pulmonary membrane by a purely 
 physical process, but quite another to prove that it can also be trans- 
 ported with sufficient speed across the thickness of the alveolar wall 
 into the blood. A direct test of this question, made by Krogh, has 
 also yielded an affirmative answer. He determined the amount of 
 carbon monoxide actually taken up in a given time in a hinnan subject. 
 It was about 10 c c. per mm. of partial pressure in the alveolar air per 
 minute when the subject was at rest, and a little above 30 c.c. when 
 breathing was forced, as it would be during heavy work. Now the 
 speed of diffusion of oxygen is somewhat greater than that of carbon 
 monoxide, so that at rest the subject could have absorbed between 
 200 and 300 c.c. of oxygen per minute with a difference of oxvgen 
 tension of only 10 mm. of mercury between the alveolar air and the 
 arterial blood. Even during hard muscular work the observed differ- 
 ences of oxygen tension seem adequate to the transport of the necessary 
 amount of oxygen. 
 
264 RESPIRATION 
 
 So far. then, as the absorption oj oxxi^en is concerned, thcr<r ir. rvcry 
 reason to conclude that it is managed by physical processes alone. 
 Haldane, it is true, still contends that under exceptional conditions 
 when the call for oxygen is much increased, as during active mus- 
 cular exercise, or when an adequate intake is hampered by reduced 
 atmospheric pressure, as at high altitudes, the oxygen tension in 
 the arterial blood may materially exceed that in the alveolar air. 
 Those who have worked with other methods do not, however, grant 
 that even under these conditions there is any excess of oxygen 
 pressure in the blood. It may, of course, be formally admitted that 
 even if diffusion can account for the absorption of the whole of the 
 oxygen, this is not of itself a proof that it is by diffusion that the 
 thing is actually done ; it is only a reason for refusing to call in the 
 aid of a more recondite hypothesis, until the necessity for doing so 
 is clearly demonstrated. 
 
 As regards the carbon dioxide the evidence is fully as clear. The 
 speed of diffusion of carbon dioxide across such a membrane as the 
 alveolar wall being much greater than that of oxygen, still smaller 
 differences of tension would suffice to permit the whole normal out- 
 put of that gas to be eliminated by diffusion. 
 
 According to the obserxations of Buhr, nearly 300 c.c. of carbon 
 dioxide per miuTite could pass out of the blood by diffx'.sion into the 
 alveolar air ipider a difference of partial pressure of i mm. of mercury. 
 This is with the ordinary breathing of a man at rest. With the in- 
 creased respiration associated with hard muscular work, this quantity 
 would be increased to between 700 and 800 c.c. The amount of carbon 
 dio.xide eliminated during rest in an average adult (300 c.c.) can there- 
 fore be easily excreted by diffusion with a tension-difference of i mm. 
 of mercury. Even during very hard work the necessary tension differ- 
 ence need not be more than 3 mm. With a movement of carbon dioxide 
 so free as this, it is obvious that if the excretion (jf that gas is solely a 
 matter of diffiision its partial pressure in the arterial blood must be 
 nearly identical with its partial pressure in the alveolar air. 
 
 A glance at the table on p. 261 shows that while the carbon di- 
 oxide tension of venous blood may sometimes, perhaps generally, 
 exceed that of the alveolar air, the difference is quite small. The 
 average for the observations on man with the pulmonary catheter 
 was 45 mm., which compares with an average alveolar tension of 
 42 mm. 
 
 Experiments made by more modern methods have placed the 
 matter bevond doubt. Krogh pro\ed, for example, that in rabbits 
 the carbon dioxide tension in the arterial blood was always slightly 
 (on the average 0-4 per cent, of an atmosphere, or 3 mm. of mercury; 
 higher than in air taken from the bifurcation of the trachea. Now 
 this air is known to contain shghtly less carbon dioxide than the 
 alveolar air. Haldane 's results on the regulation of the respiration 
 (p. 281) would be unintelligible unless the carbon dioxide pressure 
 in the arterial blood adjusted itself with great rapidity, to changes 
 
THE GASES OF THE BLOOD 265 
 
 in tlio tension of carbon dioxide in the aKiohir air, so as always 
 to preserve a definite relation. It is quite generally assumed that 
 this relation is one of practical equality, and the classical method 
 of measuring the carbon dioxide tension in the arterial blood in man 
 is to determine it in the alveolar air. 
 
 Evidence in favour of the view that there is, besides diffusion, 
 an element of selective secretion in the exchange of gases through 
 the pulmonary membrane has been found by some writers in the 
 results of a studv of the gases of the swim-bladder in fishes. This 
 study has demonstrated the existence of animal cells which actually 
 secrete gases. This fact, however, even if it removes a presump- 
 tion against, does not establish a presumption in favour of, the 
 secretion theory of external respiration. These gases consist of 
 oxygen, nitrogen, and usually a small quantity of carbon dioxide, 
 but in verv different proportions from those in which they exist in 
 the air or the water. Thus, as much as 87 per cent, of oxygen has 
 been found in the bladder of fishes taken at a considerable depth, 
 but a smaller amount in those captured near the surface. When 
 the gas is withdrawn by puncturing the bladder with a trocar, the 
 organ rapidly refills, and the percentage of oxygen increases. 
 Further, this process of gaseous secretion is under the influence of 
 nerves, for gas ceases to accumulate in the organ when the branches 
 of the vagi that supply it are cut. In the tortoise stimulation of 
 the peripheral end of the vagus causes a fall of gaseous exchange 
 in the corresponding lung, with an accompanying rise in the other 
 lung. But this is a consequence of an alteration in the pulmonary 
 circulation through the vasomotor fibres for the lungs which are 
 known to run in the vagus in this animal. In the mammal, no such 
 effect has been demonstrated, and the decisive proof that the lungs 
 are gas-secreting glands which would be afforded by the discovery 
 of secretory nerves is wanting. 
 
 We have now completed the description of the phenomena of 
 external respiration, with the discussion of its central fact, the 
 exchange of gases between the blood and the air at the surface of 
 the lungs. It remains to trace the fate of the absorbed oxygen, 
 and to determine where and how the carbon dioxide arises. 
 
 Section V. — Internal or Tissue Respiration. 
 
 Seats of Oxidation. — The suggestion which lies nearest at hand 
 and which, as a matter of fact, was first put forward, is that the 
 oxygen does not leave the blood at all, but that it meets with 
 oxidizable substances in it, and unites with their carbon to form 
 carbon dioxide. WTiile there is a certain amount of truth in this 
 \new, oxygen, as already mentioned, being to some extent taken up 
 by freshly shed blood, and also by blood under other conditions, 
 to oxidize bodies, other than hemoglobin, either naturally contained 
 
266 RF.SPIHATION 
 
 in it or artificially added, tlK-re is no cl(jubt that tlic colls of the body 
 arc the busiest seats of oxidation. TliL*^ is shown by the presence 
 of carbon dioxide in larf<e amount in lynipli and tether licjuid^ wliich 
 are, or liave been, in intimate relation with tissue elements; by its 
 presence, also in considerable amount, in the tissues themselves — 
 in muscle, for instance ; by its continued and scarcely lessened pro- 
 duction not only in a frog whose blood has been replaced by physio- 
 logical salt solution, and which continues to live in an atmosphere 
 of pure oxygen, but in excised muscles; and by the remarkable con- 
 nection between the amount of this produ<tion and the functional 
 state of those tissues. In insects the finest twigs of the trachea, 
 through which oxygen passes to the tissues, actually end in the cells ; 
 and in luminous insects, like the glow-worm, it has been noticed 
 that the phosphorescence, which is certainly dependent on oxidation, 
 begins and is most brilliant in those parts of tlie cells of the light- 
 producing organ that surround the ends of the trachea;. Microscopic 
 evidence has been obtained that intracellular oxidation proceeds 
 most rapidly near surfaces like the nuclear and plasma membranes 
 — e.g., in the indophenol (p. 272) and similar reactions the coloured 
 oxidation products are deposited chiefly in and around the nuclei of 
 such cells as liver and kidney cells and frog's red corpuscles (Lillie). 
 
 The Passage of Oxygen from the Blood into the Tissues. — A 
 fundamental fact of tissue respiration is that the amount of oxygen 
 taken up by the cells depends essentially upon their needs, and not 
 upon the amount of oxygen offered to them in the blood. In every 
 case studied, an increase of functional activity on the part of an 
 organ leads to an increased call for oxygen by that organ, and an 
 increased consumption of oxygen in it. The cells cannot be cajoled, 
 so to say, into consuming more oxygen merely by increasing the 
 available supply. Nor can they be prevented from absorbing and 
 consuming more of whatever supply is available when they are 
 caused to work harder. 
 
 For skeletal muscle at rest, Barcroft gives 0*004 ^'-C- per gramme 
 per minute as the oxygen consumption ; during maximal activity 
 twenty times as much (o«o8 gramme). In the heart of a small dog 
 through which blood was pumped by a larger dog the oxygen intake 
 when the heart was beating feebly was, on the average, about 
 O'Oi c.c. per gramme of heart-muscle per minute. Wlien the heart 
 was caused to beat very strongly under the influence of adrenalin, 
 the oxygen intake rose in one case to o«o8, and in two others to 0*04. 
 In the resting pancreas the oxygen intake has been found to be 0*03 
 to 0'05 c.c. per gramme per minute; in the active pancreas, 0*1 c.c. 
 The corresponding number for the submaxillary gland at rest is 
 0*03, and in activity 0*09; for the kidney, 0*03 at rest or during 
 scanty secretion, and 0*07 or even 0-09 during active secretion ; for 
 the liver in fasting animals o«oi. in fed animals o-ojs. 
 
IXTF.RXAL OR TISSUE Rl-SPI RATION 267 
 
 Wf arc as yet less precisely inlornied as to the manner in which 
 the tissues regulate the amount of oxygen which they take up from 
 the blood, than in the case of the passage of oxvgen into the blood 
 from tlie lungs. Tlie ])robIem, indeed, is superficially at least a 
 different and probably a more complex one. In the lungs the task 
 is to saturate, or nearly to saturate, the h;emogl(jbin with oxygen, 
 whether the blood passes fast or slow. It is a monotonous invariable 
 process of -oxygen-grabbing,' with no possibility of its ever being 
 overdone. In the tissues, the task is to meet the widely varjang 
 demand from blood which is always charged with oxygen to ap- 
 ])roximately the same degree. How is this tiling managed ? There 
 is little doubt that the process is again fundamentally a matter of 
 diffusion. The oxygen dissociated from the oxyha^moglobin in the 
 capillaries must find its way through the plasma across the capillary 
 walls into the tissue lymph, and thence into the interior of the cells. 
 There is evidence that it can do so by physical diffusion. For the 
 oxygen tension in the capillary blood is in general higher than the 
 oxygen tension in the tissues. The common statement that the 
 partial pressure of ox^'gen in the tissues is zero, or nearly zero, fits 
 in very well with the conclusion that the oxygen is transported into 
 the cells from the blood of the capillaries by a process of diffusion. 
 For the slope of oxygen pressure thus maintained would ordinarily be 
 greater than in the lungs, since even at the end of the capillary tract 
 the venous blood still has a considerable partial pressure of oxygen. 
 
 The fact that such liquids as lymph, bile, urine, the serous fluids, 
 saUva, pancreatic juice and milk contain little or no oxygen was sup- 
 posed to support the view that the pressure of oxygen must be very low 
 in the tissues by which they are secreted, or with which they have been 
 in intimate contact. From isolated muscles no free oxygen at all can 
 be pumped out, and mu.scle being taken as a type of the other tissues 
 in regard to the problems of internal respiration, it was concluded that 
 the scarcity of oxygen in the parenchymatous liquids which bathe the 
 tissues deepens in the tissues themselves into actual famine. The 
 inference seemed plain. Either the tissues used up oxygen so rapidly 
 that with an average blood flow their wants could just be supplied, 
 or without actually consimiing it they ' fixed ' and stowed it away in 
 some compound in which it was still available for oxidation in the meta- 
 bolic processes of the cell, but had lost the properties of free oxygen. 
 On the first alternative, an increased consumption of oxygen could only 
 be met by an increase in the blood flow; on the second assumption 
 the stored oxygen would supply the means of temporarily increasing 
 the metabolism even without an immediate augmentation of the blood 
 flow. Although it was recognized that even the resting metabolism 
 of certain organs was not inconsiderable, and required a good supply 
 of oxygen, it was always difficult to understand why inactive tissues 
 should have such an avidity for oxvgen that practically every molecule 
 seemed to be captured as soon as it appeared. Xor did it help much to 
 assume that some of the tissue oxidation might really take place in 
 the tissue lymph, oxidizable products split off in the metabolism of 
 the cells passing out into the lymph before being burnt, and thus 
 diminishing the oxygen tension outside the capillary walls. 
 
268 RESFIHATION 
 
 Recent work has indicated, however, that the oxygen pressure 
 in some tisbues is far from neghgible. In the nsting submaxillary 
 gland, indeed, it seems to be practically equal to the oxygen pres- 
 sure in the venous blood leaving the organ (over 40 mm. of mercury 
 in certain experiments). In general, the same was found to be 
 the case for the kidney. This does not mean, of course, that in 
 such organs there is no slope of oxygen pressure from blood to 
 tissue, in virtue of which oxygen can be moved out of the blood 
 by diffusion. For at the beginning of the capillarv tract the whole 
 difference in oxygen pressure between the arterial and the venous 
 blood would be available. At the end of the capillary tract, the 
 blood by the loss of oxygen to the tissues would have come approxi- 
 mately into equilibrium with them. These observations enable us 
 to understand better the manner in which the tissues themselves 
 can regulate their mtake of oxygen. If the glands are using little 
 oxygen their oxygen tension will be relatively high, and the passage 
 of a comparatively small amount of oxygen from the blood in the 
 capillaries will suffice to bring it into equilibrium with the tissues, 
 after which the diffusion of oxygen will cease. If, on the other 
 hand, the consumption of oxygen in the glands is suddenly in- 
 creased, their oxygen pressure will fall, the pressure gradient be- 
 tween them and the blood will become steeper, and oxygen will 
 diffuse more rapidly into them from the capillaries. It must be 
 remarked, also, that up to a certain point the existence of a sub- 
 stantial oxygen pressure in the tissues permits them at once to 
 increase their intake of oxygen from the blood without the neces- 
 sity of an immediate increase in the blood flow. For, as the cells 
 consume the oxygen already present in and between them, the 
 tissue oxygen tension falls, and the gradient between the interior 
 and the exterior of the capillaries is thus rendered more abrupt. 
 
 These results were not obtained by direct tonometric measurement 
 of the oxygen pressure in the glands investigated, but were deduced 
 from observations on the quantities of oxygen taken up by them when 
 different oxygen pressures were produced in the capillaries by altering 
 the oxygen tension in the inspired air. The quantity of oxygen which 
 diffuses out of the capillaries in a given time will be proportional to 
 the difference of oxygen pressure on the two sides of the capillary wall. 
 If the pressure on the side of the tissues is always zero, then the quantity 
 of oxygen passing out will vary directly as the intracapillary oxygen 
 pressure. Far from doing this, the amount of oxygen taken up by the 
 glands was found to be about the same with intra-capillary oxygen 
 pressures as different as 61 mm. and 16 mm. of mercury. It should be 
 distinctly understood that no great importance must be attached to 
 the actual numbers in experiments of this kind. But the general con- 
 clusion that in some tissues, at any rate in the resting condition, a 
 sensible partial pressure of oxygen exists, seems to be established 
 (Verzir). The application of the same method to muscle has led to 
 a different result. Here, the possible partial pressure of oxygen was 
 found decidedly less than that of the venous blood, although at times 
 a small oxygen pressure was detected in resting muscle (25 mm. or less) 
 
ISTERXAL OR TISSUE RESPIRATION 
 
 269 
 
 Muscle may accordingly be taken as a type of tissues in which 
 the oxygen pressure is so low that the blood-flow through them 
 cannot be much diminished without interference with their absorp- 
 tion of oxygen, while in tissues like the resting submaxillary gland 
 ■<\ considerable diminution of the blood-fiow can occur without 
 diminution of the oxygen consumption of the tissue. Whether 
 this difference is merely a quantitative one, depending upon the 
 great oxygen requirement of active muscle, or a qualitative difference 
 connected with the peculiar relations of oxygen to the muscular 
 contraction, is unknown. These relations have so great an interest 
 in connection with the problem of intracellular oxidation, and have 
 been so much more minutely studied than the relations of oxygen 
 to the functional work of other tissues, that a few words on the 
 respiration of muscle may fitly be introduced here. The subject 
 must be returned to later on (Chapters XII. and XIII.). 
 
 Fig. 123. — Fatigue of a Pair of Sartorius Muscles (Fletcher). A, in an atmosphere of 
 oxygen; B, in an atmosphere of nitrogen. A is partially restored by a rest of 
 five minutes. 
 
 Respiration of Muscle. — It is a remarkable fact that an excised 
 frog's muscle is capable of going on yielding carbon dioxide for a 
 long time, in the entire absence of oxygen, in a chamber, for instance, 
 filled with nitrogen or other indifferent gas. Not only so, but it 
 can be made to contract many times in this oxygen-free atmosphere, 
 although it loses its power of contraction sooner than in oxygen, 
 and does not show the same capacity for recuperation during an 
 interval of rest. In mammals the muscles can also be made to 
 contract repeatedly when the dissociable oxygen has, as far as pos- 
 sible, been got rid of from the blood by asphyxiating the animal, and 
 to give off a correspondingly large quantity of carbon dioxide, 
 although they lose their contractibility much more rapidly than the 
 muscles of the frog. This has usually been interpreted as meaning 
 that the carbon dioxide does not arise, so to speak, on the spot, from 
 
270 iiESPr RATIOS* 
 
 the immediate" union ul curbon .uul u.\yg(.'n, but that a stuck of 
 it is taken up by the muscle, and stored in some compound or 
 compounds, which are broken down during contraction, and more 
 slowly during rest, carbon cUoxide in both cases being one of 
 the end-products. In a normal muscle with intact circulation, 
 while carbon dioxide is gi\'en off, certain of the other decomposition 
 products are supposed, in conjunction with oxygen and some sub- 
 stance rich in carbon, like sugar, to be regenerated into the material 
 which breaks down in contraction. When oxygen is not available, 
 as in an atmosphere of nitrogen, carl)on dioxide is still given off, but 
 the other dccompositicjn products are suj)posed not to be regenerated 
 to contractile substance, but to accumulate in the muscle, producing 
 the phenomena of fatigue, and eventually of rigor. 
 
 When muscle goes into rigor (Chapter XIII.) — and this is most 
 strikingly seen when the rigor is caused by raising the temperature 
 of frog's muscle to about 40° or 41° C. — there is a sudden increase in 
 the quantity of carbon dioxide given off. Moreoxer, in an isolated 
 muscle the total quantity of carbon dioxide obtainable during rigor is 
 markedly less if the muscle has been previously tetanized. From this 
 it has been argued that the hypothetical substance (' inogen.'), the 
 decomposition of which 3'ields carbon dioxide in contraction, is also 
 the substance which decomposes so rapidly in rigor; that a given 
 amount of it exists in the muscle at the time it is removed from the 
 influence of the blood; and that this can all ' explode ' either in con- 
 traction or in rigor, or partly in the one and partly in the other. 
 However, according to Fletcher, there is no increase in the amount 
 of carbon dioxide given off during tetanus by an excised frog's 
 muscle unless the stimulation is so severe and prolonged as to 
 hasten the onset of rigor. He therefore supposes that in the con- 
 traction the decomposition does not proceecl quite to the formation 
 of carbon dioxide, which in the intact body is afterwards liberated 
 from some more complex carbon-containing waste-product. He 
 considers that the carbon dioxide yielded by excised muscles is 
 really performed carbon dioxide, already existing in a state of loose 
 combination, from which it is displaced by the lactic acid formed 
 after excision. There is no reason to suppose that any independent 
 new formation of carbon dioxide occurs witliin the isolated muscle 
 in the absence of a good supply of oxygen. However this may be, 
 there is good evidence that oxygen is used up in recovery processes 
 after the contraction is over, and that these recovery processes are 
 not completed when oxygen is lacking. Hill's work on the heat 
 production of muscle (Chapter XIII.) has tended to rehabilitate the 
 older conceptions, at least to this extent, that his results are in 
 favour of the view that oxygen is used largely during the recovery 
 after contraction in reactions ' whereby the molecular machine — like 
 a steam-engine charging an accumulator — builds up bodies contain 
 
ISTI-USAL on TISSUE kESPI h'A I ION t;! 
 
 ing considerable amouiUs ot f)otontial energy which (Hkc thr accu- 
 mulator) can be dis(lun>,'<d by ;ipi)r()priatp stimuli.' 
 
 The respiration of muscles in situ can be studied by collecting 
 samples of the blood coming to and leaving them and analyzing the 
 gases. The mere difference of colour between the \'enous and 
 arterial blood of a muscle, or other acti\e organ, is sufficient to show- 
 that oxygen is taken up and carbon dioxide given out by it to the 
 blood. This is the case in muscle s;it rest, and even in muscles 
 with artificial circulation after they have become inexcitable. In 
 active muscles more oxygen is used up and more carbon dioxide 
 produced than in the resting state. Chauveau and Kaufmann, in 
 their experiments on the levator labii superioris muscle of the horse in 
 feeding, found that the consumption of oxygen and the production 
 of carbon dioxide might be many times as great in activity as in rest. 
 
 Thus in one experiment the amount of oxygen taken in, expressed 
 in CO. per gramme of muscle per minute, was o-oo8 during rest, and 
 0T4 during work; the corresponding quantities for the carbon dioxide 
 given oft were 0-006 and om8. The respiratory quotient rose to 1-3 in 
 two experiments, and even to 1-7 in a third, showing that the increase 
 in tlie production of carbon dio.xide was relatively greater than the 
 increase in the intake of oxygen. These experiments were performed 
 under conditions so normal that the animal continued to eat its hay 
 with seeming unconcern throughout the observations, although these 
 involved the exposure of the main bloodvessels of the muscle, and the 
 collection of samples of blood from them. 
 
 By means of the modern technique permitting the use of small 
 quantities of blood for the gas analysis, similar experiments have been 
 performed on a muscle as small as the cat's gastrocnemius. In one 
 experiment it was found that as a result of stimulation of the sciatic 
 lasting about 23 seconds the intake of oxygen was increased for at least 
 220 seconds. In this time the muscle used up 0-75 c.c. of oxygen, as 
 compared with 0-26 c.c, which it would have consumed had it not been 
 stimulated (Verzar). 
 
 Nature of the Oxidative Process. — When we have recognized the 
 cells as the seat of oxidation, the question immediately presents 
 itself. How do they accomplish the feat of burning such masses of 
 food substances as can only be rapidly oxidized in the laboratory 
 at the temperature of the body by the most energetic chemical 
 reagents ? The researches of late years have furnished a key to 
 the solution of this long-standing puzzle by demonstrating the 
 existence in the tissues of oxidizing ferments or oxydases. Of these, 
 one of the most widely distributed is a ferment which splits off 
 oxygen from hydrogen peroxide. Since any oxidation produced 
 is only secondary to this decomposition, ferments which decompose 
 hydrogen peroxide are often spoken of as catalases, to distinguish 
 them from the oxydases proper. A catalase is found in practically 
 all the tissues of the body, as well as in vegetable cells, and we have 
 already mentioned instances of its action in connection with the 
 oxidation of the guaiaconic acid in tincture of guaiacum in the 
 
272 RESPIRA TION 
 
 presence of the peroxide (p. yb). As regards the activity of this 
 ferment, blood comes first; then follow spleen, liver, pancreas, 
 thymus, brain, muscle, and ovary. It is present in the blood-free 
 organs as well as in the blood. Some tissues, both animal and 
 vegetable, contain a ferment, an oxydase, which causes the oxida- 
 tion of guaiaconic acid in the presence of atmospheric oxygen, and 
 these do not need peroxide of hydrogen in order to render guaiacum 
 blue. An allied ferment which also induces the blue colour in 
 tincture of guaiacum is the so-called laccase found in the most active 
 form in the latex of the tree from which Japanese lacquer is ob- 
 tained, but also in many other plants. Many fungi contain a fer- 
 ment, tyrosinase, which oxidizes tyrosin, and in certain animals 
 tyrosinases have also been demonstrated. Another well-known 
 oxidizing ferment in fresh animal tissues is characterized by the 
 property of forming indophenol by oxidation in an alkaline solution 
 of paraphenylenediamin and a-naphthol, and may therefore be 
 termed indophenyloxydase. The colourless solution becomes 
 reddish or \'iolet. This ferment is contained in pancreas, salivary 
 glands, spleen, thymus, and bone marrow, but has not been de- 
 tected in muscle, lungs, brain, kidneys, and other organs. It is 
 to be expected that other oxydases capable of favouring oxida- 
 tion of specific kinds of food substances or their decomposition 
 products will be discovered, but it ought to be remarked that 
 those at present known are only capable of attacking relatively 
 simple organic substances, and it would be rash to conclude 
 that this is the only way in which living protoplasm can bring 
 about the rapid, but at the same time the regulated, oxidation 
 which is so characteristic a feature of its activity. Yet the capacity 
 of the cell to regulate the intensity and the extent of the intra 
 cellular oxidations would seem to find a simple explanation if we 
 assign an important role to oxidizing ferments formed by the cell 
 itself in accordance with its needs. In this connection we may 
 mention a ferment, aldehydase, which was formerly included 
 among the oxydases, but is now known to be a hydrolytic enzyme. 
 It splits aldehydes so as to yield the corresponding acid — e.g., 
 saJicylic aldehyde is split into sahcylic acid and sahgenin. Evidence 
 of its presence in most organs has been obtaimd. 
 
 The Passage of Carbon Dioxide from the Tissues into the Blood. 
 — Since nearly the whole of the carbon dioxide c\cntually found in 
 the blood is formed in the tissues, and only a small amount in the 
 blood itself, it might be supposed that the partiid pressure of the 
 gas in the tissues would necessarily be greater than in the blood. 
 This would certainly be true if the whole of the carbon dio.xide 
 was transported in the form of dissolved gas. This, however, is 
 not the case. Much of it is combined, and as the proportion of 
 free to combined carbon dioxide in the blood is variable, it may be 
 
INTl-hWAL OR TlSSUl- RESPIRATION 373 
 
 assumed that it is also variable in the tissues. There is no e\i(l<nro 
 and httle piobabiHty that the variations are always parallel. Quan- 
 titative and e\en qualitatixe differences in the substances which can 
 bind carbon dioxide are known to exist between the blood and the 
 tissues, and it is uncertain how much interchange of such compounds 
 carrying with them combined carbon dioxide, which may after- 
 wards become dissociated, takes place between the blood and the 
 tissue lymph or the cells. However probable, then, it may be that 
 the transportation of carbon dioxide from the cells to the lymph, 
 and from the lymph to the blood is managed in the same way as 
 that of the carbon dioxide from the blood to the alveolar air, namely, 
 by diffusion of the gas in solution, it cannot be said that at present 
 clear proof of this has been obtained. Results are, indeed, on 
 record, which purport to show that the partial pressure of carbon 
 dioxide in various tissues or in physiological liquids which have 
 been in contact with them is higher than that of the arterial or even 
 than that of the venous blood. But these results are of unequal 
 and some of them of doubtful value for the solution of the problem 
 under discussion. 
 
 Lymph, bile, urine, and the eerous fluids contain so much carbon 
 dioxide that the pressure of that gas in all of them is greater than in 
 arterial blood, while in lymph alone (taken from the large thoracic 
 duct) has it been found less than that of venous blood. And it is pro- 
 bable that lymph gathered nearer the primary seats of its production 
 (the spaces of areolar tissue) would show a higher proportion of carbon 
 dioxide. Strassburg found that with a pressure of carbon dioxide in 
 the arterial blood of 21 mm. of mercury, the pressure in bile was 50 mm., 
 in peritoneal fluid 58 mm., in urine 68 mm., in the surface of the empty 
 intestine 58 mm. Saliva, pancreatic juice, and milk, also contain much 
 carbon dioxide. From muscle as much as 15 volumes per 100 of carbon 
 dioxide can be pumped out, some of which is free — that is, is given 
 up to the vacuum alone — while some of it is fixed, and only comes off 
 after the addition of an acid. 
 
 Before leaving the subject of the gaseous exchange between 
 tissues and blood and between blood and air some important con- 
 sequences of the form of the dissociation curve of oxyhaemoglobin, 
 and of the modifications produced in it by change of temperature, 
 by salts and by acids, must be alluded to. They have been developed 
 in masterly fashion by Barcroft. The flattening of the hyperbolic 
 dissociation curve of dialyzed oxyhaemoglobin when the tempera- 
 ture is raised (Fig. 119) makes it obvious that for any percentage 
 saturation which can exist in blood as it leaves the systemic capil- 
 laries, the corresponding partial pressure of oxygen must be much 
 greater at the body temperature (38° C.) than at 16° C. For haemo- 
 globin which is 50 per cent, saturated it is twenty-five times as 
 great. This favours the gi\ing up of oxygen to the tissues by blood 
 in which the percentage saturation is considerably reduced. On 
 
274 Rl-.Sni RATION 
 
 the other li.unl. the iibsorption of oxygen in th< hmgs is not seriously 
 interfered with, Ijecanse the available alveolar jjartial pressure of 
 oxygen is so high (loo mm. or more) that it cyn be considerably 
 diminished without causing any appreciable diminution in the 
 percentage saturation. 
 
 There is evidence that in dialyzed haemoglobin solutions the 
 haemoglobin is all in the form of single molecules. The addition of 
 salts as they exist in blood produces a certain amount of aggrega- 
 tion or clumi)ing of the molecules, and as already pointed out, this 
 alters the shape of the dissociation curve. The S-shape of the 
 curve of blood indicates that blood will part with its oxygen at 
 low oxygen pressures, as in passing through the tissues, much more 
 readily than a corresponding solution of salt-free oxyha;mogl(j])in; 
 and that it will take up oxygen more easily at high pressures, as 
 in passing through the lungs. As regards the effect of acids, it 
 was observed by Bohr (p. 255) that an increase in the carbon dioxide 
 tension of blood diminishes its combining power for oxygen, and 
 therefore favours the giving up of oxygen to the lymph and tissues. 
 This maj? have an important influence on internal respiration. The 
 effect is much more marked where the oxygen tension is low than 
 where it is high, so that in the lungs the taking up of oxygen is 
 scarcely interfered with even by a high carbon dioxide tension. 
 
 According to Barcroft, the combined effect of the increased tem- 
 perature, the salts and the carbon dioxide of blood (at the partial 
 pressure of 40 mm. of mercury) is to make possible a diffusion of 
 oxygen into the tissues at 100 times the speed at which it would 
 diffuse from a salt-free solution of oxyhaemoglobin at a tempera- 
 ture of 16° C. This astonishing feat is accomplished without 
 sensibly decreasing the percentage saturation with oxygen of the 
 blood passing through the lungs. 
 
 Section VI. — Relation of Respiration to the Nervous 
 
 System. 
 
 The Respiratory Centre and its Connections.— Unlike the beat of 
 the heart, the respiratory mo\ements are entirely dependent on the 
 central nervous system. The ' centre ' which presides o\'er them is 
 situated in the spinal bulb. It is a bilateral centre — that is, it has 
 two functionally symmetrical halves, one on each side of the middle 
 line. Each of these halves has to do more particularly with the 
 i-esi)iratory muscles of its own side, for destruction of one-half of 
 the spinal bulb causes paralysis of respiration only on that side. 
 Anatomically the respiratory centre has not been sharply localized, 
 l)ut it lies lower than the vaso-motor centre, not far from the point 
 of the cahimus scriptorius. Stimulation of this region dming apn(X'a 
 (p. 283) is stated to cause co-ordinated inspiratory movements and 
 
Ri:i.ATli)M OF KJiSJ'JHATlON TO I'lII' NICh'VOUS SYSTRM 275 
 
 widening of tlu- opening of the glottis tiirough abduction of the 
 vocal cords. The centre is brought into relation with the muscles 
 of respiration by efferent nerves. The phrenic nerves to the dia- 
 phragm, and the intercostal nerves to the muscles which elevate 
 the ribs, are the most important of those concerned in ordinary 
 breathing. The respiratory centre is further related to afferent 
 nerves, of which the most influential are those which supply the 
 respiratory tract itself, particularly the pulmonary fibres and superior 
 laryngeal branch of the vagus. But almost any afferent nerve ma\' 
 powerfully affect the centre; and it is also influenced by fibres pass- 
 ing to it from the higher parts of the central nervous system. 
 
 Section of the spinal cord in animals above the origin of the 
 phrenic nerves causes complete paralysis of respiration, and con- 
 sequent death. The phrenics arise from the third and fourth 
 cervical nerves, and are joined by a branch from the fifth; and in 
 man fracture of any of the four upper cervical vertebrae is as a rule 
 instantly fatal. But in one case respiration was carried on, and 
 life maintained for thirty minutes, merely by the contraction of the 
 muscles of the neck and shoulders in a man entirely paralyzed 
 below this level (Bell). Section of the cord just below the origin of 
 the phrenics leaves the diaphragm working, although the other 
 respiratory muscles are paralyzed. A case has been recorded of a 
 man in whom, from disease of the spine in the lower cervical region, 
 all the ribs became completely immovable. He was able to lead 
 an active life, and to carry on his business, although he breathed 
 entirely by his diaphragm and abdominal muscles. 
 
 Section of one phrenic is followed by paralysis of the correspond- 
 ing half of the diaphragm, section of both phrenics by complete 
 paralysis of that muscle, and although respiration still goes on by 
 means of the muscles which act upon the ribs, it is usually inadequate 
 to the prolonged maintenance of life. In the horse, however, not only 
 has survival been seen after this operation, but the animal, after 
 the first temporary increase in the frequency of the breathing had 
 disappeared, could be driven in a light vehicle without any marked 
 dyspnoea. The phrenic nuclei in the two halves of the cord are 
 connected across the middle line. For when a semisection of the 
 cord is made between this level and the respiratory centre in the 
 medulla, respiratory impulses are still able to reach both phrenic 
 nerves. In some animals both halves of the diaphragm go on con- 
 tracting. But when, as usually happens, this is not the case, and 
 the diaphragm on the side of the semisection has ceased to act, it 
 at once begins to contract again when the opposite phrenic nerv€ 
 is cut, and the respiratory impulse, descending from the bulb, is 
 blocked out from the direct, and forced to follow the crossed path. 
 It has been shown that the crossing takes place at the level of the 
 phrenic nuclei, and nowhere else (Porter). 
 
276 h-HSFl NATION 
 
 The Regulation of the Respiration through the Afferent Vagus 
 Fibres. — When one vagus is divided, tlien- is little or no change in 
 the respiratory movements. Half an inch of one vagus nerve has 
 been excised in removing a tumour, and the patient showed no 
 symptoms whatever. But section of both vagi in such animals as 
 the dog, cat and rabbit causes respiration to become much deeper 
 and slower, the one change for a time compensating the other, so 
 that the total amount of air taken in and given out, the amount of 
 carbon dioxide eUminated, and the partial pressure of that gas in 
 the pulmonary alveoli are not greatly altered. The relative dura- 
 tion of the two respiratory phases is completely changed, inspira- 
 tion being much more prolonged than expiration. It has been 
 shown that the effect is really due to the loss of impulses that nor- 
 mally ascend the vagi, not to any irritation of the cut ends. For a 
 nerve can be frozen without exciting it ; and when a portion of each 
 vagus is frozen, the respiration is affected in precisely the same 
 way as when the nerves are divided. 
 
 After section of both vagi certain fibres coming from the brain 
 above the respiratory centre appear to take a share in the regulation 
 of the respiratory movements. The bloodvessels supplying these 
 fibres, or the centres from which they come, can be blocked by 
 injection of paraffin wax into the common or internal carotid, or 
 the bulb can be severed with the knife above the level of the re- 
 spiratory centre, without any effect being produced upon the breath- 
 ing, except that the rate is as a rule somewhat lessened. But 
 when both the vagi and these upper paths are cut the character of 
 the respiration is changed, exceedingly prolonged inspiratory 
 spasms alternating with long periods of complete relaxation of the 
 diaphragm till the animal dies. 
 
 From these facts it appears that the periodic automatic discharges 
 of the respiratory centre are being continually controlled and modi- 
 fied by impulses passing up the vagus, and that in the absence of 
 these impulses a certain degree of control is exercised by the higher 
 paths, which, however, do not appear to be normally in action, at 
 any rate to the full measure of their capacity. When the vagi are 
 severed, the control of the higher paths comes into play, and is 
 sufficient still to keep the breathing regular, although it is slowed. 
 When the higher paths are cut off, the vagus of itself is able to regu- 
 late the discharge. But when both are gone, the respiratory centre, 
 freed from nervous control, passes into a condition of alternate 
 spasm and exhatistion. Of the central connections of these upper 
 paths but little is surely known. The corpora quadrigemina, how- 
 ever, seem to contain centres which can affect the respiration. 
 Certain areas on the cerebral cortex have also been described, the 
 excitation of which modifies the r(;spiratory movements. There is 
 no question that the cortex is connected, and extensively connected, 
 
RELATION OF RliSPI RATION TO THE NERVOUS SYSTEM 277 
 
 with the respiratory centre, since the rate and depth of the co- 
 ordinated respiratory movements, which are universally acknow- 
 ledged to involve the activity of the centre, can be altered not only 
 by the will, but by the most varied psychical events. 
 
 The rhythmical excitation of the regulating vagus fibres must 
 be brought about by either mechanical stimulation of the nerve- 
 endings in the lungs, due to the alternate stretching and shrinking, 
 or by chemical stimulation of these endings depending on the changes 
 that occur with each respiration in the content of oxygen and carbon 
 dioxide in the alveolar air, and therefore in their pressure (p. 260) 
 in the blood. Both views have found advocates, but whatever 
 influence the chemical changes in the blood may exert, there is no 
 doubt that the mechanical factors are the more important. That 
 the vagus is really excited is shown by the fact that a negative varia- 
 tion (p. 824) is set up in the nerve when the lungs are inflated. 
 An electrical change is' also observed when air is sucked out of the 
 lungs (Alcock and Secmann, Einthoven). 
 
 When the normal excitation of the vagus fibres by expansion of 
 the lungs is exaggerated by closing the trachea at the end of in- 
 spiration, the diaphragm immediately relaxes, and a long expira- 
 tory pause ensues, broken at last by a series of inspirations much 
 deeper and more prolonged than those which were taking place 
 before occlusion. When the trachea is occluded at the end of 
 expiration, a series of deep and long-drawn inspirations occurs, the 
 iirst of which begins at the moment when the next normal inspira- 
 tion ought to have taken place had the windpipe been left free. 
 The most obvious explanation of these results is that the expansion 
 of the lungs sets up impulses in the vagi which cut short the in- 
 spiratory activity of the respiratory centre (inspiration-inhibiting 
 fibres), while in collapse impulses are set up which excite it to re- 
 newed inspiratory discharge (inspiration-exciting fibres). Since 
 ordinary expiration is in the main not associated with active muscular 
 contraction, the inspiration-inhibiting fibres would be at the same 
 time expiration-exciting. Clearly this would constitute a so-called 
 ' self-steering ' arrangement, each inspiration leading inevitably to 
 the succeeding expiration, and each expiration providing the neces- 
 sary stimulus for the succeeding inspiration. On this hypothesis 
 section of the vagi must necessarily be followed by slowing of the 
 respiratory movements, and we have seen that this is the case. 
 
 A rival hypothesis is that the automatic activity of the respira- 
 tory centre leads normally to the discharge of motor impulses to 
 the inspiratory muscles, which are cut short at each expansion of 
 the lungs by the inhibitory action of the vagus, the nerve not being 
 excited during pulmonar^^ collapse, and therefore carrying no in- 
 spiratory impulses to the centre. On this assumption, we may 
 think of the centre as being ' wound up ' hke a clock, the periodic 
 
27 S RESPIRATION 
 
 arrival of regulating impulses acting like an escapement movement, 
 and allowing a certain amount of discharge. \\'hen the vagi are 
 cut, the inspirations are greatly prolonged and deepened, because 
 the check on the discharge of the centre has been removed. 
 
 Attempts have been made by experimental stimulation of the 
 vagus trunk to determine whether, as a matter of fact, it contains 
 both inspiratory and expiratory fibres. But the results are neither 
 so clear nor so constant that we can confidently appeal to them in 
 making a decision, and even some of the investigators who main- 
 tain the existence of but one anatomical set of fibres believe that 
 these are affected differently by different kinds of stimulation — 
 momentary stimuli, for example, setting up in them impulses 
 which we may call inspiratory, and long-lasting stimuli impulses 
 which we may call expiratory. 
 
 Excitation of the central end of the cut vagus below the origin 
 (A its superior lar\-npeal branch, with induction shocks of moderate 
 
 Fig. 1^4. — Kcspiratory Tracings: Uog. .■\. U'jrinal; B, eilect of stimulation of the 
 central end of vagus; C, effect of section of both vagi. (Tracing taken as in 
 Fig- 135- P- 301) Time-tracing, seconds. 
 
 strength, certainly causes quickening of respiration. If the excita- 
 tion be strong, there is arrest in the inspiratory phase. A brief 
 mechanical stimulus, or a series of such, has a similar effect. But 
 chemical stimulation {e.g., with a strong solution of potassium 
 chloride) or long-continued mechanical excitation like that produced 
 by stretching or compression of the nerve, or certain kinds of elec- 
 trical stimulation — for instance, the very weakest induction shocks, 
 or the closure of an ascending voltaic current* — cause slowing of 
 the respiratory movements or expiratory standstill. This is also 
 the usual, though not the invariable result of stimulating the 
 superior laryngeal, even when weak induction shocks are employed. 
 With stronger stimulation energetic contractions of the expiratory 
 muscles may occur. These facts undoubtedly suggest the existence 
 in the vagus of two kinds of afferent nerve-fibres that affect the 
 * I.e., a current passiog towards the head in the nerve. 
 
RELATION OJ- UliSPl RATIOS TO THE NERVOUS SYSTEM 27* 
 
 respiratory centre in opposite ways — inspiratory fibres, which 
 stimulate it to greater activity of discharge, and expiratory fibres, 
 whicli inhibit its action. The latter variety we may suppose to be 
 more numerous in the superior laryngeal, the former in the pul- 
 monary branches of the vagus. And there is nothing forced in the 
 hypothesis that certain kinds of stimuli act particularly on the one 
 set of fibres, and certain kinds on the other, for we have already 
 seen an instance of this in studying the differences between the vaso- 
 constrictor and the vaso-dilator nerves (p. 170). 
 
 The most probable conclusion, and the one which best reconciles the 
 conflicting hypotheses, is that two sets of fibres are present : (i) Fibres 
 which inhibit inspiration {and cause expiration), and are excited in 
 ordiuai'v iu'^piration h\< the expansion of the lungs. (2) Fibres which 
 
 Fig. 125. — Effect of Stimulation of Central End of Vagus in a Cat. Upper Trac;, 
 Respiration; Lower Trace, Blood- Pressure. At the top are the time-trace 
 (seconds), and below it the signal line, the depression in which indicates the 
 duration of the excitation. Practically no eSect was produced on the respira- 
 tion, but a fall of blood -pressure with slowing of the heart. 
 
 cause inspiration {and inhibit expiration), and are excited in st/ong 
 expiration, as in dyspncsj, by the collapse of the lungs, but are not 
 active in ordinary expiration. 
 
 However this may be, the facts we have been discussing have an 
 importance of their own, apart from any hypothetical explanations 
 of them. Some of them have been more than once unintentionally 
 illustrated on man. In one case the left vagus trunk was included 
 in a ligiture with the common carotid. The respiratory move- 
 ments immediately stopped, the pulse was slowed, and death 
 occurred in thirty minutes (Rouse). The superior lar^Tigeal fibres, 
 unlike those of the vagus proper, are not constantly in action, as 
 section of both nerves has no effect on respiration. An}^ source of 
 irritation in the larynx may stimulate these fibres and produce a 
 
2S-) 
 
 RhSH RATIOS 
 
 cough, whicli may also be caused by irritation of the puhnonary 
 fibres of the vagus. 
 
 Action of Other Afferent Fibres on the Respiration. — The cutaneous 
 nervfs, and c^juTially thoM- of tlic face (fifth nrrvc), abdomen and 
 chest, havr a marked influence on respiration. They can be easily 
 excited in the intact body by thermal and mechanical stimulation. 
 A cold bath, for instance, usually causes acceleration and deepening 
 of the respiratory movements; and the efficacy of meclianical stimu- 
 lation of sensory nerves in stirring up a sluggish respiratory centre 
 iswcll known t(^ midwives, who sometimes slap the buttocks of a new- 
 
 Fig. 126. — Effect of Stimulation of Central End of Brachial Nerve on Respiration 
 (Upper Tracing) and Blood-Pressure (Lower Tracing) in the Cat. At the top of 
 the figure are the time-trace (seconds) and the signal line, showing beginning and 
 end of stimulation. 
 
 born child to start its breathing. The reflex expiratory standstill 
 caused in rabbits by inhalation of such sharp-smelling substances as 
 ammonia, acetic acid, and tobacco-smoke is due to afferent impulses 
 passing up the trigeminus fibres from the mucous membrane of the 
 nose, and is still obtained after section of the olfactory nerves. 
 
 Another set of afferent nerves which have been supposed by some 
 to bear an important relation to the respiratory centre are those 
 which supply the muscles. We have already noticed that the 
 frequency of respiration is greatly augmented by muscular exercise. 
 The simplest e.xplanation would seem tf) hv thftt afferent muscular 
 nerves are stimulated either by mechanical compression of their 
 
RELATIOX Ol- RhSril^AflON TO THIi MiRl'UUS SYSIILM 281 
 
 terminal 'spindles,' or by the chemical action on them of certain 
 waste products produced in contraction. It is quite likely that this 
 is one way in which the adjustment is achieved. But this is not 
 the only, and perhaps not the most important, way. For an in- 
 crease in the respiratory movements is caused by tetanizing the 
 muscles of a limb whose nerves have been completely severed, and 
 which is indeed connected with the rest of the body by no other 
 structures than its bloodvessels. This can only be due to two things : 
 a direct action on the respiratory centre by the blood that has 
 ])asse(l tlirough. and been altered in, the contracting muscles, or an 
 action exerted l)y the blood indirectly on the centre through the 
 excitation of afferent respiratory nerves whose connection with it 
 is still intact — for example, the other muscular nerves or the pul- 
 monary branches of the vagus. That the action is direct is shown 
 by the fact that after section of the vagi, the sympathetic, and the 
 spinal cord below the origin of the pluenics, an increase in the 
 respiratory movements is still ])ro(luct(l by tetanizing a limb. 
 
 The Chemical Regulation of the Respiration. However im- 
 portant the regulation of respiration by afferent nervous impulses 
 may be, the normal discharge of the respiratory centre is intimately 
 associated with the gases of the blood. 
 
 It is generally acknowledged that the centre may be excited both 
 by blo(xl tliat is rich in carbon dioxide and by blood that is poor in 
 oxygen. Stimulation by deiiciency of oxygen has to some minds 
 presented a metaphysical difficulty — namely, that it is not easy to 
 see how the absence of a thing could cause stimulation. The diffi- 
 culty does not exist, but none the less there is some evidence that 
 when oxygen is lacking the respiratory centre can be excited by 
 substances likv lactic acid, which are easily oxidizable and rapidly 
 disappear from properly oxygenated blood. 
 
 Be that as it may, it has been the subject of long-continued dis- 
 cussion whether excess of carbon dioxide or deficiency of oxygen is 
 the more potent stimulus for the respiratory centre. The best evi- 
 dence points to the conclusion that comparatively small alterations 
 in the amount of carbon dioxide in the inspired air cause a relatively 
 great increase in the respiration, while in the case of the oxygen the 
 departure from the normal proportion must be much more decided 
 to bring about any notable effect. Nor is it at all out of harmony 
 ^vith this that, when very large quantities of carbon dioxide (30 per 
 cent, and upwards in rabbits) are inhaled, a condition of narcosis 
 comes on without an}- previous respiratory distress. For many 
 substances act differently in large and in small doses. Haldane has 
 pointed out how exquisitely sensitive the respiratory centre is to even 
 small changes in the partial pressure of carbon dioxide in the alveo- 
 lar air, and therefore in the arterial blood and the centre itself, and 
 has demonstrated that this is the way in which the amount of the 
 
282 liESPl RATIOS 
 
 pulmonary ventilation (tlic volume of air breathed per unit of time) 
 is rhiefiy regulated in ordinary breathing. 
 
 For instance, an increase of as little as o-z per cent, of carbon 
 dioxide in the alveolar air, corresponding to an increase of 1-4 mm. 
 of mercury in the partial pressure (p. 247) of the gas. caused an 
 increase in the pulmonary ventilation of 100 per cent. The alveolar 
 oxygen pressure had to be diminished to 13 per cent, of an atmo- 
 sphere before any decided increase in the respiration occurred. 
 During moderate muscular work the percentage of carbon dioxide 
 in the alveolar air, and therefore in the blood, increases slightly, 
 causing an increase in the ventilation, and this is one of the ways in 
 which the hyperpncea associated with muscular exercise is brought 
 about. In severe work lack of oxygen, with accumulation of lactic 
 acid and other metabolic products, which increase the hydrogen-ion 
 concentration in the blood and thus stimulate the respiratory 
 centre or render it e.xcitable by smaller pressures of carbon dioxide, 
 also plays a part. There is some evidence that in the case of 
 carbon dioxide also the actual excitation of the respiratory centre is 
 due to the increased hydrogen-ion concentration. Some phvsiolo- 
 gists hold the view that the respiratory centre reacts in the same 
 way to a given increase in hydrogen-ion concentration no matter 
 what the acid may be, and that there is nothing specific in the 
 action of carbon dio.xide. If it be assumed that changes in the 
 hydrogen-ion concentration of the blood are only caused bv sub- 
 stances like carbon dioxide, which are ehminated by the lungs, 
 or by substances Hke lactic acid, which are either got rid of by oxi- 
 dation or are not liberated into the blood in the presence of a good 
 oxygen supply, no serious theoretical objection can be urged against 
 this conclusion. For increased activity of the respiratory centre 
 would favour the elimination of carbon dioxide and absorption of 
 oxygen, and in both wa^'s would tend to maintain the normal 
 hydrogen-ion concentration in the blood. If, however, the hvdrogen- 
 ion concentration can be influenced by substances which are not 
 directly affected by the respiratory process, it would seem unlikely 
 that the respiratory centre should blindly respond to such changes 
 just as if they had been produced by substances, the amount of 
 which it can effectively control. 
 
 To sum lip, the regulation of nortnal breathing is twofold — a chemical 
 regulation (through the carbon dioxide, possibly by changes produced 
 in the hydrogen-ion concentration in the blood) of the amount of air 
 moved into and out of the lungs per unit of time ; and a nervous regu- 
 lation (chiefly through the vagi) of the rate and depth of the movements 
 necessary to effect the given amount of ventilation. 
 
 When the vagi have been divided, an increase in the carbon 
 dioxide pressure within certain limits is responded to bv an increase 
 in the total ventilation, just as in the normal animal, but the form 
 oi the response is different. \Miercas in the normal animal both 
 
RELATION OF RISSPl RATION TO Tllli NERVOUS SYSTEM 283 
 
 the rate and the depth of respiration are increased, in the vagoto- 
 niized animal there is a marked increase in depth, with httle or no 
 increase in rate (Scott). 
 
 WTien the gaseous exchange in the lungs from any cause becomes 
 insufficient, the respiratory movements are exaggerated, and ulti- 
 mately every muscle which can directly or indirectly act upon the 
 chest-wall is called into play in the struggle to pass more air into 
 and out of the lungs. To a lesser and greater degree of this exag- 
 geration of breathing the terms Hyperpncca and Dyspnoea have been 
 respectively applied. If the gaseous interchange remains insuffi- 
 cient, or is altogether prevented, asphyxia sets in. Sometimes in 
 man impending asphyxia from loss of function by a part of the lungs 
 (with crippling of the lesser circulation), as in pneumonia, may be 
 warded of^ by inhalations of oxygen. Increase in the temperature 
 of the blood circulating through the spinal bulb, as when the carotid 
 arteries of a dog are laid on metal boxes through wliich hot water 
 is kept flowing, also causes dyspnoea {heat-dyspncea) (p. 302). But 
 if the temperature be too high, the respiratory movements maj^ be 
 slowed, perhaps by a partial paralysis or inhibition of the respiratory 
 centre. When the blood is cooled the respiration becomes deeper 
 and slower, but if the temperature is greatly and suddenly lowered, 
 the centre may be stimulated and the breathing quickened. In 
 man the increased temperature of the blood in fever is a cause, 
 though not the only one, of the increase in the rate of respiration. 
 
 Apnoea. — The phj^siological opposite of dyspnoea is apncei. This 
 condition may be produced in an animal by rapid or prolonged 
 artificial respiration. It is especiall^^ easy to obtain in an animal 
 in which the circulation through the brain and bulb is interrupted 
 for a time and then restored, while artificial respiration is being kept 
 up. Spontaneous respiration returns after a longer or shorter 
 interval, but if the artificial respiration be still maintained, it again 
 ceases. In a successful experiment the animal remains without 
 breathing for many seconds after the artificial respiration is stopped. 
 In apnoea the chest remains at rest in the expiratory phase if the 
 lungs have been inflated by the artificial respiration and then allowed 
 to collapse of themselves (expiratory apnoea), but in the inspiratory 
 phase if they have been emptied by suction and then permitted of 
 themselves to expand (inspiratory apnoea). The apnoea is not pro- 
 duced, as some have thought, by the accumulation of an excess of 
 oxygen in the blood, for rapid and repeated inflation of the lungs 
 with hydrogen may cause the condition. Indeed, towards the end 
 of the apnoeic period the venous blood may be very distinctly poorer 
 in oxygen than normal venous blood. Apnoea is easily caused in 
 man by a period of deep and rapid breathing and in other ways. 
 The essential thing in this chemical or true apnoea {apnoea vera) 
 is the lowering of the partial pressure of carbon dioxide in the 
 alveolar air, and therefore in the arterial blood and the respiratory 
 
284 HESPIRATION 
 
 centre. The carbon dioxide \- \va lied out of the body, so to say, 
 by the excessive pulmonary ventilation. 
 
 In addition to chemical apnoea, which is obtainable whether the 
 vagi are intact or not, a so-called mechanical apnoea, or apnax vagi, 
 exists— that is to say, a stoppage of the respiration due to an 
 inhibitory effect produced through the vagi on the respiratory centre 
 when the vagus endings in the lungs are excited mechanically by 
 inflation. Some observers state that this vagus apnoea does not 
 outlast the inflation. Others believe that the results of successive 
 inflations can be ' summated ' in the centre, giving rise to an apnoea 
 which persists after stoppage of the artificial respiration. That a 
 ' memory ' of a prolonged rhythmical inflation of the lungs can 
 impress itself in some way on the respiratory centre is shown by 
 the cmious phenomenon that in resuscitation of the bulb after a 
 period of an;emia the natural respiration, when it returns, msiy 
 have for a short time exactly the same rhythm as the artificial 
 respiration which has just been stopped. 
 
 That the blood when the gaseous exchange in the lungs is inter- 
 ferea with produces dyspnoea by acting on some portion of the brain 
 may be shown in an interesting manner by establishing what is 
 called a cross-circulation in two rabbits or dogs. The vertebral 
 arteries and one carotid are tied in both animals; the remaining 
 carotids are divided and coimected crosswise by glass tubes, or, 
 what is better, as it avoids the risk of clotting, they are crossed by 
 suturing the cut ends, so that the brain of each is supplied by blood 
 from the otheT. When the respiration is artificially hindered or 
 stopped in one of the animals, it shows no dyspnoea; it is in the 
 other, whose brain is being fed with improperly ventilated blood, 
 that the respiratory movements become exaggerated. The point 
 of attack of the ' venous ' blood has been further localized in the 
 spinal bulb by the observation that when the brain has been cut 
 away above it, the cord severed below the origin of the phrenics, 
 and all other nerves connected with the region between the two 
 planes of section divided, any interference with the gaseous ex- 
 change in the lungs is at once followed by dyspnoea.* 
 
 Automaticity of the Respiratory Centre. — The question has been 
 raised whether, in the absence of this ' natural ' stimulation by the 
 blood, and of the impulses that constantly reach the centre along 
 its afferent nerves, it would continue to discharge itself, or whether 
 it would sink into inaction. We have already discussed a similar 
 (luestion in regard to the cardiac and vaso-motor centres, and the 
 subject must again present itself when we come to examine the 
 functions of the central nervous system. In the meantime it is only 
 necessary to say that there is evidence that it is not the mere 
 
 * The conclusion is doubtless correct, but this experiment is not decisive. 
 For the phrenic nerves themselves contain afferent fibres, the stimulation of 
 which can influence the respiration after section of the vagi. 
 
REI.ATIOX OF h'i:SFlh'AriON TO Till: Ni:h'VOI'S S'^STEM 2S5 
 
 presence of carbon dioxide (or other substances) in the blood circu- 
 lating through the respiratory centre wliich determines the constant 
 excitation of the centre, but rather the a( cuinulati(Mi of tarbon 
 dioxide, or the increase of hydrogen-ion concentration, in the 
 centre itself when the partial pressure of that gas in the blood 
 is raised. The idea that the ( onti uious excitation of the centre 
 is ' autochthonous ' — in other words, that it is due to an internal 
 stimulating substance or substances manufactured in the centre 
 itself, as well as carried to it in the blood — renders it easy to under- 
 stand that the discharge of the respiratory centre, although modified 
 by the quality of the blood which circulates in it, is not essen- 
 tially dependent on it. Indeed, in cold-blooded animals whose 
 blood has been replaced by phj'siological salt solution, and (in frogs) 
 even after the circulation has been stopped altogether by excision 
 of the heart, quiet, regular breathing may be seen for a considerable 
 time. Of course, blood is essential for the continued nutrition of the 
 centre and its connections, and it eventually breaks down and ceases 
 to discharge. The respiratory discharge is still less dependent for its 
 initiation upon the arrival of afferent impulses. For after section 
 of the bulb above the centre, of the cord below the origin of the 
 l)hrenics, of the vagi and of the posterior roots of all the upper cer- 
 vical nerves, the spasmodic respiration which we have already 
 described as occurring when the vagi and the higher paths have been 
 severed continues without essential modification. It has also been 
 observed that during resuscitation of the bulb and upper cervical 
 cord after a period of anaemia, stimulation of afferent nerves, in- 
 cluding the vagi, is entirely without influence on the respiratory 
 movements for some time after respiration has returned, presumably 
 because the synapses (p. 852) on the afferent paths lying within the 
 previously anaemic area are as yet unable to conduct the nerve 
 impulses. Nevertheless, the respiratory centre continues steadily 
 to discharge itself along the efferent paths, whose sjmapses are 
 situated beyond the anaemic region. Section of the bulb above 
 the level of the respiratory centre, and of the cord below the origin 
 of the phrenic nerves, in addition to the anaemia, makes no essential 
 difference in the result. The initial rate of discharge of the centre 
 thus isolated from afferent impulses is approximately constant in 
 different experiments (about four a minute in cats). 
 
 Spinal Respiratory Centres. — Although the chief respiratory centre 
 lies in the medulla oblongata, under certain conditions impulses to 
 the respiratory muscles may originate in the spinal cord. Thus, in 
 young mammals (kittens, puppies), especially when the excitability 
 of the cord has been increased by strychnine, in birds and in alli- 
 gators, movements, apparently respiratory, have been seen after 
 destruction of the brain and spinal bulb. In adult cats, when 
 the functions of the brain, medulla, and cervical cord have been 
 abolished by occlusion of their vessels, similar movements of the 
 
286 RESPl RATION 
 
 thoracic and abdominal muscles may be seen, but they are not sufTi 
 cient for effective respiration. No proof has ever been given that 
 in the intact organism the spinal cord below the level of the bulb 
 takes any other part in respiration than that of a mere conductor of 
 nerve impulses; and it is not justifiable to assume the existence of 
 automatic spinal respiratory centres on the strength of such experi- 
 ments as these. 
 
 Death after Double Vagotomy. — Alterations in the rhj^hm of respira- 
 tion are not the only effects that follow division of both vagi (or vago- 
 sympathetics) in the neck. In certain animals, at least, this operation 
 is incompatible with life. In the rabbit, as a rule, death takes place in 
 twenty-four hours. A sheep may live three days, and a horse five or 
 six. bogs often live a week, occasionally a month or even two, and in 
 rare instances they survive indefinitely. The most prominent symp- 
 toms (in the dog), in addition to the marked and permanent slowing 
 of respiration, quickening of the pulse and contraction of the pupils, 
 are difficult deglutition, accompanied by frequent vomiting and pro- 
 gressive emaciation. The appetite is sometimes ravenous, but no 
 sooner is the food swallowed than it is rejected ; and this is particularly 
 true of water or liquid food. Sometimes the rejected food is simply 
 regurgitated after having reached the lower end of the oesophagus, 
 without entering the stomach. The fatal result is usually caused, or 
 at least preceded, by changes of a pneumonic nature in the lungs. The 
 precise significance of the pulmonary lesion is obscure. But it would 
 seem that paralysis of the laryngeal and oesophageal muscles, with the 
 consequent entrance of saliva, food, or foreign bodies, carrying bacteria 
 into the lungs, is responsible to a great extent. And when only a partial 
 palsy of the glottis is produced, by dividing the right vagus below the 
 origin of the recurrent laryngeal, and the left as usual in the neck, pneu- 
 monia either does not occur or is long delayed. It may be that the tissue 
 of the lungs is rendered particularly susceptible to such insults in conse- 
 quence of trophic or vascular changes induced by section of the pul- 
 monary and cardiac fibres in the ^'agi. It may be quite clearly demon- 
 strated, however, in animals which live for some weeks, that, not- 
 withstanding the paralysis of the glottis associated with aphonia, no 
 pulmonary symptoms may be present till a day or two before death. 
 The picture presented in these cases is that of an animal suffering, 
 above all, from alimentary disturbances. The respiration is, to be sure, 
 very different from the normal in frequency, depth, and type, but there 
 is nothing to suggest that the lungs are the seat of any pathological 
 process. Suddenly the picture changes. Pulmonary symptoms ob- 
 trude themselves. The physical signs of consolidation of the lungs 
 may be detected, and in a short time the animal is inevitably dead. 
 Occasionally the determining cause of the pulmonary lesion seems to 
 be some external circumstance, as a sudden fall of the air temperature. 
 The idea is exceedingly apt to present itself to the observer that the 
 pneumonia is an accident, an acute intercurrent affection breaking the 
 course of a chronic malnutrition, which in any case must have ended 
 in death. Of course, the vagotomizcd animal is predisposed to this 
 accident, but there is no definite time after section of the nerves at 
 which it must take place. The vomiting is certainly connected with the 
 paralysis and consequent dilatation of the oesophagus ; and by previously 
 making an artificial opening into the stomach or by a surgical prophy- 
 laxis still more heroic, the establishment of a double gastric and 
 oesophageal fistula (p. 4^1), death may be prevented for many months. 
 Elimination of all the pulmonary fibres of the vagi, by extirpation of 
 
Rlll.ATlOS OF Kr.SPrRATTON TO Ttll. SlUiVOUS SYSTJ:M 287 
 
 one lunj;, followed after an interval by section of the opposite vagus 
 in the neck, is not fatal in rabbits. This is also in favour of the vicv; 
 that in double vagotomy the stress fails mainly on the digestive system 
 
 Innervation of the Bronchial Muscles. — Both constrictor and 
 dilator fibres for the bronchi arc contained in the vagus. They are 
 not constantly in action, but can be reflexly excited, most easily 
 (in the dog and cat) by stimulating the nasal mucous membrane, 
 and particularly a small area well back upon the nasal septum. 
 Cauterization of the corresponding area in man is said to give per- 
 manent relief in certain cases of spasmodic asthma, a condition in 
 which the recurrent attacks of dyspnoea seem, according to the most 
 generally accepted view, to be associated with spasm of the bronchial 
 muscles. 
 
 Special Modifications of the Respiratory Movements. — Cheyne- 
 Stokcs Respiration is the name given to a peculiar type of breathing, 
 marked by pauses of many seconds alternating with groups of 
 respirations. In each group the movements gradually increase to 
 a maximum amplitude, and then become graduall}^ shallower again, 
 till they cease for the next pause. The phenomenon often occurs in 
 certain diseases of the brain and of the circulation, and pressure on 
 the spinal bulb may produce it. In cats in which the circulation 
 in the brain and medulla oblongata has been interrupted for a time 
 and then restored it is often noticed at a certain stage of resuscita- 
 tion of the respiratory centre. In frogs, Cheyne- Stokes breathing 
 has been observed as the result of interference with the circulation 
 in the spinal bulb, ' drowning,' or ligature of the aorta, and also as 
 a consequence of removal of the brain, or parts of it (hemispheres 
 and optic thalami). But it is not pecuHar to pathological conditions, 
 being also seen, more or less perfectly, in normal sleep, especially in 
 children, in healthy men at high altitudes, in hibernating animals, 
 and in morphine and chloral poisoning. 
 
 Well-marked Cheyne-Stokes breathing can be obtained experi- 
 mentally in normal persons in a variety of ways. If, for example, 
 the subject is caused to breathe deeply and frequently for about two 
 minutes, so as to produce a prolonged apnoea, the respiration, when 
 it is resumed spontaneously, is of the Cheyne-Stokes t\'pe (Haldane). 
 The explanation given by Haldane is that the fall in the partial 
 pressure of the oxygen in the pulmonary alveoli (p. 283) during the 
 primary apnoea, with the consequent fall of oxygen pressure in the 
 arterial blood and the respiratory centre, leads to the production 
 of lactic acid in the respiratory centre and elsewhere, which stimu- 
 lates the centre in the same way as carbon dioxide, and thus permits 
 it to be excited by a smaller partial pressure of carbon dioxide than 
 that normally necessary. As soon as the pressure of carbon dioxide, 
 which is increasing during the period of apncea, has reached the 
 exciting value breathing is resumed. The respirations, beginning 
 as very feeble movements, rapidly increase in strength till the 
 
288 RESPI/iATin>! 
 
 breathing becomes quit"' deep or actually dyspna-ic. The store of 
 oxygen is replenished by this thorough ventilation of the lungs, the 
 changes in the excitability of the respiratory centre due to lack of 
 oxygen disappear (perhaps by oxidation of the lactic acid), and the 
 centre relapses into a period of repose. During this period of apna-a 
 the oxygen pressure sinks once more to the point at which the change 
 in the excitability of the respiratory centre by carbon dioxide occurs, 
 and the breathing again starts. In pathological cases the want of 
 oxygen may be associated either with deficient circulation through 
 the bulb-centre or with deficient intake by the lungs. The adminis- 
 tration of oxygen through a mask has been shown in such cases to 
 abolish the periodicity in the respiration, and to render it more 
 normal. 
 
 Peculiarly modified, but more or less normal, respiratory acts are 
 coughing, sneezing, yawning, sighing, and hiccup. 
 
 A cough is an abrupt expiration with open mouth, which forces 
 open the previously closed glottis. It may be excited reflexly from 
 the mucous membrane of the respiratory tract or stomach through 
 the afferent fibres of the vagus, from the back of the tongue or 
 mouth, and (by cold) from the skin. 
 
 Sneezing is a violent expiration in which the air is chiefly expelled 
 through the nose. It is usually excited reflexly from the nasal 
 mucous membrane through the branch of the fifth nerve which 
 suppUes it. Pressure on the course of the nasal nerve \vi\\ often 
 stop a sneeze. A bright light sometimes causes a sneeze, and so in 
 some individuals does pressure on the supra-orbital nerve, when the 
 skin over it is slightly inflamed. 
 
 Yawning is a prolonged and very deep inspiration, sometimes 
 accompanied with stretching of the arms and the whole body. It 
 is a sign of mental or physical weariness. 
 
 A sigh is a long-drawn inspiration, followed by a deep expiration. 
 
 Hiccup, or 'hiccough, is due to a spasmodic contraction of the dia- 
 phragm, which causes a sudden inspiration. The abrupt closure of 
 the glottis cuts this short and gives rise to the characteristic sound. 
 The following readings of the intervals between successive spasms 
 were obtained in one attack: 13 sees., 12 sees., 15 sees., 9 sees., 
 14 sees., etc. — i.e., one-fourth or one-fifth of the frequency of the 
 ordinary respiratory movements. The mere fixing of the attention 
 on the observations soon stopped the hiccup. 
 
 Hiccup is generally considered to be a reflex movement, brought 
 about through the respiratory centre by afferent impulses originating 
 in the stomach. The irritation may be merely due to some slight 
 digestive disturbance set up by overfilling of the stomach, perhaps. 
 This is exceedingly common in infants. But persistent hiccup may 
 also be a distressing symptom of very formidable diseases — for 
 example, carcinoma of the pylorus. Experimentally, reflex con- 
 tractions of the diaphragm can sometimes be elicited by stimulation 
 
INFLUEXCI-: oi' in:si'ih\rnu.\ ox riii-: bloou i'ia-.ssri<E 2S9 
 
 of the central end of the \agu.s at a time when no s])Mntancous 
 respiratory movements are going on. This has been observed, for 
 instance, in cats during resuscitation of the brain after a period of 
 anjemia. In man also, in a case of Chey ne-Stokes respiration accom - 
 panied by hiccup, it was seen that tlie hiccup persisted during tlie 
 periods of apncva. If the respiratory centre is the centre for the 
 hiccup reflex, it can therefore be excitetl by afferent nervous im- 
 pulses at a time when it is not excited by the normal chemical 
 stimulus (MacKenzie and Cushny). 
 
 Section VII. — The Influen'ce of Respiration on the Blood- 
 Pressure. 
 
 We have already stated, in treating of arterial blood-pressure 
 (p. Ill), that a normal tracing shows a series of waves corresponding 
 with the respiratory movements. 
 
 The relationship between the respiratory phases and the rise and 
 fall of the blood-pressure is not by any means a simple and invariable 
 one. It depends upon a number of factors, which need not be 
 equally influential under different conditions or in different animals 
 (Lewis). Something depends upon the rate, something upon the 
 relative preponderance of costal and abdominal respiration, and 
 something probably upon the size of the animal. For instance, an 
 inspiratory rise of blood-pressiure occm^s in man with pure dia- 
 
 Fig. 127. — Respiratory Waves in ihe Blood-Pressure: Simultaneous Tracings of 
 Movements of Respiration and of Radial Pulse in Human Subject (Lewis). In 
 A the respiration was diaphragmatic; in B, costal. In A the respiratory tracing 
 was taken from the abdominal wall ; in B, from the chest. 
 
 phragmatic, and a fall with pure thoracic, breathing (Fig. 127). In 
 cats with fairly fast and not very deep respiration the blood- pressure 
 rises in expiration and sinks in inspir^.tkrn. With deep and slow 
 respiration the opposite effect may, upon the whole, be seen. In 
 dogs, according to Einbrodt," although the mean blood-pressure is 
 falling for a short time at the beginning of inspiration, it soon reaches 
 its minimum, then begins to rise, and continues rising during the 
 
 19 
 
290 
 
 RESPIRATION 
 
 rest of this p riou. At the commencement of expiration it is still 
 mounting, but soon reaches its maximum, begins to fall, and con- 
 tinues falling through the remainder of the expiratory phase. 
 
 A partial explanation is afforded by a consideration of the mechan- 
 ical changes produced in the thorax by the respiratory movements. 
 Of these, the influence of variations in the intrathoracic pressure 
 on the filling of the heart is of special importance. With deep 
 abdominal breathing the changes of intra-abdominal pressure also 
 affect the rilling of the heart, an increase of pressure (in inspiration) 
 tending to cause more blood to be squeezed from the abdominal 
 veins towards the chest. The changes of vascular resistance in the 
 lungs, due to the alteration in the calibre of the pulmonary vessels, 
 may also contribute, but, for such variations of intrathoracic 
 pressure as normally occur, only in a minor degree. The changes 
 in the vascular capacity of the lungs — that is, in the amount of 
 blood contained in the pulmonary vessels — are of importance espe- 
 cially in delajang or accelerating the alterations of blood-pressure in 
 the systemic arteries due to the other factors. 
 
 The intrathoracic pressure, which, as we have seen, is always less 
 than that of the atmosphere, unless during a forced expiration when 
 the free escape of air from the lungs is obstructed, diminishes in 
 inspiration and increases in expiration. The great veins outside the 
 chest, the jugular veins in the neck, for example, are under the 
 atmospheric pressure, which is readily transmitted through their 
 
 thin walls, while the heart and 
 thoracic veins are under a 
 smaller pressure. The venous 
 blood both in inspiration and ex- 
 piration will, accordingly, tend 
 to be drawn into the right 
 auricle. In inspiration the ven- 
 ous flow will be increased, since 
 the pressure in the thorax, and 
 therefore in the pericardial 
 cavity, is diminished; and upon 
 the whole more venous blood 
 will pass into the right heart 
 during inspiration than during expiration. Now, the right ventricle is 
 not in general working as hard as it can work. Hence, the excess of 
 blood which reaches it during an inspiration is at once sent into the 
 lungs, although not even the first of it can have passed through to 
 the left side of tJie heart at the end of the inspiration, since the 
 pulmonary circulation-time (four to five seconds in a small dog, 
 two to three seconds in a rabbit) is longer than the time of a com- 
 plete inspiration at any ordinary rate. The increase in the quantity 
 of blood pumped into the pulmonary artery will, if not counteracted 
 by other circumstances, tend to raise the blood-pressure in the 
 
 
 / 
 
 / 
 
 J 
 
 / 
 
 rig. 128.— The upper tracing shows the 
 respiratory movements in a rabbit with 
 rather deep and slow diaphragmatic 
 breathing; the lower tracing is the 
 blood-pressure curve; /, inspiration; 
 E, expiration, including the pause. 
 
iXFLUF.xcE or h'i:si'iriATio.\ o.\ Tin: Bi.ooi)i'Ri:ssrRE 291 
 
 artery and its hi am Iks, and thcn-forc at once to accelerate tlie out- 
 flow through the pulmonary veins. This will be aided if at the 
 same time the vascular resistance in the lungs is reduced, as is 
 generally stated to be the case. The left ventricle, hke the right, 
 is capable of discharging more blood than it ordinarily receives. The 
 excess of blood coming to it is easily and promptly ejected. The 
 systemic arteries are better filled and the arterial pressure rises. 
 
 In expiration the contrary will hap])en. The return of blood to 
 the thorax will be checked. This is well shown by the swelling of 
 the veins at the root of the neck in expiration, their shrinking in 
 inspiration, the so-called respiratory venous pulse. Less blood 
 being drawn into the right heart, less will be pumped into the pul- 
 monary artery, in which the pressure will, of course, fall. The out- 
 flow into the left auricle will thus be diminished — all the more if in 
 the expiratory phase the vascular resistance in the lungs is increased 
 — and the systemic arterial pressure will be lowered. In both cases, 
 however, the change seen in the blood-pressure curve will be belated, 
 and will not coincide exactly with the commencement of the inspira- 
 tion or the expiration. If it is delayed for a period about equal to 
 the length of an inspiration or an expiration, the blood-pressure 
 will be seen to sink in inspiration and to rise in expiration. If 
 the period of delay is less than this, the pressure will be mounting 
 during a part of each respiratory phase and falling during the 
 rest. As to the explanation of the delay, several factors may be 
 concerned. 
 
 The negative pressure of the thorax acts on the aorta, as well as 
 on the thoracic veins, although, on account of the greater thickness 
 of its walls, to a smaller extent than on the veins. The diminution 
 of pressure in inspiration tends to expand the thoracic aorta, and to 
 draw blood back out of the S3'stemic arteries, while expiration has 
 the opposite effect. And although the hindrance caused in this way 
 to the flow of blood into the arteries during inspiration, and the 
 acceleration of the flow during expiration may not be great, they 
 will, of course, be better marked in small animals with compara- 
 tively yielding arteries than in large animals. Yet, whether great 
 or small, the tendency will be to diminish the pressure in the one 
 phase and increase it in the other. As soon as the changes of pres- 
 sure produced by alterations in the flow of venous blood into the 
 chest and through the lungs are thorouglily established, the arterial 
 effect will be overborne; but before this happens — that is, at the 
 beginning of inspiration and expiration — it will be in evidence, and 
 will help to delay the main change. 
 
 Another factor in this delay is found in the changes of vascular 
 capacity which take place in the lungs when they pass from the 
 expanded to the collapsed condition. The expansion of the lungs 
 in natural respiration causes a widening of the pulmonary capillaries, 
 with a consequent increase of their capacity and diminution of their 
 
292 PhSPI NATION 
 
 resistance. When the vessels at the base of the heart are hgatured 
 either at the height of inspiration or the end of expiration, so as 
 to obtain the vvliole of the blood in the lungs, it is found that they 
 invariably contain more blood in inspiration than in expiration. 
 During inspiration, as we have seen, the right ventricle is sending 
 an increased supply of blood into the pulmonary artery; but before 
 any increase in the outflow through the pulmonary veins can take 
 place, the vessels of the lung must be filled to their new capacity. 
 The first effect, then, of the lessened vascular resistance of the lungs 
 in inspiration is a temporary falling off in the outflow through the 
 aorta, and therefore a fall of arterial pressure. As soon as a more 
 copious stream begins to flow through the lungs, this is succeeded 
 by a rise. In like manner the first effect of expiration, which in- 
 creases the resistance and diminishes the capacity of the pulmonary 
 vessels, is to force out of the lungs into the left auricle the blood 
 for which there is no room. This causes a rise of arterial blood- 
 pressure, succeeded by a fall as soon as the lessened blood-flow 
 through the lungs is established. 
 
 The changes in the diastolic capacity of the chambers of the heart 
 itself, with the changes of pericardial pressure, must also act in the 
 
 Fig. 129. — Effect on Blood-Pressure of Inflation of the Lungs: Rabbit. Artificial 
 respiration stt^pped in inflation at i. Interval between 2 and 3 (not reproduced) 
 51 seconds, during which the curve was almost a straight line. Time tracing 
 shows seconds. 
 
 same direction. It is obvious, then, how greatly the rate and depth 
 of respiration in relation to the size of the animal and the other cir- 
 cumstances already mentioned may influence the time relations of 
 the respiratory oscillations in the arterial pressure curve, so that we 
 ought not to expect them to be absolutely constant. 
 
 In artificial respiration oscillations of blood-pressure, synchronous 
 with the movements of the lungs, are also seen. During inflation 
 (inspiration) the arterial pressure rises; during deflation (expiration) it 
 falls. When artificial respiration is stopped at the height of inflation 
 and the lungs kept inflated (Fig. 129), the arterial blood-pressure falls 
 rapidly, and continues low until the rise of asphyxia begins. In the 
 
tKFLVENCE OF UliSPIRATION OX THE BLOOU-PRLbSURE 293 
 
 fall of pressure the increased intrathoracic pressure due to the inflation 
 is an important factor. When the respiration is stopped in collapse, 
 instead of a fall a steady rise of pressure occurs (as in Fig. 84, p. 188). 
 This ultimately merges in the elevation due to asphyxia, which shows 
 itself sooner than in inflation. When the tracheal cannula is closed in 
 natural respiration, no initial fall of pressure takes place (Fig. 130). 
 
 Besides the mechanical effects of the respiratory movements on 
 the circulation, it may be influenced by changes in the cardio- 
 inhibitory and vaso-motor centres synchronous with the rhythm of 
 the respiratory centre. In many animals (the dog, for instance) 
 and in man, it can be ver}' easily made out that the rate of the heart 
 is greater during inspiration, especially towards its end, than in 
 expiration. The phenomenon is especially distinct in deep and 
 slow respiration. It is caused by a rhythmical rise and fall in the 
 activity of the cardio-inhibitory centre, synchronous with the 
 respiratory movements, for the difference disappears after di\'ision 
 of both vagi. The normal respiratory oscillations of blood- pressure 
 are not due in any great degree to such changes in the rate of the 
 heart, for they persist after section of the vagi, and they are seen in 
 animals like the rabbit, in which in ordinary breathing little or no 
 variation in the rate of the heart is connected with the phases of 
 respiration. The most probable explanation of the respiratory 
 
 Fig. 130.— Blood-Pressure Tracing: Rabbit, under Chloral. Natural respiration 
 stopped at I in inspiration, at E in expiration. The mean blood-pressure is 
 scarcely altered; but the respiratory waves become much larger owing to the 
 abortive efforts at breathing. Time tracing shows seconds. 
 
 variations in the pulse-rate is that the respiratory centre, when it is 
 discharging itself in inspiration, sends out impulses as a sort of over- 
 flow along fibres connecting it with the cardio-inhibitory centre. 
 These increase the tone of that centre, but, owing to the long latent 
 period of the cardio-inhibitory apparatus, the inhibition does not 
 reveal itself till the succeeding expiration. It may be, however, that 
 the impulses discharged from the respiratory centre in inspiration 
 diminish the tone of the cardio-inhibitory centre, and thus lead to 
 acceleration of the heart towards the end of the inspiratory phase. 
 In certain pathological conditions the influence of the respiration on 
 the pulse-rate is exaggerated (so-called ' respiratory arhythmia '). 
 
 Traube-Hering Curves.— Rhythmical changes in the activity of 
 the vaso-motor centre, also associated with periodic discharges from 
 
294 • RESPIRA HON 
 
 the vaso-motor centre, also associated with periodic discharges from 
 the respiratory centre, may be observed under certain conditions — 
 e.g., wlicn in an animal paralyzed by curara, and therefore unable to 
 breathe spontaneously, the artificial respiration is slopped for a time. 
 If such a dose of curara be given as will still permit slight spontaneous 
 respiration to go on, and both vagi be cut, it can be seen on stopping 
 the artificial respiration that the waves on the blood-pressure curve 
 are exactly synchronous with the slow respiratory movements. The 
 Traube-Hering waves sink in inspiration and rise in expiration. 
 
 The fact that they have invariably a longer period than the 
 natural respiratory movements indicates that thej' are not concerned 
 in the production of the normal respiratory oscillations of arterial 
 pressure. Probably the reason why the Traube waves appear after 
 section of the vagi is the increased vigour of the slow respiratory 
 discharges, coupled with a hj'perexcitability of the vaso-motor 
 centre, due to the long pauses in the aeration of the blood. In the 
 asphyxial rise of pressure in a curarized dog they are constantly 
 seen, and are often observed when the circulation in the medulla 
 
 Fig. 131.— Traube-Hering Waves as the Bluod-Prcssure is falling during Occlusion 
 of the Cerebral Arteries in a Cat. 
 
 oblongata is in any way interfered with (Fig. 131). In addition to 
 the true Traube-Hering waves, other and much longer periodic 
 variations in the blood-pressure are sometimes noticed. If spon- 
 taneous respiration is going on, their long sweeping curves then show 
 the ordinary respiratory waves superposed on them. 
 
 The normal respiratory oscillations in the veins, as might be 
 expected, run precisely in the opposite direction to those in the 
 arteries, and so do the Traube-Hering curves. The increased flow 
 from the veins to the thorax during inspiration lowers the pressure 
 in the jugular vein, while it increases the pressure in the carotid. 
 The constriction of the small bloodvessels to which the Traube- 
 Hering curves are due increases the blood-pressure in the arteries, 
 because it increases the peripheral resistance to the blood-flow; in 
 
EI-FECTS Of URIiATHlNG CONDENSED AND RARhElEU MR 295 
 
 the veins it lowers the pressure, because less blood gets through to 
 them. Accordingly, when the Traube-Hcring curve is ascending in 
 the carotid, it is descending in the jugular. 
 
 The respiratory variations in the volume of the brain, wliich are 
 so striking a phcnt)nienon when a trephine hole is made in the 
 skull, but which can also take place, thanks to the displacement of 
 cerebro-spinal fluid (p. 174), when the cranium is intact, have by 
 some been attributed to interference with the venous outflow from 
 the cranial cavity during expiration, and by others to those changes 
 in the arterial pressure whose causes we have just btxin discussing. 
 The truth is that neither factor is exclusively concerned. The ques- 
 tion turns largely upon the time-relations of the movements. The 
 swelling of the brain is sometimes synchronous with expiration, and 
 the shrinking with inspiration. Here the damming back of the 
 blood in the sinuses when the outflow is checked by the expiratory 
 rise of pressure in the thoracic veins either conspires with an expira- 
 tory rise of arterial pressure or is more than enough to counter- 
 balance an expiratory fall of pressure in the cerebral arteries if the 
 respiratory conditions are such as to lead to an expiratory fall. But 
 sometimes the dura mater bulges into the trephine hole in inspira- 
 tion and sinks down in expiration. Here the increase in the volume 
 of the brain produced by the increased pressure in the arteries and 
 capillaries in inspiration is more than sufficient to counterbalance 
 the quickened escape of blood from the cerebral veins. 
 
 Section VIII.-=-The Effects of breathing Condensed and 
 
 Rarefied Air. 
 
 These are — (i) mechanical, shown chiefly by changes in the cir- 
 culation, in the blood-pressure, for instance; (2) chemical. 
 
 The mechanical effects differ according to whether the whole body, 
 or only the respiratory tract, is exposed to the altered pressure. 
 When the trachea of an animal is connected with a chamber in 
 which the pressure can be raised or lowered, it is found that at first 
 the arterial blood-pressure rises as the pressure of the air of respira- 
 tion is increased above that of the atmosphere. But a maximum 
 is soon reached; and when respiration begins to be impeded, the 
 pressure falls in the arteries and increases in the veins. When the 
 pressure of the air in the chamber is diminished a little below that 
 of the atmosphere, there is a slight sinking of the arterial blood- 
 pressure, which rises if the air-pressure is further diminished. 
 
 It is clear that any change of the air-pressure which tends to diminish 
 the intrathoracic pressure will favour the venous return to the heart, 
 and therefore, if the exit of blood from the thorax is not proportionally 
 impeded, the filling of the arteries. An increase in the intra-alveolar 
 pressure must tend on the whole to increase, and a diminution in it to 
 lessen, the pressure inside the thorax, which always remains equal to 
 the intra-alveolar pressure, minus the elastic tension of the lungs. 
 
290 
 
 liESPIRATlON 
 
 fvjvKM^^Aa.. 
 
 Breathing cdmpressetl air slioiiUl, therefore, under the conditions 
 tloscribcd, be upon the whole unfavourable to the venous return to the 
 heart and 1o the filling of the arteries, and the arterial pressure should 
 fall; while breathing rarefied air should have the opposite effect. But 
 a very great diminution of the- intrathoracic pressure is not necessarily 
 favourable to the circulation, since the auricles are then unable to con- 
 tract perfectly. 
 
 Certain chest diseases have been treated by the use of apparatus by 
 which the patient is made to breathe either compressed or rarefied air; 
 or to inspire air at one pressure and to expire into air at another pressure. 
 And it has, upon the whole, been found, in agreement with theory', 
 tliat condcu.scd air cannot help the circulation however it is applied, but 
 always hinders it; while rarefied air aids the circulation both in inspira- 
 tion and in expiration. But 
 the increased work of the in- 
 spiratory muscles may coun- 
 terbalance the advantage. 
 
 Valsalva's ex perimettt, 
 w'hich is performed by closing 
 the mouth and nostrils after 
 a previous inspiration, and 
 Fig. 132. — Pulse Tracing in Valsalva's Experi- then forcibly tryingto expire, 
 mcnt (Rollett). is an imitation of breathing 
 
 into compressed air. The 
 intrathoracic pressure is raised, it may be, to considerably more than 
 that of the atmosphere; the venous return to the heart is impeded, 
 and may b^^ stopped; and the pulse cur\'e is altered in such a way as 
 to indicate first an increase and then a decrease of the arterial blood- 
 prcssurc succeeded by a second ris:" (Fig- i.^-^)- 
 
 Muller's expeyiment, which should be bracketed with Valsalva's, 
 consists in making, after a previous expiration, a strong inspiratory 
 effort with mouth and nostrils closed. Here the intrathoracic pressure 
 is greatly diminished, more blood is drawn into the chest, and upon the 
 whole effects opposite to those of Valsalva's experiment are produced 
 (Fig. 133). Neither experiment is 
 quite free from danger. In both 
 the dicrotism of the pulse becomes 
 more marked. 
 
 When the wliolc body is sub- 
 jected to the changed pressure, 
 as in a balloon or on a mountain, 
 in a diving-bell or a caisson used 
 in building the piers of a bridge, the conditions are very different 
 For the blood-pressure, the intrathoracic pressure, and the intra- 
 alveolar pressure, all fall together when the pressure of the atmo- 
 sphere is diminished, and all rise together when it is increased. It 
 is possible not onlj^ to live, but to do hard manual labour, at very 
 di^erent atmospheric pressures. 
 
 As regards the chemical effects of condensed and rarefied air, 
 Loewy io\\n([ that the quantity of o.wgen absorbed by a man breath- 
 ing air in tlie pneumatic cabinet remained constant at all pressures 
 between about two atmospheres and half an atmosphere. At 440 mm. 
 of mercury d3'spnoea became evident ; but if the i)erson was now made 
 to work, the dyspnoea passed away, and did not again manifest itself 
 
 
 Fig. 
 
 133. — Pulse Tracing in 
 Experiment (Rollett). 
 
 Muller's 
 
/■:/-7'/y'/-.s" ni- nRr.ATiiiNc coNDhNsno a so uaiu:i-ied air 297 
 
 till tlu' pressure was reduced to 410 mm. There are towns on the 
 high tablelands of the Andes, and in the Himalayas, where the 
 barometric pressure is not more than 16 to 20 inches, yet the in- 
 habitants feel no ill effects. And in the caissons of the Forth Bridge 
 the workmen were engaged in severe toil under a maximum pressure 
 of over three atmospheres, while in the caissons of the St. Louis 
 Bridge in America a maximum pressure of over four atmospheres 
 [i.e., more than three atmospheres in addition to the ordinary air- 
 pressure) was reached. 
 
 Inside the caissons the men sometimes suffer from pain and noise in 
 the ears, due to excessive pressure on the external surface of the tym- 
 panic membrane. If the pressure in the tympanum is raised by a 
 swallowing movement, which opens the Eustachian tube and permits 
 air to enter it, the symptoms generally disappear. The suddenness of 
 the change of pressure has much to do with its effects, and it is found 
 that the men are most liable to dangerous symptoms while passing 
 through the air-lock from the cais.sons to the external air. It may be 
 concluded, from experiments on animals, that some of the most serious 
 of these — the localized paralysis usually affecting the legs (paraplegia) 
 and the circulatory disturbances — are due to the formation of gaseous 
 emboli, by the liberation of nitrogen in the blood and other body- 
 fluids when the pressure is abruptly reduced. And, indeed, it is found 
 that the symptoms can often be caused to disappear, both in animals 
 and men, by promptly subjecting them again to compressed air. To 
 avoid gis cmbohsm on decompression, the shift should be so short that 
 the body-fluids do not become fully saturated with nitrogon, and the 
 decompression should be slow. Even with a rate of decompression of 
 twenty minutes for each atmosphere of excess pressure, the equilibrium 
 between the dissolved and the atmospheric nitrogen is not entirely 
 established fifteen minutes after decompression. 
 
 But that the action of air under a high pressure is not merely mechan- 
 ical follows from the singular fact that in pure oxygen at a pressure 
 of 4 to 5 atmospheres, winch corresponds to air at 20 to 25 atmospheres, 
 convulsions arc often produced in vertebrate animals, while exposure 
 to 6 to 25 atmospheres of oxygen causes dyspnoea and coma, usually 
 without convulsions. All animals, so far as investigated, are instantly 
 convulsed and killed under a pressure of 50 atmospheres of oxygen 
 (Hill and Macleod). Even seeds and vegetable organisms in general 
 are killed in a short time in oxygen at 3 to 5 atmospheres; and an 
 atmosphere of pure oxygen, equal to 5 atmospheres of air, hinders 
 the development of eggs. Lorrain Smith has shown that in small birds 
 and mice exposure for many hours to a pressure of between i and 2 
 atmospheres of pure oxygen causes pneumonia. He confirms Bert's 
 observations on the acute toxic effects produced by higher pressures, 
 and supposes that in the production of caisson disease the special action 
 of the oxygen at high pressure may play a part as well as the rapid 
 decompression. Even atmospheres containing 80 to 96 per cent, of 
 oxygen under normal barometric pressure prodvice in rabbits, in 24 to 
 48 hours, congestion and oedema of the lungs, and finally a fibrinous 
 broncho-pneumonia. Still smaller oxygen pressures may cause similar 
 effects in a longer time (Karsner). 
 
 When the air-pressure is diminished below a certain limit, death 
 takes place from asphyxia, more or less gradual according to the 
 rate at which the pressure is reduced. Tlie haemoglobin cannot get 
 
298 kESPl RATIOS 
 
 or retain enough (•.\\{^<.ii lo enal>le it to perform its respiratory func- 
 tion; its dissociation tension is no longer balanced by an equal or 
 greater partial pressure of oxygen in the air. The tension of carbon 
 dioxide in the blood is also lessened, ovvnng to the dyspnoea and 
 the consequent increase of pulmonary ventilation. 
 
 To such changes, as well as to the cold, some of the deaths in high 
 balloon ascents must be attributed. Messrs. Glaisher and Coxwcll 
 supposed that they reached the height of 37,000 feet ; the former became 
 unconscious at 29,000 feet (8,800 metres), at which height the amount 
 of oxygen in the arterial blood would probably not exceed 10 volumes 
 per cent., but recovered during the descent. The symptoms of the 
 ' mountain sickness ' so familiar to Alpine climbers (nausea, headache, 
 and marked depression), the undue hypcrpnoea produced by muscular 
 exertion, and the sleep disturbed by irregular breathing, are also mainly 
 due to deficiencv of o.xvgen in the blood. The most rational prophy- 
 laxis is to leave the high peaks severely alone. But for the enthusiasts 
 who cannot do this a portable apparatus for generating oxygen has been 
 devised. Experiments in the pneumatic cabinet indicate that the 
 hvperpnoea is due to the indirect action of want of oxygen already 
 referred to in discussing the normal regulation of respiration (p. 281) 
 — that is, to the formation, in consequence of the insufficient oxygen 
 supply, of lactic acid or other substances which have the same influence 
 as carbon dioxide on the respiratory centre — so that less carbon dioxide 
 is required to excite the centre. Although the hyperpnoea leads to a 
 diminution in the partial pressure of carbon dioxide in the pulmonary 
 alveoli, there is no evidence that lack of carbon dioxide (' acapnia ') is 
 the primary cause of mountain sickness (Haldanc). It must be remem- 
 bered, however, that here the influence of the low barometric pressure 
 is complicated by other conditions, l-or example, while in the pneu- 
 matic cabinet, as alrcaclv stated, diminution of the pressure does not 
 affect the oxvgen consumption, it is relatively much gfeatcr on the 
 high mountain levels both during rest and during work than on the 
 plains. This is not the case in balloon ascents. And evidence has been 
 brought forward that changes in the mechanics as well as in the chem- 
 istry of respiration arc concerned (the breathing, for instance, taking 
 on a periodic character, with some approach to the Cheyne-Stokes type 
 — p. 287), and that there is something not connected with the want of 
 oxygen which diminishes the capacity for muscular work. This ' some- 
 thing ' is perhaps a peculiar excitation of the nervous system in the 
 fierce light of those high levels, which acts not only on the retina, but 
 on the skin, and may even affect the distribution of the blood. It is 
 said that a so-called light bath, as used in the treatment of certain 
 diseases, may increase the quantity of blood in rabbits by 23 per cent, 
 in four hours. The shorter wave-lengths which are relatively more 
 intense in the mountain light are most effective. Recent investigations 
 of the effects of high mountain chmatcs have been conducted by 
 Haldane, Henderson, and others, on Pike's Peak, and by Barcroft and 
 his associates on the Peak of Teneriffe and in the Alps. As already 
 mentioned, Haldane concluded that there was evidence of oxygen 
 secretion by the lungs which became more marked with the duration 
 of residence on the mountain (14,000 feet above sea-level). The total 
 oxygen capacity, and therefore the total amount of ha?moglobin, 
 gradually increased. The total volume of the blood was but slightly 
 augmented, and the percentage of haemoglobin rose decidedly. The 
 changes in the circulation have been especially studied by Schneider, 
 
CUTAXEOUS RESPIRATION icjcf 
 
 who found a marked increase in tlic rate of blood-fl(Jvv througli tlie 
 hands, associated with an acceleration of the heart beat, dilatation of 
 the arterioles and a fall in the venous pressure. In ' aviator's sick- 
 ness ' the essential factor is also oxygen deficiency. 
 
 Section IX. — Cutaneous Respiration. 
 
 It has already been remarked that a frog survives the loss of its lungs 
 for some time, respiration going on through tiie skin. Indeed, it has 
 been c^Uculatcd that in the intact frog, under ordinary conditions, as 
 much as three-quarters of the total gaseous exchange may be cutaneous. 
 Two frogs were seen to live thirty-three days, and one e\'en forty days, 
 after excision of the lungs. The effect of exclusion of the pulmonary 
 respiration on the gaseous exchange depends on the previous intensity 
 of the metabolism. If this is high the gaseous exchange sinks markedly ; 
 if it is low there is scarcely any alteration. At their ma.ximum efficiency, 
 the frog's lungs are capable of sustaining a much greater exchange 
 than the skin. Besides this quantitative, there is a qualitative differ- 
 ence, the carbon dioxide passing more easily through the skin than the 
 oxygen, so that the respiratory quotient is increased by elimination of 
 the lungs. In mammals the structure of the skin is different, and 
 respiration can only go on through it to a very slight extent. The 
 amount of carbon dioxide excreted in man, although only about 4 grm. 
 or 2 litres in twenty-four hours, is much greater than corresponds to 
 the quantity of oxygen absorbed through the skin. It has been as- 
 serted, and no doubt with justice, that some at least of the carbon 
 dioxide given off is due to putrefactive processes taking place on the 
 surface of the body. Such processes, as has already been pointed out, 
 seem also responsible in part for the heavy odour of a ' close ' room. 
 For no harmful products appear to be exhaled from the skin w^hen it is 
 prop^rly cleansed. In spite of the romantic statements to the con- 
 trary in ancient and modern books (for instance, the story of the child 
 that was gilded to play the part of an angel at the coronation of a 
 medieval popL\ but died before the ceremony began), the w-Iiole of the 
 human skin may be coated with an impermeable tarnish without any 
 ill effects. The entire surface of the body of a patient wdtli cutaneous 
 disease was covered with tar, and kept covered for ten days. There was 
 not the least disturbance of any normal function. The serious effects 
 of varnishing the skin in animals are due, not to retention of poisonous 
 substances, but to increased heat loss. Varnishing is not so rapidly 
 harmful in large animals like dogs as in rabbits, which have a relatively 
 great surface and a delicate skin. The danger of widespread superficial 
 bums is well known. But it is not due to diminished excretion by the 
 skin, for death occurs when large cutaneous areas remain uninjured. 
 The patient nearly always dies when a quarter of the whole skin is 
 burnt; yet the remaining ti.ree-quarters may surely be considered 
 capable, from all analogy, of making up the loss by increased acti\'ity. 
 One kidney is enough to eliminate the products of the nitrogenous 
 metabolism of the whole body. It is difficult to see why the excretion 
 of the trifhng amount of solid matter in the perspiration should be 
 interfered with by the loss of 25 per cent, of the sweat-glands. The real 
 explanation of the serious effects of extensive superficial bums is 
 perhaps the excessive irritation of the sensory nerves, which may lead 
 to changes in the nervous centres, or reflcxly in other organs, or the 
 chemical changes in the damaged tissue, for example, in the blood- 
 corpuscles, or the transudation of lymph at the injured part, and con- 
 seqvient increase in the concentration of the blood. 
 
300 
 
 RESPIRA TION 
 
 PKACTICAL EXERCISES ON CHAPTER IV. 
 
 I. Tracing of the Respiratory Movements in Man. — Pass a tape 
 through the rings B of the stethograph shown in Fig. 134, and then 
 
 around the neck or over 
 the shoulders, so as to sup- 
 ort the instrument on 
 the chest at a convenient 
 lieight. Fasten tapes to 
 the hooks and tie 
 them by a shp-knot 
 ' round the chest. The 
 tube E is connected 
 recording tambour, 
 writing on a drum. Or use 
 the belt stethograph or 
 spirograph of Fitz (p. 233), 
 fastening the elastic tube 
 round the chest with the 
 chain, and connecting it 
 with a tambour or the 
 bellows recorder shown in 
 Fig. 137. Compare the ex- 
 tent of the excursion when 
 
 Stethograph. 
 
 the tube is adjusted at different levels over the thorax and abdomen. 
 
 2* Production of Apnoea and Periodic Breathing in Man. — Arrange 
 for taking tracings of the respiratory movements from a fellow-student 
 as in I. Let the subject of the experiment recline in a perfectly easy 
 position in an armchair. Let him then breathe deeply and frequently 
 for about two minutes, so as to produce a prolonged apnoea of about 
 two minutes' duration. Whenever any desire to breathe returns, the 
 breathing is to be allowed to take its own course. It may be expected 
 at first to be of the periodic (Cheyne-Stokes) type. 
 
 3. Tracing of the Respiratory Movements in Animals. — (a) Set up 
 the arrangement shown in Fig. 135, and test whether it is air-tight. 
 Have also in readiness an induction machine and electrodes arranged 
 for an interrupted current. Anaesthetize a rabbit with chloral or 
 ether (p. 217), or a small dogf with morphine and ether, or A.C.E. 
 mixture. Insert a cannula into the trachea (p. 201), and connect it 
 with the large bottle by a tube. Connect the bottle with a recording 
 tambour adjusted to write on a drum, and regulate the amount of the 
 excursion of the lever by slackening or tightening the screw-clamp. 
 Set the drum off at slow speed, and take a tracing. 
 
 (b) Then disconnect the cannula from its tube. Dissect out the vagus 
 in the lower part of the neck, pass a ligature under it, but do not tie it. 
 Connect the cannula again with the bottle, and while a tracing is being 
 taken ligature the vagus. Cut below the ligature and stimulate its central 
 end with weak shocks, marking the time of stimulation on the drum. 
 Repeat the stimulation with strong shocks, and observe the results. 
 
 • This experiment is only to be attempted under the direct supervision of 
 the demonstrator. 
 
 t If a large dog is used the bottle should be omitted, the tracheal cannula 
 being connected with the stem of a T-tube. One end of the horizontal limb 
 of the T-tube is connected with the tambour; the other is provided with a 
 rubber tube, which can be partially closed by a screw-clamp to regulate the 
 excursion. ^ Ether may be given when required by connecting the horizontal 
 Umb of the T-tube with a bottle with two glass tubes in the cork (p. 201). 
 
PRACTICAL EXr:RCISF.S 
 
 301 
 
 (c) Apply a strong solution of potassium chloride with a camei's- 
 hair brush to the central end of the vagus wliile a tracing is being taken, 
 and observe the efiect. 
 
 (d) Isolate the sciatic nerve (p. 212), ligature it, and cut below the 
 ligature. Stimulate its central end while a tracing is being taken. 
 The respiratory movements will be increased. 
 
 {e) Disconnect the cannula, and isolate the vagus on the other side. 
 While a tracing is being taken, divide it. The respiratory movements 
 will probably at once become deeper and less frequent. 
 
 (f) Again disconnect the cannula. Isolate the superior laryngeal 
 bmnch of the vagus. This will be found entering the lar\nix at the 
 point where the laryngeal hom of the hyoid bone is connected with the 
 thyroid cartilage. li the finger is passed back along the upper border 
 
 ^rachful Canrtu.ia 
 
 
 Fig- 135- — -A^rrangement for Respiratory Tracing. Two glass tubes are inserted 
 through a cork in the mouth of the large bottle. One of them has a small piece of 
 indiarubber tubing on it, which is closed or opened, as may be required, by a 
 screw -clamp. The other is connected by a rubber tube with a recording tambour. 
 The tubulure at the bottom of the bottle is closed by a cork, through which 
 passes a glass tube, connected by a rubber tube with the tracheal cannula. If 
 no bottle with tubulure is available, it is only necessary to pass through the cork, 
 down to the bottom of the bottle, a third glass tube, which is connected with the 
 tracheal cannula. While a tracing is being taken the animal breathes the air 
 contained in the bottle. When this becomes vitiated the respiratory* movements 
 are exaggerated and a normal tracing is no longer obtained. For this reason 
 the tracheal cannula must be connected with the bottle only at the moment 
 when a tracing is to be taken. The arrangement is most suitable for a small 
 animal. 
 
 of the thjToid cartilage, this point mil easily be felt. Ligature the 
 ner^'e, and divide it between the lar\Tix and the ligature. Reconnect 
 the cannula. Take a tracing first with weak, and then with strong 
 stimulation of the central end of the superior lar^mgeal. 
 
 (?) Make an incision through the abdominal wall in the linea alba, 
 and study the movements of the diaphragm. Find the nerves from 
 which the phrenics take origin in the neck. In the dog they arise from 
 the fifth, sixth, and seventh cervical nerves. Di\'ide the phrenic fibres 
 
302 
 
 RESPIRATION 
 
 on one side, and observe that the diaphragm on the corresponding side 
 is now paralyzed. 
 
 {h) Insert' a cannula into the carotid artery. While a respiratory 
 tracing is being taken, allow blood to flow from the artery. Dyspnoea and 
 exaggeration of the respiratory movements will be seen when a consider- 
 able quantity of blood has been lost. Mark and varnish the tracings. 
 
 In the whole of this experiment the tracheal cannula is to be dis- 
 connected, except when the lever is actually writing on the drum, in 
 order that the period during which the animal must breathe into the 
 confined space of the bottle may be diminished as much as possible. 
 Instead of the method described, the stetliograph shown in Fig. 136 
 may be used to obtain respiratory tracings from animals, a broad canvas 
 band being put round the animal's chest. To each end of this band is 
 clamped with sufficient tension a strong thread (F), fastened to a small 
 metal disc on the inside of the 
 rubber dam closing the obliquely- 
 cut ends of the metal cylinder D. 
 The tube G is connected with a 
 tambour or with a bellows recorder 
 
 (Fig- 137)- 
 
 4. The Effect of Temperature on 
 th 3 Respiratory Centre -Heat Dysp- 
 noea. — Set up an arrangement for 
 
 Stethograph (Crile). 
 
 Fig. 137. — Bellows Recorder. B, a 
 lead tube connected with the 
 small bellows A, which consists of 
 a light wooden base and top, to 
 which is cemented very flexible 
 (organ key) leather, properly 
 creased for expansion and con- 
 traction; C, writing lever. 
 
 taking a respiratory tracmg as m 2 
 (footnote, p. 300). Anaesthetize a 
 dog, and fasten it, back dowTiward, 
 on a holder. Make an incision in 
 the middle line of the neck, com- 
 mencing a little below the cricoid 
 cartilage, and extending down for 
 
 4 or = inches. Insert a cannula into the trachea. Isolate both carotid 
 arteri'.s for as great a distance as possible, and arrange them on the 
 brass tubes shown in Fig. 138. Connect two adjacent ends of the 
 tubes by a short rubber tube. Connect one of the remaining ends to a 
 funnel , supported on a stand, and the other to a rubber tube hanging 
 over t':^' table above a large jar. Slip two or three folds of paper 
 betwec-i the tubes and the vagus nerves. Heat two or three litres ot 
 water io about 65° C. (a) Now connect the tracheal cannula with the 
 tambo.:!-. As soon as the tracing is under way, let the hot water run 
 througl' the funnel and tubes into the jar. Mark on the tracing the 
 point a. which the flow of the hot water was begun, and go on passing 
 it until it has produced an effect. Then stop the drum, and circulate 
 water at the ordinary temperature till the breathing is again normal. 
 Then, while a tracing is being taken, pass ice-cold water through the 
 tubes, and again notice the effect. 
 
PRACTICAL EXERCISES 
 
 303 
 
 (6) Expose the sciatic. Pass ice-water through the tubes, and while 
 a respiratory tracing is being taken stimulate its central end \^'ith in- 
 duction shocks so weak as just to cause an effect. Pass water at air 
 temperature through the tubes, and repeat the stimulation with the 
 coils at the same distance. Do the same while hot water is being passed 
 through the tubes, and compare the results. Always allow the water 
 to pass for a time before making an observation. 
 
 5. Measurement of Volume of Air inspired or expired — Vital Capacity. 
 — A spirometer (Fig. 114, p. 233) of sufficient accuracy for this experi- 
 ment can be made by removing the bottom of a large bottle with a 
 capacity of not less than 4 litres. A good cork, through which passes 
 a glass tube connected with a rubber tube, is fitted into the neck. The 
 bottle is fixed vertically, mouth downwards, the glass tube being closed 
 for the time, and graduated, by pouring in measured quantities of water, 
 say 100 c.c. at a time, and marking the level. The divisions are then 
 etched in. If the cork does not fit air-tight, it is covered with wax. 
 The bottle is swung on two pulleys, counterpoised and immersed, 
 bottom down, in a large 
 glass jar or a small cask 
 nearly full of water. A 
 smaller bottle may be used 
 for the detennination of the 
 tidal air, so as to reduce the 
 error of reading. 
 
 (i) Submerge the bottle -^ 
 
 to the stopper, afteropcning Fig. 138.— Arrangement for Heating or Cooling 
 
 the Blood in the Carotid Arteries. A, cylin- 
 drical portion of tube; B, flattened portion in 
 the groove, between which and A the artery 
 lies; C, cross-section, showing the lumen extend- 
 ing into B; D, rubber tube attached to a brass 
 tube soldered into A. The other end of A has 
 a similar brass tube soldered into it (not shown 
 in the figure). This is connected by a rubber 
 tube with a similar apparatus, on which the 
 other carotid lies. D is connected with a funnel 
 containing hot or cold water or with the outflow 
 tube, as the case may be. 
 
 the pinchcock on the rub- 
 ber tube. Breathe into the 
 bottle, close the cock, ad- 
 just the bottle so that the 
 level of the water is the 
 same inside and outside, and 
 then read off the level. De- 
 termine the volume of air 
 expired in — 
 
 (a) A normal expiration 
 after a normal inspiration 
 (tidal air) ; 
 
 {b) The greatest possible expiration after a normal inspiration 
 (supplemental air plus tidal air) ; 
 
 (c) The greatest possible expiration after the greatest possible 
 inspiration (vital capacity). 
 
 (2) Open the cock and raise the bottle till it is nearly full of air. 
 Determine the volume of air inspired in — 
 
 (a) A normal inspiration after a normal expiration (tidal air) ; 
 
 (6) The greatest possible inspiration after a normal expiration 
 (complemental air plus tidal air) ; 
 
 (c) The greatest possible inspiration after the greatest possible 
 expiration (vital capacity). 
 
 ^lake several observations of each quantity, and take the mean. 
 
 (3) Q)unt the rate of respiration for three minutes, keeping the 
 breathing as nearly normal as possible ; repeat the observation ; and 
 from the mean result and the amount of the tidal air calculate the 
 quantity of air taken into the lungs in twenty-four hours (pulmonary 
 ventilation). 
 
 6. Cardio-Pneumatic Movements. — Fill a U-tube with tobacco- 
 smoke. One end of the tube is placed in the nostril of a fellow-student. 
 
304 RESPIIWnON 
 
 and niadi- tight with a little cotton-wool. Tho other nostril and the mouth 
 are closed, and respiration suspended. The column of smoke moves 
 in and out at each beat of the heart. By feeling the apex-beat, try to 
 verify the fact that during systole the cardio-pneumatic movement is 
 inspiratory, and in diastole expiratory. 
 
 7. Auscultation of the Lungs. — -This is taught in the course of physical 
 diagnosis, but in connection with the subject the student may perform 
 the following experiment on a dog used for sonic other purpose: Open 
 the trachea as described on p. 201. Insert into it the cross-piece of a 
 glass T-tube of as large a bore as possible, tying the trachea over it on 
 each side of the stem. The stem projecting from the woimd is armed 
 with a short piece of rubber tubing, which can be closed at will with a 
 clip. When the tube is thus closed the animal breathes through the 
 glottis in the ordinary- way. When the tube is open, and the mouth 
 and nose covered tightly with a cloth, no air goes through the glottis. 
 The tube being closed, listen with the stethoscope or the ear alone over 
 a part of the chest where the vesicular murmur is well heard. If the 
 
 139. — Haldauc's Apparatus for measuring thr Quantity of CO.j aiul Aqueous 
 Vapour given off by an .\uimal. A, chaniLicr into wiiirh the animal is put; 
 I and 4, Woulff's bottles filled with soda-lime to absorb carbon dioxide; 2, 3, and 
 5, Woulff's bottles filled with jMimice-stone soaked in sulphuric acid to absorb 
 watery vapour; B, glass bell-jar suspended in water, by means of which the 
 negative pressure is known; P, water-pump which sucks air tiu"ough the appar- 
 atus; I and 2 are simply for absorbing the carbon dioxide and water of the 
 ingoing air. 
 
 rubbing of the hairs below the stethoscope causes disturbing sounds, 
 shave a portion of the skin. Continue listening while an assistant 
 closes the tube and covers up the animal's muzzle. Determine whether 
 any change takes place in the vesicular sound. 
 
 Repeat the observation while listening over the lower part of the 
 trachea, and determine whether any change takes place in the bronchial 
 breathing sound. 
 
 8. Respiratory Pressure. — Connect a strong rubber tube with a glass 
 bulb, and the bulb with a mercurial manometer provided with a scale. 
 (i) Fasten the tube with a little cotton-wool in one no.stril, breathe 
 through the other with closed mouth, and observe the amount by wliich 
 the level of the mercury is altered in ordinary inspiration and ex- 
 piraton. 
 
 (z) Rep?at the observation with forced breathing, pinching the tube 
 at the height of inspiration and expiration, and reading off the maximum 
 inspiratory and expiratory pressure. 
 
PRACTICAL EXERCISES 
 
 305 
 
 (3) Repeat (i) with tlic tube connected to the moutli by a glass 
 tube held between tiic lips, and the nostrils open. 
 
 (4) Repeat (2) with the tube in the nioutli and the nostrils closed. 
 
 9. Estimation of the Quantity of Water and of Carbon Dioxide given 
 off by an Animal {Haldanc's Me'/iod). — (i) Connect the appanilu.-. 
 shown in Fig. 139 with the water-pump. Allow a negative pressure 
 of 5 or 6 inches of water to be established in it, as shown by the rise of 
 water in the bell-jar B. Then close th(' open tube of carbon dioxide 
 bottle I, and clamp the tube between the water-pump and the bell-jar. 
 If the negative pressure is maintained, the arrangement is air-tight. 
 Now weigh bottle 3 and bottles 4 and 5, the last two together. Place 
 a cat in the respiratory chamiier A, connect the chamber directly with 
 the water-pump, and test wlicther it is tight. Then take the stopper 
 out of bottle I, and adjust the rate at which air is drawn through the: 
 apparatus. Let the ventilation 
 go on for a few minutes, then 
 insert bottles 3, 4, and 5 again. 
 Note the time exactly at this 
 point, and after an hour dis- 
 connect 3, 4, and 5, and again 
 weigh. The difference of the 
 two weighings of 3 shows the 
 quantity of water given ofE by 
 the animal in an hour; the dif- 
 ference in the combined weight 
 of 4 and 5, the quantity of 
 carbon dioxide . Weigh the cat . 
 and calculate the amount of 
 water and of carbon dioxide 
 given off per kilo per hour. 
 
 (2) For the student it is 
 more convenient to use smaller 
 animals. The mouse may be 
 taken as an example of a 
 warm-blooded animal, and the 
 frog of a cold-blooded. Instead 
 of the Woulff's bottles use wide 
 test - tubes connected as in 
 Fig. 140, and for the animal 
 chamber a small beaker, closed 
 with a very carefully fitted 
 
 cork which has been boiled in paraffin. The inlet and outlet tubes of 
 the chamber are to be introduced through this cork. The holes for these 
 are to be bored with the greatest care, and the tubes to be put in while 
 the cork is still hot from boiling in paraffin. Also insert a thermom- 
 eter about 6 inches long registering from o" C. to 45° C. Modeller's 
 wax is to be used finally to render all the junctions air-tight. 
 
 Add to the series of 'tubes described in the apparatus a single tube 
 containing baryta-water. This is placed to the left of tube 5, and so 
 arranged that the air-current bubbles through the water. As long 
 as the absorption of carbon dioxide is complete, the baryta-water 
 remains clear. Beyond this a water-bottle should be placed to act 
 as a valve and to indicate the negative pressure in the apparatus. It 
 can be most simply constructed by using a cylinder of stout glass 
 tubing in a wide-mouthed bottle containing some water, the inlet and 
 outlet tubes passing through a paraffined cork which seals the upper 
 end of the cylinder. 20 
 
 Fig. 140. — Absorption Tubes for CO.^ and 
 Moisture. A, soda -lime tube; B, [sul- 
 phuric acid tube; C, wooden frame, in 
 which A and B are supported by wires d ; 
 '), wire hook, which grips the glass tube 
 firmly, and by means of which the tubes 
 are lifted out of the frame in order to be 
 weighed; a, short piece of glass tubing, 
 by taking out which the absorption tubes 
 are disconnected from the rest of the 
 apparatus; e, glass tube going off to animal 
 chamber. 
 
3°^ HESPIRA] lOJ^ 
 
 Before making an observation, test whether the apparatus is air- 
 light, as cxpl;inK(l above, after introdnring fho animal into the cham- 
 ber, seahng the latter with wax and connecting it with tl)e absorption - 
 tubes. But a negative pressure of 2 or 3 inches of water is a sufficient 
 test for the small apparatus. 
 
 To make an observation, set the air-current going at the desired 
 rate. Allow it to run for a few minutes till the carbon dioxide, which 
 has accumulated duriiig the testing, has been swept out. At a time 
 which has been decided on and noted, stop the current by disconnecting 
 the water-pump. Disconnect and stopper up the animal chamber, and 
 weigh it as quickly as possible. Connect up again, using only recently- 
 weighed absorption-tubes, and finally connect with the water-pump 
 and allow the current to pass for a definite period, say an hour. 
 
 The soda-lirae should not be too dry, or absorption is not sufficiently 
 rapid. The following facts are made out: [a) Loss of weight by the 
 animal chamber (chiefly loss by th'^ animal) ; {b) gain of the sulphuric 
 acid tube in water; (c) gain of the i-oda-lime tubes in carbon dioxide. 
 
 The total loss and total gain do not correspond, the gain being always 
 greater than the loss. The surplus can only be oxj'gen absorbed by the 
 animal and added to tlie hydrogen and carbon of its substance to form 
 water and carbon dioxide. Calculate the respiratory quotient (p. 241J. 
 
 10. Muscular Contraction in the Absence of Free Oxygen (see p. 267). 
 — Pith a frog (brain and cord). Cut off one hind-leg at the middle 
 of the thigh, and strip the skin from it. Pass a thread under the tendo 
 Achillis, tie it, and divide the tendon below it. Free the tendon and 
 the gastrocnemius muscle from the loose connective tissue lying between 
 them and the bones of tlie leg. and divide the latter just below the knee, 
 l^cmove superfluous thigh muscles, and fasten the gastrocnemius in 
 a moist cliamber by means of the femur. Attach the thread on the 
 tendon to a lever. Connect the poles of the secondary coil of an induc- 
 tion machine by fine copper wires to the femur and the tendon. Put 
 a battery and simple key in the primary, and arrange it for single shocks. 
 Stimulate the muscle and observe the height of the contraction. Now 
 pass into the chamber a current of washed hydrogen gas from a bottle 
 containing granulated zinc, upon which a little dilute sulphuric acid 
 is poured from time to time. The air in the moist chamber will soon 
 be entirely displaced by the hydrogen, but the muscle will contract on 
 being stimulated, and the stimulation can be repeated many times. 
 
 11. Oxidizing Ferments. — Wash out the bloodvessels of a dog or 
 rabbit (Practical Exercises, p. 65). Chop up finely portions of pancreas, 
 spleen, muscle, lungs, and kidney, keeping each separate, and avoiding 
 any contamination of one by another. Grind up half of each portion 
 with sand in a small mortar, and extract v/lth a small quantity of water, 
 keeping all the extracts separate. Into each of eleven test-tubes put 
 10 c.c. of a colourless dilute alkaline solution of paraphenylenediamin 
 and a-naphthol (freshly made by mixing solutions of the two sub- 
 stances in equimolecular proportions* and adding a little sodium 
 carbonate). To five of the tubes add the chopped organs, to five the 
 watcr}^ extracts of the organs, and enough water to make the volume 
 equal in all the tubes. To the remaining tube add the same amount 
 of water. Observe in which tube a change of colour takes place (p. 272 ). 
 
 ♦ I.e., the weight of each of the two substances in the mixture should be 
 proportional to its molecular weight. A convenient solution contains 0144 
 per cent, ot a-naphthol and o'io8 pei cent, of paraphenylenediamin. These 
 quantities are one-hundrcdth-molecular. Sod um carbonate is added to the 
 amount of o"25 per cent. The a-naphthol can be kept as a i per cent, solu- 
 tion in 50 per cent, alcohol. 
 
CHAPTER V 
 VOICE AND SPEECH 
 
 Voice. — Sounds of various kinds are frequently produced by the 
 movements of animals as a whole, or of individual organs. The 
 muscular sound, the sounds of the heart and of respiration, we have 
 already had to speak of. Such sounds may be considered as purely 
 accidental as the footfall of a man or the buzzing of a fly. The 
 wings of an insect beat the air, not to cause sound, but to produce 
 motion; the respiratory murmur is a mere indication that air is 
 finding its way into the lungs, it is in no way related to the oxidation 
 of the blood in the pulmonary capillaries. But in many of the 
 higher animals mechanisms exist which are specially devoted to the 
 utterance of sounds as their prime and proper end. In man the 
 voice-producing mechanism consists of a triple series of tubes and 
 chambers: (i) The trachea, through which a blast of air is blown; 
 (2) the larynx, with the vocal cords, by the vibrations of which 
 sound-waves are set up ; and (3) the upper resonance chambers, the 
 pharynx, mouth, and nasal cavities, in which the sounds produced 
 in the larynx are modified and intensified, and in which independent 
 notes and noises arise. 
 
 The larynx is a cartilaginous box, across which are stretched, 
 from front to back, two thin and sharp-edged membranes, the (true) 
 vocal cords. In front the cords are attached to the thyroid carti- 
 lage, one a little to each side of the middle line; behind they are 
 connected to the vocal or anterior processes of the p)n:amidal 
 arytenoid cartilages. The thjnroid and the two arjrtenoids are 
 mounted upon a cartilaginous ring, the cricoid. The arytenoids 
 can rotate on the cricoid about a vertical axis, while the cricoid can 
 rotate on the thyroid cartilage around a transverse horizontal axis. 
 The cricoid can thus be raised by the contraction of the crico- 
 thyroid muscle, and the vocal cords stretched. By the pull of the 
 posterior crico-arytenoid muscles, attached to the external or mus- 
 cular processes of the arytenoid cartilages, the vocal processes are 
 rotated outwards, the cords separated from each other or abducted, 
 and the chink between them, the rima glottidis, widened. When 
 the vocal processes are approximated by contraction of the lateral 
 
 307 
 
3o« 
 
 VOICE AND SPEECH 
 
 crico-arytenoid muscles and the consequent forward movement of 
 the muscular processes, the vocal cords are brought close together, 
 or addncted, and the rima is narrowed. The transverse or posterior 
 arytenoid muscle, which connects the two arytenoid cartilages 
 behind, also helps, by its contraction, to narrow the glottis by shift- 
 ing the cartilages on their articular surfaces somewhat nearer the 
 middle Une. Running in each vocal cord, and, in fact, incorporated 
 with its elastic tissue, is a muscle, the thyro-arytenoid, the external 
 portion of which may to some extent cause inward rotation of the 
 vocal processes and adduction of the cords; but the main function, 
 at least of its inner part, is to alter the tension of the cords. The 
 diagrams in Figs. 141 and 142 illustrate the action of the abductors 
 and adductors of tlic vocal cords. 
 
 The crico-thj-Toid muscle and the deflectors of the epiglottis are 
 supplied by the superior laryngeal branch of the vagus, which also 
 
 z^'^^^. 
 
 Fig. 141. — Diagrammatic Hori- 
 zontal Section of Larynx to 
 show the Direction of Pull of 
 the Posterior Crico-Arytenoid 
 Muscles, which abduct the 
 Vocal Cords. Dotted lines 
 show position in abduction. 
 
 Fig. 142. — Direction of Pull- of 
 the Lateral Crico-Arytenoids. 
 which adduct the Vocal 
 Cords. Dotted lines show 
 position in adduction. 
 
 contains the sensory fibres for the mucous membrane of the larynx 
 above the vocal cords. In the dog and rabbit motor fibres also reach 
 the crico-thyroid by the so-called middle laryngeal nerve which 
 arises from the superior pharyngeal branch of the vagus. All the 
 other intrinsic muscles are supplied by the recurrent laryngeal 
 branch of the vagus. It receives these motor fibres from the spinal 
 accessory, and supplies sensory fibres to the mucous membrane of 
 the larynx below the vocal cords and to the trachea. 
 
 The voice is produced, like the sounds of a reed instrument, by 
 the rhythmical interruption of an expiratory blast of air by the 
 vibrating vocal cords. When a bell is struck, vibrations are set up 
 in the metal, which are communicated to the air. It is not the same 
 with the vibrations of the vocal cords; if they were plucked or 
 struck, they would only produce a feeble note. The air in the 
 mouth, phar^Tix, larynx, trachea, and lungs is the real sounding 
 
V01C1-: 30f 
 
 body; a pulse of alternate rarefaction and condensation is set up in 
 it by the inter-ference, at regular intervals, of the vocal cords with 
 the expiratory blast. Forced abruptly from their position of equi- 
 librium as the blast begins, they almost immediately regain and 
 pass below it, in virtue of their elasticity, and continue to vibrate as 
 long as the stream of air continues to issue in sufficient strength. 
 Not only do they vibrate up and down, but also towards and away 
 from the middle line, so that, at least in the chest voice, they come 
 into contact with each other at each swing. The sound-waves thus 
 set up spread out on every side, impinge on the tympanic membrane, 
 set it quivering in response, and give rise to the sensation of sound. 
 We may say, in a word, that the whole exquisite mechanism of 
 cartilages, hgamcnts, and muscles, has for its object the production 
 of a sufficient pressure in the blast of air driven through the wind- 
 pipe by an expiratory act, and of a suitable tension in the vibrating 
 cords. An approximation of the cords, a narrowing of the glottis, 
 is essential to the production of voice ; with a widely-opened glottis 
 the air escapes too easily, and the necessary pressure cannot be 
 attained. The pressure in the windpipe was found in a woman 
 with a tracheal fistula to be about 12 mm. of mercury for a note of 
 medium height, about 15 mm. for a high note, and about 72 mm. 
 for the highest possible note. The period of vibration of structures 
 like the vocal cords depends on their length, thickness, density and 
 tension; the shorter, thinner, more dense and less tense a stretched 
 string is, the greater is the vibration frequency, the higher the note. 
 In the child the cords are short (6 to 8 mm.), in woman longer 
 (10 to 12 mm. when slack, 13 to 15 mm. when stretched), in man 
 longest of all (14 to 18 mm. in the relaxed, and 18 to 22 mm. in the 
 stretched position) ; and the lower limit of the voice is fixed by the 
 maximum length of the relaxed cords. A boy or a woman cannot 
 utter a deep bass note, because their vocal cords are relatively 
 short, and do not vibrate with sufficient slowness. It is true that 
 by the action of the crico-thyroid muscle the cords can be length- 
 ened, and that the maximum length in a woman approaches or 
 exceeds the minimum length in a man. But the lengthening of the 
 vocal cords in one and the same individual is always accompanied 
 by other changes — increase of tension, decrease of breadth and 
 thickness — which tell upon the vibration frequency in the opposite 
 way, and more than compensate the effect of the increase of length, 
 so that for high notes the cords are longer than for low. The con- 
 traction of the thyro-arytenoid muscle is a more influential factor 
 in altering the tension of the cords than the contraction of the crico- 
 thjTToid. It is probable that, when the highest notes are uttered, 
 only the anterior portions of the cords are free to vibrate, their 
 posterior portions being damped by the approximation of the vocal 
 processes of the arytenoid cartilages by the contraction of the 
 
3IO VOICE AND SPEECH 
 
 lateral crico-arytenoid and transverse arytenoid muscles. The 
 range of an ordinary voice is 2 octaves; by training 2^ octaves can 
 be reached; but in exceptional cases a range of 3, and even 31^, 
 octaves (as in the celebrated singer Catalini) has been known. 
 
 The development of the voice in children is of great interest. At 
 the age of six years the boy's voice has a rather narrower range tlian 
 the girl's in both directions. The boy's voice reaches its full height 
 in the twelfth and its full depth in the thirteenth year, when the range 
 is almost 3 octaves, its upper limit being a semitone higher than the 
 girl's, but its lower limit a wliole tone deeper. When the voice ' breaks ' 
 in boys at the age of puberty it falls about an octave. The control of 
 the vocal organs becomes so incomplete that only in one-fourth of the 
 cases can notes of sufficient steadiness to be used in music be produced. 
 The vocal cords, as may be seen with the laryngoscope, are frequently, 
 though not always, congested. 
 
 The pilch of a note, while it depends chiefly, as has been said, on 
 the tension of the vocal cords, rises and falls somewhat with the 
 strength of the expiratory blast ; the highest notes are only reached 
 with a strong expiratory effort. The intensity of all vocal sounds 
 is determined by the strength of the blast, for the amplitude of 
 vibration of the cords is proportional to this. Besides pitch and 
 intensity, the ear can still distinguish the quality or timbre of sounds; 
 and the explanation is as follows: Two simple tones of the same 
 pitch and intensity, that is, the sounds caused by two series of air- 
 waves of the same period and amplitude — of the same frequency 
 and height, to use less technical terms — would appear absolutely 
 identical to the sense of hearing; just as the aerial disturbances on 
 which they depend would be absolutely alike to any physical test 
 that could be applied. But no musical instrument ever produces 
 sound-waves of one definite period, and one only; and the same is 
 true of the voice. When a stretched string is displaced in any way 
 from its position of rest, it is set into vibration ; and not only does 
 the string vibrate as a whole, but portions of it vibrate independently 
 and give out separate tones. The tone corresponding to the vibra- 
 tion period of the whole string is the lowest of all. It is also the 
 loudest, for it is more difficult to set up quick than slow vibrations. 
 The ear therefore picks it out from all the rest; and the pitch of the 
 compound note is taken to be the pitch of this, its fundamental 
 tone. The others are called partial or overtones, or harmonics of 
 the fundamental tone, their vibration frequency being twice, three 
 times, four times, etc., that of the latter. Now, the fundamental 
 tone of a compound note or clang produced by two musical instru- 
 ments may be the same, while the number, period, and intensity 
 of the harmonics are different; and this difference the ear recognizes 
 as a difference of timbre or quality. The timbre of the voice de- 
 pends for the most part on partial tones produced or intensified in 
 the upper resonance chambers. 
 
VOICE 
 
 3" 
 
 A great deal of our knowledge as to the mode and mechanism of 
 the production of voice has been acquired by means of the laryngo- 
 scope (Fig. 143). This consists of a small plane mirror mounted on 
 a handle, which is held at the back of the mouth in such a position 
 that a beam of light, reflected from a larger concave mirror fastened 
 on the forehead of the observer, is thrown into the larynx of the 
 patient. The observer looks through a hole in the centre of the 
 large mirror; and an image of the interior of the larynx is seen in 
 the small mirror, in which the parts that are anterior appear as 
 posterior, the arytenoid cartilages in front, the thyroid behind, and 
 the vocal cords stretching between. The small mirror is warmed to 
 body-temperature before being introduced, so as to prevent the 
 condensation of moisture on it. The tendency to retch, which is 
 
 LamfD 
 
 Conca/e Mirror 
 
 Fig. 143. — Diagram of Laryngoscope. 
 
 caused by contact of the instrument with the soft palate, may be 
 removed or lessened by the application of a solution of cocaine. 
 
 Examined with the laryngoscope during quiet respiration, the 
 glottis is seen to be moderately, though not widely, open, and the 
 vocal cords almost motionless. Although the portion between the 
 arytenoid cartilages has received the name of glottis respiratoria, in 
 contradistinction to the glottis vocalis between the vocal cords, the 
 rima in its whole extent from front to back is really concerned in 
 the respiratory act. In deep expiration the vocal cords come nearer 
 to the middle line, and the glottis is narrowed ; in deep inspiration 
 they are widely separated, and the rings of the trachea, and even 
 its bifurcation, may be disclosed to view. When a sound is produced 
 — a note sung, for example— the cords are approximated (Figs. 144 
 and 145) ; and with a high note more than with a low. 
 
312 
 
 VOICE AND SPEECH 
 
 The essential difference between the production of notes in the lower 
 register, or chest voice, and in the higher register, or falsetto, has been 
 much debated. The lowest notes which can be uttered by any given 
 voice are chest notes, the highest are falsetto notes; but there is a de- 
 batable land common to both registers, and medium notes can be sung 
 eithf^r from tlie chest or from the head. Chest notes impart a vibration 
 or fremitus to the thoracic walls, from the resonance of the lower air- 
 chambers, the trachea and bronchi; and tliis can be distinctly felt by 
 the hand. In head notes or falsetto the resonance is chiefly in the 
 upper cavities, the phar^mx, mouth, and nose. As to the mechAnical 
 conditions in the larjmx, there is a pretty general agreement that during 
 the production of falsetto notes the vocal cords are less closely approxi- 
 mated than in the sounding of chest notes. The escape of air is conse- 
 quently more rapid in the head voice, and a falsetto note cannot be 
 maintained so long as a note sung from the chest. But it is only the 
 anterior part of the rima glottidis that is wider in the falsetto voice ; 
 the whole of the glottis rcspiratoria, and even the posterior portion of 
 the glottis vocalis, are closed during the emission of falsetto notes. 
 
 Fig. 144. — Position of t!ie 
 Glottis preliminary to the 
 Utterance of Sound, rs, false 
 vocal cord; ri, true vocal 
 cord; ar, arytenoid cartilage; 
 b, pad of the epiglottis. 
 
 Fig. 145. — Position of Open Glottis, 
 /, tongue; e, epiglottis; ae, ary- 
 epiglottidean fold; c, cartilage of 
 Wrisberg; ar, arytenoid cartilage; 
 0, glottis; V, ventricle of Mor- 
 gagni; ti, true vocal cord; is, false 
 vocal cord. 
 
 Oertel has stated, and the statement has been confirmed by others, 
 that the free edge of the vocal cord alone vibrates in the falsetto voice, 
 one or more nodes or motionless lines parallel to the edge being formed 
 by the contraction of the internal part of the thyro-arytenoid muscle, 
 which thus acts like a stop upon the cord. 
 
 Approximation of the vocal cords may take place in certain 
 acts unconnected with the production of voice. Thus, a cough, as 
 has already been mentioned, is initiated by closure of the glottis. 
 During a strong muscular effort, too, the chink of tlie glottis is 
 obliterated, and respiration and phonation both arrested. The 
 object of this is to fix the thorax, and so afford points of support 
 for the action of the muscles of the limbs and abdomen. But con- 
 siderable efforts can be made even by persons with a tracheal fistula. 
 
 Speech. — Ordinary speech is articulated voice — voice shaped and 
 fashioned by the resonance of the upper air-cavities, and jointai 
 
SPEECH 
 
 313 
 
 together by the sounds or noises to which the v^arying form of these 
 cavities gives rise. Here we come upon the fundamental distinction 
 between vowels and consonants. Vowels are musical sounds; con- 
 sonants are not musical sounds, but noises — that is to say, they are 
 due to irregular vibrations, not to regularly recurring waves, the 
 frequency of which the ear can appreciate as a definite pitch. This 
 difference of character corresponds to a difference of origin: the 
 vowels are produced by the vibrations of the vocal cords; the con- 
 sonants are due to the rushing of the expiratory blast through 
 certain constricted portions of the buccal chamber, where a kind of 
 temporary glottis is established by the approximation of its walls. 
 One of these ' positions of articulation ' is the orifice of the lips; the 
 consonants formed there, such as p and b, are called labials. A 
 second articulation position is between the anterior part of the 
 tongue and the teeth and hard palate. Here are formed the dentals, 
 /, d, etc. The ordinary English r, and the r of the Berwickshire and 
 East Prussian ' burr,' also arise in this position through a vibratory 
 motion of the point of the tongue. The third position of articul;.- 
 tion is the narrow strait formed between the posterior portion of th : 
 arched tongue and the soft palate. To the consonants arising here 
 the name of gutturals has been given. They include k, g, the 
 Scottish ch, and the uvular German r. The latter is produced by 
 a vibration of the uvula. The aspirated /; is a noise set up by the 
 air rushing through a moderately wide glottis, and some have there- 
 fore included the glottis as a fourth articulation position for con- 
 sonants. Certain sounds like n, m, and ng, when final (as in pen, 
 dam, ring), although produced at the glottis, are intensified by the 
 resonance of the air in the nose and pharynx, and are sometimes 
 spoken of as nasal consonants. 
 
 As we have said, the vowels are produced by vibrations of the 
 vocal cords, but to what they owe their special timbre or quality has 
 been much discussed. According to the view with which Helm- 
 holtz's name is particularly connected this is due to the reinforce- 
 ment of certain overtones by the resonating cavities, the shape and 
 fundamental tone of which are different for each vowel. 
 
 When a vowel is whispered, the mouth assumes a characteristic 
 shape, and emits the fundamental tone proper to the form and size 
 of the particular ' vowel-cavity,' not as a reinforcement of a tone set 
 up by the vibrations of the vocal cords, but in response to the rush of 
 air through the cavity; just as a bottle of given shape and size gives out 
 a definite note when the air which it contains is set in vibration, by 
 blowing across its mouth. A whisper, in fact, is speech without voice ; 
 the larynx takes scarcely any part in the production of the sound ; the 
 vocal cords remain apart and comparatively slack ; and the expiratory 
 blast rushes through without setting them in vibration. 
 
 The fundamental tone of the ' vowel-cavity ' may be found for each 
 vowel by placing the mouth in the position necessary for uttering it, 
 then bringing tuning-forks of different period in front of it, and noting 
 
314 
 
 WILE AND -SPEECH 
 
 which of them sets up s^Tnpathctic resonance in the air of the mouth, 
 and so causes its sound to be intensified. The fundamental tone is 
 lowest for u (as in lute). Next comes o ; then a (as in path) ; then a (as 
 in fa}ie) ; then i ; while e is highest of all. A simple illustration of 
 this may be found in the fact that when the vowels are whispered in 
 the order given, the pitch rises. When « or o is sounded, the buccal 
 cavit^^ has the form of a wide-beUied flask, with a short and narrow neck 
 for u, a still shorter but wider neck for o. For e the tongue is raised 
 and almost in contact with the palate, and the cavity of the mouth 
 is shaped like a flask with a long narrow neck and a very short belly. 
 For i the shape is similar, but the neck is not so narrow. For a (as in 
 path) the vowel-caN^ty is intermediate in form between that of u and e. 
 being roughly funnel-shaped, and the mouth is rather widely opened. 
 For u {oo) the resonating cavity is made as long as possible, the larynx 
 being depressed and the lips protruded; for e the resonating cavit\ is 
 at its shortest, the lar\-nx being raised as much as possible and the lips 
 retracted (Figs. 146 to 148). 
 
 According to Helmholtz, all that the resonating cavity does is to 
 strengthen certain of the partials or overtones of the larvTigeal note. 
 
 Fig. 146 
 
 If this is true, the partials which give a vowel-sound the timbre by 
 which we recognize it as different from other vowel-sounds cannot 
 preser\'e the same numerical relation to the fundamental tone when 
 the pitch of the latter is altered. Suppose, for example, that a given 
 vowel is sounded with a pitch corresponding to 100 vibrations a second, 
 and that the partial which is particularly strengthened by the resonance 
 of the mouth cavity is the fifth overtone, corresponding to 600 vibra- 
 tions. Then when the same vowel is sounded with a pitch of 200 vibra- 
 tions, the reinforced partial which will now give the quality to the sound 
 will still correspond to 600 vibrations a second, since this is the rate 
 which most easily elicits the resonance, but it will not now be the fifth 
 but the second overtone. 
 
 Universally accepted for a time, the Helmholtz theory has been in 
 recent years assailed, especially by Hermann, wlio baises his criticism 
 on microscopic examination of curves obtained by the Edison phono- 
 graph, and on reproductions of such records obtained by photographing 
 on a mo\ing drum covered with sensitive paper a beam of light re- 
 flected from a small mirror attached to a system cf levers whose move- 
 ments follow the curves faithfully and greatly magnify them. Hermann 
 
SPEECH 315 
 
 has come to the conclusion that the mouth docs not act as a mere 
 resonator, but that for each vowel, in addition to the fundamental 
 note due to the vibration of the vocal cords, the pitch of which is, of 
 course, variable, one or, it may be, two other notes (formants, as he 
 calls them), not necessarily harmonics of the laryngeal note, but separ- 
 ated from it by a constant or nearly constant musical interval, are 
 directly produced by the passage of the regularly interrupted expiratory 
 blast through the mouth, the air contained in that cavity being for 
 an instant set into vibration at each interruption. On this view it 
 is the musical effect produced by the oscillation or continual recurrence, 
 in short series, of these vibrations which gives the vowels tlieir quality. 
 The fact that it is by no means difficult to sing (with the lan^Tix) and 
 whistle (with the mouth) at the same time, shows the possibility of 
 Hermann's view, that a fixed tone can be generated in the mouth by 
 the intermittent stream of air issuing from between the vibrating vocal 
 cords, just as a tone is generated in a pipe by blowing into or over it, 
 and his records do show continually recurring groups of vibrations as 
 his theory requires. McKendrick takes up a middle position, beheving 
 that both theories are partially true, and this seems to be the best 
 conclusion which can at present be arrived at. It seems clear, at any 
 rate, that more than one factor is concerned in the timbre of the vowel 
 sounds. 
 
 When the vowels are being uttered, the soft palate closes the 
 entrance to the nasal chambers completely, as may be shown by 
 holding a candle in front of the nose, or trying to inject water 
 through the nares. If the cavities of the nose are not completely 
 blocked off, the voice assumes a nasal character in pronouncing 
 certain of the vowels; and in some languages this is the ordinary 
 and correct pronunciation. 
 
 Many animals have the power of emitting articulated sounds; a 
 few have risen, like man, to the dignity of sentences, but these only 
 by imitation of the human voice. Both vowels and consonants can 
 be distinguished in the notes of birds, the vocal powers of which 
 are in general higher than those of mammalian animals. The latter, 
 as a rule, produce only vowels, though some are able to form con- 
 sonants too. 
 
 The nervous mechanism of voice and speech will have to be 
 again considered when we come to study the physiology of the brain 
 and spinal cord. But the curious physiological antithesis between 
 the functions of abduction and of adduction of the vocal cords may 
 be mentioned here. The abductor muscles are not employed in the 
 production of voice; they are associated with the less specialized, 
 the less skilled and purposive function of respiration. The adductor 
 muscles are not brought into action in respiration; they are asso- 
 ciated with the highly specialized function of speech. Correspond- 
 ing to this difference of function, we find that adduction is pre- 
 ponderatingly represented in the cortex of the brain, abduction in 
 the medulla oblongata. Stimulation of an area in the lower part 
 of the ascending frontal convolution, near the fissure of Rolando, in 
 the macaque monkey, causes adduction of the vocal cords, never 
 
3i6 VOICE AND SPEECH 
 
 abduction. In the cat, however, abduction of the cords may ako 
 be obtained by stimuJition of the cortex. The same is true of the 
 dog, but only when tiie peripheral adductor nerves have been 
 divided. Stimulation of tiit medulla oblongata (accessory nucleus) 
 causes abduction, never adduction. The skilled adductor function 
 is, therefore, placed under control of the cortex. The vitally im- 
 portant, but more mechanical, abductor function is governed by 
 the medulla. The abductor movements are more likely to be 
 affected by organic disease, the adductor movements by functional 
 changes. But the distinction between the two groups of muscles 
 is not entirely due to a difference of central connections, since by 
 altering the strength of the stimulus and the external conditions 
 the one or the other may be separately excited through the inferior 
 laryngeal nerve. Thus, strong stimulation of the inferior laryngeal 
 causes closure of the glottis, for although it supplies both abductors 
 
 Fig. 149. — Diagram of Vocal Cords in Paralyses of the Larynx, a. Paralysis of both 
 inferior laryngeal nerves. The vocal cords have taken up the ' mean ' position. 
 b. Paralysis of right inferior laryngeal nerve. An attempt is being made to 
 narrow the glottis for the utterance of sound. The right cord remains in its 
 ■ mean ' position, 'c. Paralysis of the abductor muscles only, on both sides. The 
 cords are approximated beyond the ' mean ' position by the action of the 
 adductors. 
 
 and adductors, the latter, as the stronger muscles, prevail. With 
 weak stimulation, and in young animals, the abductors, owing to 
 the greater excitability of the neuro-muscular apparatus, carry off 
 the victory, and the glottis is opened (Russell). 
 
 When the nerve is cooled the abductors give way before the 
 adductoi ;. The same is true when it is allowed to become dry. 
 And after death in a cholera patient it was observed that the pos- 
 terior crico-arytenoid, an abductor muscle, was the first of the 
 intrinsic larjmgeal muscles to lose its excitability. Lesions of the 
 medulla oblongata are often accompanied by marked changes in 
 the character of the voice and the power of articulation. 
 
 Section or paralysis of the superior laryngeal nerve causes the 
 voice to become hoarse, and renders the sounding of high notes an 
 '■mpossibility, oN^ing to the want of power to make the vocal cords 
 tense. Stimulation of the vagus within the skull causes contraction 
 
SPEECH 
 
 3x7 
 
 of the crico-thyroid muscle and increased tension of the cords. Sec- 
 tion or paralysis of the inferior laryngeal nerves leads to loss of voice 
 or aphonia, and dyspnoea (Fig. 149). Both adductor and abductor 
 muscles are paralyzed ; the vocal cords assume their mean position — 
 the position they have in the dead body — and the glottis can neither 
 be narrowed to allow of the production of a note, nor widened during 
 inspiration. It is said, however, that young animals, in which the 
 structures around the glottis are more yielding than in adults, can 
 still utter shrill cries after section of the inferior laryngeals, the 
 contraction of the crico-thyroid muscle alone being able, while in- 
 creasing the tension of the cords, to draw them together. 
 
 Interference with the connections on one side between the higher 
 cerebral centres and the medulla oblongata, as by rupture of an 
 artery and effusion of blood into the posterior portion of the internal 
 capsule (giving rise to hemiplegia, or paralysis of the orposite side 
 of the body), is not followed by loss of voice; the laryngeal muscles 
 on both sides are still able to act. 
 
CHAPTER VI 
 DIGESTION 
 
 In the last chapter we have described the manner in which the 
 interchange of gases between the tissues and the air is carried out. 
 We have now to consider the digestion and absorption of the soHd 
 and Hquid food, its further fate in relation to the chemical changes 
 or metabolism of the tissues, and finally the excretion of the waste 
 products by other channels than the lung. 
 
 Logically, we ought to take metabolism after absorption and 
 before excretion, tracing the food through all its vicissitudes from the 
 moment when it enters the blood or lymph till it is cast out as useless 
 matter by the various excretory organs. Unfortunately, however, 
 many of the intermediate steps of the process are as j'^et hidden from 
 us ; we know best the beginning and the end. We can follow the food 
 from the time it enters the alimentary canal till it is taken up by the 
 tissues of absorption; and we have really a fair knowledge of this 
 part of its course. We can collect the end-products as they escape 
 in the urine, or in the breath, or in the sweat; and our knowledge of 
 them and of the manner in which they are excreted is considerable. 
 But of the wonderful pathway by which the dead molecules of the 
 food mount up into life, and then descend again into death, we 
 catch only a glimpse here and there. Only the introduction and 
 the conclusion of the story of metabolism are at present in our 
 possession in fairly continuous and legible form. We will read these 
 before we try to decipher the handful of torn leaves which represents 
 the rest. 
 
 Section I. — Preliminary Anatomical and Chemical Data. 
 
 Comparative. — In the lowest kinds of animals, such as the amoeba, 
 there is neither mouth, nor alimcntars' canal, nor anus: the food, 
 wrapped round by pseudopodia, is taken in at any part of the animal 
 with which it happens to come in contact. A vacuole is formed around 
 it. Acid is secreted into the vacuole, the food is digested within the 
 cell-substance, and the part of it which is useless for nutrition is cast 
 out again at any part of the surface. 
 
 Coming a little higher, we find in the Ccelenterates a mouth and 
 alimentary' tube, which opens into the body-cavity, where a certain 
 
 31S 
 
PliELlMINARV AXATOMICAL AND CHEMICAL DATA jig 
 
 amount of digestion seems to take place, and from which the food is 
 absorbed cither through the cells of the endodcnn, or, as in Medusa, 
 by means of fine canals, which radiate from the body-cavity into its 
 walls, and form part of the so-called gastro-vascular system. In the 
 Echinodcrniata we have a further development, a complete alimentary 
 canal with mouth and anus, and entirely shut off from the body-cavity. 
 In many Arthropods it is possible already to distinguish parts corre- 
 sponding to the stoma<h, and the small and large intestines of higher 
 forms, the digestive glands being represented by organs which in some 
 groups seem to be homologous with the liver, and in others with the 
 salivary glands of the higher Vertebrates. A few Molluscs seem in 
 addition to possess a pancreas. 
 
 Among V'ertcbrates fishes have the simplest, and birds and mammals 
 the most complicated, alimentary system. In the lowest fishes the 
 stomach is only indicated by a slight widening of the anterior part of 
 the digestive tube. In water-living Vertebrates there are no sa.livar^ 
 glands. In birds the oesophagus is generally dilated to form a crop, 
 from which the food passes into a stomach consisting of two parts, 
 one pre-eminently glandular (proventriculus), the other pre-eminently 
 muscular (ventriculus). Among mammals a twofold division of the 
 stomach is distinctly indicated in rodents and cetaceae. but this organ 
 reaches its greatest complexity m ruminants, which possess no fewer 
 than four gastric pouches. The differentiation of the intestine into 
 small and large intestine and rectiun is more distinct, both anatomically 
 and functionally, in mammals than in lower forms ; but there are marked 
 dift'crences between the various mammalian groups both in the relative 
 size of the several parts of the digestive tube, and in the proportion 
 between the total length of the alimentar\- canal and the length of the 
 bodv. In general, the canal is longest in hcrbivora, shortest in carni- 
 vora. Thus, the ratio between length of body and length of intestine 
 is in the cat i : 4, dog i : 6, man i : 5 or 6, horse 1:12, cow i : 20, sheep 
 I : 27. The relative capacity of the stomach, small intestine, and large 
 intestine, is in the dog 6 :"2 : 1-5, in the horse i : 3'5 : 7, in the cow 
 7:2:1. The area of the mucous surface of the alimentary canal is 
 very considerable, in the dog more than half that of the skin, the 
 surface of the small intestine being three times that of the stomach 
 and four times that of the large intestine. In the horse the mucous 
 surface has twice the area of the skin. 
 
 Anatomy of the Alimentary Canal in Man. — The alimentary canal 
 is a muscular tube, which, beginning at the mouth, runs under the 
 various names of pharynx, oesophagus, stomach, small intestine, large 
 intestine, and rectum, "till it ends at the anus. Its walls are largely 
 composed of muscular fibres; its lumen is clad with epithelium, and 
 into it open the ducts of glands, which, morphologically speaking, are 
 involutions or diverticula formed in its course. In virtue of its muscular 
 fibres it is a contractile tube; in virtue ot its epithelial lining and its 
 special glands it is a secreting tube ; in virtue of both it is fitted to per- 
 form those mechanical and chemical actions upon the food which 
 are necessary for digestion. Its inner surface is in most parts richly 
 supplied with bloodvessels, and in special regions beset with peculiarlj'- 
 arranged lymphatics; by both of these channels the alimentary tube 
 performs its function of absorption. From the beginning of the oeso- 
 phagus to the end of the rectum the muscular wall consists, broadly 
 speaking, of an outer coat of longitudinally-arranged fibres, and a 
 thicker inner coat of fibres running circularly or transversely around 
 the tube. Between the layers lies a plexus of non-medullated nerves 
 and nerve-cells (Auerbach's plexus). In the stomach the longitudinal 
 
32« DIGESTION 
 
 fibres arc found only on the two curvatures, and a third incomplete 
 coat of obUque fibres makes its appearance internal to the circular 
 layer. In the large intestine, again, the longitudinal fibres are chiefly 
 collected into three isolated strands. In the pharynx the typical 
 arrangement is departed from, inasmuch as there is no regular longi- 
 tudinal layer; but the three con.strictor muscles represent to a certain 
 extent the great circular coat. The muscles of the mouth and of the 
 pharynx are of the striped variety. So is the muscle of the upper half 
 of the oesophagus in man and the cat, and of the whole oesophagus 
 in the dog and the rabbit. In the rest of the alimentary canal the 
 muscle is smooth, except at the very end, where the external sphincter 
 of the anus is striped. In certain situations the circular coat is de- 
 veloped into a regular anatomical sphincter, a definite muscular ring, 
 whose function it is to shut one part of the tube off from another 
 (sphincter pylori, ileo-colic sphincter), or to help to close the external 
 opening of the tube (internal sphincter of anus). Elsewhere a tonic 
 contraction of a portion of the ciicular coat, not anatomically de- 
 veloped bevond the rest, creates a functional sphincter (cardiac sphincter 
 of stomach). 
 
 Throughout the greater part of the digestive tract the peritoneum 
 forms a thin serous layer, external to the muscular coat. Internally 
 the muscular coat is separated from the mucous membrane, the lining 
 of the canal, by some loose areolar tissue containing bloodvessels, 
 lymphatics, and nerves (]\Ieissner's plexus), and called the submucous 
 coat. Between the mucous and submucous layers, but belonging to 
 the former, in the whole canal below the beginning of the oesophagus, 
 is a thin coat of smooth muscular fibres, the muscularis mucosae, con- 
 sisting in some parts, e.g., in the stomach, of two. or even three, 
 layers. Between this and the lumen of the canal lie the ducts and 
 alveoli of glands, surrounded by bloodvessels and embedded in adenoid 
 or Ivraphoid tissue, which in particular regions is collected into well- 
 defined masses (solitary follicles. Peycr's patches, tonsils), extending, 
 it may be, into the submucous tissue. In the mouth, pharynx, and 
 oesophagus, the glands lie in the submucosa. as do the glands of Brunner 
 in the duodenum; evcr^-where else they are confined to the mucous 
 membrane proper. Between the openings of the glands the mucous 
 membrane is lined with a single layer of columnar epithelial cells, some- 
 times (in the small intestine) arranged along the sides of tiny projec- 
 tions or \'illi. When the intestine is contracted the villi are long and 
 cylindrical in shape, when it is relaxed or distended they are flat and 
 conical. At the ends of the alimentary canal, viz., in the mouth, 
 pharynx, and oesophagus, and at the anus, the epithelium is stratified 
 squamous, and not colunmar. 
 
 The purpose of food is to supply the waste of the tissues, to 
 replenish the stores of material from the oxidation of which the 
 energy required for the running of the bodily machine is derived, 
 and thus to maintain the normal composition of the body. In the 
 body we find a multitude of substances marked oft from each other, 
 some by the sharpest chemical differences, others by characters 
 much less distinct, but falling upon the whole into the few fairly 
 definite groups already described (p. i). 
 
 Now, although it is by no means necessary that a substance in 
 the body belonging to one of these great groups should be derived 
 from a substance of the same group in the food, it has been found 
 
PRELIMISARY AXAIOMICAL AND CHIIMICAI. DATA 321 
 
 that upon the whoU- no diet is sufticient for man unless it contains 
 representatives of all; a proper diet must include proteins, carbo- 
 hydrates, fats, inorganic salts, and water. These proximate prin- 
 ciples have to be obtained from the raw material of the foodstuffs — 
 that is, as regards the first three groups, which can alone yield 
 energy in the body, from the tissues and juices of other living things, 
 plants or animals; it is the business of digestion to sift them out and 
 to prepare them for absorption. This preparation is partly mechan- 
 ical, partly chemical. 
 
 The water and salts and some carbo-hydrates, such as dextrose, 
 are ready for absorption without change. Fats are split into 
 glycerin and fatty acids before absorption. Indiffusible colloidal 
 carbo-hydrates, like starch and dextrin, are changed into diffusible 
 and readily soluble sugars, and the natural proteins into diffusible 
 peptones, and eventually into much simpler decomposition products. 
 These changes are obviously favourable to absorption. But this is 
 not their whole significance. For disaccharides, such as cane-sugar, 
 maltose, or lactose, although easily soluble in the contents of the 
 gut, and in themselves perfectly capable of being absorbed without 
 change, are, unless present in unusually large amount, all converted 
 into monosaccharides, such as dextrose, levulose, or galactose, either 
 in the lumen or in the wall of the alimentary tube. The reason is 
 that the disaccharides are unsuitable as pabulum for the cells. 
 Digestion is not only a preparation of the food for absorption by 
 the gut, but for assimilation by the tissues after absorption. An 
 equally important instance of this double function is seen in the 
 digestion of proteins. The complete shattering of the protein mole- 
 cule into amino-acids and the other groups jaelded by its decom- 
 position (p. 360) is required, in the case of that portion of the protein 
 which goes to build up the tissues, because of the high degree of 
 specificity of the tissue proteins. The myosinogen of beef cannot 
 be cobbled into the myosinogen of human muscle, still less we may 
 suppose into the serum-albumin of human blood. It is necessary 
 that the food protein should be completely ' wrecked ' in digestion 
 so that protein which is to take its place in protoplasm may be built 
 exactly to order from the bricks. A satisfactory ' fit ' cannot be 
 obtained with ready-made protein. Mechanical division of the food 
 is an important aid to the chemical action of the digestive juices. We 
 shall see that this mechanical division forms a great part of the work 
 of the stomach, but it is normally begun in the mouth, and it is of 
 consequence that this preliminary stage should be properly performed. 
 
 Section II. — The Mechanical Phenomena of Digestion. 
 
 Mastication. — It is among the mammaha that regular masrication 
 of the food first makes its appearance as an important aid to diges- 
 tion. The amphibian bolts its fly, the bird its grain, and the fish 
 
322 DIGESTION 
 
 its brother, without the ceremony of chewing. In ruminating 
 mammals we see mastication carried to its highest point ; the teeth 
 work all day long, and most of them are specially adapted for 
 grinding the food. The carnivora spend but a short time in masti- 
 cation; their teeth are in general adapted rather for tearing and 
 cutting than for grinding. Where the diet is partly animal and 
 partly vegetable, as in man, the teeth are fitted for all kinds of work ; 
 and the process of mastication is in general neither so long as in the 
 purely vegetable feeders, nor so short as in the carnivora. 
 
 In man there are two sets of teeth : the temporary or milk teeth, 
 and the permanent teeth. The milk teeth are twenty in number, 
 and consist on each side of four incisors or cutting-teeth, two 
 canines or tearing-teeth, and four molars or grinding-teeth. The 
 central incisors emerge at the seventh month from birth, the other 
 incisors at the ninth month, the canines at the eighteenth, and the 
 molars at the twelfth and twenty-fourth month respectively. 
 Each tooth in the lower jaw appears a little before the corresponding 
 one in the upper jaw. Each of the milk teeth is in course of time 
 replaced by a permanent tooth, and in addition the vacant portion 
 of the gums behind the milk set is now filled up by twelve teeth, 
 six on each side, three above and three below. These twelve are 
 the permanent molars; they raise the number of the permanent 
 teeth to thirty-two. The permanent teeth which occupy the 
 position of the milk molars now receive the name of premolars. 
 The first tooth of the permanent set (the first true molar) appears 
 at the age of 6| years; the last molar, or wisdom-tooth, does not 
 emerge till the seventeenth to the twenty-fifth year. 
 
 In mastication the lower jaw is moved up and down, so as to 
 alternately separate and approximate the two rows of teeth. It has 
 also a certain amount of movement from side to side, and from front 
 to back. The masseter, temporal and internal pterygoid muscles 
 raise, and the digastric, with the assistance of the mylo- and genio- 
 hyoid, depresses, the lower jaw, but its downward movement is 
 rnainly a passive one. The external pterygoids pull it forward 
 when both contract, forward and to one side when only one con- 
 tracts. The lower fibres of the temporal muscle retract the jaw. 
 The buccinator and orbicularis oris muscles prevent the food from 
 passing between the teeth and the cheeks and lips. The tongue 
 keeps the food in motion, works it up with the saliva, and finally 
 gathers it into a bolus ready for deglutition. 
 
 Deglutition. — This act consists of a voluntary and an involun- 
 tary stage. Just before the beginning of the voluntary stage 
 mastication is suspended, and a slight contraction of the dia- 
 phragm generally takes place. The anterior part of the tongue 
 is suddenly elevated and pressed against the hard palate, and the 
 elevation travels back from the tip towards the root, as the mylo- 
 
THE MECHANICAL PHENOMENA Of DIGESTION 323 
 
 hyoid muscles in the floor of the mouth contract sharply so as to 
 thrust the bolus through the isthmus of the fauces. As soon as this 
 has happened, and the food has reached the posterior portion of the 
 tongui', it has passed beyond the control of the will, and the second 
 or involuntary stage of the process begins. 
 
 This stage may be divided into two parts: (i) Pharyngeal, 
 (2) oesophageal — both being reflex acts. During the first the food 
 has to pass through the pharjmx, the upper portion of which forms 
 a part of the respiratory tract, and is in free communication with 
 the laryn.x during ordinary breathing. It is therefore necessary 
 that respiration should be interrupted and the larynx closed while 
 the food is being moved through the pharynx. But that the inter- 
 ruption may be short, the food must be rapidly passed over this 
 perilous portion of its descent. The main propelling force under 
 which the bolus is shot through the back of the pharynx is derived 
 from the contraction of the mylo-hyoid muscles already mentioned, 
 assisted to some extent by the stylo- and palato-glossi ; and that 
 none of the purchase may be lost, the pharyngeal cavity is cut off 
 from the nose and mouth as soon as the bolus has entered it. The 
 soft palate is raised by the levator palati and palato-pharyngei 
 muscles; at the same time the upper part of the phar^mx, narrowed 
 by the contraction of the superior constrictor, comes forward to 
 meet the soft palate, closes in upon it, and so prevents the food 
 from passing into the nasal cavities. The pharynx is cut off from 
 the mouth by the closure of the fauces through the contraction of 
 the palato-pharjmgeal muscles which lie in their posterior pillars. 
 The upper free end of the epiglottis (the so-called pharyngeal part) 
 aids the back of the tongue in completing a movable partition across 
 the phar^Tix, which keeps close to the bolus as it passes down 
 between the posterior surface of the epiglottis and the posterior 
 wall of the pharynx. Almost immediately after the contraction 
 of the mylo-hyoids the larynx is pulled upwards and forwards by 
 the contraction of the thyro-hyoid muscle, and the elevation of the 
 hyoid bone by the muscles which connect it to the lower jaw. 
 The base of the tongue is simultaneously drawn backwards by the 
 stylo- and palato-glossus. The lower or laryngeal portion of the 
 epiglottis is thus caused to come into contact with the upper orifice 
 of the larynx, occluding it completely, but the pharyngeal portion 
 projects beyond the larynx, and takes no share in its closure 
 (Eykman). The glottis is closed by the approximation of the vocal 
 cords and the arytenoid cartilages. The epiglottis, however, is not 
 absolutely indispensable for closing the lar^Tix, since swallo\ving 
 proceeds in the ordinary way when it is absent. The morsel of 
 food, grasped by the middle and lower constrictors as it leaves the 
 back of the tongue, passes rapidly and safeh^ over the closed lar5-nx, 
 the process being accelerated by the pulling up of the lower portion 
 
324 DIGESTION I 
 
 of the pharynx over the bolus by the action of the palato- and stylo- 
 pharyngei. 
 
 The second or oesophageal portion of the involuntary stage is 
 a more leisurely performance. The bolus is carried along by a 
 peculiar ' peristaltic ' contraction of the muscular wall of the 
 oesophagus, which travels down as a wave, constricting the tube 
 and pushing the food before it. In front of the constricting wave 
 moves a wave of inhibition, so that the part of the oesophagus into 
 which the bolus is about to pass is always relaxed, while the part 
 behind it is contracted. This exact co-ordination of inhibition 
 and contraction is the essential thing in peristalsis. When the food 
 reaches the lower end of the gullet the tonic contraction of that part 
 of the tube is for a moment relaxed by reflex inhibition, and the 
 morsel passes into the stomach. Beaumont saw, in the case of 
 St. Martin, that the oesophageal orifice of the stomach contracted 
 firmly after each morsel was swallowed, and so did the gastric walls 
 in the neighbourhood of the fistula when food was introduced b}^ 
 this opening. In the dog the whole process of swallowing from 
 mouth to stomach has been shown to occupy four to five seconds, 
 but the time is by no means constant. In man the peristaltic wave 
 requires about five to six seconds to travel from the level of the 
 glottis to the cardiac orifice. The rate of movement is greater in the 
 upper than in the lower portion of the oesophagus. 
 
 Such is the mechanism of deglutition when the bolus is of such 
 consistence and size that it actually distends the oesophagus. But 
 it has been shown that hquid food is swallowed in a different way. 
 The food lying on the dorsum of the tongue, suddenly put under 
 pressure by the sharp contraction of the mylo-hyoid muscles, is 
 shot rapidly down to the lower part of the lax oesophagus, or, occa- 
 sionally, some of it even into the stomach. So far the process has 
 only occupied one-tenth of a second. After several seconds, the 
 food, or the portion which still remains in the oesophagus, is forced 
 through the cardiac sphincter into the stomach by the arrival of 
 the tardy peristaltic contraction of the oesophageal wall (Kronecker 
 and Meltzer). Two sounds may be heard in man on listening in 
 the region of the stomach or oesophagus during deglutition of hquids, 
 especially when, as generally happens, they are mixed with air. 
 The first sound occurs at once, and is due to the sudden squirt of 
 the liquid along the gullet ; the second, which is heard after a distinct 
 interval (about six seconds), is caused by the forcing of the fluid 
 through the cardiac orifice of the stomach by the contraction of the 
 oesophagus. 
 
 There are certain peculiarities which distinguish this peristaltic 
 movement of the oesophagus from that of other parts of the alimen- 
 tary canal. It is far more closely related to the central nervous 
 system, and, unlike the peristaltic contraction of the intestine, can 
 
THE MECHANICAL PHENOMENA OF DIGESTION 325 
 
 pass over any muscular block caused by ligature, section, or crush- 
 ing, so long as the nervous connections are intact. But division 
 of the oesophageal nerves causes, as a rule, stoppage of oesophageal 
 movements; although an excised portion of the tube retains its 
 vitahty for a long time, and may, under certain circumstances, go 
 on contracting in the characteristic way after removal from the body 
 (p. 81/). Stimulation of the mucous membrane of the phar^-Tix will 
 cause reflex movements of the oesophagus, while stimulation of its 
 own mucous membrane is ineffective. From these facts we learn 
 that although the oesophageal wall may possess a feeble power of 
 spontaneous peristaltic contraction, yet this is usually in abeyance, 
 or at least overmastered by central nervous control ; so that impulses 
 discharged as a ' fusillade ' from successive portions of the vagus 
 centre, and travelling down the oesophageal nerves, excite the 
 muscular fibres in regular order from the upper to the lower end 
 of the tube. 
 
 Nervous Mechanism of Deglutition.— The centre for the whole 
 involuntary stage (both pharyngeal and oesophageal) lies in the 
 upper part of the medulla oblongata. When the brain is sliced 
 away above the medulla, deglutition is not affected; but if the upper 
 part of the medulla is removed, the power of swallowing is abolished. 
 In man, disease of the spinal bulb interferes far more with deglutition 
 than disease of the brain proper. 
 
 Normally, the afferent impulses to the centre are set up by the 
 contact of food or saH va with the mucous membrane of the posterior 
 part of the tongue, the soft palate and the fauces, the nerve- 
 channels being the superior laryngeal, the pharyngeal branches of 
 the vagus, and the palatal branches of the fifth nerve.* A feather 
 has sometimes been swallowed involuntarily by a reflex movement 
 of deglutition set up while the soft palate or pharynx was being 
 tickled to produce vomiting. Artificial stimulation of the central 
 end of the superior laryngeal will cause the movements of deglutition 
 independently of the presence of food or liquid; but if the central 
 end of the glosso- pharyngeal nerve be stimulated at the same time, 
 the movements do not occur. The glosso-pharyngeal is therefore 
 able to inhibit tlie deglutition centre, and it is owing to the action 
 of this nerve that in a series of efforts at swallowing, repeated within 
 less than a certain short interval (about a second), only the last is 
 successful. It is also through the glosso-pharyngeal nerve that 
 the respiratory movements are inhibited during deglutition. When 
 the central end of this nerve is stimulated, respiration is stopped 
 
 * It appears that the most influential reflex paths may differ in different 
 animals. In the rabbit, e.g., the reflex is set up by excitation of the ti-igeminal 
 fibres which suppl}^ the mucous membrane anterior to the tonsils, in the dog 
 and cat by excitation of the glosso-pharyngeal fibres in the posterior wall of 
 the pharynx, and in monkeys by excitation of the trigeminal branches dis- 
 tributed to the mucous membrane over the tonsils (Kahn). 
 
326 DIGESTION 
 
 for four or five seconds, and this cessation is distinguished from 
 that produced by any other afferent nerve by the circumstance 
 that it occurs not in expiration exclusively or in inspiration ex- 
 clusively, but with the respiratory muscles in the precise degree of 
 contraction in which they happened to be at the moment of stimu- 
 lation. The efferent nerves of the reflex act of deglutition are the 
 hypoglossal to the tongue and the thyro-hyoid and other muscles 
 concerned in raising the larynx; the glosso-pharyngeal, vagus, 
 facial and fifth to the muscles of the palate, fauces, and pharynx ; 
 the fifth to the mylo-hyoid; and the vagus to the larynx and 
 oesophagus. Section of the vagus interferes with the passage of 
 food along the oesophagus; stimulation of its peripheral end causes 
 oesophageal movements. 
 
 Movements of the Stomach. — The whole of the stomach does 
 not take part equally in the movements associated with digestion. 
 We may divide the organ, both anatomically and functionally, into 
 two portions — a pyloric portion, or antrum pylori, comprising about 
 a fifth of the stomach, and a larger cardiac portion, or fundus* 
 At the junction of the antrum and the fundus the circular muscular 
 coat is slightly thickened into a ring called the ' transverse band,' 
 or ' sphincter of the antrum.' In the living stomach the region 
 of the transverse band is usually contracted so strongly and con- 
 tinuously that a distinct groove is seen to separate the tubular 
 antrum from the bag-like cardiac end. The suggestion of a massive 
 constricting ring of muscle is belied by an examination of the dead 
 viscus. The transverse band is really little more than a physio- 
 logical sphincter. The empty stomach is contracted and at rest. 
 A few minutes after food is taken contractions begin in the antrum, 
 and run on in constricting undulations (in the cat at the rate of 
 six in the minute) towards the pj^loric sphincter. Each wave takes 
 about twenty seconds (in the cat) to pass from the middle of the 
 stomach to the pylorus. Feeble at first, they become stronger and 
 stronger as digestion proceeds, and gradually come to involve the 
 portion of the fundus next the sphincter of the antrum, but their 
 direction is always towards the pylorus, never, in normal diges- 
 tion, away from it. The food is thus subjected to energetic churn- 
 ing movements in the pyloric end of the stomach, and worked up 
 thoroughly with the gastric juice. Kept in constant circulation, 
 it gradually becomes reduced to a semi-liquid mass, the chyme, 
 which is at intervals driven against the pylorus by strong and 
 regular peristaltic contractions of the lower end of the stomach, 
 
 * Here ' fundus ' is used in the sense in which it is generally employed in 
 speaking of the stomach of the dog Oi cat as signifying the wnolc of the organ 
 with the exception of the antrum pyiori. By the fundus of the human stomach 
 most writers mean only the cul-'ie-sac at the cardiac end; the portion inter- 
 vening between it and the n.icrum pylori is often term.^i the body of the 
 ttomach. 
 
THE MECHANICAL PHENOMENA OF DIGESTION 
 
 327 
 
 II A.M. 
 
 the sphincter relaxing from time to time by a reflex inhibition to 
 admit the better-digested portions into the duodenum, but tighten- 
 ing more stubbornly at the impact of a hard and undigested morsel. 
 The nature, as well as the consistence of the food, influences the 
 length of its sojourn in the stomach. Carbo-hydrate food passes 
 more rapidly through the pylorus than fatty food, and fat more 
 rapidly than protein. The reason is that 
 the acidity of the gastric juice varies 
 with the different kinds of food, hydro- 
 chloric acid being secreted in abundance 
 in the presence of proteins, and to a 
 much smaller extent in the presence of 
 fats and carbo-hydrates. Now, dilute 
 hydrochloric acid when introduced into 
 the stomach remains there for a much 
 longer time than water. This depends 
 upon the fact that such portions of the 
 acid as get into the duodenum stimulate 
 afferent fibres in its mucous membrane, 
 and so cause reflex spasm of the pyloric 
 sphincter. When the acid chyme be- 
 comes neutralized to a certain point by 
 the bile and pancreatic juice, inhibitory 
 impulses pass up from the duodenum 
 and cause the sphincter to relax. The 
 cardiac division of the stomach, with 
 the exception of the portion that borders 
 the transverse band, takes no share in 
 the peristaltic movements. And, indeed, 
 it is far more difficult to cause such con- 
 tractions by artificial stimulation in the 
 fundus* than in the pyloriis. The two 
 portions of the stomach are partially, or 
 in certain animals from time to time 
 completely, cut off from each other by 
 the contraction of the sphincter of the 
 antrum. The fundus, so far as its 
 mechanical functions are concerned, acts 
 chiefly as a reservoir for the food, which, 
 like a hopper, it gradually passes into 
 the pyloric mill as digestion goes on by a tonic contraction of its 
 walls. The existence of this reservoir enables larger quantities of 
 food to be taken at one meal, which can then be digested gradually. 
 
 * The common idea, however, that the fundus is completely inactive is 
 erroneous. Rhythmical variations in tone with a period of i to 3 minutes have 
 been observed during digestion. In hunger vigorous peristaltic contractions 
 sweep over the whole stomach, beginning at the cardiac end. 
 
 Fig. 150. — Cat's Stomach seen 
 by Rontgen Rays (Cannon). 
 The outlines of the stomach 
 containing food mixed with 
 bismuth subnitrate were 
 drawn at intervals from 
 II a.m. to 4.30 p.m. 
 
3^8 
 
 DIGESTION 
 
 These farts have been mainly ascertained by observations on 
 animals, such as the dog and the cat, cither by direct inspection 
 after opening the abdomen (Rossbach), or in tht: intact body, under 
 absolutely physiological conditions, by means of the Kontgen rays 
 (Cannon). In the latter method the food is mixed with subnitrate 
 of bismuth, which is opaque to these rays, so that when the animal 
 is looked at through a fluorescent screen the stomach appears as a 
 dark shadow in the field (Fig. 150). This method has even been 
 applied with success to the study of the passage of the food along 
 the human alimentary canal from deglutition to defaecation (Hertz). 
 It has been shown in this way that in the living body in the erect 
 position the long axis of the stomach is much more nearly vertical 
 than had been supposed. When food is taken it sinks into the 
 lower (pyloric) end, and at the ui)per end gas collects. 
 
 When the j^erson lies down the lower end of the stomach passes 
 more towards the left, so that the long axis lies more transversely. 
 Other methods have thrown light on the gastric movements — e.g., 
 direct inspection through a fistula of the stomach, and the study 
 
 Fig. 131. — Human Stomnch studied by Rontgcii Rays. a. Empty stomach iu ver- 
 tical p jsitioii ; b. shortly after a meal (peristaltic contractions are occurring at 
 the pyloric end) ; c, full stomacii in vertical position. (Halliburton after Hertz.) 
 
 of records showing the changes of pressure in the viscus obtained 
 by means of small balloons introduced into it. Such balloons 
 attached to a rubber tube have been swallowed by normal men 
 and kept for long periods in the stomach (Carlson). Even in the 
 excised stomach, kept in salt solution at the body-temperature, 
 the typical movements can be observed proceeding for some time. 
 Movements of the Small Intestine.— In the small intestine two 
 kinds of movements are to be seen : (1) Gentle, swaying, ' pendulum ' 
 movements, sometimes irregular, but often recurring rhythmically 
 at the rate (in the dog) of 10 or 12 in the minute. Both the longi- 
 tudinal and the circular muscular coats contract, causing slight 
 waves of constriction, which may originate at any part of the gut, 
 but, under normal circumstances, nearly always travel from above 
 downwards, with a velocity of 2 to 5 centimetres per s(>c(md. These 
 movements cause the coils of the intestine to sway gently from side 
 
rinc MiiciiASK .11. I'lii-xoMJis.i f)i- i)i(,i:sri()\' -520 
 
 to side. Under abnormal conditions, as in the exposed ' sur\aving ' 
 intestines of the rabbit, contractions, probably sinular to the 
 pendulum movements, but running indifferently in buth direc- 
 tions, can be set up by local stimulation. The function of these 
 pendulum movements seems to be the thorough mixing of the food 
 with the digestive juices in the intestine. When an animal is fed 
 with food containing bismuth subnitrate and observed with the 
 Ront^en rays, it is seen that the food in a coil is often divided into 
 small segments, which then join together to form longer masses, 
 these being in turn again divided. This segmentation is rhyth- 
 mically repeated (in the cat at the rate of thirty times a minute). 
 Although of itself it insures only the mixing of the contents of the 
 gut, and not their onward progress, it is usually accompanied by 
 peristalsis, so that while the food is undergoing segmentation it is 
 also slowly passing down the intestine. Often, however, a column 
 of food remains for a considerable time, dividing, uniting, and divid- 
 ing again, without sensibly shifting its position. In addition to the 
 relatively rapid pendulum movements, much slower periodic varia- 
 tions of tone of the whole musculature may be normally observed. 
 
 (2) True peristaltic movements, in which a ring of constriction, 
 obliterating the lumen, moves slowly down the tube, with a speed, 
 it may be, no greater than i mm. per second. The portion of the 
 intestine immediately below the advancing constriction is relaxed 
 and motionless, so that we may say that a wave of inhibition pre- 
 cedes the wave of contraction. The peristaltic movements of the 
 small intestine, the most typical of their kind, are most easily 
 excited by mechanical stimulation of the mucous membrane, as 
 by the contact of a morsel of food or an artificial bolus of cotton- 
 wool. Travelling, under normal conditions, always downwards, 
 the constriction squeezes the contents of the tube before it, and the 
 wave usually ends at the ileo-caecal valve, which separates the small 
 intestine from the large. The cause of the definite direction of the 
 peristaltic wave is grounded in the anatomical relations of the 
 intestinal wall. For when a portion of the intestine is resected, 
 turned round in its place and sutured, so that what was before its 
 upper is now its lower end, the contraction wave is unable to pass, 
 and the obstruction to the onward flow of the intestinal contents 
 causes marked dilatation of the gut, and sometimes serious disturb- 
 ance of nutrition. The most probable explanation is that the peri- 
 stalsis is governed by a local reflex nervous mechanism (Auerbach's 
 plexus), the stimulation of which by the contact of the food with 
 the mucous membrane or by the distension of the gut causes 
 excitation of the circular muscular fibres above the point of stimula- 
 tion, and inhibition of them below it. The automatic pendulum 
 movements, and also the slow, rhythmical variations of tone, have 
 a different relation to the local nervous mechanism, for they behave 
 differently to poisons like cocaine and nicotine, which act on that 
 
330 
 
 DJGF.STIOS^ 
 
 mechanism. The pendnUim movements are, ii anytliing, increased 
 in intensity and made more regular. But the pe ista'tic waves, 
 although they can be locally excited by direct stimulation of the 
 muscular fibres, are no longer propagated, and a bolus introduced 
 into the intestine remains at rest where it is placed. Some have 
 interpreted these facts as indicating that the pendulum movements 
 are m5'ogenic in origin. But evidence has lately been obtained that, 
 although they are not reflex movements elicited by afferent impulses 
 from the mucous membrane, since the}' continue in unaltered in- 
 tensit}^ in isolated loops of intestine immersed in Ringer's (or 
 Locke's) solution (p. 66) after removal of both mucosa and sub- 
 mucosa, they are nevertheless dependent upon Auerbach's plexus. 
 For when the circular muscular coat is separated from this plexus, 
 ^he automatic movements of this coat are abolished, although the 
 
 excitability of the musculature to 
 direct stimulation is not affected. 
 The longitudinal coat, which is 
 still in connection with Auerbach's 
 plexus, goes on contracting spon- 
 taneously (Magnus). Under certain 
 conditions a movement of food or 
 secretions in the reverse of the 
 normal direction can be set up in 
 the small intestine in the intact 
 body — e.g., in the case of obstruc- 
 tion of the intestine leading to 
 vomiting of its contents. But this 
 does not necessarily indicate a re- 
 versal of the normal direction of 
 the peristalsis. Such a reversal, 
 if it occurs at all, is not easy to realize b}' artificial stimulation, and 
 even when an antiperistaltic wave is apparently started, it travels 
 up the intestine onlj' for a short distance and then dies out. A 
 third variety of intestinal movement has sometimes been described, 
 the so-called ' peristaltic rush ' (Meltzer, etc.). It consists of a 
 rapidly moving peristaltic contraction, preceded by relaxation of 
 a long portion of the tube. Such a contraction may even sweep 
 down without pause from the duodenum to the end of the ileum. 
 
 The Movements of the Large Intestine differ from those of the 
 small mainly in the great frequency of antiperistalsis. This, indeed, 
 seems to be the usual movement of the transverse and ascending 
 colon. The antiperistalsis recurs in periods about every fifteen 
 minutes, and each period generally lasts about five minutes. The 
 constrictions, running towards the caecum, thoroughly churn and 
 mix the remnants of the food, a considerable absorption of which 
 may take place in the upper part of the large intestine. Regurgita- 
 tion into the ileum in man is prevented partly by the oblique entry 
 
 Fig. 152. — Intestine Segment beating 
 in Ringer's Solution. At 6 the oxy- 
 gen stream was increased. To be 
 read from left to right. Time trace, 
 half -minutes. ( Reduced to one -half . ) 
 
THE MECHANICAL PHESuMESA Ut DIGESTION 331 
 
 of the ileum through the wall of the colon (so-called ileo-caecal 
 valve), but essentially by the tonic contraction of the ileo-colic 
 sphincter. The sphincter usually permits the passage of material 
 only in the direction from small to large intestine. But as an 
 occasional phenomenon, a reverse movement may occur. Thus 
 food may actually pass back through the ileo-colic sphincter into 
 the small intestine under the action of a long-continued and vigorous 
 antiperistalsis, and in this way a considerable portion of a bulky 
 enema may be eventually disposed of (Cannon). This so-called 
 antiperistalsis is not precisely the same kind of movement, leaving 
 out of account its direction, as the peristalsis already described in the 
 small intestine, since it is not preceded by a wave of inhibition. 
 True peristaltic contractions preceded by relaxation of the gut may 
 also be observed to start in the caecum, and to travel down the large 
 intestine. They are not very frequent in comparison with those 
 of the small intestine, and they die away before reaching the end 
 of the colon, allowing the food to be driven back again towards 
 the caecum by the antiperistalsis. A true downward peristalsis 
 is more commonly seen in the descending colon, and is here asso- 
 ciated with the propulsion and collection of the faces, which are 
 mainly stored in the sigmoid flexure. These peristaltic contractions 
 do not normally reach the rectum, which, except during defaecation, 
 remains at rest. 
 
 Influence of the Central Nervous System on the Gastro- Intestinal 
 Movements. — As we have already said, these movements are much 
 less closely dependent on the central nervous system than are those 
 of the oesophagus. They can not only go on, but are in general 
 better marked when the extrinsic nervous connections are cut ; they 
 cannot spread when the continuity of the tube is destroyed, and 
 the mere presence of food will excite them when other than local 
 reflex action has been excluded by section of the nerves. Never- 
 theless, the central nervous system does exercise some influence 
 in the way of regulation and control, if not in the way of direct 
 initiation of the movements, and the swallowing or even the smell 
 of food has been observed to strengthen the contractions of a loop 
 of intestine severed from the rest, but with its nerves still intact. 
 The vagus is the efferent channel of this reflex action: stimulation 
 of its peripheral end may cause movements of all parts of the 
 alimentary canal from oesophagus to large intestine, and may 
 strengthen movements already going on; but section of it does not 
 stop them, nor hinder the food from causing peristalsis wherever 
 it comes. The vagus also contains inhibitory fibres for the lower 
 end of the oesophagus and the whole of the stomach. Stimulation 
 of it is followed first by inhibition, and then, after an interval, by 
 an increase of tone and augmentation of the contraction of the 
 whole stomach, including the cardiac and pyloric sphincters. The 
 
332 DIGESTION 
 
 splanchnic nerves contain fibres by which the intestinal movf nients 
 can be inhibited, and they appear to be always in action, for after 
 section of these nerves the movements are strengthened. On the 
 other hand, stimulation of the peripheral end of the cut splanchnic 
 causes arrest of the movements. Occasionally, however, it has 
 the opposite effect. Contractions of the small intestine are more 
 easily caused by excitation of the vagus after the inhibitory splanch- 
 nic nerves have been cut. The splanchnics also contain inhibitor}' 
 fibres for the stomach, and it is only when these are intact that 
 complete reflex inhibition of the organ can be obtained in the rabbit 
 (Auer). The gastric movements are not permanently affected by 
 section of these nerves alone, or even by simultaneous section of 
 the splanchnics and the gastric branches of the vagi. But if the 
 vagi are cut while the splanchnics remain intact, the peristalsis of 
 the stomach is weakened, its onset delayed, and the proper emptying 
 of the viscus through the pylorus interfered with. In all probability 
 these results are due to the uncontrolled action of the inhibitory 
 libres. The splanchnics have a special relation to the ileo-colic 
 sphincter, which closes when they are stimulated, and becomes in- 
 sufficient when they are cut. The vagus does not affect it. 
 
 The lower part of the large intestine is influenced by the sacral nerves 
 (second, third, and fourth sacral in the ra,bbit), and by certain lumbar 
 nerves, in the same way as the higher parts of the alimentary canal, and 
 particularly the small intestine, are influenced by the vagus and the 
 splanchnics. Stimulation of these sacral nerves within the spinal 
 canal, or of the pelvic nerves (nervi erigentes) into which they pass, 
 causes contraction of the parts of the large intestine concerned in 
 defalcation — that is, in the dog, of the whole colon, with the exception 
 of the caecum; in the cat, of the distal two-thirds of the colon. The 
 colon first undergoes rapid shortening due to the contraction of the 
 longitudinal fibres and the rccto-coccygcus muscle. After a few 
 seconds this is followed by contraction of the circular fibres, beginning 
 at the lower limit of the region in which antiperistalsis can occur, and 
 spreading downwards, so as to empty the portion of the bowel involved 
 in the contraction. This is a very close imitation of what occurs in 
 natural defaecation. In man the parts involved in these movements 
 are probably the sigmoid flexure and rectum. In addition to these 
 characteristic motor effects on the lower part of the large intestine, 
 stimulation of the pelvic nerves causes an increase in the antiperi-stalsis 
 of its upper portions. Stimulation of the lumbar nerves or of the por- 
 tions of the sympathetic into which their visceral fibres pass (lumbar 
 sympathetic chain from second to sixth ganglia, or the rami from it to 
 the inferior mesenteric ganglia) causes inhibition of the movements of 
 the caecum and the whole colon, including the antiperistiiltic move- 
 ments. Excitation of the sacral nerves initiates or increases the con- 
 traction of both coats of the portions of the large intestine on which 
 they act, excitation of the lumbar nerves inhibits both. And in the small 
 intestine the same law holds good ; the two coats are contracted together 
 by the action of the vagus or inhibited together by that of the splanclinics. 
 
 Defaecation is partly a voluntary and partly a reflex act. But 
 in the infant the voluntary control has not yet been developed; 
 
THE MECHANICAL PHENOMENA OF DIGESTION 3J3 
 
 in tliL' lulult it may hv lost by disease; in an animal it may be 
 abolished by ojieration, and in each case the action becomes wholly 
 reflex. Owing to the tonic contraction of the rectum and the acute 
 angle formed at the pelvi-rectal flexure, the faces arc arrested at 
 this point. In consequence the pelvic colon becomes filled with 
 faeces from below upwards, and the rectum remains empty till 
 immediately before defalcation. This has been verified in man by 
 observations with the Rcintgen rays (Hertz). In persons whose 
 bowels are opened regularly after breakfast, the passage of faeces 
 into the rectum gives rise to the characteristic sensation which 
 may be termed the ' call to defaecation. ' It is the distension of the 
 rectum, and of the rectum alone, which is associated with this 
 sensation, for in persons from whom the entire rectum has been 
 removed for malignant disease the sensation is absent, and it may 
 be elicited by artificially distending the rectum, though not any 
 other part of the alimentary canal. The minimum pressure required 
 to elicit the sensation is smaller the greater the length of the gut 
 exposed to it, varying in one individual from 32 to 48 mm. of 
 mercury, according to the length of a balloon introduced into the 
 rectum. The passage of the fseces from the pelvic colon into the 
 rectum is due to the discharge of that reflex contraction of the lower 
 portion of the bowel already described (p. 332), of which the pelvic 
 nerves constitute the efferent path. This reflex peristalsis is elicited 
 by various causes, among which one of the most important is the 
 taking of food at breakfast into the empty stomach, and another 
 the muscular activity associated with getting up and dressing. 
 The desire to defaecate may for a time be resisted by the will, or it 
 may be yielded to. In the latter case the abdominal muscles, and, 
 according to Hertz, the diaphragm also, are forcibly contracted; 
 and the glottis being closed, the whole effect of their contraction 
 is expended in raising the pressure within the abdomen and pelvis, 
 and so aiding the muscular wall of the bowel itself in driving the 
 faeces from the sigmoid flexure to the rectum. The two sphincters 
 which close the anus — ^the internal sphincter of smooth muscle, 
 and the external of striated — are now relaxed by the inhibition of 
 a centre in the lumbar portion of the spinal cord, through the 
 activity of which the tonic contraction of the sphincters is normally 
 maintained. This relaxation is partly voluntary, the impulses 
 that come from the brain acting probably through the medium 
 of the lumbar centre. But in the dog, after section of the cord in 
 the dorsal region, the whole act of defaecation, including contraction 
 of the abdominal muscles and relaxation of the sphincters, still 
 takes place, and here the process must be purely reflex. Even after 
 complete destruction of the lumbar and sacral portions of the spinal 
 cord the tone of the sphincters returns after a time, and defaecation 
 is carried on as in a normal animal, the control of the sphincters 
 
334 DIGESTION 
 
 being due either to a property of the muscular tissue itself or to 
 local ganglia. The contraction of the levatores ani helps to resist 
 overdistension of the pelvic floor and to pull the anus up over the 
 faeces as they escape. The nervi erigentes carry efferent constrictor 
 fibres, and the hypogastrics, as a rule, efferent dilator fibres, to the 
 sphincters. While the internal sphincter is by itself capable of 
 maintaining a tonus of considerable strength, the external sphincter 
 contributes an important share (30 to 60 per cent.) to the closure 
 of the rectum. If the call to defalcation is neglected, the desire 
 passes away. This is not due to the faces being carried back into 
 the pelvic colon by antiperistalsis, as has generally been stated. 
 The faeces which have passed into the rectum remain there, as can 
 be shown by examination with the finger after the desire to empty 
 the bowels has disappeared. The reason for the disappearance 
 of the sensation is the relaxation of tone which occurs in the 
 muscular coat of the rectum after a period of distension. It is not 
 till it has been again distended by the entrance of a further portion 
 of faeces that the call to defaecation is again experienced. When 
 the call is repeatedly neglected, the sensibility of the rectum to dis- 
 tension becomes blunted, and this is a common cause of constipation. 
 
 The time of passage of substances through the alimentary canal 
 has been studied by administering collodion capsules filled with 
 subnitrate of bismuth to human beings, and observing their pro- 
 gress by taking shadow pictures of them at intervals with the 
 Rontgen rays. During the first twenty minutes two such capsules 
 swallowed at the same time by a healthy young man were clearly 
 seen in the greater curvature of the stomach, but in the interval 
 between the first half-hour and the seventh or eighth hour no further 
 trace of them was detected. About the eighth hour they re- 
 appeared in the caecum, where they remained with little or no 
 onward movement till the fourteenth hour. From the fourteenth 
 to the sixteenth hour they travelled along the ascending colon, and 
 tarried a long time at the left angle of the colon. From the nine- 
 teenth to the twenty-second or twenty-fourth hour they slowly 
 passed downward in the descending colon, and stopped at the sig- 
 moid flexure till their expulsion in defaecation. In some subjects 
 the entire passage of the capsules was complete in sixteen hours, in 
 others not until after thirty hours. A one cent piece swallowed by 
 a healthy child four years old was recovered in the faeces 52 hours 
 later, and a button, slightly larger, swallowed by the same child, 
 appeared after almost exactly the same interval. 
 
 Vomiting. — ^We have seen that under normal conditions the 
 movements of the alimentary canal always tend to carry the food 
 in one definite direction, along the tube from the mouth to the 
 rectum. The peristaltic waves generally run only in this direction, 
 and, further, regurgitation is prevented at three points by the 
 
THE MECHANICAL PHE\OME\A 01- DIGESTION 335 
 
 cardiac and pyloric sphincters of the stomach and the ilco-cohc 
 sphincter and valve. But in certain circumstances the peristalsis 
 may be reversed, one or more of the guarded orifices forced, and the 
 onward stream of the intestinal contents turned back. In obstruc- 
 tion of the bowel, the faecal contents of tlie large intestine may pass 
 up beyond the ilco-caecal valve, and, reaching the stomach, be driven 
 by an act of vomiting through the cardiac orifice; in what is called 
 a ' bilious attack,' the contents of the duodenum may pass back 
 through the pylorus and be ejected in a similar way; or, what is 
 by far the most common case, the contents of the stomach alone 
 may be expelled. 
 
 \'omiting is usually preceded by a feeling of nausea and a rapid 
 secretion of saliva, which perhaps serves, by means of the air 
 carried down with it when swallowed, to dilate the cardiac orifice 
 of the stomach, but may be a mere by-play of the reflex stimula- 
 tion bringing about the act, since evidence of stimulation of other 
 bulbar centres (vaso-motor and cardio-inhibitory) has also been 
 obtained. The diaphragm is now forced down upon the ab- 
 dominal viscera, first with open and then with closed glottis. The 
 thoracic portion of the oesophagus is thus placed under diminished 
 pressure, and therefore widened, while saliva and air are aspirated 
 into it out of the mouth. The abdominal muscles strongly con- 
 tract. At the same time the stomach itself, and particularly 
 the antrum pylori, contracts, the cardiac orifice relaxes, and the 
 gastric contents are shot up into the lax oesophagus, and through 
 it into the pharynx, and issue by the mouth or nose. The move- 
 ments of the stomach during vomiting induced by apomorphine 
 have been studied in the cat by the Rontgen ray method. There is 
 first observed extreme relaxation of the cardiac end; then a deep 
 constriction appears a little below the cardiac orifice, and runs 
 towards the pylorus, increasing in depth as it goes. When the 
 transverse band is reached, this contracts firmly and remains con- 
 tracted, and the constriction passes on over the antrum pylori. 
 Ten or twelve similar waves follow, at the end of which time the 
 constriction in the region of the transverse band divides the stomach 
 into the firmly-contracted antrum and the relaxed fundus. Now 
 follows a sudden contraction of the diaphragm and abdominal 
 muscles accompanied by the opening of the cardiac orifice. Either 
 the diaphragm and abdominal muscles alone, without the stomach, 
 or the diaphragm and stomach together, without the abdominal 
 muscles, can carry out the act of vomiting. For an animal whose 
 stomach has been replaced by a bladder filled with water can be 
 made to \-omit by the administration of an emetic (Magendie) ; 
 and Hilton saw that a man who lived fourteen years after an injury 
 to the spinal cord at the height of the sixth cervical nerve, which 
 caused complete paralysis below that level, could vomit, though 
 with great difficulty. In a young child in which very shght causes 
 
336 DTCRSTION 
 
 will iiuUuo vomiting, th'' stomach alone ((Mitracts duiing the a<t. 
 But in the adult such a contraction is ineffectual, and the same is 
 the case in animals, for a dog under the influence of a moderate 
 dose of curara, which paralyzes the voluntary muscles but not the 
 stomach, cannot vomit. 
 
 The nerve-centre is in the medulla oblongata. It may be 
 excited by many afferent channels: the sensory nerves of the fauces 
 or pharynx, of the stomach or intestines (as in strangulated hernia), 
 of the liver or kidney (as in cases of gall-stone or renal calculi), of 
 the uterus or ovary, and of the brain (as in cerebral tumour), are 
 all capable, when irritated, of causing vomiting by impulses passing 
 along them to the vomiting centre. 
 
 The vagus nerve in man certainly contains afferent fibres by the 
 stimulation of which this centre can be excited, for it has been 
 noticed that when the vagus was exposed in the neck in the course 
 of an operation, the patient vomited whenever the nerve was 
 touched (Boinet, quoted by Gowers). In meningitis, vomiting is 
 often a prominent symptom, and is sometimes due to irritation of 
 the vagus nerve by the inflammatory process. 
 
 Some drugs act as emetics by irritating surfaces in which efficient 
 afferent impulses may be set up, the ga.stric mucous membrane, 
 for example; sulphate of zinc and sulphate of copper act mainly 
 in this way. Apomorphine, on the other hand, stimulates the 
 centre directly, and this is also the mode in which vomiting is pro- 
 duced in certain diseases of the medulla oblongata. The efferent 
 nerves for the diaphragm are the phrenics, for the abdominal 
 muscles the intercostals. The impulses which cause contraction 
 of the stomach pass along the vagi. Dilatation of the cardiac 
 orifice is brought about by the inhibitory fibres in the vagus already 
 mentioned. 
 
 Section III. — The Chemistry of the I igestive Juices. 
 
 Ferments. — The chemical changes wrought in the food as it 
 passes along the alimentary canal are due to the secretions of 
 various glands which line its cavities or pour their juices into it 
 through special ducts. These secretions owe their power for the 
 most part to substances present in them in very small amount, 
 but which, nevertheless, act with extraordinary energy upon the 
 various constituents of the food, causing profound changes with- 
 out, upon the whole, being themselves used up, or their digestive 
 power affected. The active agents are the enzymes, sometimes, 
 spoken of as unformed or unorganized ferments — unorganized 
 because their action does not depend upon the growth of living 
 cells, which was long supposed to be the case for some other fer- 
 ments, such as yeast. Since it has been shown that specific enzymes 
 can be separated from cells which were formerly believed to act 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 337 
 
 by thoir more growth, the distinction between formed and unformed 
 ferments has lost its significance, and has to a great extent been 
 superseded by the distinction between intra- and extra-cellular 
 enzymes (also called endo- and exo-enzymcs) — i.e., between 
 ferments whicli normally act in the interior of the cells where they 
 are produced and ferments which act outside of the cells that secrete 
 them. From yeast cultures, for instance, by crushing the cells, 
 a ferment (zymase*) can be obtained which in the complete absence 
 of living yeast-cells, and, indeed, of any living micro-organism, forms 
 alcohol and carbon dioxide from sugar, just as living yeast does. 
 There is every reason to believe that it is by the intracellular action 
 of this endoenzj^me that the yeast-cell normally causes alcoholic 
 fermentation. The digestive ferments are typical extracellular 
 enzymes. Their chemical nature has not been exactly made out; 
 som(> of them at least do not appear to be proteins, or to contain 
 a protein group. Many of them apparently exist in tlue colloidal 
 condition, although this has not been shown for all. In certain 
 cases the more or less stable union of a definite inorganic substance 
 with the ferment, or its actual inclusion in the ferment molecule, 
 seems to be a condition of its action. Thus there is reason to believe 
 that in gastric digestion hydrochloric acid is loosely combined with 
 the pepsin. In the plant oxydase, laccase (p. 272), manganese is 
 present. And the fact that manganese salts oxidize certain substances 
 as laccase does suggests that it is the manganese in combination 
 with some protein or other organic compound in the ferment 
 molecule which confers upon laccase its oxidizing power. A similar 
 relation between iron and some animal oxydases is possible, though 
 not definitely proved. But none of the ferments of the digestive 
 juices has as yet been satisfactorily isolated, and at present it is 
 only by their effects that we recognize them. The difficulty of 
 isolating them is increased by the fact that, like other colloids, 
 they readily adhere to surfaces, and are carried down by the most 
 diverse precipitates of substances to which they are chemically 
 indifferent. On the other hand, this very property is taken advan- 
 tage of to procure more concentrated, although still impure, solutions 
 of them than exist in the natural secretions. Thus in the prepara- 
 tion of many ferments the first step is to produce an inert pre- 
 cipitate, such as calcium phosphate, in the juice or extract. Some 
 of the ferments act best in an alkaline, some in an acid medium. 
 They all agree in having an ' optimum ' temperature, which is more 
 favourable to their action than any other; a low temperature sus- 
 pends their activity, and boiling abolishes it for ever. The 
 optimum temperatures of the majority of enzymes lie between 
 
 * Ferments are usually designated by names with the termination ' ase.' 
 and indicating the kind of substances on which they act, or sometimes their 
 source. Thus proteases are ferments acting on proteins, amylases ferments 
 acting on starch, etc. 
 
i^,« DIGESTION 
 
 37" unci 53° C. ; the ' killing ' temperatures between 60" and 73° C. 
 when they are heated in solutions, but considerably higher when 
 they are heated dry. The action of the digestive enzymes is 
 hydrolytic — i.e., it is accompanied with the taking up of the elements 
 of water by the substance acted upon. The accumulation of the 
 products of the action first checks and then arrests it. In many 
 cases this seems to be due to combination of the ferment with one 
 or other of the end products, and the consequent segregation of 
 the ferment from the reaction mixture. The enzyme is not affected 
 indiscriminately by any of the end products. On the contrary, 
 their action is curiously selective. Thus the hydrolysis of lactose 
 by lactase is retarded by galactose, but not by the other end 
 product dextrose. The hydrolysis of cane-sugar b}^ invertase is 
 retarded by levulose, but not by dextrose. The splitting of the 
 dipeptid (p. 2) glycj^-Z-tyrosin by a ferment in the expressed juice 
 of yeast-cells is greatly delayed by one of the products (/-tyrosin), 
 but not by the other (glycocoU). Combination of the ferment with 
 an end product is not, however, the only way in which the reaction 
 may stop before the whole of the substrate, as the substance 
 acted on by the ferment is termed, has been changed. It has been 
 demonstrated in some cases that this is due to the action of the 
 enzymes being reversible. For example, lipase (p. 363) not only 
 decomposes the esters ethyl butyrate or glycerin butyrate, but 
 also builds them up again from the decomposition products — ethyl 
 butyrate from ethyl alcohol and butyric acid, glycerin butyrate from 
 glycerin and butyric acid (Kastle and Loevenhart, Hanriot). Thus: 
 C3H7COOC2H5 + HgO^ »C3H7COOH + C2H5OH, 
 
 Kthyl butyrate. Water. Butyric acid. Ethyl alcohol. 
 
 The action of the enzyme is merely to accelerate the establish- 
 ment of the proportions in which the four bodies entering into the 
 reaction are in equilibrium, and the point of equilibrium is the same 
 whether we start from one or the other side of the equation repre- 
 senting the reaction. Such reversible reactions in the presence of 
 enzymes seem to afford the key to the explanation of many of the 
 syntheses which are known to occur in the body- Sometimes the 
 action is not strictly reversible in the sense that precisely the original 
 material is reconstructed, but from the products of the hydrolysis 
 substances are synthesized or condensed, which are then incapable 
 of being split by the ferment. When a concentrated solution of 
 dextrose is acted on for a long time by yeast maltase, a ferment 
 obtained from yeast which changes maltos<-^ into dextrose, some of 
 the dextrose is reconverted into isomaltose and dextrin-like bodies. 
 Isomaltose is not again hydrolysed by maltase. The ferment 
 emulsin contained in almonds behaves in the converse way. It 
 hydrolyses isomaltose so as to form dextrose, and then condenses 
 dextrose to maltose (Armstrong). 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 3^9 
 
 Many of the ordinary substances of the laboratory will accelerate 
 a reaction which goes on slowly in their absence. These are called 
 catalysers. Some writers also speak of catalysers which retard 
 a reaction progressing quickly in their absence. The process by 
 which the reaction is accelerated (or retarded) is termed catalysis. 
 A typical catalyser can exert its action when it is present in ex- 
 ceedingly small amount in comparison with the substance acted 
 upon. However it may enter into the reaction, it does not take 
 part in the formation of the final products nor contribute to the 
 energy changes, and for this reason is often apparently unaltered 
 at the end of the process. The catalysers have therefore been 
 compared to the lubricants used for machinery as contrasted with 
 the coal or other source of energy. If it be remembered that the 
 expression is a purely metaphorical one, we may say that the 
 catalyst oils the reaction so that it sHps on smoothly and swiftly 
 to an end-point which would, however, have been reached just the 
 same in time. A classical instance of catalysis is the inversion 
 of cane-sugar by weak acids, i.e., the change of the cane-sugar into 
 a mixture of equal quantities of dextrose and levulose — a reaction 
 which may be represented by the equation 
 
 Cane-sugar, Water. Dextrose. Levulose. 
 
 This is a reaction which occurs also when the sugar is simply dis- 
 solved in water, but with exrtreme slowness at the ordinary tempera- 
 ture, although more rapidly at 100° C. The effect of the acid is 
 to catalyse the reaction, to markedly accelerate it. The hydrogen 
 ions of the free acid are responsible for the catalysis, and they are 
 not used up in the process, for the reaction at the end is unaltered. 
 The same action upon cane-sugar is exerted by an enzyme, invertase, 
 found in intestinal juice, although the laws governing the reaction 
 are somewhat different. Reversibility of the reaction can be even 
 more clearly demonstrated for catalysers than for enzymes. For 
 example, the condensation of acetone to diacetone-alcohol, which 
 is accelerated by hydroxyl ions (as by the addition of sodium 
 hydroxide, ammonia, etc.), only proceeds to a certain point, at which 
 equihbrium is established between the proportions of acetone and 
 the condensation product. Henceforth as much of the latter is 
 decomposed as is condensed. Thus: 
 
 2CH3.CO.CH3,^=>CH8.CO.CH2.C(CH8),OH. 
 
 Acetone. Acetone alcohol. 
 
 On the other hand, the final equilibrium point need not be the same 
 for a catalyser and an enzyme. For example, amyl but5rrate is 
 formed and decomposed according to the equation 
 
 CgHnOH -fCgHTCOOH^ZZ::?' CgHjCOO.CgHu +H2O. 
 
 Amyl alcohol. Butyric acid. Amyl butyrate. Water. 
 
340 DIGESTlOtJ 
 
 The roaction can be accelerated either by a catalyst — e.g., H ion<5— 
 as by addition of free hydrochloric or picric acid, or by pancreas 
 lipase. When the concentrations of the reacting substances are 
 appropriately chosen, the same equilibrium point will be reached 
 from cither side of the equation — i.e., the same percentage of the 
 butyric acid will be converted into the ester if we start with the 
 alcohol and acid, as will remain combined as ester if we start with 
 the amyl butyrate. But the proportion will not be the same when 
 the reaction is acclerated by H + as when it is accelerated by the 
 enzyme. And although it is probable that there is no fundamental 
 difference between the action of the digestive enzymes and that of 
 the inorganic catalysers, it is much too early to dogmatize. 
 
 Not even the m rkedly specific action of the digestive ferments 
 can be considered an essential distinction. It is true that invertase 
 will act upon dextrose, and not at all upon maltose or lactase. 
 But there are other sugars, e.g., raffinose, a trisaccharide with the 
 formula CjgHgjOjg, obtained from beet-sugar residues, which it will 
 hydrolyse. Rafhnose is made up of one molecule each of dextrose, 
 levulose, and galactose. On heating \\nth dilute acids, it is decom- 
 posed into these substances. Invertase, however, only splits off 
 the levulose molecule, leaving a disaccharide isomeric, but not 
 identical with lactose. Similarly lactase, which is without action 
 upon cane-sugar or maltose, will hydrolyse the ^-galactosides, and 
 maltase, inert as regards cane-sugar or lactose, will hydrolyse the 
 a-glucosides. On the other hand, emulsin decomposes the ;S-gluco- 
 sides, to which group most of the natural glucosides belong, as well 
 as the /3-galactosides and lactose. From rafhnose emulsin splits 
 off galactose, leaving cane-sugar. Since the a and /3 compounds 
 are isomeric, and differ not in their composition but in their struc- 
 ture, it has been concluded that the structure of the molecule of 
 a substance must be related to the structure of the enzyme which 
 can act on it, in some such way as a lock is related to its proper key. 
 Thus the key lactase fits in the lock lactose, but not in the lock 
 dextrose or the lo^k maltose. Although the same specificity is 
 not to be observed in the action of catalysers as in the action of 
 enzymes, it is not difficult to find many instances in which inorganic 
 substances show a marked limitation of their catalj^-ic effects to 
 particular reactions. Thus hydriodic acid is slowly oxidized in 
 presence of hydrogen peroxide, with formation of iodine and water. 
 This reaction is accelerated by the addition of many substances, 
 e.g., tungstic acid. But tungstic acid has no catalytic effect on the 
 oxidation of hydriodic acid by bromic acid. 
 
 The existence of an optimum temperature for ferment action, 
 above which it rapidly decreases, and eventually comes to a com- 
 plete stop, is also in all probability only a superficial distinction 
 between enzymes and catalysers. For enzymes are easily altered, 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 34^ 
 
 or even destroyed, at temperatures which very likely would favour 
 their action were they as thermostable as the majority of catalysing 
 agents. And inorganic catalysts are known which also sliow the 
 phenomenon of an optimum temperature depending on changes 
 produced in their physical condition when the temperature is 
 raised above this point. Thus a colloidal solution (or ' sol,' as it is 
 called) of platinum, prepared by passing electric sparks between 
 two platinum electrodes immersed in distilled water, and containing 
 the metal in the form of ultra-microscopic particles, acts as a cata- 
 lyser of a number of reactions. As the temperature is increased 
 up to a certain ' optimum,' the velocity of the catalysed reaction 
 is increased. But beyond this, as the boiling-point is approached, 
 the colloidal platinum is precipitated, and ceases to influence the 
 reaction. 
 
 As to the manner in which an enzyme increases the velocity of its 
 appropriate rciiction, it is not easy to make any verj' positive statement. 
 Several possibilities are recognized, of which two ha\e been especially 
 discussed, (i) The existence of the enzyme in colloidal solution may 
 be important. It is characteristic of colloidal solutions, in which the 
 dissolved substance is present in the form of extremely fine particles, 
 that the total surface of the particles is very great in proportion to 
 the mass of the substance in solution. Thus, a sphere of about the 
 same volume as the eyeball, with a diameter of, say, 2 centimetres, 
 would have a surface of I2'5 square centimetres. If this material were 
 subdivided into spheres of about the same volume as a leucocyte, with 
 a diameter of, say, 10 yx, it would form eight thousand million of these 
 spheres, with a total surface of over 2| square metres. If the small 
 spheres were further subdivided into spherical particles, with a diameter 
 
 only the thousandth part of that of a leucocyte, say -^, each would 
 
 form a thousand million of these particles, and the total surface of all 
 the particles would be about 2,500 square metres. 
 
 Now, it is known that the intensity of action of some of the inorganic 
 catalyse rs is proportional to the surface exposed. For example, 
 hydrogen peroxide, if left to itself, is slowly decomposed into water and 
 oxygen. The addition of finely divided platinum, in the form of 
 platinum black, greatly hastens the decomposition, and the oxygen 
 bubbles off. The colloidal platinum sol is still more effective. The 
 nature of the surface effect is not entirely clear. One factor has been 
 thought to be an increase in the concentration of dissolved substances 
 or condensation of gases at the surface, and the better opportunity 
 for mutual action thus afforded to the ferment and the substrate. 
 The great extension of the surface cannot be the only factor in the 
 catalysis; otherwise any fine powder or suspension would have a cata- 
 lytic action. But kaolin, or fine sand, or colloidal solutions of ordinary 
 proteins or gelatin, have little, if any, effect on the decomposition of 
 hydrogen peroxide. 
 
 (2) Enzymes may produce their effects by contributing to the for- 
 mation of bodies intermediate between the substrate and the end- 
 products. If the time required for the formation of a given quantity 
 of the intennediate compound and the time required for the decom- 
 position of this compound into the final products of the ferment action 
 are in sum less than the time required for the direct change of the 
 
w« 
 
 DIGESTION 
 
 substrate into the end-products, the enzyme will clearly act as a cata- 
 lyser of the reaction. It has been shown that in the case of certain 
 inorganic catalysers this does occur. Thus, in the oxidation of hydriodic 
 acid by hydrogen peroxide, which has been already referred to, 
 raolybdic acid has the power of acting as a catalyser. It has been proved 
 that the reaction occurs in two stages, pcmiolybdic acid being first 
 formed by the action of the peroxide on molybdic acid. The permol- 
 ybdic acid then acts on hydriodic acid, producing iodine and water, 
 and being itself reduced again to molybdic acid, which therefore comes 
 out at the end of the reaction unchanged. The velocity of the double 
 reaction is much greater than that of the direct oxidation of hydriodic 
 acid by hydrogen peroxide. 
 
 There is evidence that the ferment actually combines with the sub- 
 strate, the combination then breaking up to form the end-products. 
 For instance, it ha.s been shown that the amount of lactose hydrolysed 
 by lactase in a given time, when tlic ferment is present in very small 
 quantity in comparison with the substrate, is proportional to the con- 
 centration of the ferment, and independent of the concentration of 
 the lactose. Also with a given small concentration of ferment the 
 amount of lactose hydrolysed is at first the same for successive equal 
 intervals of time. These facts can only be explained by the assump- 
 tion that the ferment first combines with a portion of the substrate, the 
 rest of which remains inactive as regards the reaction, and that this 
 combination then takes up water and decomposes into the end- 
 products, in this case dextrose and galactose, setting free the ferment 
 to combine with another portion of the substrate. 
 
 The Quantitative Estimation of Ferment Action. — Since we have as yet 
 no certain method of freeing the digestive ferments from impurities, 
 our only quantitative test is their digestive activity. And since a very 
 small quantit}' of ferment can act upon a practically indefinite amount 
 of material if allowed sufficient time, we can only make comparisons 
 when the time of digestion and all other conditions are the same. If 
 we find that a given quantity of one gastric extract, acting on a given 
 weight of fibrin, dissolves it in half the time required by an equal 
 amount of another gastric extract, or dissolves twice as much of it in a 
 given time, wc conclude that the digestive activity of the pepsin is twice 
 as great in the first extract as in the second. But this does not pennit 
 us to say that the one contains twice as much pepsin as the other. For 
 it has been found that the amount of digestion in a given time is not 
 directly proportional to the quantity of ferment present, but to the 
 square root of the quantity of ferment (Schiitz's law). This law was 
 deduced by Schiitz for pepsin, but is said to hold also for tiypsin, 
 stcapsin, and ptyalin (Pawlow, Vernon). To determine the amount of 
 proteolysis the nitrogen of the protein which has gone into solution may 
 be estimated (p. 521). The following table shows the results of one 
 experiment : 
 
 Pepsin Solution used 
 in C.C. 
 
 Digested Nitrogen in Grammes. 
 
 Found. 
 
 Calculated. 
 
 I 
 
 4 
 
 9 
 
 IG 
 
 00230 
 0*0427 
 00686 
 0*0889 
 
 0*0223 
 0*0440 
 0*0669 
 00892 
 
THE CHEMISJRY Of THE DIGESTIVE JUICES m 
 
 Or a piece of a glass capillary-tulx- filled with heat-coagulated egg-white 
 may be cut ofl and placed in the digestive mixture (Mett's tubes). At 
 the end of the period oi digestion the length of the piece of tube and 
 that of the undigested remnant of the column of coagulated protein 
 are measured with a millimetre scale under a low-power microscope. 
 The difference gives the length of the column digested. If I c.c. of 
 gastric juice caused in a given time digestion of 2 mm. of the egg-white, 
 4 c.c. of the same juice would digest in the same time and under identical 
 conditions about 4 mm., and 9 c.c. about 6 mm. As a test of the 
 activity of a diastatic ferment, we take the amount of sugar formed in 
 a given time in a given quantity of a standard starch solution. To 
 determine the activity of a licjuiil, say, the pancreatic juice, as regards 
 fat-splitting ferment, the acidity (>i the emulsion formed by the juice 
 and fat after standing for a definite time at a gi\-en temperature (with 
 occasional shaking) can be estimated by titration with baryta solution. 
 
 In addition to the ferments of the digestive juices which act extra- 
 cellularly in the lumen of the ahmentary canal, and those which 
 do their work intracellularly in its walls, micro-organisms are 
 present in the gut, and even in normal digestion contribute to the 
 changes brought about in the food ; while under abnormal conditions 
 they may awaken into troublesome, and even dangerous, activity. 
 It is now known that these act by producing intracellular enzymes. 
 
 It may be noted here, although the subject must be again referred 
 to (p. 390), that specific substances capable of inhibiting the action 
 of ferments exist. Some of these antiferments are normally present 
 in the body — an antitrypsin, for instance, in normal blood-serum. 
 Numerous antiferments may be artificially obtained by immunizing 
 animals with the original ferments. Thus an antilipase is found 
 in the serum of rabbits after injection of pancreatic lipase, and an 
 antiemulsin after injection of emulsin. Injection of rennin causes 
 the formation of antirennin, which can be demonstrated in the 
 blood-serum and milk of the immunized animal. Besides the anti» 
 ferments, bodies, sometimes spoken of as ' co-enzymes,' are known 
 which aid the action of certain enzymes, not in the general way 
 in which, for instance, increase of temperature up to the optimum 
 does, but in some quite special manner. Thus, as we shall see, 
 bile salts greatly facilitate the fat-splitting action of lipase. This 
 co-operation is not to be confounded with the activation of the 
 proferment or zymogen which in many cases represents the inactive 
 form of the enzyme, while it is still within the secreting cells. For, 
 once activated, the fully formed enzyme cannot be made to revert 
 to the zymogen stage. For example, the active trj^sin of the 
 pancreatic juice cannot be changed into inactive trypsinogen, 
 whereas substances which simply co-operate or co-act with enzj^mes 
 leave the latter unaltered when they are removed. Thus hpase does 
 not preserve the increased activity conferred upon it by bile salts 
 when the bile salts are again separated from the digestive mixture. 
 
 It is now necessary to consider in detail the nature of the variou? 
 
544 DIGESTION 
 
 juices yielded by the digestive glands, and the mechanism of their 
 secretion. Since it is along the digestive tract that glandular action 
 is seen on the greatest scale, this discussion will practically embrace 
 the nature of secretion in general. And here it may be well to say 
 that, although in describing digestion it is necessary to break it up 
 into sections, a true view is only got when we look upon it as a 
 single, though complex, process, one part of which fits into the other 
 from beginning to end. It is, indeed, the business of the physiologist, 
 wherever it is possible to insert a cannula into a duct and to drain 
 off an unmixed secretion, to investigate the properties of each juice 
 upon its own basis; but it must not be forgotten that in the body 
 digestion is the joint result of the chemical work of five or six 
 secretions, the greater number of which are actually mixed together 
 in the alimentary canal, and of the mechanical work of the gastro- 
 intestinal walls. 
 
 Saliva. — The saliva of the jnouth is a mixture of the secretions 
 of three large glands on each side, and of many small ones. The 
 large glands are the parotid, which opens by Stenson's duct opposite 
 the second upper molar tooth; the submaxillary, which opens by 
 Wharton's duct under the tongue; and the sublingual, opening by 
 a number of duets near and into Wharton's. The small glands are 
 scattered over the sides, floor, and roof of the mouth, and over the 
 tongue. 
 
 Two types of sahvary glands, the serous or albuminous and the 
 mucoiis, are distinguished by structural characters and by the 
 nature of their secretion; and the distinction has been extended 
 to other glands. The parotid of many, if not all, mammals is a 
 purely serous gland; it secretes a watery juice with a general re- 
 semblance in composition to dilute blood-serum. The submaxillary 
 of the dog and cat is a typical mucous gland; its secretion is viscid, 
 and contains mucin. The submaxillary gland of man is a mixed 
 gland; mucous and serous alveoli, and even mucous and serous 
 cells, are intermingled in it. The submaxillary of the rabbit is 
 purely serous. The sublingual is, in general, a mixed gland, but 
 with fir more mucous than serous alveoli. Some of the small 
 glands are serous, others mucous in type. 
 
 The mixed sahva of man is a somewhat viscous, colourless hquid 
 of low specific gravity (1002 to 1008, average about 1005), alkaline 
 to litmus, acid to phenolphthalein, but when tested by the electrical 
 method (p. 24) almost neutral. Besides water and salts, it contains 
 mucin (entirely from the submaxillary, the sublingual and the 
 small mucous glands of the mouth), to which its viscidity is due, 
 traces of serum-albumin and serum-globulin (chiefly from the 
 parotid), and a ferment, which hydrolyscs starch, and therefore 
 belongs to the group of amlyases or diastases. It differs somewhat 
 from the amylase of pancreatic juice. But the small differences 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 
 
 345 
 
 O w 
 
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346 DIGEST] UN 
 
 usually found bctwcL-n fuiine-nts of the sanu- kind derived from 
 different sources may be due to the presence of other substances, 
 and do not necessarily indicate that the ferments are distinct. For 
 the present it may be assumed that the amylase of saliva is the 
 same ferment encountered in the pancreatic juice, and in many, 
 or all, of the tissues. An oxydase or oxidizing ferment is also 
 present in saliva. The salts are calcium carbonate and phosphate 
 (often deposited as ' tartar ' around the; teeth, occasionally as 
 aahvary calculi in the glands and ducts), sodiimi bicarbonate, 
 sodium and potassium chloride, and almost always a trace of sul- 
 pliocyanide of potassium, detected by the red colour which it strikes 
 with ferric chloride.* The total solids amount only to five or six 
 parts in the thousand. A great deal of carbon dioxide can be 
 pumped out from saliva, as much as 60 to 70 c.c. from 100 c.c. 
 of the secretion — i.e., more than can be obtained from venous blood. 
 Only a small proportion of this is in solution, the rest existing as 
 carbonates. Oxygen is also present even in saliva which has not 
 come into contact with the air, and, indeed, in somewhat greater 
 quantity than in serum (about o-6 vohmie per cent, in dog's saliva). 
 Under the microscope epithelial scales, dead and swollen leucocytes 
 (the so-called salivary corpuscles), bacteria, and portions of food, 
 may be found. All these things are as accidental as the last — 
 they are mere flotsam and jetsam, washed by the saliva from the 
 inside of the mouth. But greater significance attaches to certain 
 peculiar bodies, either spherical or of irregular shape, that are seen 
 in the viscid submaxillary saliva of the dog or cat. They appear 
 to be masses of secreted material. The quantity of saliva secreted 
 in the twenty-four hours varies a good deal. On an average it is 
 from I to 2 litres (Practical Exercises, p. 454)- 
 
 Besides its functions of dissolving sai)id substances, and so allow- 
 ing them to excite sensations of taste, of moistening the food for 
 deglutition and the mouth for speech, and of cleansing the teeth 
 after a meal, sahva, in virtue of its ferment, amylase, has the power 
 of digesting starch and converting it into the disaccharide maltose, 
 a reducing sugar (QaHaeOn)- I" ^^^ *he secretion of any of the 
 three great sahvary glands has this power, although that of the 
 parotid is most active. In the dog, on the other hand, parotid saliva 
 has little action on starch, and submaxillary none at all; while in 
 animals hke the rat and the rabbit the parotid secretion is highly 
 active. In the horse, sheep, and ox, the saliva secreted by all the 
 glands seems equally inert. 
 
 When starch is boiled, the granules are ruptured, and the starch 
 
 * In 100 student.s the saliva only once failed to give the reaction, and in 
 this individual a trace of sulphocvanule was present 3 days later. It is absent 
 from the saliva of many animal's. In 25 dogs submaxillary saliva obtained 
 by stimulation of the chorda tympani only once gave the ferric chloride 
 reaction, and then faintly. 
 
THE CIIEMISIRV or Tin- DIGESTIVE JUICES 347 
 
 passes into colloidal solution, yit-ldiiig an opalescent liquid. If a 
 little saliva be added to some boiled starch solution which is free 
 from sugar, and the mixture be set to digest at a suitable temperature 
 (say 40° C.). the solution in a very short time loses its opales«^ence 
 and becomes clear. It still, however, gives the blue reaction with 
 iodine; and Trommer's test (p. 10) shows that no sugar has as yet 
 been formed. Later on the iodine reaction passes gradually through 
 violet into red; and finally iodine causes no colour change at all, 
 while maltose is found in large amount, along with some isomaltose 
 (P- 5i^)< ^ sugar having the same formula as maltose, but differing 
 from it in the melting-point of the crystalline compound formed by 
 it with phenyl-hydrazine (p. 525). Traces of dextrose, a sugar 
 which rotates the plane of polarization less than maltose, but has 
 greater reducing power, may be found among the end-products 
 when the digestion is conducted in vitro. It is probable that this 
 is produced from the maltose by another enzyme (maltase), present 
 in smiU amount in saliva. In any case it is well known that mal- 
 tose may be a stage in the hydrolysis of starch to dextrose, and can 
 be detected among the intermediate products when the starch is 
 acted on by dilute acid under conditions which permit a gradual 
 decomposition of the fragments into which the polysaccharide 
 molecule is successively spHt. But the observation has also been 
 made that the saliva itself (in the cat) may contain a trace of dex- 
 trose (Carlson). 
 
 The red colour indicates the presence of a kind, or a group, of 
 dextrins sometimes called erythrodextrin, because of this colour 
 reaction; the violet colour shows that at first this is still mixed with 
 some unchanged starch. Soon the dextrins which give the red colour 
 disappear, and are succeeded by other dextrins, which give no colour 
 with iodine, and are therefore called achrodextrins. These are 
 partly, but in artificial digestion never completely, converted into 
 maltose, and can always at the end be precipitated in greater or 
 less amount by the addition of alcohol to the liquid. It is probable 
 that a whole series of dextrins is formed during the digestion of 
 starch. But little is known of their chemical nature. Recently, 
 however, some of these intermediate bodies have been obtained 
 in crystaUine form. One of these appears to be a hexa-amylose — 
 i.e., it consists of six CgHjoOs groups, and would therefore be 
 capable of yielding, on the assumption of water, three molecules 
 of maltose or six of dextrose. This is accordingly a relatively 
 small fragment of the big original molecule of starch. When the 
 sugar is removed as it is formed, as is approximately the case when 
 the digestion is performed in a dialyser, the residue of unchanged 
 dextrin is less than when the sugar is allowed to accumulate (Lea). 
 In ordinary artificial digestion, for instance, under the most favour- 
 able circumstances at least 12 to 15 per cent, of the starch is left 
 
348 DIGESTION 
 
 as dextrin; in dialyser digestions the residue of dextrin may be 
 little more than 4 per cent. This goes far to explain the complete 
 digestion of starch which takes place in the alimentary canal, a 
 digestion so exhaustive that, although dextrins may be found in 
 the stomach after a starchy meal, they do not occur in the intestine, 
 or only in minute traces. Here the amyjolytic ferment of the 
 pancreatic juice, vvliich is essentially the same in its action as the 
 amylase of saliva, only more powerful, must effect a very complete 
 conversion of the starch molecules accessible to its attack. It is 
 not inconsistent with this, that unchanged starch granules may 
 sometimes be excreted in the faeces, especially when imbedded in 
 raw vegetable structures. For it may be easily shown that un- 
 boiled starch is digested by amylase with far greater difficulty than 
 boiled starch, an illustration of the important part played by 
 cooking in the preparation of the food for digestion. 
 
 It is a notable fact that amylases, also called diastases, are not 
 confined to the animal body, but are widely distributed in plants. 
 
 The polysaccharide starch forms the great reserve of carbohydrate 
 material in plant nutrition, and is mobilized for the use of the 
 vegetable cells by being hydrolysed to simple sugars under the in- 
 fluence of these enzymes, just as the polysaccharide glycogen, the 
 great carbohydrate reserve of animal nutrition (p. 533), is mobilized 
 in the form of dextrose under the influence of the diastase of the 
 hver. A diastase, which is present in all sprouting seeds, and 
 may be readily extracted by water from malt, forms dextrin and 
 maltose from starch. The optimum temperature of malt diastase, 
 however, is about 55° C, while that of ptyalin is about 40" C. 
 
 While a neutral or weakly alkaline reaction is not unfavourable 
 to salivary digestion, it goes on best in a slightly acid medium. 
 It has been shown that the activity of ptyalin on starch, both 
 having been previously dialysed to get rid as far as possible of salts, 
 is increased by the addition of very small amounts of acids and of 
 the neutral salts of strong monobasic acids. The action is decreased 
 by larger amounts of acid (0-0007 to 0-0012 per cent, of hydrochloric 
 acid) and by neutral salts of weak acids. An acidity equal to that 
 of a o-i per cent, solution of hydrochloric acid stops salivar}' 
 digestion completely, although the ferment is still for a time 
 able to act when the acidity is sufficiently reduced. Strong acids 
 or alkalies permanently destroy it. These facts indicate that in 
 the mouth, where the reaction is weakly alkaline, the conditions 
 are comparatively favourable to the action of the ptyalin. They 
 are still more favourable in the stomach for some time after the 
 beginning of a meal, while the reaction is yet weakly acid. It has 
 been observed that (in cats) sahvary digestion may go on for an 
 hour or more in the cardiac end of the stomach, since free hydro- 
 chloric acid does not appear here before that time. Since the con- 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 340 
 
 tents of the cardiac end arc not freely intermixed with those of the 
 pyloric end, a greater proportion of sugar is found in the former, 
 and the difference is more marked with solid than with liquid fond 
 (Cannon and Day). But during tlie greater part of gastric digestion 
 the degree of acidit}^ is such that the ptyalin must be hinderofl. 
 Although the food stays but a short time in the mouth, there is no 
 doubt that, in man at least, some of the starch is there changed into 
 sugar (p. 350)- But this is not the case in all animals. Something 
 depends on the amylolytic activity of the saliva, and something 
 upon the form in which the starchy food is taken, whether it is 
 cooked or raw, enclosed in vegetable fibres, or exposed to free ad- 
 mixture with the secretions of the mouth. 
 
 The fact already mentioned that hydrolytic changes of the same 
 nature as those produced by enzymes can be brought about in other 
 ways holds good for the salivary amylase. If starch is heated for 
 a time with dilute hydrochloric or sulphuric acid, it is changed 
 first into dextrin, and then into a sugar, which, however, is not 
 the disaccharide maltose, but the monosaccharide dextrose — -that 
 is to say, the hydrolysis with acid proceeds a step farther than the 
 hydrolysis in the presence of ptyaUn. If maltose is treated with 
 acid in the same way, it is also changed into dextrose. When 
 glycogen (p. i) is -boiled with dilute oxalic acid at a pressure of three 
 atmospheres, isomaltose and dextrose are formed (Cremer). Facts 
 already mentioned, and others to be cited later on, show that the 
 action of the other digestive ferments can also be imitated by 
 purely artificial means. Indeed, we may say that the ferments 
 accomplish at a comparatively low temperature what can be done 
 in the laboratory at a higher temperature, and by the aid of what 
 may be called more violent methods. 
 
 Gastric Juice. — The Abbe Spallanzani, although not, perhaps, 
 the first to recognize, was the first to study systematically, the 
 chemical powers of the gastric juice, but it was by the careful 
 and convincing experiments of Beaumont that the foundation of 
 our exact knowledge of its composition and action was laid. 
 
 It is difficult to speak without enthusiasm of the work of Beaumont, 
 if we consider the difficulties under which it was carried on. An army 
 surgeon stationed in a lonely post in the wilderness that was then 
 called the territory of Michigan, a thousand miles from a University, 
 and four thousand from anything like a physiological laboratory, he 
 was accidentally called upon to treat a gun-shot wound of the stomach 
 in a Canadian voyageur, Alexis St. Martin. When the wound healed, 
 a permanent fistulous opening was left, by means of which food could 
 be introduced into the stomach and gastric juice obtained from it. 
 Beaumont at once perceived the possibilities of such a case for physio- 
 logical research, and began a series of experiments on dig.^stion. After 
 a while, St. Martin, with the wandering spirit of the voyageur, returned 
 to Canada without Dr. Beaumont's consent and in his absence. 
 Beaumont traced him. with great difficulty, by the help of the agents 
 of a fur-trading company, induced him to come back, provided for his 
 
350 DIGESTION 
 
 family as well as lor himself, and proceeded with his investigations, 
 A second time St. Martin went back to his native country, and a second 
 time the zealous investigator of the gastric juice, at heavy expense, 
 secured his return. And although his experiments were necessarily less 
 exact than would be permissible in a modem research, the modest book- 
 in which he published his results is still counted among the classics of 
 physiology. The production of artificial fistulae in animals, a method 
 that has since proved so fruitful, was first suggested by his work. 
 
 Gastric juice when obtained pure, as it can be from an acci- 
 dental fistula in man, or, better, by giving a dog with an oesophageal 
 as well as a gastric fistula a ' sham-meal ' (p. 402), is a clear, thin, 
 colourless liquid of low specific gravity (in the dog 1003 to 1006) 
 and distinctly acid reaction. The total sohds average about 
 5 parts per thousand, of which the ash (chiefly sodium and potas- 
 sium chloride, with small quantities of calcium and magnesium 
 phosphate) represents about a fourth, and heat-coagulable sub- 
 stances (proteins, nucleoprotein) about a third. None of these has 
 any special importance in digestion. Of quite a different significance 
 are the three ferments present: pepsin, which changes proteins 
 into peptones; rennin, which curdles milk; and a fat-splitting fer- 
 ment or lipase which, under certain conditions at least, spHts 
 up emulsified neutral fats — e.g., the fat of milk — into the 
 alcohol (glycerin) and the fatty acids linked with it, but has so 
 little action upon non-emulsified fat, that when this is taken into 
 the stomach, it eventually passes into the duodenum practically 
 unchanged. The acidity is due to free hydrochloric acid, the other 
 important constituent of the juice. In the dog the proportion of 
 this acid varies from 0-46 to 0-58 per cent. In such analyses as 
 have been made of approximately pure human gastric juice a smaller 
 percentage of hydrochloric acid has usually been obtained (at most 
 0-35 to 0-4 per cent.). But there is some reason to beheve that if 
 the human juice could be collected in a faultless manner, and 
 especially free from any admixture with saliva or with a pathological 
 secretion of mucus, it would show as high a percentage of acid as 
 the dog's juice. 
 
 In cases of cancer, whether the growth is situated in the stomach 
 or not. the free hydrochloric acid of the gastric juice is usually 
 much reduced, and often absent. Under such conditions some 
 lactic acid may be present in the stoni-uh. being produced from the 
 carbo-hydrates by the action of bacteria {Bacillus acidi ladici), 
 which are normally held in check by the hydrochloric acid, although 
 not rendered incapable of growth when they have passed on into 
 the intestine. Even in the strength of 007 to o-o8 per cent, hydro- 
 chloric acid prevents the formation of lactic acid from dextrose. 
 Indeed, when all the hydrochloric acid of the gastric juice is com- 
 bined with proteins, the protein-acid compound still inhibits the 
 growth of bacteria in the stomach, although not so efficiently as the 
 
7>/K CHEMlsrnV OV THE DlOLSIlVL jUlCkS 35t 
 
 saim- amount of free acid. That in normal gastric juice the acidity 
 is not due to lactic acid can be shown by shaking the juice with 
 ether which takes up lactic acid, and then applying Uffelmann's 
 test to the ethereal extract (Practical Exercises, p. 460)- 
 
 More than this, it is not due to an organic, but to an inorganic 
 acid, for healthy gastric juice causes such an alteration in the 
 colour of aniline dves like congo-red and methyl violet as would 
 be produced by dilute mineral acids, and not by organic acids, even 
 when present in much greater strength.* Finally, when the bases 
 and acid radicles of the juice are quantitatively compared, it is 
 found that there is more chlorine than is required to combine with 
 the bases; the excess must be present as free hydrochloric acid 
 In the pure gastric juice of fishes like the dogfish and skate, however, 
 the acid is said not to be hydrochloric but an organic acid. The 
 quantity of gastric juice secreted depends upon the nature and 
 amount of the food. It has been estimated at as much as 5 litres 
 in twentv-four hours, or several times the quantity of saliva secreted 
 in the same time. With sham feeding a dog may yield 200-300 c.c. 
 in an hour. 
 
 The great action of gastric juice is upon proteins. In this two 
 of its constituents have a share, the pepsin and the free acid. One 
 member of this chemical copartnery cannot act without the other ; 
 peptic digestion requires the presence both of pepsin and of acid ; 
 and. indeed, an active artificial juice can be obtained by digesting 
 the gastric mucous membrane with dilute (0-2 to 0-4 per cent.) 
 hydrochloric acid. A glycerin extract of a stomach which is not 
 too fresh also possesses peptic power, the zymogen or mother 
 substance, pepsinogen, having been activated to pepsin. Free 
 acid very readily effects this activation, but this is far from being 
 the only function of the hydrochloric acid, for active pepsin still 
 requires the addition of a sufficient quantity of acid to render its 
 proteoKi:ic power available. 
 
 Well-washed fibrin obtained from blood is a convenient protein 
 for use in experiments on digestion; although, of course, for many 
 purposes only isolated purified proteins can be employed. Since the 
 blood contains traces of pepsin, the fibrin should be boiled to destroy 
 any which may be present (see also p. 453). 
 
 If we place a little fibrin in a beaker, cover it with gastric juice 
 obtained from a dog or with 0-4 per cent, hydrochloric acid, to which a 
 small quantity of pep.^in or of a gastric extract has been added, and 
 put the beaker in a water-bath at 40° C, the fibrin soon swells up and 
 becomes translucent, then begins to be dissolved, and in a short time 
 has disappeared (see Practical Exercises, p. 458). If we examine the 
 
 * A dilute solution of congo-red is turned violet by organic and blue by 
 inorganic acids; the gastric juice turns it blue. Methyl violet is rendered blue 
 by an inorganic acid like hydrochloric acid, and tjrecn if more of the acid be 
 added. It is not altered by organic acids. Gastric juice turns it blue. 
 
552 DIGEST I OS 
 
 liquifl before cligc>stion lias proceeded very far, we shall find chiefly 
 so-called acid-albumin in solution; later on, chiefly albumoscs; and of 
 these some authors distinguish the primary albumoses (proto-albumose 
 and hctcro-albumose). the first to appear in quantity, followed by 
 secondary or deut^ro-albumoses (p. lo).* Still later, peptones in large 
 and always relatively increasing amounts will be present along with 
 the alburnoscs. From this we conclude that acid-albumin is a stage 
 in the conversion of fibrin into albumose, and albumose a half-way 
 house between acid-albumin and peptone. It must not be supposed, 
 however, that all the protein is first changed into acid-albumin before 
 any of the acid-albumin is changed into albumose, or that all the 
 protein has already reached the albumose stage before peptone begins 
 to appear. On the contrary, a certain amount of albumoses and of 
 peptones are present ver>- early in peptic digestion, while the greater 
 part of the original protein is still unaltered. Among the somewhat 
 vaguely characterized group of bodies comprised under the term 
 peptones, there are no doubt decomposition products of the proteins 
 in which the hydrolysis has b-^en carried to different degrees. Similar, 
 but not identical, intermediate substances occur in the digestion of the 
 other proteins, including that of bodies like gelatin, which are not 
 ordinary proteins, but which pepsin can digest. The generic name of 
 proteose properly includes all bodies of the albumose type, the term 
 ' albumose ' itself being sometimes reserved for such intermediate 
 products of the digestion of albumin; while those of fibrin are called 
 fibrinoses; of globulin, globuloses; of casein, caseoses; and so on. The 
 peptones produced from different proteins are also not absolutely 
 identical. If the digestion is prolonged, the peptones first formed are 
 in turn further hydrolysed, so that eventually a considerable proportion 
 of the original protein is converted into bodies which no longer give the 
 biuret reaction. 
 
 In the stomach, during the four or five hours for which gastric 
 digestion ordinarily lasts, none of the protein passes beyond the 
 stage of proteose and peptone, inchiding those relafvely simple 
 ' abiuret ' compounds which still consist of several ' building-stones, ' 
 chiefly, it would seem, the amino-acids, phenylalanin, and prolin, 
 linked together. When precautions are taken to prevent the 
 passage of any portion of the contents of the duodenum into the 
 stomach, no amino-acids can be detected in the gastnc contents 
 during the digestion of protein. In this connection it is interesting 
 to note that none of the polypeptides hitherto prepared (p. 2) are 
 decomposed by pepsin. It is not known at what points in the link- 
 age of the groups that compose the complex protein molecule the 
 pepsin ruptures the chain, but the points of attack arc different from 
 those of trypsin. The pancreatic juice, as we shall see later on, not 
 
 • In the light of modern investigation the results of fractional precipitation 
 by salts of the products of proteolysis have lost a good deal of their interest, 
 and it is seen that undue importance has often been attached to them. The 
 student should be warned that such terms as ' albumose ' and ' peptone ' do 
 not indicate precise chemical differences between the products separated in 
 this way, nor even invariably such differences in molecular weight as the 
 current schemata of the digestive processes are apt to imply. Some so-called 
 ' peptones ' may indeed have a higher molecular wei.qht and be more nearly 
 related to the original protein than some so-called ' albumoses.' 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 353 
 
 only effects a more complete conversion into peptones, but can split 
 up the whole or a very large proportion of the peptones themselves 
 into amino-acids and the other ' building-stones ' of the original 
 protein. Since the subject of protein digestion must come up again, 
 it will be well to postpone any closer discussion of the process till we 
 can view it as a whole. In the meantime it is only necessary to 
 repeat that pepsin alone cannot digest proteins at all. Its action 
 requires the presence of an acid; in a neutral or alkaline medium 
 peptic digestion stops. The precise mode of action of the acid is by 
 no means clear. 
 
 Dilute acid alone does not dissolve coagulated proteins like boiled 
 fibrin, or does so only with extreme slowness. But it causes them to 
 swell up by imbibition of water, and probably in this way facilitates 
 the entrance of the ferment. Uncoagulated proteins are readily 
 changed by acid into acid-albumin; and by the prolonged action of 
 acids, especially at a high temperature, further changes of much the 
 same nature as those produced in peptic digestion may be caused in 
 all proteins. But under the ordinary conditions of natural gastric 
 digestion, it may be said that the acid alone does little until it is 
 aided by the ferment, just as the ferment alone does nothing wdthout 
 the aid of the acid. The acid enters into a temporary combination 
 with the protein, the more highly hydrolysed proteins, such as 
 peptones, combining with a greater proportion of acid than such 
 proteins as fibrin or albumin. These compounds so easily undergo 
 hydrolytic dissociation that, in spite of its union with the proteins, 
 the hydrochloric acid is able to act along with the pepsin, so that 
 peptic digestion goes on even when enough protein is present to 
 combine with all the acid. There is some evidence that in the 
 gastric juice the pepsin exists in the form of an unstable compound 
 with hydrochloric acid, and it is probably this pepsin-hydrochloric 
 acid compound which is the actual catalytic agent in peptic digestion. 
 Although hydrochloric acid acts most powerfully, other acids, such 
 as nitric, phosphoric, sulphuric, or lactic (arranged in the order of 
 their efficacy), can replace it. 
 
 The Milk-Curdling Action of Gastric Juice. — The milk-curdling 
 ferment, rennin, or chymosin, is contained in large amount in an 
 extract of the fourth stomach of the calf, which, as rennet, has long 
 been used in the manufacture of cheese. It exists in the healthy 
 gastric juice of man, but disappears in cancer of the stomach and in 
 chronic gastric catarrh. It has been stated by a number of observers 
 that the properties of rennin are never found in gastric juice or any 
 preparation obtained from it or from the gastric mucous membrane 
 unless pepsin is present. This has suggested that there is no separate 
 milk-curdling ferment, but that the clotting or precipitation of 
 caseinogen is merely an associated action of the pepsin. Ferments 
 of the most varied origin will curdle milk. Pawlow has maintained 
 
 23 
 
351 bicj'snoM 
 
 tliattlu' niilk-curdling property not only of the gastri< juicv, but also 
 of tlic pancreatic juice and of the secretion of Brunner's glands, is 
 associated with the proteolytic ferment. 
 
 He asserts that when the comparison is instituted under proper 
 conditions there is an exact parallelism between the proteolytic and 
 the milk-curdling power of these secretions, no matter what the 
 circumstances may be in which they arc collected, or the influences 
 to which they are exposed after collection. He has found it im- 
 possible to separate from any one of them a fraction which has 
 milk-curdling power without proteol\i:ic power. On the other hand, 
 the majority of investigators maintain the separate identity of 
 rennin. Hammarsten especially states that he can destroy the 
 peptic activity without destroying the milk-curdling power of gastric 
 extracts, and vice versa. According to Burge, when a solution dis- 
 pla\ang both peptic and milk-curdling power is electrolyzed, the 
 pepsin action is abolished at a certain stage, while the rennet action 
 is miaffected. It would seem, then, that the balance of evidence 
 is in favour of the separate identity of the rennet enz^-me. 
 
 However this may be, the cm-dling of milk by the gastric ferment 
 includes two processes: (i) An action on caseinogen in the course of 
 which it acquires new properties, becoming changed into casein. 
 This substance is not capable of being converted into casein, 
 and remains in solution in the whey. {2) The altered casein- 
 ogen or casein combines with soluble calcium salts and in the 
 presence of these is precipitated as the curd. The change which 
 occurs in the caseinogen has been the subject of much discussion, 
 which has not yet led to a definite conclusion. According to some 
 observers, the change consists in a decomposition of caseinogen, in 
 the course of which a new substance, whey-protein, not previously 
 present in the milk, is split off. This substance is not capable of 
 being precipitated by hme salts, and remains in solution in the whey. 
 According to others, the molecule of caseinogen is simply changed 
 into two molecules of casein (van Slyke). Dilute acid will of itself 
 precipitate caseinogen, and the presence of acid, and particularly 
 hydrochloric acid, in the gastric juice helps its milk-curdling action. 
 But that a ferment is really concerned is indicated by the fact that 
 the juice, after being made neutral or alkaline, still curdles milk, and 
 that this power is destroyed by boiling. The optimum temperature 
 is the same as that of the other ferments of the digestive tract, about 
 40° C. (p. 337). The persistence of the milk-curdling acti\nty in the 
 presence of OH ions, while for peptic activity free H ions are neces- 
 sary, is a further and, indeed, a strong argument in favour of the 
 separate existence of the rennet ferment. 
 
 As to the exact function of the milk-curdling ferment of the 
 gastric juice in digestion, we have no precise knowledge. It seems 
 superfluous if we suppose that the free acid is able of itself to do all 
 
THE CHEMISTRY OE THE DIGESTIVE JUICES 355 
 
 that tlio fcnnent does along with it. But there is evidence tliat the 
 curd produced by tlie ferment is more profoundly changed than the 
 precipitate caused by dilute acids; for the latter may be redissolved, 
 and then again curdled by rennin in the presence of calcium salts, 
 while this cannot be done with the former. We may suppose, then, 
 that the ferment is capable of effecting changes more favourable to 
 the subsequent action of the pepsin upon the casein than those 
 which the acid alone would effect. Or it may be that the ferment 
 acts in the early stages of digestion before much acid has been 
 secreted. The curdling of milk probably plays a part in ensuring 
 the retention of this food, the proper digestion of which is all-impor- 
 tant for the suckling, for a sufficient length of time in the stomach. 
 Otherwise, hke water and watery hquids in general, it would be 
 rapidly passed into the duodenum. Even if this were not the case, 
 there is another reason for early curdling. Milk is a very dilute 
 food, and the immense proportion of water in it might weaken the 
 gastric juice too much for rapid digestion of the proteins. The 
 separation of the whey and its prompt escape through the pylorus 
 would obviate this. But caution should be exercised in giving a 
 physiological value to all the details of the milk-curdUng action of 
 the gastric juice. Milk-curdling ferments, or, at any rate, ferments 
 with a milk-curdling influence, have an extremely wide distribution, 
 both in secretions which in normal circumstances can never come 
 into contact with milk, and in the tissues of animals and plants. 
 Many bacteria produce them. And it appears that in the suckhng, 
 where it might be expected, if anywhere, to have a definite and 
 important office, the rennet action of the gastric juice is distinctly 
 less than in the adult. It is worthy of note that the curd formed by 
 rennet from human milk is more finely divided than that formed 
 from cow's milk, and therefore is more easily digested. The addition 
 of lime-water or barley-water to cow's milk keeps the curd from 
 adhering in large masses, and thus aids its digestion — a fact which 
 is sometimes usefully applied in the artificial feeding of infants. 
 
 Gastric Lipase. — On fats gastric juice has usually been supposed 
 to have no action, although everybody admits that it will dissolve 
 the protein constituents of fat-cells and the protein substances which 
 keep the fat-globules of milk apart from each other. It has, how- 
 ever, been recently shown that both in the stomach and in vitro 
 (with glycerin extracts of the gastric mucous membrane) a consider- 
 able amount of well -emulsified fat may be split up, and that this is 
 due to a ferment which is different in several respects from the 
 lipase of pancreatic juice. Gastric juice splits up tat, both in 
 neutral and in weakly acid solutions. The shghtcst excess of alkali 
 checks the action. The glycerin extract is much more resistant to 
 alkah, while very sensitive to hydrochloric acid. This indicates 
 that the fat-splitting ferment exists in the mucous membrane in a 
 
35<) 
 
 DIGESTION 
 
 different form from that in which it exists in the juice — namely, as 
 a zymogen or mother-substance. But while the zymogen of the 
 pancreatic lipase is activated by bile, this is not the case with the 
 mother-substance of the gastric lipase. It appears that in the 
 suckling the lipase of the gastric juice plays a more important part 
 than in later life. This is obviously in accordance with the fact that 
 the specific food of the suckling — milk — contains as an essential con- 
 stituent a large proportion of emulsified fat. The conditions for 
 the emulsification of fat do not exist in the gastric juice, and this is 
 the reason why the gastric lipase has so slight an effect upon un- 
 emulsified fat, which presents a surface of contact proportionally so 
 small. In any case the amount of fat hydrolysed in the stomach 
 under ordinary con litions is small in comparison with the amount 
 split in the intestine, although it has been shown that with a diet 
 rich in fat some of the intestinal contents, including pancreatic 
 lipase, may pass back into the stomach. 
 
 As regards the carbo-hydrates, the swallowed saliva will continue 
 to act on starch in the stomach, so long as the acidity is not too great ; 
 while the hydrochloric acid of the gastric juice is able to invert cane- 
 sugar, changing it into a mixture of dextrose and levulose,* and 
 also, doubtless, to hydrolyse to dextrose a portion of the maltose 
 formed by the saliva. Altogether, there is no doubt that the pro- 
 portion of the carbo-hydrates of the food digested in the stomach is 
 far from insignificant. 
 
 The Antiseptic Function of the Gastric Juice. — The stomach, with 
 its acid contents, forms during the greater part of gastric digestion 
 a valve or trap to cut off the upper end of the intestine from the 
 bacteria-infested regions of the mouth and phar^^mx, and to destroy 
 or inhibit the micro-organisms swallowed with the food and saliva. 
 The occasional presence in vomited matter of sarcinae or regularly 
 arranged groups of micrococci, generally four to a group, shows that 
 under abnormal conditions the gastric contents are not perfectly 
 aseptic; and even from a normal stomach active micro-organisms 
 of various kinds can be obtained. But upon the whole there is no 
 doubt that the acidity of the gastric juice is an important check on 
 bacterial activity during the first part of digestion, and in the upper 
 portion of the alimentary canal. Koch has shown that the acidity 
 of the gastric juice of a guinea-pig is sufficient to kill the comma 
 bacillus of cholera. Normal guinea-pigs fed with cholera bacilli 
 
 * These are both reducing sugars, but, as their names indicate, they rotate 
 the plane of polarization in opposite directions. The specific rotatory power 
 of le\ailose is greater than that of dextrose, so that when cane-sugar is com- 
 pletely inverted, although, equal quantities of dextrose and levulose are pro- 
 duced, the plane of polarization is rotated to the left. Cane-sugar itself rotates 
 it to the right. The term ' inversion ' has been extended to include the 
 similar hydrolysis of other sugars of the disacchande group — e.g.. maltose to 
 dextrose, and lactose to a mixture of dextrose and galactose, even although 
 the products axe not levo-rotatory. 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 357 
 
 were unaftected. But if the gastric juice was neutralized by an 
 alkali before the administration of the bacilli the guinea-pigs died, 
 ("harrin found, too, that digestion with pepsin and hydrochloric acid 
 causes an appreciable destruction or attenuation of diphtheria toxin. 
 Bacteria, like the lactic acid bacillus, which form acid products, may 
 be less profoundly affected by the acid gastric juice than the putre- 
 factive bacteria, which, on the whole, form alkalies, and are there- 
 fore accustomed to an alkaline medium. Yet we have seen that the 
 growth of even the lactic acid bacillus is very strictly controlled when 
 the gastric juice contains the normal amount of hydrochloric acid. 
 It has been supposed by some that this bactericidal action is the 
 chief function of the stomach, and the question has been asked why 
 we should attribute any digestive importance to the secretion of that 
 viscus, since the pancreatic juice can do all that the gastric juice 
 does, and some things which it cannot do. Further, it has been 
 shown that a dog may live five years after complete excision of the 
 stomach, comport himself in all respects like a normal dog, and when 
 killed for necropsy show every organ in perfect health (Czerny). In 
 man, too, the stomach has been excised with a successful result. 
 But if this is to be admitted as evidence against the digestive function 
 of the stomach, it is just as good evidence against the bactericidal 
 function, particularly as it has in addition been shown that even 
 putrid flesh has no harmful effect on a dog after excision of the 
 stomach, any more than on a normal dog. And, indeed, the reason- 
 ing is fallacious which assumes that what may happen under ab- 
 normal conditions must happen when the conditions are normal. 
 For nothing is impressed more often on the physiological observer 
 than the extraordinary power of adaptation, of making the best of 
 everything, which the animal organism possesses. Doubtless a dog 
 without a stomach will use to the best advantage the digestive fluids 
 that remain to him; and the pancreatic juice, with the aid of the bile 
 and the succus entericus, may be adequate to the complete task of 
 digestion. So, too, a man from whom the surgeon has removed a 
 kidney, or a testicle, or a lobe of the thyroid gland, may be in no 
 respect worse off than the man who possesses a pair of these organs. 
 But what do we deduce from this ? Not, surely, that the excised 
 thyroid, or testicle, or kidney was useless, or the gastric juice in- 
 active, but that the organism has been able to compensate itself for 
 their loss. Further, it would seem that the fate of the protein or of 
 part of the protein digested and absorbed by the stomach is different 
 from that digested and absorbed by the intestine. For after the 
 operation of gastro-enterostomy (the establishment of an artificial 
 opening between the stomach and the small intestine through which 
 the food passes rapidly without having to submit to the challenge 
 of the pyloric sphincter), the ingested nitrogen is more quickly 
 ehminated than when the protein is first subjected to full gastric 
 
358 DIGESTION 
 
 digestion. So that when the quantity of protein in the food is 
 increased abov^e that necessary for nitrogen equilibrium (p. 602), none 
 of the excess is assimilated and stored up, as is the case in a normal 
 animal (Levin, t;tc.). 
 
 Pancreatic Juice- — Pancreatic juice, bile, and intestinal juice are 
 all mingled together in the small intestine, and act upon the food, 
 not in succession, but simultaneously. But by artificial ftstulae in 
 animals they can be obtained separately; and occasionally some of 
 tluMii ran be j:)r()rured through accidental ftstulit in man. It is said 
 that under certain conditions, especially when fat or oil is introduced 
 into the stomach, the pylorus may remain open long enough to 
 permit the passage of pancreatic juice or bile from the duodenum into 
 the stomach, and this has been recommended as a practical method 
 of obtaining these secretions in man. 
 
 Human pancreatic juice, as obtained from a fistula, is a clear, only 
 slightly viscid liquid of distinctly alkaline reaction to litmus. Its 
 specific gravity is about 1007 to loio. The total solids constitute 
 about 1-5 or 2 per cent., of which a httle less than i per cent, is made 
 up of inorganic salts, chiefly sodium carbonate, with small quantities 
 of chlorides. The balance of the solids consists mainly of proteins. 
 The alkaline reaction is due to the sodium carbonate, and it is 
 worthy of remark, as showing the important part taken by this 
 secretion in the neutralization of the chyme, that when titrated 
 against standard acid the alkalinity of the pancreatic juice is not 
 much le.ss than the acidity of the gastric juice when titrated against 
 standard alkali. The quantity of pancreatic juice secreted during 
 the twenty- four hours in an average man has been estimated at 
 500 to 800 c.c. from observations on cases of fistula. Probably 
 under perfectly normal conditions it is greater. A so-called arti- 
 ficial pancreatic juice can be made by extracting the pancreas with 
 water or glycerin. Since better methods of obtaining the natural 
 juice have been developed, these extracts have lost some of their 
 importance. 
 
 Fresh pancreatic juice contains four ferments: (i) The zymogen or 
 mother-substance, trypsinogen, of a proteoljlic or protein-digesting 
 ferment, trypsin ; (2) an amylol}i:ic ferment, or amylase ; (3) a fat- 
 splitting or lipolytic ferment, steapsin ; (4) a milk-curdling ferment. 
 The question whether the last is a different body from the 
 proteol>i:ic ferment has been discussed just as in the case of the 
 gastric rennin (see p. 353). In any case, it cannot be considered as 
 taking any practical share in digestion, since it can hardly ever 
 happen that milk passes through the stomach without being curdled. 
 
 Trypsinogen has no action upon proteins, but in normal digestion 
 it is changed into active trypsin by the enterokinase of the intestinal 
 juice (p. 372). Pancreatic juice collected without contact with 
 intestinal contents or unth the mucous membrane of the intestine 
 
THE CHEMISTRY OE THE DIGESTIVE JUICES 35*} 
 
 does not digest proteins. The same, is true of extracts of perfectly 
 fresh pancreas, but if the pancreas is allowed to stand for a time, the 
 extracts contain active trypsin, perhaps because some decomposition 
 product has activated the trypsinogen. Some writers, however, 
 state that when contamination of the gland with intestinal contents 
 or contact with the mucosa has been avoided in its removal from 
 the body, such extracts will remain inactive for months, although 
 the trypsinogen can at once be activated to trypsin by the addition 
 of t-ntcrokinase. 
 
 Trypsin, to a certain extent, corresponds with pepsin in its action 
 on proteins. But it acts energetically in an alkaline as well as in a 
 not too acid medium (a very slight amount of digestion may go on in 
 distilled water) ; and its action, unhke that of pepsin — at least in 
 digestions of moderate duration — -does not stop at the peptone stage, 
 but goes on rapidly to the production of the amino-acids, the basic 
 substances arginin, lysin, and histidin, known as the hexone bases, 
 and most of the other decomposition products obtained by boiling 
 proteins with dilute acids. The most important of these products, 
 so far as they have been isolated and identified, are enumerated in 
 the table on p. 360 (see also pp. 1-3). 
 
 As to tjie chemical nomenclature of these bodies, the student should 
 refer to his textbook of organic chemistry. It need only be remarked 
 here, by way of illustration, that when, e.g., leucin is designated as 
 a-amino-isobutylacetic acid, this indicates that it can be derived from 
 the fatty acid isobutylacetic acid by the substitution of an amino group, 
 XH.,, for a hydrogen atom in the a-carbon group (see p. 556) of the 
 fatty acid — i.e., the group next the carboxyl (COOH) group. Tims, 
 
 ^JJ^NcH.CHa.CHa.COOH , ^^sXcH.CHg.CH.COOH. 
 3/ „ 3/ I 
 
 Isobutylacetic acid. Leucin. -^Hg 
 
 When norleucin, an amino-acid found especially in the proteins of 
 nervous tissue, is termed a-amino-caproic acid, it is indicated that NH2 
 replaces one H in the aCH^ group of caproic acid (CH3.CH2.CH2.CH2. 
 CHoCOOH). The long chemical name of isoleucin (a compound also 
 derived from the proteins of nervous tissue and from some plant protcinsj 
 indicates that in propionic acid, 
 
 CH3.CHa.COOH, 
 /3 a 
 NH2 is introduced into the a group, yielding 
 
 CH3.CH.COOH, 
 
 NH2 
 
 or amino-propionic acid (alanin); while in the ,3 group one H is repl.icod 
 by a methyl (CH3) group, and another H by an ::ihyl {CM^) giouu, 
 yielding finally isonuclein : 
 
 ^^^^CH.CH.COOH. 
 
 NH, 
 
i6« 
 
 DIGESTION 
 
 :t: u 
 
 CHIEF DECOMPOSITION PRODUCTS OF PROTEINS. 
 
 MONOAMINO-ACIDS AND THEIR COMPOUNDS. 
 
 /Glycin or glycocoll (aminoacetic acid), CHjlNHjjCOOH. 
 
 Alanin (aminopropionic acid), CH3Cli(NH2)COOH. 
 
 Serin or oxyalanin (oxyaminopropionic acid), 
 
 CH20H.CH(NH,).C00H. 
 
 CH \ 
 Valin or aminovalerianic acid, q|^3^CHCH(NH2)COOH. 
 
 ^ Leucin (a-aminoisobutylacetic acid) ^[j3\cHCH2CH(NH2)COOH. 
 
 ~ s Norleucin (a-amino-caproic acid), 
 
 CH3.CH2.CH2.CH2.CH(N'H2).COOH. 
 
 Isoleiicin (a-amino-/'<-metliyl-/3-ethyl-proi)ionic acid), 
 
 (?^3 ^CH.CH{NH2).COOH. 
 
 Cystein (a - amino-/3 - thiopropionic acid), CH2 (SH).CH(NH2)COOH, 
 which is unstable, two molecules of it easily yielding cystin 
 di-(a-amino-/3-thiopropionic acid) , 
 
 COOH.CH(NH2).CHa.S.S.CH2.CH(NHa).COOH. 
 
 Aspartic or aminosuccinic acid, CH(NH2).COOH. 
 
 I 
 CH2COOH. 
 
 Glutamic or glutaminic acid, ^i^z'^ ^h'^cOOH^^^ 
 
 ^ ^ ^ 
 
 c -S > CTvrosin (para-oxvphenvlaminopropionic acid), 
 
 IpI^-" ■ ' CfiH40H.CH2.CH(NH2).COOH. 
 
 S 3.> (phenylalanin (phenylanainopropionic acid), C6H5CH2CH(NH2)COOH. 
 
 
 (Prolin (pyrrolidin carboxylic acid). 
 Oxyprolin (oxypyrrolidin carboxylic acid). 
 Tryptophane (a-amino-/3-indol-propionic acid), 
 P 5 rt 1 /NH— CH 
 
 ?^c 1- 
 
 HC/" 11 
 
 ^N — C— CH2.CH(NH,).COOH. 
 Histidin ()8-imidazol-a-aminopropionic acid), CgH9N302. 
 
 DIAMINO-ACIDS AND THEIR COMPOUNDS. 
 
 «. /'Lysin (a-amino-f-amino-caproic acid, CH2NH2(CH2)3CH(NH2)COOH. 
 
 ^^ 
 
 
 .\rginin (guanidinaminovalerianic acid) 
 
 HN = c/^'"2 
 
 N H CH2 (CH2)2CH {NH,)COOH . 
 
 Ammonia (representing the so-called ' amide-nitrogen,' and liberated 
 from the products of acid hydrolysis of proteins by heating the 
 mixture after addition of alkali). It has not been shown that 
 ammonia is itself one of the ' Bansteine ' of the proteins. 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 361 
 
 In the artificial compounds of two or more amiiio-acids which have 
 been syiithcsiz.'d by Fischer and named by him polypeptides (p. 2), 
 the carboxyl group of one aniino-acid is linked with the amino group 
 of another. For example, a molecule of alanin and a molecule of glycin 
 form, with loss of a molecule of water, a molecule of alanyl-glycin, 
 according to the equation 
 
 NHa.CHa.COiOH+HiNH.CH.CHa— H20=NH2.CH2.CO.NH.CH.CH3. 
 COOH COOH 
 
 Glycin. Alanin. Glycyl-alanin. 
 
 Two or more molecules of the same amino-acid can be linked in the 
 same way; e.g., two molecules of glycin yield a molecule of glycyl-glycin, 
 and so on. It has been pro\'ed that polypeptides identical with some of 
 these synthetic bodies are present in the peptone mixtures derived from 
 the native proteins, so that it must be assumed that one of the ways 
 at least in which amino-acids are linked in the protein molecule is that 
 described. 
 
 It has been suggested that the early appearance of some of these 
 amino-acids in pancreatic digestion is not really due to trypsin, but 
 to other ferments, peptases, which act upon the peptones formed by 
 the trypsin. There is, however, no clear evidence of the existence 
 of a separate peptone-splitting enzyme in pancreatic juice, like the 
 erepsin of intestinal juice, and it is therefore most natural to suppose 
 that under the influence of trypsin the protein molecule breaks at 
 different points from those at which it ruptures under the influence 
 of pepsin. 
 
 After the most prolonged artificial digestion with trypsin, a 
 residue of the protein remains unconverted into these relatively 
 simple substances. But even this small portion of the original 
 protein has undergone a great change, for it no longer gives the 
 biuret reaction. It can be split into amino-acids, etc., by heating 
 with acid, and also by the action of the erepsin of the intestinal juice, 
 and then yields mainly prolin and phenylalanin, substances which 
 are generally not to be detected among the decomposition products 
 of protein after digestion with pancreatic juice. This illustrates the 
 important fact that some of the ' building stones ' of the protein 
 molecule can be separated from it with far greater ease than others. 
 T^TOsin, tryptophane, and cystin appear very early in the digestive 
 fluid, and tyrosin, as shown in the following example from Abder- 
 halden, may be completely liberated at a time when glutaminic acid 
 is scarcely more than beginning to appear. 
 
 The plant protein edestin, obtained from cottonseed, was digested 
 with pancreatic juice or an extract containing trypsin. The quan- 
 tities of tyrosin and glutaminic acid liberated at different periods 
 of the experiment are expressed as percentages of the total amounts 
 of these substances contained in the edestin. 
 
362 
 
 DIGESTION 
 
 
 
 
 Duration of Digestion : 
 
 I Day. 
 
 1 
 
 2 Days. 
 
 1 
 
 3 Days. 
 
 7 Days. 
 
 t6 Days. 
 
 Tyros in 
 Glutaminic acid 
 
 784 
 
 43 
 
 976 
 
 ' 74 
 
 976 
 109 
 
 100 
 31- 1 
 
 100 
 6o"2 
 
 When trypsin acts upon protein already digested by pepsin, this 
 partially hydrolyscd residue is smaller than when the trypsin acts 
 alone, no matter for how long a time. Also the decomposition of 
 a given quantity of protein by trypsin is accomplished in a notably 
 shorter time if it has been previously subjected to the action of 
 pepsin. This illustrates the co-operative relation of these two 
 ferments — a relation still more clearly implied in the fact that, 
 although trypsin readily forms albumoses and peptones from native 
 protein when such is offered to it, yet in natural digestion the great 
 albumose- and peptone-forming ferment is pepsin. In the lumen of 
 the intestine the trypsin is confronted mainly with protein already 
 hydrolysed to the albumose and peptone stage in the stomach. In 
 other words, instead of the very large molecules of the original 
 protein food with a weight of perhaps 5,000 to 7,000, the trypsin 
 begins its action on a much larger number of much smaller molecules 
 of only one-twentieth the initial weight or less. The statement is 
 sometimes made that trypsin is a stronger proteoh^ic ferment than 
 pepsin. This may be true in the sense that trypsin carries the de- 
 composition down to bodies of smaller molecular weight than pepsin. 
 But within the range of its hydrolytic action pepsin decomposes 
 certain proteins and alhed bodies more readily than trypsin — e.g., 
 the serum proteins, and especially elastin and the constituents of 
 connective tissue. 
 
 In all that we have hitherto said regarding tryptic digestion we 
 have supposed that putrefaction has been entirely prevented— d."., 
 by the addition of toluol. If no antiseptic is added to a tryptic 
 digest, it rapidly becomes filled with micro-organisms, and emits a 
 very disagreeable facal odour; and now various bodies which are not 
 found in the absence of putrefaction make their appearance, such as 
 indol, skatol, and other substances, to which the faecal odour is due. 
 They are not true products of tryptic digestion, but are formed by 
 the putrefactive micro-organisms, which can themselves split off 
 from proteins numerous decomposition products, including tyrosin, 
 and change tyrosin into indol. 
 
 Amylase or pancreatic amylase, the diastatic or sugar-forming 
 ferment of pancreatic juice, changes starch into dextrin and maltose, 
 just as the ptvalin of saliva does. The two ferments are possibly 
 identical, but under the conditions of action of the pancreatic juice 
 its diastatic power is greater than that of saliva, and it readily acts 
 
THE CHEMISTRY OE THE DIGESTIVE JUICES 363 
 
 on raw starch as well as boiled. Pancreatic amylase is mainly, 
 perhaps entirely, present in the juice in the form of active ferment. 
 If a zymogen stage exists, the mother-substance is less stable or less 
 easily extracted from the gland than is trypsinogen. In this respect 
 amylase also resemljles ptyalin. A small amount of maltatx; is 
 contained in pancreatic juice, and further hydrolyses to dextrose a 
 portion of the maltose formed by the amylase. 
 
 Steapsiii or pancreatic lipase splits up neutral fats into glycerin and 
 the corresponding fatty acids. The latter unite with the alkalies of 
 the pancreatic juice and the bile to form soaps. In this important 
 process bile acts as the helpmate of pancreatic juice; together they 
 effect much more than either or both can accomplish by separate 
 action. Many tissues contain fat-splitting ferments or lipases, some 
 of which are perhaps identical with the pancreatic lipase. The lipase 
 exists as active ferment in the pancreatic juice, but there is reason 
 to believe that a portion of it may be present as a zymogen in the 
 gland, and probably in the secretion as well. It is changed into 
 active ferment by the bile salts. Active lipase can also be extracted 
 from the pancreas by glycerin or water. It is to be noted that it is 
 only the proteolytic enzyme which is totally inactive till it reaches 
 the intestine. The significance of this will be discussed later on. 
 
 Bile. — Bile is a liquid the colour of which varies in different groups 
 of animals, and even in the same species is not constant, depending 
 on the length of time the fluid has remained in the gall-bladder and 
 other circumstances. When it is recognized that the colour is due 
 to a series of pigments, which are by no means stable, and of which 
 one can be caused to pass into another by oxidation or reduction, 
 this want of uniformity will be easily intelligible. The fresh bile of 
 carnivora is golden-red. The bile of herbivorous animals is in 
 general of a green tint, but, when it has been retained long in the 
 gall-bladder, may incline to reddish-brown. Fresh human bile, as 
 it flows from a fistula just established, is of a reddish-brown, golden- 
 yellow or yellow colour. Beaumont speaks of the yellowish bile 
 which he could press into the stomach of St. Martin by manipulating 
 the abdomen. In a case observed by the writer, it was seen that 
 when the bile flowing from a fistula was allowed to spread out in a 
 dressing, it became greenish, because of oxidation of a part of the 
 biHrubin to biliverdin, although as it actually escaped from the fistula 
 it was yellow. The bile of a monke}'- taken from the gall-bladder 
 immediately after death is dark green, but if left a few hours in the 
 gall-bladder it is brown, the green pigment having been reduced. It 
 should be remembered that human bile from the post-mortem room 
 may alter its colour in the interval which must elapse before it can 
 usually be procured after death. Bile, as obtained from fistulae in 
 otherwise healthy persons, has a specific gravity of about 1008 to 
 10 10, In the gall-bladder water is absorbed from the bile and 
 
3^4 
 
 DIGESTION 
 
 mucin added to it, so that the specific gravity of bladder bile is as 
 high as 1030 to 1040. The reaction is feebly alkaline to litmus. 
 
 The composition of two specimens of human bile— one from a fistula, 
 the other from the gall-bladder — is shown in the following table: 
 
 
 Bladder Bile. 
 
 Fistula Bile. 
 
 Water - - - - - 
 
 898-1 
 
 977-4 
 
 SoUds ----- 
 
 loi-g 
 
 22-6 
 
 Mucin and other substances insoluble 
 
 
 
 in alcohol . - - - 
 
 14-5 
 
 2-3 
 
 Sodium taurocholate and sodium 
 
 
 
 glycocholate - - . 
 
 56-5 
 
 lO-I 
 
 Inorganic salts _ - - 
 
 6-3 
 
 8-5 
 
 Fat ] 
 
 
 
 Lecithin |- - 
 
 30-9 
 
 0-05 
 
 CholesterinJ 
 
 
 0-56 
 
 The substance which renders bladder bile viscid, but which is present 
 in much smaller amount in bile from a fistula, and is probably entirely 
 absent from the fluid as it is secreted by the liver-cells, is commonly 
 termed 'mucin.' It has been shown, however, that in many animals — 
 for example, the ox, dog, sheep, etc. — the substance is not a true mucin. 
 It does not yield, like mucin, on boiling with dilute acid, a carbo- 
 hydrate group (viz., glucosamine, CgHii()5NH2, corresponding to 
 dextrose in which OH is replaced by NHg) . It is relatively rich in phos- 
 phorus, and consists — mainly, at any rate — of a phospho-protein (p. 2). 
 The mucilaginous substance of human bile consists largely of true mucin. 
 
 Mucin is scarcely to be looked upon as an essential constituent of 
 bile; it is not formed by the actual bile-secreting cells, but by mucous 
 glands in the walls and goblet-cells in the epithelial lining of the larger 
 bile -ducts, and especially of the gall-bladder. 
 
 Bile-Pigments. — It has been said that these form a series, but only 
 two of the pigments of that series are present in normal bile, bilirubin, 
 and biliverdin. In human bile, the former, in herbivorous bile and 
 that of some cold-blooded animals, such as the frog, the latter is the 
 chief pigment. But bilirubin can be extracted in large amount from 
 the gall-stones of cattle ; while the placenta of the bitch contains bili- 
 verdin in quantity, although, as in all camivora, it is either absent 
 from the bile or exists in it in comparatively small amount. These 
 facts show that the two pigments are readily interchangeable, but there 
 is no question that bilirubin is the pigment which is formed by the 
 liver-cells. 
 
 Bilirubin (C32H38N4O6) can be prepared from powdered red gall- 
 stones by dissolving the chalk with hydrochloric acid, and extracting 
 the residue with chloroform, which takes up the pigment. From this 
 solution, on evaporation, or from hot dimethyl anilin, beautiful rhombic 
 tables or prisms of bilirubin separate out. 
 
 Biliverdin (C32H3gN40g) can be obtained from the placenta of the 
 bitch by extraction with alcohol. It is insoluble in chloroform, and by 
 means of this property it may be separated from bilirubin when the two 
 happen to be present together in bile. Biliverdin can also be formed 
 from bilirubin by oxidation. By the aid of active oxidizing agents. 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 365 
 
 such as yellow nitric acid (which contains some nitrous acid), a whole 
 series of oxidation products of bilirubin is obtained, beginning with 
 biliverdin, and passing through bilicyanin, a blue pigment, and other 
 intermediate bodies, to cholctelin, a yellow substance. Tt is question- 
 able whether these are all definite compounds. This is the foundation 
 of GmeUn's test for Inle-pigments (sec Practical Exercises, p. 462)- The 
 same colours arc produced, and in the same order, when a solution of 
 bilirubin in chloroform is treated with a dilute alcoholic solution of iodine . 
 
 The positi\e pole of a galvanic current causes the same oxidative 
 changes, the same play of colours, while the reducing action of the 
 negative pole reverses the effect, if the action of the positive electrode 
 has not gone too far. These reactions can also be used for the detection 
 of bile -pigments. 
 
 By the reducing action of sodium amalgam on bilirubin, hemi- 
 bilirubin (C33H44N4O6) is obtained. It gives a beautiful red colour with 
 *-dimethylaminobcnzaldehyde (Ehrlich's reaction). Hemibilirubin is 
 identical with the urobilinogen of urine from which urobilin is derived. 
 Urobilinogen and urobilin (often called in this connection stercobilin) 
 are also found in the faeces from birth onwards, although not in' the 
 meconium (p. 424). Urobilinogen is derived from the normal bile- 
 pigment by reduction in the intestine itself, where reducing substances 
 due to the action of micro-organisms are never absent in extra-uterine life. 
 
 The bile of most animals shows no characteristic absorption spectrum. 
 But the fresh bile of certain animals, the ox, for instance, does show 
 bands. These, however, are not due to the normal bile-pigment, and 
 they are not essentially changed when this is oxidized or reduced by- 
 electrolysis. MacMunn attributes the spectrum of the bile of the ox 
 and sheep to a body which he calls cholohaematin, and which does not 
 belong to the bile-pigments proper. 
 
 The Bile-Salts. — These are the sodium salts of certain acids, of which 
 glycocholic and taurocholic are the chief. In the bile of omnivora, 
 including man, both are in general present, and in various proportions; 
 in human bile there is more glycocholic than taurocholic acid ; some- 
 times taurocholic acid is entirely absent. In the bile of many camivora 
 — e.g., the dog and cat — only taurocholic acid is found; in that of the 
 camivora generally it is by far the more important of the two acids. 
 In the bile of most herbivora there is much more glycocholic than 
 taurocholic acid. The bile acids are paired acids: glycocholic acid 
 (better named cholyl-glycin) formed by the union of glycin and cholic 
 acid, and taurocholic acid (or cholyl-taurin), consisting of cholic acid 
 united with taurin. 
 
 The decomposition of the bile-acids into these substances is effected 
 by boiling them with dilute acid or alkali, a molecule of water being 
 taken up; thus — 
 
 C26H43NOe + H2O- CH2(NH2) .COOH -1- C24H40O5 ; 
 
 Glycocholic acid. Glycin. Cholic acid. 
 
 C26H45NSO7 -^H20=CH2(NH2).CH2.S02.0H -FC24H4o05. 
 
 Taurocholic acid. Taurin. Cholic acid. 
 
 A notable difference between glycocholic and taurocholic acid is that 
 the latter contains sulphur. The whole of this belongs to the taurin. 
 Both glycin and taurin are derived from the disintegration of proteins. 
 We have already seen that among the products of protein hydrolysis a 
 sulphur-containing body, cystein, which is readily changed into cystin, 
 is found, and there is good evidence that taurin is derived from cystein 
 
36^. 
 
 DIGESTION 
 
 or cystin. In certain pathological conditions cystin appears in tho 
 urine (cystin uria). The source of the cholic acid whicli goes to form 
 the bile acids is unknown, but it has been surmised that it may be 
 derived from cholesterin. Thus, 
 
 [CH2.SH+3O CH2.SO2.OH CH2.SO2.OH 
 
 I I I 
 
 CH.NHg = CH.NH2 = CH.NH2 
 
 I I 
 
 COOH COOH— CO2 
 
 Cystein. Cysteinic acid. Taurin. 
 
 Traces of cholic acid, formed by hydrolysis from the bile-acids by 
 the action of putrefactive bacteria, are found in the intestmes, especially 
 in tlie lower portion. 
 
 Pettenkofer' s test for bile-acids (Practical Exercises, p. 462), acciden- 
 tally discovered in examining the action of bile upon sugar, depends upon 
 three facts: (i) That cholic acid and furfuraldehyde give a purple colour 
 when brought together; (2) that the bile-salts yield cholic acid when 
 acted upon by sulphuric acid ; (3) tliat when cane-sugar is decomposed 
 bv strong sulphuric acid, furfuraldehyde is formed. 
 
 Since a similar colour is given when the same reagents are added to a 
 solution containing albumin, it is necessary to remove this, if present, 
 from any liquid which is to be tested for bile-acids. 
 
 Lecithin and cholesterin, or cholesterol, are by no means peculiar to 
 bile (p. 4). They are very widely distributed in the body. Ixcithin 
 (C44H90NPO9) belongs to the group of phosphatides, fat-like phosphorus- 
 containing substances present in all cells. It is a comj)OMml of glycerin 
 with two molecules of fatty acid and one of phosphoric acid. The 
 phosphoric acid is at the same time united with a base cholin (C5H15NO2). 
 Tlie fatty acid (stearic, palmitic, oleic, etc.) varies in different varieties 
 of lecithin . Heated with baryta-water, lecithin yields the corresponding 
 fatty acid in the form of a soaji, along with cholin and glyceryl-phos- 
 phoric acid. Glycerj'l-phosphoric acid can be further split so as to 
 yield a molecule of glycerin and one of phosphoric acid. 
 
 Cholesterin is a substance with the empirical formula C27H4eO. It 
 contains an alcohol group in virtue of which fatty acids can be linked 
 to it, forming esters. It is best obtained from white gall-stones, of 
 which it is the chief, and sometimes almost the sole constituent (sec 
 Practical Exercises, p. 4')3). 
 
 All the compoimds related to cholesterin are grouped together under 
 the name of sterins. The sterins are very widely distributed both in 
 animals (zoostcrins) and in plants (phytos'terins). ICvery cell seems to 
 contain sterins and sterin esters (compounds of the same nature as the 
 compounds of fatty acids with the alcohol glycerin which constitute the 
 neutral fats). In the vertebrates cholesterin and its product co istitute 
 the chief, j^erhaps the only sterins, but in invertebrate animals and 
 plants there is a much greater variety of these substances. 
 
 The chief inorganic salts of bile are sodium chloride, sodium carbonate, 
 and alkaline sodiiun phosphate. The phosphoric acid of the ash comes 
 })artly from the phosphorus of organic comjiouiuls (lecithin and bile- 
 mucin), the sulphuric acid from tlie sulphur of taurocholic acid, the 
 sodium largely from the bile-salts. Iron is a notable inorganic con- 
 stituent of bile, although it exists only in traces, in the form of phosphate 
 of iron. Manganese is also present in minute amount. 100 c.c. of 
 fresh bile yields 50 to 100 c.c. of carbon dioxide, part of which is in 
 solution and part combined with alkalies. 
 
TMK CHEMlSTRV Of THE blCESTlVE JUICED 3C7 
 
 The quantity of bile secreted in twenty- four hours in an average 
 niiui is probably from 750 c.c. to a htre. In nine- cases of fistula ol 
 the gall-bladder in patients operated on for gall-stones or cchino- 
 coccus the daily (piaiUity varied from 500 to 1,100 c.c. (Brand). 
 
 Digestive Functions of Bile. — The great action of the bile in 
 digestion is undoubtedly the preparation of the fats for absorption. 
 In this preparation four processes are important: two chemical 
 actions, hydrolysis of neutral fats to glycerin and fatty acids, and 
 saponification, or the formation of soaps by the union of fatty acids 
 with l)ases, especially sodium ; and two physical processes, emulsifi- 
 cation, or the formation of a mechanical suspension of such fine 
 globules of unaltered neutral fat as exist in milk, and sohition of 
 soaps and fatty acids. While there has been much discussion as to 
 the relative share taken by these processes, and especially by saponi- 
 fication and emulsification in the absorption of fat (p. 441), there is 
 no doubt that they are all concerned in the digestion of fat or the 
 preparation of it for absorption and assimilation. In this, indeed, 
 the processes are complementary to each other, for an essential pre- 
 liminary to emulsification in the intestine seems to be the formation 
 of a certain amount of soaps, soluble in the intestinal contents, while 
 the formation of an emulsion enormously increases the surface of 
 contact between the unaltered fat and the digestive juices, and so 
 favours more rapid hydrolysis, saponification, and solution. In the 
 whole series of changes the bile plays a part, though not an indepen- 
 dent one; it acts always in conjunction with the pancreatic juice. 
 
 While no complete explanation has been given of the precise 
 nature of this partnership, it is certain that the fat-sphtting ferment 
 of the pancreatic juice on the one hand, and the bile-salts on the 
 other, contribute largely to the total action. An alkaline solution, 
 a solution of sodium carbonate, e.g., is unable of itself to emulsify 
 a perfectly neutral oil ; but if some free fatty acid be added, emulsifi- 
 cation is rapid and complete (p. 12). Now, there is no doubt that 
 here a soap is formed by the action of the alkali on the fatty acid, 
 and there is equally little doubt that the formation of the soap is an 
 essential part of the emulsification. But it is not clear in what 
 manner the soap acts, whether by forming a coating round the oil- 
 globules, or by so altering the surface-tension, or other physical 
 properties of the solution in which it is dissolved, that the3^ no longer 
 tend to run together. Howev^er this may be, in pancreatic juice we 
 have the two factors present which this simple experiment shows 
 to be necessary and sufiicient for emulsification ; we have a ferment 
 which can split up neutral fats and set free fatty acids, and an alkali 
 which can combine with those acids to form soaps. Accordingly, 
 pancreatic juice is able of itself to form emulsions with perfectly 
 neutral oils. It is possible that the protein constituents of pancreatic 
 juice may have a share in emulsification, since the addition of protein 
 
368 DIGESTION 
 
 — e.g., ogg-vvhjtc — to a soap solution increases the stability of the 
 emulsions formed by the soap. In bile, on the contrary, although 
 the alkali is present, there is no fat-splitting ferment, and, according 
 to the best experiments, bile alone has no emulsifying power on 
 perfectly neutral fat. But we now come to a remarkable fact: this 
 inert bile when added to pancreatic juice greatly intensifies its 
 emulsifying action, and a solution of bile-salts has much the same 
 effect as bile itself. The fact is undoubted, but the explanation is 
 obscure. What it is that the bile or bile-salts can add to the 
 pancreatic juice which so increases its power of emulsification, we dc» 
 not know. It has been surmised that a characteristic physical 
 property of bile, the diminution of the surface-tension of watery 
 liquids to which it is added, may play an important part, perhaps, 
 in enabling thq fat-splitting ferments or the emulsifying soaps to get 
 into closer contact with the unaltered fat. It is also true that 
 bile, presumably in virtue of the chemical action of its alkaline 
 salts, can, in presence of a free fatty acid, rapidly form an emulsion. 
 But the pancreatic juice itself contains so considerable a quantity of 
 sodium carbonate that it would scarcely seem to require the rela- 
 tively feeble reinforcement of the alkaline salts of the bile.* 
 
 An important part of the effect of the bile is certainly due to its 
 favouring the fat-splitting action of the pancreatic juice. By the 
 addition of bile, the quantity of fat split up by a definite amount of 
 dog's pancreatic juice may be increased two to threefold. It has 
 been shown that this is an action of the bile-salts. The sodium 
 salts of synthetically-obtained glycochoUc and taurocholic acids 
 produce the same effect. It is in virtue of this action that the bile- 
 salts are sometimes spoken of as the co-ferment of the lipase. As 
 already pointed out, this action is exerted in presence of the fully 
 formed enzyme, and should not be confounded with the effect of the 
 bile-salts in activating the lipase zymogen. The capacity of dis- 
 solving soaps, which is a property of the bile-salts, is also of great 
 importance in supplementing the solvent power of the intestinal 
 liquids for the products formed by the pancreatic juice. The 
 solution of soaps in the bile-salts has the power in its turn of dis- 
 solving free fatty acids. The significance of this in fat absorption 
 will be referred to again. A further illustration of the mutual 
 adaptation of the various digestive juices, of the remarkably precise 
 manner in which the action of each dovetails into the action of 
 others, is afforded by the facts alread}' mentioned in connection with 
 the lipase of the stomach. It is highly probable that the fatty acids 
 formed by the gastric lipase, even if formed only in small amount, 
 may exertan important influence in emulsifying the fat as soon as it 
 enters the intestine. The intestinal juice itself also unquestionably 
 takes a share in the digestion of fat along with the pancreatic 
 
 • It has lately been shown that bile-saUs accelerate the formation of soap 
 from oleic acid by sodium bicarbonate (Kingsbury). 
 
THE LllF.MISTRV OF THE DIGESTIVE JUICES 369 
 
 secretion and the bile. Tliere exists also, as will be seen later (ni, a 
 certani adajitation betvvei'n the food and the digestive secretions. 
 Not tiie best illustration of this, but one wliich suits the present topic, 
 is the fact that the food itself probably always contains some free 
 fatty acids when it contains fat at all. Although our knowledge of 
 the mutual action of the pancreatic juice and the bile on the digestion 
 of fats is still incomplete, there is no doubt that they are equally 
 necessary. For in some diseases of the pancreas fat or fatty acid 
 often appears in the stools, and this token of imperfect digestion of 
 the fatty food may be conlirmed by the wasting of the patient. The 
 same may occur when the bile is prevented by obstruction of the 
 duct or by a biliary fistula from entering the intestine. Yet in some 
 cases of fistula, where there is every reason to believe that all the bile 
 is escaping externally', the nutrition of the patient — at any rate, on a 
 diet not abnormally rich in fat — is unaffected. The mere deficiency 
 of bile in the intestine is, of course, compUcated in obstructive 
 jaundice by the harmful effects of the biliary constituents circulating 
 in the blood. 
 
 The white stools of jaundice owe their colour, not merely to the 
 absence of bile-pigment, but also to the presence of fat. Their highly 
 offensive odour used to be adduced as evidence that bile is the ' natural 
 antiseptic ' of the intestine. It seems rather to be due to the coating 
 of the particles of food with undigested fat, which shields the proteins 
 from the action of the digestive juices, while permitting the putrefactive 
 bacteria to revel in them unchecked. As a matter of fact, the bile 
 itself has little, if any, power of hindering the growth of micro-organisms, 
 although the free bile-acids are tolerably active antiseptics. In suckling 
 children it is not uncommon to see the faeces white with fat. This is a 
 less serious symptom than in adults, and perhaps betokens merely that 
 the milk in the feeding-bottle is undiluted cow's milk, which is richer 
 in fat than human milk, and ought to be mixed with water. 
 
 Bidder and Schmidt found that the chyle in the thoracic duct of a 
 normal dog contained 3*2 per cent, of fat. In a dog with the bile-duct 
 ligatured the proportion fell to 0-2 per cent. It is an instance of the 
 extraordinarily exact adaptation of the digestive juices to the nature 
 of the food, the mechanism of which will present itself for discussion 
 later on, that the reinforcing action of the bile upon the fat-splitting 
 ferment of the pancreatic juice is said to be greater when the food is 
 rich in fat (p. 414). 
 
 Bile has been credited with a physical power of aiding the passage 
 of fat through membranes moistened with it by diminishing the surface 
 tension, and it has been inferred that this has an important bearing 
 on the absorption of fat from the intestine. But the inference does 
 not follow from the statement, and the statement has been itself 
 denied. There is at present no evidence that the digestive function 
 of the bile extends beyond the preparation of the food for absorption 
 to the preparation of the mucosa for absorbing it. 
 
 On proteins bile has either no digestive action, or only a feeble 
 one. Fibrin is slightly digested by the bile of the dog and of man. 
 But the addition of it to fresh pancreatic juice considerably increases 
 the proteol\i:ic power of that secretion (Rachford), although not so 
 decidedly as in the case of the fat-splitting action. The amylol\i:ic 
 
 24 
 
37© DIGESTION 
 
 action of the pancreatic juice is also favoured by the bile, and in 
 about the same degree as its proteoI\-tic effect. Although bile some- 
 times exerts by itself a feebly amylol}i:ic action, this is not to be 
 included among its specific powers, for a diastatic ferment in small 
 quantities is widely diffused in the body. 
 
 The addition of bile or bile-salts to a gastric digest causes the 
 precipitation of any unaltered native protein, acid-albumin, albu- 
 mose, and pepsin. The precipitate, which is a salt-like compound 
 of protein with taurocholic acid, is redissolved when the liquid is 
 rendered alkaline, and therefore in excess of bile, or of a solution of 
 bile-salts, but the pepsin has no longer any power of digesting 
 proteins. Part of the bile-acids and bile-mucin is also thrown down 
 by the acid of the digest. It has been suggested that by thus 
 precipitating the constituents of the chyme which have not been 
 carried to the peptone stage bile prepares them for the action of the 
 pancreatic juice. But it is difficult to see how the precipitation of 
 a substance can prepare the way for its digestion, and it is more 
 probable that if any physiological value is to be given to this reaction, 
 it has the function of preventing the absorption of proteins which 
 have not been sufficiently split up. There is little doubt, however, 
 that the rendering of the pepsin inactive has physiological signifi- 
 cance, for pepsin exerts an injurious influence upon the ferments of 
 the pancreatic juice. In digestion, then, the bile has a iuofold func- 
 tion, favouring greatly the activity of the pancreatic ferments, especially 
 the fat-splitting ferment, and aiding in establishing the conditions 
 necessary for the transition of gastric into intestinal digestion. 
 
 Succus Entericus. — This is the name given to the special secretion 
 of the small intestine, which is supposed to be a product of the 
 Lieberkiihn's crypts or intestinal glands. In order to obtain it pure, 
 it is of course necessary to prevent admixture with the bile, the pan- 
 creatic juice, and the food." This can be done by dividing a loop of 
 intestine from the rest by two transverse cuts, the abdomen having 
 been opened in the linea alba. The continuity of the digestive tube 
 is restored by stitching the portion below the isolated loop to the 
 part above it. One end of the loop is sewed into the lips of the 
 wound in the linea alba, and the other being closed by sutures, the 
 whole forms a sort of test-tube opening externally (Thiry's fistula). 
 Or both ends are made to open through the abdominal wound (Vella's 
 fistula). Another method is to make a single opening in the intes- 
 tine, and by means of two indiarubber balls, one of which is pushed 
 down, and the other up through the opening, and which are after- 
 wards inflated, to block off a piece of gut from communication with 
 the rest. Or several openings may be made at different levels in the 
 intestine, each being allowed to heal into a w'ound in the abdominal 
 wall. When pure juice is required it is collected from the lower 
 fistulae, while the upper fistulae are opened to permit the escape of the 
 
THE CHEMISTRY OF THE DIGESTIVE JUICES 37r 
 
 secretions which enter the liigher portions of the alimentary canal 
 (gastric juice, pancreatic juice, and bile). The intestinal juice so 
 obtained is a thin yellowish liquid of alkaline reaction, generally 
 somewhat turbid from the presence of a certain number of leucocytes 
 and epithelial cells. Its specific gravity is about loio, the total 
 solids about 1-5 per cent. It contains a small amount of proteins, 
 including serum albumin and serum globulin, and about the same 
 proportion of inorganic salts as most of the liquids and solids of the 
 body, namely, 07 or o-8 per cent., chiefly sodium carbonate and 
 sodium chloride; but, hke the other digestive liquids, it is adapted 
 to the nature of the food, and therefore its composition is not quite 
 constant. Like bile, intestinal juice acts but feebly on the food 
 substances by itself, and if we contented ourselves with examining 
 the pure and isolated secretion, we should greatly underestimate its 
 importance. The sodium carbonate, in which it is relatively rich, 
 will, to be sure, form soaps with fatty acids produce! by the action 
 of the pancreatic juice or of the fat-splitting bacteria in which the 
 intestine abounds, and thus aid in the digestion of fats. A lipase, 
 feebler than that of the pancreatic juice, or present in smaller con- 
 centration, is also a constituent of the succus entericus. That a 
 great deal of fat may be split up in the ahmentary canal in the 
 absence both of bile and pancreatic juice is well ascertained. The 
 alkah of the succus entericus must at the same time aid in neutraliz- 
 ing the original acidity of the chyme, and in preserving the proper 
 reaction of the intestinal contents. A ferment called invertase, or 
 sucrase — which is not introduced with the food or formed by bacterial 
 action as has been suggested, since it occurs in the aseptic intestine 
 of the new-born child — will invert cane-sugar. The ferments maltase 
 and lactase will cause a corresponding change in maltose and lactose 
 (see footnote, p. 356). It is worthy of remark that these inverting 
 enzymes are present in the intestinal mucosa as well as in the 
 intestinal juice, and extracts of the mucosa are usually distinctly 
 more active than the juice itself. So that there is reason to believe 
 that hydrolysis of the disaccharides may take place both in the 
 lumen of the gut before absorption and in the wall of the gut during 
 absorption. Inverting enzymes appear in the intestine early in 
 embryonic life. Maltase is the most generally distributed of all 
 these enzymes, and it is found along with lactase in the intestine of 
 the embryo pig, while invertase is missing till after birth (Mendel). 
 On native proteins and starch the isolated succus entericus has little 
 or no action. But it contains a ferment, crepsin, which, although it 
 does not affect native proteins like serum- and egg-albumin (fibrin 
 and caseinogen may be slightl}' digested), exerts a powerful action 
 on the first products of protein hydrolysis, albumoses, and peptones, 
 breaking them up into bodies which no longer give the biuret re- 
 action (ammonia, mono-amino acids, hexone bases, etc.). It 
 
373 
 
 DIoL:3TI0N 
 
 destroys the diphtheria toxin, wiiich is also rendered innocuous by 
 trypsin. Erepsin, however, is not specific to the secreted intestinal 
 juice, for it occurs also, not only in the mucous membrane of the 
 intestine, which, indeed, contains a greater quantity of it than the 
 succus entericus, but in all animal tissues hitherto investigated. It 
 is said even to be sometimes present in pancreatic juice, since in- 
 activated pancreatic juice, which does not digest other proteins, will 
 sometimes digest casein. But the matter is far from being settled, 
 and the presence of erepsin in the pancreatic tissue is a complicating 
 circumstance. For under abnormal conditions, most glands pro- 
 \ided with artificial fistulse have an increased liability to injuries 
 of various kinds, which might permit constituents not normally 
 present in the secretion to pass into it from the cells. The kidney in 
 mammals is even richer in erepsin than the intestinal mucous 
 membrane. Next to these come the pancreas, spleen, and liver, 
 then at a long interval the heart muscle, while skeletal muscle and 
 brain-tissue are poorest of all in the ferment. The intestinal mucosa 
 varies in its erepsin content at different levels and on different diets. 
 In cats on a meat or a mixed diet the duodenum is about five times 
 richer in the ferment than the stomach. The ileum is about half as 
 rich as the duodenum, and the jejunum occupies an intermediate 
 position between the duodenum and ileum (\'ernon). The secretion 
 of Brunner's glands in the duodenum, which resemble in structure 
 the pyloric glands of the stomach, digests coagulated albumin, 
 although its proteohiric powers are feebler than those of the pan- 
 creatic juice. 
 
 Enterokinase. — The most characteristic constituent of succus 
 entericus is a ferment, enterokinase, which differs from all the fer- 
 ments we have hitherto described in acting not directly upon the 
 foodstuffs, but upon the trypsinogen of the pancreatic juice, chang- 
 ing it into the active enzyme trypsin. It may therefore be spoken of 
 as a ferment of ferments. It has been previously stated that freshly 
 secreted pancreatic juice is without action upon proteins. The 
 addition of succus entericus immediately confers upon it a high 
 degree of proteolytic power. In one experiment pancreatic juice, 
 obtained by a temporary fistula, required four to six hours to dissolve 
 fibrin, and did not attack coagulated albumin even in ten hours. 
 On addition of succus entericus, the same pancreatic juice dissolved 
 fibrin in three to seven minutes, and rapidly digested coagulated 
 albumin (Pawlow). In liki- manner a glycerin extract of a fresh 
 pancreas has hardly any effect on proteins; a similar extract of a 
 stale pancreas is active. The fresh pancreas contains trypsinogen, 
 which is soluble in glycerin, for the inert extract becomes active 
 when it is treated with dilute acetic acid, or even when it is diluted 
 with water and kept at the body-temperature. If the fresh pancreas 
 be first treated with dilute acetic acid, and then with glycerin, the 
 
run cii !■ mistily oi- the digestive juices 373 
 
 extract is at once active. The trypsinogen can therefore be activated 
 within the pancreatic cells, gradually when the pancreas is simply 
 allowed to stand after excision, more rapidly in presence of the dilute 
 acid. The ordinary tests for irrnient action (destruction by boiling, 
 activity in very small amounts, etc.) have shown that this property 
 of the intestinal juice is due to a ferment, although it differs in 
 certain respects from most ferments — for instance, in requiring a 
 relatively high temperature to inactivate it. The smallest trace 
 of enterokinase will convert a large quantity of trypsinogen into 
 trypsin if time be given. At the same time, although to a much 
 smaller extent, the fat-splitting and starch-digesting activity of the 
 pancreatic juice is increased. The secretion of the duodenum causes 
 a greater increase in the proteohiiic power than that of the other 
 portions of the small intestine, while no such difference has been 
 made out in the case of the amyloh-tic and hpolytic functions. It is 
 probable that the enterokinase, which is secreted mainly in the upper 
 two-sevenths of the small intestine, and solely by the intestinal 
 epithelium, acts only on the trypsinogen, and that the amj'lopsin 
 and steapsin are aided in some other way. Enterokinase is only 
 found in the intestinal juice when pancreatic juice is present in the 
 gut. It is therefore secreted in response to the presence of tryp- 
 sinogen or of some other constituent of the pancreatic juice. 
 
 Delezenne has attempted to explain the interaction of enterokinase 
 and trj-psinogen as an adaptive phenomenon of the same kind as the 
 formation of antitoxins and ha^molysins (p. 31). According to him, 
 enterokinase acts Hke a complement in haemolysis, while trypsinogen 
 plays the part of an intermediary^ body or amboceptor which enables 
 the enterokinase to attack the protein molecule. He asserts that 
 enterokinase, or a substance which produces a similar effect on tr^'p- 
 sinogen, is contained not only in the mucous membrane of the intestine, 
 but also in leucoc^^es, in fibrin (one of whose properties it is to pick 
 out ferments from liquids containing them), in lymph-glands, in snake 
 venom, and even in certain anaerobic bacteria. On tliis view trypsin 
 would not be a definite substance produced by the interaction of 
 enterokinase and trypsinogen, but only an expression for these two 
 bodies acting together. Strong evidence against this view, and in 
 favour of the independent existence of trypsin, hao been brought forward 
 by Bayliss and Starling, and it does not seem to merit further con- 
 sideration. According to Mellanby, enterokinase is really a proteolytic 
 ferment, and trypsinogen contains a protein moiety with which trypsin 
 is firmly combined. The conversion of trypsinogen into trypsin 
 depends on the digestion of this protein moiety, and the consequent 
 liberation of trypsin. Vernon has put forward the view that, while 
 enterokinase starts the activation of trypsinogen in the intestine, and 
 can no doubt in time complete it. the tn,-psin as it is formed aids in the 
 activation of more trj'psinogen to trypsin, and so on by a process of 
 so-called auto-catalysis of the trypsinogen. This idea can be har- 
 monized with Mellanby's conception by assuming that the trypsin 
 formed from trypsinogen can itself digest the protein moiety of a further 
 portion of trypsinogen. 
 
374 DIGESTION 
 
 According to P;i\vlo\v, the reason wh}' the tr\psin is not secreted 
 in the active form is that active trypsin reachly destroys the amylo- 
 lytic and hpolytic ferments. In the intestine, where trypsin is 
 rendered active by enterokinaso, these ferments are protected from 
 its attack by the proteins of the food and by the bile. Enterokinase 
 is itself immediately destroyed in the presence of free acid (centi- 
 normal hydrochloric acid). 
 
 Having now finished our review of the chemistry of the digestive 
 juices, our next task is to describe what is known as to their secre- 
 tion — the nature of the cells by which it is effected and their histo- 
 logical appearance in activity and repose, and the manner in which 
 it is called forth and controlled. 
 
 Section IV. — Thk Secretion of the Digestive Juices — 
 MiCROscopic.\L Changes in the Gland Cells. 
 
 The digestive glands are formed originally from in\'olutions of the 
 mucous membrane of the alimentary canal, the salivary glands from 
 the ectoderm, the others from the endoderm (Chap. XIX.). Some are 
 simple unbranchcd tubes, in which there is either no distinction into 
 body and duct, as in I.icbcrkiilm's cn,q:)ts in the intestines, or in which 
 one or more of the tubes open into a duct, as in the glands of the fundus 
 of the stomach. Some are branched tubes, several of which may end 
 in a common duct ; such are the glands of the pyloric end of the stomach 
 and the Brunner's glands in the duodenum. In others the main duct 
 ramiiics into a more or less complex system of small channels, into each 
 of the ultimate branches of which one or more (usually several) of the 
 secreting tubules or alveoli open. The salivary glands and the pancreas 
 belong to this class of compound tubular or racemose glands, and so 
 does the liver of such animals as the frog. But in the latter organ the 
 typical arrangement is obscured in the higher vertebrates by the pre- 
 dominance of the portal bloodA cssels over the system of bile-channels 
 as a groundwork for the grouping of the cells. 
 
 In every secreting gland there is a vascular plexus outside the cells 
 of the gland-tubes, and a system of collecting channels on their inner 
 surface ; and in a certain sense the cells of every gland are arranged 
 with reference to the bloodvessels on the one hand, and the ducts on 
 the other. But in the ordinary racemose gland the blood-supply is 
 mainly required to feed the secretion ; the cells of the alveoli have cither 
 no other function than to secrete, or if they have other functions, they 
 are not such as to entail a great disproportion between the size of the 
 cells and the lumen of the channels into which thej' pour their products. 
 For both reasons the relation of the grouping cf the cells to the duct- 
 system is vcr^' obvious, to the blood-sjstem very obscure. In the liver, 
 the conditions arc precisely reversed. We cannot suppose that the 
 manufacture of a quantity of bile less in volume than the seen t ion of 
 the salivary glands, though doubtless containing far more solids, 
 requires an immense organ Hke the liver, and a tide of blood like that 
 which passes through the portal vein. And, as we shall see, the liver 
 has other functions, some of them certainly of at least equal importance 
 with the secretion of bile, and one of them evidently requiring from 
 its ver>' nature a bulky organ. Accordingly, both the richness of the 
 blood-supply and the size of the secreting cells are out of proportion to 
 
THE SECRETION OE THE DIGESTIVE JUICES 375 
 
 ihc calibre of the ultimate channels that carry the secretion away. 
 The so-called bile-capillarios. which represent the lumen of the secreting 
 tubules, are mere grooves in the surface of adjoining cells; and the 
 architectural lines on which the liver lobule is built arc: (i) the inter- 
 lobular veins which carry blood to it; (2) the rich capillary network 
 whicii separates its cells and feeds them; and (3) the central intra- 
 lobular vein which drains it. Thus a network of cells lying in the 
 meshes of a network of blood-capillaries takes the place of a regular 
 dendritic arrangement of ducts and tubules; and in accordance with 
 this the bile-capillaries, instead of opening separately into the ducts, 
 form a plexus with each other within the hepatic lobule (see also foot- 
 note, p. 14). 
 
 The ducts and secreting tubules of all glands are lined by cells of 
 columnar epithelial t^-pe, but the type is most closely preserved in the 
 ducts. In none of the digestive glands is there more than a single 
 complete layer of secreting cells. But the alveoli of the mucous 
 salivary' glands show- here a'.:<l there a crescent-shaped group of small 
 deeply-staining cells (crescents of Gianuzzi) outside the columnar layer 
 (Fig. 15S, A". B"), and between it and the basement membrane, while 
 the gland-tubes of the fundus of the stomach have in the same situation 
 a discontinuous layer of lart'.e ovoid cells, termed parietal from their 
 position, ox^mtic (or acid -secreting) from their supposed function 
 (Figs. 155-157). Access to the lumen of the glands is provided for 
 these deeply-placed parietal cells and for the cells of the crescents by 
 fine branching channels which enter and surround the cells. The 
 serous salivary glands, the pyloric glands of the stomach, and the 
 Lieberkiihn's crypts, have but a single layer of epithelium; and since 
 there is no hepatic cell which is not in contact with at least one bile 
 capillar^-, the liver may be regarded as having no more. The same is 
 true of the pancreatic alveoli, except that in the centre of many of the 
 acini a few spindle-shaped cells (centro -acinar cells), apparently con- 
 tinued from the lining of the smallest ducts, may be seen. Remarkable 
 histological changes, evidently connected with changes in functional 
 activity, have been noticed in most of the digestive glands. In dis- 
 cussing these, it will be best to omit for the present any detailed reference 
 to the liver, since, although there are histological marks of secretive 
 activity in this gland as well as in others, and of the same general 
 character, they are accompanied, and to some extent overlaid, by the 
 microscopic evidences of other functions (p. 534). The serous salivary 
 glands and the pancreas can be taken together; so can the glands of the 
 various regions of the stomach; the mucous salivary glands must 
 be considered separately. 
 
 Changes in the Pancreas and Parotid during Secretion. — The cells 
 of the alveoli of the pancreas or parotid during rest, as can be seen 
 by examining thin lobules of the former between the folds of the 
 mesentery in the living rabbit, or fresh teased preparations of the 
 latter, are filled with fine granules to such an extent as to obscure 
 the nucleus. In the parotid the whole cell is granular, in the 
 pancreas there is still a narrow clear zone at the outer edge of the 
 cell which contains few granules or none; in both, the divisions 
 between the cells are verv indistinct, and the lumen of the alveolus 
 cannot be made out. During activity the granules seem to be 
 carried from the outer portion of the cell towards the lumen, and 
 
376 
 
 DWESTJON 
 
 there discharged. The clear outer zone of the pancreatic cell grows 
 broader and broader at the expense of the inner granular zone, until 
 at last the granular zone may in its turn be reduced to a narrow 
 contour line around the lumen (Fig. 153). In the uniformly clouded 
 parotid cell a similar change takes place; a transparent outer zone 
 
 arises; and, after prolonged 
 secretion, only a thin edging 
 of granules may remain at 
 the inner portion of the cell 
 (l-'ig. 154). In both glands 
 the outlines of the cells be- 
 come more clearly indicated, 
 and a distinct lumen can 
 now be recognized. The 
 cells are smaller than they 
 are during rest. 
 
 The disappearance of 
 granules from without in- 
 wards during activity sug- 
 gests that these are manu- 
 factured products eUminated in the secretion, and they are generally 
 spoken of as zymogen granules. 
 
 Bensley, who has made a careful study i)f the pancreas in the 
 guinea-pig, has been able to distinguish, even in fresh preparation-^ 
 examined in the animal's own serum, but better after staining with 
 such a dye as neutral red, another kind of granules, which he regards 
 
 Fig- 153. — -4. alveolus of rabbit's pancreas, 
 ' loaded ' (resting) ; B. ' discharged ' 
 (active), observed in the living animal 
 (Kiihne and Lea). 
 
 Fig. 154.— .\lveoli of Parotid Gland: A. at Rest: B, after a Short Period of .\ctivity: 
 C, after a Prolonged PeriDd of .Activity (Fresh Preparations) (Langley). In A 
 and H tlie nuclei are obscured bv the granules of zymogen. 
 
 as zymogen granules in the course of formation, and therefore 
 designates prcjzymogen granules. The resting acini show a clear 
 basal zone which is unstained, and a zone next the lumen containing 
 coarse zymogen granules which are faintly stained. In the active 
 gland — e.g.. after a meal or aftrr the injection of secretin (p. 407) — 
 prozymogen granules which stain much more intensely than the 
 zymogen granules with neutral red make their appearance between 
 the zymogen granules, now much reduced in number jnd size, and 
 
?///: SllCRl^TJON OF THE DIGESTIVE J VICES 
 
 377 
 
 the clear outer zone. Attor prolonged secretion the zymogen granules 
 may be entirely' absent from the cells, and only a narrow rim of 
 pro/.ymogen granules can be seen around the lumen. 
 
 In one respect the pancreas differs remirkably from the salivary 
 gknds — namely, in the presence of the islets of Langerhans — 
 characteristic groups of small 
 
 polygonal cells, richly sup- 
 plied with bloodvessels, but 
 not arranged in the form of 
 alveoli. Some observers state 
 that they are remarkably in- 
 creased in size, and even in 
 number when the pancreas is 
 caused to secrete actively by 
 repeated injections of secretin, 
 and also in starvation. But 
 it has been shown that this 
 conclusion was based upon 
 faulty methods of counting 
 the islets, and even of identi- 
 fying the islet cells. There 
 appears to be no foundation 
 for the view that they are 
 derived from the ordinary 
 secreting cells, and that they 
 can, in turn, give rise to new 
 alveoli by a process of pro- 
 liferation. It is far more 
 probable that they are inde- 
 pendent structures, with a 
 different function from the 
 pancreatic alveoH (p. 6 ,8). 
 
 Changes in the Glands of 
 the Stomach during Secre- 
 tion. — The mucous membrane 
 of the stomach is covered 
 with a single layer of colum- 
 nar epithelium, largely con- 
 sisting of mucigenous goblet- 
 cells. It is studded with 
 
 }^ 
 
 ll 
 
 M 
 
 Fig. 155- Fig. 156. 
 
 Fig. 155. — A Fundus Gland of Simple Form 
 from the Bat's Stomach (Osmic Acid Pre- 
 paration) (Langley). c. Columnar epithe- 
 lium of the surface; n, neck of the gland 
 with chief or central and parietal cells; 
 /, base, occupied only by chief cells, which 
 show the granules accumulated towards 
 the lumen of the gland. 
 
 Fig. 156. — A Fundus Gland prepared by 
 Golgi's Method, showing the Mode of Com- 
 munication of the Parietal Cells with the 
 Gland-Limien (Schafer, after E. MuUer). 
 
 minute pits, into which open 
 the ducts of the peptic and pyloric glands, the ducts being lined 
 with cells just like those of the general gastric surface. Three 
 varieties of gastric glands have been distinguished: (i) The 
 glands of the cardia. In man these occupy a small portion of 
 the mucous membrane at the cardiac end, near the orifice of 
 
37S DIGESTION 
 
 the ousophagus. Sonu' ol the glands are single tubules, but 
 others have two or more tubules opening into a common duct. 
 Both are lined by a single layer of short columnar epithelium, 
 which contains granules. (2) The glands of the pyloric canal 
 or antrum. These consist of short, branched tubules, which oi)en 
 by twos and threes into long ducts. (3) The glands of the 
 fundus or oxyntic glands, occupying the intermediate and greater 
 portion of the organ. The gland tubules are long and seldom 
 branched, and the ducts, into each of which open from one to three 
 tubules, are relatively short. The secreting parts of both kinds of 
 glands arc lined by short columnar granular cells; and in the pyloric 
 tubules no others arc present. But, as we have said, in the glands 
 of the fundus there are besides large ovoid cells scattered at intervals 
 like beads between the basement membrane and the lining or chief 
 cells. The cells of the pyloric glands have a general resemblance to 
 the chief cells of the fundus glands, but they are not quite the same. 
 For example, the granules are less distinct in the pyloric glands. In 
 the human stomach it is only quite near the pylorus that the parietal 
 cells disappear altogether. The parietal cells also contain granules, 
 but they are smaller and less numerous than those of the chief cells, 
 so that the deeper portions of the fundus glands are much darker in 
 appearance than the more superficial portions, since the oxyntic or 
 parietal cells are more numerous in the neighbourhood of the ducts 
 (Bensley). 
 
 The histological changes connected with gastric secretion do not 
 differ essentially from those described in the pancreas and the 
 parotid, but there is much greater difficulty in making observations 
 on the living, or at least but slightly altered, cells. For the mammal 
 the best method is to use animals with a permanent gastric fistula, 
 and to remove from time to time small portions of the mucous 
 membrane for examination in the fresh condition. During digestion 
 the granules disappear from the outer part of the chief cells of the 
 fundus glands, leaving a clear zone, the lumen being bordered by a 
 granular laj'er. Or, more rarely, there may be a uniform decrease 
 in the number of granules throughout the cell. The total volume 
 of the cell is less than in the fasting condition. The parietal cells, 
 which are small in the fasting animal, swell up, so as to bulge out the 
 mcmbrana propria. They reach their maximum size (in the dog) 
 very late in digestion (the thirteenth to the fifteenth hour). No 
 such definite changes in their contents as those observed in the other 
 cells have been made out. The granules in the ovoid cells during 
 and after activity seem to be as large and as numerous as in the 
 resting cell, or even larger. After sham feeding in dogs the histo- 
 logical changes in the gastric glands are vcrj' slight, even when con- 
 siderable amounts of gastric juice have been secreted (Noll and 
 Sokoloff). ■ 
 
THI-: SECRETION Of I'HE DIGESTIVE JUICES 
 
 379 
 
 Tlie chief colls of the oxyntic. and tlic similar if not identical cells 
 of the pyloric glands, arc bcli(>vcd to manufacture the pepsin-form- 
 ing substance. The ovoid cells of the former are supposed to secrete 
 the hydrochloric acid. The evidence on which this belief is based 
 is as follows: 
 
 The glands of the antrum pylori in the dog, in which in most 
 situations no ovoid cells are to be seen, secrete pepsin, but no acid. 
 The pyloric end of the stomach or a portion of it has been isolated, 
 
 Fig. 157. — The Gastric Glands (Ebstein). 
 
 On the left, o.xyatic; right, pyloric. 
 
 the continuity of the alimentary canal restored by sutures, and the 
 secretion of the pyloric pocket collected. It was found to be alka- 
 line, and contained pepsin. The glands of the frog's oesophagus, 
 which contain only chief cells, secrete pepsin, but no acid. It seems 
 fair to conclude that the chief cells of the fundus glands in the 
 mammal secrete none of the free hydrochloric acid, but certainly 
 some of pepsin. But it does not follow that all the pepsin is formed 
 by these cells, although it would seem that all the hydrochloric acid 
 
38o DIGESTION 
 
 must be secivtod by the only other glandular elements present, the 
 parietal or ' border ' cells. And, indeed, the glands in the fundus 
 of the frog's stomach, which are composed only of ovoid cells, whilst 
 secreting much acid, also form some pepsin, although far less than 
 the oesophageal glands. During winter sleep (in the marmot) the 
 production of hydrochloric acid in the parietal cells stops altogether, 
 while the chief cells continue to accumulate granules of pepsinogen. 
 
 That some pepsin is secreted by the pyloric end of the stomach 
 is not difficult to prove. The secretion collected from the isolated 
 pyloric portion is, indeed, like the secretion of the Brunner's glands 
 in the duodenum, quite unable to digest protein until dilute hydro- 
 chloric acid is added. But this is because in both cases the juice as 
 it flows from the glands is slightly alkaline, and, as we have already 
 seen, pepsin only acts in the presence of an acid. The milk-curdling 
 action of these two juices also unfolds itself only when the secretions 
 arc first acidulated, and later on again neutralized; in other words, 
 the ferments must be activated by the addition of an acid. In normal 
 digestion the pepsin of the (in itself) alkahne secretion of the pyloric 
 end of the stomach becomes a constituent of the acid gastric juice; 
 and it may perhaps be considered a morphological accident, so to 
 speak, that the oxyntic cells of the fundus should mingle their acid 
 products with the (presumedly) alkaline secretion of the chief cells 
 in the lumen of each gland-tube, instead of being massed as a 
 separate organ with a special duct. 
 
 We are not without other examples of digestive juices fitted or 
 destined to act in a medium with an opposite reaction to their own. 
 The ' saliva ' of the cephalopod Octopus macropus, strongly acid 
 though it is, contains a proteolytic ferment which in vitro acts, like 
 trypsin, better in an alkaline than in an acid solution. And trypsin, 
 whose precursor is a constituent of the alkaline pancreatic juice, while 
 the enterokinase which activates it is a constituent of the alkaline 
 succus entericus, performs a part at least of its work in an acid 
 medium. 
 
 Attempts made to demonstrate an acid reaction in the border cells 
 have hitherto failed. Harvey and Bcnslcy on the basis of experiments 
 with dyes (cyanimin and neutral red), which give different colours 
 according to whether the reaction is acid, alkaline, or neutral, have 
 concluded that free acid exists only on the internal surface of the 
 stomach, or at most also in the necks of the glands. The parietal cells 
 they find alkaline. They suggest that these cells form in some way, 
 of course ultimately from the chlorides of the blood, a chloride of an 
 organic base which does not decompose so as to yield free Iiydrochloric 
 acid until it reaches the mouth of the gland. Tlie nature of this decom- 
 position, if it occurs, is unknown. It may be mentioned, although only 
 as a matter of historical interest, that some observers have denied that 
 the acid is secreted in the depths of any cell from the chlorides of the 
 blood, and have asserted that it is formed at the surface of contact of 
 the stomach-wall with the gastric contents from the sodium chloride of 
 the food by an exchange of sodium ions (p. 428) for hydrogen ions from 
 
TUi: SF.CRETION 01- THI- DIGESTIVE JUICES j8i 
 
 the blood or lymph. It wiis pomted out in favour of this view tiiat 
 when, instead of sodiiun chloride, sodium bromide is given in the food, 
 the hydrochloric acid in the stomach is to a large extent replaced by 
 hydrobromic acid. And it was argued that this cannot be due to the 
 decomposition of the bromide by hydrochloric acid, since it occurs in 
 animals deprived for a considerable time of salts, and in ' salt-hunger * 
 the stomach contains no acid (Koeppc). It may be, however, that 
 even m ' salt-hunger ' the presence of sodium bromide in the stomach 
 stimulates the secretion of hydrochloric acid, which then decomposes 
 the bromide, with the formation of hydrobromic acid. The sodium 
 chloride formed in the double decomposition might be re-absorbed, 
 and the stock of chlorides in the blood remain undiminished. It is in 
 any case a decisive objection to this now defimct theory that a copious 
 secretion of gastric juice, containing hydrochloric acid in abundance, 
 can be obtained, without the introduction of any food into the stomach, 
 either by the process of sham feeding (p.401) or by psychical st.mulation 
 of the gastric glands when food is shown to an animal. 
 
 Changes in Mucous Glands during Secretion, — In the mucous salivary 
 and other mucous glands similar, but apparently more complex, changes 
 occur. During rest the cells which line the lumen may be .seen in fresh, 
 teased preparations to be filled with granules or ' spherules.' After 
 active secretion there is a great diminution in the number of the 
 granules. Those that remain are chiefly collected around the lumen, 
 although some may also be seen in the peripheral portion of the cell; 
 and there is no ver^^ distinct differentiation into two zones. That a 
 discharge of material takes place from these cells is shown by their 
 smaller size in the active gland. That the material thus discharged is 
 not protoplasmic is indicated by the behaviour of the cells to proto- 
 plasmic stains such as carmine. The resting cells around the lumen 
 stain but feebly, in contrast to the deep stain of the demilunes, while 
 the discharged cells take on the carmine stain much more readily. 
 Further, when a resting gland is treated with various reagents (water, 
 dilute acids, or alkalies), the granules swell up into a transparent sub- 
 stance identical with mucin, which fills the meshes of a fine protoplasmic 
 network. 
 
 In ordinary alcohol-carmine preparations only the network and 
 nucleus are stained ; the nucleus, small and shrivelled, is situated close 
 to the outer border of the cell. When a discharged gland is treated in 
 the same way there is proportionally more ' protoplasm ' (or ' bioplasm ') 
 and less of the clear material, what remains of the latter being chiefly 
 in the inner portion of the cell, while the nucleus is now large and 
 spherical, and not so near the basement membrane (Fig. 158). 
 
 Everything, therefore, points to the granules in what we may now 
 call the mucin-forming cells as being in some way or other precursors 
 of the fully-formed mucin ; manufactured during ' rest ' by the proto- 
 plasm and partly at its expense, moved towards the lumen in 
 activity, discharged as mucin in the secretion. It has been asserted 
 that not only is the protoplasm lessened in the loaded cell and re- 
 newed after activity, but that many of the mucigenous cells may be 
 altogether broken down and discharged, their place being supplied 
 by proliferation of the small cells of the demilunes. This conclusion, 
 however, is not supported by sufficient evidence. The cells of the 
 crescents contain fine granules, but none which can be changed into 
 
382 
 
 DIGESTION 
 
 mucin. They arc of serous and not of mucous type. But the fact 
 on which \vc would specially insist is that the granules of the resting 
 mucigenous cell may be looked upon as a mother-substance from 
 which the mucin of the secretion is derived; they are not actual, but 
 potential, mucin. 
 
 So in the pancreas, the serous or albuminous salivary glands, and 
 the glands of the stomach, there is every reason to believe that the 
 granules which appear in tlie intervals of rest, and are moved 
 towards the lumen and discharged during activity, are the pre- 
 cursors, the mother-substances, of important constituents of the 
 secretion. These granules are sharply marked off from the proto- 
 plasm in which they lie and by which they are built up. By every 
 mark, by their reaction to stains, for instance, they are non-hving 
 substance, formed in the bosom of the hving cell from the raw 
 material which it culls from the blood, or, what is more hkely. 
 formed from its own protoplasm, then shed out in granular form and 
 
 Fig. 158. — Mucous Cells (from Submaxillary of Dog) in Rest and Activity (Langley). 
 
 A. B. fresh; A', B', alter treatment with dilute acetic acid; A", B', alveoli hard- 
 ened in alcohol and stained with carmine. A, A', and A' represent the loaded; 
 
 B, B', and B", the discharged condition. 
 
 secluded from further change. The granules in the ferment-forming 
 glands are not in general composed of the actual ferments, and, 
 indeed, in several instances it has been shown that the actual fer- 
 ments are not present in the secreting cells at all. 
 
 We have already seen that the pancreas and even the fresh pan- 
 creatic juice are devoid of active trypsin. Similarly, a glycerin 
 extract of a fresh gastric mucous membrane is inert as regards 
 proteins, or nearly so. But if the mucous membrane has been pre- 
 viously treated with dilute hydrochloric acid, the glycerin extract 
 is active, as is an extract made with acidulated glycerin. Here we 
 must assume the existence in the gastric glands of a mother-sub- 
 stance, pepsinogen, from which pepsin is formed. The rennin of the 
 gastric juice, which is formed in the chief cells, also has a precursor, 
 which, if the ferment is identical with pepsin (p. 353), must be 
 pepsinogen. The proteolytic power of an extract of the pancreas, 
 
THE SECRhJJON OF THE DIGEST IV i: JUICES 383 
 
 vvhen the trypsinogen has been activated into trypsin, or of the 
 gastric mucous membrane, when the pepsinogen has been changed 
 into pepsin, seems to be, roughly speaking, in proportion to the 
 quantity of granules present in the cells. Therefore it is concluded 
 that the granules represent mother-substances of the ferments or 
 zymogens. Some observers believe they have obtained evidence of 
 stages in the elaboration of the ferments still further back than the 
 mother-substances, grandmother-substances so to speak, or pro- 
 xy mogens. Bensley, e.g., concludes that the nuclei of the chief cells 
 in the fundus glands of the stomach take part in the formation of a 
 prozymogen, the precursor of the zymogen or pepsinogen, as pepsino- 
 gen is the precursor of the enzyme pepsin. 
 
 A glycerin or watery extract of the salivary glands always con- 
 tains active amylolytic ferment, if the natural secretion is active. 
 So that if ptyalin is preceded by a zymogen in the cells, it must be 
 very easily changed into the actual ferment. 
 
 But we should greatly deceive ourselves if we supposed that granules 
 of this nature in gland-cells are necessarily related to the production of 
 ferments. The mixigenous granules have no such significance. Most 
 digestive secretions contain protein constituents, with which the 
 granules may have to do as well as with ferments. And bile, a secretion 
 which contains no mucin, no proteins, and cither no ferments or mere 
 traces, as essential and original constituents, is formed in cells with 
 granules so disposed and so affected by the activity of the gland as to 
 suggest some relation between them and the process of secretion. In 
 the liver-cells of the frog, in addition to glycogen, and oil-globules small 
 granules mav be seen, especiallv near the lumen of the gland tubules ; 
 they diminish in number during digestion, when the secretion of bile is 
 active and increase when food is withheld and secretion slow. And 
 in fasting dogs the secreting cells of Brunner's glands, the pyloric glands 
 and the pr-ncreas, as well as the lining epithelium of the bile-ducts, 
 have been found to contain many fatty granules. Possibly some of 
 these represent the fat which is known to be excreted into the alimentary 
 canal (pp. 443, 444). 
 
 The Nature of the Process by which the Digestive Secretions are 
 Formed. — \\"e have spoken more than once of the gland-cells as 
 manufacturing their secretions. It is an idea that rises naturally 
 in the mind as we follow with the microscope the traces of their 
 functional activity. And when we compare the composition of the 
 digestive juices with that of the blood-plasma and lymph, the 
 suggestion that the glands which produce them are not merely 
 passive filters, but living laboratories, acquires additional strength. 
 It is evident that everything in the secretion must, in some form 
 or other, exist in the blood which comes to the gland, and in the 
 lymph which bathes its cells. No glandular cell, if we except the 
 leucocytes, which in some respects are to be considered as unicellular 
 glands, dips directly into the blood ; everything a gland-cell receives 
 must pass through the walls of the bloodvessels. (But see footnote 
 
384 DIGESTION 
 
 on p. 14). So tliat anything which we find in thi' secrt-tion and do 
 not find in tlio blood must have been elaborated by the gland 
 epithelium (or by the capillary endothelium) from raw material 
 brought to it by the blood. 
 
 Take, for example, the saliva or gastric juice. These liquids both 
 contain certain things that also exist in the blood, but in addition 
 they contain certain things specific to themselves: mucin in saliva, 
 hydrochloric acid in gastric juice, ferments in both. It is true that 
 a trace of pepsin and a trace of a diastatic ferment may be dis- 
 covered in blood; but there is no reason whatever to believe that 
 this is the source of the pepsin of the gastric juice, or the ptyalin 
 of the salivary glands, except, perhaps, in animals like the cat. 
 whose saliva contains a diastase in still smaller concentration than 
 the serum (Carlson). On the contrary, it is possible that the fer- 
 ments of the blood may be in part absorbed from the digestive 
 glands, the rest being formed by the leucocytes and liberated when 
 they break down. 
 
 Formation of Bile. — The liver affords an even better example of 
 this ' manufacturing ' activity of gland-cells, and many facts may 
 be brought forward to prove that the characteristic constituents 
 of the bile, the bile-pigments and bile-acids, are formed in the liv-er, 
 and not merely separated from the blood. Bile-pigment has indeed 
 been recognized in the normal serum of the horse, and bile-acids in 
 the chyle of the dog, but only in such minute traces as are easily 
 accounted for by absorption from the intestine. Frogs live for some 
 time after excision of the liver, but no bile-acids are found in the 
 blood or tissues. But if the bile-duct be ligatured, bile-acids and 
 pigments accumulate in the body, being absorbed by the hniiphatics 
 of the hver (Ludwig and Fleischl). If the thoracic duct and the 
 bile-duct are both hgatured in the dog, no bile-acids or pigments 
 appear in the blood or tissues. Wertheimer and Lepage state that 
 bile or bilirubin injected into a bile-duct appears sooner in the 
 urine than in the lymph of the thoracic duct, and therefore conclude 
 that the bloodvessels are the most important channel of absorption. 
 This conclusion, however, cannot be accepted until it is shown that 
 in these experiments the injection did not cause rupture of some 
 of the hepatic capillaries and direct entrance of the bile-pigment 
 into the blood. It is not improbable that the pressure attained by 
 the bile in the bile-capillaries is a factor in determining the path 
 by which it is absorbed, and that when the pressure rises beyond 
 a certain limit it may pass both into the bloodvessels and into the 
 lymphatics. In mammals life cannot be maintained for any length 
 of time after ligature of the portal vein, since this throws the whole 
 intestinal tract out of gear. But after an artificial communication 
 has been made between the portal and the left renal vein or th« 
 inferior cava, the portal maybe tied and the animal live for months 
 
THE SECRETION OF THE DIGESTIVE JUICES ,85 
 
 (Eck). The liver can now be (•on)i)lctely R'nioved, but death 
 follows in a few hours. A good method of establisliing an Feck's 
 fistula is to make a longitudinal incision in the inferior vena cava 
 and the portal or superior mesenteric vein, and to suture the edges 
 of the two openings together with a very fine sewing-needle and 
 thread (Carrel and (iutlu-ie). In birds tlu're exists a communicating 
 branch between the })ortal vein and a vein (the renal-jiortai) which 
 passes from the posterior portion of the body to tlie kidney, and 
 there breaks up into capillaries: and not only may the portal be 
 tied, but the Uver may be completely destroyed without immedi- 
 ately killing the animal. In the hours of life that still remain to it 
 no accumulation of biliary substances (acids or pigments) takes 
 place in the blood or tissues. A further indication that bile-pig- 
 ment is produced in the liver is the fact that the Hver contains 
 iron in relative abundance in its cells (p. 21), and ehminates small 
 quantities of iron in its secretion. Now, bile-pigment, which con- 
 tains no iron, is certainly formed from blood-pigment, which is rich 
 in iron. For haematin, when injected under the skin, has been found 
 to appear almost quantitatively in the form of bile-pigment in the 
 bile, and hagmatoidin (Fig. 159), a crystalUne 
 derivative of haemoglobin found in old ex- 
 travasations of blood, especially in the brain 
 and in the corpus lutcum, is identical with 
 bilirubin. The fact that one of the derivatives 
 of haematin, haematoporphyrin (C33H38N4O6), 
 contains no iron, and is proi)ably nearly 
 
 related to bilirubin (C32H3gN406), suggests 
 
 that haematoporphyrin may be an inter- p^^ isg.Z^matoidin. 
 mediate step in the formation of bile-pigrnent 
 
 from blood-pigment. In any case, the seat of formation of bile- 
 pigment might be expected to be an organ peculiarly rich in iron. 
 The existence of hac m at oi din,, however, shows that bile-pigment 
 may, under certain conditions, be formed outside of the hepatic 
 cells. The occurrence of bihverdin in the placenta of the bitch 
 points in the same direction. But the pathological evidence in 
 favour of the pre-formation of the biliary constituents tends rather 
 to shrink than to increase. For many cases of what used to be 
 considered ' idiopathic ' or ' haematogenic ' jaundice, i.e., an accumu- 
 lation of bile-pigments and bile-acids in the tissues, due to defective 
 elimination by the liver, are now known to be caused by obstruction 
 of the bile-ducts and consequent re-absorption of bile (' obstructive * 
 or ' hepatogenic ' jaundice). 
 
 But if substances such as the ferments, mucin, hydrochloric acid, 
 the bile-salts and bile-pigments, are undoubtedly manufactured in the 
 gland-cells, it is different with the water and inorganic salts which 
 form so large a part of every secretion. No tissue lacks them; no 
 
iHo 
 
 DIGESTION 
 
 physiological process got-s on without them; they are not high and 
 special j)roducts. As we breathe nitrogen which we do not need 
 because it is mixed with the oxygen we require, the secreting cell 
 passes through its substance water and salts as a sort of by-jilay or 
 adjunct to its specific work. But this is not the whole truth. The 
 gland-cell is not a mere filter through which water and salts pass in 
 the same proportions in which they exist in the Hquids that the 
 cell draws them from. When, e.g., the salivary glands secrete 
 against the resistance of an abnormally high pressure in the ducts, 
 the percentage of salts in the sahva increases. The secretions of 
 different glands differ in the nature, and especially in the relative 
 proportions, of their inorganic constituents. They differ also in 
 their osmotic pressure and electrical conductivity, which depend 
 so largely upon those constituents, notwithstanding the fact that 
 the osmotic pressure and conductivity of the blood-serum (p. 26) 
 var}' only within narrow limits. Even the secretion of one and the 
 same gland is by no means constant in this respect, as we shall 
 have to note more especially when we come to deal with the in- 
 fluence of the nervous system on secretion (p. 395). The following 
 tables illustrate this point : 
 
 Dog. 
 
 Blood-Serum.* 
 
 Filtnte of Gastric Contents. [ 
 
 1 
 
 At KJ(5'>C.)Xio«. 
 
 A 
 
 KJ(s«"C.)xio*. 
 
 I. 
 
 II. 
 
 III. 
 
 0-643° gz-o 
 
 0-628° 87-6 
 o-6o2° 87-7 
 
 0-585" 
 0-585° 
 0-642° 
 
 312-5 
 179-4 
 351-7 
 
 Vomit of man with complete intes- 
 tinal obstruction - - - 
 
 o-433° 
 
 84-7 
 
 Pancreatic Juice of Dog [Pincussohn). 
 
 Diet. 
 
 A 
 
 Milk - - - - 
 Cauliflower . _ _ 
 Horseflesh . - _ 
 
 o-57»-^-63' 
 0-58°— 0-63° 
 0-62° — 0-63° 
 
 * The blood and gastric contents were obtained from the animals twenty- 
 four hours after tlie last meal. 
 
 ^ The depression of the freezing-point below that of distilled water. 
 
 I See footnote on p. 27. The number in brackets is the temperature at 
 which the measurement was made. 
 
THE SECRETIOi\ OF THE DIGESTIVE JUICES 
 
 387 
 
 Gastric Juice from Miniature Stomach in a Dog in Different 
 Experiments [Bickel). 
 
 Milk Diet. 
 
 Meat Diet. 
 
 A 
 
 K(asoC.)Xio*. 
 
 A 
 
 K(2soC.)xio*. 
 
 0-52' 
 0-65° 
 o-64» 
 0-69" 
 o-8i° 
 
 195-9 
 402-6 
 
 436-5 
 404-2 
 
 436-5 
 
 0-60" 
 0-71° 
 1-21° 
 
 o-79° 
 0-70° 
 
 3IO-3 
 
 473-5 
 483-3 
 514-1 
 514-1 
 
 i 
 
 A of Blood and Saliva Compared (Jappelli), 
 
 A of Blood. 
 
 A of Subma-Yillary Saliva of Dog. 
 
 1 
 
 1 
 
 0-570° 
 
 0-410° 
 
 
 o-6io° 
 
 0-350° 
 
 
 o-6oo° 
 
 0-430° 
 
 
 0-590° 
 
 0-410° 
 
 
 0-580° 
 
 0-450° 
 
 
 0-605° 
 
 0-425° 
 
 
 0-650' 
 
 0-380° 
 
 
 o-6io° 
 
 0-475° 
 
 
 A of Human Fistula Bile. 
 
 A of Human Bladder Bile. 
 
 0-56° 
 
 o-547° 
 0-615° 
 0-60° 
 o-545° 
 
 0-65° 
 
 0-865" 
 
 0-78° 
 
 0-92* 
 
 A of Dog's 
 
 Chorda stimulated : 
 
 Left submaxillary - 
 
 Both glands 
 Spontaneous secretion : 
 
 Right submaxillan- - 
 A of dog's serum 
 
 Submaxillary Saliva. 
 
 - 0-293' 
 
 - 0-408° 
 
 - 0-195° 
 
 - 0-590° 
 
 The protein substances, such as serum-albumin and globuhn, 
 common to blood and to some of the digestive secretions, take a 
 middle place between the constituents that are undoubtedly manu- 
 
388 DIGESTION 
 
 factored in the cell and those which seem by a less special and 
 laborious, though a selective, process to be passed through it from 
 the blood. Their practical absence from bile, and, as we shall see, 
 from urine, their relative abundance in pancreatic and scantiness 
 in gastric juice, point to a closer dependence upon the special 
 activity of the gland-cell than we can suppose necessary in the case 
 of the salts. 
 
 Although it is in the cells of the digestive glands that the power of 
 forming ferments is most conspicuous, it is by no means confined to 
 them. It seems to be a primitive, a native power of protoplasm. 
 Lowly animals, like the amoeba, lowly plants, like bacteria, form ferments 
 within the single cell which serves for all the purposes of their life. 
 The ferment-secreting gland-cells of higher forms are perhaps only lop- 
 sided amcebae, not so much endowed with new properties as dispro- 
 portionately developed in one direction. The contractility has been 
 lost or lessened, the digestive power has been retained or increased; 
 just as in muscle the power of contraction has been developed, and 
 that of digestion has fallen behind. The muscle-cell and the cartilage- 
 cell are parasites, if we look to the function of digestion alone. They 
 live on food already more or less prepared by the labours of other cells; 
 and it is a universal law that in the measure in which a power becomes 
 useless it disappears. But the presence of pepsin in the white blood- 
 corpuscles, the parasites as well as the scavengers of the blood, and of 
 amylolytic, proteolytic and lipolytic ferments in many tissues, should 
 warn us not to conclude that the power of forming ferments belongs 
 exclusively to any class of cells. There is good and growing e%idence 
 that food-substances absorbed from the blood are further decomposed 
 and, in turn, elaborated by ferment action within the tissues them- 
 selves; wliilc many facts show that the power of contraction is widely 
 diffused among structures whose special function is very different, 
 and a few point to its possession in some degree even by glandular 
 epithelium. On the other hand, it must be remembered that none of 
 the digestive glands absorb food directly from the alimentarj' canal to 
 be then digested within their own cell-substance ; the ferments which 
 they form do their work outside of them ; their cells feed also upon the 
 blood. 
 
 Why are the Tissues of Digestion not affected by the Digestive 
 Ferments ? — This is tlie place to mention a point which has been 
 very much debated. Why is it that the stomach or the small intes- 
 tine does not digest itself ? This is really a part of a wider question : 
 Why is it that living tissues resist all kinds of influences, which attack 
 dead tissues with success ? And we have to inquire whether the 
 immunity of the alimentary canal to the digestive juices is an 
 example of a general resistance of all living tissues to destructive 
 agencies, or a specific resistance of certain tissues to certain in- 
 fluences. 
 
 That all living tissues cannot withstand the action of the gastric 
 juice has been shown by putting the leg of a living frog inside the 
 stomach of a dog; the leg is gradually eaten away (Bernard). 
 
 It is true that it has first been killed and then digested, but the 
 question is, why the stomach- wall is not first killed and then 
 
THE SECRHTJON OF THE DICES LIVE JUICES ^Sq 
 
 digested ? When the wall has been injured by caustics or by an 
 embolus, the gastric juice acts on it. But the living epithelium 
 that covers it is able to resist the action of the acid and pepsin, 
 which destroys the tissues of the frog's leg. The explanation is not 
 to be found in the alkalinity of the blood, for the frog's blood is also 
 alkaline, and the cells that line the intestine are preserved from the 
 pancreatic juice, which is intensely active in an alkaline medium, 
 while the living frog's leg is not harmed by a weakly alkaline pan- 
 creatic extract, which does not digest the epithelium because it 
 cannot kill it. A certain amount of protection may be afforded to 
 the walls of the stomach by the thin layer of mucus which covers the 
 whole cavity, for mucin is not affected by peptic digestion. And 
 a mucous secretion seems in some other cases to act as a protective 
 covering to the walls of hollow viscera, whose contents are such as 
 would certainly be harmful to more delicate membranes, e.g., in 
 the urinary bladder, large intestine, and gall-bladder. Still, how- 
 ever important such a mechanical protection may be, it does not 
 explain the whole matter, and it is necessary to suppose that the 
 gastric epithelium has some special power of resisting the gastric 
 juice, either by turning any of the ferment which may invade it 
 into an inert substance and neutralizing any intrusive acid, or by 
 opposing their entrance as the epithelium of the bladder opposes the 
 absorption of urea. There is reason to beheve that, as a matter of 
 fact, free hydrochloric acid cannot penetrate the living cells, and 
 it is to be noted that both active pepsin and free acid must be 
 present at the same point within the cells before digestion of them 
 can take place. In the gland-cells of the pancreas the protoplasm 
 is, no doubt, shielded from digestion by the existence of the ferment 
 in an inert form as zymogen; and it is possible that this is one of the 
 reasons for the existence of the mother-substance. But no such 
 explanation is, of course, available for the intestinal epithelium. 
 Trypsin when injected below the skin causes the tissue to break 
 down and ulcerate. And while an active solution of trypsin can 
 be allowed to remain a long time in an isolated loop of small intes- 
 tine without producing any ill effect, damage is soon caused not 
 only to the intestinal wall, but also to the liver, when the mucous 
 membrane of the loop has been injured before the introduction of 
 the trypsin. We must suppose, then, that the normal mucous 
 membrane of the intestine prevents the absorption of trypsin, or, 
 if it absorbs any of it, renders it harmless. On the other hand, the 
 intestinal mucosa is injured by the natural gastric juice when intro- 
 duced directly into it unless the animal takes food simultaneously 
 or a little earlier. But for reasons already given (p. 370) injury to 
 the intestine cannot be produced in this way in normal digestion. 
 It is impossible to escape the conclusion that each membrane becomes 
 accustomed, and, so to speak, ' immune,' to the secretion normally 
 
390 
 
 DIGESTION 
 
 in contact with it, although not necessarily to other secretions. 
 It is easy to multiply illustrations of this principle. 
 
 The mucosa of the dog's urinary bladder is digested by the 
 natural activated pancreatic juice of the dog, and still more readily 
 by the natural gastric juice. Yet few tissues but the Hning of the 
 urinary tract or of the large intestine could bear the constant contact 
 of urine or faeces. When urine is extravasated under the skin, or 
 the contents of the alimentary canal burst into the peritoneal 
 cavity, they come into contact with tissues which, although ahve, 
 are much less fitted to resist them than the surfaces by which they 
 are normally enclosed; and the consequences, which are not wholly 
 due to infection, are often disastrous. Leucocytes thrive in 
 the blood, but perish in urine. Blood does not harm the endo- 
 thehal cells of the vessels, but kills a muscle whose cross-section 
 is dipped into it. The defensive or, in some cases, offensive 
 liquids secreted by many animals are harmless to the tissues 
 which produce and enclose them. A caterpillar investigated 
 by Poulton secretes a liquid so rich in formic acid that the mere 
 contact of it would kill most cells. The so-called saliva of Octopus 
 macropus contains a substance fatal to the crabs and other animals 
 on which it preys. The blood of the viper c(jntains an active 
 principle similar to that secreted by its poison-glands, but its tissues 
 are not affected by this substance, so deadly to other animals. 
 
 A step in the solution of our problem has been taken by Wein- 
 land. Starting with the idea that if special protective mechan- 
 isms against the digestive juices were anywhere to be found, it would 
 be in the intestinal parasites whose whole existence is passed among 
 them, he has made the important discovery that in these parasitic 
 worms specific antiferments exist — i.e., substances which inhibit the 
 action either of pepsin or of trypsin or of both. These substances can 
 be precipitated from the expressed juice of the worms by alcohol, 
 without completely losing their activity. Fibrin can be impreg- 
 nated with them, and it is then, just like the ' hving tissue,' rendered 
 for a longer or shorter time unassailable by the proteolytic ferments. 
 These facts are fuU of suggestion for future work, although the sup- 
 posed proof that similar antiferments are contained in the cells of 
 the mucous membrane of the stomach and intestines of the higher 
 animals appears to have broken down. Substances can indeed be 
 obtained by Weinland's method from the gastric and intestinal 
 mucosa which, when added to a digestive mixture, strongly inhibit 
 the digestion of proteins. But there is no clear proof that these sub- 
 stances are specific antiferments. They are probably merely some 
 of the split products of protein (Langenskjold). There is, however, 
 some evidence of the existence of an antipepsin in many tissues 
 including the mucous membrane of the stomach. As already men- 
 tioned, it is known that an antitrj^sin exists in the blood, with the 
 
hMLUh.XLL Uh \Ll<.VOU5 b\^iLM 0.\ DIGESTIVL GLA.SJJb 591 
 
 same properties as tlie antitrypsin in the intestinal worms (Hamill). 
 This explains the resistance of blood-serum to the digestive action 
 of trypsin. In addition to this body, which hinders the action of 
 fully-formed trypsin, and has no effect upon enterokinase, the 
 serum of some animals contains an antikinase — i.e., a substance 
 which hinders the action, not of trypsin, but of enterokinase, pre- 
 venting it from activating the trypsmogen into trypsin. 
 
 Section V. — The Influenxe of the Nervous System 
 ON the Digestive Gl.\nds. 
 
 The Influence of Nerves on the Salivary Glands. — All the salivary 
 glands have a double nerve-supply, from the medulla oblongata 
 through some of the cranial nerves, and from the spinal cord through 
 the cervical sympathetic (Fig. 160). 
 
 In the dog the chorda tympani branch of the facial nerve carries the 
 cranial supply of the sublingual and submaxillary glands. It joins the 
 lingual branch of the fifth nerve, runs in company with it for a little 
 way, and then, breaking off, after giving some fibres to the lingual, 
 passes, as the chorda tympani proper, along WTiarton's duct to the 
 siTbmaxillar\' gland. In the hilus of this gland most of its fibres break 
 up into fibrils around nerve-cells situated there, and lose their medulla 
 in doing so. A few fibres terminate in a similar manner before entering 
 the hilus, and a few deeper in the gland. The nervous path is continued 
 by the axis-cylinder processes (p. 851) of these nerve-ceUs, which, 
 passing in as non-medullated fibres, end in a plexus on the basement 
 membrane of the alveoli. From the plexus fibrils nm in among the 
 gland-cells, but do not seem to penetrate them. The lingual, the 
 chorda t^mipani proper, and Wharton's duct form the sides of what is 
 caUed the chordo-lingual triangle. Within this triangle are situated 
 many ganglion cells, a special accumulation of which has received the 
 name of the submaxillar^' ganglion. This, however, should rather be 
 called the sublingual ganglion, since its cells, as well as the others in the 
 chordo-lingual triangle, are the cells of origin of axons which proceed 
 as non-medullated fibres to the sublingual gland. The sublingual gland 
 receives its cerebral fibres partly from branches given off from the 
 lingual in the chordo-lingual triangle after the chorda tympani proper 
 has separated from it, and ending around the nerve-cells within that 
 triangle, partly from the chorda itself in the terminal portion of its 
 course. These statements rest on anatomical and physiological evi- 
 dence. The latter we shall return to. 
 
 The cerebral fibres for the parotid (in the dog) pass from the tympanic 
 branch of the glosso-phar^-ngeal (Jacobson's nerve) through connecting 
 filaments to the small superficial petrosal branch of the facial, with 
 this nerve to the otic ganglion, and thence by the auriculo-temporal 
 branch of the fifth to the gland. 
 
 The sympathetic fibres for all the salivary glands appear to arise from 
 nerve-cells in the upper dorsal portion of the spinal cord. Issuing 
 from the cord in the anterior roots of the upper thoracic nerves (first to 
 fifth, but mainly second thoracic for the submaxillary), they enter the 
 sympathetic chain, in which they run up to the superior cervical 
 ganglion. Here they break up into terminal twigs, and thus come into 
 
302 
 
 DIGESTION 
 
 n-Lition with ganglion cells, whose axons pass out as non-mcdullated 
 fibres, and, surrounding the external carotid, reach the salivary glands 
 along its branches. Langlev has shown, by means of nicotine (p. 182), 
 that the sympathetic fibres for the submaxillary- and sublingual, and, 
 indeed, for the head in general in the dog and cat, are connected with 
 nerve-cells in this ganglion, b\it not between it and their termination, 
 or between it and tlieir origin from the spinal cord. 
 
 Stimulation of the 
 
 Cranial Fibres. — When 
 in a (log a cannula is 
 placed in \\ barton's 
 duct, and the saliva 
 collected (p. 45O), it is 
 found that stimulation 
 of the peripheral end 
 of the divided chorda 
 causes a brisk flow of 
 watery saliva, and at 
 the same time a dila- 
 tation of the vessels 
 of the gland, which we 
 have already described 
 in dealing with vaso- 
 motor nerves (p. 179). 
 Notwithstanding the 
 vaso - dilatation, the 
 volume of the gland 
 is in general dimin- 
 ished, owing to the 
 rapid passage of water 
 into the duct (Bunch). 
 The blood has been 
 shown to lose water in 
 making the circuit of 
 the submaxillary 
 gland during excita- 
 tion of the chorda, 
 but doubtless some 
 of the water of the 
 saliva comes directly 
 from tlie cells or from 
 the lymph. That the increased secretion is not due merely to the 
 greater blood-supply, and the consequent increase of capillary pres- 
 sure, is shown by the injection of atropine, after which stimulation 
 of the nerve, although it still causes dilatation of the vessels, is not 
 followed by a flow of saliva. This can be shown fully as well by 
 injecting a small quantity of yohimbin into the subrmixillary artery. 
 Great dilatation of the vessels is produced, but no saliva is secreted; 
 
 Fig. 160 — Nerves oi the Salivary Glands. SM and SL, 
 submaxillary and sublingual glands; P, parotid; 
 A', fifth nerve; VII. facial; GP, glosso-pharyngeal; 
 L. lingual; CT, chorda tympani; CL, chordo-lingual; 
 1>. subma.Killary (Wharton's) duct; C. ganglion cell 
 of so-called submaxillary ganglion in the chordo- 
 lingual triangle, connected with a nerve fibie going 
 to sublingual gland; C. ganglion cell in hilus of sub- 
 maxillary gland: SSP, small superficial petrosal 
 branch of the facial; OG. otic ganglion; IM, inferior 
 maxillary division of fifth nerve: AT, auriculo- 
 temporal branch of fifth: JN, Jacobson's nerve: 
 C, gang'ion cells in superior cervical ganglion (SG) 
 connected with sympathetic fibres going to parotid, 
 submaxillarv' and sublingual glands. The figure is 
 schematic. 
 
JMLLl-XCr: Of S'ElilUiS SYSTEM OS DlGLSTIVJi CLASDS 393 
 
 nor i? ilie amount of oxygen consumed by the gland increased. 
 Mere increase of pressure could not in any case of itself account for 
 the secretion, since it has been found that the maximum pressure 
 in the salivary duct when ;iie outflow of saliva from the duct is 
 prevented mav. during stimulaiion of the chorda, much exceed the 
 arterial blood-pressure (Ludwig). In one experiment, for example, 
 the pressure in the carotid of a dog was 125 mm., in Wharton's 
 duct 195 mm. of mercury. 
 
 Even in the head of a decapitated animal a certain amount of 
 sali\a may be caused to flow by stimulation of the chorda, but too 
 much may easily be made of this. And since the blood is the ultimate 
 source of the secretion, we could not expect a permanent or copious 
 flow in the absence of the circulation, even if the gland-cells could 
 continue to live. In fact, when the circulation is almost stopped by 
 strong stimulation of the sympathetic, the flow of saUva caused by 
 excitation of the chorda is at the same time greatly lessened or 
 arrested, even though the sympathetic itself possesses secretory 
 fibres. So that, while there is no doubt that the chorda tympani 
 contains fibres whose function is to increase the activity of the 
 gland-cells, its vaso-dilator action is, under normal conditions, 
 closely connected with, and. indeed, auxihary to. its secretory action, 
 although the dilatation of the vessels does not directly produce the 
 secretion. This is only a particular case of a physiological law of 
 wide application, that an organ in action in general receives more 
 blood than the same organ in repose, or, in other words, that the 
 tissues are fed according to their needs. The contracting muscle, the 
 secreting gland, is flushed with blood, not because an increased blood- 
 flow can of itself cause contraction or secretion, but because these 
 high efforts require for their continuance a rich supply of what blood 
 brings to an organ, and a ready removal of what it takes away. 
 Evidence exists that in the saUvary glands, as in muscle (p. 178), 
 metabolic products given off during functional acti\-ity contribute 
 to the dilatation of the vessels. This is the simplest explanation of 
 the fact that the dilatation caused by chorda stimulation lasts longer 
 when saliva is being secreted than when the secretion has been 
 abohshed by atropine. 
 
 The quantity of blood passing through the parotid of a horse 
 when it is actively secreting during mastication may be quadrupled 
 (Chauveau). The parallel between the muscle and the gland is 
 drawn closer when it is stated that electrical changes accompany 
 secretion (p. 83S), and that the rate of production of carbon dioxide 
 and consumption of oxygen (in the submaxillary gland) is three or 
 four times greater during activity than during rest . The temperature 
 of the saliva flowing from the dog's submaxillary during stimulation 
 of the chorda has been found to be as much as i^^** C. above that 
 of the blood of the carotid, although with the gland at rest no con- 
 stant difference could be detected between the arterial blood and 
 
394 DICESTIOS 
 
 the interior of Wharton's duct. But such measurements arc open 
 to many fallacies; and while there is no doubt that more heat is 
 produced in the active than in the passive ejland, it will not be 
 surprising, when the vastly-increased blood-flow is remembered, 
 that no difference of temperature between the incoming and out- 
 going blood has been satisfactorily demonstrated. 
 
 It has already been mentioned that most of tlie fibres of the chorda 
 tympani proper become connected with ganghuu-cells, and lose their 
 nii-dulla inside the submaxillary gland, only a few having already lost 
 it by a similar connection with ganglion-cells in the chordo-Ungual 
 triangle. These facts have been made out by means of the nicotine 
 method previously described (p. 182). Thus, it is found that, after 
 the injection of nicotine (5 to 10 mg. in a rabbit or cat, 40 or 50 mg. in 
 a dog), stimulation of the chorda tj-mpani proper or of the chordo- 
 lingual nerve causes no secretion from the submaxillary gland; but 
 stimulation of the lulus of the gland is followed by a copious secretion — 
 as much, if the stimulation is fairly strong, as was caused by excitation 
 of the nerve before injection of nicotine. That this is due neither to 
 any direct action on the gland-cells, nor to stimulation of the sympa- 
 thetic plexus on the submaxillary artery-, but to stimulation of chorda 
 fibres beyond the hilus, is shown by the fact that after atropine has 
 been injected in sufficient amoimt to paralyze the nerve endings of the 
 chorda, but not of the sympathetic, stimulation of the hilus causes little 
 or no flow of saliva. The application of nicotine solution to the chordo- 
 Ungual triangle does not affect the submaxillary secretion caused by 
 stimulation of the chordo-lingual nerve, even in cases where a few 
 secretory fibres for the submaxillary do not leave the chordo-lingual 
 nerve in the chorda tympani proper, but are given off to the chordo- 
 lingual triangle. This shows that none of the ganglion-cells in the 
 triangle are connected with the secreton,- fibres of the submaxillar}' 
 gland. By observations of the same kind they are kno%vn to be con- 
 nected with fibres going to the sublingual. In a similar way, by observ- 
 ing the effects of stimulation of the chorda on the bloodvessels before 
 and after the application of nicotine, it has been found that the vaso- 
 dilator fibres are connected with ganglion-cells in the same positions as 
 the secretory fibres (Langley). 
 
 Stimulation of the Sympathetic Fibres. — The sympathetic, as has 
 been already indicated, contains both vaso-constrictor and secretory 
 fibres for the salivary glands. If the cervical sympathetic in the 
 dog is divided, and the cephalic end moderately stimulated, a few 
 drops of a thick, viscid and scanty saliva flow from the submaxillary 
 and sublingual ducts, while the current of blood through the glands 
 is diminished. As a rule, no visible secretion escapes from the 
 parotid, but microscopic examination shows that many of the 
 ductules are filled with fluid, which is apparently so thick as to plug 
 them up (Langley) ; while the cells sliow signs of ' activity ' (p. 376). 
 
 Simultaneous Stimulation of Cranial and Sympathetic Fibres. — 
 When the chorda and sympathetic are stimulated together, the 
 former prevails so far, with moderate stimulation of the iatter, that 
 the submaxillary saliva is secreted in considerable quantity, and is 
 not particularly viscid. It is, however, richer in organic matter 
 than is the chorda saliva itself. When the chorda is weakly, and 
 
INFLUEi\CE OF NERVOUS SYSTEM OS DIGESTIVE (JLASDS 395 
 
 the sympathetic strongly, excited, the scanty secretion (if there is 
 arty) is of sympathetic type, thick and rich in organic matter. With 
 strong stimulation of both nerves, the secretion, at first plentiful 
 and watery, soon diminishes, even below the amount obtained by 
 stimulation of the chorda alone, because of the diminution in the 
 blood- flow, and therefore in the oxygen-supply, produced by the 
 vaso -constrictors of the sympathetic (Heidenhain). With stimula- 
 tion just strong enough to cause secretion when apphed separately 
 to either nerve, there is no secretion when it is applied simul- 
 taneously to both. 
 
 All this refers to the dog. In this animal, then, there seems to be 
 a certain amount of physiological antagonism between the secretory 
 action of the two nerves. But it differs in one respect from the 
 antagonism between their vaso-motor fibres; for with strong stimu- 
 lation the constrictors of the sympathetic always swamp the dilators 
 of the chorda, while the secretory fibres of the chorda appear upon 
 the whole to prevail over those of the sympathetic. And in all 
 probability this apparent secretory antagonism is very superficial, 
 and is due largely to the difference in the vaso-motor effects of the 
 two nerves. For it has been shown that, when the blood-flow 
 through the submaxillary gland is artificially diminished by gradu- 
 ated compression of its artery, stimulation of the chorda gives rise 
 to a thick, viscid and scanty saliva, relatively rich in organic soHds 
 (Heidenhain). When the amount of blood passing through the 
 gland is made approximately the same as during stimulation of the 
 sympathetic, the chorda saliva becomes practically identical in 
 composition with the sympathetic saliva. This is one reason, 
 perhaps the chief one, why the sympathetic, when both nerves are 
 stimulated together, without artificial interference with the blood- 
 supply, always appears to add something to the common secretion 
 when there is a secretion at all, this something being represented 
 by an increase in the percentage of organic matter. The observation 
 that the sympathetic effect persists after stimulation has been 
 stopped, and that excitation of the chorda after previous stimula- 
 tion of the sympathetic causes a flow of saliva richer in organic 
 matter than would have been the case if the sympathetic had not 
 been stimulated, has long been considered a proof that the secretory 
 hbres of the two nerves are widely different in function. To explain 
 this result, Heidenhain assumed the existence in the sympathetic 
 of a preponderance of fibres concerned in the building up in the 
 cells of the organic constituents of the saUva (so-called ' trophic,' 
 or, better, since the word ' trophic ' is usually associated ^vith the 
 building up of the bioplasm itself, ' trophic-secretory ' fibres). It 
 would seem, however, that the increase in organic constituents is 
 only reahzed when a sufficient time has not been allowed, after 
 stimulation of the S3'mpathetic, for the normal circulation to become 
 re-established in the gland. The saliva obtained by stimulation of 
 
396 DIGESTJON 
 
 the churda immediately after a period of artificially diminished 
 blood-flow, without any previous excitation of the bympathetic, 
 also contains a surplus of organic matter (Carlson). 
 
 Indeed, the distinction between chorda and sympathetic saliva, 
 which, by taking account of the parotid as well as the submaxillary 
 and sublingual glands, has been generalized into a distinction 
 between cerebral and sympathetic saliva, and which, when the 
 vaso-motor conditions arc left out of account, appears to hold good 
 in the dog and the rabbit, breaks down before a wider induction. 
 For in the cat the sympathetic sahva of the subma.xiilary gland, 
 although more scanty, is more watery than the chorda saliva 
 (Langley), which, however, is by no means viscid; and the two 
 secretions differ far less than in the dog. The discovery of Carlson 
 that the usual effect of stimulation of the cat's cervical sympathetic 
 with a weak interrupted current is a marked augmentation in the 
 blood-flow* through the submaxillary gland affords an explanation. 
 In accordance with this functional similarity, there is a much 
 smaller difference in the action of atropine on the two sets of fibres 
 in the cat than in the dog, although even in the cat the sympathetic 
 is less readily paratyzed than the chorda. 
 
 In their secretory action there is not even an apparent antagonism 
 in the cat, with minimal stimulation of both nerves, which causes 
 as much secretion as would be produced if both were separately 
 excited. Further, even in the dog, after prolonged stimulation of 
 the sympathetic, the submaxillary saliva is no longer viscid, but 
 watery-, the proportion of solids, and especially of organic sohds, 
 being much lessened, as it is also in chorda saliva after long excita- 
 tion. When the cerebral nerve of the resting gland is strongly 
 excited, it is found that up to a certain limit the percentage of 
 organic matter in a small sample of sali\a subsequently collected 
 during a brief weak excitation increases with the strength of the 
 previous stimulation ; this is also true of the inorganic solids. But 
 there is a striking difference when the experiment is made on a gland 
 after a long period of activity ; here increase of stimulation causes 
 no increase in the percentage of organic material, while the inorganic 
 solids are still increased. In both cases the absolute quantity of 
 water, and therefore the rate of flow of the secretion, is augmented. 
 
 All this points to the same conclusion as the microscopic appear- 
 ances in the gland-cells, that the cells during rest manufacture the 
 organic constituents of the secretion, or some of them, and store 
 them up, to be discharged during activity. The water and the 
 inorganic salts, on the other hand, seem rather to be secreted on 
 the spur of the moment, so to speak, and not to require such 
 elaborate preparation. And it has been stated that when the 
 
 * The increased blcx)d-flow, which can be even better elicited by injection of 
 adrenalin, immediately succeeds the secretion of saliva, and seems to be due 
 not to the presence of vaso-dilator fibres in the sympathetic, but to metabolic 
 products. 
 
IXFLUEXCE OF \ERVOUS SYSTEM O.V DIGESTIVE GEAWDS 307 
 
 chorda tympani is stimulated with currents of varying strength, 
 the quantity of organic substances in small samples of sahva 
 collected from a fresh gland is more nearly proportional to the rate 
 of secretion than is the quantity of water and salts, which varies 
 also with the blood-supplv. 
 
 Lest the apparently insignificant resuh of artificial stimulation 
 of the sympathetic in such animals as the dog should cause its 
 secretory action to be aopraised at too low a value, it should be 
 remembered that in tne mtact body the sympathetic secretory fibres, 
 when they are excited, are, it may be assumed, excited independently 
 of the vaso-constrictors. and even in conjunction with the vaso- 
 dilators of the salivary glands. 
 
 It is conceivable that such differences between chorda and 
 sympathetic saliva as are not accounted for by the differences in 
 the blood-flow during their stimulation are due, not to the nerve 
 fibres, but to the end organs with which they are connected; that 
 is, the two nerves may supply, not the same, but different gland- 
 cells. And it is well known that even after prolonged stimulation 
 of the chorda or chordo-lingual alone, some alveoli of the dog's 
 submaxillary gland remain in the ' resting ' state ; after stimulation 
 of the sympathetic alone, the number of unaffected alveoli is much 
 greater; while after stimulatipn of both nerves, few alveoli seem 
 to have escaped change. If there is no essential difference between 
 the cranial and sympathetic secretory fibres, it is easy to understand 
 that they will be distributed to different secreting elements. The 
 supposed proof that there must be some overlapping in the nerve- 
 supply — i.e., that some cells must be suppUed from both sources, 
 since excitation of the sympathetic influences the amount of organic 
 material in the saliva obtained by subsequent stimulation of the 
 chorda — is, as we have just seen, by no means so cogent as has been 
 assumed. And, indeed, we know nothing of a division of labour 
 between the cells of a gland, except when there are obvious anatom- 
 ical distinctions. Thus, the submaxillary gland in man contains 
 both serous and mucous acini, and mucin-making cells are scattered 
 over the ducts of most glands, and, indeed, on nearly every surface 
 which is clad with columnar epithelium. In these cases we cannot 
 doubt that one constituent — mucin — of the entire secretion is manu- 
 factured by a portion only of the cells. In the cardiac glands of the 
 stomach, too, the ovoid cells, in all probability, yield the whole of 
 the acid of the gastric juice. But, so far as we know, every hepatic 
 cell is a liver in little. Every cell secretes fully- formed bile; every 
 cell stores up, or may store up, glycogen. So it is with the secretory 
 alveoU of the pancreas, if we consider the islands of Langerhans as 
 having no connection with the alveoli; one cell is just Hke another; 
 all apparently perform the same work; each is a unicellular pan- 
 creas. (See p. 638.) 
 
 Paralytic Secretion. — When the chorda tympani is divided, a slow 
 ' paral^-tic ' secretion from the submaxillary gland begins in a few 
 
■?q8 DIGESTION 
 
 hours, and continues for a long time accompanied by atrophy of the 
 gland. There is also a secretion of the same kind from the submaxillary 
 on the opposite side, but it is less copious. This is called the ' antilytic ' 
 secretion, which is most pronounced in the first few days after the 
 operation, and seems to be a transient phenomenon. It can be at once 
 abolished by section both of the chorda and the sympathetic on the 
 corresponding side, ana is therefore due to impulses arising in the 
 central ner^•ous system. The cause of the paral^-tic secretion has not 
 been fully made out. If within two or three days of division of the 
 chorda the sympathetic on the same side is cut. the secretion is greatly 
 diminished or stops altogether; and it is concluded that up to this time 
 it is maintained by impulses passing along the sympathetic to the gland 
 from the salivary centre, the excitability of which has been in some way 
 increased by division of the chorda, possibly by some such degenerative 
 process in the cells as the changes seen in cerebro-spinal motor cells 
 whose axons have been divided (p. 858). This may also account for the 
 antilj^ic secretion. But if section of the sympathetic is not performed 
 for several days, it has no effect on the paralj-tic secretion, which at 
 this stage seems to depend on local changes in or near the gland itself, 
 leading to a mild continuous excitation of those nerve-ceUs on the 
 course of the fibres of the chorda to which reference has already been 
 made. Section of the sympathetic alone causes neither secretion nor 
 atroph}-. nor does removal of the superior cervical ganglion. The 
 histological characters of the gland-cells during paral}i:ic secretion are 
 those of ' rest.' 
 
 Reflex Secretion of Saliva. — The reflex mechanism of salivary 
 secretion is very mobile, and easily set in action by physical and 
 mental influences. It is excited normally by impulses v.'hich arise 
 in the mouth, especially by the contact of food with the buccal 
 mucous membrane and the gustatory nerve-endings. The mere 
 mechanical movement of the jaws, even when there is nothing 
 between the teeth, or only a bit of a non-sapid substance like india- 
 rubber, causes some secretion. The vapour of ether gives rise to a 
 rush of saliva, as does gargling the moutli with distilled water. 
 The smell, sight, or thought of food, and even the thought of saUva 
 itself, may act on the saUvary centre through its connections with 
 the cerebrum, and make 'the teeth water.' A copious flow of 
 saliva, reflexly excited through the gastric branches of the vagus, 
 is a common precursor of vomiting. The introduction of food into 
 the stomach also excites salivary secretion. 
 
 The researches of Pawlow and his pupils have shown that the 
 saUvary glands are not excited indifferently by everything which 
 comes into contact with the buccal mucous membrane. A remark- 
 able adaptation exists between the properties of food or foreign 
 bodies introduced into the mouth and their effects upon the secre- 
 tion of sahva. When solid dry food is given to a dog saliva is 
 copiously poured out; much less is secreted when the food is moist. 
 
 Acids or salts induce an abundant flow, in order that they may 
 be neutralized, diluted or washed out of the mouth. In this case 
 a watery liquid, poor in mucin, flows from the nmcous glands. 
 Mucin is a lubricant to facilitate the swallowing of solid food, and 
 
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 399 
 
 here it could be of no use. When clean pebbles are put in the dog's 
 mouth the animal may try to chew them, but eventually ejects 
 them. Either no saliva or very little is secreted, since it could 
 not aid in their expulsion. If, however, the very same stones are 
 reduced to sand and again introduced into the animal's mouth, 
 saliva is plentifully secreted to wash it out. 
 
 The serous and mucous salivary glands are not necessarily excited 
 by the same food materials, and here again we can trace an astonish- 
 ingly exact adaptation. A permanent parotid or submaxillary 
 fistula can easily be made in a dog by freeing Stenson's or Wharton's 
 duct from the surrounding mucous membrane for a little distance, 
 bringing the natural orifice of the duct out through a small wound 
 in the cheek, and stitching it in position there. When it is desired 
 to collect sahva, the wide end of a funnel-shaped tube, whose stem 
 is bent so as to hang vertically, can be attached by a little shellac 
 of low melting-point to the skin around the orifice of the duct and 
 at some distance from it, and on the naiTow end can be hung a small 
 graduated tube, into which the sahva drops. When fresh meat is 
 given to the animal little or no parotid sahva is secreted, while a 
 copious flow takes place from the submaxillary gland, mucin being 
 required to lubricate it for deglutition, while water is not specially 
 needed. But if the meat is in the form of a dry powder the parotid 
 pours out a plentiful secretion, while the submaxillary also secretes 
 a fluid relatively rich in mucin. The same difference is seen between 
 fresh moist bread and dry bread. The afferent nerve-endings from 
 which impulses are carried to the reflex centres (or the portions of 
 the salivary centre) which preside over the various salivar\' glands 
 must possess the power of very delicate selection as regards the 
 kinds of stimulation b}' which they are affected. The mere relish 
 of the animal for the different kinds of food plays but a small part. 
 Most dogs display a much livelier interest in a piece of meat than 
 in a piece of dry biscuit, yet it is the biscuit which excites the parotid 
 to activity. 
 
 The sight of dry food causes an abundant flow of vi^atery saliva 
 from the parotid, and a flow of fluid rich in mucin from the sub- 
 maxillary. Various uneatable substances, including substances 
 which in contact with the mucous membrane of the mouth produce 
 strong and disagreeable stimulation of it, and excite disgust, cause 
 also, when viewed from a distance, secretion by all the salivary 
 glands; but the submaxillary saliva, as ought to be the case for 
 substances unfit for food, and therefore not destined to be swallowed, 
 is poor in mucin. When the animal is shown pebbles and sand 
 the phenomena are qualitatively the same as when they are put 
 into its mouth — the glands remaining inactive in presence of 
 the pebbles, but secreting plentifully at sight of the sand. In 
 short, the same adaptation is observed in the case of the so-called 
 psychical secretion as when the stimulating substances act directly 
 
400 DIGEST lOS 
 
 upon the endings of the afferent salivary nerves in the huecal 
 mucous membrane. It is further worthy of note that when the 
 animal is hungry the psychical secretion is most copious and most 
 easily obtained. Aft(;r a full meal it cannot be excited at all. 
 When food (or other exciting sul>stance) is repeatedly shown to a 
 fasting animal the reaction Ix'comes each time weaker, and finally 
 the glands cease to respond. All that is then necessary to restore 
 the reaction is to put into the animal's mouth a little of the food 
 (or other object). When it is now shown it at a distance the ordinary 
 effect follows promptly. This indicatt^s that the condition of the 
 salivary centre exercises an important inllumce upon the psychical 
 secretion, its excitability to the weaker stimulus set up by the sight 
 of the object being increased by the stronger reflex stimulation 
 coming directly from the mouth. In the condition of satiety the 
 inexcitability of the centre may be du(? to the action of food- 
 products in the blood. 
 
 In most animals and in man the activity of the large salivary 
 glands is strictly intermittent. But the smaller glands that stud 
 the mucous membrane of the mouth never entirely cease to secrete, 
 and the same is the case with the parotid in ruminant animals. 
 
 The centre is situated in the medulla oblongata, stimulation of 
 which causes a flow of saliva. The chief afferent paths to the 
 salivary centre are the Hngual branch of the fifth and the glosso- 
 pharyngeal; but stimulation of many other nerves may cause reflex 
 secretion of saliva. In experimental reflex stimulation, the sole 
 efferent channel seems to be the cerebral nerve-supply of the glands. 
 After section of the chorda, no reflex secretion by the submaxillary 
 gland can be caused, although the sympathetic remains intact. 
 
 It was alleged by Bernard that, after division of the chordo- 
 lingual, a reflex secretion could be obtained from the submaxillary 
 gland by stimulating the central end of the cut lingual nerve between 
 the so-called submaxillary ganglion and the tongue, the ganglion 
 being supposed to act as ' centre.' It has been shown, however, that 
 this is not a true reflex effect, but is due to the excitation of certain 
 (recurrent) secretory fibres of the chorda that run for some distance 
 in the lingual, then bend back on their course and pass to the gland. 
 It may be in part a pseudo- or axon-reflex (p. 91.3), ehcited by 
 excitation of efferent fibres, which send branches to some of the 
 ganglion-cells. 
 
 The salivary centre can also be inhibited, especially by emotions 
 of a painful kind — for instance, the nervousness which often dries 
 up the saliva, as well as the eloquence, of a beginner in public 
 speaking, and the fear which sometimes made the medieval ordeal 
 of the consecrated bread pick out the guilty. 
 
 In rare cases the reflex nervous mechanism that governs the 
 salivary glands appears to completely break down; and then two 
 opposite conditions may be seen — xerostomia, or ' dry mouth,' in 
 
IKFLVENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 401 
 
 which no sahva at all is secreted, and chrunie ptyaHsni, or hydro- 
 i^iomia, where, in the absence of any discoverable cause, the amount 
 of secretion is permanently increased. Both conditions are said 
 to be more common in women tlian in men. 
 
 The Influence of Nerves on the Gastric Glands.— Like saliva, gastric 
 juice is not secreteil continuously, except in animals such as the 
 rabbit, whose stomachs are never empty. The normal and most 
 efficient stinmlus is the eating of food and its presence in the 
 stomach. Mechanical stimulation of the gastric mucous membrane 
 with a non-digestible substance, such as a feather or a glass rod, 
 causes secretion of mucus, but not of gastric juice. But the 
 observations mentioned above on the difference of response of the 
 salivary glands to different substances suggest that the local mechan- 
 ical stimulation of the food on the gastric glands may be more 
 effective. There is also at first thought much to indicate that the 
 gastric glands are stimulated chemically in a more direct manner 
 than the saliv^ary glands by the local action of food substances 
 reaching the cells by a short-cut from the cavity of the stomach, 
 or in a more roundabout way by the blood. And it might be very 
 plausibly argued that the gastric glands are favourably situated 
 for direct stimulation, while the large salivary glands are not; and 
 that the great function of saliva being to aid deglutition, an almost 
 momentary, and at the same time a perilous act, it is necessary to 
 provide by a nervous mechanism for an immediate rush of secre- 
 tion at any instant, while it is not important whether the gastric 
 juice is poured out a little sooner or a little later, and therefore it is 
 left to be called forth by the more tardy and haphazard method of 
 local action. Nevertheless, on looking a little closer, we find that 
 this does not exhaust the subject, and that the gastric secretion 
 can be influenced by events taking place in distant parts of the 
 body, just as the salivary secretion can. In a boy whose oesophagus 
 was completely closed by a cicatrix, the result of swallowing a strong 
 alkah, and who had to be fed by a gastric fistula, it was found 
 that the presence of food in the mouth, and even the sight or smell 
 of food, caused secretion of gastric juice (Richet). 
 
 Here there must have been some nervous mechanism at work. 
 The secretion cannot have been excited by the direct action of 
 absorbed food-products circulating in the blood — ^an explanation 
 which might be given, though an insufficient one, of the secretion 
 seen in an isolated portion of the cardiac end of the stomach during 
 the digestion of food in the rest. The efferent nervous channels 
 through which these effects are produced have been defined by 
 Pawlow's experiments on dogs. He first made a gastric fistula, 
 then a few days afterwards divided the oesophagus through a 
 wound in the neck, and stitched the two cut ends to the edges of 
 the wound. After the animals had recovered, it was observed that 
 when meat was given to them by the mouth, a copious secretion of 
 
 <:6 
 
402 
 
 DIGESTION 
 
 Pylorus 
 
 P/exus gastricu. 
 anterior veg, ' 
 
 sophagus 
 
 Plexus gastricus 
 oosterior vagi 
 
 gastric juice folldwrd in five or six minutes, notwithstanding thi- 
 fact that in this ' sham feedinf^ ' the food inunechately escaped from 
 the opt-ning in the upper portion of tlie divided (esophagus. Much 
 the same result was seen when the food was simply shown to the 
 animal. Indeed, when a hungry animal is tempted with the sight 
 of meat, the flow of gastric juice, always occurring after a latent 
 period of five or six minutes, may be even greater than with sham 
 feeding. Division of the splanchnic nerves had no effect on this 
 reflex secretion, while it could not be obtained after division of both 
 vagi below the origin of their cardiac and pulmonary branches, by 
 which disturbance of the heart and respiration are avoided. 
 Further, stimulation of the peripheral end of the vagus in the neck* 
 caused secretion. These experiments show that secretory fibres 
 for the gastric glands run in the vagi. It is probable that the vagi 
 
 also contain 
 efferent fibres 
 which inhibit 
 the gastric 
 secretion. The 
 excitation of 
 the secretory 
 fibres is not 
 produced re- 
 flexly by the 
 processes of 
 mastication 
 and deglutition 
 as such. Di- 
 lute acid is the 
 most powerful 
 chemical stim- 
 ulus for the 
 buccal mucous 
 membrane, and 
 
 when it is introduced into the mouth of a dog with a double 
 oesophageal and gastric fistula, an abundant secretion of saliva at 
 once ensues. But no matter how long the animal continues to 
 swallow the mixture of saliva and acid, no gastric juice is formed. 
 The same is the case in sham feeding with salt, pepper, mustard, 
 smooth stones, and even extract of meat. It is the desire for food 
 — the appetite, as we call it — and the feeling of satisfaction associa- 
 ated with eating food that the animal relishes, which is the efficient 
 cause of the gastric secretion in sham feeding. The more eagerly 
 the dog eats, the greater is the flow of gastric juice. 
 
 * The nerve was not stimulated till a few days after the section, so as to 
 allow the cardio-inhibitory fibres to degenerate. Otherwise the heart would 
 have been stopped by the stimulation. 
 
 Fig. i6i. — Pawlow's Stomach Pouch. AB, line of incision; 
 C, flap for forming the stomach pouch. At the base of the 
 flap the serous and muscular coats are preserved, and only 
 the mucous membrane divided, so that the branches of the 
 vagus going to the pouch are not severed. 
 
Muscularis 
 
 INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 403 
 
 Pawlow also performed the converse experiment. In dogs in 
 which a pouch had been isolated from the stomach and made to 
 open to the exterior by the surgical procedure illustrated in Figs. 161 
 and 162, he introduced into the large stomach, without the animal's 
 knowledge, food of various kinds. This is best done in a sleeping 
 dog. The secretion of gastric juice, both in the main stomach and 
 in the pouch or miniature stomach, which is known in a great 
 variety of conditions to present an exact picture of the process of 
 secretion in the large, is markedly delayed and scanty when it does 
 appear. Bread and coagulated egg-white did not yield a single 
 drop during 
 the first hour 
 or more. Raw 
 flesh excited a 
 secretion, but 
 after an inter- 
 val of fifteen 
 to forty - five 
 minutes, in- 
 stead of five 
 or six to ten, 
 as in sham 
 feeding. It was 
 very scanty 
 during the 
 first hour 
 (only one- 
 third the nor- 
 mal amount), 
 and possessed 
 a very low di- 
 gestive power. 
 The impor- 
 tance of the 
 psychical ele- 
 ment is shown by the fact that in one dog, which, after a weighed 
 amount of meat had been introduced into its stomach (without its 
 knowledge) , received a sham meal of meat, the amount of protein 
 digested after one and a half hours was five times greater than in 
 another animal treated exactly in the same way, except that the sham 
 meal was omitted. But even after division of the vagi, gastric secre- 
 tion is still caused by the introduction of various substances into the 
 stomach, especially water and meat extract. The active substances 
 in the meat extract are, for the most part, insoluble in alcohol. 
 Kreatin is inactive. It is in virtue of these substances that raw 
 meat placed directly in the stomach causes some secretion after a 
 
 Fig. 162. — Pawlow's Stomach Pouch. S. the completed pouch; 
 V, cavity of stomach. 
 
404 DIGESTION 
 
 time. Milk and gelatin solution are also direct excitants of gastric 
 secretion apart from the water in them. Starch, fat, and egg-white 
 are totally inert. After section of both vagi in dogs, no marked 
 qualitative or quantitative changes have been observed in the 
 gastric juice. The secretion caused by the presence of food in the 
 stomach is still obtained when, in addition to the vagi, all other 
 nerves which can possibly connect the central nervous system with 
 the organ have been severed and the sympathetic abdominal 
 plexuses have been destroyed (Popielski). We must therefore sug- 
 pose that the gastric glands, while normally under the control of a 
 nervous mechanism in the upper portion of the cerebro- spinal axis 
 whose efferent fibres run in the vagi, are also capable of being locally 
 stimulated through i the peripheral ganglia in the stomach walls or 
 the chemical action of the products of digestion absorbed into the 
 blood. Edkins showed that the injection of food substances or the 
 products of their digestion (broth, dextrin, peptone) or of acid into 
 the blood caused no secretion of gastric juice, while the injection 
 of an extract of the pyloric mucous membrane, made by boiling it 
 with water, acid, or peptone, excited a certain amount of secretion. 
 He therefore concluded that the secondary secretion of gastric juice 
 is determined, not by local stimulation of a reflex mechanism in the 
 gastric wall, but by the production in the mucous membrane of the 
 pyloric end of a chemical substance, the gastric secretin or gastric 
 hormone,* which is absorbed by the blood, and acts as an excitant 
 to all the gastric glands. The cardiac mucosa was found incapable 
 of forming this substance. 
 
 It is not to be imagined that the ' psychical ' secretion and the 
 secretion called forth by the direct action of the food or food- 
 products in the stomach perform independent offices. They can, 
 in various instances, be shown to supplement each other. For 
 example, not more than one-half or one-third of the gastric juice 
 secreted during the digestion of bread or boiled egg-albumin can 
 be ascribed to the psychic effect. Yet these substances, when 
 introduced directly into the stomach, cause practically no secretion. 
 We must suppose that during the digestion of the bread and albu- 
 min by the psychically secreted juice certain products analogous to 
 those in the meat extract are formed, which act as chemicd excitants 
 of the local secretory apparatus. The psychic juice is indispensable 
 in this case to start the process, ' to set the stove ablaze,' as Pawlow 
 puts it. In the case of meat it is not indispensable, since the meat 
 can chemically excite the gastric glands; but it greatly hastens the 
 process of digestion. These facts emphasize the importance of 
 
 * ' Hormone ' (from opfiaw, I arouse or excite) is the name given to a sub 
 stance which, carried by the blood from the place where it is formed, acts a.s 
 a chemical messenger in exciting the activity of some more or less distant 
 organ. The classical example is the pancreatic secretin which, manufactured 
 in the intestinal mucosa, excites the secretion of the pancreatic juice. 
 
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS i(05 
 
 appetite in digestion, a truism in treatment which thus receives 
 for the first time a rational explanation. The influence of good- 
 humour upon nutrition, which experience has crystallized into the 
 proverb ' Laugh and grow fat,' has also been shown to depend — 
 in great part, at least — upon a beneficial action on the digestive 
 functions, both motor and chemical. The movements of a cat's 
 stomach and intestines have been observed to cease when the 
 animal became angry or excited by unpleasant emotions; and in a 
 dog wliose gastric glands were pouring out a copious psychical 
 secretion in response to a sham meal, secretion stopped abruptly 
 when the animal's wrath was awakened by what is probably to the 
 normal dog the most specifically ' adequate ' stimulus for the emotion 
 of anger — the sight of a cat which he was restrained from chasing. 
 
 By means of experiments with the miniature stomach it has been 
 further shown that each kind of food has its own characteristic 
 curve of gastric secretion. With flesh diet the maximum rate of 
 secretion occurs during the first or second hour, and in each of the 
 first two hours the quantity of juice furnished is approximately 
 the same. With bread diet we have always a sharply-indicated 
 maximum in the first hour, and with milk a similar one during the 
 second or the third hour (Fig. 163). The juice secreted on different 
 chets also differs in digestive power — i.e., in the amount of protein 
 which a given quantity of it will digest in a given time. ' Bread 
 juice ' is much stronger in ferment than ' meat juice,' and ' meat 
 juice ' somewhat stronger than ' milk juice ' (Fig. 164). But 
 ' meat juice ' has a higher acidity than ' bread juice,' ' milk juice ' 
 being intermediate. These differences do not necessarily indicate 
 that the gastric mucous membrane responds in a specific way to 
 each kind of food substance, as suggested by Pawlow. They may 
 depend on several circumstances, and particularly on this — that the 
 quantity, though not the quality, of the psychical or ' appetite ' 
 juice is related to the relish with which the animal eats the food. 
 The products formed in the digestion of the different foods by the 
 psychical juice may therefore be different in nature and amount, 
 and thus the quantity of the gastric hormone which determines the 
 secondary secretion may vary with the food. 
 
 The young mammal, like the adult, secretes gastric juice before 
 the food reaches the stomach. In puppies from one to eighteen 
 days old sham feeding (sucking the teats of the mother after an 
 oesophageal fistula has been made in the younger animals and a 
 double oesophageal and gastric fistula in the older) causes a liquid 
 with the properties of gastric juice to gather in the stomach. This 
 power, then, is a congenital one. The individual does not gain it 
 by experience; it comes into the world with him (Cohnheim). 
 
 The Influence of Nerves on the Pancreas. — Like the stomach, the 
 pancreas receives secretory fibres through the vagus. These are 
 
4o6 
 
 DIGESTION 
 
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 Xj 
 
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 — 
 
 
 Flesh, 200 grm. 
 
 Bread, 200 grm. 
 
 Milk, 600 c.c 
 
 Fig. 163. 
 
 -Rate of Secretion of Gastric Juice with Diets of Meat, 
 Bread, and Milk (Pawiow). 
 
 probably connected with a reflex centre in the medulla oblongata. 
 It has long been known that when the medulla is stimulated a flow 
 of pancreatic juice is occasionally set up, or is increased if already 
 going on. The same is true when the vagus is stimulated in the 
 ordinary way in the neck. But the experiment often failed, for 
 
 the pancreas 
 is peculiarly 
 susceptible 
 to circulatory 
 disturbances, 
 and stimula- 
 tion of the 
 bulb or the 
 vagus may 
 interfere with 
 the blood- 
 flow through 
 the gland by 
 exciting its 
 vaso-con- 
 strictor fibres or causing inhibition of the heart. These disturbing 
 influences may be avoided, as Pawiow has shown, by stimulating the 
 vagus, three or four days after dividing it, with slowly-recurring 
 stimuh (induction shocks or light blows from a small hammer 
 worked by an 
 electro - mag- 
 net at the 
 rate of about 
 one in the 
 second). The 
 secretory 
 fibres are still 
 susceptible of 
 excitation, 
 while the car- 
 dio-inhibitory 
 fibres, which 
 degenerate 
 more rapidly, 
 are almost or 
 altogether in- 
 excitable, and the vaso-constrictors are but little affected by 
 these slow rhythmical stimuli, which excite the secretory nerves 
 (p. 175). A pancreatic fistula has previously been established by 
 excising a small portion of the duodenal wall containing the open- 
 ing of the pancreatic duct, closing the intestine by sutures, and 
 
 Hours I 2 
 10.0 
 
 345678234 567 
 
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 2 3 4 5 6 
 
 
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 !• lesh, 200 grm. 
 
 Bread, 200 grm. 
 
 Milk, 600 c.c. 
 
 Fig. 164. — Digestive Power of Gastric Juice (Pawiow). The 
 digestive power of the juice, as measured by the length of the 
 protein column digested in Mett's tubes, is represented hour by 
 hour, Mth diets of flesh, bread, and milk. 
 
INFLUENCE OF NER VOUS SYSTEM ON DIGESTI VE GLANDS 407 
 
 stitching the orifice of the duct into the abdominal wound. On 
 stimulation of the vagus the juice will begin in two to three minutes 
 to drop from a cannula in the duct, and will continue to flow for 
 several minutes after cessation of the stimulus. The sympathetic 
 also contains secretory fibres for the pancreas. Efferent fibres 
 which inhibit the secretion have been also discovered in the vagus. 
 Their presence may be most clearly demonstrated when that nerve 
 is stimulated during the flow of pancreatic juice excited by the 
 introduction of dilute acid into the duodenum. Stimulation of the 
 central end of the vagus and of the other nerves is capable of 
 reflexly inhibiting 
 the pancreatic secre- 
 tion. Painful im- 
 pressions have a 
 strong inhibitory in- 
 fluence. This is one 
 of the reasons why 
 many observers 
 failed to detect the 
 secretory nerves. 
 The inhibition 
 caused by vomiting 
 is probably due to 
 impulses ascending 
 the vagus. It is pos- 
 sible that through 
 these nervous chan- 
 nels the pancreatic 
 secretion is affected 
 by the psychical con- 
 ditions connected 
 with eating and the 
 desire for food, just 
 as in the case of the 
 gastric secretion ; but 
 our information on 
 this subject is scantier and less precise. A flow of juice may un- 
 doubtedly take place within three or four minutes after food is taken, 
 but it is not quite certain whether this is not determined by the 
 passage of some of the acid gastric contents into the duodenum. 
 
 Secretin.— We have already referred to the fact that pancreatic 
 secretion is excited by the presence of acid in the duodenum. The 
 mechanism of this action is of great interest. Two or three minutes 
 after the introduction of 04 per cent, hydrochloric acid into the 
 duodenum, pancreatic juice begins to flow. A similar effect is seen 
 when the acid is placed in the jejunum, but not when it is injected 
 
 Fig. 165. — Secretion of Pepsin. C shows the quantity 
 of pepsin(ogeii) in the mucous membrane of the 
 cardiac end of the stomach at different times during 
 digestion; P, the quantity of pepsin(ogen) in the 
 mucous membrane of the pyloric end; S, the quantity 
 of pepsin in the secretion of the cardiac glands. The 
 numbers marked along the horizontal axis are hours 
 since the last meal. About five hours after the 
 meal, S reaches its maximum. From the very be- 
 ginning of the meal C falls steadily down to the 
 tenth hour, and then begins to rise — i.e., the gland- 
 cells of the cardiac end of the stomach become 
 poorer in pepsin(ogen) as secretion proceeds. 
 
408 DIGESTION 
 
 into tlie lower part of the iloum. It is obtained as stronp;ly and as 
 promptly from an isolated loop of intistine when all the nerves 
 passing to it have been cut, and the solar plexus extirj)ated, and also 
 after the administration of atropine, wliich paralyzes the endings of 
 secretory nerves elsewhere. The secretion accor lingly does not 
 depend upon a local reflex mechanism, with its afferent endings in 
 the intestinal mucous membrane, but upon some substance which is 
 carried to the pancreas by the blood, and acts directly upon its cells. 
 This substance is not the acid, for the injection of 04 per cent, 
 hydrochloric acid into the blood produces no effect upon the pan- 
 creas. It has been shown by Bayliss and Starling that the exciting 
 substance is a diffusible body of low molecular weight, probably of 
 organic natuie, but not a protein, which the}' call sccrelin. It is 
 soluble in alcohol or alcohol and ether, and is not flestroyed by 
 boiling. It is produced in the mucous membrane of the jejunum or 
 duodenum on exposure to dilute hydrochloric acid. Extracts of 
 mucous membrane so treated cause a copious pancreatic secretion, 
 and a smaller secretion of bile, when injected in small quantities into 
 the blood of animals in which no such secretion is taking place, but 
 have no influence on any other gland. At the same time the arterial 
 blood-pressure falls somewhat. The substance which produces the 
 fall of blood-pressure is different from secretin, since acid extracts 
 of the lower end of the ileum, which have no effect on the flow of pan- 
 creatic juice, diminish the blood-pressure. A precursor of secretin, 
 called prosecretin, exists in the intestinal mucous membrane, and 
 can be extracted from it b}' physiological salt solution. It dnes not 
 affect the pancreatic secretion. By boiling or by the action of acid 
 secretin is split off from it. Pro-secretin is most abundant in the 
 duodenum, and diminishes as we pass down the intestine. 
 
 Secretin is very widespread in the animal kingdom. In the 
 monkey, dog, cat, rabbit, man, ox, sheep, pig, squirrel, goose, 
 tortoise, salmon, dog-fish, and skate evidence of its presence has 
 been obtained. The secretin of one animal will excite a flow of pan- 
 creatic juice in an animal of a different kind as well as in one of the 
 same kind. In normal digestion secretin is formed under the 
 influence of the acid chyme, not in the stomach, but after it has 
 passed into the duodenum. The passage of the chyme tlirough the 
 pylorus, as previously mentioned (p. 337), is regulated by the re- 
 action of the duodenal contents, as well as by the consistence of the 
 gastric contents. vSo long as the liquid in the duodenum is acid, the 
 pylorus remains closed. As soon as the first small portion of acid 
 chyme ejected from the stomach has been neutralized by the in- 
 creased secretion of the pancreatic juice and the outpouring of bile 
 from the gall-bladder in response to the stimulus of the acid, the 
 pylorus opens again. 
 
 According to Pawlow, certain food substances, notably fat, and 
 
hWFLUENCE OF NER VOUS SYSTEM O.V DIGESTI VE GLA NDS 409 
 
 water stimurate the pancreatic secretion, and with great promptness, 
 even before any acid has been produced in the stomach, and there- 
 fore before any can have passed into the duodenum. Possibly this 
 effect is ehcited through the lon^ rcfiex paths already described as 
 running in the vagi or through a local nervous mechanism, which, 
 although it does not take part in the excitation of the pancreatic 
 secretion by acid, may yet exist for the performance of other offices. 
 It is more probable, however, that it is due to the passage of some of 
 the gastric contents through the pylorus; for when oil is introduced 
 into the small intestine, it causes the production of secretin, although, 
 unhke dilute acid, it is quite ineffective in forming secretin when 
 rubbed up with the scraped-off mucous membrane. That secretin 
 acts on the pancreatic cells in a different way from the secretory 
 nerve fibres contained in the vagus is indicated by the difference in 
 the characters of the juice secreted under the influence of the two 
 mechanisms. The nervous secre- 
 tion is thick and opalescent, rich 
 in enzymes, including trypsin in 
 the active form, and proteins, but 
 its alkaU content is low. Like 
 other secretions excited through 
 nerves, it is inhibited by atropine. 
 The chemical secretion due to 
 secretin, is thin and watery, rich F"ig- 166.— Rate of Secretion of Pan- 
 
 11 1- • , • J creatic Juice. S shows the variation 
 
 in alkalies, poor m protems and i„ ^^e rate of secretion of the pan- 
 
 in enzymes, and among the latter, creatic juice in a dog; p. the varia- 
 
 trypsin occurs only in the inactive ^io^i i" ^^e percentage of solids in 
 
 r /c > -ux ^^^ juice. It will be seen that the 
 
 lOrm ^bawiTSCnj. maxima of S fall at the same time 
 
 The pancreatic, like the gastric, as the maxima of p. The numbers 
 
 juice is said to vary as regards ^lo°g ^^^ horizontal axis are hours 
 
 ., J- , ■ , • -,1 .-t since the last meal, 
 
 its digestive properties with the 
 
 nature of the food. On a diet of bread the juice is very poor 
 in fat-splitting ferment, while on a diet of flesh it is richer, and 
 on a diet of milk richest of all. With bread the juice is relatively 
 rich in amylolytic ferment. When we take the quantity of the 
 juice as well as its strength in ferments into consideration, it is 
 stated that bread occasions the secretion of a juice with a greater 
 quantity of proteolytic ferment than either milk or meat, although 
 it is relatively dilute (Fig. 169). The vegetable proteins require 
 more ferment to digest them than proteins of animal origin. There 
 is no more evidence that the adaptation of the pancreatic juice to the 
 nature of the food is due to a specific sensibility of the duodenal 
 mucosa to the various food-stuffs than there is in the case of the 
 adaptation of the gastric juice. If the volume of the chyme and its 
 acidity are related to the nature of the food, then the amount of 
 secretin formed, and therefore the intcnsitv of secretion in the 
 
410 
 
 DIGESTION 
 
 I II III IV V I II 111 IV V VI vn viii 1 n in IV v vi 
 
 pancreas, will be similarly related. The one apparently proved 
 example of specific adaptation of the pancreatic juice has not stood 
 the test of a critical examination. It was asserted that in dogs fed 
 for some days with food containing lactose (milk) the ferment, 
 lactase, is present in that secretion, while the pancreatic juice of 
 dogs whose food is free from lactose does not contain lactase. The 
 adaptation of the pancreas to lactose was supposed to be achieved 
 through some substance produced by the action of lactose on the 
 
 intestinal mucous 
 membrane, which 
 plays the part of 
 a specific chemical 
 stimulus to the 
 pancreatic cells or 
 their secretory 
 nervous mechan- 
 ism, causing them 
 Xo form lactase. 
 But it has been 
 conclusively shown 
 that when dogs 
 are fed with lac- 
 tose for weeks no 
 lactase appears in 
 the pancreatic 
 juice (Phmmer). 
 
 The natural se- 
 cretion of pan- 
 creatic juice is by 
 no means so inter- 
 ]iiittent as that of 
 saliva. In the rab- 
 bit the pancreatic, 
 like the gastric, 
 juice flows con- 
 tinuously. In the 
 dog it begins al- 
 most as soon as 
 a maximum, then 
 
 Flesh, loo grm. Bread, 250 grm. 
 
 Milk, 600 grm. 
 
 Fig. 167.— Secretion of Pancreatic Juice with Different 
 Diets (Pawlow). The hours are in roman numerals. 
 
 food is taken, rises in two or three hours to „ ...«^,,.^.„ ,,,cii 
 falls tiU the fifth or sixtli hour, after which it may mount 'again 
 somewhat, and then, gradually diminishing, ultimatelv stops (Figs 
 166, 167). During normal activity the bloodvessels of 'the gland are 
 dilated. But under experimental conditions the increased secretion 
 caused by secretin is accompanied sometimes by an increase and 
 sometimes by a diminution in the blood- flow, and secretion may 
 continue for some time after complete cessation of the circulation 
 
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 411 
 
 while the increased consumption of oxygen which goes hand in hand 
 with the increased secretion is also independent of the blood-supply 
 (May, Barcroft and Starling). This shows how far the secretory pro- 
 cess is from a mere mechanical filtration, although it does not follow 
 that, under normal conditions, a decreased blood-flow ever does 
 accompany an increased secretion. There is one difference between 
 the normal secretion of pancreatic juice and of saliva which may still 
 be mentioned : the pressure of the latter in the submaxillary duct may, 
 as we have seen, greatly exceed the arterial blood-pressure, without 
 reabsorption and consequent oedema of the gland occurring; but the 
 secretory pressure of the pancreatic cells is very low, not more than 
 a tenth of that of the salivary glands. 
 (Edema begins before a manometer in 
 the duct shows a pressure of 20 mm. 
 of mercury, the secreted fluid passing 
 very easily into the lymph spaces. 
 
 The mutual relations of the spleen 
 and pancreas have formed the subject 
 of numerous inquiries. Some authors 
 maintain that the spleen plays an im- 
 portant role in the elaboration of the 
 proteolytic ferment of the pancreas, 
 forming a substance which we may call 
 pro-trypsinogen, since it is supposed to 
 be carried in the blood to the pancreatic 
 cells, and changed by them into trypsin- 
 ogen. There is some evidence that 
 extracts of the spleen prepared from it 
 when congested during digestion exert a 
 favourable influence on the proteolytic 
 power of the pancreas (Mendel). And 
 there is no doubt that the spleen, hke 
 other organs, contains an intracellular 
 enzyme which can aid in the digestion 
 of protein. The products of the action 
 in an acid medium of this enzyme are the same as those formed by 
 trypsin in an alkaline medium (Leathes). But this is not enough to 
 prove that the spleen has any special relation to pancreatic digestion. 
 
 The Influence of Nerves on the Secretion of Bile. — Although bile is 
 secreted constantly, it only passes at intervals into the intestine. 
 For the liver in many animals, unlike every other gland except the 
 kidney, has in connection with it a reservoir, the gall-bladder, in 
 which its secretion accumulates, and from which it is only expelled 
 occasionally. We have therefore to distinguish the bile-secretion 
 from the bile-expelhng mechanism. To study the rate of secreting 
 of bile (Fig. 168), a fistula of the gall-bladder can be estabhshed. 
 
 Fig. 168.— Rate of Secretion of 
 Bile. S show-s how the rate of 
 secretion of bile falls in a dog 
 when a biliary fistula is first 
 made, and the bile thus pre- 
 vented from entering the intes- 
 tine ; P shows the fall of the per- 
 centage of solids. The numbers 
 along the horizontal axis are 
 quarters of an hour since bile 
 began to escape through the 
 fistula. The numbers along 
 the vertical axis refer only to 
 curve S, and represent the rate 
 of secretion in arbitrary units. 
 
412 DIGESTION 
 
 But to learn the function of bile in digestion it is more important 
 to know when and at what rate it enters the intestine. For tliis 
 purpose a fistula is made by cutting the natural orifice of the common 
 bile-duct with a piece of the surrounding mucous membrane out of 
 the intestine and transplanting it upon the serous coat, where it is 
 sutured. The loop of intestine, with the orifice of the duct facing 
 outwards, is then stitched into the abdominal wound, where it is 
 allowed to heal. Of course, since a circulation of the bile-acids 
 takes place — i.e., an absorption from and re-excretion into the 
 intestine — the formation of that juice cannot proceed upon abso- 
 lutely normal lines when the bile no longer enters the duodenum. 
 The only condition under which fistula bile could have the same 
 composition as normal bile would be that in which as great an 
 amount of bile-acids is introduced into the gut as escapes through 
 the fistula. A circulation of a smaller proportion of the bile-pig- 
 ments is also probable. A circulation of the biliary cholesterin is 
 denied by some observers (Stadelmann) but affirmed by others. It 
 is certain that cholesterin is of importance in the body, and if the 
 supply of sterins (p. 570) in the food is insufficient it is to be sup- 
 posed that some of the biliary cholesterin would be used over again. 
 
 Of the direct influence of nerves, either on the secretion of bile or on 
 its expulsion, we have scarcely any knowledge, scarcely even any guess 
 which is worth mentioning here. It is true the secretion of bile may 
 be distinctly affected by the section and stimulation of nerves which 
 control the blood-supply of the stomach, intestines, and spleen, for the 
 quantity of blood passing by the portal vein to the liver depends upon 
 the quantity passing through these organs, and the rate of secretion is 
 diminished when the blood-supply is greatly lessened. In this way 
 stimulation of the medulla oblongata, the spinal cord, or the splanchnic 
 nerves stops or slows the secretion of bile by constricting the abdominal 
 vessels; and the same effect can be reflexly produced by the excitation 
 of afferent nerves. 
 
 The right splanchnic nerve contains inhibitory with some motor 
 fibres, and the vagi (especially the left) contain motor fibres for the 
 gall-bladder. Probably its contraction takes place naturally in 
 response to reflex impulses from the mucous membrane of the duo- 
 denum, for the apphcation of dilute acid to the mouth of the bile- 
 duct causes a sudden flow of bile,* and the acid contents of the 
 stomach, when projected through the pylorus into the intestine, 
 have a similar effect. But, in addition, as we have seen, the secretin 
 formed will cause an increase in the rate of secretion of the bile. In 
 studying the effect of secretin it is necessary to obtain it free from 
 bile-salts, since these cause of themselves an increased secretion of 
 bile. When this is done by dissolving out with alcohol any bile-salts 
 which may be present in the extract of intestinal mucous membrane, 
 
 ♦ This result seems to be difficult to realize experimentally. Bainbridge 
 and Dale could not elicit reflex contraction of the gall-bladder (in anaesthetized 
 animals) in this way. 
 
INFLUE.WCE OF XER VOUS S YSTEM ON DIGESTI VE GLASDS 413 
 
 a solution of the residue containing the secretin still evokes a rapid 
 secretion of bile. The fact that the same hormone excites the 
 formation both of pancreatic juice and bile is obviously related to 
 that common action of the two juices in digestion on which we have 
 already dwelt. 
 
 When food passes into the stomach, there is at once a sharp rise in 
 the rate of secretion of bile. A maximum is reached from the fourth 
 to the eighth hour — that is, while the food is in the intestine. There 
 is then a fall, succeeded by a second smaller rise about the fifteenth 
 or sixteenth hour, from which the secretion gradually declines to its 
 minimum. Upon the whole, the curves of secretion of pancreatic 
 juice and bile show a fairly close correspondence, except that the 
 latter is more nearly continuous. But when we compare the curves 
 lepresenting the rate at which the bile actually enters the intestine 
 with the curve of pancreatic secre- 
 tion (Fig. 169), we are struck by 
 their almost absolute parallelism. 
 This lends additional support to 
 the conclusion deduced from their 
 chemical and physical properties, 
 that in digestion they are partners 
 in a common work. 
 
 While the rate at which bile 
 passes into the intestine seems to be 
 
 influenced by digestion much in the Fig^ibg.-Pancreatic juke and Bile 
 
 - '^ . (Pawlow). The upper curves repre- 
 
 Same way as the rate of pancreatic sent the hourly rate of pancreatic 
 
 secretion, the details are as yet less secretion, and the lower the rate ^t 
 
 exactly known. In the fasting which the bile enters the intestine; 
 
 •; , ., ,, , -^., '=' a, a, milk diet ; &, 6 , meat; c, c, 
 
 animal no bile enters the gut. W hen bread. Only the general form of 
 
 food is taken, the flow begins after the curves is to be compared. The 
 
 a definite interval, which varies for ^""^^^ °* ^^^ ordinates of the various 
 
 ,, ,.„ ,1-1 r r 1 A curves was not the same. 
 
 the diflerent kinds of food. As 
 
 long as digestion lasts bile continues to escape, but both the 
 quantity and quality depend upon the nature of the food. Water, 
 raw egg-white, and starch paste, whether given by the mouth or 
 introduced directly into the stomach of a dog, cause no flow of bile. 
 But fat, the extractives of meat, and the products of digestion of 
 egg-white produce a copious discharge. This discharge may be 
 determined by the relatively large amount of acid chyme passed 
 through the pylorus when proteins are digested in the stomach and 
 the stimulus to the formation of secretin occasioned by the presence 
 of this chyme or of fatty material in the duodenum. In the case of 
 fat a further favourable influence on the secretion of bile is the 
 absorption of bile-salts which accompanies the absorption of the 
 fatty acids and soaps produced in fat digestion. Bile-salts stimulate 
 the secretion of bile, including bile-salts themselves. An increased 
 
4X4 DIGESTION 
 
 flow of bile-salts into the intestine accelerates the splitting of fats by 
 the pancreatic juice, and therefore the absorption of bile-salts acting 
 as solvents for, or chemically united to, the fatty acids and soaps. 
 A circle analogous to the ' vicious circle ' of the logicians, but con- 
 stituting a physiological adaptation of most potent \-irtue in the 
 digestion of fats, is thus estabhshed. Not only is the quantity of 
 bile poured into the intestine increased on a diet rich in fat, but it 
 is said that a given amount of it aids the fat-splitting action of the 
 pancreatic juice more powerfully than if the diet were poor in fat. 
 This mav depend upon an increase in the concentration of the bile- 
 salts in bile secreted when a large amount of fat is ingested. But it 
 is well to recognize that we do not at present know with any great 
 exactness the mechanism by which the rate of secretion and ex- 
 pulsion of bile and the properties of that juice are influenced by 
 digestion. It has been conjectured that the first abrupt rise may be 
 started bv reflex nervous action, and that later on secretin and, in the 
 case of fat digestion, bile-salts may directly excite the hepatic cells. 
 
 The pressure under which the bile is secreted is higher than the 
 pressure of the portal blood, and therefore the hver ranges itself with 
 the high-pressure salivary glands rather than with the low-pressure 
 pancreas. But although the biliary pressure is high relatively to 
 that of the blood with which the secreting cells are supplied, it is 
 absolutelv low, the maximum being no more than 25 mm. of mer- 
 curv.* This is a point of practical importance, for a comparatively 
 slight obstruction to the outflow, even such as is offered by a con- 
 gested or inflamed condition of the duodenal wall about the mouth 
 of the duct, may be sufficient to cause reabsorption of the bile 
 through the lymphatics, and consequent jaundice. Of course, 
 complete plugging of the duct by a biliary calculus is a much more 
 formidable barrier, and inevitably leads to jaundice, just as ligature 
 of a sahvary duct, in spite of the great secretory pressure, inevitably 
 causes oedema of the inland. 
 
 The Influence of Nerves on the Secretion of Intestinal Juice. — As 
 to the influence of nerves on the secretion of the succus entericus, our 
 knowledge is almost hmited to a single experiment, and that an in- 
 conclusive one. Moreau placed four ligatures on a portion of the 
 small intestine, so as to form three compartments separated from 
 each other and from the rest of the gut. The mesenteric nerves 
 going to the middle loop were di\nded. and the intestine returned to 
 the abdomen. After some time a watery secretion was found in the 
 middle compartment, little or none in the others. This is a true 
 * paral>i:ic ' secretion, and not a mere transudation depending 
 simply on the vascular dilatation caused by section of the vaso- 
 
 • In the dog, cat, and monkey the average maximum pressure at which 
 as much bile is secreted as is taken up from the bile-paths by the portal 
 lymphatics is about 300 mm. of bile. The highest pressure recorded was 
 373 mm. of bile in a cat {Herring and Simpson). 
 
tNFLULSCE OF NER VOUS SYSTEAf 0^' DIGEST 1 VE GLA SDS 41 J 
 
 constrictor nerves, for it has the same composition and digestive 
 action as normal succiis entericus obtained from a fistula. The 
 secretion bcfiins about four hours after section of the nerves, goes on 
 increasing for about twelve hours, and then rapidly diminishes, so 
 that after about two days the middle loop, as well as the other 
 two, will be found empty. The interpretation usually put upon the 
 experiment is that nerves which normally inhibit the local secre- 
 tory mechanism have been divided. But there is no real proof of 
 the existence of such nerves. 
 
 The same adaptation is seen in the secretion of the succus entericus 
 as in the secretion of the other digestive juices, and the adaptation 
 is naturally most striking in regard to those points in which the 
 intestinal juice is pecuhar. While mechanical stimulation of the 
 stomach is ineffective as regards the secretion of gastric juice, 
 mechanical stimulation of the intestine, as by the contact of a 
 cannula, produces a free flow of succus entericus. The reaction is a 
 localized one, the secretion only taking place from the portion of the 
 mucous membrane stimulated. This fact acquires significance when 
 we reflect that the food moves very slowly in the intestine, and a 
 secretion could be of use only at the points where the food happened 
 to be. The juice secreted in response to mechanical stimulation is 
 poor in enterokinase. But if a little pancreatic juice be put into the 
 intestine, and left there for some time, the juice afterwards secreted 
 is rich in enterokinase. 
 
 Summary. — Here let us sum up the most important points relat- 
 ing to the secretion of the digestive juices. They are all formed hy 
 the activity of glmid-cells originally derived from the epithelial lining 
 of the alimentary canal- The organic constituents or their precursors 
 {including the mother-substances of the ferments) are prepared in the 
 internals of rest — absolute in some glands, relative in others — and 
 stored up in the formr of granules, which during activity are moved 
 towards the lum-en of the gland tubules, and there discharged. 
 
 The nerves of the salivary glands are, as regards their origin, {a) 
 cerebral, {b) sympathetic ; the former group is vaso-dilator, the latter 
 {usually) vaso-constrictor ; both are secretory. Secretion of saliva 
 depends strictly on the neroous system. That nerves influence the 
 gastric and pancreatic secretions is also made out. The psychical secre- 
 tion is of greater importance for the saliva and gastric juice than for 
 the pancreatic juice. The direct action of secretin {produced in the 
 intestinal mucous membrane by the influence of the chym^) is the most 
 characteristic factor in pancreatic secretion. As regards the intestinal 
 glands and the liver, it has not been proved that their secretive activity 
 is under the control of the nervous system, except in so far as the latter 
 may indirectly govern it through the blood-supply, although various 
 circumstances suggest the probability of a more direct action. All the 
 digestive juices show a certain adaptation to the nature of the food. 
 
4i6 DIGESTION 
 
 although it hus not been demonstrated that this is due to a specific sensi- 
 bility of the niiuons membranes for each kind of foodstuff. The 
 action of one juice on the secretion of another is also of great significance. 
 Thus, the water of the saliva directly excites a flow of gastric juice when 
 it reaches the stomach ; the acid of the gastric juice excites a flow of 
 pancreatic piice when it reaches the duodenum : and the pancreatic 
 juice excites the intestinal mucous membrane to the production of 
 enterokinase, the most characteristic constituent of the succus entericus. 
 In all the glands the blood-flow is increased during activity ; in some 
 {salivary glands) this is knoivn to be caused through vaso-motor nerves. 
 In the salivary glands electro-motive changes accompany the active 
 state, and more heat is produced. Both in the salivary glands and the 
 pancreas it has been shown that much more carbon dioxide is given off, 
 and much more oxygen used up. during secretion than during rest. In 
 the other glands we may assume that the same occurs. This is one 
 proof that work is done in the separation or manufacture of the con- 
 stituents of the various secretions. 
 
 Section VI. — Survey of Digestion as a Whole. 
 
 Having discussed in detail the separate action of the digestive 
 secretions, it is now time to consider the act of digestion as a whole, 
 the various stages in which are co-ordinated for a common end. 
 The solid food is more or less broken up in the mouth and mixed 
 with the saliva, which its presence causes to be secreted in consider- 
 able quantity. Liquids and small sohd morsels are shot down the 
 open gullet without contraction of the constrictors of the pharynx, 
 and reach the lower portion of the oesophagus in a comparatively 
 short time (y^y second) ; while a good-sized bolus is grasped by the 
 constrictors, then by the oesophageal walls, and passed along by a 
 more dehberate peristaltic contraction. 
 
 Chemical digestion in man begins already in the mouth, a part of 
 the starch being there converted into dextrins and sugar ^maltose), 
 as has been shown by examining a mass of food containing starch 
 just as it is ready for swallowing (p. 456). This process is no doubt 
 continued during the passage of the food along the oesophagus. 
 
 The first morsels of a meal which reach the stomach find it free 
 from gastric juice, or nearly so. They are alkaline from the ad- 
 mixture of sahva ; and the juicewhich is now beginning to be secreted, 
 in response to the psychical e.xcitoment, and reflexly through the 
 presence of the food and the water of the saliva in the stomach, is for 
 a time neutralized, and amylolytic digestion still permitted to go on. 
 For 20 to 40 minutes after digestion has begun there is no free 
 hydrochloric acid in the stomach, although some is combined with 
 proteins, and during this period the ptyalin of the swallowed saliva 
 will be able to act even better than in the mouth, being favoured by 
 
SURVEY OF DIGESTION AS A WHOLE 41? 
 
 a weakly acid reaction. Indeed, for a time, as the meal goes on, the 
 successive portions of food which arrive in the stomach will find the 
 conditions more and more favourable for amylolytic digestion. But 
 as the acidity continues to increase, the activity of the ptyalin will 
 first be lessened, and ultimately abolished; and, upon the whole, a 
 considerable proportion of the starches must usually escape com- 
 plete conversion into sugar until they arc acted upon by the pan- 
 creatic juice. This is particularly tlie case with unboiled starch, as 
 contained in vegetables which are eaten raw; and, indeed, we know 
 that sometimes a certain amount of starch may escape even pan- 
 creatic digestion, and appear in the faeces. Meanwhile, pepsin and 
 hydrochloric acid are being poured forth; the latter is entering into 
 combination with the proteins of the food ; and before the end of an 
 ordinary meal peptic digestion is in full swing. The movements of 
 the pyloric end of the stomach increase, and eddies are set up in its 
 contents, which carry the morsels of food with them, and throw them 
 against its walls. In this way not only are the contents thoroughly 
 mixed, and fresh portions of food constantly brought into contact 
 with the gastric juice secreted mainly in the more passive cardiac 
 end, but a certain amount of mechanical disintegration is brought 
 about. This is aided by the digestion of the gelatin-yielding con- 
 nective tissue which holds together the fibres of muscle and the cells 
 of fat, and the digestible structures in vegetable tissue which enclose 
 starch granules. Such nucleo-proteins as come into contact with the 
 gastric juice will be split up and the proteins digested to peptone. 
 The globin of the blood pigment will undergo the same change, while 
 the haematin is not much affected. If milk has formed a portion of 
 the meal, the caseinogen will have been curdled soon after its 
 entrance into the stomach, by the action of the rennet ferment alone 
 (see p. 353) when the milk has been taken at the beginning of 
 digestion before the gastric contents have become distinctly acid, by 
 the acid and ferment together when it has been taken later. The 
 caseinogen and other proteins of milk, like the myosinogen and other 
 proteins of meat, and the globulins, albumins, and other proteins of 
 bread and of vegetable food in general, are acted upon by the pepsin 
 and hydrochloric acid, yielding ultimately peptones; while variable 
 quantities of these proteins and of the acid-albumin and proteoses 
 derived from them may escape this final change, and pass on as such 
 into the duodenum. In the dog, indeed, a very large proportion of 
 a meal of flesh has been found to be digested to the peptone stage 
 while still in the stomach, leaving for the juices that act on it in the 
 intestine only its further hydrolysis to amino-acids, etc. But we 
 may safely assume that, in the case of a man li\'ing on an ordinary 
 mixed diet, a good deal of the food proteins passes through the 
 pylorus chemically unchanged, or having undergone only the first 
 steps of hydration. For, even a few minutes after food has been 
 
418 DIGESTION 
 
 swallowed, especially liquid food or water, the pyloric sphincter 
 may relax and allow the stomach to propel a portion of its contents 
 into the intestine ; and such relaxations occur at intervals as diges- 
 tion goes on, although it is not for several hours (three to five) that 
 the greater portion of the food reaches the duodenum. During this 
 period the acidity has at first been constantly increasing, although 
 for a time the hydrochloric acid has combined, as it is formed, with 
 the proteins of the food. Then comes a stage where the hydrochloric 
 acid has so much increased that, after combining with all the proteins, 
 some of it remains over as free acid. After a time the total acidity 
 begins to fall, the partially digested proteins continually i)assing on 
 through the pylorus, while a considerable proportion is so fully 
 digested as to be absorbed by the gastric mucous membrane itself. 
 Thus, in one experiment on the digestion of meat in a dog, it was 
 found that 30 per cent, was absorbed in the stomach, while 40 per 
 cent, passed through the pylorus as peptone, over 20 per cent, as 
 undissolved or soluble protein (acid-albumin), and a little more than 
 8 per cent, as proteose (Tobler). The large proportion of peptone 
 is noteworthy, as indicating some kind of selective passage of the 
 different digestive products from the stomach into the duodenum. 
 For the gastric contents contain plenty of proteose, although only 
 traces of peptone. The total ' titratable acidity ' goes on diminishing 
 till the third or fourth hour, the proportion of free to combined acid 
 continuing, nevertheless, to rise, since nearly all that is now secreted 
 remains free. In addition to a certain amount of protein, small 
 quantities of soluble and easily diffusible substances, like sugars and 
 some of the organic crystalline constituents of meat — e.g., kreatin — 
 may also be absorbed into the blood by the gastric mucous membrane. 
 The substances which reach the duodenum are — (i) The greater 
 part of the fats. The partial digestion in the stomach of the enve- 
 lopes and protoplasm of the cells of adipose tissue, and of the protein 
 which keeps the fat of milk in emulsion, prepares the fats which are 
 not spUt up by the gastric juice for what is to follow in the intestine. 
 (2) All the proteins which have not been carried to the stage of 
 peptone, and much peptone. (3) All the starch and dextrins — and 
 glycogen, if any be present — which have not been converted into 
 sugars, and probably a portion of the sugars. (4) Nucleins, haematm, 
 cellulose, and other substances not digestible, or digestible only with 
 difficulty, in gastric juice. (5) The constituents of the gastric juice 
 itself, including pepsin. Most of the pepsin is soon destroyed in the 
 unfavourable environment of the intestinal contents. But it has 
 been shown that a certain amount of active pepsin may be present 
 for a time in the intestine, even in the free condition, and still more 
 when enclosed in the interior of masses of protein which protect it, 
 and which still continue to be digested by it. This is particularly 
 true of certain materials, like elastin and connective tissue, which are 
 
SURVEY OF DIGESTION AS A WHOLE 419 
 
 more readily hydrolysed by pepsin than by trypsin. The ptyalin 
 of the sahva has been ah-eady destroyed in the stomach. 
 
 It must be remembered that all this time, even from the beginning 
 of digestion, a certain amount of pancreatic juice has been finding 
 its way into the duodenum in response first perhaps to the psychical 
 excitation, and later to that action of the acid chyme on the in- 
 testinal mucous membrane which has been described. In the 
 duodenum its trypsinogen is becoming activated to trypsin by the 
 cnterokinase of the intestinal juice. The secretion of bile, too, has 
 quickened its pace, the gall-bladder is getting more and more full as 
 the meal proceeds and gastric digestion begins, and some of the bile 
 may very soon escape into the intestine. The pylorus opens occa- 
 sionally for a moment whenever the small portions of chyme which 
 at this stage are beginning to pass through have been sufficiently 
 neutralized by the pancreatic juice and bile, although it is not 
 necessary that the reaction should become actually neutral. When 
 the acid chyme, a greyish liquid, turbid with the debris of animal and 
 vegetable tissues — with muscular fibres, fat globules, starch granules, 
 and dotted ducts — gushes through the pylorus and strikes the 
 duodenal wall, the muscular fibres of the gall-bladder contract, and 
 sudden rushes of bile take place from the common duct. By-and-by 
 as bile and pancreatic juice continue to be poured out, the reaction 
 in the duodenum becomes less acid and even weakly alkaline. 
 The observations purporting to show changes in reaction of the 
 intestinal contents at different levels made with indicators like 
 litmus, phenolphthalein, methyl orange, etc., have lost much of 
 their value since the introduction of physico-chemical methods for 
 measuring the hydrogen-ion concentration. However, properly 
 chosen colour indicators can still be employed for estimating the 
 acidity of the gastric contents, at least with sufficient accuracy for 
 most clinical purposes. It must be remembered that the differ- 
 ences in true reaction at different stages of intestinal digestion and 
 at different levels of the gut below the duodenum are slight. There 
 is never a great preponderance either of hydroxyl or of hydrogen 
 ions between the point at which the pancreatic juice and bile are 
 mingled with the gastric chyme and the lower part of the ileum. 
 
 In the duodenal contents of adult human beings a hydrogen-ion con- 
 centration of 000000002 (or 2X 10-') normal has been found by the 
 gas chain method (McClendon) and about the same in the intestinal 
 contents of dogs (Auerbach and Pick). This is a sHghtly alkaUne 
 reaction, the hydrogen-ion concentration of pure water being about 
 five times as great ^o-ooooooi, or i x 10-7). In the stomach, of course, 
 a very different state of affairs is found. The hydrogen-ion concen- 
 tration rises in the course of i to 3 or 4 hours after a meal to a maxi- 
 mum which is very considerable. In a series of patients, including a 
 number suffering from gastric disorders, the hydrogen-ion concentra- 
 tion ranged from 0-03 to 0-00000007 i^^ 7^ 10-'). The lowest concen- 
 
420 DIGESTION 
 
 tration is practically the same as that of water. In other words, in 
 this patient the gastric contents after the test meal were neutral, and 
 it would be impossible for peptic digestion to proceed. It must be 
 distinctly noted that the acidity of the gastric contents during the 
 digestion of test meals is not the same thing as the acidity of the pure 
 gastric juice. Observations on juice obtained from a case of gastric 
 fistula without admixture with saliva showed that in ' hunger ' juice, 
 where continuous secretion was going on, the hydrogen-ion concentra- 
 tion varied from o-055 to o-ioo normal in several samples collected on 
 different days (Menten). 
 
 This question of reaction has significance in two ways : in the first 
 place the reaction determines whether a given ferment shall be 
 destroyed or not by another ferment or b\- the alkalinity or acidity 
 of the medium. Thus pepsin can be destroyed by the alkali of the 
 pancreatic juice, enterokinase and trypsin by the hydrochloric acid 
 of the gastric juice, trxpsinogen by the pepsin and hydrochloric 
 acid. Tr\^sin has no destructive effect on enterokinase or tryp- 
 sinogen (Mellanby). Secondly, the reaction affects the actiNuty of 
 this or that ferment on the food substances. The optimum hydro- 
 gen-ion concentration for peptic digestion is relatively high (0'02 
 to 0-03 normal). WTien it is decreased to o«ocoi normal the rate 
 of digestion is only one-half to one-fifth as rapid. The high con- 
 centration of hydrogen-ions in the gastric contents of healthy persons 
 is clearly advantageous, and the low concentration in the gastric 
 contents in cases of hypoacidity clearly disadvantageous. Trypsin 
 acts best in a medium which contains more hydro.xyl than hydrogen 
 ions. WTien the alkalinity is diminished it becomes less active, 
 although it is not entirely inhibited even by an acid reaction until 
 the hydrogen-ion concentration reaches about o-oooi (or 1x10-4) 
 normal. (See footnote, p. 1139.) 
 
 In the intestine it is possible that trypsin may perform its work 
 in a medium which is sometimes acid; and although the cause of 
 the aciditv and the character of the medium are far from being the 
 same as in the gastric juice, it is ob\aously an advantage that the 
 chief proteolytic ferment should be able to act upon the proteins in 
 all parts of the intestine and at every stage of intestinal digestion 
 whether the reaction is acid or alkaline. The proteins of the chyme 
 are all carried by the trypsin to the stage of peptone, and the pep- 
 tone, even in perfectly normal digestion, is further spHt up into 
 amino- and diamino-acids by the trypsin and b}' the erepsin of the 
 succus entericus. 
 
 In the lower portions of the small intestine bacteria of various 
 kinds are present and active; and it is not unlikely that even 
 throughout its whole length a certain range of action is permitted 
 to them, checked by the acidity of the chyme, though scarcely by 
 the feeble antiseptic properties of the bile. 
 
 The lower end of the small intestine is not cut off by any bacteria- 
 proof barrier from the large intestine, in which putrefaction is con- 
 
SURVEY OF DIGESTION AS A WHOLE 421 
 
 stantly going on. It has been actually shown that small particles, 
 such as lycopodium spores, suspended in water, soon reach the 
 stomach when injected into the rectum. So that micro-organisms, 
 aided by the antiperistalsis of the colon, may be able to work their 
 way above the ileo-colic sphincter and valve, even against the 
 downward peristaltic movement of the small intestine. But even if 
 this were not the case, a few bacteria or their spores, passing through 
 the stomach with the food, would be enough to set up extensive 
 changes as soon as they reached a part of the alimentary canal 
 where the conditions were favourable to their development. In- 
 deed, from the time when the first micro-organism enters the diges- 
 tive tube soon after birth, it is never free from bacteria; and their 
 multiplication in one part of it rather than another depends not so 
 much on the number originally present to start the process, as on 
 the conditions which encourage or restrain their increase. 
 
 A certain amount of already emulsified fats is broken up into 
 their fatty acids and glvcerin in the stomach, unemulsified fats 
 entirelv by the fat-splitting ferment of the pancreatic juice. The 
 acids will form soaps with alkalies wherever they meet them in the 
 intestinal contents, or even in the mucous membrane. A portion 
 of those soluble soaps may be immediately absorbed; the rest will 
 aid in the emulsification of the fats not yet chemically decomposed, 
 and thus greatly hasten the fat -splitting action of the pancreatic 
 juice. The phosphatides are in all probability acted upon in the 
 alimentary canal much in the same way as the fats. Lecithin is 
 decomposed by pancreatic and intestinal juice into fatty acids and 
 glyceryl-phosphoric acid, and cholin is hberated. As regards the 
 beha\nour of the sterins of the food little is known, but it is not 
 unlikely that their esters are spht up, and the sterins thus set free 
 as well as those originally free in the food may then be absorbed, 
 in part at least, without further change. The starch and dextrin 
 which have escaped the action of the sahva are changed into 
 maltose by the amylase of the pancreatic juice, and the maltose 
 into dextrose by the maltase of the same secretion and of the succus 
 entericus. 
 
 The succus entericus, in addition to its important functions 
 already mentioned, aids as an alkahne hquid in lessening the acidity 
 of the chyme and establishing the reaction favourable to intestinal 
 digestion. It will convert into monosaccharides any cane-sugar, 
 maltose, or lactose, which may reach the intestine; but it cannot 
 be doubted that some cane-sugar may be absorbed by the stomach, 
 after being inverted by ':he hydrochloric acid of the gastric juice 
 or by inverting ferments taken in \uth the food, or on its way 
 through the gastric walls. 
 
 Upon the whole no great amount of water is absorbed in the small 
 intestine, or at least the loss is balanced by the gain, for the intestinal 
 
422 DIGESTION 
 
 contents are as concentrated in the doudenum as in the ileum. But 
 as soon as they pass beyond the ileo-caecal valve water is rapidly 
 absorbed, and the contents thicken into normal faeces, to which the 
 chief contribution of tlic large intestine is mucin, secreted by the 
 vast number of gobl(;t cells in its Lieberkiihn's crypts. 
 
 Bacterial Digestion.— So far we have paid no special attention to 
 other than the soluble ferments of the digestive tract, although 
 we have incidentally mentioned the action of the lactic acid bacilli 
 on carbo-hydrates and of the fat-splitting bacteria on fats. It is 
 now necessary to recognize that the presence of bacteria is an 
 absolutely constant feature of digestion; and although their action 
 must in part be looked upon as a necessary evil which the organism 
 has to endure, against the consequences of which it has to struggle, 
 and to which in all probability it has to a great extent adapted 
 itself, it is not unlikely that in part it may be ancillary to the pro- 
 cesses of aseptic digestion. But bacteria are not essential (in mam- 
 mals, at any rate, Hving on milk), as some have supposed. For it 
 has been shown that a young guinea-pig, taken by Caesarean section 
 from its mother's uterus with elaborate aseptic precautions, and 
 fed in an aseptic space on sterile milk, grew apparently as fast as one 
 of its sisters brought up in the orthodox microbic way. The ali- 
 mentary canal remained free from bacteria (Nuttall and Thierfelder). 
 On the other hand, chickens hatched from sterile eggs and kept in 
 a sterile enclosure lived, indeed, for a time, but did not thrive in 
 comparison with the control animals, and died at latest after eighteen 
 days (Schottelius). It is probable that the difference in the results 
 is to be attributed to the difference in the food, purely vegetable 
 food requiring the aid of bacteria for its proper digestion, especially 
 for the decomposition of the cellulose, v/hile an easily-digestible 
 food like milk docs not. 
 
 Among the more important actions of bacteria on the protein 
 food-products in the intestines may be mentioned the formation 
 of indol, phenol, and skatol, the first having tyrosin for its precursor, 
 and being itself after absorption the precursor of the indican in the 
 urine; the second being to a small extent thrown out with the faeces, 
 but chiefly absorbed and eliminated by the kidneys as an aromatic 
 compound of sulphuric acid; the third passing out mainly in the 
 faeces. 
 
 The view put forward by Metchnikoff, that in the putrefactive 
 bacteria of the intestine the body carries within itself the seeds of 
 premature decay, owing to the harmful effects of absorbed products 
 of decomposed protein, cannot be looked upon as established, 
 although certainly the prophylaxis suggested by him (the increase 
 of the lactic acid content of the intestine by the addition of sour 
 milk, butter-milk, etc., to the diet) might well be a useful modifica- 
 tion of the dietetic habits of many persons, especially if associated 
 
SURVEY OF DIGESTION AS A WHOLE 423 
 
 with a reduction in the total amount of protein consumed. That 
 the intestinal contents may include substances capable of inducinj^ 
 severe toxic sympton"vs if absorbed unchanged scarcely needs proof. 
 Filtered extracts of fseces from normal persons made with salt 
 solution cau.ic, when injected in small amounts into the circulation 
 of dogs, a fall of blood-pressure which may be speedily recovered 
 from or may be quickly fatal according to the specimen (Fig. 170). 
 The large intestine is the chosen haunt of the bacteria of the 
 ahmentary canal; they swarm in the faeces, and by their influence, 
 especially in the caecum of herbivora, but also to some extent in 
 man, even cellulose is broken up, the final products comprising 
 certain fatty acids, such as but^Tic, acetic and valerianic acids, 
 carbon dioxide and marsh gas. A cellulose-dissolving enzyme of 
 great activity is, present in the hepatic secretion of the snail, which 
 rapidly produces sugar from that polysaccharide. Dextrose is also 
 formed when it is hydrolysed by dilute acid. Apart from the im- 
 portance of solution of the cellulose in facilitating the action of the 
 digestive juices on the starch and other nutrient materials enclosed 
 by it, it can be assumed that some of the intermediate products of 
 its hydrolysis by the bacteria — e.g., bodies analogous to the dex- 
 trins which appear in the hydrolysis of starch — can be acted on by 
 the ferments of the succus entericus and the pancreatic juice, so 
 as to form dextrose, which on absorption then takes its place in 
 the carbo-hydrate metabolism just as if it had been derived from 
 starch. In the herbivora the contribution thus made to the nutri- 
 tion of the animal may be of considerable importance; in omnivora 
 it is not negligible. In man as much as 40 per cent, of the cellulose 
 of young vegetables is said to be capable of assimilation. In car- 
 nivorous animals, however, it appears that cellulose when taken in 
 the food is quantitatively excreted in the fsces. In addition to 
 the action of the intestinal flora on cellulose, certain of the bacteria 
 of the alimentary canal affect some of the other carbo-hydrates in a 
 not unimportant way. Dextrose, for instance, can be decomposed 
 into two molecules of lactic acid, according to the equation 
 
 CgHiaOe^aCsHgOj. 
 
 This is called the lactic acid fermentation^ and is due to a special 
 bacillus. 
 
 Another micro-organism splits up dextrose into butyric acid, 
 carbon dioxide and hydrogen, the so-called butyric acid fermenta- 
 tion, according to the equation 
 
 CfiHiaOg = C4H8O2 -f- aCOj -I- aHg. 
 
 The contents of the large bowel are generally acid from the 
 products of bacterial action, although the wall itself is alkaline. 
 Faeces.— In addition to mucin, secreted mainly by the large 
 
424 
 
 DIGESTION 
 
 intestine, the faeces consist of indigestible remnants of the food, such 
 as clastic fibres, spiral vessels of plants, and in general all vegetable 
 structures chiefly composed of cellulose. They are coloured with a 
 pigment, stercobilin, derived from the bilc-pigmints. Stercobilin 
 is identical with urobilin, which forms a common, tliough not an 
 
 Fig. I/O. 
 
 -Eflect of Extract of Faeces on Blood-Pressure. The extraot was injected 
 at 2. Time-trace, seconds. 
 
 invariable, constituent of bile itself. A portion of it is absorbed by 
 the intestine and then excreted in the urine, the urobilin in which 
 is often much increased in fever (' febrile ' urobilin). No bilirubin 
 or biliverdin occurs in normal faeces, although pathologically they 
 may be present. The dark colour of the faeces with a meat diet is 
 due to haematin and sulphide of iron, the latter being formed by 
 the action of the sulphuretted hydrogen which is constantly present 
 in the large intestine on the organic compounds of iron contained in 
 the food or in the secretions of the alimentary canal. A small 
 amount of altered bile-acids and their products is also found; and 
 in respect to these, and to the altered pigments, bile is an excretion. 
 And although its entrance into the upper instead of the lower end 
 of the intestine, the ascertained importance of its function in diges- 
 tion, and the fact that the greater part of the bile-salts is reabsorbed, 
 show that in the adult it is very far from being solely a waste product, 
 the equally cogent fact, that the intestine of the new-born child 
 is filled with what is practically concentrated bile (meconium), 
 proves that it is just as far from being purely a digestive juice. 
 Skatol and other bodies, formed by putrefactive changes in the 
 proteins of the food, are also present in the faeces, and are responsible 
 for the faecal odour. Masses of bacteria are invariably present, and 
 often make up a very considerable proportion of the total fcccal 
 
SURVEY OF DIGESTION AS A WHOLE 425 
 
 solid:.. 01 the inorganic substances in faeces the numerous crystals 
 ot triple phosphate arc the most characteristic. When the diet is 
 too large, or contains too much of a particular kind of food, a con- 
 siderable quantity of digestible material may be found in the faeces — 
 eg., muscular fibres and fat. But it should be remembered that 
 under all circumstances the composition of the faeces differs from 
 that of the food. Tlie intestinal contribution is always an important 
 one, although relatively more important with a flesh than with a 
 vegetable diet. The purin bases normally found in human faces 
 come both from the food directly and from the metabolism of 
 the tissues. They arc increased in amount on a diet rich in 
 purin bodies (such as meat extract or thymus), but are also formed 
 on a diet like milk, from which purin bases cannot be obtained. 
 An interesting constituent of faeces on which light has recently been 
 thrown, especially by the researches of Gardner, is the so-called copro- 
 sterin (dihydrocholesterin), which appears to be produced from 
 cholesterin by reduction, j)robably under the influence of bacteria, 
 and perhaps also from the phytosterins of vegetable food. 
 
CHAPTER VII 
 ABSORPTION 
 
 Section I. — Preliminary Physico-Chemical Data. 
 
 Imbibition, or molecular imbibition, is the term applied to the en- 
 trance of liquid into a colloid, without the loss of its properties as a solid, 
 when no preformed capillary spaces are present. The entrance of water 
 into a piece of gelatin, or an epidermic scale, is an example of molecular 
 imbibition. IMost animal and vegetable tissues possess this property, 
 which is believed to be of importance in such physiological processes as 
 absorption, secretion, and the excretion of water from the lungs and 
 skin. The process by which liquid passes into a solid with preformed 
 capillary spaces — e.g., a sponge — is sometimes spoken of as capillary 
 imbibition. 
 
 Diffusion. — When a solution of a sub.stance is placed in a vessel, and 
 a layer of water carefully run in on the top of it, it is found after a time 
 that the dissolved substance has spread itself through the water, and 
 that the composition of the mixture is uniform throughout. The 
 result is the same when two solutions containing different proportions 
 of the same substance, or containing different substances, are placed in 
 contact. The phenomenon is called diffusion. The time required for 
 complete diffusion is comparatively short in the case of a substance like 
 hydrochloric acid or sodium chloride, exceedingly long in the case of 
 albumin or gum. In both it is more rapid at a high temperature than 
 at a low. 
 
 Osmosis. — If the solution be separated from water by a membrane 
 absolutely or relatively impermeable to the dissolved substance, but 
 permeable to water, water passes through the membrane into the solu- 
 tion. This phenomenon is called osmosis. E.g., a membrane of ferro- 
 cyanide of copper, nearly impermeable to cane-sugar, can be formed 
 in the pores of an unglazed porcelain pot by allowing potassium ferro- 
 cyanide and cupric sulphate to come in contact there. If the pot is 
 filled with, say, a i per cent, solution of cane-sugar. clo.scd by a suitable 
 stopper, connected to a manometer, and then placed in a vessel of water, 
 water passes into it till the pressure indicated by the manometer rises 
 to a certain height. With a 2 per cent, solution it reaches twice this 
 height, and in general the osmotic pressure, as it is called, is in any 
 solution proportional to the molecular concentration* of the solution, 
 
 * The molecular concentration is strictly defined as the number of 
 grammes of the dissolved substance in a litre of the solution divided by the 
 gramme-molecular weight. The gramme-molecular weight, or gramme 
 molecule, is the number of grammes corresponding to the molecular weight. 
 Thus, the gramme-molecular weight of sodium chloride (NaCl) is 5S"36 
 grammes, and of cane-sugar (C 121122^11) ■ 34^ grammes. 
 
 426 
 
PRELIMINARY PHYSICO-CHEMICAL DATA 
 
 427 
 
 or, in otlicr words, to the number of molecules of the dissolved substance 
 in a given volume of the solution. If in this sentence we substitute 
 ' gaseous pressure ' for ' osmotic pressure,' and ' gas ' for ' solution,' 
 we have a statement of Boyle's law, which asserts that the pressure of a 
 gas is proportional to its density. Indeed, it has been shown that the 
 osmotic pressure of the dissolved substance is the same as the pressure 
 that would be exerted by a gas, say hydrogen, if all the water were 
 removed, and a molecule of hydrogen substituted for each molecule of 
 the substance, or as would be exerted by the sub.stance itself if, after 
 removal of the solvent, it could be left as a gas filling tlie 
 same volume. And the osmotic pressure of a solution of 
 one substance is the same as that of a solution of any 
 other substance which contains in a given volume the 
 same number of molecules of the dissolved substance. 
 In other words, the osmotic pressure is not dependent on 
 the nature, but on the molecular concentration, of the 
 substance. The analogy of the laws of osmotic to those 
 of gaseous pressure becomes still more obvious when 
 it is added that the osmotic pressure of a substance with 
 any given molecular concentration is proportional to the 
 absolute temperature ; and that when a solution contains 
 more than one dissolved substance the total osmotic pres- 
 sure is the sum ol the partial osmotic pressures 
 vvliich each substance would exert if it were 
 present alone in the same volume of the solution. 
 The osmotic pressure of a solution may reach 
 an enormous amount. Thus, a i per cent, solu- 
 tion of cane-sugar has a pressure at 0° C. of 
 493 mm. of mercuiy. A 10 per cent, solution 
 of cane-sugar would have an osmotic pressure of 
 more than six atmospheres, and a 17 per cent, 
 solution of ammonia a pressure of no less than 
 224 atmospheres. The manner in which the 
 phenomenon known as osmotic pressure is de- 
 veloped is not definitely known. One theory 
 attributes it to the attraction between the 
 dissolved molecules and the molecules of the 
 solvent on the other side of the membrane. 
 The most commonly accepted view is that the 
 osmotic pressure is due to the kinetic energy 
 of the moving molecules. Where the mole- 
 cules are hindered from passing a bounding 
 membrane, the pressure exerted by their im- 
 pacts on the boundary is greater than where 
 the membrane is easily permeable, because in 
 the latter case many of the molecules pass 
 through, carrying with them their kinetic 
 energy. The pressure must be still less when 
 a dissolved substance diffuses freely into water ; 
 but however small it may become, it is in the same force which gives 
 rise to the osmotic pressure of the molecules of the dissolved substance 
 that the cause of diffusion must be sought. Recently interest in the 
 nature of the membrane itself as an important factor in osmosis has been 
 revived (Kahlenberg. Armstrong, etc.). There are many facts which 
 indicate that in physiological processes the affinity of the dissolved sub- 
 stances for, or their solubility in, the cell envelopes or the cytoplasm 
 plays an important role. 
 
 Fig. 171. — Beckmann's 
 Apparatus. For de- 
 scription, see p, 52c. 
 
42 S ABSORPTION 
 
 It is as yet impossible or at least very (iillitult to directly measure 
 the osmotic pressure with accuracy by means of a scmi-permcablc mem- 
 brane. Recourse is therefore had to indirect methods, especially one 
 which depends on the fact that the freezing-point of a solution is lower 
 tiian that of the solvent, salt water, c./j., freezing at a lower temperature 
 than fresh water. The amount by which the freezing-point is lowered 
 depends on the molecular concentration of the dissolved substance, to 
 which, as we have seen, the osmotic pressure is also proportional. When 
 a gramme-molecule of a substance is dissolved in water, and the volume 
 made up to a litre, the freezing-point is lowered by i86° C. ; the osmotic 
 jiressurc is 22-33 atmospheres {16,986 mm. of mercury). It is therefore 
 easy to calculate the osmotic pressure of any solution if we know the 
 amount by which its freezing-point is lowered. A i per cent, solution of 
 cane-sugar, for example, would freeze at about — 0'054° C. Its osmotic 
 
 pressure= .J^^^ 16,986=493 mm. of mercury. 
 
 A convenient apparatus for making freezing-point measurements is 
 shown in Fig. 171. The details of the method are given in the Practical 
 I'lxcrcises, p. 5^9. 
 
 The osmotic pressure of different solutions may also be compared 
 by observing the effect produced on certain vegetable and animal cells. 
 When a solution with a greater osmotic pressure than the cell-sap (a 
 hypcyisotonic solution) is left for a time in contact with certain cells in 
 the leaf of Tradcscantia discolor, plasmolysis occurs — that is, the proto- 
 plasm loses water and shrinks away from the cell-wall. If the osmotic 
 pressure of the solution is lower than that of the coloured cell-sap 
 {hypoisotonic solution), no shrinking of the protoplasm takes place. By 
 using a number of solutions of the same substance but of different 
 strength, two can be found, the stronger of which causes plasmolysis, 
 and the weaker not. Between these lies the solution which is isotonic 
 with the cell-sap — that is, has the same molecular concentration and 
 osmotic pressure. The strength of an isotonic solution of some other 
 substance can then be determined in the same way with sections from 
 the same leaf. 
 
 Animal cells (red blood-corpuscles) may also be employed, the libera- 
 tion of haemoglobin or the swelling of the corpuscles, as measured by 
 tlie ha3matocrite (p. 27), being taken as evidence that the solution in 
 contact with tliem is hypoisotonic to the contents of the corpuscles. 
 Here we may suppose that the impacts of the molecules of the salts of 
 the corpuscle on the inside of its envelope, not being balanced by 
 similar impacts on the outside, tend to distend it, and thus to create a 
 potential vacuum for the surrounding water, which accordingly enters. 
 If the corpuscles shrink, the solution is hyperisotonic to their contents. 
 But since the cells are much more permeable to certain substances than 
 to others, this method does not always yield trustworthy results. 
 
 Electrolytes. — We have said that the osmotic pressure is proportional 
 to the concentration of the solution, but this statement must now be 
 qualified. For certain compoumls, including all inorganic salts and 
 many organic substances, the osmotic pressure decreases less rapidly 
 than the theoretical molecular concentration as the solution is diluted. 
 The explanation is that in solution some of the molecules of these bodies 
 are broken up into simpler groups or single atoms, called ions. Each 
 ion exerts the same osmotic pressure as the molecule did before. The 
 proportion between the average number of these dissociated molecules 
 and of ordinary molecules is constant for a given concentration of the 
 solution and agiven temperature. But as the solution is diluted, the 
 proportion of dissociated molecules becomes greater. The bodies which 
 
PRELIMLWIKY PHYSICO-CHEMICAL DATA 419 
 
 behave in this way are electrolytes — that is, their solutions conduct a 
 current of electricity; bodies vvhicii do not exhibit this behaviour do 
 not conduct in solution. And there arc many reasons for believing 
 that the dissociation of tiie elect rolj'les is the essential thing in elec- 
 trolytic conduction. We may suppose that in a solution of an electro- 
 lyte — sodium chloride, for instance — a certain number of the molecules 
 fall asunder into a kation (Na+),* carrying a charge of positive elec- 
 tricity, and an anion (CI—), carrying an equal negative charge. These 
 electrical charges, it must be remembered, are not created by the 
 passage of a current through the solution. Wc do not know how they 
 arise, but the ions must be supposed to be electrically charged at the 
 moment when the molecule is broken up. And the ions of ditterent sub- 
 stances must each be supposed to carry the same quantity of electricity. 
 But since they are all wandering freely in the solution, no excess of 
 negative or of positive electricity can accumulate at any part of it — in 
 other words, no difference of potential can exist. When electrodes 
 connected with a voltaic battery are dipped into a solution of an elec- 
 trolyte, a difference of potential, an electrical slope, is established in the 
 liquid, and the positively charged kations are compelled to wander 
 towards the negative pole, the negatively charged anions towards the 
 positive pole. In this way that movement of electricity which is called 
 a current is maintained in the solution. It is clear that the greater 
 the number of ions, and the faster they move in the solution, the greater 
 will be the quantity of electricity carried to the electrodes in a given 
 time, when the difference of potential between the electrodes, or the 
 steejmess of the electric slope, remains constant. In other words, the 
 specific conductivity of a solution of an electrolyte varies as the number 
 of dissociated molecules in a given volume and the speed of the ions. 
 It increases up to a certain point with the concentration, because the 
 absolute number of dissociated molecules in a given volume increases. 
 The molecular conductivity — that is, the conductivity per molecule, or, 
 strictly, the ratio of the specific conductivity to the molecular concen- 
 tration — increases with the dilution, because the relative number of 
 dissociated molecules, as compared with undissociated, increases. At 
 a certain degree of dilution the molecular conductivity reaches its 
 maximum, for all the molecules are dissociated. The ratio of the 
 molecular conductivity of any given solution to this maximum or 
 limiting value is therefore a measure of the proportion between the 
 number of dissociated, and the total number of molecules. The molec- 
 ular conductivity of the salts dissolved in the liquids of the animal 
 body, for the degree of dilution in which they exist there, is such that 
 we must assume them to be for the most part dissociated. 
 
 Surface Tension. — This is a property of surfaces which is typically 
 illustrated in such instances as a globule of mercury, a drop of water 
 on a greasy slide, or a drop of oil suspended in a liquid with which it 
 does not mix. The tendency of such drops to assume the spherical 
 form when not large enough'to be distorted by gravity is due to the 
 fact that the surface layer is under a certain tension in virtue of which 
 it strives to contract and to render the surface of the drop as small as 
 
 * It has been shown that the chemical atoms themselves are not homo- 
 geneous, but are all built up of simpler particles and possess a certain struc- 
 ture. All atoms, e.g., contain electrons, minute particles charged with negative 
 electricity. The number of electrons in an atom appears to be not far from 
 half its atomic weight. Thus in the carbon atom there are 6 electrons, in the 
 oxygen atom 8, and in the hydrogen atom probably only i. There is 
 evidence that the electrons in the atom are divided into groups or rings 
 one within another (Thomson). 
 
430 
 
 ABSORPTION 
 
 possible, just as if it were a stretched elastic membrane. Tlie cause 
 of this tension is to be sought in the mutual attraction exerted by mole- 
 cules which arc very^ close to each other. This molecular pull is 
 enormously strong. It has been calculated, for instance, that the 
 so-called internal pressure which is due to it is in the case of water not 
 less than 23,000 atmospheres. In the interior of tlie drop each mole- 
 cule, being surrounded by other molecules, is pulled by this attractive 
 force equally in all directions — that is to say, on the whole it is not 
 pulled at all, since the pulls of all the surrounding molecules balance 
 each other. At the free surface, on tlie contrary-, the molecules are 
 pulled towards the surface, but not away from it, and the pull of the 
 molecules below the surface layer is not balanced by the pull of mole- 
 cules above it. The resultant tension on this layer is the surface tension. 
 Changes in the amount of this surface tension in the case of a given 
 liquid can be produced by bringing gases, solids, or other liquids into 
 contact with the surface layer — that is, by bringing molecules of other 
 substances so near the surface molecules of the liquid that they can 
 attract them, and so to a greater or less degree, depending upon the 
 nature of the substances, balance the attraction of the molecules 
 beneath the surface of the drop. Another way in which the surface 
 tension can be altered is by changing the temperature. The higher 
 the temperature, the greater is the average velocity with which the 
 molecules of the liquid are moving, and the greater the average distance 
 between the molecules (expressed as the expansion of the liquid) . Increase 
 of temperature therefore causes the molecules, through the kinetic 
 energy of heat imparted to them, say. from an external source, to 
 repel each other, and to that extent counteracts their mutual attrac- 
 tion. Accordingly, at the surface the tension, which, as stated, depends 
 upon the excess of this attraction acting towards the interior of the 
 drop, will be diminished. When the temperature is diminished the 
 surface tension will increase. The surface tension can also be altered 
 by altering the electrical charge on the surface. An instance of this 
 is described on another page in connection with the capillar)- electrom- 
 eter (p. 702). In such ways, then, the surface tension at the inter- 
 face where the cells lining the intestine come into contact with the 
 contents of the gut or with the tissue lymph, or at the interfaces within 
 the cells where solid and liquid ' phases ' come into contact with each 
 other or where different liquids touch, may undergo alterations in 
 either direction. If the tension of the surface is altered, the surface 
 energ)^ or power of doing work inherent in the existence of this tension 
 will, of course, be altered too. In this way the energ\-, or a portion of 
 it, which is unquestionably expended in absorption may be supplied 
 ultimately at the expense of the chemical energy of cell constituents 
 or of food substances on their way tlirough the cells, by means of which 
 the original surface tensions are restored. It has been surmised fhat 
 changes of surface tension may also be concerned in the secretion of 
 glands, in muscular contrrxtion (p. 744), and other functions (Macallum, 
 Bernstein, etc.). 
 
 Adsorption. — Connected with the peculiar properties of surfaces 
 referred to in the last paragraph are certain phenomena spoken of as 
 adsorption phenomena. Adsorption is typically seen when a solid in 
 such a form that the surface is greatly increased [e.g.. a fine powder or 
 a colloidal solution in which the substance is suspended in the form 
 of exceedingly small particles) is placed in contact with a gas or a 
 solution. There occurs a diminution in the concentration of the gas 
 or the dissolved substance, and a corresponding accumulation of it on 
 the suvtace of the solid. Equilibrium is rapidly established, and the 
 
MECHANISM OF ABSORPTION 43^ 
 
 characteristic thing about adsorption is that at the equilibrium-point 
 the concentration of the dissolved substance (or the ga^j on the surface 
 is immensely greater than in the general mass of the solution. The con- 
 centration on tlie surface can, indeed, be increased by increasing the 
 concentration of the solution, but in a far smaller proportion. Accord- 
 ing to the thcrmod\Tiamic law enunciated by Willard Gibbs, sub- 
 stances wliich diminish the surface tension must tend to accumulate 
 at the surface, and substances which increase the surface tension must 
 tend to diminish in concentration at the surface. If a small quantity 
 of a substance diminishes the surface tension at a given surface more 
 in proportion than a larger quantity, not only will there be an accumula- 
 tion of the substance at the surface, but this will be proportionally 
 greater for small than for larger concentrations of the substance in the 
 solution. This characteristic feature of adsorption may thus depend 
 entirely on surface forces due to the conditions under which the attrac- 
 tion of the molecules for each other acts at the surface. It has not been 
 shown, however, that chemical forces due to the interaction of the 
 electrically charged ions are not also concerned. What is especially 
 important to point out is that in the tissues of the body there is a 
 great development of surfaces. The cell walls or cell envelopes come 
 into contact with the tissue hinph or the contents of the digestive 
 tube or the secretions in the alveoli of glands on the one side, and the 
 cell contents on the other, and constitute in the aggregate an immense 
 surface. The surfaces separating the nuclei from the cytoplasm, and. 
 above all, the surfaces of the particles of the contents of cytoplasm 
 and nuclei suspended in colloid solution, offer prodigious opportunities 
 for such surface phenomena as adsorption. 
 
 Section II. — Mechanism of Absorption. 
 
 In the preceding chapter we have traced the food in its progress 
 along the alimentary canal, and sketched the changes wrought in 
 it by digestion. We have next to consider the manner in which it 
 is absorbed. Then, for a reason which has alread}^ been explained, 
 instead of following its fate within the tissues, until it is once more 
 cast out of the body in the form of waste products, it will be best 
 to drop the logical order and pick up the other end of the clue — in 
 other words, to pass from absorption to excretion, from the first 
 step in metabohsm to the closing act, and afterwards to return and 
 fill in the interval as best we can. 
 
 Comparative. — And here, first of all, it should be remembered that 
 the epithelial surfaces, through which the substances needed by the 
 organism enter it, and waste products leave it, are, physiologically con- 
 sidered, outside the body. The mucous membranes of the alimentary', 
 respiratory- , and urinar\- tracts are in a sense as much external as the 
 foHrth great division oi' the physiological surface, the skin. The two 
 latter surfaces are in the mammal purely excretory. Absorption is 
 the dominant function of the alimentan,- mucous membrane, but a 
 certain amount of excretion also goes on through it. The pulmonary 
 surface both excretes and absorbs, and that in an equal measure. But 
 it is by no means necessary- that the surface through which oxvgen is 
 taken in and gaseous waste products given off should be buried deep in 
 the body, and communicate only by a narrow channel with the exterior. 
 
432 
 
 ABSORPTION 
 
 In the frog the skin is largely an absorbing as well as an excreting 
 surface ; oxygen passes freely in through it, just as carbon dioxide passes 
 freely out. In most fishes, and many other gill-bearing animals, the 
 whole gaseous interchange takes place through surfaces immersed in 
 the surrounding water, and therefore distinctly external. In certain 
 forms it has even been shown that the alimentary canal may serve con- 
 spicuously for absorption and excretion of gaseous, as well as liquid 
 and solid substances. Still lower down in the animal scale, the surface 
 of a single tube may perform all the functions of digestion, absorption 
 and excretion. Lower still, and even this tube is wanting, and everj-- 
 thing passes in and out through an external surface pierced by no per- 
 manent openings. 
 
 Indeed, even in man the functions of the various anatomical divisions 
 of the phvsiological surface are not quite sharply marked off from each 
 other. Though gaseous exchange goes on far more readily through the 
 pulmonary membrane than anywhere else, swallowed oxygen is easily 
 enough absorbed from the alimentary canal and carbon dioxide given 
 off into it ; and to a small extent these gases can also pass through the 
 skin. Though water is excreted chiefly by the skin, the pulmonary 
 and the urinary surfaces, and on the whole absorbed chiefly from the 
 digestive tract, there is no surface which in the twenty-four hours pours 
 out so much water as the mucous membrane of the stomach. Under 
 normal conditions, it is true, by far the greater part of this is reabsorbed 
 in the intestine, yet in diarrhoea, whether natural or caused by purga- 
 tives, the intestines themselves may, instead of absorbing, contribute 
 largely to the excretion of water. Again, although the solids of the 
 excreta are normally given off in far the greatest quantity in the urine 
 and faeces (only part of the latter is truly an excretion, since much of 
 the faeces of a mixed diet has never been physiologically inside the 
 body at all), yet salts and traces of urea are constantly found in the 
 sweat, and salts and mucin in the excretions of the respiratory tract. 
 Further, although the solids and liquids of the food are usually taken 
 in by the alimentary mucous surface, it is possible to cause substances 
 of both kinds to pass in through the skin ; and a certain amount of 
 absorption may also take place through the urinary bladder. So that 
 really it may be considered, from a physiological point of view, as more 
 or less an accident that a man should absorb his food by dipping the 
 villi of his intestine into a digested mass, rather than by dipping his 
 fingers into properly prepared solutions, as a plant dips its roots among 
 the liquids and solids of the soil; or that he should draw air into organs 
 lying well in the interior of his thorax, instead of letting it play over 
 special thin and highly vascular portions of his skin ; or that the surface 
 by which he excretes urea should be buried in his loins, instead of lying 
 free upon his back. 
 
 It has been already explained that, although digestion is a 
 necessary preliminary to the absorption of most of the solids of 
 the food, we are not to suppose that all the food must be digested 
 before any of it begins to be absorbed. On the contrary, the 
 two processes go on together. As soon as any peptone, or, at 
 least, any amino-acids, have been formed from the proteins, or 
 any dextrose from the starch, they begin to pass out of the ali- 
 mentary canal ; and by the time digestion is over, absorption is well 
 advanced. 
 
 Even in the mouth it has already begun, although the amount of 
 
MECHANISM OF ABSORPTION 433 
 
 absorption here is quite insignificant, and it is continued with 
 greater rapidity in the stomach. Here a not inconsiderable part 
 of the proteins — at k^ast, in the easily digested form of animal food — 
 a certain amount of the sugar representing the carbo-hydrates and 
 diffusible substances like alcohol, and the extractives of meat, 
 which form an important part of most thin soui:)S and of beef-tea, 
 are undoubtedly absorbed. Water is very sparingly taken up by 
 the stomach. It is in the small intestine that absorption reaches its 
 height. The mucous membrane of this tube offers an immense 
 surface, nniltiplied as it is by the valvul?e conniventes, and studded 
 with innumerable villi. Here the whole of the fat, much sugar, 
 proteose and peptone, or rather the products of the further action 
 of the ferments of the intestine on these derivatives of the native 
 proteins, and certain constituents of the bile are taken in. In the 
 large intestine, as has been already said, water and soluble salts are 
 chiefly absorbed. 
 
 \\'hat now is the mechanism by which these various products are 
 taken up from the digestive tube, and what paths do they follow on 
 their way to the tissues ? 
 
 Theories of Absorption. — Not so v^ery long ago it was supposed by 
 many that the processes of diffusion, osmosis and filtration offered a 
 tolerably complete explanation of physiological absorption. At that 
 time the dominant note of physiology was an eager appeal to chemistry 
 and physics to ' come over and help it ' ; and as new facts were dis- 
 covered in these sciences they were applied, with a confidence that was 
 almost naive, to the problems of the animal organism. The phenomena 
 of the passage of liquids and dissolved solids through animal membranes, 
 upon which the work of Graham had cast so much light, seemed to find 
 their parallel in the absorptive processes of the alimentary canal. 
 And when digestion was more deeply studied, facts appeared which 
 seemed to show that its whole drift was to increase the solubility and 
 diffusibility of the constituents of the food. But as time went on, and 
 more was learnt of the phenomena of absorption and the powers of 
 cells, these crude physical theories broke down, and discarded ' vital- 
 istic ' hypotheses began once more to arouse attention. Then came 
 the investigations of De Vries, Van 'T Hoff, and others in the domain 
 of molecular physics, which gave to our notions of osmosis the precision 
 that was wanted before its relation to many physiological processes 
 could be profitably discussed. At the present time it must be admitted 
 that we possess no full explanation of absorption, none which is much 
 more tnan a confession of ignorance, and does not itself need to be 
 explained. Yet some progress has been made at least in defining the 
 boundary between what is clearly known and what is still dark, and 
 in showing that familiar physical processes are not without influence. 
 Some physiologists, impressed with the vast progress of physics and 
 chemistry, believe that it will eventually become possible to explain 
 on mechanical and chemical principles all the peculiar phenomena which 
 we observe in the passage of substances through the walls of the ali- 
 mentary canal. As an aid to the framing of practical working hypo- 
 theses this attitude has everything in its favour. Others, taking 
 account of the number and nature of these peculiarities, oppressed with 
 the perennial paradox of vital action, incline to the less sanguine view, 
 
 28 
 
434 ABSORPTION 
 
 that after all physical explanations have been exhausted, the real secret of 
 the cell will still' lurk in some ultimate ' vital ' property of structure or of 
 function and still elude our search. The only sense in which thisattitude 
 can be said to be a useful one is that it presents a standing protest against 
 the acceptance of superficial ' physical ' explanations merely because they 
 are physical. Both the optimists and the pessimists, the adherents 
 of the physical and the adherents of the vitalistic hypothesis, liave. 
 unfortunately, as a rule taken up an extreme position, as if their theories 
 were mutually exclusive. They agree, however, in adnaitting that the 
 phenomena of absorption are essentially connected with the cells that 
 line the alimentar\- canal, and not with any more or less inert ' cement ' 
 substance between them. But the one school must confess what the other 
 proclaims, that while the processes carried on in these cells are definite, 
 well ordered, and evidently guided by laws, these laws have as yet 
 for the most part denied themselves to the modem physiologist, with 
 chemistry- in one hand and physics in the other, as they denied them- 
 selves to his predecessor, equipped only with his scalpel, his sharp eyes, 
 and his mother-wit. So that in the present state of our knowledge all 
 we can really say is that, while absorption is certainly aided by physical 
 processes, like osmosis and diffusion, possibly by physical processes 
 like imbibition, and is verj' likely not unrelated to the molecular proper- 
 ties of surfaces (surface tension, adsorption), it is at bottom the work 
 of cells with a selective permeability which we do not fully understand, 
 or at least which we cannot as yet ex:! in in terms of known physical 
 processes acting through a membrane of known physico-chemical 
 structure. 
 
 Thus, dissolved substances pass with equal ease in either direc- 
 tion through an ordinary diffusion membrane, but in general they 
 pass, with the water in which they are dissolved, more readily out 
 of the intestine than into it. This normal direction of the stream 
 is still maintained for a considerable time after stoppage of the 
 circulation, provided that the intestine is kept in good condition — 
 for example, by being suspended in well-oxygenated blood. Water 
 or solutions of sodium chloride or sugar disappear from the lumen. 
 And this is not due to mere imbibition by the intestinal wall, but 
 the liquid is actually transported across it. The theory that liquids 
 might be taken up from the gut by imbibition, and the water then 
 mechanically removed by the blood flowing on the other side of the 
 imbibing cells, is incompatible with this experiment (Cohnheim). 
 Nor is it necessary that differences of concentration of the dissolved 
 substances on the two sides of the absorbing intestinal membrane, 
 which would permit osmosis and diffusion to go on, should exist. 
 \\'hen the excised intestine of a holothurian was filled with sea- 
 water and suspended in the same sea-water, its contents continued 
 to diminish in bulk for hours or entirely disappeared. Here a liquid 
 identical in composition and concentration with the external liquid 
 was moved in a definite direction across the wall of the intestine 
 from the lumen to the exterior surface. In like manner, when a 
 piece of intestine from a newly-killed rabbit is stretched across a 
 vessel of salt solution so as to divide i«- into two separate compart- 
 ments, the solution continues for ^ while to leave the compartment 
 
MECHANISM OF ABSORPTION 435 
 
 to which the mucosa is turned, and to accumulate in the other. In 
 the cases mentioned the transportation of the liquid depends upon 
 the survival of those properties of the mucous membrane which 
 characterize its elements as living cells. For when the cells that 
 line the intestine are injured or destroyed, or subjected to the 
 action of certain poisons, absorption from it is diminished or 
 abolished. In the dead intestine the characteristic set of the tide 
 out of the lumen across the mucosa can no longer be observed. It 
 must be remarked further, in this connection, that in its normal state 
 the mucous membrane does not take up indiscriminately all kinds 
 of diffusible substances, or absorb those which it does take up in 
 the direct ratio of their diffusibility. Nor does it reject everytliing 
 which does not diffuse. Albumin, for example, which does not 
 pass through dead animal membranes, is to a certain extent taken 
 up from a loop of intestine without change. Cane-sugar (after 
 inversion) and dextrose are absorbed more rapidly than their 
 velocity of diffusion would indicate, when compared with inorganic 
 salts. Glauber's salt diffuses in water fifteen times as fast as cane- 
 sugar, but cane-sugar is absorbed from the intestines ten times faster 
 than Glauber's salt. The velocity of absorption is different even 
 for simple stereoisomeric sugars — i.e., sugars whose molecule, with 
 the same number of atoms combined in the same way, has a dif- 
 ferent form (Nagano). Nor is there any clear relation between the 
 rate of absorption of the various sugars and their osmotic pressure. 
 Dextrose and cane-sugar are always absorbed in greater amount 
 than lactose from solutions of the same osmotic pressure. Indeed, 
 as we shall see, lactose is practically not taken up at all as such 
 (p. 445), and in concentrated solutions may even cause a reversal 
 of the normal movement of water, and act as a purgative. Even the 
 water, organic and inorganic solids of the serum of an animal, are 
 absorbed from a loop of its intestine when the blood-pressure in the 
 capillaries of the intestinal wall is considerably greater than the 
 pressure in the cavity of the gut. Since the serum in the intestine 
 and the plasma in the capillaries must be isotonic, and practically 
 identical in chemical composition, the absorption cannot be due 
 to ordinary osmosis or diffusion. Nor can it be due to filtration, 
 since the slope of pressure is from the capillaries to the lumen of 
 the gut (Reid). It is therefore extremely difficult to reconcile this 
 experiment with any purely physical theory of absorption. The 
 same investigator, summing up the result of careful experiments on 
 the absorption of weak solutions of glucose, concludes that, ' with 
 the intestinal membrane as normal as the experimental procedure 
 will permit, phenomena present themselves which are as distinctly 
 opposed to a simple physical explanation as those previously 
 studied in the absorption of serum.' 
 There is also evidence that even during the absorption of fiquids 
 
436 ABSORPTION 
 
 which undergo no chemical changes in the gut — e.g., salt solutions 
 of different kinds and different concentrations — chemical energy 
 must be transformed, and on no mean scale, in the intestinal 
 mucosa, for the consumption of oxygen and the production of 
 carbon dioxide by the intestine is markedly increased (Brodie and 
 Vogt). 
 
 It may be taken, then, as quite certain that in absorption from 
 the ahmentary canal an essential factor is the activity of the hving 
 cells of the mucosa, which, in some way at present unknown, main- 
 tain the ' set of the tide ' from the lumen to the bloodvessels (or 
 lymph spaces), whether the slope of concentration of the dissolved 
 substances favours or opposes it, or when the concentration is the 
 same on both sides of the membrane. It is even probable that this 
 action of the cells is much the most important of all the factors 
 involved. It would be highly misleading, however, to assume that, 
 because this is so, other factors — osmosis, diffusion, possibly even 
 filtration due to differences of pressure caused by the intestinal 
 movements or the contractions of the muscular fibres of the villi 
 (p. 443) — are of necessity negligible. On the contrary, these other 
 factors cannot be adequately taken account of, nor can there be 
 any possibility of assigning to them their proper value until it is 
 recognized that their influence in absorption from the digestive 
 tract is never under ordinary conditions expressed as a simple and 
 uncomplicated effect, such as may be observed in experiments with 
 dead membranes, but, on the contrary, is constantly overlaid, 
 thwarted, or totally reversed, by the special action of the cells. 
 For this reason the discussion of the mechanism of absorption under 
 the time-honoured captions of ' mechanical or physical theory ' 
 versus ' physiological or vital theory,' as if the process must of 
 necessity be purely ' physical ' or purely ' vital,' has lost interest. 
 It may be confidently assumed, indeed, that just because the 
 physiological factor is so dominant, the famiHar physical forces 
 must often appear to exert a smaller influence than is really the 
 case, and that, could we disentangle the currents which they create 
 and sustain from that steady drift of material out of the lumen of 
 the gut maintained at the expense of its chemical energy by the 
 still unknown machinery of the cells, we should be impressed with 
 the magnitude rather than the insignificance of their total effect. 
 
 The following attempt by Hober to analyze on these lines an old 
 experiment of Heidenhain, which the latter observer had interpreted 
 as showing that diffusion and osmosis play no essential part in absorp- 
 tion from the alimentary canal, is of interest in this connection. A 
 loop of small intestine was tied of! at both ends, but its circulation was 
 not otherwise interfered with. Solutions of sodium chloride of dif- 
 ferent strengths were introduced into the loop, and in each observation 
 after fifteen minutes the contents of the loop were recovered and 
 analyzed for the chloride. 
 
MECHANISM OF ABSORPTION 
 
 437 
 
 Introduced. 
 
 Recovered, 
 
 C.C. 
 
 Percentage of 
 NaCl. 
 
 Total NaCl in 
 (iraiiiines. 
 
 C.C. 
 
 Percentage of 
 NaCl. 
 
 Total NaCl in 
 Grammes. 
 
 I20 
 
 I20 
 
 120 
 
 0-30 
 
 0-50 
 I -00 
 1-46 
 
 0-36 
 0-60 
 I-I7 
 
 18 
 35 
 
 75 
 109 
 
 0-60 
 0-66 
 0-90 
 1-20 
 
 0-108 
 0-230 
 0-670 
 I-3IO 
 
 Here it is seen that, from the markedly hypotonic solutions of the 
 first two observations, sodium chloride was absorbed, of course, along 
 with much water. But from the strongly hypertonic solution of the 
 last observation some water was also taken up, instead of water passing 
 into it from the blood. The suggested explanation of these and other 
 data yielded by the experiment is that an osmotic stream of water out 
 of the loop into the blood is established on introduction of the hypo- 
 tonic solutions, which raises their percentage of salt, while in the case of 
 the hypertonic solution a diffusion stream of sodium chloride is estab- 
 lished in the same direction, and its salt content falls. The volume of 
 the hypotonic solutions in the loop rapidly diminishes because the 
 osmotic current conspires with the normal ' physiological ' drift from 
 the lumen outwards. In this drift both salt and water are involved, 
 as if the cells were filters which maintained through expenditure of 
 their own energy a slope of hydro.static pressure from free surface to 
 depth. The hypertonic solution diminishes only slowly in bulk, be- 
 cause the ' physiological ' current out of the lumen is opposed by the 
 osmotic stream of water into the lumen. Nevertheless, even the hyper- 
 tonic solution is gradually absorbed, because the pull of the cells — the 
 suction, if it may be so expressed, of the cellular pump — is powerful 
 enough to overcome the osmotic current and to force water up the 
 slope mto the blood or into the tissue liquid, whose osmotic pressure is 
 not much more than half that of the solution. 
 
 Permeability of the Intestinal Epithelium and Lipoid-Solubility 
 of Absorbed Substances. — If the cells of the intestinal mucosa are 
 to move materials out of the lumen of the gut, it is obvious that 
 these materials must first be able to enter the cells. The ease or 
 difficulty with which different substances are absorbed may there- 
 fore depend upon the degree in which the cells are permeable for 
 them. The question of the factors on which the permeabiUty of 
 cells depends has already been discussed to some extent in the case 
 of the coloured blood-corpuscles. A famous theory attributes the 
 degree of permeability of erythrocytes and many other animal and 
 plant cells to given substances to the degree of the solubility of 
 these substances in the lipoids which are supposed to form the 
 essential constituents in the outer layer or envelope of cells (Overton) 
 Substances which are readily soluble in lipoids are supposed to gain 
 an easy entrance by going into solution in the envelope ; those which 
 are insoluble in lipoids are checked at the boundary. Attempts 
 have been made to apply this theory to the explanation of selective 
 
438 ABSORPTION 
 
 absorption by the intestine, but without much success. The very 
 fact that the theory is held to apply to practically any cell greatly 
 circumscribes at the outset its power of dealing with cells like those 
 hning the intestine, which are adapted to absorb nutrient materials 
 for all the body, and must necessarily differ in their permeability 
 from cells adapted for some hmited function involving only a 
 limited and specialized nutritive exchange. Thus sodium chloride 
 practically does not penetrate the red blood-corpuscles, the muscle 
 fibres, and many other tissue elements. It is a lipoid-insoluble sub- 
 stance, and the lipoid theory says that this is the reason why it 
 penetrates these cells with such difficulty. But sodium chloride 
 must and does penetrate the intestinal mucosa, and with consider- 
 able ease, in order that the body, especially its extracellular liquids, 
 may obtain a sufficient supply of this indispensable material. It is 
 still a lipoid-insoluble substance, and pays no heed to the lipoid 
 theory at all. It is perfectly true that some substances — e.g., ethyl 
 alcohol — which are much more soluble in lipoids than sodium 
 chloride, are also even more readily absorbed from the intestine. 
 It has been stated also that, as regards the velocity of their absorp- 
 tion, the three alcohols, glycerin, erythrite, and mannite, are related 
 to each other in the Same way as in regard to their lipoid-solubility. 
 There is, of course, some reason for this, and also some reason why 
 ethyl alcohol is taken up more easily than salt, but we do not know 
 that it has anything to do with Upoid-solubility. If there is a 
 hpoid layer at the free ends of the cells covering the vilh, it is very 
 possible that a substance soluble in Hpoids may be able to enter cells 
 which would otherwise have denied it entrance. It may even inflict 
 temporary or permanent injury on the cells in doing so, and may 
 thus be taken up in greater amount than by normal cells, and this 
 possibility has to be reckoned with in giving a physiological value 
 to experiments with materials essentially foreign to the intestine, 
 and to which it cannot have developed any adequate adaptation. 
 For the essential food materials it is quite certain that, apart from 
 any general relations of cell envelope and environing liquids which 
 are common to the intestinal and to other cells, special relations of 
 an adaptive nature have been developed between the intestinal cells 
 and the very special hquids, elsewhere unknown in the body, with 
 which they come in contact in the lumen of the gut. It is unlikely 
 that the mucosa has developed a special adaptation for lipoid- 
 solublc food materials; it must have developed an adaptation for 
 such food materials, lipoid-soluble or not, as have been offered to 
 it through (ountless ages, and as are necessary for the nutrition of 
 the organism. 
 
 But if it be true that the action of the columnar epithelium of the 
 intestinal mucous membrane in the absorption of the food is in the 
 main a process of selective secretion such as is found in glandular 
 
MECHASISM OF ABSORPTION 435 
 
 organs, an action which wc may perhaps describe as making use 
 of jMiroly physical processes, hut not mastered by tliem, the possi- 
 bihty must be admitted that in the cells of endothelial type which 
 line the serous cavities, the lymphatics, the bloodvessels, the alveoli 
 of the lungs, and the Bowman's capsules of the kidney (p. 489), the 
 element of secretion may be less marked, and more overshadowed 
 by the physical factors. And it may very plausibly be urged that 
 changes of considerable physiological complexity can only be 
 wrought on substances that have to pass through a cell of con- 
 siderable depth, while a mere film of protoplasm suffices for, and 
 indeed favours, mechanical filtration and diffusion. We have 
 already seen (p. 26i), in the case of the lungs, that whatever the 
 complete explanation may be of the gaseous exchange which takes 
 place through the alveolar membrane, physical diffusion undoubtedly 
 plays an important part. We shall see, too (p. 500), that in the case 
 of the kidney the endothelium of the Bowman's capsule, although 
 by no means devoid of selective power, does seem to have allotted to 
 it a simpler task than falls to the share of the ' rodded ' epithelium. 
 
 Absorption from the Peritoneal Cavity. — Further, it has been stated 
 that interchange between blood-serum, circulated artificially in the 
 vessels of dogs and rabbits which have been dead for hours, and 
 liquids introduced into the peritoneal cavity, is essentiall}- the same 
 as in the living animal, and can be explained on purely physical 
 principles (Hamburger). But there is one experiment, at any rate, 
 which is certainly difficult so to explain — viz., the absorption from 
 the peritoneal ca\'ity of sodium chloride solution isotonic with the 
 blood-serum, an absorption which goes on with considerable 
 rapidity. Starling has supposed that this is due to the circum- 
 stance that the proteins of the serum exert osmotic pressure, the 
 peritoneal membrane being almost or altogether impermeable for 
 them in comparison to its permeability for the salt solutions. In 
 consequence, water passes into the bloodvessels from the peritoneal 
 cavity. The solution thus becomes more concentrated as regards 
 sodium chloride, some of which accordingly enters the blood 
 by diffusion, and so on. But even isotonic serum is absorbed 
 from the peritoneal ca\nty, and it seems to savour of special pleading 
 to suggest, as has been done, that this takes place through the 
 lymphatics, and not at all through the bloodvessels. 
 
 Up to a certain point an increase in the intraperitoneal pressure 
 favours absorption, but beyond this it hinders it by interfering with 
 the circulation. The removal of a portion of the fluid in this con- 
 dition facilitates the absorption of the rest — a fact which has long 
 been applied in the operation of tapping. Ligation of the thoracic 
 duct has little effect on the fate of liquids injected into serous 
 cavities, since the bloodvessels play the chief part in their absorp- 
 tion, just as strjxhnine, when injected under the skin — i c, into 
 
uo 
 
 ABSORPTION 
 
 the lymph spaces of areolar tissue — is taken up by the blood and 
 does not appear in the lymph. 
 
 But even if we admit that substances can pass, by physical pro- 
 cesses alone, from serous cavities into the blood, and from the blood 
 into serous cavities, this has little bearing upon the question of 
 intestinal absorption. For we can hardly put anything into the 
 peritoneal cavity which is not foreign to it. It was never intended 
 to come into contact with the hundred and one solutions, extracts, 
 suspensions, and what not, which the industrious experimenter has 
 offered to its unsophisticated endothelium. It cannot possibly have 
 developed any high degree of ' selective ' power. In the intestine 
 everything is different. The mucosa is adapted to come into 
 contact with an immense variety of materials, all kinds of food- 
 substances mingled with many kinds of refuse, the products of 
 the action of numerous digestive ferments, and of a \agorous and 
 varied bacterial flora. All these it has to sift and try. It cannot fail 
 to have properties which suggest a severe and searching selection. 
 
 The difference between a serous cavity and the intestine is well 
 illustrated by the following experiment, in which the clianges in the 
 composition of a hypotonic (3 per cent.) solution of dextrose introduced 
 into the peritoneal sac and into a loop of intestine respectively were 
 compared (Cohnheim). 
 
 Introduced. 
 
 After 1 Recovered. 
 
 1 
 
 Peritoneum - 
 Intestine - - 
 
 50 c.c. 
 
 44 » 
 
 f 19-5 C.C, containing I percent. 
 90 mins. dextrose and 0'55 per cent. 
 
 1. XaCl. 
 
 j 19 c.c, containing 3-8 per cent. 
 25 „ - dextrose and 0-04 per cent. 
 
 1' NaCl. 
 
 J 
 
 Here the water and sugar are both taken up from the intestine and 
 the peritoneal cavity; but while the sugar concentration in the serous 
 sac falls markedly, as ought to be the case if the sugar is diffusing into 
 the blood along the slope of concentration, the percentage of sugar in 
 the intestine actually increases. Still more striking is the fact that 
 sodium chloride accumulates in the peritoneal liquid in a concentration 
 obviously tending to equality with that of the blood, as would happen 
 if the peritoneal lining were a dead diffusion membrane. On the other 
 hand, practically no sodium chloride passes into the lumen of the gut. 
 
 Closely connected with the question of absorption from and 
 secretion (or transudation) into the serous cavities is the question 
 of the factors concerned in the formation of the lymph (which will 
 be considered in the next chapter), even although recent researches 
 throw grave doubt on the common view that these sacs are merely 
 expanded lymph spaces, and indicate that the liquid found in them 
 has a different origin from lymph. 
 
ABSORPTION OF THE VARIOUS FOOD SUBSTAACES 44i 
 
 Section III. — ^Absorption of the Various Food Substances. 
 
 Absorption of Fat — How the Fat gets into the Intestinal Epithelium. 
 — It has been already mentioned that fat is split up in the intestine 
 into the corresponding alcohols (mostly glycerin) and fatty acids, 
 but it has been a subject of discussion whether it all undergoes this 
 change or only a portion of it. The common view has long been 
 that the gi'eater part of the fat escapes decomposition, and, after 
 emulsification by the soaps formed from the liberated fatty acids, 
 is absorbed as neutral fat by the epithelial cells covering the villi. If 
 an animal is killed during digestion of a fatty meal, these cells are 
 found to contain globules of different sizes, which stain black with 
 osmic acid, are dissolved out by ether, leaving vacuoles in the cell 
 substance, and are therefore fat (Fig. 172). It has always been 
 difficult to explain how droplets of 
 emulsified fat could get into the 
 interior of the epithelial cells, al- 
 though, perhaps, no more difficult 
 than to explain the passage of living 
 tubercle bacilli from the contents of 
 the intestine into the chyle of the 
 thoracic duct — a fact which has been 
 clearly demonstrated (Ra venel) . The 
 fat is certainly contained within the 
 cells, and not between them. When 
 fat is found in the cement sub- 
 stance between the cells, it has been 
 mechanically squeezed out of them 
 by the shrinking of the villi in 
 preparation. This difficulty is obviated if we suppose that the 
 whole of the fat is spht up in the intestine, the products being 
 absorbed in solution, the glycerin as such, and the fatty acids either 
 as soaps or in the free state, or partly free and partly saponified. 
 If this is the true theory — and the evidence of its truth has of late 
 years been continually growing — neutral fat must again be built 
 up in the epithelial cells from the absorbed glycerin and the fatty 
 acids or soaps. Now, it has been shown that when an animal is fed 
 with fatty acids they are not only absorbed, but appear as neutral 
 fats in the chyle of the thoracic duct, having combined with glycerin 
 in the intestinal wall; and the epithelial cells contain globules of 
 fat, just as they do when the animal is fed with neutral fat. Further, 
 it is known that fat-splitting goes on in the alimentary canal to a 
 much greater extent than would be necessary merely for the forma- 
 tion of a quantity of soap sufficient to emulsify the whole of the fat 
 in the food. Indeed, at certain stages of digestion most of the 
 
 Fig. 172. — Mucous Membrane of 
 Frog's Intestine during Absorp- 
 tion of Fat (Schiifer). ep, epithe- 
 lial cells; str, striated border; 
 C, lymph corpuscles; /, lacteal. 
 
442 ABSORPTION 
 
 fatty material, both in the small and large intestine, has been found 
 to consist of fatty acids. The reversibility of tlie reaction under 
 the influence of lipase, whicli has already been alluded to, does not 
 enter into the question so far as fat-splitting in the intestine is con- 
 cerned, for the products of the reaction can be absorbed as quickly 
 as they are formed. To clinch the matter, it has been proved that 
 when mixtures of paraffin and fat, which can be emulsified in a 
 watery solution of sodium carbonate, are eaten, the paraffin is com- 
 pletely excreted with the faeces, while the greater part of the fat is 
 absorbed. And fatty substances which are not easily split up and 
 saponified (for example, lanolin, the fat of sheep's wool, a mixture 
 of compounds of fatty acids with isocholesterin, a substance closely 
 related to cholesterin and allied bodies) are not absorbed even when 
 they are easily emulsified. Even fats with a melting-point far 
 above the temperature of the body can be absorbed after being split 
 up. The palmitate of cetyl alcohol, the chief constituent of sper- 
 maceti, melting at 53° C, was absorbed to the extent of 15 per 
 cent., 85 per cent, being excreted in the faeces. It appeared as 
 palmitin in the chyle of a human being flowing from a fistula, the 
 palmitic acid having been absorbed as such, or as a sodium soap, and 
 having then united with glycerin to form the neutral fat, palmitin. 
 
 Some observers have endeavoured to show that the fat is absorbed 
 without change by introducing into the intestine fat stained with 
 dyes, such as alkanna red or Sudan III., which are insoluble in 
 water. The stained fat was found in the epithelial cells of the villi, 
 in the lacteals, and, in the case of a patient suffering from chyluria, 
 in the urine. But this evidence is not conclusive, for it has been 
 shown that the pigments might easily have been absorbed after 
 decomposition of the fat, since, although insoluble in water, they are 
 soluble in fatty acids, and therefore to some extent in the intestinal 
 contents, and readily pass into the lymph. 
 
 As already pointed out, the bile plays an important part in the 
 solution of the fatty acids, which may form loose compounds with 
 the amide group of the bile-acids. In these loose combinations, 
 soluble in water, the fatty acids can be absorbed from the intestinal 
 contents (Pfliiger). In whatever way the fat which can be seen 
 in the epithelial cells during absorption of fat gets into them, it 
 must be carefully noted that there is no quantitative proof that it 
 represents all or even the greater part of the absorbed fat. So far 
 as microscopic observations go, much of the fat may pass through 
 the mucosa in the form of soluble decomposition products without 
 appearing in ]xirticulate form in the epithi'lium. 
 
 How the Fat gets out of the Intestinal Epithelium. — Leucocytes 
 have been asserted to be active agents in the absorption of fat. 
 They have been described as pushing their way between the 
 epitheUal cells, fishing, as it were, for fatty particles in the juices 
 
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 443 
 
 of the intestine, and then travelling back to discharge their cargo 
 into the lymph. This view, however, is erroneous. But, although 
 the leucocytes do not aid in the absorption of fat from the intestine, 
 they may take up a certain amount of it from the epithelial cells, 
 and convey it through the spaces of the network of adenoid tissue 
 that occupies the interior of the villus, to discharge it into the 
 central lacteal, where it mingles with the lymph and forms the so- 
 called molecular basis of the chyle. It has been supposed that a 
 part of the fat ma}^ reach the lacteal in another way. The con- 
 traction of the smooth muscular fibres of the villus and the peristaltic 
 movements of the intestinal walls, which alter the shape of the 
 villi, alter as well the capacity of the lacteal chamber, and so 
 alternately fill it from the lymph of the adenoid reticulum, and 
 empty it into the lymphatic vessel with which it is connected. By 
 this kind of pumping action the passage of fat and other substances 
 into the lymphatics may be aided. There is, however, no proof 
 that all the fat accumulated in the intestinal epithelium leaves 
 it without further change. It is quite as probable that the lipase 
 which is known to be contained in the cells again hydrolyses the 
 fat, or a portion of it, and that the constituents then pass out into 
 the lymph, or even in part into the blood. In the dog most of the 
 fat goes into the lacteals, and thence by the general lymph-stream 
 through the thoracic duct into the blood. And in man the chyle 
 collected from a lymphatic fistula contained a large proportion of 
 the fat given in the food (Munk). But this bare statement would 
 be misleading if we did not add that the fat taken in can never be 
 entirely recovered in the chyle collected from the thoracic duct. 
 A small fraction of the deficit might be accounted for as fat directly 
 used up for the nutrition of the intestinal wall itself. But even after 
 ligation of the thoracic and right lymphatic ducts a large proportion 
 of a meal of fat (32 to 48 per cent.) is absorbed from the intestine, 
 obviously by the channel of the bloodvessels, since the fat-content 
 of the blood increases up to, it may be, six times the highest amount 
 present in the blood of fasting animals. The statement that only 
 fatty acids can be absorbed under these conditions is erroneous 
 (Munk and Friedenthal). 
 
 A dog normally absorbs g to 21 per cent, of the fat in a meal in 
 three to four hours; 21 to 46 per cent, in seven hours; and 86 per 
 cent, in eight ieen hours (Harley). After excision of the pancreas 
 the absorption of fat is hindered, though not abolished. More fat, 
 indeed, can be recovered from the intestine than is given in the food. 
 This at first sight paradoxical result is explained by the well-estab- 
 lished fact that a certain amount of fat is normally excreted into 
 the intestine. 
 
 Mechanism of Fat Synthesis in the Intestinal Mucosa. — As to the 
 manner in which the synthesis of the fat in the intestinal epithelium 
 
444 ABSORPTION 
 
 is accomplished, the most fascinating theory is that wliicli attributes 
 it to the reversed action of Hpase, possibly the very same lipase as 
 originally split it up in the intestine. The reversibility of the action 
 of various enzymes under changed conditions, especially changes in 
 the relative concentration of the bodies concerned in the reaction, 
 has been previously mentioned. It has been shown, e.g., that the 
 pancreas, intestinal mucous membrane, lymph glands, etc., and 
 even cell-free extracts of these organs have the power of synthesizing 
 the ester ethyl butyrate from butyric acid and ethyl alcohol 
 (P- 338), as well as the power of decomposing the ester into the 
 fatty acid and the alcohol. Moore, however, states that in the 
 case of ordinary fats the synthesis takes place in the intestinal wall 
 only in situ, and while the circulation is going on. In the intestinal 
 mucosa the greater part of the fatty acid is already combined with 
 glycerin as neutral fat, although considerable quantities of free fatty 
 acid are also present. In the lymph coming directly from the 
 mesenteric glands practically the whole of the fatty acids are in 
 the form of neutral fat. 
 
 An additional, and in some respects even more remarkable, illus- 
 tration of the synthesizing powers of the intestinal wall is the dis- 
 covery of Munk, already referred to (p. 441), that fatty acids given 
 by the mouth appear in the lymph of the thoracic duct as neutral 
 fats, having somewhere or other, in all probability on their way 
 through the epithelium of the gut, been combined with glycerin. 
 
 Since, however, the amount of neutral fat recovered from the 
 thoracic duct is not equivalent to more than one-third of the fatty 
 acids given, it has been suggested that this synthesis of fat is only 
 apparent, and that the whole of the fat which appears in the chyle 
 after a meal of fatty acids comes from the fat excreted into the 
 intestine (Frank), which is increased when fatty acids are given by 
 the mouth. But the suggestion is more ingenious than the e\ndence 
 advanced in its support is convincing. And, as we have seen 
 (p. 443), a part of the deficit may be accounted for by absorption 
 directly into the bloodvessels. 
 
 In concluding our review of the absorption of fat, certain general 
 considerations which have a close relation to the question may be 
 alluded to. There is some reason to think that the lipises are 
 enzymes less finely adjusted to minute differences in the structure 
 of the fats on which they act than other digestive ferments — eg., 
 maltase or lactase, to details in the chemical structure of their 
 substrates. If this be so, a very few lipases, or even a single one. 
 may suffice to accomplish all the enzymatic changes which occur 
 in the fats both in the lumen of the intestine and in all the various 
 tissue cells. At the same time the possible variation in those decom- 
 position products which constitute the ' building-stones ' of the fats 
 is less than in the case of, say, the proteins. Two consequences 
 
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 4^5 
 
 follow as regards the absorption of fat: (i) Each cell may be capable 
 of dealing with the original neutral fats of the food, and of adapting 
 them to its needs by decomposing and resynthesizing them so far 
 as is necessary in its own substance. In this case it would not be 
 necessiiry for assimilation by the cells that the fats should be com- 
 pletely split or even split at all in the alimentary canal, however 
 important this might be for their absorption from its lumen. 
 (2) If it were necessary for absorption that decomposition of the 
 fats should take place in the lumen of the digestive tube, the whole 
 of the fat, or at any rate such portion of it as was not at once needed, 
 might without disadvantage for the tissues be resynthesized after 
 absorption. It is not difficult to see that it might even be advan- 
 tageous that not only the relatively fixed reserve in the fat cells, 
 but also what might be termed the floating or circulating reserve 
 constituted by the emulsified fat in the blood should be in the 
 insoluble form of neutral fat. 
 
 Absorption of Carbo-Hydrates. — Carbo-hydrates are normally 
 absorbed from the alimentary canal only in the form of mono- 
 saccharides, such as dextrose, levulose or fructose, and galactose, 
 but especially dextrose. These monosaccharides are readily 
 formed from polysaccharides like starch and dextrin, and the disac- 
 charide maltose, which they yield on digestion with amylase, as 
 well as from disaccharides like cane-sugar and lactose, by the fer- 
 ments already studied. That, as a matter of fact, the hydrolysis 
 in the intestine must convert practically all the carbo-hydrate into 
 monosaccharides before absorption, can be shown in various ways. 
 The ferment lactase, while present in the small intestine of all 
 young mammals, is regularly absent in some mammalian groups 
 in the adult. In other species, including man, it is found in some 
 adults, but not in all. In birds and other animals below the mam- 
 mals, it has not hitherto been found at any age. It has been sur- 
 mised that these differences depend upon the presence or absence 
 of lactose (milk) as a regular constituent of the food. (But see 
 p. 410.) If, now, lactose is introduced into a loop of intestine in an 
 animal which does not possess lactase — e.g., an adult rabbit — it is 
 not ajDsorbed, but remains in the lumen till it is at last decomposed 
 by bacterial action. In animals in which lactase is present the 
 lactose is rapidly absorbed. Maltose is easily taken up from the 
 intestine because of the action of the ferment maltase, which is the 
 most widely spread of all the inverting ferments. The dextrose formed 
 by the maltase is so rapidly absorbed that none, or only traces, of it 
 can be detected in the contents of the intestinal loop. But if absorp- 
 tion be interfered with by injuring the intestine, maltose disappears, 
 and the dextrose produced from it accumulates in the lumen. The 
 reason for the discrimination exercised bj^the intestinal mucosa in 
 favour of the monosaccharides becomes apparent when an attempt is 
 
446 ABSORPTION 
 
 made to circumvent it by injecting the sugars parenterally — ie-, into 
 subcutaneous or intramuscular connective tissue, into a serous sac, 
 or directly into the blood. Cane-sugar and lactose so introduced 
 are excreted unchanged in the urine. Dextrose, levulose, and 
 galactose are used u]) in the body, and some maltose likewise, 
 thanks to the presence of maltase in the blood and tissues. The cells 
 of the body in general will burn only monosaccharides, and not di- or 
 poly-saccharides. Galactose and fructose are probably first con- 
 verted into dextrose before being utilized by the tissues, a change 
 which can also be readily induced in the test-tube. Therefore the 
 intestine admits the simple, but rejects the more complex sugars. 
 It is only in the presence of abnormally great quantities or ab- 
 normally great concentrations of the sugars which are not directly 
 utilizable that they are to a certain extent taken up unaltered, 
 to be for the most part quickly excreted as such (p. 540). In like 
 manner we have seen that the native proteins can, so to speak, 
 force their way by storm through the intestinal mucosa when 
 offered to it in exceptionally large a.mount. The sugar absorbed 
 from the intestine passes normally into the rootlets of the portal vein, 
 not into the chyle, for no increase in the quantity of that substance 
 in the contents of the thoracic duct takes place during digestion, 
 while the sugar in the portal blood is increased after a starchy meal. 
 The blood of the portal vein of a dog in the fasting condition con- 
 tained 0-2 per cent, of dextrose. During absorption of a meal rich 
 in carbo-hydrates it contained as much as 0-4 per cent. In the 
 lymph issuing from the thoracic duct the amount was the same in 
 both conditions — viz., o-i6 per cent. In a case of lymph (chyle) 
 fistula in a human being, where almost all the lymph from the 
 digestive tract escaped through the fistula, out of 100 grammes of 
 carbo-hydrate taken (50 grammes starch and 50 grammes sugar), 
 only ^ gramme, or not i per cent, of the sugar corresponding to the 
 carbo-hydrates of the food, could be recovered in the chyle. But 
 when a large amount of a dilute solution of sugar is introduced into 
 the intestine, some of it is taken up by the lacteals. 
 
 Absorption of Water and Salts. — The main channel for absorption 
 of these is the bloodvessels of the intestine. As much as 3 to 5 litres 
 of water can be absorbed in a day in the intestine of a healthy man, 
 exceptionally even 6 to 10 litres, without the faeces altering their 
 normal consistence. Absorption of the water and dissolved salts 
 may theoretically take place either through the epithelial cells (intra- 
 epithelial absorption), or between the cells (interepithelial absorp- 
 tion). According to Hober, most metallic salts (silver, mercury, 
 lead, bismuth, copper, manganese, etc.) are absorbed interepitheli- 
 ally, while iron salts form an exception, and pass into the epithelial 
 cells. The distinction between interepithelial and intra-epithelial 
 absorption does not rest upon an absolutely sure foundation. Yet 
 
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 
 
 447 
 
 it is probable that everything whicli is usiful in the nutrition of 
 the body is taken up by the cells, while such substances as metaUic 
 salts which are foreign to the organism, and an; denied entrance 
 into the cells, may pass in small amount between them, their passage 
 being perhaps associated with more or less injury to the interstitial 
 substance. The vigilant selection exercised by the mucosa is well 
 illustrated by the facts that, although manganese and iron are 
 chemically so closely related, iron, which is necessary for the 
 formation of the blood-pigment, is absorbed in immensely greater 
 amount than manganese; and that chlorides, especially sodium 
 chloride, are readily taken up, sulphates with difficulty. Iron is 
 absorbed by the bloodvessels, but also to some extent by the lacteals. 
 From the blood it is carried to various organs, especially the spleen 
 and liver. There is reason to believe that the eosinophile leucocytes 
 take some share in its transportation. 
 
 It was supposed by Bunge that only organic compounds of iron 
 could be absorbed, and that the undoubted benefit derived from 
 the administration of inorganic iron compounds, such zz ferric 
 chloride, in chlorosis, was due not to their direct absorption, but 
 to their shielding the organic compounds from the attack of the 
 sulphuretted hydrogen in the intestine (p. 424)- But this theory 
 has been shown to be inconsistent with the facts. For instance, 
 after the administration of salts of iron, the iron in the blood, 
 liver, spleen, and other organs increases, but there is no accumula- 
 tion of iron in the liver of an animal to which salts of manganese 
 have been given, although these are equally decomposed by sul- 
 phuretted hydrogen. 
 
 Absorption of Proteins. — -The proteins of the food or their digested 
 products also pass directly into the blood-capillaries which feed 
 the portal system. For it has been shown that after ligature of 
 the thoracic duct protein substances are still absorbed from the 
 intestine, and the urea corresponding to their nitrogen appears in 
 the urine. The total nitrogen in the chyle flowing from a fistula 
 of the thoracic duct in a man was not found to be increased during 
 the digestion of protein food. The quantity of chyle escaping in a 
 given time was also unaffected, whereas during the digestion of fats 
 it was greatly augmented (-Munk). 
 
 Although a certain amount of egg-albumin, serum-albumin, alkali- 
 albumin, and other native or slightly altered protein substances 
 can be absorbed as such by the small, and even by the large, in- 
 testine, there is no evidence that, under ordinary conditions, this 
 mode of absorption is of any practical importance in nutrition, 
 although in another relation it may possess a certain interest (p. 32), 
 For when native proteins, with the possible exception of the 
 serum proteins from an animal of the same species, are introduced 
 ' parenterally,' so that they do not reach the tissues by way of 
 
448 ABSORPTION 
 
 the alimentary canal, they behave in a very different manner from 
 the same proteins when given by the mouth. One notable differ- 
 ence is that the parenterally administered proteins give rise in 
 general to the formation of antiboches — e.g., specific precipitins 
 (p. 31). This is not the case when they are administered per as, 
 unless, like raw egg-white, which, as already mentioned (p. 404), 
 evokes no secretion of gastric juice, they remain long undigested 
 in the alimentary canal, when an amount sufficient to cause the 
 production of precipitins may eventually be absorbed unaltered. 
 Tills has also been shown by means of the anaphylactic reaction. 
 Secondly, they are not, as a rule, utilized in the metabolism of the 
 body, or are utilized very incompletely. Egg-albumin, for instance, 
 when injected into the blood, is excreted in the urine. It has been 
 previously pointed out that the various proteins differ remarkably 
 not so much in the kinds as in the relative quantities of the amino- 
 and diamino-acids which can be obtained from them (p. 2). This 
 is unquestionably one important reason why the food proteins are — 
 for the most part, at any rate — so thoroughly hydrolysed before 
 absorption. Another may be that it is easier for the intestine to 
 take up the small molecules of the decomposition products than 
 the large colloid aggregates of the original protein solutions. 
 
 So far as the first reason is concerned, the degree of decomposi- 
 tion need not be the same for all the food proteins, although all 
 must be decomposed, for even among the proteins the products of 
 whose hydrolysis do not exhibit qualitative differences, no two 
 have hitherto been discovered which show the same quantitativ.^ 
 relations among the ' building-stones. ' A new house has to be built 
 fiom the materials of an old one. How far the work of demolition 
 must be carried will depend upon the difference between the plans 
 of the two houses. Sometimes the main part of the old building 
 may be saved, and only the wings require reconstruction. In like 
 manner it is conceivable that the central group or nucleus of the 
 molecule of a given food protein may be identical with that of a 
 given body protein, and that only the side-chains maybe so different 
 that they must be broken up and reconstructed. Or, again, the 
 whole architectural plan of the new house may be so distinct from 
 that of the old that the only feasible method is to completely 
 demolish the latter, and then to use the individual bricks in the 
 new construction; just as a protein in the food may differ so 
 radically from a tissue protein into which it is to be transformed 
 that it must be decomposed into the simplest products of proteo- 
 lysis before the reconstruction of the molecule can begin. It is not 
 known what the minimum degree of hydrolysis is which will permit 
 of effective absorption and utilization. But it would seem that it 
 must be very complete. Even a body so simple in comparison with 
 the proteins as the tripeptide (p. 2) alanyl-glycyl-tyrosin, con- 
 
ABSORFTIUN UF THE VARIOUS FOOD SUBSTANCES 449 
 
 taining only three ' building-stones,' can only be changed into the 
 tripeptide alanyl-tyrosyl-glycin by first hydrolysing it into its three; 
 components and then synthesizing these afresh. On the other 
 hand, in obtaining the tripeptide glycyl-tyrosyl-alanin from alanyl- 
 glycyl-tyrosin, the dipcptide group glycyl-tyrosin can remain un- 
 decomposed, and it is only necessary to split alanin off and link it 
 up to the dipeptide to obtain the desired glycyl-tyrosyl-alanin 
 (Abderhalden). There can be no doubt that by far the greater 
 part, if not tlie whole, of the proteins of the food is first changed into 
 proteoses and peptones. But proteose and peptone are absent 
 from the blood, and, indeed, when injected into the blood they 
 are excreted in the urine. When injected in larger amount, they 
 pass also into the lymph, from which they gradually reach the blood 
 again, and are eventually, as before, eliminated by the kidneys. 
 The clear inference is that if they are absorbed as such from the 
 alimentary canal, they must be changed in their passage through its 
 walls. The fact that a portion at any rate of the peptones and 
 proteoses is decomposed into amino-acids, etc., in the lumen 
 of the intestine has been already alluded to. It is certain that 
 this portion is a very large proportion of the whole, although the 
 question how much, if any, of the peptone passes as such from the 
 lumen into the mucosa must still be left undecided. It is true 
 that along with amino-acids peptones are always found in the 
 intestine during the digestion of protein, and the quantity of 
 amino-acids actually present in the lumen at any moment may 
 De small in proportion to the quantity of peptone. But this is 
 precisely what is to be expected if the peptone as such is incapable 
 of absorption. For the easily absorbed amino-acids will disappear 
 from the gut as fast as they are formed, leaving behind the peptone 
 for further hydrolysis. The fact that all the amino-acids which the 
 proteins are capable of yielding can be detected in the contents of 
 the intestine, including even those which appear late and, as it 
 were, reluctantly in artificial digestion, is a proof that the decom- 
 position of the protein goes fast and far in the alimentary canal. 
 If it is not complete, if some of the partially hydrolysed protein is 
 taken up by the mucous membrane in the form of peptones or 
 possibly even of proteoses, it would seem that this is similarly 
 decomposed by the action of erepsin in the intestinal wall. 
 
 It has been stated that during the digestion of a protein meal the 
 mucosa of the stomach and intestine contains proteose and pep- 
 tone, while none is present in the muscular coat or in any other 
 organ. They rapidly disappear from a portion of the mucous mem- 
 brane kept at a temperature of about 40° C outside of the body, and 
 their disappearance is due, not to their regeneration into serum 
 proteins, as was once supposed, but to their decomposition by the 
 
 erepsin. We must suppose that the serum and organ proteins are 
 
 29 
 
450 ABSORPTION 
 
 built up from tlic products of this decomposition. But whether the 
 mucosa of the ahmentary tract is especially a seat of the synthesis 
 is unknown (p. 573). On a priori grounds, it is at least equally 
 probable that it occurs in all the cells of the body, each one building 
 up for itself the particular kind of protein which it needs. The 
 direct way of testing the question would be to examine the blood 
 coming from the intestine during the absorption of proteins, and to 
 determine quantitatively any changes which might have occurred in 
 the nitrogenous constituents. But the flow of blood through the 
 intestine is so great, the absorption of the digestive products so 
 gradual, and their removal from the blood by the tissues, in all 
 probability, so rapid, that there is no reason for surprise that till 
 lately the results of such determinations were ambiguous. Leathes, 
 however, showed some time ago that when peptone, proteose, or the 
 final products of trj^ptic digestion are introduced into a ligated 
 segment of a dog's small intestine, there is always, when absorption 
 occurs, an increase in the nitrogenous substances in the blood, in the 
 form of compounds which are not precipitated by tannic acid, and 
 therefore are neither native proteins nor proteose. Urea accounts 
 for about one-half of the increase ; the rest he considered to represent 
 probably amino-acids and similar substances. Quite recently it 
 has been conclusively demonstrated by improved methods that the 
 digestion of protein is associated with an increase of non-protein 
 nitrogen in the blood, due, there is every reason to believe, toamino- 
 bodies derived from the hydrolysed protein (Folin and Denis, Van 
 Slyke, Abel). This proves for the mammal what had been deduced 
 by Cohnheim for a much lower form from experiments made on the 
 intestines of certain octopods, which, when excised and suspended 
 in the oxygenated blood, will live for many hours. A solution of 
 peptone was introduced into the isolated intestine, and after twenty 
 hours the crystalline products, leucin, t^Tosin, lysin, and arginin, 
 were found in the blood. In the intact animal none of these bodies 
 could be detected in the blood (Cohnheim). The inference was 
 that protein in these animals is absorbed in the form of amino-acids, 
 etc., which are then carried to the tissues and utilized there. In 
 the mammal the same thing appears to be true. For the increase 
 in the amino-acids during digestion of proteins occurs not only in 
 the portal blood, but in the blood of the general circulation. So 
 that, although a part of the absorbed amino-bodies may be removed 
 by the liver, a portion at least is available for the tissues in general. 
 That the tissues actually take up such decomposition products of 
 proteins is indicated by the fact that during and after the digestion 
 of protein in a loop of intestine the non-protein nitrogen of the 
 tissues is increased (Folin). It may be that some of the proteose 
 and peptone are regenerated bv a shorter process, and without 
 having been further split up, but of this, too, there is no definite 
 
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 451 
 
 proof. The regeneration, wherever it occurs, must presumably take 
 place in cells, and the only available cells in the digestive mucous 
 membrane are those which line the tube, or the leucocytes which 
 wander between them. Accordingly, both have been credited with 
 the power of absorbing (and perhaps transforming) these substances, 
 but the balance of evidence is in favour of the epithelial cells. We 
 cannot, however, as in the case of the fat, single out any particular 
 tract of epithelium as alone engaged in the absorption (and possibly 
 in the resynthesis) of the products of the digestion of the proteins. 
 In all likelihood the cells covering the viUi are actively concerned, 
 but there is no valid reason for den5dng a share to the general lining 
 of the stomach and small intestine, even perhaps including the 
 iJeberkuhn's crypts or intestinal glands, which morphologically 
 form a kind of inverted villi. It is, indeed, true that the crypts 
 do not take part in the absorption of fat, for no granules blackened 
 by osmic acid occur in them during digestion of a fatty meal. But 
 this is a ground for attributing to them other absorptive functions 
 rather than for altogether denying to them a share in absorption, 
 unless, indeed, we assume that the secretion of the succus entericus 
 engrosses the whole activity of this extensive sheet of cells. Even 
 within physiological limits distension of the gut causes the crypts 
 to become shorter and broader, by a process of partial unfolding 
 which permits a greater part of their epithelium to come into con- 
 tact with the intestinal contents. In extreme distension they may 
 be completely smoothed out. 
 
 The extraordinary efficiency of the small intestine in digestion 
 and absorption is shown by the fact that, after removal of even 
 70 to 83 per cent, of the combined jejunum and ileum in dogs, the 
 metabolism is not necessarily much affected. On a diet poor in 
 fat the animals absorb as much of the fat as a normal dog, although 
 a smaller proportion when the diet is rich in fat. It has been 
 generally stated that it is never permissible to remov^e more than 
 one-third of the small intestine in man. But in one case 2f metres 
 was resected, or quite one-half, and the patient recovered. Even 
 the large intestine, which possesses Lieberkiihn's crypts, but no villi, 
 is able to absorb not only peptones and sugar, especially mono- 
 saccharides like dextrose, but also fats and native proteins. And 
 although these are powers which can be rarely exercised to any great 
 extent in normal digestion, they form the physiological basis of the 
 important method of treatment by nutrient enemata. The observa- 
 tion already mentioned (p. 331), that considerable quantities of 
 food administered by the rectum can pass through the ileo-colic 
 sphincter and valve into the lower part of the ileum, thanks to the 
 antiperistaltic movements of the large intestine, indicates that an 
 important part of the preliminary digestion and of the absorption 
 of enemata may occur in the small intestine. ' But remnants of the 
 
452 ABSORPTION 
 
 proteolytic, amyloljrtic, fat-splitting, and inverting ferments which 
 have done their work in the small intestine are passed on into the 
 large, and may be demonstrated in its contents. Doubtless these 
 are able to act upon food substances which may have escaped com- 
 plete digestion and absorption in the higher parts of the alimentary 
 canal, as well as upon food substances injected into the rectum. 
 
 Summary. — With the proviso that in the case of the fats the 
 statement may in the present condition of our knowledge be some- 
 what ' diagrammatic,' we may sum up in a few words the chief 
 points in the absorption of the food materials. All the fats must be 
 split in order to he absorbed in soluble form from the intestine, but 
 need not be split in the lumen of the gut in order to be utilized by the 
 cells. For this reason they are to a great extent resynthesized to 
 neutral fat after absorption, ard find their way into the blood, mainly 
 by way of the lymph, in particulate form. Proteins could perhaps to 
 a small extent be absorbed as such, but must be thoroughly hydrolysed 
 in order to be utilized by the tissues, and also in order to be freely 
 taken up from the gut. Carbo-hydrates in certain forms {mono- 
 saccharides) are capable without change of being both freely absorbed 
 from the intestine and thoroughly utilized by the cells ; only the more 
 complex carbo-hydrates need to be hydrolysed in order to be absorbed, 
 but all above the monosaccharides must be hydrolysed to tnonosac- 
 charides in order to be utilized. The substances which eventually 
 circulate in the blood in solution reach it through the gastro-intestinal 
 capillaries ; the substances which eventually circulate in the blood in 
 particulate form reach it through the lymphatics. 
 
 PRACTICAL EXERCISES ON CHAPTERS VI. AND VII. 
 
 I. Contraction of Isolated Intestines in Ringer's Solution. — Arrange 
 a good-sized water-bath (a water-tight garbage-can holding 20 litres 
 will do) so that the temperature of the water is kept at 37° to 38° C. 
 For this a gas regulator is most convenient, and also a stirring arrange- 
 ment worked by a small motor. But if neither of these is available, 
 a student, by a. little care, can easily keep the water at the required 
 temperature by raising and lowering the gas flame and stirring occasion- 
 ally by hand. In the bath, support (a) a stock bottle of Ringer's 
 solution (footnote, p. 66), {h) a wide-mouthed bottle containing Ringer 
 for the reception of the stock of intestine, (c) a small cylinder for 
 segments of intestine whose contractions are to be recorded, (c) is 
 conveniently made in different sizes by cutting down glass T-pieces. 
 One which holds 4 or 5 c.c. is convenient. The bottom is plugged with 
 a rubber cork in wliich is fastened a hook. In the side-piece is fixed 
 by a rubber cork a glass tube ending in the cylinder in a narrow 
 orifice. This is connected with the oxygen-supply, conveniently ob- 
 tained under constant pressure from a small gas-container which is 
 periodically replenished from an oxygen cylinder. A separate oxygen 
 cylinder is connected with a tube passing to the bottom of (6). A lever 
 with two arms is arranged on the same stand as (c), so that it can be 
 thrown on and off a slow-moving drum by a single movement of the stand. 
 
 All being ready, a rabbit is killed by being struck on the back of the 
 
PRACTICAL EXERCISES 453 
 
 head. Ilic small intestine is immediately removed. It may be cut 
 between double lif^aturcs into several pieces for this purjxjse. The 
 contents arc rapidly washed out by a stream of warm Ringer, and 
 the pieces placed in (/>), through which oxygen is kept bubbling. The 
 pieces are conveniently supported in the liquid by threads fixed by 
 the cork of the bottle. There is a hole in the cork for the escape of 
 the oxygen. The movements of the intestines in {b) can be studied 
 very well by inspection. Or a separate length of intestine maybe kept 
 for this purpose, the contents not being removed, but prevented from 
 escaping by ligatures at each end. This can be mo.st easily observed in a 
 shallow dish of warni Ringer. Or a separate experiment can be made 
 in which the whole alimentary canal of a rabbit is carefully removed 
 and examined in oxygenated Ringer's solution. 
 
 A .segment of intestine about 2 or 2^ cm. in length is now cut off 
 one of the pieces. A small ring of platinum or aluminium is tied to 
 a point on the circumference of one end of the preparation by a silk 
 thread passed through the wall. The other end is caught by a serre- 
 fine at a point exactly corresponding to the attachment of the ring, so 
 that the pull of the contracting longitudinal muscle should be in the 
 straight line joining these two points. The serre-fine has attached to 
 it a thread with a hook on the other end. In preparing the intestinal 
 segment it lies on a plate of glass above a vessel of warm water. The 
 small cylinder (c) is now partially filled with warm Ringer's solution. 
 The ring is grasped by fine forceps, and made to engage with the hook 
 at the bottom of the c^dinder, care being taken not to injure the prepara- 
 tion in the process. The cylinder is then fastened on its stand and. 
 lowered into the bath. The thread is connected by its attached hook 
 to the lever, and oxygen allowed to bubble slowly and regularly through 
 the cylinder. Very soon rhythmical contractions begin (Fig. 173), and 
 continue for a long time. The effect on these contractions of abolish- 
 ing, reducing, or increasing the oxygen-supply may first be studied. 
 
 2. Effect of Blood-Serum on the Contractions of Intestinal Segments. 
 — While a tracing is being taken as in i, fill a small bent pipette with 
 serum already warmed in the bath, pass the point of the pipette down to 
 the bottom of the cylinder without interfering with the preparation, and 
 allow the serum to flow in till the Ringer's solution is displaced. Almost 
 at once the lever will begin to rise, indicating strong tonic contraction. 
 The increase of tone lasts for some time, but can soon be removed on 
 washing the preparation with Ringer. This is most easily done, while the 
 drum is stopped, by introducing pipetteful after pipetteful of Ringer's 
 solution into the cylinder in the way described, allowing the liquid to 
 overflow into the bath. The subsequent addition of serum causes a 
 renewed increase of tone, and this may be many times repeated. 
 
 Determine the greatest dilution of the serum which still produces a 
 distinct effect upon the intestinal segment. 
 
 3. Action of Epinephrin (Adrenalin) on Intestinal Segments. — Pro- 
 ceed as in 2, but use various dilutions of adrenalin chloride instead of 
 serum. They must be freshly prepared. Instead of increase of tone, 
 inhibition of the movements and decrease of tone will be obtained 
 (Fig. 173). 
 
 This experiment may be performed at another stage in the course 
 (p. 720). 
 
 4. Quantitative Estimation of Ferment Action. — For pepsin an easy 
 method, although not a very accurate one, of estimating the rate at 
 which the fibrin disappears is to use fibrin stained with carmine. As 
 solution goes on, the dye colours the liquid more and more deeply, and 
 by comparing the depth of colour at any time with standard solutions 
 of carmine, we get the quantity of dye set free, and therefore of fibrin 
 
454 
 
 DIGESTION AND ABSORPTION 
 
 digested. This mt thod cannot be used for trypsin. A mucli better 
 method is that of Mett (p. 343). Fluid egg-white is sucked up into 
 fine glass tubes (of i to 2 mm. bore). The tubes are then heated in a 
 bath at 95° C. For use short pieces (i or 2 cm. long) are cut off and 
 placed in I or 2 c.c. of the liquid to be tested, the whole being kept at 
 38° to 40° C. 
 
 For amylolytic ferments where rapid work is required, glass tubes 
 filled with tinted starch paste may be used in the same way as the 
 Mett's tubes. A more accurate method, and yet a rapid and convenient 
 one, is based upon the time which is necessary in order that the iodine 
 reaction with starch may just disappear when a standard starch solution 
 
 is digested with a dilution 
 of the ferment solution 
 at 40° C. 
 
 5. Saliva — Collection 
 and Microscopic Examina- 
 tion of Saliva. — Chew a 
 piece of paraffin -wax, or 
 inlir.leetherorthe vapour 
 of strong acetic acid. The 
 flow of saliva is increased. 
 Collect it in a porcelain 
 capsule. Examine a drop 
 imder the microscope. It 
 may contain a few fiat 
 epitheUal scales from the 
 mouth and a few round 
 granular bodies, the sali- 
 vary corpuscles, the gran- 
 ules in which often show 
 a lively, dancing move- 
 ment (Brownian motion). 
 Filter the saliva to free it 
 from air-bubbles, and per- 
 form the following ex- 
 periments : 
 
 (a) Test the reaction 
 with litmus paper. It is 
 usually alkaline. An acid 
 reaction may indicate 
 that bacterial processes 
 are abnormally active in 
 the mouth. 
 A precipitate indicates the presence of 
 
 Fig. 173. — Effect of Scrum and Adrenalin on Con- 
 tractions of a Segment of Intestine. Rabbit's 
 intestine contracting in Ringer's solution. At 
 55 the Ringer's solution was replaced by dog's 
 serum, and this at 56 by adrenalin {1:5,000,000) 
 in serum. At 57 this weak adrenalin solution was 
 replaced by a stronger one (i: 500,000) in serum. 
 Time-trace, half-minutes. (Reduced to half.) 
 
 (b) Add dilute acetic acid, 
 mucin (p. 344). Filter. 
 
 (c) Add a drop or two of silver nitrate solution to the filtrate from 
 (b). A precipitate insoluble in nitric acid, soluble in ammonia, pro\es 
 that chlorides ar.^ present. 
 
 {d) Add to another portion a few drops of dilute ferric chloride 
 slightly acidulated with dilute hydrochloric acid, and the same quantity 
 to as much distilled water in a control test-tube. A reddish coloration 
 is obtained, due to the presence of sulphocyanic acid, which is com- 
 bined with potassium and other bases in the saliva. The colour is dis- 
 charged by mercuric chloride. Or, a drop of saliva may be allowed to 
 fall from the mouth on a test-paper (prepared by soaking filter-paper 
 with a dilute starch solution, containing a little iodic acid, and allowing 
 it to dry in the air). The paper is coloured blue by the union of the 
 
PRACTICAL EXERCISES 453 
 
 starch wit h iodine set free from the iodic acid by the acticn of the sulpho- 
 cyanic acid. 
 
 (e) Take some boiled starch mucilage, and tist it for reducing sugar 
 by Trommer's test (p. 10). If no sugar is found, take three test- 
 tubes, label them A, B. C, and nearly half fill each with the boiled 
 starch. To A add a little saliva,* to B some saliva which has been 
 boiled, to C a little saliva which h;us been neutralized, and as much 
 0-4 per cent, hydrochloric acid as has been taken of the mucilage, so as 
 to make the strength of the acid iu the mixture 0-2 per cent., a propor- 
 tion well below that of the gastric juice. Put the test-tubes into a water- 
 bath at 40° C. In a few minutes test the contents for reducing sugar. 
 Abundance will be found in A, none in B or C. In B the ferment 
 ptyalin has been destroyed by boiling; in C its action has been inhibited 
 by the acid. If the test-tubes have been left long enough in the bath, 
 no blue colour will be given by A on the addition of iodine, but a strong 
 blue colour by B and C — i.e., the starch will have completely disappeared 
 from A. 
 
 (/) Put some starch in a test-tube, add a little saliva, and hold in the 
 hand or place in a bath at 40° C. On a porcelain slab place several 
 separate drops of dilute iodine solution. With a glass rod add a drop 
 of the mixture in the test-tube to one of the drops of iodine at intervals 
 as digestion goes on. At first only the blue colour given by starch will 
 be seen; a little later a violet colour, due to the presence of erythro- 
 dextrin in addition to some unaltered starch. A little later the colour 
 will be reddish, the starch having disappeared and the erythrodextrin 
 reaction being no longer obscured. Later still no colour reaction will 
 be obtained, the erythrodextrin having undergone further changes, and 
 only sugar (maltose, isomaltose, and perhaps a trace of dextrose) and 
 achroodextrin — a kind of dextrin which gives no colour with iodine — • 
 being present. 
 
 {g) Put two pieces of glass tube filled with tinted starch paste (p. 454) 
 into separate test-tubes. Cover one with 3 c.c. and the other with 
 6 c.c. of saliva. The saliva must all be taken from the same stock, and 
 must not be collected separately. Put in a bath at 38° C, and when a 
 fair amount of digestion has taken place in each, measure the length 
 of the column digested, and determine the relation between the amount 
 digested in the two tubes (p. 342). 
 
 (A) Dilute 2 c.c. of saliva with distilled water up to 20 c.c, and filter. 
 Take six test-tubes of the same width, and label them A, B, C, etc. 
 Measure into A 3 c.c. of the diluted saliva, into B 2 c.c, into €1-3 c.c, 
 intoD 0-9 c.c, into Eo'6c c, and into F 0-4 c.c. Thus a series is obtained 
 in which each tube contains (approximately) two-thirds as much ferment 
 as the one it follows. Add distilled water to tubes B to F, sufficient to 
 make up the volume in each to 3 c.c. Place the tubes in a beaker of 
 iced water; add to each 10 c.c of a i per cent, solution of boiled starch 
 previously cooled in iced water, and shake so as to mix the contents. 
 Each tube now contains starch in uniform concentration, and ferment 
 in var^'ing concentration. The low temperature prevents digestion till 
 all the tubes are ready. Now put the tubes simultaneously into a water- 
 bath at 40° C. for half an hour, and then back again into iced water 
 to prevent furlner digestion. Move them about in the iced water to 
 cool rapidly. Fill up the tubes with distilled water nearly to the top, 
 add a drop or two of iodine solution to each, and mix uniformly. The 
 tubes to which the smallest amounts of saliva were added will probably 
 
 * As it filters slowly, unaltered saliva may be used for Experiments («). 
 (/) and(i). 
 
456 
 
 DIGEiiTiU.\ AAL) ABSORFTluS 
 
 still show a distinct blue colour, while those at the other end of the 
 scries will be brown or yellow, and the intermediate tubes bluish -violet. 
 Suppose D is the last tube still showing a bluish tint, then in the next 
 higher tube, C. all the starch has been hydrolysed at least to dextrin — 
 that is. i'3 c.c. of the ten-times diluted saliva, or 0'i3 of the original 
 saliva, has been sufficient to change all the starch in lo c.c. of the i per 
 cent, solution. With another specimen of saliva the same result might 
 be reached in tube E, containing an amount of ferment equal to that 
 in 0'o6 c.c. of the original saliva. We could then conclude that the 
 diastatic power of the second saliva was about twice as great as that 
 of the first. A closer approximation can now be made by setting up 
 two fresh tubes (C and E respectively for the two salivas) and deter- 
 mining the time required for the blue reaction with iodine to disappear, 
 taking out a drop from time to time and testing on a porcelain slab. 
 
 (t) Put a little distilled water into a porcelain capsule, and bring the 
 water to the boil. Now put into the mouth some boiled starch paste, 
 and move it about as in mastication. After half a minute spit the 
 starch out into the boiling water. Divide the water into two portions. 
 Test one for sugar, and the other for starch. Repeat the experiment, 
 but keep the starch two minutes in the mouth. Report the result. 
 
 (;) Starch solution to which saliva has been added is placed in a 
 diaiyser tube of parchment-paper for twenty-four hours. At the end 
 of that time the dialysate (the surrounding water) should be tested for 
 sugar and for starch. Sugar will probably be found, but no starch. 
 If no reaction for sugar is obtained, the dialysate should be concen- 
 trated on the w^ater-bath. and again tested. 
 
 6. Stimulation of the Chorda Tympani. — fi) Having previously 
 studied the anatomy of the mouth and submaxillary region in the dog 
 by dissecting a dead animal (Fig. 174). put a good-sized dog under 
 morphine. Set up an induction-machim for a tetanizing current 
 (p- 200), and connect it with fine electrodes. Fasten the dog on the 
 holder, give ether if necessary, and insert a cannula in the trachea 
 (p. 202). Then make an incision 3 or 4 inches long through skin and 
 platysma muscle, along the iimer border of the lower jaw, beginning 
 about the angle of the mouth, and continuing backwards towards the 
 angle of the jaw. Such branches of the jugular vein as come in the way 
 may be generally pushed aside, but if necessary thoy may be doubly 
 ligated and divided. Feel for the facial arter\', so as to be able to 
 avoid it. Divide the digastric muscle about its anterior third, and 
 clear it carefully from its attachments; or, without dividing it, pull it 
 outwards with a hook. The broad, thin mylo-hyoid muscle will now 
 be seen with its motor nerv'e lying on it. Divide the muscle about its 
 middle at right angles to its fibres, and raise it carefully. The lingual 
 nerve will be seen emerging from under the ramus of the jaw. It runs 
 transversely towards the middle Une, and then, bending on itself, passes 
 forwards parallel to the larger hypoglossal nerve. In its transverse 
 course the lingual will be seen to cross the ducts of the submaxillar\- 
 and sublingual glands. These structures having been identified, the 
 lingual nerve is to be ligatured before it enters the tongue and cut 
 peripherally to the ligature. Then a glass cannula of suitable size is to 
 be inserted into the submaxillary duct (the larger of the two), just as if 
 it were a bloodvessel (p. 63). A short piece of narrow rubber tubing 
 is carefully slipped on the end of the cannula. The lingual is now to be 
 lifted by means of the ligature, and traced back towards the jaw till its 
 chorda tympani branch is seen coming off and nmning backwards along 
 the duct. The chordo-lingual nerve (Fig. 160, p. 392) is then to be 
 cut centrally to the origin of the chorda tjinpani, which can now be 
 
PRACTICAL EXERCISES 
 
 457 
 
 easily laid on electrodes by means of the ligature on the lingual. On 
 stimulating the chorda, the flow of saliva through the cannula will be 
 increased. The current need not be very strong. Jf the flow stops 
 after a short time, it can be again caused by renewed stimulation after 
 a brief rest. A quantity of saliva may thus be collected, and the experi- 
 ments already made with human saliva repeated. 
 
 (2) Expose the vago-sympathetic nerv^ in the neck on the same 
 side ; ligature it ; divide below the ligature ; and note the effect pro- 
 duced by stimulation of the upper end on the flow of saliva. 
 
 (3) Siet up another induction-machine, and connect it with electrodes. 
 Stimulate the chorda, and note the rate of flow of the saliva. Then, 
 while the chorda is still being excited, stimuLae the vago-sympathetic, 
 and observe the effect. If the experiment is successful, finish by 
 stimulating the chorda for a long time. Then harden both sub- 
 
 .Mylo-hyoid 
 Muscle (cut). 
 
 Lingual Wharton's 
 Nerve. Duct. 
 
 Fig. 174. — Dissection for Stimulation of Chorda Tympani (after Bernard). 
 
 maxillary"- glands in absolute alcohol, make sections, stain with carmine, 
 and compare them. 
 
 7. Effect of Drugs on the Secretion of Saliva. — (i) Proceed as in 
 6 (i), but, in addition, insert a cannula into the femoral vein (p. 218). 
 On the cannula put a short piece of rubber tubing, filled with 0*9 per 
 cent, salt solution and closed by a small clamp, or a small piece of 
 glass rod, or a pair of bulldog forceps. While the chorda is being 
 stimulated inject into the vein 10 to 15 milligrammes of sulphate of 
 atropine by pushing the needle of a hyf)odermic syringe through the 
 rubber tube. This will stop the flow of saliva, and abolish the effect 
 of stimulation of the chorda. See whether the sympathetic is also 
 inactive, and report the result. 
 
 (2) Now empty the cannula in the submaxiUar}' duct by means of a 
 feather, and fill it with a 2 per cent, solution of pilocarpine nitrate by 
 means of a fine pipette. Fill also the short rubber tube attached to 
 the cannula, and close it again. Compress the tube, and so force into 
 
^58 DIGESTIOX AND ABSORPTION 
 
 the duct a small quantity of the solution. Open the tube. Secretion 
 of Siiliva will again begin, and stimulation of the chorda will again cause 
 an increase in tlu- flow. But after a few minutes the action of the 
 atropine will reassert itself, and the flow will stop. Renewed secretion 
 may be cau.sed by a fresh injection of pilocarpine. 
 
 8. Gastric Juice — (a) Preparation of Artificial Gastric Juice. — Take 
 a portion of the pig's stomach provided, strip off the mucous membrane 
 (except that of the pyloric end, which is relatively poor in pepsin), cut 
 it into small pieces with scissors, and put it in a bottle with loo times 
 its weight of 0-4 per cent, hydrochloric acid. Label and put in a bath 
 at 40° C. for three hours, and then in the cold for twelve hours. Then 
 filter. 
 
 {b) Take another portion of the mucous membrane, cut it into pieces, 
 and rub up with clean sand in a mortar. Then put it in a small bottle, 
 cover it with glycerin, label, and set aside for two or three days. The 
 glycerin extracts the pepsin. 
 
 (c) Take five test-tubes, A, B, C, D, E, and in each putfa little washed 
 and boiled fibrin or a small cube of coagulated egg-white. To A add a 
 fv'w drops of glycerin extract of pig's stomacja, and fill up the test-tube 
 with 0-4 per cent, hydrochloric acid. To B add glycerin extract and 
 distilled water; to C glycerin extract and i per cent, sodium carbonate; 
 to D 0'4 per cent, hydrochloric acid alone ; to E glycerin extract which 
 has been boiled, and 0*4 per cent, hydrochloric acid. 
 
 Put np another set of five test-tubes in the same way, except that a 
 few drops of a watery solution of a commercial pepsin are substituted 
 for the glycerin extract. Label the test-tubes A', B'. C, D', E'. 
 
 Into another test-tube put a little fibrin (or an egg- whit? cube), and 
 fill up with the filtered acid extract from (a). Label it F. Place all 
 the test-tubes in a tumbler, and set them in a water-bath at 40° C. 
 Put a piece of a Mett's tube (p. 343) into each of two test-tubes, and 
 add 15 c.c. of 0'4 per cent, hydrochloric acid. To one tube add 5 drops 
 and to the other 10 drops of the same filtered glycerin extract of gastric 
 mucous membrane. Put the tubes in the bath, and when digestion is 
 distinct at the ends of both tubes measure the length of the column 
 digested in each. What is the relation between the two (p. 342) ? 
 The experiment can be repeated with the hydrochloric acid extract of 
 the mucous membrane. 
 
 After a time the fibrin (or egg-white) will have almost completely dis- 
 appeared in A, A', and F, but not in the other test-tubes. Filter the 
 contents of A, A', and F into one dish. 
 
 {d) Test the fiJtiate for the products of gastric digestion: 
 
 (a) Neutralize a portion carefully with dilute sodium hydrox- 
 ide. A precipitate of acid-albumin may be thrown 
 down. Filter. 
 (/3) To a portion of the filtrate from (a) add excess of sodium 
 hydroxide and a drop or two of very dilute copper 
 sulphate. A rose colour indicates the presence of 
 proteoses or peptones. The cupric sulphate must be 
 very cautiously added, because an excess gives a violet 
 colour, and thus obscures the rose reaction. If still 
 mere cupric sulphate be added, blue cupric hydroxide 
 is thrown down, and nothing can be inferred as to the 
 presence or the nature of proteins in the liquid. 
 (y) Heat another portion of the filtrate from («) to 30* C, 
 and add crystals of ammonium sulphate to saturation. 
 A precipitate of proteoses (albumoses) may be ob- 
 tained. Filter off. 
 
PRACTICAL EXERCISES 459 
 
 (6) Add to the filtrate from (y) a trace of cupric sulj^hatc .-i,n(l 
 excess of sodium hydroxide. A rose colour indicates 
 that peptones arc present. More sodium hydroxide 
 must be added than is sufficient to break up all the 
 ammonium sulphate, for the biuret reaction requires 
 the presence of free fixed alkali. A strong solution of 
 the sodium hydroxide should tlierefore be used, or the 
 stick caustic soda. The addition of ammonium sul- 
 phate will cause the red colour to disappear; so will the 
 addition of an acid. Sodium hydroxide will bring it 
 back. Ammonia docs not affect the colour. 
 {e) To some milk in a test-tube add a drop or two of rennet extract, 
 
 and place in n bath at 40" C. In a short time the milk is curdled by 
 
 the rcnnin. (Sec p. 353) 
 
 9. (i) To obtain Normal Chyme.— Inject subcutancously into a dog, 
 
 one and a lialf hours after a meal of minced meat and water, 2 mg. of 
 
 apomorphine. Half of one of the ordinary tabloids is enough. Collect 
 
 the vomit. 
 
 (2) To obtain Pure Gastric Juice. — If the laboratory possesses a dog 
 with Pawlow's double oesophageal and gastric fistula, the juice may 
 be obtained in large amount by sham feeding with meat (p. 402). If 
 not, proceed as follows: Put a fasting dog under ether, and fasten on 
 the holder. Clip the hair and shave the skin in the middle line below 
 the sternum. Make a longitudinal incision 
 through the skin and subcutaneous tissue 
 from the xiphoid cartilage downwards for 
 3 or 4 inches. The linea alba will now be seen 
 as a white mesial streak. Open the abdomen 
 by an incision through it. Pull over the 
 stomach towards the right, and stitch it to 
 the abdominal wall, open it, and insert a 
 stomach cannula (Fig. 175). Make an incision Fig. 175. — Stomach 
 through the serosa and muscularis. Doubly Cannula, 
 ligate and divide any vessels exposed in the 
 
 submucosa. Then make an opening in the mucosa of sufficient size to 
 just admit the gastric cannula. This will go into a smaller opening if it 
 is provided with a nick in the flange which enters the stomach. Be 
 careful to prevent blood from getting into the stomach. Immediately 
 stitch the wound in the stomach over the flange of the cannula, but 
 do not pass the stitches through to the internal surface of the mucosa. 
 Suture the muscles and skin separately. Then stitch up the wound in 
 the abdomen. Wash out any stomach contents with warm water. Put 
 a cork in the cannula, and cover the animal with a cloth. The follow- 
 ing experiments may now be performed : Expose both vagi in the neck. 
 Connect two pairs of electrodes with the secondary coil of an induc- 
 torium arranged for single shocks. By means of a key in the primary 
 stimulate the nerves with slow rhythmical induction shocks at the rate 
 of about one a second. Continue the stimulation for fifteen minutes, 
 collect any juice that may have been .secreted, and apply the tests in (3). 
 If secretion is slow, a little distilled water may be put into the stomach, 
 and the vagus stimulation repeated. Mechanical stimulation of the 
 mucous membrane with a feather causes no secretion of acid gastric 
 juice, but may cause a secretion of alkaline mucus. 
 
 (3) (*) Test the reaction to litmus of the chyme obtained in (i), and 
 of the pure juice obtained in (2). 
 
 [b) Test their proteolytic powers by putting in a bath at 40° C. for 
 two hours two test-tubes containing respectively filtered chyme and 
 
^f^ DIGESTION AND ABSORPTION 
 
 fibrin, and gastric juice and fibrin. The fibrin will be digested in both. 
 Estimate the proteolytic power quantitatively by Mctt's tubes (p. 454). 
 
 (c) Add a few drops of the chyme and gastric juice to milk in two 
 test-tubes, and place them in a bath at 40° C. Repeat (c) after neutral- 
 izing the liquids, 
 
 (d) Examine a drop of the unfiltered chyme under the microscope. 
 Partially digested fragments of the food will be seen — muscular fibres 
 or fat cells. Filter, and proceed as in 8 {d) (p. 458). 
 
 (4) Test the filtrate from the chyme and the gastric juice for lactic 
 acid by Uffelmann's test or Hopkins's test (p. 821), and for hydrochloric 
 acid by Giinzburg's reagent. 
 
 Uffelmann's Test for Lactic Acid. — The reagent is a dilute solution 
 of carbolic acid to which dilute ferric cliloride has been added till the 
 colour is bluish (say a drop of a i per cent, ferric chloride solution to 
 5 c.c. of a I per cent, carbolic acid solution). The blue colour of the 
 mixture is turned yellow by lactic acid, but not by dilute hydrochloric 
 acid. Since Uffelmann's test is given also by phosphates, alcohol, and 
 sugar, which may sometimes be present in the stomach contents, it is 
 best to shake the gastric contents with ether, dissolve the ethereal 
 extract in water, and then make the test on the watery solution. 
 
 Giinzburg's Reagent for Free Hydrochloric Acid in Gastric Juice is 
 made by dissolving 2 parts of phloroglucinol and i part of vanillin in 
 30 parts by weight of absolute alcohol. A few drops of the reagent 
 are added to a few drops of the filtered gastric juice in a small porcelain 
 capsule, and the whole evaporated to dryness over a small bunscn 
 flame. If free hydrochloric acid is present, a carmine-red residue is 
 left. If all the hydrochloric acid is united to proteins in the stomach 
 contents, the reaction does not succeed. It is also hindered by the 
 presence of Icucin. 
 
 10. Pancreatic Juice. — (a) Take a piece of the pancreas of an ox or 
 dog which has been kept twenty-four hours at the temperature of the 
 laboratory, and make a glycerin extract in the same way as in the 
 case of the pig's stomach in 8 (6). Put in a small bottle, and set aside 
 for a day or two. 
 
 {b) Put a little boiled fibrin into each of six test -tubes. A, B, C, D, E, 
 F. To A add a few drops of glycerin extract of pancreas, and fill up 
 with a I per cent, sodium carbonate solution ; to B add glycerin extract 
 and distilled water; to C glycerin extract and excess of 005 per cent, 
 hydrochloric acid; to D i per cent, sodium carbonate alone; to E i per 
 cent, sodium carbonate in which a few drops of glycerin extract of 
 pancreas have been previously boiled; to F glycerin extract and excess 
 of 0-2 per cent, hydrochloric acid.* 
 
 Set up six test-tubes, A', B', C, D', E', F', in the same way, but 
 substitute a few drops of a solution of commercial pancrcatin for the 
 glycerin extract. Set up two test-tubss as in cxp:riment 8 (p. 458) 
 with Mett's tubes. Put all the test-tubes in a tumbler, and place in a 
 bath at 40° C. The fibrin will be gradually eaten away in A and A^ 
 by the action of the trypsin, but will not swell up or become clear 
 before disappearing, as it does in dilute hydrochloric acid with glycerin 
 
 * With hydrochloric acid of different strengths the rapidity of digestion 
 of boiled fibrin by glycerin extract of dog's pancreas (i volume of extract 
 to 25 of acid) was found about the same for o"3 and o'ly per cent, acid; much 
 less for o-o8 per cent., while in 0*04 per cent, acid there was practically no 
 digestion at all. In 0-4 per cent, acid digestion took place more rapidly than 
 in o-o8 per cent., but much less rapidly than in o'lj per cent. In acid of all 
 strengths digestion was markedly slower than in i per cent, sodium car- 
 bonate. 
 
PRACTICAL EXERCISES 461 
 
 extract of stomach. Filter the contents of these test -tubes. Neutralize 
 the filtrate witli dilute acid; a precipitate will consist of alkali-albumin. 
 If such a prc'cij)itatc is obtained, filter it off and test the filtrate for 
 proteoses and peptones as in 8 [d) (p. 438). Some digestion, and perhaps 
 a considerable amount, may also liave taken place in F and F'; less 
 or none at all in C and C ; and none in the other Lest -tubes (pp. 359, 420). 
 
 (c) Add a few drops of the glycerin extract to a test-tube containing 
 starch mucilage, which has been previously found free from reducing 
 sugar. Put in a bath at 40° C. After a short time abundance of 
 reducing sugar will be found, owing to the action of the ferment, 
 amylopsin, or pancreatic amylase. 
 
 {d) Mince thoroughly a good-sized piece of fresh pancreas, and shake 
 up well with three or tour times its bulk of water. Put 5 c.c. of fresh 
 cream into a test-tube, then 10 c.c. of the extract, a few drops of chloro- 
 form to prevent the growth of bacteria, a few drops of litmus solution, 
 and if necessary enough of very dilute sodium hydroxide to just render 
 the colour distinctly blue. Shake up, and divide the mixture into two 
 portions, A and B. Boil one portion (B), and place the test-tubes at 
 40° C. Examine from time to time . The blue colour will disappear in 
 A, owing to the formation of fatty acids from the neutral fats, and 
 sodium hydroxide must be added to it to restore the colour. In B the 
 fat-splitting ferment has been destroyed by boiling, and fat-splitting 
 will not occur. Probably a distinct result will not be obtained for 
 several hours, and it will be best to leave the tubes in the incubator 
 overnight. 
 
 (e) If the laboratory possesses an animal with a pancreatic fistula, 
 the following experiment may be done by a limited number of students 
 with fresh pancreatic juice* collected from the fistula. Take five test- 
 tubes, A, B, C, D, E. Add 5 c.c. of pancreatic juice to each tube. Boil 
 E, and then cool it. Put into A and B small pieces of heat-coagulated 
 egg-white, into C a little starch mucilage, and into D and E 5 c.c. of 
 fresh cream. Add further to B a scraping of the mucous membrane of 
 the upper part of the small intestine which has first been washed free of 
 contents. To D and E add a drop or two of litmus solution, and, if 
 necessary, enough of dilute sodium hydroxide to just establish a blue 
 colour. Then put the test-tubes at 40° C, and examine after a time. 
 No digestion will have taken place in A, because the pancreatic juice, as 
 secreted, does not contain active trypsin. In B digestion may take 
 place, because the entero kinase in the intestinal mucous membrane 
 will activate the trypsinogen to trypsin. In C and D there will be 
 evidence of the production of reducing sugar and fatty acids respec- 
 tively, since the pancreatic juice, as secreted, contains active amylase 
 and steapsin. E will be unchanged unless by bacterial action. 
 
 (/) Leucin and Tyrosin. — As examples of amino-acids formed when 
 pancreatic digestion of proteins (fibrin or casein, e.g.) is allowed to go 
 on for some days, f leucin and tryosin maybe isolated. Add bromine- 
 water by drops to 5 c.c. of the digest; a pink colour indicates trypto- 
 phane. If the ' digest ' be neutralized, then filtered, and the filtrate 
 concentrated and allowed to stand, a crop of tyrosin crystals will 
 separate out, since tyrosin is only slightly soluble in watery solutions 
 of neutral salts. These crystals having been filtered off, the proteoses 
 (albumoses) and peptones can be precipitated together by alcohol, and 
 
 * A considerable flow of pancreatic juice can be obtained from a dog with 
 a pancreatic fistula by injecting intravenously an extract of intestinal mucous 
 membrane containing secretin (p. 407). 
 
 I A little chloroform is added to prevent bacterial growth. 
 
46a DIGESTION AND ABSORPTION 
 
 afterwards separated, if that is desired, by redissolving the precipitate 
 in water and throwing down the proteoses by saturation with am- 
 monium sulphate. The alcohohc filtrate will contain any leucin that 
 may be present, since that body is moderately soluble in alcohol, as 
 well as traces of tyrosin, which, however, is much less soluble in this 
 medium. On concentration, crystals of both substances will be ob- 
 tained. Tyrosin crystallizes characteristically from animal liquids in 
 beautiful silky needles united into sheaves, leucin in the form of in- 
 distinct fatty-looking balls, often marked with radial striae and coloured 
 with pigment (Figs. i86 and 187, p. 488). 
 
 Tests for 'Tyrosin by Morner's Test. — Put a small quantity of tyrosin 
 into a test-tube. Add about 3 c.c. of the reagent,* and heat gradually 
 and gently to the boiling-point. A green colour is obtained. 
 
 II. Bile. — {a) Test the reaction of ox bile. It is alkaline to litmus. 
 
 (b) Add dilute acetic acid. A precipitate of bile-mucin (really 
 nucleo-albumin) falls down. Some of tlie bile-pigment is also pre- 
 cipitated. Filter. (Pig's bile contains more of the mucin-hke sub- 
 stance than ox bile.) 
 
 (c) Put a little of the filtrate from {b) or of the original bile into a 
 porcelain capsule, add a drop or two of a dilute solution of cane-sugar, 
 and mix with the bile. Then add a few drops of strong sulphuric acid, 
 and stir; then a few drops more of the sulphuric acid, stirring all the 
 time. A purple colour appearing at once, or after gentle heating, 
 shows the presence of bile-acids (Pettenkofer's reaction). The bile 
 may be diluted before the addition of the sulphuric acid. In this case 
 a greater amount of the acid must be added. Examine the purple 
 liquid in a test-tube with a spectroscope (p. 74). Dilute the liquid with 
 water, adding some sulphuric acid to partially clear up the precipitate 
 caused by the water. Two absorption bands are seen, one to the red 
 side of D, and the other, a stronger and broader band, over and to the 
 right of E. When only a very small amount of bile -salts is present, 
 the reaction is made more sensitive if a solution of furfuraldehyde (i to 
 1,000) is used instead of cane-sugar. 
 
 (d) Hay's Sulphur Test. — Sprinkle a little sulphur (in the form of 
 the fine powder known as flowers of sulphur) on the surface of some 
 bile in a small beaker or deep watch-glass. The sulphur will soon sink 
 to the bottom. Repeat with water; the sulphur will float. The 
 reaction is due to the diminution of the surface tension produced by 
 the bile-acids, and succeeds also in a solution of bile-salts. The test 
 is very sensitive. But in stomach contents, vomit, or stools, it rarely 
 gives good results, since alcohol or acetic acid is often present in the 
 gastric liquid, and phenol and its derivatives in intestinal contents, 
 and all of these cause such an alteration in the surface tension that the 
 sulphur sinks. Ether, chloroform, turpentine, benzine and its deriva- 
 tives, anilin and soaps, also vitiate the test in the same way. 
 
 {e) Add yellow nitric acid (containing nitrous acid) to a little bile on 
 a white porcelain slab. A play of colours, beginning with green and 
 running through blue to yellow and yellowish-brown, indicates the 
 presence of bile-pigment (Gmelin's reaction). The reaction may also 
 be obtained by putting some yellow nitric acid into a test-tube, and 
 then running a little bile from a pipette on to the surface of the acid. 
 The play of colours is seen at the surface of contact. Where the bile- 
 pigment is present only in traces, some of the liquid may be filtered 
 
 • The reagent for this test is prepared by mixing thoroughly i volume of 
 formalin, 45 volumes of distilled water, and 53 volumes of concentrated 
 sulphuric acid. 
 
PRACTICAL EXERCISES 463 
 
 through white filter-paper, and the test apphcd by putting a drop of 
 the nitric acid on the paper. 
 
 (/) Cholesterin or Cholesterol (Fig. 176) — Preparation. — Extract a 
 powdered gall-stone (preferably a white one) with hot alcohol and ether 
 in a test-tube. Heat the test-tube in warm water, not in the free flame. 
 Put a drop of the extract on a slide. Flat crystals of cholesterin, often 
 chipped at the corners, separate out. (a) Carefully allow a drop of 
 strong sulphuric acid and a drop of dilute iodine to run under the cover- 
 glass. A play of colours — violet, blue, green, red — is seen. 
 
 (yS) Evaporate a drop of the solution of cholesterin in a small porce- 
 lain capsule, add a drop of strong nitric acid, and heat gently over a 
 flame. A yellow stain is left, which becomes red when a drop of am- 
 monia is poured on it while it is still warm. 
 
 (7) Dissolve a little cholesterin in chloroform. Add an equal bulk 
 of strong sulphuric acid, and shake gently. The solution turns red 
 and the subjacent acid shows a green fluorescence. 
 
 (i^) Put a drop or two of water in a watch-glass, and add a drop of an 
 ethereal solution of cholesterin. The cholesterin is precipitated, and 
 will not dissolve in the water even on heating. Repeat the observation 
 with bile instead of water. The cholesterin dissolves in the bile. 
 
 (g) To a little of the filtrate from a 
 peptic digest {e.g., flbrin which has been 
 digested for twenty-four hours with 
 pepsin and hydrochloric acid) add some 
 bile. A precipitate is thrown down, 
 which is redissolved in excess of the 
 bile (p. 370). 
 
 (A) Shake up a little bile with some 
 rancid olive-oil in a test-tube. An emul- 
 sion is formed. Repeat the experiment 
 with the same quantities of bile and oil, 
 but use perfectly fresh oil. Compare the 
 stability of the two emulsions, allowing 
 the tubes to stand together for a while, pig. 176. — Crystals of Cholesterin 
 
 (t) To some starch mucilage, shown (Frey). 
 
 to be free from sugar, add a little bile, 
 
 and place in a bath at 40° C. After a time test for reducing sugar. 
 Report the result. Bile often has a slight diastatic power. 
 
 (/) To demonstrate the Presence of Iron in the Liver Cells. — Steep sec- 
 tions of liver in a solution of potassium ferrocyanide, and then in dilute 
 hydrochloric acid. Or a i -5 per cent, solution of potassium ferrocyanide 
 in 0-5 per cent, hydrochloric acid may be used. (The iron may pre- 
 viously be fixed in the tissue by hardening it in a mixture of alcohol 
 and ammonium sulphide.) The sections become bluish from the 
 formation of Prussian blue. A fine-pointed glass rod or a platinum 
 lifter should be used in manipulating them. A steel needle cannot be 
 employed. Mount in glycerin or Farrant's solution, or (after dehy- 
 drating with alcohol and clearing in xylol) in xylol-balsam. Blue 
 granules may be seen under the microscope in some of the hepatic cells. 
 Sections of spleen may also be examined for this reaction. 
 
 12. Microscopical Examination of Faeces. — Examine under the micro- 
 scope the slides provided. Draw, and as far as possible determine the 
 nature of, the objects seen (p. 424). 
 
 13. Absorption of Fat. — (a) Feed a rat or frog with fatty food; kill 
 the rat in three or four hours, the frog in two or three days. Imme- 
 diately after killing the rat open the abdomen, carefully draw out a 
 loop of intestine, and look through the thin mesentery. The white 
 
464 DIGESTION AND ABSORPTION 
 
 lactcals will probably be seen ramifying in tlic mesentery. They 
 appear white on account of the presence of globules of fat in the chyle 
 with which they arc filled. Strip off tiny pieces of the mucous mem- 
 brane of the small intestine, and steep them in J per cent, solution of 
 osmic acid for forty-eight hours. Then tease fragments of the mucous 
 membrane in glycerin and examine under the microscope. To preserve 
 the specimens take off the glycerin with blotting-paper and mount in 
 Farraut's medium, which is a preservative glycerin mixture. Other 
 portions of the mucous membrane may be hardened for a fortnight in 
 a mixture of z parts of Miiller's fluid and i part of a i per cent, solution 
 of osmic acid. Sections are then mauc with a freezing microtome after 
 embedding in gum. No process must be used by which the fat would 
 be dissolved out (Schafer). (See Fig. 172, p. 441.) 
 
 (6) Feed a cat with 30 grammes of butter stained a deep red with the 
 dye Sudan III. After five hours anaesthetize the animal with ether, 
 insert a cannula in the carotid artery, and obtain a sample of blood. 
 Defibrinate the blood, and separate the serum by the centrifuge. If 
 digestion and absorption of the fat have proceeded normally, the 
 serum will contain numerous fat droplets, and will be tinged pink by 
 the dye, which can be dissolved out of it by shaking up with ether. On 
 opening the abdomen it will be seen that the mucous membrane of the 
 small intestine, as far down as the fat has reached, is stained pink, and 
 that the lacteals in the mesentery are also pink. Observe whether any 
 of the pigment has passed into the urine. 
 
 14* Time required for Digestion and Absorption of Various Food 
 Substances. — Feed three dogs, A, B, and C", which have previously fasted 
 for twenty-four hours, with a meal containing starch (proved to be free 
 from sugar), lard, and meat. 
 
 (i) After fifteen minutes inject subcutaneously into A 2 c.c. of a 
 O'l per cent, solution of apomorphine. Note the time which elapses 
 before the animal vomits. Collect the vomit. 
 
 (a) Examine a little of it imder the microscope, and make out fat 
 globules, muscular fibres and starch granules. The latter can be recog- 
 nized by their being coloured blue by a drop or two of iodine solution. 
 
 (6) Filter the chyme, mixing it, if necessary, with a little water, and 
 test it as in 8 (d) (p. 458) for the products of digestion of proteins. In 
 addition, test for starch, dextrin, and reducing sugar. 
 
 (2) One and a quarter hours after the meal inject apomorphine into 
 dog B, and proceed as in (i). 
 
 (3) Two and a half hours after the meal inject apomorphine into 
 dog C, and proceed as in (i). Compare the results from the three 
 specimens of chyme. 
 
 15.* Quantity of Cane-Sugar inverted and absorbed in a Given Time. — 
 Take three dogs, A, B. and C, which have fasted for twenty-four hours. 
 The animals should be about the same size. Feed A and B with 
 100 c.c. of a standard solution of cane-sugar (about a 20 per cent, solu- 
 tion), or as much more as they will take. If the dogs have been kept 
 without water for a day they will more readily take the sugar solution. 
 Or it may be given through a tube passed into the stomach, and in 
 this case a larger quantity of sugar can be given. A gag consisting of 
 a piece of wood with a hole in the middle of it, through which the tube 
 is passed, must first be secured in the dog's mouth. Feed C with 
 
 * Experiments 14 and 15 are conveniently done in a class by assigning 
 each of the three animals to a separate set of students. The contents of the 
 stomach and intestine are divided into three portions, so that each set has 
 a sample from each dog. 
 
PRACTICAL EXhRCISES 465 
 
 50 grammes of powdered cane-sugar mixed with lard, tin- mixture bemg 
 rolled into little balls. 
 
 (i) After a quarter of an hour put A under chloroform or the A.C.E. 
 mixture, and fasten it on a holder. Kill the animal witli chloroform, 
 open the abdomen, tie the oesophagus, place double ligatures on the 
 pyloric end of the stomach and the lower end of the small intestine, and 
 divide between them. Cut out the stomach imd intestine ; wash their 
 contents into separate vessels, and test th.' reaction with litmus paper. 
 Add water and rub up thoroughly. Filter. Wash the residue re- 
 peatedly with small quantities of water, and pass all the washings 
 through the filter. Make up each of the two filtrates to 200 c.c. 
 
 (a) Test the filtrates from the contents of the stomach and intes- 
 tines qualitatively for dextrose by Trommcr's (p. 10) or Fehling's 
 (p. 526) and the phenyl-hydrazine test (p. 525). 
 
 (b) li no reducing sugar is present, add to 20 c.c. of each filtrate I c.c. 
 of hydrochloric acid, boil for half an hour, and again test for reducing 
 sugar. If it is now found, some cane-sugar is present. 
 
 (c) If reducing sugar is found, estimate its amount as dextrose bj- 
 Fehling's solution (p. 527) in a measured quantity of the original 
 filtrate of the gastric or intestinal contents before and after boiling 
 with one-twentieth of its volume of hydrochloric acid. 
 
 {d) Estimate in the same way the amount (as dextrose) of the invert 
 sugar in the standard solution of cane-sugar after inversion, and before 
 inversion if it gives the qualitative test for reducing sugar before it has 
 been boiled with acid. 
 
 From the data obtained (and taking 95 parts of cane-sugar as equal 
 to 100 parts of dextrose) calculate the amount of cane-sugar absorbed, 
 left unchanged, and inverted, though not absorbed. 
 
 (2) One and a half hours after the meal anaesthetize B, and proceed 
 as in (i). 
 
 (3) Two hours after the meal proceed in the same way with C. But 
 in addition observe the lacteals in the mesentery, by gently lifting up 
 a loop of intestine immediately after opening the abdomen. If the 
 absorption of the fat has begun, they will be easily visible, as a network 
 of fine milk-white vessels. Also examine the gastric and intestinal 
 contents with the microscope for fat globules. Compare your results 
 on the amount of sugar obtained from the three animals. Probably 
 much more unabsorbed sugar will be found in C than in B, as the lard 
 hinders it from being dissolved. 
 
 16. Auto-Digestion of the Stomach. — In some of the previous experi- 
 ments the stomach of an animal killed during digestion should be 
 removed from the body after double ligation of oesophagus and duo- 
 denum, and placed in a water-bath at 40° C. After several hours the 
 contents should be washed out and the mucous membrane examined. 
 It may be entirely eaten away in parts. 
 
 30 
 
CHAPTER VI IT 
 FORMATION OF LYMPH 
 
 Different Kinds of Lymph. — We ought to distinguisli the lymph 
 as we collect it from the great lymphatic trunks, not only from the 
 liquids of the serous cavities, but still more sharply from the hquid 
 which fills the multitudinous clefts and spaces of the tissues. It is 
 now pretty definitely established that the tissue spaces do not com- 
 municate by actual passages with the lymphatic vessels, but that 
 the latter form everywhere a closed system like the blood-vascular 
 system, the lymph capillaries merely lying in the tissue spaces 
 (Sabin, etc.). This conception entails a radical change in the 
 current views of lymph production. If the lymphatics form a 
 closed system, the lymph cannot be actual tissue fluid, but only 
 tissue fluid modified by its passage through the walls of the lymph 
 capillaries, just as tissue fluid is not actual blood-plasma, but plasma 
 modified by its passage thrcagh the walls of the blood capillaries 
 as well as by exchange with the tissue elements. 
 
 Although it is customary to speak of the lymph obtained from 
 the lymphatic vessels as if it were perfectly homogeneous, there is 
 no experimental ground for supposing that the lymph from different 
 tracts, or the tissue liquid in contact with the cells of different 
 organs, or even the tissue liquid in contact with one and the same 
 cell at different parts of its periphery, has a uniform composition, 
 or even a uniform molecular concentration. There are, indeed, 
 certain general considerations which show that this cannot be so. 
 Still less can it be assumed that the serous cavities, although they 
 come into relation with lymphatics and bloodvessels in their walls, 
 are analogous to colossal tissue spaces or even to expansions of the 
 closed lymphatic system, or that the liquids contained in them, 
 normally in scant amount, are simply tissue, or if not tissue, then 
 simply lymphatic lymph. The cerebrospinal fluid, which bathes 
 the external surface of the central nervous system and fills its 
 cavities, and the special liquids of the eyeball — the aqueous humour 
 and the liquid of the vitreous humour — although no doubt, in 
 addition to their other functions, they may in some degree minister 
 to the nutrition of the tissues with which they are in contact, are 
 
 466 
 
FACTORS CONCERNED IN LYMPH FORMATION 467 
 
 as regards their composition and mode of formation scarcely nnjre 
 closely allied to lymph than sweat is. They are almost free from 
 protein, and are secreted by special structures — the choroid plexus 
 and the uveal epithelium — quite different from any that can be 
 concerned in the formation of ordinary lymph. 
 
 It is very true these liquitls are not blood, but that is scarcely a 
 sufficient reason for calling them lymph, else we might classify 
 sweat or even milk as lymph also. If a term is desirable to indicate 
 that they have certain relations with lymph, they might perhaps 
 be spoken of as lymphoid secretions. It may be that the essentiaJ 
 difference in the chemical composition of these lymphoid secretions 
 and lymph — -the practical absence of protein — -is related to the 
 difference in the manner of their formation. The uveal and choroidal 
 epithelial cells, interposing the depth of their columns or cubes 
 between the blood and the free surface at which the liquid escapes, 
 may well be suited to hinder the passage of the protein molecules 
 which find their way with greater ease through the thin endothelium 
 of the capillary wall into the tissue spaces, and from these into the 
 lumen of the closed lymphatics (see p. 439)- Nevertheless, we shall 
 recognize later on in the glomeruli of the kidney an instance of 
 blood capillaries but little pervious to proteins, and there are several 
 other facts which show that the capillaries may differ considerably 
 in different organs in the readiness with which the}' permit the 
 various constituents of the plasma to pass through their walls. 
 Further, in discussing the mechanism by which lymph is formed, 
 we shall see reason to doubt whether mechanical filtration, due to 
 differences of hydrostatic pressure on the two surfaces of the 
 capillary endothelium, has much, if anj^thing, to do with the 
 passage either of protein or of the other constituents of the lymph 
 from the lumen of the capillaries into the tissue spaces. At first 
 glance, indeed, such a process would seem to be admirably fitted to 
 explain the fact that, while lymph differs but little from blood- 
 plasma in the proportions of its other constituents, it is at most no 
 more than half as rich in protein. For there are many filters which 
 allow substances in ordinary solution and their solvent to pass 
 through without alteration in their relative proportions, while 
 substances like proteins in colloid solution are kept back to a 
 greater or less extent. 
 
 Factors concerned in Lymph Formation. — ^The teaching of Ludwig, 
 that lyinph is formed by the filtration, and in a minor degree by the 
 diffusion, of the constituents of blood-plasma through the walls of the 
 capillaries into the tissue spaces, was based on such facts as the 
 increase in the tissue liquid of a limb or organ which occurs when 
 the exit of blood from it by the veins is hindered, or when the 
 quantity of the circulating liquid is increased by the injection of 
 blood or salt solution. It was first seriously called in question by 
 
468 FORMATION OF LYMPH 
 
 Heidenhain, who advanced the theory that lymph is secreted by 
 the endothelium of the blood capillaries. One of Heidenhain's 
 strongest arguments in favour of his secretion theory was the 
 existence of substances which, when injected into the blood, in- 
 creased the flow of lymph from the thoracic duct of the dog without 
 affecting appreciably the arterial pressure. He divided these so- 
 called lymphagogues into two classes: (i) Substances like peptone, 
 extracts of the head and liver of the leech, extract of crayfish 
 muscle, egg-albumin, etc., which cause not onh^ an increase in the 
 rate of flow, but an increase in the specific gravity and total solids 
 of the lymph; (2) crystalloid substances, hke sugar, salt, etc., which 
 cause an increased flow of lymph more watery than normal. 
 
 Starling has shov. ;i that, although the lymphagogues of the second 
 class do not raise the arterial pressure, they do, by attracting water 
 from the tissues and thus causing hydreemic plethora (an excess of 
 blood of low specific gravity), bring about a marked rise of venous, 
 and therefore, what is the important thing for lymph filtration, of 
 capillary pressure. But it can be demonstrated that vaso-dilata- 
 tion with increase of capillary pressure is not in itself sufficient to 
 increase the fornicition of lymph. We have seen, e.g. (p. 179), that 
 when the chorda tympani nerve is stimulated in the dog the arteri- 
 oles of the submaxillar}' gland are dilated, and no doubt the pres- 
 sure in the capillaries is increased. No increased flow of lymph, 
 however, takes place from the submaxillary lymphatics during even 
 prolonged excitation of the chorda, nor do the lymph spaces of the 
 gland become distended (Heidenhain). In the horse also the spon- 
 taneous flow of lymph from the quiescent parotid is not appreciably 
 altered by excitation of the secretory nerves of the gland or by 
 pilocarpine (Carlson). There is every reason to believe that during 
 active secretion of saliva tissue liquid is really formed from the 
 blood in increased amount, and that it is from the tissue spaces 
 that the gland-cells directly obtain the increased supply of water 
 and other substances necessary to sustain the increased secretion. 
 But a balance is maintained between the production of tissue liquid 
 and its removal by the gland-cells. When the gland is quiescent, 
 the small amount of tissue liquid normally formed from the blood 
 capillaries for the nutrition of the cells is balanced by, upon the 
 whole, an equal amount of lymph secreted from the tissue spaces 
 into the lymph capillaries. 
 
 We may say, indeed, that the closed lymphatic system has for 
 its great function the regulation of the quantity and quality of the 
 tissue liquid. In glands with an external secretion increased irriga- 
 tion of the tissue spaces from the blood does not as a rule lead to 
 increased flow of lymph, because the surplus fluid is required to 
 form the secretion. In other organs, however, such as the muscles 
 and the ductless glands, it is probable that the augmented irriga- 
 
FACTORS CONCERNED IN LYMPH FORMATION 469 
 
 tion rendered necessary by functional activity is always associated 
 with an accelerated flow of lymph, which carries off the surplus 
 liquid, including a ])ortion of the waste products. It is probable 
 that an important factor in the production of oedema may be the 
 derangement of the mechanism, whatever it is, through which the 
 adjustment of the rate of formation of tissue liquid to that of 
 lymphatic lymph is achieved. But it must be remembered that in 
 all the organs the blood capillaries not only supply materials to the 
 tissue spaces, but take up materials from them. Indeed, there are 
 facts which indicate that in general water and dissolved substances 
 pass more easily and in greater amount back from the tissues into 
 the blood than into the lymphatics. So that, while the lymphatics 
 constitute an accessory drainage system, the bloodvessels irrigate 
 the tissues and drain them as well. A consequence of this, as well 
 as of the great difference in the capacity of the different tissues for 
 storing water, is that the amount of tissue lymph formed can never 
 be estimated from the amount of lymphatic lymph leaving an organ. 
 Thus the flow of lymph from the limbs at rest is very small in com- 
 parison with the flow from the abdominal viscera, which constitutes 
 the great bulk of the lymph passing along the thoracic duct. This, 
 however, does not prove that very little liquid passes out of the 
 limb capillaries, for the chief tissue of the limbs, the muscles, pos- 
 sesses a far greater storage capacity for water than the intestines and 
 digestive glands. In the one case we have a field whose soil takes 
 up a great deal of water and is not easily saturated ; in the other a 
 field whose soil soon becomes water-logged and refuses to take up 
 any more. With the same supply from the irrigating ditch, little 
 or no water may drain off at the foot of the first field, a great deal 
 at the foot of the second. 
 
 Where the main lymphatics are themselves blocked by mechanical 
 pressure or by inclusion in a ligature, the balance is, of course, 
 grossly upset by the failure of the outflow of lymph to keep pace 
 with its formation. Where an obstruction on the course of the 
 veins is responsible for the oedema, the lymphatic outflow, to be 
 sure, is not directly interfered with. But the nutrition and the 
 respiration of the vascular walls themselves, including the endo- 
 thelium of the capillaries, necessarily suffers from the insufficiency 
 of the blood-flow, and the crippled capillaries may very well become 
 abnormally permeable for water, salts, and the other constituents 
 of lymph. And while ordinary mechanical filtration may not be a 
 factor, or a very unimportant one, in the passage of Uquid through 
 the normal capillary wall, it may become far more effective when 
 it acts on a damaged wall. The tissue cells also suffer from lack 
 of oxygen and nutritive material, and from the accumulation of 
 waste products, including acid substances, which cause them to 
 take up and to hold more water than normal. Even in the absence 
 
470 FORMATION OF LYMPH 
 
 of changes in the mechanical conditions of tiie blood and lymph 
 circulations, alterations in the tissues must be recognized as among 
 the causes of cedema (Fischer). Thus it is clear that the interpre- 
 tation of such an apparently simple experiment as the production 
 of oedema by the ligation of a vein needs great care. Whatever it 
 proves, it may be said with confidence that it does not prove that 
 the increased capillary pressure is the direct cause of the oedema. 
 
 A mere increase in the capiUary blood-pressure does not of itself 
 accelerate the formation of tissue liquid from the blood any more 
 than that of lymph from the tissue liquid, as is shown by the fact 
 that, when the chorda tympani is stimulated after injection of a 
 dose of atropine sufficient to prevent all salivary secretion, there is 
 neither oedema of the gland nor increase in the flow of lymph from 
 it, although the arterioles are as widely dilated as before. When the 
 blood-pressure is greatly increased in the anterior portion of an 
 animal by clamping the aorta, or in the whole animal by continued 
 stimulation of the cut medulla oblongata or the splanchnic nerves, 
 the blood does not alter in concentration in the least, showing that 
 no sensible increase in the passage of water into the lymph has 
 occurred. After division or embolism of the medulla oblon- 
 gata, and consequent paralysis of the vaso-motor centre and 
 general vascular dilatation, it is stated that the injection of sodium 
 chloride produces an increase in the lymph- flow as great and as 
 durable as in the normal animal, and which can continue even after 
 death (Pugliese). The action of the first class of lymphagogues, 
 which cannot be explained as the consequence of an increase of 
 capillary pressure, because the pressure in the capillaries is not 
 consistently increased, and may even in the case of some of these 
 lymphagogues be diminished, is attributed by Starling to an injurious 
 effect on the capillary endothelium (and especially on the endo- 
 thelium of the capillaries of the liver, since nearly the whole of the 
 increased 13'mph-flow comes from that organ), which increases its 
 permeability. But it is not easy to distinguish an increase of per- 
 meability produced by lymphagogues from an increase of secretory 
 activity of the endothelial cells. 
 
 Hamburger, too, has brought forward results which it is difficult 
 to reconcile with a theory of filtration even for the second class of 
 lymphagogues. Further, Heidenhain has shown that some time 
 after injection of a crystalloid substance, like sugar, into the blood, 
 a greater percentage of the substance may be found in the lymph 
 than in the blood. Now, when a mixture of crystalloitls and col- 
 loids is filtered through a thin membrane, the percentage of crystal- 
 loids in the filtrate is never, at most, greater than in the original 
 liquid. And although Cohnstein states that, if time enough be 
 allowed, the maximum concentration of sodium chloride in the 
 lymph, after intravenous injection, becomes approximately the 
 
FACTORS CONCERNED IN LYMPH FORMATION 47X 
 
 same as the maximum in the blood, this fact loses its weight as 
 an argument in favour of the filtration hypothesis when we re- 
 member that, according to Asher, all the solids of the lymph are 
 inurkcdly increased when even small quantities of crystalloids are 
 injected into the veins. Upon the whole, tlien, it may be con- 
 cluded that up to the present it has not been shown that filtration 
 due to the excess of pressure in the capillaries over that in the 
 lymph spaces is an effective factor in the formation of lymph. Nor 
 is it at all easier to explain lymph formation as a matter of pure 
 osmosis or diffusion. Lazarus-Barlow found, for example, that in 
 the great majority of his experiments the injection of a concen- 
 trated solution of sodium chloride, dextrose or urea into a vein was 
 followed, not by an initial diminution in the outflow of lymph (as 
 might have been expected if the exchange of water between the 
 blood and the tissue spaces, and between the tissue spaces and the 
 lymph capillaries, was regulated solely by differences in osmotic 
 pressure), but by an immediate increase. And Carlson has shown 
 that the osmotic pressure of lymph coming from the active salivary 
 glands, as measured by the freezing-point method, may, under 
 chloroform or ether anaesthesia, be distinctly less than that of the 
 blood-serum. Water must therefore be passing from a liquid of 
 higher to one of lower osmotic concentration. 
 
 Nevertheless, it would be erroneous to assume that because 
 osmosis and diffusion have not been sho\NTi to satisfactorily account 
 for all the phenomena of lymph formation, they exert no influence 
 upon it. It is probable, indeed, that their action is fully as im- 
 portant as in absorption from the alimentary canal, although, as in 
 absorption, it is often overlaid and always modified by the specific 
 permeability of the blood-capillary walls, the lymph-capillary walls, 
 and the tissue cells in general, in virtue of which they exert an 
 action upon the quantity and composition of the lymph analogous 
 to the action exerted in a higher degree by the cells of the digestive 
 glands upon the quantity and composition of the liquids passing 
 into their ducts. 
 
 It is not difticult to illustrate the fact that phenomena of osmosis and 
 diffusion emerge, although not of course in such purity as in physical 
 experiments, when we study the interchange between the blood and 
 the tissue liquids. If, for example, a hypertonic solution of sodium 
 chloride is injected into the blood, water rapidly passes from the tissues 
 to the blood as it would through a semipermeable membrane, and the 
 blood becomes diluted. At the same time sodium chloride leaves the 
 blood and passes into the tissues, as it would do by diffusion from a 
 place of higher to a place of lower concentration. But after this has 
 gone on for some time, and the concentration of the blood in salt has 
 sunk, it may be, to that in the lymph, salt still continues to pass out 
 of the blood, and the excess of water also leaves the bloodvessels till the 
 osmotic pressure of the blood has again become normal. When isotonic 
 and even hypotonic solutions of sodium chloride are injected, salt also 
 
472 FORMATION OF LYMPH 
 
 leaves the blood and enters the lymph, although it ought not to do so 
 by ditfusion, while water, which might pass from the hypotonic bloo<l 
 into the lymph by osmosis, moves in the same direction from the blood 
 to which the isotonic salt solution has been added. Regulative mechan- 
 isms, in short, exist which tend, with, but also without, the co-opera- 
 tion of diffusion and osmosis, and even, so to say, in their teeth, 
 to bring back the quantitative and qualitative composition of the 
 blood to the normal. Exactly similar phenomena are witnessed when 
 the equilibrium is upset from the other side by the injection of salt 
 solutions into the subcutaneous tissue or the intramuscular connective 
 tissue. Hypotonic sodium chloride solution injected into the sub- 
 conjunctival connective tissue quickly loses water and gains sodium 
 chloride, as it ought to do if under the influence of osmosis and diffusion, 
 and hypertonic salt solutions gain water. But eventually hypertonic, 
 hypotonic, and isotonic solutions, and even serum itself, are completely 
 absorbed, which could not occur in the presence of diffusion and 
 osmosis alone. Sometimes in dropsy it appears that the oedema liquid 
 is absorbed when the patient is put on a diet free as far as possible 
 from salts. The suggestion is that the regulative mechanism which 
 tends to keep the molecular concentration of the blood and lymph 
 approximately constant provides that as the salt content of the body 
 falls, which it does through continued excretion of salts in the urine, 
 water is eliminated in corresponding amount. 
 
 The Contribution of the Tissue-Cells to the Lymph. — So far we 
 have considtTed the passage of the Ij'mph constituents, on the one 
 hand through the endotlieUum of the blood capillaries into the 
 tissue spaces; on the other, from the tissue spaces through the endo- 
 thelium of the lymph capillaries. But it is not to be supposed that 
 the liquid lying in clefts, partly bounded by blood capillaries, partly 
 by h-mph capillaries, partly by tissue-cells, should be affected solely 
 by the first two. The third anatomical element must contribute 
 something to, or withdraw something from, the tissue liquid, and 
 may thus play a part in the formation of lymph from the latter. 
 The recent researches of Asher and his pupils have raised the ques- 
 tion of the relation between the physiological activity of the organs, 
 and especially of the glands, and the formation of the lymph. They 
 conclude that the common doctrine that lymph is simply a diluted 
 blood-plasma is erroneous. Lymph, they say, far from being a 
 mere filtrate or even a secretion from the blood, is formed b}' the 
 activity of the organs, and may actually be absorbed by the blood 
 from the tissue spaces. In fact, according to their view, the in- 
 travenous injection of lymphagogues, both crystalloid and colloid, 
 only causes an increased flow of lymph in so far as it leads to in- 
 creased glandular secretion. But this generalization has had only 
 a short-lived vogue, and one by one some of the main results which 
 seemed to support it have been disproved or shown to be capable 
 of interpretation in a different sense. For example, it was stated 
 that secretin causes a flow of lymph from the lymphatics of the 
 pancreas, as well as a flow of pancreatic juice. But it has been 
 shown that the increased production of lymph is not due to the 
 
INFLUENCE OF NERVES ON LYMPH FORMATION 473 
 
 secretin at ull, but to lymphagogue substances, including proteose, 
 extracted with the secretin from the intestinal mucous membrane. 
 A solution of secretin can be prepared which causes a considerable 
 increase in the secretion of pancreatic juice and bile, but no augmen- 
 tation whatever in the flow of lymph from the thoracic duct. 
 Again, it was asserted that peptone, a noted lymphagogue, produces 
 a great increase in the biliary secretion. It has been demonstrated, 
 however, that the action of the peptone is merely to cause expul- 
 sion of the contents of the gall-bladder by the mechanical effect of 
 the swelling of the liver, and not at all to stimulate the liver-cells 
 to form more bile. For it produces no effect on the flow of bile 
 if the gall-bladder be emptied or the cystic duct tied before the 
 injection (Ellinger). That active salivary secretion is not accom- 
 panied by increased lymph-flow from the lymphatics of the salivary 
 glands has been mentioned above. Nevertheless, we may safely 
 assume that the activity of the organs does make a contribution to 
 the lymph — to its solids, if not in any important degree to its water- 
 content, although to say that they alone are concerned in its forma- 
 tion, to the exclusion of the capillaries, is altogether an over-state- 
 ment. The waste-products of the tissues pass into the lymph, and 
 possibly, as Koranyi suggests, may, by increasing its molecular 
 concentration, cause the passage of some water into it from the 
 blood. Or the decomposition of the large protein molecules, which 
 in tissue metabolism are breaking down into numerous smaller 
 molecules, may entail an increase of osmotic pressure in the cells 
 themselves, which in turn may lead to withdrawal of water by the 
 cells from the tissue liquid. The osmotic pressure of the liquid 
 may thus rise, and water may pass into the tissue spaces from the 
 blood. The molecular concentration of lymph (except in anaesthe- 
 tized animals as mentioned above) is in general somewhat greater 
 than that of blood-serum — e.g., in one observation A of serum 
 was 0605° C, and of lymph o-6io° C. For the solid tissues, the 
 freezing-point of which, however, cannot be as satisfactorily deter- 
 mined as that of liquids, the following values of A were obtained: 
 Brain, 0-65°; muscle, 068°; kidney, 094°; hver, 0-97°; while for 
 blood it was 057° (Sabbatani). 
 
 To sum up, we may say that while the physical processes of filtra- 
 tion, osmosis and diffusion may play a part in the passage of water 
 and solids through the walls of the blood capillaries, as well as from 
 the tissue-cells into the tissue spaces, and from these spaces into the 
 lymph capillaries, there is much which they leave unexplained, and 
 which at present, for the want of a more precise term, we must attribute 
 to secretory activity. 
 
 Influence of Nerves on Lymph Formation. — 'In one instance 
 it appears to have been shown that lymph may be formed 
 under the influence of secretory nerves. In the males of certain 
 
474 FORMATION OF LYMPH 
 
 aquatic birds erection is due to the filling of the corpus cavernosum. 
 not \\'ith blood, but with lymph. The lymph is secreted rapidly by 
 the so-called bodies of Tannenberg when certain sympathetic nerve- 
 fibres are experimentally stimulated, and passes into the corpus 
 cavernosum, which swells up. If a small incision is made in the 
 corpus, a large quantity of clear lymph, \\ hich clots slowly on stand- 
 ing, escapes. There is a simultaneous vasodilatation. After erection, 
 the lymph is rapidly and completely reabsorbed (Eckhard, Miiller). 
 
 .\lthough no definite lymph-secretor}^ nerve-fibres have as yet 
 been discovered in mammals and for ordinary tissues, it is possible 
 that they exist (Sihlen. As already pointed out, the same volume 
 of liquid as escapes into the ducts of the active submaxillary gland 
 must, upon the whole, pass out of the blood capillaries. On what 
 principle shall we distinguish one only of these processes as physio- 
 logical secretion ? They begin together when the chorda tympani 
 is stimulated. A drug which paralyzes secretory nerve-endings 
 abolishes both effects. The simplest explanation is that the chorda 
 contains secretory fibres which influence the formation both of 
 saliva and of the tissue liquid from which it is recruited; and, so 
 far as this consideration goes, it is just as logical to consider the 
 increase in the supply of tissue liquid as the cause of the increase 
 in the flow of saliva as to consider the increased salivary secretion 
 as the cause of the increased flow of liquid into the tissue spaces. 
 The increased flow of liquid may be brought about either by an 
 action of the nerve on the gland-cells, causing them to produce a 
 hormone, which then effects the blood capillaries (Carlson), or by 
 a direct action on the capillary endothelium. The advantage to 
 cells engaged in the active secretion of saliva of being immersed in 
 an abundant bath of tissue liquid is ob\nous. 
 
 The post-mortem flow of l3rmph, which may continue in some 
 cases long after complete cessation of the circulation — for an hour 
 after injection of dextrose to produce hydremic plethora; for as 
 much as four hours after injection of extract of the strawberry, 
 which is a . ly mphagogue of Heidenhain's first group (Mendel and 
 Hooker) — is a phenomenon whose relation to normal lymph forma- 
 tion has not been definitely settled. 
 
 It ought to be remembered in this whole discussion that the 
 epithelium of ordinary glands derives its suppHes of material from 
 the tissue lymph. The vicissitudes of blood-pressure affect it only 
 in a secondary and indirect manner. On the other hand, tho endo- 
 thelial cells of the capillaries are in direct contact with the blood. 
 And it is interesting to observe that in this respect the glomeruli 
 of the kidney and the alveoli of the lungs (if the endothelial lining 
 of Bowman's capsule and the alveolar membrane are assumed to 
 be complete) taki- a middle place between the glands proper and 
 the quasi-glandular capillaries. 
 
CHAPTER IX 
 EXCRETION 
 
 We have now followed the ingoing tide of gaseous, liquid, and solid 
 substances within the physiological surface of the body. There we 
 leave them for the present, and turn to the consideration of the 
 channels of outflow, and the waste products which pass along them. 
 In a body which is neither increasing nor diminishing in mass the 
 outflow must exactly balance the inflow; aU that enters the body 
 must sooner or later, in however changed a form, escape from it 
 again. In the expired air, the urine, the secretions of the skin, and 
 the faeces, by far the greater part of the waste products is elimin- 
 ated. Thus the carbon of the absorbed solids of the food is chiefly 
 given off as carbon dioxide by the lungs; the hydrogen, as water 
 b}' the kidneys, lungs and skin, along with the unchanged water 
 of the food; the nitrogen, as urea by the kidneys. The faeces in 
 part represent unabsorbed portions of the food. A small and 
 variable contribution to the total excretion is the expectorated 
 matter, and the secretions of the nasal mucous membrane and 
 lachrymal glands. Still smaller and still more variable is the loss 
 in the form of dead epidermic scales, hairs, and nails. The dis- 
 charges from the generative organs are to be considered as excre- 
 tions with reference to the parent organism, and so is the milk, and 
 even the fretus itself, with respect to the mother. 
 
 Excretion by the lungs and in the faeces has been already dealt 
 with. All that is necessary to be said of the expectoration and 
 the nasal and lachrymal discharges is that the first two generally 
 contain a good deal of mucin, and are produced in small mucous 
 and serous glands, the cells of which are of the same general type 
 as those of the mucous and serous salivary glands. The lachrymal 
 glands are serous like the parotid ; and the tears secreted by them 
 contain some albumin and salts, but little or no mucin. The sexual 
 secretions and milk will be best considered under reproduction 
 (Chap. XIX.), so that there remain only the urine and the secre- 
 tions of the skin to be treated here. 
 
 475 
 
476 EXCRETION 
 
 Section I. — Excretion by the Kidneys— The Chemistry of 
 
 THE Urine. 
 
 Normal urine is a clear yellow liquid acid to litmus and similar 
 indicators, but nearly neutral or very weakly acid in the physico- 
 chemical sense (p. 24). The average specific gravity is about 1020, 
 the usual limits being 1015 and 1025, although when water is taken 
 in large quantities, or long withheld, the specific gravity may fall 
 to 1005, or even less, or rise to 1035, or even more. The quantity 
 passed in twenty-four hours is very variable, and is especially 
 dependent on the activity of the sweat-glands, being, as a rule, 
 smaller in summer when the skin sweats much, than in winter when 
 it sweats little. The average quantity for an adult male is 1,200 to 
 1,600 c.c. (say, 40 to 50 oz.).* 
 
 Composition of Urine. — This is very closely related to the quantity 
 and quality of the food. Hence it is impossible to speak of a 
 definite normal composition of the urine. It is essentially a solu- 
 tion of urea and inorganic salts, the proportion of the latter being 
 generally about 15 per cent., or double the usual amount of physio- 
 logical liquids. Besides urea, there are other nitrogenous bodies 
 in much smaller quantity, such as ammonia, uric acid, and the 
 allied purin bases, hippuric acid, and kreatinin. Some of these at 
 least are products of the metabolism of proteins within the tissues. 
 And besides the inorganic salts there are certain organic bodies — 
 indoxyl, phenyl, pyrokatechin', skatoxyl — united with sulphuric 
 acid, which are primarily derived from the products of the putre- 
 faction of proteins within the digestive tube. 
 
 Folin has published analyses of ' normal ' urines from six persons, 
 weighing from 56-6 to 70-9 kilos (average 63-4 kilos), who were kept 
 for seven days on one standard uniform diet. The diet consisted of 
 500 c.c. of milk, 300 c.c. of cream (containing 18 to 22 per cent, of fat), 
 '450 grammes of eggs, 200 grammes of Horlick's malted milk, 20 grammes 
 of sugar, 6 grammes of sodium chloride, water enough to make the 
 whole up to two litres, and 900 c.c. of additional water. The ingredients 
 contained 119 grammes of protein, about 148 grammes of fat, and 
 225 grammes of carbo-hydrates. The average results of all the deter- 
 minations are given in the following table : 
 
 * The average quantity of urine varies not only with the season, but also 
 with the habits of the person, especially as reganls the amount of liquid 
 taken. The average for seventeen healthy (American) students, whose urine 
 was collected for six to eight successive days in winter, was 1,166 c.c. The 
 highest average in any one individual for the observation period was 1,487 c.c. 
 (for seven days), and the lowest 743 c.c. (for eight days). The greatest quan- 
 tity passed in any one perio<l of twenty-four hours was 2,286 c.c. (by the in- 
 dividual whose average was the highest). The smallest quantity passed in 
 twenty-four hours was 650 c.c. (by the individual whose average was the 
 lowest. 
 
CHEMISTRY OF URINE 
 
 477 
 
 
 Grammes. 
 
 Containing 
 
 Nitrogen 
 
 (Grammes). 
 
 Percentage 
 of Total 
 Nitrogen. 
 
 Urea ----- 
 Ammonia - - . - 
 Kreatinin - - - - 
 Uric acid - - - - 
 Nitrogen in other compounds 
 
 29-8 
 
 1-55 
 0-37 
 
 13-9 
 0-70 
 0-58 
 
 0-I2 
 
 o-6o 
 
 87-5 
 
 4-3 
 3.6 
 0-8 
 3-75 
 
 ~ i 
 
 Total nitrogen - - - 
 
 — 
 
 i6-oo 
 
 Inorganic SO3 _ _ - 
 Ethereal SO3 - - - - 
 ' Neutral ' SO3 
 
 Total sulphur as SO3 
 
 Total phosphates as P20g - 
 Chlorine . - - - 
 
 2 '92 
 0'22 
 0-17 
 
 3-31 
 
 3-87 
 
 6-1 
 
 Percentage of Total 
 Sulphur. 
 
 87-8 
 
 6-8 
 5-1 
 
 Titratable acidity in c.c. of decinormal acid - 617 \ „-._JL:„' ^,t' 
 
 Indican (Fehling's solution = 100*) 
 Volume of urine 
 
 77 
 1430 c.c. 
 
 The great influence of diet on the composition of the urine is illus- 
 trated in the following table. Urine I. was obtained from a man weigh- 
 ing 87 kilos on the standard protein-rich diet described above. Urine II. 
 was obtained from the same person on a diet very poor in protein 
 (400 grammes of starch and 300 c.c. of cream), containing only about 
 I gramme of nitrogen, as against 19 grammes in the first diet. 
 
 
 I. 
 
 II. 
 
 Volume of urine 
 
 1170 c.c. 
 
 385 c.c. 
 
 
 Grammes. Per Cent. 
 
 Grammes. Per Cent. 
 
 Total nitrogen - - - 
 
 i6-8 
 
 3-60 
 
 Urea-nitrogen - - - 
 
 1470 = 87-5 
 
 2-20 = 6l«7 
 
 Ammonia-nitrogen 
 
 0-49 = 3-0 
 
 0-42 = II«3 
 
 Uric acid-nitrogen 
 
 o-i8 = I'l 
 
 0-09 = 2'5 
 
 Kreatinin -nitrogen 
 
 0-58 = 3-6 
 
 o-6o = I7'2 
 
 Nitrogen in other compounds - 
 
 0-85 = 4-9 
 
 0-27 = 7-3 
 
 Total SO3 - - - 
 
 3-64 
 
 
 Inorganic SO3 . - - 
 
 3-27 = 90-0 
 
 0-46 = 6o'5 
 
 Ethereal SO, . - - 
 
 0-19 = 5-2 
 
 o-io = 13-2 
 
 Neutral SO3 
 
 o-i8 = 4-8 
 
 0-20 = 26'3 
 
 Total phosphates as P.2O5 
 
 4-1 
 
 I'O 
 
 Chlorine 
 
 6-1 
 
 1-6 
 
 Titratable acidity in c.c. ^^ acid - Sosj^/g^^'^'f^^; \f^ 324{^rgan?c: 201' 
 
 Indican (Fehling's solution = 100) - 120 - - - o 
 
 * The indican is given in arbitrary units, the indigo blue being obtained 
 from the urine and then estimated colorimetrically, using Fehling's solu- 
 
47S 
 
 EXCRETION 
 
 The titrable acidity of urine (see p. 25) is chiefly due to the acid (mono- 
 basic) phosphates, such as acid sodium phosphate (Nai^l2P04), but in 
 an important degree also to organic acids. According to Fohn. indeed, 
 the organic acidity may be more than lialf the total acidity. Normally 
 the acidity diminishes distinctly, or even gives place to alkalinity, 
 during digestion, when the acid of the gastric juice is being secreted. 
 'J1iis is sometimes fancifully denominated the alkaline tide. After a 
 fast, as before breakfast, the opposite condition, the acid tide, occurs. 
 
 The acidity varies with the quantity of vegetable food in the diet. 
 The urine of herbivora and vegetarians is alkaline, and is either turbid 
 when passed, or on standing soon becomes turbid from precipitated 
 carbonates and phosphates of earthy bases, while that of camivora 
 and of fasting herbivora, which arc living on their own tissues, is 
 strongly acid and clear. Normal human urine may deposit urates soon 
 after discharge, as they are more soluble in warm tiian in cold water. 
 They carry down some of the pigment, and therefore usually appear as 
 a pink or brick-red sediment. When urine is alloyved to stand after 
 being voided, what is generally described as ' acid fermentation ' occurs. 
 The acidity gradually increases; acid sodium urate is produced from 
 the neutral urate, and comes down in the form of amorphous granules, 
 while the liberated uric acid is deposited often in ' whetstone ' crystals, 
 coloured yellow by the pigment (Fig. 177). Calcium oxalate may also 
 
 Uric Acid. 
 
 Fig. 178. — Calcium Oxalate 
 
 be thrown down as ' envelope,' a. b, or less frequently, ' sand-glass ' 
 crystals, c (Fig. 178). If the urine is allowed to stand for a few days, 
 especially in a warm place, or in a place where urine is decomposing, 
 the reaction becomes ultimately strongly alkaline ,^ owing to the forma- 
 tion of ammonium carbonate from urea by the action of micro-organ- 
 isms {Micrococcus iirece. Bacterium urecB, and others) which reach it 
 from the air, and produce a soluble lennent urease, in whose presence 
 the urea is split up with assumption of water. Thus: 
 
 C.^ 
 
 NH2 
 
 o 
 
 NNHj 
 
 Urea. 
 
 + 2H2O 
 
 /O.NH4 
 
 c=o 
 
 NO.NH^, 
 
 Amiiiontum carbonate. 
 
 This is a reaction of considerable interest, for the reverse reaction 
 occurs when blood containing ammonium carbonate is circulated 
 tlirough the liver, the ammonium carbonate being converted into urea 
 with loss of water. The enzyme urease is present in higher plants than 
 ba-cteria and fungi. A solution containing it, conveniently prepared 
 from the soy bean, can be used for the quantitative estimation of urea, 
 and this is probably the easiest and most accurate method. 
 
 tion as a standartl. Fehling's solution is employed because it is a blue liquid 
 of a definite depth of tint already prepared in every physiological laboratory. 
 
CHEMISTRY OF innxE 
 
 479 
 
 The substances insoluble in alkaline urine are tlirowii 'lown. the 
 deposit containing atiimonio-magnesic or trif^le phosphate, iormed by 
 the union of ammonia with the magnesium phosphate present in friish 
 urine, and precipitated as clear crystals of ' knife-rest ' or ' coffin-lid ' 
 shape (Fig. 179), along with amorphous earthy phosphates, and often 
 acid ammonium urate in the form of dark balls occasionally covered 
 with spines (Fig. i8j). Calcium phosphate (CaHP04) is another phos- 
 phate found in sediments deposited from alkaline or faintly acid urine. 
 It is usually amorphous, but sometimes in the form of long prismatic 
 crj'stals arranged in star fasldon, and hence spoken of as stellar phos- 
 phate (Fig. 181). It is not pigmented. 
 
 It is only in pathological conditions that the alkaline fermentation 
 takes place within the bladder. The reaction of the uruie can readily 
 
 i^ 
 
 # o 
 
 Kig. 179. — Triple Phosphate. Fig. 180. — Cystin. Fig. 181. — Stellar Phos- 
 
 phate Crystals. 
 
 be niadc alkaline by the administration of alkalies, alkaline carbonates, 
 or the salts of vegetable acids like malic, citric, and tartaric acid, which 
 are broken up in the body and form alkaline carbonates with the alkalies 
 of the blood and lymph. It is not so easy to increase the acidity of the 
 urine, although mineral acids do so up to a certain limit. If the admin- 
 istration of acid be pushed farther, ammonia is split off frona the pro- 
 teins, and is excreted in the urine as the ammonium salt of the acid. 
 
 Determination of the Acidity. — A titration method is described in 
 the Practical Exercises (p. ^15). In speaking of the reaction of blood, 
 it has already been mentioned (p. 25) that we can- 
 not determine by titration the true acidity or alka- 
 linity of a liquid in the physico-chemical sense — i.e., 
 the concentration of the dissociated hydrogen and 
 hydro xyl ions respectively. E.g.. when we titrate 
 equal quantities of decinormal* acetic acid and deci- 
 normal hydrochloric acid with decinormal potassium 
 hydroxide, using, say, phenolphthalein as the indi- 
 cator, nearly the same volume of the potassium 
 hydroxide solution will be needed to neutralize each 
 acid. Yet it can be shown by physico-chemical 
 methods that the acetic acid in the strength used is 
 only dissociated to the extent of a little more than i per cent., while 
 about 80 per cent, of the hydrochloric acid is dissociated. The concen- 
 tration of the hydrogen ions is therefore eighty times as great in the 
 hydrocliloric as in the acetic acid solution. What we determine by the 
 titration is not the true acidity, but the total amount of hydrogen which 
 can be replaced by metal. The concentration of the hydrogen ions in 
 normal urine is very small, on the average only about 0'003 mUli- 
 
 * A normal solution of a substance contains in a litre a number of grammes 
 of the substance equal to the number wliich expresses its equivalent weight 
 — a decinormal (usually written -^) solution one-tenth of this amount, a 
 centinormal one-hundredth, etc. Thus, a normal solution of potassium 
 hydroxide contains 56 grammes of KOH, and a decinormal solution 5*6 
 grammes in 1,000 c.c. 
 
 Ammo- 
 
 nium Urate (after 
 Milroy). 
 
48o EXCRETION 
 
 graiiiiue in tli<' litre, or about thirty times as much as is present in the 
 purest distilled water. Urine departs about as much from neutrality in 
 the one direction as blood does in the other. 
 
 Urea, CO(NH2)2' '^ ^^^^ form in which by far the greater part of the 
 nitrogen is under ordinary conditions discharged from tlic body. Its 
 amount is as important a measure of protein metabolism as the quantity 
 of carbon dioxide given out by the lungs is of the oxidation of carbon- 
 aceous material. Yet a glance at the table on p. 477 shows that, when 
 the total protein metabolism is greatly reduced by diminishing the 
 protein in the food, the relative as well as the absolute amount of 
 nitrogen eliminated as urea sutlers a great diminution. The relative 
 amount of the other nitrogenous urinary constituents, especially of 
 the kreatinin, is markedly increased. The significance of this difference 
 is alluded to in speaking of the kreatinin content of urine, and will have 
 to be again considered under Protein Metabolism. Urea is soluble in 
 water and in alcohol, and crystallizes from its solutions in the form of 
 long colourless needles, or four-sided prisms with pyramidal ends. It 
 can be easily prepared from urine. Urea can also be obtained artificially 
 by heating its isomer, ammonium cyanate (NH4 — O— CN), to 100" C. 
 This reaction is of great historical interest, as it forms the final step 
 in Wohlcr's famous synthesis of urea, the first example of a complex 
 product of the activity of living matter being formed from the ordinary 
 materials of the laboratory. Heated in watery solution in a sealed 
 tube to 180° C, urea is entirely split up into carbon dioxide and am- 
 monia, a change which can also be brought about, as already mentioned, 
 by the action of micro-organisms. Nitrous acid, hypochlorous acid, and 
 salts of hypobromous acid carry the decomposition still farther, carbon 
 dioxide, nitrogen, and water being the products of their oxidizing action 
 on urea. Thus: C0.2(NH2) +3NaBrO-3NaBr + 2H20-i- COg-f- No. 
 This reaction is the basis of the h^^pobromite method of estimating the 
 quantity of urea in urine (Practical Exercises, p. 519). 
 
 Ammonia. — The ammonia in urine is united with acids in the form 
 of salts. Its formation from proteins is determined, as w-e shall see 
 later on, by the necessity of neutralizing certain acids produced in 
 metabolism — e.g., those derived from the sulphur and phosphorus of the 
 proteins, or acids administered experimentally. According to some 
 observers, the percentage amount of the total nitrogen in the urine 
 in the form of ammonia remains the same whether the food be rich or 
 poor in protein (Schittenhelm. etc.), but others state that when the 
 protein is reduced there is a relative increase in the ammonia-nitrogen 
 (see tabic on p. 477) (Folin). 
 
 Uric acid (C5H4N4O3) exists in large amount in the urine of birds. 
 The excrement of serpents consists almost entirelj^ of uric acid. In 
 both cases it is mainly in the form of acid ammonium urate. In con- 
 trast to urea, uric acid is very insoluble, requiring 1.900 parts of hot 
 and 15,000 parts of cold water to dissolve it. In man and mammals 
 the quantity is comparatively small in health, but is increased after 
 a meal containing material {e.g., thymus gland) rich in nucleins, 
 from the nucleic acid of which purin bodies are derived, or sub- 
 stances containing purin bases in the free state — e.g.. hypoxanthin 
 in meat. In mammals the amount of uric acid excreted depends 
 little, if at all, upon the quantity of protein in the food, but a great deal 
 upon the quantity of purin bodies, whether free or combined. When 
 nitrogenous food is omitted altogether, the absolute quantity of uric 
 acid is diminished, but the proportion of the total nitrogen of the urine 
 eliminated rs uric acid is increased, since the ' endogenous ' uric acid 
 (p. 596) still continues to be formed and excreted. 
 
CHEMISTRY OF URINE 
 
 481 
 
 Tlic purin bases (somitimcs called the nuclcin bases, the ulioxuric 
 bases, or the xanthiu bases) are a group of substances allied to uric 
 acid, and including, besides xanthin itself, hypoxanthin, guanin, adenin, 
 and other bodies. Thev exist in very small amount in urine, but, like 
 uric acid, are increased in amount by the ingestion of nuclcin-contain- 
 ing substances. Tlie greater part of the purin bases produced in the 
 body is transformed into uric acid ; it is only the untransformed residue 
 which appears in the urine. An interesting fraction of the purin bases 
 in the urine which is not related to the nuclein metabohsm is composed 
 of the so-called heteroxanthin. derived from caffeine in the coffee and 
 tea. /-methylxauthin, derived from theobromine in the cocoa, and para- 
 xanthin, derived from theophyllin in the tea, consumed as beverages. 
 
 Hippuric acid (C9H9NO;,) occurs in considerable quantity in the urine 
 of herbivora (Practical Exercises, p. 324); in the urine of carnivora and 
 of man only in traces; in that of birds not at all. Its amount is much 
 more dependent on the presence of particular substances in the food 
 than that of the other organic constituents of urine. Anything which 
 contains benzoic acid, or substances which can be readily changed into 
 it (such as cinnamic and quinic 
 acids), causes an increase of the 
 hippuric acid in urine. In fact 
 one of the best ways of obtaining 
 the latter is from the urine of a 
 person to whom benzoic acid is 
 given by the mouth; the sweat 
 
 Fig. 183.— Creatin. 
 
 Great inin-Zinc-C!iloride. 
 
 may also in this case contain a trace of hippuric acid. Chemically it 
 is a conjugated acid formed by the union of benzoic acid and glycin. 
 
 Amino-Acids. — The only amino-acid hitherto detected with certainty 
 in normal urine is glycin. 
 
 Oxalic acid is always present, although in very small amount. Some 
 of it comes from the oxalates of the food, but a portion of it arises in 
 the metabolism of the tissues, probably from the decomposition of uric 
 acid. It is known that outside of the body uric acid may be made to yield 
 oxalic acid. Calcium oxalate crystals are often seen in urinary sediments. 
 
 Creatinin (C4H7N3O). — Creatinin is the anhydride of creatin 
 (Fig. 183). Its formula differs from that of creatin only in possessing 
 the elements of one molecule of water less ; and creatinin can be 
 obtained by boiling creatin with dilute sulphuric acid. From its 
 alcoholic solution it crystallizes in colourless prisms. Creatinin forms 
 crystalline compounds with various acids and salts. One of the best 
 known of these is creatinin-zinc-chloride, formed on the addition of 
 zinc chloride to an alcoholic or watery solution of creatinin, often in 
 the shape of beautiful thick-set rosettes of needles (Fig. 184). A por- 
 
 31 
 
482 EXCRETION 
 
 tion of the urinary creatinin is derived from the creatin of the meat 
 taken as food. But this is not its only source, for on a meat-free diet 
 and in starvation creatinin is still excreted. The absolute c|uantity in 
 the urine on a meat-free diet is constant for one and the same individual, 
 although different in different persons, and independent of the total 
 amount of nitrogen eliminated. Hence on a diet poor in protein the 
 percentage of the total nitrogen excreted as creatinin is much greater 
 than on a protein-rich diet, as shown in the table on p. 477. So constant 
 is the quantity that a determination of the creatinin may be used as a 
 check upon the complete collection of the urine. 
 
 Carbo-hydrates are normally present in human urine, but only in 
 ver>' small amounts. Three arc knowTi with certainty — dextrose, 
 isomaltose, and the so-called animal gum or urine dextrin. Glycuronic 
 acid (CgHioO;), a body which can be derived from dextrose, is con- 
 stantly present in small amount as a conjugated acid, paired with 
 phenol or indoxyl. It gives Fehling's test, and thus may easily be 
 mistaken for sugar. Glycuronic acid becomes coupled ver^' easily with 
 a large variety of substances, including many drugs, and care must be 
 taken after the administration of camphor, chloral hydrate, chloro- 
 form, nitrobenzol, etc., not to confound the largely increased excretion 
 of conjugate glycuronates in the urine with glycosuria. The yeast test 
 will turn out negative if the reduction is due to glycuronic acid, and 
 the polarimetcr will show rotation to the right if it is due to dextrose. 
 The total quantity of carbo-hydrates, including glycuronic acid, 
 excreted in the urine of the twenty-four hours has been estimated at 
 2 to 3 grammes. The quantity of dextrose in normal human urine is 
 about 0-02 per cent., or about one-fifth of the proportion in blood. 
 
 Proteins, mainly serum-albumin, are also found in normal urine in 
 minute quantities, on the average about 0-0036 per cent. (Momer). 
 
 Pigments of Urine. — The pigments of urine have not hitherto been 
 exhaustively studied ; but we alreadv know that normal urine contains 
 several, and pathological urines probably additional, pigmentary sub- 
 stances. The best-known pigments in normal urine are urochrome, 
 the yellow substance which gives the liquid its ordinary colour; 
 uroerythrin. the pink pigment which often colours the deposits of urates 
 that separate even from healthy urine ; and urobilin, which, as has been 
 already stated, is identical with the fa;cal pigment stercobilin, and occurs 
 not only in many febrile conditions, but also in cases with no fever, such 
 as functional derangements of the liver, dyspepsia, chronic bronchitis, 
 and valvular diseases of the heart. The urobilin of urine represents, 
 mainly at least, the portion of the stercobilin which is not excreted with 
 the faeces, but absorbed from the intestine into the blood. The urobilin 
 in normal urine only exi.sts in small amount in the fully-formed con- 
 dition, most of it being present as a chromogen or mother-substance 
 (urobilinogen), which by oxidation, as on standing exposed to the air, 
 is converted into urobilin. On the addition of ammonia and zinc 
 chloride to a solution of urobilin a beautiful green fluorescence is 
 obtained, and the solution now shows an absorption band between 
 b and F. Urobilin and urochrome are related substances, bat the exact 
 nature of the relation has not been settled. There is some evidence 
 that a portion of the urobilin of urine is not derived from the intestine, 
 but manufactured probably in the liver. In hunger urobihn is still 
 excreted in the urine, although in greatly reduced amount. During 
 menstruation it is markedly increased, both in fasting and in normally 
 fed individuals. Urorosein is a red pigment which is produced from 
 its chromogen by the action of mineral acids — e.g., strong hydrochloric 
 acid — in the presence of an oxidizing agent, especially nitrites. 
 
CHEATISTRY OP TJRINE 
 
 48.^ 
 
 The pigments of the blood and bile and some of their derivatives are 
 of common occurrence in the urine in disease. Hcvmatoporphyrin has 
 not only been found in some pathological conditions, but is constantly 
 present in minute traces in normal urine. Certain drugs — e.g., sulphonal 
 — cause an increase in its amount. In paroxysmal haemoglobinuria, 
 victhcBmoglobin . mixed with some oxyhaemoglobin, is found in the urine in 
 large amount; and it is worthy of note that it is not formed in the urine 
 after secretion, but is already present as such when it reaches the bladder. 
 
 In the rare condition termed alkaptonuria, a body, alkapion, now 
 known to be identical with homogentisinic acid, CfiH3.(OH)2CH2.COOH, 
 a dioxyphenylacetic acid, is present. The urine becomes dark brown 
 on the addition of an alkali, or simply on exposure to air. It gives 
 Fehling's test for sugar. The substance has relations to the aromatic 
 amino-acids tyrosin and phcnyl-alanin, and when either of these is 
 given to a person suttcring from alkaptonuria, the amount of alkapton 
 excreted is increased. We may suppose, therefore, that in this con- 
 dition the normal decomposition of these products of proteolysis is 
 interfered with. 
 
 Ferments. — The urine contains traces of proteolytic cmd amylolytic 
 ferments (Fig. 185). These may be easily separated from it by putting 
 a little fibrin, which has the power of fixing (adsorbing) enzymes, into 
 the urine. 
 
 Of the inorganic constituents of urine the most important and 
 most easily estimated are the chlorine, phosphoric acid, and sul- 
 phuric acid. 
 
 Fig. 
 
 185. — Pepsin in Urine. Diastatic Ferment in Urine. 
 At Different Times of the Day (Hoffmann). 
 
 Chlorine. — IMuch the greater part of the chlorine is united with 
 sodium, a smaller amount with potassium. The chlorides of the urine 
 arc undoubtedly to a great extent derived directly from the chlorides 
 of the food, and have not the same metabolic significance as the organic, 
 and even as some of the other inorganic constituents. But it is note- 
 worthy that in certain diseased conditions the chlorine may disappear 
 entirely from the urine, or be greatly diminished — e.g., in pneumonia, 
 and in general in cases in which much material tends to pass out from 
 the blood in the form of effusions (p. 515). 
 
 Phosphoric Acid. — The phosphoric acid of the urine is chiefly derived 
 from the phosphates of the food, but must partly come from the waste 
 products of tissues rich in phosphorus-containing substances, such as 
 lecithin and nuclein. The phosphoric acid is united partly with alkalies, 
 especially as acid sodium phosphate, and partly with earthy bases, as 
 phosphates of calcium and magnesium. The earthy phosphates are 
 precipitated by the addition of an alkali to urine, or in the alkaline 
 
484 
 
 LXLHETIUN 
 
 'icrmcntation. In some pathological urines they come down when the 
 carbon dioxide is driven off by heating; a precipitate of this sort differs 
 from heat-coagulated albumin in being readily soluble in acids (Practical 
 Exercises, p. 524). A small amount of phosphorus may appear in the 
 urine in a less oxidized form than phosphoric acid. 
 
 Sulphuric Acid. — Tliis is only to a slight extent derived from ready- 
 formed sulphates in the food. The greater part of it is formed by 
 oxidation of the sulphur of proteins. About nine-tenths of the sulphur 
 in normal urine is present as inorganic sulphates, mainly those of 
 potassium and sodium. Of the other tenth, a portion is represented 
 by ethereal sulphates, and the remainder by the so-called ' neutral ' 
 sulphur, including the sulphur associated with the pigment urochrome. 
 A small amount of sulphur occurs in less oxidized forms than sul- 
 phates in such compounds as the sulphocyanide , which is probably, 
 in part but not entirely, derived from that of the saliv^a, and ethyl 
 sulphide, a substance with a penetrating odour, which appears to be a 
 constant constituent of dog's urine (Abel). 
 
 Thiosulphuric acid (H2S2O3) occurs almost constantly in cat's urine, 
 often in dog's. It is not free, but combined with bases. 
 
 The ethereal sulphates are compounds in which the sulphuric acid is 
 united with aromatic bodies (indol, phenol, etc.). Such are potassium- 
 phenyl-sulphate (CeH5KS04), potassium-kresyl-sulphate (C7H7KSO4), 
 potassium-indoxyl-sulphate (QHgN KSO4) , potas.=?ium-skatoxyl-sulphate 
 (C9H8NKSO4), and two double sulphates of potassium and pyrocatechin. 
 The formation of potassium indoyxl sulphate may be thus represented : 
 
 Indol, QH4C ^tt' on absorption from the intestine is changed into 
 mdoxyl, C6H4/^-2^'^^' which + ^^z(^i (potassium hydrogen 
 
 sulphate) yields S02< qj^ ' (potassium indoxyl sulphate) -h HgO. 
 
 The ' pairing ' of these aromatic bodies with sulphuric acid renders 
 them innocuous to the organism. Most of the compounds are present 
 in greater amount in the urine of the horse than in the normal urine of 
 man. But in disease the quantity of indican in the latter may be much 
 increased ; and to a certain extent it must be looked upon as an index 
 of the intensity of putrefactive processes in the intestine and of absorp- 
 tion from it. Munk made the observation that in the urine of a starving 
 dog the phenol-forming substances are absent, while in the urine of a 
 starving man they are present in abnormally large amount. The 
 indigo-forming substances (indican), on the other hand, are in hunger 
 excreted in considerable quantity by the dog, and not at all by man 
 (Practical Exercises, p. 518). According to Folin, the indoxyl potassium 
 sulphate or indican of the urine is not to any appreciable extent related 
 to protein metabolism, but for the most part to the putrefaction of 
 protein in the intestine. The indoxyl-potassium sulphate taken by itself 
 may therefore afford a rough index of the intensity of the intestinal 
 putrefactive processes. On the other hand, the total ethereal sulphuric 
 acid cannot be taken as an index of the extent of the putrefaction, for, 
 although absolutely diminished, it is increased relatively to the total 
 excretion of sulphur on a diet poor in protein, or even protein-free 
 (see tables on p. 477). 
 
 Phenol and kresol can easily be obtained from horse's urine by 
 mixing it with strong hydrochloric acid and distilUng. These aromatic 
 bodies pass over in the distillate. Pyrocatechin remains behind, and 
 can be extracted by ether. It gives a green colour with ferric chloride, 
 which becomes violet on the addition of sodium carbonate. 
 
CHEMISTRY OF URINE 
 
 485 
 
 The sulphur of the inorganic sulphates is the fraction of the total 
 sulphur which fluctuates in proportion to the total protein metabolism. 
 In this regard it follows the variations in the urea. It represents 
 ' exogenous ' metabolism. The neutral sulphur occupies a position 
 analogous to that of the creiatinin : the smaller the amount of protein 
 in the food, and the smaller therefore the total protein decomposed, the 
 larger is the fraction which the neutral sulphur forms of the total 
 sulphur. The neutral sulphur accordingly represents endogenous 
 metabolism. The ethereal sulphur takes an intermediate position in 
 this regard, but upon the whole it also becomes a more prominent 
 fraction of the total sulphur when the food contains little or no protein. 
 The ethereal sulphates are therefore not entirely derived from the 
 putrefaction of protein. 
 
 Carbonates of sodium, ammonium, calcium, and magnesium occur 
 in alkaline urine. Their source is the carbonates and the vegetable 
 organic acids of the food. In acid urine a certain amount of carbon 
 dioxide is present, although not firmly united with bases, so that most 
 of it can be pumped out. 
 
 So-called Physico-Chemical Analysis of Urine. — The freezing-point 
 of urine has often been determined to obtain a measure of the mole- 
 cular concentration, which with the total quantity of urine secreted 
 in a given time was erroneously assumed to afford an index of the 
 work done by the kidney. Clinically the method is of little use, but 
 for certain physiological questions freezing-point determinations are 
 of value and are sometimes combined with determinations of the 
 electrical conductivity, by which we obtain an approximate measure 
 of the number of dissociated ions in unit volume, mainly the inorganic 
 salts. Normally, A has a higher value for urine than for blood — i.e., 
 the molecular concentration of the urine is higher than that of the 
 serum. But when large draughts of water are taken a may be lower 
 for urine than for blood, and in general it varies within far wider 
 limits (from 0'ii5** to 2'54t)° C, according to Koppe). The following 
 table from Kovesi and Roth-Schulz shows the changes in A under the 
 influence of water: 
 
 Time. 
 
 Urine in C.C. 
 
 A 
 
 10 to 2 
 
 240 
 
 I -So 
 
 2 to 6 
 
 255 
 
 172 
 
 6 to ID 
 
 l6i 
 
 1-93 
 
 10 to 2 
 
 131 
 
 2-l8 
 
 2 to 6 
 
 160 
 
 2*23 
 
 6 to I* 
 
 120 
 
 I -91 
 
 II to 12 
 
 I'S litres ' Salvator ' water taken 
 
 — 
 
 12 to 12.30 
 
 500 
 
 0'12 
 
 12.30 to I 
 
 444 
 
 O'll 
 
 I to 1.30 
 
 442 
 
 O'lO 
 
 1.30 to 2 
 
 46 
 
 078 
 
 2 to 2.30 
 
 45 
 
 I -30 
 
 1 
 
 The Urine in Disease. — Although, strictly speaking, a truly patho- 
 logical urine has no place in physiology, the line which separates the 
 urine of health from that of disease is often narrmv, sometimes invisible; 
 while the study of abnormal constituents is not only of great importance 
 in practical medicine, but throws light upon the physiological processes 
 
486 EXCRETION 
 
 takinj^ place in the kidney, and upon the j,'cncral problems of metabolism. 
 Even in health the (|aantity of the urine, its specific gravity, its acidity, 
 may vary within wide limits. A hot day may increase the secretion 
 of sweat, and correspondingly diminish the secretion of urine, and the 
 deficiency of water may lead to a deposit of brick-red urates. A meal 
 rich in fruit or vegetables may render the urine alkaline, and its alkalinity 
 may determine a precipitate of earthy phosphates. But neither the 
 scanty acid urine with its sediment of urates, nor the alkaline urine 
 with its sediment of phosphates, comes into the category of pathological 
 urines; the deviation from the normal does not amount to disease. 
 The maximum deviation from the line of health is the total suppression 
 of the urine. If this lasts long, a train of symptoms, oi which con- 
 vulsions may be one of the most prominent, and which are grouped 
 under the name of uraemia, appears. At length the patient becomes 
 comatose, and deatffctoses the scene. Suppression of urine may be 
 the consequence of many pathological conditions, but there is one case 
 on record in the human subject which, in effect, though not in intention, 
 belongs to experimental physiology. A surgeon diagnosed a floating 
 kidney in a woman. With a natural impatience of loose odds and 
 ends of this sort, he offered to remove it, and in an evil hour the patient 
 consented. The surgeon, a perfectly skilful man, who acted for the 
 best, and to whom no blame whatever attached, carried the kidney to 
 a well-known pathologist for examination. The latter, to the horror 
 of the operator, suggested, from the appearance of the organ, that it 
 was the only kidney the woman possessed. This turned out to be the 
 fact. Not a drop of urine was passed. Apart from this ominous 
 symptom, all went well for seven or eight days; but then uraemic 
 troubles came on, and the patient died on the eleventh or thirteenth 
 day after the operation. The necropsy showed that her only kidney 
 had been taken away. 
 
 In disease the urine may contain abnormal constituents, or ordinary 
 constituents in abnormal amounts. Of the normal constituents which 
 may be altered in quantity, the most important are the water, the inor- 
 ganic salts, the urea, the uric acid, and the aromatic substances. 
 
 Water. — A marked and persistent diminution in the quantity of 
 urine — ^that is to say, practically in the water, with or without an 
 increase in the specific gravity — is suggestive of disorganization of the 
 renal epithelium. In some infective diseases the kidney is liable to 
 be secondarily involved, its secreting cells being perhaps crippled in the 
 attempt to eliminate the bacterial poisons. In the form of paren- 
 chymatous or tubal nephritis wliich so frequently complicates scarlet 
 fever, the quantity of urine has in some cases fallen to 50 or 60 c.c. in 
 the twenty -four hours. 
 
 In chronic interstitial nephritis (' granular kidney '), on the other 
 hand, where the structural changes in the tubules are, for a long time 
 at least, comparatively circumscribed, the quantity of urine is often 
 increased and of low specific gravity. In chese cases the incpcasc in 
 the blood -pressure, associated with hypertrophy of the hearf^'may be 
 a factor in the exaggerated renal secretion. In diabetes mellitus the 
 quantity of urine is greatly increased, perhaps in some cases because 
 more urea is excreted than normal, and urea acts as a^iuretic, perhaps 
 also because the elimination of sugar draws withlfan increased excretion 
 of water to hold it in solution. Although a specific gravity as low as 
 1002 has been seen in healthy persons (after copious potations), the 
 persistence of a density below loio shoukl suggest hydruria. Watson 
 mentions the case of a boy with diabetes insipidus, who voided in 
 twenty-four hours 9 or 10 pints (5 to 6 Utres) of urine with a specific 
 gravity of 1002. On the other hand, while the specific gravity has been 
 
CIII-MISTRY ni- rRI\E 487 
 
 occasionally observed tu mounl 111 health toal least 1036, its persistence 
 at 1025 or 10 ^o cr anytiiing above this, especially if the urine is pale 
 and a^parcutly dilute, should suggest diabetes niellitus. 
 
 Inorganic Salts. — -The changes in the (juantity of the inorganic con- 
 stituents of the urine in disease are not, in the present state of our 
 knowledge, of as mlich importance as the changes in the organic con- 
 stituents. The chlorides are diminished in most acute febrile diseases 
 and may even totally disappear from the urine, and their reappearance 
 after the crisis is, so far as it goes, a favourable symptom. In most 
 cases in which the quantity of the urine is markedly lessened, all the 
 inorganic substances are diminished in amount. 
 
 Urea. — The quantitj- of urea is, as a rule, increased in fever, either 
 absolutely or in proportion to the amount of nitrogen in the food. In 
 the interstitial varieties of kidney disease the urea is usually not 
 diminished, but when the stress of the change falls on the tubules 
 (parenchymatous nephritis), it is distinctly decreased — it may be even 
 to one-twentieth of the normal. 
 
 Uric acid is diminished in the urine in gout (perhaps to one-ninth of 
 the normal), not only during the paroxysms, but in the intervals. It 
 accumulates in the blood and tissues, and, as sodium urate, may form 
 concretions in the joints, the cartilage of the ear, and other situations. 
 Watson relates the case of a gentleman who used to avail himself of his 
 resources in this respect by scoring the points at cards on the table with 
 his chalky knuckles. In leukaemia the quantity of uric acid and purin 
 bases in the urine is greatly increased, not only absolutely, but also in 
 proportion to the urea. As much as 4^ grammes of free uric acid, in 
 addition to about i J grammes of ammonium urate, has been found in a 
 urinary sediment in a case of leukaemia. 
 
 The aromatic bodies, of which indoxyl may be taken as the type, 
 are increased when the conditions of disease favour the growth of 
 bacteria in the intestine — e.g., in cholera, acute peritonitis, and carci- 
 noma of the stomach. A marked increase in the amount of the indican 
 in the urine may, as far as it goes, be taken as an indication that the 
 bacteria are gaining the upper hand in the intestinal tract; a marked 
 diminution is usually a sign that the battle has begun to turn in favour 
 of the organism (Practical Exercises, p. 517). Tryptophane, a sub- 
 stance which we have already recognized among the products of the 
 tryptic digestion of proteins, has been showm to be a precursor of indol, 
 which is formed from it under the influence of bacteria. When trypto- 
 phane is injected into the caecum of rabbits, the indican in the urine 
 is markedly increased. Putrefactive processes in other parts of the 
 body than the intestine may also increase the indican in the urine — • 
 e.g., a collection of putrid pus in the pleural cavity. 
 
 Abnormal Substances in Urine. — Sugar, proteins, the pigments of bile 
 and blood, or their derivatives, are the most important abnormal sub- 
 stances found in solution in the urine. Normal urine, as has been 
 stated, contains a trace of dextrose, but so little that it cannot be 
 detected by ordinary tests, and for practical purposes it may be con- 
 sidered absent. Dextrose is the sugar found in the urine in diabetes. 
 In the urine of nursing mothers lactose may be present. Pentoses, 
 sugars with five carbon atoms in the molecule (instead of six, as in the 
 hexoses, of which group dextrose is a member), may also occasionally 
 occur in urine. Pentoses give the ordinary reduction tests for sugar, 
 and yield osazones, but do not ferment with y-east. Various plants 
 contain pentoses, and when these are eaten the pentoses are excreted 
 in the urine, but in cases of true pentosuria they originate in the body, 
 possibly from nuclco-proteins. The condition has not the same sinister 
 significance as diabetes. Specific toxic substances produced by bac- 
 
488 KXCRIiTlON 
 
 tcrial aclidii ha\c bcon dcmonslratccl in tlic urine in certain diseases. 
 Red blood-corpuscles and leucocytes (pus corpuscles, white blood- 
 corpuscles, mucous corpuscles) are the chief organized deposits; but 
 spermatozoa may occasionally be found, as well as pathogenic bacteria — 
 e.g., the typhoid bacillus; and in disease of the kidney casts of the renal 
 tubules arc not uncommon. These tube-casts may be composed chiefly 
 of red blood-corpuscles, or of leucocytes, or of the epithelium of the 
 tubules, sometimes fattily degenerated, or of structureless protein, 
 or of amyloid substance. Abnormal cr^'stallinc substances, such as 
 the amino-acids, leucin (Fig. i86), tyrosin (Fig. 187), and cystin 
 (Fig. 180), may be on rare occasions found in urinary sediments; but 
 generally the unorganized deposits of pathological urine consist of 
 bodies actually contained in, or obtainable from, the normal secretion, 
 but present in excess, cither absolutely, or relatively to the solvent 
 power of the urine. Cystin is of interest because of its relations to the 
 sulphur of the protein molecule (p. 360)- It is not found in the normal 
 organism. It very occasionally formfe calculi in the bladder. There 
 are individuals who constantly pass as much as one-fourth of all the 
 sulphur in the form of cystin, without any other symptoms. 
 
 Various amino-acids are present in solution in the urine in man 3' 
 pathological conditions. Of these the least soluble are leucin and 
 tyrosin, and this is the reason why they are most easily detected. A 
 general reaction for amino-acids is their precipitation as sparingly 
 soluble compounds (/^-naphthalinsulphones) by /3-naphthalinsulpho- 
 chloride in the presence of an alkali (sodium hydroxide). In acute 
 yellow atrophy of the liver leucin and tyrosin have been found in large 
 amounts in the liver itself, as well as in the urine. In phosphorus 
 poisoning these amino-acids, as well as glycocoll, have been detected in 
 the urine, and there is no doubt that other amino-acids, arising from 
 the decomposition of proteins, are also present in such conditions. 
 
 Sugar. — In diabetes mellitus, although the quantity of urine is usually' 
 much increased, its specific gravity is above the normal; and this is due 
 cliiefly to the presence of sugar (dextrose), which generally amounts 
 to I to 5 per cent., but may in extreme cases reach 10 or even 15 per 
 cent., more than half a kilogramme being sometimes given off in twenty- 
 four hours. 
 
 The name of the tests for dextrose is legion. They are mostly 
 founded on its reducing action in alkaline solution. Hydrated oxide of 
 bismuth (Boettcher), salts of gold, platinum and silver, indigo (Mulder), 
 and a host of other substances, are reduc-d by dextrose, and may 
 be used to show its presence. The reduction of cupric salts (Trommer), 
 
 Fig. 186.— Leucin Crystals. Fig. 187.— Tyrosin Crystals 
 
 fermentation by yeast, and the formation of crj'stals of phenyl-gluco- 
 sazone are the best established tests. (See Practical Exercises, p. 517.) 
 Proteins. — Serum-albumin and scrum-globulin arc the proteins most 
 commonly found in pathological urine. Both arc coagulated by heating 
 the urine, slightly acidulated if it is not already acid, or by the addition 
 
CHEMISTRY OF URINE 489 
 
 of strong nitric acid in the cold. Proteoses (albumoses) are also occa- 
 sionally present, e.g.. in the diseiisc called ' osteomalacia ' and in con- 
 ditions associated with the formation and especially with the decom- 
 position of pus. They may be recognized by the tests given in the 
 Practical Exercises (p. 525). It is doubtful whether the presence of 
 true peptone has as yet been satisfactorily made out. 
 
 The presence of bile-salts may be shown by Hay's test or Petten- 
 kofer's test (p. 40^). 
 
 The pigments of blood and bile may be detected by the characters 
 described in treating of these substances ; the spectrum of oxyhaemo- 
 globin, or methaemoglobin, or any of the other derivatives of haemoglobin, 
 with the formation of hasmin crystals, would afford proof of the presence 
 of the former, and Gmelin's test of the latter. The red blood-corpuscles, 
 seen with the microscope , are the most decisive evidence of the presence of 
 blood, as leucocv-tes in abundance arc of the presence of pus. It should 
 be remembered that pus in the urine of women has sometimes no signifi- 
 cance except as showing that there has been an admixture of leucorrhcal 
 discharge from the vagina. (See Practical Exercises, pp. 74, 531-) 
 
 Section II. — The Secretion of the Urine. 
 
 We have now to consider the mechanism by which the urine is 
 formed in the kidney from the materials brought to it by the blood. 
 And here the same questions arise as have already been discussed 
 in the case of the salivary and other digestive glands: (i) Are the 
 urinary constituents, or any of them, present as such in the blood ? 
 (2) If they do exist in the blood, can they be shown to be separated 
 from it by processes mainly physical or mainly ' vital ' — in other 
 words, by ordinary filtration, diffusion and osmosis, or by the selec- 
 tive action of living cells ? In the case of the digestive juices it 
 has been seen that some constituents are already present in the 
 blood, but that physical laws alone, so far as we at present under- 
 stand them, cannot explain the proportions in which they occur in 
 the secretions, or the conditions under which they are separated; 
 while other constituents — and these the more specific and important 
 — are manufactured in the gland-cells. 
 
 In the kidneys the conditions seem at first sight favourable to 
 physical separation, as opposed to physiological secretion. Urine 
 has been described as essentially a solution of urea and salts, and 
 both are ready formed in the blood. The arrangement of the blood- 
 vessels, too, suggests an apparatus for filtering imder pressure. 
 
 Bloodvessels and Secreting Tubules of Kidney. — The renal arter>' splits 
 up at the hilus into several branches, which pass in between the Mal- 
 pighian pyramids, and form at the boundary of the cortex and medulla 
 vascular arches, from which spring, on the one side, interlobular arteries 
 running up into the cortex between the pyramids of Ferrein, and, on 
 the other, vasa recta running down into the boundary layer of the 
 medulla (Fig. 18S). The interlobular arteries give ofi at intervals 
 afferent vessels. Each of these soon breaks up into a glomerulus or tuft 
 of vascular loops, which gather themselves up again into a single 
 efferent vessel of somewhat smaller calibre than the afferent. The 
 glomerulus is fitted into a cup or capsule (of Bowman), which is closely 
 
490 
 
 EXCRETION 
 
 Fig. 1 88.— Diagram of Blood- 
 vessels of Kidney {Klein, after 
 Ludwig). at, interlobular ar- 
 tery; vi, interlobular vein; 
 g, glomerulus, to which an 
 afferent artery is seen coming 
 from the interlobular artery, 
 and from which an efferent 
 artery proceeds to break up 
 into a capillary network sur- 
 rounding the renal tabules; 
 vs, vena stellata; ar, artcria 
 rect.TC ; vb, leash of vena; rcctae ; 
 ;•/', vascular network round 
 ducts at apex of a papilla. 
 
 Fig. 189. — Diagram of Renal Tubule (Klein). 
 A, corte.x; a, layer of cortex immediately under 
 capsule containing no Malpighian corpuscles; 
 a' , inner layer of corte.x devoid of Malpighian cor- 
 puscles; B, boundary layer; C, papillary zone of 
 medulla; i. Bowman's capsule; 2. neck of cap- 
 sule; 3, proximal convoluted tubule; 4, spiral 
 tubule; 5, descending part of Henle's loop- 
 tubule; 6, the loop; 7, 8, and 9, ascending limb 
 of loop-tubule; 10, irregular tubule; ir, distal 
 convoluted tubule; 12, junctional tubule; 13, 
 collecting tubule in a medullarv' ray or pyra- 
 mid of Ferrein; 14, collecting tubule in the 
 boundary layer; 15. large collecting tubule 
 ending in a duct of Belliai. 
 
THE SECRET IDS OF THE VRINE 491 
 
 reflected over it, except where the afferent and efferent vessels pass 
 through, and forms the beginning of a urinaiy tubule. If wc suppose 
 tlic tuft pi'slicd into the bhnd end of the tubule so as to indent it, it will 
 be easily understood that the single layer of flattened epithelium reflected 
 on the glomerulus is continuous with that lining the capsule, which in 
 its turn is continuous with the epithelial layer of the rest of the urinary 
 tubule. This has been divided by histologists into a number of parts 
 which it is unnecessary to enumerate here, further than to say that the 
 urinarA' tubule proper begins in the cortex in Bowman's capsule and 
 the proximal convoluted tubule (with its continuation, the spiral tubule), 
 and ends in the cortex with the distal convoluted tubule, the connection 
 between the two being made by a long loop (Henle's) with a descending 
 and an ascending limb (Fig. 189). Between the ascending limb and 
 the distal convoluted tube is interposed the zigzag tubule. The tubule 
 throughout its length is bounded by a basement membrane lined by a 
 single layer of epithelium, which differs in its character in different 
 parts of the tubule 
 
 The distal convoluted tube joins by means of the short connecting 
 tubule one of the straight tubules which form the pyramids of Fcrrein 
 or medullary rays in the cortex, and which run down into the medulla, 
 always uniting into larger and larger tubes as they go. until at length 
 they open as ducts of Bellini on the apex of a papilla. The two convo- 
 luted tubules (with the spiral and zigzag tubules) are lined by similar 
 epithelial cells with granular contents, and the tendency of the granules 
 to be arranged in rows perpendicular to the basement membrane gives 
 them a striated or ' rodded ' appearance (Fig. 190). The granules arc 
 eosinophile (p. 17), which is also a character of the granules of other 
 secreting cells. Towards the lumen the cells may show a brush of pro- 
 cesses, looking like cilia, but in mammals these are not motile. The 
 ascending part of Henle's loop also has cells of the same general char- 
 acter, with numerous granules, although the ' rodding ' may not be so 
 distinct. We shall see directly that the morphological resemblance is 
 the index of a functions! likeness. The blood-supply of the tubules, 
 especially of the convoluted portions, is exceedingly rich, the efferent 
 vessels of the glomeruli breaking up around them into a close-meshed 
 network of capillaries, from which the blood is collected into inter- 
 lobular veins running parallel to the interlobular arteries between the 
 pyramids of Ferrein. The straight tubules of the medulla are also 
 surrounded by capillaries given off from straight arteries (arteriae 
 rectae) running down into it partly from the arterial arches and partly 
 from efferent vessels of the glomeruli nearest the boundary layer, the 
 blood passing away by straight veins (venae rectae) which join the larger 
 veins accompanying the arterial arches. The greater part of the 
 blood going through the kidney has to pass through two sets of capil- 
 laries, one in the glomeruli, the other around the tubules. Even the 
 portion of it which does not go through the glomeruli has for the most 
 part a long route to traverse in narrow arterioles and venules to and 
 from its capillary distribution. And the mean circulation-time through 
 the kidney has been found to be longer thari that through most other 
 organs (p. 137). 
 
 Theories of Renal Secretion. — To come back to our problem of 
 the nature of renal secretion, the anatomical structure of the kidney 
 might be expected to throw light upon the question. And, indeed, 
 it was on a purely liistological foundation that Bowman established 
 his famous * vital ' theory of renal secretion. Impressed \\At\\ the 
 
492 
 
 EXCRETION 
 
 resemblance between the renal epithelium and the epithelial cells 
 of otht-r glands, and with the distribution of the bloodvessels in the 
 kidney, he came to the conclusion that the characteristic con- 
 stituents of urine, including urea, were secreted from the blood by 
 the tubules. To the Malpighian bodies he assigned what he doubt- 
 less considered the humbler office of separating water from the 
 blood for the solution of the all-important solids. To Ludwig, on 
 the other hand, with iiis whole attention fastened on the mechanical 
 factors by which the flow of urine could be influenced, the tubules 
 
 
 Fig. 190. — From a Vertical Section of Dog's Kidney to show the Structure of Different 
 Portions of the Renal Tubule (Klein), a. Bowman's capsule enclosing glomerulus, 
 the capillaries of which are arranged in lobules separated by a little coimective 
 tissue. The capsule and glomerulus together constitute a Malpighian body or 
 corpuscle; n, neck of capsule; c, c, convoluted tubules, cut in various directions; 
 b, irregular or zigzag tubule; i, e, and/ are straight tubules, which take part in the 
 formation of a medullary ray or pyramid of Ferrein ; d. collecting tubule ; e, e, spiral 
 tubule; /, narrow part of ascending limb of Henle's loop-tubule; b, c, and e are 
 lined with rodded epithelium. 
 
 seemed of secondary importance, while the glomeruli appeai'ed a 
 complete apparatus for filtering urine from the blood into Bow- 
 man's capsule. He saw that the efferent vessel was smaller than 
 the afferent ; that it was therefore easier for blood to come to the 
 glomerulus than to get away froiii it, and that the pressure in the 
 capillaries of the tuft must be higher than in ordinary capillaries, 
 because the resistance beyond them in the comparatively narrow 
 efferent vessel, and especially in the second plexus, is greater than 
 the resistance beyond a single capillary network. And experi- 
 mental investigation soon showed him that the rate at which urine 
 
THE SECRETION OF THE UETNE 493 
 
 was fornu'd could be greatly influenced by changes in the blood- 
 pressure. 
 
 On such considerations, Ludwig founded the ' mechanical ' theory 
 of urinary secretion, which, although in a much modified form, still 
 divides with the ' vital ' theory the allegiance of physiologists. 
 It is impossible here to enter in detail into a controversy that has 
 extended over more than half a century and produced an extensive 
 literature. The result of the discussion has been, in our opinion, 
 to establish in its essential principles the ' vital ' theory of Bowman, 
 or at least to show that no purely physico-chemical theory as yet 
 constructed will account for all the facts. 
 
 Ludwig supposed that the urine, qualitatively complete in all its 
 constituents, was simply filtered through the glomeruli, the work 
 done in this filtration being performed entirely at the expense of 
 the energy of the heart-beat represented as lateral pressure in the 
 vessels of the tufts. But as the proportion of salts, and especially 
 of urea, is very far from being the same in urine as in blood, it had 
 further to be assumed that the liquid which passes into Bowman's 
 capsule is exceedingly dilute, and that absorption of water, and 
 perhaps of other constituents, takes place in its passage along the 
 renal tubules. This process of reabsorption he pictured as a purely 
 physical diffusion between the dilute urine in contact with the free 
 ends of the epithelial cells lining the tubules and the much more 
 concentrated lymph with which their deep ends are bathed. The 
 great length of these tubules, as compared with those of most other 
 glands, might indeed seem to indicate a long sojourn of the urine 
 in them, and the probability of important changes being caused in 
 its passage along them. But if we consider the immense length 
 (60 to 70 cm.) of the seminal tubules and of their gigantic ducts 
 (epididymis 6 metres), where, of course, absorption of water on a 
 large scale is out of the question, it will be granted that little can 
 be built upon the mere length of the renal tubules. On the other 
 hand, the sahvary glands, where there are no glomeruli, secrete as 
 much water as the kidneys are supposed to filter; and the pancreas, 
 whose capillaries form the first of a double set, and therefore in this 
 respect correspond to the renal glomeruli, secretes less water than 
 the liver, whose capillaries correspond to the low-pressure plexus 
 around the convoluted tubules of the kidney. So that deductions 
 drawn from the anatomical relations of the bloodvessels are not in 
 this case of much value, unless supported by physiological results. 
 
 It is somewhat unfortunate that systematic writers have fallen 
 into the habit of discussing the mechanism of urinary secretion as 
 if the Ludwig theory and the Bowman theory presented an exact 
 antithesis, as if the one offered a complete ' mechanical ' explana- 
 tion of a process, which the other viewed as entirely ' vital,' and 
 therefore withdrawn from physical explanation. 
 
 We need not concern ourselves here with the historical develop- 
 
494 EXCRETION 
 
 ment of tliis discussion. Three main questions require our 
 attention : 
 
 1. Is there any evidence that reabsorption actually occurs in the 
 tubules ? If reabsorption on an important scale does take place, it 
 follows at once that there must be a difference of function between 
 the two parts of the renal apparatus, through which urinary con- 
 stituents pass in opposite directions. 
 
 2. But if there is no reabsorption, or none of im])ortance, it may 
 still be asked whether, the direction of movement of the urinary 
 constituents through the glomeruli and the tubular epithelium being 
 the same, some quantitative or qualitative difference in their 
 activity may not exist, certain constituents, e.g., passing mainly or 
 exclusively through the one or the other. 
 
 3. When these questions have been settled, we are in a position 
 to consider the nature of the process by which the urinary con- 
 stituents find their way from the blood into the lumen of the 
 capsules and the tubules, or, if there is reabsorption, out of the 
 tubules into the lymph and blood again, and to see whether or no 
 
 -it can be entirely explained on mechanical and physico-chemical 
 principles. 
 
 The Question of Reabsorption from the Tubules. — That some 
 absorption can take place from the kidney wlu-n the pressure in 
 the ureter is abnormally raised need not be doubted, and when 
 substances like potassium iodide or strychnine are introduced into 
 the ureter or the pelvis of the kidney untler these circumstances, 
 they can speedily be detected in the blood. When the ureter 
 pressure (in dogs) is only slightl}^ increased, instead of evidence of 
 reabsorption, we obtain evidence of increased secretion. The 
 volume of urine, the total quantity of sulphate in the urine when 
 sodium sulphate is injected into the blood as a diuretic, and the 
 total amount of reducing sugar when phlorhizin is injected, are all 
 greater on the obstructed than on the normal side. These facts are 
 quite opposed to the idea that filtration and reabsorption are im- 
 portant factors in the preparation of normal urine (Brodie and 
 CuUis) . Changes in the blood- flow through the kidney have nothing 
 to do with the results, since the small increase in pressure in the 
 ureter was shown not to affect the rate of flow of the blood. The 
 attempt has been made to decide whether absorption normally 
 occurs by removing as much of the tubules as possible, and seeing 
 whether the character of the urine is altered. In rabbits the whole 
 or a large portion of the medulla has been excised from one kidney 
 and the other then extirpated. From the mutilated kidney two or 
 three times as much urine was said to flow as was secreted by a 
 control rabbit operated on in the same way, except for the removal 
 of the renal medulla (Ribbert). The conclusion was drawn that 
 the greater quantity of urine escaping was due to the smaller 
 opportunity for reabsorption of the water. But experiments men- 
 
THE SECRETION Ob' THE URINE 
 
 493 
 
 tioned in Chapter XI. suggest a different interpretation of these ob- 
 servations. And Boyd, who repeated Ribbcrt's work, ol)tained quite 
 • iilierent results after ]Kutial removal of the medulla. He found 
 .it impossible to remove the whole. So that hitherto the direct 
 method of eliminating the tubules has left the matter where it was. 
 Some hght has been thrown on this question, by taking advantage 
 of the anatomical fact that the kidney of batrachians, and, indeed, 
 that of fishes and ophidia as well, has a double blood-supply. The 
 renal artery gives oft afferent vessels to the glomeruli; the vena 
 advehens. or renal portal vein, breaks up, like the portal vein in the 
 liver, into a plexus of capillaries surrounding the tubules, and there 
 seems to be no communication between the two vascular systems. 
 By tying all the arteries going to the kidneys in frogs the circula- 
 tion through the glomeruli can be completely cut off, while ligation 
 of the renal portal vein does not affect the blood-supply of the 
 glomeruli, though markedlj^ interfering with that of the tubules. 
 Gurwitsch has found that, after ligation of the renal portal vein of 
 one kidney in (male) frogs, the flow of urine from that kidney is 
 much diminished as compared with the other. He argues that if 
 reabsorption of dilute urine filtered through the glomeruli takes 
 place in the tubules, the opposite result ought to be obtained, since 
 the glomeruli are not affected, while any absorptive power of the 
 tubules must be crippled or abolished. 
 
 Experiments on the Excretion of Pigments by the Kidney. — In 
 connection with the second question, and also incidentally with the 
 first, the results of experiments on the distribution of pigments in 
 
 the kidney after their injection into 
 the blood have often been appealed to. 
 Heidenhain injected indigo - carmine 
 into the blood of rabbits, and after a 
 variable time killed them, cut out the 
 kidneys, and flushed them with alcohol, 
 in which the pigment is insoluble. His 
 results were as follows: (i) When the 
 
 "t^'oV^Sme^™ "f/id^eyaft"; ^P™=" ^°'\''^^ ^"^ h<:lore the injec 
 
 Injection into Blood. The cor- tion m order to reduce the blood- 
 te.x between a and b and be- pressure, the blue granules were found 
 
 tween c and d was cauterized j^ the ' rodded ' epithelium of the 
 before the injection. In the ^.^J^^^■,^^ ■,. 
 
 blank wedge-shaped portions, i, convoluted tubules and the ascendmg 
 there was no pigment. In the limb of Henle's loop, and in the lumen 
 zones shaded like 2 there was ^f ^he tubules, but nowhere else. 
 
 some pigment, but no< so much „ , 
 
 as in the areas shaded like 3. Bowman s capsules contamed no pig- 
 ment. The renal cortex was coloured 
 blue. (2) When the spinal cord was not cut, the pigment was found 
 in the medulla and pelvis of the kidney, as well as in the cortex, 
 but always in the lumen of the tubules, and not in the epithelium, 
 except in the situations mentioned. (3) If a portion of the cortex 
 
496 EXCRETIO>J 
 
 of the kidney liad been cauterized with nitrate of silver before in- 
 jection of the pigment, the spinal cord being left intact, a wedge of 
 the renal substance, corresponding to this area, remained coloured 
 only in the cortex, although the rest was blue in the medulla 
 also. The ' rodded ' epithelium was filled with blue granules as 
 before (Fig. 191). 
 
 (i) shows that the epithelium is capable of excreting some sub- 
 stances at least. (2) appears to show that when the bkjod-pressure 
 is normal water is poured out from some part of the tubule, and 
 washes the pigment separated by the ' rodded ' epithelium down 
 towards the papillae. (3) suggests that it is through the glomeruli 
 that most of the water passes. For cauterization has not destroyed 
 the power of the epithelium to excrete pigment, and therefore, 
 presumably, would not have destroyed its power to excrete water 
 if it possessed this power in any great degree; and the glomeruli 
 and their capsules are the only other part of the renal mechanism 
 which can have been affected. It must be carefully noted that 
 these experiments do not prove that urea is secreted by the tubular 
 epithelium. Indeed, after section of the cord no accumulation 
 of urea takes place in the kidney (Cushny). It would be equally 
 erroneous to conclude from this that the cells of the tubules do not 
 secrete urea. For the reduction of the blood-supply may have 
 rendered them incapable of doing so. 
 
 When pigments are injected into the dorsal lymph-sac of a frog 
 without interference with the renal circulation, they are found 
 pl^tifuUy in the lumen of the convoluted tubules, and also in the 
 epithelial cells hning them. The suggestion has been made that 
 the pigments have been absorbed by the cells from the lumen, and 
 not excreted by them into it. And certainly pigments soluble in 
 the cytoplasm or in the substances that form the envelopes of cells, 
 and therefore capable, like methylene blue, of staining them during 
 Hfe, might be taken up by the renal epithelium if excreted into the 
 tubules by the glomeruli, and might cause staining of them, par- 
 ticularly, of course, of the free ends of the cells next the lumen. 
 But this suggestion is inadmissible, since, on injection of the same 
 pigments after ligation of the renal portal vein, the convoluted 
 tubules contain little or no pigment in their lumen. And when the 
 urinary flow is stopped on one side in mammals by temporary com- 
 pression of the renal artery, the corresponding kidney takes up fully 
 as much carmine as its fellow (Carter). There is no doubt that not 
 only pigments capable of ' vital staining,' like methylene blue, but 
 also pigments which do not stain living cells, are taken up from 
 the blood (or lymph) by the epithelial cells, and, lying in vacuoles 
 in their cytoplasm, are transported towards the lumen, and there 
 extruded. It is not the solubility of the pigments in lipoids, and 
 therefore their solubility in the supposed lipoid envelope of the cells, 
 which determines whether they shall be excreted. The degree in 
 
THE SECRETION OF THE URINE 4$7 
 
 which they are capable of being presented to the cells in non-colloid 
 solution appears to some extent to be a determining factor. The 
 pigments not taken up are highly colloidal (Gurwitsch, Hober). 
 Shafer has recently confirmed Heidenhain's statements as to the 
 place of excretion of indigo-carmine. When leuco-indigo-carmine 
 (a colourless reduction-product of indigo-carmine) was injected, the 
 blue oxidized substance was found in the lumen of the convoluted 
 tubules and in the collecting tubules, but not at all in the Bow- 
 man's capsule. The cells of the convoluted tubules were colour- 
 less, because they kept the pigment in its reduced condition, and it 
 only became oxidized in the lumina of those parts of the tubules 
 whose contents, according to Dreser, show an acid reaction. On oxi- 
 dation by peroxide of hydrogen the cells of the convoluted tubules 
 became faintly green, but the Bowman's capsule remained colourless. 
 This can only be explained on the assumption that the lenco-product 
 of the pigment was excreted by the cells of the convoluted tubules. 
 
 But these cells are far from taking up all pigments indifferently. 
 Some pigments are extruded mainly by one part, others mainly by 
 another part, of the renal tubule, and some even by the glomeruli, 
 as shown long ago for ammonium carminate. The glomeruli, how- 
 ever, are in general far less active in this regard than the epithelial 
 cells, and the fact that the latter pick out from the blood such sub- 
 .stances as these foreign pigments, which pass through the Mal- 
 pighian tufts unchallenged, renders it likely that the tubules also 
 exercise a special function in the secretion of the normal con- 
 stituents of urine. More direct evidence of this is not wanting, 
 for Bowman saw crystals of uric acid in the epithelium of the 
 convoluted tubules of birds. Heidenhain found that urate of soda 
 injected into the blood of a rabbit is excreted by the epithelium of 
 the convoluted tubules and the ascending part of Henle's loop, 
 just as is the case with indigo-carmine. And Nussbaum's experi- 
 ments, although not quite conclusive, have made it probable that 
 in the frog urea is actually separated by the epithelium of the 
 tubules. They were founded on the anatomical peculiarity in the 
 renal circulation of the frog already mentioned. By tying the renal 
 arteries in that animal, he thought he could at will stop the circula- 
 tion in the glomeruli, and he found that after this was done there 
 was no further spontaneous secretion of urine. But when urea was 
 injected intravenously the secretion of urine again began, urea 
 being ehminated by the kidneys, and water along with it. Sugar, 
 peptone, and egg-albumin, injected into the blood, no longer passed 
 into the urine, even when the secretion was excited by simultaneous 
 injection of urea, although they readily did so when the arteries 
 were not tied. He concluded that the Malpighian corpuscles have 
 the power of excreting water, sugar, peptone, and albumin, while 
 the epithelium of the tubules excretes urea as well as water. 
 
 Beddard has confirmed Nussbaum's statement that when all th(? 
 
 32 
 
49S EXCRETION 
 
 arteries going to the kidney are tied the glomeruli are completely 
 and permanently deprived of blood. The spontaneous secretion 
 of urine is totally stopped, as Nussbaum found, but only in three 
 experiments out of eighteen was it possible to start the secretion 
 by injection of urea. The epithelium of the tubules degenerated 
 and desquamated after complete ligation of all the renal arteries, 
 showing that it requires some arterial blood as well as the venous 
 blood from the n-nal portal to maintain its vitality- The degenera- 
 tion of the epithelium can be prevented by keeping the frogs in an 
 atmosphere of oxygen after ligation of the arteries. In six such 
 frogs, in which the complete elimination of the glomeruli was con- 
 trolled by subsequent injection, secretion of urine followed the 
 injection of urea, alone or in combination with dextrose, phlorhizin, 
 or di -sodium hydrogen phosphate (Xa2HP04). In all the cases the 
 urine contained urea, chlorides, and sulphates, and was acid to 
 phenolphthalein. In one case after injection of urea and dextrose, 
 and in another after urea and phlorhizin, the urine reduced Fehling's 
 solution, and therefore presumably contained dextrose (Beddard 
 and Bainbridge). When the frog's kidney is perfused in situ with 
 oxygenated salt solution a certain flow of urine takes place. Sub- 
 stitution of non-oxygenated sahne markedly slows the flow (Cullis). 
 
 Apparently, then, the tubules have the capacity to secrete prac- 
 tically all the constituents of urtne, and when the flow of urine is 
 small, probably most of it comes from the tubules. When, as in 
 the diuresis produced by salt solutions, large quantities of water 
 and salts have to be rapidly excreted, the bulk of the liquid comes 
 from the glomeruli, but also by a process of secretion. 
 
 Lindemann has endeavoured to exclude the glomeruli in mam- 
 mals by injecting oil through the renal artery. After a short time, 
 according to him, the oil emboh clear away from practically all 
 parts of the kidney except the glomeruU, which remain plugged. 
 If indigo-carmine be subsequentlv injected into the blood, it is not 
 only taken up from it by the embolizcd kidney as well as by a normal 
 one, but is excreted. The quantity of urine is much diminished, 
 and its specific gravity increased, but its composition is not essen- 
 tially altered. He infers that the tubules are in a high degree 
 independent of the glomeruli as an apparatus for the secretion of 
 urine. More conclusive observations have lately been reported in 
 which the tubules were eliminated by producing an artificial nephritis 
 in rabbits bv the subcutaneous injection of sodium tartrate. Tar- 
 trates act mainly upon the tubules, causing no, or a much smaller, 
 effect upon the glomeruli. After the intravenous infusion of a 
 solution containing sodium chloride and urea during pronounced 
 tartrate nephritis, all the chlorine appears in the urine within forty- 
 eight hours, but little, if any, of the urea. In the light of the 
 histological findings, this is interpreted to mean that under normal 
 conditions chlorides and water are passed through the glomerular 
 
THE SECRETION OF THE URINE 409 
 
 mechanism, and urea througli the convoluted tubules (Uiidcrhill, 
 WVUs, and Goldschmidt). These results constitute a direct and 
 striking confirniation of the Bowman hypothesis. 
 
 As regards our first two questions, we may rom lude thai there is 
 no good evidence that reahsorplion of xcater oy other constituents of the 
 urine in the renal tubules plays an important part in the preparation 
 of that secretion. Manx facts favour the conclusion that the glomeruli 
 and the renal epithelium act as distinct, although, of course, mutually 
 supplementary mechanisms, the glomeruli separating the larger portion 
 of the water and salts, the epithelium the larger portion, if not the 
 whole, of the characteristic organic constituents. 
 
 As regards the third question, it is now generally admitted, even 
 by those who uphold a modified ' mechanical ' theory, that if 
 the urine is originally separated from the blood by filtration at the 
 expense of the energy of the heart-beat represented by the pressure 
 of the blood in the glomeruli, the reabsorption in the tubules cannot 
 be attributed to simple diffusion, but must be a selective process 
 analogous to absorption in the intestine and entailing the expendi- 
 ture of a large amount of work at the expense of the food materials 
 or the protoplasm of the epithelial cells. Every attempt at a 
 strictly mechanical explanation breaks down for the kidney, as for 
 other glands. 
 
 The practical absence from urine of the proteins and sugar of the 
 blood under normal circumstances, and the elimination by the 
 kidney of egg-albumin, peptone, and other bodies when injected 
 into the veins, show a selective permeability inexplicable by refer- 
 ence to any known structural or physico-chemical property of the 
 renal epithelium or the glomeruli, but precisely the kind of thing 
 which the physiologist has, without being hitherto able to explain 
 it, learnt to associate with the activity of living cells. Urea and 
 dextrose, both highly diffusible substances, circulate side by side 
 in the bloodvessels of the kidney. The one is taken and the other 
 left. The urea is a waste-product of no further use in the economy. 
 The sugar is a valuable food-substance. The kidney selects with 
 unerring certainty the urea, of which only 4 parts in 10,000 are 
 present in the blood, but rejects the sugar, of which there is three 
 times as much. The theory that the dextrose of the blood or a 
 part of it is combined with substances in the colloid state, and not 
 in ordinary solution, has been advanced from time to time as an 
 explanation of the practical impermeability of the kidney for this 
 sugar under normal conditions. But no proof of the truth of this 
 hypothesis has ever been given. On the contrary, there is good 
 evidence that all the dextrose which is estimated in blood by 
 analytical methods is in the free condition. For instance, dextrose 
 easily escapes from blood circulating in the vivi-diffusion apparatus 
 previously described (p. 48). And when the plasma of shed blood is 
 placed in a dialyser tube of animal membrane surrounded by a liquid 
 
500 EXCRETION 
 
 in which dextrose is dissolved in exactly the safrie concentration a.s 
 that determined in the plasma by the ordinary chemical methods, 
 the contents of the dialyser neither lose nor gain dextrose. Now, 
 the plasma ought to gain sugar by diffusion if a portion of the 
 dextrose in it exists in a combination which prevents its diffusion, 
 just as it does gain dextrose when the liquid outside the dialyser 
 contains sugar in greater concentration than the plasma (Michaelis 
 and Rona). 
 
 Egg-albumin injected into the blood passes through the renal 
 circulation side by side with the serum-albumin of the plasma. 
 Both are indiffusible tlirough membranes, and to the physical 
 chemist the differences between them may appear superficial and 
 minute. But the kidney does not hesitate for an instant. A large 
 part of the egg-albumin is promptly excreted as a foreign substance; 
 the serum-albumin passes on untouched. 
 
 Not only does the kidney exercise a power of qualitative selec- 
 tion; it also takes cognizance of the quantitative composition of 
 the blood. So long as there is less sugar in the plasma than about 
 1-5 to 2 parts in 1,000, it is refused passage into the renal tubules. 
 But when this limit is passed, and the proportion of sugar in the 
 blood becomes excessive, the kidney begins to excrete sugar, and 
 continues to do so till the balance is redressed. 
 
 The advocates of the theory of filtration tlirough the glomeruli 
 under the influence of the difference of hydrostatic pressure in the 
 capillaries and in the lumen of the capsules have made their firmest 
 stand on the excretion of the inorganic constituents of the urine. 
 Thev have laid stress particularly on the fact that the hydraemic 
 plethora caused by intravenous injection of salts is accompanied 
 by diuresis. It is true that the direct introduction of water into 
 the blood, or its attraction from the lymph-spaces when the osmotic 
 pressure of the blood is increased by the injection of substances like 
 urea, sugar, and sodium chloride, may cause a condition of hydrcemic 
 plethora, and that this plethora may sometimes be associated with 
 an increase of pressure in the capillaries in general, and therefore 
 in the vessels of the Malpighian tuft. It may also be admitted that 
 such an increase of pressure might be accompanied by an increased 
 filtration of water and salts into Bowman's capsule. Even in the 
 excised kidne}', after the vital activity of its cells may be presumed 
 to have ceased, filtration of the most varied solutions occurs when 
 the organ is perfused with them through the renal artery. The 
 liquid which escapes from the ureter always has the same composi- 
 tion as the perfusion fluid (SoUmann). It would certainly appear 
 unlikely that the glomerular epithelium should make no use what- 
 ever for the furtherance of its task of the difference of hydrostatic 
 pressure on its two surfaces. It is in taking advantage of such 
 circumsta ces for the promotion of its specific work up to the 
 point at which they cease to favour it that a great part of the true 
 
THE SECRETION OF THE URINE 501 
 
 secretory activity of cells may be supposed to consist. When we 
 see a barge passing through a lock, and bt-ing gradually lifted to 
 the proper level by the inrush of water, wt- never dream of saying 
 that the whole thing is an affair of the laws of hydrostatics. We 
 know that the part played by the lock-keeper, the opening and 
 closing of the gates and sluices at the proper time, is all-important, 
 although he does not lighten by one ounce the weight which the 
 water must lift. He uses the head of water for a specific purpose 
 — namely, to lift the barge. In like manner it is to be expected 
 that the glomerular epithelium, when the difference of pressure 
 on its two surfaces is increased by hydraemic plethora, will use the 
 increased facility of filtration to rapidly excrete a portion of the 
 water. But who will believe that the addition of a tumbler of 
 water, absorbed from the alimentary' canal, to 4 or 5 litres of blood 
 circulating in a system of vessels whose capacity can and does vary 
 within wide limits, should cause in the capillaries of the kidney 
 an increase of pressure exactly proportional to the increase in the 
 elimination of water in the urine, lasting for the same time and 
 disappearing at the moment when the normal composition of the 
 blood is restored ? Nor is it easier to explain on any mechanical 
 hypothesis how it is that in a starving animal the quantity of 
 inorganic substances eliminated in the urine drops almost to zero, 
 while the proportional amount in the blood and tissues is little, if 
 at all, affected. In a rabbit rendered poor in sodium chloride by 
 feeding it with salt-free food, the injection of a solution of sodium 
 chloride isotonic with the blood produces no diuresis for a con- 
 siderable time, but, on the contrary, a diminished flow of urine, 
 while a similar solution injected into the veins of a rabbit previously 
 fed with salted food causes an immediate and considerable diuresis. 
 When small quantities of isotonic solutions of various salts are 
 injected, those not normally present in the blood produce a greater 
 diuresis than normal constituents. Sodium chloride, which is 
 present in normal plasma in greater amount than any other salt, 
 causes the smallest diuresis of all (Haake and Spiro). 
 
 Such facts suggest that the secreting cells of the kidney are stimu- 
 lated or inhibited by the contact of blood or lymph in which the 
 normal constituents are present in too great or in too small amount, 
 and that the intensity of the action is proportional to the degree of 
 deficiency or excess. The greater the velocity of the circulation 
 in the kidney, the more effective will be the stimulation produced 
 by any given substance present in excess, and therefore the greater 
 the total amount of it eliminated in a given time. For in making 
 the round of the renal circulation the concentration of the sub- 
 stance in any given portion of blood will fall less, and therefore the 
 average stimulation exerted by it during the round will be greater 
 the faster the blood flows. It is quite in agreement with this that 
 when plethora is occasioned by transfusion of blood there is little 
 
502 EXCRETION 
 
 or no diuresis, although the increase of arterial, capillary, and 
 venous })ressure, and the dilatation of the kidney, arc evident. 
 For the rapid passage of liquid out of the \essels would lead to a 
 great increase in the relative proportion of corpuscles to i^lasma — 
 that is to say, to an abnormal condition of the blood. On the other 
 hand, when plethora is produced by injection of serum diuresis 
 occurs (Cushny). This, again, is what we should expect, since the 
 elimination of the superfluous liquid will restore the normal pro- 
 portion. The diminished viscosity of the blood (p. 23) produced 
 by the excess of scrum will aid the flow through the kidney and 
 therefore increase the diuresis, while in the case of the plethora 
 produced by injection of blood the elimination of liquid will at once 
 increase the viscosity, diminish the velocity of the renal flow, and 
 tend to lessen diuresis. 
 
 There is, then, little more reason to assume that the copious flow 
 of urine which follows the absorption of a large quantity of water 
 is due to a mere process of filtration than there is to beheve that 
 filtration, and not selective secretion, is the cause of the gush 
 of saliva which precedes vomiting, or the sudden outburst of 
 sweat on sudden and severe exertion. In addition, there are the 
 positive proofs already mentioned that the ' rodded ' epithelium 
 of the tubules, which no one supposes to be abandoned more 
 to mere physical influences than the epitheUum of the salivary 
 glands, plays a part in the secretion of some of the urinary 
 constituents. 
 
 Cushny has recently stated more clearly than had previously been 
 done a theory which he designates as the ' modern theory ' of urine 
 formation. He assumes that blood-plasma is filtered through the 
 glomeruli under the hydrostatic pressure of the blood, only the colloid 
 proteins being kept back. The filtrate contains the non-colloid con- 
 stituents approximately in the proportions in which they exist in 
 plasma. It is therefore very poor in urea and very rich in sugar as 
 compared with urine. In the tubules some of the constituents, which 
 he terms ' threshold bodies ' are reabsorbed. These are the sub- 
 stances like sugar, the sodium and chlorine ions, etc., which are only 
 excreted when they exceed a certain threshold value in the plasma. 
 Other constituents of the filtrate, like urea, are not reabsorbed. These 
 are called 'no-threshold bodies,' and are excreted in proportion to 
 their absolute amount in the plasma. The cells of the tubules are 
 supposed in some way at present unknown to take up from the filtrate 
 the threshold bodies, 'and always in a definite concentration — namely, 
 that in w^hich they normally exist in blood. As Cushny puts it, the 
 filtrate is deproteinized plasma, from which ' Locke's fluid ' (p. 66) 
 is reabsorbed by the tubule cells. Apparently he thinks it simpler to 
 make the assumption that the renal cells are organized to absorb from 
 the lumen of the tubules a solution of invariable composition, leaving 
 a variable residue to be excreted, than to make the assumption, under- 
 lying the Bowman-Heidenhain theory, that they are organized to 
 leave behind in the blood or lymph an'invariable residue by absorbing 
 from them a solution of variable composition. In reality, however, the 
 two assumptions are precisely on the same footing : they are equally 
 
THE SECRETION OF THE URIXE 503 
 
 simple or ecjually abstruse. For a cell wliich is able to take up 
 ' Locke's fluid ' from a deprotcinized plasma is able in that very act 
 to reject any constituent which does not belong to ' Locke's fluid,' 
 as well as an excess of any constituent which docs belong to it. What is 
 rejected and its amount are quite as important, if the final product is 
 to be constant, as what is accepted and its amount. If we are willing 
 to attribute a power of this kind to the free end of a tubule cell we 
 need not shrink on the ground of added complexity from investing 
 the attached end of the cell with the power of refusing passage to 
 ' Locke's fluid ' from the plasma or the lymph while accejjting crys- 
 talloid constituents like urea which do not belong to it, as well as an 
 excess of any constituent which does belong to it. There is nothing 
 more ' occult ' about a cell which bars out sodium chloride till it 
 exceeds 0-9 per cent, in the fluid offered to it, and then lets the surplus 
 through, than there is about a cell which takes up sodium chloride 
 from the fluid offered to it till it has amassed a concentration of o-c) 
 percent., and then bars out the surplus.* In like manner, the financial 
 organization required by a Government to take from a citizen in taxes 
 the surplus of his income above one hundred pounds would be of the 
 same general nature as that required to take from him his whole income, 
 returning him one hundred pounds to live on. If a machine could 
 manage the one operation, a mandarin would not be needed for the other. 
 It is impossible in this place to go further into the discussion of the 
 reabsorption theory so ably presented by Cushnj'. In the absence of 
 definite evidence of reabsorption on the great scale required by the 
 theory, it remains simply a working hypothesis, which is all that can 
 be claimed at present for any theory of urine formation. One of the 
 objections always urged against filtration (with reabsorption) theories 
 has been the enormous amount of liquid which must under certain con- 
 ditions be poured into the renal tubules. Heidenhain calculated that 
 in a man no less than 70 litres of liquid per day must be filtered through 
 the glomeruli in order that the urea found in the urine may be obtained 
 from a glomerular filtrate containing 0-05 per cent, of urea. This is 
 probably a moderate estimate, and considerably larger amounts of 
 filtrate in proportion to body and kidney weight have been deduced 
 from data obtained in animals. It has been argued by advocates of 
 the reabsorption theory that equally great quantities of lymph con- 
 taining urea in the small concentration in which it exists in the plasma 
 must be poured out around the attached ends of the tubule cells on 
 the hypothesis of direct secretion. This argument, however, is based 
 upon an erroneous conception of the manner in which exchange between 
 the blood and the tissues proceeds. There is no reason to suppose 
 
 * The reabsorption theory is perhaps inferior to the ' direct secretion ' 
 theory in one point. If a solution of constant composition is always absorbed 
 from the glomerular filtrate, the smaller the concentration in the filtrate of 
 any substance capable of being taken up by the cells, the greater will be the 
 proportion of it absorbed; and the greater its concentration in the filtrate, 
 the smaller will be the proportion of it absorbed. On the direct secretion 
 theory, the greater the concentration of a substance in the blood or lymph 
 in contact with the cells, the more of it will pass into the cells and be ex- 
 creted by them. The ' modern ' theory which sets out by saj-ing to the 
 Bowman-Heidenhain theory. ' Stand by thyself, come not near to me, for I 
 am more physical than thou,' thus abandons a physical process, diffusion, 
 which its rival utilizes. The fact is that the simphfication attained by postu- 
 lating filtration as the first stage in urine formation has to be paid for in 
 the reabsorption. The boat having shot the rapids in the glomeruli with 
 next to no physiological expense has straightway to be more or less painfully 
 locked a certain distance upstream. 
 
504 EXCRETION 
 
 that the exchange between blood and tissue lymph is mainly accom- 
 plished by filtration from the capillaries of vast quantities of liquid 
 containing the crystalloid constituents and the gases in the concen- 
 tration in which they exist in plasma. On the contrary, the dissolved 
 substances are currently antl no doubt correctly assumed to move to 
 a great extent by diffusion through the capillary walls (perhaps with 
 a certain amount of active intervention of the endothelial cells) and 
 across the thin sheets of tissue lymph on their way to and from the 
 cells. In other words, they move mainly through the water and not 
 with the water. An attempt to explain the gaseous exchani^e between 
 the blood and the tissues as a matter purely of filtration of plasma 
 containing dissolved gases, and not at all of diffusion of the gases, 
 would lead to curious results. There is no more reason to believe that 
 urea passes from the blood to the boundary of the tubule cells by a 
 filtration process independent of diffusion, and therefore entailing the 
 irrigation of the cells with a very large amount of lymph, than there 
 is to believe that when loo c.c. of arterial blood loses lo c.c. of oxygen 
 in passing through the capillaries, this is accomplished by filtration 
 into the Ivmph spaces of 4,000 c.c. of plasma containing 0-25 c.c. of 
 oxygen in 100 c.c. (p. 252). 
 
 As to the nature of tiie mechanism set in motion, and the series 
 of events that take place as the constituents of the urine journey 
 from the interior of the bloodvessels to the lumen of the tubules, 
 we know no more than in the case of other glands. This alone 
 is clear, that the separation of the urine from the blood implies the 
 performance of a large amount of work by the kidney. A token of 
 the intensity of the metabolic effort required is the marked increase 
 in the absorption of oxygen which occurs during diuresis. In one 
 experiment the oxygen absorbed by a dog's kidneys was 11 per cent, 
 of what would have been used up by the entire animal under normal 
 conditions. 
 
 The mere fact that urine differs in its quantitative composition 
 from blood-plasma is sufficient to show that work must be done in 
 its separation from the blood. Although the amount of work 
 cannot be calculated from the difference in the osmotic pressures 
 of the two liquids, a comparison of the freezing-points affords quali- 
 tative evidence of the performance of work by the kidney. For 
 average urine, the value of A is several times as great as for the 
 plasma. Blood-plasma freezes at -0-55° to - o>t)5° C. (average, 
 - 0-6°, corresponding to an osmotic pressure of 5,662 mm. of mercury, 
 or about 75 metres of water). Human urine has been found to 
 freeze at -i'38° to -2«ii°C. (average, - i-8°C., corresponding to 
 an osmotic pressure of about 17,000 mm. of mercury, or 225 metres 
 of water). For highly concentrated urines, the depression of the 
 freezing-point mav be considerably greater. Even when the 
 freezing-point is foimd in ver>' dilute urines to be approximately 
 the same as in the blood-plasma, work may still have been done in 
 the separation of the urine, because although the total molecular 
 concentration may be the same in the two liquids, the concentra- 
 tion of each of the substances in solution mav be different. For 
 
TUF. SFCRFTWX OF I'HF URINE 503 
 
 example, cvtn in tlie most dilute urine, the concentration of urea 
 will in general be much greater than in the blood. It is of interest 
 in connection with the work performed by the kidney that when 
 the flow of urine is increased by diuretics like caffeine or sodium 
 sulphate, whicli cause the secretion of urine with a very different 
 crystalloid composition from that of the plasma, more oxygen is 
 used up, whereas the diuresis caused by the injection of Ringer's solu- 
 tion where the urine and plasma do not differ materially in the amount 
 or kind of the non-protein constituents, is accomplished practically 
 without change in the oxygen consumption of the kidney. 
 
 Significance of the Glomeruli. — What is the significance of the 
 peculiar arrangement of the glomerular bloodvessels, if the epithelium 
 of the capsules has secretive powers like that of ordinary glands ? 
 It is difficult to believe that these unique vascular tufts have not a near 
 and important relation to the renal function: but it is b}' no means 
 clear what that relation is. The secretion of water, and even its rapid 
 secretion, is not at all bound up with any set arrangement of blood- 
 vessels. Gland-cells all over the body secrete water under the most 
 varied conditions of blood-pressure, although a comparatively liigh 
 pressure is upon the whole favourable to a copious outiiow. 
 
 But the kidney has perhaps other functions than excretion 
 (Chapter XI.). And it may be that the simplest part of the latter 
 process, the elimination of water and salts, is largely thrown upon the 
 Malpighian corpuscles, as a physiologically cheaper machine than the 
 epithelium of the tubules, which is left free for more complex labours. 
 These may include not only the separation of nitrogenous metabolites, 
 but also synthetic processes possibly concerned in the regulation of 
 protein metabolism. One characteristic synthesis, the union of benzoic 
 acid and glycin to hippuric acid, has already been referred to. As will 
 be shown later (p. 380), it takes place mainly, in some animals perhaps 
 exclusively, in the kidney. The epithelium of the glomerulus, being a 
 less highly organized and less delicately selective mechanism than that 
 of the convoluted tubules, may more easily respond to increase of blood- 
 pressure by increased secretion. At the same time, placed as it is at 
 the last flood-gate of the circulation, where the escape of anything 
 valuable means its total loss, the glomerular epithelium may be endowed 
 with a general power of resistance to transudation, which renders a 
 comparatively high blood-pressure a necessary condition of its acting 
 at all. And as a matter of fact water ceases to be secreted by the 
 kidney long before the blood-pressure in the glomeruli can have fallen 
 below that which suffices for the highest activity of the liver. Perhaps, 
 however, the high minimum pressure required (30 to 40 mm. of mercury 
 in the dog) is merely the necessary consequence of the long and difficult 
 path which most of the blood going through the kidney has to take, and, 
 that a sufficient blood-fiow cannot be kept up with less. It may be, 
 too, that the comparatively small surface of the glomeruli, restricted 
 in order to leave room for the more highly organized parts of the renal 
 mechanism, entails the more intense and concentrated activity which 
 the high blood-pressure renders possible, and the simplicity of work 
 and organization renders harmless. 
 
 An obvious result, and perhaps an important one, of the peculiar 
 arrangement of the bloodvessels of the kidney is that the renal tubules 
 proper are shielded from an excessive blood-pressure by the inter- 
 position of the glomeruli as a block. This may be either because the 
 epithelium of the tubules would not perform its work so well under a 
 
5o6 EXCRETION 
 
 Jiigh blood -prcs.su re, or because there would be a danger of substances 
 which ought to be retained being cast out into the urine. In this con- 
 nection it is interesting to note that the specific constituents of urine 
 are separated by epithelium surrounded by capillaries of the second 
 order, and therefore with a smaller blood-pressure. than exists in the 
 capillaries of most glands, while the same is true of bile, another 
 (practically) protein-free secretion. 
 
 The maximum secretory pressure in the kidney, as shown by a 
 manometer tied into tlie divided ureter, is about 60 mm. of mercury 
 in the dog, or less than half that of saliva. If the escape of the 
 urine is opposed by a greater pressure than this, or if the ureter is 
 tied, the kidney becomes u.'dematous. Whether the oedema is due 
 to reabsorption of urine or to the pouring out of lymph owing to 
 the pressure of the dilated tubules on the veins has not been de- 
 finitely settled. It has been already pointed out that there is no 
 necessary relation between the blood-pressure in the capillaries of 
 a gland and its secretory pressure; and, so far as this goes, water 
 might just as well be secreted at a pressure of 60 mm. of mercury 
 from the low-pressure blood of the second set of renal capillaries 
 as from the high-pressure blood of the glomeruli. By obstruction 
 the molecular concentration of the urine is diminished to half or 
 three-quarters of the normal. 
 
 The Influence of the Circulation on the Secretion of Urine. — 
 Although the activity of no organ in the body is governed more 
 by the indirect effects of nervous action than that of the kidney, 
 no proof has been given of the existence of secretory fibres for it 
 comparable to those of the salivar}' glands. All the changes in the 
 rate of renal secretion which follow the section or stimulation of 
 nerves can be explained as the consequences of the rise or fall of 
 local or general blood-pressure, and of the corresponding variations 
 in the velocity of the blood in the renal vessels. 
 
 The best way to study variations in the calibre of the renal vessels is 
 the plethysmographic method, and the oncometer of Roy is a pkthysmo- 
 graph adapted to the kidney (Fig. 192). It consists of a metal capsule 
 lined with loose membrane, between which and the metal there is a 
 space filled with oil. The two halves of the capsule open and shut on a 
 hinge; and the kidney, when introduced into it, is surrounded on all 
 sides by the membrane, the vessels and ureter passing out through an 
 opening. The oil-space is connected with a cylinder also filled with oil, 
 above which a piston, attached to a lever, moves. The lever registers 
 on a drum the changes in the volume of the kidney — i.e., practically the 
 changes in the quantity of blood in it, and therefore in the calibre of 
 its vessels. A still better oncometer is that of Schafer, in which air is 
 employed instead of oil. 
 
 Nerves of the Kidney. — Both vaso-constrictor and vaso-dilator fibres 
 for the renal vessels, but most clearly the former, have been shown 
 to leave the cord (in the dog) by the anterior roots of the sixth thoracic 
 to second lumbar nerves, and especially of the last three thoracic. 
 They run in the splanchnics, and then through the renal plexus — around 
 the renal artery — into the kidney. The vaso-constrictors predominate, 
 
THE SECRETION OF THE URINE 
 
 507 
 
 so that the general effect of stimulation of the nerve-roots, the splanch- 
 nics, or the renal nerves is shrinking of the kidney, with diminution or 
 cessation of the secretion of urine. But slow rhythmical stimulation 
 of the roots causes increase of volume, the scanty dilators being by this 
 method excited in preference to the constrictors. 
 
 The renal nerves, entering at the liilum, branch repeatedly, so as to 
 form a wide-meshed plexus around the arteries, and accompany them 
 even to their finest ramifications in the cortex. Coming off from the 
 nerves surrounding the arteries are fine fibres which are distributed to 
 the convoluted tubules. Some of them terminate in globular ends, 
 others in fine threads that pass through the membrana propria (Berkely)- 
 
 Section of the renal nerves is followed by relaxation of tlie small 
 arteries in the kidney, and consequent swelling of the organ. The 
 flow of urine is greatly increased, and sometimes albumin appears 
 in it, the excessive pressure in the capillaries (particularly in those 
 
 of the glomeruli) being 
 supposed to favour the 
 escape of substances to 
 which a passage is refused 
 under normal conditions. 
 An experiment which is 
 sometimes quoted as a de- 
 cisive test of the relative 
 importance of changes in 
 the rate of flow, and in 
 the pressure of the blood 
 within the glomeruli, is 
 that of tying the renal 
 vein. This undoubtedly 
 does not lower the intra- 
 glomerular pressure — on 
 the contrary, it must in- 
 crease it — but the secretion of urine stops. If the venous outflow 
 from the kidnej^ is only partially interfered with, the flow of urine is 
 immediately diminished, but the administration of a diuretic like 
 potassium nitrate causes an increase. It is more than likely that 
 in these experiments the secretion stops or slackens not because a 
 high blood- pressure, but because an active circulation is its necessary 
 condition. When the blood stagnates in the kidney the natural 
 stimulus to the renal apparatus speedily disappears owing to the 
 elimination of the urinary constituents to the neutral or indifferent 
 point (p. 501). The experiment, however, is not perfectly conclu- 
 sive. For few glands can go on performing their function after the 
 circulation has ceased. The kidney must be able to feed itself in 
 order to continue its work. Above all, it needs oxygen; and it 
 might be urged that if the blood in the glomeruli could be kept at 
 the normal standard of arterial blood, secretion might still go on 
 after ligation of the renal vein. 
 
 Fig. 192. — Diagram of Organ-Plethysmograph or 
 Oncometer. B, metal box in two halves open- 
 ing on the hinge H ; M, thin membrane ; A, space 
 filled with oil; O, organ enclosed in oncometer; 
 V, vessels of organ; /, tube for filling instrument 
 with oil; T, tube connected with D, which opens 
 into cylinder C; C is also filled with oil; P, pis- 
 ton attached by E to a writing lever. 
 
So8 EXCRETION 
 
 According to Ludwig, indeed, the flow of urine stops, in spite 
 of continued filtration through the glomeruli, because the swelling 
 of the veins in the boundary layer compresses the tubules, and may 
 even obliterate their lumen. There is no conclusive experimental 
 evidence, however, and no a priori probability, that the obstruction 
 so produced is sufficiently sudden or sufficiently complete to cause 
 instant and total cessation of the flow. It is even less justifiable 
 to conclude from the experiment that the liquid part of the urine 
 is, at any rate, not separated by the epithelium of the tubules, since 
 the blood-pressure in the capillaries around the tubules must rise 
 very greatly after ligature of the vein, and yet secretion is stopped. 
 It might equally well be argued that the renal epithelium normally 
 secretes water under a low blood-pressure, but is disorganized under 
 the excessive and entirely unaccustomed pressure which follows the 
 closure of the vein. 
 
 It is not only through nerves directly governing the calibre of the 
 vessels of the kidney that the rate of urinary secretion can be 
 affected. Any change in the general blood-pressure, if not counter- 
 acted by, still more if conspiring with, simultaneous local changes 
 in the renal vessels, may be followed by an increased or diminished 
 flow of urine ; and the law which explains all such variations, or at 
 least serves to sum them up, is that in general an increase in the 
 rate of the blood- flow through the kidney is followed by an increase in 
 the rate of secretion. It will be remarked that this is the converse 
 of the great law, of which we have already seen so many illustra- 
 tions, that functional activity increases blood-flow. It is probable 
 that this law holds for the kidney as well as for other organs, but 
 that the influence of activity on blood-supply is subordinated to 
 that of blood-supply on activity, while in most tissues, as in the 
 muscles, the opposite is the case. It is evident that an increase in 
 the blood-flow would favour the secretory activity of the renal cells, 
 since the average concentration of the blood presented to them as 
 regards those constituents which they select would remain relatively 
 high in its circuit through the kidney. The ' stimulus ' to secretion 
 would, therefore, be relatively intense. 
 
 Destruction of the medulla oblongata {i.e., of the vaso-motor 
 centre), or section of the cord below it, diminishes the secretion of 
 urine, because the arterial pressure is lowered so much as to over- 
 compensate the dilatation of the renal vessels, which the operation 
 also brings 'about. If the blood-pressure falls below 40 mm. of 
 mercury, the secretion is abolished. Stimulation of the medulla or 
 cord also lessens the flow of urine by constricting the arterioles of 
 the kidney so much as to over-compensate the rise of general blood- 
 pressure, caused by the constriction of small vessels throughout the 
 body. 
 
 If the renal nerves have been cut, stimulation of the medulla 
 
THE SECRETION OF THE URINE je? 
 
 oblongata increases the urinary secretion, because now the rise of 
 general blood-pressure is no longer counterbalanced by constriction 
 of the renal vessels. An increase in the urinary flow can be pro- 
 duced in the rabbit by a lesion in a part of the funiculi teretes, 
 which can be reached in the floor of the fourth ventricle (Eckhard), 
 perhaps by destroying the portion of the vaso-motor centre governing 
 the renal nerves, while the rest remains uninjured, or is even stimu- 
 lated, and thus keeps up or even increases the general blood- 
 pressure. There is either no glycosuria, or it is very slight. 
 
 Section of the splanchnic nerves causes a fall of arterial pressure, 
 which is, however (in animals like the dog, in which compensation 
 soon takes place), more than balanced by the simultaneous dilata- 
 tion of the renal vessels, and therefore for some time the flow of 
 urine is increased, but not so much as when the renal nerves alone 
 are cut. In the rabbit there is no increase. On the other hand, 
 stimulation of the splanchnics stops the urinary secretion, because 
 the general rise of pressure is not enough to make up for the con- 
 striction of the renal vessels. 
 
 Diuretics are substances that increase the flow of urine. Some of 
 them act mainly on the circulation, as by increasing the general blood- 
 pressure, others mainly by a direct influence on the secreting mechanism. 
 Digitalis is a representative of the first class ; urea and caffein belong to 
 the second. The action of digitalis is to strengthen the beat of the 
 heart, which is at the same time somewhat slowed, and to constrict the 
 arterioles. Both eftects contribute to the increase of pressure. The 
 accompanying diuresis, seen practically only in cardiac disease with 
 dropsical effusions, is due to the improvement of the renal circulation 
 and the absorption of the oedema fluid. Caffein, when injected into the 
 blood, affects the pressure but little. It causes dilatation of the renal 
 vessels after a passing constriction, and an increase in the flow of urine 
 after a temporary diminution. The vascular dilatation is not the 
 chief reason for the diuretic effect, for the latter is still obtained when the 
 vaso-motor mechanism has been paralyzed by chloral hydrate, and 
 even after the secretion of urine has been stopped by the fall of pressure 
 consequent on section of the spinal cord. Caffein, therefore, acts 
 directly on the renal epithelium. When these cells are asphyxiated by 
 temporary clamping of the renal artery, caffein after removal of the 
 clamp causes no diuresis, while the injection of Ringer's fluid still 
 causes a secretion of urine possessing the same crystalloid composition 
 as the plasma, just as it would have done if perfused through the excised 
 kidney. The action of urea, potassium nitrate, and saline diuretics 
 such as sodium sulphate is probably also a direct action on the secret- 
 ing structures, although some have supposed that their primary effect 
 is to cause vaso-dilatation in the kidney. 
 
 Summary. — Our knowledge of renal secretion may be thus 
 summed up: The water and salts of the urine are chiefly separated 
 by the glomeruli ; the process is not a mere physical filtration, but 
 a true secretion. Substances like sugar, peptone, egg-albumin, and 
 hcemoglobin, when injected into the blood, are probably excreted mainly 
 by the glomeruli ; and so is the sugar of diabetes. Urea, uric acid, 
 and presumably the other organic constituents of normal urine, with 
 
5^0 EXCRETION 
 
 <( portion of the li-'aler and satts, are excreted by the physiological 
 activity of the ' redded ' epithelium of the renal tubules. The rate of 
 secretion of urine rises and falls ivith the pressure, and still more with 
 the velocity, of the blood in the renal vessels. No secretory nerves for 
 the kidney have been found ; the effects of section or stimulation of 
 nerves on the secretion can all be explained by the changes produced in 
 the renal blood-flow. Some diuretics act by increasing the blood-flow, 
 others directly on the epithelium of the tubules or the glomeruli. 
 
 Section III. — Expulsion of the Urine. 
 
 Micturition. — The urine, like the bile, is being constantly formed; 
 although scMTction varies in its rate from time to time, it never 
 ceases. Trickling along the collecting tubules, the urine reaches 
 the pelvis of the kidney, from which it is propelled along the ureters 
 by peristaltic contractions of their walls, and drops from their valve- 
 like orifices into the bladder. When this becomes distended, rhyth- 
 mical peristaltic contractions are set up in it, and notice is given 
 of its condition by a characteristic sensation, which is perhaps aidetl 
 by the squeezing of a few drops of urine past the tonically con- 
 tracted circular fibres that form a sphincter round the neck of the 
 bladder, and into the first part of the urethra. The desire to empty 
 the bladder can be resisted for a time, as can the desire to empty 
 the bowel. If it is yielded to, the smooth muscular fibres in the 
 wall of the viscus are thrown into contraction. This is aided by an 
 expulsive effort of the abdominal muscles. The sphincter vesica; 
 is relaxed; and the urine is forced along the urethra, its passage 
 being facilitated by discontinuous contractions of the ejaculator 
 urinae muscle, which also serve to squeeze the last drops of urine 
 from the urethral canal at the completion of the act. 
 
 Regurgitation into the ureters is to a great extent prevented by 
 their compression between the mucous and muscular coats of the 
 bladder, where they run for more than half an inch before opening 
 at the posterior angle of the trigone. But it has been shown that 
 a certain amount of back flow can take place. Small bodies like 
 (hatoms suspended in water and pigments dissolved in it have been 
 found in the pelvis of the kidney, the renal tubules, and even the 
 circulation after being injected into the bladder. 
 
 The pressure in the bladder of a man may be made as high as 
 10 cm. of mercury during the act of micturition; about half this 
 amount is due to the contraction of the vesical walls alone, the 
 rest to the contraction of the abdominal muscles. A pressure of 
 i6 to 26 mm. of mercury is required to open the sphincter of a 
 rabbit's bladder in life. 
 
 Although the whole performance seems to us to be completely 
 voluntary, there are facts which show that it is at bottom a reflex 
 
EXPULStOM OF THE J' RISE 511 
 
 series of co-ordinated movements, that can be started by impulses 
 passing to a centre in the spinal cord from above or from below — 
 from the brain or from the bladder. In dogs, with the spinal cord 
 divided at the upper level of the lumbar region, micturition takes 
 place regularly when the bladder is full, and can be excited by such 
 slight stimuli as sponging of the skin around the anus (Goltz). 
 Here, of course, the act is entirely reflex; and the centre is situated 
 at the level of the fifth lumbar nerves. The efferent nerves of the 
 bladder, like those of the rectum, come partly from the cord directly 
 through the sacral nerves, and partly through the lumbar sympa- 
 thetic chain (second to sixth ganglia). The sacral fibres are con- 
 nected with nerve cells in the hypogastric plexus, and the sympa- 
 thetic, partly at least, in the inferior mesenteric ganglia. This 
 anatomical coincidence acquires interest in view of the striking 
 physiological similarity between the processes of micturition and 
 defsecation, a similarity which is emphasized by the fact that the 
 latter is almost invariably accompanied by the former. An im- 
 portant difference, however, is that the will can far more readily 
 set in motion the machinery of micturition than that of defsecation; 
 a man can generally empty his bladder when he likes, but he cannot 
 empty his bowels when he likes. 
 
 Sometimes in disease, and especially in disease of the spinal cord, 
 the mechanism of micturition breaks down; the bladder is no 
 longer emptied ; it remains distended with urine, which dribbles 
 away through the urethra as fast as it escapes from the ureters. 
 To this condition the term incontinence of urine is properly 
 applied. 
 
 Reflex emptying of the bladder, without an act of will or during 
 unconsciousness, is not true incontinence. The involuntary mic- 
 turition of children during sleep, for example, is a perfectly normal 
 reflex act, although more easily excited and less easily controlled 
 than in adults. Section either of both nervi erigentes, or of both 
 hypogastrics, is never followed by more than quite temporary dis- 
 turbance of function of the bladder in clogs, both male and female. 
 In a few days the urine is normally passed. In bitches the same 
 is true when both pairs of nerves are divided. But in male dogs 
 true incontinence of urine follows section of the four nerves, as well 
 as intense tenesmus due to paralysis of the lower part of the large 
 intestine. 
 
 Section IV. — Excretion by the Skin. 
 
 Besides permitting of the trifling gaseous interchange already 
 referred to (p. 299), the skin plays an important part in the ehmina- 
 tion of water by the sweat-glands. 
 
 Sweat is a clear colourless liquid of low specific gravity (1003 to 
 1006), consisting chiefly of water with small quantities of salts, 
 
jtl EXCRETIOH 
 
 neutral fats, volatile fatty acids, and the merest traces of proteins 
 and urea. It is acid to litmus except in profuse sweating, when it 
 may become neutral or even alkaline. It is secreted by simple 
 gland-tubes, which form coils lined with a single layer of columnar 
 epithelium, in the subcutaneous tissue, with long ducts running up 
 to the surface through the true skin and epidermis. Unless col- 
 lected from the parts of the skin on which there are no hairs, such 
 as the palm, it is apt to be mixed with sebum, a secretion formed 
 by the breaking down of the cells of the sebaceous glands, which 
 open into the hair follicles, and consisting chiefly of glycerin and 
 cholesterin fats, soaps, and salts. Sebum is probably of consider- 
 able importance for maintaining the normal condition of the hair 
 and skin. 
 
 Although it is only occasionally that sweat collects in visible 
 amount on the skin, water is always being given off in the form of 
 vapour. This invisible perspiration leaves behind it on the skin, 
 or in the glands, the whole of the non-volatile constituents, which 
 may be to some extent reabsorbed ; and since even the visible per- 
 spiration is in large part evaporated from the very mouths of the 
 glands in which it is formed, the sweat can hardly be considered a 
 vehicle of solid excretion, even to the small extent indicated by its 
 chemical composition. 
 
 The total quantity of water excreted by the skin, and the relative 
 proportions of visible and invisible perspiration, vary greatly. A 
 dry and warm atmosphere increases, and a moist and cold atmo- 
 sphere diminishes the total, and, within limits, the invisible per- 
 spiration. Visible sweat — given the condition of rapid heat-produc- 
 tion in the body as in muscular labour — is more readily deposited 
 on freely exposed surfaces when the air is moist than when it is dry. 
 The air in contact with surfaces covered by clothing is never far 
 from being saturated with watery vapour. Here, accordingly, a 
 comparatively slight increase in the activity of the sweat-glands 
 suffices to produce more water than can be at once evaporated; 
 and the excess appears as sweat on the skin, to be absorbed by 
 the clothing without evaporation, or to be evaporated slowly, as 
 the pressure of the aqueous vapour gradually diminishes in con- 
 sequence of diffusion. The power of imbibition (p. 426) of water 
 by the various layers of the skin diminisJies as we pass outwards, 
 and the cells of the epidermis are characterized by the rapidity with 
 which they return from a condition of excessive imbibition to their 
 normal state. This constitutes a protective mechanism against 
 excessive loss of water. When the skin is thoroughly moistened, its 
 degree of imbibition is three times the normal. 
 
 The quantity of sweat given off by a man in twenty-four hours 
 varies so much that it would not be profitable to quote here the 
 numerical results obtained under different conditions of tempera- 
 
l:xcri:tio\ b) iiii. skin 513 
 
 tiire ami lnmiidity o{ the air (hut sec p. 691). It is eiKMit^h to say 
 that the excretion of water from the skin is of tlie same order of 
 magnitude as that from the kidneys: a man loses upon tlie whole 
 as much water in sweat as in urine. But it is to be carefully noted 
 that these two channels of outfiovv are complementary to each 
 other; when the loss of water by the skin is increased, the loss by 
 the kidneys is diminished, and vice versa. 
 
 The Influence of Nerves on the Secretion of Sweat. — The sweat- 
 glands are governed directly by the nervous system ; and though 
 an actively perspiring skin is, in health, a flushed skin, the vascular 
 tlilatation is a condition, and not the chief cause of the secretion. 
 Stimulation of the peripheral end of the sciatic nerve causes a 
 copious secretion of sweat on the pad and toes of the corresponding 
 foot of a young cat, and this although the vessels are generally 
 constricted by excitation of the vasomotor nerves. Not only so, 
 but when the circulation in the foot is entin^ly cut off by compres- 
 sion of the crural artery or by amputation of the limb, stimulation 
 of the sciatic still calls forth some secretion. As in the case of the 
 salivary glands, injection of atropine abolishes the secretory power 
 of the sciatic, while leaving its vaso-motor influence untouched; and 
 pilocarpine increases the flow of sweat by direct stimulation of the 
 endings of the secretory nerves in the glands. 
 
 That the sweating caused by a high external temperature is 
 normally brought about by nervous influence, and not by direct 
 action on the secreting cells, is shown by the following experiments. 
 One sciatic nerve is divided in a cat, and the animal put into a hot- 
 air chamber. No sweat appears on the foot whose nerve has been 
 cut, but the other feet are bathed in perspiration. Similarly, a 
 venous condition of the blood (in asphyxia) causes sweating in the 
 feet whose nerves have not been divided, but none in the other 
 foot; and stimulation of the central end of the cut sciatic has the 
 same effect. All this points to the existence of a reflex mechanism ; 
 and it is certain that asphyxia acts by direct stimulation of the 
 centre or centres. The vaso-motor centre is at the same time 
 stimulated, and the bloodvessels constricted, as in the cold sweat 
 of the death agony. Fear may also cause a cold sweat, impulses 
 passing from the cerebral cortex to the vaso-motor and sweat 
 centres. 
 
 It is probable that a general sweat - centre exists in the medulla 
 oblongata, but its position has not been exactly determined nor even 
 its existence definitely proved. On the other hand, it is known that 
 in the cat there are at least two spinal centres, one for the fore-limbs 
 in the lower part cf the cervical cord, and another for the hind-limbs 
 where the dorsal portion of the cord passes into the lumbar. That this 
 latter centre docs not exist or is comparatively inactive in man is 
 indicated by the following case : A man fell from a window and fractured 
 his backbone at the fifth dorsal vertebra. The lower half of tlic liody 
 was paralyzed for a time, but recovered. Ultimately, however, the 
 
 33 
 
514 EXCRETION 
 
 paralysis returned; and shortly before his death (twenty-one years after 
 the aecident) it was noticed tliat a copious perspiration broke out 
 several times on the upper part of the body, while tlic lower portion 
 remained perfectly dry. If there is any functional spinal centre in man, 
 it appears to lie above the fifth spinal segment. For it was seen in a 
 professional diver who fractured his neck at that level, and lived three 
 months after the accident, that sweat frequently appeared on parts of 
 the body above the lesion, but never below. At the autopsy the whole 
 thickness of the cord, except perhaps a small portion of tlic anterior 
 columns, was found destroyed. Of course, it may be that in man the 
 spinal centres, although normally active, lose their function for a long 
 time after such severe injuries to the cord, owing to the condition known 
 as shock. 
 
 The secretory fibres for the fore-limbs (in the cat) leave the cord in 
 the anterior roots of the fourth to ninth thoracic nerves. They pass by 
 white rami communicantes to the sympathetic chain, in which they 
 reach the ganglion stellatum, where they are all connected with nerve- 
 cells. Then, as non-meduUated fibres, they gain the brachial plexus 
 by the grey rami, and run in the median and ulnar to the pads of the 
 feet. The fibres for the hind-limbs leave the cord in the anterior roots 
 of the twelfth thoracic to the third or fourth lumbar nerves ; pass by the 
 white rami to the sympathetic ganglia, in which they form connections 
 with ganglion cells; then, as non-meduUated fibres, run along the grey 
 rami, and are distributed to the foot in the sciatic. 
 
 The evidence of the direct secretory action of nerves on the sweat- 
 glands is singularly striking and complete, in contrast to what we 
 know of the kidney. In the latter, blood-fiov; is the important 
 factor; increased blood-flow entails increased secretion. In the 
 former, the nervous impulse to secretion is the spring which sets 
 the machinery in motion; vascular dilatation aids secretion, but 
 does not generally cause it. It would, however, be easy to lay too 
 much stress on this distinction, for in the horse the mere dilatation 
 of the bloodvessels of the head after section of the cervical sympa- 
 thetic has been found to be accompanied by increased secretion of 
 sweat, and urinary secretion can certainly be affected by the direct 
 action of various substances on the secretory mechanism, indepen- 
 dently of vascular changes. But the broad difference stands out 
 clearly enough, and the reason of it lies in the essentially different 
 purpose of the two secretions. The water of the urine is in the 
 main a vehicle for the removal of its solids; the solids of the sweat 
 are accidental impurities, so to speak, in the water. The kidney 
 eliminates substances which it is vital to the organism to get rid 
 of; the sweat-glands pour out water, not because it is in itself 
 hurtful, not because it cannot pass out by other channels, but 
 because the evaporation of water is one of the most important 
 means by which the temperature of the body is controlled. In 
 short, urine is a true excretion, sweat a heat-regulating secretion. 
 No hurtful effects are produced when elimination by the skin is 
 entirely prevented by varnishing it, provided that the increased 
 loss of heat is compensated. A rabbit with a varnished skin dies 
 
PRACTICAL EXERCISES 
 
 515 
 
 of cold, as a rabbit with a closely-clippod or shaven skin does; 
 suppression of the secretory function of the si<in has nothing to do 
 with death in the first case any more than in the second (p. 299). 
 
 PRACTICAL EXERCISES ON CHAPTER IX. 
 
 Urine. 
 
 For most of the experiments human urine is employed — in the 
 quantitative work the mixed urine of the twenty-four hours. Urine may 
 also be obtained from animals. In rabbits pressure on the abdomen 
 will usually empty the bladder. Dogs may be taught to micturate at 
 a set time or place, or kept in a cage arranged for the collection of urine. 
 Or a catheter may be used (p. 716). 
 
 I. Specific Gravity, — Pour the urine into a glass cylinder, and remove 
 froth, if necessary, with filter-paper. Place a urinometer (Fig. 193) 
 in the urine, and see that it does not come in contact 
 with the side of the vessel. Read off on the graduated 
 ,0 stem the division which corresponds with the bottom 
 
 ,Q of the meniscus. This gives the specific gravity. 
 
 ,g 2. Reaction. — (a) Test with litmus-paper. Generally 
 
 ,g the litmus is reddened, but occasionally in health the 
 
 urine first passed in the morning is alkaline. Some- 
 times urine has an amphicroic reaction — i.e., affects 
 both red and blue litmus-paper. This is the case when 
 there is such a relation between the bases and acids 
 that both acid and ' neutral ' (dibasic) phosphates are 
 present in certain proportions. The acid phosphate 
 reddens blue litmus, and the ' neutral ' phosphate 
 turns red litmus blue. 
 
 (b) Titratable Acidity. — To 25 c.c. of urine add 15 
 to 20 grammes of powdered potassium oxalate, and 
 one or two drops of a i per cent, solution of phenol- 
 phthalein. Shake the mixture rapidly for a minute 
 Fig. 193. — Urin- or two, and then titrate with decinormal sodium hy- 
 ometer. droxide at once (while still cold from the solution of the 
 
 oxalate) till a faint pink colour remains permanent on 
 shaking. The potassium oxalate is added to counteract the tendency 
 of the calcium present in urine to form basic phosphates, which would 
 be precipitated, and the acidity of the urine thus increased (Folin). 
 
 3. Chlorides — (a) Qualitative Test. — Add a drop of nitric acid and a 
 drop or two of silver nitrate solution. The nitric acid is added to 
 prevent precipitation of silver phosphate. A white precipitate soluble 
 in ammonia shows the presence of chlorides. The precipitate appears 
 to be incompletely soluble in ammonia, since the ammonia brings down 
 a small precipitate of earthy phosphates. 
 
 [b] Quantitative Estimation. — The quantitative estimation of the 
 chlorine in urine without previous evaporation and incineration is best 
 made by one of the modifications of Volhard's method. It depends upon 
 the complete precipitation of the chlorine combined with the alkaline 
 metals, and also of sulphocyanic acid, by silver from a solution con- 
 taining nitric acid in excess ; and avoids the error introduced into simpler 
 methods, like Mohr's, by the imion of some of the silver with other 
 substances than chlorine. A given quantity of a standard solution of 
 
5i6 EXCRETION 
 
 silver nitrate (more than suf&cient to combine with all the chlorine) is 
 added to a given volume of urine. The excess of silver is now estimated 
 by means of a standard solution of ammonium sulphocyanide, which 
 precipitates the silver as insoluble silver sulphocyanide. A fairly strong 
 solution of the double sulphate of iron and ammonium (known as iron- 
 ammonia-alum) is taken as the indicator, since a ferric salt does not 
 give the usual red colour with a sulphocyanide so long as any silver in the 
 solution is uncombined with sulphocyanic acid. The iron-ammonia- 
 alum forms the red salt, ferric sulphocyanide, when any excess of 
 ammonium sulphocyanide is present, but it does not react with silver 
 sulphocyanide. 
 
 The standard solution of silver nitrate can be made by dissolving 
 29'o63 grammes of pure fused silver nitrate in distilled water and making 
 up the volume of the solution accurately to i litre. The solution should 
 be kept in the dark. One c.c. of this solution corresponds to 
 o-oi gramme NaCl or 0-00607 gramme CI. 
 
 The standard solution of ammonium sulphocyanide is prepared as 
 follows: Dissolve 13 grammes of pure ammonium sulphocyanide 
 (NH4CNS) in a litre of distilled water. Measure with a pipette into 
 a beaker 20 c.c. of the standard silver nitrate solution, and add 5 c.c. 
 of the iron alum solution and 4 c.c. of pure nitric acid (specific gravity 
 I -2). Fill a burette with the sulphocyanide solution, and run it into 
 the silver nitrate solution until a faint permanent red tinge is obtained. 
 Note the number of c.c. of the sulphocyanide solution required, and 
 then dilute the solution till 2 c.c. of the sulphocyanide solution corre- 
 spond exactly to i c.c. of the silver solution, so as just to allow of the 
 end reaction with the iron solution being seen, and no more. 
 
 To carry out the method, put 10 c.c. of urine, which must be free 
 from albumin, in a stoppered flask, with a mark corresponding to 100 c.c. 
 or a graduated cylinder. Add 50 c.c. of water, 4 c.c. of pure nitric acid 
 (specific gravity 1-2), and 15 c.c. of the standard silver solution; shake 
 well, fill with water to the mark, and again shake. After the precipitate 
 has settled, filter it off. Take 50 c.c. of the filtrate, add 5 c.c. of the 
 solution of iron-ammonia-alum, and run in from a burette the standard 
 solution of ammonium sulphocyanide until a weak but pennanent red 
 coloration appears. 
 
 Suppose X c.c. of the sulphocyanide solution are required, then the 
 chlorine in 10 c.c. of urine evidently corresponds to (15 —x), o'oi gramme 
 NaCl 
 
 4. Phosphates — (i) Qualitative Tests. — (a) Render the urine alkaline 
 with ammonia. A precipitate of earthy phosphates (calcium and mag- 
 nesium phosphates) falls down. Filter. The filtrate contains the 
 alkaline phosphates. To the filtrate add magnesia mixture.* The 
 alkaline phosphates (sodium, potassium, or ammonium phosphates) 
 are precipitated as ammonio-magnesic or triple phosphate, (fe) Add to 
 urine half its volume of nitric acid and a little molybdate of ammonium, 
 and heat. A yellow precipitate of ammonium phospho-molybdate 
 shows that phosphates are present. This test is given both by alkaline 
 and earthy phosphates. 
 
 (2) Quantitative Estimation. — The quantitative estimation of phos- 
 phoric acid in urine is best done volumetrically, by titration with a 
 standard solution of uranium nitrate, using fcrrocyanide of potassium 
 as the indicator. Uranium nitrate gives with phosphates, in a solution 
 containing free acetic acid, a precipitate with a constant proportion of 
 
 * Magnesium chloride no grammes, ammonium chloride 140 grammes, 
 ammonia (specific gravity 0*91) 250 c.c, and water 1,750 c.c. 
 
PRACTICAL EXERCISES 517 
 
 phosphoric acid. As soon as there is more uranium in the solution than 
 is required to combine with all the phosphoric acid, a brown colour is 
 given with potassium Icrrocyanidc, due to the formation of uranium 
 ferrocyanide. In carrying out the method, 5 c.c. of a mixture of acetic 
 acid and sodium acetate (there are 10 grammes of sodium acetate and 
 10 grammes of glacial acetic acid in 100 c.c. of the mixture) are added 
 to 50 c.c. of urine, which is then heated in a beaker on the water-bath 
 almost to boiling. The standard uranium solution (which contains 
 35 '5 grammes of uranium nitrate in the litre, and i c.c. of which corre- 
 sponds to 0-005 gramme P2O5) is now run in from a burette, until a drop 
 of the urine gives, with a drop of potassium ferrocyanide solution, on a 
 porcelain slab, a brown colour. Uranium acetate may be used instead 
 of uranium nitrate, but the latter keeps best. When uranium acetate 
 is employed it is not necessary to add the sodium acetate mixture. 
 
 5. Sulphates — (i) Qualitative Test. — Add to urine a drop of hj'^dro- 
 chloric acid and then a few drops of barium chloride. A white pre- 
 cipitate comes down, showing that inorganic sulphates are present. 
 The hydrochloric acid prevents precipitation of the phosphates. 
 
 (2) Quantitative Estimation of the Sulphates {Inorganic and Ethereal). 
 — Add to 50 c.c. of albumin-free urine in a 200-c.c. Erlenmeyer flask 
 5 c.c. of a 4 per cent, potassium chlorate solution and 5 c.c. of strong 
 hydrochloric acid, and boil the mixture to break up the ethereal sul- 
 phates. In five to ten minutes it becomes perfectly colourless. While 
 it continues to boil, 25 c.c. of a 10 per cent, solution of barium chloride 
 are added by drops, at such a rate that it takes about five minutes to 
 add this quantity. The flask is now put on the water-bath for one-half 
 to one hour, till the precipitate has settled. Then filter through an 
 ash-free filter. Wash the precipitate on the filter for half an hour with 
 hot water. During the first twenty minutes of the washing, at intervals 
 of a few minutes, substitute hot 5 per cent, ammonium chloride solution 
 for the water. At the end of the half-hour's washing, as soon as the 
 water has run through the filter, fold up the latter and press it gently 
 between drj^ fiJter-papers to remove a portion of the water. Then place 
 the filter in a weighed porcelain crucible. Pour into the crucible 3 or 4 
 c.c. of alcohol, and ignite it, to dry and partially bum the filter-paper. 
 Then incinerate till all the carbon is burned off, cool, and weigh. From 
 the weight of the barium sulphate, the sulphuric acid in 50 c.c. of urine 
 is easily calculated (SO4 in i gramme of barium sulphate, 0-41 187 
 gramme) (Folin). 
 
 (3) Quantitative Estimation of the Sulphuric Acid united with Aromatic 
 Bodies {Aromatic or Ethereal Sulphates). — Put 200 c.c. of the same urine 
 as used in (2) into a beaker. Add 100 c.c. of 10 per cent, barium 
 chloride solution in the cold. Let stand for twenty -four hours. Then 
 decant off the clear supernatant liquid, and filter it. Measure 150 c.c. 
 of the clear filtrate, corresponding to 100 c.c. of the urine, into a 400-c.c. 
 Erlenmeyer flask. Add 10 or 15 c.c. of concentrated hydrochloric acid 
 and 10 to 15 c.c. of 4 per cent, potassium chlorate. Heat the mixture 
 to boiling, and proceed as in (2). From the weight of the barium sul- 
 phate, the ethereal sulphuric acid in 100 c.c. of urine can be calculated. 
 Deducting this from the quantity per 100 c.c. of urine obtained in (2), 
 we get the amount of inorganic sulphuric acid per 100 «.c. (Folin). 
 
 6. Indoxyl (contained in the urine as indican, the potassium salt of 
 indoxj-l-sulphuric acid) can be oxidized into indigo, and so detected 
 and estimated. 
 
 A qualitative test is the following: Ten c.c. of horse's urine is mixed 
 with 10 c.c. of Obermayer's reagent (pure concentrated hydrodhloric 
 acid containing 2 to 4 parts of ferric chloride in 1,000), and shaken well 
 
51 8 EXCRETION 
 
 for a minute or two; a bluish colour appears if, as is generally the case, 
 indoxyl is present, indigo (Ci6HioN'2^2) being formed by the oxidizing 
 action of the ferric chloride on the indoxyl, the compound of which 
 with sulphuric acid has been broken up by the hydrochloric acid. The 
 urine must be free from albumin. In performing the test in human 
 urine, which contains a smaller quantity of the indigo-forming sub- 
 stance, the faint blue liquid should be shaken up with a few drops of 
 chloroform. The latter takes up the colour, which is thus rendered 
 more evident. If there is difficulty in obtiiining the reaction, the urine 
 may first be decolorized by precipitating it with acetate of lead, 
 avoiding excess. The precipitate is filtered off, and the test then 
 applied to the clear filtrate. The skatoxyl of urine can also be oxidized 
 to indigo, but it is present in far smaller amount. The average quantity 
 of indigo obtained from a litre of horse's urine is about 150 milligrammes ; 
 from a litre of human urine, not a twentieth of that amount. 
 
 For comparative quantitative determinations the method of Folin 
 may be used. One-hundredth of the twenty-four hours' urine is taken. 
 In this the indigo is developed by the addition of an equal volume of 
 Obermayer's reagent (p. 5i'7), and the indigo-blue dissolved by means 
 of 5 c.c. of chloroform. The chloroform solution is then compared 
 colorimetrically with Fehling's solution. This can be done by putting 
 the indigo solution and 5 c.c. of the Fehling's solution respectively into 
 small test-tubes of equal calibre, and comparing the depth of tint. 
 If the Fehling's solution is stronger than the indigo solution, run water 
 into the former from a pipette, graduated in tenths of a c.c, shaking 
 up after each addition, till equality of tint has been reached. If the 
 indigo solution has a stronger blue colour than the Fehling's solution, 
 dilute a measured amount of it first of all with such a quantity of 
 chloroform (say an equal volume) as will make its tint distinctly weaker 
 than that of the Feliling's solution. Then dilute the Fehling's solutmn 
 with water, as before, till the tint is the same. From the amount of 
 dilution the quantity of indigo can be expressed in arbitrary units, 
 taking Fehling's solution as 100. Thus, if i c.c. of water must be 
 added to the 5 c.c. of Fehling's solution, the indican can be expressed 
 
 as = 5^ = 83. The comparison can be made more accurately by 
 
 a colorimeter, if one is available. To determine the absolute amount 
 of indigo obtained, comparison must be made with a standard solution 
 of indigo. 
 
 7. Urea — (i) Decomposition of Urea. — Heated dry in a test-tube, it 
 gives off ammonia. The residue contains biuret, which, when dissolved 
 in water, gives a rose colour with a trace of cupric sulphate and excess 
 oi sodium hydroxide (or of the hydroxides of certain other metals of 
 the alkalies and alkaline earths (p. 8). Some proteins — peptones and 
 alb imoses — in the presence of the same reagents, give a similar colour, 
 the so-called biuret reaction. 
 
 (2) Quantitative Estimation — Marshall's Urease MetJiod. (According 
 to Van Slyke). — One-half c.c. of urine is measured into the bottom of 
 tube A (Fig- 194). Five c.c. exactly of a 0-6 per cent, solution of 
 KH2PO4 is then run in from a burette, and i c.c. exactly of a 10 per 
 cent, watery solution of the dry urease powder. The phosphate is 
 added as a ' buffer ' to maintain the enzyme action near its maximum 
 rate, by preventing the development of alkalinity as the production of 
 ammonium carbonate goes on. The solutions in the tube are well 
 
PRACTICAL KXERCISES 
 
 519 
 
 mixet-l, 2 drops of caprylic alcohol are added to prevent foaming during 
 the subsequent aeration (by Folin's method, p. 521), and the stopper 
 bearing the ;u rating tubes is put into place. Let stand twenty minutes 
 at room temperature of 15', or fifteen minutes at 20° ('. or above, for 
 complete decomposition of urea. This time must not be shortened 
 unless more enzyme is used, but no harm is done if it is longer. Mean- 
 while measure into tube B 25 c.c. ?J, hydrochloric or sulphuric acid, 
 I drop of I per cent, sodium alizarine sulphonate indicator, and 
 1 drop caprylic alcohol, and connect the 
 tubes as shown in I'Mg. i{)4. After the 
 twenty minutes for decomposition of urea 
 has elapsed, the air current is passed for 
 half a minute to sweep into B, a small 
 amount of ammonia which has escaped 
 into the air space of A during the decom- 
 position. Then A is opened, and 4 to 
 5 grammes potassium carbonate added to 
 liberate the ammonia from the ammonium 
 carbonate formed. Now let the air cur- 
 rent pass gently through the tubes for 
 the first mmute and then rapidly until 
 all the ammonia has been brought into 
 the acid in B. The time necessary for 
 this will depend upon the speed of the 
 air current (varying from five minutes to 
 half an hour, according to the efhciency 
 of the pump or vacuum by which the air 
 is moved) and should be determined once 
 for all. The excess acid in B is now 
 titrated with |L sodium hydroxide. The 
 weight of nitrogen contained in the urea of 100 fc.c. of urine is 
 (25 - *•) X 0-056, where x is the number of c.c. of the sodium hydroxide 
 solution necessary to neutralize the acid. Included in the urea 
 nitrogen is the nitrogen of any ammonia originally present in the 
 urine. This can be determined separately, if desired, by putting 
 5 c.c. of urine into A without urease, adding the carbonate at once, 
 and then aerating through the acid in B. The acid neutralized in 
 this case is multiplied by 0'0056 to give the ammonia nitrogen in 100 c.c. 
 of urine, and this being deducted from the previous result, the net urea 
 nitrogen is obtained. 
 
 The method as above described is adapted for urine containing not 
 more than 3 per cent, urea, which is about the maximum found in human 
 urine. Cat's or dog's urine should first be diluted to reduce the urea 
 below 3 per cent. 
 
 Clinical Urease Method by Direct Titration of Urine. — Two 5 c.c. 
 portions of urine are put into flasks a and b of 200 to 300 c.c. capacity, 
 and diluted with distilled water to about 100 to 125 c.c. One c.c. of 
 10 per cent, urease is added to flask a, and a few drops of toluene to 
 each. The flasks are allowed to remain, w-ell stoppered, at room tempera- 
 ture over night, then titrated to a distinct pink colour with ^^ hydro- 
 chloric acid, using methyl orange as indicator. From the amount of 
 hydrochloric acid needed for a is deducted the amount needed for b; 
 and also the amount previously determined to be necessary to neutra- 
 lize the alkalinity of the enzyme solution. The remaining number of 
 c.c. multiplied by 0-6 gives the urea in grammes per litre of urine, since 
 
 Fig. 194- — Apparatus for deter- 
 mining Urea Content by means 
 of Urease. (After Van Slyke.) 
 
5^0 
 
 EXCRETION 
 
 I c.c. of N hydrochloric acid is equivalent to 3 miiligrainmcs of urea. 
 Instead of the drictl urease preparation, an extract of finely powdered 
 soy beans can be made by mixing 25 grammes of the powder with 
 250 c.c. of distilled water, and allowing it to stand with occasional 
 shaking for an hour. Twenty-five c.c. of ^^ hydrochloric acid are then 
 added, and the mixture allowed to remain a few minutes longer (best 
 at about 35" C). The mixture is filtered, treated with a few drops of 
 toluene, and preserved for use in a stoppered bottle. It must be made 
 
 up fresh after a few days as it does 
 not keep long. The solution is alka- 
 line to methyl orange, and 2 c.c. (the 
 quantity used in the above clinical 
 determination of urea) generally re- 
 (juircs about 0*3 c.c. of .N. hydro- 
 chloric acid for neutralization. 
 
 A less exact method which is very 
 rapid, and is therefore much used in 
 clinical determinations, is the Hypo- 
 bromite Method. The urea is split up 
 by sodium hypobromite (p. 480), and 
 the carbon dioxide being absorbed by 
 the excess of sodium hydroxide used 
 in preparing the hypobromite, the 
 nitrogen is collected over water in an 
 inverted burette. It is easy to calcu- 
 late the weight of urea corresponding 
 to a given volume of nitrogen measured 
 at a given temperature and pressure. 
 The nitrogen of urea is j^Jj, or ^^ of the 
 whole molecular weight. Now, i c.c. 
 of N weighs, at 760 millimetres of 
 mercury and 0° C, 0'00i23 gramme. 
 Therefore, i c.c. of N corresponds to 
 0-00125 X J^ = 0*00268 gramme urea. 
 Suppose, now, that i c.c. of urine was 
 found to yield 10 c.c. of N measured 
 at i7°C. and 750 millimetres barome- 
 tric pressure. Since a gas expands 
 
 Fig. 195. — Hypobromite Method 
 of estimating Urea. A, glass 
 thimble; B, bottle, through the 
 rubber cork of which pass two 
 short glass tubes, one connected 
 by the rubber tube C with a 
 burette D, and the other armed 
 with a short piece of rubber tube 
 F. F is provided with a pinch- 
 cock. The burette is supported 
 on a stand, and immersed in 
 water contained in the glass 
 cylinder E. 
 
 ^i., part of its volume at 0° for every 
 
 degree above 0°, we must correct the 
 apparent volume of nitrogen by multi- 
 plying by 'il^. Since the volume of a 
 gas is inversely proportional to the 
 pressure, we must further multiply 
 by l^. Thus we get 10 x |^ x i^% ^ 
 -.V.^,^f- =9*29 c.c. as the volume of the 
 nitrogen reduced to 0° C. and 760 milli- 
 metres of mercury. Multiplying this by 0'00268, we get 0-0249 gramme 
 urea for i c.c. urine, which for a daily yield of 1,200 c.c. would corre- 
 spond to 2Q-88 grammes urea. 
 
 A.s a matter of fact, however, it has been found that there is always 
 a deficiency of nitrogen^that is, a gi^•en quantity of urea yields less 
 than the estimated amount of gas. .\ gramme of urea in urine, instead 
 of giving off 373 c.c. of nitrogen, gi\es only 354 c.c. at o^ C. and 760 
 millimetres pressure. We must therefore take i c.c. of N as correspond- 
 
PRACTICAL EXERCISES 521 
 
 ing to 0-00282 gramme, instead of o'oo2()8 gramme urea. But it is 
 affectation to make this correction if, as is selclom done in hospitals, the 
 temperature is not taken into account. 
 
 A convenient apparatus is shown in Fig. 195. In B place 10 c.c. 
 of a solution made by adding bromine to ten times its volume of 40 per 
 cent, sodium hydroxide solution. Mix 5 c.c. of urine with 5 c.c. of 
 water. Put 3 c.c. of the mixtnre into the thimble A, which is then set 
 in the small bottle B. The cork is now carefully fixed in B, and the 
 tube F being open, the level of the water in the burette is read off. 
 The pinchcock having been closed, the bottle B is now tilted so that 
 the urine in the thimble is gradually mixed with the hypobromite solvi- 
 tion, and the nitrogen given off is added to the air in the burette and 
 its connections. The level of the water in the burette is therefore 
 depressed. When gas ceases to be given off, and a short time has been 
 allowed for the whole to cool, the tube is raised till the level of the 
 water is once more the same inside and out. The level is again read 
 off; the difference of the two readings gives the volume of nitrogen at 
 the temperature of the air and the barometric pressure. In order that 
 the temperature of the water may be the same as that of the air, the 
 cylinder should be filled a considerable time before the observations 
 are begun. 
 
 8. Estimation of the Ammonia in Urine (Folin's Method).— Ammonia 
 is liberated by addition of a weak alkali (sodium carbonate). Then 
 the ammonia is driven out at ordinary temperature by a strong current 
 of air and taken up in decinormal acid, which is then titrated with 
 decinormal alkali. 
 
 The apparatus employed consists of — (i) A cylinder of about 45 cm. 
 diameter, with a rubber stopper through which pass two glass tubes. 
 One of the tubes goes nearly to the bottom of the cylinder, and the 
 other end is connected, through a U-tube filled with cotton, with a tube 
 containing sulphuric acid. The second tube is cut off short below the 
 rubber cork, and its other end is connected, through a U-tube con- 
 taining cotton, with a sulphuric acid tube (or with two in series). (2) A 
 water-pump to draw or force air through the apparatus (600 to 700 
 litres in an hour). 
 
 Put into the first svdphuric acid tube 25 c.c, into the second 10 c.c. 
 decinormal acid and some water; into the cylinder 25 c.c. of filtered 
 urine, 8 to 10 grammes sodium chloride, 5 to 10 c.c. of petroleum or 
 toluol to prevent foaming, and last of all i gramme dried sodium 
 carbonate. At once close the cylinder and allow a strong stream of air 
 to pass through the apparatus. At a temperature of 20° to 25° (room 
 temperature), and using 600 to 700 litres of air an hour, all the ammonia 
 is in the sulphuric acid in one to one and a half hours. The contents 
 of the sulphuric acid tubes are put into a beaker and titrated with 
 decinormal alkali, using lacmoid (litmoid) or rosolic acid as indicator. 
 Deduct the number of c.c. of alkali used from the number of c.c. of the 
 decinormal acid originally taken, and multiply the remainder by 1*7034 
 to get the quantity of ammonia in milligrammes. The method can be 
 employed also for albuminous urine. 
 
 9. Estimation of the Total Nitrogen. — It is sometimes more important 
 to determine the total nitrogen of the urine than the urea alone. This 
 IS conveniently done by Kjeldahl's method (or some modification of 
 it), which can also be applied to the estimation of the nitrogen in the 
 faeces, or in any of the solids or liquids of the body. It depends on the 
 oxidation of the nitrogenous matter (or, rather, in the case of urine, 
 mainly its hydrolysis) in such a way that the nitrogen is all represented 
 
52 2 EXCRETION 
 
 as ammonia. The ammonia is then distilled over, collected and esti- 
 mated, and from its amount the nitrogen is easily calculated. In urine 
 the method can be carried out by adding to a measured quantity of it 
 (say 5 CO.) four times its volume of strong sulphuric acid, and boiling 
 in a long-necked flask (capacity 200 c.c). after the addition of a globule 
 of mercur>' (about o-i c.c), 'which hastens oxidation and obviates 
 bumping. A part of the mercuric sulphate formed remains in solution ; 
 the rest forms a crystalline deposit. The heating should continue for 
 half an hour, or until the liquid is decolourized. It should be kept 
 gently boiling. This completes the process of oxidation ; and the next 
 step is to liberate the ammonia from the substances with which it is 
 united in the solution, and to distil it over. Dilute the liquid with 
 water, after cooling, up to about 150 c.c, and pour into a larger long- 
 necked flask. Add enough of a solution of sodium hydroxide (specific 
 gravity about 1-25) to render the liquid alkaline, avoiding excess, as 
 this favours bumping. The proper quantity can be found by deter- 
 mining beforehand how much of the alkali is needed to neutralize the 
 acid used for oxidation, and a little more than this amount should be 
 added. Twenty c.c. of strong sulphuric acid needs about 75 c.c. of 
 40 per cent, sodium hydroxide to neutralize it. Bumping mav further 
 be prevented by the addition of a little granulated zinc. Shake the 
 flask two or three times. Add also about 12 c.c. of a concentrated 
 solution of potassium sulphide (i part to i^ parts water), which favours 
 the setting fiee of the ammonia from the amino-compounds of mercury 
 that have been formed during oxidation . Commercial ' liver of sulphur'' 
 will do quite well. Immediately connect the distilling-flask with a 
 worm or Liebig's condenser, and distil the ammonia over into 50 c.c. 
 of standard (decinormal) sulphuric acid (see footnote, p. 473) con- 
 tained in a flask into which a glass tube connected with the lower end 
 of the \yorm dips. Heat the distilling-flask at first gentlv, then strongly, 
 and boil for three-quarters of an hour, or until about t'wo-thirds of the 
 liquid has passed over. Then lift the tube out of the standard acid, and 
 continue the distillation for two or thiee minutes longer. The ammonia 
 is now all united with the standard acid, a certain amount of which is 
 left over. By determining this amount we arrive at the quantity com- 
 bined with ammonia, and therefore at the quantity of ammonia. Fill 
 a burette with a decinormal solution of potassium or sodium hydroxide. 
 Add a little methyl-orange solution to the standard sulphuric acid, to 
 serve as indicator. Then run in the potassium or sodium hydroxide 
 till the pink tinge gives place to a permanent but just recognizable 
 yellow. Let x be the number of c.c. run in. Since i c.c. of any deci- 
 normal solution is equivalent to i c.c. of any other, x represents also the 
 number of c.c. of the standard sulphuric acid left uncombincd with 
 ammonia; and 50 — jt, the quantity combined with ammonia. Then, 
 I c.c. of decinormal sodium or potassium hydroxide being equivalent 
 to I c.c. of decinormal ammonium hydroxide, and i c.c. of decinormal 
 ammonium hydroxide containing 0-0014 gramme nitrogen, we get 
 {50 - x)x 0-0014 ^s the quantity of nitrogen in 5 c.c of urine. 
 
 Instead of mercury, potassium sulphate and copper sulphate may be 
 added to the sulphuric acid in order to aid the decomposition in the 
 first stage of the estimation. About 3 grammes of potassium sulphate 
 and I gramme of copper sulphate are added to p c.c of urine, and then 
 5 c.c. of sulphuric acid. The liquid is gently boiled for an hour, or until 
 it is quite clear. The neutralization and distillation are conducted as 
 before, the proper quantity of sodium hydroxide being determined in 
 advance. No potassium sulphide is added, but a small quantity of 
 
PRACTICAL EXERCISES 523 
 
 talc may be put in to prevent bumping. Instead of methyl orange, 
 ' alizarin red,' which is bright red in the presence of the slightest trace 
 of alkali, mav be used. 
 
 10. Uric Acid — (i) Qualitative Test for Uric Acid — Murexide Test. — 
 A small quantity of uric acid or one of its salts is heated with a little 
 dilute nitric acid. The colour of the residue left by evaporation 
 becomes yellow, and then red. and on the addition of ammonia changes 
 to deep purple-red. Potassium or sodium hydroxide changes the 
 yellow to violet. In the reaction alloxantin is formed by oxidation of 
 the uric acid. When ammonia acts on alloxantin it is changed into 
 purpuric acid, and this into its ammonium purpurate, the purple-red 
 substance called murexide. Thus: 
 
 CsHeN^Og-l- NH3 =C8H5N508-h 2H2O. 
 
 Alloxantin. Purpuric Acid. 
 
 The reaction is also given by theobromine (dimethylxanthin), an alkaloid 
 in cocoa, and thcine or caffeine (trimethylxanthin), an alkaloid in tea 
 and coffee, which are also purin derivatives (p. 481')- 
 
 (2) Quantitative Estimation — Folin's Modification of Hopkins's 
 Method. — The chief reagent is a solution of 500 grammes ammonium 
 sulphate, 5 grammes uranium acetate, and 60 c.c. 10 per cent, acetic 
 acid, in 650 c.c. of water. 
 
 One hundred and fifty c.c. of urine is measured into a tall, narrow 
 beaker or a cylinder, and 37I c.c. of the reagent added. If enough 
 urine is available, 200 c.c. of urine and 50 c.c. of reagent are to be used. 
 Allow the mixture to stand without stirring for about half an hour. 
 The uranium precipitate has then settled, and the clear supernatant 
 liquid is removed by siphoning or decantation. One hundred and 
 twenty-five c.c. of this liquid is measured into another beaker, 5 c.c. 
 of strong ammonia added, and the mixture set aside till next day. The 
 precipitate is then filtered off, and washed with 10 per cent, ammonium 
 sulphate solution until the filtrate is quite or nearly free from chlorides. 
 The filter is then removed from the funnel, opened, and the precipitate 
 rinsed back into the beaker. Enough water to make about 100 c.c. is 
 added, and the precipitate is then dissolved by means of 15 c.c. con- 
 centrated sulphuric acid, and at once titrated with ^^ (one -twentieth 
 normal) potassium permanganate solution (made by dissolving 
 i'58i grammes of the permanganate in a litre of water), each c.c. of 
 which corresponds to 375 milligrammes of uric acid. The very first 
 pink coloration, extending through the entire liquid on the addi- 
 tion of two drops of permanganate solution, marks the end point. 
 A correction of 3 milligrammes, owing to the solubility of ammonium 
 urate, is added to the result. 
 
 11. Creatinin. — Qualitatively, creatinin may be recognized in very 
 small amounts by Weyl's test. A few drops of a dilute solution of 
 sodium nitro-prusside are added to urine, and then dilute sodium 
 hydroxide drop by drop. A ruby-red colour appears, which soon turns 
 yellow. If the urine is now strongly acidified with acetic acid and 
 heated, it becomes first greenish and then blue. Enough acid must be 
 added to more than neutralize the alkali. 
 
 Another test which has been made the basis of a quantitative method 
 by Folin is Jake's test. A little urine (say 5 c.c.) is put in a test-tube, 
 and then a solution of picric acid in water. The mixture is rendered 
 alkaline by the addition of potassium or sodium hydroxide solution, 
 and a reddish colour is produced, which turns yellow on the addition of 
 
52 4 EXCRETION 
 
 acid. A similar red colour is given by dextrose, but not unless the 
 solution is heated. 
 
 Quantitative Estimation of Creatinin by Folin's Method. — It depends 
 upon the comparison of the colour which* creatinin gives with picric 
 acid in an alkaline solution with that of a standard solution of potassium 
 bichromate. Ten c.c. of urine is measured into a 500 c.c. measuring- 
 flask; 15 c.c. of a saturated picric acid solution (containing about 
 12 grammes per litre) and 5 c.c. of a 10 per cx»nt. solution of sodium 
 hydroxide are added. The mixture is allowed to stand for five minutes. 
 Then water is added up to the 500 c.c. mark, and the flask shaken to 
 mix uniformly. Samples of the liquid are then at once compared 
 colorimetrically with a half-normal solution of potassium bichromate 
 containing 24*55 grammes per litre. The colour of the urine does not 
 introduce a sensible error on account of the great dilution. For exact 
 work the comparison must be made with a good colorimeter. It has 
 been found experimentally that, when 10 milligrammes of creatinin 
 arc present in 500 e.g. of a solution made as described, a layer of the 
 solution 8*1 millimetres in thickness has the same depth of tint as 8 milli- 
 metres of the bichromate solution. Suppose it takes 9 millimetres of 
 the urine-picrate solution to equal 8 millimetres of the bichromate, 
 
 8*1 
 then the 10 c.c. of urine contains 10 x — =9-0 milligrammes of 
 
 creatinin . 
 
 12. Hippuric Acid. — From horse's or cow's urine hippuric acid is 
 prepared by evaporating to a small bulk, and adding strong hydrochloric 
 acid. The crystalline precipitate is washed with cold water, then 
 dissolved in hot water, and filtered hot. Hippuric acid separates out 
 from the filtrate in the cold in the form of long four-sided prisms with 
 pyramidal ends. Heated dry in a test-tube, the crystals melt, and 
 benzoic acid and oily drops of benzonitrilc, a substance with a smell 
 like that of oil of bitter almonds, are formed. 
 
 ABNORMAL SUBSTANCES IN URINE, 
 
 13. Proteins — (i) Qualitative Tests. — {a) Boil and add a few drops 
 of nitric acid. A precipitate on boiling, increased or not affected by 
 the acid, shows the presence of coagnlable proteins (scrum-albumin or 
 globulin). A precipitate of earthy phosphates sometimes forms on 
 boiling. It is distinguished from a precipitate of proteins by dissolving 
 on the addition of acid. 
 
 (b) Heller's Test. — Put some nitric acid in a test-tube. Pour care- 
 fully on to the surface of the acid a little urine. A white ring at the 
 junction of the liquids indicates the presence of albumin or globulin. 
 If much albumose is present, a white precipitate, which disappears on 
 heating, may be formed. When this test is performed with undiluted 
 urine, uric acid may be precipitated and cause a brown colour at the 
 junction. A similar ring may be found in the absence of proteins when 
 the test is made on the urine of a patient who has been taking copaiba. 
 In very concentrated urine a white ring of nitrate of urea may be 
 formed. A coloured ring is frequently seen, owing to the oxidation of 
 certain chromogens of urine. 
 
 (c) Filter some urine, and add to the filtrate its own volume of acetic 
 acid. A precipitate mav indicate mucin or nucleo-albumin. If any is 
 formed, filter ft off, and add to the filtrate a few drops of potassium 
 ferrocyanide. A white precipitate shows the presence of proteins. 
 
 {d) Test for Globulin in Urine. — Serum-globulin probably never 
 
PRACTICAL EXERCISES 525 
 
 occurs in iiniic apart from serum-albumin. It may be detected thus: 
 Make the urine alkahne with ammonia, let it stand for an hour, and 
 filter. Half saturate the filtrate with ammonium sulphate — i.e., add 
 to it an equal volume of a saturated solution of ammonium sulphate. 
 Serum-globulin is precipitated, serum-albumin is not. 
 
 {e) Test for Albiiniose in Urine {Albumosuria). — Coagulable proteins 
 are removed by boiling the urine (acidulated if necessary), and filtering 
 off the precipitate if any. The filtrate is neutralized. If a further 
 precipitate falls down it is filtered off, the clear filtrate is heated in a 
 beaker placed in a boiling water-bath, and there saturated with crystals 
 of ammonium sulphate. A precipitate indicates that albumoses 
 (proteoses) are present. A slight precipitate might possibly be due to 
 the formation of ammonium urate. A further test may be performed 
 on the original urine if it is free from coagulable proteins, or on the 
 filtrate after their removal. Add a drop or two of pure nitric acid. 
 If albumoses are present, a precipitate. is thrown down which disappears 
 on heating, and reappears on cooling the test-tube at the cold-water tap. 
 
 (2) Quantitative Estimation of Coagulable Proteins {Serum- Albumin 
 and Globulin) — {a) Gravimetric Method. — Heat 50 to 100 c.c. of the 
 urine to boiling, adding a dilute solution (2 per cent.) of acetic acid by 
 drops as long as the precipitate seems to be increased. Filter through 
 a weighed filter. Wash the precipitate on the filter with hot water, 
 then with hot alcohol, and finally with ether. Dry in an air-bath at 
 110° C, and weigh between watch-glasses of known weight. 
 
 {b) Esbach's Method. — Esbach's reagent is made by dissolving 
 10 grammes of picric acid and 20 grammes of citric acid in boiling 
 water (800 or 900 c.c), and then making up the volume to a litre. The 
 so-called albuminimeter is simply a strong glass tube graduated and 
 marked in a certain way. Fill the tube up to the mark U with the 
 urine. Then add the reagent up to the mark R. Close the tube with 
 the rubber cork, and invert it a dozen times without shaking. Set the 
 tube aside for twenty -four hours, then read off the graduation on the 
 tube which corresponds with the top of the precipitate. The figures 
 indicate the number of grammes of dry protein in a litre of the urine. 
 Suppose the top of the sediment is at 4 , this will indicate 4 grammes per 
 litre, or 0-4 per cent. The method is of some clinical importance, owing 
 to its simplicity, although it is, of course, not very accurate. 
 
 14. Sugar — (i) Qualitative Tests — (a) Trammer's Test (p. 10). — It is to 
 be remarked that some substances present in small amount in normal 
 urine reduce cupric sulphate — e.g., uric acid (present as urates) and 
 kreatinin — but although a normal urine may thus decolourize the 
 copper solution, it rarely causes so much reduction that a yellow or red 
 precipitate is formed, as is the case in diabetic urine. Glycuronic acid 
 (p. 4S2) also reduces cupric salts, as does alcapton or homogentisinic 
 acid, a substance found in rare cases in disease (p. 483)- 
 
 {b) Fehling's Test. — Fehling's solution (p. 526) is brought to the boil iu 
 a test-tube, a little of the, urine then added, and the change of colour 
 noted. Benedict's modification of Fehling's solution may also be used. 
 It has the advantage that it keeps indefinitely, and therefore is always 
 ready for use, and is also said to be more delicate. 
 
 (c) Phenyl-Hydrazine Test. — This test depends upon the fact that 
 phenyl-hydrazine forms with sugars such as glucose (dextrose), maltose, 
 isomaltose, etc., but not with cane-sugar, characteristic cr^'stalline 
 substances (phenyl-glucosazone, phenyl-maltosazone, etc.) which can 
 be recognized under the microscope, and are distinguished from each 
 other by melting at different temperatures. Phenyl-glucosazone 
 
526 
 
 EXCRETION 
 
 (C18H22N4O4) melts at 205° C. To perform the test for dextrose m the 
 unnc. proceed thus: Put 5 c.c. of urine in a test-tube, add i decigramme 
 of hydrochlorate of phenyl-hydrazine and 2 decigrammes of sodium 
 acetate. It is sufi&ciently accurate to add as much phenyl-hydrazine 
 as will lie on a sixpence (or a dime) and twice as much sodium acetate. 
 Heat the test-tube in a boiling water-bath for half an hour. Then cool 
 at the tap and examine the deposit under the microscope for the yellow 
 phenyl-glucosazone crystals (Fig. 196). Sometimes the osazone pre- 
 cipitate is amorphous. If this should be the case, the precipitate, if no 
 crj'stals can be seen, must be dissolved in hot alcohol. The solution is 
 then diluted with water and the alcohol boiled off, when the osazone. 
 
 if any be present, will crystallize out. 
 Very minute traces of sugar can be 
 detected in this way (as little as O'l per 
 cent, in urine). Often in normal urine 
 yellow crystals are deposited during 
 the first fifteen minutes' heating. 
 They must not be mistaken for gluco- 
 sazonc. They probably consist of a 
 compound of glycuronic acid and 
 phenyl-hydrazine. They are changed 
 as the heating goes on into an amor- 
 phous brownish - yellow precipitate 
 (Abel). 
 
 {d) The Yeast Test is an importanl 
 confirmatory test for distinguishing 
 the fermentable sugars from other re- 
 ducing substances, but it is not very 
 delicate, and will with difficulty detect 
 sugar when less than 0-5 per cent, is 
 present. It can be performed thus: 
 A little yeast (the tablets of com- 
 pressed yeast do very well) is added 
 to a test-tube half filled with urine. 
 The test-tube is then filled up with 
 mercury, closed with the thumb, and 
 inverted over a dish containing mer- 
 cury. The dish may be placed on the 
 top of a water-bath whose temperature 
 is about 40° C. After twenty-four 
 hours the sugar will have been broken 
 up into alcohol and carbon dioxide. The latter will have collected 
 above the mercurj^ in the test-tube, and the former will be present in 
 the urine. The tests for sugar will either be negative or will be less 
 distinct than before. A control test-tube containing water and yeast 
 should also be set up, as impurities in the yeast sometimes j-ield a small 
 amount of carbon dioxide. Specially-constructed tubes are also often 
 used for performing the test. 
 
 (2) Quantitative Estimation of Sugar in Urine. — (a) V olumetrically , 
 the sugar can be estimated by titration with Fehling's solution. As 
 this does not keep well, two solutions containing its ingredients should 
 be kept separately and mixed when required. Solution I.: Dissolve 
 34-64 grammes pure cupric sulphate in distilled water, and make up the 
 volume to 500 c.c. Solution II.: Dissolve 173 grammes Rochelle salt 
 in 400 c.c. of water, add to this 51-6 grammes sodium hydroxide, and 
 make up the volume with water to 500 c.c. Keep in well-stoppered 
 
 Fig. 196. — Phenyl-Glucosazone and 
 Phenyl-Maltosazone Crystals (Mac- 
 leod). The phenyl - glucosazone 
 crystals are in the upper part of 
 the figure, the phenyl-maltosazone 
 in the lower. 
 
PRACTICAL EXERCISES 527 
 
 bottles in the dark. For use, mix together equal volumes of the two 
 solutions. Ten c.c. of this mixture is reduced by 0-05 gramme dextrose. 
 To estimate the sugar in urine, put 10 c.c. of the mixture into a porcelain 
 capsule or glass flask, and dilute it four or five times with distilled water. 
 Dilute some of the urine, say ten or twenty times, according to the 
 quantity of sugar indicated by a rough determination. Run the 
 diluted urine from a burette into the Fchling's solution, bringing it to 
 the boil each time urine is added, until, on allowing the precipitate 
 to settle, the blue colour is seen to have entirely disappeared from the 
 supernatant liquid. The observation of the colour must be made while 
 the liquid is still hot. Benedict's modification of Fehling's solution* 
 may also be employed. 
 
 Suppose that 10 c.c. of Fehling's solution is decolourized by 20 c.c. 
 of the ten-times diluted urine. Then 2 c.c. of the original urine contains 
 0-3 gramme dextrose. If the urine of the twenty-four hours (from 
 which this sample is assumed to have been taken) amounts to 4,000 c.c, 
 the patient will have passed 0-05 x 2,000= 100 grammes sugar, in 
 twenty-four hours. 
 
 {b) The polarinieter affords a rapid and, with practice, a delicate 
 means of estimating the quantity of sugar in pure and colourless solu- 
 tions, but diabetic urine must in general be first decolourized by adding 
 lead acetate and filtering off the precipitate. What is measured is the 
 amount by which the plane of polarization of a ray of polarized light of 
 given wave-length (say sodium light) is rotated when it passes through 
 a layer of the urine or other optically active solution of known thickness. 
 Let a be the observed angle of rotation, I the length in decimetres of 
 the tube containing the solution, w the number of grammes of the 
 optically active substance per c.c. of solution, and (a)n the specific 
 rotation of the substance for light of the wave-length of the part of the 
 spectrum corresponding to the D line {i.e., the amount of rotation 
 expressed in degrees which is produced by a layer of the substance 
 I decimetre thick, when the solution contains i gramme of it per c.c). 
 
 Then {a)o=±—,. In this equation a and / are known from direct 
 
 measurement; {a)o has been determined once for all for most of the 
 important active substances, and therefore w is easily calculated. For 
 dextrose {a)o may be taken as 52-6°. It varies somewhat with the 
 concentration, but for most investigations on the urine these variations 
 may be neglected. 
 
 It is not possible to describe here the numerous forms of polarimeter 
 that are in use. Those constructed on what is called the ' half -shadow ' 
 system (Fig. 197) give sufficiently satisfactory results. A half-shadow 
 polarimeter consists, like other polarimeters, of a fixed Nicol's prism 
 (the polarizer), and a nicol capable of rotation (the analyzer). In 
 addition, there is an arrangement which rotates by a definite angle the 
 plane of polarization in one-half of the field, but not in the other — 
 e.g.. a small nicol occupying only half of the field. In the zero position 
 of the analyzer, both halves of the field are equally dark. The solution 
 to be investigated is placed in a tube of known length, the ends of which 
 
 ♦ It contains i7"3 grammes of cupric sulphate, i73'o grammes of sodium 
 citrate, loo'o grammes of anhydrous sodium carbonate made up with 
 distilled water exactly to one litre. In making the solution the citrate and 
 carbonate are dissolved with the aid of heat in about 600 c.c. ot water, and 
 then made up to about 800 c.c. The cupric sulphate is dissolved in about 
 100 or 150 c.c. of water and added to the other solution, the whole being then 
 made up to a litre. 
 
52 i> 
 
 EXCRETION 
 
 arc closed by glass discs secured by brass screw caps. The glass discs 
 must be slid' on, so as to exclude all air. The tube having been intro- 
 duced between the polarizer and analyzer, the sharp vertical line which 
 indicates the division between the two half-fields is focusscd with the 
 cyc-piece, and then the analyzer is rotated till the two lialves are again 
 equally shadowed. The angle of rotation, a, is read off on the graduated 
 arc. which is provided with a vernier. 
 
 Pentoses reduce Fehling's solution, but do not give the yeast test. 
 Tliey give the following characteristic tests, which may be performed 
 with gum arable, a substance containing arabinose, one of the pentoses: 
 
 (i) Phloioglucin Reaction. — -Warm in a test-tube some pure concen- 
 trated hvdrochloric acid to which an equal volume of distilled water 
 has been added. Add phloroglucin until a little remains undissolved. 
 
 Fig. 197. — Mitscherlich's Polarimeter. (Half-shadow instrument.) (Simple form.) 
 
 Add a small quantity of gum arable, and keep the test-tube in a water- 
 bath at 100° C. The solution becomes cherry-red, and a precipitate 
 gradually separates, which may be dissolved in amyl alcohol. The 
 solution shows with the spectroscope a band between D and E. 
 
 (2) Orcin Reaction. — Use orcin instead of phloroglucin in (i). The 
 solution becomes reddish-blue on warming, and shows a band between 
 C and D, near D. The colour quickly changes from violet to blue, red, 
 and finally green. A bluish-green precipitate separates, which is 
 soluble in amyl alcohol. Glycuronic acid gives all the above reactions 
 of pentoses. 
 
 Bile-Salts [Hay's Test). — Put a little finely-divided sulphur, m the 
 form of flowers of sulphur, on the top of a glass of urine. If bile-salts 
 are present the sulphur will sink to the bottom. If there are no bile- 
 
PRACTICAL EXERCISES 5^9 
 
 salts il will float on the top. The difference is due to an alteration in 
 the surface tension of the urine produced by the bile-salts. We must 
 exclude the presence of acetic acid, alcohol, ether, chloroform, turpen- 
 tine, benzine and its derivatives, piienol and its derivatives, anilin and 
 soaps, all of which also cause such an alteration in the surface tension 
 of urine tluit the sulphur sinks to the bottom. The urine should be 
 fresh, and if it has to be kept it should be preserved from decomposition 
 by cyanide of mercury, which does not alter the surface tension. The 
 reaction has the great advantage over other tests of being easily carried 
 out at the bedside. 
 
 Acetone — (i) Legal' s Test (Rothera's modification). — To 5 to 10 c.c. 
 of the acetone-containing urine add enough ammonium sulphate crystals 
 to form a layer at the bottom of the test-tube, then 2 or 3 drops cf 
 a fresh 5 per cent, solution of sodium nitro-prusside and i to 2 c.c. of 
 strong ammonia. The development of a colour like that of perman- 
 ganate of potassium, often in the form of a ring a little above the 
 undissolved salt, indicates the presence of acetone. The reaction must 
 not be declared negative till half an hour has elapsed. The colour 
 slowly fades. 
 
 {2) Where there is doubt as to the presence of acetone, it is best first 
 to distil it over. Put 250 to 500 c.c. of the urine suspected to contain 
 acetone into a litre flask. Add a few c.c. of phosphoric acid; connect 
 the flask with a worm, and distil over the urine into a small flask. 
 For qualitative tests it is best to collect only the first 20 to 30 c.c, 
 as most of the acetone is contained in this. Test the distillate for 
 acetone by (i) or by 
 
 Lieben's Test. — To a few c.c. of the distillate in a test-tube add a few 
 drops of solution of iodine in potassium iodide, and then sodium or 
 potassium hydroxide. A precipitate of yellow iodoform crystals (six- 
 sided tables) is thrown down if acetone be present. Examine them 
 under the microscope. On heating, the odour of iodofonn may be 
 recognized. If the precipitate is amorphous it may be dissolved in 
 ether (free from alcohol), which is allowed to evaporate on a slide, 
 when crystals may be obtained. 
 
 Determination of the Freezing-Point of Urine.* — Study Beckmann's 
 apparatus shmvn in Fig. 171, p. 427. Note the large thermometer D 
 graduated in hundredths of a degree centigrade. It is inserted through 
 a rubber cork into the inner test-tube A. A platinum wire, F, bent 
 at the lower end into a circle or a spiral, which passes easily up and 
 down between the bulb of the thermometer and the tube, serves to stir 
 the urine. The thermometer must be so supported by the rubber 
 cork that the bulb is in the axis of the tube and a centimetre or two from 
 the bottom of it. The side-piece E on the tube A is not absolutely 
 necessary, but it is convenient for ' inocidating ' the urine with a crystal 
 oi ice at the proper time. A passes through a rubber cork into a shorter 
 and wider outer glass tube B. The space between A and B serves as a 
 badly conducting mantle, which prevents too rapid cooling of the 
 contents of A. B passes through a hole in the metal or wooden cover 
 of a strong glass jar, C, w-hich contains the freezing mixture. B should 
 fit the hole so tightly that it does not bob up out of the mixture when 
 A is removed. In C is a stirreir, G, of strong copper wire, the end of 
 which passes through the lid. This serves to stir up the freezing 
 mixture from time to time. 
 
 Pulverize some ice by pounding it in a strong wooden box with a 
 heavy piece of wood. Take the inner tube with the thermometer out 
 of the apparatus. It is convenient to take the thermometer out of the 
 
 * This is not often of cUnical value, but it affords an opportunity for the 
 student to practise a method of great importance in physiology. 
 
 34 
 
530 £XCRETI0>! 
 
 tube, and to hang it up carefully on a stand by means of a fine flexible 
 copper wire passing through the eye. The rubber cork can be taken 
 out with the thermometer, and the platinum wire also, the bent free 
 end of the latter supporting it in the cork, or it may be fiistened tempor- 
 arily to the thermometer stem by a small rubber band, which is slid 
 up over the cork when the thermometer is reinserted. Tube A can be 
 set temporarily in a specially heavy test-tube rack. Remove the lid 
 of C, and with it tube B. Now put ice and salt alternately into C until 
 it is nearly full, mixing them up well. Add some cold water from the 
 tap till the stirrer G can mo\ c freely up and down in the mixture. For 
 very exact work the temperature of the freezing mixture must not be 
 more than a few degrees below the freezing-point of the liquid which is 
 being examined. Put on the lid. and immerse tube B. Into A. which 
 must be perfectly clean, put enough pure distilled water to fully covet 
 the bulb of tlie thermometer, and introduce the latter. For ordinary 
 purposes distilled water previously boiled to expel the carbon dioxide, 
 and then cooled in a stoppered flask, is sufficiently pure. Immerse A 
 directly in the freezing mixture through the hole by which G comes out, 
 or through a separate hole (not shown in the figure) till some ice has 
 formed in the water. Take A out of the mixture, wipe it with a cloth, 
 and hold the lower part of it in the hand till nearly the whole of the 
 ice has melted. If there is a cake of ice at the bottom see that it is 
 displaced by the platinum stirrer. A trace of ice being still left floating 
 in the water, place A in B, and allow the temperature to fall to a few 
 tenths of a degree below tiic freezing-pcint you expect to get, as deter- 
 mined bj- a previous rough experiment. The freezing mixture is 
 stirred up occasionally . The meniscus of the thermometer is to be 
 carefully followed, as it goes on falling, bv means of a weak hand lens. 
 Now stir the water in A briskly. Suddenly it will be seen that the 
 mercury' begins to rise. Keep stirring with the platinum wire, and 
 read off the maximum height of the mercury, at which it is stationary 
 for some time. The temperature can be estimated between the gradu- 
 ations to thousandths of a degree. Take out A, and obser\e the fine 
 ice crystals in the water. Heat A in the hand as before till nearly all 
 the ice has disappeared ; then replace A in B. and make another freezing- 
 point determination. A third one may also be made, and the mean 
 of the three readings taken . 
 
 Take out the thermometer, and drj' it and the platinum wire with 
 clean filter-paper, or dip them in some of the urine, which is then thrown 
 awav. Dr\' A or rinse it with urine. Then make a determination of 
 the freezing-point of the urine in the same way as was done with the 
 water. The freezing-point of the urine will lie much lower on the scale. 
 
 Instead of freezing the liquid first and then leaving a little ice in it 
 when A is placed in B, A may be put into B before any ice has formed. 
 Cooling is then allowed to go on with gentle stirring to a few tenths of 
 a degree below the anticipated freezing-point. A small crystal of 
 clean dry ice is then introduced through the side-piece on a clean 
 splinter of wood or the loop of a cooled platinum wire, the end of which 
 passes through a piece of cork, by which it is held to prevent conduction 
 of heat. The platinum stirrer can be raised to receive the crystal. The 
 liquid is now vigorously stirred ; freezing occurs, and the observation is 
 made as before. 
 
 Instead of the above method, the liquid may first be cooled directly 
 in the freezing mixture, but not so much that ice forms. A is then put 
 in B, and cooling allowed to go on while it is being stirred. Wlien it 
 has been undercooled to a certain extent — i.e., cooled below its freezing- 
 point — the vigour of the stirring is increased. Ice forms suddenly, as 
 before, and the temperature rises to the freezing-point. With urine 
 
PRACTICAL EXERCISES 
 
 531 
 
 this method is sufficiently satisfactory, but it is not usually easy to get 
 freezing of the distilled water till the undercooling is considerable, and 
 it has been sliown that this introduces some error. 
 
 Suppose the freezing-point of the distilled water on the scale of the 
 thermometer was 5-245* and that of the urine 3-625°, the value of A 
 for the urine is 1-620°. Since for most purposes it is sufficient to fix 
 the second decimal point, much smaller and less expensive thermometers 
 than the ordinary Bcckmann may be employed. 
 
 In the same way the freezing-point of blood-serum (or blood), bile, 
 and other physiological liquids can be determined. 
 
 Systematic Examination of Urine. — In examining urine, it is con- 
 venient to adopt a regular plan, so as to avoid the risk of overlooking 
 anything of importance. 'I"he following simple scheme may serve as 
 an example; but no routine should be slavishly followed, the object 
 being to get at the important facts with the minimum of labour. More 
 extensive information must be sought in the treatises on examination 
 of the urine for clinical purposes. 
 
 1 . Anything peculiar in colour or smell ? If the colour suggests 
 blood, examine with spectroscope, hsemin test, guaiacum te^.. (pp. 76, 
 
 2-2) ; if it suggests bile, test for bile-pigments by Gmelin's test (p. 4O2), 
 and for bile-salts by Pettenkofer's test (p. 462) and by Hay's test 
 (pp.462. 528). 
 
 2. Reaction. 
 
 3. Sediment or not ? Sediment may be procured by letting the 
 urine stand in a conical glass, or in a few minutes by the centrifuge. 
 If the appearance of the sediment suggests anything more than a little 
 mucus, examine with the microscope. The sediment may contain 
 organized or unorganized deposits. 
 
 Organized Sediments. — (a) Red blood-corpuscles (considerably altered 
 if they have come from the upper part of the urinary tract). 
 
 {b) Leucocytes. A few are present in health. A large number 
 indicates pus. When pus is present the sediment may be white to the 
 naked eye. 
 
 (c) Epithelium from the bladder, ureters, pelvis of the kidney or the 
 renal tubules. A few squamous epithelial cells from the urethra are 
 always present in normal urine. 
 
 (d) Tube casts. 
 
 (e) Spermatozoa (occasional). 
 (/) Bacteria. 
 
 {g) Parasites (rare). 
 
 {h) Portions of tumours (rare) . 
 
 Unorganized Sediments. 
 
 IN ACID URINE. 
 
 Uric Acid. — Crystals coloured 
 brownish - yellow with urinary 
 pigment. Various shapes, espe- 
 cially oval ' whetstones,' rhom- 
 bic tables, and elongated crystals, 
 often in bundles (Fig. 177). 
 
 Urates. — Usually amorphous, in 
 the form of fine granules, often 
 tinged with urinary pigment, 
 sometimes brick-red. Soluble on 
 heating. On addition of acids 
 (including acetic acid) they dis- 
 
 IN ALK.\LINE URINE. 
 
 Triple Phosphate. — Clear, col- 
 ourless, coffin - lid or knife - rest 
 crystals. Also deposited in the 
 form of feathery stars (Fig. 179). 
 
 Calcium Hydrogen Phosphate 
 (' stellar ' phosphate), CaHP04. — 
 Crystals often wedge-shaped and 
 arranged in rosettes. May also 
 occur in a dumb-bell form. (A 
 phosphate of calcium is also occa- 
 sionally seen in weakly acid urine.) 
 (Fig. 181, p. 479 .) 
 
53» 
 
 EXCRETION 
 
 Unorganized Sediments (continued)—' 
 
 IN ACID URINE. 
 
 solve and uric acid cystals appear 
 in their place. Acid urate of 
 sodium and of ammonium occa- 
 sionally found in the crystalline 
 form (rosettes of needles). 
 
 Calcium Oxalate. — Octahedral, 
 ' envelope ' crystals, not coloured. 
 Insoluble in acetic acid. Soluble 
 in hydrochloric acid (Fig. 178, 
 
 P- 478). 
 
 Cystin. — Hexagonal plates . 
 Rare (Fig. 180, p. 470). 
 
 Lencin and Ty rosin (Figs. 186, 
 187, p. 488). — Rare. Also found 
 in alkaline urine, but rarely. 
 
 Triple Phosphate. — Sometimes 
 found in weakly acid urine. 
 
 IN ALK.M.IXE URINE. 
 
 Calcium Phosphate, Ca3(PO,)o. — 
 Amorphous. 
 
 Magnesium Phosphate. — Long 
 rliombic tablets, which arc dis- 
 solved at the edges by ammonium 
 carbonate solution, unlike triple 
 phosphate. All the above are 
 soluble in acetic acid without 
 effervescence. 
 
 Calcium Carbonate. — Small 
 spherical or dumb - bell - shaped 
 bodies soluble in acetic acid with 
 effervescence. 
 
 Ammonium Urate. — Dark balls, 
 often covered with spines. Soluble 
 in acetic or hydrochloric acid, 
 with formation of uric acid crys- 
 tals (Fig. 182, p. 479). 
 
 4. Specific gravity. 
 
 5. Quantity of urine in twenty-four hours. If the quantity is 
 abnormally large and the specific gravity high, test for sugar. 
 
 6. Inorganic constituents not generally of clinical importance, but 
 in special diseases they should be examined — e.g., chlorides in pneu- 
 monia. 
 
 7. Normal organic constituents. Sometimes quantitative estima- 
 tion of urea or total nitrogen in fever, and in diabetes and Bright's 
 disease. 
 
 8. Chemical examination for abnormal organic constituents, especi- 
 ally albumin and sugar. 
 
 Albumin.— (i) Heat to boiling some of the urine in a test-tube. A 
 precipitate insoluble on addition of a few drops of acetic acid consists 
 of coagulable protein. A precipitate soluble in acetic acid consists of 
 earthy phosphates. 
 
 (2) Heller's test. Put some strong nitric acid in a test-tube and 
 run on to it some urine. A white ring indicates protein. 
 
 A very rough quantitative estimation may be made by the method 
 of Ksbach (p. 523). 
 
 Sugar. — (i) Trommer's test. (Fehling's solution may be used.) 1* 
 the result is indecisive^ 
 
 (2) Phenyl-hydrazine test (p. 525)- 
 
 (3) In case of doubt confirm by yeast test. 
 
 A quantitative estimation may be made with Fehling's solution or 
 the polarimeter. 
 
CHAPTER X 
 
 METABOLISM, NUTRITION AND DIETETICS 
 
 We return now to the products of digestion as they are absorbed 
 from the ahmentary canal, and, still assuming a typical diet con- 
 taining carbo-hydrates, fats, and proteins, we have to ask, What 
 is the fate of each of these classes of proximate principles in the 
 body ? what does each contribute to the ensemble of vital activity ? 
 It will be best, first of all, to give to these questions what roughly 
 qualitative answer is possible, then to look at metabolism in its 
 quantitative relations, and lastly to focus our information upon 
 some of the practical problems of dietetics. 
 
 Section I. — Metabolism of Carbo-Hydrates — Glycogen. 
 
 The carbo-hydrates of the food, passing into the blood of the 
 portal vein in the form of dextrose, are in part arrested in the liver, 
 and stored up as glycogen in the hepatic cells, to be gradually given 
 out again as sugar in the intervals of digestion. The proof of this 
 statement is as follows : 
 
 Sugar is arrested in the liver, for during digestion, especially of a 
 meal rich in carbo-hydrates, the blood of the portal contains more 
 sugar than that of the hepatic vein. Popielski, on the basis of 
 experiments in which he fed with known quantities of sugar dogs 
 whose inferior vena cava and portal vein had been united by an 
 Eck's fistula, and determined the amount of sugar which passed 
 into the urine, estimates the quantity of sugar kept back by the 
 liver at from 12 to 20 per cent, of the whole. In the liver there 
 exists a store of sugar-producing material from which sugar is 
 gradually given ofi to the blood, for in the intervals of digestion the 
 blood of the hepatic veins contains more dextrose (2 parts per 1,000) 
 than the mixed blood of the body or than that of the portal vein 
 (about I part per 1,000). When the circulation through the liver 
 is cut off in the goose, the blood rapidly becomes free, or nearly free, 
 from sugar (Minkowski). And a similar result follows such inter- 
 ference with the hepatic circulation as is caused by the ligation of 
 the three chief arteries of the intestine in the dog, even when the 
 animal has been previously made diabetic by excision of the pancreas 
 
 (p. 636). 
 
534 METABOLISM. \CTRITIOX AXD DIETETICS 
 
 The nature of the sugar- forming substance is made clear by the 
 following experiments: (i) A rabbit after a large carbo-hydrate 
 meal, of carrots for instance, is killed and its liver rapidly excised, 
 cut into small pieces, and thrown into acidulated boiling water. 
 After being boiled for a few minutt-s, the pieces of liver are rubbed 
 up in a mortar and again boiled in the same water. The opalescent 
 aqueous extract is filtered off from the coagulated proteins. No 
 sugar, or only traces of it, are found in this extract; but another 
 carbo-hydrate, glycogen, a polysaccharide giving a port-wine 
 colour with iodine and capable of ready conversion into sugar by 
 amylolytic ferments, is present in large amount. (See Practical 
 Exeicises, p. 715.) 
 
 {2) The liver after the death of the animal is left for a time in 
 situ, or, if excised, is kept at a temperature of 35° to 40° C, or for 
 a longer period at a lower temperature; it is then treated exactly 
 as before, but no glycogen, or comparatively little, can now be 
 obtained from it, although sugar (dextrose) is abundant. The 
 inference plainly is that after death the hepatic glycogen is con- 
 verted into dextrose by some influence which is restrained or de- 
 stroyed by boiling. This transformation might theoretically be 
 due to an unformed ferment or to the direct action of the liver-cells, 
 for both unformed ferments and living tissue elements are destroyed 
 at the temperature of boiling water. It ha- been clearly shown 
 that the action is brought about by a diastatic enzyme, which some 
 wTiters call glycogenase, for it readily occurs when the minced liver 
 is mixed with, chloroform water, and chloroform kills all living 
 tissues. Although blood contains a diastase in small amount, the 
 change does not depend essentially upon this, since the glycogen 
 also undergoes hydrolysis (glycogenolysis) to dextrose when all the 
 blood has been washed out of the organ. Lymph also contains a 
 diastase, but there is evidence that the post-mortem glycogenolysis 
 is chiefly due to an enzyme contained in the hepatic cells (an endo- 
 enzyme) (Macleod). The diastases in the blood and lymph seem 
 to be ' discards ' of the tissues which are on the way to destruction 
 or ehmination (Carlson). The post-mortem change is to be regarded 
 as an index of a similar action which goes on during life: sugar in 
 the intact body is changed into glycogen; glycogen is constantly 
 being changed into sugar. There is no reason to doubt that here, 
 too, the hydrolysis is effected by the endo-enzyme. It might be 
 supposed, indeed, that the adjustment of the two processes glyco- 
 gi;nesis and glycogenolysis is simply a matter of the alteration of 
 the equilibrium in a reversible reaction (p. 338), according to 
 whether the dextrose content of the blood tends to rise or fall. If 
 the concentration of dextrose in the blood is increased, more dex- 
 trose might be expected to ' diffuse ' into the hepatic cells, whose 
 content of dextrose in proportion to glycogen would increase till 
 the equilibrium was restored by the conversion of the excess of 
 
METABOT.ISM OF CARBO-HYDRATES— GLYCOGEN 535 
 
 sugar into glycogen. Contrariwise, a diminution in the dextrose 
 content of the bK)od might be expeote<l to lead to diffusion of 
 ilextrose out of the liver-cells, and a consetjuent acceleration of the 
 hydrolysis of the glycogen. We have already learnt, however, that 
 in physiology — above all, perhaps, in the physiology of the glands 
 — ' simple ' explanations are usually suspect. And when we come to 
 study those conditions in which, as a consequence of the derange- 
 ment of the mechanisms which regulate the carbo-hydrate metabo- 
 lism, sugar appears in the urine, it will be seen that the matter is 
 more complicated. For one thing, the nervous system seems to 
 take a hand in the regulation, and where the nervous system takes 
 a hand things are generally doing which the experienced physiologist 
 does not expect to be simple. We may be certain, as in the case of 
 the intracellular proteolytic ferments, that the vital action of the 
 hepatic cells is a most important factor in controlling the rate of 
 production of the ferment, and therefore its concentration in rela- 
 tion to that of the substrate and the rate at which it works. 
 
 (3) With the microscope, glycogen, or at least a substance which 
 is very nearly akin to it, which very readily yields it, and which 
 gives the characteristic port-wine colour with iodine, can be actually 
 seen in the liver-cells. The liver of a rabbit or dog which has been 
 fed on a diet containing much carbo-hydrate is large, soft, and very 
 easily torn. Its large size is due to the loading of the cells with a 
 hyahne material, which gives the iodine reaction of glycogen, and 
 is dissolved out by water, leaving empty spaces in a network of cell- 
 substance. If the animal, after a period of starvation, has been 
 fed on protein alone, less glycogen is found in the shrunken liver- 
 cells; if the diet has been wholly fatty, little or no glycogen at all 
 may be found. Glycogen can even be formed by an excised liver 
 when blood containing dextrose is circulated through it. 
 
 A fact of great interfst recently demonstrated is that ir; animals 
 where the mobilization of the hepatic glycogen is accelerated (as 
 in rabbits after puncture of the medulla), glycogen in the form of 
 granules and small masses can be seen in the blood capillaries 
 (or rather sinusoids) between the liver cells, and in the sublobular 
 veins (Huber and Macleod). Chemical evidence has also i.icen 
 obtained of the presence of a glycogen-like polysaccharide in the 
 blood leaving the liver. 
 
 Formation of Glycogen from Protein. — In the liver-cells of the 
 frog in winter-time a great deal of this hyaline material — this 
 glycogen, or perhaps loose glycogen compound — is present; in 
 summer, much less. The difference is remarkable if we con- 
 sider that in winter frogs have no food for months, while summer 
 is their feeding-time; and at first it seems inconsistent with the 
 doctrine that the hepatic glycogen is a store laid up from surplus 
 sugar, which might otherwise be swept into the general circulation 
 and excreted by the kidneys. It has been found, however, that 
 
5.^6 METABOLISM. NUTRITION AND DIETETICS 
 
 the quantity of glycogen is greatest in autumn at the beginning of 
 the winter-sleep, and slowly diminishes as the winter passes on, 
 to fall abruptly with the renewal of the activity of the animal in 
 the spring. The glycogen T)resent at any moment is, therefore, 
 believed to be a residue, which represents the excess of glycogen 
 formed over gh'cogen used up; and the amount is larger in winter, 
 Rot because more is manufactured than in summer, but because 
 less is consumed. It is possible, indeed, to produce the ' summer ' 
 condition of the hepatic cells merely by raising the temperature of 
 the air in which a winter frog lives; at 20° or 25° C. glycogen dis- 
 appears from its liver. Conversely, if a summer frog is artificially 
 cooled, a certain amount of gljxogen accumulates in the liver. The 
 meaning of this seems to be that at a low temperature, when the 
 wheels of life are clogged and metabolism is slow, some substance, 
 probably dextrose, is produced in the body from proteins in greater 
 amount than can be used up, and that the svirplus is stored as 
 glycogen; just as in plants starch is put by as a reserve which can 
 be drawn upon — which can be converted into sugar — when the 
 need arises. That carbo-hydrates may be formed from proteins 
 (or their constituent amino-acids) has been shown in various ways — 
 for example, by feeding dogs with almost pure protein (casein) after 
 the production of permanent glycosuria by removal of the pancreas 
 (p. 636). To induce the animal to take the casein it had to be 
 mixed with a certain amount of butter, or serum, or meat extract. 
 The amount of sugar excreted was much more than could possibly 
 have come from the glycogen originally present in the animal's body, 
 computing it on the most generous scale (41 grammes per kilo- 
 gramme of body-weight, according to Pfliiger), or from free carbo- 
 hydrate present in traces in the food, or as prosthetic groups (p. 2) 
 in the ingested protein. That the source of the sugar was protein 
 and not fat was indicated by the fact that when the amount of 
 protein food was increased, the dextrose and the nitrogen excreted 
 increased proportionally (see also p. 538). 
 
 Glycogen-Formers. — ^As true glycogen-formers in the higher 
 animals — that is, compounds whose elements (particularly the 
 carbon) actually enter into the composition of the glycogen mole- 
 cule — may be mentioned such substances as proteins (including 
 gelatin), the fermentable sugars, and glycerin. In the case of 
 proteins it is, of course, not the entire molecule which is transformed 
 bodily into glycogen, but amino-acids yielded by them, or dextrose 
 derived from the amino-acids. The Hver is of itself capable of 
 dealing only with the dextrose, and not with the amino-acids. At 
 least, when the isolated liver (of the tortoise) is perfused with 
 blood containing amino-acids no increase in the glycogen of the 
 liver occurs. When glycerin is added to the blood the glycogen 
 content of the liver is very distinctly increased. Glycerin is a tri- 
 valent alcohol (CgHgOa) whose aldehyde, obtained from it by gentle 
 
METABOLISM OF CARBO-HYDFATF.S-GLYCOGEN 537 
 
 oxidation, is glyccrose (CjHgOg), a substance with the typical 
 properties of a sugar. In the laboratory it has been shown that 
 two niolc<mles of glyccrose can be combined to form one molecule of 
 sugar of the hexose type with six carbon atoms (CgHigOg). A similar 
 transformation is accomplished in the liver, and then a number of 
 the monosaccharide molecules (CgHigOg) are condensed with loss of 
 water to form glycogen. Thus, «(CgHi20g) -mH20 = (CgHioOg)^. 
 Since glycerin is a normal product of the hydrolysis of fats, the 
 possibility that the fats of the food may contribute through their 
 glycerin component to glycogen formation must be admitted. The 
 monosaccharides dextrose, levulose, and galactose gave a similar 
 result, while the disaccharides cane-sugar and lactose caused no 
 increase in the glycogen of the perfused liver, since the liver contains 
 no ferment capable of splitting them into monosaccharides. And 
 although the lirst step in the linking of the monosaccharide mole- 
 cules would seem to be the formr.tion of a disaccharide such as 
 maltose, the glycogen molecule must apparently be built up from 
 single ' bricks,' the monosaccharides, and cannot be constructed 
 from bricks which are already coupled in pairs, the disaccharides. 
 Of course, since the disaccharides are hydrolysed in the digestive 
 tube to simple sugars, they are to be reckoned with the true glycogen- 
 formers, for in the intact body they are presented to the hepatic 
 cells in the form of monosaccharides. It is probable that levulose 
 and galactose are first changed into dextrose. 
 
 By the action of alkalies such structurally related sugars can easily 
 be transformed into each other. Thus dextrose is an aldehyde of an 
 alcohol with six carbon atoms, and levulose the corresponding keto- 
 hexose . 
 
 By oxidizing the alcohol we get an aldehyde or a ketone, according 
 to whether a primary alcohol group (CHg.OH) or a secondary group 
 (CH.OH) is oxidized, with the loss of two atoms of hydrogen. The 
 
 aldehyde is characterized by the presence of the group C^'jr, the 
 
 ketone by the group CO. Both the aldehyde and the ketone are 
 sugars, and since each contains six carbon atoms, they are both sugars 
 of the group known as ' hexoses.' Dextrose, being not onlj- a hexose 
 but an aldehyde, may be called an ' aldohexose,' and levulose, being 
 not only a hexose but a ketone, a ' ketohexose.' 
 
 CH.OH C<0 CH,.0. 
 
 CH.OH CH.OH CO 
 
 I I I 
 
 CH.OH CH.OH CH.OH 
 
 I J i 
 
 CH.OH CH.OH CH.OH 
 
 I I I 
 
 CH.OH CH.OH CH.OH 
 
 J I I 
 
 CH2.OH CH2.OH CH2.OH 
 
 6-valent alcohol. Aldehyde, Ketone. 
 
538 METABOLISM. NUTRITION AND DIETETICS 
 
 That Icvulose can be changed into dextrose in the body is indi- 
 cated by the observation that after extirpation of the pancreas in 
 dogs the administration of levulosc is followed by an increase in 
 the excretion of dextrose nearly equal to the amount of levulose 
 ingested. It is also stated that, when the sur\iving liver of a 
 normal dog is perfused with a suspension of washed blood-corpuscles 
 to which levulose has been added, dextrose accumulates in the blood 
 and levulose disappears from it. 
 
 It has not hitherto been proved that the fatty acid component of 
 the food fats can be converted into glycogen. But a fattv acid, 
 propionic acid, is capable of complete transformation into dextrose 
 when given either by the mouth or subcutaneously to dogs under 
 the influence of phlorhizin (Ringer). Many other bodies are known 
 to influence the formation of glycogen by ' sparing ' substances 
 which are true glycogen-producers, but their carbon does not actu- 
 alty take its place in the glycogen molecule. It has been shown that 
 proteins can directly form glycogen or sugar apart from carbo- 
 hydrate groups contained in the protein molecule. For the proteins 
 of meat, gelatin, and casein are capable of forming 60 per cent, of 
 their own weight of dextrose in diabetic metabolism, and even the 
 end-products of pancreatic digestion of meat yield so much sugar 
 that the greater part of it must have come from the amino-bodies, 
 and not from a sugar-group in the protein. When given to dogs 
 with total phlorhizin glycosuria (p. 551), glycin and alanin are 
 completely, glutamic and aspartic acids in great part (corresponding 
 to about three carbon atoms of their respective molecules), converted 
 into dextrose (Lusk and Ringer), and there is no reason to doubt 
 that when such substances are produced by hydrolysis of protein 
 in the normal body, and are not all utilized in rebuilding the bio- 
 plasm, a portion of the surplus, after deamidization, can be trans- 
 formed into glycogen. 
 
 Extra-Hepatic Glycogen. — While the liver in the adult (con- 
 taining as it does from 2 to 10 per cent, of glycogen, or even, with 
 a diet rich in sugar or starch, more than 18 per cent.) may be looked 
 upon as the main storehouse of surplus carbo-hydrate, depots of 
 glycogen are formed, both in adult and foetal life, in other situations 
 where the strain of function or of growth is exceptionally heavy — 
 in the muscles of the adult (03 to 0-5 per cent, of the moist skeletal 
 muscle, or on a carbo-hydrate regimen 07 to 37 per cent.), in the 
 placenta, in many developing organs in the embryo (muscles, lungs, 
 epithelium of the trachea, oesophagus, intestine, ureter, pelvis of 
 kidney, and renal tubules). The fa'tus, however, is not, compared 
 with the adult, especially rich in glycogen. In the adult under 
 favourable circumstances the absolute amount of glycogen in the 
 muscles may be several times greater than that in the Hver, and 
 
MF.TAHOLISM OF CARBO-HY DRATES— GLYCOGEN 539 
 
 usually the hepatic glycogen makes up considerably less than half 
 the total glycogen of the body. That the muscles do not derive 
 their glycogen by the migration of hepatic glycogen, but can them- 
 selves form it from dextrose, has been shown by injecting that sugar 
 subcutaneously into frogs after excision of the liver. The muscle 
 glycogen was found to be increased. 
 
 Function and Fate of the Glycogen. — ^The glycogen store of the 
 liver fulfils a different function from that of the muscles. This is 
 indicated by the fact that when dogs, after being put on a given diet 
 for two or thr(>c days, are starved for a time, and then put again on 
 the original diet, the hepatic and the muscular glycogen behave 
 differently at first during the period of re-alimentation. While 
 glycogen accumulates in the liver in greater quantity than under 
 normal conditions of nutrition, in the muscles it at first accumulates 
 much less rapidly than normally. This is entirely in accordance 
 with the view that the hepatic glycogen store has for its great func- 
 tion the regulation of the sugar content of the blood in the interest 
 of all the tissues, while the gljxogen store of the muscles and other 
 tissues is mainly in the interest of their own nutrition and a source 
 of energy for their own work. This does not imply that, when sugar 
 is being absorbed in quantities too great for the liver to deal with 
 after the current needs of the tissues have been satisfied, they do 
 not add to their glycogen reserves. There is every reason to suppose 
 that they do so, and thus act as a subsidiary regulating mechanism, 
 although a less elastic one than that supplied by the liver. A third 
 way in which a portion of the surplus sugar can be stored is in the 
 form of fat. 
 
 When a fasting dog is made to do severe muscular work, the 
 greater part of the glycogen soon disappears from its liver. When 
 a dog is starved, but allowed to remain at rest, the glycogen still 
 markedly diminishes, although it takes a longer time; and at a 
 period when there is stiU plenty of fat in the body, there may be 
 only a trace of hepatic glycogen left. The glycogen which is usually 
 contained in the skeletal muscles also diminishes very rapidly in the 
 first days of hunger, but the heart contains the normal amount of 
 glycogen at a time when the proportion in the skeletal muscles has 
 sunk to ^ to y\p of the normal. 
 
 Tliese facts have been taken to indicate that glycogen and the sugar 
 formed from it are the readiest resources of the starving and working 
 organism, for the transformation of chemical energy into heat and 
 mechanical work. To borrow a financial simile, the fat of the body 
 has sometimes been compared to a good, but rather inactive security, 
 which can only be gradually realized; its organ-proteins to long-date 
 bills, which will be discounted sparingly and almost with a grudge; 
 its glycogen, its carbo-hydrate reserves, to consols, which can be turned 
 into money at an hour's warning. Glycogen, on this view, is especiall} 
 
540 METABOLISM. NUTRITION AND DIETETICS 
 
 drawn upon for a sudden demand, fat for a steady drain, tissue-protein 
 lor a life-and-death struggle. While there may be some such diflercnce 
 in the tenacity with which the different kinds of reser\e material are 
 held back from consumption when the floating supplies are wearing 
 low, modern investigation tends to the conclusion that the interchange- 
 ability of the various groups of nutritive substances is greater than 
 had been supposed, and that in the long-run the cells — in normal cir- 
 cumstances at least — never work without dextrose, even after the 
 glycogen store has been practically all consumed, but secure it from 
 other sources. 
 
 Pavy has put forward the heterodox view that the glycogen formed 
 in the liver from the sugar of the portal blood is never reconverted 
 into sugar under normal conditions, but is changed into some other 
 substance or substances, and he denies that the post-mortem formation 
 of sugar in the hepatic tissue is a true picture of what takes place 
 during life. But in spite of the brilliant manner in which he has 
 defended this thesis, both by argument and by experiment, it must be 
 said that the older doctrine of Bernard, which in the main we have 
 followed above, is attested by such a cloud of modem witnesses that it 
 seems to be firmly and finally established. 
 
 Fate of the Sugar — Glycolysis. — ^What, now, is the fate of the 
 sugar which either passes right through the portal circulation from 
 the intestine without undergoing any change in the liver, or is 
 gradually produced from the hepatic glycogen ? When the pro- 
 portion of sugar in the blood rises above a certain low limit (about 
 1-5 or 2 parts per 1,000), some of it is excreted by the kidneys 
 (Practical Exercises, p. 716). 
 
 A large meal of carbo-hydrates is frequently followed by a 
 temporary glycosuria, but much depends upon the form in which 
 the sugar-forming material is taken. We have seen that poly- 
 saccharides are quite incapable of absorption as such, and that they 
 must be very completely hydrolysed in the lumen of the alimentary 
 canal before their constituent sugars have any chance of reaching the 
 blood. It is therefore not to be expected that the rapid absorption 
 of such considerable quantities of sugar as would lead to its excretion 
 should easily occur when the carbo-hydrate is in this form. Miura 
 for example, after an enormous meal of rice (equivalent to 64 
 grammes of ash- and water-free starch per kilo of body-weight), 
 which, as he mentions, tasked even his Japanese powers of digestion 
 for such food to dispose of, found not a trace of sugar in the urine. 
 Dextrose, cane-sugar and lactose, on the other hand, when taken in 
 large amount, were in part excreted by the kidneys, as was also 
 the case with levulose and maltose in a dog (Practical Exercises, 
 p. 717).* The amount of any carbo-hydrate which can be eaten 
 
 * Twenty-four healthy students, whose urine had previously been shown 
 to be free from sugar, ate quantities of cane-sugar varying from 250 grammes 
 to 750 grammes. The urine was collected in separate portions for twelve 
 to twenty- four hours after the meal. In only three cases was reducing sugar 
 found in the urine (by Fehling's and the phenyl-hydrazine test), and then 
 merely in traces. In eight cases cane-sugar was found, and estimated by the 
 polarimeter, and, after boihng with hydrochloric acid, by Fehling's solutioa. 
 
METABOLISM OF CARBO-HYDRATES 54^ 
 
 without the appearance of sugar in the urine is sometimes called the 
 assimilation limit for that carbohydrate. The attempt has been 
 made to fix the limit of tolerance of dextrose for normal persons 
 and persons suffering from incipient diabetes, with the object of 
 aiding in early diagnosis of that condition. But the limit varies with 
 so many conditions, only some of which can be controlled, that such 
 observations are not easily interpreted. 
 
 Except as an occasional phenomenon, glycosuria other than ali- 
 mentary is inconsistent with health; and therefore in the normal 
 body the sugar of the blood must be either destroyed or transformed 
 into some more or less permanent constituent of the tissues. The 
 transformation of sugar into fat we have alreadj^ mentioned, and 
 shall have again to discuss; it only takes place under certain con- 
 ditions of diet, and no more than a small proportion of the sugar 
 which disappears from the body in twenty-four hours can ever, in 
 the most favourable circumstances, be converted into fat. The 
 dextrose which is taken up from the blood by the tissues and there 
 condensed to glycogen suffers sooner or later the converse change, 
 in all probability under the influence of diastases or glycogenases 
 produced in the cells, and reappears as dextrose to take its place 
 in the cellular katabolism and begin the series of cleavages and 
 oxidations by which its chemical energy is set free. Accordingly, 
 it is the destniction of sugar which concerns us here, and there is 
 every reason to believe that this takes place, not in any particular 
 organ, but in all active tissues, especially in the muscles, and to a 
 less extent in glands. 
 
 It has been asserted that the blood which leaves even a resting 
 muscle, or an inactive salivary gland, is poorer in sugar than that 
 coming to it ; and the conclusion has been drawn that in the metabo- 
 lism of resting muscle and gland sugar is oxidized, the carbon 
 passing off as carbon dioxide in the venous blood. This is indeed 
 extremely likely, for we know that, when the skeletal muscles of a 
 rabbit or guinea-pig are cut off from the central nervous system by 
 curara, the production of carbon dioxide falls much below that of 
 an intact animal at rest ; and the carbon given off by such an animal 
 on its ordinary vegetable diet can be shown, by a comparison of 
 the chemical composition of the food and the excreta, to come 
 largely from carbo-h\^drates. But, considering the relatively feeble 
 metabolism of muscles and glands when not functionally excited, 
 the large volume of blood which passes through them, the difftculty 
 of determining small differences in the proportion of sugar in such 
 a liquid, the possibilit}^ that even in the blood itself sugar may be 
 
 The greatest quantity of cane-sugar recovered from the urine was 8 grammes 
 (7-92 grammes by FehUng's method and 8-29 grammes by the polarimeter) ; 
 the highest proportion of the quantity taken which appeared in the urine was 
 2-5 per cent. When dextrose was found, cane-sugar was always present as 
 well. 
 
54^ METABOLISM, NUTRITION AND DIETETICS 
 
 destroyed, or that it may pass from the blood, without being oxi- 
 dized, into the lymph, too much weight may be easily given to the 
 results of direct analysis of the in-coming and out-going blood. 
 And although the results of Chauveau and Kaufmann, obtained in 
 this way, lit in fairly well with what we have already learnt by less 
 direct, but more trustworthy, methods, such as the study of the 
 respiratory exchange, they cannot be accepted as yielding exact 
 quantitative information. They found that in one of the muscles 
 of the upper lip of the horse the quantity of dextrose used up during 
 activity (feeding movements) was 35 times as much as in the same 
 muscle at rest, and this corresponded with the deficit of oxygen in 
 the blood entering the muscle, and with the excess of carbon dioxide 
 in the blood leaving it. More dextrose was also destroyed in the 
 active than in the passive parotid gland of the horse, but the excess 
 per unit of weight of the organ was far less than in muscle. In dogs 
 whose abdominal viscera have been removed, so that they constitute 
 practically preparations composed of skeletal muscles it has been 
 found that theamountof dextrosewhichdisappearsfrom 100 grammes 
 of blood per minute varies from 047 to 18 milligrammes, the irregu- 
 larities probably depending largely upon the irregular consumption 
 by the muscles of the glycogen stored in them (Macleod and 
 Pearce) . 
 
 Intermediary Metabolism of Carbo- Hydrates. — Concerning the pro- 
 cesses and the stages by which dextrose is destroyed in the tissues, 
 we have no very exact information, and it cannot be definitely stated 
 at present what share is taken by cleavage and what by oxidation, 
 or rather through what intermediate products, formed, it may be, 
 now by simple cleavage, now by oxidation, again by a combination 
 of cleavage and oxidation, the dextrose molecule is finally resolved 
 into carbon dioxide and water. It must be remembered that the 
 synthetic powers of animal cells are now known to be very extensive. 
 They build carbo-hydrates, fats, phosphatides, and proteins, as 
 well as destroy them, and at any of the earlier stages at any rate 
 the degradation products of dextrose, or some of them, may be 
 utilized in the construction of new compounds — for example, of fat — 
 either in the cells where they arise or elsewhere in the body. In 
 like manner the decomposition of a molecule of dextrose begun in 
 one cell or in one tissue may be consummated in another to which 
 intermediate products are conveyed in the blood. In such ways 
 it is obvious that the katabolic processes may be finely regulated 
 both qualitatively and quantitatively in accordance with the 
 specific wants of different organs and the intensity of their func- 
 tional activity from time to time. It must be said, however, that 
 at present there are few definitely ascertained facts to guide us in 
 trying to form a scheme of the actual changes which occur in the 
 intermediate katabolism of carbo-hydrates, and the sequence which 
 
METABOLISM Oh' CARBO-HYDRATES 543 
 
 they normally follow, dlycuronic acid has been previously men- 
 tioned as a substance occurring even in normal urine in small 
 amount. It is very closely related to dextrose, as a comparison of 
 their constitutional formulae shows: 
 
 C( )H COOH COH 
 
 I I I 
 
 H— C— OH H— C— OH H— CO— H 
 
 I I I 
 
 OH— C— H OH— C— H OH— C— H 
 
 I I I 
 
 H— C— OH H— C— OH H— C— OH 
 
 I I I 
 
 H— C— OH H— C— OH H— C— OH 
 
 I I I 
 
 CHgOH CHaOH COOH 
 
 d-de.\trose. <i-glyconic acid. <i-glycuronic acid. 
 
 Glycuronic acid agrees with dextrose in containing the character- 
 istic aldehyde group C^yj. but differs in that by oxidation two 
 
 atoms of hydrogen in the primary alcohol group CHgOH have been 
 replaced by one atom of oxygen. There is reason to believe that 
 in the tissues glycuronic acid can be formed from dextrose in the 
 same way, possibly through the mediation of an enzyme, and it 
 may therefore represent a stage in the katabolism of sugar. But 
 it is not known whether this is a normal transformation through 
 which the whole or the greater part of the dextrose passes, or only 
 a transformation involving a small part of the sugar under normal 
 conditions. The appearance in the urine of large quantities of 
 glycuronic acid, paired as already explained with various com- 
 pounds, in certain pathological states or after the administration 
 of certain drugs (p. 48-.-'), might be explained either as the result of 
 an increased production of that substance through a deflection of the 
 normal trend of carbo-hydrate degradation, or as the result of a failure 
 on the part of the cells to further transform the glycuronic acid in 
 the quantities normally produced. 
 
 Lactic acid is the one intermediate stage in the decomposition of 
 dextrose in the tissues whose importance seems to be definitely 
 ascertained. The muscles and the liver have been proved to possess 
 the power of producing lactic acid from dextrose obtained directly 
 from the blood or from the hydrolysis of their own store of glycogen, 
 and there is little doubt that this power is shared by many, perhaps 
 by all, of the other organs. There is also good evidence that the 
 lactic acid thus formed can be, and under normal conditions is, in 
 large part oxidized so as eventually to yield carbon dioxide and 
 water, although there is reason to believe that a portion of it may 
 be utilized for the synthesis of more complex bodies. 
 
 The chemistry of the change or series of changes by which lactic 
 acid is produced from dextrose and the end-products, carbon dioxide 
 
544 
 
 METABOLISM. NUTRITION AND DIETETICS 
 
 and water, from lactic acid has given rise to much discussion, and is 
 not yet clearly known. The following scheme, based on the researches 
 of Embden and others, and quoted from Abderhalden, illustrates one 
 suggestion as to the course of the series of transformations, although 
 it must be taken only as a diagram of the sequence of some of the 
 possible stages. A molecule of dextrose is represented as giving rise 
 to two molecules of glyceric aldehyde, each of which then yields a mole- 
 cule of lactic acid. Each molecule of lactic acid, losing two atoms of 
 hydrogen, becomes converted into a molecule of pyruvic acid, which 
 by the loss of the elements constituting a molecule of carbon dioxide 
 becomes acetaldehyde or acetic aldehyde, and this by oxidation acetic 
 acid, which is then oxidized to carbon dioxide and water. Thus — 
 
 <g 
 
 H— C— OH 
 
 I 
 HO— C— H 
 
 I 
 H— G— OH 
 
 I 
 H— C— OH 
 
 I 
 CH2OH 
 
 (i-dextrose. 
 
 COOH 
 
 CO - CO2 
 
 I 
 CH3 
 
 Pyruvic acid. 
 
 [\H 
 H— C— OH 
 
 I 
 CHgOH 
 
 p/O 
 |\H 
 
 H— C— OH 
 
 CH2OH 
 
 2 molecules 
 glyceric aldehyde. 
 
 r^O 
 ^\H 
 
 \ 
 
 y" 
 
 COOH 
 
 I 
 H— C— OH -Ho 
 
 I 
 CH, 
 
 <f-lactic acid. 
 
 COOH 
 
 -> 
 
 + 
 
 + 4O 
 
 CH3 
 
 Acetaldehyde. 
 
 CH3 
 
 Acetic acid. 
 
 2CO3 
 
 2H2O 
 
 Carbon dioxide 
 and w.iter. 
 
 It has been shown that acetaldehyde and carbon dioxide are formed 
 from pyruvic acid by the action of a ferment contained in yeast, and 
 there is some evidence that a similar transformation may occur in the 
 liver. 
 
 It is to be particularly remarked that according to this scheme 
 the whole of the dextrose molecule is still represented in the lactic 
 acid formed from it. Up to this stage no part of the molecule has 
 been burnt. Nearly the whole of the chemical energy — ie., all but 
 about 3 per cent, of it — is still available. For a gramme of lactic 
 acid yields 3,661, and a gramme of dextrose 3,762, small calories on 
 complete combustion. The intermediate products of the decom- 
 position may therefore be transported from the place of origin and 
 utilized elsewhere with scarcely any loss of energy. Further, it is 
 indicated in the scheme that the degradation process is not merely 
 a series of cleavages and oxidations, but that these may be inter- 
 spersed with stages of reduction. It is also clearly suggested that 
 at certain points the metabolism may become recessive and syn- 
 
METABOr.fSM OF CARBO.HY DP ATES 545 
 
 theses be started, which may go far to retrace the steps of the pre- 
 ceding katabohsm in respect to a portion of the dextrose. 
 
 Thus, lactic acid can be retransformed into dextrose (Mandel and 
 Lusk). and this, of course, into glycogen. Pyruvic acid can be 
 changed into lactic acid by reduction, and dextrose can in this way 
 be again produced. There is evidence also that under certain 
 conditions pvrmic acid can yield dextrose in the organism by a 
 cUffert-nt reaction, being changed into acetaldehyde, which can 
 tlien undergo transformations leading back to dextrose (Ringer). 
 The formation of fat from sugar may also start from some of the 
 stages displayed in the scheme, for it is only a short step to obtain 
 by the reduction of glyceric aldehyde its alcohol glycerin. And 
 from acetaldehyde fatty acids can be derived. 
 
 Not only does lactic acid afford a point of contact between the 
 metabolism of carbo-hydrates and that of fats — a junction, so to 
 speak, where these two great metabolic currents cross each other, 
 and where material originating in the one may be shunted into the 
 other- — but it also affords a point of junction and interchange with 
 the current of protein metabolism. For example, the amino-acid, 
 alanin, yields as a decomposition product a compound called 
 methylglyoxal (CH3.CO.CHO), a ketonic aldehyde, which by the 
 assumption of a molecule of water can be changed into lactic acid. 
 It may also be one of the intermediate stages in the decomposition 
 of dextrose as a precursor of lactic acid, and one of the ways in 
 which the conversion of amino-acids into dextrose is accomplished 
 may be through this link. The presence of a ferment glyoxalase, 
 or probably more than one ferment which rapidly changes methyl- 
 glyoxal into lactic acid, has been demonstrated in tissue extracts 
 and in leucocytes. The same change is effected when blood con- 
 taining methylglyoxal is perfused through an excised surviving 
 liver. The reaction can be reversed for methylglyoxal like lactic 
 acid when given to an animal rendered diabetic by phlorhizin can be 
 shown to yield dextrose, possibly being first converted into glyceric 
 aldehyde. The conversion of methylglyoxal into lactic acid is also 
 a reversible reaction, for in vitro, at any rate, lactic acid readily 
 yields methylglyoxal (Dakin). 
 
 Pyruvic acid is another possible link. As has just been mentioned, 
 it probably forms a stage in the decomposition of dextrose, and has, in 
 addition, chemical relations on the one hand to certain of the amino- 
 acids, especially to alanin, and on the other to glycerin and even to 
 fatty acids. Thus — 
 
 CH, 
 
 1 ^ 
 
 CH, 
 
 1 ^ 
 
 CH2.OH 
 
 CH, 
 
 1 ' 
 
 CH.NHo + O 
 
 1 " 
 
 = CO 4-NH3 
 
 CH.OH+2O 
 
 = CO + 2H 
 
 1 
 
 COOH 
 
 Alanin (a-amino-pro- 
 pionic acid. 
 
 COOH 
 
 Pyruvic acid. 
 
 CHg.OH 
 
 Glycerin. 
 
 COOH 
 
 Pyruvic acid. 
 
 35 
 
5j6 METABOLfSM, Nl'TRfTlOS AXD DIETETICS 
 
 The following scheme, doubtless incomplete, illustrates a probable 
 chemical sequence through which the interconversion of alanin, lactic 
 acid, methylglyoxal and dextrose may be brought about by reactions 
 only involving the addition or removal of water or ammonia (Dakin) : 
 
 Dextrose 
 
 i! 
 
 Lactic acid ZH Methylglyoxal Z^ Alanin 
 
 (CH3.CHOH.COOH) (CHg.CO.CHO) (CH3CH.NHj.COOH) 
 
 Since pyruvic acid can be reduced to lactic acid, any reaction in 
 which it plays a part in the intermediary metabolism of carbohydrates 
 or proteins can also be fitted into the scheme. 
 
 The more completely the various steps in the metabolism of the 
 three great groups of food substances are unveiled, the more 
 clearly does it appear that, far from being independent circuits, 
 the three currents are constantly exchanging materials with each 
 other. 
 
 It is to be supposed that in many of these transformations 
 enzvmes are concerned, although comparatively little is definitely 
 known as to this. Normal blood itself has been credited \vith a 
 ferment which has the power of destroying sugar (glycolysis). 
 But with rigid aseptic precautions the loss of sugar, even in several 
 hours, is small, and it is doubtful whether such a ferment exists. 
 Even under the most favourable circumstances the quantity of 
 dextrose which blood can destroy is so small a fraction of that which 
 disappears in the same time in the body, that it is probably of no 
 importance in carbo-hydrate metabolism (Macleod). On the 
 other hand, Cohnheim stated that while no glycolytic ferment can 
 be demonstrated in the pancreas, and only an exceedingly' weak 
 glycolytic action in muscular tissue (Brunton), by combining ex- 
 tracts of pancreas and extracts of muscles, distinct glycolysis, due 
 to a ferment action, could be produced. He suggested that the 
 glycolytic ferment is activated by another substance, as trypsinogen 
 is activated by enterokinase (p. 372). This announcement aroused 
 great interest, since it is known that the pancreas is intimately 
 concerned in the metabolism of sugar. That sugar disappears 
 under the conditions of Cohnheim's experiments has been confirmed 
 by a number of observers. But his interpretation of his results lias 
 not been generally accepted. According to Levene and Meyer, 
 the dextrose, far from being burnt, seems to be condensed to a poly- 
 saccharide, and can be recovered by hydrolysing this compound 
 when the mixture is acted on by dilute acid. The action of the 
 pancreas- muscle mixture is, therefore, not a true glycolysis. In- 
 deed, of all the tissues investigated by Levene, leucoc^'tes alone can 
 be credited with a real glycolytic action. Excision of the pancreas 
 in dogs causes permanent glycosiuria (pancreatic diabetes) (v. Mering 
 and Minkowsla), which is prevented if a portion of the pancreas be 
 
METABOLISM OF CARBO-HYDRATES— GLYCOSl^RTAS 547 
 
 loft (p. 636). Diabetes in man is known to be frequently associated 
 with pancreatic lesions. Although much still remains obscure, the 
 study of this pathological form of glycosuria and of the experimental 
 glycosurias has thrown light upon the normal metabolism of carbo- 
 hydrates and upon those regulative mechanisms whose breakdown 
 is responsible for the excretion of sugar. It will be best to discuss 
 the experimental glycosurias first, and to begin with the form which 
 probably is better understood than any other, the so-called punc- 
 ture glycosuria. 
 
 Puncture Glycosuria — Sugar-Regulating Mechanism. — An arti- 
 ficial and temporary glycosuria, in which the sugar in the urine un- 
 doubtedly arises from the hepatic glycogen, can be caused by punc- 
 turing the medulla oblongata in a rabbit — for example, at a lev^el 
 between the origins of the auditory nerves and the vagi. It is stated 
 that a puncture of the thalamencephalon, or 'tween-brain (p. 850), 
 produces the same effect. If the animal has been previously fed with 
 a diet rich in carbo-hydrates — that is, if it has been put under con- 
 ditions in which the liver contains much glycogen — the quantity of 
 sugar excreted by the kidneys mil be large. The immediate cause 
 of the glycosuria is an increase in the sugar content of the blood 
 (hyperglycaemia), an increase which is most pronounced in the blood 
 of the hepatic vein. If, on the other hand, the animal has been 
 starved before the operation, so that the liver is free, or almost free, 
 from glycogen, the puncture will cause little or no sugar to appear 
 in the urine, and the proportion of sugar in the blood will remain 
 normal. That nervous influences are in some way involved in the 
 mobilization of the glycogen reserve of the liver is shown by the 
 absence of glycosuria if the splanchnic nerves, or the spinal cord 
 above the third or fourth dorsal vertebra, be cut before the puncture 
 is made. But sometimes these operations are themselves followed 
 by temporary glycosuria, due, it is believed, to irritation of the 
 same eferent nervous path whose elimination when the splanchnics 
 are divided prevents the glycosuria. The simplest explanation of 
 the phenomena is that a ' sugar centre ' — that is to say, a centre 
 which has the important ofhce of regulating the sugar content of the 
 blood by governing the rate at which glycogen is built up and de- 
 composed in the liver, as the salivary centre regulates the rate at 
 which the constituents of saliva are formed and discharged — has 
 been injured or irritated by the puncture. If a nervous centre does 
 in fact preside over this internal secretion of the liver, it will, of 
 course, be connected with efferent and afferent nerves. The former, 
 as defined by the experiments alluded to, seem to be confined to 
 the splanchnic nerves; the latter are believed to run especially, 
 though not exclusively, in the vagus. Section of the vagi has no 
 effect either in causing glycosuria of itself or in preventing the 
 ' puncture ' glycosuria, but stimulation of the central ends of these 
 
54'^ METABOLISM. NUTRITION AND DIETETICS 
 
 and of otluT afferent nerves may cause sugar to appear in the 
 urine, altfiough not, it is said, if precautions are taken to prevent 
 any degree of asphyxia. Asphyxia produces an increase in the 
 sugar content of the blood, an increase in the flow of urine and 
 glycosuria. 
 
 It has usually been assumed that this action of asphyxia is due to 
 the effect upon the centre of blood over-rich in carbon dioxide (and 
 other metabolic products) or impoverished as regards oxygen. But 
 there is some evidence that the altered blood may also affect the 
 liver-cells directly, or, what comes to the same thing in the long-run, 
 that interference with the internal respiration of the hepatic tissue, 
 operating, it may be, through an increase in the concentration of the 
 hydrogen ions, upsets the equilibrium of those intracellular reactions 
 by which glycogen is formed from dextrose and dextrose from 
 glycogen. In like manner it may be supposed that under normal 
 conditions the rate of transformation of the hepatic glycogen into 
 dextrose is adjusted to the dextrose content of the blood, not only 
 by reflex nervous impulses passing through the sugar-regulating 
 centre, but also by the direct influence of the dextrose itself circu- 
 lating in the blood, upon whose concentration the reaction of the 
 centre on the one hand and of the liver-cells on the other may in 
 part depend. So that when the proportion of sugar in the blood 
 tends to sink we may perhaps picture the centre as sending impulses 
 to the liver which increase the rate at which the glycogen is hydro- 
 lysed; and when the proportion tends to rise, we may think of it as 
 sending impulses which inhibit the hydrolysis, both effects being 
 accentuated by the direct influence of the changes of concen- 
 tration on the hepatic cells. Whatever the mechanism may be 
 through which the puncture hastens the transformation of glycogen 
 into dextrose in the liver, there is no evidence that the amount of i lie 
 enzyme which hydrolyses the glj^cogen is increased. Whether the 
 action of the enzyme is favoured in some other way — e.g., by the 
 production of a co-ferment or by some change in the condition of 
 the glycogen which renders it more open to attack — is unknown. 
 
 Certain facts have recently been brought forward which go to 
 show that the action of the splanchnic fibres on the liver is not 
 a direct action, but that in some way or other tlie concomitant 
 activity of the adrenal glands is essential. For if the adrenals have 
 been previously extirpated, the puncture does not cause glycosuria. 
 It was at first thought that the reason for this was that the removal 
 of the adrenals is itself followed by the disappearance of glycogen 
 from the liver, and, as has been pointed out, the presence of glycogen 
 in the liver is essential to the success of the puncture experiment. 
 The matter, however, is not so simple. For although in certain 
 animals — e.g., the dog — the liver does lose all its glycogen when the 
 adrenals have been taken away, this is not the case in the rabbit. 
 
METABOLISM OF CARBO-HYDRATES-GLYCOSURIAS 549 
 
 and yet in the rabbit also the urine remains free from sugar after 
 puncture in the absence of the adrenal glands. In some way or 
 other, then, the adrenals do intervene in the production of puncture 
 glycosuria. The observation, which is easily confiimed, that the 
 injection of adrenalin (or epinephrin) (p. 550) under the skin or into 
 the blood, or into one of the serous sacs, does cause a pronounced 
 increase in the sugar content of the blood, and the appearance of 
 dextrose in the urine, seemed at first to supply the missing link n 
 the chain of evidence. What could be simpler than the assumpt: n 
 that the splanchnic fibres stimulated in the puncture experimi nt 
 were fibres going not to the liver, but to the adrenals, which ocra- 
 sioned an outpouring of adrenalin into the blood, and that puncture 
 glycosuria was therefore merely a particular case of adrenalin glvco- 
 suria ? It is known that excitation of the splanchnic nerves cau es 
 the passage of adrenalin into the blood of the adrenal veins (p 661). 
 It is known that puncture of the medulla oblongata diminishes tlie 
 epinephrin content of the adrenal glands. The argument seened 
 straightforward, and the adrenal hypothesis of puncture glycos^:ria 
 triumphant. As soon, however, as the matter was put to the test 
 of quantitative experiments, the hypothesis began to crumble. It 
 was shown, for example, that during a stimulation of the splanchnic 
 nerves sufficient to cause a decided increase in the dextrose content 
 of the blood, a quantity of adrenalin was given off to the adrenal 
 veins, which, when mingled with the rest of the blood on its way 
 to the liver, could not possibly amount to more than one in a hundred 
 million parts of blood, a concentration in which adrenalin, when 
 introduced artificiall}' into the blood-stream, produces no glj-coiU-ia 
 whate\'er. Still more significant is the fact that, after destroying the 
 hepatic plexus, stimulation of the splanchnic nerves causes no in- 
 crease in the blood-sugar in spite of the increased output of adrenalin 
 by the way of the adrenal veins. On the other hand, excitation 
 of the hepatic plexus causes hyperglycaemia (Macleod and Pearce). 
 It is not, then, a direct action on the liver of epinephrin secreted in 
 response to stimulation of splanchnic fibres supplying the adrenal 
 glands which is responsible for the increase in the dextrose content 
 of the blood. The adrenals, however, pla}' some part. For in their 
 absence stimulation of the hepatic plexus is not followed by hyper- 
 glycaemia. But whether this is due to general derangement of the 
 normal carbo-hydrate metabolism in their absence, or to the loss of 
 some special influence on the liver, without which stimulation of the 
 hepatic plexus is ineffective, is unknown. 
 
 Although several of the operations which lead to temporary 
 glycosuria undoubtedly bring about changes in the hepatic circula- 
 tion, it is as yet impossible to say whether vaso-motor effects con- 
 tribute essentially to the result, or whether it is due entirely to 
 nervous stimulation of the liver-cells, or to withdiawal of such 
 
550 METABOLISM, NUTRITION AND DIETETICS 
 
 stimulation or control (sec also p. 509). There is some c\adence 
 that excitation of the uncut great splanchnic nerve (on the left side) 
 in dogs may cause hyperglycaemia, diuresis, and glycosuria, even 
 imder conditions in which as far as possible circulatory effects are 
 eliminated. Contrariwise, when in the puncture experiment on an 
 unnarcotized animal the small instrument does not wound the 
 medulla oblongata in the right place, a rise of blood-pressure due 
 to excitation of the vaso-motor centre may occur without any 
 glycosuria. But absolute proof of the existence of glycogenolytic 
 nerve fibres going to the liver — that is, fibres whose stimulation 
 accelerates the hydrolysis of glycogen into dextrose (Macleod) — has 
 not yet been brought forward. 
 
 Adrenalin Glycosuria.— In adrenalin glycosuria the sugar-content 
 of the blood is increased. A given quantity of adrenalin introduced 
 subcutancously produces a more marked hyperglycemia and 
 glycosuria than the same amount injected into a vein or into muscle. 
 The best evidence is that the glycosuria is produced by some action 
 on the liver, possibly through the excitation of sympathetic fibres 
 controlling the production of dextrose from glycogen (Underbill and 
 Closson), or by a direct effect on the hepatic cells, which hastens the 
 normal transformation of glycogen into dextrose, or hinders the 
 normal transformation of dextrose into glycogen. It has been 
 stated that in the isolated surviving liver of the frog adrenalin causes 
 the glycogen to be rapidly converted into dextrose. While this 
 confirms the view that experimental adrenalin glycosuria is due to 
 an action on the liver which increases the sugar-content of the blood, 
 it docs not necessarily show that the action is exerted directly on 
 the hepatic cells without the intervention of nerve fibres. For the 
 sympathetic nerve-endings may survive a considerable time. The 
 theory that epinephrin causes glycosuria by inhibiting the internal 
 secretion of the pancreas, and that the condition is therefore a par- 
 ticular variety of pancreatic diabetes, is erroneous. Adrenalin 
 glycosuria does not seem to be in any way related to true 
 diabetes. The complete metabolism of dextrose is not interfered 
 with. Indeed, a much larger proportion of tlie total heat produced 
 comes from the destruction of sugar after the subcutaneous injection 
 of epinephrin into dogs than in the normal animals (Lusk and Riche). 
 If in spite of this glycosuria ensues, it is only because the carbo- 
 hydrate reserve of the body is mobilized so rapidly that it cannot 
 possibly be all consumed. Nor does epinephrin cause any increased 
 production of sugar from protein or from fat. For in dogs rendered 
 diabetic by phlorhizin and freed from glycogen by shivering, injec- 
 tion of epinephrin is not followed by an increase of either sugar or 
 nitrogen in the urine (Ringer). After repeated injections of adren- 
 alin, a tolerance for it is established, and glycosuria is no longer 
 caused. 
 
MET.inOlJSM OF CARIiO-ini)jrt IliS -Cl.yCOSIJ^IAS 551 
 
 Fhlorhizin Glycosuria, produced by subcutaneous injection of the 
 glucoside phlorhizin, agrees vvitli pancreatic, but differs from punc- 
 ture diabetes in this, that it can be produced in an animal free 
 from glycogen, and is accompanied by extensive destruction of 
 proteins. It differs from other forms of diabetes in being associated, 
 not with an increase, but with a diminution, in the sugar of the blood. 
 This is best explained by supposing that the phlorhizin acts on the 
 kidney in such a way as to increase the permeability of the glomeru- 
 lar epithelium for sugar, or (in terms of the secretion theory of urine 
 formation) in such a way as to increase its sensitiveness to the 
 stimulus of sugar circulating in the blood. The sugar is therefore 
 rapidly swept out of the circulation, and this leads secondarily to 
 an increased production of sugar to make good the loss. In addi- 
 tion, within certain limits there is a total inability on the part of 
 the body to consume dextrose. 
 
 After the preliminary sweeping out of the sugar already in the 
 bod}^ a definite ratio is established between the dextrose and the 
 nitrogen eliminated in the urine (dextrose : nitrogen : : 3-6or 37 : i). 
 The sugar at this stage is produced entirely from proteins, and not 
 at all from fat. It is a fact of considerable interest that, if small 
 quantities of dextrose are now given, the amount of protein de- 
 stroj'ed is reduced to some extent, although all of the dextrose is 
 excreted, and none of it is burnt (Ringer). This supports the 
 hypothesis of Landergren that in starvation some of the protein is 
 metabolized for the formation of the indispensable dextrose, and 
 that this fraction can be ' spared ' by carbohydrate, though not by 
 fat. The protein metabolized is so much increased under the 
 influence of phlorhizin that it exceeds the starvation requirement 
 by a greater amount than in pancreatic diabetes, perhaps because 
 the diminished content of sugar in the blood constitutes a more 
 insistent call upon the proteins to produce sugar. In pancreatic 
 diabetes, where hyperglycaemia exists, there can at least be no 
 reason for the formation of sugar from protein for the maintenance 
 of the normal sugar-content of the blood, and it is interesting that 
 in this condition the giving of dextrose does not seem to spare any 
 protein (p. 606). The degree of intolerance for carbo-hydrates in 
 pathological diabetes may be arrived at by putting the patient on 
 a diet of protein and fat (rich cream, meat, butter, and eggs), and 
 determining the ratio of dextrose to nitrogen excreted. If it is 
 3-6 or 37: I, intolerance is complete, none of the dextrose produced 
 from protein being burned (Lusk and Mandel). 
 
 Glycosuria can be caused in many other ways than those already 
 mentioned. Sometimes the action seems to be a direct one on the 
 sugar-regulating centre — e.g., in concussion of the brain, occlusion 
 and subsequent release of the arteries supplying the brain and 
 cervical cord, and acute haemorrhage. Carbon monoxide has a 
 
552 MI^T.IBOLISM. SLTh'lTIOX AXl) DIETETICS 
 
 similar action owing to the dcticicncy of oxygen occasioned by it. 
 Many drugs also cause glycosuria, including curara, morphine, 
 strychnine, phosphorus, chloroform, ether, and other substances, 
 some of which may act on the ' sugar centre,' although others — e.g., 
 phosphorus and chloroform — are poisons which can affect the liver 
 directly. It is probable that some of the experimental hypcr- 
 glycccmias are due to an associated acidosis. For when the hydrogen- 
 ion concentration of the blood is increased the transformation of 
 glycogen into dextrose in the liver is accelerated. The adminis- 
 tration of alkali is said to have a beneficial influence upon the 
 oxidation of dextrose in dogs after total or partial extirpation of the 
 pancreas (Murlin and Kramer). Injection of water or physiological 
 salt solution into the bile-ducts, or into the mesenteric veins, or of 
 salt solution in considerable amount into the general circulation, 
 is followed by glycosuria (Fischer, etc.). It is a mistake to apply 
 the term diabetes to most of the forms of artificial hyperglycremia 
 and glvcosuria. The condition produced by removal of the pan- 
 creas, which will be returned to in Chapter XL, is, however, a true 
 diabetes, a derangement of metabolism of the sam** general nature 
 as that which underUes human diabetes. 
 
 Diabetes Mellitus. — In the natural diabetes of man, as in all 
 the forms of glycosuria mentioned, with the exception of that pro- 
 duced bv phloriiizin, the immediate cause of the ghxosuria is the in- 
 crease of sugar in the blood. Instead of the i part per 1,000, or a 
 little more or less, which constitutes the normal proportion in a 
 healthy man, in diabetes 3 or 4 parts, and in exceptional cases even 7 
 to 10 parts per i.ooo may be present. The riddle of diabetes is the 
 explanation of this persistent hyperglycsemia. Innumerable hypo- 
 theses have been framed to account for this, but on the whole 
 three possibilities have been emphasized: (i) That the power of 
 temporarily storing carbohydrates is deranged; (2) that the power 
 of the tissues to utilize carbo-hydrates [i.e., eventually dextrose) 
 is diminished or abolished; (3) that too much sugar is produced in 
 the body. In addition, some writers have postulated a fourth 
 factor to explain certain cases (of so-called ' renal diabetes ') — to wit, 
 an increase in the permeability of the kidneys for sugar, as in 
 phlorhizin glycosuria. Lest the student should be bewildered 
 amongst all these theories, he should take note that while the second 
 factor is now recognized as the essential one, there is some reason 
 to believe that diabetes mellitus is not in every case a single patho- 
 logical condition, but may comprise a group of such conditions. 
 Some cases mav therefore present a picture conforming closely to 
 one or to another of the experimental glycosurias, but others a 
 picture compounded of features characteristic of two or of several 
 of these experimental conditions. 
 
MI'TABOl.lSM OF CA h'BO-HY Dh'AI l-S CLYCOSU /^ I A S 553 
 
 It is possible that in some cases the sugar coming from the aH- 
 mentary canal passes entirely or in too large amount through tl:c 
 liver, owing to a deficiency in its power of forming glycogen. But 
 although in certain cases of diabetes specimens of the hepatic cells, 
 obtained by plunging a trocar into the liver, have been found free 
 from glycogen, in others gtycogen has been present. The muscles 
 also are usually stated to be much poorer in glycogen than normal 
 muscles, but this might just as well be the case because glycogen 
 was being transformed into sugar with abnormal ease as because 
 there was interference with glycogen formation. Indeed, it is said 
 that in the heart muscle of depancreatizcd dogs there is more glycc- 
 gcn than in normal heart muscle. It must be carefully remembered 
 that the amount of glycogen present in a tissue gives no information 
 as to the rate at which it is being formed or decomposed. And if 
 the cause of the supposed defect in glycogen-forming power be the 
 absence of a glycogen-forming ferment, or its production in too small 
 an amount, the same circumstance may occasion a too tardy 
 transformation into sugar of whatever glycogen happens to be 
 present. In this case the sugar-regulating function of the glyco- 
 gen store would be equally lost, whether the storehouses were 
 permanently filled with long-formed glycogen or only half-filled or 
 empty. 
 
 In addition to an interference with the due and regulated storage 
 of the surplus sugar as glycogen, it has usually been thought neces- 
 sary for a rational explanation of the facts of diabetes, to assume 
 that from some change in the tissues sugar has ceased to be a food 
 for them, or is used up in smaller amount than in the healthy body. 
 More and more the evidence points to this as the fundamental 
 change both in the human disease and in experimental pancreatic 
 diabetes. 
 
 Why the tissues cannot decompose and utilize dextrose as they 
 normally do, if it be really the case that they fail in this regard, is a 
 question of great interest, but as yet no satisfactory answer can 
 be given. It appears probable that the failure occurs at one or more 
 of the earliest stages in the intermediate metabohsm of carbo- 
 hydrates (p. 542) or in the preliminary processes, whatever they 
 may be, which, without profoundly altering the dextrose molecule, 
 prepare it for the series of decompositions, in the course of which it 
 eventually parts with all its chemical energy. For it has been 
 shown that many of the products of the cleavage or oxidation of 
 sugar, even those in which the decomposition has proceeded but a 
 httle way — e.g., glyconic and glycuronic acids (p. 543) — are com- 
 pletely utilized by the tissues of diabetics and of depancreatizcd 
 dogs. And the derangement in the normal sequence of events, of 
 whatever nature it may be, is not so deep-reaching as to prevent 
 
554 METAIiOLIUM. \UTRlTION A\D DIETETICS 
 
 the retracing of the chcinical steps by which sugar is synthesized 
 from such derivatives of the proteins as amino-acids or tlieir further 
 degradation prochicts. As to the actual cause of the alleged in- 
 capacity of the tissues to consume dextrose, the change has by some 
 been supposed to be the loss or diminution of a glycolytic ferment 
 or a substance necessary for the activation of such a ferment. And 
 although the sugar-destroying power of blood from diabetic patients, 
 or from animals in which glycosuria has been caused by phlorhizin, 
 is not at all inferior to that of healthy blood, it has been maintained 
 that the intracellular glycolytic ferments, if such really exist, are 
 much less active, especially in the more severe forms of the disease, 
 which conform so closely in their clinical manifestations to the pic- 
 ture presented by the depancreatized animal. Nevertheless, up to 
 the present all attempts to satisfactorily demonstrate for isolated 
 tissues a loss or even a diminution in the capacity to utilize dextrose 
 have broken down. In eviscerated dogs, for example — that is, in 
 preparations consisting mainly of skeletal muscle — it has been found 
 impossible to make out any deficiency as compared with normal 
 animals in the amount of dextrose disappearing in a given time 
 from the blood, even when the animals have been deprived of the 
 pancreas as long as a week before the experiment, and therefore 
 exhibit the condition of pancreatic diabetes in full intensity 
 {Macleod and Pearce). This conclusion has been confirmed for the 
 isolated heart-lung preparation. 
 
 As regards the hypothesis that an increased production of sugar 
 from proteins, or it may be from fat, is the essential proximate cause 
 of the hyperglycaemia and the glycosuria, there is no good evidence 
 that this factor, acting by itself in the absence of a derangement of 
 the regulative influence of the glycogen store, and in the absence of 
 a derangement of the normal katabolism of dextrose, is ever respon- 
 sible for pathological diabetes. But a secondary overproduction 
 of sugar unquestionably occurs in many cases. The tissues, bathed 
 as they are in liquids rich in dextrose, are nevertheless starving for 
 sugar,^if they cannot use what is offered to them, and the body 
 labours to avert the famine by increasing its production of sugar, 
 the sugar- forming tissues being stimulated to their task either 
 through nervous influences or by chemical messengers circulating 
 in the blood. 
 
 In depancreatized dogs, and in dogs under the influence 
 of phlorhizin, glycerin, given by the mouth, causes an increase in 
 the excretion of sugar up to two or three times the original amount. 
 The giving of fat does not increase the amount of sugar excreted, 
 which, however, is increased by such substances as egg-yolk, which 
 contain lecithin. These should accordingly be avoided in cases in 
 which a strictly antidiabetic diet is desired. It is mm h more ii :- 
 portant to exclude carbo-hydrates largely or entirely from the food. 
 
METABOLISM 01- CARbOllV URATES— GLYCOSVRl AS 555 
 
 although (latmeal and potatoes arc said to occupy an exceptional 
 position, and have even been recommended as beneficial. Calcium 
 chloride has been stated to diminish the sugar excretion in diabetes 
 (Boigev). and it has a similar effect in certain of the artificial glyco- 
 surias (Brown, Fischer). 
 
 In manv cases, even when carbo-hydrates are completely, or 
 almost completely, omitted from the food, sugar, derived from the 
 breaking-down of proteins, and possibly to some extent from fats, 
 still continues to be excreted, although in smaller quantity. Other 
 products formed or imperfectly transformed in the deranged meta- 
 bolism, cspeciallv of fats, such as acetone, aceto-acetic acid, and 
 oxvbutyric acid (the so-called acetone bodies), may also appear in the 
 urine (ketonuria), or, accumulating in the blood, may, by uniting with 
 its alkahes, seriously diminish the quantity of carbon dioxide which 
 that liquid is capable of carrying, and thus lead to the condition 
 known as diabetic coma. The small amount of carbon dioxide in 
 the venous blood may also be partly due to the hyperpnoea, marked 
 by increased depth of the respirator}^ movements produced by 
 stimulation of the respiratory centre by other substances than carbon 
 dioxide. The increased ventilation causes a fall in the carbon 
 dioxide pressure in the alveolar air, and therefore an increased 
 ehmination of that gas from the blood. This form of coma appears 
 to be really in part an acid-poisoning comparable to the condition 
 produced in animals by doses of mineral acids too large to be 
 neutralized by the ammonia split off from the proteins. The ad- 
 ministration of very large doses of alkalies (sodium bicarbonate, 
 for instance, to the amount even of hundreds of grammes) has 
 been recommended for the treatment of this serious complication, 
 and in some cases it is successful in staving it off for a time. Often, 
 however, in spite of a prolonged course of treatment, during w-hich 
 the urine has continued distinctly alkaline, fatal coma eventually 
 occurs. The coma then is not merely a symptom of acidosis, 
 but is also due to the specific toxic effects of the acids ev'en when 
 neutrahzed. Other toxic products may also be formed in the 
 deranged metabolism. The appearance of the acetone bodies in 
 diabetes presents a problem which cannot be said to have been as 
 yet completelv solved. Oxybutyric acid, from which aceto-acetic 
 acid and acetone are easily derived (p. 567), seems to be one of the 
 intermediate steps in the normal metabohsm of fats. But whereas 
 under ordinary circumstances it is readily oxidized in the body, in 
 diabetes the power of the tissues to burn oxybutyric acid seems to 
 suffer just as does the power to utihze dextrose. The suggestion 
 that in diabetes the abnormally great consumption of fat entailed by 
 the loss of availability on the part of the carbo-hydrates causes the 
 intermediary metabolism of fats to be scamped, as it were, is not 
 satisfactory. For many animals and some races of men dwelling 
 
356 METABOLISM. NUTRITION AND DIETETICS 
 
 in cold climates consume with impunity much greater quantities 
 of fat than any diabetic (*-ganism.* 
 
 Section II. — The Metabolism of Fat. 
 Chemistry of Fats. — J'he fats are compounds (esters) of an alcohol 
 with fatty acids, and can be spUt, with assumption of water, into these 
 constituents by the action of acids or alkalies or of enzymes (lipases). 
 In the majority of the ordinary fats, and in all those wliich are of 
 physiological importance (the triglycerides), the alcohol is glycerin. 
 The fatty acid components which may be united with the glycerin are 
 \cry numerous, and the physical properties of the different fats — e.g., 
 their melting-points and solubilities — are closely n'latcd to the physical 
 jiropcrtics of the corresponding fatty acids. Thus palmitic and 
 stearic acids are solid at ordinary temperatures, and so are palniitin 
 and stearin, the glycerin esters or fats formed with these acids. Oleic 
 acid, on the contrary, is fluid at the ordinary temperature, and the 
 corresponding fat, olcin, is a liquid fat or oil. On the chemical side 
 the fatty acids can be distinguished as saturated and unsaturated. 
 The fatty acids of the series CnHgre+i-COOH are saturated acids. 
 Where n is o we have formic acid, H.COOH; where n is i, acetic acid, 
 CH3.COOH; where n is 2, propionic acid, CHg.CHj.COOH; where 
 n is 3, butyric acid, CH3.CH2CH2.COOH, and so on, each acid in the 
 series differing from the one immediately preceding it in possessing an 
 additional CHg group. In the case of the higher members of the series 
 these carbon chains become very long. In palmitic acid, for instance, 
 CH3.(CH2)i4.COOH, there are fourteen CHj groups, and in stearic acid, 
 
 CH3.(CH,)ie.COOH, sixteen. Oleic acid, ^ ^Ji"/^ = ^*\(CH ) COOH, 
 is a representative of a series of unsaturated fatty acids whose general 
 formula is C„H2n-iCOOH. As the formula of oleic acid shows, the 
 unsaturated fatty acids contain in their molecule two carbon atoms 
 united by a double link, and one of these valencies can be occupied by 
 halogens {e.g., chlorine) or by oxygen. Erucic acid, a fatty acid occur- 
 ring in certain vegetable oils — for example, in rape oil — also belongs to 
 this series, and linolic acid, found in linseed oil, to another series of 
 unsaturated fatty acids. Then there arc the so-called oxyfatty acids, 
 which in their turn comprise saturated and unsaturated acids. They 
 differ from the ordinary fatty acids in containing one or more OH 
 groups. Thus a dioxystearic acid, Ci7H33(OI-J)2.C"OOH, in which two 
 of the H atoms in stearic acid are replaced by OH. is found in castor-oil. 
 It is clear, from the great variety of the fatty acids, that b}' their union 
 with glycerin (with loss of water) a very large number of different fats 
 can be formed. Thus, when all the OH groups in the trivalcnt alcohol are 
 replaced by palmitic acid we have tripalmitin ; when they are replaced 
 by stearic acid, tristearin ; when they are replaced by oleic acid, triolein ; 
 and so on . As a group such fats may be termed homo-acid fats, since all 
 the OH groups are replaced by the same fatty acid. Thus — 
 
 CH2.OH Ci7H3,.COOH CHa.O:OC.Ci7H3, 
 CH.OH + C17H35.COOH = CH.O.OC.C17H35-1-3H2O 
 CHjOH Ci7H36.COOH CHa.O.OC.Ci7H36 
 
 Glycerin. 3 molecules stearic acid. Tristearin. Watet. 
 
 * The importance of controlling the diet, even to the extent of introducing 
 periods of fasting, so as to keep the diabetic free from acidosis and glycosuria, 
 has been receatly emphasised (Allen) . 
 
THE METABOLISM OF l-AT 557 
 
 But it is not necessary that each OH group in the alcohol should be 
 replaced by the same fatty acid, and when tnis does not occur wc have 
 hetcro-acid fats. For instance, one can be replaced by stearic acid, 
 and the remaining two by palmitic acid, yielding a fat called ' stearo- 
 dipahnitin.' Conversely, one OH may be replaced by palmitic and two 
 by stearic acid, forming palmito-distearin. Similarly, a dioleo-stearin 
 (glycerin combined with two molecules of oleic and one of stearic acid), 
 and an oleo-distearin (glycerin combined with two molecules of stearic 
 and one of oleic acid) are known. Such compounds have been isolated 
 from the fat of animals, and also formed synthetically. Again, each 
 of the OH groups in the alcohol can be re})laced by a different fatty acid. 
 
 It is obvious, then — and this is the point to which these chemical 
 details arc intended to lead up — ^that the number of different fats 
 which the animal organism has at its disposal for concocting those 
 varied mixtures designated as body fat is very great, and that there 
 is room for a considerable degree of specificity in the fat stores of 
 different animals, and it may be in the fat contained in different 
 organs of the same animal, even if this specificity is not as marked 
 as in the case of the proteins. It may be added, in connection with 
 the composition of the body fat, that small quantities of free fatty 
 acids and of glycerin may be present ; but there is reason to believe 
 that these are simply the surplus of raw materials which is about to 
 be synthetized to neutral fat, or the surplus of decomposition 
 products of the neutral fat which have not yet left the fat depots 
 to take their place in the metabolism of the tissues. 
 
 The discussion of the metabolism of fat involves a study — (i) of 
 the transformations and migrations of the food fat before it begins 
 to be utilized ; (2) of the possible production of fat from other con- 
 stituents of the food ; (3) of the processes and the stages by which 
 fat, whatever its origin, undergoes katabolism to its end products. 
 The fat of the food, passing along the thoracic duct into the blood- 
 stream, is soon removed from the circulation, for normal blood 
 contains only traces, except during digestion. Where does it go ? 
 What is its fate ? 
 
 Transformation and Migration of the Food Fat. — The presence 
 of adipose tissue in the body might suggest a ready answer 
 to these questions. The fat-cells of adipose tissue are ordinary 
 fixed connective-tissue cells which have become filled with fat, 
 the protoplasm being reduced to a narrow ring, in which the 
 nucleus is set like a stone. It would, at first thought, seem natural 
 to suppose that the fat of the food is rapidly separated by these 
 cells from the blood, and slowly given up again as the needs of the 
 organism require, just as carbo-hydrate is stored in the liver for 
 gradual use. And it has been found that a lean dog, fed with a 
 diet containing much fat and little protein, puts on more fat, as 
 estimated by direct analysis, or keeps back more carbon, as esti- 
 mated by measurements of the respiratory exchange, than can be 
 accounted for on the supposition that even the whole of the carbon 
 of the broken-down protein corresponding to the excreted nitrogen 
 
538 METABOLISM. NUTRfTION AND DTF.TF.TICS 
 
 has been laid up in the form of fat. Even with a diet of pure fat— 
 and with such a diet digestion and absorption are carried on under 
 unfavourable conditions — more carbon is retained than can have 
 come from the metabolism of the proteins of the body, as measured 
 by the nitrogen given off in the urine and faces: the fat passes 
 rapidly from the blood into the organs, and especially into the liver 
 (Hofmann, Pettenkofer and Voit). It is thus certain that some of 
 the absorbed fat may be stored up as fat in the body. 
 
 This is borne out by the careful experiments of Munk and Lebe- 
 deff, who found that, when dogs are fed with excess of foreign fat 
 (Unseed oil, rape oil, mutton fat), a fat is laid down which is quite 
 different from dog's fat, and has the greatest resemblance to the fat 
 of the food. Thus, when rape oil, which contains a fatty acid, 
 erucic acid, not found in animal fat, was given, erucic acid could be 
 detected in the fat laid on. When the dogs were fed with mutton 
 fat, whose melting-point is much higher than that of dog's fat, the 
 fat laid on did not melt till it was heated to 40° C or more. When 
 they were fed with linseed oil, the body-fat was found liquid even 
 at 0° C. We have already referred (p. 444) to the fact that neutral 
 fat can be built up in the wall of the intestine from fatty acids given 
 in the food. Munk has shown that fat formed in this way can also 
 be laid down as body-fat. But besides the fat and fatty acids of 
 the food, the fat of the body has other sources, and some of it is 
 produced by more complex processes. 
 
 The fat of a dog consists of a mixture of palmitin, olein, and 
 stearin. When a starved dog was fed on lean meat and a fat con- 
 taining palmitin and olein, but no stearin, the fat put on contained 
 all three, and did not sensibly differ in its composition from the 
 normal fat of the dog (Subbotin). Stearin must, therefore, have 
 been formed in some way or other in the bod}'. If it was produced 
 from the olein and palmitin of the food, the portion of these deposited 
 in the cells of the adipose tissue must have undergone changes before 
 reaching this comparatively fixed position. But there is conclusive 
 evidence that fat may be derived from other sources, certainly 
 from carbo-hydrates, and probably from proteins; and the stearin 
 may have been formed from the carbo-hydrates or proteins of the 
 food or tissues, and not directly from fat. And if the stearin was 
 produced from proteins or carbo-hydrates, it is evident that the 
 olein and palmitin might have been formed in this way too, the 
 portion of the carbo-hydrate or protein devoted to this purpose 
 being sheltered from oxidation by the combustion of the fats of the 
 food. It is well known that not only neutral fats, but also fatty 
 acids, exert such a ' protein-sparing ' action. It is possible also that 
 the fat which is normally excreted into the intestine (p. 443), and 
 which is perhaps derived from broken-down proteins, may be re- 
 absorbed, and take its place among the fat ' put on.' 
 
TIIF MF.TABOIIS^T OF FAT 550 
 
 At this point in the discussion it is necessary to remark that a 
 distinction ought to be estabhshed between that store of surplus fat 
 laid down in the connective tissue which, in order to avoid com- 
 plicating the matter unduly, has hitherto been referred to as if it 
 constituted the whole of the body-fat, and the fat which is contained 
 in greater or less amount in all the tissue cells. The fat con- 
 tained in the tissue elements — e.g., in the liver cells — in the visible 
 form of droplets, and which can be easily extracted from them by 
 solvents such as chloroform, should also be distinguished from the 
 fat which is so intimately incorporated or combined with the cell 
 substance that it can only be extracted after this has been digested 
 by the aid of proteolytic ferments or acids. The latter fraction of 
 the body-fat is probably an integral and indispensable constituent 
 of the protoplasm. Now, it is in the great fat depots of the sub- 
 cutaneous tissue and the mesentery and omentum that variations 
 in the proportions of the various fatty acids corresponding to varia- 
 tions in the nature of the food-fat are most easily produced, or, at 
 least, most easily observed. These depots are laid down, not in 
 the interest of the fat cells themselves, but to serve the purpose of 
 a reserve of fat which may be drawn upon for the nutrition of the 
 body as a whole, just as the glycogen store of the liver forms a 
 general carbo-hydrate reserve. The free fat in the cells of the organs 
 is superficially analogous to the glycogen reserves of such tissues 
 as muscles and glands, and certain facts are known which might 
 be interpreted as indicating that this fraction of the body-fat, like 
 the fat of the connective tissue, is not a definite and specific mixture 
 of fats with an unvarying composition for each kind of animal, but 
 a mixture whose composition can be made to vary by altering the 
 nature of the fats in the food. On the other hand, the fat combined 
 in the tissues appears to preserve a certain specificity which is inde- 
 pendent of the fats supplied in the food. Thus, when dogs were 
 fed with rape oil, and had accumulated considerable quantities of 
 this fat of low melting-point in the subcutaneous and other fat 
 depots, Ihe fat combined in the organs remained in all respects the 
 same as normal dog's fat. This was also the case with animals 
 fed on fat of high melting-point, such as sheep's tallow (Abderhalden). 
 Although the liver appears to have a special relation to the metabo- 
 lism of fat, it is not known whether any particular organ is more 
 than the rest responsible for the manufacture of this specific mix- 
 ture of fats. It appears more probable that each cell has the power 
 of forming for itself the characteristic fats from the crude materials 
 represented by the food-fat directly absorbed from the tissue lymph, 
 or the fat of the depots after it has been mobilized and has found 
 its way again into the blood, or, finally, from other materials than 
 fats, such as dextrose or some of its decomposition products. 
 
 Even in the case of the subcutaneous and similar collections of 
 
56o METABOLISM. NUTRITION AND DIETETICS 
 
 fat, it must be noted that upon the whole, under normal conditions, 
 it is their specificity of composition rather than their dependence 
 upon the composition of the fat mixture in tlie food which is the 
 striking fact, and undue weight can easily be given to the results 
 of feeding experiments where great quantities of quite foreign fats 
 are administered. When small quantities of fats very far removed 
 in their properties from the normal fat of an animal are given 
 in the food, they are either completely utilized before reaching 
 the fat depots, or transformed into normal body-fat, since no change 
 whatever can be detected in the latter. If they have been utilized, 
 then it may be that a corresponding amount of fat, formed, say, 
 from dextrose, has been laid down in the fat stores. If this fat is 
 formed from dextrose, it will, of course, be the kind of fat which 
 the particular animal is accustomed to form from dextrose — ^that 
 is, the fat characteristic of the animal. If the foreign fat is itself 
 transformed into body-fat when given in small amount, this same 
 feat can without doubt be gradually accomplished in the case of 
 the surplus of foreign fat laid down in the depots when a large 
 quantity of it is given in the food. 
 
 Formation of Fat from Other Sources than the Fat of the Food — 
 (i) From Carbo-Hydrates. — It has been found that the addition of 
 protein to a diet of fat, and especially to a diet of carbo-hydrate, 
 in larger amount than is just necessary for nitrogenous equilibrium 
 (p. 602), leads to a more rapid increase in the carbon deficit — that 
 is, in the fat put on — than if the minimum quantity of protein 
 required for nitrogenous equilibrium had been given. From this it is 
 inferred that the carbonaceous residue of the broken-down protein is 
 shielded from oxidation by the fat, and to a still greater extent by 
 the carbo-hydrates, and so retained in the body as fat. And there 
 is little doubt that the high repute of carbo-hydrates as fattening 
 agents is in part due to their taking the place of proteins and fats 
 in ordinary ' current ' metabolism, and so allowing body- fat to be 
 laid down from these. Voit, indeed, has gone so far as to assert 
 that this is the only sense in which carbo-hydrates can be said to 
 form fat, and that, in carnivorous animals at least, a direct con- 
 version never occurs. But the experiments of Rubner have shown 
 that in a dog fed with a diet rich in carbo-hydrates, and containing 
 but little fat and no proteins at all, the carbon deficit was greater 
 than could be accounted for by the proteins being broken down in 
 the body and the fat of the food. In the pig and goose, too, the 
 direct formation of fat from carbo-hydrates has been demonstrated. 
 
 For example, in an experiment by Tscherwinsky two young pigs 
 of the same litter were taken. They weighed respectively 7,300 grammes 
 aud 7,^90 grammes. One was killed, and the amount of fat and nitrogen 
 in its body directly estimated. From the nitrogen the maximum 
 quantity of protein which could be present was calculated. The other 
 pig was fed for four months with barley, which was analyzed. The 
 excreta were also analyzed to determine the amount of unabsorbed 
 
THE METABOLISM OP PAT 561 
 
 fat and protein. At the end of the lour months the pig vveis killed. 
 It now wtighcd 24 kilogrammes, and contained 2-52 kilogrammes 
 protein and 9-25 kilogrammes fat. Subtracting the protein (0-96 kilo- 
 gramme) and fat (0*69 kilogramme) originally present, 1-56 kilogrammes 
 of protein and 8-56 kilogrammes of fat must have been put on. The 
 amount of protein taken in the food was 7-49 kilogrammes, and of fat 
 O'bb kilogramme. Therefore, 5-93 kilogrammes of protein must have 
 been used up, and 7-90 kilogrammes of fat laid on. At least 5 kilo- 
 grammes of this fat must have come from the carbo-hydrate of the 
 food. Only a small amount of the fat put on could possibly have come 
 from the protein. 
 
 The production of wax by bees, which used to be given as a proof 
 of the formation of fat from sugar, is not decisive, for in raw honey 
 proteins are present ; and even when bees fed on pure honey or sugar 
 vnanufacture wax, it may be derived from the broken-down proteins 
 of tlieir own bocUes. 
 
 It is probable that in the formation of fats the carbo-hydrates 
 are first spht up to some extent, and that the fats are then con- 
 structed from their decomposition products, oxygen being lost in 
 the process, since fat is much poorer in oxygen than carbo-hydrate. 
 But the chemistry of the transformation as it takes place in the body 
 is still imperfectly known, and all that can be done here is to indicate 
 one or two of the ways in which chemists conceive that it may occur. 
 
 The formation of the glycerin component of the neutral fats from 
 carbo-hydrates would appear to present little difficulty. In dis- 
 cussing the formation of glycogen from glycerin fp. 536), it was stated 
 that two molecules of glycerose (glycerin aldehyde), a triose or sugar 
 with three carbon atoms, can be condensed to form a hexose or sugar 
 with six carbon atoms like dextrose, from the condensation or union 
 of a number of molecules of which, with abstraction of water, glycogen 
 is built up. The reaction can be worked equally well in the reverse 
 direction — that is, from the hexose dextrose two molecules of glycerin 
 aldehyde can be formed, and then from each molecule of the alde- 
 hyde ,'by reduction, a molecule of the alcohol glycerin. As a matter of 
 fact, it has been demonstrated that glycerin is produced when the cor- 
 responding aldehyde is brought into contact with minced liver. 
 
 As regards the fatty acid components of the fats, it will be seen from 
 the schematic representation of the katabolism of dextrose on p. 544 
 that acetic acid, a fatty acid, is represented at one of the stages as being 
 formed by the oxidation of a molecule of acetaldehyde. Lactic acid 
 is represented in the same scheme as a previous stage in the decom- 
 position of dextrose, and lactic acid can be converted into acetaldehyde 
 and formic acid, the lowest of the same series of fatty acids of wdiich 
 acetic acid is the next highest member. Thus : 
 
 ^^sVh.COOH = CH3.C<^JJ + H.COOH 
 
 Lactic acid. Acetaldehyde. Formic acid. 
 
 Aldehydes (as well as ketones) ha\e a great capacity for entering into 
 reactions with other substances, and their molecules show also a marked 
 tendency to combine with one another, forming new compounds by 
 their condensation. Thus, from two molecules of acetaldehyde one 
 
 36 
 
362 METABOLISM. SLTRITIOS A\D DILTLTICS 
 
 molecule ot aldol is formed, which by transposition of certain groups, 
 hecomcs butyric acid, the fourth member of the fatty acid scries of 
 which acetic acid is the second memljer, and palmitic and stearic acids, 
 which form such important constituents of the ordinary body -fats, 
 the sixteenth and eighteenth members respectively. By oxidation aldol 
 becomes /3-oxybutyric acid, which by further oxidation yields aceto- 
 acetic acid, compounds already referred to in connection with diabetes 
 (p. 555). The following equations illustrate these reactions: 
 
 CH3.C^g + CH3.C^g = CH3.CH(OH).CH,.c/g 
 
 Aceuldehyde. Acetaldebyde. Aldol. 
 
 CH3.CH(OH).CH2.CHO-CH3.CH2.CHa.COOH 
 
 Aldol. Butyric acid. 
 
 CH3.CH(OH).CH2.CHO + 0=CH3.CH(OH).CH,.COOH 
 
 Aldol. /S-oxybutyric acid. 
 
 CH3.CH(OH) .CH2.COOH + O = (CH3.CO).CH2.COOH + HjO 
 
 /S-oxybutyric acid. Oxygen. Aceto-acetic acid. Water. 
 
 By reduction aceto-acetic acid is reconverted into /3-oxybutyric acid. 
 Other aldehydes can react in similar ways, and thus many of the other 
 fatty acids can be formed. 
 
 It may be added that acetone (another of the so-called acetone 
 bodies which appear in the urine in diabetes mellitus) is easily obtained 
 from aceto-acetic acid by the splitting off of carbon dioxide. Thus: 
 
 (CH3.CO).CHj.COOH =CH3.CO.CH3-i- CO, 
 
 Aceto-acetic acid. Acetone. Carbon dioxide. 
 
 Formation of Fat — (2) From Protein. — Dry protein contains on 
 the average 16 per cent, of nitrogen and 50 per cent, of carbon, and 
 urea contains 46 per cent, of nitrogen and 20 per cent, of carbon. 
 Urea is therefore three times as rich in nitrogen as the protein from 
 which it is derived, but two and a half times poorer in carbon; and 
 less than one-seventh of the carbon of protein will be eliminated 
 in a quantity of urea sufficient to carry off all the nitrogen. It 
 is probable that a portion of the remaining carbon may, after passing 
 through various stages, take its place as the carbon of fat. We 
 have seen that certain amino-acids derived from proteins can be 
 converted into dextrose, and that de.xtrose can be converted into 
 fat. So that the mere question whether carbon atoms or carbon 
 chains originally present in protein molecules are ever capable of 
 appearing in fat molecules can be straightway answered in the 
 affirmative. But it is still in doubt whether amino-acids can be 
 transformed into glycerin or into fatty acids, or into both, by 
 processes which do not involve the production of dextrose from 
 them. And in any case proof is required that the extent of the 
 transformation, let the steps be what they may, is great enough 
 to be satisfactorily demonstrated. In regard to this point it must 
 be said that absolutely flawless experiments to prove the direct 
 production of fat from protein seem still to be wanting. 
 
THE METABOLISM OF FAT 5«3 
 
 Phosphorus Poisoning and Migration of Fat. — In tiic cxiCJ'iriicnts 
 of liaiKT, the HiiumnL of oxjgcn consuinctl and of carbon dioxide 
 and nitrogen excreted was dctennincd in starving dogs. Phosphorus, 
 which, as is well known, causes extensive fatty changes in the 
 organs, was then administered in small doses for se\cral days. 
 The excretion of nitrogen was doubled, the excretion of carbon 
 dioxide and the consumption of oxygen diminished to one-half. When 
 the animals died, in a few days, the organs were all found loaded with 
 fat. In one case 42-4 per cent, of the solids of the muscles and 30 per 
 cent, of the solids of the liver consisted of fat. This is much more than 
 the normal amount. It was iissumed that the fat could not have been 
 simply transferred from the adipose tissue, since the dog had been 
 starved for twelve days before the phosphorus was given, and died on 
 the twentieth day of starvation. Now^ after such a period of hunger 
 the amount of fat in the adipose tissue is greatly reduced. It was there- 
 fore concluded that the source of the fat could rnly have been the 
 broken-down protein. Since the nitrogen excretion was increased, while 
 the carbon excretion was diminished, it was supposed that a residue 
 rich in carbon must have been split off from the proteins, and, remaining 
 unbumt in the body, must have been converted into fat. Experiments 
 of this kind are open to criticism on several grounds, but especially on 
 this : that unless the fat-content of the whole body before the adminis- 
 tration of the poison is known, it is impossible to be sure that the fat 
 in a particular tissue has not been increased simply by the transportation 
 of fat from some other tissue. It has been conclusively shown that 
 migration of preformed fat does occur, and on an extensive scale, in 
 phosphorus poisoning. For example, a dog was fed for a time with 
 sheep's tallow, and fat was laid down in its adipose tissue with the 
 physical and chemical characters, not of dog's, but of sheep's fat. The 
 animal was then poisoned with phosphorus, and the fat which accumu- 
 lated in the liver examined. It also resembled sheep's fat, as it should 
 have done had it migrated from the adipose tissue, and not dog's fat, 
 as it might have been expected to do had it been formed in the hepatic 
 cells from protein. The ease with which connective-tissue fat — i.e., food 
 fat — migrates to the liver suggests, with other facts, that the liver has a 
 special relation to the transformation of this fat into the fat of the organs. 
 This ' organized ' intracellular fat differs in various ways from the fats 
 of adipose tissue. Its ' iodine value ' (p. 4) is higher (Leathes), and a 
 large proportion of it consists of phosphatide lipoids (p. 571.) 
 
 The most convincing evidence that fat is not produced in increased 
 amount under the influence of phosphorus has been obtained by deter- 
 mining by actual analysis the total fat in animals, then poisoning 
 similar animals with phosphorus and again estimating the total fat. 
 Far from being increased, the fat may even be decreased in the poisoned 
 animals (Taylor, etc.). There is no ground, then, for the assumption 
 that phosphorus and other substances, like arsenic, antimony, etc., which 
 bring about so-called ' fatty degeneration ' of the organs, act by causing 
 or accelerating the transformation of protein into fat. Yet there is good 
 evidence that they do accelerate the decomposition of protein, or at 
 least interfere with its normal metabolism, for after phosphorus poison- 
 ing amino-acids (leucin, ty rosin, glycin) appear in the urine. The 
 observations of Lusk and his pupils indicate that phosphorus does not 
 directly increase the amount of protein broken down, but does so 
 indirectly, by favouring the conversion of the carbohydrate -like radicle 
 of the protein molecule into leucin, tyrosin, and perhaps fat, and 
 thereby necessitating an increased consumption of protein. 
 
 A celebrated experiment, performed nearly forty years ago, was long 
 
564 METABOLISM. NUTRITION AND DIETETICS 
 
 supposed to furnish an absolute proof of the formation of fat from 
 protein, under strictly physiological conditions, although in a humble 
 form of animal life. Maggots were allowed to develop from the egg on 
 blood containing a known amount of fat. The quantity of fat in the 
 eggs was also known. After the maggots had grown, ten times as 
 much fat was found in them as had been contained in the blood and 
 eggs together. The trifling quantity of sugar in the blood was utterly 
 inadequate to account for the fat, which, it was concluded, must there- 
 fore have come from the proteins of the blood (Hofmann). It can be 
 objected to this experiment that no precautions were taken to prevent 
 the growth of micro-organisms on the blood, and fat might have been 
 formed by them from the proteins. Further, the fat estimations would 
 scarcely pass muster according to the present standards. 
 
 The "experiments of Pettcnkofer and Voit, which were supposed to 
 have demonstrated that in the higher animals also fat is formed from 
 proteins imdcr norini.l conditions, are in the same position. According 
 to them, a dog fed for a time on a liberal diet of lean meat may go on 
 excreting a quantity of nitrogen equal to that in the food, while there 
 is a deficiency in the carbon given ofif. Or if the dog is not in nitrog- 
 enous equilibrium (p 602), but putting on nitrogen in the form of 
 ' flesh,' the deficiency in the carbon given off may be too great in pro- 
 portion to the nitrogen deficit to warrant the assumption that all the 
 retained carbon has been put on in the form of protein. In either case, 
 carbon in large amount can only come from the proteins of the food, 
 and can onlv be stored up in the body in the form of fat. For lean meat 
 contains but a trifling quantity of carbon in any other proximate 
 principle than protein, and the non-protein carbon of the animal body 
 is only to a very small extent contained in carbo-hydrates or other 
 substances than fat. 
 
 Pfliiger has criticized these experiments, and has shown that lean 
 meat contains more fat than was supposed, and this is now generally 
 admitted. He has endeavoured to show that the fat and ghcogen in 
 the meat given to the animals full)- accounts for the carbon retained. 
 Pfliiger, indeed, takes up the position that the fat of the body comes 
 exclusively from the carbo-hydrates and fats of the food, and not at all 
 from the proteins. But there is little doubt that in this he has gone too 
 far, although his criticism has rendered it impossible any longer to appeal 
 to Pettenkofer and Voit's results as good evidence on the other side. 
 
 If none of the supposed quantitative proofs of the conversion of 
 proteins into fat which have hitherto been brought forward are 
 free from flaw, the same is true of the alleged qualitative indications 
 of its possibility and of its actual occurrence. The accumulation 
 of fat between the hepatic cells caused by phlorhizin is, at the best, 
 no better evidence than the accumulation within the cells in phos- 
 phorus poisoning. The formation of adipocere (a cheesy substance, 
 rich in fatty acids united with calcium or ammonium), sometimes 
 seen in dead bodies which have remained a long time under water 
 or in moist graveyards, is largely, if not entirely, due to the fat 
 already present in the parts which have undergone the change, 
 or to fat removed by the water from other parts of the body. 
 If any portion of the adipocere represents fat formed from protein, 
 this transformation may well be credited to the numerous micro- 
 organisms present, and throws no light upon the question of fat 
 formation in the normal organism. The fat in the ceils of the 
 
THF ^f^TA^lnTr^^r of fat 565 
 
 sebaceous glands, and of the mammary glands, may be produced 
 from protein by a transformation of the cell-substance. But abso- 
 lutely convincing proof is wanting. The old idea that the cells of 
 these glands underwent a physiological process of transformation 
 into fat analogous to the fatty degeneration of pathology, and then 
 broke down bodily into the secretion, has been long since disproved 
 for milk formation, and is probably erroneous also as regards the 
 secretion of sebum. The rule which experience has taught, that 
 a woman during lactation requires an excess of proteins in her food 
 corresponding not only to the proteins, but also to the fat given off 
 in the milk, suggests such an origin for the milk-fat, but does not 
 prove it. Other fat-containing secretions are the ear-wax formed 
 by glands in the wall of the external auditory meatus, and the 
 smegma formed by the glands of the prepuce, but nothing is known 
 of the sources from which the fatty substances are derived. 
 
 The Intermediary Metabolism of Fat. — The mechanism and the 
 stages of the transformation, including the migration, of fats is 
 not well understood — indeed, not as well as that of the carbo- 
 hydrates. Many of the tissues contain intracellular, soluble, 
 fat-splitting ferments called lipases, especially the liver, the 
 active mammary gland, and the intestinal mucosa. We have 
 already seen that there is evidence that these lipases, like some 
 other enzymes, have a reversible action. They are either fat- 
 splitting or fat-forming ferments, according to the conditions 
 (Kastle and Loevenhart). It is stated that the perfectly aseptic 
 blood does not split ordinary neutral fats, although it contains a 
 ferment which splits up monobutyrin (glycerin but^Tate) into 
 glycerin and butyric acid. 
 
 The question how the fat, after absorption from the intestine, 
 passes from the blood into the cells, and how- it is enabled again to 
 pass out of the fat-cells when the needs of the tissues call for its 
 mobilization, cannot at present be definitely answered. It is 
 possible that just as fat is split in the lumen of the intestine before 
 being absorbed, and then rebuilt in the epithelium, so it is split in 
 the blood or in the lymph before being taken up by the fat-cells. 
 The lipase in these cells would then be capable of synthetizing the 
 glycerin and fatty acids to fat in their interior. \Vhen the fat is 
 about to pass out of the cells in response to the call, of whatever 
 nature it is, of the tissues for fat, it may again be split, resynthetized 
 in the blood, and again hydrolysed for entrance into the tissue 
 cells. Or it may be carried to the cells in the form of glj'cerin and 
 fatty acids, or soaps, in such small concentration as to be harmless, 
 and there built up again into the original fat, or transformed into 
 other fats" characteristic of the particular tissues, including the fatty 
 acid components of the phosphatides, or utilized without synthesis 
 into fat. An alternative hypothesis avoids this series of decomposi- 
 
566 METABOLISM. NUTRITION AND DIETETICS 
 
 tions and syntheses by assuming that the fat passes in the lorm of 
 very fine droplets tlirougli the walls of the cells and of the capil- 
 laries. The reader will observe that we seem to be discussing again, 
 and almost in the same terms, the question of the absorption of fat 
 from the intestine. It is indeed at bottom the same question, and 
 it might be argued that by analogy it should receive the same solu- 
 tion. Analogy, however, is a dangerous guide in such matters, and 
 it is even more difficult to secure an unambiguous experimental test 
 of the manner in which the internal migration of fat is accomplished 
 than to secure the like for its absorption from the digestive tube. 
 
 As to the ultimate fate of the fat, from whatever source it may 
 be derived, our knowledge may be compressed into very few sen- 
 tences: Sooner or later it is split and oxidized to carbon dioxide and 
 water, its energy being converted into heat or, directly or indirectly, into 
 mechanical or other fnnctional work ; some of the fat absorbed from the 
 intestine rapidly undergoes this change without entering the fat-cells of 
 the adipose tissue. A portion of the fat may be changed into carbo- 
 hydrt^^es. This has been proved for the glycerin component ; its possi- 
 bility must be admitted for the fatty acids, but proof has not yet been given. 
 
 Of the intermediate stages by which the fatty acids are degraded 
 into the simple end products but little is surely known. Included 
 among these stages must be the compounds with which the forma- 
 tion of the acetone bodies (p. 563) starts, if and in so far as their 
 formation is a normal event which is merely unveiled by the dis- 
 turbance of the ordinary course of the metabolism in diabetes. 
 Among these intermediate stages must also be included, it is to be 
 supposed, the compounds, whatever they may be, which act as 
 connecting links between the currents of fatty acid and of carbo- 
 hydrate metabolism, and with which the transformation of fatty 
 acids into carbo-hydrates commences, if this occurs at all. 
 
 According to tlic observations of Knoop, the saturated as well as 
 some of the other series of fatty acids when oxidized decompose in a very 
 characteristic way. As already remarked, these acids are made up of a 
 larger or smaller number of CHj groups forming a chain whicli at one 
 end terminates with a carboxyl (COOH) group, and at the otlier with a 
 CH3 group. The carbon atoms in the chain are designated by Greek 
 letters, a, /3, etc., the a position being that next the carboxyl group, 
 the ^ position one remove from the carboxyl group, and so on . Accord- 
 ing to Knoop, the oxidation of the fatty acid chain takes place in such 
 a way that the chain is shortened by the cutting off from the carboxyl 
 end the a CH2 group along with the carboxyl group, wliile in place of the 
 /3CH2 group there is left a carboxyl group, an operation which might 
 be fancifully compared to the naval manoeuvre of breaking the enemy's 
 ,. T,, , . , CH3.CH2.CH2.CH2. 1 CHj.COOH. ^^ 
 
 line. Thus from caproic acid c^yft\a 
 
 get by oxidation butyric acid, CH3.CH2.CHa.COOH, ^^^rbon dioxide 
 
 and water. It appears that the oxidation proceeds in two stages, the 
 hydrogen of the /3 group being first oxidized with formation of an 
 
THE METABOUSM OF FAT ^r,j 
 
 oxyacid oxycaproic ackl, CiI3.CPJ2.Cil2.CllOH.CH2.COOH, which is 
 then by further oxidation converted, with loss of two carbon atoms, 
 into butyric acid. The oxidation process may then start afresh on 
 the /3 group of butyric acid. On the long carbon chains of the higher 
 fatty acids this operation may be repeated again and again, the chain 
 losing two atoms of carbon at each attack. If this represents what 
 occurs in the normal metabolism, the groups cut off may then and there 
 undergo the fate of the ships isolated by a successful application of[the 
 manoeuvre alluded to, complete destruction — that is to say, oxidation 
 to the end products carbon dioxide and water, a portion of the energy 
 of the fatty acid being thus liberated at each oxidation of the /3 group. 
 Eventually a fatty acid or acids with very few carbon atoms will be 
 left. There is some reason to think that acetic acid (and perhaps 
 similar simple acids) may be one of the normal stages in the decom- 
 position. Thus, butyric acid may first yield by oxidation of the 
 
 a ., •, /3 K ^ • -A CHo.CHOH.CHo.COOH, 
 
 /3 group the oxyacid /3-oxy butyric acid, ^^ ^ ' 
 
 which by further oxidation of the /3 group and the cutting off of the a 
 and carboxyl groups would give CH3.COOH, or acetic acid. 
 
 If this is the general course of the oxidation of the fatty acids in 
 the body, it is to be assumed that numerous intermediate stages 
 unrepresented in such a simple scheme may exist. Thus it is known, 
 as has been mentioned more than once in other connections (p. 562), 
 that ^-oxybutyric acid by oxidation yields aceto-acetic acid, by 
 losing from the /3 group two atoms of hydrogen which unite with 
 oxygen to form water. A molecule of aceto-acetic acid contains 
 the elements of two molecules of acetic acid minus the elements of 
 one molecule of water. It is therefore possible that aceto-acetic 
 acid, if it is a normal stage in the katabolism of fatty acids, yields 
 by its hydrolysis as a further step acetic acid, according to the 
 equation 
 
 CH3.CO.CH2.COOH + HaO =2(CH3.COOH). 
 
 Aceto-acetic acid. Acetic acid. 
 
 It is worth while, perhaps, to point out once more that even the 
 relatively simple products now arrived at are not necessarily at 
 once completely oxidized to their end products. That, it is to be 
 assumed, will depend upon the needs of the organism. Acetic acid, 
 for example, when added to blood and perfused through the sur- 
 viving liver, can be transformed into aceto-acetic acid, and may 
 thus become the starting-point of new syntheses. 
 
 The Liver and Fats. — The liver seems to play an important part in 
 the metabolism of fat, as it does in the metabolism of carbo-hydrates 
 and of proteins. It contains an oxidizing ferment, /S-oxybutyrase 
 (or ,8-hydroxybut}Tase) , which transforms /3-oxybutyric acid into 
 aceto-acetic acid (Dakin). This oxidation appears to occur in the 
 normal as well as in the diabetic organism. The liver seems also to 
 possess the power of transforming aceto-acetic acid into acetone, a 
 reaction which does not involve an oxidation, and this may also be 
 accompHshed by means of an enzyme. But it is not at all likely 
 
3(*8 METABOLISM. NUTRITIOX AXD DIETETICS 
 
 that acetone forms a stage in the normal kataboHsm of the fatty 
 acids or of the /3-oxyacids derived from them. The importance of 
 the Hver in the metabohsm of fats is further indicated by the extent 
 of the migration of fat to that organ when tlic fat stores are mobihzed 
 in unusual amount (p. 5bj). The reason for this migration seems 
 to be that the fats undergo preparatory changes which facilitate 
 their utilization by the tissues. For example, there is evidence 
 that saturated fatty acids are changed in the liver into unsaturated 
 acids, which are then carried to the organs to be metabolized. 
 The desaturation may serve the purpose of facilitating the rupture 
 of the long carbon chains, or their capacity for entering into reac- 
 tions with other substances, at the points where double links exist 
 between carbon atoms (p. 55b). 
 
 Non -Nutritive Functions of Fat. — In connection with the metabo- 
 lism of fat, it ought to be noted that, in addition to their value as 
 reserve material for the nutrition of the body, the deposits of fat 
 under the skin and in other situations perform important functions 
 in protecting delicate structures from mechanical injury, in facili- 
 tating their movements upon each other, and in hindering the loss 
 of heat. It would doubtless be a gross exaggeration to say that the 
 mechanical and physical properties of the fat depots are as im- 
 portant in comparison to their chemical relations as is the case for 
 the bones and ligaments, but it would be an error not less gross to 
 consider them as of little account. It will even, perhaps, be 
 \hought not unworthy of mention, from the point of \new of the 
 propagation of the race, that in the human species, at least, the 
 amount and distribution of the cutaneous fat play a part of r-om? 
 consequence in the aggregate of qualities which determine the 
 physical attractiveness of the individual, especially of the female, 
 although the standard in this regard varies wdely in different 
 communities. 
 
 It is perhaps partly because the fat depots have important 
 mechanical functions that the fat reserve is far less mobile than the 
 glycogen reserve. The semi-solid panniculus adiposus, the fatty 
 tissue around the great nerve trunks, between the muscles, around 
 the eyeball, on the soles of the feet, etc., possesses as a protective 
 packing the good qualities of a water cushion with none of its dis- 
 advantages. But if the fat-cells were subject to sudden depletion, as 
 the hepatic cells are — nay, in still greater degree, since they contain 
 hardly any protoplasm — ^they would never serve for such a function. 
 Of course, in the emergency of starvation, when even the glands 
 and the muscles themselves are wasting, the fat reserves are neces- 
 sarily mobilized, let their mechanical functions suffer as they may. 
 
 Obesity. — The proportion of tlie total mass of the body wliicli is made 
 Tip of fat varies greatly in different individuals, and often in the same 
 individual at different stages in hfe. When the accumulation of fat 
 
THE MF.T.WOLJSM OF FAT 369 
 
 passes beyond a certain point it causes obvious changes in the contours 
 of the body, and often some embarrassment in its movements. Thia 
 condition is termed obesity. It is extremely difficult to say when the 
 condition oversteps the physiological bounilary and becomes actually 
 pathological. Some individuals who are notoriously stout are noted 
 also for tlicir intellectual activity, and may not fall below the average 
 even in the ordinary kinds of physical ettort. It would be an exaggera- 
 tion to speak of such persons as suffering from a disease . In other cases 
 the pathological stamp is clearly imprinted upon the metabolic anomaly 
 which leads to the overfilling of the fat depots. This is perhaps best 
 illustrated in those cases of extreme obesity in children where, in spite 
 of the intense metabolism associated with growth, with the restless 
 muscular acti\ity characteristic of that age, and with the relatively 
 great surface through which heat is lost, great quantities of fat continue 
 to be put on. Muscular activity by itself is no certain antidote to or 
 prophylactic against obesity, and it is a mistake to suppose that the 
 condition is cxceedinglj' rare among manual workers sufficiently well 
 paid to be able to gratify their tastes in the quality and quantity of 
 their food. Statistics or rough estimates covering the whole of the 
 hand-workers of a country- throw no light on such a question, for few 
 indeed are the lands where the masses of the people have such well-filled 
 purses that they are able to nourish themselves according to their wishes. 
 While it is true that the great majority of normal individuals (although 
 not all, since even in the fattening of stock for market some animals are 
 rejected as bad feeders) can be compelled to lay on fat when overfed 
 with fat and especially with carbo-hydrates, and prevented from takmg 
 much exercise or from losing heat freely, the most important factor in 
 the excessive storing of fat b}- human beings leading a free life seems to 
 be an anomaly in the metabolism which permits the machine to be run on 
 less than the usual amount of fuel. From the point of view of thenno- 
 djTiamics the fat man, in verj- many instances at least, grows fat and 
 fatter because his body is a machine whose ' efficiency ' is greater than 
 the normal — that is to say, a machine which is capable of doing a given 
 amount of work and of keeping itself in repair with a food intake of 
 smaller heat value than is usually needed. Whether this anomaly is to 
 be considered a metabolic fault or a metabolic virtue depends largely 
 upon the ease with which the intake is adjusted to the actual require- 
 ment of the body. If the adjustment is rendered accurate, the man 
 with the anomalous tendency to put on fat, the adiposophil . ashe might 
 be called, is in all probability j ust as well off in every physiolog ical sense 
 on a smaller diet than a so-called normal individual of the same age, 
 weight, and daily routine, on a larger quantity of food, and on this 
 smaller diet he does not become fat. In this connection it may be 
 recalled that, in speaking of the blood-flow in the hands and feet (p. 127), 
 which are in this relation to be regarded as essentially an ' outcrop ' 
 of the cutaneous circulation, it was pointed out that some healthy 
 persons have habitually small flows and a habitually cool skin which 
 perspires little, in comparison witYi others living practically the sam e life. 
 It was suggested that this difference in the blood-flow through the skin, 
 .vhich of course would correspond with a difference in the rate of heat 
 loss, and therefore in the rate of heat production, may be correlated with 
 a difference in the intensity of the metabolism and the intake of food. 
 
 The difficulty- of adjusting the appetite to the actual physiological 
 requirement is perhaps the real anomaly in adiposophilia. Several 
 factors seem to be involved in the group of sensations comprised under 
 appetite and hunger (Chapter XVIII), and the onset and intensity of 
 these sensations are imquestionably influenced by habit. The real 
 
570 METABOLISM. XUTRITJON AND DIETETICS 
 
 question in many cases of obesity may be not why the metabolism is 
 managed so parsimoniously — that is, in the physiological sense, so 
 thriftily — but why the fat man or the man tending to Income fat still 
 experiences so strong a desire for food after he has eaten what in pro- 
 portion to his metabolic wants is enough, whereas the man with no 
 tendency to obesity is no longer hungrj- after he has eaten an amount 
 of food sufficient for the requirements of his tissues. Is there here 
 perhaps an anomaly in the nervous mechanism in virtue of which, for 
 instance, the gastric himgcr contractions are more readily initiated 
 and less easily stilled than in the normal person ? It is recognized 
 that in the usually much more serious anomaly of the carbo-hydrate 
 metabolism, diabetes mcllitus, the nervous element may be important. 
 The influence of the loss of certain of the internal secretions on the 
 deposit of fat will be alluded to in the next chapter. 
 
 In the treatment of obesity the factor of appetite and hunger control 
 has to be specially kept in mind. Bulky but comparatively innu- 
 tritious food, such as green vegetables, e.g., in the form of salads, should 
 form an important constituent of the dietary-, since the mere distension 
 of the stomach staves off hunger. The total heat value of the food 
 must be reduced gradually. Carbo-hydrates must be largely excluded, 
 and also fats, although a certain amount of fat, say in the form of 
 butter, is permissible and even beneficial as aiding in the passage of 
 the food along the digestive tube. Alcoholic beverages are in general 
 contra-indicated, because alcohol, as an easily oxidizable substance, 
 protects the carbo-hydrates and fats from oxidation, and perhaps also 
 because the normal oxidative power of the tissues nxa.y be depressed by 
 its habitual use. On the other hand, tobacco smoking, which has some 
 power of inhibiting the gastric hunger contractions, may be permitted. 
 Muscular exercise, cold baths, light clothing both during the day and 
 at night, and a cool environment, are favourable to the reduction of 
 fat by increasing the consumption of material and the loss of heat, 
 just as a sedentary life in an o\erheated house in a person predisposed 
 to obesity, and eating too much for his requirements, favours the 
 putting on of fat. But if the appetite of the patient is allowed to 
 govern the intake of food, the increased decomposition brought about 
 by exercise, etc., is ver\- likeh- to be balanced by an increased ingestion, 
 and no progress will be made. 
 
 Metabolism of Sterins or Sterols. — It has been previously stated 
 that cholesterin appears to be the only representative of the sterins 
 in the higher animals. Its source and function have been much 
 discussed of late years. As to its source, there seems to be no 
 reason to believe that any part of the cholesterin of the tissues is 
 formed from decomposition products of ordinary fats, carbo- 
 hydrates, or proteins. It is probably entirely derived from the 
 cholesterins of animal, and the phytosterins of vegetable food. On 
 this assumption, its metabolism, imlike that of the great groups of 
 food substances, is carried on in a closed circuit. E\ndence that 
 it can be s\Tithesized from other substances in the body is lacking. 
 No increase in the cholesterin lias been observed during the develop- 
 ment of eggs, and the cholesterin content of gro\nng chickens 
 appears to correspond to the sterins taken in the food (Gardner). 
 The portion of the cholesterin which is ingested in the form of esters 
 
THE METABOLISM Of tAT 571 
 
 is probably split, with liberation of the fatty acid, in the course of 
 digestion. But if this be so, cholesterin esters are again formed 
 in the tissues, for the cells and the blood contain both cholesterin 
 esters and free cholesterin. While some cholesterin is excreted in 
 the faeces (p. 423), there is evidence that a portion of the cholesterin 
 of the bile may be reabsorbed, a ' circulation ' of cholesterin taking 
 place analogous to the circulation of bile-salts. The appearance of 
 cholesterin in the bile has been connected by some writers with the 
 destruction of erythrocytes in the liver, or the conveyance of the 
 products of their decomposition to that organ (p. 21), but there 
 are no means of distinguishing between the cholesterin set free from 
 blood-corpuscles and that liberated from other cells. Since it is 
 contained in all cells, every cell may be supposed to contribute 
 something from time to time to the cholesterin excretion. 
 
 As to the office of the tissue-cholesterin, it can only be suggested 
 that a substance so ubiquitous must be important. There is some 
 evidence that cholesterin, free or combined, plays a part in con- 
 ferring on the cells those peculiarities in their permeability upon 
 which their functions, and indeed their integrity, depend. Free 
 cholesterin, for instance, hinders the haemolytic action of the 
 saponins (p. 28), apparently by forming compounds with them 
 Whether it or its esters are actually concentrated at the surface of 
 the cell, and contribute to the formation there of the so-called 
 ' lipoid ' envelope, is not definitely known, although there are facts 
 in favour of this idea. 
 
 Metabolism of Phosphatides. — The lecithins, which are the best- 
 known members of this class of compounds, have been already 
 described (p. 366). They are built up of gl3^cerin, fatty acids, 
 phosphoric acid in the form of glyceryl-phosphoric acid, and a 
 nitrogenous base cholin. There is some reason to think that the 
 lecithins of the tissues are, in part at least, not free, but combined 
 with proteins or with carbo-hydrates. Other bodies belonging to 
 the phosphatide group are kephalin, a constituent of nervous tissue 
 and of yolk of egg, cuorin found in heart muscle, etc. 
 
 It is probable, as stated in the chapter on Digestion, that the 
 phosphatides of the food are hydrolysed in the alimentary canal 
 with liberation of the glycerin, fatty acids, and the other com- 
 ponents. It is not known whether they are resynthesized in the 
 intestinal wall, but it is more probable that they pass directly to 
 the tissues, where they can be utilized for building up the phos- 
 phatides of the cells. Chohn is found in small quantities free in the 
 tissues, and also, it is said, in the blood-plasma. Glyceryl-phos- 
 phoric acid has also been obtained in small amount from various 
 tissues. The other components of lecithin are, of course, never 
 wanting, and there can be no doubt that the cells possess the power 
 of reconstructing phosphatides from such materials. They can do 
 
572 METABOLISM, NUTRITION AND DIETETICS 
 
 more than this: they can prepare the 'building-stones 'themselves. 
 For even when the ingestion of phosphatides in the food is excluded, 
 or the intake is so small as to be negligible, the formation of phos- 
 phatides in the body goes on apparently without chock. An instance 
 of this will be given on a future page in discussing experiments on 
 the relative value of different proteins for nutrition and growth. 
 A very striking observation has been recorded by McCollom, who 
 fed three hens on a diet almost free from fat. In about three and a 
 lialf months they laid fifty-seven eggs, containing over 9 per cent, of 
 phosphatides. Calculation showed that here, first of all, fats or their 
 components must have been constructed from carbo-hydrates. 
 Then the nitrogenous component of the phosphatides (cholin in the 
 case of lecithin, at least) must have been obtained from some source, 
 possibly from an amino-acid by the addition of methyl groups 
 
 /CH3 
 
 (CH3), of which cholin, OH-H^CHgC -NC^fJs (trimethyl-oxyethyl- 
 
 OH 
 ammonium hydroxide) contains three. 
 
 Section III. — Metabolism of Proteins. 
 
 Blood-Proteins. — The two chief proteins of the plasma, serum- 
 globulin and serum-albumin,* must, as has been already pointed out, 
 be recruited from proteins absorbed from the intestine and for the most 
 part, at any rate, profoundly altered in its lumen and in their passage 
 through the epithelium which lines it. Even when proteins are being 
 actively absorbed, the plasma, after the blood-proteins have been 
 separated, contains no substances which give the biuret reaction 
 (p. 449). So that the peptones, which can be demonstrated in the 
 intestinal contents, suffer great changes before or during their 
 absorption. The physiological reasons for this alteration are in a 
 measure known, and have already been alluded to in connection 
 with the digestion of proteins. No doubt the far-reaching decom- 
 position of the protein molecule may to some extent facilitate the 
 absorption of protein food. No doubt also it is imperative that 
 such comparatively slightly hydrolysed products as peptone, and 
 particularly proteose, should not appear in quantity in the blood, 
 for when injected they cause profound changes in that liquid, one 
 expression of which is the loss of its power of coagulation, and are 
 rapidly excreted by the kidneys, or separated out into the Ij-mph. 
 But the passage of the food from the stomach is so gradual an affair, 
 the quantity of digesting protein present at one time in any loop 
 of intestine is so small, and the rush of blood which irrigates the 
 
 * It is probable that plasma contains a mixture of different albumins anc* 
 
 globulins. 
 
METABOLISM OF PROTEINS 573 
 
 active mucosa is so large, that the concentration of peptone or 
 proteose necessary to procUice injurious eltects could hardly in any 
 case be realized. Again, there is no evidence tluU: the simpler 
 decomposition products of further hydrolysis are not in equal con- 
 centration as poisonous as proteose and peptone. 
 
 Apart from any influence which it may have in favouring absorp- 
 tion, the complete shattering of the protein molecule has a double 
 significance. In the first place, as already pointed out, the food- 
 proteins cannot be used directly in the upbuilding and repair of the 
 protoplasm (p. 448), since the tissue-proteins differ from them and 
 from each other in the amount and nature of the amino-acids and 
 other groups in their molecule (p. 2). Secondly, under ordinary 
 dietetic conditions a surplus of nitrogen in the protein food has to 
 be got rid of by being converted into urea without being built up 
 into the tissue substance. Here we come upon the fundamental 
 fact that the protein katabolism is not a single uniform process. 
 Two forms may be distinguished which are essentially independent 
 in course and character. One kind varies extremely in its quantita- 
 tive relations, according to the amount of protein in the food. Its 
 chief end-products are urea, representing the nitrogen, and inorganic 
 sulphates, representing the sulphur of the proteins. Since this form 
 of katabolism, as we shall see directly, is not essentially connected 
 with the life and nutrition of the living substance, it is termed 
 exogenous. The other variety is practically constant in amount 
 for one and the same individual, and independent of the quantity 
 of protein in the food. Its characteristic end-products are creatinin 
 and neutral sulphur. This form of protein katabolism is essentially 
 an expression of the waste of the living substance itself, and is 
 therefore spoken of as endogenous. 
 
 Some have supposed that the intestinal mucosa has as one of its 
 special functions the resynthesis of a great part of the digestive 
 decomposition products into the proteins of the blood-plasma. If 
 this is the case, these proteins must be again decomposed in the 
 cells of the various tissues in order that the ' building-stones ' may 
 be recombined to form the tissue-proteins. For the proteins of the 
 organs are not the same as those of the blood, and the proteins of 
 different organs differ characteristically from each other. The 
 significance of the synthetic function of the intestinal wall would 
 then lie in this: that from the varjdng mixture of amino-acids, etc., 
 derived from the food-proteins an always uniform and suitable 
 protein mixture (the blood-proteins) is fabricated for the feeding 
 of the tissues. Experiments intended to test this hypothesis have 
 hitherto yielded a negative result. No accumulation of protein in 
 the wall either of the intestine in situ or of the isolated surviving 
 intestine has been detected during absorption of the decomposition 
 products of protein. An alternative assumption, and superficially 
 at least a simpler one, is that no more extensive synthesis of proteins 
 
574 METABOLISM. NUTRITION AND DIETETICS 
 
 occurs in the wall of the ahmentary canal than is necessary for the 
 needs of the tissues composing it, and, perhaps in addition, for the 
 maintenance of the normal composition of the ])lasma, and that the 
 decomposition products of the proteins are mainly absorbed as such, 
 and pass in the blood to the tissues for which they are destined. If 
 this is the case, the blood-proteins can no longer be looked upon as 
 representing the main current of protein supply for the organs, but 
 rather the store of protein material proper to the circulating tissue 
 blood itself, and which confers on it certain chemical and physio- 
 chemical properties {e.g., the due degree of viscosity) necessary for 
 its function. Slowly accumulated, under ordinary conditions, and 
 slowly consumed, this protein store may, of course, be at the dis- 
 posal of the organs in an emergency — for instance, in starvation — 
 or may be rapidly recruited from the organ-proteins, as after 
 haemorrhage, just as in prolonged hunger the proteins of skeletal 
 muscle may be utiUzed to feed the heart. That the blood-proteins 
 can serve as nutritive material for the cells without undergoing 
 digestion in the alimentary canal is well shown by the observations 
 of Carrell and Burrows on the growth of isolated tissues in a medium 
 composed of clotted blood-plasma. But, as previously pointed out 
 in another connection (p. 449), a portion, and probably a large 
 portion, of the digested protein is absorbed from the intestine by 
 the blood in the form of amino-acids. Considerable quantities of 
 these compounds can be separated by dialysis from blood drawn 
 off during the absorption of proteins or by the process of vivi- 
 diffusion (p. 48) (Abel). Among these amino-acids, glycocoU, 
 alanin, glutaminic acid, and leucin, have been identified. While 
 the quantity of amino-acids in the blood, which is very small in the 
 fasting animal, is decidedly increased during protein digestion, it 
 is probable that even in starvation amino-acids derived from the 
 decomposition of the body-proteins are not entirely lacking. The 
 normal concentration of amino-acids in the general blood of man and 
 of the dog is about 01 per cent. — i.e., about the same as that of 
 dextrose, and it may be nearly twice as great in the portal blood 
 of dogs after a heavy protein meal. The amino-acids are very 
 rapidly absorbed by the tissues from the blood, and can be demon- 
 strated in muscles and other organs as free amino-acids. They 
 accumulate there in much greater concentration than that in which 
 they exist in the blood. Accordingly, the tissues take them up from 
 the blood by some other process than simple diffusion (Van Slyke). 
 It has been surmised that amino-acids constitute the form in which 
 proteins are transported from tissue to tissue, as well as the form in 
 which proteins are normally utilized by the cells.* Although this 
 cannot be regarded as yet established, there is reason to believe that 
 
 • Recent experiments of Abel tend to rehabilitate the old view that some 
 protein is absorbed as proteoses, which can also be isolated from the tissues 
 
METABOLISM OF PROTEINS 
 
 573 
 
 the amino-acids play a great part in protein metabolism, perhaps as 
 great a part as the dextrose docs in the metabohsm of the carbo- 
 hydrates. There is some evidence that serum-albumin is more 
 directly related to thf proteins of the food than scrum-globulin. 
 And it is said that during starvation the albumin is relativelv 
 diminished, and the globulin relatively increased. It is, of course, 
 not at all improbable that the plasma-proteins have a double source 
 — organ-proteins on the one hand, food-proteins on the other. In 
 any case, it is certain that serum-albumin and serum-globulin 
 c annot be intercliangeable without far-reaching decomposition, for 
 their composition is very different. The globulin, e.g., yic^lds glyco- 
 coll, but the albumin does not. That the plasma-protein mixture 
 maintains a very constant composition in the face of wide variations 
 in the composition of the food-protein is indicated b}' the following 
 experiment: 
 
 A horse fed mainly on hay and oats was bled to the amount of 
 6 litres, and in the total protein of the serum the content of tyrosin and 
 glutaminic acid was detennined. In order to eliminate the influence 
 of remains of the food in the digestive canal, nothing was given to the 
 animal for a week. 'Ihen 6 litres of blood were again removed, and the 
 tyrosin and glutaminic acid in the serum-protein again estimated. 
 The horse was now fed with gliadin (one of the prolamins or alcohol- 
 soluble proteins obtained from flour), a substance which contains 36'5 per 
 cent, glutaminic acid and 2-37 per cent, tyrosin — that is, about the 
 same amount of tyrosin as the serum-protein, but about four times as 
 much glutaminic acid. The serum-protein was again analyzed for the 
 two amino-acids after this diet. The results of one experiment are 
 shown in the table : 
 
 
 Normal. 
 
 After 8 Days' 
 Hunger. 
 
 After Feeding 
 
 with 1,500 
 
 Grammes 
 
 Gliadin. 
 
 After Feeding 
 
 again with 1,500 
 Grammes 
 Gliadin. 
 
 Tyrosin - - - 
 Glutaminic acid 
 
 2-43 
 8-85 
 
 2 -60 
 8-20 
 
 2-24 
 
 7-88 
 
 2-52 
 
 8-25 
 
 No increase in the glutaminic acid content of the serum-protein 
 occurred, although, owing to the loss of blood, much new scrum-protein 
 must have been formed. If the amino-acids of the gliadin were used 
 without change to build up the new serum-protein, three-quarters of 
 the glutaminic acid must have been superfluous, and the nitrogen of 
 this portion may have been straightway changed into urea and excreted. 
 But the possibility that the glutaminic acid, or a portion of it, may 
 have been changed into other amino-acids in the body cannot be 
 excluded. In the case of some of the amino-acids it has been shown 
 that such a transformation occurs (p. 613) (Abderhalden). 
 
 The high degree of independence of the food and body proteins is 
 still more clearly exhibited in the table from Abderhalden on p. 57b, 
 in which the proteins of milk are compared with some of the proteins 
 which must be formed from them in the body of the suckling. The 
 numbers represent percentages of the weight of each protein. 
 
576 
 
 METABOLISM. NUTRlTlOX AND DIETETICS 
 
 Living and Dead Proteins. — Carried to the tissues, the decomposition 
 produLls of the food -proteins, or the regenerated proteins of the plasma, 
 which in ordinary language are still to be regarded as dead material, 
 arc built up into the living protoplasm, at any rate to the extent neces-, 
 sary to make good its waste. In this form they sojourn for a time 
 within the cells, and then they become dead material again. The 
 nature of this tremendous transformation has, of course, been the 
 subject of speculation, but the truth is that we do not understand 
 wherein the difference between a living and a dead cell, between a living 
 and a dead particle in one and the same cell, really consists. All we 
 know is that now and again a protein molecule or an aggregate of such 
 molecules incorporated in the colloid mass which constitutes the proto- 
 plasm of a muscle-fibre, or a gland-cell, or a nerve-cell, must fall to 
 pieces. Now and again a molecule of protein , hitherto dead (or perhaps, 
 to speak more correctly, hitherto not a constituent of living protoplasm, 
 since protoplasm is certainly more than protein), or a molecule of a 
 particular amino-acid, or perhaps a polypeptide group intermediate in 
 complexity between amino-acid and protein, coming within the grasp 
 of the molecular forces or chemical affinities of the living substance, is 
 caught up by it, takes on its peculiar motions, acquires its special powers, 
 and is, as we phrase it, made alive. Each cell has tlic power of selecting 
 and, if necessary, further decomposing or further synthesizing the 
 protein materials offered to it ; so that a particle of sx-rum-albumin or a 
 mixture of amino-acids may chance to take its place in a liver-cell and 
 help to form bile, while an exactly similar particle or mixture may 
 furnish constituents to an endothelial scale of a capillary and assist in 
 forming lymph, or to a muscular fibre of the heart and help to drive on 
 the blood, or to a spermatozoon and aid in transferring the peculiarities 
 of the father to the offspring. And just as a tomb and a lighthouse, a 
 palace and a church, may be, and have been, built with the same kind 
 of material, or even in succession with the verj^ same stones, so every 
 organ builds up its own characteristic structure from the common 
 quarry of the blood. 
 
 1 
 
 6 
 
 
 il 
 4 
 
 
 3 
 
 O 
 
 5 
 
 
 ft 
 
 =;5 
 
 c 
 •3 
 
 5 
 
 2 
 
 
 
 
 
 
 
 
 
 
 
 Glycocoll - 
 
 o 
 
 O 
 
 o 
 
 3 -.5 
 
 o 
 
 3-0 
 
 0-5 
 
 26-0 
 
 47 
 
 1 Alanin 
 
 0-9 
 
 2-5 
 
 2-7 
 
 2-2 
 
 4-2 
 
 3-6 
 
 3-5 
 
 6-6 
 
 1-5 
 
 : Valin 
 
 I-O 
 
 0-9 
 
 some 
 
 
 
 some 
 
 I-O 
 
 
 i-o 
 
 0-9 
 
 { Leucin 
 
 10-5 
 
 I9-.5 
 
 20*0 
 
 18-7 
 
 29-0 
 
 I5-0 
 
 II-8 
 
 21-4 
 
 7-1 ! 
 
 1 Serin 
 
 0-2 
 
 
 0-6 
 
 
 0-6 
 
 some 
 
 — 
 
 
 _ i 
 
 1 Cystin 
 
 o-oy 
 
 — 
 
 2-3 
 
 0-7 
 
 0-3 
 
 — 
 
 — 
 
 — 
 
 0-6 
 
 Asparaginic acid 
 
 1-2 
 
 I'O 
 
 3-1 
 
 2-5 
 
 4*4 
 
 2-0 
 
 — 
 
 — 
 
 lO-O 
 
 Glutaminic acid 
 
 II-O 
 
 lO'O 
 
 77 
 
 8-=i 
 
 17 
 
 8-0 
 
 0'3 
 
 0-8 
 
 37 
 
 Lysin 
 
 .V« 
 
 — 
 
 
 
 4-3 
 
 — 
 
 6-q 
 
 — 
 
 
 Arginin 
 
 4-8 
 
 — 
 
 — 
 
 — 
 
 5'4 
 
 
 
 I5'5 
 
 o-^ 
 
 
 
 Phenylalanin - 
 
 3-2 
 
 2-4 
 
 3-1 
 
 3-8 
 
 4-2 
 
 2-0 
 
 2-2 
 
 3-9 
 
 — 
 
 Tyrosin - 
 
 4*5 
 
 I-O 
 
 2-1 
 
 2-5 
 
 1-5 
 
 3-3 
 
 .5-2 
 
 0-34 
 
 3-2 
 
 Prolm 
 
 3-1 
 
 4-0 
 
 i-o 
 
 2-8 
 
 2-3 
 
 2-5 
 
 1-5 
 
 1-7 
 
 3 "4 
 
 Histidin - 
 
 2-6 
 
 
 
 
 — 
 
 II-O 
 
 
 1-5 
 
 
 
M ETA HOLISM OF PROTEINS 577 
 
 It is not any difference in tlic kind of protein oflcrcd tliem which 
 determines the difference in structure and action between one organ 
 and another. In tliis quarry alongside of the plasma proteins the tissue 
 cells find what is probably more important for their individual nutrition, 
 the building-stones of the shattered food-protein molecules. They are 
 only under exceptional circumstances confronted with intact molecules 
 of food-proteins. ' The body cells do not know what the kind of food 
 was ' (Abderhalden). In the case of the more highly developed tissues, 
 at least, no mere change of food will radically alter the structure of the 
 cells, nor even, as we have seen, the composition of the tissue proteins. 
 A cell may be fed with different kinds of food, it may be overfed, it may 
 be ill-fed, it may be starved; but its essential peculiarities remain as 
 long as it continues to live. What may be called its organization, per- 
 haps at bottom a more or less metaphorical expression for its tssential 
 physico-chemical make-up, dominates its nutrition and function. 
 
 ' We must assume that many of the enigmatical properties of living 
 matter depend upon the activity of intact protein molecules. We can 
 obtain some idea of the possible variety in the combinations of the 
 '' building-stones " of the proteins by recalling the fact that they are as 
 numerous as the letters of the alphabet, which are capable of expressing 
 an infinite number of thoughts. Every peculiarity of species and every 
 occurrence affecting the individual may be indicated by special com- 
 binations of the "building-stones " — that is to say, by specific proteins. 
 Consequently we may readily understand how peculiarity of species 
 may find expression in the chemical nature of the proteins constituting 
 living matter, and how they may be transmitted through the material 
 contained in the generative cells ' (Kossel). Add to the great variety 
 of compounds rendered possible by the enormous number of permuta- 
 tions and combinations of the protein ' building-stones,'* the still greater 
 variety rendered possible by the fact that the quantitative relations of 
 given amino-acids may vary greatly in different proteins, and it will be 
 seen what a practically infinite power of functional adjustment and 
 reaction, correlated with a practically infinite variety of chemical 
 changes in the midst of which the cell still preserves its specificity 
 through and through, may be conferred upon the living substance by 
 its content of protein. 
 
 Some have supposed that the protein of the living substance is es- 
 sentially different from dead protein, especially in possessing a character- 
 istic instability, a prodigious power of dissociation and reconstruction. 
 All the older theories which attempted to explain this alleged difference 
 require revision in accordance with the newer chemistr^^ of proteins, 
 and speculations on the subject are probably in any case premature 
 till the constitution of the proteins is thoroughly understood. In the 
 meantime it is enough to say that the velocity of the reactions into 
 which the proteins of living protoplasm or their constituent amino- 
 acids may enter must depend upon intracellular conditions, which may 
 vary rapidly and within wide limits. For example, enz^-mes may be 
 present ia greater or smaller concentration, or be activated and aided 
 more or less powerfully by other substances, or by a more or less favour- 
 able chemical reaction of the medium. The protein itself, too, or such 
 part of it as is ready for decomposition, may exist in a physical con- 
 dition now more and again less favourable to the attack of the enzymes. 
 
 * Twenty different amino-acids, each used only once, but in a different order, 
 would be capable of forming about 2,000,000,000,000,000,000 (two thousand 
 million times a thousand millions) of different poI\-peptides, all contaimng the 
 various amino-acids in the same proportions (Abderhalden). 
 
 37 
 
578 M ETA HOLISM. NUTRITION AND DIETETICS 
 
 It may not be superfluous at tliis point to again warn the reader that 
 protoplaspi and tissuc-profeins are by no means synonymous. The 
 physical, physico-chemical, and chemical changes involved in the 
 katabolism of the colloid aggregates, including water, salts, phosphatides, 
 sterins, and probably fats and dextrose as well as proteins, to which 
 the term protoplasm is applied, may be many and complex before the 
 individual proteins known to the chemist come face to face in the 
 interior of the cells with the ferments which decompose them. On the 
 other hand, it has not been proved that in the katabolic processes of the 
 living substance isolated proteins ever form a stage. It may well be 
 that without the complete decomposition of the protein molecules, or 
 even without their complete detachment from the protoplasm, indi- 
 vidual amino-acids or mixtures cf amino-acids, or polypeptide groups, 
 are cut out of the protoplasmic mass. 
 
 It is now necessary to follow, as far as is possible*, the steps 
 in the degradation of the body-proteins. Since there is reason to 
 believe that these, like the food-proteins, are first split up into the 
 amino-acids from which they were originally synthesized before 
 undergoing further decomposition, a study of protein metabolism 
 is to a great extent r study of the metabolism of amino-acids. In 
 this study it is for most purposes impracticable, even if it were 
 desirable, to distinguish between amino-acids directly derived from 
 the food, and which have not yet been, and may never be, built up 
 into tissue-proteins, and those derived from the tissue proteins. 
 There is nothing to indicate that the fate of a given amino-acid, 
 once it has reached the blood, depends in the least upon its source. 
 It may be said at once that the katabolism of the amino-acids is not 
 a single and uniform process, one step in which inevitably follows 
 another till the final end-products are reached. On the contrary, 
 certain of the stages may become the starting-points of syntheses, 
 which may lead back to the original or to another protein, or it 
 may be to sugar or to fat. The extent of such synthesis, and 
 even in some degree the stage from which it starts, may be assumed 
 to depend upon the needs of the tissues and the relative abundance 
 of protein and of other foods. 
 
 Formation of Amino-Acids from Tissue-Proteins. — That amino- 
 acids are formed in the metabolism of the cells and by the action of 
 intracellular enzymes is indicated by the fact that proteolytic en- 
 zymes (proteases) are invariably present in the tissues, and can 
 be obtained from them by appropriate methods — e.g., by subjecting 
 the organ in a finely divided state to a high pressure and collecting 
 the expressed juice. Not only do imicellular organisms, like leuco- 
 cytes, yeast cells, and bacteria, which must naturally depend upon 
 themselves alone for all enzymatic reactions, yield ferments which 
 have the power of splitting proteins, peptones, and polypeptides 
 into amino-acids, but their existence has been demonstrated in 
 practically all the organs of the higher animals and man. When a 
 piece of liver, e.g., is removed with aseptic precautions and kept at 
 
METABOLISM OI- PROTniNS 57O 
 
 body-temperature, extensive auto-digestion occurs, and ammonia 
 and otlu-r basic substances, glycin, and tryptophane, appear among 
 the prochicts. Tyrosin appears so early that it is scarcely possible 
 to doubt that it must be a product of protein decomposition in the 
 liver-cells under normal conditions — a decomposition which could 
 be observed also in the organ in situ were the circumstances as 
 favourable. The circumstances are less favourable in an organ 
 whose circulation is going on, becaiise the amino-acids are removed 
 by the blood as they are formed. Further, it is to be assumed that 
 the regulation of the ferment action, which is a characteristic 
 property of the normal cell, becomes feebler the longer it is with- 
 drawn from normal conditions. Similar autolytic processes have 
 been observed in the spleen, muscle, lymph-glands, kidneys, lungs, 
 stomach wall (independently of pepsin), thymus, and placenta; 
 also in pathological new growths like carcinoma, in the breaking 
 down of which anti in the removal of such exudations as occur in 
 the alveoli in pneumonia, these proteolytic ferments seem to play 
 a part. It is to be assumed that the syntheses of the proteins or 
 their products, which are scarcely less characteristic of the tissue 
 cells than the decompositions effected by them, are also due to 
 the action of separate intracellular ferments or upon the reversed 
 activity of the proteolytic ferments. 
 
 More direct proofs of the production of amino-acids in the tissues 
 are not lacking. A rare condition known as cystinuria has been 
 alluded to on a previous page (p. 488). Here there is a continuous 
 excretion of the sulphur-containing amino-acid cystin in the urine. 
 Sometimes the cystin is accompanied by other amino-acids, as 
 leucin and tyrosin, a condition which might be called amino- 
 aciduria. Cystinuria, while of course resulting from a.gross anomaly 
 in metabolism, is of little clinical importance unless the sparingly 
 soluble cystin should form calculi somewhere in the urinary tract. 
 The most plausible explanation of the condition is that in the 
 normal course of the metabolism each of the ' building-stones ' of 
 the proteins is sooner or later further decomposed by special fer- 
 ments, and that for some reason the ferment which acts on cystin 
 is absent, or if it is still produced, the conditions are more or less 
 unfavourable to its action. Unable to take its place in the meta- 
 bolic current, except in so far as it can be utilized to form taurin, 
 and therefore taurocholic acid — for this property it has not lost — 
 cystin becomes a chemical outcast in the body of the cystinuric 
 individual, and is got rid of by the kidneys as an ' unemployable.' 
 By comparing the amount of cystin excreted with the amount 
 ingested in the food-proteins and with the (undiminished) amount 
 contained in the tissues (especially the hair and the nails, since 
 keratin is exceptionally rich in cystin), it has been shown that a 
 portion of the cystin in the urine must have come from the tissues 
 
5?^! METABOLISM. NUTRITION AND DIETETICS 
 
 (Abdcrlialilcn). Observations on animals in prolonged starvation 
 afford additional evidence. The hair and nails continue to grow 
 and to maintain the high cystin content, and taurocholic acid con- 
 tinues to be excreted. In like manner glj'cin continues to be pro- 
 duced and to unite with cholic acid to form the glycocholic acid of 
 the bile. 
 
 There are other and more striking proofs that glycin can be 
 formed in the body in large amount. For example, as already 
 stated (p. 481), when benzoic acid is ingested it is not excreted as 
 such in the urine, but coupled with glycocoll as hippuric acid. 
 Thus— 
 
 CjHb.COOH + CH2(NH2).COOH - HgO =CaH6.CO.NH.CH2.COOH 
 
 Ben7oic acid. Glycocoll. Hippuric acid. 
 
 Benzoic acid, therefore, meets glycin in the body, and combines 
 with it, as fatty acids meet glycerin and combine with it. Even 
 starving animals fed with benzoic acid excrete large quantities of 
 hippuric acid. Yet their tissues, as shown by analysis after death, 
 yield as much glycocoll as starving animals which have received no 
 benzoic acid, and excreted little or no hippuric acid. Many other 
 acids which are totally foreign to the body are, when ingested, 
 paired in the same way with glycocoll and excreted in the urine. 
 Even substances whose chemical nature does not permit of a direct 
 union with the glycin are often altered by oxidation or reduction 
 till they can unite with it, and then the coupling takes place, and 
 the conjugated acid is eliminated by the kidneys. The paired or 
 aromatic sulphuric acid which we have already recognized as a 
 normal constituent of the urine affords another instance of this 
 coupling. Cystein among the derivatives of proteins, and glycu- 
 ronic acid (p. 482) among the derivatives of carbo-hydrates, can 
 also unite in the same way with numerous compounds. There is 
 some evidence that the physiological significance of this process is 
 that the toxicity of the foreign substances, or, as in the case of the 
 aromatic sulphuric acid of the urine, of substances formed by 
 bacteria in the intestine, or even produced in the metabolism of the 
 tissues, is diminislied by the pairing. 
 
 The place and manner of formation of hippuric acid have been 
 investigated with the following result: If an excised kidney is per- 
 fused with blood containing benzoic acid, or, better, benzoic acid 
 and glycin, hippuric acid is formed. Oxygen is required, for if the 
 blood is saturated with carbon monoxide, or if serum is employed 
 for perfusion, the synthesis does not take place. The kidney cells 
 must be intact, for if a mixture of blood, glycin, and benzoic acid 
 be added to a minced kidney immediately after its removal from 
 the body, hippuric acid is produced, but not if the kidney has been 
 crushed in a mortar. Nevertheless, there is some evidence that a 
 
METABOLISM OF PROTEINS 581 
 
 ferment is concerned, and the known mechanism of similar reactions 
 in the body scarcely permits the physioloi^ist to acquiesce in any 
 other explanation. It must not be forg(jtten that the urinary 
 constituents which must come into contact with the ferment when 
 the kidney is crushed may injure or inhil^it the enzyme. In 
 herbivora hippuric acid cannot normally be detected in the blood; 
 it is present in large quantities in the urine; it must therefore be 
 manufactured in the kidney, not merely separated by it. In certain 
 animals, as the dog, the kidney is the sole seat of the production 
 01 hippunc acid. But in the rabbit and the frog some of it must 
 also be formed in other tissues, for after extirpation of the kidneys 
 the administration of benzoic acid causes hippuric acid to appear 
 in the blood. It has, indeed, been recently shown that when the 
 rabbit's liver is perfused with blood containing benzoic acid, hip- 
 puric acid is produced. The benzoic acid required for the normal 
 excretion of hippuric acid comes mainly from substances of the 
 aromatic group contained in vegetable food, but a small amount is 
 produced in the body, since hippuric acid does not entirely dis- 
 appear from the urine in starvation. 
 
 The differences which may exist in the metabohsm of different 
 groups of animals is well illustrated by the fact that in birds, when 
 benzoic acid is given in the food, it unites not with glycin, but with 
 ornithin, a derivative of arginin, forming not hippuric acid, but 
 ornithuric acid (dibenzoyl-ornithin). A much more important 
 instance of such a difference will be seen when we come to consider 
 the formation of urea and uric acid. 
 
 The method by which the presence and the production of glyco- 
 coll in the body are demonstrated by coupling it with benzoic acid, 
 and so sa\ang it from decomposition and bringing it to excretion, 
 can also be applied to other amino-acids. If instead of fishing 
 with the bait benzoic acid we fish with a bait called brom-benzol or 
 bromo-benzene (CgHg.Br), a substance derived from benzol by 
 the substitution of an atom of bromine for an atom of hydrogen, 
 we capture the amino-acid cj-stein in the form of a compound 
 called mercapturic acid, produced by the union of brom-benzol with 
 cystein and acetic acid, with oxidation and loss of water. In other 
 words, when this substance is administered, mercapturic acid is 
 excreted in the urine, the cystein, which is very unstable and readily 
 changes into cystin (p. 360), being thus preserved from decom- 
 position. Another instance in which amino-acids (tyrosin and 
 phenylalanin), which would normally be decomposed and so escape 
 detection, come to the surface by being excreted in the urine, has 
 a'ready been alluded to in connection with alkaptonuria (p. 483). 
 In this condition, which seems to have no serious significance so 
 far as the well-being of the patient is concerned, not only does the 
 taking of food containing the aforesaid amino-acids lead to an 
 
582 RIETABOLISM. NVTIilTlOK AND DIETETICS 
 
 increased cx( vction of homogentisinic acid, but even in starvation 
 this substance still continues to appear in tlie urine. Since liomo- 
 gcntisinic acid is undoubtedly formed from tyrosin and from phenyl- 
 alanin, this observation constitutes a convincing proof that these 
 amino-acids are produced from tissue-proteins. A striking illus- 
 tration of the fact that the amino-acids of the tissues are not simply 
 a store of reserve material derived directly from the alimentary canal 
 is the failure of a period of starvation to make any impression upon 
 their amount. They normally constitute 2 to 4 per cent, of the dry 
 weight of the tissues, and if anything, tend somewhat to increase 
 in the tissues of a starving animal. 
 
 Fate of Amino- Acids in the Body. — The problem of the kata- 
 bolism of proteins is thus reduced to the question, What becomes of 
 the amino-acids ? Where, how, by what stages, and to what end- 
 products are they decomposed ? Some possible or probable steps 
 in their metabolic history have been already suggested in dealing 
 with the intermediary metabohsm of carbohydrates (p. 54-)- 
 Something more will have to be said of the where and the how of 
 their chemical degradation in treating of the place and manner of 
 urea formation. As to the end-products by which they are repre- 
 sented in the final balance-sheet of the bodily economy, the answer 
 is easy. The amino-acids, whatever intermediate stages they may 
 pass through, whatever cleavages, oxidations, or reductions they may 
 undergo, yield eventually carbon dioxide, water, and comparatively 
 simple nitrogen-containing substances, which after further changes 
 appear in the urine principally as urea, and in birds and reptiles as 
 uric acid. When amino-acids are fed to mammals or introduced 
 parenterally, a very large proportion of the nitrogen appears in the 
 urine as urea. The same is true when, instead of simple amino- 
 acids, polypeptides, hke glycyl-glycin, alanyl-alanin, or leucyl-leucin, 
 are given. When amino-acids are administered to birds, the great 
 bulk of the nitrogen is excreted in the form of uric acid. Whether 
 in mammals, and if so to what extent, uric acid is also one of the 
 nitrogenous end-products of the decomposition of ordinary proteins 
 or of the amino-acids which they yield, are moot questions. In 
 any case, the most important and characteristic source of the uric 
 and in mammals and the other groups of animals whose chief 
 nitrogenous end-product is urea, is not the ordinary proteins, but 
 the nucleins which form constituents of the nucleo-proteins. 
 
 We have no definite information as to the production of water from 
 the hydrogen of the tissues, except what can be theoretically deduced 
 from the statistics of nutrition (p. 620). A few words will be said 
 a little farther on about the production of carbon dioxide from 
 proteins; we have now to consider the seat and manner of formation 
 of the nitrogenous metabolites. And since in man and the other 
 mammals urea contains, under ordinary conditions, by far the 
 
METABOLISM OF PROTEINS 583 
 
 greater part of the excreted nitrogen, it will be well to take it 
 
 first. 
 
 Formation of Urea. — The starting-point of all inquiries as to the 
 place of formation of urea is the fact that it occurs in the blood in 
 small amount (4 to 6 parts per 10,000 in man; 3 to 15 parts per 
 10,000 in the dog), the largest quantity being found when the food 
 contains most protein and at the height of digestion, the smallest 
 quantity in hunger (Schondorff). Evidently, then, some, at least, 
 of the urea excreted in the urine may be simply separated by the 
 kidney from the blood; and analysis shows that this is actually 
 the case, for the blood of the renal vein is poorer in urea than that 
 of the renal artery, containing only one-third to one-half as much. 
 If we knew the exact quantity of blood passing through the kidneys 
 of an animal in twenty-four hours, and the average difference in 
 the percentage of urea in the blood coming to and leaving them, 
 we should at once be able to decide whether the whole of the urea in 
 the urine reaches the kidneys ready made, or whether a portion of 
 it is formed by the renal tissue. Although data of this kind are as 
 yet inexact and incomplete, it is not difficult to see that all, or most 
 of, the urea may be simply separated by the kidney. 
 
 If we take the weight of the kidneys of a dog of 35 kilos at x6o grammes 
 (olyth of the body-weight is the mean result of a great number of 
 observations in man), and the average quantity of blood in them at 
 rather less than one-fourth of their weight, or 35 grammes, and con- 
 sider that this quantity of blood passes through them in the average 
 time required to complete the circulation from renal artery to renal 
 vein, or, say, ten seconds, we get about 300 kilos of blood as the flow 
 through the kidneys in twenty-four hours. Even at 0*3 per 1,000, the 
 urea in 300 kilos of blood would amount to 90 grammes. Now, Voit 
 found that a dog of 35 kilos body-weight, on the minimum protein diet 
 (450 to 500 grammes of lean meat per day) which sufficed to maintain 
 its weight, excreted 35 to 40 grammes of urea in the twenty-four hours. 
 If, then, tlae renal epithelium separated somewhat less than half of the 
 90 grammes urea offered to it in the circulating blood, the whole excre- 
 tion in the urine could be accounted for, and the blood of the renal vein 
 would still contain more than half as much urea as that of the renal 
 artery. So that the whole of the urea in the urine may be simply 
 separated by the kidney from the ready-made urea of the blood. 
 
 Another line of evidence leads to the same conclusion : that the 
 kidney is, at all events, not an important seat of urea-formation. 
 When both renal arteries are tied, or both kidneys extirpated, in a 
 dog, urea accumulates in the blood and tissues; and, upon the whole, 
 as much urea is formed during the first twenty-four hours of the 
 short period of Ufe which remains to the animal as would under 
 normal circumstances have been excreted in the urine. 
 
 Where, then, is urea chiefly formed ? The answer to this question 
 is that, while some urea is probably produced from amino-acids in 
 all the tissues, one organ is particularly associated with this function 
 — namely, the liver. 
 
5S4 Min'ABOLISM. NUTRITION AND DIETETICS 
 
 Tlieic is no reason to suppose that the hepatic cells, so far as the 
 repair of their own protoplasm or the supply of energy for their own 
 special work is concerned, require to metabolize particularly large 
 quantities of amino-acids as compared, for instance, with the 
 muscles. Glycin, however, they must have for the manufacture of 
 glycocholic, and cystin for the manufacture of the taurin of taurocholic 
 acid. In addition, the liver is known to possess the power of utilizing 
 amino-acids for the formation of dextrose and eventually of glyco- 
 gen, and a portion of the surplus amino-acids of the food may be 
 withdrawn from the blood of the portal vein for this purpose, just 
 aj the surplus of dextrose is withdrawn. 
 
 The liver contains a relatively large amount of urea, and there is 
 strong evidence that it is the manufactory in which a great part of 
 the nitrogenous relics of broken-down proteins, including amino- 
 acids, reach the final stage of urea. This evidence may be summed 
 up as follows: 
 
 (i) An excised ' surviving ' liver forms urea from ammonium 
 carbonate mixed with the blood passed through its vessels, while 
 no urea is formed when blood containing ammonium carbonate is 
 sent through the kidney or through muscles. Other salts of am- 
 monium, such as the lactate, the formate, and the carbonate, under- 
 go a like transformation in the liver. It is difficult, in the hght of 
 this experiment, to resist the conclusion that the increase in the 
 excretion of urea in man, when salts of ammonia are taken by the 
 mouth, is due to a similar action of the hepatic cells. 
 
 (2) If blood from a dog killed during digestion is perfused through 
 an excised liver, some urea is formed, which cannot be simply 
 washed out of the liver-cells, because when the blood of a fasting 
 animal is treated in the same way there is no apparent formation 
 of urea (v. Schroeder). This suggests that during digestion certain 
 substances which the liver is capable of changing into urea enter the 
 blood in such amount that a surplus remains for a time unaltered. 
 These substances may come directly from the intestine; or they 
 may be products of general metabolism, which is increased while 
 digestion is going on; or they may arise both in the intestine and in 
 the tissues. Leucin — which, as we have seen, is constantly, or, at 
 least, very frequently, present in the intestine during digestion — 
 can certainly be changed into urea in the body. So can other 
 amino-acids of the fatty series, like glycocoll or glycin. and aspartic 
 acid, and it has been shown by perfusion experiments that this 
 change can take place in the liver. I'-urther, the blood of the portal 
 vein during digestion contains several times as much ammonia as 
 the arterial blood, and the e.xcess disappears in the li\cr. 
 
 (3) During digestion the blood loses a greater proportion of its 
 amino-nitrogen (amino-acids) in passing through the liver than in 
 passing through other organs, as shown by the fact that the excess 
 
METABOLISM 01- PROTEINS 585 
 
 in the portal blood, as compared with the blood of the hepatic vein, 
 is greater than the difference between the arterial and the vena 
 cava blood. Now it has been proved that the liver does not store 
 amino-acids to an appreciable extent as such, and therefore it must 
 either have destroyed or condensed them into proteins. There is no 
 evidence that the liver forms a store of reserve protein from amino- 
 acids as it does of glycogen from carbohydrates, although this is 
 possible. But there is good reason to believe that a portion at least 
 of the amino-acids taken up by the liver is quickly broken down, 
 and that urea is formed from them. For when amino-acids were 
 injected into a vein in such amount that the content of amino-acids 
 in all the tissues was considerably increased, they disappeared far 
 more rapidly from the liver than from muscle or kidney, and their 
 disappearance from the liver was accompanied by an increase in the 
 urea content of the blood (Van Slyke) . 
 
 (4) Uric acid — which in birds is the chief end-product of protein 
 metabolism, as urea is in mammals — is formed in the goose largely, 
 and almost exclusively, in the liver. This has been most clearly 
 shown by the experiments of Minkowski, who took advantage of 
 the communication between the portal and renal-portal veins 
 (P- 385) to extirpate the liver in geese. When the portal is ligated 
 the blood from the alimentary canal can still pass by the round- 
 about road of the kidney to the inferior cava, and the animals 
 survive for six to twenty hours. While in the normal goose 50 to 
 60 per cent, of the total nitrogen is eliminated as uric acid in the 
 urine, and only 9 to 18 per cent, as ammonia, in the operated goose 
 uric acid represents only 3 to 6 per cent, of the total nitrogen, and 
 ammonia 50 to 60 per cent. A quantity of lactic acid equivalent 
 to the ammonia appears in the urine of the operated animal, none 
 at all in the urine of the normal bird. The small amount of urea in 
 the normal urine of the goose is not affected by extirpation of the 
 liver. And while urea, when injected into the blood, is in the 
 normal goose excreted as uric acid, it is in the animal that has lost 
 its liver eliminated in the urine unchanged. 
 
 (5) After removal of the liver in frogs, or in dogs which have 
 survived the previous connection of the portal vein with the inferior 
 vena cava by an Eck's fistula (p. 385), the quantity of urea excreted 
 is markedly diminished, and the ammonium salts in the urine are 
 increased. When the Eck's fistula is estabhshed and the portal 
 vein tied, without any further interference with the hepatic circula- 
 tion, the amount of urea in the urine is not lessened to nearly the 
 same extent, evidently because the substances from which urea is 
 formed still, for the most part, gain access to the liver through the 
 hepatic artery and by means of the back-flow which is known to 
 take place through the hepatic vein. Yet while in normal dogs the 
 proportion of ammonia to urea in the urine is only i :22 to i : 73, 
 
586 METABOLISM. XVTRITIOS ASD DIETETICS 
 
 in dogs with Erk's fistula it rises to 1 : 8 to i: ^^. If the animals 
 are ktpt on a diet poor in proteins, no symptoms may develop for 
 a considerable time. But if much protein is given, characteristic 
 symptoms, including convulsions, always appear. These may be 
 produced by the saturation of the organism with ammonia com- 
 pounds, which are formed from the proteins as in the normal animal, 
 but which the liver, with its circulation crippled, is unable to cope 
 with, and to completely change into urea, although the statement 
 has been made that when ammonia or ammonium salts are injected 
 into the blood larger quantities must be present to produce these 
 symptoms than are found in animals with the Eck's fistula. 
 Although the portal vein <?arries to the liver a greater supply of 
 blood than the hepatic artery (about twice as much, according to 
 Opitz and Macleod and Pearce), ligation of the latter causes a 
 greater diminution in the ratio of the amount of urea to the total 
 nitrogen in the urine than ligation of the former. WTiile the blood 
 of the hepatic artery is, of course, nearly saturated with oxygen, 
 that of the portal vein is not half saturated, so th^t the total quan- 
 tity of oxygen transported to the liver by the hepatic artery is 
 actually greater than the quantity transported by the portal vein. 
 This indicates that a good supply of oxygen is an important factor 
 in the formation of urea in the liver (Doyen and Dufourt). But 
 this is no proof that the process by which it is formed is an oxidation. 
 The work of the liver, like that of other tissues, is no doubt deranged 
 by lack of oxygen. 
 
 (6) In acute yellow atrophy, and in extensive fatty degeneration 
 of the liver, urea may almost disappear from the urine, and leucin, 
 tvrosin, and other amino-acids may appear in it along with a much 
 larger amount of ammonia than normal. Here it may be supposed 
 that the amino-acids and ammonia formed in the intestine in 
 the digestion and absorption of proteins, perhaps also ami no-groups 
 formed in the tissues which would normally be culled from the blood 
 bv the hepatic cells for the manufacture of uiea, pass unchanged 
 through the degenerated liver, and are excreted by the kidney. 
 
 It would, however, be very easy to overdo this argument ; for it 
 is sometimes observed that in pathological and experimental condi- 
 tions in which the liver has suffered severely considerable quantities 
 of urea continue to be excreted. Urea does not entirely cease to 
 be produced ev-en when the liver is removed; and it must again 
 be pointed out that there is reason to believe that the formation 
 of urea is not a function peculiar to the liver, but one shared prob- 
 ably with all tissues. The liver certainly does not arrest the whole 
 of the amino-acids coming from the alimentary canal ; for the non- 
 protein nitrogen in the muscles is distinctly increased during the 
 absorption of amino-acids, and the muscular tissue, even when freed 
 from blood, contains some urea, which in all probability is formed 
 
METABOLISM OF PROTEINS SSI 
 
 tliere in the decomposition of aniino-acids. Some writers, indeed, 
 take the view that the muscles, containing as tlicy do three-fourths 
 of the proteins of the body, and utilizing as they appear to do a 
 large proportion of the amino-acids of the food-protein, are more 
 important seats of urea formation than the liver. Yet the fact that 
 it is far easier to demonstrate this power — e.g., by perfusion experi- 
 ments — for the liver than for such tissues as the muscles, renders it 
 difficult to avoid the conclusion that in the preparation of an end- 
 product so important as that in which the great bulk of the nitrogen 
 leaves the body, a certain degree of specialization has been developed, 
 and that this preparation has been largely entrusted to a special 
 organ. And, while it may be true that larger amounts of amino-acids 
 are taken up and utilized by the muscles than by the liver under 
 certain conditions, this does not show that amino-groups removed 
 from the amino-acids in the muscles may not be largely transferred 
 to the liver before being changed into urea. Further, the transforma- 
 tion of amino-acids into dextrose (and glycogen) may be assumed to 
 entail a considerable absorption of amino-acids by the hepatic cells. 
 
 Processes by which Urea is formed. — In the case of only one of the 
 amino-acids derived from proteins can urea be obtained by a simple 
 process of hydrolytic cleavage. This is arginin (a-amino-5-guanidin- 
 «-valerianic acid) — that is to say, normal valerianic acid, 
 
 CH3.CH2.CHa.CH2.COOH, 
 
 i y 13 a 
 
 in which an amino group is attached to the a carbon atom, while 
 guanidin tTir^^CNH is attached to the S carbon atom (p. 566)- 
 
 When arginin is hydrolysed by barium hydroxide it yields urea and 
 ornithin (diamino-valerianic acid), half of the nitrogen of the arginin 
 appearing in each. Thus, 
 
 NH2 
 
 JJJJaXc.NH.CHg.CHaCHa.CH.COOH + HgO = 
 
 Arginin. 
 
 NHj 
 ^^aXc^o + NHg.CHa.CHaCHaCH.COOH 
 
 Urea. Ornithin. 
 
 The amount of arginin, and therefore the amount of urea which can be 
 artificially obtained in this way, varies extremely with the different 
 proteins. Thus, salmin, a protamin (p. 2), prepared from the milt 
 of salmon, yields 84-3 per cent, of its weight of arginin, while the 
 casein of cow's milk yields only 4-8 per cent., and gluten-fibrin, one of 
 the proteins of wheat, only 3 per cent. In the body the hydrolysis of 
 a'"ginin to urea and ornithin is accomplished by the ferment arginase 
 (Kossel and Dakin). This ferment is found in the liver, and also in 
 many other organs. The urea formed in this way appears very 
 rapidly in the urine . The ornithin itself is then more slowly transformed 
 into urea. Since the ordinary food-proteins are poor in arginin, the 
 
583 METABOLISM, NUTRITION AND DIETETICS 
 
 amount of urea which can possibly be formed in mammalian metabolism 
 by this process cannot be large, even if most of the arginin, as is the 
 case when it is fed to an animal, is transformed into urea. 
 
 There is no reason to suppose that urea can be directly split off from 
 the other amino-acids with which we are concerned. A comparison 
 of their constitutional formula^ with that of urea (or with that of uric 
 acid) shows that a more far-reaching decomposition must take place 
 before products are obtained from which urea (or uric acid) can be 
 formed. Urea has been artificially obtained from protein by oxidation 
 with an ammoniacal solution of permanganate at body-tcmperaturc. 
 When the protein is first split into its cleavage products, and these are 
 then oxidized, a very large amount of urea is produced — e.g., as much 
 as 3 grammes of urea from lo grammes of glycm. 
 
 While these facts suggest possible ways of formation of urea in the 
 body, we cannot assume that what happens in the test-tube must 
 happen in the tissues. The best evidence is to the effect that in the 
 body the removal of the amino-group (NHj) in the form of ammonia 
 from the amino-acids is the essential step in the formation of at least 
 a great part of the urea, which is then synthesized from ammonia and 
 carbonic acid. The possibility exists that this deaminization (or deamidi- 
 zation) of the amino-bodies is the result of hydrolysis, or of oxidation, or 
 of reduction, or of a combination of these processes. Evidence has been 
 found that in the case of some of the amino-acids the deaminization is 
 associated not with hydrolysis in which hydroxyl is substituted for 
 the NHj gioup, but with oxidation (Neubauer). But this has not been 
 shown to hold good for all amino-acids. In either case, however, 
 whether the deaminization process is oxidative or hydrolytic tlie nitrogen 
 is split off as ammonia, and it is to such ammonium compounds as have 
 been already mentioned as being transformed into urea when circulated 
 through an excised liver (p. 584) that w^e have to look for the source of, 
 at any rate, a large portion, of the urea. Ammonia in the form of 
 carbonate or carbamate is constantly found in the blood (p. 583). The 
 excess of ammonia in the portal blood, which, however, is not admitted 
 by all observers to be very large or very constant, has been interpreted 
 as indicating that a considerable decomposition of iamino-acids with 
 liberation of the amino-groups occurs in the intestinal lumen or the 
 intestinal wall. It is not established beyond doubt that ammonia is 
 itself present in the protein molecule, or that its liberation in the 
 hydrolysis of proteins can take place except at the expense of further 
 decomposition of amino-bodies. It has been shown, however, that a 
 great part of the ammonia in the blood is produced in the decomposition 
 of protein in the digestive tube by putrefactive bacteria (Folin and 
 Denis). This is a necessary part of the reaction by which phenol and 
 indol are formed in tlie intestine. 
 
 It has been generally taught that the deaminization of the surplus of 
 amino-bodies takes place chiefly in the liver, the extra nitrogen being 
 thus ' shunted ' out of the blood-stream before it has had a chance to 
 reach the tissues. It would seem more advantageous in tlie light of 
 our present knowledge that a large and, so to say, a miscellaneous 
 assortment of amino-bodies should be placed at the disposal of the 
 tissues to facilitate the selection of those which are indispensable. 
 We have seen that tissues such as muscle can and do take up amino- 
 acids when protein is digested in the intestine, and it is very probable 
 that they take up not merely the relatively small amount necessary to 
 replace their wear and tear, but also a portion of the surplus, which 
 after deaminization in the cells takes its place as a source of energy 
 to drive the machine. The nitrogen in the form of ammonia may pass 
 
METABOLISM OF PROTEINS 589 
 
 back into the blood, and may thus be carried to the liver for conversion 
 into urea. It is not necessary, however, to suppose that all of the 
 nitrogen must perforce make this journey before being changed into 
 urea. There i.s evidence that all the tissues share to some extent with 
 the liver the power of forming urea just as they share with the liver the 
 power of splitting off NHg from the amino-bodies. It may be that 
 the liver surpasses other tissues in its deamidizing power just as it seems 
 to surpass other tissues in its power of transforming ammonium com- 
 pounds into urea. But this does not prevent at least a considerable 
 proportion of the amino-substances absorbed from the intestine from 
 passing into the general circulation. It is of importance to remark 
 that such hydrolytic cleavages as are associated with the splitting of 
 protein into amino-acids, etc., only slightly reduce the available energy 
 of the compounds. In so far as the liberation of the nitrogen from 
 the amino-acids is also accomplished by hydrolytic cleavage (sup- 
 posedly by a ferment dcsaminase), the residue, relatively rich in carbon, 
 will still be available for yielding to the bodv by its oxidation an amount 
 of energy not much less than could be obtained from the original protein. 
 The combination of ammonia with carbon dioxide and the conversion 
 of the carbonate into urea, perhaps through the intermediate stage of 
 ammonium carbamate, does not require any oxidation. Thus, 
 
 /OH /O.NH4 /O.NH4 /NHo 
 
 C^O -f2NH,=C=0 ; -HaO=C<-0 ; -H20=Cf^0 
 
 \OH \0.NH4 \NH2 \nH2 
 
 Carbonic acid. Ammonium Ammonium Urea. 
 
 carbonate. carbamate. 
 
 Another way in which some of the urea may be produced is by the 
 direct formation of ammonium carbamate in the katabolism of amino- 
 acids without the preliminary liberation of ammonia. By the loss of a 
 molecule of water the carbamate would then become urea. But if, as 
 there is every reason to believe, a part of the carbonaceous residue is 
 converted into carbo-hydrate, a certain amount of oxidation must 
 occur in the transformation. 
 
 Such compounds as guanin, sarkin or hypoxanthin, xanthin, uric 
 acid, and creatin, used to be cited as among the possible intermediate 
 substances between protein and urea. But while there is now complete 
 evidence that the first three bodies can be and are converted into uric 
 acid, there is nothing at all to indicate that they are stages on the 
 way to urea. Uric acid is, indeed, very closely related to urea, and 
 can be made to yield it by oxidation outside the body. Not only so, 
 but it is, in part at least, excreted as urea when given to a mammal 
 by the mouth and it replaces urea as the great end-product of nitro- 
 genous metabolism almost wholly in the urine of birds and reptiles. 
 But none of these things can be admitted as evidence that in the 
 normal metabolism of mammals uric acid lies on the direct line from 
 protein to urea. Creatin exists in the body in greater amount than 
 any of these, muscle containing from 0-2 to 0-4 per cent, of it; and the 
 total quantity of nitrogen present at any given time as creatin is not 
 only greater than that of the nitrogen present in urea, but greater 
 than the whole excretion of nitrogen in twenty-four hours. But 
 although there are facts which indicate that creatin is an important 
 derivative of the decomposed tissue proteins (p. 597) there is no 
 evidence that it is related to urea formation. 
 
 b'ummary : Here may be summed itp the most probable view of the 
 normal decomposition in the body of the amino-acids, whether they undergo 
 decomposition without being incorporated into the tissue proteins or prater- 
 
590 METABOLISM. NUTRITION . I S'D DIETETICS 
 
 plasm, or are liberated as the protof>lasm breaks down. The first step may 
 be conceived of as the splitting off of the NHo group, which yields ammonia. 
 The ammonia is transformed into urea. The non-nitrogenous residue 
 after removal of the amino-group differs according to the amino-acid. 
 Some of the amino-acids, such as alanin, glycin, prolin and aspartic acid, 
 yield substances which can be changed into dextrose in the body, as shown 
 by the increased amount of dextrose excreted by phlorhizinized animals 
 when the amino-acids are fed to them.* Other amino-acids — e.g., lysin, 
 histidin and tyrosin, phenylalanin, etc., have such a chemical structure 
 that the non-nitrogenous compounds derived from them cannot form dextrose. 
 From certain amino-acids, such as histidin, phenylalanin, tyrosin and 
 leucin, it has been shown that acetone bodies can be derived. These facts 
 explain how sugar can be formed and the acidosis associated ivith the 
 acetone bodies developed in diabetes, even wheti the diet consists of protein 
 only or when the patient is living on his own tissues. 
 
 Formation of Uric Acid. — Uric acid, like urea, is separated from 
 tlie blood by the kidne\'S, not to any appreciable extent formed in 
 them. In birds, and often in man, it can be detected in normal 
 blood. It is present in increased amount in the blood and transuda- 
 tions of gouty patients, in whose joints and ear-cartilages it often 
 forms concretions. ' Chalk-stones ' may contain more than half 
 their weight of sodium urate. 
 
 As to the place and. manner of formation of uric acid, it has already 
 been stated that in birds, after extirpation of the liver, the uric acid 
 excretion is greatly diminished, and that ammonium lactate appears 
 instead in the urine. The simplest interpretation of this result is, 
 that ammonia and lactic acid pass into the urine because they can 
 no longer be utilized for the synthesis of uric acid. Chemical 
 schemata can indeed be constructed, which show more or less 
 plausibly how lactic acid, pyruvic acid (p. 545) and other substances 
 reacting with ammonia or with the urea derived from it (and birds 
 form some urea) might yield uric acid. It has been further stated 
 that when blood containing ammonium lactate is circulated through 
 the surviving liver of the goose, an increase in the uric acid content 
 of the blood occurs. As demonstrated by control experiments, this 
 increase is too great to be due merely to the sweeping out of pre- 
 viously formed uric acid from the hepatic cells ; also the feeding of 
 lactic acid, pyruvic acid, and other organic acids leads to an increased 
 output of uric acid. The story seems fairly complete, although 
 criticisms have not been lacking. It has been suggested, for instance, 
 that for some reason the loss of the liver leads to acidosis, an in- 
 creased production of acids, especially lactic acid, in the organism ; 
 that ammonia, which would otherwise be employed in the formation 
 of uric acid, is needed to neutralize these acids, and that the appear- 
 ance of this ammonia in the urine is only a secondary consequence 
 of the elimination of the liver. The deficiency in the uric acid 
 
 • In animals under the influence of phlorhizin sugar is formed from all 
 substances capable of producing it in the organism. 
 
METABOLISM OF PROTEINS 591 
 
 excreted, it is said, is therefore due, not to inability on the part of 
 the remannng tissues to form uric acid, but to the absence of the 
 ammonia which they require for its formation. This criticism, if 
 it were admitted as apjainst the current interpretation of such ob- 
 servations on the bird's hver, coidd scarcely be denied some vahdity 
 as against the current interpretation of similar observations on the 
 results of interference with the mammalian liver. It is therefore 
 important to point out that there is still the same deficiency of uric 
 acid when alkali is administered to neutralize the acids, although 
 ammonia ought now to be available. There can be no question, 
 then, that the liver in birds is the seat of an extensive synthesis of 
 uric acid, and there is little doubt that ammonia compounds are 
 essentially concerned in the process, whatever the role of the lactic 
 or other acids may be. A similar synthetic formation of uric acid 
 from ammonia and a derivative of lactic acid may take place in 
 mammals, and probably exclusively in the liver, but it is of much 
 less importance. Another way in which uric acid arises both in 
 mammals and in birds is by the splitting and oxidation of nucleins. 
 This is by far the most important mode of formation in mammals, 
 as synthesis is the chief mode of formation in birds. In both groups 
 of animals the oxidative production of uric acid takes place, not in 
 any particular organ, but in the tissues in general, including the liver. 
 It has been shown that when air is blown through a mixture of 
 splenic pulp and blood, uric acid is formed from purin bodies already 
 present in the spleen. When the quantity of these is increased by 
 the decomposition of nucleins induced by slight putrefaction, the 
 yield of uric acid is also increased. Uric acid is also formed by the 
 perfectly fresh surviving spleen, liver, and thymus in the presence 
 of oxygen, and the quantity is increased when purin bodies are 
 artificially added. 
 
 Sources of the Uric Acid. — It is well established that in the bird 
 it arises both from amino-acids derived from the hydrolysis of 
 protein and from nuclein compounds and their derivatives in the 
 food and tissues. The amino-acids constitute by far the greatest 
 source of uric acid in these animals and in the reptiles, and it is 
 practically certain that the course of the decomposition of the 
 amino-acids and the form in which nitrogen is liberated from them 
 in its transformation into this end-product are not essentially differ- 
 ent from what obtains in the formation of urea in the mammal and 
 the amphibian. This is sufficiently illustrated by the role played by 
 ammonia and ammonia compounds in the production of uric acid 
 in the birds and their congeners. In the mammal, the taking of 
 food rich in nucleated cells, and therefore in nucleo-proteins and 
 nucleins, the characteristic conjugated proteins of nuclei (thymus 
 gland, pig's pancreas, and herring roe), or of food rich in purin 
 bases (Liebig's meat extract), increases the quantity of uric acid in 
 
592 METABOLISM. NUTRITIOX .1\D DIETETICS 
 
 the urine. The increase is mainly due to the produt tion of uric 
 add from the nuclein substances of the food. But this is not the 
 only source of the uric acid, since extracts of the thymus glanrl 
 containing only traces of nucleins or nucleic acid cause, when in- 
 jected, a characteristic increase in the uric acid excretion, just as 
 the entire gland does when taken by the mouth. And during the 
 period of increased nitrogen excretion occasioned by a meal contain- 
 ing protein, the increase in the uric acid occurs particularly in the 
 hours immediately following the ingestion of the food, and does not 
 last so long as the increa.se in the urea. Now, the nucleins of the 
 food are comparatively little affected during the earlier stages of 
 digestion (Hopkins and Hope). Whether in mammals any portion 
 of the uric acid comes from amino-acids is still in doubt, but there 
 are facts which indicate that a fraction of it may do so. We may 
 conclude, therefore, that in the mammal, as well as in the bird, a 
 portion of the uric acid, although certainly a far smaller portion in 
 the mammal, is derived from bodies other than the nuclein substances 
 of the food — that is Lo say, from the nuclein substances of the tissues 
 contained particularly in the cell-nuclei and probably from the 
 ordinary proteins of both food and tissues. The portion derived 
 irom tne protems may be assumed to be that small fraction which 
 has already been spoken of as sjmtheticallv formed. 
 
 Metabolism of the Nucleic Acids and Purin Bases. — Our know- 
 ledge of the metabolism of the nucleo- proteins and nucleins has 
 been greatly augmented in recent years. When nucleo- protein is 
 digested by gastric juice, a certain amount of protein is easily split 
 off and hydrolysed to peptone and the other ordinary products 
 of proteolysis. An insoluble residue of nuclein remains. This is 
 acted upon with difficulty by gastric juice, although eventually an 
 active juice will split it up also. By the action of pancreatic juice, 
 or b}' heating with dilute acids, it is more easily hydrolysed, yielding 
 a further quantity of protein along with nucleic acid. This second 
 fraction of protein, which is split off with so much more difficulty 
 than the first, undergoes proteolysis in the usual way. The result- 
 ing amino-acids no doubt take their place in the general metabolism 
 precisely like the amino-acids derived from ordinary proteins, and 
 yield the same end-products. As regards the nucleic acid (or rather 
 acids, since different nucleo- proteins contain different nucleic acids), 
 pancreatic juice is practically inert, although succus entericus can 
 effect a partial hydrolysis. For their complete decomposition more 
 drastic treatment is required — namely, heating with hydrochloric 
 acid in a sealed tube. Thus treated, nucleic acids yield a number 
 of components, out of which they may be assumed to be built up, 
 as the proteins are built up out of amino-acids, etc. The charac- 
 teristic components are purin bases (adenin, C5H3N4.NH2; guanin, 
 C5HJN4O.NH2; hypoxanthin, C6H4N4O; and xanthin, C5H4N4O2); 
 
METABOLISM OF PROTEINS 
 
 593 
 
 pvrimidin bases (uratil. C.H.N.Pj; oytosin, C4H.,X2^.NH2; thymin 
 
 QHgNjOj.CHg); phosphoric acid and a carbo-hydrate group. 
 
 Some of the nucleic acids contain all these components; they are 
 sometimes spoken of as the true nucleic acids. In others certain of the 
 components arc absent, and to these nucleic acids the name nucleotids 
 has been applied. The purin bases are always present. The carbo- 
 hydrate group varies in different nucleic acids, being in some a hexose 
 (p. 537), in others a pentose (p. 487). The pentose d-ribosc is especially 
 often met with. It is probable that the nucleotids are merely simpler 
 decomposition products of the true nucleic acids. Thus, inosinic acid, 
 a nucleotid first isolated from meat extract, yields phosphoric acid, 
 rf-ribose, and the purin base hypoxanthin. The nucleotid guanylic acid 
 found in the pancreas yields phosphoric acid, rf-ribose, and the purin 
 base guanin. There is evidence that nucleic acids may be built up out 
 of a number of nucleotid groups, and for this reason they have been 
 termed polynucleotids (Levene). The purin bases have a very close 
 chemical relationship to uric acid, which, like them, is characterized by 
 the possession of a group called the purin nucleus. For convenience 
 of reference the atoms composing the purin nucleus are numbered, 
 and the purin bodies are named with reference to the position of the 
 carbon atom or atoms at which oxygen or the amino-group (NH^) is 
 introduced. Purin consists of the nucleus with H atoms introduced at 
 the pomts shown in the constitutional formula. Adenin is a 6-;imino- 
 purin- — i.e., purin in which NH2 replaces the H attached to C(«). Guanin 
 is 2-amino-6-oxypurin, NHg bemg united with C(2) and oxygen with C(9) 
 in purin. Uric acid is 2, 6, 8-trioxypurin — i.e., purin in which oxygen 
 is united to the carbon atoms 2,6, and 8. Hypoxanthin is 6-oxypurin, 
 ox^'gen being introduced at the position of C(6) in purin. By removal 
 of the amino-group from adenin hypoxanthin is formed. Xanthin is 
 2, 6, dioxy purin, oxygen being introduced at C(2) and C(6) in the purin 
 molecule. Xanthin can be derived from guanin in the same way as 
 hypoxanthin from adenin. 
 
 N(i)— C(8) 
 
 C(2) C{5) N(7) 
 
 N=CH 
 
 I I 
 HC C— NH 
 
 /C(8) 
 
 N(3) _C(4, N(9) 
 
 Purin nucleus. 
 
 NH— CO 
 
 / 
 
 CH 
 
 N— C— N 
 
 NHgC C— NH 
 
 Purin. 
 
 NH— CO 
 
 1 i 
 
 CO C— NH 
 
 N =C.NHj 
 
 I I 
 HC C— NH 
 
 il '! \cH 
 
 N— C— N 
 
 Adenin. 
 
 ;CH 
 
 N — C— N 
 
 Guanin. 
 
 NH— C— NH 
 
 Uric acid. 
 
 CO 
 
 N =C.OH NH— CO 
 
 I L II 
 
 HC C— NH CO C— NH 
 
 II II >« I II >« 
 
 N— C— N NH— C— N 
 
 Hypoxanthin. Xanthin. 
 
 Besides the purin bases combined in the nuclein substances, purin bases 
 and uric acid are widely spread in the tissues in the free state, although 
 in very small amounts. 
 
 A portion of the intake of purin bodies is therefore ready formed, 
 especially in the animal constituents of the food, and does not require 
 the decomposition of nucleic acid for its liberation. The nuclei of 
 vegetable cells contain nucleo-proteins, and accordingly can contribute 
 to the purin intake. The most interesting contribution of vegetable 
 
 38 
 
594 METABOLISM, SVTRITIOS ASD DlJiTLTlCS 
 
 origin has been previously alluded to (p. 481) — namely, the methyl 
 purins forming tlio active principles of lea, coffee, and cocoa, caffcin, 
 or I, 3, 7-trimclhylxanthin (^81110X402), thcobromin, or 3, 7-dinK-thyl- 
 xanthin (C7HgN402). and theophyllin, or i, 3-dimethylxanthin 
 
 CHj.N— CO NH— CO CH3.N— CO 
 
 :0 C— N.CH, CO C— N.CH3 CO C— NH 
 
 :h 
 
 I I >" I \^^- I / 
 
 CH3.N— C— N CH3.N — C-^ CH3.N— C— N 
 
 CafTein. Theobromin. Theophyllin. 
 
 Nucleic acid, as stated, can be partially decomposed by the 
 succus entericus, by means of a ferment called nuclease or, more 
 accurately, nucleic-acidase. The groups into which it is split 
 are nucleotids (see above). By another ferment, nucleotidase, a 
 portion, at any rate, of the nucleotids is further decomposed to 
 yield nucleosides, bodies of the glucoside class containing a com- 
 pound of a purin base with the carbo-hydrate group of the nucleic 
 acid, to which phosphoric acid is also coupled. Beyond this stage 
 the liydrolysis of nucleic acid does not proceed in the intestine. 
 The resultant products, probably along with unchanged nucleic 
 acid, are absorbed, mainly at least, by way of the bloodvessels. 
 
 It will be well, however, to remember that our knowledge of 
 the digestion of the nuclein bodies is still incomplete, and the 
 natural tendency of the mind to think in diagrams is apt to give it 
 greater precision than is justified by the facts; for example, it is 
 known that even gastric juice is capable of liberating some of the 
 phosphoric acid from nucleo-proteins. 
 
 In the tissues the absorbed products of the digestion of nucleic 
 acids may be partially utilized without further decomposition for 
 the synthesis of nucleo-proteins, to take the place of those which are 
 destroyed in the metabolism of the cells; or they may be split com- 
 pletely into their components, and these resynthesized. Finally, 
 and this fate is probably not long delayed in the case of the surplus 
 of purin compounds contained in ordinary dietaries, both the purins 
 of the food and the purins arising from the waste of the tissues are 
 for the most part converted into uric acid and excreted in the urine. 
 Small quantities of purins leave the body in the faeces (p. 425). 
 The phosphoric acid can be utilized not only for the building of 
 nucleu-])roleins, but for the synthesis of phosphatides. Eventually 
 it is eliminated as phosphates in the urine. The carbo-hydrate 
 groups, so far as they are not utilized in the synthesis of nucleic 
 acids, may be supposed to undergo metabolism like other carbo- 
 hydrates. The metabolic history of the pyrimidin bases has not 
 been made clear. 
 
 Steps in Formation of Uric Acid. — As to the manner in which 
 
METABOLISM OF PROTEINS 593 
 
 liri'; acid arises from the nuclcin substances, we may picture the 
 process as taking place by the following steps : Certain organs have 
 been shown to contain ferments which split up nucleo-proteins into 
 protein and nucleic acid. This nucleic acid, or nucleic acid arising 
 in other ways in the metabohsm of nuclein, and also any nucleic 
 acid absorbed as such from the alimentary canal in the digestion of 
 nuclein-containing substances, are then decomposed by another 
 ferment, similar to or identical with the nuclease or nuclcic-acidase 
 previously encountered in the intestine. The resulting nucleotids are 
 split up by a special ferment (nucleotidase) so as to yield nucleosides. 
 These are in turn decomposed by appropriate enzymes (nucleo- 
 sidases), so that we finally arrive at the individual ' building-stones,' 
 the nucleic acid molecule, phosphoric acid, the carbo-hydrate group, 
 pyrimidin and purin bases, especially adenin and guanin. Then 
 follows the action of ferments (adenase and guanase), which remove 
 the amino-group from these purin bases, transforming adenin into 
 hypoxanthin, and guanin into xanthin (Jones). The deaminiza- 
 tion is associated with hydrolysis. Thus : 
 
 CsHsNs + HjO -C5H4N40-fNH3; C5H6N6O + HgO =C6H4N40j+ NH3. 
 
 Adenin. Hypox.-inthin. Guanin, Xanthin. 
 
 By oxidation hypoxanthin is changed into xanthin and xanthin 
 into uric acid, and the oxidation seems to be accomplished by a 
 separate oxidizing ferment, xanthin oxidase, whose action may be 
 thus represented : 
 
 C5H4N4O + O =C5H6N402 ; C6H6N4O3+ O =C6H4N40,. 
 
 Hypoxanthin. Xanthin. Xanthin. Uric Acid. 
 
 Evidence of the existence of these ferments, and of their wide dis- 
 tribution, has been obtained by making experiments on the various 
 substances mentioned with extracts of different tissues. 
 
 The portion of the uric acid which comes from the food (mainly 
 from the purin bodies in it) is sometimes denominated the exogenous 
 portion, while that which arises from the tissues is called the endog- 
 enous portion. The latter moiety, which generally amounts to 
 about 0-6 gramme in the twenty-four hours, can be estimated by 
 restricting the diet to articles of food free from purin bodies, such as 
 bread, milk, cheese, eggs, and butter. It is stated that the endog- 
 enous uric acid remains practically constant in the same individual 
 under constant conditions, and is unaffected by changes in the diet. 
 
 The total excretion of uric acid (and the other purin bodies) is 
 by no means identical with the sum of the uric acid taken in as 
 purin bases in the food and that produced in the body. A con- 
 siderable destruction of uric acid (and other purin bodies) goes on 
 in the body, and mainly in the Uver. The quantity of endogenous 
 uric acid excreted by the kidneys bears a certain ratio to the total 
 amount which has entered the circulation. This ratio varies much 
 in different mammalian species. In man a full half is said to be 
 
396 METABOLISM, NUTRITION AND DIETETICS 
 
 excreted and about a half destroyed, being mainly changed into urerx. 
 Some of the exogenous moiety is also broken down. When uric acid 
 is heated in a sealed tube with strong hydrochloric acid, it is broken 
 up into glycin, carbon dioxide, and ammonia. There are grounds 
 for believing that a similar decomposition takes place in the body, 
 and that the products are then transformed to urea in the liver. 
 
 The process of uricolysis, or destruction of uric acid, is usually 
 attributed to a ferment called the uricolytic ferment, and it has been 
 supposed that one of the factors in the production of gout may be 
 a diminution in the amount or activity of this ferment. In some 
 cases it is said to be entirely absent. It is doubtful, however, 
 whether in man and the anthropoid apes the oxidizing enzyme, 
 uricase or uricoxydase, which oxidizes uric acid to allantoin 
 {C^H6N403), exists. In all other mammals hitherto investigated it 
 has been found in some of the tissues. In accordance with this, 
 only a trace of allantoin is present in human urine and in the urine 
 of the higher apes, while in the other mammals — for example, in 
 the dog — a large proportion of the purin excretion assumes this 
 form. It is probable that there is more than one way in which 
 uric acid may be decomposed in the body, and, if so, that there is 
 more than one ferment concerned in its transformation. It would 
 be well, therefore, not to speak of uricolysis as if it were synonymous 
 with the well-ascertained process by which allantoin is formed 
 from uric acid, and not to identify all enzymes which may take 
 part in uricolysis with uricoxydase. 
 
 It is worthy of remark in this connection, as a further illustration 
 of the differences which may exist in the purin metabolism in 
 different kinds of animals, that in man and the anthropoid apes the 
 quantity of purin bases in the urine is small in proportion to the 
 quantity of uric acid. In the pig, which is included among the 
 animals that form allantoin from uric acid, the purin bases exceed 
 the uric acid in amount, whereas in the dog, which likewise excretes 
 allantoin, the purin bases exist in very small amount compared 
 with the uric acid. 
 
 In concluding our consideration of the metabolism of the nucleic 
 acids, the question may be raised whether it is related to the metabo- 
 lism of the other substances — carbo-hydrates, fats, and proteins — 
 in such a way that derivatives of nucleic acid can contribute to the 
 formation of any of these, or derivatives of carbo-hydrares, fats, or 
 proteins contribute to the formation of any of the components of 
 nucleic acid. It has been already mentioned that the phospiioric 
 acid can aid in the synthesis of phosphatides, and that the carbo- 
 hydrate groups probably take their place in the ordinary carbo- 
 hydrate metabolism. There is no evidence that the purin bases can 
 take part or can yield products capable of taking part in the forma- 
 tion of any of the other substances. The piirin metabolism, so far 
 
METABOLISM OF PROTEINS 597 
 
 as is known, moves in a closed circuit. Of (lie fate of the pyrimidin 
 bases nothing is surely known. Without doubt nucleic acid can be 
 formed in the body when none is contained in the food. More than 
 one source of the phosphoric acid and the carbo-hydrate are known 
 and ha\e been already pointed out, but how and from what 
 materials the purin and pyrimidin bases are formed cannot yet 
 be stated. 
 
 It has been suggested that arginin and histidin constitute the 
 raw material for the synthesis of the purin ring. Rats will grow 
 when fed with an amino-acid mixture prepared by hydrolyzing 
 caseinogen and lactalbumin, but they rapidly lose weight if arginin 
 and histidin have been removed from the mixture, and the allantoin 
 in the urine decreases. Restoration of the missing amino-acids 
 causes growth to be resumed and a rise in the allantoin excretion to 
 normal. This is true, although in lesser degree, even when one of 
 these amino-acids is restored to the mixture, as they seem to be inter- 
 convertible (Ackroyd and Hopkins). Recently the synthesis of 
 nucleosides has been accomplished in the laboratory (Fischer). 
 It only needs the introduction of phosphoric acid in the appropriate 
 way into the molecule to give nucleic acid. 
 
 The Significance of Creatin and Creatinin in Protein Metabolism. 
 — A glance at the tables of composition of the urine (p. 477) will show _ 
 that creatinin, as regards the quantity excreted, is a much more 
 important product of nitrogenous m.etabolism than uric acid, stand- 
 ing, indeed, with the ammonia compounds, next in order to urea; 
 but our information as to its source and significance is very 
 scanty. 
 
 Creatin is a-methylguanidin-acetic acid, and creatinin is derived 
 from it by loss of the elements of water : 
 
 /XH, /NH, /NHo /NH— CO 
 
 C4XH C^NH CH3.COOH C^XH C^XH 
 
 \nH2 \XH.CH3a \X(CH3).CH.2.C00H\N(CH3).CH2 
 
 Guanidin. Methylguanidin. Acetic acid. Creatin. Creatinin. 
 
 On heating with baryta-water creatin is decomposed, yielding urea, 
 methylglycocoll or sarcosin, and other substances. It can be prepared 
 synthetically from sarcosin and cyanamid. Thus: 
 
 ^NH^ H.X(CH3) /XHa 
 
 C^N +1 = C^XH 
 
 CHa-COOH \x(CH3).CH2.COOH 
 
 Cyanamid. Methylglycocoll. Creatin. 
 
 Creatin is found in considerable amount in muscular tissue 
 (much less in children than in adults), and in traces in other 
 tissues and in blood, which also contains small amounts of 
 creatinin. 
 
 Creatinin can be so readily obtained from creatin outside the 
 body that it is tempting to suppose that the portion of the creatinin 
 
598 METABOUFM. NUTRITION AND DIETETICS 
 
 of the urine which is not formed from the creatin in the f(jO(l is 
 derived from tlie creatin of the muscles and other tissues, and many 
 theories have been evolved to connect the creatinin of urine with 
 the creatin of the muscles. But it is doubtful whether there is any 
 direct connection. The fact that persons who have been long ill 
 and are feeble and wasted have a low creatin content in their 
 muscles, and a low creatinin content in their urine relatively to the 
 total nitrogen (Shaffer) is, so far as it goes, in favour of some re- 
 lationship between the two. The alleged absence of creatinin from 
 muscle seemed to be opposed to the idea that the creatin store of the 
 muscular tissue was an important source of urinary creatinin; for 
 if a constant transformation of this kind was going on, traces of 
 creatinin not yet absorbed by the blood might have been expected 
 to be present in the muscles. Recently, however, it has been 
 reported that small quantities of creatinin do exist in fresh muscle 
 (4 to 8 milligrarrmes in 100 grammes of tissue), and that when the 
 muscle is allowed to undergo autolysis the creatinin increases at a 
 very uniform rate at the expense of the creatin. Added creatin 
 experiences the same fate as the creatin originally present, while 
 added creatinin inhibits the reaction, or even reverses it (Myers and 
 Fine). A parallelism with the conversion of glycogen into dextrose 
 in the liver easily suggests itself, and it is possible that we are here 
 in the presence of a normal reaction which may account for at 
 least a portion of the creatinin excretion. It is probable that both 
 creatin and creatinin can undergo changes in the body, especially 
 in the liver, and it is possible that the products may be further 
 utilized in metabolism. If this were so, the creatin store of the 
 muscles would acquire new significance as a reserve of useful material 
 with perhaps a long and varied metabolic career before it, and would 
 not constitute merely a temporary depot of waste material whose 
 metabolic history was ended, and which was waiting to be excreted. 
 The novel view has recently been advanced that the living muscles 
 contain little or no creatin, but that the creatin found on analysis 
 is a post-mortem product original^ constituting a part of the 
 living protoplasm (I'olin and Denis). 
 
 However this may be, the constancy of the creatinin elimination 
 on a meat-free diet (p. 4S2), and its complete independence of the 
 changes in the total nitrogen excretion, show that it has a diflfcrent 
 significance in protein metaboHsm from the urea. Evidence is accumu- 
 lating that it is especially in the metabolism of the organized or tissue 
 protein that the product eventually excreted as creatinin arises ; in other 
 words, that it represents especially the nitrogenous waste connected 
 with the wear and tear of the bodily machinery, while urea represents 
 also, and under ordinary conditions of diet chiefly, the nitrogen of the 
 surplus amino-acids which are not utilized in the building of new or the 
 repair of old tissue elements. The fact that the amount of creatinin 
 excreted by different persons seems to be related to the weight of active 
 tissue in the body, excluding fat, is in favour of tliis suggestion, and 
 
METABOLISM OF PROTEINS 599 
 
 there is other evidence pointing in the same direction; for example 
 in ordinary circumstances crcatin is either absent from the nrine or 
 present in very small amovint, except in yonng children. When, how- 
 ever, the decomposition of tissue-protein is abnormally increased, as in 
 starvation, in fevers, in women after delivery, while involution of the 
 uterus and the associated destruction of a considerable mass of smooth 
 muscle is taking place, crcatin appears in larger cpiantities in the urine, 
 perhaps because it can no longer be all converted into creatinin. Now, 
 the increased excretion of creatin in starvation can be prevented by 
 giving carbo-hydrate food, which is known (p. 606) to lead to sparing 
 of tissue-protein (Mendel and Rose). That the depletion of the body 
 of carboliydrate is in some way related to the elimination of creatin 
 is further shown by the fact that creatinuria is associated with diabetes 
 and with the action of substances like phlorhizin, hydrazin, phosphorus, 
 etc., all of which cause carbo-hydrate deficiency. Something more is 
 involved, however, for under conditions of diet which produce acidosis 
 (an increase in the hydrogen-ion concentration of the blood), creatin 
 appears in the urine no matter how rich the food may be in carbo-hy- 
 drate. For example, a diet of oats and maize, which are typical acid- 
 producing foods, causes creatinuria in rabbits, which promptly disappears 
 when carrots, a base-prodvicing food, are added (Underbill). 
 
 The statement that the content of the urine. in creatinin is increased 
 by muscular work may indicate that the muscular machine wears out 
 faster during activity than during rest, or perhaps only that already- 
 formed creatin leaves the muscles in greater amount when the blood-flow 
 in increased ; but recent observations tend to show that this statement 
 may require revision. 
 
 As to the manner in which creatin is changed into creatinin in the 
 body, a highly suggestive fact is the presence of ferments in various 
 organs which possess this power. Ferments also exist which can 
 decompose both creatin and creatinin. The existence of such enzymes 
 is presumptive evidence that the changes which they are capable of 
 producing actually occur in the organism ; but the seat of the changes 
 if they do take place, and their metabolic significance, are unknown. 
 Creatin when given by the mouth or injected into the blood does not 
 cause any increase in the virinary creatinin, nor when administered in 
 moderate quantities does it seem to be excreted as creatin. Like urea, 
 creatinin, and amino-acids, it is taken up very rapidly by the muscles. 
 Creatinin, on the other hand, when added to the food, causes an increase 
 in the creatinin of the urine. 
 
 Intracellular Ferments — Autolysis. — As to the agencies by which 
 the decomposition of the proteins is carried out in the cells, we have 
 already spoken of the oxidizing cell ferments, or oxydases (p. 272). 
 Reducing ferments, or reductases, are also known, and can be ex- 
 tracted from most organs, if not all. Like oxydases, they act in a 
 weakly alkaline medium, causing in the presence of hydrogen such 
 reductions as the formation of nitrites from nitrates. There is some 
 evidence that one and the same ferment may act as an oxydase or 
 a reductase according to the conditions. Recent researches have 
 brought to light in addition hydrolytic intracellular ferments, which 
 split up proteins very much in the same way as the proteoh'tic 
 ferments of the digestive juices. 
 
 The significance of these autolytic enzymes in the normal metabo- 
 
6oo METABOLISM. NUTRITION AND DIETETICS 
 
 lism of prott'ins lias been already discussed (p. 578) ; indeed, so many 
 of the chemical reactions of the body have been found to depend 
 upon enzymes that modern physiology may at first thought seem 
 almost to have reverted to the position of Van Helmont and his 
 school in the seventeenth century, who resolved all difficulties by 
 murmuring the magic word ' ferment.' No fewer than eleven fer- 
 ments lune been stated to be present and active in the liver alone 
 — viz., a proteolytic and a nuclein-splitting ferment, a ferment 
 which splits off ammonia from amino-acids, a milk-curdling ferment, 
 a fibrin ferment, a bactericidal ferment, an oxydase, a lipase, a 
 maltase, a ferment called glycogenase, which changes glycogen into 
 dextrose, and an autolytic ferment. In the presence of such an 
 array of enzymes the organs might seem to be little more than 
 incubators in which the ferments do their work. It must not be 
 supposed, however, that the intracellular ferments, whether they 
 cause decomposition or synthesis, oxidation or reduction, work in- 
 dependently of what, for want of a better name, we must call the 
 organization of the cell. We may be sure they are the servants 
 and not tlie masters of the protoplasm, and that a drop of an extract 
 containing intracellular ferments has very different powers from a 
 living cell. ' It is not in the existence of the ferments, but in their 
 combined action at the proper time and in the proper intensity, that 
 the riddle of metabolism lies ' (Hober) . 
 
 Summary.~At this point let us sum up wliat we have learnt as 
 to the relation between the approximate principles of the tissues and 
 the proximate principles of the food. Inside the body we recognize 
 representatives of the three groups of organic food-substances in a 
 typical diet — proteins, carbo-hydrates, and fats. But we should 
 greatly err if we were to imagine that the three streams of food- 
 materials have flowed from the intestines into the tissues each in its 
 separate channel, neither giving to nor taking from the others. 
 The fats of the body may, indeed, in part be composed of molecules 
 which xvere present as fat in the food ; but they may also be formed 
 from carbo-hydrates, and probably from proteins. The carbo-hydrates 
 of the body — the glycogen of the liver and muscles, the sugar of the blood 
 — may undoubtedly be derived from carbo-hydrates in the food, but they 
 may also be derived from proteins and from fats {certainly from their 
 glycerin constituent, perhaps from the fatty acids as well). The pro- 
 teins of the body come mainly, if not solely, from the proteins of the food. 
 Although, of course, neither fats nor carbo-hydrates can by themselves 
 form protein, being devoid of nitrogen, it is possible that products 
 arising in the intermediary metabolism of either may, by combining 
 li'ith nitrogenous groups, be tranfsormed into amino-bodies, -which can 
 then take part in the synthesis of proteins. In any case there is no 
 doubt that both carbo-hydrates and fats can economize proteins and 
 shield them from an overhasiy metabolism. 
 
STATISTICS OF NUTRITION 
 
 60 1 
 
 Section IV.— Statistics of Nutrition — The Income and 
 Expenditure of the Body in Terms of Matter * 
 
 Preliminary Data. — The office of the food is to maintain the con- 
 stituents of the body upon the whole in their normal proportions. A 
 knowledge of the chemical composition of the body is, therefore, an 
 important datum in the consideration of the statistics of its metabolism. 
 The body of a man analyzed by Volkmann had the following composition : 
 
 , . ,. (Water - - - - 65-9 per cent. 
 
 Inorganic substances I ^.j^^j.^^^^^^^ J. . . ^.^^ ^^ 
 
 rCarbon 18-4 per cent."\ 
 
 Organic substances ^Nrtrogfr 2-6 ','. [^97 -. 
 (.Oxygen 6'0 ,, J 
 The muscles, the adipose tissue, and the skeleton form nearly four- 
 fifths of the total body-weight in the adult. The following table shows 
 the percentage amount of each of these tissues in a man, a woman, and 
 a child (Bischoff) : 
 
 
 Man. 
 
 Woman. 
 
 New-born 
 Child. 
 
 Voluntary muscles 
 Adipose tissue - 
 Skeleton - 
 Rest of body 
 
 41.8 
 l8-2 
 
 15-9 
 24-1 
 
 35-8 
 
 2 8-2 
 
 15-1 
 
 20*9 
 
 23-5 
 
 13-5 
 157 
 47-3 
 
 The nitrogen is contained chiefly in the muscles, glands, and nervous 
 system, and in the constituents of the connective tissues, which yield 
 gelatin, various mucoids, and elastin. The ordinary proteins make up 
 about 9 per cent, of the weight of the body, or 22 per cent, of its solids; 
 the albuminoids or sclero-proteins (gelatin-yielding material, etc.) (p. 2) 
 about 6 per cent, of the body-weight. Nitrogen exists in proteins to 
 the extent of 16 per cent., so that the 6-5 kilos of protein of a 70-kilo 
 body contain about i kilo of nitrogen. 
 
 The carbon is contained chiefly in the fat, which forms a very large 
 proportion of the water-free substance of the body, and in the proteins. 
 A small amount is present as calcium carbonate in the bones. In the 
 body of a strong young man weighing 68-6 kilos, Voit found the following 
 quantities of dry fat in the various tissues : 
 
 - 8809*4 grammes. 
 
 Adipose tissue 
 
 Skeleton 
 
 Muscles 
 
 Brain and spinal cord 
 
 Other organs 
 
 Total - 
 
 26I7-2 
 
 636-8 
 
 226-9 
 
 73-2 
 
 12363-5 
 
 equivalent to 18 per cent, of the whole body-weight, or 44 per cent, of 
 the solids. In dry fat rather more than 75 per cent, of carbon is present, 
 and in protein about 50 to 55 per cent. ; so that while the fat of the body 
 analyzed by Voit contained more than 9 kilos of carbon, only about a 
 third of this amount would be found in the proteins. 
 
 * The income and expenditure of the body in terms of energy are considered 
 in Chapter XII. 
 
6o2 METABOLISM. NUTRITION AND DIETETICS 
 
 In the fat there is, roughly speaking, 12 per cent, of hydrogen, in 
 proteins only 7 per cent. ; so that from three to four times as much 
 hydrogen is contained in the fat of the body as in its proteins. 
 
 Oxygen forms about 12 per cent, of fat, and 20 to 24 per cent, of 
 proteins; the protein constituents of the body, therefore, contain about 
 as much of its oxygen as the fat. 
 
 Of the inorganic salts, calcium phosphate, Ca3(P04)2, is much the 
 most abundant, owing to tlie large amount of it in bone, in the ash of 
 which it is found to the extent of 83 per cent., along with 13 per cent, 
 of calcium carbonate. 
 
 Income and Expenditure of Nitrogen — The Nitrogen 
 Balance-Sheet. 
 
 Nitrogenous Equilibrium. — It is a matter of cornmon experi- 
 ence that the weight of the body of an adult may remain approxi- 
 mately constant for many months or years, even when the diet varies 
 greatly in nature and amount. And not only may the weight remain 
 constant, but the relative proportions of the various tissues of the 
 body, so far as can be judged, may remain constant too. Here it 
 is evident that the expenditure of the body must precisely balance 
 its income : it must lose as much nitrogen as it takes in, otherwise 
 it would put on flesh; it must lose as much carbon as it takes in, 
 otherwise it would put on fat. Or, again, the body may be losing 
 or gaining fat, giving off more or less carbon than it receives, while 
 its ' flesh ' (its protein constituents) remains constant in amount, 
 the expenditure of nitrogen being exactly equal to the income.* 
 In both cases we say that the body is in nitrogenous equilibrium. 
 
 A starving animal or a fever patient, on the other hand, is living 
 upon capital, the former entirely, the latter in part; the expenditure 
 of nitrogen is greater than the income. A growing child is living 
 below its income, is increasing its capital of flesh. In neither case 
 is nitrogenous equilibrium present. 
 
 The starving animal, as long as life lasts, excretes urea, kreatinin, 
 and other nitrogenous substances, and gives off carbon dioxide; 
 but its expenditure, and especially its expenditure of nitrogen, is 
 pitched upon the lowest scale. It lives penuriously, it spins out 
 its resources; its glycogen goes, its fat goes, a certain part of its 
 protein goes, and when its weight has fallen from 25 to 50 per cent, 
 it dies. At death the heart and central nervous system are found 
 to have scarcely lost in weight ; the other organs have been sacrificed 
 to feed them. Fig. 199 shows the percentage loss of weight and 
 the proportion of tlie total loss which falls upon each of the organs 
 of a cat in starvation (Voit). 
 
 ♦ For long experiments extending over many days the nitrogen balance 
 may be considered as practically the same as the protein balance, but this 
 is not necessarily true of short periods of time, since the stock of nitrogen 
 present in the body in other forms than proteins, although relatively small, 
 is subject to variations. 
 
STATISTICS OF NUTRITION 
 
 603 
 
 For the first day of starvation the excretion of urea in a dog or 
 cat is not diminished; it takes about twenty-four hours for all the 
 nitrogen corresponding to the proteins of the last meal to be elimin- 
 ated. On the second day the quantity of urea sinks abruptly; 
 then begins the true starvation period, during which the daily output 
 of urea remains constant or diminishes very slowly until a short time 
 before death, when it rapidly falls, and soon ceases altogether. An 
 increase in the excretion may precede the final abrupt decline (pre- 
 mortal increase). This seems to indicate the time at which all the 
 available fat has been used up, and after which protein is no longer 
 ' spared ' by the fat.* If the animal has little fat in its body to 
 begin with, the rise in the urea excretion takes place even after the 
 first few days. So long as the fat lasts the rate at which it is 
 
 / 
 
 
 
 
 
 
 n 
 
 «•/ Muscle 
 
 W-r: 
 
 .^.ijlIl.C ,.,..;-.^__ J!.i_, 
 
 ^itfitf 
 
 -Hc-Tlf-I 
 
 r- 
 
 Bra'-n i 
 
 262 Fat 
 a-7 Sk'in 
 
 J 
 
 '!^!||ji!liiliilii;iliiiiiliiilil 
 
 
 
 Heart J 
 Bones '"■ 
 
 J -5 Bones 
 
 
 
 Pancreas i7 
 
 ■^■U Liver 
 2-6 Blood 
 
 
 
 r- 
 
 
 
 Intestines '8 
 L ungs 10 
 
 ZO Intestine:. 
 0-6 Kidney i 
 i^O-5 Spleen 
 
 _.„q^rrrr 
 — ii — 
 
 
 Skin il 
 
 Kidnevs 2S 
 Blood 27 
 
 0-3 Lungs 
 
 i ' 
 
 
 Vusdes 31 
 
 O'l Pancreas 
 
 
 
 
 Teste < 40 
 
 ■ Oil Testes 
 
 
 |7 
 
 
 
 
 
 Liver S4 
 
 jO-l Brain i Cora 
 
 
 
 ' 
 
 
 Spleen 67 
 
 (0-1 Heart 
 
 , 
 
 ,: ,-, 
 
 
 \ 
 
 
 Fof^ 97 
 
 Fig. igs- — Diagram showing Loss of Weight of the Organs in Starvation. The 
 numbers under I. are the percentages of the total loss of body -weight borne by 
 the various organs and tissues. The numbers under II. give the percentage loss 
 of weight of each organ calculated on its original weight as indicated by com- 
 parison with the organs of a similar animal killed in good condition. 
 
 destroyed — as estimated from the amount of carbon given off minus 
 the carbon corresponding to the broken-down proteins — remains 
 very nearly constant after the first day. The fat to a certain extent 
 economizes the proteins of the starving body, but however much 
 fat may be present, a steady waste of the tissue-proteins goes on. 
 If non-nitrogenous food in the form of sugar is supplied to an other- 
 wise starNang animal, the premortal rise in the nitrogen excretion 
 does not occur. By giving a sufficient quantity of sugar, or of 
 sugar and fat, but practically no protein (so-called nitrogen starva- 
 tion), the excretion of nitrogen may be reduced to one-third of its 
 amount when no food at all is given. This is true both in animals 
 
 * If the animal has been for some time on a diet containing an abundance 
 of proteins, several days may elapse before the constant excretion of urea 
 is reached; if the previous diet has been poor in protein, the constant star- 
 vation output may be at once established. 
 
6o4 
 
 METABOLISM. NUTRITION AND DIETETICS 
 
 and man In this way the daily excretion of nitrogen in a man has 
 been reduced to 4 grammes. It is a remarkable fact that while a 
 mixture of carbo-hj'drate and fat will act just as well as carbo- 
 hydrate alone in bringing about this reduction in the nitrogen 
 output, fat without carbo-hydrate is much less effective. The 
 hypothesis suggested by Landergren to explain this is alluded to 
 on another page (p. 551). 
 
 The results obtained on fasting men differ in some respects from 
 those obtained on starving animals. In ten days of hunger, Cetti, 
 a professional ' fasting man ' of meagre habit, excreted 112 grammes 
 nitrogen, or an average of 11 grammes a day. The excretion was 
 least on the eighth, ninth, and tenth days — namely, about 9 grammes 
 a day. On the third day it was higher than on the second, and 
 almost as high on iS^ra/vs 
 the fourth as on the 
 third. A similar rise 
 in the nitrogen 
 excretion on the 
 second day has been 
 observed in other 
 fasting men, but is 
 either rare or absent 
 in fasting dogs. The 
 explanation appar- 
 ently is that in the ^ig. 
 ordinary food of 
 man there is a 
 greater abundance 
 of carbo - hydrates 
 and fats, the pro- 
 tein - sparing action 
 of which is most 
 
 !0 
 
 Cjrarr,^ 
 
 6 grary?s 
 
 A 60 
 
 ^2U 
 
 •99.' 
 
 Excretion of Urea in Starvation. .\ is a curv« 
 representing the quantity of urea e.\creted daily by a 
 fat dog in a starvation period of si::ty days. B is the 
 curve of urea excretion in a lean young dog in a 
 starvation period of twenty-four days. Both are con- 
 structed from Falck's numbers, but in A only every 
 third day is put in, in order to save space. The num- 
 bers along the vertical axis represent grammes of urea; 
 those along the horizontal axis days from the beginning 
 of star\'ation. 
 
 pronounced at the very beginning of the starvation period. The 
 quantity of chlorine and alkalies in the urine was also diminished, 
 while the phenol was increased. The respiratory quotient sank to 
 0-66 to 0-69 — even less than the quotient corresponding to oxida- 
 tion of fats alone. The meaning of this, in all probability, is that 
 some of the carbon of the broken-down proteins was laid up in the 
 body as glycogen (Zuntz). In another professional fasting man 
 (Succi) with a considerable amount of body-fat, the excretion of 
 nitrogen was found to diminish continuously during a fast of thirty 
 days, being less than 7 grammes on the tenth day. In another fast 
 of twenty-one days by the same person it was a little less than 
 3 grammes on the last day. The surprisingly small nitrogenous 
 waste in this case is perhaps to be accounted for by the protein- 
 sparing action of the abundant body-fat. The nitrogenous metabo- 
 
STATI:iTICS OF NUTRITION 
 
 605 
 
 lism has also been investigated during long-continued liypnotic sleep 
 (Hoover and Solhnann). The results were very much the same as 
 in an ordinary starvation experiment 
 
 It might be supposed that if an animal was given as much nitrogen 
 in the food in the form of proteins as corresponded to its daily loss 
 of nitrogen diu-ing starvation, this loss would be entirely prevented 
 and nitrogenous equilibrium restored. The supposition would be 
 very far from the reality. If a dog of 30 kilos weight, which on 
 the tenth day of starvation excreted 11-4 grammes urea, had then 
 received a daily quantity of protein equivalent to this amount — 
 that is to say, about 34 grammes of dry protein, or 175 grammes of 
 lean meat — the excretion of nitrogen would at once have leaped 
 up to nearly double its starvation value. If the quantit}^ of protein 
 in the diet was progressively increased, the output of urea would 
 increase along with it, but at an ever-slackening rate; and at length 
 a condition would be reached in which the income of nitrogen 
 exactly balanced the expenditure, and the animal neither lost nor 
 gained flesh. 
 
 In an experiment of Volt's, for instance, the calculated loss of flesh 
 in a dog with no food at all was 190 grammes a day. The animal was 
 now fed on a gradually increasing diet of lean meat, with the following 
 result : 
 
 Flesh in the 
 
 Flesh used up in 
 
 Net Loss oJ 
 
 Food. 
 
 the Body. 
 
 Body-flesh. 
 
 
 
 190 
 
 190 
 
 250 
 
 341 
 
 91 
 
 350 
 
 411 
 
 61 
 
 400 
 
 454 
 
 54 
 
 450 
 
 471 
 
 21 
 
 480 
 
 492 
 
 12 
 
 The loss of nitrogen in the urine and faeces is what was measured. 
 Knowing the average composition of ' body-flesh ' (muscles, glands, 
 etc.), it is possible to translate results stated in terms of nitrogen into 
 results stated in terms of ' flesh.' Muscle contains approximately 
 3'4 per cent, of nitrogen. Here, with a diet of 480 grammes of meat, the 
 dog was still losing a little flesh ; it would probably have required from 
 500 to 600 grammes for equilibrium. The results are graphically 
 represented in Fig. 200, p. 007. 
 
 The quantity of protein food necessary for nitrogenous equili- 
 brium varies with the condition of the organism ; an emaciated body 
 requires less than a muscular and well-nourished body. The least 
 quantity which would suffice to maintain in nitrogenous equilibrium 
 the famous 35 kilo dog of Voit, even in very meagre condition, was 
 480 grammes of lean meat, corresponding to 16 grammes of nitrogen, 
 or 35 grammes of urea — that is, about three times the daily loss 
 
6o6 METABOLISM. NUTRITION AND DIETETICS 
 
 during starvation. From this lower limit up to 2,500 grammes of 
 meat a day nitrogenous equilibrium could always be attained, the 
 animal putting on some flesh at each increase of diet, until at length 
 the whole 2,500 grammes was regularly used up in the twenty-four 
 hours. A further increase was only checked by digestive troubles. 
 A man, or at least a civilized man, can consume a much smaller 
 amount both absolutely and in proportion ' to the body- weight. 
 Rubner, with a body-weight of 72 kilos, was able to digest and absorb 
 over 1,400 grammes of lean meat; Ranke, with about the same 
 body-weight, could only use up 1,300 grammes on the first day of 
 his experiment, and less than 1,000 grammes on the third. But 
 whether the surplus of protein food above the necessary minimum 
 is great or small, nitrogen equilibrium is eventually attained, and 
 thereafter all the nitrogen of the food regularly appears in the 
 excreta; the explanation of this fact will be considered a little 
 later (p O09). 
 
 So much for a purely protein diet. When fat is given in addition 
 to protein, nitrogenous equilibrium is attained with a smaller quantity 
 of the latter. A dog which, with protein food alone, is putting on 
 flesh, will put on more of it before nitrogenous equihbrium is reached 
 if a considerable quantity of fat be added to its diet. Fat, therefore, 
 economizes protein to a certain extent, as we have already recog- 
 nized in the case of the starving animal. On the other hand, when 
 protein is given in large quantities to a fat animal, the consumption 
 of fat is increased; and if the food contains little or none, the body- 
 fat will diminish, while at the same time ' flesh ' may be put on. 
 The Banting cure for corpulence consists in putting the patient 
 upon a diet containing nuicli protein, but little fat or carbo-hydrate; 
 and the fact just mentioned throws light upon its action. 
 
 All that we have here said of fat is true of carbo-hydrates. To a 
 great extent these two kinds of food substances are complementary. 
 Carbo-hydrates economize proteins as fat does, but to a greater 
 extent, so that with an abundant supply of carbo-hydrate in the 
 food the minimum protein requirement can be forced down much 
 below what is possible on a diet of protein and fat alone. Carbo- 
 hydrates also economize fat, so that when a sufficient quantity of 
 starch or sugar is given to an otherwise starving animal, all loss of 
 carbon from the body, except that which goes off in the urea, krea- 
 tinin, etc., still excreted, can be prevented. Of course, the animal 
 ultimately dies, because the continuous, though diminished, loss of 
 protein cannot be made good. The fact that carbo-hydrates econo- 
 mize proteins so much more efficiently than fat indicates that sugar 
 is essential in the bodily metabolism, so that when carbo-hydrates 
 are absent from the food some of the protein must be broken down 
 so as to yield eventually the compounds necessary for the formation 
 of carbo-hydrate. It is probable, indeed, that purified proteins, 
 
STATISTICS OF NUTRITION 
 
 607 
 
 Grarr}5 
 joo 
 
 300 
 200 
 100 
 
 
 WO ip 
 
 absolutely free from admixture with carbo-hydrates, which, of 
 course, is not the case with the natural protein foods, will not per- 
 manently suffice for nutrition, but that the protein must be supple- 
 mented by a certain amount of carbo- 
 hydrate in some form available for the 
 tissues. It would appear, indeed, that 
 fats are not absolutely indispensable 
 either for maintenance or for growth. 
 White rats have been seen to grow nor- 
 mally over long periods with dietaries 
 devoid of fat ; for example, mixtures of the 
 purified protein edestin (from hemp seed) 
 or casein with starch, sugar, and ' protein- 
 free milk ' freed from fat by extraction 
 with ether (Osborne and Mendel). While 
 in these experiments the food might not 
 have been free from the so-called ' lipoids,' 
 it has been demonstrated that an impor- 
 tant group of substances of this class, the 
 phosphatides, can be S5mthesized in the 
 body, the necessary phosphorus being ob- 
 tainable even from inorganic phosphates 
 (McCollom). 
 
 Relation between Nitrogen excreted and 
 the Quantity of Protein Food. — At this 
 point we may consider a little more 
 closely a phenomenon already alluded to, 
 and to which much discussion used to be 
 devoted by writers on metabolism. It 
 has been stated that within the limits of 
 nitrogenous equilibrium, which is the nor- 
 mal state of the healthy adult, the body 
 lives up to its income of nitrogen ; it lays 
 by nothing for the future. In the actual 
 pinch of starvation the organism, when 
 its behaviour is tested by a comparison 
 of the intake and excretion of nitrogen, 
 appears to have become suddenly econo- 
 mical. When a plentiful supply of protein 
 is presented to the starving body, it seems, 
 judged by the same criterion, to pass at 
 once from extreme frugality to luxury. 
 Some flesh may be put on for a short time, some nitrogen may be 
 stored up; but the excretion of nitrogen is soon adjusted to the new 
 scale of supply, and the protein income is apparently spent as freely 
 as it is received. These facts were usually summed up in the 
 
 Fig. 200. — Curves constructed 
 to illustrate Nitrogenous 
 Equilibrium (from an Ex- 
 periment of Voit's). The 
 loss of flesh in grammes is 
 laid off along the horizontal 
 axis. The income and 
 expenditure corresponding 
 to a given loss are laid ofl' 
 (in grammes of ' flesh ') 
 along the vertical axis. The 
 continuous curve is the 
 curve of income; the dotted 
 curve, of expenditure. With 
 no income at all the expen- 
 diture is 190 grammes; 
 with an income of 480 
 grammes the expenditure 
 is 492 and the loss 12 
 grammes. Nitrogenous 
 equilibrium is represented 
 as being reached with an 
 income of about 530 
 grammes; here the two 
 curves cut one another. 
 
6o8 METABOLISM. NUTRITION AND DIETETICS 
 
 dictum, often dignified as a ' law ' of nitrogenous metabolism that*. 
 Consxnnption of protein is largely determined by supply (Practical 
 Exercises, p. 720). 
 
 To explain this many hypotheses were invented. The famous theory 
 of Voit assumed that the food-protein after absorption (the so-called 
 ' circulating-protein ') is carried to the tissues and taken up by the 
 cells, where the greater part of it, without being incorporated with the 
 protoplasm, is nevertheless acted upon, rendered unstable, shaken to 
 pieces, as it were, by the whirl of life (by the intracellular enzymes we 
 might now say less dramatically) in the organized framework, the 
 interstices of which it fills. 
 
 Pfliiger, on the other hand, maintained that we have no right to 
 draw a distinction between the consumption of organ- and circulating- 
 protein; that the whole of the latter ultimately rises to the height of 
 organ- or tissue-protein, and passes on to the downward stage of 
 metabolism only through the topmost step of organization . An increase 
 in the supply of nitrogenous material in the blood must, on this view, 
 be accompanied with an increased tendency to the break-up, the dis- 
 sociation, as Pfliiger put it, of the living substance. The actual organ- 
 ized elements, however, the existing cells, were not supposed to be 
 destroyed; the building remained, for although stones were constantly 
 crumbling in its walls, others were being constantly built in. 
 
 A much less plausible view was that the tissue elements themselves are 
 short-li\-ed ; that the old cells disappear bodily and are replaced by new 
 cells ; and that the whole of the proteins of the food take part in this 
 process of total ruin and reconstruction. Histological evidence, as soon 
 as the methods of examining tissues with the microscope became 
 sufficiently refined, told strongly against this idea. Although the cells 
 of certain' glands, such as the mammary, perhaps the mucous glands, 
 and especially the sebaceous glands (p. 565), exhibit changes which, 
 hastily interpreted, might seem to indicate that they break dovra 
 bodily, as an incident of functional activity, no proof could be obtained 
 of the production of new cells on the immense scale which this theory 
 would require. The relatively small and constant amount of the 
 endogenous metabolism indicates that the actual protoplasmic sub- 
 stance, the living framework of the cell, is comparatively stable; 
 that it does not break down rapidly; and that only a small and 
 fairly constant amount of food- or circulating-protein, or of the 
 decomposition products of protein, is required to supply the waste 
 of the organ -protein. 
 
 We have referred to these theories because there could scarcely be a 
 more instructive instance of the way in which theories become obsolete 
 with the adv^ance of knowledge and of the way in which, with the 
 advance of knowledge, a phenomenon which appears an absolute riddle 
 to one generation may become fairly intelligible to the next, perhaps 
 childishly simple to a third. The student will not derive much benefit 
 from the perusal of this page should he fail to recognize that the 
 hypotheses of the twentieth century are mortal too, and bound for the 
 same bourne as those of the nineteenth. 
 
 It is apparent in the first place from our study of the metabolism 
 of the proteins that the conclusion, ' consumption of protein is pro- 
 portional to supply,' cannot be drawn from the equality of nitrogen 
 intake and nitrogen output. The amino-acids derived from proteins, 
 except that relatively small fraction employed in repairing the 
 
STATISTICS OF NUTRITION 609 
 
 waste of the tissues, which in nitrogen equilibrium is exactly com- 
 pensated for by a corresponding release of amino-acids or their 
 equivalent from the cell-proteins, are indeed speedily deaminated 
 and the nitrogen of the amino-groups excreted as urea (with 
 ammonia compounds and creatinin). But, as we have seen, only a 
 small proportion of the chemical energy of the amino-acids and only 
 a small fraction of their carbon are liberated in this process. The 
 carbon-containing residues are katabolized only to the extent re- 
 quired by the momentary needs of the tissues, any balance being 
 stored as part of the reserve of carbo-hydrate or of fat. The body 
 does not possess the means of storing surplus amino-acids as such 
 or even in the form of proteins, except to the small extent corre- 
 sponding to any increase which may occur in the body-protein 
 when the food-protein is increased beyond the minimum required 
 for nitrogen equilibrium. Why the organism has not developed 
 the capacity to store large quantities of protein is, of course, an 
 interesting question, but it need scarcely be discussed here. One 
 obvious reason is that protein is not a suitable source, nor are amino- 
 acids apparently a suitable source of energy for the tissues until 
 they have been deaminated and have probably undergone further 
 decomposition and transformation. Therefore they are decomposed 
 at once and their available residue stored, if it is in any case to be 
 stored, in the more available form of carbo-hydrate (or fat). 
 Where the food-proteins differ greatly from the body-proteins in 
 the proportions of the various amino-acids, there would be no object 
 in storing a great surplus of those which are most plentiful in the 
 food, if they were at the same time the scarcest in the tissues, or, 
 in the case of gland-cells, the scarcest in the proteins which they 
 manufacture for their secretions. 
 
 At any moment the magnitude of this non-utilizable surplus will 
 depend upon the quantity of that one of the indispensable amino- 
 acids which is present in the smallest amount. For the proper 
 proportion must be preserved between the different ' stones ' out of 
 which the molecule is built. \M"ien a single amino-acid is intro- 
 duced into the body, it is at once changed into urea and excreted, 
 since it cannot be utihzed by itself for building up protein. 
 
 When the cells have once culled from the mixture circulating in 
 the blood the amino-acids, a full supply of which they have most 
 difficulty in obtaining, a residue, large or small, according to the 
 quantity and quality of the protein intake, will be left, and this can 
 only be utilized to supply energy or to add to the fat and carbo- 
 hydrate stores. For these uses removal of the amino-group is an 
 essential preliminary. The question whether the deamination of a 
 large part of the amino-acids coming from the intestine takes place 
 in the liver, so that the surplus nitrogen is shunted out of the main 
 metabolic current at its verv source, has been already touched upon 
 
 39 
 
6io METABOLISM. NUTRITION AND DIETETICS 
 
 (p. 5&S). Some writers conceive that in such a short-cut from pro- 
 tein to urea we have a kind of physiological safety-valve to protect 
 the tissues from the burden of an excessive metabolism. And if 
 by this is meant that it is advantageous to the tissues that a special 
 mechanism should exist to eliminate a surplus of nitrogen which they 
 do not require, and which they cannot store, and to present them 
 with a residue which they can utilize, the conception is certainly 
 correct. But there is no good evideuce that in the presence of an 
 over-abundant supply of amino-acids the endogenous protein meta- 
 bolism would be essentially modified. 
 
 Relation of Nitrogenous Metabolism to Muscular Work. — This is 
 another of those classical physiological problems which it is difficult 
 to present properly apart from its historical setting. The general 
 result of much experimental work and long-continued discussion is 
 that when the work does not transgress what may be called ' normal 
 limits,' the excretion of nitrogen is nearly independent of mus- 
 cular work — ^that is to say, the quantity of nitrogen excreted by a 
 man on a given diet is practically the same whether he rests or works. 
 Before this was known it was maintained by Liebig that proteins 
 alone could suppl}^ the energy of muscular contraction — that, in 
 fact, proteins were solely used up in the nutrition and functional 
 activity of the nitrogenous tissues, while the non-protein food 
 yielded heat by its oxidation. As exact experiments multiplied, it 
 was found that muscular work, the production of which is the 
 function of by far the greatest mass of protein-containing tissue, 
 had little or no effect upon the excretion of urea in the urine. More 
 than this, it was shown that a certain amount of work accomplished 
 (by Fick and Wislicenus in climbing a mountain) on a non-nitrog- 
 enous diet had double the heat equivalent of the whole of the pro- 
 tein consumed in the body, as estimated by the urea excreted during, 
 and for a given time after, the work. On the assumption that all 
 the urea corresponding to the protein broken down was eliminated 
 during the time of this experiment, a part at least of the work must 
 have been derived from the energy of non-nitrogenous material. 
 And other experiments in which account was taken of the increase 
 in the carbon dioxide given off (as conspicuous an accompaniment 
 of muscular work as the constancy of the urea excretion), showed 
 that during muscular exertion carbonaceous substances other than 
 proteins — that is to say, fats and carbo-hydrates — are oxidized in 
 gi eater amount than during rest. 
 
 So the pendulum of physiological orthodoxy came full-swing to the 
 other side. Liebig and his school had taught that proteins alone were 
 consumed in functional activit}-; the majority of later physiologists 
 following Voit denied to the proteins any share whatever in the energy 
 which appears as muscular contraction. The proteins, they said, 
 ' repair the slow waste of the framework of the muscular machine, 
 replace a loose rivet, a worn-out belt, as occasion may require : the 
 
STATISTICS OF NUTRITION 6ii 
 
 carbo-hydrates and fats are the fuel which feeds the furnaces of life, 
 the materal which, dead itself, is oxidized in the interstices of the 
 living substance, and yields the energy for its work.' 
 
 Now, it is a singular circumstance, and full of instruction for the 
 ingenuous student of science, that the facts which were supposed 
 absolutely to disprove the older theory, and absolutely to establish its 
 more modem rival, are now seen to do neither the one thing rtor the 
 other. The fact — and it is a fact — that the excretion of nitrogen is 
 but little affected by muscular contraction, docs not prove that none 
 of the energy of muscular work comes from proteins; the fact that, 
 under certain conditions, some of the muscular energy must apparently 
 come from non-nitrogenous materials, does not prove that these are the 
 normal source of it all. The distinction had again been made too 
 absolute. The pendulum must again swing back a little; and the 
 experiments of Pfli'igcr and his pupils were soon to set it moving. 
 
 In the first place, it is not perfectly correct to say that work 
 causes no increase in the excretion of nitrogen; excessive work in 
 man, and work, severe but not excessive, in a flesh-fed dog (Pfliiger), 
 do cause somewhat more nitrogen to be given off. On the first day 
 of work the increase is always much less than on the second and third ; 
 and on the first and second rest days, following work, the elimina- 
 tion of nitrogen is still increased. After excessive exercise in man 
 not only is the urea increased, but also the ammonia, kreatinin, and 
 if the subject is in poor training, the uric acid and purin bases (Pat on. 
 Stockman, etc.). Moderate exercise causes no increase on the first 
 day, but a slight increase on the second. The meaning of these 
 facts seems to be that during muscular work the intensity of which 
 does not exceed certain limits, the protein waste of the muscular 
 substance itself is no greater than during rest. When, however, the 
 machine is ' speeded up ' beyond a certain point the wear and tear 
 is sensibly increased and an excess of tissue-protein is katabolized. 
 There is no reason to suppose that the tissue-protein thus broken 
 down will not yield energy for the muscular work by the oxidation 
 of its non-nitrogenous residue, just as well as the surplus amino- 
 bodies derived from food-protein. The muscular machine has the 
 peculiarity that it is constructed of combustible material; even the 
 dust and the splinters, if we may so express it, which represent the 
 wear and tear of the machine can be burnt in the furnace which keeps 
 it going. 
 
 In the second place, even if the excretion of nitrogen were entirely 
 unaffected by work, this would not prove that none of the 
 energy of the work comes from proteins. For, as we have seen, 
 it is after the nitrogen has been split off and converted into urea 
 that the energy of a great part of the food-protein is developed by 
 oxidation. Further, since the animal body is a beautifully-balanced 
 mechanism which constantly adapts itself to its conditions, it is 
 conceivable that it may, when called upon to labour, save proteins 
 from lower uses to devote them to muscular contraction. In this 
 
6i2 METABOLISM. NUTRITION AND DIETETICS 
 
 case the excretion of nitrogen would not necessarily be altered; the 
 proteins which, in the absence of work, would have been oxidized 
 within the muscular substance or elsewhere, their energy appearing 
 entirely as heat, may, wlien the call for protein to take the place of 
 that broken down in muscular contraction arises, be diverted to this 
 purpose. 
 
 In any case, there is no doubt that a dog fed on lean meat may 
 go on for a long time performing far more work than can be yielded 
 by the energy of fat and carbo-hydrates occurring in traces in the 
 food, or taken from the stock in the animal's body at the beginning 
 of the period at work. A large portion, and perhaps the whole, of 
 the work, must in this case be derived from the energy of the pro- 
 teins (Pfiiiger). On the other hand, it is well established that when 
 fats and carbo-hydrates are present in sufficient quantity in the 
 tissues or the food, they constitute the main source of the energy 
 of muscular contraction (p. 772), and there is some evidence that of 
 the two classes of food materials carbo-hydrates in the form of 
 dextrose (or glycogen) is the material of election. 
 
 The outcome, then, of this famous controversy is essentially a 
 compromise. Everybody now admits that the muscular machine 
 can and does utilize predominantly any one of the great groups 
 of food substances, be it carbo-hydrate, fat, or protein, when the 
 dietetic conditions are such that only one of these is offered to it 
 in large amount, the others being either absent or offered in small 
 amount. To be sure, amino-acids are not the first choice, but if 
 it must do so the muscle can make shift with them, and can indeed 
 make them serve excellently well. When all the food substances 
 are present in abundance, carbo-hydrate is favoured above fat, and 
 fat above protein. 
 
 Experience has shown that the mininmm quantity of nitrogen 
 required in the food of a man whose daily work involves hard 
 physical toil is higher than the minimum required by a person lead- 
 ing an easy, sedentary life. This is evidently in accordance with 
 the view that protein is actually used up in muscular contraction ; 
 but it is not inconsistent with the opposite view. For the body of a 
 man fit for continuous hard labour has a greater mass of muscle 
 to feed than the body of a man who is only fit to handle a composing- 
 stick, or drive a quill, or ply a needle ; and the greater the muscular 
 mass, the greater the muscular waste. But if an animal just in 
 nitrogenous equilibrium on a diet of lean meat when doing no work 
 is made to labour day after day, it will lose flesh unless the diet 
 be increased. This must mean that some of the protein is being 
 diverted to muscular work, and that the balance is not sufficient 
 to keep up the original mass of ' flesh ' (see p. 628). 
 
 Relative Value of Different Proteins in Nutrition — Synthesis of 
 Amino-Acids. — The fact that the various proteins differ quantita- 
 
STATISTICS OF NUTRITION 6i-{ 
 
 ti vely and qualitatively in respect to their amino-acids raises the ques- 
 tion of the relative value of different proteins in nutrition. In this is 
 involved the further question, whether the body can itself synthesize 
 from other materials any of the amino-acids which may be deficient, 
 or change one amino-acid into another. That the ' peptones ' derived 
 from a protein which is itself capable of permanently supplying 
 the whole nitrogenous intake of the organism can be substituted 
 for the protein scarcely needs demonstration, since it is known that 
 the protein is converted into peptones in digestion. Nevertheless, 
 this has been proved conclusively by feeding experiments with 
 peptones. It was to be expected, too, leaving out of account all 
 consideration of the means of overcoming the repugnance of animals 
 to accepting such unnatural food substances, that the further 
 products of protein hydrolysis, the amino-acids, etc., could be 
 substituted for the original proteins when these were themselves 
 adequate. For it is in the form of amino-acids or at most of such 
 relatively simple polypeptide groups as may still hang together 
 after complete digestion and absorption, that the nitrogenous food 
 substances are normally offered to the tissues. Experimental 
 demonstration of the feasibility of this substitution has also been 
 obtained. The split products of meat, for example, will keep an 
 animal in nitrogen equilibrium as well as the meat from which they 
 are derived. But what happens when one or more of the amino- 
 acids found in the proteins of the body are missing from the protein 
 of the food ? That the components of an amino-acid like ^rginin 
 (ornithin and urea), into which it can be split not only by the 
 possibly crude and violent methods of the chemical laboratory, but 
 also by the delicate and precisely-adapted ' biological ' action of a 
 special enzyme (arginase), should be able to replace the original 
 amino-acid is a fact which does not greatly help towards an answer. 
 For when these components, or ornithin alone, since urea is al\Vays 
 present in the body, are given instead of arginin, the reversal of the 
 enzyme reaction by which arginin is decomposed is all that is neces- 
 sary for its synthesis, and the reversal of such a reaction is doubtless 
 a very commonplace affair in tissue metabolism. The formation 
 of one amino-acid from another, or from materials which do not 
 originate exclusively from protein, is a different thing, and the 
 answer to the question raised, so far as it can yet be given, is that 
 the way in which the body deals with a deficiency in the protein 
 ' building stones ' depends upon the nature of the missing amino- 
 acids. Thus, the phospho-protein casein does not yield glycin on 
 hydrolysis; yet it has been shown that casein is a perfectly adequate 
 or complete protein food capable of covering the whole nitrogen 
 requirement of the body over long periods. The same is true of the 
 cleavage products of casein which has been subjected to pancreatic 
 digestion. In an animal fed on no other protein than casein, with 
 
6i4 METABOLISM. NUTRITION AND DIETETICS 
 
 suitable quantities of carbo-hydrate and fat in addition, the G:lycin 
 contained in certain of the body proteins must therefore have been 
 produced in the body itself. We have already seen (p. 580) that 
 for the synthesis of hippuric acid after the administration of benzoic 
 acid, glycin is necessary, and the quantity of hippuric acid which 
 can be thus produced is so great that it is impossible to suppose 
 that it all comes from glycin preformed in the body or from glycin 
 in the food substances. It may accordingly be taken as pro\ed 
 that the tissues have the power of synthesizing at least this one of 
 the amino-acids (amino-acetic acid), reckoned among the protein 
 ' building stones. ' It is said that if the casein has been hydrolysed 
 by acid, the products will not preserve nitrogen equilibrium, per- 
 haps because the acid has broken up all the polypeptides (p. 2), 
 some of which the cells may need as the starting-point of protein 
 s}Tithesis. This, however, is uncertain. 
 
 Lysin also appears to be capable of being s\iithesized in the body, 
 and protein foods free from lysin, or containing only a trace of it, 
 may yet be adequate for nutrition and growth. Prohn, too, is not 
 indispensable, and this is of special interest, for the amino-acids 
 hitherto mentioned as capable of being built up in the tissues are 
 all more or less directly related to each other, being derivatives of 
 the series of saturated fatty acids. The task of changing one of 
 these into another in which the food is deficient may, therefore, be 
 considered a comparatively easy one. But prolin has no obvious 
 relation to most of the other amino-acids. 
 
 It is a-pyrrolidin carboxylic acid, 
 
 CH2— CH^ CH2— CH, 
 
 CH. CH.COOH—i.e.. pyrrolidin, CH, CHg 
 
 NH NH 
 
 in which H in one of the CH2 groups is replaced by carboxyi (COOH). 
 It lias been suggested Dial prolin may be formed in the body from 
 glutaminic (amino-glutaric) acid, which by loss of a molecule of water 
 can be made to jdeld a-pyrrolidon carboxylic acid. Thus, 
 
 CHa.CH«.CH.COOH CHj— CH, 
 
 COOH XHo -HoO = CO CH.COOH 
 
 \ / 
 NH 
 
 Glutaminic acid. a-pyrrolidoB carboxylic acid. 
 
 By reduction the latter compound might be changed into prolin. 
 
 With proteins deficient in certain other amino-acids a totally 
 different result has been obtained. Gelatin, for example, contains 
 most of the amino-acids and other groups which compose the body 
 proteins, but tyrosin, cystin, and tryptophane are lacking in the 
 
STATISTICS Of NUTRITION 615 
 
 gelatin molecule. Zein, an alcohol-soluble protein or prolamin* 
 derived from maize, yields no tryptophane, glycin, or lysin. Now, 
 it is found that neither gelatin nor zein can replace tlic whole of 
 the ordinary proteins in the food. When only enough protein is 
 taken to prevent loss of nitrogen from the body, one-fifth of the 
 necessary nitrogen can be supplied in the form of gelatin. When 
 the food is much richer than this in ordinary protein, a correspond- 
 ingly greater proportion of the protein can be replaced by gelatin. 
 The surplus is not used in the endogenous metabolism of the cells 
 (p. 573), but supplies energy to the body after the elimination of 
 its nitrogen as urea, just as the surplus protein would do. Thus 
 gelatin economizes protein in the same way that fat and carbo- 
 hydrates do, but also to some extent in a different way by supplying 
 ' building stones ' for the protoplasm. It is therefore an interesting 
 question whether gelatin can fully replace protein when the missing 
 substances are given in addition. Kauffmann has stated that his 
 own nitrogen requirement (15 2 grammes) was almost completely 
 covered by a mixture containing 93 per cent, of the nitrogen in the 
 form of gelatin, 4 per cent, as tyrosin, 2 per cent, as cystin, and 
 I per cent, as tryptophane, in addition to the same amounts of 
 carbo-hydrate and fatty food as in the comparison diet, in which 
 the nitrogen was supphed in the form of plasmon, a commercial 
 preparation of casein. 
 
 Similar results have been reported in experiments on animals in 
 which attempts have been made to ' complete ' such inadequate 
 proteins by addition of the missing amino-bodies, with fair but, 
 according to Osborne and Mendel, not entirely satisfactory results. 
 The converse experiment, in which an amino-acid such as trypto- 
 phane has been purposely eliminated from the food mixture, has 
 also been tried, with the result that rapid deterioration in the 
 condition of the animal ensued. It would seem, indeed, that 
 whatever capacity the animal body may have for synthesizing 
 certain of the amino-acids, this power does not extend to the cyclic 
 compounds tr5^tophane, tyrosin, phenylalanin, and histidin, which 
 must be supplied in the food. It has been suggested by Osborne 
 that in this regard an essential difference exists between the animal 
 and the plant, the latter alone being endowed with the function of 
 ' cyclopoiesis,' or formation of substances of the cychc type. It 
 is not clearly understood as yet on what this difference really hinges, 
 whether, as some have supposed, on the inability of the animal 
 organism to form the appropriate fatty acid radicals, or on some 
 
 * The prolamins are so called because on hydrolysis they yield exceptionally 
 large amounts of prolin (p. 360) and ammonia. They are insoluble in water 
 and absolute alcohol, but soluble in 70 to 80 per cent, alcohol and in dilute 
 acids and alkalies. Besides zein they include gliadin (from wheat and rye), 
 hordein (from barley), and bynin (from malt). They are extraordinarily rich 
 in glutaminic acid, hordein yielding more than any protein hitherto investi- 
 gated (over 41 per cent). 
 
6i6 METABOLISM, NUTRITIOX AKD DIETETICS 
 
 other limitation of its chemical powers. While the cyclic (and hetero- 
 cyclic) compounds cannot be replaced by other ' Bausteinc ' of the 
 proteins, they may to some extent replace each other. Thus it would 
 seem that t\Tosin can be replaced by phenylalanin (Abderhalden). 
 While some of the food proteins like casein are sufficient by 
 themsehes to supply all the amino-bodies necessary not only for 
 the maintenance, but also for the growth of the body, and can 
 accordingly be termed adequate or complete protein food sub- 
 stances, others, like gelatin, are insufficient by themselves to supply 
 the protein required for mere maintenance, still less for growth. 
 
 Fig. 201 . — Two Female Rats of the Same Age (140 days). The upper one was fed on 
 an ordinary diet, and is of the normal weight for its age. The lower one was 
 fed on a diet composed of a mixture of isolated food-stuffs. Its weight is only 
 equal to that of a normal rat thirty-six days old (Osborne and Mendel). 
 
 and may be spoken of as inadequate or incomplete proteins. There 
 is a third intermediate group, comprising proteins which suffice 
 when given as the sole protein food to maintain the body for an 
 indefinitelv long period, and to repair the tissue waste without per- 
 mitting growth of the animal to take place. Gliadin and hordein 
 (see footnote, p. 615) are representatives of this group. The ex- 
 periments of Osborne and Mendel with gliadin are of special interest, 
 since this substance is very differently constituted from the ordinary 
 food proteins, as well as from the tissue proteins of the animal 
 body. While, as already stated, it yields very large quantities of 
 glutaminic acid, prolin, and ammonia, it either contains no lysin 
 
STATISTICS Of XUTI^ri ION G17 
 
 and no glycin, or yields too little to be detected with certainty. 
 It also yields comparatively little histidin and arginin. Now, it 
 has been found that a dietary containing carbo-hydrate in the form 
 of starch, fats in the form of lard, and inorganic salts, but no pro- 
 tein except gliadin* suffices to maintain adult rats in good condition 
 for very long periods (up to 290 days), and also to maintain young 
 rats in a stationary condition as regards growth, but in perfect 
 health. The youthful appearance of the rats whose growth was 
 thus inhibited was very striking, and corresponded with their size 
 rather than with their age. The capacity for growth on a normal 
 diet was apparently not in the least diminished; the growth pro- 
 cesses simply remained in abeyance. 
 
 ' In one rat, after a continuous suppression of growth lasting 277 days, 
 when the animal was 314 davs old — an age at which normally little or 
 no growth takes place — satisfactory growth was resumed on a suitable 
 diet.' A still more remarkable experiment was the following: ' A male 
 rat, kept for 154 days with gliadin as the sole protein in the food, was 
 paired with a female also on the gliadin diet. At the end of 178 days 
 on the gliadin diet she gave birth to four young, which were satisfactorily 
 nourished by the mother, still on gliadin, during the first month of 
 their existence. After a month three of the young rats were removed 
 from the mother and put on diets of casein food [i.e., casein plus suitable 
 proportions of carbo-hydrate, fat, and inorganic materials), edestin 
 food and milk food respectively. The fourth was left with the mother. 
 The fourth rat began to evince a failure to grow at about the period 
 (thirty days) when young rats are wont to depend upon extraneous 
 food. 
 
 The meaning of this last observation can only be that the young 
 animal, when obliged to depend upon its share of the ghadin food 
 left with the mother in place of the milk formed by the mother 
 from this same gliadin food mixture, showed the topical failure to 
 grow on a diet inadequate as regards the power of producing growth 
 in respect to the protein contained in it. On the other hand, in the 
 body of the mother this inadequate diet had been so transformed 
 that not only had she maintained her body-weight and repaired 
 
 * Certain accessory substances of unknown nature, contained in some of 
 the natural foods must also be supplied (p. <>;i-L). Osborne and Mendel, for 
 instance, gave their animals a certain amount of ' protein-free milk,' contain- 
 ing the salts of milk, but only traces of milk proteins. The important thing 
 in the ' protein-free milk ' is neither the slight residue of protein nor the salt, 
 but an unknown substance, a so-called 'water-soluble vitamine.' When this 
 was supplied in the ' protein-free milk ' the animals were maintained on the 
 artificial diet for very long periods, although they did not grow. It has since 
 been rendered probable that in addition to the water-soluble vitamine, fat- 
 soluble vitamine (McCollom) is necessary' for full growth of rats and the main- 
 tenance in health of the adults, upon otherwise complete artificial diets, for 
 a great part of their natural life-span. Such fat-soluble vitamines may be 
 supplied by replacing a part of the lard by butter-fat. egg-yolk fat, beef fat, 
 or codliver oil. 
 
6i8 METABOLISM. NUTRITION AND DIETETICS 
 
 her tissue waste completely, but she had produced from it every- 
 thing necessary for the development of the embryo rats up to full 
 term, and after that everything necessary (in the form of milk) 
 for their normal growth during the period of suckling. On the 
 whole, a very large amount of body tissue in proportion to the 
 original weight of the mother must have been formed or renewed 
 in the 200 days or more during which the experiment continued, 
 and during which gliadin was being steadily transmuted into tissue 
 protein, and latterly into the proteins of milk as well, by what 
 might almost be called a feat of chemical legerdemain. There must 
 have occurred a synthesis ' not only of the Bausteine (the " building- 
 stones ") deficient in the protein intake, but likewise of tissue and 
 milk components like the nucleic acids (with their content of purins, 
 pyrimidins, and organically combined phosphorus) and phospho- 
 proteins like casein, etc., which were completely missing ' in the food. 
 
 It has been suggested that the bacteria of the alimentary canal, 
 which, of course, are plant cells, may have and may exercise on a large 
 scale the power of building up new amino-acids from a variety of 
 materials in the intestinal contents, and that they may thus be synthe- 
 sizing agents, thanks to which inadequate proteins may be reshaped to 
 proteins adequate to the needs of the body. It is precisely, however, 
 in the case of incomplete proteins like gelatin deficient in cyclical 
 compounds, that the body fails to effect the necessary transformation 
 in spite of the fact that plant cells are supposed to be specially capable 
 of forming these compounds. In any case bacterial action would not 
 explain wliy proteins like gliadin and hordein are only adequate for the 
 renewal of tissue, and not for its growth. This points rather to the 
 possibility that the processes by which the nitrogenous compounds 
 degraded in cellular metabolism are replaced are not of the same char- 
 acter as the processes by which new nitrogenous complexes are built 
 up into growing protoplasm. If, for instance, the protein molecule is 
 not completely disrupted in ordinary metabolism, it will not need to be 
 completely reconstructed, while in the formation of new tissue complete 
 protein molecules will have to be synthesized. Incomplete proteins 
 like gliadin may furnish building-stones adequate for repairing the 
 house, but inadequate for building it from the foundations. 
 
 Income and Expenditure of Carbon — The Carbon Balance-Sheet. — 
 This division of the subject has been necessarily referred to in 
 treating of the nitrogen balance-sheet, and may now be formally 
 completed. 
 
 Carbon Equilibrium. — A body in nitrogenous equiUbrium may or 
 may not be in carbon equihbrium. It has been repeatedly pointed 
 out that the continued loss or gain of carbon by an organism in 
 nitrogenous equilibrium means the loss or gain of fat ; and, since 
 the quantity of fat in the body may vary within wide limits without 
 harm, carbon equilibrium is less important than nitrogen equili- 
 brium. It is also less easily attained when the carbon of the food 
 is increased, for the consumption of fat is not necessarily increased 
 
STATISTICS OF NUTRITION 619 
 
 with the supply of fat or fat-producing food, and there is by no 
 means the same prompt adjustment of expenditure to income in 
 the case of carbon as in the case of nitrogen. 
 
 Carbon equiHbrium can be obtained in a flesh-eating animal, like 
 a dog, with an exckisively protein diet; but a far higher minimum 
 is required than for nitrogenous equilibrium alone. Voit's dog 
 required at least 1,500 grammes of meat in the twenty- four hours 
 to prevent his body from losing carbon. For a man weighing 
 70 kilos, the daily excretion of carbon on an ordinary diet is 250 to 
 300 grammes. About 2,000 grammes of lean meat would be re- 
 quired to yield this quantity of carbon; and, even if such a mass 
 could be digested and absorbed, more than three times the necessary 
 nitrogen would have to undergo preliminary cleavage and excretion 
 as urea or be thrown upon the tissues. 
 
 Not only may carbon equilibrium be maintained for a short time 
 in a dog on a diet containing fat only, or fat and carbo-hydrates, but 
 the expenditure of carbon may be less than the income, and fat may 
 be stored up. But, of course, if this diet is continued, the animal 
 ultimately dies of nitrogen starvation. 
 
 So far we have spoken only of the income and expenditure of 
 carbon and nitrogen; and from these data alone it is possible to 
 deduce many important facts in metabolism, since, knowing the 
 elementary composition of proteins, fats, and carbo-hydrates, we 
 can, on certain assumptions, translate into terms of proteins or fat 
 the gain or loss of an organism in nitrogen and carbon, or in carbon 
 alone. But the hydrogen and oxygen contained in the sohds and 
 water of the food, and the oxygen taken in by the lungs, are just as 
 important as the carbon and nitrogen; it is just as necessary to take 
 account of them in drawing up a complete and accurate balance- 
 sheet of nutrition. Fortunately, however, it is permissible to 
 devote much less time to them here, for when we have determined 
 the quantitative relations of the absorption and excretion of the 
 carbon and nitrogen, we have also to a large extent determined 
 those of the oxygen and hydrogen. 
 
 Income and Expenditure of Oxygen and Hydrogen. — The oxygen 
 absorbed as gas and in the solids of the food is given off chiefly as 
 carbon dioxide by the lungs; to a small extent as water by the lungs, 
 kidneys, and skin; and as urea and other substances in the urine 
 and faeces. The hydrogen of the solids of the food is excreted in 
 part as urea, but in far larger amount as water. The hydrogen and 
 oxygen of the ingested water pass off as water, without, so far as 
 we know, undergoing any chemical change, or existing in any other 
 form within the body. But it is important to recognize that 
 although none of the water taken in as such is broken up, some 
 water is manufactured in the tissues by the oxidation of hydrogen. 
 
6iO METABOLISM. NUTRITION AND DILIETICS 
 
 We have already considered (p. 241) the gaseous exchange in the 
 lungs, and we have seen that all the oxygen taken in does not 
 reappear as carbon dioxide. It was stated there that the missing 
 oxygen goes to oxidize other elements than carbon, and especially 
 to oxidize hydrogen. We have now to explain more fully the cause 
 of this oxygen deficit 
 
 The Oxygen Deficit. — The carbo-hydrates contain in themselves 
 enough oxygen to form water with all their hydrogen ; they account for 
 a part of the water-formation in the body, but for none of the oxygen 
 deficit. 
 
 The fats are very different ; their hydrogen can be nothing like com- 
 pletely oxidized by their oxygen. A gramme of hydrogen is contained 
 in 8-5 grammes of dry fat, and needs 8 grammes of oxygen for its com- 
 plete combustion. Only i gramme of oxygen is yielded by the fat 
 itself; so that if a man uses 100 grammes of fat in twenty-four hours, 
 rather more than 80 grammes of the oxygen taken in must go to 
 oxidize the hydrogen of the fat. 
 
 The proteins also contribute to the deficit. In 100 grammes of 
 dry proteins there are 15 grammes of nitrogen, 7 grammes of hydrogen, 
 and 21 grammes of oxygen. The carbon docs not concern us at present. 
 The 33 grammes of iirea, corresponding to 100 grammes of protein, 
 contains 15 grammes of nitrogen, a little more than 2 grammes of 
 hydrogen, and a little less than 9 grammes of oxygen. There remain 
 5 grammes of hydrogen and 12 grammes of oxygen. But 5 grammes of 
 hydrogen needs for complete combustion 40 grammes of oxygen ; there- 
 fore 28 grammes of the oxj^gen taken in must go to oxidize the hydrogen 
 of 100 grammes of protein. Taking 140 grammes of protein as the 
 amount in a liberal diet for a man, we get 39 granmies as the required 
 quantity of oxygen. This, added to tlie 80 grammes needed for the 
 hydrogen of the fat, makes a total of, say, 120 grammes, equivalent to 
 about 85 litres of ox\-gen. A small amount of oxygen also goes to 
 oxidize the sulphur of proteins. 
 
 With a diet containing less fat and protein and more carbo-hydrate, 
 the oxygen deficit would of course be less. 
 
 The Production of Water in the Body. — One gramme of hydrogen 
 corresponds to 9 grammes of water. In 140 grammes of proteins and 
 100 grammes of fat there are, in round numbers, 22 grammes of hydro- 
 gen ; in 350 grammes of starch, 21 -5 grammes. With this diet, 
 43'5 grammes of hydrogen is oxidized to water within the body in 
 twenty-four hours, corresponding to a water production of 391 grammes, 
 or 15 to 20 per cent, of the whole excretion of water. It has been 
 observed that during starvation the tissues sometimes become richer 
 in water, even when none is drunk. The only explanation is that the 
 elimination of water does not keep pace with the rate at which it is 
 produced from the liydrogen of the broken-down tissue-substances, or 
 set free from the solids with which it is (physically ?) united. 
 
 Inorganic Salts. — The inorganic salts of the excreta, like the 
 water, are for the most part derived from the salts of the food, 
 which do not in general undergo decomposition in the body. A 
 portion of the chlorides, however, is broken up to yield the hydro- 
 chloric acid of the gastric juice. Within the body some of the salts 
 
STATISTICS 01- NUTRTTION 621 
 
 are more or less intimately united to the proteins ot the tissues and 
 juices, some simply dissolved in the latter. The chlorides, phos- 
 phates and carbonates are the most important; the potassium salts 
 belong especially to the organized tissue elements, the sodium salts 
 to the liquids of the body; calcium phosphate and carbonate pre- 
 dominate in the bones. The amount and composition of the ash 
 of each organ only change within narrow limits. In hunger the 
 organism clings to its inorganic materials, as it clings to its tissue- 
 proteins; the former are just as essential to life as the latter. In a 
 starving animal chlorine almost disappears from the urine at a time 
 when there is still much chlorine in the body; only the inorganic 
 salts which have been united to the used-up proteins are excreted, 
 so that a starving animal never dies for want of salts. 
 
 When sodium chloride is omitted as an addition to the food of 
 man, the decomposition of protein seems to be shghtly accelerated, 
 but for a time, at least, there are no serious symptoms (Belli). 
 
 It is a general rule that purely carnivorous animals do not desire 
 salt, and the same is true of human beings living on a purely animal 
 diet, while vegetable feeders eagerly seek it. On the other hand, 
 when an animal, even a carnivore, is fed with a diet as far as possible 
 artificially freed from salts, but otherwise sufficient, it dies of salt- 
 hunger. The blood first loses inorganic material, then the organs. 
 The total loss is very small in proportion to the quantity still 
 retained in the body; but it is sufficient to cause the death of a 
 pigeon in three weeks, and of a dog in six, with marked symptoms 
 of muscular and nervous weakness. A deficiency of lime salts 
 causes changes particularly in the skeleton, although the nutrition 
 of the rest of the body is also interfered with. These changes are 
 of course most marked in young animals, in which the bones are 
 growing rapidly. In pigeons on a diet containing very little calcium 
 the bones of the skull and sternum become extremely thin and 
 riddled with holes, while the bones concerned in movement scarcely 
 suffer at all (E. Voit). 
 
 It is not indifferent in what form the calcium is taken, nor can it be 
 replaced to any great extent by other earthy bases, as magnesium or 
 strontium. Weiske fed five young rabbits of the same litter on oats, 
 a food relatively poor iu calcium. One of the rabbits received in 
 addition calcium carbonate, another calcium sulphate, a third mag- 
 nesium carbonate, and a fourth strontium carbonate. At the end of a 
 certain time it was found that the skeleton of the rabbit fed with calcium 
 carbonate was the heaviest and strongest of all, and contained the 
 greatest proportion of mineral matter. Then came the rabbit fed with 
 calcium sulphate. The animal which received only oats had the worst- 
 developed skeleton; the condition of the animals fed with magnesium 
 and strontium carbonates was but little better. 
 
 Milk as a Food. — Milk is a food rich in calcium and also in phos- 
 phorus, a circumstance evidently related to the rapid development 
 
622 METABOLISM. NUTRITION ASD DIETETICS 
 
 of the skeleton in the young child. As in the other natural foods, 
 the calcium and phosphorus are partly in the form of organic com- 
 pounds, united with the proteins, the calcium especially with 
 caseinogen, and partly in the form of inorganic salts. Both of these 
 elements are more easily assimilated by the body in the organic 
 than in the inorganic form. The same is true of iron, which exists 
 in organic combination in the bran of wheat, in the haemoglobin of 
 the blood and of muscular fibres, in the nuclei of most cells, vegetable 
 and animal, and conspicuously in the nuclein compounds of the yolk 
 of the egg. Attempts have been made to increase the amount of 
 iron in hen's eggs by giving them food mixed with preparations of 
 iron — e.g., iron citrate. An increase takes place, but only after a 
 long time. Thus in one experiment loo grammes of egg-substance 
 contained 44 milligrammes of FeaOj before the administration of 
 the iron was begun; after feeding with iron for three and a half 
 weeks the amount was 45 milligrammes, after more than two 
 months 74 miHigrammes; and after a year only 73 milligrammes. 
 Although, as we have seen, inorganic iron can be absorbed, it is 
 certainly the case that under ordinary conditions all the iron that 
 the body receives or needs is taken in the form of organic com- 
 pounds, since there is no inorganic iron in the natural food sub- 
 stances. Stockman, from careful estimations of the quantity of iron 
 in a number of actual dietaries, finds that it only amounts to about 
 8 to 10 milligrammes a day. He concludes that the greater part of 
 it must be retained in the body and used over and over again. 
 
 Milk is poor in iron, but this does not hinder the development of 
 the young child, except when it is weaned too late, when it is apt to 
 become anaemic unless the milk is supplemented with a food rich 
 in iron, such as yolk of egg. The explanation rs that the foetus, 
 especially in the last three months of intra-uterine life, accumulates 
 a store of iron in the liver and other organs; so that, in proportion 
 to its body-weight, it is at birth several times richer in iron than the 
 adult. This iron, of course, all comes from the mother, and the 
 loss is not exactly balanced by the excess of iron in her food ; certain 
 of her organs, the spleen, for instance, though not apparently the 
 liver, are impoverished as regards their content of iron. 
 
 Section V. — Dietetics. 
 
 There are two ways in which we can arrive at a knowledge of the 
 amount of the various food substances necessary for an average 
 man: (a) By considering the diet of large numbers of people doing 
 fairly definite work, and sufficiently, but not extravagantly, fed — 
 e.g., soldiers, gangs of navvies, or plantation labourers; (6) by making 
 special experiments on one or more individuals. 
 
 Voit, bringing together a large number of observations, concluded 
 
nrr.TFTTCS 621 
 
 that an ' average workman,' weighing 70 to 75 kilos, and working 
 ten hours a day, required in the twenty-four liours 118 grammes 
 protein, 56 grammes fat, and 500 grammes carbo-hydrate, corre- 
 sponding to about 18 -8 grammes* nitrogen, and at least 328 grammes 
 carbon. 
 
 Ranke found the following a sufficient diei for himself, with a 
 body- weight of 74 kilos : 
 
 Proteins ------ 100 grammes. 
 
 Fat 100 
 
 Carbo-hydrates - - • - 240 
 
 This corresponds to only 16 grammes nitrogen and, say, 230 grammes 
 carbon. 
 
 A German soldier in the field receives on the average: 
 
 Proteins - - - - - -151 grammes. 
 
 Fat 46 ,, 
 
 Carbo-hydrates - - - - 522 ,, 
 
 representing about 24 grammes nitrogen and 340 grammes carbon. 
 The average ration for four British regiments in peace-time con- 
 tained 133 grammes protein, 115 grammes fat, and 424 grammes 
 carbo-hydrate ( = 3,400 calories). But in addition the soldiers 
 constantly obtained at their own expense a supper, generally com- 
 prising meat (Pembrey). The Russian army war ration in the 
 Manchurian campaign is said to have comprised 187 grammes 
 protein and 775 grammes carbo-hydrate, but only 27 grammes fat 
 ( = 4,900 calories). The diet of certain miners (Steinheil) and lum- 
 berers (Liebig) contained respectively 133 and 112 grammes protein, 
 113 and 309 grammes fat, and 634 and 691 grammes carbo-hydrates. 
 The diet of a Japanese jinricksha man with a body-weight of 
 62 kilos contained 158 grammes protein, and its total heat value 
 was 5,050 calories. The work of these men in running long dis- 
 tances with passengers is very laborious. They consume large 
 amounts of fish, eggs, beef, and pork during their periods of rest, 
 and large quantities of rice during their working periods (McCay). 
 The diet of prize-fighters and of athletes in training is richer in 
 protein than any of these. The members of two college football 
 teams are stated to have consumed on the average 225 grammes 
 protein, 334 grammes fat, and 633 grammes carbo-hydrates 
 ( = 6,800 calories). Caspari, from a study of the phenomena of 
 training, concluded that continuous bodily work at a rate above 
 the ordinary requires a large amount of protein (2 to 3 grammes a 
 day per kilo of body- weight). But there seems to be a considerable 
 difference between different individuals. So that a definite and 
 typical diet for severe labour does not exist. And although perhaps 
 the hardest physical work ever done in the world is to break athletic 
 
 * Taking the percentage of nitrogen in protein at 16. 
 
6*4 METABOLISM, NUTRITION AND DIETETICS 
 
 records, to cut and handle timber, to mineTcoal, and to make war, 
 the diet on which these things are accomphshed is very variable. 
 
 Recent observations tend to reduce the amount of protein con- 
 sidered necessary for a person under ordinary conditions. Siven 
 remained in nitrogen equilibrium, for a time at least, with an intake 
 of only 007 to 008 gramme of nitrogen (04 to 05 gramme of 
 protein) per kilo of body-weight, or not much more than one-third 
 of the amount in Kanke's diet. It is obvious that the endogenous 
 protein katabolism sets the limit below which it must be impossible 
 permanently to reduce the allowance of protein. But it would be 
 very hazardous to assume that this theoretical minimum limit 
 corresponds with the permissible physiological limit. From ex- 
 periments on men of various callings extending over many months, 
 Chittenden has concluded that the average man eats at least twice 
 as much protein as he really requires. We have already seen that 
 the amount of nitrogen required to repair the actual waste of the 
 tissues is comparatively small, and that with the ordinary amount 
 of protein in the food a very large fraction of the total nitrogen is 
 rapidly excreted as urea. There is no doubt, also, that many 
 persons consume too much protein, at any rate in the form of 
 animal food, and would feel better, work better, and probably live 
 longer, if they restricted themselves in this regard. But there is 
 no evidence that the digestion of such quantities of protein as the 
 average healthy man eats, or the elaboration and excretion of the 
 corresponding amounts of urea, ' strain ' in the least the digestive 
 apparatus, the liver, or the kidneys. And it may just as well be 
 argued that it is advantageous that much more than the minimum 
 protein requirement should be offered to the tissues, so that the 
 appropriate amino-acids, even the scarcest of them, may be sure 
 to be present in sufficient amount, rather than that the organs 
 should be subjected to the unnecessary ' strain ' of reconstructing 
 some of the amino-acids themselves, supposing that they possess 
 this power. In a question of this sort tlie immemorial experience 
 and instinct of mankind cannot be hghtly waved aside. 
 
 McCay points out that while Bengalis in Lower Bengal subsist on 
 food containing only about one-third the amount of protein in such 
 a ' standard ' diet as Voit's (6 to 7 grammes of nitrogen a day), and 
 may therefore be supposed to be immune from the dangers of an 
 excessive protein metabolism, the large intake of carbo-hydrate 
 rendered necessary by the poverty of the food in protein is associated 
 with perhaps greater evils, among them a marked predisposition to 
 diabetes and renal troubles. Their weight, chest measurement, and 
 muscular development are inferior to those of other Asiatics living 
 in the same climate, but with dietetic habits or economic conditions 
 which ensure them a larger supply of protein. Thus the natives of 
 Behar, with a larger intake of nitrogen, derived from wheat, and the 
 natives of Eastern Bengal with a larger intake of nitrogen, derived 
 
DIETETICS 625 
 
 from wheat and fish, arc pliysically much superior to the rice-eating 
 Bengahs of Lower Bengal, although all belong to the same race. 
 
 If we decide the matter merely on physiological grounds, we may 
 say that for a man of 70 kilos, doing fairly hard, but not excessive, 
 work, 15 grammes nitrogen and 250 grammes carbon are a sufficient 
 allowance. The 15 grammes nitrogen will be contained in 95 
 grammes dry protein, which will also yield 50 grammes of the 
 required carbon. The balance of 200 grammes carbon could 
 theoretically be supplied either in 450 grammes starch or in 
 260 grammes fat. But it has been found by experiment and by 
 experience (which is indeed a very complex and proverbially expen- 
 sive form of experiment) that for civilized man a mixture of these 
 is necessary for health, although the nomads of the Asian steppes, 
 and the herdsmen of the Pampas, are said to subsist for long periods 
 on flesh alone, and a dog can live very well on proteins* and fat. 
 The proportion of fat and carbo-hydrates in a diet may, however, 
 be varied within wide limits. Probably no ' work ' diet should 
 contain much less than 40 grammes of fat, but twice this amount 
 would be better; 80 grammes fat give about 60 grammes carbon, 
 so that from proteins and fat we have now got no grammes of the 
 necessary 250, leaving 140 grammes carbon to be taken in about 
 310 grammes starch, or an equivalent amount of cane-sugar or 
 dextrose. Adding 30 grammes inorganic salts, we can put down as 
 the solid portion of a normal diet sufficient from the physiological 
 point of view for a man of 70 kilos: 
 
 95 grammes proteins - - =y^o of body-weight. 
 
 80 ,, fat - - - =9^ ,, 
 
 310 ,, carbo-hydrates =225 >> 
 
 30 ,, salts. 
 
 5 15 „ solid food - =1^5 
 
 Now, knowing tlie composition of the various food-stuffs, we can 
 easily construct a diet containing the proper quantities of nitrogen 
 and carbon, by using a table such as appears on p. 626. 
 
 Economic and social influences — prices and habits — and not 
 purely physiological rules, fix the diet of populations. The Chinese 
 labourer in a rice district, for example, is apt to live on a diet which 
 no physiologist would commend. In order to obtain 15 grammes 
 nitrogen or 95 grammes protein, he must consume more than 
 1,500 grammes rice, which will yield 700 grammes carbon, or twice 
 as much as is required. But if many of the Chinese labourers could 
 not live on rice, or often on grains cheaper than rice, they could not 
 live at all. The Irish peasant, in the days when the potato was his 
 staple, was even in worse case; he would have been obhged to 
 consume nearly 4 kilos of potatoes to obtain his 15 grammes nitrogen,- 
 while little more than half this amount would have furnished the 
 
 * A little glycogen is. of course, supplied in the meat. 
 
 40 
 
626 
 
 METABOLISM, NUTRITION AND DIETETICS 
 
 necessary 250 grammes carbon. Of course a diet consisting, week 
 in week out, entirely of potatoes or rice, would represent an extreme 
 case, and no doubt the total nitrogen ingested would be considerably 
 below the usual proportion. A certain amount of the necessary 
 nitrogen is obtained even by the poorest populations, in the form 
 of fish, milk, eggs, or bacon. A man attempting to live on flesh alone 
 would be well fed as regards nitrogen with 500 grammes of meat, 
 but nearly four times as much would be required to yield 250 
 grammes of carbon. Oatmeal and wheat-flour contain nitrogen and 
 carbon in nearly the right proportions (i N: 15 C), oatmeal being 
 rather the better of the two in this respect ; and the best-fed labour- 
 ing populations of Europe still live largely on wheaten bread, while, 
 one hundred years ago, the Scotch peasant still cultivated the soil, 
 as the Scotch Reviewer the Muses, ' on a little oatmeal.' But 
 although bread may, and does, as a rule, form the great staple of 
 diet, it is not of itself sufficient. 
 
 
 Quantity 
 
 Quantity 
 
 
 
 
 
 Carbo- 
 
 
 I 
 
 required 
 
 required 
 
 Nin 
 
 Gin 
 
 Proteir. 
 
 Fat in 
 
 hydrate 
 
 Water 
 
 I 
 
 :o yield 
 
 to yield 
 
 100 
 
 100 
 
 in 100 
 
 100 
 
 in 100 
 
 
 IS Grms. 
 
 N. 
 
 250 Grms. 
 
 c. 
 
 Grms. 
 
 Grms. 
 
 Grms. 
 
 Grins. 
 
 in zoo 
 Grms. 
 
 Grms. 
 
 Chfese» 
 
 
 
 
 
 • 
 
 
 
 
 (Gruyere) - 
 
 300 
 
 040 
 
 5 
 
 39 
 
 31 
 
 31 
 
 — 
 
 34 
 
 Peas (dried) 
 
 430 
 
 700 
 
 3-5 
 
 35-7 
 
 22 
 
 2 
 
 55 
 
 15 
 
 Lean meat - 
 
 440 
 
 i860 
 
 3-4 
 
 13-5 
 
 21 
 
 3-5 
 
 — 
 
 74 
 
 Wheat- flour 
 
 650 
 
 625 
 
 2-3 
 
 39-8 
 
 12 
 
 2 
 
 70 
 
 15 
 
 Oatmeal- - 
 
 580 
 
 620 
 
 2-6 
 
 40-3 
 
 13 
 
 5-5 
 
 65 
 
 15 
 
 Eggs - - - 
 
 790 
 
 1700 
 
 1-9 
 
 14-7 
 
 11-5 
 
 12 
 
 — 
 
 75 
 
 Maize 
 
 810 
 
 610 
 
 1-85 
 
 40-9 
 
 IO-5 
 
 7 
 
 65 
 
 15 
 
 Wheat- 
 
 
 
 
 
 
 
 
 
 bread - - 
 
 1200 
 
 U20 
 
 1-25 
 
 22-4 
 
 8 
 
 1-5 
 
 49 
 
 40 
 
 Rice - - - 
 
 1530 
 
 685 
 
 0-9 
 
 36-6 
 
 5 
 
 I 
 
 83 
 
 10 
 
 Milk - - - 
 
 2380 
 
 3540 
 
 0-6 
 
 7 
 
 4 
 
 4 
 
 5 
 
 85 
 
 Potatoes 
 
 3750 
 
 2380 
 
 0.4 
 
 IO-5 
 
 2 
 
 0-15 
 
 21 
 
 75 
 
 Good butter 
 
 1 0000 
 
 360 
 
 0-I5 
 
 69 
 
 I 
 
 90 
 
 
 8 
 
 It is necessary to recognize that habit has much to do with the 
 quantity as well as the quality of the food used by an individual 
 or a community. Some concession may be made to custom in 
 what is after all, not a purely physiological question, and in this 
 country it is probable that 20 grammes of nitrogen and 300 grammes 
 of carbon, while a liberal is not an excessive allowance, although 
 it is certain that a man can maintain a normal body-weight and 
 perform a normal amount of work on considerably less, in some 
 cases even with advantage to his health. 
 
 We may take 500 grammes of bread and 250 grammes of lean 
 meat as a fair quantity for a man fit for hard work. Adding 
 
 * A cheese manufactured from whole milk, curdled before the cream has 
 had time to rise, and therefore rich in fat. 
 
DIETETICS 
 
 617 
 
 500 graninies milk, 75 grammes oatmeal (as porridge), 30 grammes 
 butter, 30 grammes fat (with the meat, or in other ways), and 
 450 grammes potatoes, we get approximately 20 grammes nitrogen 
 and 300 grammes carbon contained in 135 grammes protein, rather 
 less than 100 grammes fat, and somewhat over 400 grammes carbo- 
 hydrates. Thus — 
 
 
 N. 
 
 C. 
 
 Proteins. 
 
 Fat. 
 
 Carbo- 
 hydrates. 
 
 Salts. 
 
 (9 oz.) 250 grms. lean meat - 
 (18 oz.) 500 grms. bread 
 (i pint) 500 grms. milk 
 fi oz.) 30 grms. butter 
 (I oz.) 30 grms. fat 
 (16 oz.) 450 grms. potatoes - 
 (3 oz) 75 grnas. oatmeal 
 
 8 
 6 
 3 
 
 1-5 
 
 1-7 
 
 33 
 112 
 
 35 
 20 
 22 
 47 
 30 
 
 55 
 
 40 
 20 
 
 10 
 10 
 
 8-5 
 7-5 
 20 
 
 27 
 30 
 
 4 
 
 245 
 25 
 
 95 
 
 48 
 
 4 
 
 6-5 
 3-5 
 0-5 
 
 4-5 
 2 
 
 20-2 
 
 299 
 
 135 
 
 97 
 
 413 
 
 21 
 
 This would be a fair ' hard work ' diet for a well-nourished labourer. 
 But the great elasticity of dietetic formulae is shown in the following 
 tables, which give the ration of the German soldier in peace and war 
 and the minimum allowance per ' statute adult ' prescribed in the 
 British regulations concerning passenger- ships from Great Britain 
 to America. 
 
 Ration of the German Soldier. 
 
 Peace. 
 
 
 War. 
 
 
 Bread 
 
 750 grammes. 
 
 Bread - - - 
 
 750 grammes 
 
 Meat 
 
 150 
 
 Biscuit 
 
 500 
 
 Rice - 
 
 50 
 
 Meat - 
 
 375 
 
 or barley groats 
 
 120 ,, 
 
 Smoked meat 
 
 250 
 
 Legumes - 
 
 230 
 
 or fat 
 
 170 ». 
 
 Potatoes - - I 
 
 ■ 500 
 
 Rice - - - 
 
 125 
 
 
 
 or barley groats 
 
 125 
 
 
 
 Legumes 
 
 250 „ 
 
 Minimum Ration fo^ 
 
 ' Passenger Ships. 
 
 
 Bread or biscuit - 
 
 227 grammes. 
 
 Sugar - - - 
 
 65 grammes 
 
 Wheaten flour 
 
 65 
 
 or treacle - 
 
 97 
 
 or bread - 
 
 81 
 
 Tea - 
 
 8 
 
 Oatmeal 
 
 97 
 
 or coffee or cocoa 
 
 14 
 
 Rice - - - 
 
 97 
 
 Salt - 
 
 8 
 
 Peas - - - 
 
 97 
 
 Mustard 
 
 2 ,, 
 
 Potatoes 
 
 130 
 
 Pepper 
 
 I •> 
 
 Beef - 
 
 81 
 
 Vinegar or pickles 
 
 20 c.c. 
 
 Pork or preserved 
 
 
 
 
 meat 
 
 65 .. 
 
 
 
 In prisons the object is to give the minimum amount of the plamest 
 food which will suf&cc to maintain the prisoners in health. A ' hard 
 work ' prison diet in Munich was found to contain 104 grammes proteins, 
 38 grammes fat, and 521 grammes carbo-hydrates; a 'no-work' diet, 
 only 87 grammes proteins, 22 grammes fat, and 305 grammes carbo- 
 hydrates. Here we recognize the influence of price; carbon can be 
 much more cheaply obtained in vegetable carbo-hydrates than in 
 
628 METABOLISM. NUTRITION AND DIETETICS 
 
 animal fats; the cheapest possible diet contains a minimum of animal 
 fat and proteins. 
 
 Many poor persons live on a diet which would not maintain a strong 
 man, for an emaciated bodv has a smaller mass of ficsh to keep up, and 
 therefore needs less protein ; it can do little work, and therefore needs 
 less food of all kinds. A London needlewoman, according to Play- 
 fair, subsists, or did subsist forty years ago, on 54 grammes protein, 
 29 grammes fat, and zqz grammes carbo-hydrates. But this is the 
 irreducible minimum of the deep>est poverty, not so much in the protein 
 content, perhaps, £is in the very low heat equivalent (1,600 calories); 
 and a woman, with a smaller mass of flesh and leading a less active life 
 than a man, requires less food of all sorts. Even the Trappist monk, 
 who has reduced asceticism to a science, and, instead of eating in order 
 to live, lives in order not to cat, consumes, according to Voit, 68 grammes 
 protein, 11 grammes fat, and 469 grammes carbo-hydrates; but manual 
 labour is a part of liie discipline of the brotherhood, and this must be 
 still above the lowest subsistence diet. 
 
 The question whether it is best to derive the proteins (and fats) of 
 the food mainly from plants or mainly from annnals is one which is 
 never left to physiology alone to decide. But it has been definitely 
 proved that vegetable proteins and vegetable fats are (when properly 
 prepared) digested and absorbed as completely as those of animal origin, 
 and plav the same part in the metabolism of the body. Nor is there 
 any difference in the basal metabohsm (p. 686) of vegetarians and 
 persons living on an ordinary diet. 
 
 A growng child needs far more food than its weight alone would 
 indicate; the expenditure of organisms of different size in the same 
 physiological condition is proportional not to the mass, but more 
 nearly to the surface area. Now, speaking roughly, the cube of the 
 surface of an animal varies as the square of the mass; when the 
 weight is doubled, the surface only becomes ^^4, or one and a half 
 times as great. The surface of a boy of six to nine years, with a 
 body-weight of 18 to 24 kilos, is two-fifths to one-half that of a man 
 of 70 kilos ; and this would indicate that he should have about half 
 as much food as the man. This is not all, the child is not in the same 
 physiological condition as the adult. It is growing. Its income 
 must exceed its expenditure, and by a far greater amount than the 
 actual gain in weight, for growth is a ph\'siologically expensive 
 process. It needs many pounds of food to put on one pound of 
 flesh. And in accordance \nth this it has been found that the basal 
 metabolism of a child per unit of surface is decidedly greater than 
 that of an adult (p. (^gj). 
 
 An infant for the first seven months should have nothing except 
 milk. Up to this age vegetable food is unsuitcd to it ; it is a purely 
 carnivorous animal. By careful observations on the ainount of 
 carbon dioxide and nitrogen excreted by a child nine weeks old, fed 
 exclusively on its mother's milk, it has been shown that the ab- 
 sorption and assimilation of milk in the infant is very complete, 
 over 91 per cent, of the total energ}' being utilized; while an adult, 
 taking as much milk as is necessary for the maintenance of nitrog- 
 
DIETETICS 629 
 
 rnous equilibrium, does not utilize at most more than 84 per cent. 
 Human milk contains about 2 per cent, of protein (mainly caseino- 
 gi-n), J \K'\- cent, of fat, 5 or 6 per cent, of carbo-hydrate (lactose or 
 milk-sugar), and from 0*2 to 0*3 per cent, of salts. Cow's milk 
 contains about 4 per cent, of protein, 4 to 6 per cent, of fat, 4 per 
 cent, of lactose, and 0*7 per cent, of salts. When given to infants it 
 should, as a geiieral rule, be diluted with water, and some sugar 
 should be added to it. Ass's milk has about the same amount of 
 protein, lactose, and salts as human milk, but less than half as much 
 fat. It is very well borne and very completely absorbed. 
 
 As to the place of water and inorganic salts in diet, it is neither 
 necessary nor practicable to lay down precise rules. In most well- 
 settled countries they cost little or nothing; very different quantities 
 can be taken and excreted without harm ; and both economics and 
 physiolog}^ may well leave every man to his taste in the matter. 
 Salt is indeed for the most part used, not as a special article of diet, 
 but as a condiment to give a rehsh to the food, just as a great deal 
 more water than is actually needed is often drunk in the form of 
 beverages. It is certain that the quantity of salt required, in 
 addition to the salts of the food, to keep the inorganic constituents 
 of the body at their normal amount, is very small. When the food 
 is entirely animal, no additional salt is necessary. A 30-kilo dog 
 obtains in his diet of 500 grammes of lean meat only o -6 gramme 
 sodium chloride, and needs no more. An infant in a litre of its 
 mother's milk, which is a sufficient diet for it at six to nine months, 
 gets only 0-8 gramme sodium cliloride. The Hererosin Damaraland, 
 who are physically one of the finest races in Africa, do not use salt 
 (Reclus). In this they resemble other tribes in different parts of 
 the world who eat no vegetable food, for example the Kirghiz, who 
 live on meat and milk, and the Todas, a pastoral tribe in Southern 
 India, who are ignorant of the use of vegetable foods and know 
 nothing of salt (IMcCay). Bunge has explained the difference 
 between the flesh and the vegetable feeder by showing that the 
 proportion of potassium and sodium salts in the food is a factor in 
 determining the quantity of sodium chloride required. A double 
 decomposition takes place in the body between potassium phosphate 
 and sodium chloride, potassium chloride and sodium phosphate 
 being formed and excreted; and the loss of sodium and chlorine in 
 this way depends on the relative proportions of potassium and 
 sodium in the food. In most vegetables the proportion of potassium 
 to sodium is much greater than in animal food, so that vegetable- 
 feeding animals and men as a rule desire and need relatively great 
 quantities of sodium chloride. But it is stated that the inhabitants 
 of a portion of the Soudan use potassium chloride instead of sodium 
 chloride, obtaining the potassium salt by burning certain plants 
 which leave an ash poor in carbonates, and then extracting the 
 residue with water and evaporating (Dybowski). A beef-eating 
 
630 METABOLISM. NUTRITION AND DIETETICS 
 
 English soldier in India consumes about 7 grammes (J oz.), a 
 v^egetarian Sepoy about 18 grammes ()-; oz.), of common salt per day. 
 
 Stimulants. Wine, beer, tea, coffee, cocoa, etc., belong to the 
 important class of stimulants. Some of them contain small quanti- 
 ties of food substances, but these are of secondary interest. In 
 beer, for example, tliere are not inconsiderable amounts of proteins, 
 dextrin, and sugar. But 14 litres of beer would be required to yield 
 15 grammes nitrogen, and 10 litres to give 250 grammes carbon; 
 and nobody, except a German corps student, could consume such 
 quantities. The minimum nitrogen requirement, however, as well 
 as the necessary heat value, could theoretically be covered by 6 or 
 7 litres of good German beer. 
 
 In some cocoas there is as much as 50 per cent, of fat, 4 per cent, 
 of starch, and 13 per cent, of proteins; and in the cheaper cocoas 
 much starch is added. Still, a large quantity of the ordinary 
 infusion would be needed for a satisfying meal. Frederick the 
 Great, indeed, in some of his famous marches dined off a cup of 
 chocolate, and beat combined Europe on it; but his ordinary menu 
 was much more varied and substantial. 
 
 Alcohol. — The great social and hygienic evils connected with the 
 abuse of alcohol, as well as its applications in therapeutics, render 
 it necessary, or at least permissible, to state a little more fully, 
 though only in the form of summary, some of the chief conclusions 
 that may be drawn as to its action and uses. 
 
 (i) In small quantities alcohol is oxidized in the body, a little of it, 
 however, being excreted unchanged in the breath and urine. A certain 
 amount of protein is saved from decomposition when alcohol is taken, 
 just as when fat or sugar is taken. For example, the addition of 
 130 grammes of sugar to the daily food of an individual caused a 
 ' sparing ' of 0-3 gramme nitrogen. The substitution of 72 grammes 
 alcohol for the sugar caused 0-2 gramme nitrogen to be spared (Atwater 
 and Benedict). Alcohol is therefore to some extent a food substance, 
 although it is not, under ordinary circumstances, taken for the. sake of 
 the energy its oxidation can supply, but as a stimulant. 
 
 (2) There is no reason to suppose that this energy cannot be utilized 
 as a source of work in the body. Indeed, a certain amount of alcohol 
 may be normally formed in the tissues as one of the intermediate 
 products in the oxidation of sugar. Heat can certainly be produced 
 from it, but this is far more than counterbalanced by the increase in 
 the heat loss which the dilatation of the cutaneous vessels caused by 
 alcohol brings about. 
 
 (3) It is a valuable drug, when judiciously employed, in certain 
 diseases — e.g., pneumonia and puerperal insanity (Clouston). 
 
 (4) Alcohol is occasionally of use in disorders not amounting to 
 serious disease — e.g., in some cases of slow and difficult digestion. In 
 these cases it may act by increasing the flow of certain of the digestive 
 secretions, as saliva and gastric juice. This effect seems to more tlian 
 counterbalance the retarding influence which, except when well diluted, 
 it exerts on the chemical processes of digestion. 
 
 The action of alcohol on the secretion of gastric juice has been studied 
 in a dog with a double gastric and oesophageal fistula. Before or 
 during a sham meal of meat, alcohol diluted with water was given as 
 
DIETETICS 631 
 
 an enema. After the enema the quantity of hydrochloric acid secreted 
 increased in about the same proportion as the quantity of juice, but the 
 pepsin was diininishccl, reaching a minimum after three-quarters to 
 one and a quarter hours. The increase in the total quantity of the 
 juice and in the acid over-compensated the moderate diminution in the 
 digestive power, so that the net result was beneficial (Pekelharing). 
 But it must be remembered that strong alcoholic beverages, when mixed 
 with the gastric juice, and therefore when taken by the mouth, retard 
 the proteolytic action, so that any favourable effect on the secretion of 
 the juice may easily be lost in the subsequent digestion, unless the 
 alcohol is dilute (Chittenden and Mendel). The action of alcohol intro- 
 duced into the rectum on the gastric secretion is both reflex and direct. 
 
 (5) Alcohol is of no use for healthy men. 
 
 (6) Alcohol in strictly moderate doses,* properly diluted and especi- 
 ally when taken with the food, is not harmful to healthy men, living 
 and working under ordinary conditions. 
 
 (7) Modern experience goes to show that in severe and continuous 
 exertion, coupled with exposure to all weathers, as in exploring expedi- 
 tions, alcohol is injurious, and it is well known that it must be avoided 
 in mountain climbing. 
 
 The drastic restrictions placed upon the use of alcoholic beverages in 
 most of the belligerent countries during the present war, although 
 adopted for economic as well as for physiological reasons, do not favour 
 the view that the efficiency of the fighting man, or of the man who works 
 at high pressure to equip and supply him, is increased by alcohol. But 
 it would be quite erroneous to conclude that because alcohol, as such, 
 may not at all improve the working or staying power of men accustomed 
 to use it moderately, it can be suddenly and completely prohibited 
 without detriment to their work. The factor of habit and its influence 
 on efficiency has been far too little considered in connection with this 
 question. The man who craves his wonted glass of beer, even if he 
 does not resent its withdrawal, will almost certainly suffer in efficiency 
 for a while, although the beer in itself may not have aided him in his 
 work. 
 
 Alcohol in small doses, when given by the stomach or (in animals) 
 injected into the blood, causes stimulation of the respiratory centre and 
 increase in the pulmonary ventilation. In man, this increase usually 
 amounts to 8 to 15 per cent., but is occasionally much greater. But the 
 limit which separates the favourable action of the small dose from the 
 hurtful action of the large, is easily overstepped. When this is done, 
 and the dose is continually increased, the activity of the respiratory 
 centre is first diminished and finally abolished. In dogs, for instance, 
 after the injection of considerable quantities of alcohol into the stomach, 
 death takes place from respiratory failure, and the breathing stops 
 while the heart is still unweakened (Fig. 85, p. 191). This is the final 
 outcome of a progressive impairment in the activity of the centre, of 
 which the slow and heavy breathing of the drunken man represents an 
 earlier stage. 
 
 Tea, coffee, and cocoa are more suitable stimulants for healthy 
 persons, because they are less dangerous than alcohol, and they 
 leave no unpleasant effects behind them. But it should be remem- 
 
 * Not more than i^ oz. of absolute alcohol, corresponding to about 4 oz. of 
 whisky, or 2 to 3 wineglasses of sherry or port, or a pint of claret, or a couple 
 of pints of light beer in 24 hours. 
 
63* METABOLISM. S'UTRITION AND DIETETICS 
 
 bered that there is no stimulant which is not liable to be abused. 
 It has been shown by ergographic experiments (p. 750) that, lik: 
 alcohol, tea, coffee, mate, and cola-nut, which all contain the alka- 
 loid theine or caffeins, restore the power of performing muscular 
 work after exhaustion, but only if food has been recently or is 
 simultaneously taken. 
 
 Vitamines. — Certain substances, although neither in the ordinary 
 sense foods nor condiments, seem to be necessary for the main- 
 tenence of health, for in circumstances in which these cannot be 
 obtained for long periods so-called ' deficiency diseases,' such as 
 scurvy, are liable to occur. Scurvy used to be the scourge of the 
 sailing-ship in the days when fresh meat, and particularly fresh 
 vegetables and fruits, were unobtainable on long voyages. It has 
 long been known that it is prevented by the use of lime or lemon- 
 juice, in which citric and a trace of maUc acid are contained, and 
 it used to be thought that it was the organic vegetable acids which 
 were the important thing. Recent researches have shown, how- 
 ever, that scurw is only one of a group of diseases, including beri- 
 beri, and probablv pellagra, rickets, and others which are induced 
 by deficiency in the food of certain substances minute in amount 
 but essential to proper nutrition. 
 
 The importance of such accessory components in the food has been 
 already pointed out, in discussing the influence of artificial diets upon 
 the growth and maintenance of animals (p. 617). These substances are 
 sometimes termed ' vitamines.' But their chemical nature is im- 
 perfectlv known, and there is no e\adence that the bodies which exert 
 the beneficial influence belong to the same chemical group.* 
 
 McCollom prefers to designate provisionally the two substances or 
 groups of substances essential, in addition to a diet of purified proteins, 
 carbohydrate, fats and inorganic salts, for growth and maintenance of 
 rats, as ' fat-soluble A ' and ' water-soluble B,' rather than to use the 
 unsatisfactory term vitamines. The first is soluble in fats and is 
 abundant in butter-fat, egg-fat, and ether extract of kidney. It is also 
 found in considerable amount in the leaves of plants, but is represented 
 in the seed in too small amount to supply the needs of a young animal. 
 The second, which is soluble in water and in alcohol, is plentifullv 
 present in wheat, wheat germ, maize, alfalfa leaves, cabbage, and in a 
 number of foods of animal origin. 
 
 One representative of the important food constituents in question is a 
 basic substance separated by Funk from the polishings of rice, and 
 named by him, ' vitamine.' Polished rice is rice deprived of the outer 
 coats by modem milling processes, and the polishings arc the coats which 
 have been removed. Since the introduction of steel rollers instead of the 
 primitive millstones which used to crush the whole grain, beri-beri, a 
 disea.se characterized by inflammatory and degenerative changes in the 
 
 * It might be better in the present state of our knowledge to avoid giving 
 those bodies a name which may eaisily mi.slead. They might possibly be pro- 
 visionally spoken of as " vitincs," a term involving no assumption as to their 
 chemical nature, and imphnng only their importance in the nutritional pro- 
 cesses associated with the life (and growth) of the tissues. 
 
DIETETICS 633 
 
 peripheral nerves (peripheral nciinlis) iti d consequent paralysis, has 
 greatly increased among the rice-eating Jiipaiic^c. in Bengal, although 
 much rice is eaten, there is practically no bcri-beri, as country rice and 
 not the highly polished variety is consumed. When birrls- e.g.; 
 pigeons — arc fed on polished rice, polyneuritis similar to that seen in 
 human beri-beri is produced, and both in man and in birds the condi- 
 tion is quickly cured by reverting to rice prepared according to the 
 old-fashioned methods, or by adding the polishings or an alcoholic 
 extract of them containing the essential substance, or the isolated 
 base itself. 
 
 The addition of various legumes to the diet, or alcoholic extracts 
 of these, will produce the same beneficial effect (McCay). Potatoes, 
 carrots, fresh vegetables, lime and other fruit juices, also certain 
 animal foods, such as fresh milk, fresh meat, and yolk of egg, are 
 all valuable, in addition to their ordinary nutritive constituents, for 
 their content of vitamines. Yeast contains them in exceptionally 
 large amount, and it is possible, though not proved, that such fer- 
 mented liquors as beer, or some varieties of it, may derive some part 
 of their value from these substances liberated both from the yeast 
 and the barley and not destroyed in the process of brewing. 
 
 The addition of yeast to artificial diets accelerates the growth of 
 young rats. Yeast also prevents and cures polyneuritis developed in 
 birds by a diet of polished rice. It is not known whether the growth- 
 promoting component is identical with the anti-neuritic one or a different 
 substance. 
 
 Since vitamines exert so great an effect on nutrition and growth, 
 it might be expected that their absence would tell on those glands 
 of internal secretion which appear to be concerned in the metabolism 
 of growth. As a matter of fact, it has been found that in pigeons 
 suffering from the typical deficiency disease beri-beri, certain of these 
 glands show marked changes. The thymus gland, normally very 
 large and persistent in these birds, can be caused to atrophy com- 
 pletely by a diet of polished rice. Changes also occur in the 
 pituitary, and decided atrophy in the testes and ovaries (Funk and 
 Douglas). 
 
 In bringing this chapter to a close, it may be useful to point out 
 again that indispensable as the data of physiology are for intelligent 
 and fruitful criticism of the dietetic habits of individuals or communi- 
 ties, they must be applied with due regard to the other factors. 
 Nothing is more sure than that a certain minimum number of calories 
 must be supplied to an average man of given weight and age, living 
 and working under definite conditions, in order that his body may 
 be maintained in health. It is also well made out that a certain 
 balance, which, however, is by no means rigidly fixed, between the 
 great groups of food-stuffs is of the essence of a good dietary. Yet 
 of two rations each containing the proper number of calories, and 
 the conventional proportions of protein, carbohydrate and fat, one 
 may be good and sufficient, and the other so gravely deficient that 
 malnutrition or disease may follow the use of it. Where natural 
 foods are obtainable in abundance and variety, there is seldom 
 danger of a lack of the indispensable accessories. This danger in- 
 creases when economic or social conditions lead to an excessive use 
 
634 MIirABOLISM, NUTRITION AND DIETETICS 
 
 of ' artificial ' foods. The factor of safety, however, is very large 
 and the dietary of an individual or the dietetic habits of a nation 
 may be changed from top to bottom, if the change is scientifically 
 effected, without serious detriment, at least for a long time. The 
 greatest experiment of this kind in the history of the world is now 
 being worked out over a large part of Europe. 
 
CHAPTER XI 
 
 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 It is long since Caspar Friedrich Wolff expressed the idea that 
 ' each single part of tlie body, in respect of its nutrition, stands to 
 the whole body in tiie relation of an excreting organ,' and thus 
 emphasized the importance of substances produced by the activity 
 of one kind of cell for the normal metabolism of another. But it is 
 only in recent years that it has become possible to illustrate this 
 mutual relation by any large number of experimental facts. 
 
 Certain of the substances taken in from the blood by the liver 
 find their way, after undergoing various changes, into the biliary 
 capillaries, and are excreted as bile; certain other substances, such 
 as sugar and the precursors of urea, are taken up by the hepatic 
 cells, transformed and sometimes stored for a time within them, 
 and then given out again to the blood. Bile we may call ihe-^extetual 
 secretion of th e hver. g lycogen, and urea constituents of its internal 
 secretio n. In one sense it is evident that all tissues, whether glands 
 in the morphological sense or not, may be considered as manufac- 
 turing an internal secretion. For ever^^thing that an organ absorbs 
 from the blood and lymph it gives out to them again in some form 
 or other except in so far as it forms or separates a secretion that 
 passes away by special ducts. But it is usual to employ the term 
 only in relation to organs of glandular build, whether provided with 
 ducts or not. Typical endocrine* glands (that is, glands producing 
 an internal secretion) are the adrenals, thyroid, parathyroid, 
 pituitary, thymus, etc. For convenience the action of extracts of 
 some other tissues, such as nervous tissue, will also be considered here, 
 although there is no reason to suppose that they form any specific 
 internal secretion. 
 
 The capacity of manufacturing internal secretions of high im- 
 portance can neither be attributed to all glands with ducts nor 
 denied to all other organs. For the salivary, mammary, and gastric 
 glands may be completely removed without causing any serious 
 effects, while death follows excision of the, so far as mere bulk is 
 concerned, apparently insignificant masses of tissue in the ductless 
 thyroid, parathyroid, suprarenal or pituitary bodies. 
 * From iv^ov. mthin, and Kpiva, I separate. 
 635 
 
636 TNTERXAL SECRETION— F.XDOCRINE GLASDS 
 
 It is known that in the case of the Uver the internal secretion is 
 more important than the external, for an animal cannot survive 
 without its liver, wliilc it may be but little affected by the con- 
 tinuous escape of the bile through a fistulous opening. 
 
 Pancreas. — The internal secretion of the pancreas is also indis- 
 pensable. For when the pancreas is excised death follows in many 
 species of animals, and especially in carnivorous animals; and in 
 man severe and ultimately fatal diabetes is often associated with 
 pancreatic disease, while the mere loss of the pancreatic juice 
 through a fistula does not necessaril\' shorten life although the 
 absorption of fat is seriously interfer* d with. 
 
 The ultimate cause of death seems to he a profoimd disturbance 
 of metabolism, of which the most significant token is the increased 
 proportion of sugar in the blood, and its speedy appearance in the 
 urine— in dogs always within twenty-four hours following total 
 removal of the organ. Associated with the glycosuria is an increase 
 in the quantity of the urine (polyuria), excessive thirst (polydipsia), 
 and a ravenous appetite (polyphagia accompanied by intense 
 hunger contractions of the stomach — Luckhardt), in spite of which 
 the animal becomes more and more emaciated — in short, the 
 classical symptoms of a severe type of pathological diabetes in man, 
 but, of course, far more acute in their onset, and far more rapid 
 in their progress towards the inevitable end. Dogs rarely survive 
 more than two or three weeks, the immediate cause of the rapidly 
 fatal result being perhaps the extensive suppuration which is apt 
 to ensue on slight and practically unavoidable superficial injuries. 
 The resistance of the tissues to bacterial invasion and their tendency 
 to spontaneous healing are reduced by the overloading of the blood 
 and tissue liquids with sugar. Even when carbo-hydrates are ex- 
 cluded from the food, or when no food at all is given, sugar continues 
 to be excreted in large amounts. The destruction of proteins is 
 increased. It is a significant fact that glycosuria does not appear 
 or is only transient when the pancreas is partially removed, so long 
 as a comparatively small fraction of the gland (one-ciuarter or one- 
 fifth) is left. Even when such a remnant is dislocated from its 
 original position, care being taken not to interfere with its circula- 
 tion, and sutured in the peritoneal cavity or, indeed, under the skin, 
 the animal remains in good health. In the dog this operation can 
 be practised on the lowest part of the descending division of the 
 pancreas, which is not united with the duodenum, but lies free in 
 the mesenterv. Removal of the fragment of pancreas is followed 
 by the whole train of symptoms associated with total extirpation 
 of the organ. 
 
 When the portion of pancreas left is smaller than is sufficient to 
 completely prevent diabetes, only one-eighth of the total mass of 
 the gland, for instance, the symptoms come on more gradually than 
 
PASCREAS 637 
 
 after total extirpation, and the resemblance to human diabetes 
 becomes closer. The animals rapidly deteriorate if supplied with 
 too much carbohydrate, while they may be kept alive for a long 
 time in good licaltli if the limit of their tolerance for carboh\'drates 
 is not exceeded (Tliiroloix, Allen et al.). 
 
 Although as yet we are ignorant of the precise manner in which 
 the pancreas influences the metabolism of the body, it is impossible 
 to doubt, in view of the facts we have mentioned, that, like the liver, 
 in addition to carrying on the exchanges necessary for the prepara- 
 tion of the ordinary or external secretion, the gland has other 
 important relations with the circulating fluids, giving to them or 
 taking from them substances on the manufacture or destruction of 
 which the normal metabolic processes depend. It has been sug- 
 gested that the pancreas neutralizes or renders harmless some 
 toxic substance formed elsewhere in the body, the action of which 
 produces glycosuria. But no evidence of the existence of any such 
 substance has been obtained, and the transfusion into a norma 
 dog of blood from a depancreatized animal, which ought to be laden 
 wdth the hypothetical toxic material, does not cause glycosuria. It 
 is much more probable that the h^^perglycsemia on which the 
 glycosuria depends is caused by the absence of something normally 
 produced by the pancreas, and which is indispensable for the due 
 regulation of the sugar-content of the blood. This something, as 
 already pointed out in discussing pathological diabetes, may be 
 necessary to regulate the transformation of sugar into glycogen, 
 or eventually, it may be, into fat, so that too great a surplus oi 
 sugar does not remain unchanged ; or to regulate the transformation 
 of glycogen into dextrose, and prevent too hasty and too extensive 
 action by the glycogenase; or to regulate the production of sugar 
 from sources other than the carbo-hydrates; or, finally, to regulate 
 and to aid in the normal utilization of the sugar in the organs 
 (p. 553). 
 
 While the liver contains less than the normal content of glycogen, 
 its power to form glycogen is certainly not abolished. On the con- 
 trary, there is some reason to think that a great deal of this reserve 
 carbo-hydrate may be synthesized in the diabetic organism, and 
 that the comparative poverty of the hepatic cells in glycogen may 
 be due to rapid glycogenolysis, despite the hyperglycaemia, in 
 response to the insistent demand for sugar on the part of the tissues, 
 which in the midst of plenty are hungry for dextrose on account of 
 their inability to utilize it, or some of its decomposition products, 
 in the normal way. It has indeed been sho\vn b^^ numerous ex- 
 periments that interference with the formation or with the hydrol- 
 ysis of glycogen, although it may be a factor, is not of itself sufficient 
 to explain pancreatic glycosuria. 
 
 Failure in the katabolism of dextrose, as already mentioned 
 
638 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 (P- 554). iias been asserted by some observers and denied by others. 
 A great production of sugar from proteins {i.e., from amino-acids) 
 has been demonstrated, but it is quite possible that just as much is 
 produced from this source in the normal organism, although here 
 its formation is masked by a corresponding utilization. 
 
 The clearest evidence that the pancreas produces something of 
 high importance in carbo-hydrate metabolism has been obtained 
 by experiments in which animals were united in such a way 
 that substances could pass from one to the other (parabiosis, see 
 Chap. XIX.). Wlien two young dogs were so united and the pancreas 
 then removed from one, no glycosuria followed. The internal 
 secretion of the remaining pancreas was sufficient for both (Forsch- 
 bach). In like manner the removal of the pancreas from pregnant 
 bitches not far from full term caused no glycosuria or very little 
 till the pups were born, when the usual train of events associated 
 with pancreatic diabetes ensued. Obviously the pancreatic tissue 
 of the embryos in the uterus supplied the mother with the indis- 
 pensable secretion (Carlson and Drennan). 
 
 The question has often been raised why it should not be possible 
 to supply animals or human beings suffering from pancreatic defi- 
 ciency with the missing material by administering pancreas or 
 pancreatic extracts. Hitherto, however, little if any success has 
 attended attempts of this kind, perhaps because the active substance 
 or substances are very easily destroyed. This has been all the more 
 disappointing, as in the case of the internal secretion of the thyroid 
 the so-called ' substitution therapy ' has been brilliantly successful 
 (p. 649)- 
 
 The seat of the internal secretion of the pancreas seems to be the 
 very vascular epithelioid tissue which is peculiar to this gland, and 
 occurs in islands between or imbedded in the alveoh (islands or 
 islets of Langerhans) (Schafer). For animals survive the complete 
 atrophy of the ordinary secreting epithelium caused by the injec- 
 tion of paraffin into the ducts, and no sugar appears in the urine. 
 The islets remain intact. When a portion of the pancreas is 
 separated from the rest, and its duct ligated, it undergoes extensive 
 atrophy, a tissue remaining which is apparently composed of en- 
 larged islands of Langerhans and remains of pancreatic ducts. If 
 the rest of the gland is now removed, no glycosuria occurs, even 
 when considerable quantities of dextrose are injected. But when 
 the atrophied remnant is also removed, typical pancreatic glycosuria 
 at once ensues (W. G. MacCallum). 
 
 As further evidence that the islets have a different function from 
 the pancreatic alveoli may be cited the statement that in teleostean 
 fishes, in which the islands are so large that they can be separated 
 from the rest of the tissue, the cells of the islets, instead of containing 
 an amylolytic ferment like the alveolar cells, contain a glycolytic 
 
PANCREAS 639 
 
 ferment, or at least possess the power of destroying sugar. Yet the 
 question of the significance of the islets can hardly be considered 
 settled, although, as previously mentioned, the supposed experi- 
 mental basis of the theory that they do not differ essentially from 
 the alveolar tissue, but are formed by certain changes in the arrange- 
 ment and properties of the alveolar elements, appears to have 
 collapsed under the criticism of Bensley and others. Far from 
 being interchangeable with the cells of the acini, the islet cells 
 present definite and permanent criteria by which they can be sharply 
 distinguished from the alveolar epithelium. At least two types of 
 islet cells may be identified by their staining reactions, the so-called 
 A and B cells (Lane). The B cells are the most abundant in 
 all the islets, and many of the small islets are composed of them. 
 In the guinea-pig, on account of the great size of some of the islets, 
 and because many of them are situated in the interstitial tissue 
 (between the acini), it is not difficult to pick out an islet, isolate it 
 from the surrounding tissue, and examine it in serum or salt solu- 
 tion. The cells are crowded with very fine granules exhibiting 
 Brownian movement. In the fresh preparation the granules of the 
 A cells cannot be distinguished from those of the B cells. 
 Both varieties stain intensely with neutral red and other dyes, and 
 the islet tissue can in this way be easily differentiated from the 
 tissue of the acini. By differences in their staining reactions and 
 certain properties of their nuclei, which need not be gone into here, 
 the two varieties of islet cells can be identified. The important 
 point for our purpose is that by an appropriate histological tech- 
 nique the islet tissue can be studied in all the functional vicissitudes 
 of the gland. When this is properly done, it is not found that 
 there is any close connection between the secretory activity of the 
 cells of the acini and the islets. Nor is there any evidence that the 
 amount of islet tissue in the pancreas is ever affected by the forma- 
 tion of new islets out of acini. On the other hand, it seems that the 
 islets, or the great majority of them, consist of epithelial cells which 
 are in direct continuity with the pancreatic ducts, and that after 
 removal of a portion of the pancreas, establishing an insufficiency of 
 islet tissue, new islets can be developed from the duct epithelium, 
 in addition to the increase by interstitial growth in the size of islets 
 already existing (Bensley, etc.). If the islets are connected with 
 the ducts, the possibility may be admitted that they yield some- 
 thing to the external secretion of the pancreas as well as to its 
 internal secretion. But if this be so, there is no improbability in 
 the idea that the alveolar epithelium, which is undoubtedly mainly 
 concerned in the preparation of the pancreatic juice, may also 
 contribute something to the internal secretion of the gland. While, 
 then, the importance of the pancreas in carbo-hydrate metaboHsm 
 is certain, and the dependence of this function upon an internal 
 
640 TNTERNAL SECnETlOK—^E^^DOCRINE GLANDS 
 
 secretion is highly probable, it is not yet definitely settled whether 
 this secretion is formed in the organ as a whole, or only in the islets. 
 That lesions of the pancreas may be concerned in pathological 
 diabetes is well estabhshed, and it is of interest in connection with 
 the question we have just been discussing that in a certain number 
 of cases the changes observed have been in the islands (Opie). And 
 in diabetes accompanying cirrhosis of the liver, which has usually 
 been considered to depend upon the hepatic changes, it has been 
 shown that in many, if not all, of the cases the pancreas is also 
 affected by a growth of connective tissue outside the acini (Stein- 
 haus). Some authors, indeed, have gone so far as to say that in all 
 cases of diabetes mellitus there is disease of the pancreas, but of this 
 there is no evidence. 
 
 Ligation, or the establishment of a fistula, of the thoracic duct, 
 causes glycosuria in dogs. It is possible that this is really a mild 
 form of pancreatic diabetes, due to interference with the supply oi 
 the internal secretion of the pancreas, or of that part of it which 
 reaches the blood by the lymph-stream (Tuckett). 
 
 Pfliiger long maintained that it is not the removal of the pancreas, 
 as such, but the section of certain nerves running into or through it 
 from the duodenum, which is the cause of the glycosuria. For, 
 according to him, .when these nerves are divided or the duodenum re- 
 moved while the pancreas remains untouched, the result is the sam.e as 
 if the pancreas itself had been excised. He imagined that these nerve! 
 arc ' antidiabetic ' — that is, in some way oppose the production of 
 sugar — while nerves coming from the so-called ' sugar centre ' in the 
 bulb (the centre assumed to be affected in the puncture experiment) 
 favour sugar production. Between the.sc the normal balance is struck 
 in health ; it is the upsetting of this balance by the crippling of the 
 duodenal fibres which is at the bottom of ' pancreatic ' diabetes. 
 But it has been shown that this hypothesis is without foundation, 
 AJthough in frogs removal of the duodenum does cause a certain degree 
 of glycos\iria, this is not the case in dogs. And it has been demon- 
 strated clearly in the dog, by special experiments, that section of all the 
 old connections of a dislocated remnant of the pancreas does not cause 
 permanent glycosuria, whereas removal of the pancreatic tissue does. 
 
 Sexual Organs. — The influence of castration in preventing the 
 development of the sexual characters, and especially the physical 
 and psychical changes that normally occur at puberty, is also due 
 to the loss of the internal secretion of the generative glands, and 
 does not appear to depend at all upon the loss of nervous impulses 
 arising in these organs. In Herdwick sheep an outstanding sexual 
 difference is the presence of horns in the males, their absence in 
 the females. Removal of the testes from ram lambs arrests further 
 growth of horns forthwith and at any stage of development. The 
 retention of the epididymes, provided that the testes proper are 
 removed, does not alter the result of castration in the least. The 
 removal of one testicle slows horn growth without arresting it 
 (Marshall and Hammond). In partially castrated cocks it has been 
 
SICXUAL ORGANS fi.^I 
 
 seen that, so Umg as a portion of one testicle remains, tlie male 
 characters are preserved, but after removal of this residue the 
 comb and wattles wither in a few weeks (Hanau). At the breeding- 
 time the muscles of the forearm of the brown land frog {Rana 
 fused) become hypertrophied in the male, so that it can more tightly 
 hold the female. At the same time the balls of the toes increase 
 in size, and become covered with a peculiar black growth. After 
 the breeding season these secondary sexual characters disappear. 
 If the male frog is castrated, the periodic return of these phenomena 
 does not occur, but the prei^ence of one testicle suffices for their 
 development on both sides. When pieces of testicle from normal 
 frogs are introduced under the skin of the castrated frogs, the 
 phenomena occur just as if the animals had not been castrated 
 (M. Nussbaum). 
 
 Many facts indicate that the internal secretion is not furnished by the 
 proper reproductive elements (those which form the spermatozoa), 
 but by the interstitial cells of Leydig, which are distributed in groups 
 throughout the substance of the testes between the seminal tubules. 
 The spermatogenic cells may be atrophic or absent, as in cryptorchids, 
 or after ligation of the vas deferens (Bouin and Anc«l) ; or they may be 
 destroyed by X-rays, without interfering with the development of the 
 secondary sexual characters. Steinach has shown that when the testes 
 of a young rat or guinea-pig are transplanted to another part of its 
 body (the peritoneal cavity or subcutaneous tissue), the animal de- 
 velops all the secondary sexual characters at the proper time. The 
 penis grows to the normal size. The seminal vesicles and prostate 
 develop in the ordinary way, and yield a plentiful secretion. Sexual 
 desire and potency appear in due season, and in normal or, in not a few 
 cases, indeed, increased intensity. Yet histological examination shows 
 that not a single spermatocyte or spermatid (Chapter XIX.) has de- 
 veloped, while outside the seminal tubules the interstitial cells ft)rm 
 large masses which much surpass in size the interstitial islands of the 
 normal testis. Similar clianges are observed, though with less cer- 
 tainty and after a longer interval, when the vas deferens is ligated, a 
 method often recommended and occasionally practised for the steriliza- 
 tion of the human male. On account of the influence, thus demon- 
 strated, of the interstitial cells in producing the sexual development 
 observed at puberty, Steinach designates these cells collectively as the 
 'puberty gland.' 
 
 When the ovaries of a young female rat or guinea-pig are trans- 
 planted into the peritoneal cavity or under the skin of a previously 
 castrated male animal of the same kind (preferably, to facilitate acciirate 
 comparison, a male of the same litter), only the interstitial cells 
 survive (in about half the cases). There is this difference in the fate 
 of the ovary and the testis when auto-transplanted,* that the genera- 
 tive elements of the former, the Graafian follicles, with the ova contained 
 in them, generally develop as well as the large interstitial cells rich 
 in protoplasm lying in the stroma, which cells appear to constitute 
 
 * An auto-transplant or auto-graft is a portion of tissue transplanted into 
 another part of the same animal's body. A homceo-graft is a portion of tissue 
 transplanted into the body of another individual of the same species; a hetero- 
 graft is a portion of tissue transplanted into an animal of a different speciM. 
 
 -41 
 
642 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 the female puberty sl^"*^!- l^t-' strict isolation of the female 
 ])ubcrtv ^'laiid is only realized in those cases in which bv some 
 accident of healing the stroma of the transplanted ovary maintains 
 itself while the generative elements disappear. In these cases the 
 influence of the ovary on the development of the sexual characters 
 is the same as when the reproductive elements proper persist and 
 grow. 
 
 A more general influence of the sexual organs on metabolism 
 seems also to be well established. The exact experiments of Loewy 
 and Richter on the metabolism of bitches before and after cas- 
 tration throw light upon the changes which follow that operation, 
 and afford decisive proof that tluy are connected with the absence 
 of substances specific to the ovary. They conclude that in the 
 castrated animal the oxidative energy of the cells is lessened. The 
 oxygen consumption sinks, even although protein is laid on and the 
 total amount of active tissue thus increased. Under certain cir- 
 cumstances this specific diminution of metabolism may be balanced 
 by conditions which cause an increase in the metabolism. The 
 lessening of the oxidative power is due to the loss of ovarian sub- 
 stance, for the administration of an extract of the ovary (oophorin) 
 not only neutralizes it, but actually causes an increase in the gaseous 
 metabohsm to far above the original amount, while it has no effect 
 on the metabolism of the uncastrated animal. It is not the de- 
 composition of proteins, but of non-nitrogenous substances, whicli 
 is accelerated. Oophorin also brings about a notable increase in 
 metabolism in the castrated male dog, while, curiously enough, 
 extract of testicle causes only a small increase, due to a basic sub- 
 stance, spermin (CgHj^Ng), which can be isolated from the testicle. 
 But the orchitic extract is not without influence in other ways. 
 It certainly increases the capacity for muscular work (Zoth and 
 Pregl), as tested by the ergograph (p. 750), and this distinct physio- 
 logical action is sufficient to encourage the hope that it ma}' possess 
 some therapeutic value, although far from what has been claimed 
 for it by its more enthusiastic advocates. The only constituent of 
 extracts of the testicle made with salt solution which causes any 
 pronounced effect on the blood-pressure when injected into the 
 circulation is a nucleo-protein, the most plentiful of the protein 
 substances. The pressure falls, mainly owing to inhibition of the 
 heart, but partly through vaso-dilatation in the splanchnic area 
 (Dixon). 
 
 The testicles also influence the growth of the bones. In eunuchs 
 and in young men with atrophy of the testicles a tendency has been 
 observed for the long bones to go on growing far beyond the usual 
 period. This has been shown by the Rontgen rays to be due to 
 delay in the ossification of the epiphyses. The same has been 
 observed in animals, and is supposed to be caused by the loss of 
 
THYMUS 643 
 
 some substance normally toiinod in the testicle vvliicli influences tne 
 metabolism ol the bones and the deposition of the l)one salts. 
 
 A temjiorarv diminution in the ha-moglobin and in the number 
 of the erN-throcytes has been observed in castrated bitches, an 
 observation which, so far as it goes, is in favour of the view that an 
 insufficient internal secretion of the ovaries is the cause of the 
 form of anaemia known as chlorosis. 
 
 While these effects on general metabohsm and nutrition, as well 
 as the influence on the development of the sexual characters, are 
 probably to be ascribed to changes in the internal secretion of the 
 interstitial cells, there are facts which indicate that other elements 
 may be concerned. For example, evidence has been brought 
 forward that the corpus luteum is a gland with an internal secretion, 
 whose function is connected with menstruation and with the im- 
 plantation of the ovum and the subsequent growth of both ovum 
 and uterus in pregnancy (Born, Fraenkel) (Chapter XIX.). Removal 
 of the corpora lutea occurring during the first half of pregnancy 
 causes abortion. 
 
 Thymus. — Our knowledge of the function of the thymus is very 
 incomplete. Even its histological structure, and especially the 
 source and nature of its cellular elements, have long been, and still 
 are, the subject of controversy. It is developed as a pair of diver- 
 ticula, mainly from the ventral part of the third branchial cleft, and 
 to a slight extent from the fourth. These pouches grow downwards 
 into the thorax. At this stage the organ is a purely epithelial 
 structure. Soon connective tissue and bloodvessels begin to grow 
 into it, the two halves coalesce in the middle line, and the thvmus 
 becomes transformed by degrees into a structure with a general 
 resemblance to a big lymph gland, and consisting mainly of small 
 cells like lymphocytes. Some observers beheve that these cells 
 are true lymphocytes, derived from the mesoderm, which have 
 migrated into and displaced the earher epithelial tissue. Others 
 maintain that the resemblance is merely superficial, and that they 
 are simply epithelial cells diminished in size and altered in shape, 
 but derived from the original epithelium by repeated division, and 
 remaining epithehal to the end. Any theory of the function of 
 the thymus must needs depend largely upon the view adopted as to 
 its structure. For if it is in its fully developed state merely a large 
 collection of lymphocytes, it would appear quite unlikely that it 
 should possess functions very different from those of other collections 
 of lymphocjles. On the other hand, if the essential elements in 
 the organ are epithelial, they may well, like the epithelial elements 
 of the thyroid or of other glands with an internal secretion, be con- 
 cerned in the elaboration of substances which exercise an important 
 influence upon nutrition and growth. On the whole, the best histo- 
 logical evidence seems to favour the view that the thymus cells are 
 
644 [XTi:iy\AL SECRETION— EN DOGKIXF. GLANDS 
 
 differrnt liom the cells ol lympli glands. Chemical differences also 
 exist. For example, nuclein substances characteristic of the nuclear 
 framework of the true glands are much more abundant in the thymus 
 than in lymph glands. 
 
 After a period of further development, which varies in duration in 
 different animals, the organ undergoes involution. In mammals (in- 
 cluding man) the thymus does not completely disappear in the adult. 
 Islands of thymus tissue are found at all ages among the fat by which 
 the bulk of the organ is replaced. In certain diseases, as exophthalmic 
 goitre, myxoadema and Addison's disease, an actual regeneration of 
 the involuted thymus may occur. It is usually stated that in man 
 the thymus begins to diminish in size about the end of the second year, 
 but the careful observations of Hammar indicate that this is incorrect. 
 According to him, the organ continues to grow till puberty is reached, 
 weighing on the average 13 grammes at birth, 37 grammes at eleven 
 to fifteen years, 23 grammes at sixteen to twenty years, and only 6 
 grammes at sixty-six to seventy-five years. Besides this involution 
 with age, great changes in the size of the thymus may occur at any 
 time under the influence of toxic substances or of deficient nutrition. 
 In starvation, even in the first three days of hunger, the weight of the 
 thymus in rabbits has been observed to shrink to one-halt, and during 
 prolonged underfeeding even to one-thirtieth, of the normal (Jonson). 
 The opposite effect, namely, cessation of the involution process, or 
 even new formation of thymus tissue, may also occur, leading to the 
 presence of an unusually large so-called persistent thymus in the adult 
 — the so-called status thymicus, or status lymphaticus. 
 
 The point most clearly established in the physiology of the thymus 
 seems to be its relation to the gonads or sex glands. It is well known 
 that in castrated animals the thymus is larger and persists longer than 
 in entire animals. In bulls and unspayed heifers the normal atrophy of 
 the thymus, which begins after the period of puberty, is greatly acce- 
 lerated when the bulls have been used for breeding, and when the 
 heifers have been pregnant for several months. There is a reciprocal 
 influence of the thymus on the testicles, and removal of the thymus 
 before the time at which it naturally atrophies is followed by a more 
 rapid growth of the testes (in guinea-pigs) (Paton). The remarkable 
 atrophy or involution of the gland at puberty is a striking indication 
 of this relation. That the nexus between the thymus and the gonads 
 is chemical and not nervous is shown by the fact that when the thymus 
 is autografted under the skin (a situation in which grafts readily take 
 and grow after removal of the main portion of the gland in sexually 
 immature rabbits) these grafts behave in the same way as the gland 
 in situ, showing earlier involution both in the male and in the female 
 when the animals arc allowed to breed (Marine and Manley). The 
 relation of the thymus to the growth of bones is less well established, 
 but according to some observers extirpation of the gland retards their 
 calcification. 
 
 In young mammals the loss of the thymus is said to cause transient 
 disturbances of nutrition, as temporary decrease in the number of 
 all varieties of leucocytes, and a diminished resistance to the pus- 
 forming micrococci, probably connected with the relatively feeble 
 loucocytosis (or increase in the number of leucocytes) by which the 
 animals react to the infection. In the frog the thymus persists through- 
 out life. Yet the removal of it is not fatal if precautions against in- 
 fection be taken. The contention that the thvmus is indispensable for 
 
THYROIDS AND PARATHYROIDS 
 
 64; 
 
 life in mammals, and that its removal is always followed by a characteris- 
 tic cachexia (Klose) has been overthrown by later experiments on the 
 effects of extirpation of the gland (Pappenheim, Ilowland, etc.). The 
 thymus of young mammals can be readily auto-grafted into the subcu- 
 taneous or subperitoneal tissues. Such grafts involute at sexual 
 maturity with the main thymus. Homcco-grafts are not permanently 
 successful in mammals, except that they take and survive for two or 
 three weeks (Marine and Mauley). 
 
 The chief effect of intravenous injection of extract of human or ox 
 thymus is a lowering of blood-pressure; but there is nothing specific 
 in this, a similar effect being given by thyroid extract and the extracts 
 of many other tissues. The heart may be at the same time accelerated. 
 When thymus substance is fed to tadpoles, growth is markedly stimu- 
 lated and metamorphosis delayed (Gudernatsch), the opposite of the 
 effect produced by thyroid substances. This direct evidence supports 
 the observations on mammals above referred to that removal of the 
 thymus hastens sexual ditferentiation ; that delayed sexual differentia- 
 tion, as in myxccdema, lymphatism, etc., is associated with enlarged 
 thymus; and that castration delays the involution of the thymus. 
 
 Thyroids and Parathyroids. — The thyroid consists of two lobes 
 connected by an isthmus across the middle Una in man and some 
 animals, but often separate. 
 In the neighbourhood of the 
 thyroid, or embedded in its 
 tissue, are certain bodies 
 called parathyroids, consist- 
 ing of solid columns of epi- 
 thelial cells. The number 
 and situation of the para- 
 thyroids are not constant. 
 As a rule, there are four in 
 mammals, two on each side, 
 but this number is subject 
 to variations in different 
 individuals of the same 
 species. The variability in 
 their anatomical relations to 
 the thyroid is of greater 
 significance. For much of 
 the uncertainty in which the 
 whole question of the symp- 
 toms following extirpation 
 of the thyroids was until 
 lately involved arose from 
 ignorance or insufficient re- 
 cognition of this variabihty. 
 In most animals the inferior, anterior, or external pair of para- 
 thjToids is more or less distinctly separated from the thyroid. 
 The separation is especially evident in the herbivcra, in the monkey, 
 
 
 Fig. 202. — Parathyroid (Vincent and Jolly). 
 A small portion of parathyroid of cat em- 
 bedded in thyroid tissue. It consists for 
 the most part of solid colimins of epithelial 
 cells (3, 5, 8) with strands of vascular con- 
 nective tissue (6). A thyroid vesicle (11) 
 and portions of two others (i, 10) are seen 
 in the lower part of the figure, separated 
 from the parathyroid by a fibrous capsule 
 (2). 4, 7, bloodvessels; 9, lower boimdary 
 of the parath3T:oid tissue. ( x 500.) 
 
646 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 and in man, and this pair of jKirathyroids is nuirh larger than the 
 (tier. In carnivorous animals, as the dog and cat, the anterior 
 pair of parathyroids is closely adherent to the thyroid capsule. 
 The superior, posterior, or internal pair, both in hcrbivora and carni- 
 vora, is always very closely associated with the capsule of the 
 thyroid, and frequently embedded in the substance of the gland. 
 The consequence of this arrangement is that in the older experiments 
 the chief masses of parathyroitl tissue were much more likely to 
 escape removal with the thyroid in the case of herbivorous than in 
 the case of carnivorous animals. 
 
 But even in one and the same species considerable variations may 
 exist. It is easy to see, then, that in removing the th3Toid the 
 parathyroids would sometimes be completely removed as well, 
 while at other times all or some of the parathyroid tissue would be 
 spared. Add to this that sporadic masses of thyroid tissue (acces- 
 sory thyroids), often existing as far down as the root of the aorta 
 (always, indeed, in certain animals — e.g., the dog), must necessarily 
 be spared in the most complete thyroidectomy, and it vAU cease to 
 excite surprise that the symptoms and pathological changes de- 
 scribed after that operation should have been so various and so 
 contradictory. We know now that the parathyroids are perfectly 
 distinct organs from the thyroid in development, in structure, in 
 function, and in the consequences of their removal. The para- 
 thyroids, for instance, contain no iodine, while iodine is a character- 
 istic constituent of the thyroid. Nor do the parathyroids show any 
 compensatory hypertrophy when the thyroid alone is excised, or 
 any changes which would indicate a definite relation to, still less, an 
 active participation in, the pathological processes occurring in the 
 thyroid in goitre. This does not mean, however, that there are 
 no points of contact between the functions of the two glands. The 
 more the matter is probed, the more clearl}^ does it appear that none 
 of the organs is quite independent of the rest, and the reciprocal 
 relations of the ductless glands are probably of exceptional im- 
 portance. But the premature attempts which have been made, 
 in the absence of a sufficiency of exact data, to represent their 
 mutual influence by crude schemata, have retarded rather than 
 advanced our knowledge, and need not be referred to here. 
 
 Parathyroidectomy.— Total extirpation of the parath3'roids is 
 followed by a train of acute symptoms, ending fatally, as a rule in 
 from one to ten days. The typical nervous symptoms following the 
 operation are those of ' tetany ' (tetania parathyreopriva), and the 
 tetany which used to be included among the consequences of re- 
 moval of the thyroid is now known to be due to the simultaneous 
 excision of the parathyroids (Kocher). A cat, after the combined 
 operation, is perfectly well on the first day. On the second day a 
 curious shaking of the paws is seen, tremors of central origin soon 
 
THYROIDS AND PARATHYROIDS 647 
 
 appear, and incii-asc in severity, until at K'ngth they culminate in 
 general spasmodic attacks. Even when the animal is at rest the 
 fore-legs tend to be ilexed, while the hinrl-legs are extended, and this 
 attitude is exaggerated in the convulsions. In the later stages un- 
 consciousness is associated with the onset of the convulsions. Similar 
 results follow excision of the parathyroids alone in dogs. Although 
 the tetany is the most striking symptom, it is only one token of a 
 profound general disturbance of nutrition. The pulse-rate and the 
 rate of respiration arc markedly increased. There is fever and pro- 
 fuse salivation, with dilatation of the stomach and duodenum, due 
 to the loss of muscular tonicity. In the intervals between attacks 
 the tonus returns to the normal. The secretion of the gastric 
 juice, pancreatic juice, and bile are interfered with (Carlson, etc.). 
 The excitability of the vaso-constrictor mechanism is said to be 
 increased. The exact significance of these symptoms is unknown. 
 It has been suggested that the loss of the parathyroid function is 
 in some way associated with an augmentation of the irritability of 
 the whole sympathetic system (Hoskins). The administration of 
 calcium completely relieves the symptoms, and by its use death may 
 be long or perhaps indefinitely postponed (W. G. MacCallum) . The 
 mode of action of the calcium has not been made clear as yet. It 
 does not seem to be so efficacious in rabbits as in dogs (Arthus) . 
 
 A suggestive fact is the increased amount of guanidin, methyl and 
 (Umethyl-guanidin in the urine of dogs after parathyroidectomy (Koch). 
 Recently the hypothesis has been put forward that the parathyroids 
 regulate the metabolism of guanidin in the body and bv doing so, 
 probably exercise a controlling influence on the tone of the muscles. 
 In support of this, it is pointed out that in tetania parathyreopriva 
 there is a marked increase in the amount of guanidin and methyl- 
 guanidin in the blood, as well as in the urine. This is also true of the 
 urine of children suffering from the disease known as idiopathic tetany, 
 in which the parathyroids are supposed to be implicated (Paton, etal.). 
 Symptoms and metabolic changes like those in experimental and patho- 
 logical tetany are said to be caused by guanidin and methyl-guanidin. 
 
 Thyroidectomy. — The symptoms that follow removal of the 
 thjToid alone are perfectly different. The metabolic disturbance is 
 eventually, in most animals, not less far-reaching than that which 
 ensues when the parathyroids are alone excised. But it is far more 
 chronic, reveals itself by totally distinct changes, is not amenable 
 to calcium, and is completely corrected by the administration of 
 thyroid substance. While no animals which have been examined 
 survive the total removal of the parathyroids, certain species — 
 e.g., the goat — are but shghtly affected by thyroidectomy, and 
 survive indefinitely. In man, before the consequences of th}Toid- 
 ectomy were known, the whole gland was not infrequently excised 
 for goitre. If the parathyroids happened also to be completely 
 involved in the operation, death quickly followed. But where only 
 
648 ISTERSAL SECRIiiloS—LSUULRIM. CLANDS 
 
 the thyroid itself, or the thyroid plus the small internal pair of 
 parathyiviids, was cxtiipated, the condition called cachexia 
 struniipii\a was observed to supervene. The symptoms rcsf^mble 
 those of the disease known as myxoedema, in which the charac- 
 teristic anatomical change is an increase (a hyperplasia) of the 
 connective tissue in and under the true skin. Newly-formed connec- 
 tive tissue always contains an excess of mucoids, and for this reason 
 in the early stages of myxoedema there is somewhat more than the 
 usual amount of these substances in the subcutaneous tissue. The 
 skin is dry, and tlie hair falls off. The features are swollen and 
 heavy, and movements clumsy and trembling. As the disease 
 progresses the mental powers deteriorate too; the patient becomes 
 stupid and slow, and perhaps, at last, imbecile. When the gland 
 is so affected in early life that extensive atropliy of the true secreting 
 tissue occurs, a peculiar condition of idiocy (cretinism) results. 
 
 In animals there is a great difference in the results of total ex- 
 cision of the thyroids, both between different groups and between 
 different individuals of the same group. In young animals the 
 symptoms come on more rapidly and are more severe than in old. 
 Monkeys develop symptoms resembling those of myxoedema. 
 
 The older descriptions of the very acute onset of the symptoms 
 and the quickty fatal result in carnivorous animals were vitiated 
 by the circumstance that, for the anatomical reason already alluded 
 to, the parathyroids were also involved in the operation. Never- 
 theless, the consequences of complete removal of the thyroid proper 
 are in general more serious in the carnivora than in the herbivora. 
 Muscular weakness soon becomes marked; the tissues waste, the 
 temperature becomes subnormal, and this is associated with changes 
 in the heat regulation (p. 699). 
 
 If a portion of the thyroid be left, or an autograft be made in any 
 part of the body, these effects are permanently obviated. Homoeo- 
 grafts, although they take, rarely survive and function. Working with 
 rabbits, Marine and Manley have found that thyroid autografts take 
 and grow when placed in any tissue, spleen and bone marrow being the 
 least favourable tissues, while the sex glands and the adrenals are 
 probably the most favourable. The extent of the growth of thyroid 
 autografts depends on the age of the animal, being more marked in 
 young animals, on the amount of the thyroid gland removed, and on the 
 administration or withholding of iodine. Thyroid homoeografts rarely 
 succeed. In a series of 5O7 thyroid homoeografts in rabbits, 92 per cent, 
 underwent absorption in ten to thirty days; (> per cent, remained active 
 from two to six months before being absorbed: and 2 per cent, were 
 permanent and beha\ed in all respects like autografts. The outlook 
 for the therapeutic application of thyroid grafts in the treatment of 
 thyroid insufficiencies is therefore not hopeful, imlcss some means is 
 discovered to overcome the power of the host to destroy foreign 
 proteins. It has been established that a hetcro-thyroid graft does not 
 even temporarily succeed. The alien thyroid cells arc destroyed by 
 cytolysins (p. 31) in the scrum and tissue liquids of the animal. 
 
TUVROtnS AND PA RAI HY IU)1 1)^ 649 
 
 When a small part of a thyroid is left, it may undergo gi eat hyper- 
 trophy, and the same is true of the accessory thyroids. The ad- 
 ministration of extracts of the thyroid glands or the glands them- 
 selves by the mouth brings about a cure, permanent so long as the 
 thyroid treatment is continued, in cases of myxoedcma in man, and 
 prevents the development of the symptoms in animals, or removes 
 them when they have appeared. The same is true of a compwund 
 rich in iodine, the so-called thyToiodin, which has been extracted 
 from the organ. Under this treatment the total metabolism, which 
 in myxcedema is below the normal, is markedly increased. This is 
 partly due to an increase in the metabolism of protein. An increase 
 in the destruction of protein is also caused in normal persons and in 
 normal animals by feeding with thyroid or with thyroid prepara- 
 tions. The excretion of nitrogen, carbon dioxide, and phosphoric 
 acid, and the intake of oxygen, are augmented. But in spite of in- 
 creased appetite the body-weight falls off, and diarrhoea is often 
 caused. For these reasons the use of thyroid preparations to reduce 
 weight in cases of obesity, without evidence of thyroid insufficiency, 
 is a dangerous remedy. For while a fat man can very well spare a 
 great deal of his fat, he cannot spare much of his tissue-protein. 
 That the gland exerts in some way an important influence on the 
 metabolism of proteins is also indicated by other facts. The ques- 
 tion whether the thyroid or parathyroid is, in addition, concerned 
 in the carbo-hydrate metabolism is at present the subject of dis- 
 cussion, but the data are so contradictory that it would not be advis- 
 able to enter into the matter here. 
 
 The ready response of the thyroid by hyperplasia or involution 
 to changes in the nutritive conditions is one of its most .striking 
 characteristics, and further illustrates the significant role which it 
 plays in the chemical activities of the body. The thyroid swells 
 and shrinks almost as easily and under almost as great a variety 
 of conditions as the spleen. One of the most interesting of the 
 physiological changes is the hypertrophy and sometimes hyperplasia 
 of the gland, which is a normal accompaniment of menstruation 
 and pregnancy. This is a classical instance of a definite inter-rela- 
 tion of endocrine functions. Although known to the ancients in its 
 crudest manifestations, the underlying physiology of the condition 
 is as yet only slightly understood. A pathological change of great 
 interest, because of the careful manner in which it has been studied, 
 is the endemic goitre (sometimes erroneously termed ' carcinoma ') 
 of brook trout kc})t under artificial conditions in hatcheries. Marine 
 has shown that this depends upon overfeeding with unsuitable food 
 (such as livers of cattle, pigs, or sheep), overcrowding, and insuffi- 
 ciency of water-supply, and that the goitre can be readily cured or 
 prevented by changing the conditions in these respects. Similar 
 results have been obtained in mammals fed exclusively with meat. 
 
6iO 
 
 INTERNAL SnCRRTlON— ENDOCRINE GLANDS 
 
 Thus, lion cubs at the Zoological Gardens in London on a diet con- 
 sisting only of raw aneat de\'elo])cd rickets and goitre, as did pu])])ies 
 fed with meat, lungs, liver, or heart, and nothing else, whereas when 
 milk, bread, and bone were added to meat the puppies grew nor- 
 mally (Marine). A meat diet caused hyperplasia of the thyroid in 
 rats (Chalmers Watson). The relation of the disease known as 
 exophthalmic goitre to the thyroid has been much debated. The 
 best evidence is against the hypothesis that the symptom complex 
 is of thyroid origin. The increased thyroid activity partially 
 accounts for the increased metabolism characteristic of the disease; 
 but this is secondary and symptomatic. All attempts to produce 
 
 anything resembling the 
 pathological condition by 
 the administration of large 
 amounts of thyroid or of 
 thyroid products have failed. 
 Nor has it ever been shown 
 that the changes in the 
 gland are the primary cause 
 of the syndrome. Indeed, 
 no specific anatomical or 
 chemical changes have as 
 yet been demonstrated in 
 the thyroid in this condition. 
 The thyroid gland of ex- 
 ophthalmic goitre has the 
 same action on animals and 
 on patients suffering from 
 exophthalmic goitre as any 
 other thyroid gland with 
 like iodine content (Marine). 
 The relations of iodine to 
 the gland itself, and the 
 modifications in its structure and function determined by the giving 
 or withholding of iodine, recently studied by Marine, are of great 
 interest. In all animals, so far as examined, the normal thvroid 
 contains iodine. The amount is variable, but the minimum per- 
 centage of iodine necessary, if the normal histological structure is 
 to be maintained, is quite constant for a given species. So also the 
 highest percentage of iodine associated with any degree of active 
 hyperplasia (developing goitre) is always below the normal minimum 
 of O'l per cent, of the dried gland as shown by Marine in the dog, 
 sheep, man, and other mammals. As active hyperplasia of the 
 thyroid (goitre) (Fig. 203) develops, the iodine content of the gland, 
 both relative and absolute, decreases, until in extreme degrees of 
 the condition there may be no demonstrable iodine present at all. 
 
 Fig. 203. — Microphotograph of Active Thyroid 
 Hyperplasia from a Case of Exophthalmic 
 Goitre (Marint^). The characteristic changes 
 in the hyperplastic gland — the infoldings 
 and plications of the adveolar epithelium, 
 the great reduction in the colloid, and 
 the increase in the stroma — are shown. 
 
TlfVh'niDS AND P.lRATIlVI^OfnS 
 
 G51 
 
 vSincc the iodine is contiiiucd in the colloid as an io(lint'-])rot(in 
 compound, the generahzation may be made that in the thyroid 
 the iodine varies directly 
 with the amount of colloid, 
 and inversely with the de- 
 gree of hyperplasia. The ad- 
 ministration of any iodine- 
 containing substance to 
 animals with actively hyper- 
 plastic thyroids (goitres) re- 
 sults in a rapid storage of 
 iodine in the gland, and 
 quickly (in two to three 
 weeks in dogs) induces a 
 histological change, the end 
 stage of which is the so-called 
 colloid goitre (Fig. 204). 
 This is an involution to the 
 normal histological structure 
 
 Fig. 204.— Microphotograph of a Colloid 
 Gland (Goitre) (Marine). The effect of ad- 
 iiiiuistration of iodine is shown in the return 
 towards the normal structure from a pre- 
 ceding active hyperplasia, such as is shown 
 in Fig. 203. 
 
 (F"ig. 205), SO far as this is 
 possible in a gland which 
 has once undergone hyper- 
 plasia. This storage of 
 iodine in the thyroid is of unusual interest because it affords the 
 best opportunity for the quantitative study of an essential inor- 
 ganic constituent of the body. Iron is another such substance, 
 
 but it is impossible to follow 
 its absorption quantitatively 
 with the same ease and 
 accuracy, since it is so widely 
 distributed. Iodine is con- 
 tained in the thyroid, and to 
 all intents and purposes in 
 the thyroid alone. And the 
 tliyroid is so situated ana- 
 tomically that it is a simple 
 matter to remove a portion 
 of it for examination. The 
 extraordinary affinity of the 
 thyroid for iodine and its 
 salts has been demonstrated 
 both in vivo and in vitro. 
 There is little difference 
 whether the iodine salt is 
 injected into the circulation of the living animal, or perfused 
 through the excised sur\i\-ing gland, so long as the gland is not 
 
 Fig. 205. — Microphotograph of Normal 
 Human Thyroid (Mca4ne). 
 
652 INTERNA L SECRETION— ENDOCRINE GLANDS 
 
 already saturated with iodine. The greatest quantitative absorption 
 takes place in those glands with the smallest iodine content, or. 
 what comes to the same thing, those glands with the most marked 
 hyperplasia. 
 
 Thus, a dog's thyroid (in early hyperplasia) weighing i6 grammes, 
 and containing 0-54 milligramme of iodine per gramme of the dry 
 tissue was perfused for thirty minutes with a mixture of blood and 
 Ringer's solution to which was added 5 milligrammes of potassium 
 iodide. The gland was then washed out thoroughly with Ringer's 
 solution to remove remaining iodide. It was now found to contain 
 I 38 milligramme of iodine per gramme of dry tissue. Ten minutes 
 after the injection of 50 milligrammes of potassium iodide into the 
 femoral vein of a dog, from which one thyroid lobe had been removed 
 as a control, the remaining lobe was excised and all loose iodide re- 
 moved by thorough washing. The iodine in it was then determined and 
 found to be i 3S milligramme per gramme of the dry tissue, as com- 
 pared with 079 milligramme in the control lobe, an increase of 75 
 per cent. Only traces of iodine can be demonstrated in other organs 
 under such conditions, even when they have not been washed. Even 
 m five minutes, an absorption of iodine of practically the same magni- 
 tude has been shown to occur. So that the thyroid has the power of 
 taking up considerable amounts of iodine almost instantaneously. 
 While, however, the time required for the absorption of iodine by the 
 thyroid from the blood, and the binding of it m such a way that it 
 cannot be washed out, is so short as to be measured in minutes, the 
 time required for the elaboration of the iodine into the active iodine- 
 containing substance, which exhibits the specific action of the gland, 
 is much greater. In dogs, the earliest period at which an increase in 
 the amount of active iodine could be made out was eight hours after 
 the injection of an iodine salt into the circulation. 
 
 Summary : — The physiological significance of iodine in the thyroid 
 mav be summed up as follows : Iodine is absolutely essential for the 
 normal activity of the gland. Tlie amount in the gland at any given 
 time represents the store or reserve. Iodine prevents spontaneous hyper- 
 plasia [goitre] in all mammals, and also the compensatory hyperplasia 
 which follouS partial removal of the thvroid. It exercises a curative 
 effect on CKtive hyperplasias. It is present in an active and an in- 
 active form. The inactive form represents the newly acquired iodine, 
 which is usually a very small fraction of the total content, but may 
 undergo a great temporary increase after the administration of iodine. 
 Accordingly, the physiological and therapeutic activity of thyroid 
 substance appears in general to' vary with the total amount of iodine 
 in it. although in reality with the amount -which exists in the specific 
 compound. The nature of this compound is unknown. 
 
 No other body has been shown to possess its specific activating effect 
 on metabolism. It is sometimes spoken of as the iodine-containing 
 hormone. Kendall has been able to separate it both from its protein 
 combination and from the inactive iodine by alkaline hydrolysis of the 
 thyroid, and to obta'n it in a cn,'stalline form containing about 60 per 
 cont , by weight, of iotlinc. 
 
THYh'niDS AND HA RATHY ROI DS 653 
 
 Tlie most sensitive and accurate test object for estimating the pharma- 
 cological activity of thyroid substance, or of its hydrolytic products, is 
 the tadpole. Its growth is hindered and its differentiation accelerated 
 by the active iodine compound, so that the limbs grow and the tail 
 atrophies, while the tadpole remains small (Gudernatsch). By means 
 of this test, it has been possible to demonstrate the presence of active 
 and inactive iodine in the gland, and to estimate the rate at which the 
 thyroid can elaborate the active iodine-containing substance from the 
 inactive iodine (Figs. 206, 207). 
 
 Fig. 206. — Tadpoles after seven days feeding: A, with iodine-free hyperplastic lamb 
 thyroid in 50 milligramme doses on alternate days; B, with sheep thyroid 
 hydrolytic product (containing 17-9 milligrammes of iodine per gramme) in 10 
 milligramme doses on alternate days; C, with ox thyroid hydrolytic product 
 (containing 14*8 milligrammes of iodine per gramme) in 10 milligramme doses 
 on alternate days. On the other days all the tadpoles received fresh liver. 
 In A, normal growth similar to control. Great emaciation with differentiation 
 in B and C (Rogoff and Marine). 
 
 While the precise role played by the thyroid in the economy re- 
 mains obscure, it is evident that in most animals and in man its 
 secretion is of great importance, whether it be solely the quasi- 
 external secretion of 'colloid,' with its specific iodine-containing 
 substance that collects in its alveoli and slowly passes out of them 
 by the lymphatics, or perhaps, in addition, some other substance, 
 which, like the glycogen of the liver, never finds its way into the 
 lumen of the gland-tubes at all. It may also be admitted that, by 
 aiding in the maintenance of the normal level of general nutrition, 
 particularly that of the central nervous system, the ability of the 
 organism to cope with toxic substances introduced from the outside 
 or manufactured in the body is favoured. There is, however, no 
 e\adence that an actual destruction or neutralization of toxic sub- 
 stances occurs in the gland itself. 
 
 It is uncertain whether the secretion of the thyroid is influenced by 
 nerves. Section of most of the nerves entering the gland does not 
 obviously alter its activity. Thyroid tissue may be transplanted into 
 any part of the body, and there exhibit all the morphological, chemical, 
 and functional changes seen in the gland in situ. Transplantation in 
 the same nerve field as the original thyroid has no advantage over 
 transplantation into any other region of the body (Marine and Manley). 
 This is an indication that specific secretory nerves are not indispensable 
 for thyroid activity. 
 
Ov 
 
 54 
 
 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 It has long been known that vaso-motor fibres for the dog's thyroid run 
 up in the cervical sympathetic to the superior cervical ganglion, ami 
 
 Sampl 
 
 Thyroid. 
 
 Fig. 207. — Effect of Desiccated Human Thyroid on Tadpoles of Different Ages 
 The upper row shows the older, the lower row the younger tadpoles. The older 
 ones had posterior leg buds slightly over 2 centimetres long, but no foreleg. The 
 younger tadpoles had just visible posterior leg buds and no foreleg buds. The ind'- 
 viduals of each age were alike at the beginning of the experiment as to size ai d 
 condition of development. One of each age was killed in formalin at the beginning 
 of the experiment (designated as ' Sample ' in the figure). Another of each a^^e 
 was used for control, and fed fresh liver every second day. A third specimen nt 
 each age (under * Thyroid' in the figure) was fed 50 milligrammes of desiccated 
 human thyroid every second day, alternating with fresh liver. The thyroid 
 showed the condition of multiple adenoma and contained 4-3 milligrammes of 
 iodine per gramme of the dry weight. The difference at the end of the experi- 
 ment between the thyroid-fed and control tadpoles of the younger set is especially 
 seen in the atrophy of the tail and the appearance of the hind-legs in the former. 
 In the older set, at each stage in the experiment differentiation was more ad- 
 vanced in the thyroid-fed specimen. This is still the case at the end, especially 
 in the much greater atrophy of the tail. The difference is less than in the younger 
 set, simply because even the control is approaching the end of the metamor- 
 phosis (Graham). 
 
 thence to the lobe of the same side. These were first discovered bv 
 the eflfect produced b^- their stimulation on the thyroid circulation 
 time (p. 135^ Some evidence of the existence of secretory fibres has 
 
ADRENALS 055 
 
 been brought forward bj- Aslier and Flack. They compared the excita- 
 bihty ol the depressor nerve, and also the effect on the bhjod-pressure 
 of the intra\ enoiis injection of adrenalin, before and during stimulation 
 of the thyroid nerves. They conclude that, when all the other con- 
 ditions remain unchanged, both the effect of excitation of the depressor 
 and the effect of adrenalin are greater during stimulation of the thyroid 
 nerves than shortly before it without such stimulation. The difference 
 is really connected with the internal secretion of the thyroid, since it is 
 not obtained if the thyroids are previously extirpated, and injection 
 of thyroid extracts influences the result exactly in the same way as 
 stimulation of the thyroid nerves. Similar indirect evidence has been 
 obtained bv other observers (Oswald, Lew). 
 
 Adrenal Bodies. — It had been observed by Addison that the 
 malady which now bears his name, and in which certain vascular 
 changes, with muscular weakness, anamia. and pigmentation or 
 ' bronzing ' of the skin, are prominent symptoms, was associated 
 with disease, usually tuberculous, of the adrenal bodies, commonly 
 called in human anatomy the ' suprarenal capsules.' This clinical 
 result was soon supplemented by the discovery that extirpation of 
 the adrenals in animals is incompatible with life (Brown-Sequard). 
 Our knowledge of the functions of these hitherto enigmatic organs 
 was extended by the experiments of Oliver and Schafer, who in- 
 vestigated the action of extracts of the adrenals (of calf, sheep, 
 dog, guinea-pig, and man) when injected into the veins of animals. 
 The arteries are greatly contracted, and this mainly through direct 
 action on the vaso-motor nerve-endings or some structure inter- 
 mediate between them and the smooth muscle of the vessels, but 
 parth^ through the vaso-motor centre. The blood-pressure rises 
 rapidly, although the heart may be inhibited through the vagus 
 centre. The heart is at the same time directly stimulated, so that, 
 although it beats slowly, the beats are stronger than before. When 
 the vagi are cut the action of the heart is markedly augmented, 
 and the arterial pressure rises enormously (it may be to four or five 
 times its original amount) . Stimulation of the depressor is of no avail 
 in combating this increase of blood-pressure. The generalization 
 may be made that the active principle of the medulla — epinephrin 
 or suprarenin, also called adrenin* — acts upon all plain muscle 
 and gland-cells that are supplied with sj'mpathetic nerve-fibres, and 
 the result of the action, whether augmentation or inhibition, is the 
 same as would be produced by stimulation of the sympathetic fibres 
 going to the muscle or gland in question. Yet it is not through 
 excitation of these fibres that epinephrin acts, for its effect is even 
 more pronounced when the nerve-fibres have been caused to de- 
 generate, in the case of the pupillo-dilator fibres, e.g., by excision 
 of the superior cer\acal ganglion. Nor is the effect a direct one on 
 
 * It is advisable to restrict the term ' adrenalin ' to the well-known com- 
 mercial preparation of the active substance. 
 
656 INTERNAL SEC RETION— ENDOCRINE GLANDS 
 
 the muscular fibres. For smooth nuisclc which is not, and never has 
 been, in functional miion willi symi)ath(tic nerve-fibres is indifferent 
 to adrenalin (KUiott). It seems, then, to act on some structure 
 intermediate between the nerve and the muscle, but so related to the 
 latter that it continues to live so long as it is in connection with the 
 muscle-fibre. Instead of a definite histological structure, the seat 
 of the action may be a special ' receptive ' substance at the myo- 
 neural junction. Thus adrenalin causes marked diminution of 
 tone in the small intestine, with disappearance of the peristalsis 
 and pendulum movements. The same effect is produced on an 
 isolated loop of intestine immersed in Locke's solution, and the action 
 is therefore local. The drug is effective in a dilution of i : 10,000,000, 
 or even in much greater dilution. A similar effect has been ob- 
 served on the stomach. The vessels of the conjunctiva are con- 
 stricted by local action when an extract of the capsules is dropped 
 into the eye, a fact which has proved of value in ophthalmological 
 practice. Inhibition of the contraction of the stomach, intestine, 
 urinary bladder, and gall-bladder; contraction of the uterus, vai 
 deferens, and seminal vesicles ; dilatation of the pupil and retraction 
 of the nictitating membrane ; stimulation of the salivary and lachry- 
 mal secretions, are among its actions (Langley). 
 
 Meltzer has shown that the dilatation of the pupil caused by the 
 intravenous injection of adrenalin is distinct, though fleeting, in cats, 
 less marked in rabbits. Subcutaneous injection has no effect. Instilla- 
 tion of the drug into the conjunctival sac is without effect on the pupil 
 in the normal rabbit's eye, but causes dilatation if the superior cervical 
 ganglion has been removed. 
 
 The influence of adrenalin in increasing the sugar content of the 
 blood, and thus causing glycosuria, has been previouslj' discussed 
 (p. 550). A new and interesting action has been added to the already 
 long list of the effects of adrenalin, by the discovery that small doses 
 (0001 milligramme per kilo of body-weight) injected intravenously, 
 and larger doses injected subcutaneously into cats shorten the coagula- 
 tion time of the blood to one-half or one-third of its previous duration, 
 probably by stimulating the liver to greater activity in discharging 
 some substance or substances concerned in clotting (Cannon). The 
 injection of adrenalin into the blood is said to cause a temporary im- 
 provement in the response to stimulation of a fatigued muscle still in 
 connection with the circulation, and this improvement does not seem 
 to be entirely due to augmentation of the blood fiow (Gruber, Cannon 
 and Nice). 
 
 Methods for the detection and the assay of epinephrin in the small 
 quantities in which it can only be supposed to be present in physio- 
 logical liquids have been based upon certain of these actions. Such, 
 for example, is the extraordinary power of this active principle that 
 a dose of one-millionth of a gramme per kilo of body-weight is suflficient 
 to cause a distinct effect upon the heart and bloodvessels (a rise of 
 pressure of 14 millimetres of mercury) when injected into the veins 
 of a mammal. The reaction is rendered more constant, although less 
 dehcate, when the brain is previously destroyed and the animal used 
 as a spinal preparation. In pithed cats the assay can be accurately 
 
ADRENALS 657 
 
 performed to 001 niilligranimc. Another delicate, and for certain pur- 
 poses a con\cnicnt, reaction for the detection and the physiological 
 assay of epincphrin is the perfusion test on the legs of frogs already 
 alluded to (p. 40). The dilatation of the pupil in the excised eyeball 
 of the frog, the contraction of stretched artery rings (p. 66), the increase 
 in the tone of isolated segments of the uterus of rabbits, and the diminu- 
 tion in the tone of isolated segments of rabbits' intestine (Practical 
 Exercises, p. 453), have also been employed as physiological tests. 
 
 A dilute solution of adrenalin chloride is used in medicine as a styptic, 
 and* for reducing congestion in accessible parts. The intense loc^,! 
 ana'mia which it causes when given subcutaneously or by the mouth 
 is one reason, perhaps the most important, for the slow absorption on 
 which depends the absence of its general effects, including that on the 
 blood-pressure, when it is administered in this way. 
 
 Function of Epinephrin. —The striking effects produced by adrenalin 
 have naturally led to the assumption tliat the function of epinephrin 
 in the body must be important. But there is perhaps no chapter of 
 recent physiology in which the rash appHcation of qualitative data to 
 what is essentially a quantitative problem has led to greater errors. 
 Because adrenalin in a certain amount and concentration raises the 
 blood-pressure when injected intravenously (a fact certainly of some 
 pharmacological interest), it has been assumed that the naturally 
 secreted epii:.ephrin must be an important factor in the maintenance 
 of the normal vascular tone and arterial pressure. From this assump- 
 tion it was only a short step to the announcement that the blood in 
 cases with permanently increased blood-pressure (so-called arterial 
 hypertonus, etc.), and even the urine contained truly incredible con- 
 centrations of epinephrin. Because the injection of what in proportion 
 to the normal output of epinephrin must be designated as monstrous 
 doses of adrenalin causes an increase in the sugar of the blood and the 
 appearance of sugar in the urine, it has been supposed by many that all 
 the experimental hyperglycaemias and glycosurias (p. 547) are directly 
 due to increased liberation of epinephrin from the adrenals. The fallacy 
 of giving a physiological value to the details of the pharmacology and 
 toxicology of a substance produced in the body or known to exist in 
 the blood in the absence of information as to its amount and condition 
 would have been very' evident in the case, for example, of ammonium 
 or potassium, and nobody would have dreamt that the effects produced 
 by massive injections of ammonium or potassium compounds of various 
 kmds would inform us of the role played by the ammonium and potas- 
 sium compounds circulating in normal blood. The whole question of 
 the function of epinephri^i turns, therefore, upon the quantity wh'ch 
 can possibly be present in the systemic arteries or capillaries. Direct 
 assays of such blood by trustworthy observers using the most delicate 
 methods available have hitherto yielded negative results, both in health 
 and in disease. This is due to the great dilution and rapid removal 
 or oxidation of the epinephrin known to be given off bv the adrenal 
 glands. 
 
 That epinephrin is continuously liberated into the blood from the 
 adrenals is readily shown by tving off a long segment of the inferior 
 vena cava in such a way that only the adrenal veins discharge into it. 
 The cava pocket is temporarily clipped above the level of the orifices 
 of the adrenal veins and allowed to fill with adrenal blood. When the 
 blood is now released into the circulation bv removing the clip, a rise 
 of blood-pressure (l"ig. 208) is produced, beginning after an interval 
 sufficient for the blood from the pocket to pass round to the systemic 
 arterioles. Another method is to 'i^^crve the effect of the released blood 
 
 42 
 
b5b 
 
 ISTERSAL SECRET JON— £S DOCRI >J E GLASDS 
 
 in causiiig dilatation of the pupil and retraction of tlic nictitating mem- 
 brane of the eye of a cat from which the superior cervical ganglion on 
 one side has been removed a week or two before the experiment. It is 
 well known that alter this procedure these reactions are elicited by 
 adrenalin with great ease. 
 
 Fig. 2o3.^Showiag Spoataaeous Liberation of Epiaephrin in a Cat. 8 to 9, Pockst. 
 Epinephrin rise on release. Time trace half-minutes (^^ reduction). 
 
 Or the adrenal vein blood can be collected directly from a cannula 
 in the cava pocket, and then tested on rabbit's uterus and intestine 
 segments (.Fig. 209). 
 
 209. — Inlestinr' Segmont Tracings with Adrenal Blood from a Cat. At 30, 
 Ringer's solution was replaced hy indifferent (jugnlar vein) blood, and this at 31 
 by a specimen of adrenal vein blood collected during asphyxia. At 3^, Ringer's 
 solution was replaced by jugular blood, and this at 33 by a specimen ^f adrenal 
 vein blood collected previously without asphy.\ia. The bloods were diluted 
 with eight volumes of Ringer's solution The concentration of epinephrin in 
 the specimens is seen to be about the same. Time, half-minutes (reduced to 
 two-thirds). 
 
 The amount of epinephrin in the blood can be as.savcd bv comparing 
 the effects produced by it with those produced bv known' amounts of 
 adrenalin. In such ways it has been shown that in cats the amount of 
 
ADRENALS 
 
 659 
 
 fpiiiephrin given off per minute varied from 0001 milligramme to 0002 
 nulligrammc. All the epinephrin seems to be contained in the plasma 
 and none in the corpuscles (Figs. 210, z 11). 
 
 Fig. 210- — Comparison of Effect of Adrenal Vein Blood and its Sediment on Rabbit's 
 Intestine Segments. 11, Ringer replaced by indifferent blood, and this at 12 
 by adrenal vein blood. 13, Ringer replaced by sediment of indifferent blood, 
 and this at 14 by sediment of adrenal vein blood. The bloods and sera were 
 diluted with 2 volumes Ringer. Time-trace, half-minutes (reduced to one-half). 
 
 If we suppose chat a cat, weighing 25 kilos, and containing 200 c.c. 
 of blood was giving off 0001 milligramme of epinephrin per minute, the 
 concentration which this output would maintain in the mixed blood, 
 supposing that there was no loss in passing through the lungs and up to 
 the systemic capillaries, would be at most only i ; 400,000,000 or 
 1 : 500,000,000. For at Ica^t 400 or 500 c.c. of blood would pass through 
 
 /--^^--^^ ' 
 
 
 
 ' 
 
 lb 
 
 /(o 
 
 
 f f r .' t f' 
 
 T ■» J i i til 
 
 Fig. 211. — Effect of Adrenal Blood (16), Serum (15), and Sediment (iS), on Rabbit's 
 Uterus Segment. All the specimens were diluted with 5 volumes Ringer. 
 
 the heart in one minute. Now. with such concentration.! of adrenalin 
 no known reaction has ever been demonstrated in the normal intact 
 animal. Of course, in the cava pocket experiments described above, 
 the concentration in the blood will be much greater because a relatively 
 considerable quantity of epinephrin-containing blood is accumulated 
 in the pocket and then suddenly discharged. 
 
660 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 The function of the spontaneously liberated epinephrin, once it 
 has entered the circulation, is accordingly involved in doubt. The 
 common view that it exerts an important physiological action u]>()n 
 the sympathetic system, contributing especially to the maintenance 
 of the normal blood-pressure is opposed to all the best evidence. 
 Whatever influence the relatively small quantities of adrenalin dis- 
 charged from time to time may have upon the nutrition of the smooth 
 or of other muscles, it is quite unlikely that such amounts are 
 continuously entering the blood as injection experiments have 
 shown to be necessary for the maintenance of even a small excess 
 of blood-pressure. Statements which connect the increased blood- 
 pressure in such conditions as chronic nephritis with hypertrophy of 
 the chromaffin tissue (p. 665), an increased adrenalin production, 
 and an increased adrenalin content of the blood, must be received 
 with scepticism. The so-called experimental arteriosclerosis pro- 
 duced by repeated injections of adrenahn into the blood of rabbits 
 throws little light upon the question, for the vascular changes, in 
 so far as they have not been confounded with similar lesions occur- 
 ring spontaneously in a considerable proportion of rabbits, differ 
 from those observed in pathological arteriosclerosis (M. C. Hill). 
 
 Certain facts indicate, indeed, that doses of adrenalin considerably 
 smaller than those which give the effects described above, and 
 usually considered the ' normal ' effects, produce a reversal of the 
 reaction, very small doses causing, for instance, a diminution of 
 blood-pressure (Moore and Purington), an increase in intestinal 
 tonus and peristalsis, and a diminution in the tone of uterine seg- 
 ments. The actions associated with these small doses are more 
 likely to be the normal actions than those associated with the 
 larger doses, and the normal action of adrenalin, if it is a continuous 
 action, would therefore more probably be to iphibit than to excite 
 the sympathetic mechanism. But there is no evidence that even 
 quantities of this order of magnitude are continuously discharged. 
 The continuous introduct'on of epinephrin at a vvvy slow rate 
 produces no demonstrable effect at all, and tlie sudden ligation of 
 all the adrenal blv>odvessels has not the slightest influence upon 
 the blood-pressure until the lapse of a period far greater than would 
 be required for the destruction or removal — a quite rapid process — 
 of any epinephrin already present in the blood or tissues (Tren- 
 delenburg, Hoskins). The injection of a quantity of adrenahn 
 sufficient to cause and to long sustain even a minimal increase of 
 blood-pressure creates conchtions highly hazardous to life or in- 
 compatible with it — namely, complete inhibition of the muscula- 
 ture of the gastro-intestinal tract. 
 
 The only cttecl of interference with the passage into the blood of 
 the spontaneously liberated epinephrin which has hitherto been demon- 
 strated is upcm a mechanism rendered abnormally sensitive — namely, 
 
ADRENALS 66l 
 
 the iris of the cat's eye after removal of the superior cervical gangUon. 
 When the pupil has been dilated by epinephrin, the dilatation passes otf 
 sooner if the adrenal vein blood is prevented from entering the circula- 
 tion. This shows that the dilatation of the pupil must have been in 
 jiart sustained by the epinephrin continuously entering the blood from 
 the adrenal veins. 
 
 The suggestion that enough epinephrin may be continuously liberated 
 to exert an influence upon the nutrition and metabolism of the sym- 
 pathetic system, or of the myoneural junction, which is necessar\' for 
 normal excitability, without ever rising to the threshold of actual 
 excitation, is a mere hypothesis, and a hypothesis which does not seem 
 easily reconciled with the result of Hoskins, that after ligation of the 
 adrenals the excitability of the vaso-motors remains absolutely un- 
 diminished. 
 
 It has been supposed by some that although usually liberated in an 
 amount too small to cause demonstrable effects, epinephrin can be dis- 
 charged at a greatly increased rate under certain conditions — for 
 example, under emotional stress (the so-called emergencv function of 
 epinephrin). There is no evidence, however, that such outbursts 
 of epinephrin ever occur, and experimentally it is by no means easy 
 to produce decided alterations in the rate of discharge. 
 
 Whatever the function of epinephrin may be, it is not indispens- 
 able for hfe and health. For cats after removal of one adrenal and 
 section of the nerves which govern tlie epinephrin discharge from 
 the other, not only sur\-ive indefinitely, but show no apparent differ- 
 ences from normal animals, although, when the nerve section is com- 
 plete, no epinephrin can be detected by the most delicate tests in the 
 adrenal vein blood, and the possible concentration in the arterial 
 blood cannot at most amount to i : loo thousand millions. 
 
 Nervous Mechanism Controlling the Liberation of Epinephrin. 
 — The spontaneous liberation of epinephrin from the adrenals is 
 entirely dependent upon nerve fibres, reaching the glands from the 
 lower dorsal and upper lumbar portions of the sympathetic chain. 
 The splanchnics form the most important path. When in the cat 
 the fibres coming to a semilunar ganglion from the sympathetic, 
 including the splanchnics, are cut, the secretion of epinephrin by 
 the corresponding adrenal into the blood comes at once to an end. 
 It is not resumed when the animal is allowed to survive. When 
 the peripheral ends of the cut splanchnics are stimulated electrically, 
 secretion is caused, and the amount of epinephrin discharged per 
 minute may exceed that spontaneously liberated (Figs. 212, 213). 
 
 This was first indicated by the experiments of Dreyer, w^ho col- 
 lected blood from the adrenal vein of a dog during splanchnic stimu- 
 lation, and caused a rise of blood-pressure in another dog by injecting 
 the blood. The effect of stimulation of the splanchnic can be de- 
 monstrated very clear!}' by the eye reactions already alluded to. 
 After the interval required for the blood to pass from the adrenals 
 to the eye, dilatation of the pupil and retraction of the nictitating 
 membrane are seen to occur. In this way it has been shown that 
 
662 
 
 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
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ADRENALS 
 
 663 
 
 the latent period of the secretion is so short that the reaction follows 
 the cumnuncemcnt of stimulation of the nerve after a time-interval 
 sensibly the same as when it is elicited by the corresponding amount 
 
 
 .^^\^vV%^^\\'l.ViMV;Jl^wuww«*lA;J^*ww\m'*^^' 
 
 '^V\\utt\#Ww^^^^^^,j^ 
 
 -^^^ 
 
 Pi^ .J, _^o Pocket Experiment with Stuualatiou wf ^Rii^ht Splauclinic 111 Aljd(>- 
 °" meu after Section of Both Splanchiiics. 21, repetition of 20, but with a shorter 
 time of stimulation. The epiuephrin rise of blood-pressure after 20 is consider- 
 ably greater than after 21. Time-trace, hali-miuutes (| reduction). 
 
 of adrenahn injected at the level of th? adrenal veins. Even when 
 the glands have ceased to respond to stimulation of the nerves, 
 epinephrin can still be liberated into the blood by massaging the 
 ff'mds with the fingers (Fig. 214). 
 
 -^.v.«^,'■•''''''••"■■■'■''»*'■■Vv^v^w^v.,.ww,,,^^^^^ 
 
 Ficr .T.— Showing the Effect of Massage in Liberating Epinephrin from the Left 
 Adrenal whose Nerves had been Cut Five Weeks before. 27, cava pocket wi h 
 massage, the left adrenal vein being open to the pocket. 47 to 49, POcket with 
 massage the left adrenal vein having been closed at 45 and opened at 48, after 
 dosure of the pocket. Massage begun at 45-A, stopped at 46. Blood-pressure 
 tracing from carotid artery. Time-trace, half-minutes (reduced to t). 
 
 A centre for epinephrin secretion seems to exist in the upper part 
 of the thoracic region of the spinal cord. After section of the cord 
 in the cervical region, even as low as the level of the last cer\acal 
 segment, the secretion persists, but it is abolished when the cord is 
 di\nded at the third or fourth dorsal segment. 
 
o64 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 The relation of the nervous system to the adrenal medulla has been 
 further illustrated by comparison of the amount of epinephrin which 
 can be extracted from the two adrenals when the nerves of one have been 
 cut. Under the influence of anaesthetics and some other drugs, bac- 
 terial toxins, such as diphtheria toxin, etc., the epinephrin store is 
 markedly diminished in the gland whose nerve supply has been left 
 intact as compared with the other. 
 
 For example, in a cat the fibres coming from the sympathetic to the 
 left semilunar ganglion, including the left splanchnic nerves, were cut, 
 and the animal allowed to recover. Several days later when it is kno^n 
 that equality of epinephrin load in the two adrenals would have been 
 restored, morphin was administered to the animal, and after a few 
 hours it was killed, and the epinephrin in the adrenals assayed. The 
 left gland contained 028 milligramme, the right, 01 1 milligramme. If 
 the animal had been suddenly killed without morphin, the two ac'.renals 
 would have been found to contain equal amounts of epinephrin. There- 
 fore the deficiency in the right gland must have been due to the fact 
 that it was not protected by section of its nerves. 
 
 A similar deficiency has been found in the unprotected gland aftei 
 administration of a drug, /3-tetrahydronaphthylamine, after surgical 
 operations (post-operative deficiency), and in many other conditions. 
 When the animal recovers the deficiency is gradually made good, the 
 adrenal having the power of forming and storing epinephnn up to a 
 cc tain point in the absence of its nerve supply, although it is unable 
 to liberate it into the blood. 
 
 There is no foundation for the statement that emotional disturb- 
 ances, as fright or anger, cause a depletion of the epinephrin store of the 
 adrenals. 
 
 Summary : — The existence of a nervous mechanism through which 
 the gland is stimulated to secrete epinephrin info the blood can there- 
 fore be considered as definitely established. It is the function of the 
 epinephrin, once it has entered the circulation that is involved in doubt. 
 Although it is highly improbable that the concentrations necessary for 
 direct stimulation of sympathetic endings ever e.xist in the general mass 
 of the blood, it is quite possible that a ' sensitizing ' influence is exerted 
 by epinephrin upon the sympathetic peripheral mechanisms which 
 renders them more susceptible to nerve impulses originating in other 
 wavs. The possibility of a more direct action of epinephrin upon the 
 chemistry of carbo-hydrate metabolism, particularly upon glycogenolysis 
 or even upon glycogen formation has been emphasized by some writers. 
 But glycogen can be formed abundantly, and certain experimental 
 hvperglyccBmias which depend upon the rapid transformation of 
 glycogen into dextrose can be produced after the epinephrin secretion 
 of the adrenals has been abolished. 
 
 Chemistry and Formation of Adrenalin .—It has been shown (Stolz. 
 Dakin) that adrenalin (CgHjgXOg) is a dioxyphenyl-ethauol-methy- 
 lamin, 
 
 CH 
 OH.C/\C.CH(OH).CH,NH.CH, 
 
 ! ! 
 
 OH.C\/CH 
 CH 
 
ADRENALS 665 
 
 It has been prepared synthetically, and in the body appears to be 
 formed, probably by the introduction of a methyl (CHg) group, from 
 a compound arising from an aromatic amino-acid (tyrosin or phenyl- 
 alanin). While the natural adrenalin rotates the plane of polarization 
 to the left, the artificial substance is optically inactive. This is because 
 it consists of equal parts o." laevo-rotatory and dextro-rotatory adrenalin. 
 The artificial adrenalin has approximately half the effect of the natural 
 on the blood-pressure, from which it may be inferred that the dextro- 
 rotatory isomer has only a very slight j^ressor effect. 1 he left and right 
 rotatory moieties have been separated. The former has exactly the 
 same power of raising the blood-pressure as the natural adrenalin, the 
 latter only yV,- to j^. as mvich. Practically the same proportion holds 
 when the power of the two isomers in producing glycosuria is compared. 
 This constitutes important corroboration of the view already referred 
 to (p. 550), that adrenalin glycosuria is caused by an action on the 
 sympathetic system, for the effect on the blood-pressure is known 
 to be thus produced (Cushny). 
 
 It is in the medulla of the adrenals that the epinephrin is formed. 
 The medullary cells contain a substance which gives a yellow or brown 
 stain with chromic acid or chromates, and for this reason the cells are 
 called chromaffin or chromaphil. Similar cells are found elsewhere in 
 the body — e.g., within the sympathetic ganglia, and also strung out 
 in clumps along the course of the abdominal aorta below the level of 
 the adrenal glands (Vincent). These outlying masses of chromaffin 
 tissue appear to contain epinephrin, or a substance with similar physio- 
 logical actions, so that the formation of this compound seems to be a 
 property common to chromaphil tissue, no matter what its situation 
 may be. A remarkable fact, and one calculated to induce caution 
 in assigning a physiological function to epinephrin, is that the so-called 
 parotid gland of a Jamaican toad secretes it in a concentration not 
 much short of 5 per cent. (Abel). 
 
 Function of the Adrenal Cortex. — The function of the cortical cells is 
 obscure, but there is evidence that they, and not the chromaffin cells 
 of the medulla, are concerned in the production of the internal secretion, 
 whatever its nature may be, the loss of which leads so speedily to death 
 on removal of the adrenals. For example, the period of survival after 
 this operation is practically unaffected by the continuous intravenous 
 administration of adrenalin, although the loss of the medulla might 
 be supposed to be compensated in this way. Still more convincing 
 is the fact already referred to that after removal of one adrenal and 
 denervation of the other in cats, epinephrin ceases to be discharged 
 in detectable amount, and yet the animal survives in good health. In 
 Addison's disease adrenalin is likewise powerless. 
 
 The weakness (asthenia) of the skeletal, and to some extent of the 
 cardiac, musculature which is characteristic of Addison s disease, is 
 produced experimentally within a few hours by ligation of both adrenals, 
 and all the evidence goes to 'show that it is the cortical and not the 
 medullary region which is related to this disease. When the adrenals 
 are not completely extirpated, compensatory hypertrophy of the re- 
 maining portions may occur, and the animal survive indefinitely. In 
 such cases it has been found that the hypertrophy is confined to the 
 cortex. 
 
 In animals like the rabbit in which accessory adrenals are not un- 
 common, when these are present complete removal of both adrenals 
 does not cause death. Now, the accessory adrenals consist of cortical 
 substance without medulla. Portions of the adrenal are readily- 
 grafted under the skin, but only the cortex survives and grows. 
 
666 TNTERWAL SF.CRETTOS'—EXDOCRTXr. CI AXDS 
 
 The functional difference between cortex and medulla is easily under- 
 stood when we reflect that the morphological history of the two tissues 
 is (^uite different. The medulla is developed from cells which push 
 their way into the gland from the rutlim jnts of the sympathetic ganglia 
 at that level, and is therefore of cctodermic origin. The cortex is 
 (.lerived from the same mesodermic structure which gives rise to the 
 kidneys and genital organs. 
 
 Embryologicallv, the cortical cells are related to the interstitial cells 
 of the ovaries and of the testes, and like these are characterized by their 
 richness in lipins (or lipoids). There is some evidence of an inter- 
 relation between the thyroid and all these groups of sex cells (interstitial 
 cells of ovary and testes, cortex of adrenal). Removal of a large part 
 of the adrenals in the rabbit causes slight though defuiite hypertrophy 
 of the thyroid and lymphoid hyperplasia. This is also seen in 
 Addison's (li>eHse in man. 
 
 ^f^^ 
 
 ^^'>' Pituitary Body or Hypophysis.— In the pituitary body two parts 
 
 r^d-y^' essentially different in origin and function may be distinguished: 
 
 ^ V^Ov (^) The large anterior lobe, or pars anterior, consisting of epithehal 
 
 ?9^ 9\^ cells, many of whicli are filled with granules of the type seen in 
 
 ^trf -i^ glandular epithelium, and abundantly provided with bloodvessels; 
 
 ^ (2) the smaller posterior or ner\ous lobe, or pars nervosa, also 
 
 called the infundibular portion, consisting chiefly of neuroglia, the 
 
 whole connected with the floor of the third ventricle by a stalk 
 
 called the infundibulum. 
 
 A further subdivision of the epithelial portion is made into the 
 anterior lobe proper and the pars intermedia or intermediate lobe, con- 
 sisting of epithelial cells, less granular and less richly supplied with 
 bloodvessels than those of the pars anterior. Ttie__pars intermrdia 
 forms an epithelial investment of the pars nervosa, almost completely 
 surrounding it and throwing out offshoots of epithelial cells into its 
 substance, which is also invaded by colloid material secreted by the 
 cells of the intermediate lobe. The differences in the structure of the 
 anterior and posterior lobes of the pituitary body correspond to a 
 difference in their development. The anterior lobe is developed (in 
 man in the fourth week of intra-uterine life) from an ectodermal pouch 
 (Kathke's pouch), which is pushed up from the roof of the bucco- 
 pharyngeal cavity towards the mid-brain. The posterior lobe is 
 developed from an extension of the neural ectoderm, which grows back- 
 wards as the infundibular process till it meets and blends with that 
 portion of the buccal pouch which gives rise to the pars inic media. 
 The pars intermedia is separated from the anterior lobe proper by a 
 cleft which represents what is left of the lumen of Kathkc's pouch. 
 In connection with the interpretation of the results of exjx^riments on 
 removal of the pituitary body, it is of consequence to remember that 
 a residue of the same epithelium which develops into the anterior lobe 
 appears always to get cut off in the vault of the pharynx, constituting 
 the so-called pharyngeal hypophysis, and consisting of a cord of cells 
 identical with those of the anterior lolie (Haberfeld). Kmbryonic 
 ' rests ' of hypophyseal tissue are also often found in the dura of the 
 sella turcica, in which the pituitary body lies, and in the body of the 
 sphenoid bone. Cells of the intermediate lolx> also run up the stalk 
 of the infundibulum, and even stretch for a little distance along the 
 floor of the third ventricle. Add to this the formidable nature of the 
 
operations required for the extirpation of the hypophysis from its 
 sheltered position within the skull, and it will not be wondered at that 
 complete liarmonv has not been attained as to the ccjnsequences of its 
 removal. The best evidence at present is to the following effect: 
 
 When the pituitary body is completely removed, death speedily 
 and in\ariably ensues, in clogs, on the average within twenty-four 
 to forty-eight hours. Puppies often live as long as two or three 
 weeks. The mucii longer periods of survival occasionally witnessed 
 are due to failure to remove some small portion of the hypophyseal 
 epithehum. On the day after the operation the animals may be 
 able to walk about, to eat and drink, and may show an interest in 
 their surroundings. The temperature, pulse, and respiration at 
 this time may be normal. Soon, however, they become lethargic, 
 then comatose, with characteristically incurved spine, slow respira- 
 tion, with long-drawn inspiration, a feeble pulse, perfectly hmp 
 muscles, and often a subnormal temperature, and the appearance 
 of sugar in the urine. This deep coma passes into death, wdth no 
 perceptible transition, and without a struggle (Paulesco, Gushing). 
 The ablation of a part of the cortical substance of the anterior 
 (epithelial) lobe of the hypophysis is compatible with permanent 
 surxival, and gives rise to no symptom of disorder. The same is 
 true when only the posterior lobe is removed. This does not seem 
 to be followed by an3^ recognizable symptoms. In some animals, 
 however, kept under observation for long periods after partial 
 removal of the anterior lobe, a marked tendency to accumulate 
 fat has been noted, accompanied by hypoplasia of the generative 
 organs in adults or the persistence of the infantile condition in 
 immature animals. On the other hand, complete removal of the 
 anterior lobe causes death, just as if the whole gland had been 
 taken away. Of all the structures included in the pituitary body, 
 the most important from the functional point of view appears to be 
 the superficial layer of the anterior lobe. 
 
 Mere separation of the stalk of the hypophysis may produce 
 effects sometimes as serious as those of total removal of the gland, 
 probably o\^'ing to the disturbance caused in the circulation. It is 
 stated, indeed, by some observers that the vulnerable point is the 
 base of the infundibulum, and that if this is not injured extirpation 
 of the hypophysis is not incompatible with continued existence, 
 and that in adult animals the resultant changes are only shght, 
 although much more pronounced, especiallv as regards the disturb- 
 ances in metabolism and development in young animals. It has 
 been asserted that the pituitary undergoes (compensatory ?) hyper- 
 trophy after thyroidectom5^ Some observers have accordingly 
 assumed a similarity of function for these organs. It has even been 
 stated that the production of colloid material bv the cells of the pars 
 intermedia is increased, and that colloid accumulates in the 
 
568 INTERNAL SECRETION— ENDOCRINE GLANDS 
 
 nervous portion of the posterior lobe. But this colloid, whatever 
 its function may be, is very different from that of the thyroid 
 aheoU, for the (sheep's) pituitary contains no iodine after extir- 
 pation of the thyroid any more than before (Simpson and 
 Hunter). And in man pathological changes (tumours) in the 
 pituitary body are associated, not with myxoedcma, or other 
 disease connected with changes in the thyroid, but frequently with 
 another condition, called acromegaly, in which the bones of the 
 limbs and face, especially the hands and feet and the; lower jaw, 
 become hypertrophied. 
 
 Another condition often associated with tumours of the pituitary- 
 is gigantism — a condition occurring before the normal growth of 
 the bones is completed, and resulting in a great increase in the 
 length of the bones both in the limbs and the trunk. 
 
 Action of Intravenous Injection of Extracts of the Pituitary. — 
 The effects on the vascular system of intravenous injection of 
 extracts of the pituitary gland are also very different from those 
 caused by thyroid extracts. The posterior lobe, or infundibular 
 body, including the pars intermedia, contains two active substances, 
 one pressor and the other depressor. The former is soluble in salt 
 solution, but insoluble in absolute alcohol and ether; while the 
 latter is soluble in salt solution as well as in alcohol and ether. The 
 pressor substance (obtained in fairty pure form in the preparation 
 called pituitrin, and in still greater concentration in a preparation 
 to which the name hypophysin has been given) causes a rise of 
 blood -pressuie, due partly to constriction of the arterioles and 
 partly to an increase in the force of the heart-beat, both of which 
 are brought about by direct action. This rise of pressure lasts for 
 a considerable time, and is sometimes accompanied by a slowing 
 of the heart. A second dose injected before the effect of the first 
 has passed off is inactive; and this distinguishes the pituitary from 
 the suprarenal extract. Associated with the pressor effect is an 
 increase in the flow of the urine. Whether this is due to a separate 
 diuretic substance, as some maintain, has not been definitely settled. 
 
 Indeed, the factors on which the diuretic action depends are 
 complex, and sometimes in spite of an increase of general arterial 
 pressure, and of the volume of the kidney, there is no increased flow of 
 urine. In diabetes insipidus pituitrin has been found to produce pre- 
 cisely the opposite effect — namely, diminution in the excessive urinarv 
 flow. The pressor substance, unlike adrenalin, directly stimulates 
 smooth muscle fibres (especially the arteries, uterus, and spleen) irrespec- 
 tive of their innervation ^Dale). 
 
 Many other points of difference exist between the pressor principles 
 of the infundibular body and the adrenal medulla. For example, 
 pituitrin constricts the pupil and diminishes the flow of saliva from the 
 submaxillary gland, whereas adrenalin dilates the pupil and causes an 
 increased flow of saliva. Hypophy.sin and other preparations of the 
 posterior lobe have been employed to stimulate the uterine contractions 
 in obstetrical practice, but their use does not seem to be free from 
 
i^'l 
 
 ^/s 
 
 669 
 
 danger. When injected intramuscularly, regular and powerful con- 
 tractions of the uterus are excited in two or three minutes at any stage 
 in parturition. Another effect of extracts of the infundibular body is 
 on the mammary gland. An increased flow of milk follows the injec- 
 
 Pig. 215. — Action of Extract of Infundibular Lobe (Pars Nervosa of Ox Pituitaiy). 
 P, Carotid pressure; K, kidney volume; U, drops of urine; S, signal showing point 
 at which pituitary extract was injected; T, time-trace in lo-second intervals. 
 T is also the zero of the blood-pressure (Hering). 
 
 tion of pituitrin (Simpson). But it is in doubt whether this is due to 
 increased secretion and not solely to stimulation of the smooth muscle 
 of the organ with expulsion of milk already formed. The depressor 
 substance produces a marked fall of blood-pressure, even when it is 
 injected during the rise of pressure caused by an injection of the pressor 
 
 Fig. 216. — Action of Extract of Hypophyseal Lobe of Pituitary on the Blood- Pressure 
 (W. VV. Hamburger). The signal line at the top shows the time and length of 
 injection of the saline extract into the blood. Time-trace (at bottom) shows 
 second intervals. The figure is to be read from left to right. 
 
 substance. The anterior lobe, or hypophysis, also contains a depressor 
 substance. Intravenous injection of a sahne extract causes a distinct 
 fall of blood-pressure, accompanied usually by acceleration and weaken- 
 ing of the heart (Fig. 216). A second injection immediately following 
 the first produces no change in the pressure (W. W. Hamburger). 
 
070 INTERNAL SECRET tON— ENDOCRINE GLANDS 
 
 An active substance which lias l)ccn termed ' tcthehn,'* because of its 
 influence on growth, has been separated from the anterior lolx>. On 
 intravenous injection into rabbits, it causes a slight fail of blood pres- 
 sure and rto diuresis. Its eriects are therefore quite different from those 
 
 of the posterior lobe. Mixefl with the food 
 of mice, it has lieen fountl to exert a charac- 
 teristic influence upon their growth, retarfl- 
 ing it at certain stages, and accelerating it 
 "1 at other stages (Robertson). 
 
 It is not at present possible to deduce 
 from such clinical and experimental 
 observations as those described any co- 
 herent theory of the function of the 
 pituitary. That there is some connection 
 between the normal action of the gland, 
 and in particular of its interior lobe, and 
 the normal growth and nutrition of the 
 body, including the skeleton, is scarcely 
 to be doubted. The fact that administra- 
 tion of the dried gland substance to dogs 
 causes an increased excretion of calcium 
 on a diet rich in calcium is a further 
 indication of its influence on the meta- 
 bolism of bone (Malcolm). But so far 
 is the precise nature of this influence, if 
 it exists, from being fully understood, 
 that authorities of repute are still divided 
 on the question whether the symptoms 
 of acromegaly and gigantism are due to 
 
 iniii mi ii m ii iiii i ii iiii i iiiiiiiii i ii i iiiiiiii 
 30' 
 
 Fig. 217. — Action of hifundi- 
 bular Extract upon Virfjiii 
 Uterus of Guinea- Pig. Tlie 
 same dose was applied three 
 times in succession to an iso- 
 lated segment, at the points 
 marked by the arrows at 
 the bottom of the curves. 
 After each application the 
 segment was washed with 
 Ringer's solution at R. The 
 tracings have been made to 
 overlap. (Reduced to one- 
 half.) (Dale.) 
 
 atrophy or to hypertrophy of the active 
 elements of the gland, to loss of its internal secretion, or to its 
 manufacture in excessive amount. There is evidence that the 
 colloid secretion of the posterior lobe, probably formed by the 
 epithelial cells of the pars intermedia, passes through the nerxous 
 portion to enter the infundibulum and the third ventricle of the brain, 
 where it breaks down in the cerebro-spinal fluid (Hering). And 
 it has been suggested that in virtue of the action of the hormones 
 (p. 404) in this secretion on the vascular system in general, and on 
 the renal cells and the renal circulation in particular, the posterior 
 lobe constitutes a mechanism for the control of the secretion of urine. 
 But this suggestion is still in the realm of h\pot liesis. Some support 
 is given to it by the observation that continued irritation of the 
 posterior lobe by a plug of the gutta-percha compound used by 
 dentists for temporarily filling teeth introduced through the floor 
 of the sella turcica caused permanent polyuria in dogs, analogous 
 to the diabetes insipidus seen in man (Matthews). 
 * i'l'om Ti$i]\ws, growing, tiounshing. 
 
^ 
 
 671 
 
 Pineal Gland. — Extracts of the pineal gland injected into the circula- 
 tion have 10 citcct other than that due to the inorganic constituents 
 of the calcareous concretions or ' brain sand,' which are its cliaractcr- 
 istic feature. Since in early life the organ has a glandular structure 
 which is later replaced bv librous tissue, it has been supposed that it 
 may exercise some function in connection with growth. But so far 
 the physiology of the pineal body is practically a blank sheet, or, at 
 best, a budget of contradictory statements from which nothing certain 
 can be deduced. Thus in two of the niost recent papers, each based 
 on a large number of carefid experimeiLs, one author concludes that 
 removal of the gland in male guinea-pigs is associated with hastened 
 development of the sexual organs, and ni females with a tendency to 
 breed earlier than the normal conti'ols (Horrax). The other observer 
 finds that feeding young guinea-pigs with pineal tissue from young 
 animals determines an earlier sexual maturity than normal, and in- 
 creases the rate of growth of the body (McCord). 
 
 The alleged influence of the invasion of the gland in young children 
 by pathological growths in accelerating the development of the skeleton 
 and reproductive organs, which has been supposed to indicate that it 
 normally exerts a restraining or regulative influence on this develop- 
 ment, is at present purely fanciful. 
 
 Kidney. — The experiments of Bradford, which seemed to indicate 
 that the kidney, in addition to its function as an excretory organ, plays 
 an important, and indeed indispensable, part in protein metabolism, 
 possibly by forming something of the nature of an internal secretion. 
 
 1-ig. 218.— Effect of b.me-.Marrow on Blood-Prcs.^uie. Intravenous Injection of 
 Saune Extract V ag. Intact. The uppermost line is a signal trace showing the 
 time and lenglli ot nijection. Below this is the record of the respirai -v move- 
 ments, and lowest the blood-pressure tracing. To be read from leii 10 right. 
 
 have not been confirmed. He stated that, when the half or two-thirds 
 of one kidney and the whole of the other have been removed from a 
 dog by successixe operations., death ensues, although the quantity both 
 of water and urea excreted by the fragment of renal substanc'e that 
 remains is far above the normal. In spite of the increased elimination 
 of urea, that substance was said to accumulate in the tissues showin- 
 that the destruction of protein was increased-a conclusion which 
 seemed to derive support from the wasting of the animal. It has since 
 been shown that an increased output of nitrogen is not of constant 
 occurrence, and only takes place under the same condii ons a m 
 starvation (p. 603). As a matter of fact, the animals waste and d"e 
 
67 J IXTERXAL SECRETION— ENDOCRINE GLANDS 
 
 within a few days or weeks largely t>ecaiisc they refuse to eat. Polyuria 
 (increase of urine beyond the normal) does not necessarily occur. It 
 is well known that, when only one kidney is extirpated the other hyjjer- 
 trophios, and no ill-effects ensue. 
 
 The statement that extracts of the kidney when injected into the 
 
 veins of an animal cause a rise of arterial blood-pressure, essentially 
 
 through direct action on the peripheral vaso-motor mechanism, is of 
 
 considerable interest, for it may possibly have some bearing on the rise 
 
 of pressure and consequent hypertrophy of the heart associated with 
 
 certain renal diseases. But there is not as yet sufficient evidence that 
 
 the hv]iothctical pressor sub.-itance, to which the name ' renin ' has 
 
 been given, in anv sense represents an internal secretion of the kidney. 
 
 ^L^^^ The pressor substance (so-called 
 
 ^d||PW||L ' urohypertensine ') which can be 
 
 J0r Tk extracted by ether from normal 
 
 ,^Jr \ human urine (Abelous) is probably 
 
 ^laL^gfr \| only excreted by the kidney, and 
 
 PIP^^ ^^ »».«A perhaps arises from the putrefac- 
 
 \jM|N ^''^*" "^ proteins in the intestine. 
 
 ^^ lor it has been shown that in the 
 
 putrefaction of fhorse-^ meat bases 
 
 •"^MJM^^iW^^ unraveS.llv,^'cause^'a" riie'^ol 
 
 _^ , ■■ blood-pressure. The most active 
 
 Fig. 219.— Injection ol Extract of Bone- of these is a body known as 
 Marrow with the Vagi Cut. To be read /J-hydroxyphenylethylamine, 
 from left to right. formed from tyrosin (Barger and 
 
 Walpole). Whether the pressor 
 (vaso-constrictor) substance which appears to be liberated from the 
 platelets when blood is shed, and may therefore be presumed to be more 
 slowly liberated from such platelets as normally break down in the 
 circulating blood, has any relation to the pressor substance of urine 
 is unknown. It is also quite uncertain whether, as has been stated by 
 some observers, extracts of the kidney or blood from the renal vein 
 stave off for a time the onset of the uraemic symptoms that follow 
 removal of both kidneys or ameliorate them when they have already 
 appeared. 
 
 Spleen. — The spleen does not produce an internal secretion 
 necessary to life, for it can be removed both in animals and in 
 man, without the development of serious symptoms. Its blood- 
 forming and blood-destroying functions (p. 22) are taken on by 
 other structures (particularly the red bone-marrow). 
 
 The most definite changes following splenectomy are transient 
 anaemia, increased resistance to haemolytic agents, and an increase 
 in the content of cholesterol in the blood (Pcarce). These effects 
 are more pronounced in the young. This is intclHgible if the spleen 
 normally plays a considerable part in the destruction of worn-out 
 erythrocytes with liberation of hiemoglobin, the source of the bile- 
 pigment. The formation of the bile-pigment is said to be inter- 
 fered with, and its amount reduced by more than 50 per cent. 
 (Pugliese). 
 
 The spleen can be auto-transplanted readily into the subcutaneous 
 tissues of animals. There is a great difference in the behaviour of 
 
f>7^ 
 
 such transplants according to the age of the animal (Marino and 
 Manley). In young rabbits, the transplants grow rapidly if the 
 spleen is removed at the time of transplantation, while in sexuallv 
 mature rabbits they do not grow and often undergo gradual absorp- 
 tion. Likewise, transplants which have grown rapidly in young 
 animals decrease in size after adult life is reached, indicating that 
 the function of the spleen is more necessary in young than in older 
 animals ; or that its function is more easily and completely assumed 
 by other tissues, probably the bone marrow, in adults. A further 
 and very suggestive fact, is that a subcutaneous spleen graft which 
 has ' taken,' but is not growing, in a young animal whose spleen has 
 not been removed, can be made to grow by removal of the spleen. 
 These results indicate that splenic insufficiency is a necessar}^ con- 
 dition of growth of a splenic transplant, just as thyroid insufficiency 
 is a necessary condition of growth of a thyroid transplant. The 
 stimulus to growth in the one case, as in the other, must be assumed 
 to be a chemical stimulus transmitted through the blood, and not 
 dependent upon the nervous system. 
 
 The salivary glands may be extirpated without any sensible change 
 being produced in the normal metabolism. It has been stated how- 
 ever, that the secretion of the gastric juice is diminished. It has been 
 supposed that this may be due to the absence of a hormone (p. 404) 
 normally produced in the salivary glands. A temporary increase in 
 the gastric secretion is said to be caused when extracts of the glands 
 of normal dogs are injected into the veins or into the peritoneal cavitv 
 of dogs deprived of their salivary glands (HemmiCter). But later 
 experiments contradict the theorv r;f the existence of a hormone in the 
 salivary glands, which stimulates the secretion of gastric juice. The 
 average rate of secretion into a Pawlow gastric pouch (p. 403) was not 
 diminished in dogs after extirpation of the glands (Swanson.) 
 
 Extracts of nervous tissue (sciatic nerve, white matter of brain, and 
 spinal cord, but especially grey matter of brain) cause, on injection into 
 the veins, a decided fall of arterial blood-pressure, which soon passes 
 off, and can he renewed by a fresh injection. The fall of pressure is 
 due to direct action upon the bloodvessels of a depressor substance in 
 the extracts, and not to the action of vaso-motor nerves. It can be 
 obtained after section of the vagi. 
 
 Extracts of muscular tissue also cause a distinct though transient 
 fall of pressure, but not so great a fall as in the case of extracts of 
 nervous tissue. Saline decoctions of other tissues (testis, kidney, 
 spleen, pancreas, liver, mucous membrane of stomach and intestine, 
 lung, and mammary gland) all produce a fall of blood-pressure (Osborne 
 and Vincent). The same is true of bone marrow (Brown and Guthrie; 
 Figs. 218, 219). It must be repeated that there is no evidence that 
 these depressor substances are specific internal secretions in the same 
 sense as epinephrm. 
 
 43 
 
CHAPTER XTI 
 
 ANIMAL HEAT 
 
 From the earliest ages it must have been noticed that the bodies of 
 many animals, and particularly of men, are warmer than the air 
 and than most objects around them. The ' vulgar opinion ' of 
 Bacon's time, ' that fishes are the least warm internally, and birds 
 the most,' if it does not imply a very extensive knowledge of animal 
 temperature, at least shows that the fundamental distinction of 
 warm and cold-blooded animals, which is to-day more accurately 
 expressed as the distinction between animals of constant tempera- 
 ture (homoiothermal) and animals of variable temperature (poikilo- 
 thermal), had been grasped, and was even popularly known. Since 
 that time the accumulation of accurate numerical results, and the 
 advance of physical and physiological doctrine, have given us 
 definite ideas as to the relation of animal heat to the metabohc 
 processes of the body. It is impossible to understand the present 
 position of the subject without an elementary knowledge of the 
 science of heat. For this the student is referred to a textbook of 
 physics. All that can be done here is to preface the physiological 
 portion of the subject by a few remarks on the physical methods and 
 instruments employed: 
 
 Section I. — Thermometry and Calorimetry. 
 
 Temperature. — Two bodies are at the same temperature if, when 
 placed in contact, no exchange of heat takes place between them. 
 They are at different temperatures if, on the whole, heat passes from 
 one to the other, and that body from which the heat passes is at the 
 higher temperature. It is known by experiment that if two bodies of 
 different temperature are placed in contact, heat will pass from one to 
 the other till they come to have the same temperature. If, then, we 
 have the means of finding out the temperature of any one body, we 
 can arrive at the temperature of any other by placing the t^^-o in con- 
 tact for a sufficiently long time, under the proviso that the quantity of 
 heat necessary to bring the temperature of the first body, which may be 
 called the ' measuring ' body, to equality with that of the second is so 
 small as not to make a sensible difference in the latter. This is the 
 principle on which thermometric measurements depend. A mercurial 
 thermometer consists of a quantity of mercur\' ordinarily contained in 
 a thin glass bulb, the cavity of which is continued into a tube of very 
 
 674 
 
THERMOMETRY AND CALORIMETRY 675 
 
 fine bore in the stem. Like most other substances, mercury expands 
 when the temperature rises, and contracts when it sinks, and the amount 
 of expansion or contraction is shown by the rise or fall of the mercurial 
 column in the stem of the thermometer. The point at which the 
 meniscus stands when the bulb is immersed in melting ice or ice-cold 
 water is, on the centigrade scale, taken as zero ; the point at which it 
 stands when the thermometer is surrounded by the steam rising from 
 a vessel of boiling water is taken as 100 degrees. The intermediate 
 portion of the stem is divided into degrees and fractions of degrees. 
 When, now, we measure the temperature of any part of an animal with 
 such a thermometer, we place the bulb in contact with the part until 
 the mercury has ceased to rise or fall. We know then that the mercury 
 has ceased to expand or contract, and therefore that its temperature 
 is stationary, and presumably the same as that of the part. It is to 
 be noted that we have gained no information whatever as to the amount 
 of heat in the body of the animal. We have only observed that the 
 mercury of the thermometer when its temperature is the same as that 
 of the given part expands to an extent marked by the division of the 
 scale at which the column is stationary. And we know that if the 
 mercury rises to the same point when the thermometer is applied to 
 another part, the temperature of the latter is the same as that of the 
 first part ; if the mercury rises higher, the temperature is greater ; if 
 not so high, it is less. The thermometer, then, only informs us whether 
 heat would flow from or into the part with which it is in contact if 
 the part were placed in thermal connection with any other body of 
 which the temperature is known. In other words, the temperature is 
 a measure of the heat ' tension,' so to speak; and difference of tempera- 
 ture between two bodies is analogous to difference of potential between 
 the poles of a voltaic cell (p. 724), or to difference of level between the 
 surface of a mill-pond and the race beiow the wheel. 
 
 The temperature of an animal is measured in one of the natural 
 cavities, as the rectum, vagina, mouth, or external ear, or in the axilla, 
 or at any part of the skin. For the cavities a mercury thermometer 
 is nearly always used ; the ordinarj^ little maximum thermometer is most 
 convenient for clinical purposes. The temperature of the skin may be 
 measured by an ordinary mercury thermometer, the outer portion of 
 the bulb of which is covered by some badly conducting material. An 
 uncovered thermometer, heated nearly to the temperature expected, 
 will also give results sufficiently accurate for most purposes, especially 
 if the bulb is flat or in the form of a flat spiral, which can be easily 
 applied to the surface. A theoretically better method, but more 
 laborious in practice, is the use of a thermo-electric junction, or a resist- 
 ance thermometer formed of a grating cut out of thin lead-paper or tin- 
 foil (Fig. 220). This is especially useful for comparing the temperature 
 of two portions of skin . The temperature of the solid tissues and liquids 
 of the body may also be measured or compared by the insertion of mer- 
 curial or resistance thermometers or thermo-electric junctions (p. 764). 
 
 Calorimetry. — The quantity of heat given off by an animal is generally 
 measured by the rise of temperature which it produces in a known 
 mass of some standard substance. Sometimes, however, as in the ice- 
 calorimeter of Lavoisier and Laplace, and the ether calorimeter of 
 Rosenthal, a physical change of state — in the one case liquefaction of 
 ice, in the other evaporation of ether — is taken as token and measure 
 of heat received by the measuring substance, the number of imits of 
 heat corresponding to liquefaction of unit mass of ice or evaporation of 
 unit mass of ether being known. The unit generally adopted in the 
 measurement of heat is the quantity required to raise the temperature 
 
r.76 
 
 ANIMAL HEAT 
 
 G 
 
 of a kilogramme of water 1° C, which is called a calorie,* or kilocalorie 
 or large calorie. The thousandth part of this, the quantity needed to 
 raise the temperature of a gramme of water by 1°, is termed a small 
 calorie or millicalorie or gramme-calorie. 
 
 In the calorimeters which have been chiefly used in physiology either 
 water or air has been taken as the measuring substance. The simplest 
 form of water calorimeter is a box with double walls, the space between 
 whi' h is filled with a weighed quantity of water. The animal is placed 
 inside the vessel, and the temperature of the water notetl at the begin- 
 ning and end of the experiment. Suppose that the quantity of water 
 is 10 kilos, and that the temperature rises 1° in thirty minutes, then the 
 amount of heat lost by the animal is 
 ID calories in the half -hour, or 480 
 calories in the twenty-four hours; and 
 if the rectal temperature is unchanged, 
 this will also be the amount of heat 
 produced. 
 
 Here we assume (i) that all the heat 
 lost by the animal has gone to heat the 
 water and none to heat the metal of the 
 calorimeter; (2) that none has been 
 radiated away from the outer surface of 
 the latter. The first assumption will 
 seldom introduce any sensible error in a 
 prolonged physiological experiment ; but 
 it is very easy to determine by a separate 
 observation the water-equivalent of the 
 calorimeter — that is, the quantity of 
 water whose temperature will be raised i ° 
 by a quantity of heat which just suffices 
 to raise the temperature of the metal by 
 1° (p. 721). Then the water-equivalent 
 is added to the quantity of water actu- 
 ally present, and the sum is multiplied by 
 the rise of temperature. If the tempera- 
 ture of the room is constant, as will be 
 approximately the case in a cellar, any 
 error due to interchange of heat between 
 the calorimeter and its surroundings may be eliminated by making the 
 initial temperature of the water as much less than that of the air as the 
 final temperature exceeds it. Then if the loss of heat by the animal is 
 uniform, as much heat is gained during the first half of the experiment 
 by the calorimeter from the air as is lost by it to the air during the last 
 half. Or, without lowering the temperature of the water, the amount 
 of heat lost by the calorimeter during an experiment may be previously 
 determined by a special observation, and added to the quantity cal- 
 culated from the observed rise of temperature. Or, finally, two similar 
 calorimeters may be used, one containing the animal and the other a 
 hydrogen flame, or a coil of wire traversed by a voltaic current, which 
 is regulated so as to keep the temperature the same in the two calorim- 
 eters. From the quantity of hydrogen burnt, or electricity passed, 
 the heat-production of the animal can be calculated. 
 
 In Atwater's great respiration calorimeter (Fig. 221) both the heat 
 production and the respiratory exchange are measured. The heat pro- 
 duced by the person in the calorimeter is carried away from it by a 
 
 * The student should carefully note that when the term ' calorie ' is used 
 without qualification, a large calorie, i.e., 1,000 gramme-calories, is meant. 
 
 w 
 
 Fig. 220. — Resistance Thermom- 
 eter for measuring Temperature 
 of Skin. G, grating of lead- 
 paper, attached to a cover -slip, 
 and mounted on a holder; W, 
 W, wires to the Wheatstone's 
 bridge. An increase of tem- 
 perature causes an increase in 
 the resistance of the lead. The 
 balance of the bridge is thus dis- 
 turbed. By experimental grad- 
 uation the temperature value 
 of the deflection, or of the change 
 of resistance that balances it, is 
 known (p. 725). 
 
THERMOMETRY ASf) CALORIMETRY 
 
 677 
 
 stream of water nowinf^ tlirou^h llic c li.unl)cr in a scries of tubes, the 
 temperature within the calorimeter beiiiK kept constant by regulating 
 the temperature and vch)city of the entering stream of water. The 
 quantity of the escaping water and tlie increase in its temperature are 
 measured, and the heat-prochiction can tlien be calculated. The 
 apparatus consists of a chamber in wlucii a human being can liv^c for 
 several days and nights. A stream of air is supplied, and the chemical 
 changes produced in this arc investigated in the manner already 
 described (p. J 40). 
 
 Fig- -21- — Respiration Calorimeter (Atwater). Interior of chamber. A corner (f 
 the inner copper wall is supposed to be taken away. The ventilating air-current 
 enters the chamber at the lower end of W, and leaves the chamber through the- 
 long tube fastened above W. The copper tubes H, H are surrounded by copper 
 discs I, I, fastened on them like a string of beads to increase the surface. These 
 tubes constitute the arrangement through which the stream of water flows which 
 removes the heat formed in the chamber. J, J are copper troughs which receive 
 the water dropping from H, H. M, .M, M are electrical thermometers which show 
 the temperature of the chamber; N, N, similar thermometers which show the 
 temperature of the copper wall. 
 
 This calorimeter, improved in various ways, has served as the model 
 for all subsequent constructions used for calorimetrical studies in man. 
 A large amount of work of fundamental importance, both on normal 
 and diseased persons, has already been carried out, especially by Bene- 
 dict and by Lusk with their numerous co-workers, and our quantitative: 
 knowledge of the energy transformations in the body has been notably 
 extended. 
 
678 
 
 AXIMAL HEAT 
 
 All the modern respiration calorimeters permit the direct estimation 
 not only of the carbon dioxide produced, but also of the oxygen con- 
 sumed. This allows the amount of heat to be calculated indirectly 
 (so-called indirect calorimetry), as well as measured directly. For if we 
 know how much of the oxygen taken in goes to oxidize protein, fat and 
 carbohydrates, respectively, we can calculate the amount of heat pro- 
 duced in the body with a given consumption of oxygen. The amount of 
 protein oxidized is easily obtained from the nitrogen excretion. The 
 respiratory quotient (corrected for the influence of the protein meta- 
 bolized) informs us, with certain limitations, as to the proportions of fat 
 
 Fig. 222. — Qinical Respiration Calorimeter. The patient is shown on the Led half 
 way in. The tube of a stethoscope strapped over the heart is seen. Coiled up 
 on the wall is the (electric resistance) rectal thermometer not yet inserted. To 
 the right of this is shown a telephone for communicating with the patient if 
 necessary (Lusk, et al-)- 
 
 and carbohydrates being consumed. Thus, a respiratory quotient of 
 070 represents the oxidation of fat alone, a quotient of i-oo the oxida- 
 tion of carbohydrate alone (p 241). 
 
 If the respiratory quotient is intermediate between these extremes — 
 e.g., 0-85, it would represent the oxidation of fat and carbohydrate in 
 such a proportion that 49 per cent, of the number of calories produced 
 are due to the burning of carbohydrate, and 51 per cent, to the oxidation 
 of fat. With this respiratorv quotient, the absorption of 1 litre of 
 oxygen would indicate that 4,^63 gram-calories had t^en produced in the 
 b©dy. In a similar way the amount of heat produced can be calculated, 
 
THERMOMETRY AND CALORIMETRV 
 
 670 
 
 although in general with less accuracy, from the amount of carbon 
 dioxide given off. With careful technifjue, the results obtained by 
 indirect agree closely with those obtained by direct calorimetry, which 
 is tantamount to saying that the law of conservation of energy holds 
 in the animal body (Rubner). 
 
 Air calorimeters have sometimes been used for physiological pur- 
 poses, but at present they have little more than historical interest. 
 A diagram of one is shown in Fig. 223. Such calorimeters are really 
 thermometers with an immense radiating surface, for only a small 
 proportion of the heat given off by the animal goes to heat the measuring 
 substance. The heat required to raise the temperature of a litre of air 
 by 1° is very small in comparison with that required to raise the tern- 
 
 
 Fig. 223. — Air Calorimeter: (/.) Cross-Section; (//.), Longi- 
 tudinal Section. A, cavity of calorimeter for animal ; B, copper 
 cylinder corrugated so as to increase the radiating surface; C, air 
 space enclosed between B and a concentric copper cylinder F ; 
 C is air-tight, and is connected by the tube 2 with the manometer M. The 
 other end of the manometer is connected with an exactly similar calorimeter, in 
 which a hydrogen flame is burnt in the space corresponding to A, or in which the air 
 in A is heated by a coil of wire traversed by an electrical current. The flame or 
 current is regulated so as to keep the coloured petroleum or mercury in the manometer 
 M at the same level in both limbs; the amount of heat given off to the one calorimeter 
 by the flame or current is then equal to that given off by the animal to the other. 
 D is an external cylinder of copper or tin perforated by holes (6, 7) at intervals. The 
 purpose of it is to prevent draughts from affecting the loss of heat from F; 4, 5, are 
 tubes through which thermometers can be introduced into C; i is the terminal of a 
 spiral tube, which is coiled in the end portion of the air space C. The sections of the 
 coils are indicated by small circles. The other end of the spiral tube is 3; through 
 this tube air is sucked out, and so the proper ventilation of the animal is kept up. 
 The object of the spiral arrangement is that the air aspirated out of A may give up 
 its heat to the air in C before passing out. E is a door with double glass walls. 
 
 perature of a litre of water by the same amount. Hence a given 
 quantity of heat raises the temperature of an air calorimeter much more 
 than that of a water calorimeter of the same dimensions ; and the loss 
 of heat to the surroundings being proportional to the elevation of tem- 
 perature, in the water calorimeter the chief part of the heat is actuallv 
 retained in the water, while in an air calorimeter the greater portion 
 passes through the air space, and is radiated away. When the amount 
 of heat lost by the calorimeter becomes equal to that gained from the 
 animal, the ' steady ' reading of the instrument is taken, and from this 
 the heat-production can be deduced by an experimental graduation of 
 the apparatus. The one advantage of an air calorimeter is that it 
 follows more closely rapid variations in th« heat-production of th« 
 
68o AXJMAL 1 1 LAV 
 
 animal, or, to spc.iU more conccUy, in the heat loss. It .should be 
 carefully noted that in calorimctry what is directly measured is the 
 (}uantity of heat fj;i\en out by the animal, not the quantity produced. 
 The t\vo(juantities are identical only when the temperature of the animal 
 has remained unchanged throughout the experiment. If the tempera- 
 ture has fallen, the quantity of heat produced is equal to the quantity 
 measured by the calorimeter minus the difference between the quantity 
 in the animal at the beginning and at the end of the observation. This 
 difference is equal to the average specific heat of the animal multiplied 
 by its weight and by the fall of temperature. It can Ije approximately 
 found by multiplying the weight (in kilogrammes or grammes) by the 
 fall of rectal temperature (in degrees), since the average specific heat 
 of the body is not \'ery difficult from that of water, and the specific 
 heat of water is taken as unity. 
 
 The diticrential micro-calorimeter of A. \'. Hill Is the most accurate 
 apparatus for measurjug \cry small quantities of heat — e.g., the heat 
 given off by resting muscles, or by muscles during the process of heat 
 rigor, or in such reactions as the souring of milk by the lactic acid 
 bacillus. It consists of a pair of Dewar flasks (ordinary thermos oi 
 vacuum bottles), in which loss of heat to the surroundings is greatly 
 hindered by exhausting the air from the space enclosed by the double 
 wall of the flask. The bottles are packed in sawdust in cylindrical tins. 
 The tissue or liquid experimented with is put into one flask, and water 
 into the other (control) flask, and the amount of the water is adjusted 
 so that the change of temperature of each flask due to conduction and 
 radiation to or from the outside is the same. Loss of heat is thus 
 automaUcally eliminated, and from the excess of temperature of the 
 experimental over that of the control flask the heat production in the 
 former can be calculated. The temperatures are measured by thermo- 
 electric junctionsof an alloy called constantan and copper, one junction 
 being in each flask. To economize time in making such observations, 
 a number nf pairs of flasks can be simultaneously employed. The 
 apparatus is so sensitive that a liberation in ten hours of i gramme- 
 calorie per gramme of contents of the flask can be followed and esti- 
 mated with an error not exceeding 3 per cent. 
 
 Body-Temperature. — All the higher aninials (mammals and birds) 
 have a practically constant internal temperature (fowl 41° to 44° C, 
 mouse 37*^ to '^^°, dog 38° to 39°, man 37° in the rectum), but a few 
 hibernating mammals, such as the marmot, are homoiothermal in 
 summer, poikilothermal during their winter sleep. In the lower 
 forms the body-tem])erature follows closely the temperature of the 
 environment, and is never very much above it (frog 0-5° to 2° above 
 external temperature). Both in a frog and in a pigeon heat is 
 evolved as long as life lasts; but per unit of weight the amphibian 
 produces far less than the bird, and loses far more readily what it 
 does produce. The temperature of the frog may be 25° C. in June 
 and 5° in January. The structure of its tissues is unaltered, and 
 their vitality unimpaired by such violent fltictuations. But it is 
 necessary, not only for health, but even for life, that the internal 
 temperature (the temperature of the blood) of a man should vary 
 only within relatively narrow limits around the mean of '^y'^ to 
 38° C. 
 
INCOME AND EXPENDITURE OF THE BODY 68 1 
 
 Why it is that a comparatively high temi^erature slio'ild be 
 needed for the full physiological activity of the tissues of a mammal, 
 while the, in many respects, similar tissues of a ftsh work perfectly, 
 although perhaps more sluggishly, at a much lower temperature, is 
 not quite clear. Nor do we know the precise significance of that 
 relative constancy of temperature in the warm-blooded animal, 
 which is as important and peculiar as its absolute height. The 
 higher animals must possess a superior delicacy of organization, 
 hardly revealed by structure, which makes it necessary that they 
 should be shielded from the shocks and jars of varying temperature 
 that less highly endowed organisms endure with impunity. Leaving 
 the discussion of the local differences and periodic variations of the 
 temperature of warm-blooded animals to a future page, let us 
 consider now the mechanism by which the loss of heat is adjusted 
 to its production, so that upon the whole the one balances the other. 
 
 Section II. — Income and Expenditure of the Body in Terms 
 
 OF Energy. 
 
 Heat-Loss. — Heat is lost (i) from the surfaces of the body by 
 radiation, conduction, and convection; (2) as latent heat in the 
 watery vapour given off by the skin and lungs; and (3) in the 
 excreta. Even in the bulky excrement of herbivora a compara- 
 tively trifling part of the total heat is lost. The second channel 
 of elimination is much more important; the first is in general the 
 most important of all. 
 
 The loss of heat by direct radiation from a portion of the skin or 
 clothes, or from hair, fur, or feathers covering the skin, may be measured 
 by means of a thermopile or a resistance radiometer (bolometer). Tlie 
 latter instrument is similar in principle and allied in construction to the 
 resistance thermometer used in measuring superficial temperatures, 
 and already described (Fig. 220, p. 676). It may consist of a grating 
 of lead-paper 6r tinfoil fixed vertically in a small box which protects 
 it from draughts. The box has a sliding lid, which is kept closed till 
 the moment of the observation, when it is withdrawn and the portion 
 of skin applied to the opening at a fixed distance (5 to 10 cm.) from the 
 grating. The intensity of radiation depends on the excess of tempera- 
 ture of the radiating surface over that of the surroundings, as well as 
 on the nature of the surface. The uncovered parts of the skin (face 
 and hands in man) radiate more per unit of area than the clothes or 
 hair; and the warm forehead mare than the comparatively cool lobe 
 of the ear or tip of the nose. When a man is sitting at rest in a still 
 atmosphere, pure radiation plays a greater, and conduction and con- 
 vection play a smaller, part in the total loss of heat from the skin than 
 when he is walking about or sitting in a draught. The more rapidly 
 the air in contact with the skin and clothes is renewed, the lower, other 
 things being equal, the temperature of the radiating surfaces is kept, 
 the greater is the loss of heat by conduction to the adjacent portions of 
 air, and the smaller the loss by radiation to the walls of the room, the 
 furniture, and other surrounding objects. It is probable that, under 
 
6^7 
 
 ANIMAL HEAT 
 
 the moot favourable conditions, the amount of heat lost from the sur- 
 face by true radiation does not exceed the amount lost by conduction 
 and convection. 
 
 The loss of heat by evaporation of water from the skin can be calcu- 
 lated if we know the quantity of water so given off. For a gramme of 
 water at the ordinary temperature (say 15° C.) needs 0-555 calorie to 
 convert it into aqueous vapour at the average temperature of the skin. 
 If we take the average quantity of water excreted as sweat in twenty- 
 four hours as 750 c.c, this will be equivalent to a heat-loss of 416*25 — 
 say, in round numbers, 400 larg^ calories. 
 
 The quantity of heat given off by the lungs may be also deduced 
 from calculation, the data being (i) the weight, temperature, and 
 specific heat of the expired air, and (2) the excess of water it contains 
 in the form of aqueous vapour over that contained in the inspired air. 
 Helmholtz calculated the quantity of heat needed to warm the air 
 expired by a man in twenty-four hours from an initial temperature oi 
 20° to body-temperature, at 70 calories, and that required to evaporate 
 the water given off by the lungs at 397, making the total heat-loss by 
 the lungs in these processes from 400 to 500 calories. A certam amount 
 of heat is also absorbed in connection with the escape of the carbon 
 dioxide. The reason why a great deal more water and therefore more 
 heat is not given off by the lungs with their enormous surface, and the 
 high degree of imbibition (p. 426) of the epithelium of the alveoli, is 
 
 Fig. 224. — Calorimeter for 
 Measuring Heat given off in 
 Respiration. B, copper tube 
 with mouthpiece, connected with 
 the thin brass capsule 4; 4 is 
 connected with a similar capsule 
 3 by a short tube, which passes 
 out from it at the side opposite 
 to that at which B enters; 2 and 
 I are similar capsules. From i 
 an outlet tube C passes off. 
 The whole is set in a copper 
 cylinder A filled with water. 
 A piece is supposed to be cut out 
 of .\ in order to show the cap- 
 sules. A is placed in another 
 wider copper cylinder. 
 
 that the air is already saturated with aqueous vapour, or nearly so, 
 before it reaches the alveoli. By direct calorimetric observations it 
 was found that a man of 70 kilos weight gave off in normal breathing, 
 with an air-temperature of 12° to 15° C, from 350 to 450 calories. 
 Forced respiration, as might be expected, increased the amount often 
 to double or even treble. A diagram of a calorimeter for measuring 
 the heat given off in respiration is shown in Fig. 224. (Se« Practical 
 Exercises, p. 721) 
 
 The following table gives an analysis of the heat-loss of an average 
 man. It must be understood that the figures are only approximate. 
 In round numbers we may say that two-thirds of the heat-loss is 
 due to radiation, conduction, and convection, and one-third to the 
 evaporation of water. 
 
INCOME AND EXPENDITURE OF ENERGY G83 
 
 (Evaporation of water 
 Radiation* - - - - 
 Conduction (and convection) 
 _ I Evaporation of water - 
 
 l-ungs|p^^^^^g the expired air - 
 
 Heating the excreta 
 
 Per Cent. 
 
 Calories 
 
 25 ' 80 
 40 J 
 
 400 
 
 650 
 
 1,000 
 
 %] .7-5 
 
 .400 
 I 70 
 
 2-5 
 
 70 
 
 2 
 
 590 
 
 In the rabbit, according to Nebelthau, the heat lost by evaporation 
 of water is about 16 per cent, of the whole, or about half the proportion 
 in man, according to the above calculation. This is not surprising 
 when we reflect that the rabbit does not sweat, and drinks comparatively 
 little water. 
 
 Sources of the Heat of the Body — Heat Production. — Some heat 
 enters the body as such from without — in the food, and by radiation 
 from the sun and from fires. The ultimate source of all the heat 
 produced in the body is the chemical energy of the food substances. 
 For this reason, the distinction between much of the subject matter 
 of this chapter and that of Chapter X. is scarcely even a formal 
 one. Whatever intermediate forms this energy may assume— 
 whether the mechanical energy of muscular contraction; the energy 
 of electrical separation by which the currents of the tissues are 
 produced; the energy of the nerve impulse; or the energy, be it 
 what it may, which enables the living cells to perform their chemical 
 labours — it all ultimately, except so far as external mechanical 
 work may be done, appears in the form of heat. As already pointed 
 out (p. 544), the fraction of the total energy liberated in the pro- 
 cesses of hydrolytic cleavage is comparatively small. Most of the 
 heat is set free in the oxidative processes which accompany or follow 
 the hydrolytic changes. 
 
 Thus the energy-value of a gramme-molecule (p. 426) of maltose, 
 cane-sugar, or lactose is a little more than 1,350 calories; that of the 
 two gramme-molecules of dextrose formed by hydrolysis of the maltose 
 is I347'4 calories; that of the gramme-molecule each of dextrose and 
 levulose formed from the cane-sugar, i349'6; and that of the gramme- 
 molecule each of dextrose and galactose formed from the lactose, 
 1 343-6 calories. That is to say, the hydrolysis of these disaccharides 
 to monosaccharides, which is the first step in their metabolism, is accom- 
 plished with the liberation of very little heat. The same is true of the 
 splitting of the fats and proteins. The dried residue of a filtered pan- 
 creatic digest was found to yield, when burned in the calorimetric 
 bomb, only 10 per cent, less heat than the same weight of dry meat. 
 Much the greater part of this deficiency was accounted for by the leucin 
 and tyrosin which had crystallized out, and the derivatives of higher 
 fatty acids in the meat, as these would be removed from the digest 
 by filtration. 
 
 It has been shown that the law of the conservation of energy holds 
 for the animal body; in other words, there is a practically exact 
 
 * ITie relative amounts lost by radiation and conduction cannot b« accur- 
 ately fixed. The proDortion is extremely variable. 
 
684 AXIMAL HEAT 
 
 agreement between the potential energy of the food and the kinetic 
 energy into which it is transformed in the body both during rest 
 and during work. This kinetic energy is represented by the heat 
 'given off plus the heat-equivalent of any mechanical work done 
 (Atwater). In other words, the food, whether it is burned in a 
 calorimeter to simple end-products hke carbon dioxide and water, 
 or more slowly oxidized in the body, yields the same amount of 
 heat, provided alwa3^s that in both cases it is entirely consumed, and 
 that no work is transferred to the outside. In the body the com- 
 bustion of carbo-hydrates and fats is complete; but the nitrogenous 
 residues of the proteins — urea, uric acid, etc. — can be further 
 oxidi/.ed, and the remnant of energy which they yield must be 
 taken into account in any calculation of the total heat-production 
 founded on the heat of combustion of the food substances. Froni 
 careful experiments, it has been found that a gramme of dry protein 
 (egg-albumin), when burned in a calorimeter, yields 5735 calorics 
 of heat, a gramme of dextrose 3742, and a gramme of animal fat 
 9-500 calories (Stohmann). 
 
 Calories. 
 
 Heat-equivalent of i gramme of albumin - 5 "735 
 
 Albumin (minus urea produced from it) - - 4*949 
 
 Cane-sugar ----- 3'955 
 
 Kreatin (water-free) - - - - 4*275 
 
 Starch ------ 4-182 
 
 In applying such results to the calculation of the heat-production of 
 the bodv, it is not sufficient to deduct from the heat of combustion of 
 the proteins the heat which the residual urea would yield if fully 
 oxidized. For other incompletely oxidized products arise from pro- 
 teins when consumed in the body, and Rubner has shown, by actually 
 determining the heat of combustion of the urine and faeces, that the 
 real equivalent of a gramme of albumin is at most only 4'4-o calories. 
 The heat-equivalent of our less liberal spccunen diet (p. 625) will be 
 approximately: ^,^^.^^ 
 
 Protein, 95 grammes x 4*420 = 41 9*9 
 
 Fat, 80 grammes x 9*500 = 760-0 
 
 Carbo-hydrate (reckoned as 
 
 dextrose), 320 grammes x 3*74- = ^'^97 *4 
 
 2, 377 "3 
 
 The heat-equivalent of the more generous specunen diet (p. 627) would 
 be 2,878 calories. 
 
 But this is the diet of a man doing a fair day s work, and to get the 
 quantitv of energy which actually appears as heat, the heat-equivalent 
 of the inechanica'l work performed must be deducted. A fair day's 
 work is about 150,000 kilogramme-metres— that is, an amount equal 
 to the raising of 150,000 kilogrammes to the height of a metre. Now. 
 a kilogramme-degree or calorie of heat is equivalent to 425-5 kilo- 
 gramme-metres of work, and a kilo gramme -metre to -.-;Tr: calorie. 
 The heat-equivalent of the day's work is, therefore,i50,ooox — 7_ = 
 352 calories. Deducting this from the heat-equivalent of the food. 
 
INCOME AND EXPENDITURE OF ENERGY 
 
 685 
 
 we get in round numbers 2,520 large calorics as the heat given off on 
 the more liberal diet. This corresponds fairly well with the calculated 
 heat-loss (p. 081). 
 
 The table on this page, based on the direct calorimetric observations 
 of Atwater and Benedict, shows the average heat-production in a large 
 number of experiments on several individuals at rest and doing measured 
 amounts of work, with a stationary bicycle, for instance. This was 
 connected with a small dynamo, which transformed the greater part 
 of the work into electrical energy. Tlie electrical energy in its turn 
 was changed into heat, the current passing through a lamp. 
 
 1 he heat-production during the hours of sleep, in the second night 
 period, is much less than in the waking hours of rest, and of course 
 enormously less than in the hours of work. After work the heat pro- 
 duction in the period of sleep is only a little greater than after rest. 
 
 As already indicated (p. 683), it is permissible to calculate the heat- 
 production from the diet, and Rubner has done this for various classes 
 of men, reducing everything to the standard of a body-weight of 
 67 kilos. The fasting man, of 67 kilos body-weight, produces 2,303 calo- 
 ries in the twenty-four hours. The class of brain-workers, represented 
 by physicians and of&cials, produce only a little more heat than the 
 fasting man, viz., 2,445 calories. The second class, represented by 
 soldiers (presumably in time of peace) and day-labourers (probably of 
 a cautious and conservative type), work up to 2,868 calories. The 
 third class, composed of men who work with machines and other skilled 
 labourers, attain a heat-production of 3,362 calories. The fourth class, 
 typified by miners (who are engaged, usually by the piece and not by 
 the day, in severe and exhausting toil), produce as much as 4,790 calo- 
 ries. In the fifth and last class, represented by lumberers and other 
 out-of-door labourers (who, in addition to excessive exertion, have 
 often to face intense cold), the heat-production rises to 5,360 calories. 
 The diet of ordinary prisoners in Scotland, doing light work, chiefly of 
 a sedentary character, was found to correspond to 3,115, and that of 
 convicts on ' hard labour ' to 3,707 calories. It is a fair presumption 
 that in Scotch prisons the total heat value supplied is not excessive. 
 From the general agreement of calculated results with actual measure- 
 ments we can safely conclude that most healthy adults produce between 
 2,000 and 3,000 large calories (35 to 40 per kilo of body-weight) on a ' rest' 
 day, or a day of light labour, and between 3,000 and 4,000 (45 to 60 per 
 kilo of body-weight) on a day of hard manual work. 
 
 
 .si 
 
 So 
 K.S 
 
 1 = 
 Ha 
 
 Heat eliminated per Hour. 
 
 Percentage of Total Heat 
 in 24 Hours. 
 
 Day-time. 
 
 Night-time. 
 
 Average 
 
 per Hour 
 
 for 24 
 
 Hours. 
 
 Day-time. 
 
 Night-time. 
 
 7 a.m. 
 
 to 
 I p.m. 
 
 I p.m. 
 
 to 
 7p.m. 
 
 7 p.m. 
 
 to 
 I a.m. 
 
 I a.m. 
 
 to 
 7 a.m. 
 
 7 a.m. 
 
 to 
 I p.m. 
 
 I p.m. 
 
 to 
 7 p.m. 
 
 7 p.m. 
 
 to 
 I a.m. 
 
 I a.m. 
 
 to 
 7 a.m. 
 
 Rest experi- 
 ments - 
 
 Work experi- 
 ments - 
 
 Heat-equiva- 
 lent of work 
 
 Total for work 
 experiments 
 
 2,262 
 4.225 
 
 4,676 
 
 Io6'3 
 2317 
 
 58-5 
 290-2 
 
 104.4 
 
 235-6 
 56-8 
 
 292-4 
 
 98-3 
 I18-I 
 
 iiS-i 
 
 67-9 
 
 78-4 
 
 78.4 
 
 94-3 
 166-6 
 
 194-8 
 
 28-2 
 
 37-5 
 
 27.7 
 
 37-2 
 
 26-1 
 15-2 
 
 18-0 
 lO-I 
 
686 ANIMAL HEAT 
 
 ^^^ at has been already said in connection with standard dietaries 
 (p. 624) indicates that the work of the world might possibly be accom- 
 plished as well with a smaller transformation of energy in the human 
 machine, at least in the more prosperous countries, and that in the 
 body, as in an engine, more careful ' stoking ' might result in a saving 
 of fuel. It is extremely improbable, however, that any argument of 
 tliis sort will have much effect upon the deep-rooted dietetic habits of 
 mankind. 
 
 In any case it must be carefully remembered that the question of 
 the minimum amount of protein necessary in a permanent diet is 
 quite distinct from the question of the minimum heat value of the diet 
 for a man of given body-weight doing a definite amount of work under 
 definite conditions. Whether the protein allowance be scanty or liberal, 
 the total heat value cannot be permanently reduced below a certain 
 minimum depending on the work done, the climate, and other conditions. 
 
 Basal Metabolism.— The total metabolism of a normal man or animal 
 as measured by the heat-production is so greatly affected by the taking 
 of food, by the kind as well as the quantity of the food, by the amount 
 and nature of the work done, even by the position of the body, that for 
 many pui poses it is necessary to simplify the conditions in order to 
 disentangle the various factors. The greatest degree of simplification 
 which is practicable is attained when the observations are made upon a 
 subject a considerable time (at least twelve, but better eighteen hours) 
 after the last meal, in the recumbent posture, and in a condition of rest 
 as absolute as possible. The metabolism under those conditions is 
 termed the basal metabolism. In 89 normal men, the basal metabolism, 
 indirectly calculated from the calorific value of the oxygen consumed, 
 was found to vary from 08 to 13 calories per kilo of body- weight, and 
 from 28-9 to39 calories per square metre of surface per hour (Benedict). 
 The average heat-production per square metre of surface was 34-7 
 calories per hour (or calculated on surface measurements made by newer 
 methods, 40 calories per hour). This agrees very closely with the 
 average obtained by direct determination of the heat with the ' bed ' 
 calorimeter (Du Bois). 
 
 Specific Dynamic Action of the Food-Stuffs. — The old idea that the 
 increase in the metaboHsm above the basal level which follows the inges- 
 tion of food is chiefly due to increased work of the alimentary canal 
 in digestion and absorption has been disproved. A large meal of meat 
 given to a dog may cause the heat-production to be nearly doubled. 
 This phenomenon is spoken of as the specific dynamic action of the 
 food-stuffs. It is especially well marked in the case of the proteins. 
 The best evidence is that the action is due to some kind of stimulation 
 of the protoplasm by decomposition products of the amino-acids; in 
 the case of alanin, for instance, probably lactic acid produced in the 
 process of deaminization. It is not merely the oxidation of the amino- 
 acids themselves which is mainly responsible for the increase in meta- 
 bolism. P'or it has been found that glycoco'.l and alanin when fed to 
 phlorhizinized animals, in which they do not yield energy by oxidation, 
 being excreted as sugar and urea, still exert the specific dynamic action, 
 and increase the heat-production (Lusk). 
 
 The Seats of Heat-Production. — We have already recognized the 
 skeletal muscles as important seats of heat-production. A frog's 
 muscle, contracting under the most favourable conditions, does not 
 
INCOME AND EXPENDITURE OF ENERGY 
 
 6«7 
 
 convert at most more than one-fourth or one-fifth of the energy it 
 expends into mechanical work; at least three-fourths or four-fifths 
 of the energy appears as heat. The muscles of mammals and of 
 man in the intact body work, upon the whole, more economically 
 than the excised frog's muscles at their maximum efficiency. Under 
 the best conditions — ^that is. when the work is moderate and not too 
 
 NOTPiiNTS. ■;o,vs 
 
 i PCTENTIAL ENCR-Y. CALORIES 
 
 i DIETARY STANDARDS. 
 
 jUBSistence diet (playfaib) 
 
 VAN AT MODERATE WORK^OIt) 
 
 MAN AT HARD WORK cATWATEr") 
 
 '.^AN WITH MODERATE EXERCISE CpLAYFAIR) 
 
 ACTUAL DIETARIES. 
 
 ■i^s^^il 
 
 l^l 
 
 ■■■ 
 
 
 Hiiini^^^ 
 
 ^kH 
 
 1 I^B^^^HI 
 
 Wlillli^^^^^^^ 
 
 Fig. aas. — Diagram showing the Heat-equivalent of various Dietaries. 
 A, proteins; B, fats; C, carbo-hydrates; D, heat -equivalent, 
 
 rapidly done — about one-third of the chemical energy expended 
 may be transformed into mechanical work, and only two-thirds into 
 heat (Zuntz). In hard work three-quarters of the energy may be 
 changed into heat; but even then the- efficiency of the muscles far 
 outstrips that of the best steam-engines, which convert only an 
 eighth of the total energy into work. 
 
 Notwithstanding the splendid efficiency of the muscular machine, 
 the gaseous metabolism easily rises during muscular work to five 
 times, and in severe labour to nine times its resting value, although 
 persons inured to toil work more economically than amateurs. 
 In one of Atwater's ' severe work ' experiments the work done in 
 twenty-four hours had a heat-equivalent of 1,482 calories (equal to 
 
688 
 
 ANIMAL HEAT 
 
 over 630,000 kilogramme-metres). The total heat-production (in- 
 cluding the equivalent of the work) was 9,314 calories. It is not 
 difficult to show that the greater part of the metabolism and heat- 
 production of a man doing ordinary work is accounted for by the 
 contraction of the voluntary and involuntary muscles. 
 
 Even in muscles completely at rest metabolism goes on. and some 
 heat is produced. In resting frogs, newts, and snakes, the rate of heat- 
 production per gramme of tissue is about 0'5 gramme-calorie per lioiir 
 with a room temperature of 20° C, or about a third of that of a resting 
 man (Hill). Of course, this must be above tlie heat-production of 
 muscles of these poikilothermal animals absolutely at rest. For not 
 only must the active heart and glands contribute something, but the 
 muscles of frogs lying huddled in a micro-calorimeter not only maintain 
 the normal tonus, but are certainly liable to contract acti\-ely from 
 time to time. By analyzing the gases of the arterial and venous blood, 
 Zuntz compared the oxygen consumption and carbon dioxide produc- 
 tion in the hind-legs of dogs when the sciatic and anterior crural nerves 
 were divided and intact. In both cases the muscles were at rest in 
 the ordinary' sense. But in the second experiment the central ' tonus ' 
 (p. 917) was preserved, while in the first it was abolished. In one 
 experiment in which the nerves were intact the oxygen consumed 
 amounted to 122 c.c, and the carbon dioxide produced to 1*32 c.c, 
 per kilo of tissue per minute. In the experiment in which the nerves 
 were severed, the corresponding numbers were 0-68 c.c. for the oxygen, 
 and 0'63 c.c. for the carbon dioxide. Although it is probable, from 
 the results of Chauveau and Kauffmann already referred to (p. 271), 
 that these figures are too low for the normal resting muscle, they still 
 demonstrate that, even in the absence of innervation from the central 
 nervous system, the metabolism, and therefore the heat-production of 
 the muscles, are by no means negligible; 0'68 c.c. of oxygen per minute 
 corresponds to 40-8 c.c. per hour, or more than one-tenth of the oxygen 
 consumption per kilo per hour of a fasting dog lying at rest (Zuntz). 
 
 If the work of the heart is taken as 16.600 kilogramme-metres in 
 twenty-four hours (p. 138), the total heat produced by this organ will 
 be equi\-alent (on the assumption that it converts one-third of its 
 energy into work) to about 50,000 kilogramme-metres, or not much 
 less than 120 calories, since, practically, the whole work is expended 
 in overcoming the friction of the vessels, and finally appears as heat. 
 Enough energy is transformed in twenty-four hours in the heart of the 
 colonel of a regiment of 1,000 men to lift the whole regiment to the 
 height of the mess-table, if it could be all changed into mechanical 
 work. Barcroft and Dixon have calculated the energ>^ of the heart's 
 contraction on the assumption that it is derived from the oxidation 
 of a carbo-hydrate by the oxygen absorbed bv the organ. They con- 
 cluded that the energy set free in the heart of a dog weighing 12 kilos 
 corresponds on the average to 7-86 kilogramme-metres per minute, 
 which is equivalent to 26*6 calories in twenty-four hours. Allowing for 
 the fact that the heart of a small animal pumps more blood in propor- 
 tion to the body-weight than the heart of a large animal (p. 139). this 
 result agrees very well with that deduced from the work of the heart. 
 The work of the inspiratory muscles may be reckoned at 13,000 kilo- 
 gramme-metres, equal to 30-5 calories, and the heat produced by them 
 at, say, 90 calories. In sum, the muscular work of the circulation and 
 
INCOME AND EXPENDITURE OF ENERGY 689 
 
 respiration is responsible for the production of about 210 calories 
 (without including the heat produced by the smooth muscle of the 
 bronchi and bloodvessels), or nearly one-twelfth of the total produc- 
 tion of a man doing ordinary labour. 
 
 The glands, and then the central nervous system, rank after the 
 muscles, though at a great distance, as seats of heat-production. 
 The liver and brain (?) are the hottest organs in the body; and that 
 this is not altogether due to their being well protected against loss 
 of heat is shown, in the case of the hver, by the excess of tempera- 
 ture of the blood of the hepatic over that of the portal vein. In 
 view, however, of the exaggerated importance which some have 
 given to these organs as foci of heat-production, it may be well to 
 point out that although many of the chemical changes in the animal 
 body are undoubtedly associated with the setting free of heat 
 (exothermic reactions), other, and not less weighty and character- 
 istic, reactions may cause the absorption of heat (endothermic 
 reactions) ; and it is possible that some of the syntheses which many 
 of the tissues are capable of performing may be included in this 
 latter category. For example, when urea is decomposed so as to 
 yield ammonium carbonate (p. 478), heat is set free. We must 
 assume that if ammonium carbonate were transformed into urea in 
 the liver, an equal amount of heat would be, on the whole, absorbed. 
 So that the heat-production of an organ may depend, not only upon 
 the quantity, but also upon the quality, of its chemical activity. 
 In all the tissues, including the muscles, it is necessary to assume 
 that some of the energy transformed is expended in so-called ' resti- 
 tution ' processes — that is, in replenishing the store of nutritive 
 material within the cells and in building up the protoplasm. Claude 
 Bernard observed an excess of 06° C in the temperature of the 
 blood of the hepatic vein over that of the portal during hunger, and 
 as much as i-6° at the height of digestion, although at the beginning 
 of digestion the portal blood was the hotter by 0-4°. But such 
 observations, like the corresponding ones on the salivary glands, are 
 open to many errors, and when we consider the enormous tide of 
 blood which during digestion sets through the portal system, we 
 shall look with suspicion upon results that announce a difference 
 of more than a small fraction of a degree in the temperature of the 
 incoming and outgoing blood of the liver. Probably not less than 
 200 litres of blood pass in twenty-four hours through the hver of a 
 2-kilo rabbit. If the temperature of this blood is raised even one- 
 tenth of a degree in its passage through the hepatic capillaries, this 
 would correspond to a heat-production of 20,000 small calories, or 
 one-tenth of the whole heat produced in the animal. 
 
 In the case of the brain there is some evidence, obtained b^- com- 
 parison of the gases of blood taken from the carotid and from the venous 
 sinuses (torcula Herophili), that the metabolism is feeble as compared 
 
 44 
 
690 ANIMAL HEAT 
 
 even with that of resting muscles (Hill). Nor is it possible to demon* 
 stratc any marked or constant increase when the cerebral cortex is 
 roused to such an active discharge of impulses as leads to general 
 epileptiform convulsions. The rise of temperature of certain regions, 
 especially the occipital portion, of the scalp, which some observers have 
 stated to take place during mental activity, cannot be due to con- 
 duction of heat from the brain through the skull. It might be caused 
 by vaso-motor changes in the scalp, associated with corresponding 
 changes in related areas of the cortex. The alleged increase in the 
 temperature of the brain during intense psychical activity, sometimes 
 to o'2° C, or 0'3° C. above the rectal temperature (Mosso), may also, 
 if genuine, be due to vascular changes. And if we remember how 
 large a proportion of the central nervous system is made up of nerve- 
 fibres, in which no sensible production of heat has ever been demon- 
 strated, it will not appear surprising if even a considerable increase 
 in the metabolism of the really active elements should fail to make 
 itself felt. 
 
 Section III. — Regulation of Temperature or Thermotaxis. 
 
 What, now, is the mechanism by which the balance is maintained 
 in the liomoiothermal animal between heat-production and heat- 
 loss ? In answering this question we have to recognize that both 
 of these quantities are variable, that a fall in the production of heat 
 may be compensated by a diminution of heat-loss, and an increase 
 in the loss of heat balanced by a greater heat-production. 
 
 The loss of heat from the surfaces of the body may be regulated 
 both by involuntary and by voluntary means. It is greatly affected 
 by the state of the cutaneous vessels, and these vessels are under the 
 influence of nerves. A cold skin is pale, and its vessels are con- 
 tracted. In a warm atmosphere the skin is flushed with blood, its 
 vessels are dilated, its temperature is increased; an effort, so to 
 speak, is being made by the organism to maintain the difference of 
 temperature between its surface and its surroundings on which the 
 rate of heat-loss by radiation and conduction depends. A still 
 more important factor in man, and in animals like the horse, which 
 sweat over their whole surface, is the increase and decrease in the 
 quantity of water evaporated and of heat rendered latent. It is 
 owing to the wonderful elasticity of the sweat-secreting mechanism, 
 and to the increase of respiratory activity and the consequent 
 increase in the amount of watery vapour given off by the lungs, 
 that men are able to endure for days an atmosphere hotter than the 
 blood, and even for a short time a temperature above that of boiling 
 water. The temperature of a Turkish bath may be as high as 
 65" to 80° C. Blagden and Fordyce exposed themselves for a few- 
 minutes to a temperatiu-e of nearly 127° C Although meat was 
 being cooked in the same chamber by the heat of the air, they 
 experienced no ill-effects, nor was tlieir body-temperature even 
 increased. But a far lower temperature than this, if long con- 
 
THERMOTAXIS 691 
 
 tinued, is dangerous to life. During the ' hot waves ' not infre- 
 quently experienced in summer in the United States, hundreds of 
 persons have died within a few days from the excessive heat. It is 
 stated that during the unusually hot summer of 1819 the tempera- 
 ture at Bagdad ranged for a considerable time between 108° and 
 120° F. (42° to 49° C), and there was great mortahty. A much 
 higher temperature may be borne in dry air than in air saturated 
 with watery vapour. A shade temperature of 100° F. (377° C.) in 
 the dry air of the South African plateaux is quite tolerable, while a 
 temperature of 85° F. (294° C.) in the moisture-laden atmosphere 
 of Bombay may be oppressive. The reason is that in dry air the 
 sweat evaporates freely and cools the skin, while in moist air, 
 although according to Rubner the loss of heat by radiation and 
 conduction is increased, the loss of heat by evaporation of sweat is 
 diminished in a still greater degree. In saturated air at the body- 
 temperature no loss of heat by perspiration or by evaporation from 
 the pulmonary surface is possible ; the temperature of an animal in 
 a saturated atmosphere at 35° to 40° C. soon rises, and the animal 
 dies. In animals like the dog; which sweat little or not at all on 
 the general surface, the regulation of the heat-loss by respiration is 
 relatively more important than in man. 
 
 The observations of Boycott and Haldane in a deep mine, in the 
 incubating-room of a laboratory, and in a Turkish bath illustrate the 
 important influence of the humidity of the air. In still air the body- 
 temperature rose above normal when the wet-bulb thermometer rose 
 above 31* C. (88° F.), and it remained normal whatever the external 
 temperature might be so long as the reading of the wet-bulb thermo- 
 meter did not exceed that level. The more the wet-bulb thermometer 
 rose above 31° the more rapid was the increase in the body-temperature. 
 In moving air a greater degree of humidity could be borne without 
 increase in the body-temperature, which did not occur till the tem- 
 perature shown by the wet-bulb thermometer exceeded 35° C. The 
 great increase in the evaporation of sweat when the temperature of the 
 air is high is shown by the observation that on a warm day (dry bulb, 
 79" F. ; wet bulb, 67*5° F.) the average loss of moisture from the body 
 was 1,816 grammes for four soldiers during a march of seven miles, 
 while on a cold day (dry bulb, 45° F. ; wet bulb, 38° F.) it was only 
 419 grammes during the same march by the same men (Pembrey). 
 
 The winter fur of Arctic animals is a special device of Nature to 
 meet the demands of a rigorous climate, and combat a tendency to 
 excessive loss of heat. The experiments of Hosshn, and the experi- 
 ence of squatters in Australia, go to show that even domesticated 
 animals have a certain power of responding to long-continued 
 changes in external temperature by changes in the radiating surfaces 
 which affect the loss of heat. It is said that in the hot plains of 
 Queensland and New South Wales the fleeces of the sheep show a 
 tendency to a progressive decrease in weight. And Hosslin found 
 that a young dog exposed for eighty-eight days to a temperature 
 
69t ANIMAL HEAT 
 
 of 5° C developed a thick coat of tine woolly hairs. Another dog 
 of the same Utter, exposed for the same length of time to a tem- 
 perature of 315° to ^2° C, had a much scantier covering. The 
 increased protection against heat-loss in the case of the ' cooled ' 
 dog was not sufficient fully to compensate for the lowered external 
 temperature. The metabolism — ^that is to say, the heat-production 
 — was also increased. And although the food was exactly the same 
 for both animals in quantity and quahty, the dog at 5° C. put on 
 less than half as much fat in the period of the experiment as the 
 ' heated ' dog, but the same amount of ' flesh.' 
 
 The voluntary factor in the regulation of the heat-loss is of great 
 importance in man. Clothes, hke hair and other natural coverings, 
 retai d the loss of heat from the skin chiefly by maintaining a zone 
 of still air in contact with it, for air at rest is an exceedingly bad 
 conductor of heat. A man clothed in the ordinary way has two or 
 three concentric air-jackets around him. The air in the intervals 
 between the inner and outer garments is of importance as well as 
 that in the pores of the clothes themselves ; and it is for this reasou 
 that two thin shirts put on one above the other are warmer than the 
 same amount of material in the form of a single shirt of double 
 thickness. When a man feels himself too hot and throws off his 
 coat, he really removes one of the badlj' conducting layers of air, 
 and increases the rate of heat-loss by radiation and conduction. 
 At the same time the water-vapour, which practically saturates 
 the layer of air next the skin, is allowed a freer access to the surface, 
 and the loss of heat by the evaporation of the sweat becomes greater. 
 The power of voluntarily influencing the heat-loss must be looked 
 upon in man as one of the most important means by which the 
 equilibrium of temperature is maintained. In the lower animals 
 this powei also exists, but to a much smaller extent. A dog on a 
 hot day puts out its tongue and stretches its limbs so as to increase 
 the surface from which heat is radiated and conducted. The mere 
 placing of a rabbit on its back, Nnth its le.ss apart, may cause in an 
 hour or two a fall of 1° to 2° C in the rectal temperature. The 
 power of covering themselves with straw or leaves, of burrowing 
 and of forming nests, may be included among the voluntary means 
 of regulation of the heat-loss possessed by animals. A man opens 
 the window when he is too hot, and pokes the fire when he feels 
 cold. Both actions are a tribute to his status as a homoiothermal 
 animal, and illustrate the importance of the voluntary element in 
 the mechanism by wliich his temperature is controlled. 
 
 The production of heat, hke the loss, is to a certain extent under 
 voluntary control. Rest, and especially sleep, lessen the pro- 
 duction; work increases it. The inhabitants of the tropics, human 
 and brute, often tide ov^er the hottest part of the day by a siesta; 
 and it is as natural, and as much in accordance with physiological 
 
THERMOTAXIS 693 
 
 laws, that a man overpowered by the heat should lie down, as it is 
 that he should walk about and stamp his feet or clap his hands on 
 a cold winter morning. In the one case a diminution, in the other 
 an increase, in the heat-production is aimed at by a corresponding 
 change in the amount of muscular contraction. The quantity and 
 quality of the food also influence the production of heat. The 
 Eskimo, who revels in train-oil and tallow-candles, unconsciously 
 illustrates the experimental fact that the heat of combustion of fat 
 is high; the rice diet of the ryot of the Carnatic, with its low heat- 
 equivalent, seems peculiarly adapted to the dweller in tropical 
 lands. But it would be easy to attach too much weight to con- 
 siderations such as these. The Arctic hunter eats animal fat, and 
 the Indian peasant vegetable carbo-hydrate, not only because fat 
 has a high and carbo-hydrate a low heat-equivalent, but because 
 in the climate of the Far North animals %vith a thick coating of 
 badly-conducting fat are plentiful, and vegetable food scarce; 
 whereas in the river-valleys of India Nature favours the growth of 
 rice, and religion forbids the killing of the sacred cow. 
 
 The production of heat is also controlled by an involuntary nervous 
 mechanism, through which the ' chemical ' regulation of the body- 
 temperature is achieved, as the ' physical ' regulation is accom- 
 plished by the nervous mechanisms that control the circulation, 
 the sweat-glands, and the respiratory movements. It is a matter 
 of everyday experience that cold causes involuntary shivering — 
 involuntary muscular contractions — ^the object of which seems to be 
 a direct increase in the heat-production. But besides this visible 
 mechanical effect, the apphcation of cold to a warm-blooded animal, 
 when not carried so far as to greatly reduce the rectal temperature, 
 is accompanied by a marked increase in the metabolism, as shown 
 by an increased production of carbon dioxide and consumption of 
 oxygen. In cold-blooded animals like the frog the metabolism, 
 on the other hand, rises and falls with the external temperature; 
 there is no automatic mechanism which answers an increased drain 
 upon the stock of heat in the body by an increased supply. Or, in 
 the light of recent experiments, we ought rather to say that, 
 although the rudiments of a heat-regulating mechanism may exist 
 in such animals as the frog, the newt, and even the earthworm 
 (Vernon), it is only able to modify to a certain extent the effects of 
 changes of external temperature, not to balance or even override 
 them, as in the homoiothermal animal. In resting frogs and snakes 
 the rate of heat-production, as measured by the micro-calorimeter, 
 increases two to three times when the temperature rises 10" C. 
 (Hill). The warm-blooded animal loses its heat-regulating power 
 when a dose of curara sufficient to paralyze the voluntary muscles 
 is given. A curarized rabbit, kept alive by artificial respiration, 
 reacts to changes of external temperature like the cold-blooded 
 frog. Now, the only action of curara adequate to account for this 
 
694 ANTMAL HEAT 
 
 effect is its power of paralyzing the motor innervation, and so 
 cutting off from the skeletal muscles impulses which in the intact 
 animal would have reached them. The excitation by cold of the 
 cutaneous nerves, or some of them, which in the unpoisoned animal 
 is reflected along the motor nerves to the muscles, and causes the 
 increase of metaboHsm, is now blocked at the end of the motor 
 path; and the muscles, the great heat-producing tissues, are aban- 
 doned to the direct influence of the external temperature (Pfliiger). 
 How is it, then, that nervous impulses from the skin produce in 
 the intact animal their effect upon the chemical processes in the 
 muscles ? We know that the heat-production of a muscle is greatly 
 increased when it is caused to contract; but it has not hitherto been 
 possible by artificial stimulation to demonstrate that any chemical 
 or physical effect is produced in a muscle by excitation of its motor 
 nerve unless as the accompaniment of a mechanical change. When 
 the gastrocnemius of a frog poisoned with not too large a dose of 
 curara is laid on a resistance thermometer (p. 783), and its nerve 
 stimulated from time to time as the curara paralysis deepens, 
 heating of the muscle is observed as long as, and only as long as, 
 there is any visible contraction. The gaseous metabolism of a 
 rabbit immersed in a bath of constant temperature may sink by 
 as much as 30 to 40 per cent, when curara is given. One obvious 
 cause of this is the complete muscular relaxation. And the whole 
 secret of the regulation of the heat-production might be plausibly 
 supposed to lie in the bracing effect of cold upon the skeletal muscles 
 and the relaxing effect of heat. Indeed, in man it has been observed 
 that exposure to moderate cold causes no metabolic increase when 
 shivering is prevented by a strong effort of the will (Loewy). 
 Nevertheless, the explanation is inadequate in the case of small 
 animals, such as guinea-pigs, rabbits, and cats; for very great 
 changes in the metaboUsm may be brought about by external cold 
 without any outward token of increased muscular activity. In a 
 man also a fall in the external temperature from 23° to 15° C. caused 
 a certain increase in the output of carbon dioxide (from 27-9 to 
 32 3 grammes per hour), although no shivering was observed. As 
 the temperature of the air is lowered, the point is soon reached at 
 which shivering can no longer be suppressed, and then it is neither 
 practicable nor perhaps very important to distinguish clearly the 
 portion of the increased heat-production associated with the visible 
 muscular contractions and the portion due to quickened muscular 
 metaboUsm without contraction. Lefevre found that in man a 
 marked increase in the heat-loss, such as is caused by immersion 
 for a considerable time (one to three hours) in cold water (at a tem- 
 perature of 7° to 15° C), was accompanied by a great increase in 
 the production of heat, so that the axillarj^ temperature fell com- 
 paratively little — e.g., only 1° C. during a stay of three hours in a 
 bath at 15° C. With short periods of immersion, a characteristic 
 
THERMOTAXIS 695 
 
 reaction occurs after the person comes out of the bath. The rectal 
 temperature falls to a minimum, which is reached in twenty to 
 thirty minutes after exit from the bath, and then gradually returns 
 to normal. This fall of internal temperature is due to the heating 
 of the superficial portions of the body at the expense of the central 
 portions. By training, the fall of temperature is greatly lessened, 
 the heat-regulating mechanism acquiring, so to speak, with practice, 
 greater promptitude and precision of adjustment. 
 
 It must be admitted, then, that the metabolic changes normally 
 going on in the resting muscles may be reflexly increased — especially 
 in the smaller homoio-thermal animals- — without the usual accom- 
 paniment of mechanical contraction,* and that such an increase of 
 ' chemical tone ' is an important means by which the temperature 
 is regulated. It is possible that other organs besides the muscles 
 may be concerned, though not to a sufficient extent to secure the 
 due regulation of temperature during curara paralysis. It is 
 obvious that in man, whose environment is so much under his own 
 control, a mere automatic regulation is less required than in the 
 inferior animals, and that a regulative power, if present in rudiment, 
 would tend to ' atrophy ' by disuse, or, at all events, to become less 
 sensitive to slight changes of temperature. In the larger animals, 
 again, mere bulk is an important safeguard against any sudden 
 change of internal temperature. To reduce the temperature of a 
 horse or an elephant by 1°, a considerable quantity of heat must 
 be lost, while a very slight loss would suffice to cool a mouse by 
 that amount. Not only so, but the surface by which heat is lost is 
 greater in proportion to the mass of the body in small than in large 
 rnimals. The power of rapidly increasing the heat-production to 
 meet a sudden demand is, therefore, far more important to the 
 mouse than to the horse; and the fact (p. 628) that the metabolism 
 of an animal varies approximately as its surface, and not as its 
 mass,f is an illustration of the nice adjustment by which heat- 
 
 * Increased tonus of the muscles might, however, account for a portion 
 of the increased heat-production. 
 
 t The relation between mass (M) and surface (S) in man is approximately 
 
 S-v/M 
 given by the equation ^ = K, and the relation between surface, mass, 
 
 length of body (L), and circumference of chest (C) just above the nipples in 
 
 Sv'M* L* C3 
 the ' mean ' position of respiration, by the equation — vr~T~?^ ~ =K'. M is 
 
 expressed in grammes, S in square centimetres, L and C in centimetres. K is 
 a constant whose mean value is I2'3, and K' a constant whose mean value is 
 4*5 (Meeh). 
 
 It has been shown that this formula gives somewhat too high results. In 
 any case, a formula of this nature is accurate only for objects of similar shape. 
 Many other formulae ha\-e been proposed. A more accurate ' height-weight ' 
 formula is A = W^^^x Ro 725^ C, where A is the surface area in square 
 centimetres, W, the weight in kilograms, and C, a constant 7i'84. Another 
 method is based on the principle of raultipljang the length by the average cir- 
 
696 
 
 ANIMAL HEAT 
 
 equilibrium is niaiutaincd. There is reason to believe that at a 
 tt-mprraturc equal to that of the human body, the heat-production 
 of a frog })cr unit of inass would equal that of a man or other large 
 mammal, although it would be far less than that of a small homoio- 
 thermal animal. This is in favour of the view that in the larger 
 mammals a nervous regulation of the intensity of the metabohsm 
 is not of prime importance. 
 
 Relations between Heat-Production, Surface Area, and Blood-Flow. — 
 
 The t\)!l()wing tabic shows how close is the agreement in the heat- 
 production per unit of surface for animals of different species and very 
 different body-weight: 
 
 
 Weight in 
 Kilos. 
 
 Calories produced in 34 Hours. 
 
 Per Kilo. 
 
 Per Sq. Metre 
 of Surface. 
 
 948 
 1,042 
 1,036 
 
 917 
 
 943 
 1,188 
 
 Horse - - ' - 
 
 Man ----- 
 
 Dog 
 
 Rabbit (without ears) - 
 Fowl - . - - - 
 Mouse . . . - 
 
 441 
 64-3 
 
 2-3 
 
 2 
 
 o-oiS 
 
 II-3 
 32-1 
 
 51-5 
 75-1 
 71-0 
 
 212-0 
 
 The relation between heat-production and surface area has been rein- 
 vestigated by modern method.s. Some observers, notably Benedict, 
 are inclined to deny that any simple proportion exists between the 
 basal metabolism and the area of the skin. They consider that the 
 magnitude of the metabolism is related rather to the mass of active 
 protoplasm, w^hich is a different quantity from the w'eight of the body, 
 the fatty tissues — e.g., contributing largely to the body-weight, but 
 little to the metabolism. On the other hand, Lusk, Du Bois, and their 
 fellow-workers, believe that when the surface area is accurately cal- 
 culated there is no reason to doubt the hitherto accepted view of a 
 proportionalit}' between heat-production and area of surface. It must 
 be remembered that it is only for subject.s in the same general physio- 
 logical state that the proportionality is supposed to hold. Nobody 
 imagines, for instance, that a patient with exophthalmic goitre will 
 have the same heat-production per unit of surface as a normal indi- 
 vidual. Nor can an infant be expected to be exactly comparable with 
 an adult, since it differs so much not only in the proportions of the 
 body and the relative size of the various organs, but also in its meta- 
 bolism. It has been found, as a matter of fact, that the heat-produc- 
 
 cumference or width of each of the characteristic parts of the body. Con- 
 stants have been worked out for each part by comparison of the actual area 
 of a mould applied to the skin with the data obtained by the measurements. 
 This so-called ' linear formula ' docs not involve the body-weight, and gives 
 good results with bodies of very dilferent size and shape (Du Bois). Bene- 
 dict has also developed a photographic method of obtaining the surface area. 
 The main interest of such measurements hes in their bearing upon the relation 
 between the metabohsm and the body-surface. 
 
THF.IJMOT.IXIS 
 
 697 
 
 tion per square uK^tre of body-surface, which is low at birth, increases 
 rapidly during the hrst year, reaches a maximum between the ages 
 of one" and six, then falls steeply until tlie age of twenty, and thereafter 
 very slowly. The basal metabolism of boys of twelve or thirteen years 
 old per unit of suiface is 25 per cent, higher than that of the adult. 
 
 The next table, calculated by Kubner from the quantity of tissue- 
 protein and fat consumed, gives the relative intensity of heat-produc- 
 tion in fasting dogs of different sizes: and along with it is given for 
 comparison some of the results on the output of the heart in dogs of 
 different weight, obtained by the method of injecting salt solution 
 into the ventricle described on p. 139. 
 
 Weight in 
 Kilos. 
 
 Calories per Kilo 
 per Hour. 
 
 Weight in Kilos. 
 
 Output per Kilo 
 per Second inc.c. 
 
 31 
 
 1-58 
 
 27-89 
 
 1-92 
 
 24 
 
 1-70 
 
 18-20 
 
 2-31 
 
 20 
 
 1-87 
 
 12-82 
 
 3-28 
 
 18 
 
 1-92 
 
 11-68 
 
 3-56 
 
 10 
 
 2-55 
 
 10-32 
 
 3-86 
 
 6 
 
 2.84 
 
 7-165 
 
 4-13 
 
 3 
 
 3-78 
 
 4-975 
 
 5-36 
 
 Number of 
 Dogs. 
 
 Range of Weight in 
 Kilos. 
 
 Average Weight. 
 
 Average Output 
 per Second in c.c. 
 
 Average Output 
 
 per Kilo per 
 
 Second. 
 
 2'40 
 
 3-25 
 3-55 
 
 3-69 
 4-42 
 
 3 
 
 2 
 2 
 
 34*5 to 27-9 
 
 i8'2 ,, ii'7 
 
 10-3 .. 9-3 
 
 8-4 ,. 7-2 
 
 6*5 .. 5-0 
 
 31-5 
 14-3 
 
 9-8 
 7-8 
 5-7 
 
 75-7 
 
 46-6 
 
 34-8 
 28-8 
 25-2 
 
 It is obvious that the two quantities, heat-production (or loss) and 
 heart-output, vary in the same general way. The reason is clear. 
 Oxygen must be absorbed by the lungs in proportion to the heat 
 produced, and where more oxygen is to be absorbed, more blood passe? 
 through the lungs to take it up.* It is interesting to inquire whether 
 
 * For sirapHcity, the possibility that the coefficient of utilization of the oxy- 
 gen-carrying capacity of the blood {i.e., the quantity of oxygen absorbed by 
 a litre of blood during its passage through the lungs divided by the total 
 quantity of oxygen which it can take up) may vary, is disregarded. This 
 possibility would imply that the average oxygen content of the venous blood 
 coming to the right side of the heart varied in animals of different size, more 
 oxygen being abstracted, for example, from the blood in passing through the 
 tissues of small animals than of large. The greater the utilization of the 
 oxygen the smaller would the quantity of blood passing through the lungs 
 require to be. There is no evidence, however, that such differences exist be- 
 tween animals of the same species of different size, although it has been sug- 
 gested that a higher coefficient of utilization coupled with a proportionately 
 smaller heart output may be one way in which training diminishes the diffi- 
 culty and discomfort of hard, muscular effort. 
 
698 ANIMAL HEAT 
 
 in the smaller animals the contact of the alveolar air with the rela- 
 tively increased quantity of blood is obtained by a similar increase in 
 the area covered by capillaries (or in what is doubtless approximately 
 proportional to this area, the mass of the lung tissue), or by a shortening 
 of the pulmonary circulation time (p. 137). The answer is that the pul- 
 monary circulation time is markedly shortened as the size of the 
 animal diminishes, although not in proportion to the diminution in 
 weight, but rather in proportion (roughly speaking) to the square root 
 of the surface. This could not be the case if the area of the pulmonary 
 surface bore the same proportion to the area of the skin as the output 
 of the heart does. For in this case the vascular capacity of the lungs 
 (or the quantity of blood contained in them) would be proportional to 
 the heart output, and the time required for the blood discharged by 
 the right ventricle to displace the whole of the blood contained in the 
 lungs at any given moment — that is to say, the average pulmonary 
 circulation time — would be the same for animals of all sizes. But it 
 may very well be the case if the vascular capacity of the lungs (or 
 the mass of the lung tissue) decreases more rapidly than the surface 
 decreases, say in proportion to the body-weight. At first thought it 
 might appear advantageous that the area of the surface through which 
 oxygen is absorbed should be proportional to the area through which 
 the heat produced in the oxidations of the body is chiefly eliminated, 
 so that the greater the necessary heat loss, the greater should be the 
 facilities for absorption of oxygen. We have, however, already seen 
 (p. 251) that the blood, even when it passes through the pulmonary 
 capillaries at its maximum speed, has still sufficient time to practically 
 saturate itself with oxygen. Within the limits where this holds good 
 there would be no advantage in increasing the relative size of the 
 lungs rather than in increasing the linear velocity of the blood passing 
 through them — that is, diminishing the pulmonary circulation time — 
 and on general principles it may be assumed that a larger pulmonary 
 reservoir than is necessary for the maximum possible intake of oxygen 
 would not be provided. For if the pulmonary reservoir holds an ex- 
 cessive amount of blood, some other tissues must have too little. It 
 has been stated, indeed, that in animals of different size in the same 
 species the total quantity of blood in the body is a function not of the 
 body-weight, but of the surface, so that the smaller animals have 
 a relatively larger amount of blood (p. 56). If this be so, it is probably 
 related to the greater intensity of metabolism and the greater loss of 
 heat from the surface of small animals, which entails a greater cir- 
 culation through the skin. This greater cutaneous circulation means 
 the permanent withdrawal of blood from the rest of the body, which 
 can be compensated by a corresponding increase in the total circulating 
 mass. The fact that the blood contained in the living skin must 
 form a substantial fraction of the total blood, and a fraction rela- 
 tively more important in the smaller than in the larger animals, 
 would of itself help to establish a relation between surface area 
 and total quantity of blood. The greater volume of the blood 
 will contribute to the increased output of the heart in the smaller 
 animals. In this connection the fact already alluded to more than 
 once may be again emphasized, that it is not the quantity of blood con- 
 tained in an organ or an organism, but the quantity passing through 
 the capillaries in a given time, wliich is the important thing for its 
 function, in the case of the lungs for the function of the gaseous ex- 
 change, in the case of the skin for the regulation of the heat-loss. 
 
THERMOTAXIS 699 
 
 There is reason to suppose that the average amount of blood contained 
 in the cutaneous vessels, as well as the average amount flowing through 
 them per unit of time, is greater in proportion to the total area of the 
 skin in animals like man, with a skin devoid of fur and well supplied 
 with sweat glands, than in animals well protected by hair and with 
 few sweat glands. For in the latter the cutaneous circulation cannot 
 take as great a share in the regulation of the heat-loss as in the former, 
 although, of course, the nutrition of the hair itself requires a certain 
 supply of blood. The relatively insignificant proportion of the total 
 bk)od usually assigned to the skin of such an animal as the rabbit 
 (p. 56) probably gives quite an erroneous idea of the proportion in 
 the skin of a living man. It must be remembered that such determin- 
 ations as have been carried out have been made on dead animals whose 
 skin under ordinary conditions contains less blood than during life. 
 
 Rubner has found that animals abundantly fed do not show so much 
 change in the production of heat when the external temperature is 
 varied as starving animals, perhaps because the thicker coat of sub- 
 cutaneous fat so steadies the rate at which heat is lost that it becomes 
 easy for the vaso-motor mechanism alone to hold the balance between 
 loss and production. In well-fed animals it is the heat-loss which is 
 chiefly affected, and it may be that this has something to do with the 
 explanation of Loewy's results on man (p. 694). 
 
 Lorrain Smith discovered the interesting fact that after removal of 
 the thyroid glands (in cats), the heat-production, as measured by the 
 amount of carbon dioxide given off, is more sensitive to changes of 
 external temperature than in the normal animal. 
 
 Effect of Excessive Loss of Heat — Varnishing of the Skin. — it 
 must not be imagined that the production of heat can be in- 
 creased indefinitely to meet an increased heat-loss. The organism 
 can make considerable efforts to protect itself, but the loss of heat may 
 easily become so great that the increase of metabolism fails to keep 
 pace with it. The internal temperature then falls, and if the fall be 
 not checked, the animal dies. A mammal, when cooled artificially 
 to the temperature of an ordinary room (15° to 20° C), does not recover 
 of itself, but may be revived by the employment of artificial respiration 
 and hot baths, even when the rectal temperature has sunk to 5° to 
 10° C. If the skin of a rabbit be varnished, and the air which it is 
 the function of the fur to maintain at rest around it be thus expelled, 
 the animal dies of cold, unless the loss of heat is artificially prevented. 
 If, without varnishing at all, the greater portion of the skin of a rabbit 
 or guinea-pig be closely clipped or shaved, similar phenomena are 
 observed. Prevented from covering itself with straw, the animal dies, 
 sometimes in twenty-four hours. The radiation from the skin, as 
 measured by the resistance-radiometer (p. 681), is greatly increased; 
 the animal shivers constantly, and the rectal temperature falls. Placed 
 in a warm chamber before the temperature in the rectum has fallen 
 below 25°, the animal recovers perfectly. If the fall is allowed to go 
 on, it dies. If it is kept from the first in the warm chamber, no faU of 
 temperature occurs. When the increased loss of heat is less perfectly 
 compensated — when, for example, the animal is left at the ordinary 
 temperature, but supplied with sufficient straw to cover itself, or 
 allowed to crouch among other animals — a curious phenomenon may 
 sometimes be seen. The rectal temperature, which has fallen sharply 
 during the operation, remains subnormal (as much as 2° to 3° below 
 the ordinary temperature) for a time (a week or more), and then 
 
700 ANIMAL HEAT 
 
 gradually rises as the coat again begins to grow. The meaning of this 
 seems to be that the power of regulating the temperature by increasing 
 the metabolism is overtasked by the removal of the natural protective 
 covering, unless the escape of heat is artificially diminished. When the 
 loss of the fur is entirely compensated, no fall of temperature occurs; 
 when it is not compensated at all, the animal cools till it dies ; when it is 
 partially compensated, the increased metabolism may only suffice to 
 maintain a temperature lower than the normal, although constant 
 muscular contractions (shivering) are brought in to supplement the 
 efforts of the regulative chemical processes. 
 
 Hitherto we have only spoken of a reflex regulation of the heat- 
 production called into play by external cold. It might be sup- 
 posed — and, indeed, has often been assumed — that heat would lessen 
 the metabolism, as cold increases it; and there are indications that 
 in the smaller animals this is the case, although the influence of 
 heat seems to be much smaller than the influence of cold. But 
 neither experimental results nor general reasoning have as yet 
 shown that in man, either in the tropics (Eykman) or in the north 
 temperate zone (Loewy), the chemical tone is diminished by a rise 
 of external temperature much above the mean of an ordinary 
 English summer, apart from the effect of the muscular relaxation 
 which heat induces. In a man, indeed, at rest in a hot atmosphere, 
 the production of carbon dioxide and consumption of oxygen are, 
 if an3i:hing, greater than at the ordinary temperature. The regu- 
 lation of temperature in an environment warmer than the normal 
 seems, in fact, to be brought about more by an increase in the loss 
 than a decrease in the production of heat. Evaporation from the 
 skin and lungs is an automatic check upon overheating as important 
 as the involuntary increase of metabolism upon excessive cooling. 
 
 Nervous Mechanism of Thermotaxis. — While the skeletal 
 muscles, and perhaps the glands, are at one end of the reflex arc by 
 which the impulses pass that regulate the temperature through the 
 metabolism, we are as yet ignorant of the precise paths by which 
 the afferent impulses travel, of the nerve-centres to which they go, 
 and even of the end-organs in which they arise. There are nerves 
 in the skin which minister to the sensation of temperature 
 (Chap. XVIII.). A change of temperature is their ' adequate ' and 
 suflicient stimulus; and it is a tempting hypothesis that these are 
 the afferent nerves concerned in the reflex regulation of temperature 
 — that impulses carried up by them to some centre or centres in 
 the brain or cord are reflected down the motor nerves to control 
 the metabolism of the skeletal muscles, and down the vaso-motor 
 nerves to control the loss of heat from the skin. 
 
 It is more than doubtful, however, whether the whole chemical regu- 
 lation can be attributed to such stimuli. For it has been found that the 
 relation between heat-production and extent of surface in animals 
 
THERMOTAXJS 701 
 
 (guinea-pigs) of different size is unaltered wh^ the air temperature is 
 made so nearly the same as that of the skin that the temperature nerves 
 can hardly be supposed to be excited. 
 
 There is some evidence that the bioplasm — the living substance — of 
 different animals, even when the external conditions are the same, may 
 differ specifically in the average intensity of metabolism to which it is 
 pitched. When exposed to a temperature about equal to that of warm- 
 blooded animals, the green lizard [Lacerta viridis) and the bull-frog, 
 which live in the temperate zone, and for which a temperature of 
 37* C. is highly abnormal, double their heat-production, and soon die. 
 Tropical poikilothermal animals, such as the alligator, also double 
 their heat-production, but the highest values reached are only one-half 
 that of the lizard at 25° C. Apparently the bioplasm of the tropical 
 animals has adapted itself to a high external temperature, and works 
 very economically even at the highest temperatures (Krehl). 
 
 Heat Centres. — It is known that certain injuries of the central 
 nervous system are related to disturbance of the heat-regulating 
 mechanism. Injury to various portions of the cortex cerebri in 
 the dog and other animals, and lesions of the pons, medulla oblongata 
 and cord in man, may be followed by increase of temperature. 
 When the spinal cord is cut below the level of the vaso-motor centre, 
 the increased loss of heat from the skin due to dilatation of the 
 cutaneous vessels masks any increase of the heat-production which 
 may possibly have taken place, and the internal temperature falls; 
 but if the loss of heat is diminished by wrapping the animal in 
 cotton-wool the temperature may rise. From such phenomena it 
 has been surmised that certain ' centres ' in the brain have to do 
 with the regulation of temperature by controlHng the metabolism 
 of the tissues; that they cause increased metabohsm when the 
 internal temperature threatens to sink, diminished metabolism 
 when it tends to rise. The cutting off, it is said, of the influence 
 of the ' heat centres ' by section of the paths leading from them 
 allows the metabolism of the tissues to run riot, and the temperature 
 to increase. But diversity of opinion still reigns as to the existence 
 or, if they exist, as to the precise location of the nervous centres 
 which preside over this function. It is stated by some workers 
 that animals deprived of the cerebral hemispheres, the corpora 
 striata and one of the optic thalami, still maintain to a remarkable 
 degree a body temperature independent of their environment, but 
 that when both optic thalami have been removed they become 
 poikilothermal (Krehl, etc.). The greatest mass of evidence points, 
 however, to the corpora striata as structures more intimately con- 
 cerned in temperature regulation than any other. Puncture of the 
 median portion of the corpus striatum in the rabbit by a needle 
 thrust through a trephine hole in the skull is followed in a few- 
 hours by a rise of temperature in the rectum (1° to 2°), and still 
 more in the duodenum, which is normally the hottest part of tht 
 body in this animal. The heat-production, the respiratory exchange 
 
7oa ANIMAL HEAT 
 
 and the nitrogen excretion are increased. These phenomena mav 
 last for several days (Ott, Richet, Aronsohn, and Sachs), and are 
 due to stimulation of the portions of the brain in the immediate 
 neighbourhood of the injury. Electrical stimulation of this region 
 has a similar effect. When the temperature has returned to 
 normal, a fresh puncture may again cause a rise. 
 
 As to the manner in which these centres are excited, there is 
 some evidence that, in addition to any influence exerted on them 
 by afferent nerves, they are capable of being directly affected by 
 the temperature conditions of the blood passing through them, as 
 well as by numerous drugs. Thus it is stated by Barbour and Wing 
 that direct application of cold to the region of the corpus striatum, 
 especially its caudate nucleus, in rabbits causes a rise in the rectal 
 temperature, associated with shivering and consequent increase of 
 heat-production in the contracting muscles, and with peripheral 
 vaso-constriction and consequent diminution in the heat-loss. 
 The application of warmth has the opposite effect : the peripheral 
 bloodvessels dilate, the animal becomes quiet, and the rectal tern 
 perature falls.* 
 
 Some observers hold that the chief seat of the increased metab- 
 olism in the puncture fever is the skeletal muscles, others the Hver. 
 The question turns largely upon the success of the puncture ex- 
 periment after the previous administration of curara on the one 
 hand, and of strychnine on the other. For curara cuts out the 
 motor innervation of the skeletal muscles, and strychnine convul- 
 sions exhaust the store of hepatic glycogen. Certain investigators 
 have found that after an adequate dose of curara no puncture fever 
 can be obtained, and they locate the increased metabolism asso- 
 ciated with the fever in the muscles. Others maintain that even 
 after curara the puncture is followed by fever, but is not followed 
 by fever if strychnine has first been given. They accordingly con- 
 clude that the rapid combustion of the glycogen (or the dextrose 
 derived from it) is the primary factor in the increased metabolism. 
 It may be pointed out, however, that neither experiment is a crucial 
 test. For if strychnine reduces the liver glycogen, it also reduces 
 the glycogen of the muscles. And if in the puncture fever the liver 
 glycogen is transformed into dextrose more rapidly than usual^ the 
 dextrose is probably in great part used up in the muscles more 
 rapidly than usual, eh?, it would appear in the urine. The effect 
 of strychnine on the puncture fever, then, is no proof that the 
 muscles are not essentially concerned in it. On the other hand, the 
 alleged absence of the fever after curara is not sufficient to show 
 that the muscles are alone concerned. For curara causes a lowering 
 of the body-temperature, which, if it be not overcompensated, may 
 
 * Other observers, however, have failed to coa&rm these results (Cloetta 
 and Waser). 
 
PEVER 703 
 
 mask the fever. The positive result of the puncture in curarized 
 animals, which some observers say they have obtained, would, if 
 animals, which some observers say they have obtained, would, if 
 confirmed, be important evidence that the primary effect is not on 
 the muscles, or, at least, not solely on them, but would not prove 
 that it is on the liver. That the liver is concerned, however, is more 
 directly indicated by the fact that during the puncture fever the 
 hver continues to be what it is under normal conditions, the warmest 
 organ in the body, warmer than the blood in the root of the aorta 
 by about 1° C. The most probable conclusion is that the increased 
 production of heat in this form of experimental fever is due to an 
 increased metabolism of carbo-hydrate (glycogen) both in the liver 
 and in the muscles. 
 
 Temperature Regulation in Hibernating Animals. — The behaviour 
 of hibernating mammals, such as the marmot, dormouse, hedgehog, 
 and bat, is of interest in connection with the temperature regulation. 
 In the active waking state these animals are homoiothermal, but in 
 profound winter sleep they are poikilothermal, the body-tempera- 
 ture rising and falHng with that of the air. The rectal temperature 
 may be as low as 2° C. There is an intermediate state in which the 
 animal is partially awake, though inactive, and its temperature is 
 much below the normal, but considerably above that of its environ- 
 ment. In this condition it has an imperfect thermotaxis, something 
 Hke that of an ordinary mammal (including the human infant) in 
 the period of immaturity, immediately after birth. When the 
 hibernating mammal awakes the rise of temperature is enormous 
 and abrupt. The temperature of a dormouse rose in an hour from 
 135° C to 357° C, and that of a bat in fifteen minutes from 17° C. 
 to 34" C. (Pembrey). 
 
 Fevers. — Fever is a pathological process generally caused by the 
 poisonous products of bacteria, and characterized by a rise of 
 temperature above the Hmit of the daily variation (p> 712). It is 
 further associated with an increase in the rate of the heart and the 
 respiratory movements, and a diminution in the alkalies and carbon 
 dioxide of the blood. The total excretion of nitrogen is increased, 
 at least in proportion to the amount of protein ingested, indicating 
 an increase in the consumption of tissue-protein. The distribution 
 of the nitrogen among the urinary constituents is altered. The 
 ammonia (in the form of ammonium salts of organic acids), the 
 uric acid, and to a smaller extent the creatinin (Leathes), are in- 
 creased, while the urea is relatively decreased, evon when its abso- 
 lute amount is greater than normal. Creatin, which is not normally 
 present in urine, unless the food contains it, may also appear in 
 fever (Shaffer). It has been suggested that the proximate cause of 
 fever is the action of bacterial poisons or of other substances on the 
 * heat centres,' and that antipyretics, or drugs which reduce the 
 temperature in fever, do so by restoring the centres to their normal 
 
704 ANIMAL HEAT 
 
 State, by preventing the development of the poisons, aiding their 
 elimination, or antagonizing their action. In favour of this view, 
 it has been stated that when the basal ganglia are cut off, by section 
 of the pons, from their lower nervous connections, fever is no longer 
 produced by injection of cultures of bacteria which readily cause it 
 in an intact animal, while antipjTin has no influence upon 
 the temperature (Sawadowski). And while it is almost certain 
 that some pyrogenic or fever-producing agents — cocaine, e.g. — act 
 indirectly, through the brain or cord, it is quite possible that others 
 affect directly the activity of the tissues in general, just as some 
 antipyretics or fever-reducing agents, such as quinine, act imme- 
 diately upon the heat-forming tissues, so as to diminish their 
 metabohsm, while others, like antipyrin, affect them through the 
 nervous system. Quinine has no influence upon ' puncture ' fever 
 in rabbits. A still more important action of antip}Tin, and the 
 group of antipyretics to which it belongs, is the increase in the heat- 
 loss which they bring about by the dilatation of the bloodvessels 
 of the skin. This effect is also produced through the nervous system. 
 Fever is a condition so interesting from a physiological point of 
 view, and of such importance in practical medicine, that it will be 
 well to consider a little more closely the possible ways in which a 
 rise of temperature may occur. It must not be forgotten that the 
 febrile increase of temperature is always accompanied by other 
 departures from the normal, and that all the fundamental febrile 
 changes may even, in certain cases, be present without elevation, 
 and even with diminution of temperature. But here we have only 
 to do with the disturbance of the normal equilibrium between the 
 loss and the production of heat; and it is evident that any of the 
 five conditions illustrated in the diagram (Fig. 226) may give rise 
 to an increase of temperature. It is not necessary to discuss 
 whether cases of fever can actually be found to illustrate every one 
 of these possibihties. It is probable that not infrequently dimin- 
 ished loss and increased production may be both involved; and it 
 ought to be remembered that the healthy standard with which the 
 heat-production of a fever patient should be compared is not that 
 of a man doing hard work on a full diet, but that of a healthy person 
 in bed, and on the meagre fare of the sick-room. When this is kept 
 in view, the comparatively low heat-production and respiratory 
 exchange which have sometimes been found in fever cease to excite 
 surprise. But in any case, no mere change in the absolute quantities 
 of heat formed and lost is sufficient to explain the febrile rise of 
 temperature; there must be a change in the relative proportion. 
 That an increase in heat-production is not of itself enough to produce 
 fever is proved by the fact that severe muscular work, which in- 
 
FEVER 
 
 705 
 
 creases the metabolism more than high fever, only causes in a 
 healthy man a rise of about 1° C. in the rectal temperature. When 
 the work is over, the temperature comes rapidly back to normal. 
 The essence of the change in fever is a derangement of the mechanism 
 by which in the healthy body excess or defect of average metab- 
 olism, or of average heat- 
 loss, is at once compensated 
 and the equilibrium of tem- 
 perature maintained. 
 
 This derangement only lasts 
 as long as the temperature 
 is rising. When it becomes 
 stationary at its maximum 
 we have again adjustment, 
 again equality of production 
 and escape of heat; but the 
 adjustment is now pitched 
 for a higher scale of tempera- 
 ture. A rough analogy, so 
 far as one part of the process 
 is concerned, may be found 
 in the behaviour of the 
 ordinary gas-regulator of a 
 water-bath. It can be ' set ' 
 for any temperature. That 
 temperature, once reached, 
 remains constant within nar- 
 row limits of oscillation; but 
 the regulator can be equally 
 well adjusted for a higher or 
 a lower temperature. It is, 
 however, important to note that the equilibrium is more unstable 
 in fever than in health, so that changes of external temperature more 
 easily depress or increase the temperature of a fever patient than of 
 a healthy man. 
 
 Rosenthal has concluded from calorimetric observations that, in 
 the first stage of fever, while the temperature is rising, there is 
 always increased retention of heat. Maragliano actually found 
 evidence, by means of the pletliysmograph, that the cutaneous 
 vessels are at this stage constricted, and that the constriction may 
 even precede the rise of temperature. The blood-flow in the feet 
 in cases of typhoid fever investigated by the calorimetric method 
 (p. 122) was not found to exceed the normal flow, and was usually 
 decidedly below the normal. Hyperexcitability of the vaso-con- 
 strictor mechanism of the peripheral parts, especially of the skin, 
 
 45 
 
 Fig. 226. — Diagram to show the Possible 
 Relations between Heat- Production and 
 Heat-Loss in Fever. 
 
706 AXIMAL HEAT 
 
 was present. All these observations lend support to the famous 
 ' retention ' theory of Traube. It has been suggested that the 
 significance of the increased action of the cutaneous vaso-constrictor 
 mechanism in typhoid fever is that the peripheral vaso-constriction 
 is a compensatory arrangement which secures for the organs mainly 
 suffering from the infective process an increased flow of blood to 
 combat the infection. On this hypothesis the rise of temperature 
 in so far as it depends upon diminished loss of heat is a secondary 
 phenomenon inevitably following the redistribution of the blood, 
 and unavoidable except by a corresponding diminution in the total 
 metabolism. In the great majority of cases the production of heat 
 is also increased, on the average by 20 to 30 per cent, of the normal 
 production of a resting man. The increase may be much greater 
 during the chill which ushers in so many infections on account of 
 the muscular contractions in shivering. During the period of rising 
 temperature the production of heat is not necessarily increased. 
 At the height of the fever there is often, though apparently not 
 always, an increase in the heat-production. After the crisis, while 
 the fever is subsiding, the rate at which heat is lost rises sharply. 
 As to the explanation of the increase of metabolism in fever, 
 and especially of the increased metabolism of tissue-protein, 
 various \news have been held. Some have gone so far as to say 
 that the increase is merely the consequence, not the cause, of 
 the rise of temperature. But the rebutting evidence which has 
 been brought against this view is strong and, indeed, overwhelming. 
 It is perfectly true that, when the temperature of the body is 
 artificially raised by preventing the free loss of heat for a sufficient 
 time (so-called ph3-siological fever), the destruction of protein is 
 augmented. A fasting dog whose temperature was increased to 
 40° or 41° C for twelve hours eliminated ^y per cent, more nitrogen 
 than when the body-temperature was normal. But this increase 
 in the protein metabolism could be entirely prevented by gi\nng 
 the animal a sufficient amount of carbo-h\-drate. Similar r^^sults 
 have been obtained in man. The carbon dioxide excretion and 
 oxygen absorption are, of course, also markedly increased. But the 
 increase in the nitrogen excretion is often much greater in fever than 
 any increase which can be brought about by artificially raising the 
 temperature of a health}' individual by means of hot baths. A 
 typhoid patient was found to lose 10 8 grammes of nitrogen a day 
 (corresponding to 318 grammes of muscle) during eight days of 
 fever (F. Miiller). A portion of the loss of nitrogen on the routine 
 fever regimen may be due to the fact that the ordinary typhoid 
 patient is really on a semi-starvation diet, the heat-equivalent of 
 which is not much more than half his heat-production. Yet it 
 has not been found possible to completely prevent the loss of 
 
FEVER 
 
 707 
 
 nitrogen by putting the fever patient on a diet rich in protein, or 
 on a diet containing a moderate amount of protein with a large 
 quantity of fat and carbo-hydrate, even when the total heat- value 
 of the diet is much in excess of the 32 or 33 calories per kilo of body- 
 weight which corresponds to the heat-production of a resting man. 
 Another suggestive fact is that the excessive excretion of nitrogen 
 does not run parallel with the rise of temperature in fever, but is 
 often most marked after the crisis. During the stage of defer- 
 vescence an enormous amount of urea is sometimes given off. In a 
 case of typhus, in the mixed urine of the third and fourth days after 
 the crisis, no less than 160 grammes of urea was found (Naunyn), or 
 nearly three times the normal amount for a man on full diet. Again, 
 when fever is caused by the injection of bacteria or their products, 
 the increase in the carbon dioxide eliminated and oxygen consumed 
 occurs even when the temperature is prevented from rising by cold 
 baths. It seems perfectly clear, then, that the increase of metab- 
 olism is, in many cases at least, a primary phenomenon of fever. 
 Its course and incidence, falling as it does so largely upon the 
 proteins, the steady loss of tissue nitrogen, and the inability of the 
 tissues to recoup their losses from the protein of the food or to 
 shield their own protein by burning more carbo-hydrate or fat, all 
 suggest that the cells are poisoned by toxic products of the infective 
 process. The poisoned bioplasm falls an easy prey to the hydro- 
 lysing and oxidizing agents always present in the tissues. It breaks 
 down more rapidly and builds itself up more slowly than normal 
 bioplasm. This increased, and to some extent perverted, metab- 
 olism, far from being occasioned by the febrile temperature, is quite 
 probably the cause of the thermo-regulative upset which we call fever. 
 For Mandel has shown — (i) that one of the purin bases (xanthin) 
 causes fever in monkeys; (2) that the purin bases in the urine are 
 increased both in infective fevers and the so-called aseptic or surgical 
 fever — 'that is, in cases where the temperature rises after such injuries 
 as extensive crushing of tissues without infection. There is a con- 
 stant relation between the height of the fever and the quantity of 
 purin bases excreted. The source of the purin bases in aseptic fever 
 is presumably the autolysis of the injured tissue, from which they 
 pass into the blood without being oxidized to uric acid. The xanthin 
 fever can be prevented by salicylates, though not by antipyrin. 
 
 It has been very generally admitted that the chief seat of excessive 
 metabohsm in fever is the muscles; but U. Mosso has stated that 
 cocaine fever — the marked rise of temperature produced by injec- 
 tion of cocaine — can be obtained in animals paralyzed by curara. 
 This, even if true, would not support the conclusion that a ' nervous 
 fever ' — that is to say, a fever due solely to increased metabolism 
 in the nervous system — exists; for in a curarized animal a large 
 
7o8 ANIMAL HEAT 
 
 amount of 'active' tissue (glands, heart, smooth muscle) still 
 remains in i)hysiol()gical connection with the brain and cord. But, 
 as a matter of fact, in an animal under a dose of curara sufficient 
 to completely paralyze the skeletal muscle cocaine causes no appre- 
 ciable rise of rectal temperature; and this is strongly in favour of 
 tlie view that the fever produced in the non-curarized animal is 
 connected with excessive muscular metabolism. 
 
 Significance of the Increased Temperature in Fever. — It remains 
 to ask whether the rise of temperature is unytliing more than a 
 superticial and, so to speak, an accidental circumstance. The 
 question has already been raised in discussing the changes in the 
 circulation in fever (p. 706). The orthodox view for many ages 
 has undoubtedly been that the increase of temperature is in itself 
 a serious part of the pathological process, a symptom to be fought 
 with and, if possible, removed. And, indeed, it is not denied by 
 anyone that the excessive rise of temperature seen in some cases of 
 febrile disease (to 43° C., or even to 45") is, apart from all other 
 changes, a most imminent danger to life, unless, as is sometimes the 
 case (in influenza, e.g. , where a temperature of 44° has been observed) , 
 the high temperature lasts only a short time. Experimental heat 
 paralysis, a condition in which all voluntary and reflex movements 
 are abolished, is produced in frogs by raising the internal tempera- 
 ture to about 34° C. On cooling, the animal recovers. A similar 
 condition can be induced in mammals, but, of course, at a higher 
 temperature. The central nervous system succumbs before the 
 peripheral structures. The superior cervical ganglion in the cat or 
 rabbit loses the power of transmitting nerve impulses at 50° C 
 But some evidence has been brouglit forward, mostly from the field 
 of bacteriology, to support the idea that in infective processes the 
 rise of temperature is of the nature of a protective mechanism, that 
 the fever is, indeed, a consuming fire, but a fire that wastes the body, 
 to destroy the bacteria. The streptococcus of erysipelas, for ex- 
 ample, does not develop at 39° to 40° C, and is killed at 39'5° to 
 41° C, and erysipelas infections in rabbits are less virulent if the 
 body -temperature be artificially raised. Anthrax bacilli, kept at 
 42° to 43° C. for some time, are attenuated, and when injected into 
 animals confer immunity to the disease. Heated for several days 
 to 41° to 42° C, pneumococci render rabbits immune to pneumonia, 
 and in rabbits in which ' puncture ' fever has been induced pneumo- 
 coccus infections run a milder course. These bacteriological results 
 are sup])orted to a certain extent by clinical experience. For it has 
 been observed that a cholera patient witli distinct fever has a 
 better chance of recovery than a case which shows no fever. But 
 too much weight ought not to be given to isolated facts of this sort, 
 and adverse evidence can be produced both from the laboratory 
 
TEMPI'. HA TURE TOPOGh'A J'UY 
 
 709 
 
 and tlie hospital. For although hens are immune to anthrax under 
 ordinary conditions, but can be infected by inoculation when 
 artificially cooled, frogs, equally immune at the temperature of the 
 air, become susceptible when artificially heated. And it is impos- 
 sible to deny that the use of cold baths in typhoid fever is sometimes 
 of remarkable benefit. This benefit, however, while very unlikely 
 to be connected with any directly unfavourable action of the reduced 
 body-temperature on the growth of the bacilli, may perhaps be due, 
 in some part at least, to an increase in the cutaneous vaso-con- 
 striction which helps to send through the infected intestine a more 
 copious stream of blood. 
 
 Section IV. — Distribution of Heat — -Temperature 
 Topography. 
 
 The great foci of heat-formation — the muscles and glands — would, 
 if heat were not constantly leaving them, in a short time bcconn; 
 much warmer than the rest of the body; while structures like the 
 bones, skin, and adipose tissue, in which chemical change and heat- 
 production are slow, would soon cool down to a temperature not 
 much exceeding that of the air. The circulation of the blood 
 insures that heat produced in any organ shall be carried away and 
 speedily distributed over the whole body; while direct conduction 
 also plays a considerable part in maintaining an appro.ximately 
 uniform temperature. The uniformity, however, is only approxi- 
 mate. The temperature of the liver is several degrees higher than 
 that of the skin, and the temperature of the brain several degrees 
 higher than that of the cornea. The blood of the superficial veins 
 is colder than that of the corresponding arteries. 
 
 The crural vein, for example, carries colder blood than the crural 
 artery, and the external jugular than the carotid. The heat produced 
 in the deeper parts of the regions which they drain is more than counter- 
 balanced by the heat lost in the more superficial parts. When loss of 
 heat from the surface is sufficiently diminished by an artificial covering, 
 or prevented by the protected situation of any organ with an active 
 metabolism, the venous blood leaving it is warmer than the arterial 
 blood coming to it. The temperature of the blood passing from the 
 levator labii superioris muscle of the liorse during mastication may be 
 sensibly higher than that of the blood which feeds it ; the blood in the 
 vena profunda femoris, and in the crural vein of a dog with the leg 
 wrapped in cotton- wool, is warmer byO'i°to 0*3° than of the crural 
 artery. The difference is due to the heat produced in the muscles, and it 
 ought to be of this order of magnitude. The quantity of blood in a 
 7-kilo dog is about J kilo ; J of this, or ^ kilo, is in the skeletal muscles, 
 and the average circulation-time through them may be taken as ten 
 seconds. Six times in the minute, or 360 times in the hour, | kilo of 
 blood passes through the muscles, and is heated on the average by 0-2°. 
 
 This represents a heat-production of about '-q- x — , or 9 calories per 
 
 hour. Now, the total heat-production of a 7-kilo dog is about 
 
yio ANIMAL HEAT 
 
 1 1) calorics per hour, of which somewhat less than one-half is formed 
 in tne skeletal muscles. 
 
 The blood of the inferior vena cava at the le\cl of the kidneys may 
 be o*i° colder than that of the abdominal aorta, but is warmer than 
 the blood of the superior cava. The right heart, therefore, receives 
 two streams of blood at different temperatures, which mingle in its 
 cavities. A controversy was long carried on as to the relative tem- 
 perature of the blood of the two sides of the heart ; but the researches 
 of Heidenhain and Korner have shown that a thermometer passed into 
 the right ventricle through the jugular vein stands, as a rule, slightly 
 higher than a thermometer introduced through the carotid into the 
 left ventricle. The method gives not so much the temperature of the 
 blood in the two cavities as that of their walls. The thin-walled right 
 ventricle is heated by conduction from the warm liver, from which it is 
 only separated by the diaphragm, while the left ventricle loses heat 
 to the cooler lungs. The difference of temperature is not caused by 
 cooling of the blood in its passage through the pulmonary capillaries, 
 for even when respiration is suspended, a difference of temperature 
 between the two sides of the heart is found. Under ordinary circum- 
 stances, the inspired air is already heated almost to body-temperature 
 before it reaches the alveoli. But, while this is the case, a fall of less 
 than ^■\y° in the temperature of the blood passing through the lungs 
 would account for all the heat lost by the expired air. If half of the 
 loss took place in the upper air-passages, less than ;^V)'' would be suffi- 
 cient. A slight difference of temperature in the blood of the two ven- 
 tricles might be caused, even in the absence of respiration, by the heat 
 developed in the cardiac muscle itself during contraction, a large pro- 
 portion of which must be conveyed by the coronary veins into the right 
 heart. 
 
 The surface temperature varies between rather wide limits with the 
 temperature of the environment. The temperature of cavities like 
 the rectum, vagina, and mouth, and of secretions like the urine, approxi- 
 mates to that of the blood in the great vessels or the heart, and under- 
 goes only slight changes. An increase in the velocity of the blood causes 
 the internal and surface temperatures to come nearer to each other, 
 the former falling and the latter rising. When the loss of heat from 
 a portion of the surface is prevented, the temperature of this portion 
 approaches the internal temperature. For this reason a thermometer 
 placed in the axilla approximately measures the internal temperature, 
 and not that of the skin; and a thermometer in tlie groin of a rabbit, 
 and completely covered by the flexed thigh, may stand as high as, or, 
 it is said, even higher than, a thermometer in the rectum (flale White). 
 The temperature in the mouth is not a very reliable index of the deep 
 temperature of the body, especially in cold weather or after exercise, 
 as it is apt to be influenced by the inspired air. The mouth must, of 
 course, be kept closed during the measurement. On the average its 
 temperature is about the same as that of the axilla, and 0*4° C. below 
 that of the rectum. The rectal temperature is o->° or 0-3° alx)ve that 
 of the urine. In point of accuracy rectal observations are the best, and 
 next to them determinations of the temperature of the stream of urine. 
 The latter method, although subject to obvious limitations, is rapid and 
 free from the danger of conveying infection to the person (Pembrey). 
 
 The surface temperature is a rough index of the rate of heat-loss; 
 the internal temperature, of the rate of heat-production. A normal 
 skin temperature and a rising rectal temperature would probably in- 
 dicate increased production of heat; an increased rectal temperature, 
 
TEMPERATURE TOPOGRAPH Y 7H 
 
 in conjunction with a diminished surface temperature, as in the cold 
 stage of ague, might he duo cither to diminished heat-loss while the 
 heat-production remained normal, or to diminished heat-loss plus 
 increased heat-production. 
 
 Tlie following tables illustrate the differences of temperature found 
 in the body. It should be remembered that the numbers are not 
 strictly comparable with each other; the temperature of the mammals 
 in which direct observations have been made on the blood is not 
 exactly the same as that of man, the temperature of the dog. for 
 example, being a little (about i° C.) higher. Then in the same animal 
 there is no very constant ratio between the temperature of the blood 
 in two vessels or of the skin at two points. Even in the same vessel 
 the temperature may vary with many circumstances, such as the 
 velocity of the stream, and the state of activity of the organ from which 
 it comes. Apart from physiological variations, experimental fallacies 
 sometimes cause a want of constancy, especially in measurements of 
 blood temperature. The insertion of a mercurial thermometer into a 
 vessel is very likely to obstruct the passage of the blood; and if the 
 blood lingers in a warm organ, it will be heated beyond the normal. 
 In man the blood-temperature in the arteries at the wrist has been 
 estimated indirectly by the calorimetric method of measuring the 
 blood-flow in the hand (p. 122), probably with greater accuracy than 
 would be attainable by the direct insertion of a thermometer, were 
 this permissible. The temperature of the calorimeter is determined at 
 which it neither imparts heat to the blood nor gains heat from the blood. 
 On the assumption that the heat-production of the resting hand is 
 negligible for this purpose,* the temperature so fixed will be that at 
 which the blood enters the hand — i.e., the temperature of the arterial 
 blood at the wrist. 
 
 Blood. {Dog.) 
 
 Right heart - . . . 38-8° C. 
 
 Left ,, - - - - - 38-6 
 
 Aorta 38-7 
 
 Superior vena cava - - _ 36-8 
 
 Inferior ,, - - - 38-1 
 
 Crural vein - - _ . _ 37-21 
 ,, artery - . . _ 38'o 
 
 Profunda femoris vein - - 38-2 
 
 Portal vein - - - - 38-39 "I Varies with activity 
 
 Hepatic vein - . . 38'4-39'7 J of digestive organs. 
 
 Arterial blood at wrist in man - 0-5 below rectal temperature. 
 
 * Since, of course, some heat is produced in the hand even at rest, although 
 doubtless less per unit of weight than in the resting body as a whole, the 
 arterial blood temperature as thus determined must be somewhat too high. 
 No error is caused by this in the calculation of the blood-flow in the hand 
 (p. 122) ; for while the factor T — T' in the denominator is somewhat too great, 
 thv corresponding quantity of heat produced in the hand is included in H in 
 the numerator. 
 
 t The following numbers were obtained (in an anaesthetized dog whose 
 rectal temperature had fallen 2° C.) for the temperature of the walls of the 
 crural artery and vein, as measured by an electrical resistance thermometer. 
 Leg of dog lightly wrapped in wool. '\ 
 
 Crural artery 34'95 
 
 vein ------ 34-761 Rcclum, 36*2 
 
 Leg more carefully wrapped up. [Air, i6'3 
 
 Crural artery ----- 34' 70 
 
 vein - - - - - - 34' 82 J 
 
712 
 
 ANIMAL HEAT 
 
 Tissues. 
 
 Bniin 
 
 Liver ------ 
 
 Subcutaneous tissue 2-i lower than 
 
 tliat of subjacent muscles (man). 
 
 Anterior chamber of eye 
 
 Vitreous humour 
 
 40° C 
 4o*6-40*9 
 
 - 3 
 
 3^';;}(rabbit). 
 
 Cavities. 
 Axilla - - - . 
 Rectum - - - - 
 Moutli - - - - 
 Vagina - . - _ 
 Uterus - - - - 
 External auditory meatus - 
 Bladder (temperature of the 
 escaping urine) 
 
 (Man.) 
 
 36-3-37-5° 
 
 36-37-8 
 
 37'-5 
 
 37-5-38 
 
 37-7-38-3 
 
 37-3-37-8 
 
 C. (97-3-99-5" F-). 
 
 36-0-37-5 
 
 Air 
 
 temperature, 
 
 4-5" " 
 
 trachea - 
 
 C. 
 
 [Horse.) 
 
 - ^3-4° C. 
 
 - 32-4 in inspiration. 
 
 - 34'4 in expiration. 
 
 (Man) 
 
 Room 
 
 temperature. 
 
 I/O 
 
 Respiratory Passages. 
 TMiddle of nasal cavity 
 
 I :: " ' 
 
 Natural Surfaces. 
 Cheek (boy, immediately after running) 
 'Anterior surface of forearm 
 Posterior 
 
 Skin over biceps - . - _ 
 
 head of tibia - - . 
 immediately below xiphoid carlik; 
 over sternum - - - - 
 On hair (boy) ----- 
 Under hair over sagittal suture (boy) 
 Shaved skin of neck (rabbit) 
 On hair 
 
 ,, between eyes ,, 
 
 Artificial Surfaces. 
 
 k ' Surface of trousers over thigh 
 
 Room , ° 
 
 , . - ,, coat over arm - 
 
 temperature. waistcoat - - 
 
 17-5 I 
 
 36-23° 
 
 33-5-34-4 
 
 34-0 
 
 35-0 
 
 31-9 
 
 34-7 
 
 33 2 
 
 30-0 
 
 33-7-34-0 
 
 36-5 
 
 31-5 
 
 30-7 
 
 23-7- 
 j6-8 
 26-0 
 
 2ii-r 
 
 Normal Variations in the Temperature. — The internal tempera- 
 ture, as has been already said, is not strictly constant. It varies 
 with the time of day; with the taking of food; with age; to some 
 extent with violent changes in the external temperature, such as 
 those produced b}^ hot or cold baths; and possibly with sex. On 
 the average the range of variation in tlie temperature of the rectum 
 or urine of a healthy man is from 36-0° C. (96-8° F.) to 37*8° C. 
 (100-0° F.). 
 
 In the monkey a very distinct and constant diurnal variation has 
 been observed, and the range is much wider than in man (as much 
 as 5-4° F.), the maximum falling between 6 and 8 p.m. and the 
 minimum between 2 and 4 a.m. (Simpson). 
 
TEMPERA T URE TOPOGRAPH Y 
 
 713 
 
 The daily curve of temperature shows a niininiuin in the early 
 morning, between two and six o'clock (36-3° C), and a maximum 
 in the evening, between five and eight o'clock (37*5° C) (Fig. 227). 
 The daily range in health may be taken as a little over i" C, 01 
 about 2° F. In fever it is generally greater, but the maximum and 
 minimum fall at the same periods; and it is of scientific, and also 
 of practical, interest that the early morning, when the temperature 
 and pulse-rate are at their minimum, is often the time at which the 
 flagging powers of the sick give way. From two to six o'clock in 
 the morning the daily tide 
 of life may be said to reach 
 low- water mark. Even in 
 a fasting man the diurnal 
 temperature curve runs its 
 course, but the variations 
 are not so great. The ta- 
 king of food of itself causes 
 an increase of temperature, 
 although in a healthy man 
 this rarely amounts to more 
 than half a degree. The rise 
 of temperature is certainly 
 due in part to the increased 
 work of the alimentary 
 canal, but it is in the main 
 connected with the increase 
 of metabolic activity which the entrance of the products of digestion 
 into the blood brings about. The heat-production is especially 
 increased by proteins. 
 
 A dog weighing I5'3 kilos, the heat-production of which was 22-3 calo- 
 ries during an hour previous to feeding, was given 1,200 grammes of 
 meat at noon. The heat-production rose to 36 calories in the 2nd hour, 
 and 42 calories in the 3rd. It remained above 40 calories per hour 
 beyond the loth hour, and in the 14th hour it had only fallen to 37 calo- 
 ries, to reach 25 calories in the 21st hour. On the whole, the increase 
 in heat-production ran parallel with, and was proportional to, the 
 increase in the excretion of nitrogen (Williams, Richie and Lusk). 
 The relati\-ely unimportant share taken by the increased work of the 
 gastro-intestinal tract in the augmentation of the metabolism is illus- 
 trated by the fact that a high rate of heat-production was maintained till 
 the 14th hour, even although by this time three-quarters of the nitrogen 
 corresponding to the food protein had been eliminated in the urine, and 
 the work of digestion and absorption must have been largely completed. 
 
 The rise of temperature during digestion is gradual, the maximum 
 being reached during the fourth hour, or even later. 
 
 The cause of the daily variation of temperature has been much 
 discussed. There is no doubt that several factors are concerned, 
 among the most important being the variation in the amount of 
 contraction of the skeletal muscles and the influence of food. Mus- 
 
 2?7. 
 
 Curve showing the Daily Variation 
 of Body-Temperature. 
 
7M 
 
 ANIMAL HEAT 
 
 d2S 
 38 
 
 36 
 
 J^ 
 
 32 
 
 ■5i5 4iJ i25 M5 S6 
 
 \—r 
 
 
 
 
 
 ' "'\ 
 
 ^, 
 
 
 
 
 
 \| 
 
 
 
 
 
 
 \, 
 
 
 
 ip t& 
 
 
 \ 
 
 
 ^ 
 
 cular exercise is capable of causing a considerable rise in the tem- 
 perature of the rectum and urine, to 38'5° C. (101-3° F.) or even 
 38-9° C. (102° F.) without producing any feeling of distress. Other 
 unknown influences seem also to be involved, as is shown by the 
 fact that in persons who work at night and sleep during the day 
 the curve of temperature, although greatly altered, is not reversed. 
 Recent observations on this subject are those of Benedict. By 
 means of a resistance thermometer in the rectum, readings were 
 
 taken usually every four minutes. 
 With such a thermometer no disturb- 
 ance of the person's sleep is n<*cessary 
 to obtain a reading. He can sit with- 
 out discomfort in any position, walk 
 about the room (returning to the ob- 
 server's table for the observations), 
 and even ride a stationary bicycle. 
 Even years of night-work do not elim- 
 inate the tendency to a fall of tempera- 
 ture at night, a minimum in the early 
 morning, and a morning rise. 
 
 As to the relation of age and se.x to 
 temperature, it is only necessary to 
 remark that the mean temperature 
 both of the young child and of the 
 old man is somewhat higher than 
 that of the vigorous adult; but a 
 point of more importance is the rela- 
 tive imperfection of the heat-regulation 
 in infancy and age, and the greater 
 effect of accidental circumstances on 
 the mean temperature. Thus, old people and young children are 
 specially liable to chills, and a fit of crying may be sufficient to 
 send up the temperature of a baby. In infants an hour or two old 
 the temperature may be as low as 34° C. (93*2° F.) or 33*0° C. 
 (91-4° F.) even when they are fully clothed in a room at 15° C 
 (59° F.). It rises gradually during the first day or two, but shows 
 marked variations. On the fifth day after birth, e.g., the rectal 
 temperature ranged from 36-2° C (97* 16° F.) to 33*5° C. (92-3° F.) 
 in a child weighing ^\ pounds (Babak). The temperature of women 
 is generally a little higher than that of men, and is also somewhat 
 more variable. A fall of temperature, rarely amounting to more 
 than 1° F., is associated with the menstrual jx-riod. 
 
 After death the body cools at first rapidly, then more slowly 
 (Fig. 2:8). But occasionally a post-mortem rise of temperature 
 may take place. In certain acute diseases (like tetanus) associated 
 with excessive muscular contraction this has been especially noticed ; 
 in bodies wasted by prolonged illness it does not occur. Nearly an 
 
 30 
 
 28 
 
 Fig. 228. — Curve of Cooling after 
 Death : Guinea - Pig. Time 
 marked along horizontal, and 
 temperature along vertical axis. 
 At a ether and chloroform 
 given to kill animal; death, as 
 indicated by stoppage of the 
 heart, took place at h. The 
 dotted line shows the course 
 the curve would have taken if 
 death had occurred at the 
 moment the anx-sthetics were 
 given. Air of room I7-6"'. 
 
PRACTICAL EXERCISES 715 
 
 hour after death, in a case of tetanus, the temperature was found 
 to be 45*3°, while before death it was 447° (Wunderhch). In dogs 
 a shght post-mortem rise may be demonstrated, especially when 
 the body is wrapped up; but when an animal has been long under 
 the influence of anaesthetics no indication whatever of the phenom- 
 enon may be obtained. The explanation of post-mortem rise of 
 temperature is to be found: (i) In the continued metabolism of the 
 tissues for some time after the heart has ceased to beat, for the cell 
 dies harder than the body. (2) In the diminished loss of heat, due 
 to the stoppage of the circulation. (3) To a small extent in physical 
 changes (rigor mortis, coagulation of blood) in which heat is set free. 
 
 PRACTICAL EXERCISES ON CHAPTERS X., XL, AND XII. 
 
 I. Glycogen* — (i) Preparation. — {a) Cut an oyster into two or three 
 pieces, throw it into boiling water, and boil for a minute or two. Rub 
 up in a mortar with clean sand, and again boil. Filter. Precipitate 
 any proteins which have not been coagulated, by adding alternately 
 a drop or two of hydrochloric acid and a few drops of potassio-mercuric 
 iodide so long as a precipitate is produced. Only a small quantity of 
 these reagents will be required, as the greater part of the proteins has 
 been already coagulated by boiling. Filter if any precipitate has formed. 
 The filtrate is opalescent. Precipitate the glycogen from the filtrate (after 
 concentration on the water-bath if it exceeds a few c.c. in bulk) by the 
 addition of four or five times its volume of alcohol. Filter off the precipi- 
 tate, wash it on the filter with alcohol, and dissolve it in a little water. 
 To some of the solution add a drop or two of iodine ; a reddish-brown 
 (port wine) colour is produced, which disappears on heating, returns on 
 cooling, is removed by an alkali, restored by an acid. Add saliva to some 
 of the glycogen solution, and put in a bath at 40° C. In a few minutes 
 reducing sugar (maltose) will be found in it by Trommer's test (p. 10). 
 
 Note that dextrin (erythrodextrin) gives the same colour with iodine 
 as glycogen does. Dextrin is also precipitated by alcohol, but a 
 greater proportion must be added to cause complete precipitation. 
 Glycogen is completely precipitated by saturation with magnesium 
 sulphate or ammoniuni sulphate, so that the filtrate no longer gives 
 the reddish colour with iodine. A pure solution of erythrodextrin is 
 not precipitated. On the addition of a drop or two of a solution of 
 basic lead acetate to a solution of glycogen in distilled water, a pre- 
 cipitate forms immediately. When the same reagent is added to a 
 solution of dextrin in distilled water there is no immediate precipitate. 
 Maltose is formed when dextrin is digested with saliva. 
 
 {b) Cut another oyster into pieces, throw it into boiling water acidu- 
 lated with dilute acetic acid, and boil for a few minutes. Rub up in a 
 mortar with sand, boil again, and filter. Test a portion of the fil- 
 trate with iodine for glycogen. Precipitate the rest with alcohol, 
 filter, dissolve the precipitate in water, and test again for glycogen. 
 On boiling some of the opalescent solution for a few minutes after the 
 addition of a few drops of sulphuric acid the opalescence disappears, and 
 
 * For the quantitative estimation of glycogen in organs, Pfliiger's method 
 is the best. The organ is minced and heated with strong (60 per cent.) potas- 
 sium hvdroxide. The glycogen is precipitated with alcohol, and then, after 
 hydrolysis with hj^drochloric acid, estimated as dextrose. 
 
7l6 METABOLISM AND ANIMAL HEAT 
 
 when the solution has been neutralized with sodium hydroxide it gives 
 Tronimer's test, owing to the hydrolysis of the glycogen into dextrose. 
 (j) Deeply etherize a dog or rabbit five hours'after a meal rich in 
 carbo-hydrates — e.g., rice and potatoes in the case of the dog, carrots 
 in the case of the rabbit. Fasten it on a holder. Clip off the hair 
 over the abdomen in the middle line. Make a mesial incision through 
 the skin and abdominal wall from the ensiform cartilage to the pubis. 
 The liver will now be rapidly cut out (by the demonstrator) and divided 
 into two portions, one of which will be (distributed among the class 
 and) treated as in (a) or {b) ; the other will be kept for an hour at a 
 temperature of 40° C., and then subjected to process (a) or (b). Little, 
 if any, sugar and much glycogen will be found in the portion which 
 was boiled immediately after excision. Abundance of sugar will be 
 found in the jiortion kept at 40° C. ; it may or may not contain glycogen. 
 
 2. Catheterism. — In many physiological experiments it is necessary' 
 to obtain urine from the bladder by means of a catheter. It is possible 
 to pass a fine rubber catheter into the bladder of a male dog. A 
 larger one is easily passed in a male rabbit, and a still larger in a bitch, 
 which is often used for experiments on metabolism. Even in the bitch 
 the opening of the urethra lies entirely concealed within the vagina, 
 much deeper than the cul-de-sac in the mucous membrane, into which 
 the beginner usually tries to force the catheter. For a first attempt 
 tile animal should be etherized and fastened on a holder. The little 
 or index finger of the left hand is passed into the vagina till the sjmi- 
 physis pubis can be felt. A little below this is the opening of the 
 urethra. With the riglit hand the point of a catheter of suitable 
 calibre is directed along the finger, and after a little ' guess and trial ' 
 it slips into the bladder, its entrance being announced by the escape of 
 urine. A glass tube drawn out to a sufticiently small calibre and bent 
 near the point is the easiest form of catheter to pass in a bitch. The 
 point must, of course, be rounded in the flame. The insertion of the 
 catheter is much facilitated by the use of a speculum. 
 
 When the bitch is to be used in a long series of experiments an 
 operation is sometimes performed first of all to render the urethral 
 orifice more accessible. 
 
 3. Glycosuria. — (i) (o) Weigh a dog (female by preference) or rabbit. 
 Fasten on a holder, and etherize. Insert a glass cannula into the 
 femoral or saphena vein of the dog, or into the jugular of the rabbit 
 (p. 214). Fill a burette with a 2 per cent, solution of dextrose in 
 physiological salt solution, connect it with the cannula bv means of an 
 indiarubber tube, taking care that there are no air-bubbles in the tube, 
 and sloivly inject as much of the solution as will amount to |- or J grm. 
 of sugar per kilo of body-weight. Tie the vein, remove the cannula, and 
 in half an hour evacuate the bladder by passing a catheter, by pressure 
 on the abdomen, or. if both of these methods fail, by tapping the bladder 
 with a trocar pushed through the linea alba (suprapubic puncture). 
 In an hour again draw off the urine. Test both specimen" for sugar. 
 
 In this experiment the opportunity may also be taken to demon- 
 strate that egg-albumin, when injected into the blood, is excreted by 
 the kidneys, a filtered solution containing the albumin of one egg and 
 sugar in the quantity mentioned being injected. 
 
 The catheter may be inserted before the injection is begun, and the 
 bladder evacuated. After the injection the urine that drops from the 
 catheter may be collected in test-tubes, first every two minutes, and 
 then, as soon as sugar is found, every ten minutes. Determine the 
 interval between injection and the appearance of the first trace of 
 sugar and albumin. If a sufficient amount of urine is obtained, the 
 
PRACTICAL EXERCISES 71? 
 
 quantity of sugar in successive specimens may be estimated and com- 
 pared. The rate of How of the urine as measured by the number of 
 drops falling from the catheter may also be estimated from time to time 
 in order to determine whether diuresis is taking place. 
 
 If a rabbit is used for this experiment, the sugar solution may be 
 injected into the ear vein. The vein is caused to swell up by pressing 
 on it with the finger and thumb, and the hypodermic needle is then 
 inserted towards the heart. 
 
 {b) Instead of collecting the urine by a catheter in the bladder, the 
 abdomen of the dog may be opened, and a cannula tied into each ureter. 
 The two cannuke are then connected by sliort rubber tubes with a 
 glass Y-piece, on the stem of which a test-tube is tied for collecting the 
 urine. Replace the test-tube by a fresh one from time to time. The 
 urine already in the bladder is removed by pressure or by a trocar, and 
 tested for sugar, since the anaesthetic itself may cause a certain amount 
 of glycosuria. Test the samples of urine obtained from the ureters 
 for sugar, and in those in which it is present estimate its amount. Note 
 also any changes in the rate of secretion of urine, and any abnormal 
 constituents, as albumin. 
 
 (2) Phlorhizm Glycosuria. — Dissolve ^ grm. of phlorhizin in warm 
 water, and inject it subcutaneously into a rabbit. Obtain a sample of 
 the urine at the end of two hours, by pressure on the abdomen with 
 the thumb or by passing a catheter, and test for sugar. If none is 
 present, wait some time longer, and again test the urine. 
 
 This experiment can also be performed without risk on man. One 
 grm. of phlorhizin has been injected twice a day without disturbing the 
 individual. Much sugar is found in the urine, but it disappears the 
 day after the administration of phlorhizin is stopped. The phlorhizin 
 may also be given by the mouth, but more is required, and it is not 
 very easily absorbed, and often causes diarrhoea (v. Mering). 
 
 (3) Aliynentary Glycosuria. — The urine having been tested for sugar 
 for two successive days, and none being found — • 
 
 (fl) A large quantity of dextrose is to be taken in the form which is 
 most agreeable to the student some hours after a meal. The urine of 
 the next twenty-four hours is to be collected and measured. A sample 
 of it is then to be tested for reducing sugar by Trommer's and the 
 phen^d-hydrazine test. If any sugar is found, the reducing power of a 
 definite quantity of the urine is to be determined by titration wath 
 Fehling's solution (p. 326). 
 
 {b) Instead of dextrose use cane-sugar and proceed as in {a). But 
 estimate the reducing power of the urine («) before and (/3) after boiling 
 with hydrochloric acid (p. 465). 
 
 (c) A large meal of rice and arrowroot, sweetened with as much dex- 
 trose as the observer can induce himself to swallow, is to be taken, and 
 the urine treated as in {a). 
 
 (d) A large number of sweet oranges may be eaten.* 
 
 4. Esfimation of the Sugar in Blood — Method of Lewis and Benedict, 
 somewhat modified. — The blood must be used immediately after being 
 drawn. When only a single sample is required it can be obtained by 
 puncturing a vein with a large-sized hypodermic needle. If a number 
 of students have to be provided with blood an animal may be killed 
 by decapitation. Long anaesthetization is to be avoided, as this causes 
 hyperglycaemia. To take blood from a vein, place a few crystals of 
 potassium oxalate in the tip of a 2 c.c. pipette, and having punctured the 
 vein with a needle, draw up blood into the pipette to a little above the 
 
 * These experiments may be distributed among the class so that each 
 student does one. 
 
7i8 METABOLISM AND ANIMAL HEAT 
 
 m^rk. Allow the blood to run back just to the mark, and immediately 
 discharge the contents of the pipette into a large test tidie (about 50 c.c. 
 capacity) containing 8 c.c. of distilled water. Shake until haemolysis 
 is complete. Then add 15 c.c. of saturated aqueous solution of pure 
 picric acid; shake thoroughly to precipitate the proteins of the blood, 
 and filter through a small filter paper. Into each of two long narrow 
 test tubes (capacity ab(jut 23 c.c), which have been marked accurately 
 with a tile at 10 c.c, measvire 7 c.c. of the fdtrate, add 2 c.c. of the 
 saturated solution of picric acid and i c.c. of a 10 per cent, solution of 
 anhydrous sodium carbonate. A duplicate determination will thus be 
 made. The test tubes are placed in an autoclave (according to Pearce's 
 modification of the method), and the pressure gradually brought up to 
 20 to 25 pounds to the scjuare inch (2 '5 kilogrammes to the square centi- 
 metre), and kept at this level for twenty-five minutes, j^icramic acid is 
 formed by the reducing action of the sugar, and from the amount of 
 picramic acid estimated by a colorimeter the amount of sugar is de- 
 duced. Let the autoclave cool down till the pressure is zero, remove 
 the tubes and allow them to cool to room temperature. Sufficient 
 water is now added to each tube to bring the volume back to the 10 c.c. 
 mark, and after shaking the contents are filtered through cotton into 
 the (Duboscq) colorimeter bottles. The determination is made by 
 comparison with a solution containing a known amount of pure dex- 
 trose which has been carried through the same process, or with a 
 picramic acid standard solution.* 
 
 A solution of pure dextrose may be used as a standard instead of the 
 picramic acid, as follows : Into a test tube place 4 c.c. of a solution, 
 corresponding to o*56 milligramme dextrose ; add 5 c.c. of the saturated 
 picric acid solution, and i c.c. of 10 per cent, solution of anhydrous 
 sodium carbonate. Place in the autoclave and proceed as above 
 described, bringing the final volume again to 10 c.c, and filtering 
 through cotton into one of the colorimeter bottles. 
 
 Calculation : 
 Reading of standard mgm. dextrose in standard'k mgm. dextrose per 
 Reading of unknown c.c. blood used ) " c.c. blood. 
 
 The amount of blood taken for each of the duplicate determinations 
 is 2^5X2 c.c.=o-56 c.c. The standard=o-5() milligramme dextrose in 
 10 'c.c, so that the second fraction on tlie left sick- of the eqiiation 
 becomes unity, and the reading of the standard divided by the reading 
 of the unknown gives at once the number of millignimmes of dextrose 
 in I c.c. of blood. 
 
 5. Milk. — (i) Examine a drop of fresh cow's milk with the micro- 
 scope. Note the fat globules of various sizes. 
 
 (2) Determine the specific gravity of the milk with a hydrometer 
 (lactometer). Then centrifugalize some of the milk to separate the 
 cream, which rises to the top of the tubes. Remove the cream and 
 determine the specific gravity of the skimmed milk. It will be found 
 to have increased, since the fat is of lower specific gravity than the 
 rest of the milk. Normal cow's milk has a specific gravity of 1,028 
 to 1,034, skimmed milk i,o33"to 1,037. 
 
 * Picramic acid, 56 milligrammes, anhydrous sodium carbonate, roo 
 milligrammes, and distilled water to make up 1,000 c.c. Dissolve the sodium 
 carbonatr in about 30 c.c. of water, add the picramic acid and dissolve it 
 with the aid of heat. When cooled to room temperature add onough water 
 to make 1,000 c.c. Picramic acid obtained on the market varies in the amount 
 of colour produced in the preparation of this sohition. The standard sliould 
 thereiore be compared with a solution of pure dextrose which has been standard- 
 ized by another method, and then treated by the Lewis and Benedict method. 
 
PRACTICAL EXIUtCISES 
 
 719 
 
 (3) Test the reaction of the milk to litnuis-iKiiicr. J t is slightly alkaline. 
 
 (4) {a) Put 10 c.c. of milk in a test-tube, and nearly fill it up with 
 water. Add strong acetic acid drop by drop. A precipitate of casein- 
 ogen is thrown down wliich entangles the fat, and carries it down 
 mechanically along with it. Filter olt the precipitate. Keep the 
 filtrate for (b). Wash the precipitate with water, scrape a portion of 
 it off the filter, and add to it .some 2 per cent, sodium carbonate solution. 
 The caseinogen dissolves, while the fat remains in suspension. The 
 solution gives the colour reactions for proteins (p. 8). 
 
 [h) lest st)me of the filtrate (p. 10) for lactose. Add dilute sodium 
 carbonate solution to another portion till it is only slightly acid. Boil, 
 and lactalbumin is coagulated. Remove the lactalbumiu by liltering, 
 and test this tiltrate for earthy {i.e., calcium and magnesium) phos- 
 phates by adding a few drops of ammonia, which precipitates them as 
 a slight cloud. 
 
 (c) To 5 c.c. of milk add an equal volume of saturated ammonium 
 sulphate solution. The caseinogen is precipitated, entangling the fat. 
 Filter off. The filtrate may be used to test for lactalbumin by boiling. 
 The addition of water to the precipitate of caseinogen (and fat) on the 
 filter causes the caseinogen to dissolve, as it is soluble in weak salt 
 solutions. Caseinogen can also be precipitated by saturating milk 
 with sodium chloride or magnesium sulphate. 
 
 (5) To 5 c.c. of milk add a couple of drops of 20 per cent, sodium or 
 potassium hydroxide, and then a few c.c. of ether. Shake up. The 
 ether dissolves the fat, and the opacity of the milk diminishes. Take 
 off the ether with a pipette, evaporate away most of it on a water-bath, 
 and place a drop or two of the remainder on a filter-paper. A greasy 
 stain is left, showing the presence of the fat of the milk, or butter. 
 
 (6) Clotting of Milk. — (a) To a few c.c. of milk in a test-tube add a 
 few drops of rennet. Place the tube in a bath at 40° C. In a short 
 time a clot or curd is formed, consisting of casein, which is derived from 
 the caseinogen. The fat is entangled in the clot. On standing some 
 time the clot contracts, and exudes the whey. Boil some of the whey 
 after slight acidulation with acetic acid; the lactalbumin and whey- 
 protein are coagulated. Test another portion of whey for proteins by 
 one of the general protein tests (p. 8) — e.g., the xanthoproteic. 
 
 lb) Repeat (a) but use rennet which has been previously boiied. The 
 milk is not curdled, because the ferment has been inactivated by boiling. 
 
 (c) To 10 c.c. of milk add 3 c.c. of i per cent, potassium oxalate. 
 Divide the oxalated milk into three portions — A, B, and C. To A add 
 a few drops of rennet, to B i c.c. of 2 per cent, calcium chloride solu- 
 tion and a little rennet, and to C i c.c. of 2 per cent, calcium chloride 
 solution alone. Put the tubes at 40° C. Clotting will occur in B, but 
 not in A or C. 
 
 0. Cheese. — (i) Rub up some finely-grated cheese in a mortar with 
 2 per cent, sodium carbonate solution. Filter. The filtrate contains 
 casein, which can be precipitated by adding dilute acetic acid by drops 
 to a portion of the filtrate. The precipitate is soluble in excess of the 
 acid. With another portion of the filtrate perform some of the general 
 protein tests (p. 8). 
 
 (2) Shake up some finely-grated cheese in a dry test-tube with ether. 
 Take off the ether with a pipette, and evaporate on a water-bath till 
 only a few drops remain. With a glass rod put a drop of the ether on 
 a piece of filter-paper. A greasy spot is left, showing that fat is present. 
 
 7. Flour. — (i) Mix some wheat-flour with a little water into a stiff 
 dough. Let it stand for a few minutes at body-temperature to facilitate 
 the formation of gluten. Wrap a piece in cheese-cloth, forming a kind 
 
720 METABOLISM AND ASIMAL HEAT 
 
 of bag, and knead it with the fingers in a capsule of water. The 
 starch grains come througli the cheese-cloth. Pour the water into a 
 beaker. It is opaque, and on standing the starch grains sink to the 
 bottom, (fl) Test for starch with the iodine test, and also examine 
 microscopically. The grains are round, with a central hilum, and are 
 smaller than those of potato starch (p. ii). (6) Test for sugar by 
 Trommer's test (p. lo). None is present unless the flour has been made 
 from inferior grain in which some germination has taken place. 
 
 (2) Go on kneading the dough till no more starch comes through. 
 The sticky mass which remains in the bag is a protein called gluten, 
 which is formed from certain globulins and other proteins in the flour 
 on addition of water. Oatmeal, ground rice, and other grains poor in 
 gluten-forming globulins do not form dough when mixed with water. 
 Suspend some of the gluten in water in a test-tube, and apply to it the 
 general protein colour tests (p. 8). 
 
 8. Bread. — (i) Rub up a small piece of the crumb of a stale loaf in a 
 mortar w^ith water. Strain through cheese-cloth. The fluid which 
 passes through contains starch grains, (a) Filter it, and test a portion 
 of the filtrate for dextrose by Trommer's test. A positive result 
 is obtained. Test another portion with iodine for erythrodextrin. 
 (fc) Test a portion of the residue of the bread which has not passed 
 through the cheese-cloth for protein by the general protein tests — e.g., 
 the xanthroproteic or Millon's tests. 
 
 (2) Repeat (i) using the crust of the bread. Both dextrose and 
 er^^throdextrin are present in the cold-water extract, but the dextrose 
 is less plentiful than in the crumb, having been converted into caramel 
 in the baking. The sugar and dextrin are formed from the starch of the 
 flour by the ferments of the yeast employed to make the bread rise. 
 
 9. Variations in the Total Nitrogen (p. 521) and in the Quantity of 
 Urea excreted, with Variations in the Amount of Proteins in the Food. — 
 The student should put himself, or somebody else if he can, for two days 
 on a diet poor in proteins, then (after an interval of forty-eight hours 
 on his ordinary food) for two ds-ys on a diet rich in proteins. A suitable 
 table of diets will be supplied. The urine should be collected on ths 
 six days of the period of experiment, on the day before it begins, and 
 on the day after it ends. Small samples of the mixed urine of the 
 twenty-four hours for each of these eight days should be brought to the 
 laboratory', and the quantity of urea determined by the hypobromite 
 method. The volume of the urine passed in each interval of twenty- 
 four hours being known, the total excretion of urea for the twenty-four 
 hours can be calculated, and a curve plotted to show how it varies 
 during the period of experiment.* If sufficient time is available, the 
 experiment will be made still more instructive by determining the 
 total nitrogen in each sample in addition to the urea. A curve showing 
 the variation in the total nitrogen can then be p>lotted on the same paper 
 as the urea curve, and a table calculated giving the percentage of the 
 total nitrogen contained in the urea for eacli day of the experiment. 
 
 10. Action of Epinephrin (Adrenalin). — Several experiments to illus- 
 trate this are given in the Practical Exercises following other chapters, 
 but may equally well be performed here. (See Experiment 8, p. 66; 
 Experiment 3, p. 453;) 
 
 * In 17 healthy students the average amount of urea excreted in twenty 
 four hours on the ordinary diet was 29-51 grammes (minimum 1935 grammes 
 maximum 4601 grammes) ; on a diet poor in protein, average 20- 75 grammes 
 (minimum 9-52 grammes, maximum 32- 86 grammes) ; on a diet rich in protein, 
 average 38'83 grammes (minimum 2326 grammes, maximum 67'82 grammes). 
 
PRACTICAL EXERCISES 721 
 
 11.* Measurement of the Quantity of Heat given off in Respiration. — • 
 
 This may be done approximately as follows: Put in the inner coi)j)er 
 vessel, A, of the calorimeter shown in Fig. 224 (p. 682) a measured 
 quantity of water sufficient to completely cover the series of brass discs. 
 Place A in the wide outer cylinder, the bottom of which it is prevented 
 from touching by pieces of cork. The outer cylinder hinders loss of 
 heat to the air. Suspend a thermometer in the water through one of the 
 holes in the lid. In the other hole place a glass rod to serve as a stirrer, 
 Read off the temperature of the water. Put the glass tube connected 
 with the apparatus in the mouth, and breathe out through it as regu- 
 larly and normally as possible, closing the opening of the tube with 
 the tongue after each expiration and breathing in through the nose. 
 Continue this for live or ten minutes, taking care to stir the water fre- 
 quently. Then read off the temperature again. If W be the quantity 
 of water in c.c, and t the observed rise of temperature in degrees Centi- 
 grade, W^ equals the quantity of heat, expressed in small calories 
 (p. 675), given off by the respiratory tract in the time of the experiment, 
 on the assumptions (i) that all the heat has been absorbed by the water, 
 (2) that none of it has been lost by radiation and conduction from the 
 calorimeter to the surrounding air. Calculate the loss in twenty-four 
 hours on this basis; then repeat the experiment, breathing as rapidly 
 and deeply as possible, so as to increase the amount of ventilation. 
 The quantity of heat given off will be found to be increased. "f" 
 
 In an experiment of short duration (2) is approximately fulfilled. 
 As to (i), it must be noted that in the first place the metal of the 
 calorimeter is heated as well as the water, and the water-equivalent 
 of the apparatus must be added to the weight of the water (p. 676). 
 The water-equivalent is determined by putting a definite weight of 
 water at air temperature T into the calorimeter, and then allowing a 
 quantity of hot water at known temperature T' to run into it, stirring 
 well, and noting the temperature of the water when it has ceased to 
 rise. Call this temperature T". Enough hot water should be added 
 to raise the temperature of the calorimeter about 2° C. The quantity 
 run in is obtained by weighing the calorimeter before and after the 
 hot water has been added. Suppose it is m. Let the mass of the cold 
 water in the calorimeter at first be M, and let M'=the mass of water 
 which would be raised 1° C. in temperature by a quantity of heat suffi- 
 cient to increase the temperature of all the metal, etc., of the calorimeter 
 by i" — in other words, the water-equivalent of the calorimetor. 
 
 The mass ni of hot water has lost heat to the amount of m (T' — T"), 
 and this has gone to raise the temperature of a mass of water M, 
 and metal equivalent to a mass of water M', by (T" — T) degrees. 
 .-. m (T'— T") = M(T"— T) + M'(T"— T). Everything in this equation 
 except M' is known, and .". M', the water-equivalent of the calorimeter, 
 can be deduced, and must be added in all exact experiments to the mass 
 of water contained in it. 
 
 Secondly, all the excess of heat in the expired over that in the inspired 
 air is not given off to the calorimeter, for the air passes out of it at a 
 slightly higher temperature than that of the atmosphere. At the 
 beginning of the experiment this excess of temperature is zero. If 
 at the end it is i" C, the mean excels is 0*5° C. Now, when respiration 
 
 * This experiment is given as an example of a simple calorimetric measure- 
 ment, which can be easily performed with sufficient accuracy by students, 
 and involves the essential principles of such determinations. 
 
 f The average heat-loss by the lungs for 51 men (calculated for the 24 hours) 
 was 312,000 small calories for normal, 919,000 for the fastest, and 195,000 for 
 the slowest breathing. 
 
METABOLISM AND AMMAL NF.AT 
 
 is carried on in a room at a temperature ol lo" C, the expired air has 
 its temperature increased by nearly 30° C. About ^ of the heat 
 given oil by the respiratory tract in raising the temperature of the air 
 of respiration would accordingly be lost in such an experiment. But 
 since the portion of the heat lost by the lungs which goes to heat the 
 expired air is only ^ of the whole heat lost in respiration (p. 682). the 
 error would only amount to ;.vj,j of the whole, and this is negligible. 
 
 Thirdly, the air leaves the calorimeter saturated with watery vapour 
 at, say. iO'5°, while the inspired air is not saturated for 10° C. Now, 
 the quantity of heat rendered latent in the evaporation of water suffi- 
 cient to Stiturate a given quantity of air at 40° C. (the expired air is 
 saturated for body-temperature) is six times that required to saturate 
 the same quantity of air at 10°. If, then, the inspired air is half 
 saturated, the error under this head is ^.^. or 8^ per cent. If theinspired 
 air is three-quarters saturated, the error is .}i. or about 4 per cent. If the 
 air is fully saturated before inspiration, as is the case when it is drawn 
 in through a water-valve (Fig. 229) by a tube fixed in one nostri), the 
 only error is that due to the slight excess of temperature of the air 
 leaving the calorimeter over that of the inspired air. The latent heat 
 of the aqueous vapour in saturated air at 10-3° C. is about ^^j more 
 tha n the latent heat of the aqueous vapour in the same 
 mass of saturated air at 10° C, or about jl„ of the 
 latent heat in saturated air at 40°. The error in this 
 case would therefore be under i percent. Th.c tubes 
 must be wide and tiie bottle large. 
 
 12. In the observations on the blood-flow in the 
 hands (Experiment 31, p. 219) data on the quantity 
 of heat given off by the hands when immerhed in water 
 at a given temperature have already been obtained. 
 .'Vdditional data should be got by putting the hand 
 into the calorimeter without previous immersion in 
 the bath, and comparing the heat given off during 
 the period when the hand is acquiring the temperature 
 of the calorimeter with that sjiven off when the steady 
 state has been reached. Different calorimeter trni- 
 peratures should be employed. It will be found that 
 as the calorimeter temperature is diminished the 
 quantity of heat given off maybe increased although 
 the blood-flow is diminished, each gramme of blood passing through 
 the hand giving off more heat the lower the calorimeter temperature. 
 
 The quantity of heat lost by the hand, at a given temperature 
 of the calorimeter, per square centimetre of skin surface can be cal- 
 culated. If no special instrument for measuring the area of irregular 
 surfaces is available, the surface of the hand can be arrived at ap- 
 proximately by covering it with strips of gummed paper of known 
 breadth, and noting the length used to cover the whole hand up to the 
 lower level of the styloid process of the ulna. Or an old thin glove 
 which fits the hand can be cut off at this level and weighed. As large 
 a piece as possible of regular shape is then cut from the glove, weighed, 
 and its area deduced by measuring it with a rule. The area of the 
 whole glove, on the assumption that it is of uniform thickness, is thus 
 known. Or, without cutting the glove, it may be laid flat on a piece 
 of paper, an outline of it traced, and the paper cut out. The weight 
 of the paper cut out is compared with that of a piece of i)aper of known 
 area, and its area deduced. Obviously this is approximately equal to 
 half the surface of the hand. 
 
 Fig. 229. — Bottle 
 arranged for 
 Water-Valve. 
 
CHAPTER XIII 
 
 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Section I. — Preliminary Observations — Physical and 
 Technical Data. 
 
 In all the great functions of the body muscular movements play 
 an essential part. The circulation and the respiration, the two 
 functions most immediately essential to life, are kept up by the 
 contraction and relaxation of muscles. The movements of the 
 digestive canal, the regulation of the blood-supply to its glands and 
 to all parts of the body, and that immense class of movements 
 which we call voluntary, are all dependent upon muscular action, 
 which, again, is indebted for its initiation, continuance, or control, 
 to impulses passing along the nerves from the nerve-centres. 
 Hitherto we have not gone below the surface fact, that muscular 
 fibres have the power of contracting, either automatically, or in 
 response to suitable stimuH. In this chapter and the two next we 
 shall consider in detail the general properties of muscle, nerve, and 
 the other excitable tissues. 
 
 Lying deeper than the pecuharities of individual muscles, muscular 
 tissue has certain common properties — physical, chemical, and 
 physiological. The biceps muscle flexes the arm upon the elbow, 
 and the triceps extends it. The external rectus rotates the eyeball 
 outwards. The intercostal muscles elevate the ribs. The sphincter 
 ani seals up by a ring-Hke contraction the lower end of the ahmentary 
 canal. These actions are very different, but the muscles that carry 
 them out are at bottom very similar. And it cannot be doubted 
 that the functional differences are due entirely, or almost entirely, 
 to differences of anatomical connection, on the one hand with bones 
 and tendons, on the other with the nerve-cells of the spinal cord and 
 brain. The common properties in which all the skeletal muscles 
 agree are the subject-matter of the general physiology of striated 
 muscle. 
 
 The cardiac muscle differs more, both in structure and in function, 
 from the skeletal muscles than these do among themselves; the 
 smooth muscle of the intestines and bloodvessels still more. But 
 every muscular fibre, striped or unstriped, resembles every other 
 
 723 
 
724 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 muscular fibre more than it does a nerve-fibre or a gland-cell or an 
 epithelial scale. The properties common to all muscle make up the 
 general physiology of muscular tissue. 
 
 A nerve-fibre is at first sight very different from a muscular fibre. 
 It has diverged more widely from the primitive type of undiffer- 
 entiated protoplasm, but it retains, in common with the muscle- 
 fibre, susceptibility to stimulation, or excitability, the capacity for 
 growth, and to a limited extent the capacity for reproduction ; and 
 while it has lost the power of contraction or contractility, it has 
 developed in a higher degree than any Other tissue the power of 
 conducting the excited state. This inheritance of primitive pro- 
 perties, retained aliko by both tissues, is the basis of the general 
 physiology of muscle and nerve. 
 
 The electrical organ of Torpedo oi Malapterurus is inter- 
 mediate in some respects between muscle and nerve, and has 
 properties common to both. In the gland-cell the chem'cal powers 
 of native protoplasm have been specialized and developed. Con- 
 tractility has been, in general, entirely lost ; but excitabihty remains. 
 The idea that certain common en- 
 dowments find expression in the 
 action of muscle, nerve, electrical 
 organ, gland, etc., in the midst 
 of all their apparent differences, is 
 the basis of the general physiology 
 of the excitable tissues. 
 
 It is impossible to understand the 
 general physiology of muscle and 
 nerve without some acquaintance 
 with electricity. It would be out of 
 place to give even a complete sketch 
 of this preliminary but essential 
 knowledge here; and the student is expressly warned that in this book 
 the elementary facts and principles of physics are assumed to be part 
 of his mental outfit. But in describing some of the electrical apparatus 
 most commonly used in the study of this portion of our subject, and 
 which are employed in the Practical Exercises, it may be useful to recall 
 some of the pliysical facts involved. 
 
 Batteries. — The Daniell cell is perhaps better suited for physiological 
 work than any other voltaic element, although for special purposes 
 Grove, Leclanchc, bichromate of potassium or dry batteries may be 
 employed (p. 197). Storage batteries or current from the street supply 
 may also be used. 
 
 Inside the Daniell cell the current (the positive electricity) passes 
 from zinc to copper; outside, from copper to zinc. The copper is called 
 the positi\e. the zinc the negati%c. pole. When the current is passed 
 through a tissue, the electrode by which it enters is termed the anode, 
 and tliat by whicli it leaves the tissue the kathode. The anode is, 
 therefore, the electrode connected with the copper of the Daniell's cell; 
 the kathode is connected with the zinc. 
 
 Potential — Current Strength— Resistance. — We do not know what 
 in reality electricity is, but we do know that when a current flows along 
 
 Fig. 230. — Daniell Cell. A, outer vessel; 
 B, copper; C, porous pot; D, zinc rod; 
 D is supposed to be raised a little so as 
 to be seen. 
 
PRELIMINARY DATA 
 
 725 
 
 a wire energy is expended, just as energy is expended when water flows 
 from a higlier to a lower level. Many of the phenomena of current 
 electricity can, in fact, be illustrated by the laws of flow of an incom- 
 pressible liquid. The difference of level, in virtue of which the flow 
 of liquid is maintained, corresponds to the difference of electrical level, 
 or potential, in virtue of which an electrical current is kept up. The 
 positive pole of a voltaic cell is at a higher potential than the negative. 
 When they are connected by a conductor, a flow of electricity takes 
 place, which, if the difference of level or potential were not constantly 
 restored, would soon equalize it, and the current would cease; just as 
 the flow of water from a reservoir would ultimately stop if it was not 
 replenished. If the reservoir was small, and the discharging-pipe large, 
 the flow would only last a short time; but if water was constantly being 
 pumped up into it, the flow would go on indefinitely. This is prac- 
 tically the case in the Daniell cell. Zinc is constantly being dissolved, 
 and the chemical energy which thus disappears goes to maintain a 
 constant difference of potential between the poles. Electricity, so to 
 speak, is continually running down from the place of higher to the place 
 of lower potential, but the cistern is always kept full. 
 
 The difference of electrical potential between two points is called 
 the electromotive force ; and from its analogy with difference of pressure 
 in a liquid, it is easy to understand that the intensity or strength of the 
 current — that is, the rate of flow of the electricity between two points of 
 a conductor — does not depend upon the electromotive force alone, 
 any more than the rate of discharge of water from the end of a long 
 pipe depends alone on the difference of level between it and the reser- 
 voir. In both cases the resistance to the flow must also be taken account 
 of. With a given difference of level, more water will pass per second 
 through a wide than through a narrow pipe, for the resistance due to 
 friction is greater in the latter. In the case of an electrical current, a 
 wire connecting the two poles of a Daniell's cell will represent the pipe. 
 A thick short wire has less resistance than a thin long wire; and for a 
 given difference of potential, of electric level, a stronger current will 
 flow along the former. But for a wire of given dimensions, the in- 
 tensity of the current will vary with the electromotive force. The 
 relation between electromotive force, strength of current, and resistance 
 
 were experimentally determined by Ohm, and the formula C= ^5. 
 
 which expresses it, is called Ohm's Law. It states that the current 
 varies directly as the electromotive force, and inversely as the resist- 
 ance. 
 
 For the measurement of electrical quantities a system of units is 
 necessary. The common unit of resistance is the ohm, of current 
 the ampire, of electromotive force the volt. The electromotive force 
 of a Daniell's cell is about a volt. An electromotive force of a volt, 
 acting through a resistance of an ohm, yields a current of one ampere. 
 But the current produced by a Daniell's cell, with its poles connected 
 by a wire of i ohm resistance, would be less than an ampere, because 
 the internal resistance of the cell itself — that is, the resistance of the 
 liquids between the zinc and the copper — must be added to the external 
 resistance in order to get the total resistance, which is the quantity 
 represented by R in Ohm's Law. 
 
 Measurement of Resistance. — To find the resistance of a conductor, 
 we compare it with known resistances, as a grocer finds the weight of a 
 packet of tea by comparing it with known weights. The Wheatstone's 
 bridge method of measuring resistance depends on the fact that if four 
 resistances, AB, AD, BC, CD, are connected, as in Fig. 231, with each 
 
726 THE PHYSIOLOGY Of THE COSTRACTILE TISSUES 
 other, and with a galvanometer G, and a battery, F, no current will 
 flow through the galvanometer wl.cn Ars^rns- 
 
 In making the measurement, a resistance box, containing a large 
 number of coils of wire of different resistances, is used. The resistances 
 conospondini; to AB and AD may be made equal, or 
 may stand to each other in a ratio of i : lo, i : loo, 
 etc. Then, the unknown resistance being CD, BC 
 is adjusted by taking plugs out of the box till, on 
 closing the current, there is either no deflection, or the 
 deflection is as small as it is possible to make it with 
 the ,L;i\en arrangement. 
 
 Galvanometers. — A galvanometer is an instrument 
 used to detect a current, to determine its direction, 
 anfl to measure its intensity. Since, bv Ohm's law, 
 electromotive force, resistance, and current strength 
 are connected together, any one of them may be 
 measured by the galvanometer. A galvanometer of 
 Fig. 231. Wheat- fhe kind ordinarily used in physiology consists es.scn- 
 stone's Bridge, tially of a small magnet suspended in the axis of a 
 coil of wire, and free to rotate under the influence 
 of a current passing through the coil. The most sensitive instruments 
 possess a small mirror, to which the magnet is rigidly attached. A ray 
 of light is allowed to fall on the mirror, from which it is reflected on 
 to a scale ; and the 
 rotation ol the mir- 
 ror is magnified and 
 measured by the ex- 
 cursion of the spot 
 of light on the scale. 
 The method of read- 
 ing by a telescope 
 can be applied to any 
 mirror galvanometer, 
 and is often extreme- 
 ly convenient in 
 physiological work. 
 Sometimes a small 
 scale is fastened on 
 the mirror itself, and 
 ol). -served directly 
 through a low-power 
 microscope. 
 
 Fig. 232. — Diagram of String Galvanometer. The string or fibre CC is stretched be- 
 tween the poles of a powerful electromagnet. When a current passes down the 
 string it is deflected in the direction of the larg» arrow a — i.e., at right angles to 
 the magnetic field NS. When tha current is reversed, the string moves in the 
 opposite direction. The movements of the string can be observed by a micro- 
 scope, A (objective E), passing through a hole bored through the centre of the 
 magnet poles. For obtaining records a source of light is placed at B and con- 
 centrated on the fibre by a condenser, F, and the movements of the shadow are 
 recorded by photography. 
 
 In the d'Arsonval galvanometer the current passes through a small 
 coil of fine wire suspended in the field of a strong magnet. When 
 the current passes the coil is deflected, carrying with it a small mirror 
 attached to the suspending filament. A great advantage of this galvano- 
 meter in many situations is that it is unaffected by neighbouring currents. 
 
PRELIMINARY DATA 
 
 7V 
 
 The string galvanometer of Einthoven has peculiar merits for certain 
 physiological purposes. It consists of a silvered quartz- or glass-fibre 
 stretched in a very strong magnetic field. When traversed by a current 
 
 the fibre is deflected, and by means 
 of a beam of light the deflection is 
 greatl\- iiKignificfl (Fig- -3-2). 
 
 .\ rheocord is an instrument by 
 means of wliicli a current may be 
 divided, and a definite portion of it 
 sent through a tissue (Fig. 233). 
 
 A compensator is simply a rheo- 
 cord from whii. liabranchof a current 
 is led off, to balance or ' compen- 
 sate ' any electrical difference in a 
 tissue, like that which gives rise to 
 the current of rest of a muscle, for 
 example (Fig. 234). 
 
 An electrometer is an instrument 
 for measuring electromotive force — 
 
 Fig. 233 — Diagram of Rheocord (after 
 Du Bois-Reymond's Model). 
 
 Fig. 234. — Compensator. 
 
 Description of Fig. 233 : I to VII are pieces of brass connected with the wires a to / 
 in such a way that, by taking out any of the brass plugs i to 5. a greater or less 
 resistance may be interposed between the binding-screws A and B. The two wires 
 a are connected by a slider s, filled with mercury or otherwise making contact between 
 the wires. The current from the battery B divides at A and B, part of it passing 
 through the rheocord, part through N, the nerve, muscle, or other conductor which 
 forms the alternativ-e circuit. When a sufficient resistance R is interposed in the 
 chief circuit to make the total strength of the current independent of changes in the 
 resistance of the rheocord. the strength of the current passing through N will vary 
 inversely as the resistance of the rheocord. When all the plugs are in, and the slider 
 close up to A, there is practically no resistance in the rheocord, and all the current 
 passes across the brass pieces and plugs to B, and thence back to the battery. As s 
 is moved father away from A, the resistance of the rheocord is increased more and 
 more, and the intensity of the current passing through N becomes greater and greater. 
 The scale S shows the length of wire interposed for any position of s, and this gives a 
 rough measure of the fraction of the current passing through N. When plug i or 2 is 
 taken out, a resistance equal to that of the two wires a is interposed; plug 3, twice 
 that of a ; plug 4, five times; plug 5, ten times. 
 
 Description of Fig. 234 : W is a wire stretched alongside a scale S. A battery B is 
 connected to the binding-screws at the ends of the wire. A pair of unpolarizable 
 electrodes are connected, one with a slider moving on a wire, the other through a 
 galvanometer with one of the terminal binding-screws. In the figure a nerve is 
 shown on the electrodes, one of which is in contact with an uninjured portion, the 
 other with an injured part. The slider is moved until the twig of the compensating 
 current just balances the demarcation current of the nerve and the galvanometet 
 shows no deflection. 
 
728 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 tluit is, differences of electric potential. Lippmann's capillary elec- 
 trometer has been much employed in physiology. A simj)le form, 
 suitable for students working in a class where a consiflerable number of 
 copies of the instrument is needed, can be eoiueniently made as fcjUows: 
 A glass tube is drawn out to a capillary at one end and filled with mer- 
 cury. The tube is inserted into a small glass bottle,* and fastened in 
 its neck by a cork or a plug of sealing-wax which does not quite fill the 
 opening, so that the interior of the bottle is still in communication with 
 the external air. The upper end of the tube is connected by a short 
 piece of rubber tubing with a glass T-tube as in Fig. 235. The bottle 
 is partially filled with 5 to 10 per cent, sulphuric acid, under which the 
 capillary dips. By means of a small reservoir made from a piece of 
 glass tubing filled with mercury, and connected with the stem of the 
 T-tube, a little mercury is forced through the capillary so as to expel 
 the air in it. When the pressure is lowered again, sulphuric acid is 
 drawn up, and now lies in the capillary in contact with the meniscus 
 of the mercury. A platinum wire fused through the tube, or simply 
 inserted through its upper end, dips into the mercury. Another, 
 passing through the cork, or, better, fused through the bottom of the 
 bottle, makes contact witli the sulphuric acid through some mercury. 
 The bottle is fastened on the stage of a microscope, the capillary brought 
 into focus, and the meniscus adjusted by raising or lowering the reser- 
 voir. When the platinum wires are connected with points at different 
 potential, a current begins to pass through the instrument, and the 
 meniscus of the mercury in the capillary tube, where the current density 
 is the greatest, becomes polarized by the ions sejmrated from the 
 sulphuric acid at the surface of contact between the acid and the mer- 
 cury, so that the meniscus is no longer in ecjuilibrium in the tube. 
 The surface tension (p. 429) is diminished when the direction of the 
 current is from mercury to acid (mercury at a higher potential than 
 acid), and is no longer able to counterbalance the hydrostatic pressure 
 of the mercury. The meniscus therefore moves down in the tube. 
 Witfi the opposite direction of current (mercury at a lower potential 
 than acid) the surface tension is increased, and the meniscus moves 
 up. The polarization develops itself almost instantaneously, and thus 
 an electromotive force is at once established in the opposite direction to 
 that between the points connected with the electrometer, and equal to 
 it so long as the external electromotive force is not sufiiciently great to 
 cause continuous electrolysis of the acid — that is, so long as it is below 
 about 2 volts. The external current is therefore at once compensated, 
 and after the first moment no current passes through the instrument, 
 which is accordingly not a measurer of current, but of electromotive 
 force. 
 
 Induced Currents. —When a coil of wire in which a current is flowing 
 is br(juglit uj) suddenly to another coil, a momentary current is developed 
 in the stationary coil in the opposite direction to that in the moving 
 coil. Similarly, if instead of one of the coils being moved a current is 
 sent through it, while the other coil remains at rest in its neighbour- 
 
 * A parallel-sided bottle is best, as it gives the clearest image of the menis- 
 cus. But it is easiest to make a cylindrical boitlc from a piece of wide glass 
 tubing, and to insert a platinum wire into it before closing it at the bottom in 
 the blow-pipe flame. The tube can then be firmly fastened with sealing wax 
 in a dej)ression in a piece of wood, the wire being brouglit out Ihrougli a 
 hole in the wood. Onee the instrument is arranged, there is little chance 
 of the capillary getting broken, and there is very httle evaporation of the 
 acid. 
 
PRELIMINARY DATA 
 
 729 
 
 hood, a transient oppositely-directed current is set up in the latter. 
 When the current in the hrst coil is broken, a current in the same 
 direction is induced in the other coil. 
 
 Fig. 236. 
 
 Pi„ 2,, __\ Simple Capillary Elec romettr. R bottle containing sulpnuric acid ; 
 ii" mercury E E' , platinum wires. E dips into tlie mercury in the vertical 
 tube and £''is fused through the bottom of B, so as to make contact with the 
 merc'urv in B, the other end of it passing out through a small hole in the 
 wooden platform F, on which B rests. F is fastened to the stage of the 
 microscope S by a pin, G, passing through one of the clip-holes, and to 
 L wooden upright D by the pin H. D fits tightly over the microscope 
 stage but can be moved laterally a little so as to brmg the capillary mto the 
 middle of the field. /. stem of glass T-tube passing through a hole in £). 
 L rubber tube connecting the capillary point with the vertical portion of the 
 T-tube ^ is a reservoir containing mercury connected by tlie rubber tube 
 M to /. A can be raised or lowered by sliding it in the clips A . C, magnified 
 portion of the capillary tube showing the meniscus. 
 
 Fig. 236.— Capillary Electrometer (after Frey). 
 
 Du Bois-Reymonds Sledge Inductorium (Fig. 237)— This consists of 
 tNvo coils the primary and the secondary, the former havmg a com- 
 paratiyely small number of turns of fairly thick copper wire, the latter 
 alar-e number of turns of thin ^y ire. The object of this is that the 
 resistance of the primary, which is connected with one or more voltaic 
 
730 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 cells, may not cut down the current too much; while the currents 
 induced in the secondary', having a high electromotive force, can readily 
 pass througii a iiigh resistance, and are directly proportional in intensity 
 to the number of turns of the wire. 
 
 By means of various binding-screws and the electro-magnetic inter- 
 rupter or Necf's hammer, shown in the figure and explained below it, 
 the current can be made once in tlic primary or broken once, or a con- 
 stant alternation of make and break can be kept up. We can thus get 
 a single make or break shock in the secondary, or a series of shocks, 
 sometimes called an interrupted or faradic current. Such a series of 
 stimuli can also be got by making and breaking a voltaic current at any 
 given rate. 
 
 A ' self-induced ' current can also be obtained from a single coil; for 
 instance, from the primary coil alone of tlie induction apparatus. The 
 
 Fig. 237. — Du Bois-Reymond's Inductorium. B, primary, B', secondary, coil, 
 H, guides in which B' slides, with scale; 1), electro-magnet; E. vibrating spring; 
 i, wire connecting wire of I) to end of primary; v, screw with platinum point, 
 connected with other end of primary ; A, A', binding-screws, to which are attached 
 the wires from battery. A' is connected with the wire of the electro-magnet D; 
 and through it and i with the primary. 
 
 reason of this is, that when a current begins to flow through any turn 
 of a coil of wire it induces in all the other turns a current in the opposite 
 direction, and, when it ceases to flow, a current in the same direction 
 as itself. The former current, ' the make extra shock,' being in the 
 opposite direction to the inducing current, is retarded in its develop- 
 ment, and reaches its maximum more slowly than ' the break extra 
 shock.' But, as we shall see, the suddenness with which an electrical 
 change is brought about is one of the most important factors in elec- 
 trical stimulation, and therefore the break extra shock is a much more 
 powerful stimulus than the make. Owing to these self-induced cur- 
 rents, the stimulating power of a voltaic stream may be much in- 
 creased by putting into the circuit a coil of wire of not too great 
 reristance. 
 
 The self-induction of the primary also affects the stimulating power 
 of the currents induced in the secondary; the shock induced m the 
 secondary by break of the primary current is a stronger stimulus than 
 that caused "at make of the primary. The reason is that with a given 
 distance of primary and secondary, and a given intensity of the voltaic 
 current in the primary, the abruptness with which the induced current 
 
PRELIMINARY DATA 731 
 
 In tHe secondary is developed depends upon the rapidity with which the 
 primary- current reaches its maximum at closing, or its minimum (zero) 
 at opening. Now, the make extra current retards the development of 
 the primary current, while in tlie opened circuit of the primary coil the 
 current intensity falls at once to zero. 
 
 The inequality between the make and break shocks of the secondary 
 coil can be greatly reduced by means of Helmholtz's wire. Connect one 
 pole of the batter^' witli i' (Fig. 2J7), and the other with A'. Join A 
 and A' by a short, thick wire. With this arrangement tlie primary cir- 
 cuit is never opened, but the current is alternately allowed to flow- 
 through tlie primary, and short-circuited when the spring touches v. 
 The ' make ' now corresponds to the sudden increase of intensity of 
 the current in the primary- when the short-circuit is removed, and the 
 ' break ' to its sudden decrease when the short-circuit is established. 
 In both cases self-induced currents are developed, and therefore both 
 shocks are weakened. But the opening stimulus is now slightly the 
 weaker of the two, because the opening extra shock has to pass th-ough 
 a smaller resistance (the short-circuit) than the closing extra shock 
 (which passes by the batter^'), and therefore opposes the decline of 
 current intensity on short-circuiting more than the closing shock 
 opposes the increase of 
 current intensit}- on long- 
 circuiting through the 
 primary^ 
 
 By means of wires con- 
 nected with the terminals 
 of the secondary coil, 
 and leading to electrodes, 
 a nerve or muscle may pjg 238. — Unpolarizable Electrodes. A, hook- 
 be stimulated. It is usual shaped; B, U-tubes; C, straight; D. clay in 
 to connect the wires to contact with tissue; S, saturated zinc sulphate 
 a short-circuiting key solution; Z, amalgamated zinc wire. 
 (Fig. 240), by opening • . .u .■ ^ k ^• 
 
 which the induced current is thrown mto the tissue to be stimu- 
 lated. For some purposes the electrodes may be of platinum; 
 but all metals in contact with moist tissues become polarized when 
 currents pass through them — that is, have decomposition products of 
 the electrolysis of the tissues deposited on them. And as any slight 
 chemical difference, or even perhaps a difference of physical state, be- 
 tween the two electrodes will cause them and the tissues to form a 
 battery evolving a continuous current, it is often desirable to use t<«- 
 polarizable electrodes. 
 
 Unpolarizable Electrodes. — Some convenient forms of these are 
 represented in Fig. 238. A piece of amalgamated zinc wire dips into 
 saturated zinc sulphate solution contained in the upper part of a glass 
 tube. The lower end of the tube may be straight, but drawn out so 
 as to terminate in a not very large opening, or it may be bent into a 
 hook, in the bend of which a hole is made. Before the tube is filled 
 with the zinc sulphate solution, the lower part of it is plugged with 
 china clay made up with physiological salt solution. The clay just 
 projects through the opening, and thus comes in contact with the 
 tissue. When these electrodes are properly set up, there is ver>- little 
 polarization for several hours, but for long experiments, U-shaped 
 tubes, filled with saturated zinc sulphate solution, are better. The 
 amalgamated zinc dips into one limb, and a small glass tube fiUed with 
 clav, on which the tissue is laid, into the other. 
 
732 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Pohl's Commutator or Reverser (Fig. 239) consists of a block of paraf- 
 fin or wood witli six mercury cups, each in connection with a binding- 
 screw (not sliown in the figure). Cups i and 6 and 2 and 5 are connected 
 by copper wires, which cross each other without touching. The bridge 
 consists of a glass or vulcanite cross-piece a, to which are attached two 
 wires bent into semicircles, each connected with a straight wire dip- 
 ping into the cups 3 and 4 respectively. With the bridge in the posi- 
 tion shown in the figure, a current coming in at 4 would pass out by 
 the wire connected with i, and back again by that connected with 2, in 
 the direction shown by the arrows. When the bridge is rocked to the 
 other side so that the bent wires dip into 5 and 6, the direction of the 
 current is reversed. The cross-wires may be taken out altogether, and 
 the commutator used to send a current at will through either of two 
 circuits, one connected with i and 2, and the other with 5 and 6. 
 
 Du Bois -Raymond's Short- 
 circuiting Key. — A cheap and 
 convenient form is shown in 
 Fig. 240. 
 
 Time - Markers — Electric Sig- 
 nal. — It is of importance to know 
 the time relations of many 
 physiological phenomena which 
 are graphically recorded ; for 
 
 Fig. 239. — Pohl's Commutator. 
 
 Fig. 240. — Short-Circuiting Key. 
 
 example, the contraction of a skeletal muscle or the beat of a heart. 
 For this purpose a tracing showing the speed of the travelling sur- 
 face in a given time is often taken simultaneously with the record 
 of the movement under investigation. For a slowly-moving surface 
 it is sufficient to mark intervals of one or two seconds, and this is 
 very readily done by connecting an electro-magnetic marker (such 
 as the electric signal of Deprez) with a circuit which is closed and 
 broken by the seconds pendulum of an ordinary clock or ,1 metronome 
 (Fig. 88, p. 195). Special clocks have also been constructed which 
 permit of the time intervals being varied. For shorter intervals a 
 tuning-fork is used, which makes and breaks a circuit including an 
 electromagnetic marker, or writes on the drum directly by means of 
 a writing-point attached to one of the prongs. 
 
 Amoeboid movement (p. 16) is the most primitive, the least 
 elaborated form of contraction. The maximum velocity of the 
 movement has been reckoned at o 008 millimetre a second. Stimu- 
 
CILIA 733 
 
 lation with the constant current or induction shocks causes the 
 whole of the pseudopodia to be drawn in. This ilkistrates a 
 universal property of protoplasm, excitability, or the power of re 
 sponding to certain influences, or stimuli, by manifestations of the 
 pecuhar kind which we distinguish as vital or physiological. Many 
 unicellular organisms and the chief varieties of the white blood- 
 corpuscles possess the power of amoeboid movement ; and we have 
 aJready dwelt upon some of the important functions fulfilled bv 
 such movement in the higher animals and in man. A great dis- 
 tinction between this kind of contraction and that of a muscular 
 fibre is that it takes place in any direction. 
 
 Cilia. — Cilia possess a higher and more speciaHzed grade of 
 contractility. They are very widely distributed in the animal 
 kingdom; and analogous structures are also found in manv low 
 plants, such as the motile bacteria. 
 
 In the human subject ciliated epithelium usually consists of 
 several layers of cells, the most superficial of which are pear-shaped, 
 the broad end being next the surface, and covered with extremely 
 fine processes, or ciha, about 8 ^ in length, which are planted on 
 a clear band. It lines the respiratory passages, the middle ear and 
 Eustachian tube, the Fallopian tubes, the uterus above the middle 
 of the cer\nx, the epidid^'mis, where the cilia are extremelv long, 
 and the central cavity of the brain and spinal cord. 
 
 Ciliary motion can be readily studied by placing a scraping from 
 the palate of a frog or a small portion of a gill of a fresh-water mussel 
 under the microscope in a drop of physiological salt solution. The 
 motion of the cilia is at first so rapid that it is impossible to make 
 out much, except that a stream of liquid, recognized by the solid 
 particles in it, is seen to be driven by them in a constant direction 
 along the ciHated edge. When the motion has become less quick, 
 which it soon does if the tissue is deprived of oxygen, it is seen to 
 consist in a swift bending of the cilia in the direction of the stream, 
 followed by a slower recoil to the original position, which is not at 
 right angles to the surface, but sloping streamwards. All the cilia 
 on a tract of cells do not move at the same time ; the motion spreads 
 from cell to cell in a regular wave. The energy of ciliary motion 
 may be considerable, although far inferior to that of muscular con- 
 traction. The work which cilia are capable of performing can be 
 calculated by remo\ing the membrane, fixing it on a plate of glass, 
 cilia outwards, putting weights on the glass plate, and allowing the 
 ciUa, like an immense number of feet, to carry it up an inclined plane. 
 Bowditeh found in this way that the cilia on a square centimetre of 
 mucous membrane did nearly 7 gramme-millimetres of work per 
 minute (equal to the raising of 7 grammes to a height of a milli- 
 metre). 
 
734 
 
 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Since the cilia in the respiratory tract all lash upwards, they 
 must play an important part in carrying up foreign particles taken 
 
 in with the air, and the mucus in which 
 they are entangled, as well as patho- 
 logical products. Engelmann found 
 that the energy of ciliary motion in- 
 creases as the temperature is raised 
 up to about 40° C, afber which it 
 
 Fig. 2)1.- Ciliated Cell (M. 
 Heidenhain). From a 
 ' liver duct ' of the garden 
 snail X 2,500. 
 
 Fig. 242.— Ciliated Cell (Schneider). 
 From a flatworm (Planocera folium). 
 I, space between two adjoining 
 ciliated cells; 2, basal bodies; 4, 
 inner granule ; 5, ' cilia roots ' ; 
 6, boundary layer. 
 
 diminishes quickly. Over-heating causes cilia to come to rest, but 
 if the temperature has not been too high, and has not acted too 
 long, they recover on cooling, thus exhibiting the phenomena of 
 heat standstill which we have already studied in the heart. 
 
 It is not well understood in what way the contraction of the cilia 
 depends upon their connection with the body of the ciliated cell. Very 
 few cases occur in which cilia have the power of independent motion 
 when severed from the cell-body. It has been observed in certain low 
 forms of animals that cilia which have been broken off from the cell 
 are still able to contract when a small portion of the substance of the 
 cell-body at the point where the ciHum is attached to the cell, the 
 so-called basal piece, or basal body (Fig. 24^), has come off along with 
 them. In other forms isolated cilia can contract in the absence of 
 anything corresponding to the basal piece. It cannot, therefore, be 
 said that continuity with the basal piece is absolutely necessary. Nor 
 is it known wliat significance for the ciliary movements is possessed 
 by the long fibrills, called the ' roots of the cilia,' which in some animals 
 
PHYSICAL PROPERTIES OF MUSCLE 735 
 
 run down through the cell from the basal bodies (h'igs. 241, 242). In 
 some worms and molluscs ciliated cells are supplied with nerve-fibres, 
 but this has not been demonstrated for the higher animals. 
 
 Section II. — Physical Properties and Stimulation of Muscle. 
 
 Since most of our knowledge of the general physiology of muscle 
 has been gained from striped muscle, in what follows we always 
 refer to ordinary skeletal muscle, unless it is otherwise stated. 
 The sartorius and the gastrocnemius are the classical objects for 
 experiments on striated muscle. For smooth muscle the adductor 
 muscle of Anodon, the fresh-water mussel, a ring cut from the middle 
 portion of the frog's stomach, the rabbit's ureter and uterus, and 
 the cat's bladder, have been most used. 
 
 Physical Properties of Muscle — Elasticity. — All bodies may have their 
 shape or volume altered by the application of force. Some require a 
 large force, others a small force, to produce a sensible amount of dis- 
 tortion. The elasticity of a body is the property in virtue of which it 
 tends to recover its original form or bulk when these have been altered. 
 Liquids and gases have only elasticity of volume; solids have also 
 elasticity of form. Most solids recover perfectly, or almost perfectly, 
 from a slight deformation. The limits of distortion within which this 
 occurs are called the limits of elasticity, and they vary greatly for 
 different substances. Living muscle has very wide limits of elasticity; 
 it may be deformed — stretched, for example — to a very considerable 
 extent, and yet recover its original length when the stretching force 
 ceases to act. 
 
 The extensibility of a body is measured by the ratio of the increase 
 
 of length, produced by unit stretching force per unit of area of the 
 
 cross-section, to the original length of a uniform rod of the substance. 
 
 Is 
 If e is the extensibility, e= :p=, where I is the increase of length, 
 
 L the original length, s the cross-section, and F the stretching force. 
 Suppose we wish to compare the extensibility of two substances. 
 Let A and B be strips or rods of the substances, the length of A being 
 500 mm., that of B 1,000 mm.; the cross-section of A, 100 sq. ram., of 
 B, 200 sq. mm. Let the elongation produced by a weight of i kilo 
 
 be 10 mm. in each, then the extensibility of A is = 2 ; and that 
 
 •^ 500 X I 
 
 of B is = 2; that is, the substances are equally extensible, 
 
 1,000 XI -i J 
 
 Young's modulus of elasticity, or the coefficient of elasticity, is the 
 quotient of tlie deforming force acting on unit area of the given body 
 by the deformation produced (within the limits of elasticity). In the 
 
 above example it is -^f, that is, -p, the reciprocal of the extensi- 
 bility e. For steel the coefficient of elasticity is very large, for muscle 
 small. Or, as we may otherwise express it, living muscle within its 
 limits of elasticity is very extensible ; a small force per unit area of 
 cross-section of a prism of it will produce a comparatively great elonga- 
 tion. The extensibilitv. however, diminishes continually with the 
 elongation, so that equal increments of stretching force produce always 
 
736 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 less and less extension. If, for instance, the sartorious or semi-mcm- 
 branosus of a frog be connected with a lever writing on a blackened 
 surface, and weights increasing by equal amounts be successively 
 attached to it, the recording surface being allowed to move the same 
 distance after the addition of each weight, a series of vertical lines, 
 representing the amount of each elongation, will be traced. When the 
 lower ends of all the vertical lines are joined, a smooth curve with the 
 concavity upwards is obtained (Fig. 243). This is a property common 
 to living and dead muscle and to other animal structures, such as 
 arteries. Marey's method, in which the weight is continuously in- 
 creased from zero and then continuously decreased to zero again by 
 the flow of mercury into and out of a vessel attached to the muscle, 
 gives directly the curve of extensibility. 
 
 The elongation oi a steel rod or other 
 inorganic solid is proportional within 
 limits to the extending force per unit of 
 cross-section ; and a curve plotted with the 
 weights for abscissae and the amounts of 
 elongation for ordinates would be a straight 
 line. But this is not a fundamental dis- 
 tinction between animal tissues, and the 
 materials of unorganized nature, as some 
 writers seem to suppose. For when the 
 slow after-elongation which follows the 
 first rapid increase in length in tlie loaded. 
 Pig 243 —Curves of Extensi- excised muscle is waited for, tlie curve of 
 bility. M, of muscle ; S, of on extensibility comes out a straight line 
 ordinary inorganic solid. (Wundt), and within limits this is also the 
 
 case for human muscles in the intact body. 
 And although a steel rod much more quickly reaches its maximum 
 elongation for a given weight when loaded, and its original length when 
 the weight is removed, than does a muscle, time is required in both cases, 
 and the difference is one of degree rather than of kind. When muscle 
 (striated or smooth) is not stretched beyond the limit of phj-siological 
 relaxation, the amount of stretching is proportional to the weight, and 
 the same is true of all the simple tissues of the body (Haycraft). 
 
 Dead muscle is less extensible than living, and its limits of elasticity 
 are much narrower. In the state of contraction the extensibility is 
 increased in excised frog's muscle. When fatigue comes on after many 
 excitations, the after-elongation becomes more pronounced, but the 
 return after unloading is very incomplete. Bonders and Van Mans- 
 veldt have found that contraction causes little difference in the muscles 
 of a living man, although fatigue increases the extensibility. 
 
 The great extensibility and elasticity of muscle must play a con- 
 siderable part in determining the calibre of the vessels, and in lessening 
 the shocks and strains which the heart and the vascular system in 
 general are called upon to bear, and must contribute much to the 
 smoothness with which the movements of the skeleton arc carried out, 
 and immensely reduce the risk of injury to the bones as well as to the 
 muscles themselves, the tendons and the other soft tissues. And not 
 only is smoothness gained, but economy also ; for a portion of the 
 energy ot a sudden contraction, which, if the muscles were less ex- 
 tensible and elastic, might be wasted as heat in the jarring of bone 
 against bone at the joints, is stored up in the stretched muscle and 
 again given out in its elastic recoil. The skeletal muscles, too, are 
 even at rest kept slightly on the stretch, braced up, as it were, and 
 
SriMULA IION OF MUSCLE 
 
 737 
 
 ready to act at a moment's notice witliout taking in slack. This is 
 shown by the fuct that a transverse wound in a muscle ' gapes,' the 
 fibres being retracted, in virtue of their elasticity, towards tiie fixed 
 points of origin and insertion. Smooth muscle, as we meet it in the 
 hollow viscera, is highly distensible and elastic, as is suited to organs 
 whose capacity is continually varying within wide limits (Fig. 244). 
 
 In the further study of muscle it is necessary first of all to consider 
 the means we have of calling forth a contraction — in other words, the 
 various kinds of stimuli. 
 
 Stimulation of Muscle. — A muscle may be excited or stimulated 
 either directly or through its motor nerve. It is usual to classify 
 stimuli as electrical, mechanical, chemical, or thermal. Electrical 
 stinuili are by far the most commonly employed, and will be dis- 
 cussed in detail. A prick, a cut, or a blow are examples of mechani- 
 
 Fig. 244. — Extensibility of Smooth Muscle (Griitznet). The upper group of four 
 ceils (i to 4) is from a hollow organ, whose walls are contracted, and its lumen 
 almost abolished; the under group represents the same fibres when the organ is 
 full. The fibres are longer and somewhat darker. They are also displaced 
 somewhat along each other. 
 
 cal stimuli. The action of a fairly strong solution of common salt 
 or of a dilute solution of a mineral acid is usually described as 
 chemical stimulation. But in considering the excitation of nerve 
 (p. 783) we shall see that physical changes are often mixed up with 
 so-called chemical stimulation. The contraction caused is not a 
 single brief twitch, as is the case with a not too severe mechanical 
 excitation, but a sustained contraction or a tetanus. Sudden cooling 
 or heating acts as a stimulus for muscle, but thermal stimulation is 
 somewhat uncertain. It is not quite settled whether the contrac- 
 tion which can be obtained from a muscle when it is subjected to 
 brief local heating — to a ' thermic shock,' as some writers prefer 
 to say {e.g., by the momentary glow of a platinum wire below but 
 not touching it) — is an ordinary muscular contraction, or a physical, 
 although transient, contracture analogous to that caused by certain 
 drugs (Waller). Smooth, like striped, muscle is susceptible to 
 electrical, mechanical, thermal, and chemical stimulation. In 
 addition, in certain situations it can be excited by light (photic 
 stimulation), as in the case of the excised iris of fish and amphibia. 
 In all artificial stimulation there is an element of sudden or abrupt 
 change, of shock, in other words; but we cannot tell in what the 
 ' natural ' or ' physiological ' stimulus to muscular contraction in 
 
 47 
 
738 THE PHYSIOLOGY OF THE COKTRACTILE TISSUES 
 
 the intact body really consists, nor how it differs from artificial 
 stimuli. All we know is that there must be a wide difference, and 
 that our methods of excitation must be very crude and inexact 
 imitations of the natural ])roress. 
 
 Direct Excitability of Muscle. — The famous controversy on the 
 existence of mdependent ' muscular irritability ' has long been 
 forgotten, and has no further interest except for the antiquaries of 
 science, if such exist. The direct excitability of muscle in the modern 
 sense is not quite the same as the ' muscular irritability,' the dis- 
 cussion of which occupied Haller and his contemporaries. What 
 the modern physiologists have been called upon to decide is whether 
 muscular fibres can be caused to contract except by an excitation 
 that reaches them through their nerves. In this sense there can 
 exist no doubt that muscle is directly excitable, and some of the 
 proofs are as follows: 
 
 (i) The ends of the frog's sartorius contain no nerves, yet they 
 respond to direct stimulation. (2) Certain chemical stimuli — 
 ammonia, for instance — excite muscle but not nerve. (3) When 
 the motor nerves of a limb are cut they degenerate, and after a 
 certain time stimulation of the nerve-trunk causes no muscular 
 contraction, while the muscles, although atrophied, can be made 
 to contract by direct stinmlation. (4) Finally, there is the cele- 
 brated curara experiment of Claude Bernard, which is described in 
 a somewhat modified form in the I^ractical Exercises, p. 811. A 
 ligature is tied firmly round one thigh of a frog, omitting the sciatic 
 nerve; then curara is injected, and in a short time the skeletal 
 muscles are paralyzed. That the seat of the paralysis is not the 
 contractile substance of the muscles itself is shown by their \agorous 
 response to direct stimulation. The ' block ' is not in the nerve- 
 trunk, nor above it in the central nervous system, for the ligated 
 leg is often drawn up — -that is, its muscles are contracted — although 
 the poison has circulated freely in the sacral plexus and the spinal 
 cord. Further, if the nerve of the ligated leg be prepared as high 
 up above the ligature as possible, where the curara must undoubtedly 
 have reached it (just above the ligature the nerve has been isolated 
 and the circulation in it more or less interrupted), stimulation 
 of it will cause contraction of the muscles of the limb; while excita- 
 tion of the other sciatic is ineffective. 
 
 It can be also shown, by means of the negative variation or 
 current of action (p. 824), that a nerve-trunk on which curara has 
 acted remains excitable, and capable of conducting the nerve- 
 impulse. The conclusion, therefore, is that the curara paralyzes 
 neither nerve-fibre nor the contractile substance of the muscular 
 fibre, but some link between the two. If the assumption be made 
 that the efferent mcdullated nerve-fibres within the muscle, since 
 
STIMJ'I.ATION OF MUSCLE 
 
 739 
 
 they arc anatomically similar to those in the nerve-trunk till near 
 their terminations, are similarly affected by curara- — and it is a 
 justifiable assumption — the seat of the curara paralysis must either 
 be the nerve-ending or some mechanism, physiological if not 
 anatomical, interposed between the nerve-ending and the con- 
 tractile substance. Now, Langley has shown that the contractions 
 caused by the local application of dilute nicotine solution to points 
 of the skeletal muscles of the frog, both in normal muscles and in 
 muscles whose motor nerves and nerve-endings have degenerated 
 after section of the nerves, are prevented by curara He there- 
 
 Fig. 245. — Frog's Motor Nerve-Ending (Wilson). A, B, C, three muscle-fibres. The 
 meduUated nerve a loses its medullary sheath and breaks up on B at i. It gives 
 off at 2 a large non-medullated branch, which also breaks up on B. The nerve- 
 endings send ultraterminal fibrillaj to A, B, and C, some of which were seen to 
 ead in small knobs. A separate non-medullated nerve, n. is shown, which forms 
 a small plexus on B, one fibre of which penetrates to a lower plane than the other, 
 and ends by forming a knob under the sarcolemma. 
 
 fore concludes that, since nicotine produces its effects by a 
 direct action on muscle, and not by an action on nerve-endings 
 or on any special structure (such as the protoplasmic mass or ' sole ' 
 at the nerve-ending in many animals) interposed between the nerve 
 and the muscle, no such special structure existing in the frog 
 (Fig. 245), curara must also act directly on the muscle. But 
 obviously curara does not paralyze the general contractile substance 
 of the muscle, else the curarized muscle would not contract on direct 
 stimulation. Langley accordingly assumes that, in addition to the 
 contractile or ' general ' substance, ' receptive ' substances exist 
 in the fibre, through which the excitation is transferred to the con- 
 tractile substance when the motor nerve is stimulated. He pictures 
 these receptive substances as ' side-chains ' of the contractile mole- 
 cule, in accordance with Ehrlich's theory of immunity (p. 31), 
 and distinguishes those in the neighbourhood of the nerve-ending 
 
740 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 from those present throughout the muscle fibre. Both the slow 
 local tonic contraction and the quick, brief conducted contractions 
 or twitches set up in a muscle fibre by nicotine, but especially the 
 latter, are much more easily elicited in that part of it which lies 
 under the nerve-ending than elsewhere. Indeed, the position of 
 the nerve-endings in the superficial fibres of a muscle can be ascer- 
 tained by observing the points which respond most readily to nico- 
 tine. Nicotine and curara, etc., are supposed to combine with the 
 receptive substance, which is then in both cases rendered incapable 
 of being affected by nerve impulses. In the case of nicotine an 
 ', additional action results from the combination with the receptive 
 I substance — viz., the change in the contractile substance which leads 
 to contraction. Curara paralyzes the transmission of the excitation 
 from the motor nerves to smooth muscle — the muscles of the 
 
 Fig. 246. — Tonic Contraction of Muscle during Passage of Constant Current. Two 
 sartorius muscles of frog connected by pelvic attachments. Current from 12 
 small Daniell cells in series passed through their whole length. Current closed 
 at Ml, opened at b. Time trace, two-second intervals. 
 
 bronchi, for instance — with much greater difliculty than to ordinary 
 skeletal muscle, and the same is true of the inhibitory nerves of 
 the heart. 
 
 The action of curara gives us the means of stimulating muscle 
 directly; when electrical currents are sent through a non-curarized 
 muscle, there is in general a mixture of direct and indirect stimula- 
 tion, for the nerve-fibras within the muscle are also excited. Induced 
 currents stimulate nerve more readily than muscle. Voltaic currents 
 may excite a muscle whose nerves have degenerated, while induced 
 currents are entirely without effect. 
 
 For direct stimulation, a curarized frog's sartorius or semi-mem- 
 branosus is generally used on account of their long parallel fibres. For 
 indirect excitation, a muscle-nerve preparation, composed of a frog's 
 gastrocnemius with the sciatic nerve attached to it, is commonly em- 
 ployed, as it is easy to isolate the muscle without hurting its nerve. 
 
STIMULATION OF MUSCLE 
 
 741 
 
 Stimulation by the Voltaic Current. — While the current continues to 
 pass through a nerve without any sudden or great change in its in- 
 tensity, there is no stimulation, and the muscle connected with the 
 nerve remains at rest. The same is true of striated muscle when a 
 weak current is passed directly through it. But in muscle the con- 
 stancy of the rule is more and more frequently broken by exceptional 
 results as the curreut is strengthened, a state of permanent contrac- 
 tion being very apt to show itself during the whole time of flow (Wundt) 
 (Fig. 24b). Above a certain intensity of current a greater or less 
 degree of permanent contraction is invariably produced. This is some- 
 times called the ' closing tetanus.' It is, however, not a true tetanus, 
 but a tonic contraction, which is strongest in the neighbourhood of the 
 kathode, and does not spread far from it. A similar condition, the 
 so-called galvanotonus, is normally seen in human muscles when they or 
 their motor nerves are 
 traversed by a stream 
 of considerable inten- 
 sity. Under certain con- 
 ditions, too — e.g., when 
 a strong current is 
 allowed to flow for a 
 comparatively long time 
 through a muscle — the 
 muscle remains contrac- 
 ted after the opening of 
 the current (so-called 
 ' opening or Ritter's tet- 
 anus '). Smooth muscle 
 is excited to contraction 
 even when a voltaic cur- 
 rent is very gradually 
 passed into it and slow- 
 ly increased, and again 
 when it is caused very 
 gradually to disappear. 
 But striped muscle is 
 not stimulated under 
 these conditions. 
 
 For nerve, and with these qualifications for muscle, too, the law 
 holds that the voltaic current stimulates at make and at break, but not 
 during its passage. Or, generalizing this a little, since it has been 
 shown that a sudden increase or decrease in the strength of a current 
 already flowing also acts as a stimulus, we may say that the voltaic 
 current stimulates only when its intensity is suddenly and sufficiently 
 increased or diminished, but not while it remains constant.* 
 
 When a strong current is closed through a muscle there is an im- 
 mediate sharp contraction (initial contraction). The muscle then 
 promptly relaxes, but incompletely. When the current is opened, 
 there is another contraction (Fig. 247). The force of the initial con- 
 traction, as measured by the resistance necessary to prevent it, is 
 greater than that of the tonic contraction which follows it. 
 
 A second law of great theoretical importance is that of polar stimula- 
 tion. At make the stimulation occurs only at the kathode ; at break only 
 at the anode. This is true both for muscle and nerve, but it is most 
 
 * This law of Du Bois-Reymond has been questioned by Hoorweg and others. 
 It seenLs to need modification, but the subject cannot be discussed here. 
 
 Fig. 247. — Tonic Contraction during and after Flow 
 of Voltaic Current. Curve from frog's gastroc- 
 nemius. At M constant current closed, at B broken. 
 Contracture continues after opening of current. 
 Time trace, two-second intervals. 
 
74= THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 directly and simply demonstrated on muscle. A long parallel-fibred 
 curarized muscle is supported about its middle; the two ends, wliiLh 
 hang down, are connected with levers writing on a revolving drum, and 
 a current is sent longitudinally through the muscle. It is not difficult 
 to see from the tracings that at make the lever attached to the kathodic 
 end moves first, and that the other lever only moves when the contrac- 
 tion started at the kathode has had time to reach it in its progress 
 along the muscle. Similarly, at break the lever connected with the 
 anodic end moves first. The law of polar excitation holds both for 
 striated and for smooth muscle. Not only is there no excitation of 
 unstrip>ed muscle at the anode on closure of the current, but a previ- 
 ously existing contraction disappears. For skeletal muscle the make is 
 stronger than the break contraction. It has not been proved that this 
 is the case for smooth muscle. 
 
 Section III. — Physical and Mech.wical Phenomena of the 
 Muscular Contraction. 
 
 When a muscle contracts, its two points of attachment, or, if it 
 be isolated, its two ends, come nearer to each other; and in exact 
 proportion to this shortening is the increase in the average cross- 
 section. The contraction is essentially a change of form, not a 
 change of volume. The most delicate observations fail to detect 
 the smallest alteration in bulk (Ewald). Living fibres kept con- 
 tracted by successive stimuli can be examined under the microscope ; 
 or fibres may be ' fixed ' by reagents like osmic acid, and sometimes 
 a very good opportunity of stud\nng the microscopic changes in 
 contraction is given by a group of libres in which the ' fixing ' 
 reagent has caught a wave of contraction, and, so to speak, pinned 
 it down. It is then seen that the process of contraction in the fibre 
 is a miniature of that in the anatomical muscle. The individual 
 fibres shorten and thicken, and the sum-total of this shortening 
 and thickening is the muscular contraction which we see \nth the 
 naked eve. The phenomena of the muscular contraction may 
 be classified thus: (i) Optical, (2) Mechanical, (3) Thermal, 
 (4) Chemical, {5) Sonorous, (6) Electrical. (5) will be treated under 
 ' Volimtan,' Contraction ' ; (6) in Chapter XV. 
 
 (i) Optical Phenomena — Microscopic Structure of Striped Muscle. — 
 The structure of striped muscle has long been the enigma of histology-; 
 and the labours of many distingviished men have not sufficed to make 
 it clear. On the contran,-, as investigations have multiplied, new 
 theories, new interpretations of what is to be seen, have multiplied in 
 proportion, and a resolirte brevity has become the chief duty of a writer 
 on elementar>- physiology* in regard to the whole question. 
 
 The muscle-fibre, the unit out of which the anatomical muscle is 
 bviilt up, is surrounded by a structureless membrane, the sarcolemma. 
 The length and breadth of a fibre var>- greatly in different situations. 
 The maximum length is about 4 cm. ; the breadth may be as much 
 as 70 ft and as little as 10 fi. When we come to analyze the muscle- 
 fibre and to determine out of what units it is built up, the difficulty 
 begins. The fibre shows alternate dim and clear transverse stripes, and 
 
OPTICAL PHENOMENA OF MUSCULAR CONTRACTION 743 
 
 can actually be split up into discs by certain reagents. It also shows 
 a longitudinal striation, and can be separated into fibrils. Some have 
 supposed that the discs are the real structural units which, piled end 
 to end, make up the fibre. The fibrils they consider artificial. This 
 view is erroneous. It seems certain that the fibres are built up from 
 fibrils ranged side by side, and that the discs are artificial. The con- 
 tents of the muscle-fibre appear to consist of two functionally different 
 substances, a contractile substance, and an interstitial, perhaps nutri- 
 tive, non-contractile material of more fluid nature. The contractile 
 substance is arranged as longitudinal fibrils embedded in interfibrillar 
 matter (sarcoplasm). In a muscle impregnated with chloride of gold 
 the interfibrillar matter appears as a network. 
 
 Schafer has described the contractile elements of the muscle-fibre 
 (Figs. 24S, 249) as fine columns (sarcostyles), divided into segments 
 
 (sarcomeres) by thin transverse 
 ^______^_ discs (Krause's membranes), occu- 
 
 t • ^!S?'i"i'iIii mii!i!l!?^PIUfflBMniuu I . ■ ' i;i: ■ pying the position of the middle of 
 
 each light stripe. Each sarcomere 
 contains a sarcous element (a. por- 
 tion of the dark stripe) with a clear 
 substance at its ends, filling up the 
 
 n 
 
 Fig. 24S. — Living .Muscle of Water- 
 Beetle (highly magnified) (Schafer). 
 s, sarcolemma ; a, dim stripe ; 
 b, bright stripe; c, row of dots in 
 bright stripe, which appear to be 
 the enlarged ends of rod-shaped 
 particles, d, but in reality represent 
 expansions of the interstitial sub- 
 stance (sarcoplasm). 
 
 '■-'■[■'-K 
 
 l"ig. 249. — Portion of Leg 
 Muscle of Insect, treated 
 with Dilute Acetic Acid 
 (Schafer). S, sarco- 
 lemma; D, dot-like en- 
 largement of sarcoplasm; 
 K, Krause's membrane. 
 The sarcous elements 
 have been swollen and 
 dissolved by the acid. 
 
 space between the sarcous element and Krause's membrane, and con- 
 stituting a portion of the light stripe. The sarcous element is itself 
 double, and if the fibre be stretched, the two portions separate at a 
 line which runs transversely across the middle of the dim stripe (Hensen's 
 line) . Schafer considers that the appearance of longitudinal fibrillation 
 in the sarcous elements is due to the presence in them of fine longi- 
 tudinal canals or pores. 
 
 The Krause's membrane of the individual fibrils is scarcely ever 
 visible in an intact mammalian fibre, and the apparent line in the clear 
 stripe of an intact fibre is an optical appearance due to interference of 
 light. Kiihne. who was fortunate enough to find one day a small 
 nematode worm moving in the interior of a fibre, saw it pass along 
 the fibre with perfect freedom, ignoring Krause's membrane. Possibly, 
 however, it was moving in the sarcoplasm, the fibrils being simply 
 pushed aside. 
 
744 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 ChangesduringContraction— Theories of Contraction. — Incontractions, 
 according to Scliafcr, llie clear substance between Krause's membrane 
 and the sarcous element passes into the canals, wliich arc open towards 
 Krause's membrane, but closed towards Hensen's line. The sarcous 
 element therefore swells up, and the sarcomere is shortened. In the 
 extended muscle tlie clear substance leaves the pores of the sarcous 
 element, and accumulates in the space between it and Krause's mem- 
 brane. The sarcomere is thus lengthened and narrowed. Vvliile the 
 existence of Schafer's pores is not admitted by all ol servers, there is a 
 pretty general agreement that the sarcomere, like the cytoplasm of an 
 amoeboid cell, does consist of two substances, one of which (the hyalo- 
 plasm of the cell, the clear material of the sarcomere) interpenetrates 
 the other (spongioplasm of the cell, substance of the sarcous element); 
 and that in relaxation the clear fluid passes from the sarcous element 
 to the ends of the sarcomeres, whereas in contraction it passes in the 
 reverse direction into the sarcous elements. Whether the fluid passes 
 into and out of the meshes of an actual network, or along actual physical 
 pMDies in the sarcous element, or whether it is transferred by some 
 process like molecular imbibition (p. 426), need not be discussed here, 
 since it is not definitely known. The fundamental question by what 
 process the transference is determined when the muscle is excited also 
 remains unsettled. So far as is known at present, it is probable that 
 the mechanical energy of the contracting muscle must be derived from 
 the transformation of chemical energ\' into one of three forms : energy 
 associated with osmotic processes, energy associated with imbibition, 
 and energy associated with changes of surface tension. It is not diffi- 
 cult to see that a sudden increase in the osmotic concentration in the 
 sarcous element, due to the breaking up of large molecules or colloid 
 aggregates into small molecules, or the liberation of electrolytes from 
 the colloids, might lead to the rapid passage of water into it from 
 the bright bands. A sudden change of permeability of the sarcous 
 elements for dissolved substances in the clear fluid would have a 
 similar efi^ect. The same is true of a change in their power of imbibi- 
 tion. But, according to Bernstein, it is scarcely to be supposed that 
 the extraordinarily rapid movement of water molecules which must 
 occur in contraction can be accounted for either bj- osmosis or by im- 
 bibition. A more plausible theory is that the surface tension — say 
 between the substance of the sarcous element and the clear fluid — is 
 altered. That the shortening of the muscle in fatigue (p. 749) and 
 rigor (p. 774), as well as its shortening in normal contraction, is due in 
 some way to the liberation of metabolic products, especially lactic acid, 
 is a theory of some standing, and fresh evidence in its favour has been 
 recently supplied. Thus it has been pointed otit that the course of 
 heat production in the active muscle, and its relation to the time of 
 the mechanical response, and the development and time relations of 
 the electrical change which precedes that response, can be very naturally 
 explained on the supposition that the liberation of lactic acid on or 
 near some surface in the contractile substance is an essential factor in 
 the contraction (Mines, etc.). It is known that in the presence of acid 
 on the surface of certain colloid structures shortening occurs (Fischer 
 and Strietman). 
 
 The substance of the sarcous element which forms the dark stripe 
 is doubly refracting, and therefore rotates the plane of polarization, 
 but the clear substance of the light stripe is singly refracting. When 
 an uncontracted fibre is viewed with crossed nicols. the dim stripe 
 accordimjly appears bright in the otherwise dark field. In the con- 
 tracted fibre the doubly refractive material remains in the stripe which 
 
MECHANICAL PHEXOMEiWA OF MUSCULAR CONTRACTION 745 
 
 is dim in ordinan,' light. Tliere is no transference of it, but, according 
 to most writers, the bands which are dim in ordinary- light increase in 
 size by tlie transference of liiiiiid from the isotropous band. 
 
 Diffraction Spectrum of Muscle. — When a beam of white light passes 
 through a sirited muscle, it is broken up into its constituent colours, 
 and a series of diffraction spectra are produced, just as happens when 
 the light passes through a diffraction grating (a piece of glass on which 
 are ruled a number of fine parallel equidistant lines). The nearer the 
 lines are to each other, the greater is the displacement of a ray of light 
 of any given wave-length. It has accordingly been found that when a 
 muscular fibre contracts, the amount of displacement of the diffraction 
 spectra increases. At the same time the whole fibre becomes more 
 transparent. 
 
 (2) Mechanical Phenomena. — The muscular contraction may be 
 graphically recorded by connecting a muscle with a lever which is 
 moved either by its shortening or by its thickening. The lever writes 
 on a blackened surface, which must 
 travel at a uniform rate if the form 
 and time-relations of the muscle 
 curve are to be studied, but may be 
 at rest if only the height of the con- 
 traction is to be recorded. The whole 
 arrangement for taking a muscle- 
 tracing is called a myograph (Fig. 
 287, p. 812). The duration of a 
 ' twitch ' or single contraction (in- 
 cluding the relaxation) of a frog's 
 muscle is usually given as about 
 one-tenth of a second, but it may 
 var\- considerably with temperature, 
 fatigue, and other circumstances. 
 It is measured by the vibrations of 
 a tuning-fork written immediately 
 below or above the muscle curve. 
 When the muscle is only slightly 
 weighted, it but ven.' gradually 
 reaches its original length after con- 
 traction, a period of rapid relaxation 
 being followed by a period of ' resi- 
 dual contraction,' during which the 
 
 descent of the lever towards the base-line becomes slower and slower, 
 or stops altogether some distance above it. The duration of the con- 
 traction of smooth muscle evoked by a single momentary stimulus is 
 much greater than that of stiiped muscle (two to seven seconds for the 
 rabbit's ureter; five to fifteen seconds for the cat's nictitating mem- 
 brane ; one to two minutes for the frog's stomach). 
 
 Latent Period. — If the time of stimulation is marked on the tracing, 
 it is found that the contraction does not begin simultaneously with it, 
 but only after a certain interval, which is called the latent period. 
 
 This can be measured by means of the spring myograph (Fig. 251) 
 or of the pendulum myograph, a pendulum which in its swing carries 
 a smoked plate against the writing-point of a le^"er connected with a 
 muscle. The carrier of the recording plate opens, at a definite point 
 in its passage, a key in the priman,- coil of an induction machine, and 
 so causes a shock to be sent through the muscle or nerve, which is con- 
 nected with the secondary-. The precise point at which the stimulus 
 is thrown in can be marked on the tracing by carefully bringing the 
 
 Fig. 250. — Living Muscular Fibre (from 
 Geotrupes stercorarius). i, in or- 
 dinary; 2, in polarized light. (Van 
 Gehuchten.) In li\ing muscle (at 
 least in fibres which are not extended) 
 in contrast to dead muscle after treat- 
 ment with reagents, the doubly re- 
 fracting or anisotropous substance is 
 present in the greater part of the fibre ; 
 and with crossed nicols the position of 
 the singly refracting or isotropous 
 material is indicated only by narrow 
 transverse black lines or rows of dark 
 dots. 
 
745 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 plate to the position in which the key is just opened, and allowing 
 the lever to trace lierc a vertical line (or, rather, an arc of -a circle). 
 The portion of the time-tracing between this line and a parallel line 
 drawn through the point at which the contraction begins gives the 
 latent period. 
 
 Hehiiholtz measured the length of the latent period by means of the 
 principle of Pouillet, that the deflection of a magnet by a current of 
 given strength and of very short duration is proportional to the time 
 during which the current acts on the magnet. He arranged that at 
 tlie moment of stimulation of the muscle a current should be sent 
 through a galvanometer, and should be broken by the contraction of 
 the muscle the moment it began. In this way he obtained the value 
 of ,^0 second for the latent period of frog's muscle. The tendency of 
 
 Fig. 251.— Spring Myograph. A, B. iron uprights, between which are stretched the 
 guide-wires on which the travelling plate a runs; k, pieces of cork on the guides 
 to gradually check the plate at the end of its excursion, and prevent jarring; 
 b, spring, the release of which shoots the plate along; h, trigger-key, which is 
 opened by the pin d on the frame of the plate. 
 
 later observations has been to make the latent period shorter. Burdon 
 Sanderson found that tlie change of form licgins in unweighted or verv 
 slightly weighted muscle with direct stimulation in ,;/„„ second after, 
 and the electrical change (p. 824) simultaneouslv witli, the excitation! 
 It is known that the apparent latent period depends upon the resistance 
 which the muscle has to overcome in bcginninj,' its contraction. 
 
 The maximum shortening, or ' height of the lift,' depends upon the 
 length of the muscle, the direction of the fibres, the strength of the 
 stimulus, the excitability of the tissue, and the load it has to raise. 
 
 In a long muscle, other things being equal, the absolute shortening, 
 and therefore the maximum height of the curve, will be greater than 
 
 in a short muscle; in a muscle with fibres parallel to its length the 
 
 sartorius. for instance — it will be greater than in a muscle like the 
 gastrocnemius, with the fibres directed at various angles to the long 
 axis. For stimuli less than maximal, the absolute contraction increases 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 7 i7 
 
 with the strength of stimulation, and a given stimulus will cause a 
 greater contraction in a muscle witli a given excitability than in a 
 muscle which is less excitable. Under ordinary experimental condi- 
 tions .vt least, weak stimuli cause a smaller contraction than strong, 
 not only because each stimulated fibre contracts less, but because a 
 smaller number of fibres are excited (p. 155). The objects used for the 
 study of muscular contraction contain many fibres, and it is not in 
 
 Fig. 25.:. — Curve of a Single Muscular Contraction or Twitch taken on Smoked Glass 
 with Spring Myograph and photographed. Vertical line A nr.aiks the point at 
 which the muscle was stimulated; time tracing shows , Jn of a second (reduced). 
 
 general possible to distribute the stimulus equally to all. This is true 
 fbr smooth muscle a3 well as for striped. Finally, increase of the load 
 per imit of cross-section of the muscle diminishes above a certain limit 
 the ' lieight of the lift.' 
 
 Influences which affect the Time-Relations of the Muscular Contrac- 
 tion. — Many circumstances attect the form of the muscle curve and its 
 time-relations. 
 
 [a) Influence of the Load — Isotonic and Isometric Contraction. — The 
 first effect of contraction is to suddenly stretch the muscle, and the 
 more the muscle is loaded the greater will this 
 elongation be. So that at the beginning of the 
 actual shortening part of the energy of contraction 
 is already expended without visible effect, and has 
 to be recovered from the elastic reaction during 
 the ascent of the lever. 
 
 The contraction of a muscle loaded by a weight 
 which is not increased or diminished during the 
 contraction is said to be isotonic, for here the 
 tension of the muscle is the same throughout, and 
 its length alters. When the muscle is attached very 
 near the fulcrum of the lever, so that it acts upon 
 a short arm, while the long arm carrying the 
 writing-point is prevented from moving much by 
 a spring, the muscle can nnly shorten itself very 
 slightly; but the changes of tension in it will be 
 related to those in the spring, and therefore to the 
 curve traced by the writing-point. Such a curve 
 is called isometric, since the length of the muscle 
 remains almost unaltered. In the body muscles 
 usually contract under conditions more nearly 
 allied to those of the isometric than to those of 
 the isotonic contraction. 
 
 The work done by a muscle in raising a weight is equal to the product 
 of the weight by the height to which it is raised. Beginning with no 
 load at all, it is found that the weight can be increased up to a certain 
 limit without diminishing the height of the contraction; perhaps the 
 height may even increase. Up to this limit, then, the work evidently 
 increases with the load. If the weight is made still greater, the con- 
 
 Fig. 253. — Contrac- 
 tions ol Smooth Mus- 
 cle: Cat's Bladder 
 (C. C. Stewart). 
 Stimulated with pro- 
 gressively stronger 
 induction shocks. 
 The lowest line is the 
 time trace (lo-second 
 intervals). Immedi- 
 ately below the mus. 
 cular contractions are 
 marked the points at 
 which the stimuli 
 were thrown in. 
 
748 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 traction becomes less and less, but up to another limit the increase of 
 weight more than compensates for the diminution of ' lift.' and the 
 work still increases. Beyond this, further increase of weight can no 
 
 Fig. 254. — Influence of Load on the Form of the Muscle Curve, i, curve taken with 
 unloaded lever; 2, 3, 4, weight successively increased; 5, abscissa line: time trace, 
 ■j^ second (reduced). 
 
 longer make up for the lessening of the lift, and the work falls oflf till 
 ultimately the muscle is unable to raise the weight at all. 
 
 The ' absolute contractile force ' of an active muscle may be measured 
 by determining the weight which, brought to bear upon the muscle at 
 
 Fig. 255 — Influence of Temperature on the Striated Muscle Curve. 2, air tempera- 
 ture; I. 25°— 3o'C.; 3. 7°— io°C.; 4. ice in contact with muscle. The fifth curve 
 was taken at a little above air temperature. 
 
 the instant of contraction, is just able to prevent shortening without 
 stretching the muscle. It, of course, depends, among other things, on 
 the cross-section of the muscle. During the contraction the absolute 
 force diminishes continually, so that a smaller and smaller weight is 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 749 
 
 sufficient to stop any further contraction the more the muscle has 
 already shortened before it is apjiHcd. At the maximum of the con- 
 traction the absohite force is zero. Hence a muscle works under the 
 most favourable conditions when the weight decreases as it is raised, 
 and this is the case with many of the muscles of the body. During 
 flexure of the forearm on the elbow, with the upper arm horizontal, a 
 weight in the hand is felt less and less as it is raised, since its moment, 
 which is proportional to its distance from a vertical line drawn through 
 the lower end of the humerus, continually diminishes. 
 
 (b) Influence of Temperature on the Muscular Contraction. — Increase 
 of temperature of the muscle up to a certain limit diminishes the latent 
 period and the length of the curve, and increases 
 the height of the contraction, but beyond this limit 
 the contractions are lessened in height (Fig. 255). 
 Marked diminution of temperature causes, in 
 general, an increase in the latent period and length, 
 and a decrease in the height of the contraction. In 
 the heart the effect of cold in strengthening the 
 beat is often very marked. Temperature affects 
 the contraction curve of smooth muscle much in the 
 same way as that of striated muscle (Fig. 256). 
 
 (c) Influence of Previous Stimulation — Fatigue. 
 —U a muscle is stimulated by a series of equal 
 shocks thrown in at regular intervals, and the 
 contractions recorded, it is seen that at first 
 each curve overtops its prede- 
 cessor by a small amount.* This 
 phenomenon, which is regularly 
 V. observed in fresh skeletal muscle 
 
 Fig. 256. — Influence of Temperature on the Smooth Muscle Curve: Cat's Bladder 
 (C. C. Stewart). Contractions at different temperatures with the same strength 
 of stimulus. The temperatures (Centigrade) are marked on the curves. 
 
 (Fig. 260), although it was at one time supposed to be peculiarly a 
 
 property of the muscle of the heart (Fig. 2bi), is called the staircase,' 
 
 and seems to indicate that within limits the muscle is benefited by 
 
 contraction and its excitability increased for a new stimulus. Soon, 
 
 however, in an isolated preparation, the contractions begin to decline 
 
 in height, till the muscle is at length utterly exhausted, and reacts 
 
 no longer to even the strongest stimulation (Figs. 258, 259, 288). 
 
 A conspicuous feature of the contraction-curves of fatigued 
 
 muscle is the progressive lengthening, which is much more mark«cd 
 
 in the descending than in the ascending p?riods; in other words, 
 
 * Guthrie has recently described an interesting series of phenomena illus- 
 trating the influence of previous stimulation on the irritabihty of muscle. 
 Under given conditions, for example, strong stimulation increases the response 
 
 of skeletal musclei to subsequent single stimuli, it may be, by hundreds per 
 
 cent. 
 
750 THE PHYSIOLOGY Ol- THL CONTRACTILE TISSUES 
 
 relaxation becomes more and more difficult and imperfect (Fig. 288. 
 p. 814). In smooth muscle (cat's bladder or ring from frog's stomach) 
 fatigue can be very easily demon- 
 strated in the same way, and the 
 curves present similar features, with 
 the exception that, instead of be- 
 coming longer in fatigue, the suc- 
 cessive contractions become shorter. 
 It is by no means so easy to 
 fatigue a muscle still in connection 
 with the circulation as an isolated 
 muscle. But even the latter, if left 
 to itself, will to some extent re- 
 cover, and be again able to con- 
 tract, although exhaustion is now 
 more readily induced than at first. 
 
 Fig. 258. — Fatigue Curve of Muscle-. 
 Frog's Gastrocnemius. The arrange- 
 ment with which the curve figured 
 was obtained was a so-called auto- 
 matic muscle interruptor (Fig. 257). 
 A wire on the lever is made to close 
 and open the primary circuit of an 
 inductorium. the muscle or nerve 
 being connected with the secondary. 
 Every time the needle touches the 
 mercury the muscle is stimulited 
 automatically. 
 
 fr 
 
 'B^ 
 
 Fig. 25-. — Automatic Muscle Interruptor. 
 K, battery; P, primary; S, secondary coil; 
 A, axis of lever; N. needle; Hg, mercury 
 cup. 
 
 In man, muscular fatigue can be studied by means of an arrange- 
 ment called an ergograph (Fig. 2()2). A record of successive con- 
 
 259. — fatigue curse taken on a Slowly-moving Drum (reduced to Half): Frogs 
 Gastrocnemius. Excited through the sciatic nerve by maximal shocks once lu 
 six seconds. 
 
 Fig. 259.— Fatigue Cur 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 751 
 
 tractions, say, of one of the flexor muscles of a finger, in raising a 
 weight (isotonic method) or in cU'forming a spring (isometric method) 
 is taken on a drum. When the contractions are repeated every 
 second, or every half-second, distinct evidence vi fatigue is seen on 
 the tracing after a longer or shorter 
 period, according to the conditions.* 
 What is the cause of muscular 
 fatigue ? An exact answer is not 
 possible in the present state of our 
 knowledge, but we may fairly con- 
 clude that in an isolated preparation 
 it is twofold : (i) Waste products, 
 among which some are so directly 
 related to the onset of fatigue as to 
 deserve the name of ' fatigue sub- 
 stances,' are formed by the acti\c 
 muscle faster than they can be re- 
 moved, oxidized or otherwise decom- 
 posed. (2) The material necessary for 
 contraction is used up more quickly 
 than it can be reproduced or brought 
 to the place where it is required. That the accumulation of fatigue 
 products has something to do with the exhaustion is shown by the 
 fact that the muscles of a frog, exhausted in spite of the continuance 
 of the circulation, can be restored by bleeding the animal, or washing 
 out the vessels with physiological salt solution, while injection of a 
 watery extract of exhausted muscle into the bloodvessels of a 
 
 Fig. 260. — ' Staircase ' in Skeletal 
 Muscle: Frog. Stimulation by an 
 automatic arrangement. 
 
 Fig. 261. — 'Staircase' in Cardiac Muscle. Contractions recorded on a much more 
 quickly moving drum than in Fig. 260. The contractions were caused by stimu- 
 lating a heart reduced to standstill by the tirst Stannius' ligature (p. 199). The 
 contractions gradually increase in height. 
 
 curarized muscle renders it less excitable (Ranke). This observer 
 supposed that it was specially the removal of the acid products of 
 contraction which restored the muscle. Such acid products as 
 carbon dioxide and lactic acid, or the lactates which it may form 
 with bases in the blood, lymph or tissues, when they act on muscle 
 
 * Recent observations (by Ryan and Agnew) with improved methods have 
 emphasized the necessity for care in the interpretation of ergographic records. 
 This caution is timely, inasmuch as in modern war the question of the rela- 
 tion of fatigue to industrial practice acquires tirst-class importance. 
 
75^ THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 in more than a certain concentration, produce the same effects on 
 its power of contraction as are produced by fatigue, and there is 
 some reason to suppose that lactic acid is tlie most influential of the 
 fatigue substances. In smaller concentration, on the contrary, they 
 increase the excitability of the muscle, and, according to Lee, the 
 phenomenon of the ' staircase ' is due to the augmenting action of 
 thise, and perhaps otlier f: tigue substances, before they have accu- 
 mulated sufficiently to cause fatigue. 
 
 The lack of oxygen holds a conspicuous place among the con- 
 ditions which permit an excessive accumulation of fatigue substances, 
 and may contribute also to the failure of the processes normally 
 going on in the muscle which replenish the store of materials 
 needed for contraction. An isolated muscle is necessarily an 
 asphyxiated muscle, and the favourable action of an atmosphere 
 of oxygen on restoration of its contractile power after exhaustion 
 
 Fig. 2f>2. — Ergograph (Mosso's, modified by Lombard). 
 
 (Fig. 123, p. 269) shows that asphj-xia is itself an important factor 
 in the onset of fatigue. Injection of arterial blood, or even of 
 an oxidizing agent like potassium permanganate, into the vessels 
 of an exhausted muscle causes restoration (Kronecker). The 
 depletion of the available store of carbo-hydrate in the form of 
 glycogen (and dextrose) seems to be another factor in fatigue, 
 although not the chief direct cause of the phenomena associated 
 with that condition. 
 
 Seat of Exhaustion in Fatigue. — When a fatigued muscle responds 
 no longer to indirect stimulation, it can still be directl}^ excited. 
 The seat of exhaustion must therefore be either the nerve-trunk 
 or the nerve-endings. It is not the nerv-e-trunk which is first 
 fatigued, for this still shows the negative variation (p. 824) on being 
 excited. And if the two sciatic nerves of a frog or rabbit be stimu- 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 75i 
 
 latocl continuously with interrupted currents of equal strength, 
 while the excitation is prevented from reaching the muscles of one 
 limb till those of the other cease to contract, it will be found that 
 when the ' block ' is removed the corresponding muscles contract 
 vigorously on stimulation of their nerve. The passage of a constant 
 current tlirough a portion of the nerve or the ai)plication of ether 
 between the point of stimulation and the muscles may be used to 
 prevent the excitation from passing down (p. 813)- Or a dose of 
 curara just sufficient to paralyze the motor innervation may be 
 given to a rabbit, and the animal kept alive by artificial respiration. 
 The sciatic is now stimulated for many hours. As soon as the 
 influence of the curara begins to wear off, the muscles of the leg 
 contract. 
 
 The possible seats of fatigue caused by voluntary muscular con- 
 traction are (i) the nmscle; (2) the nerve-endings (or the receptive 
 substances in the muscles, p. 739); (3) the nerve-trunk; and (4) the 
 path of the voluntary motor impulses in the central nervous 
 system, which includes the pyramidal cells in the motor region of 
 the cerebral cortex (p. 875), the fibres of the pyramidal tract, and 
 the motor cells in the anterior horn of the spinal cord. 
 
 The two weak links in this chain appear to be the motor nerve- 
 endings and the muscles. The nerve-fibres, whether peripheral 
 or central, are certainly the strongest link. Ergographic experi- 
 ments have hitherto yielded results too discordant to justify any 
 very definite statement as to the point at which the chain snaps in 
 complete fatigue, if, indeed, it al vays necessarily breaks at the same 
 point. The muscles and motor endings appear to be always affected. 
 The position of the nerve centres, including the synapses (p. 852), 
 is in doubt. That the synapses easily lose their power of con- 
 ducting nerve impulses under the influence of repeated excitations 
 is indicated by the experiments of Sherrington on fatigue of reflex 
 mechanisms in which two or more afferent paths can cause discharge 
 along a common efferent path (p. 902). When excitation of one 
 of the afferent paths has ceased to be effective, the reflex contrac- 
 tions can still be obtained on exciting the other. In this case the 
 motor neuron from cell-body to nerve-ending and the muscle are 
 eliminated as the seats of the fatigue block. Whether the tem- 
 porary loss of conduction in this case is comparable to the fatigue 
 of muscle, or is a perfectly different phenomenon (' pseudo- fatigue ' 
 of Lee), scarcely bears on our present question. For if ' pseudo- 
 fatigue ' of afferent synapses can cause a reflex to miss fire, this at 
 least shows that the conductivity of the synapse is very easily affected 
 by repeated excitation, just as it is known to be very easily affected 
 by anaemia. The fact that a muscle, ct)mpletely fatigued by direct 
 electrical stimulation, can still be voluntarily contracted, has been 
 supposed to indicate that the voluntary excitation is more effective 
 
754 THE PHYSIOLOGY 01- TJIE CONTRACTILE TISSUES 
 
 than any artificial stimulus. But tlu- alternative explanation that 
 the electrical stimuli cannot be applied to a muscle in situ, so as to 
 cause uniform excitation, and therefore uniform fatigue, of all the 
 fibres of the muscle, is more probable (Hough). 
 
 It has been shown that the injection of the blood of an animal 
 exhausted by running or other muscular effort into the circulation 
 of a normal animal produces in the latter all the symptoms of fatigue. 
 Here the fatigue-producing substances will have the opportunity 
 of acting on both the central and the peripheral mechanisms. There 
 are reasons for believing that the fatigue process is fundamentally 
 the same in different tissues. The fatigue substances produced in 
 
 Fig. 2 )3. — Influenrf of >STitaI Fatigue on Muscular Contraction, i, series of con- 
 tractions of Uexors of middle finger before, and 2, series of contractions imme- 
 diately after, a period of three and a half hours' hard mental work. In both 
 cases the muscles were stimulated directly every two seconds by an electrical 
 current, and caused to raise a certain weight till temporary exhaustion occurred. 
 In the first series fifty-three contractions were found possible, in the second only 
 twelve (Maggiora). 
 
 muscle, and not immediately eliminated or transformed during 
 active muscular exertion, may therefore very well be a factor in 
 inducing fatigue of the central nervous mechanisms in addition to 
 the formation of fatigue products, and the using up of necessary 
 material in these mechanisms themselves. Conversely, active 
 and long-continued mental exertion may occasion muscular fatigue 
 (Fig. 2(.3). The sensation of fatigue is alluded to in Chapter XVIII. 
 
 {d) The Influence of Drugs on the Contraction of Muscle. — The total 
 wor*K, which a muscle can perform, its excitability and the absolute 
 force of the contraction, may all be altered either in the plus or the 
 minus sense by drugs. But in connection with our present subject 
 those drugs wliich conspicuously alter the form and time-relations of 
 the muscle-curve have most interest. Of these veratrine is especially 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 755 
 
 importiuit. W licii a small i|uantity of this subs'.aiice is injected below 
 tlie skin oi a frog, spasms of the voluntary muscles, well marked in the 
 limbs, come on in a few minutes. These are attended with great 
 stiffness ojj movement, for while the animal can contract the extensor 
 muscles of its legs so as to make a spring, they relax very slowly, and 
 some time elapses before it can spring again. If it be killed before the 
 reflexes are completely gone, the peculiar alterations in the form of the 
 muscle-curve caused by veratrine will be most marked. The poisoned 
 
 1 
 
 F^ig. 264- — Veratrine Curve compared with Normal: Frog's Gastrocnemius. The 
 tuning-fork marks hundredths of a second. Between i and 2 a portion of the 
 tracing corresponding to one and a half seconds has been cut out, and between 
 2 and 3 a portion corresponding to one second. The veratrine curve does not 
 show a peak. At 3 it has not yet fallen to the base-line. 
 
 muscle, stimulated directly or through its nerve, contracts as rapidly 
 as a normal muscle, while the height of the curve is about the same, 
 but the relaxation is enormously prolonged (Fig. 204). This effect 
 seems to be to a considerable degree dependent on temperature, and 
 it may temporarily disappear when the muscle is made to contract 
 se^■eral times without pause. Barium salts, and. in a less degree, those 
 . of strontium and calcium, have an action on muscle similar to that of 
 veratrine. Sometimes the curve shows a peak (Fig. 265). due to a 
 rapid descent of the lever for a certain distance. This is followed by 
 a slow relaxation. The 
 peak appears to be analo- 
 gous to the initial con- 
 traction when a strong 
 voltaic current is passed 
 through a muscle, and 
 the rest of the curve to 
 the tonic contraction. 
 
 [e) The individuality of 
 the muscle itself has an 
 influence on the muscle- 
 curve. Not only do the 
 muscles of different animals vary in the rapidity of contraction, but 
 there are also differences between the skeletal muscles of the same animal. 
 
 In the rabbit there are two kinds of striped muscle, the red and the 
 pale (the semitendinosus is a red. and the adductor magnus a pale 
 muscle), and the contraction of the former is markedly slower than 
 that of the latter. In many fishes and birds, and in some insects, a 
 similar difference of colour and structure is present. 
 
 Even where there is no distinct histological difference, there may be 
 great variations in the length of contraction. In the frog, for instance, 
 the hyoglossus muscle contracts much more slowly than the gastroc- 
 
 Fig. 265. — Veratrine Curve: Frog's Gastrocnemius. 
 The curve shows a peak, the lever falling a little 
 before the sustained contraction begins. 
 
?5f> THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 nemius. The \va\e of contraction, which in frogs' striped muscle lasts 
 only about 0-07 second at any point, may last a second in the forceps 
 muscle of the crayfish . though only half as long in the muscles of the tail. 
 In the muscles of the tortoise the contraction is also very slow. The 
 muscles of the arm of man contract more quickly than those of the leg. 
 Summation of Stimuli and Superposition of Contractions. — Hitherto 
 we have considered a single muscular contraction as arising from a 
 single stimulus, and we have assumed that the muscle has completed 
 its curve and come back to its original length before the next stimulus 
 was thrown in. We have now to inquire what happens when a second 
 stimulus acts upon the muscle during the contraction caused by a fi.rst 
 stimulus, or during the latent period before the contraction has actually 
 begun; and what happens when a whole series of rapidly-succeeding 
 stimuli are thrown into the muscle. 
 
 First let us take two stimuli separated by a smaller interval than 
 the latent period (p. 745)- If they are both maximal — i.e., if each by 
 itself would produce the greatest amount of contraction of which the 
 muscle is capable when excited by a single stimulus — the second has 
 no effect whatever ; the contraction is precisely the same as if it had 
 
 ne^'er acted. But if they are less 
 than maximal, the contraction, 
 although it is a single contraction, 
 is greater than would have been 
 due to the first stimulus alone ; in 
 other words, the stimuli have been 
 summed or added to each other 
 during the latent period, so as to 
 produce a single result. 
 
 Next let us consider the case of 
 two stimuli separated by a greater 
 _ . . . _ interval than the latent period, so 
 
 Fig. 2fi6 .-Superposition of Contractions, that the second falls into the 
 I IS the curve when only one stimulus j^^j^^j^ during the contraction pro- 
 IS thrown m; 2, when a second stimulus , j 1 ^.u ^ j. -ri ij. -u 
 
 acts at the time when curv-er has nearly ^uced bv the first^ The result here 
 reached its maximum height. '^ very different : tracesof two con- 
 
 tractions appear upon the muscle- 
 curve, the second curve being that which the second stimulus would have 
 caused alone, but rising from the point which the first had reached at the 
 moment of the second shock (Fig. 266). Although the first curve is 
 cut short in this manner, the total heiglit of the contraction is greater 
 than it would have been had only the first stimulus acted ; and this is 
 true even when both stimuli are maximal. Under favourable circum- 
 stances, when the second curve rises from the apex of the first, the total 
 height may be twice as great as that of the contraction which one 
 stimulus would have caused (p. 816). It is worthy of note that striated 
 muscle has no power of summation of subminimalstimuli each of which 
 is just too weak to cause contraction. No matter how rapidly they are 
 thrown in, the muscle remains at rest. It is otherwise with smooth 
 muscle. Stimuli which are singly ineffective cause contraction when 
 repeated. 
 
 Tetanus. — Not only may we have superposition or fusion of two 
 contractions, but of an indefinite number; and a series of rapidly 
 following stinuili causes complete tetanus of the muscle, which 
 remains contracted during the stimulation, or till it is exhausted 
 (Fig. 267). 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 757 
 
 The meaning of a complete tetanus is readily grasped if, beginning 
 with a series of shocks of such rapidity that the muscle can just 
 completely relax in the intervals between successive stimuli, we 
 gradually increase the frequency (p. 8i6). As this is done, the 
 ripples on the curve become smaller and smaller, and at last fade 
 out altogether. The maximum height of the contraction is greater 
 than that produced by the strongest single stimulus; and even after 
 complete fusion has been attained, a further increase of the fre- 
 quency of stimulation may cause the curve still to rise. 
 
 Fig. 267. — Analysis of Electrical Tetanus (reduced to f ). Four curves showing the 
 effect of increasing frequency of stimulation of the frog's gastrocnemius through 
 its nerve. In the lowest curve the frequency is such that the muscle relaxes 
 almost completely betweeH the successive contractions. In the uppermost 
 curve, with a frequency more than three times greater, the contractions are 
 almost completely fused. In all the curves the fusion becomes more nearly 
 complete as stimulation goes on, owing to the slower relaxation of the fatigued 
 muscle. 
 
 It is evident from what has been said that the frequency of 
 stimulation necessary for complete tetanus will depend upon the 
 rapidity with which the muscle relaxes; and everything which 
 diminishes this rapidity will lessen the necessary frequency of 
 stimulation. A fatigued muscle may be tetanized by a smaller 
 number of stimuli per second than a fresh muscle, and a cooled by 
 a smaller number than a heated muscle. The striped muscles of 
 insects, which can contract a million times in an hour, require 
 300 stimuli per second for complete tetanus, those of birds 100, 
 of man 40, the torpid muscles of the tortoise only 3. The pale 
 muscles of the rabbit need 20 to 40 excitations a second, the red 
 
758 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 muscles only lo to 20; the tail muscles of the crayfish 40, but the 
 muscles of the claw only 6 in winter and 20 in summer. The 
 gastrocnemius of the frog requires 30 stimuli a second, the hyo- 
 glossus muscle only half that number (Richet). The frequency of 
 stimulation necessar\' for complete tetanus of unstrip^d muscle 
 is much less than for striped muscle. Smooth tetanus of a band of 
 muscle from the frog's stomach was obtained \sith strong opening 
 induction shocks at the rate of i in 5 seconds. 
 
 Tlitrc appears also to be an upper limit bevond which a series of 
 stimuli becomes too rapid to produce complete tetanus, and at which an 
 interrupted current acts like a constant current, causing a single twitch 
 at its commencement or at its end, but no contraction during its pas- 
 sage. This limit docs not depend upon the frequency of stimulation 
 alone ; the intensity of the individual excitations, the temperature of 
 the muscle, and probably other factors, affect it. For Bernstein found 
 that with moderate strength of stimulus tetanus failed at about 230 
 per second, and was replaced by an initial contraction ; with strong 
 stimuli at more than 1,700 per second, tetanus could still be obtained. 
 Kronecker and Stirling saw tetanus even with 4,000 shocks a second. 
 Kries in a cooled muscle found tetanus replaced by the simple initial 
 twitch at 100 stimuli per second, although in a muscle at 38^ C. stimu- 
 lation of ten times this frequency still caused tetanus. Einthoven, 
 exciting the nerve of a frog's nerve-muscle preparation with extremely 
 frequent oscillatory condenser discharges, observed tetanus up to even 
 a million vibrations a second, if the current intensity was at the same 
 time very greatlv increased (to more than 16,000 times the intensity 
 needed with a constant current). These results are not really so dis- 
 cordant as they appear ; for it is known that with electrical stimulation 
 the number of excitations is not necessarily the same as the nominal 
 number of shocks. By applying a telephone to a muscle excited through 
 its motor nerve, it has been shown that the pitch of the note produced 
 by the tetanized muscle corresponds exactly to the rate of excitation 
 up to a certain frequency. This frequency is about 200 per second for 
 frog's and about 1,000 per second for mammalian muscle under the 
 best conditions. If the rate of excitation is still further increased, there 
 is no corresponding increase in the pitch. Therefore, some of the 
 stimuli are now producing no effect—' falling flat,' so to speak (Weden- 
 sky). A physical reason for this is the overlappmg of the make and 
 break shocks (Erlanger and Garrey) ; and a physiological reason, the 
 alterations of conductivity and excitability, which even very brief 
 currents leave behind them (Sewall), and which we shall have to discuss 
 in another chapter. 
 
 It is only while the actual shortening is taking place that a tetanized 
 muscle can do external work. But, although during the maintenance 
 of the contraction no work is done, energy is nevertheless being ex- 
 pended for the metabolism of a muscle during tetanus is greater than 
 during rest, and, among other changes, lactic acid is produced. There 
 are great differences in the case with which different muscles can be 
 exhausted by tetanus. For example, the muscles which close the 
 forceps of the cravfish or lobster have, as everyone knows, the power 
 of most obstinate contraction. Richet tetanized one for over seventy 
 minutes, and another for an hour and a half, before exhaustion came 
 
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 759 
 
 on, while a tetanus of a single minute exhausted the ^inu^c^es of ti.e 
 crayfish's tail. The gastrocnemius of a summer frog kept up for twelve 
 minutes, and a tortoise muscle for forty minutes. 
 
 Continuous stimulation is not always necessary for the production 
 of continuous contraction ; in some conditions a single sti.nulus is suffi- 
 cient. A blow with a hard instrument may cause a dying or exhausted, 
 and in thin persons even a fairly normal, muscle to pass into long- 
 continued contraction. This so-called ' idio-muscular ' contraction 
 seems to depend, in part at least, on the great intensity of the stimulus. 
 It can sometimes be obtained in the frog's gastrocnemius, partici larly 
 in spring after the winter fast. It is not a tetanus and is not propa- 
 gated along the muscular fibres, as an electrical tetanus is, but remains 
 localized at the spot wlicre it arises. Similar non-tetanic contr. ctions 
 have already been mentioned, such as the tonic contraction during the 
 passage of a strong voltaic current and the sust;uncd veratrinc contrac- 
 tion. Amnaonia causes also a long but non-tetanic contraction, and this, 
 too, does not spread when the substance has acted only on a portion 
 of the muscle. The contraction force of all these tonic contractions, 
 as measured by the rv?sistance necessary to overcome or prevent them, 
 is less than the contrc'.clion force in electrical tetanus (Schenck). 
 
 The rate at which the wave of muscular contraction travels may be 
 measured by stimulating the muscle at one end, and recording, by 
 means of levers, the movements of two points of its surface as far 
 apart from each other as possible. Time is marked on the tracing by 
 means of a tuning-fork, and the distance between the points at which 
 the two curves begin to rise from the base-line divided by the time gives 
 the velocity of the wave. Another method is founded upon the measure- 
 ment of the rate at which the negative variation (p. 824) passes over 
 the muscle, this being the same as the velocity of the contraction-wave. 
 In frog's muscle it is about three metres a second, or six miles an hour. 
 Rise of temperature increases, fall of temperature lessens it. When a 
 muscle is excited through its nerve, the contraction springs up first of 
 all about the middle of each muscular fibre where the nerve-fibre enters 
 it, and then sweeps out in both directions towards the ends. But so 
 long is the wave, that all parts of the fibre are at the same time involved 
 in some phase or other of the contraction. 
 
 The wave of contraction in unstriped muscle lasts a relatively long 
 time at any given point, and in tubes like the intestines and ureters, 
 the walls of which are largely composed of smooth muscle arranged in 
 rings, the wave shows itself as a gradually-advancing constriction 
 travelling from end to end of the organ. There is no evidence that 
 the contraction of smooth muscular fibres is discontinuous — that is, 
 ;omposed of summated contractions like a tetanus ; it appears to be a 
 d;reatly-prolonged simple contraction. An artificial stimulus, mechani- 
 cal or electrical, causes, after a long latent period, a ver^' definitely- 
 localized contraction in a rabbit's ureter, which slowly spreads in a 
 peristaltic wave in one or both directions along the muscular tube. 
 Here, as in the cardiac muscle, the excitation passes from fibre to fibre, 
 while in striped skeletal muscle only the fibres excited directly or 
 through their nerves contract. That the rh^'thmical contraction of 
 the heart is not a tetanus has already been seen. It is a simple con- 
 traction, intermediate in its duration and other characters between the 
 twitch of voluntary muscle and the contraction of smooth muscle. The 
 contraction both of unstriped and of cardiac muscle is lengthened and 
 made stronger by distension of the viscera in whose walls they occur, 
 just as a skeletal muscle contracts more powerfully against resistance. 
 
76o THE PJIYSIOLCGY OF THE CONTRACTILE TISSUES 
 
 Voluntary Contraction. — There is evidence that the voluntary 
 contraction is a tetanus. One of the strongest buttresses of the 
 theory of natural tetanus has been the muscle-sound, a low rumbling 
 note which can be heard by listening witli a stethoscope over the 
 contracting biceps, or, when all is still, by stopping the ears with the 
 fingers and strongly contracting the masseter and the other muscles 
 concerned in closing the jaws.* Discovered about ninety years 
 ago, first by Wollaston and then by Erman, half a century passed 
 away before it was investigated more fully by Helmholtz. The 
 latt(^r observer, confirming the results of his predecessors, put down 
 the pitch of the sound at 36 to 40 vibrations per second. He found, 
 however, that little vibrating reeds with a rate of oscillation of about 
 19 5 per second were more affected when attached to muscle thrown 
 into voluntary contraction, than those that vibrated at a smaller 
 or a greater rate. He therefore concluded that the fundamental 
 tone of the muscle corresponded to this frequency, although, since 
 such a low note is not easily appreciated, the sound actually heard 
 was really its octave or first harmonic (p. 310). 
 
 The objection has been brought forward that the resonance tone of 
 the ear also corresponds to a vibration frequency of 36 to 40 a second. 
 In other words, this is the natural rate of swing of the elastic struc- 
 tures in the middle ear, the rate they will most easily fall into if set 
 moving by an irregular mixture of faint, low-pitched tones and noises, 
 and not compelled to vibrate at some other rate by a distinct sound 
 of definite pitch. Now, tliis resonance tone might be elicited by a 
 quivering muscle if, among many diverse rates of oscillation of different 
 portions of its substance, the rate of 36 to 40 a second anywhere ap>- 
 peared, and the note corresponding to the real rate of vibration of the 
 muscle as a whole might be overpowered. Or, even if there were no 
 regular rate of vibration of the whole muscle, but, instead, a series of 
 irregular tremors or pulls due to irregularities in the contraction, con- 
 nected with a want of co-ordination of all the fibres (Haycraft), the ear 
 might from time to time pick out of the turmoil of feeble aerial waves 
 those corresponding to its resonance tone, just as a tuning-fork or a 
 piano-string attuned to a particular note would catch it up amid a 
 thousand other sounds and strengthen it. 
 
 But while this renders it highly probable that the resonance of the 
 ear contributes to the production of the muscle-sound, and shows that 
 we cannot from the pitch of the musclc-.sounci alone deduce the rate 
 at which the muscle-substance is vibrating, it does not invalidate 
 Helmholtz's objective observjitions with the oscillating reeds. 
 
 And several observers (Schafer, Horsley, v. Kries) have noticed 
 periodic oscillations, at the rate of 10 or 12 per second, in the 
 curves taken from muscles (Fig. 268), contracted voluntarily 
 against a small resistance. When the resistance is greater, the 
 rate may be as much as 18 or 20 a second, and in quick and rapidly 
 
 * In order that a muscular sound may be produced there must be a certain 
 abruptness in the contraction. Thus, the slowly-tontracting smooth muscles 
 do not produce a sound, nor the slowly-contracting heart-muscle of cold- 
 blooded animals. 
 
MECHANICAL PHENOMENA 01' MUSCULAR CONTRACTION 761 
 
 repeated movements of the fingers even 40 a second. In habitual 
 movements, such as those employed by a man in his trade, the 
 tremors are much less coarse than in unaccustomed movements. 
 For this reason the tremors of the left hand are greater than those 
 of the right in executing a movement usually made with the latter 
 (Eshner). In disease these tremors are often increased — e.g., in 
 the clonic convulsions of epilepsy — but the frequency is the same. 
 
 ;1 
 
 ^M^W*i« 
 
 Fig. 268.- 
 
 -Vibrations of Contracted Arm Muscles (Griffiths). The arm was stretched 
 out, holding a weight of about 6 kilos. 
 
 Similar vibrations, and at about the same rate, are seen in curves 
 traced by muscles excited through stimulation of the motor areas 
 of the surface of the brain. Since this rate remains the same whether 
 the motor cortex, the corona radiata, or the spinal cord is excited, 
 and, unlike the rate of response to excitation of peripheral nerves, 
 is independent of the frequency of stimulation (so long as the rate 
 of stimulation is greater than 10 or 12 a second), it has been supposed 
 to represent the 
 rhythm with which 
 impulses are dis- 
 charged from the 
 motor cells of the cord 
 (Fig. 269). It is prob- 
 able that the cortical 
 centres discharge at 
 about the same rate, 
 for not only is it im- 
 possible to articulate 
 more rapidly than 
 eleven syllables per 
 second, but it is impossible to reproduce the act of articulation in 
 thought at a greater rate than this (Richet). But while this rate 
 of 10 or 12 a second does seem to represent a fundamental rhythm 
 of the central discharge, there are facts which indicate that upon 
 this relatively slow rhythm a quicker rhythm is superposed. In 
 other words, each of these discharges is itself discontinuous, and 
 made up of a number of separate impulses. 
 
 Fig. 269. — Contractions caused by Stimulation of the 
 Spinal Cord. 
 
762 • THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Thus, according to Piper, the total number ot simple discharges, 
 each associated with an electrical change in the muscle, as recorded by 
 the string galvanometer, is 47 to 50 a second. The rhythm of strych- 
 nine tetanus in the frog is about 8 to 12 per second. By means of the 
 capillary electrometer (p. 729) large electrical oscillations at this rate 
 can be demonstrated, each of which represents a short tetanic spasm, 
 as is shown by the fact that a number of smaller electrical oscillations 
 are superposed upon the large ones (Sanderson). The electrical changes 
 suggest that each discharge causes a simple contraction much more 
 prolonged than the twitch of a directly stimulated muscle. This 
 removes the difficulty of understanding how such a small number as 
 10 contractions per second could be smoothly fused, and indicates that 
 even the stiortest possible voluntary^ movement, which can be executed 
 in ^ to T^fj of a second, is not caused by a single impulse, but is a 
 tetanus. For these brief mo\ements the frequency of oscillation, as 
 shown by the action currents, is the same as for sustained contractions. 
 The electrical changes in the voluntarily- contracted muscle seem to 
 differ in amplitude or abruptness from those produced in experimental 
 tetanus. For secondarj' tetanus (p. 833) is not caused by muscle in 
 volimtary contraction. But this is also the case with the ftthcr pro- 
 longed contractions caused by continuous artificial stimulation — e.g., 
 Ritter's tetanus (p. 74T) and the contraction produced by sodium 
 chloride or ammonia. We need not hesitate to conclude, then, that 
 the voluntary contraction is discontinuous, in the sense that it is not 
 a perfectly smooth and uniform tonic contraction, although we still 
 lack a decisive proof that it is maintained by a strictly intermittent 
 outflow of nervous energy, and not by^ a continuous outflow causing a 
 sustained contraction, which, it may^ be, remits and is reinforced at 
 intervals. The apparent discrepancies as to the rate of discharge in 
 the results obtained by^ dilierent observers, and by different methods, 
 far from exciting distrust of them all, really lend support to the idea 
 of a fundamental and fairly constant rhythm in the outflow as soon 
 as it is recognized that the higher rates are approximately- multiples 
 of the lower. Thus, the number deduced by Helmholtz from the ex- 
 periment of the springs is twice the lowest rate calculated from graphic 
 records of the contraction. The rates corresponding to the muscle- 
 sound and to the frequency of the electrical oscillations are about four 
 times this number. Now, in a vibrating elastic body like a contracting 
 muscle, a simple mathematical relation of this sort might be expected 
 to appear when determinations of the rate of oscillation and of accom- 
 panying periodic changes are made by methods varying in principle and 
 in delicacy. For instance, an arrangement suited to record and to 
 count coarse vibrations could not be expected to give the same result 
 as an arrangement suited to record and count fine vibrations. But if 
 both the coarse and the fine vibrations were related to a fundamental 
 rhythm, a simple proportion might be expected to exist between tlic 
 two sets of results. 
 
 (3) Thermal Phenomena and Transformation of Energy in the 
 Muscular Contraction. — When a muscle contracts, its temperature 
 rises; the production of heat in it is increased. This is most dis- 
 tinct when the muscle is tetanized, but has also been proved for 
 single contractions. The change of temperatuie can be detected 
 by a delicate mercury or air thermometer; and, indeed, a ther- 
 mometer thrust among the thigh-muscles of a dog may rise as much 
 
THERMAL PHENOMENA OF MUSCULAR CONTRACTION 7(>i 
 
 as 1° to 2° C. wlu-n the muscles are thrown into tetanus. In the 
 isolated muscles of cold-blooded animals the increase of tempera- 
 ture is much less; and tliermo-electrical methods, which are the 
 most delicate at present known, have generally been used for its 
 detection and measurement. 
 
 They de^>end upon the fundamental fact of thermo-electricity, that 
 in a circuit composed of two metals a current is set up if the junctions 
 of the metals are at different tempera- 
 tures 
 
 Where no very fine differences of 
 temperature are to be measured, a single 
 thermo-j unction of (ierman silver and 
 iron, or copper and iron, is inserted into 
 a muscle or between two muscles. But 
 the electromotive force, and therefore 
 the strength of the thermo-electric cur- 
 rent, is proportional for any given pair 
 of metals to the number of junctions, 
 and for plicate measurements it may 
 be necessary to use several connected 
 together in series. A thermopile of 
 antimony - bismuth junctions gives a 
 stronger current for a given difference of 
 temperature than the same number of 
 German silver-iron couples, but from its 
 brittle nature is otherwise less convenient . 
 
 The direction of the current in the cir- 
 cuit is such that it passes through the 
 heated junction from bismuth to anti- 
 mony and from copper or German silver 
 to iron. Knowing this direction, we are 
 aware of the changes of temperature 
 which take place from the movements 
 of the mirror of the gah'anometer with 
 which the pile is connected. In the 
 thermopiles emploj-ed in the recent ex- 
 tensive investigations of Hill the alloy 
 constantan is coupled with iron, the 
 electromotive force of this combination 
 being exceptionally great. 
 
 The muscle which is to be excited is 
 brought into close contact with one 
 junction or set of junctions, the other 
 set being kept at constant temperature. 
 The image will now come to rest on the 
 scale; and excitation of the muscle will 
 cause a movement indicating an increase 
 of temperature in it, the amount of which 
 can be calculated from the deflection. In 
 one form (Fig. 270) the thermopile con- 
 stitutes a hollow cone, in which a muscle can be arranged so as to eliminate 
 largely the errors due to differences of temperature of the muscle, or to 
 the "slip" of the contracting muscle over the junctions. 
 
 In this way Helmholtz observed a rise of temperature of 0-14° to 
 18° C. in excised frogs' muscles when tetanized for a couple of minutes . 
 
 5 
 
 Fig. 270. — Conical Thermopile 
 containing Gastrocnemius Mus- 
 cle Reversed. C, copper leads 
 to galvanometer; S, stimulating 
 wire. The straight lines indicate 
 iron, the crossed lines constan- 
 tan, the external junctions em- 
 bedded in the ebonite frame 
 being at a, the internal junc- 
 tions, b, in contact with the 
 muscle. 
 
764 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Heidenhain, with a very delicate pile, found a rise of 0001° to 
 0-005° C. f(jr a single contraction of a frog's muscle. On the assump- 
 tion that the pile had time to take on the temperature of the 
 muscle before there was any appreciable loss of heat, this would 
 be equal to the production by every gramme of muscle of a thou- 
 sandth to five-thousandths of a gramme-calorie (p. 676) of heat. 
 From Pick's observations we may take about three-thousandths 
 of a gramme-calorie as the maximum production of a gramme of 
 frog's muscle in a single contraction. 
 
 Hill has shown that in the case of the single contraction or twitch 
 the evolution of heat may be so rapid as to be practically instan- 
 taneous, indicating that it depends upon some sudden ' explosive ' 
 chemical reaction; or, on the other hand, under certain conditions 
 
 it may last as long as two 
 seconds — that is, from four 
 to ten times as long as the 
 contraction itselff In the 
 absence of oxygen, when 
 the muscle is left, for in- 
 stance, in an atmosphere of 
 hydrogen, the heat produc- 
 tion becomes markedly pro- 
 longed. When abundant 
 oxygen is supplied, the dura- 
 tion of the discharge of heat 
 is decreased. In a tetanus 
 the evolution of heat lags 
 behind the excitation, and 
 the discharge associated 
 with each stimulus is not 
 complete till 0-5 to 2*5 
 seconds after the stimulus. In a prolonged complete tetanus 
 the heat production corresponding to the first tenth of a second 
 of excitation is far greater than that corresponding to the second 
 tenth of a second, and so on. until eventually a uniform dis- 
 charge of heat, at a rate much smaller than the initial rate, is 
 reached. When frogs' muscles are rapidly stimulated indirectly 
 (through the nerves) till fatigue has occurred, the maximum value 
 of the heat evolved approximates to 09 gramme - calorie per 
 gramme of muscle, about 70 or 80 per cent, being liberated in the 
 first two minutes (Peters). 
 
 A fact of great significance in regard to the relation of the reaction 
 upon which the heat production depends and the mechanical 
 conditions in the active muscle is that the production of heat is 
 determined by the length of muscular fibres existing at the time 
 when the heat is being evolved. From this it has been assumed 
 that the production of heat in active muscle is a surface effect, and 
 
 Fig. 271. — A, a single copper-iron thermo- 
 ckciric couple; B.two pairs, one inserted into 
 the tissue b, the other dipping into water in a 
 beaker a. The temperature of the water 
 maj' be adjusted so that the galvanometer 
 shows no deflection. The temperature of the 
 tissue is then the same as that of the water. 
 
THERMAL PHENOMENA OF MUSCULAR CONTRACTION 765 
 
 not an effect taking place uniformly throughout the muscle substance 
 and related accordingly to the volume or mass of the muscular 
 substance (Blix). Much evidence has been accumulated in favour 
 of this hypothesis. For example, a muscle contracting isometrically 
 (p. 747) produces more heat the greater is the initial tension (the 
 more it is stretched at the begining of the excitation) — that is, 
 the greater its length during contraction (Heidenhain). When a 
 muscle is allowed to shorten in a tetanus, the heat production as 
 compared with that of an isometric contraction of the same dura- 
 tion, and evoked by the same strength of stimulus, is diminished 
 by as much as 40 per cent. 
 
 Relation between the Development of Mechanical Energy and 
 Heat Production in Active Muscle. — There is no simple relation 
 between the external work done in a muscle twitch and the heat 
 set free. The efficiency of the muscular machine, as estimated 
 by the proportion of the work done to the total energy degraded, 
 varies with a number of factors — e.g., the load, the number of fibres 
 excited, and the intensity of the excitation of each fibre, the two 
 latter factors depending upon the strength of the stimulus. 
 
 The greater the resistance, so long as the muscle can overcome 
 it so as to do its utmost amount of external work,* the larger is 
 the proportion of energy which appears as work, the smaller the 
 proportion which appears as heat. For every muscle, under given 
 conditions, there is a certain load which can be raised more advan- 
 tageously than any other; but even in the most favourable case, 
 an excised frog's muscle never does work equal to more than J of 
 the heat given off. Generally the ratio is much less, and may sink 
 as low as ^. In the intact mammahan body the muscles work 
 somewhat more economically than the excised frog's muscles at 
 their best; for both experiment and calculation show (p. 687) 
 that in a normal man under the most favourable conditions as 
 much as J of the energy is converted into work. According to 
 Zuntz and Katzenstein, 35 per cent, of the total energy appeared 
 as muscular work in cUmbing a mountain, and in bicycling onlv 
 25 per cent. Movements which have been much practised are 
 more economically performed than unaccustomed ones, and this 
 explains the superior efficiency of the muscles concerned in climbing, 
 for no movements can possibly be more familiar than those con- 
 cerned in locomotion. So far as this indication goes, it would seem 
 that in the treatment of obesity unfamiliar, and therefore physio- 
 logically expensive, forms of exercise should be recommended, in 
 so far, of course, as they do not injuriously react upon the general 
 condition, especially upon the circulation. 
 
 • This statement, based on experiments with excised frog's muscles, is not, 
 of course, inconsistent with the fact mentioned on p. 687, that in the intact 
 body the fraction of the energy transformed into heat is greater in hard than 
 in moderate work. 
 
766 THE PHYSIOLOGY 01- THE CONTRACTILE TISSUES 
 
 When a muscle, excited by maximal stimuli, is made to lift con- 
 tinuously increasing weights, both the woik done and the heat given 
 out increase up to a certain limit. The muscle, as it were, burns the 
 candle at both ends. The heat-production reaches its maximum some- 
 what sooner than the work. 
 
 It is certain that when work is done by a muscle an equivalent 
 amount is subtracted from its sum-total of energy, and under proper 
 conditions this can be actually demonstrated by the deficiency in the 
 heat-production. This is done by means of a contrivance called a 
 work-adder. It consists of a wheel, the rotition of which raises a 
 weight attached to a cord wound round its axle. The muscle acts on 
 the periphery of the wheel, and by rotating it raises the weight a little 
 at each contraction. At the end of the contraction the wheel is pre- 
 vented from moving back by a catch. The work done in a series of 
 contractions is calculated from the total height to which the weight 
 has been raised. Suppose a frog's gastrocnemius is made to contract 
 a certain number of times while attached to the work-adder, and that 
 simultaneously the heat-production is measured by means of a thermo- 
 pile. Let H represent the heat actually produced, and h the heat 
 equivalent of the work done. Now let the muscle be disconnected from 
 the adder and made to raise the same weight, directly attached to it, 
 by a series of contractions elicited in precisely the same way as the 
 previous ones, except that the weight is allowed to fall with the muscle 
 when it relaxes after each contraction. Here heat corresponding to the 
 external work disappears from the muscle during the contraction just 
 as in the first experiment, but this heat is returned to the muscle during 
 the relaxation, since on the whole no external work is done. The heat 
 produced in the second experiment is found, as a matter of fact, 
 allowing for unavoidable errors, to be equal to H + h. 
 
 According to Hill, the true ' efficiency ' of the muscle is not the 
 fdtio W/H, where W is the external work and H the total heat liberated, 
 but T/H where T is the maximum increase of tension set up during the 
 twitch when the muscle is contracting isometrically. This fraction TjH 
 IS constant whatever be the initial tension, the number of fibres excited, 
 or the strength of excitation of each fibre. For the theory of the 
 muscular contraction the tension auring an isometric muscle twitch, 
 which represents the potential energj^ suddenly developed in conse- 
 quence of the excitation, is accordingly much more important than the 
 height of the contraction, which is related to the work actually done. 
 The essential thing in muscular contraction may be the abrupt develop- 
 ment of this tension thiough a chemical reaction which liberates certain 
 substances at some membrane or surface in the muscle. The potential 
 energy once in being may or may not be transformed into work, and if 
 so transformed the change may be accomplished economically or waste- 
 fully, according to the conditions of the contraction. The ratio T/H 
 decreases in fatigue, and with the time during which the muscle has 
 been deprived of its blood-supply. Hill has calculated the absolute 
 value of the heat-production in tetanus of a sartorius or semimem- 
 branosus muscle of the frog. This quantity, reckoned per centimetre 
 of length of the muscle, per gramme weight of the tension developed 
 and per second of maintenance of the tension, is relatively constant at 
 about 0-000015 gramme-calorie. Including the recovery processes of 
 oxidation following the contraction the total heat-production would 
 amount to about 0-000025 calorie. The potential energy possessed by 
 a muscle of a length of a centimetre when maintaining a tension of a 
 gramme is about ()'00ooo4 calorie. So that to maintain this state of 
 potential energy six or seven times as much energy must be liberated 
 
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 767 
 
 per second. The maintenance of prolonged tension is, therefore, from 
 the point of view of the mechanical result, an exceedingly wasteful 
 process, with a very low efficiency in comparison with the high efficiency 
 in a rapid twitch. This enables U5 to see how important a part in heat- 
 production, and therefore in temperature regulation, the tonusof muscle 
 and the prolonged contractions of shivering may possess (p. 695). 
 
 We are as yet in the dark as to the precise relation of the energy 
 which appears as heat and of that which is converted into work. 
 The ultimate source of both is, of course, the oxidation (and 
 cleavage) of the food substances. It was at one time a favourite 
 theory that in a muscle, as in a heat-engine, the chemical energy 
 is first converted iaito heat, and part of the heat then transformed 
 into work. There is no evidence that this is the case. It is, 
 indeed, impossible that such differences of temperature can exist 
 as would be compatible with the known efficiency of the muscular 
 machine. Hypotheses based on the assumption that the chemical 
 energy is immediately changed into work, perhaps through the pro- 
 duction of surface effects, have met with increasing favour, but 
 data are as yet too few for the formulation of any really satisfactory 
 theory. The close relation between the heat-production and the 
 formation of lactic acid in contraction which have been shown to 
 exist, is a suggestive fact whose full significance will only be revealed 
 by further investigation. The restitution processes by which the 
 original state of the muscle is restored after contraction are, of 
 course, intimately related to those concerned in the actual shorten- 
 ing; but unless we know how, and in consequence of what chemical 
 or physical changes, the equilibrium of the resting muscle has been 
 disturbed, we cannot know how, or in consequence of what chemical 
 or ph\'sical changes, it is restored. 
 
 Section TV. — Chemical Phenomena of the Muscular 
 Contraction. 
 
 The composition of dead mammalian muscle of the striped variety may 
 be stated, in round numbers, as follows, but there are con-siderable 
 variations, even within the same species: 
 
 Water -------- 73 per cent. 
 
 Proteins -------- 20 ,, 
 
 Fats, lecithin, and cholesterin - - - - 2 ,, 
 
 Nitrogenous extractives, creatin (about 04 per>| 
 cent.), carnosin, phospho-carnic acid, inosinic 
 acid, purin bodies, such as uric acid, hypoxan- 
 thin, xanthin, etc. ------ 
 
 Carbo-hvdrates (glycogen, dextrose, maltose) 
 
 Non-nitrogenous organic substances (lactic acid, 
 inosit) - - - - - - - -J 
 
 Pigment (myohsematin or myochrome, a haemoglobin not precisely- 
 identical with that of blood). 
 
 Inorganic substances less than i per cent, (chlorides, carbonates, 
 phosphates, and sulphates of potassium, sodium, iron, calcium, 
 magnesium). Potassium is absent from the nuclei (Frontispiece). 
 
758 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Of the nilropcnniis extractives, crcatin (p. 597) and carnosiii are 
 present in greatest quantity, muscle containing 0-2 to 0-4 per cent, of 
 krcatin. Carnosin (C9H14N4O3) is a substance with basic properties, 
 and can be split up into histidin and /3-aniino-propionic acid, an 
 aniino-acid not identical with alanin (or "-amino-propionic acid), but 
 having the NH2 coui)led to the fi instead of the a carbon atom (p. 56O*. 
 
 There is more water in the muscles of young than of old anim. Is 
 (v. Bibra), and more in tetanized than in rested muscle (Ranke). The 
 fats are variable in amount, and belong to a small extent to the actual 
 muscle-fibres. For even when the visible fat is separated with the 
 utmost care, nearly i per cent, of fat still remains (Steil). 
 
 The glycogen content varies extremely in different muscles and in 
 the same muscle under different nutritive and functional conditions. 
 Thus, in one and the same dog the biceps brachii- contained o'ly and 
 the quadriceps femoris 0-53 per cent. In dogs on a diet rich in carbo- 
 hydrate and protein the percentage in the whole skeletal musculature 
 ranged from 0*7 to 3*7, and in the heart from o-i to 1*2. The average 
 for human muscles has been given as 0-4 per cent. In lean horse-flesh 
 Pfliiger found 0-35 per cent, of glycogen, but no sugar. The total 
 nitrogen was 3*21 per cent, of the moist tissue. The lactic acid of 
 muscle and other tissues is the d-lactic acid, which rotates the plane of 
 polarization to the right. By the action of certain bacteria on cane- 
 sugar /-lactic acid is obtained, which is left rotatoiy. The optically 
 inactive fermentation lactic acid is obtained by the fermentation of 
 lactose. 
 
 Smooth muscle is somewhat richer in water than the striated variety 
 from the same species, because skeletal muscle is richer in fat. Glycogen 
 is either absent or present only in traces in the smooth muscle (of the 
 stomach and bladder). Lactic acid, creatin, and creatinin are also 
 found in much smaller amount than in striped muscle (Mendel and Saiki). 
 As in striated muscle, hypoxanthin is the conspicuous purin base 
 occurring in the free form — i.e., obtainable in muscle extracts. The 
 most remarkable difference in the quantitative relations of the inorganic 
 constituents is that in striated muscle potassium preponderates over 
 sodium and magnesium over calcium, whereas in the smooth variety 
 this relation is reversed. 
 
 It would be natural to expect that the proteins, which bulk so 
 largely among the solids of the dead muscle, and which are so obvi- 
 ously important in the living muscle, should be affected by contrac- 
 tion. But up to the present time no quantitative difference in the 
 proteins of resting and exhausted muscle has ever been- made out. 
 The quantity of creatin (and creatinin) is said by some authorities 
 to be increased. The following chemical changes have been defi- 
 nitely established. In an active muscle — 
 
 (a) More carbon dioxide is produced, (b) More oxygen is consumed, 
 (c) Lactic acid is formed, {d) Glycogen is used up. (c) The substances 
 soluble in water diminish in amount; those soluble in alcohol increase. 
 
 Production of Carbon Dioxide and Consumption of Oxygen during 
 Contraction. — This subject has already been dealt with in jiart in 
 connection with tissue respiration (p. 266). The fact that nmscular 
 exercise increases the carbon dioxide output and the oxygen absorp- 
 tion at the pulmonary surface, shows that oxidation processes 
 involving ultimately the combustion of carbon-containing substances 
 
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 7^9 
 
 axe associated with the activity of the muscular tissue, but does 
 not of itself prove that the final steps of the oxidation occur in the 
 nuiscles themselves. This has been demonstrated, however, by 
 observations on isolated muscles. When well supplied with 
 oxygen, these, in addition to the stock of carbon dioxide in solution, 
 in the form of carbonates and in other combinations, which they 
 possess at the moment of isolation, continue to produce carbon 
 dioxide, and this production is markedly increased by stimulation. 
 The best evidence is to the effect that only preformed carbon dioxide 
 is given off by isolated muscles in the absence of oxygen. They 
 can go on contracting indeed, as previously stated, in an atmosphere 
 of hydrogen or nitrogen, and may seem to be producing carbon 
 dioxide, but the increased output appears to be due simply to an 
 accelerated decomposition of already existing carbonates, or perhaps 
 other combinations in which carbonic acid is loosely held, brouglit 
 about by lactic acid, which in the absence of oxygen, is not trans- 
 formed as it is under normal conditions, and accumulates in the 
 muscular substance, uniting with bases, and thus displacing 
 carbonic acid. 
 
 Formation of Lactic Acid — Reaction of Muscle. — To litmus-paper 
 fresh muscle is amphicroic — that is, it turns red litmus blue and blue 
 litmus red. This is due, partly at least, to the phosphates. Mono- 
 phosphate (tribasic phosphoric acid, H3PO4, in which one hydrogen 
 atom is replaced, say, by sodium or potassium) reddens blue litmus, 
 while diphosphate (where two hydrogen atoms are replaced) turns red 
 litmus blue. Litmoid (lacmoid) differs from litmus in not being affected 
 by monophosphates. Diphosphates turn red litmoid blue, and so does 
 fresh muscle, which has no effect on blue litra.oid. A cross-section 
 of fresh muscle is about neutral (sometimes faintly acid) to turmeric 
 paper, which is turned yellow by monophosphates. A muscle which 
 has entered into rigor or has been fat\gued by prolonged stimulation is 
 distinctly acid to blue litmus and to brown turmeric, reddening the 
 former and turning the latter yellow, but does not affect blue litmoid. 
 
 Perfectly fresh resting muscle excised with avoidance of all un- 
 necessary manipulation contains very little lactic acid (as little as 
 0-02 per cent, expressed as zinc lactate). Mechanical injury, 
 heating, and chemical irritation cause a marked increase in the 
 amount. Under anaerobic conditions — in an atmosphere of 
 hydrogen, for instance — lactic acid is spontaneously developed in 
 the resting muscle so long as irritability persists, but not longer. 
 In air, which for even small excised muscles corresponds to a partial 
 asphyxia, there is a small increase in the lactic acid, but its pro- 
 duction is very slow in comparison with that in the hydrogen 
 atmosphere. In pure oxygen not only is there no accumulation 
 of lactic acid for a long time after excision, but a portion of the 
 amount originally present in the resting excised muscle disappears. 
 The same is true of the lactic acid formed in a muscle fatigued by 
 stimulation when it is afterwards placed in an atmosphere of pure 
 
 49 
 
770 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 oxv^t-'ii. There is no doubt that the pro(kiction of lactic acid in 
 functional activity and its transformation into other substances 
 are processes that go on also in the muscles of the intact body. 
 The formation of the acid in the excised nuiscle, far from being a 
 sign of death, is an index of the ' survival ' of a process by which 
 it is normally formed, as the accumulation of it is an index of the 
 crippling, in the absence of oxygen, of a mechanism by which it is 
 normally transformed. 
 
 The lactic acid which accumulates in the excised muscle in rigor 
 and activity docs not remain free, since blue litmoid paper is not 
 reddened as it would be by free lactic acid. It causes a repartition 
 of the bases at the expense of the sodium carbonate and disodium 
 phosphate, the latter being changed into monophosphate, which, 
 in part at least, accounts for the acid reaction to turmeric (Koh- 
 mann). It is of great interest that this oxidative transformation 
 of lactic acid only occurs in muscle whose structure is so far pre- 
 served that its irritability is not lost. In minced or triturated 
 muscle it does not take place. 
 
 The relations between the heat production, the formation of 
 carbon dioxide, and the production of lactic acid indicate that 
 liberation of lactic acid from some precursor is an essential stage 
 in the sudden, ' explosive ' reaction or series of reactions which 
 precedes and induces the mechanical response to stimulation. This 
 stage takes place whether oxygen be present or absent, and it seems 
 to be accompanied by a considerable liberation of energy, at the 
 expense of which alone the anaerobically contracting muscle works. 
 It is most probable that the liberation of lactic acid follows the same 
 course in the muscle abundantly supplied with oxygen, although it 
 has not been shown that oxidative processes, resulting in the forma- 
 tion of carbon dioxide, do not contribute also at this stage to the 
 energy which is transformed into the mechanical effect. But while 
 in the absence of oxygen the reaction stops at the formation of 
 lactic acid, when oxygen is available the cycle is completed by 
 restitution processes which lead to the disappearance of the lactic 
 acid either by restoration to its original position in the precursor 
 from which it is derived, or perhaps in the case of a portion of the 
 "lactic acid to its combustion to carbon dioxide and water. For 
 these restitution processes oxygen is essential, and it is to be 
 supposed that the energy required for the rebuilding of the lactic 
 acid precursor, or, to speak more generally, for the restoration of 
 the muscle to its original state in readiness for a fresh contraction, 
 is derived largely from oxidations in which carbon dioxide makes 
 its appearance. 
 
 The Precursor of Lactic Acid. — What material is the lactic acid 
 formed from ? There are reasons for thinking that lactic acid is an 
 interniediate substance which in metabolism serves as a link between 
 
CHEMICAL PHENOMENA Of MUHCULAU CONTRACTION 771 
 
 the products of protein decomposition and carbo-hydrates, and 
 between carbo-hydrates and fat. From what we know of the 
 production of lactic acid both outside the body and in the intestine 
 from carbo-hydrates, it might seem a most plausible suggestion 
 that in the active muscle it comes from glycogen. 
 
 Glycogen is the one solid constituent of muscle which has been 
 definitely proved to diminish during activity. It accumulates in 
 a resting muscle, especially in a muscle whose motor nerve has been 
 cut; but rapidly disappears from the muscles of an animal made 
 to do work while food is withheld; or from the muscles of an animal 
 poisoned by strychnine, which causes violent muscular contractions. 
 But the best evidence points the other way — e.g., in rigor mortis 
 lactic acid is produced just as in muscular contraction. Nay, 
 more, the amount of lactic acid (as much as 0-5 per cent, expressed 
 as zinc lactate) produced in full heat rigor (at 40° to 45° C.) is con- 
 stant for similar excised muscles. This * acid-maximum ' is the 
 same when fresh muscle is at once put into rigor; or when fatigue 
 is first induced, with formation of lactic acid, before rigor; or, 
 finally, when the lactic acid of the fatigued muscle is caused to 
 disappear under the influence of oxygen, and heat rigor is then 
 brought about in the muscle (Fletcher and Hopkins). Yet in rigor 
 mortis the quantity of glycogen is unaltered (Boehm). Further, 
 under certain conditions an excised muscle is capable of producing 
 a quantity of lactic acid much greater than could be derived from 
 the glycogen contained in it. 
 
 An indirect argument against the view that the lactic acid pre- 
 cursor is glycogen has been based by Hill on the results of his studies 
 on the heat production of surviving muscle. From the amount 
 of heat evolved, he calculates that the precursor of lactic acid 
 must have a heat value 10 per cent, greater than that of lactic acid. 
 Now, the heat of combustion of dextrose is only about 3 per cent, 
 more than that of lactic acid. He concludes that the precursor 
 which yields lactic acid is a body of greater energy than dextrose. 
 This, of course, does not preclude the possibility that the complex, 
 whatever it is, from which lactic acid is liberated, contains a carbo- 
 hydrate group. But it would not be profitable to pursue these 
 speculations at present. The facts just mentioned suggest that it 
 is the same precursor which yields the lactic acid developed with 
 the onset of rigor. Further evidence of the close relations between 
 the chemical changes occurring in contraction and those occurring 
 in rigor will be developed in considering the latter phenomenon. 
 
 The Substances metabolized in Muscular Contraction. — If the 
 liberation of lactic acid were assumed to be the immediate cause of 
 the mechanical changes in muscular contraction, if the nature of 
 the body which yields lactic acid were known, and if it were proved, 
 which is far from being the case, that the whole of the energy con- 
 
772 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 cerned in initiating and carrying out the mechanical effect is derived 
 from the decomposition of this precursor, the question would still 
 confront us, What are the materials at the expense of the energy 
 of which the muscle is restored to its original condition ready for 
 another contraction ? If the lactic acid is used over and over 
 again, it is indeed the metabolism of these substances which will 
 be chiefly represented in the waste products given off by the muscle ; 
 the lactic acid complex will merely represent a chemical machine 
 through which the energy of these other substances is transformed 
 into mechanical energy, and they will constitute the ultimate source 
 of energy of the muscular contraction. In this sense the muscular 
 glycogen, whether it yields lactic acid or not, is almost certainly 
 one source of energy for the active muscle, being converted into 
 dextrose, of course, before utilization. Dextrins and maltose, the 
 intermediate products of this decomposition, have been detected 
 in muscle, more maltose, indeed, than dextrose being present 
 (Osborne), since the dextrose is rapidly oxidized. Glycogen cannot 
 be the only source of muscular energy, for its amount is too small. 
 
 For example, the heart of an average man, which weighs 280 grammes, 
 contains about 60 grammes of solids, and among these certainly not 
 more than i gramme of glycogen. In twenty-four hours it produces 
 120 calories of heat (pp. 138, 688), equivalent to the complete com- 
 bustion of a little less than 30 grammes of glycogen. To supply this 
 amount, the whole store of glycogen in the heart would ha\'e to be used 
 and replaced every fifty minutes. But the accumulation of glycogen 
 is immensely slower in the muscles of a rabbit made glycogen-free by 
 strychnine, and therefore we have to look around for some other source 
 of energy to supplement the glycogen. We have already brought 
 forward evidence (p, 610) that, under ordinary circumstances, not a 
 great deal, at any rate, of the energy of muscular contraction comes 
 from the proteins. Of carbo-hydrates, the only one except the glycogen 
 of the heart muscle which is at all adecjuate to the task of supplying so 
 much energy is the dextrose of the blood. The quantity of blood 
 passing through the coronary circulation has been estimated at 30 c.c. 
 per TOO grammes of cardiac muscle per minute (Bohr and Henriques), 
 which would be equivalent for an average man to about 120 litres in 
 twenty-four hours. This quantity of blood will contain at least 
 120 grammes of dextrose, and about 32 grammes will suffice to supply 
 all the heat produced by the heart. There is no reason to suppose that 
 this dextrose must first be changed into muscular glycogen, which only 
 represents a certain amount of reserve carbo-hydrate. Of proteins a 
 little less than 30 grammes would be needed, of fat a little more than 
 12 grammes. We see, therefore, how intense must be the metabohsm 
 that goes on in an actively contracting muscle. On any probable 
 assumption as to the source of muscular energy, a quantity of material 
 equal to half of its solids must be used up by the heart in twenty-four 
 hours. Or, to put it in another way, the heart requires not less than 
 two-fifths of its weight of ordinary solid food in a day. The body as a 
 whole requires ^ to -^ of its weight. 
 
 The general conclusions to which physiologists have been led 
 as to the relative importance of the different food substances for 
 
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 773 
 
 muscular work have been previously given (p. 612), and need not 
 be repeated here. It may be added that the various food substances 
 yield muscular energy in isodynamic relation. In other words, a 
 given amount of muscular work requires the expenditure of approxi- 
 mately the same quantity of chemical energy, whether it comes 
 almost entirely from protein, or chiefly from carbo-hydrates, or 
 chiefly from fat. Some observers have stated that the taking of 
 even a comparatively small quantity of sugar vastly increases the 
 capacity for muscular work as measured by the ergograph (p. 750). 
 But although it is not to be doubted that sugar is under normal 
 circumstances one of the most important substances used up in 
 muscular contraction, the claim that sugar is, par excellence, the 
 food for muscular exertion has not yet been made out. 
 
 Physico- Chemical Conditions of Muscular Contraction. — For excised 
 fresh muscle A (p. 427) has been estimated at o-68° C. But this is 
 probably higher than in the living body, for after excision waste products, 
 with their relatively smaJ and numerous molecules, are still for a time 
 produced, and are no longer removed by the blood. In salt solutions 
 isotonic with the muscle substance — e.g., for the frog's gastrocnemius 
 at room-temperature a 0*75 per cent, solution of sodium chloride — the 
 resting muscle neither gains nor loses water for some hours. The active 
 muscle behaves quite differently. When a muscle immersed in isotonic 
 salt solution is tetanized, water enters it, leading to an increase in 
 weight and a diminution in specifig gravity (Ranke, Loeb, Barlow). 
 The same occurs even when blood is circulated through active muscles, 
 the blood becoming poorer in water (Ranke). This may be explained 
 by the increase of osmotic pressure in the muscle substance which must 
 accompany the decomposition of large molecules into small. As fatigue 
 progresses, a movement of water in the reverse direction occurs, and 
 the muscle rapidly loses water. Exposure of the fatigued muscle for a 
 sufficient time to an atmosphere of oxygen restores the osmotic proper- 
 ties of the resting muscle. Striking differences have also been demon- 
 strated in the behaviour of resting and fatigued muscle to hypotonic 
 solutions or water. Hales observed long ago that, on injecting large 
 quantities of water into the bloodvessels of a dog, so as to replace the 
 blood, marked swelling of the muscles occurred. This physiological fact 
 is well known to the pork-butchers in China, who have given it a 
 practical, if not a very praiseworthy, application in sophisticating their 
 product by increasing its weight (MacGowan). 
 
 So long as the muscular fibres are uninjured they are permeable or 
 impermeable for exactly the same compounds as other animal and 
 vegetable cells. All substances easily soluble in media like ether or 
 oli\e oil readily penetrate them (Overton). To most salts they are 
 relatively impermeable, as is shown by the fibres retaining their original 
 v^olume in isotonic solutions of them. In particular, they cannot easily 
 take up or retain the .salts of the blood-plasma, otherwise the observed 
 qualitative differences — e.g., the preponderance of potassium in the 
 muscle and sodium in the plasma — could not be maintained. There are 
 facts which indicate that temporary changes in the permeability to ions, 
 not only of muscular fibres, but also of nerve fibres and other excitable 
 structures, are concerned in their stimulation. Potassium salts after a 
 time seem to produce an effect upon frog's muscle, which alters its 
 permeability so that it takes up water from hypertonic solutions. 
 
774 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Calcium salts have the opposite effect (Loeb). Sodium (and in a minor 
 degree lithium) salts have a peculiar relation to the contraction of 
 skeletal muscle, for which they appear to be indispensable. Yet sodium 
 cliloride produces a paralyzing action on the frog's motor nerve-endings, 
 so that after perfusion with a solution of that salt stimulation of the 
 motor nerve causes no contraction, or with a slighter degree of jiaralysis 
 contraction only after a long interval. The eilect can be counteracted 
 by solutions containing calcium salts (Locke, Gushing). 
 
 Rigor Mortis. — When a muscle is dying, its excitability, after 
 perhaps a temporary rise at the beginning, diminishes more and 
 more until it ultimately responds to no stimulus, however strong. 
 The loss of excitability is not in itself a sure mark of death, for, 
 as we have seen, an inexcitable muscle may be partially or com- 
 pletely restored; but it is followed, or, where the death of the muscle 
 takes place very rapidly, perhaps accompanied, by a more decisive 
 event, the appearance of rigor. The muscle, which was before soft 
 and at the same time elastic to the touch, becomes firm; but its 
 elasticity is gone. The fibres are no longer translucent, but opaque 
 and turbid. If shortening of the muscle has not been opposed, it 
 may be somewhat contracted, although the absolute force of this 
 contraction is small compared with that of a living muscle, and a 
 slight resistance is enough to prevent it. The reaction is now 
 distinctly acid to litmus. This is rigor mortis, the death-stiffening 
 of muscle. 
 
 An insight into the real meaning of this singular and sometimes 
 sudden change was first given by the experiments of Kiihne. He 
 took living frog's muscle, freed from blood, froze it, and minced it 
 in the frozen state. The pieces were then rubbed up in a mortar 
 with snow containing i per cent, of common salt, and a thick neutral 
 or alkaline liquid, the ' muscle- plasma,' was obtained by filtration. 
 This clotted into a jelly when the temperature was allowed to rise, 
 but at 0° C. remained fluid. The clotting was accompanied by a 
 change of reaction, the liquid becoming acid. An equally good, 
 or better, method is to use pressure for the extraction of the plasma 
 from the frozen fragments of muscle. A low temperature is essential, 
 otherwise the plasma will coagulate rapidly within the injured 
 muscle. A similar plasma can be expressed from the skeletal 
 muscles of warm-blooded animals (Halliburton), and with greater 
 difficulty from the heart. 
 
 When the muscle, after exhaustion with water, is covered with a 
 solution of a neutral salt, a 5 per cent, solution of magnesium sulphate 
 or 10 per cent, solution of ammonium chloride being the best, certain 
 proteins are extracted which clot or are precipitated much in the same 
 way as the muscle-plasma obtained by cold and pressure; and the 
 process is hastened by keeping them at a temperature of 40° C. 
 
 In the extracts of mammalian muscle three chief proteins are present: 
 paramyosinogen (v. Fiirth's myosin), coagulating by heat at 47° to 
 50° C; myosinogen (v. Fiirth's myogen), coagulating at 55° to 60° C, 
 usually about 56°); and serum-albumin, coagulating about 73°. The 
 
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 775 
 
 serum-albumin belongs to the blood and lymph, and is not a constituent 
 of the muscle-fibre. The most recent work on the subject is that of 
 Botazzi, who obtained muscle juice without the addition of water or 
 salt solutions, by rubbing muscles up with sand, ;ind then subjecting the 
 triturated material to a pressure of many atmospheres. >le iinds that, 
 leaving out of account the serum-albumin, muscle juice contains only 
 one protein in solution, and this corresponds upon the whole in its 
 properties to myosinogen. A second protein, and only these two have 
 been proved to exist in muscle juice, is not in solution, but in tiie form 
 of very line granules re\'caled by the ultramicroscope. This corresponds 
 in a general way to paramyosinogen. Botazzi supposes tliat it repre- 
 sents the substance of the muscular fibrils. The granules show a ten- 
 dency even at the ordinary temperature to agglutinate and to be pre- 
 cipitated. The process is hastened by dilution with water, removal of 
 the salts by dialysis, addition of acids, and the agglutination and pre- 
 cipitation are accomplished very rapidly at 45° to 55° C, giving rise 
 to ' heat coagulation.' The protein in solution (myosinogen) is in- 
 soluble in distilled water when thoroughly freed from salts, and is pre- 
 cipitated by dialysis, but not so easily as paramyosinogen. The total 
 proteins in the juice obtained by pressure varied from 5*3 to 9*5 per 
 cent., a great deal of the muscle protein being, of course, left in the 
 residue. The granules (paramyosinogen) constituted from a third to 
 two-thirds of the protein in dilferent experiments, and the true pro- 
 portion must have been considerably higher, since on account of their 
 small size the loss in separating them by filtration was great. The 
 ' myosin ' precipitate, which rapidly forms in muscle-plasma at body 
 temperature, is sometimes called the muscle-clot, and the liquid which 
 is left the muscle-serum, but it would probably be better to avoid these 
 terms, as they sugge.st an analogy with the coagulation of blood-plasma, 
 which is apt to be misleading. A similar precipitate or clot seems to 
 be formed in the interior of the muscular fibres in natural rigor and in 
 the rapid rigor produced by heating a muscle to a little above the body- 
 temperature. But in natural rigor the whole of the paramyosinogen 
 and myosinogen do not undergo the change, since a certain amount of 
 these substances can asa rule be extracted from dead muscle by saline 
 solutions. Thus, in rabbit's muscles, before the onset of rigor mortis, 
 87'3 per cent, of the total protein was found to be soluble in 10 per cent, 
 ammonium choride solution, and only 12-7 per cent, coagulated; while 
 after rigor had occurred, 71 -5 per cent, was coagulated, and only 28-5 per 
 cent, remained soluble (Saxl). It is not known whether in the living 
 muscle paramyosinogen and myosinogen exist as such. It has, indeed, 
 been stated that, if a tracing is taken from a muscle which is gradually 
 heated, it first shortens at the temperature of coagulation of para- 
 myosinogen, and then again at that of myosinogen, and that in frog's 
 muscle there is an additional shortening at 40°, the temperature at 
 which in extracts an additional heat precipitate occurs. The conclusion 
 has been drawn that these substances must be present as such in the 
 living fibres, and that the successive shortenings are mechanical phe- 
 nomena due to their heat coagulation. Similar shortenings have been 
 described in nerve and liver tissue at about the temperatures at which 
 the proteins in extracts of these tissues are coagulated by heat. But 
 Meigs has shown that the supposed correspondence is far from being 
 exact, and that muscles whose proteins have been already coagulated in 
 a mixture of alcohol and salt solution still show the typical shortening 
 on being heated. The heat shortening is, therefore, dependent on 
 some other process than aggregation of the particles of coagulable 
 protein. 
 
776 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 Certain analogies between rigor and muscular contraction were 
 early pointed out. In both there is (i) shortening; (2) heat-pro- 
 duction; (3) formation of lactic acid; (4) discharge of carbon 
 dioxide; (5) electrical changes. As regards the production of lactic 
 acid, there is reason to believe that the process is fundamentally 
 the same as in contraction, and the study of rigor, especially of 
 certain of the artilicially induced forms — e.g., heat rigor — in relation 
 to the liberation of lactic acid, carbon dioxide, and heat, has thrown 
 light upon the changes normally occurring in muscle. Another 
 analogy might be forced into the list by anyone who was deter- 
 mined to see only rigor in contraction: the rigor passes off as the 
 contraction passes off, although the ' resolution ' of a rigid muscle 
 takes days, the relaxation of an active muscle a fraction of a second. 
 The disappearance of rigor is not dependent on putrefaction; it 
 takes place when growth of bacteria is prevented (Hermann). 
 Possibly it is connected with autolytic processes due to intracellular 
 ferments (p. 599). 
 
 Why does coagulation of m\'osin occvir at the death of the muscle ? 
 To this question no clear answer can be given. Some have looked 
 on the process as analogous to the clotting of blood when it is shed, 
 and it has even been suggested that just as a fibrin ferment is 
 developed when the leucocytes and blood-plates begin to die, a 
 myosin ferment, which aids coagulation, is developed in dead or 
 dying muscle. But no proof has been given of the existence of such 
 a ferment. And it is easy to make too much of the apparent 
 analogy between the clotting of muscle and the clotting of blood, 
 for there are differences as well as resemblances. For instance, the 
 addition of potassium oxalate does not prevent coagulation of 
 muscle extracts, as it does of blood and blood-plasma. If the 
 development of lactic acid in the muscle is not the primary cause 
 of the coagulation which constitutes the essential feature of rigor 
 mortis, it seems to be closely related to it. For when excised 
 muscles are abundantly supplied with oxygen, no lactic acid 
 accumulates in them, and the final loss of excitability of the muscle 
 is not followed by rigor. In any case, direct precipitation of 
 hitherto unclotted muscle proteins may be induced by the acid, or 
 the acid salts formed in its presence. Deficiency of oxygen is 
 associated with the occurrence of rigor mortis, as it is with the 
 accumulation of lactic acid, and a developing rigor can be abolished 
 by oxygen, and its onset long or indefinitely delayed. When strict 
 aseptic technique is observed an excised sartorius muscle of the 
 frog may remain irritable in sterile Ringer's solution, even without 
 oxygenation, for as long as three weeks (Mines). 
 
 Various influences affect the onset of rigor. Fatigue hastens 
 it; heat has a similar effect; the contact of caffeine, chloroform, 
 and other drugs causes most pronounced and immediate rigor. 
 
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 777 
 
 Blood applied lo the cross-section of a muscle first stimulates the 
 fibres with which it is in contact, and then renders them rigid. 
 But it is to be remembered that normally the blood does not come 
 into direct contact even with the sarcolemma, much less with its 
 consents. 
 
 The effect of heat is of special interest. A skeletal muscle of 
 a frog, like the gastrocnemius, if dipped into physiological saline 
 solution at 40° or 41° C. goes into rigor at once; the frog's heart 
 requires a temperature 3° or 4° higher; the distended bulbus aortae 
 can withstand even a temperature of 48° for a short time. An 
 excised mammalian muscle passes into immediate rigor at 45° to 
 50°. In heat rigor the reaction of the muscle becomes strongly 
 acid owing to the formation of lactic acid, and the evolution of 
 carbon dioxide is also increased. 
 
 The total discharge of carbon dioxide in heat rigor induced at 40° 
 amount.s to 35 to 40 c.c. per 100 grammes of muscle. An additional 
 15 to 20 per cent, is obtained on heating to 75° C. to completely coagu- 
 late the proteins, and a further 15 to 20 per cent, on heating to about 
 100° C. When a muscle is scalded by being suddenly immersed in 
 boiling salt solution, lactic acid is not formed, but carbon dioxide to the 
 amount of 60 to 70 per cent, is discharged. An excised muscle kept in 
 oxygen for many hours, during which it has discharged several times 
 as much caibon dioxide as is ever liberated by heating, still yields the 
 normal discharge on heating whether to 40° C. or to 100° C. On the 
 other hand, previous survival in an anaerobic atmosphere (of nitrogen) 
 reduces greatly or abolishes the yield of carbon dioxide at 40° C, 
 although not that at 100° C, the sum of the carbon dioxide given off to 
 the atmosphere of nitrogen and that given off on heating to 100° C. 
 being about equal to the total amount which would have been dis- 
 charged by a freshly-excised muscle on heating first to 40° C. and then 
 to 100° C. If acid is added to a fresh muscle at about 0° C. even more 
 carbon dioxide is liberated than in heat rigor, while the yield of lactic 
 acid is, even after many hours, very little increased above the normal 
 amount for fresh resting muscle. When the acidified muscle after the 
 discharge of the carbon dioxide is now heated to 40° C, the yield of 
 lactic acid is increased, but only traces of carbon dioxide are given off. 
 
 From these and similar observations, Fletcher concludes that the 
 carbon dioxide discharged during heat rigor at 40° C. is pre-existent 
 carbon dioxide set free from carbonates or other compounds by 
 the lactic acid known to be produced in heat rigor. The carbon 
 dioxide discharged at 75° and 100° C he regards as held by 
 muscle colloids or in combination with amino-acid groups. These 
 results tend to discredit the ' inogen ' theory (p. 270), with its 
 assumption that ' intramolecular oxygen ' is stored away in the 
 muscle, which was largely based upon erroneous observations on 
 the discharge of carbon dioxide from heated muscles. According 
 to this theory, carbon dioxide and lactic acid were supposed to arise 
 from a common precursor into which oxygen had been previously 
 introduced. 
 
778 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES 
 
 The production of heat in heat rigor is also of great interest. 
 Hill has shown that it amounts to from oO to i-o gramme calorie 
 per gramme of muscle. Of this no more than 005 calorie can be 
 due to the heat of neutralization of lactic acid by the sodium 
 bicarbonate in the muscle, with which it reacts as soon as it is 
 liberated. The rest of the heat is associated with the chemical 
 reaction by which lactic acid is formed from its precursor, a reaction 
 which, there is every reason to believe, is the same as that which 
 occurs in muscular contraction. The heat production can only 
 be due in very slight degree to the physical alteration (clotting or 
 precipitation) of the muscle proteins. 
 
 The so-called rigor caused by water, which is not a true rigor, 
 causes no increase in the carbon dioxide given off. Chloroform, 
 on the other hand, produces a marked increase in the carbon 
 dioxide production, and this is evidently related to its action in 
 hastening the onset of rigor. Rigor mortis is to some extent in- 
 fluenced by the nervous system, for section of its nerves retards 
 the onset of rigor in the muscles of a limb. Ante-mortem stimula- 
 tion of the peripheral ends of the vagi, even with currents too weak 
 to cause a perceptible effect upon the heart-beats, prolongs the 
 period of spontaneous contraction and the irritability of the ven- 
 tricles after death, and retards the onset of rigor (Joseph and 
 Meltzer). Cold rigor is obtained when frog's muscles are cooled 
 to —15° C. The muscles remain perfectly translucent. They 
 do not recover their irritability on thawing, but if cooled only to 
 — 7° C. they recover (Folin). 
 
 In a human body rigor generally appears not earlier than an 
 hour, and not later than four or five hours, after death. In ex- 
 ceptional cases, however, it may come on at once, and the annals 
 of war and crime contain instances where a man has been found 
 after death still holding with a firm grip the weapon with which 
 he had fought, or which had been thrust into his hand by his 
 murderer (so-called cataleptic rigor). It is related that after 
 one of the battles of the American Revolutionary War some of the 
 dead were found with one eye open and the other closed as in the 
 act of taking aim. A high temperatuie favours a rapid onset; a 
 body wrapped up in bed will, other things being equal, become rigid 
 sooner than a body lying stripped in a field. Muscular exhaustion, 
 as we have said, is another favouring condition: hunted animals 
 and the victims of wasting diseases go quickly into rigor. It is 
 a rule, but not an invariable one, that rigor, when it comes on 
 quickly, is short, and lasts longer when it comes on late. All the 
 muscles of the body do not stiffen at the same time; the order 
 is usually from above downwards, beginning at the jaws and neck, 
 then reaching the arms, and finally the legs. After two or three 
 days the rigor disappears in the same order. The position of the 
 
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 779 
 
 limbs in rigor is the same as at death; the m.uscles stiffen without 
 any marked contraction. This can be strikingly shown on a newly- 
 killed animal by cutting the tendons of the extensors of one foot 
 and the flexors of the other ; when natural rigor comes on, the feet 
 remain just as they were. If heat rigor, however, is caused, the 
 one foot becomes rigid in flexion and the other in extension; and 
 the contraction-force is considerable, although not so great as that 
 of an electrical tetanus in a living muscle. 
 
 The Possibility of Recovery of Muscles after Rigor. — Wlien the circu- 
 lation in the hind legs of rabbits is interrupted by compression or 
 ligation of the abdominal aorta (Stenson's experiment), the muscles lose 
 their excitability, but speedily recover, if they have not been deprived 
 of arterial blood for too long a time, when the blood is again allowed to 
 reach them. A longer interruption of the circulation leads not only 
 to total inability to respond to stimulation, but also to rigor, and most 
 observers are agreed that, as regards the skeletal muscles at least, this 
 is the irrevocable end of excitability. Brown-Sequard, indeed, stated 
 that after the full development of rigor in the rabbit's muscles (Stenson's 
 experiment), and also in the hand of an executed criminal through 
 which an artificial circulation was established, recovery ensued. But 
 probably the rigor was incomplete or did not involve all the fibres. In 
 heart muscle the conditions appear to be somewhat different, and Heubel 
 has alleged that rhythmical contractions of the frog's heart can be 
 restored by filling its cavity with blood, after rigor has been caused by 
 heat and in other ways, and we have already seen that the same is true 
 of the mammalian heart alter the onset of rigor. Excised frog's 
 muscles which have undergone rigor mortis become less stiff when 
 exposed to an atmosphere of oxygen. 
 
CHAPTER XIV 
 NERVE 
 
 The voluntary movements are originated by efferent or outgoing 
 impulses from the brain, which reach the muscles along their 
 motor nerves. The involuntary movements and the secretions 
 are in many cases able to go on in the absence of central connec- 
 tions, but are normalh' under central control. Afferent impulses 
 are continually ascending to the cord and brain from the skin, 
 joints, bones, muscles, and organs of special sense like the eye and 
 the ear. Everj^vhere the connection between the nervous centres 
 and the peripheral organs, and between different parts of the 
 central nervous system, is made by nerve-fibres. Those which 
 run outside the brain and cord are called peripheral nerve-fibres 
 to distinguish them from the intracentral fibres of the central 
 nervous system itself. 
 
 In this chapter we propose to consider certain of the general 
 properties of nerve-fibres. Most of our knowledge of these proper- 
 ties has been derived from experiments on the peripheral, and 
 particularly the peripheral motor nerves ; but there is every reason 
 to believe that the main results are true of all nerve-fibres, afferent 
 and efferent, peripheral and central. 
 
 What we call nerve-fibres were known and named, and many im- 
 portant facts in their physiology discovered, long before their true 
 morphological significance was recognized. The researches of recent 
 years have shown that every nerve-fibre is, as regards its essential con- 
 stituent the axis-cylinder, a process of a nerve-cell. The nerve-cells, 
 each of which, including all its processes, may be conveniently termed 
 a neuron, are the essential elements of the nervous system. The cell- 
 bodies of most of the neurons are situated in, or in close relation to, the 
 spinal cord and the brain, and therefore the detailed description of 
 them will be reserved till we come to treat of the central nervous system 
 (see p. 850 and Figs. 328 to 340). It is enough to say here that in 
 general a nerve-cell gives off two kinds of processes: (i) one or more 
 dendrites or protoplasmic processes, which repeatedly bifurcate like the 
 branches of a tree into thinner and thinner twigs, and extend only for 
 a relatively short distance from the cell-body; {2) an axis-cylinder 
 process or axon, which as a rule runs for a considerable distance without 
 altering its calibre, and either gives off no branches (as in the peripheral 
 nerves) or only a comparatively small number of lateral twigs (col« 
 
 780 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 781 
 
 laterals). Ultimately the axis-cylinder process and its collaterals, if it 
 has any, end by breaking up into a brush, a plexus or a feltwork or 
 baskctwork of hbrils. The axons of different nerve-cells vary greatly 
 in length. Some terminate within the grey matter of the brain or spinal 
 cord not far from their origin; others run in the white tracts of the 
 central nervous system or in the peripheral nerves for half the height 
 of a man. All except the shortest axis-cylinder processes become 
 clothed at a little distance from the cell-body with a protective covering, 
 which continues to invest them (and their collaterals) throughout the 
 rest of their course, disappearing only when they begin to break up at 
 their terminations. An axis-cylinder process (spoken of simply as the 
 axis-cylinder, when considered apart from the nerve-cell) constitutes, 
 with its covering, a nerve-fibre. 
 
 The axis-cylinder is the essential conducting part of the fibre, for it is 
 present in every nerve-fibre, running from end to end of it without break, 
 and towards the periphery it is alone present. It is made up of fine 
 longitudinal fibrils embedded in interstitial substance (Fig. 329, p. 851). 
 Such a fibrillar structure is best shown after treatment of the nerve- 
 fibres with certain reagents, although it is certain that it exists pre- 
 formed in the living fibres. 
 
 Section I. — The Nerve-Impulse or Propagated Disturbance: 
 ITS Initiation and Conduction. 
 
 So far as we know, the only function of nerve-fibres is to conduct 
 impulses from nerve-centres to peripheral organs, or from peripheral 
 organs to nerve-centres, or from one nerve-centre to another. 
 In the normal body these impulses never, or only very rarely, 
 originate in the course of the nerve-fibres; they are set up either 
 at their peripheral or at their central endings. By artificial stimu- 
 lation, however, a nerve-impulse may be started at any part of a 
 fibre, just as a telegram may be dispatched by tapping any part of 
 a telegraph wire, although it is usually sent from one fixed station 
 to another. 
 
 Nature of the Nerve- Impulse. — What the nerve-impulse actually 
 consists in we do not know. All we know is that a change or dis 
 turbance of some kind, of which the most evident token is an 
 electrical change, passes over the nerve with a measurable velocity, 
 and gives tidings of itself, if it is travelling along efferent fibres — 
 that is, out from the central nervous system — by the contraction 
 or inhibition of muscle or by secretion; if it is travelling along 
 afferent fibres — that is, up to the central nervous system — by sensa- 
 tion, or by reflex muscular or glandular effects. 
 
 Whether the wave which passes along the nerve is a wave of 
 chemical change (such, to take a very crude example, as runs 
 along a train of gunpowder when it is fired at one end), or a wave 
 of mechanical change, a peculiar and most delicate molecular 
 shiver, if we may so phrase it, or a shear in a definite direction along 
 the colloidal substance of the axis-cyhnder (Sutherland), there is 
 no absolutely definite experimental evidence to decide. An 
 
782 NERVE 
 
 electrical change accompanies the nervc-inipulse travelling at the 
 same rate, and although this is to be distinguished from the impulse 
 itself, there is little doubt that the latter is essentially connected 
 with a disturbance of the electrical equilibrium of the nerve- 
 substance. 
 
 An attempt has been made to settle the question by determining the 
 temperature coeflicient of the velocity of conduction of the impulse — 
 i.e., the quantity which measures the change of velocity for a given 
 change of temperature. For most physical processes the quotient 
 velocity at T«+ 1 o° , ™ . . , ^ ■ i. j. 
 
 — r rj^ — Yt . where T« is any given temperature, is not greater 
 
 than i'2, while for frog's sciatic nerve the temperature coefficient for 
 the most part lies between 2 and 3 (Snyder). The mean value of a 
 large number of observations is i'79, with T«= 8° to 9° C. (Lucas). For 
 the pedal nerve of the giant slug the mean value of the temperature 
 coefficient is 1-78 (Maxwell). In other words, while for the majority of 
 physical processes an increase of 10° C. increases the velocity of the 
 process by at most one-fifth, the same increase of temperature increases 
 the velocity of conduction of the nerve-impulse by four-fifths, or even 
 more. While it is true that it may not be entirely safe to apply such a 
 criterion to a biological process which need not be either entirely chemical 
 or entirely physical, and very likely is a complex one, the suggestion, 
 so far as it goes, is undoubtedly in favour of the chemical hypothesis. 
 That chemical changes go on in living nerve we need not hesitate to 
 assume; and, indeed, if the circulation through a limb of a warm- 
 blooded animal be stopped for a short time, the nerves lose their 
 excitability. Even the nerves of cold-blooded animals gradually 
 become inexcitable and incapable of conduction when placed in an 
 oxygen-free medium, as the oxygen already contained in the tissue is 
 exhausted. The excitability and conductivity of the nerve are restored 
 by oxygen. It is clear, then, that even a resting nerve requires oxygen, 
 and it can be shown that the loss of function is acceleiated by stimulation 
 in the absence of oxygen. But the metabolism is very slight compared 
 with that in muscle or gland. Until recently even in active nerve no 
 measurable production of carbon dioxide had ever been observed, nor, 
 in fact, had any chemical difference between the excited and the resting 
 state ever been unequivocally made out. However, it has been 
 announced that by the aid of an extremely delicate method of estimating 
 small quantities of carbon dioxide, a measurable production of carbon 
 dioxide can be detected even in resting frogs' nerves, and that this pro- 
 duction is increased two to three times on stimulation (Tashiro). This 
 result is somewhat puzzling in view of the fact that neither in cold- 
 blooded nor in mammalian nerves is there any sensible rise of temper- 
 ture during stimulation. With the apparatus shown in Fig. 272 (an 
 electrical resistance thermometer or bolometer whose use depends upon 
 the fact that the electrical resistance of a metallic conductor varies 
 with its temperature) an increase even of 0-0003° C. in the temperature 
 of the sciatic nerves of dogs could not be detected during tetanization. 
 Rolleston failed to find evidence of a rise of even 0-0002° C. in frog's 
 nerves during stimulation. And according to the latest investigation 
 with a more suitable and much more sensitive thermo-electric arrange- 
 ment, the passage of a single nerve impulse along a frog's nerve cannot 
 be associated witli an increase of temperature in the nerve of even the 
 hundredth million of a degree (A. V. Hill). The difficulty of inducing 
 fatigue in nerves under ordinary conditions has been considered a strong 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 
 
 783 
 
 support of the physical nature of the conduction process. Neverthe- 
 less, it is possible to show by special methods that nerve can be tempor- 
 arily fatigued, although it recovers very rapidly. When a mcduUated 
 nerve is stimulated, a brief period ensues during which it refuses to 
 resp)ond to a second stimulus. This refractory period is normally very 
 short — not more than 0-002 second for the frog's sciatic. But it can 
 be greatly piolongcd by cold, asphy.xia, or anaesthesia, especially by 
 the alkaloid yohimbine (Tait and Gunn), and when tiie refractory period 
 is thus prolonged, fatigue phenomena are readily induced by stimulation. 
 And while the nerves of warm-blooded animals at body temperature 
 and those of cold-blooded animals at about 32° C. can hardly be shown 
 to undergo fatigue when tetanized in atmospheric air, fatigue phe- 
 nomena are easily elicited wlien the temperature is lowered even 
 although air is supplied (Thorner). 
 
 Stimulation of Nerve. — With some differences, the same stimuli 
 are eftcctivo for nerve as for muscle (p. 737) ; but chemical stimula- 
 tion is not in general so easily obtained. The so-called thermal 
 
 Fig. 272. — Electrical - Resistance 
 Thermometer (Natural Size) as 
 used for investigating heat-pro^ 
 duction in mammalian nerves in 
 situ. A, a piece of hard rubber in 
 the hook-shaped part of which the 
 fine platinum wire P is fixed, and 
 covered with insulating varnish; 
 c, c, thick copper wires connected 
 with P, fastened in grooves, and 
 covered with paraffin. Above they 
 end in contact with the small 
 binding posts, Bj, B,. B is a hard 
 rubber sliding piece, with a slot s. 
 When B is in position the screw, a, 
 projects througli the slot. By a nut 
 on this screw B is fixed on A when 
 the nerve has been arranged in the 
 groove. 
 
 B B 
 
 B 
 
 ikak 
 
 stimulation is not a real stimulation due to the sudden change of 
 temperature. The irregular contractions of the muscle caused by 
 the local application of heat to the nerve are dependent on desicca- 
 tion of the nerve. 
 
 Chemical Stimulation. — When hyper- or hypotonic solutions arc em- 
 ployed, the withdrawal or entrance of water may be an important factor. 
 
 For salts which penetrate the fibres with equal difficulty this factor 
 can be eliminated by applying them as isotonic solutions. There is 
 evidence that chemical stimulation proper, as distinguished from the 
 stimulation produced by changes in the water content of the fibres by 
 osmosis, is connected with the electrical charges on the dissociated ions 
 of the salts (p. 428). Electrical stimulation, indeed, may only be a 
 variety of chemical stimulation (Loeb. Mathews, etc.). 
 
 Mechanical Stimulation may be applied to a nerve by allowing a small 
 weight to fall on it from a definite height or by permitting mercury to ,i rop 
 upon it from a vessel with a fine outflow tube. A regular tetanus may 
 thus be obtained. Tigerstedt found that the smallest amount of .vork 
 spent on a frog's nerve which would suffice to excite it was a little less 
 
784 KERVE 
 
 than a gramme-millimetre — that is, the work done by a gramme falling 
 through a distance of a millimetre, or (taking an erg as equivalent to 
 ii/ro gramme-centimetre) about 100 ergs. No doubt a great part of 
 this is wasted, as a much smaller quantity of work done by a beam of 
 light on the retina or by an electrical current on an isolated nerve, both 
 of which may be supposed to act more directly on the excitable con- 
 stituents, suffices to cause stimulation. Thus, the work done by the 
 minimal, natural or specific, stimulus for the retina in the form of green 
 
 hght may be as little as — g erg (S. P. Langley), or only one-ten-thousand- 
 
 millioneth part of the minimum work necessary for mechanical stimula- 
 tion. Again, with electrical stimulation (closure of a voltaic cuirent, 
 or condenser discharges) it has been shown that an amount of work 
 
 equal to —^ erg may be enough to cause excitation of a frog's nerve. 
 
 This is ten thousand times as great as the minimal luminous stimulus, 
 but a million times less than the minimal mechanical stimulus. 
 
 The laws of electrical stimulation for nerve are essentially the same 
 as those we have already discussed for muscle (p. 741). The voltaic 
 current stimulates a nerve, as it does a muscle, at closure and opening. 
 During the flow of the current, so long as its intensity- remains constant, 
 there is as a rule no excitation, or at least none which is propagated 
 along the nerve, so that the muscles supplied by it remain uncontracted. 
 But under certain conditions — for example, when the nerve is more 
 excitable than usual (as is the case with nerves taken from frogs which 
 have been long kept in the cold) — a closing tetanus may be seen while 
 the current continues to pass through the nerve, and an opening tetanus 
 after it has ceased to flow^ just as when the current is led directly 
 through the muscle. Sensory- nerve-fibres, too, are stimulated by a 
 voltaic current during the whole time of flow. Induction shocks are 
 relatively more powerful stimuli for nerve than the make or break of a 
 voltaic current. The opposite, as we have seen, is true of muscle; and, 
 upon the whole, we may say that muscle is more sluggish in its response 
 to stimuli, and is excited less easily- by very brief currents, than nerve 
 is. An apparent illustration of this difference is the fact that the 
 nervous excitation has no measurable latent period, while muscular 
 excitation has. But it is quite possible that, if the conditions of experi- 
 ment were as favourable in nerve as in muscle, a sensible latent period 
 might be found here too. 
 
 In nerve as in muscle, strength of stimulus and intensity of response 
 correspond within a fairh- wide range, when we take the height of the 
 muscular contraction or the amount of the negative variation (p. S24) 
 as the measure of the nervous excitation. Summation of stimuli, super- 
 position of contractions, and complete tetanus, are caused by stimulating 
 the muscle through its nerve, just as by stimulating the muscle itself 
 (P- 736). 
 
 Excitability of Nerve.^ — It has usually been stated that the ex- 
 citability of frog's nerve, as measured by the muscular response to 
 stimulation, is increased by rise of temperature, and diminished by 
 fall of temperature. It has, however, been shown that this increase 
 of excitabilit}- is only apparent, and due to the strengthening of 
 the current by diminution of the resistance, since the resistance 
 of all animal tissues, like that of electrolytic conductors in general, 
 diminishes as the temperature rises (Golch). When precautions 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 785 
 
 are taken to keep the current intensity the same at the various 
 temperatures compared, it is found that coohng of a (frog's) nerve, 
 even to 5° C, increases the excitabihty for currents of long duration 
 (several hundredths of a second). It has, indeed, been shown both 
 for muscle and for nerve that the cooler tissue requires a smaller 
 current strength for its excitation when the current is of long dura- 
 tion. With brief currents this effect is masked, either partially or 
 completely, by the greater increase of current strength needed in the 
 case of the cooler tissue to compensate fora given decrease in duration 
 (p. 789) (Lucas and Mines). This is the reason that for induction 
 shocks or voltaic currents of short duration, the excitabihty of the 
 nerve seems to be increased by a rise of temperature (up to about 
 30° C. in the case of frog's nerve), and diminished by cooling. 
 
 Drjnng of a nerve at first increases its excitability; and the same 
 is true of separation of a nerve from its centre. In the latter case 
 the increase of irritability begins at the proximal end of the nerve, 
 and travels towards the periphery. As time goes on, the excita- 
 bility diminishes, and ultimately disappears in the same order 
 (Ritter-Valli Law). At a certain stage it may be found that a 
 given stimulus causes a smaller and smaller contraction the farther 
 down the nerve — that is, the nearer to the muscle — it is applied. 
 On this was based the now abandoned ' avalanche theory,' according 
 to which the impulse continually unlocked new energy as it passed 
 along the nerve, and so gathered strength in its course like an 
 avalanche. It is now known that no material change takes place 
 in the intensity of the excitation while it is being propagated along 
 a normal uninjured nerve. For instance, experiments on the 
 phrenic nerve, in its natural position, and with all its connections 
 intact, have shown that with a given strength of stimulus the 
 amount of contraction of the diaphragm is the same whether the 
 nerve be excited in the upper, middle, or lower portion of its course. 
 In the above experiment on the isolated, and therefore injured, 
 nerve, the contraction varies in height with the distance of the 
 point of stimulation from the muscle, not because the excitation 
 grows as it travels, but because it is already greater at the moment 
 when it sets out from a point near the central end of the nerve 
 than at the moment when it sets out from a point near the muscle. 
 
 Electrotonus. — Although the constant current does not, unless 
 it is very strong or the nerve very irritable, cause stimulation during 
 its passage, it modifies profoundly the excitabihty and conductivity 
 of the nerve. In the neighbourhood of the kathode the excitabihty 
 is increased (condition of kat electrotonus), while around the anode 
 it is diminished (anelectrotonus). Immediately after the opening 
 of the current these relations are for a brief time reversed, the 
 excitability of the post-kathodic area (area which was at the kathode 
 during the flow) being diminished, and that of the post-anodic 
 
 50 
 
786 
 
 NERVE 
 
 increased. In the intrapolar area there is one point the excita- 
 blHty of whicli is not altered. This inchfferent point, as it is called, 
 shifts its position when the intensity of the current is varied, moving 
 towards the katliodc when the current is increased, towards the 
 anode when it is diniinislied. 
 
 It is only under certain definite condition.s tliat these phenomena, first 
 described by Pfliigcr, appear in their purity and uncomplicated by other 
 changes. The nerve should be quite fresh, the current a weak or at 
 most a modciatcly strong one, and the stretch of nerve employed 
 should be as far as possible from the cross section, and from the cross 
 sections of branches. The middle region of the frog's sciatic nerve is 
 the best. Wlien all these conditions are fulfilled, the whole stretch 
 of nerve in katelcctrotonus — i.e., the part on both sides of the kathode 
 and at the kathode itself shows an increased stimulation clfect, the 
 more pronounced the nearer to the kathode the point of stimulation. 
 This condition, however, only lasts an instant. Then the excitability 
 begins to sink sharply fir^t at the kathode, then on both sides of it, till 
 
 it ultimately becomes decidedly less than 
 the initial excitability- This secondary 
 depression of excitability, always most 
 marked at the very kathode, is just as con- 
 
 Fig. 273.— Katelcctrotonus. Weak 
 tetanus of muscle (the right-hand 
 elevation), greatly intensified in 
 katelcctrotonus of the motor nerve 
 (the left-hand elevation). 
 
 Fig. 274.— .Xnclectrotonus. Strong 
 tetanus of muscle (left-hand t le- 
 vatinii), lessened in strength by 
 aiielectrotonic condition of the mo- 
 tor nerve (right-hand elevation). 
 
 stant a phenomenon as the preliminary increase. The stronger the cur- 
 rent the more profound is the depression, the more (pjickly it is de- 
 veloped, and the greater is the distance to which it spreads along the 
 nerve. With a certain strength of current the depression ajipears so 
 rapidly that the preliminary increase of excitability ma}' be completely 
 missed. When the current is opened the excitability cjuickly increases 
 again, but with strong currents it may remain depressed for a while. At 
 the anode changes in the reverse direction may be observed, although 
 they are less pronounced than at the kathode. Thus at the anode 
 during the passage of the current the initial depression of the excitability 
 tends to give place to an increase (Werigo). 
 
 These statements have been made on the strength of experiments in 
 which the height of the muscular contraction was taken as the index of 
 the excitability of the nerve at any given point. It is difficult, however, 
 to disentangle the effects of alterations in the excitability from the 
 effects of alterations of conductivity — i.e.. of the power of a portion of 
 the nerve to conduct an impulse set up elsewhere. Whether these two 
 properties arc distinct or not is a question which will be considered a 
 little later on. But it is perfectly clear that in deducing conclusions 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 787 
 
 as to the effect produced on a nerve by excitation at a given point from 
 tlie resultant effect on tlie muscle to which the nerve is attached (or 
 on a galvanometer or electrometer if we arc following the effect by 
 means of the electrical changes), we must know whether the change 
 set up in the nerve at the 
 
 f)oint of excitation can pass 
 reely along the nerve to the 
 muscle or to the point at 
 which it is led ofE to the 
 galvanometer. Now, changes 
 of conductivity are certainly 
 produced in a nerve by the 
 constant current, which even 
 outlast its flow. For all 
 currents above a certain 
 strength the conductivity at 
 the kathode and in its neigh- 
 bourhood is eventually dim- 
 inished, and with currents 
 still only moderately strong 
 the block deepens into im- 
 passability. The conduc- 
 tivity at the anode is, during 
 this stage, higher than at the 
 kathode, so that at the time 
 of full kathodic block tire 
 nerve - impulse still passes 
 through the region around 
 the positive pole. With still 
 stronger currents the con- 
 ductivity here, too, dimin- 
 ishes, until the anode as well 
 as the whole intrapolar re- 
 gion is blocked. After the 
 opening of the current, the 
 relation between kathodic 
 and anodic conductivity is 
 reversed, for now the post- 
 kathodic region conducts the 
 nerve-impulse relatively bet- 
 ter than the post-anodic. It 
 will be seen that these 
 changes of conductivity up- 
 on the whole run parallel to 
 the (secondary) changes of 
 excitability, depression of 
 excitability corresponding to 
 depression of conductivity, 
 and vice versa. With the 
 relatively strong currents re- 
 quired to produce decided 
 effects on the conductivity, 
 
 any preliminary change in the same sense as the (so-called primary) 
 effects on the excitability (increase at kathode, decrease at anode) 
 might be expected to be fleeting, and therefore less eas}- to detect. 
 
 The above facts serve to explain the manner in which the effects of 
 stimulation of a nerve with the constant current vary with the strength 
 
 Fig. 275. — Diagram of Changes of Excitability 
 and Conductivity produced in a Nerve by a 
 Voltaic Current. E, changes of excitability 
 during the flow of the current, according to 
 Pfliiger. These are seen most typically with 
 the weaker currents. In particular the in- 
 creased excitability at and around the kathode 
 when the current is strong very quickly gives 
 place to depression. The ordinates drawn 
 from the abscissa axis to cut the curve repre- 
 sent the amount of the change. C(i), changes 
 of conductivity found shortly after the closure 
 and during the flow of a moderately strong 
 current. Conductivity greatly reduced around 
 kathode; little affected at anode. C(2), 
 changes of conductivity during flow of a very 
 strong current. Conductivity reduced both in 
 anodic and kathodic regions, but less in the 
 former. C, changes of conductivity just after 
 opening a moderately strong current. Con- 
 ductivity greatly reduced in region which was 
 formerly anodic; little affected in region for- 
 merly kathodic. 
 
788 
 
 NERVE 
 
 and direction of the stream. These effects, so far as the contraction of 
 tlie muscles supplied by the nerve is concerned, have been formulated 
 in what lias been somewhat loosely termed the law of contraction. In 
 this formula the direction of the current in the nerve is commonly dis- 
 tinguished by a thoroughly bad but now ingrained phraseology, as 
 ascending when the anode is next the muscle, and descending when the 
 kathode is next the muscle. 
 
 Current. 
 
 Ascending. 
 
 Descending. 
 
 M. 
 
 B. 
 
 c 
 c 
 
 M. 
 
 B. 
 
 Weak - 
 Medium - 
 Strong - 
 
 c 
 c 
 
 c 
 c 
 c 
 
 c 
 
 Here M means ' make, 
 traction follows.' 
 
 B, ' break,' of the current; C means ' con- 
 
 The explanation generally given is as follows: Wherever there is an 
 increase of excitability sufficiently rapid and sufficiently large, stimula- 
 tion is supposed to take place; where there is a fall of excitability, 
 stimulation does not occur. Accordingly, at closure the kathode stimu- 
 lates — the anode does not; while at opening, the anode, at which the 
 depressed excitability jumps up to normal or more, is the stimulating 
 pole; the kathode, at which it declines to normal or under it, is inactive. 
 
 With a tveak current, (i) contraction only occurs at make, and (2) the 
 diiection of the current is indifferent. The explanation of the first fact 
 is that the make is a stronger stimulus than the break, and when the 
 current is weak enough the break is less than a minimal stimulus. No 
 sensible change of conductivity is caused by weak currents, which 
 suffices to explain (2). 
 
 With a ' medium ' current, contraction occurs at make and break with 
 both directions. Here the break excitation is effective as well as the 
 make. With anode next the muscle (ascending current), there is, of 
 course, nothing to prevent the opening excitation, which starts at the 
 anode, from passing down the nerve and causing contraction ; and since 
 there is no block around the anode or in the intra polar region with 
 ' medium ' currents, there is nothing to keep the closing (kathodic) 
 excitation from reaching the muscle too. With the kathode next the 
 muscle (descending current), the closing excitation, which starts from 
 the kathode, has no reigon of diminished conductivity to pass through, 
 nor has the opening (anodic) excitation, for the kathodic block, caused by 
 moderately strong currents, is removed as soon as the current is broken. 
 
 With ' strong ' currents there are only two cases of contraction out 
 of the four, just as with ' weak,' but for very different reasons. There 
 is a break-contraction with ascending, and a make-contraction with 
 descending current. With ascending current the anode is next the 
 muscle, and the break-excitation starting there has nothing to hinder 
 its course. The make-excitation, although as strong or stronger, has to 
 pass through the whole intrapolar region and over the anode, and here 
 the conductivity is depressed and the nerve-impulse blocked. With 
 descending current the kathode is next the muscle, and there is no 
 hindrance to the passage of the make-excitation. The break-excitation, 
 however, has to traverse the whole intrapolar region, and this does not 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 789 
 
 at once, after a strong current, become passable. The break-excitation, 
 
 accordingly, rannot get through to the muscle. 
 
 A formula similar to the law of contraction has been shown to hold 
 for the inhibitory fibres of the vagus (Bonders), ' inhibition ' being 
 substituted for ' contraction.' There is also some evidence that a 
 similar law obtains for sensory nerves. 
 
 It is not difficult to see that with currents of brief duration the break 
 follows so quickly on the make that interference of theii opposed effects 
 may occur. This is the reason — or, at least, one reason — why, r bove 
 a certain frequency, a muscle or nerve ceases to respond to all of a 
 series of rapidly recurring electrical stimuli (p. 7.58). It is aUo the 
 reason why, with single very brief stimuli, a greater current intensity 
 must be emploved in order to cause excitation than when the duration 
 of the stimulating current is greater (Woodworth, Lucas). 
 
 The Law of Contraction for Nerves ' in Situ.' — When a nerve is stimu- 
 lated without previous isolation — in the human body, for instance, 
 through electrodes laid on the skin — the current wiU not enter and 
 leave it through definite small portions 
 of its sheath, nor will it be possible to 
 make the lines of flow nearly parallel to 
 each other and to the long axis of the 
 nerve, as is the case in a slender strip of 
 tissue when there is a considerable dis- 
 tance between the electrodes. 
 
 On the contrary-, when, as is usual in 
 electro-therapeutical treatment, a single 
 electrode — say, the positive — is placed 
 over the position of the nerve, and the 
 other at a distance on some convenient 
 part of the body, the current will enter 
 the ner\-e by a broad fan of stream-lines 
 cutting it more or less obliquely, and pass 
 out again into the surrounding tissues; 
 so that both an anode (surface of en- 
 trance) and a kathode (still larger surface 
 of exit) will correspond to the single 
 positive pole. Similarly, the single nega- 
 tive electrode will correspond to an 
 anodic surface where the now narrowdng 
 
 Fig. 276- — Diagram of Lines of 
 Flow of a Current passing 
 through a Nerve. A, an isolated 
 nerve; B, a nerve t>ts:<M. Secon- 
 dary anodes ( + ) are formed 
 where the current re-enters the 
 nerve below the negative elec- 
 trode after passing through the 
 tissues in which it is embedded 
 and secondary kathodes { - ) 
 where the current passes out of 
 the nerve into the surrounding 
 tissues below the positive elec- 
 trode. 
 
 sheaf of lines of flow enters the nerve, and 
 a smaller kathodic surface, where they emerge. Even if the two elec- 
 trodes were on the course of the nerve, the stream-lines would still cut 
 it in such a way that each electrode would correspond both to anode and 
 kathode (Fig. 276). 
 
 It is impossible under these circumstances to take account of the 
 direction of a current in a nerve, or to connect direction with any specific 
 effect. When we place one of the electrodes over the nerve and the 
 other at a distance, the law of contraction only appears in a disguised 
 form; for since a kathode and an anode exist at each pole, there is, with 
 a current of sufficient strength (' strong current '), excitation at each, 
 both at make and break. The negative make contraction is, however, 
 stronger than the positive, for the excitation corresponding to the latter 
 arises at the secondary kathodic surface, where the sheaf of current-lines 
 spreading from the positive electrode passes out of the nerve. Now. 
 this is much larger than the primary kathodic surface, through which 
 the narrow wedge of stream-lines passes to reach the negative electrode, 
 and the current density at the latter is accordingly much greater. The 
 
790 NERVE 
 
 positive break-contraction is, for a similar reason, stronger than the 
 negative. 
 
 With a ' weak ' current, the only contraction is a closing one at the 
 kathode; with a ' medium ' current there are both opening and closing 
 contractions at the positive pole, and a closing but no opening con- 
 traction at the negative (Practical Exercises, p. 846). 
 
 Conductivity of Nerve. — The disturbance which is called the 
 nerve-impulse, once set up, is propagated along the fibres. Are 
 the changes in the nervous substance involved in the initiation of 
 the disturbance at a given point identical with those involved in 
 its transmission from one point to the next, or are they different ? 
 This is a question which has been much discussed, and many 
 attempts have been made to prove that the two processes can be 
 dissociated by acting on nerves with substances like carbon dioxide, 
 ether, and alcohol, which gradually suspend their functions, by 
 cutting nerves off from the circulation and allowing them to die 
 gradually, by depriving them of oxygen and in other ways. Many of 
 the results obtained from such experiments seem at first sight to 
 be favourable to the view that the local change is different from the 
 propagated disturbance. Nevertheless, careful examination of the 
 results on which such statements are based indicates that none of 
 them supplies a crucial test of the question at issue. For example, 
 when a stretch of frog's sciatic nerve is treated with ether or another 
 of the narcotics which act on nerve, and the strength of stimulus 
 determined which is necessary to elicit a contraction when applied 
 to an untreated portion more remote from the muscle than the 
 narcotized area, this strength is found, for some time after the 
 application of the narcotic, to be just the same as it was previous 
 to the application. ' The conductivity ' of the narcotized stretch 
 appears to be unaltered. On the other hand, the stimulus, when 
 applied within the narcotized region, must be strengthened, and 
 the narcotic appears to have diminished the ' excitability ' of the 
 nerve. When the narcotic has acted for a longer time, the reverse 
 effect appears. No stinnilus, however strong, applied to the central 
 non-narcotized stretch will cause a contraction, the ' conductivity ' 
 having been apparently totally abolished by the narcotic, whereas 
 a strong stimulus applied in the narcotized region will still cause 
 a contraction, showing that ' excitability ' still remains. As to 
 the facts there is general agreement; it is their interpretation 
 which is in doubt. Now, it has been shown that in passing along 
 a narcotized nerve the propagated disturbance diminishes in pro- 
 portion to the length of nerve which it has to traverse. Accordingly 
 in the second stage of narcosis the failure of the stimulus applied 
 to the upper part of the nerve to elicit a contraction is explained 
 most naturally as due to the extinction of the distiu-bance, which 
 must pass through the whole narcotized region, whereas the dis- 
 turbance set up by stimulation in that region succeeds in reaching 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 7<Jl 
 
 the muscle, sinr(> it has a sliorter strelcli of narcotized nerve to 
 traverse. This expiM'inient, then, in reahty affords no proof that 
 excitability and conchictivity can vary independently. Facts are 
 also known, to which allusion need not be made here, but which 
 greatly modify the ordinary interpretation of the experimental 
 results obtained in the first stage of narcosis, and upon the whole 
 it may be said that these direct methods of determining the question 
 have failed to yield a satisfactory answer. Indirect evidence 
 exists, however, that the local process initiated by stimulation is 
 not quite the same as the process involved in the propagation of 
 the disturbance (Lucas). Thus, a brief current too weak to set up a 
 propagated disturbance, nevertheless causes some change at the point 
 of stimulation, since a second current, also too weak to be effective 
 by itself, will, when thrown in a short time after the first, cause 
 a disturbance which is propagated along the nerve. There is good 
 reason to believe that the change produced by the first current is 
 not the same in kind as that produced by the second, only weaker, 
 but that it is inherently different in quality. Above all, it is a 
 local change incapable of being itself propagated, but constituting 
 the necessary prelude to the starting of the propa.gated disturbance. 
 Lucas has called this preliminary local effect the ' local excitatory 
 process.' 
 
 There are many facts which indicate that the capacity of different 
 functional or anatomical groups of nerve-fibres for responding to stimu- 
 lation and for conducting the nerve-impulse can be differently affected 
 by one and the same influence. For example, pressure abolishes the 
 conductivity of sensory fibres sooner than that of motor fibres. 
 
 Cocaine locally applied to a nerve diminishes or abolishes its con- 
 ductivity, according to the dose. It exercises a selective action as 
 regards nerve-fibres of different kinds, picking out and paralyzing 
 sensory fibres before motor; vagus fibres conducting upwards before 
 those conducting downwards, vaso-constrictors before vaso-dilators, 
 and broncho-constrictors before broncho-dilators (Dixon). 
 
 The conduction or propagation of a definite disturbance or impulse is 
 a phenomenon not confined to nervous tissue. It is also characteristic- 
 ally seen in muscle, although there the mechanical effect which con- 
 stitutes the normal respon.?e to the arrival of the propagated disturbance 
 obtrudes itself and tends to divert attention from the latter. It is 
 unlikely that the conduction process m muscle should be essentially 
 different from that in nerve, and in muscle, as in nerve, there is 
 evidence that it is associated with only a small, perhaps not even a 
 detectable, liberation of heat. The main heat-production in muscle 
 is essentially a feature not of conduction, but of contraction. Con- 
 duction in muscle can be completely dissociated from the contraction 
 process in various ways. For example, if a portion of a muscle is 
 immersed for a time in distilled water, so-called water rigor ensues, and 
 the altered muscle has lost the power of contraction. It will never- 
 theless conduct the impulse which on reaching the unaltered part of the 
 muscle causes it to contract normally. 
 
 Double Conduction. — When a nerve (or muscle) is stimulated 
 artificially, the excitation runs along it in both directions from the 
 
792 NERVE 
 
 point of stiimilation; so that nervc-libres which in the intact body 
 are afferent can conduct impulses towards the periphery and 
 efferent fibres can conduct impulses away from the periphery. In 
 the normal state, however, double conduction must seldom occur, 
 for efferent fibres are connected centrally, and afferent fibres 
 peripherally, with the structures in whicli their natural stimuli 
 arise. In general, too, an impulse, if it did pass centrifugally along 
 an afferent fibre, would not give any token of its existence, for the 
 peripheral organ would not be able to respond to it; and there is no 
 ground for assuming that the central mechanisms connected with 
 afferent fibres are better fitted to answer such foreign and un- 
 accustomed calls as impulses reaching them along normally efferent 
 nerves. There is good evidence that muscular excitation is no' 
 carried over to the motor nerve- fibres; in other words, the v.ave 
 of action flows from the nerve to the muscle, but cannot be got 
 to flow backwards. Excitation of the central end of an efferent 
 (anterior) spinal root is not transferred to the corresponding afferent 
 (posterior) root, the connection between the efferent and afferent 
 neurons presenting the character of a physiological ' valve,' which 
 permits impulses to pass only in one direction. We have seen that 
 vaso-dilator impulses possibly pass out to the limbs over fibres 
 which, morphologically speaking, are afferent fibres (p. i8i). And 
 we shall see that a nutritive influence is exerted over the afferent 
 fibres of the spinal nerves by the ganglion cells of the posterior root 
 ganglia (p. 796), an influence which must spread along these fibres 
 in the opposite direction to that of the normal excitation. 
 
 The best proofs of double conduction in nerves, with artificial stimu- 
 lation, are: (i) The propagation of the negative variation or action 
 current in both directions. This holds for sensory as well as for motor 
 fibres, as du Bois-Reymond showed on the posterior roots of the spinal 
 nerves of the frog and the optic nerves of fishes. (2) Stimulation of the 
 posterior free end of the electrical nerve of Malaptcrurus (p. 841) causes 
 discharge of the electric organ, although the nerve-impulse travels nor- 
 mally in the opposite direction. (3) If the lower end of the frog's 
 sartorius is split into two, gentle stimulation of one of the tongues causes 
 contraction of individual fibres in the other. This is supposed to be due 
 to conduction of the nerve-impulse up a twig of a nerve-fibre distributed 
 to the one tongue, and down another twig of the same fibre going to the 
 other tongue. A similar experiment can be done on the gracilis of the 
 frog. This muscle is divided by a tendinous inscri]Hion into two parts, 
 each supplied by a branch of a nerve which divides after entering the 
 muscle. Stimulation of either twig is followed by contraction of both 
 parts of the muscle (Kiihne). 
 
 Bert's much-quoted experiment on the rat is valueless as a proof of 
 double conduction. lie caused union of the point of the tail with the 
 tissues of the back, then divided the tail at the root, and found that 
 stimulation of what was now the distal end caused pain. From this he 
 concluded that the sensory fibres of the ' transposed ' tail conducted 
 in the direction from root to tip. But the conclusion is not warranted, 
 for sensation disappeared in the tail after the section, and did not 
 
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 70S 
 
 return till some months later, when the nerve-fibres, after degenerating, 
 woulil i-.avc been replaced by new sensory fibres growing down from 
 the (I rl nerves (Ranvier). For a similar reason the so-called union 
 of the riphcral end of the cut hypoglossal nerve (motor) with the 
 central end of the cut lingual (sensory) proves nothing as to double 
 conduction, nor as to the possibility of motor nerves taking on a sensory 
 funrtion. For while sensation is after a time restored in the affected 
 portion of the tongue, this is due to the growth of sensory fibres from the 
 central stump of the lingual down through the degenerated hypoglossal, 
 and not to the conduction upwards of sensory impulses by the motor 
 fibres of the latter. 
 
 Every fibre of a nerve is physiologically isolated from the rest, 
 so that an impulse set up in a fibre runs its course within it, and 
 does not pass laterally into others (law of isolated conduction). In 
 connection with this physiological fact there is the anatomical fact 
 that nerve-fibres do not normally branch in the trunk of a peripheral 
 nerve. (But see p. 802.) It has, however, been shown that bifurca- 
 tion of nerve-fibres may occur in the spinal cord (Sherrington). 
 The axis-C3dinder of a peripheral nerve-fibre only begins to branch 
 where complete isolation of function is no longer required, as within 
 a muscle. The expteriment of Kiihne on double conduction, men- 
 tioned above, shows that an excitation set up in one twig or one 
 fibril of an axis-cyhnder which has branched can spread to the rest. 
 
 Velocity of the Nerve- Impulse. — We have said that the nerve- 
 impulse travels with a measurable velocity. It is now time to 
 describe how this has been ascertained (p, 818). For motor fibres 
 the simplest method is to stimulate a nerve successively at two 
 points, one near its muscle, the other as far away from it as possible, 
 and to record the contractions on a rapidly-moving surface (pendu- 
 lum or spring myograph) (p. 746). The apparent latent period of 
 the curve corresponding to the nearer point will be less than that 
 of the curve corresponding to the point which is more remote, by 
 the time which the impulse takes to pass between the two points. 
 The distance between these points being measured, the velocity is 
 known. Helmholtz found the velocity for frog's nerves at the 
 ordinary temperature of the air to be a little under, and for human 
 nerves, cooled so as to approximate to the ordinary temperature, 
 a little over 30 metres per second. For observations on man the 
 contraction curves of the flexors of one of the fingers or of the 
 thumb may be recorded, first with stimulation of the brachial plexus 
 at the axilla, and then with stimulation of the median or ulnar 
 nerve at the elbow. Probably at the same temperature there is 
 little difference in the rate of transmission in the nerves of warm- 
 blooded and cold-blooded animals, but temperature has a con- 
 siderable influence (p. 782). 
 
 By cooling a frog's nerve Helmholtz reduced the rate to y^y of its value 
 at the ordinary temperature. In the human arm he found a variation 
 from 30 to 90 metres per second, according to the temperature, 50 metres 
 
794 N/ii? VE 
 
 being about the normal rate. This is greater than the speed of the 
 fastest train in the world. According to Piper's recent measiireiiients 
 the velocity in human mediillated nerve is even greater than Helmiioltz 
 concluded, about 120 metres a second under ordinary condition.?. The 
 rate is independent of the intensity of the excitation. The velocity 
 with which the negative variation is propagated (p. 824) is the same as 
 that of the nerve-impulse. 
 
 In sensory nerves there is no reason to believe that the velocity of the 
 nerve-impulse difters from that in motor nerves, but experiments on 
 man really free from objection are as yet wanting. 
 
 The usual method is to stimulate the skin first at a point distant from 
 the brain, and then at a much nearer point. The person experimented 
 on, as soon as he feels the stimulation, makes a signal, say, by closing 
 or opening with the hand a current connected with an electric time- 
 marker, writing on a moving surface. There is, of course, a measurable 
 interval between the excitation and the signal, and this being in general 
 longer the more remote the point of stimulation is from the brain, it is 
 assumed that the excess represents the time taken by the nerve-impulse 
 to pass over a length of sensory nerve equal to the difference in the 
 length of the path. But there is this difficulty, that the propagation 
 of the impulse from the point of stimulation to the brain is only one 
 link in the chain of events of which the signal marks the end. The 
 impulse has first to be transformed into a sensation, and then the will 
 has to be called into action, and an impulse sent down the motor nerves 
 to the hand. And while the time taken by the excitation in travelling 
 up and down the peripheral nerve-fibres is probably fairly constant, the 
 time spent in the intermediate psychical processes is very variable. 
 
 Section II. — Chemistry, Degeneration, and Regeneration of 
 
 Nerve. 
 
 Chemistry of Nerve. — Our knowledge of this subject is still scanty; 
 and most of what we do know has been obtained from analyses, 
 not of the peripheral nerves, but of the white matter of the central 
 nervous system 
 
 Proteins are present, especially in the axis-cylinder. The proteins of 
 nervous tissue include two globulins, one coagulated by heat at 47° C, 
 the other at 70° to 75° C, and a nuclco-protein coagulating at 56** to 
 60° C. 
 
 Very important constituents are certain substances soluble in organic 
 solvents, like benzol and ether, and comprising cholesterin, certain 
 phosphatides {kephalin and lecithin), and certain cerebri )is or cerebrosides. 
 The cerebrins are glucosides containing nitrogen, but no phosphorus, 
 and they yield a reducing sugar (galactose) on hydrolysis. In the 
 nervous tissue there is also present, according to some authorities, a 
 compound called protagon. Others consider it a mere mixture of phos- 
 phatides and cerebrosides. The lipoids of nerve-fibres belong largely to 
 the medullary sheath, but they are not confined to it, since non-medul- 
 lated nerves also yield a considerable quantity of lipoids (ii"5 per cent, 
 of the solids as against 46'6 per cent, for medullatcd nerves). Non- 
 medullated nerves (splenic nerves of the ox) are distinguished from 
 meduUated nerves (human sciatic) by the high proportion of their total 
 lipoids constituted by the phosphatides (kephalin and lecithin) and 
 cholesterin. Thus, in non-meduUated fibres 47 per cent, of the lipoid 
 
CHEMISTRY OF NERVE 795 
 
 extract consisted of cholcstcrin, and 23*7 per cent, of kephalin; while 
 in the mcdulhited fibres cholcstcrin made up only 25 per cent, of the 
 extract, and kephalin 12*4 per cent. On the other hand, the cere- 
 brosides arc present, both relatively and absolutely, in much larger 
 quantity in medullated than in non-medullatcd nerves. In both 
 varieties of fibres kephalin, and not lecithin, is the chief phosphorus- 
 containing body (Falk). The medullary sheath further contains a 
 kind of network of a peculiar resistant substance, neurokeratin. The 
 netcr ilem ma consists oi substances insoluble in dilute sodium hydroxide. 
 Gelatin is obtained from the connective tissue which binds the nerve- 
 fibres together. There may also be ordinary fat in the meshes of the 
 epineurium connecting the bundles. Small quantities of xanthin, 
 hypoxanthin, and other extractives, can also be obtained from nerve. 
 According to Halliburton's analyses, the water in sciatic nerves amounts 
 to 65'i per cent., and the solids to 34*9 per cent. The proteins make up 
 29 per cent, of the solids. 
 
 For an analysis of the white matter of the brain, see Chapter XVI. 
 
 Nerve-cells contain no potassium, according to Macallum; and this 
 is true both of the dendrites and the axons. In medullated nerves, how- 
 ever, potassium compounds are present external to the axons, chiefly at 
 the nodes of Ranvier (Frontispiece) and in the neurokeratin framework 
 of the sheath. 
 
 The only chemical difference between living and dead nervous tissue 
 which has been made out with any degree of certainty is that the former 
 is neutral or faintly alkaline, and the latter acid, in reaction to such 
 indicators as litmus. This is especially true of the grey matter of the 
 central nervous system, although the white matter also is often found 
 acid. The change of reaction is due to the accumulation of lactic acid. 
 Such a change has not hitherto been clearly demonstrated in peripheral 
 nerves, either after death or after prolonged stimulation. The (non- 
 medullated) splenic nerves of the dog, even after stimulation for six 
 hours, never became acid (Halliburton and Brodie). 
 
 Degeneration of Nerve. — Nerve-fibres are ' bound in the bundle 
 of life ' with the nerve-cells from which their axis-cylinders arise; 
 the connection between cell and axon once severed, the nerve- 
 fibre dies inevitably. This is an illustration of a general law that 
 no portion of a cell can live once it is separated from the nucleus. 
 We shall see later on that changes also occur in the nerve-cell whose 
 axon has been divided from it, although they are of a different 
 nature (rather a slow atrophy than an acute degeneration), and 
 do not necessarily lead to the destruction of the cell. We must 
 regard the neuron not only as a morphological unit, a single cell 
 from nucleus to remotest end-brush, but also as a functional and 
 nutritive unit, the fortune of any portion of which is not in- 
 different to the rest. Thus, when a man's arm is amputated the 
 arm fares worse than the man, for the arm dies. But the man is 
 not unaffected. He lives, but he suffers much temporary disturb- 
 ance and some permanent loss. What is left of him is not quite 
 the same as it was. The acute changes that occur in severed nerve- 
 fibres are most conveniently studied in the peripheral nerves, 
 although essentially similar phenomena take place also in the fibres 
 of the central nervous system. 
 
796 
 
 NERVE 
 
 A spinal nerve is composed of efferent fibres whose cells of origin 
 are in the grey matter of the anterior horn, and afferent fibres 
 whose cells of origin are in the posterior root ganglion. When such 
 a nerve is cut below the junction of its roots, muscular paralysis 
 and impairment of sensation at once follow in the region supplied 
 by the nerve; but for a time the nerve remains excitable to direct 
 
 stimulation. The excitability 
 gradually diminishes, and in a 
 few days is completely gone. 
 If portions of the nerve distal 
 to the lesion are examined at 
 different periods after section, a 
 remarkable process of degenera- 
 tion (commonly spoken of as 
 Wallerian degeneration) is seen 
 to be going on. In the medul- 
 lated fibres this begins on the 
 second or third day with a 
 swelling of the axis-cylinder, 
 which breaks up into detached 
 pieces (fragmentation), and as- 
 sumes a granular appearance. 
 The medullary sheath also under- 
 goes fragmentation at the lines 
 of Lantermann, and a little later 
 separates into clumps and drop- 
 lets of myelin. The nuclei under 
 the neurilemma increase in size, 
 proliferate by mitosis, and in- 
 sinuate themselves between the 
 fragments of the medullary 
 sheath and axis-cylinder, which 
 ultimately disappear, leaving the 
 nerve- fibre represented onl^^ by a 
 kind of mummy of connective 
 tissue, in which the neurilemma 
 with its abnormally numerous 
 nuclei can still be recognized. 
 The fragmentation of the myelin 
 sheath is not dependent upon the proliferation of the nuclei, since it 
 occurs also in nerves removed from the body and kept under con- 
 ditions in which the nuclei do not proliferate (Feiss and Cramer). 
 The protoplasm around the nuclei of the neurilemma also increases in 
 amount, and undergoes other changes, which will be more particularly 
 referred to in describing the regeneration of nerve. The degenerative 
 process begins near the cut end, and extends gradually to the peri- 
 
 Fig- 277. — Degeneration of Nerve-Fibres 
 after Section (Bari<er, after Thoma). 
 I, normal fibre; II, degenerating fibre; 
 III, further stage of degeneration; 
 S. neurilemma; m, medullary sheath; 
 A, axis-cylinder; L, Lantcrmann's line 
 or cleft; R, node; mt, drops of myelin; 
 a, remains of axis-cylinder ; w, prolifera- 
 ting cells of neurilemma. 
 
DEGENERATION OF NERVE 
 
 797 
 
 phory, and more rapidly in warm- than in cold-blooded animals. At 
 any rate, that is the interpretation generally given to the fact that at 
 a given period after section the changes — especially the breaking- 
 up of the myelin — are more pronounced near the proximal end of 
 the peripheral stump. In a mammal degeneration is far advanced 
 in a fortnight, although the last renmants of the myelin may not 
 be absorbed for months. In the degenerated nerve (cat's sciatic) 
 the percentage of phosphorus undergoes a diminution from about 
 the third day. About the eighth day the loss of phosphorus — i.e., 
 of the phosphatides (lecithin, kephalin) — is markedly accelerated, 
 coinciding with the appearance of a strong ]\Iarchi* staining re- 
 action. By the twenty-ninth day the degenerated nerve is prac- 
 tically devoid of phosphorus. A progressive increase in the water 
 and a diminution in the total 
 solids also culminate about the 
 same time (Mott and Halli- 
 burton). In the portion of the 
 nerve-fibre still connected with 
 the nerve-cell the degeneration 
 only extends as far back as the 
 next node of Ranvier, and seems 
 to be due to the direct effect of 
 the injury. In non-medullated 
 fibres, such as the fibres arising 
 from the cells of the superior 
 cervical ganglion (Tuckett), the 
 degeneration is confined to the 
 axis-cylinders. It begins in 
 about twenty-four hoiirs after section, and the loss of excitability 
 and conducti\'ity is complete by the fortieth hour. 
 
 It follows from what has been said as to the position of the cells 
 of origin of the root fibres of the spinal nerves that section of 
 the anterior root causes degeneration on the peripheral, but not on 
 the central side of the lesion, f Only the anterior root fibres in the 
 mixed nerve degenerate. Section of the posterior root above the 
 ganglion causes degeneration of the central stump, but not of 
 the portion still connected with the ganglion, nor of the posterior 
 root fibres below the ganglion or in the mixed nerve. Section of 
 the posterior root below the ganglion causes degeneration of the 
 fibres of the root below the section and in the mixed nerve, but not 
 above it. 
 
 * The chief constituents of Marchi's solution are potassium bichromate and 
 osmic acid. It stains meduUated nerve-fibres black in the earlier stages of 
 degeneration. 
 
 t A few fibres in the peripheral stump of the anterior root do not degenerate, 
 and a few fibres in the central stump do. These are the ' recurrent fibres,' 
 whose course is described on p. 892. 
 
 Fig. 278. — Degeneration of Spinal Nerves 
 and their Roots after Section. The 
 shading shows the degenerated portions. 
 
798 NERVE 
 
 Regeneration of Nerve. — Degeneration of nerve is followed, if 
 its divided ends are not kept artiticially apart, by a process of re- 
 generation, already distinct under favourable conditions in from 
 three to four weeks after the section, and indeed in some cases 
 commencing as early as the second week. This consists in the 
 outgrowth of new axis-cylinders, in the form of fine fibres, from 
 the ends of the divided axis-cylinders of the central stump of the 
 nerve. These push their way into and along the degenerated 
 fibres, ultimately acquire a medullary sheath, and develop into 
 complete nerve-fibres, restoring first sensation, and later on volun- 
 tary motion, to the paralyzed part. The process needs several 
 months for its completion, even in warm-blooded animals. It 
 takes place under the influence of ths nucleated portion of the 
 neuron (the cell-body), and is never completed if the peripheral 
 and central portions of the nerve are permanently separated by a 
 substance through which the new axis-cylinders cannot grow or 
 ]m a gap too wide for them to bridge over. When the cut ends of 
 me nerve are carefully sutured together, the conditions for com- 
 plete and speedy regeneration are rendered more favourable — a 
 fact which finds its application in the surgical treatment of injured 
 nerves. The cycle of chemical changes described in the degenerating 
 nerve is retraced in the reverse order. In the cat's sciatic the 
 first sign of the return of the phosphorus was seen with the beginning 
 of the normal myelin reaction about the sixtieth day after section. 
 At the one-hundredth day the phosphorus content was almost as 
 great as that of the normal nerve (a little under i per cent, of the 
 solids for the regenerated, as compared with a little over i per cent, 
 for the normal nerve). 
 
 It is not as yet well understood how the regenerating fibres are 
 directed in their growth, so that they join their centres to the appro- 
 priate end-organs without mistake. That they have a high capacity 
 for finding their way is indicated by the results of cross-suturing 
 such nerves as the median and ulnar^ — i.e., of uniting the central end 
 of the one with the peripheral end of the other. Howell and Huber 
 found that after this operation in the dog, both co-ordinated volun- 
 tary motion and sensation returned in large measure in the parts 
 supplied by the nerves. Here the motor fibres of the median nerve 
 must, of course, have made connection with muscles previously 
 supplied by the ulnar, being guided to them along the nerve-sheaths 
 of the latter. Doubtless the old nerve-sheaths serve to some 
 extent as mechanical guides by offering to the new axons a path of 
 least resistance. And when a nerve-trunk containing motor and 
 sensory fibres is simply crushed so as to destroy all physiological 
 continuity, but is not cut, no distortion of the motor and sensory 
 ' patterns ' of the nerve — in other words, no ' straying ' of the fibres 
 from their old paths — can be detected on regeneration. When the 
 
REGENERATION OF NERVE 
 
 799 
 
 nerve is cut and then sutured, a certain amount of distortion of the 
 pattern is inevitable. The mechanical apposition of central and 
 peripheral stumps is, of course, much more nearly perfect in the 
 crushed nerve than in the cut nerve, however exact the suturing 
 may be (Osborne and 
 Kilvington). Yet, even 
 after crusiiing or liga- 
 tion of nerves, or after 
 section and suturing, 
 the regenerating fibres 
 do not pass straight 
 through the scar tissue 
 from the central to the 
 peripheral stump, but 
 cross and mingle, ap- 
 parently in the most 
 inextricable confusion 
 (Feiss) (Fig. 279). This 
 is due to the prolifera- 
 tion of cells in the scar 
 which run in all direc- 
 tions, and show no 
 signs of following the 
 parallel arrangement of the nerve-sheaths in the central or the 
 distal segment. These being formed before the regenerating 
 nerve-fibres, the latter must necessarily grow also in all direc- 
 tions in the scar. 
 
 Fig. 279. — Regenerating Fibres crossing in the Scar 
 after Ligation of a Dog's Sciatic Nerve 165 Days 
 previously. Weigert-Pal stain. Drawn under oil- 
 immersion (Feiss). 
 
 ^nl^foglileal 
 
 # 
 
 Nturomu.'^ 
 
 This, however, is a 
 local phenomenon. 
 Beyond the scar the 
 arrangement of the 
 regenerating axis- 
 cylinders recovers 
 its regularity, and 
 the amount of dis- 
 tortion of the nerve 
 pattern, as indicated 
 by histological ex- 
 amination and 
 functional tests, is 
 by no means so 
 great as the com- 
 plete effacement of the pattern in the scar might appear to promise. 
 That the degenerated peripheral stump directs the growth of 
 the axons from the central stump in some other than a merely 
 mechanical way is evident from the experiments of Langley on 
 
 EP- 
 
 Fig. 280. — Semidiagrammatic Representation of Longi- 
 tudinal Section through Neuroma or Scar produced by 
 ligating the Sciatic Nerve with Catgut, and crushing it 
 with a haemostat just above its Division into the Ex- 
 ternal and Internal Popliteal Nerves. Weigert-Pal 
 preparation (Feiss). 
 
8oo NERVE 
 
 regeneration of the cervical sympathetic in the cat after section 
 below the superior cervical ganglion. The nerve contains fibres 
 of various functions which reach it from the upper thoracic nerves. 
 The anterior roots of the first and third thoracic nerves supply the 
 cervical sympathetic mainly with fibres which end in the ganglion 
 around cells that give off dilator fibres for the pupil. The fibres 
 connected with the cells in the ganglion which send vaso-motor 
 fibres to the vessels of the ear are for the most part contained in 
 the anterior roots of the second and fifth thoracic nerves; and the 
 fibres connected with the cells that give origin to the pilo-motor 
 fibres for the hairs of the face and neck in the anterior roots of the 
 fourth to the seventh. Stimulation of any one of the upper thoracic 
 roots accordingly causes a specific effect, which, according to 
 Langley, is in general the same after regeneration as before section 
 of the cervical sympathetic. We must assume, therefore, that each 
 regenerating fibre seeks out either the ganglion cell with which it 
 was originally connected, or one belonging to the same class. No 
 mere mechanical guidance of the growing axons by the old neuri- 
 lemmas will suffice to explam this selective growth. It is necessary 
 to postulate, in addition, an attraction of a chemical or physico- 
 chemical nature (chemiotaxis), dependent upon a specific relation 
 between the new axons and the scaffolding of the peripheral stump 
 or the ganglion cells. But it is not possible at present to form any 
 very precise conception of the properties on which the chemiotactic 
 phenomena depend. And the specificity is not an absolute one. 
 Under certain conditions these pre-ganglionic nerve-fibres (that is 
 to say, nerve-fibres running from the spinal cord to end around the 
 sympathetic ganglion cells) can form connections with nerve-cells 
 of a different class — e.g., pupillo-dilators with cells whose axons 
 end in the erector muscles of the hairs. Further, after section of 
 the sympathetic above the superior cervical ganghon, the post- 
 ganglionic nerve-fibres {i.e., the fibres coming off from the cells of 
 the ganghon) may also, if the opportunity be favourable during 
 regeneration, exchange their old end-organs for new ones; pilo- 
 motor fibres, for instance, finding their way into the iris and becoming 
 pupillo-dilators. After excision of the superior cervical ganglion, 
 the cervical sympathetic does not recover its function. Accordingly 
 the pre-ganglionic fibres cannot form direct functional connection 
 with the post-ganglionic fibres, but can become connected with 
 them only indirectly through the ganglion cells. Nor can efferent 
 post-ganglionic fibres achieve regenerative union with a cerebro- 
 spinal (somatic) motor nerve, although they can themselves re- 
 generate, as has been shown, e.g., in the case of the vaso-constrictors 
 of the limbs. On the other hand, union easily takes place between 
 pre-ganglionic fibres and efferent somatic fibres, and vice versa. 
 For example, the cervical sympathetic can unite with the phrenic 
 
RnGENERATinN OF NEUVE Soi 
 
 norve, and cause contraction of the diaphragm, or with the iccunent 
 laryngeal nerve, and cause movement of the vocal cords, or with 
 the spinal accessory, and cause contraction of the sterno- mastoid 
 muscle. Conversely, the j^hrenic nerve, when united wit h the cer- 
 vical sympathetic, can, when stimulated, produce the usual effects 
 observed on exciting the latter nerve (I.angley and Anderson). 
 
 Central and Autogenetic Theories of Regeneration. — Although 
 the establishment of connection with tlie central end of the 
 cut nerve is necessary for complete regeneration, it must not 
 be supposed that no share wliatever is taken in the process by 
 the peripheral stump. Even while it remains completely isolated 
 from the central nervous system, changes occur which are often 
 described as the third or final stage of degeneration, but which are 
 more correctly interpreted as forming a stage in the regenerative 
 cycle. Spindle-shaped cells or fibres with elongated nuclei make 
 their appearance, produced by the proliferation of the nuclei of the 
 primitive sheath already described, and the increase of the proto- 
 plasm in which these nuclei are embedded. These so-called axial 
 strand fibres or this fibrillated protoplasm may appear long before 
 the remains of the degenerated axis-cylinder and myehn sheath 
 have been completely removed. It is generally acknowledged that 
 in the adult they do not develop beyond this, so long as the peri- 
 pheral portion of the nerve remains completely isolated, but neither 
 do thty disappear even after a very long interval. When strict 
 precautions against union with other nerve-trunks were taken, the 
 radial nerve of an adult cat was found in this resting-stage nearly 
 a year and a half after division, and the same was true after two 
 years and a half in a nerve divided in a human being. The fibres 
 are incapable of being excited or of conducting nerve impulses. 
 The precise relation between these axial strand fibres of the peri- 
 pheral stump and the myelinated fibres found there after regenera- 
 tion has been much debated. All are agreed that nerve- fibrils 
 sprout from the central stump, and the weight of evidence is in 
 favour of the long-accepted view that it is by the growth of these 
 fibrils along the peripheral stump that the new axons are formed, 
 and that all the changes in the distal portion of the nerve, however 
 important for directing and perhaps sustaining the growth of the 
 central fibrils, are subsidiary to this. But some maintain that the 
 outgrowing central fibrils meet and unite with corresponding fibrils 
 sprouting from the peripheral stump, and that the new axis- 
 cylinders arise from the fibrils of the axial strand. It is said that 
 very shortly after being brought into connection with the central 
 portion of the same or of another nerve by careful suturing the 
 spindle cells begin to lengthen, and form non-medullated fibres, 
 like those of the sympathetic. Four weeks after union the afferent 
 fibres, although still non-medullated, are capable of being stimulated 
 
 51 
 
8o2 NERVE 
 
 meclianically and iltrtrically, and of conducting ini])iilscs towards 
 t'v centre, in about eight weeks they become nirdullated, but at 
 fust are of small calibre (Head and I lam). Bethe, the most strenuous 
 defender of the inherent regenerative power of the isolated peri- 
 pheral stump (autogenetic theory), has even stated that complete 
 regeneration occurs in young animals in nerves entirely separated 
 from their centres. There is no doubt that this result is due to 
 st)me error of technique or of interpretation. The controversy 
 turns largely upon the precautions judged necessary to prevent the 
 ingrowth of central fibres. And while it is comparatively easy to 
 make sure, by removing a large part of it, that the central end of 
 the nerve under observation shall remain completely unconnected 
 with the peripheral end, it is often a matter of the greatest difftculty 
 to prevent tlic union of the distal stump with central fibres from 
 other sources — e.g., from the nerves cut in the wound. Many of the 
 results which seemed to favour the autogenetic theory were cer- 
 tainly due to this cause. 
 
 The most conclusive evidence in favour of central and against 
 autogenetic regeneration, because the most direct and uncompli- 
 catecl. has been afforded by the demonstration that the development 
 of axis-cylinders occurs in vitro in a suitable plasmatic medium, in 
 the absence of any other elements than the nerve-cells from which 
 they arise (Harrison). This observer, working with the medullary 
 plates of tadpoles, in which the nerve-cells originate in the embryo, 
 showed further that peripheral nerves do not develop when the 
 nerve-centres are removed, and that the sheath-cells of Schwann are 
 not essential to the growth of axis-cylinders, since in their absence 
 the latter continue to grow and reach their normal length. It has 
 also been proved that nerve-fibres grow out from pieces of the cere- 
 bellum and spinal ganglia (Fig. 281) of young mammals when cul- 
 tivated on clotted plasma outside of the body (Fig. 337, p. 857). 
 Many fibres sprouting out from the spinal ganglia attain a length of 
 more than half a millimetre in forty-eight hours, and their growlh 
 need not be accompanied by either neuroglia or connective tissue. 
 When portions of normal peripheral ner\-e are incubated in plasma 
 no growth of axis cvlinders is ever observed, nor does the \\'allerian 
 degeneration occurring in peripheral nerves incubated in Ringer's 
 solution take place (F'g. 282). On the other hand, if nerves in which 
 Wallerian degeneration has been produced by section are placed in 
 plasma on the fifth day after section or later, growth of the elements 
 of the sheath of Schwann may be seen, again unaccompanied by any 
 growth of axis cylinders (Ingebrigtsen). 
 
 A fact of great physiological interest, and also of practical impor- 
 tance, in connection with the anastomosis of nerves for tlic relief of 
 certain forms of paralysis, is the bifurcation of axons in regeneration, 
 wluMi the conditions arc such that the axons of the central stump are 
 oticrcd more than one path along which to regenerate. If. for instance, 
 a limb nerve-trunk containing motor fibres is cut, and its central end 
 
REGEWEHATfOS OF NERVE 
 
 803 
 
 Sutured both to its own ilistal end and to the distal end of an adjacent 
 ner\e-tnink, the sum of the nerve-fibres in the two distal trunks after 
 regeneration has occurred is greater than the numlK-r of fibres in the 
 central stump ^Kilvington). That this is due to splitting of axons is 
 
 Fig. 281.— Two-day-old Culture of Spinal Ganglia of a Guinea Pig Six Days Old 
 
 (Ingebrigtseu). ^ 
 
 Fig. 282. — Microphotograph of Nerve Fibres from the Sciatic Nerve of a Rabbit, 
 incubated in Plasma for Twelve Days. Hardened in formalin and stained 
 with hematoxylin. No trace of Wallerian degeneration (Ingebrigtsen). 
 
 shown by the fact that an axon reflex (p. 913) can be elicited on dividing 
 one of the distal trunks and stimulating its central end after complete 
 separation of the proximal or parent stem from the central nervous 
 system. Even when the second path offered to the regenerating motor 
 axon is a sensory path, bifurcation of the axon occurs, one branch 
 
So4 NERVE 
 
 passing down along tlic previous motor path to its proper muscular 
 termination, and the other passing down the sensory jjath. Although 
 there is no evidence that etierent fibres can unite with alferent fibres, a 
 degenerated atterent path can therefore serve as a cheniiotactic scaffold- 
 ing or guide for the growth of regenerating motor axons, though not 
 such an efficient one as a degenerated motor path. Sensory fibres, 
 however, cannot regenerate along motor paths or make functional union 
 with the receptive substance of skeletal muscle. 
 
 Regeneration of the fibres of the central nervous system either does not 
 in general occur, or is exceedingly difficult to realize. This lends support 
 to the doctrine of the importance of the neurilemma in regeneration, 
 since its elements are scantily developed in the fibres of the brain and 
 cord (p. Sflo). Kegeneration of the fibres which proceed from the cells of 
 the spinal ganglia along the posterior roots into the cord may take place 
 after the roots have been cut, so that the normal reflexes through the res- 
 piratory, cardiac, and vaso-motor centres may be once more obtained. 
 
 Degeneration of Muscle. — Experimental section or, in man, 
 traumatic division or compression of a nerve leads not only to its 
 degeneration, but ultimately, if regeneration of the nerve does not 
 take place, to degeneration of the muscles supplied by it as well. 
 The muscle- fibres dwindle to a quarter of their normal diameter; 
 the stripes disappear; the longitudinal fibrillation fades out; and at 
 length only hyaline moulds of the fibres are left, filled, and separated 
 by fatty granules and globules and surrounded by engorged capil- 
 laries. Amidst the general decay, the muscular fibres of the 
 tciminal ' spindles ' with which the afferent nerves of muscles are 
 coimected alone remain unchanged (Sherrington). Certain dis- 
 eases of the cord which interfere with the cells of the anterior horn 
 cause degeneration of motor nerves, and ultimately of muscles. 
 The motor nerve-endings degenerate sooner than the sensory. 
 Both may, under suitable conditions, regenerate (Huber). 
 
 Reaction of Degeneration. — Muscles whose motor nerves have been 
 separated from their trophic centres show, when a certain stage in 
 degeneration has been reached, a peculiar behaviour to electrical 
 stimulation, called the ' reaction of degeneration.' To the constant 
 current the muscles are more excitable, and the contraction slower and 
 more prolonged than normal. When a current, either constant or 
 induced, is passed through a normal muscle, the muscular fibres may be 
 stinuilated either directly, or indirectly through the intramuscular 
 nerves. Under ordinary conditions the nerves respond more readily 
 than the muscular fibres, especially to momentary stimuli like induction 
 shocks, and therefore the so-called direct stimulation of uncurarized 
 muscle is as a rule an indirect stimulation. When the muscle is 
 curarized and the nerves thus eliminated, the excitability to induced 
 currents is found to be diminished. The same is the case in a muscle 
 which exhibits the reaction of degeneration after section of its motor 
 nerve, only the loss of excitability to induced currents is greater, and 
 may even be complete. The common statement that the closing anodic 
 contraction is stronger than the closing kathodic — the opposite ot the 
 ordinary law — is subject to so many exceptions that it has no diagnostic 
 value. The nerves are inexcitable either to constant or induced 
 currents. The reaction of degeneration is only obtained from paralyzed 
 muscles when the paralyzing lesion is situated in the cells of the arterior 
 
TROPHIC NERVES 805 
 
 horn from which the motor nerves take origin, or below that level. 
 Accordingly, it is sometimes of use in localizing the position of a lesion. 
 For instance, a group of muscles might be paralyzed by a lesion in the 
 grey matter of the brain or in the nerve-fibres connecting this with the 
 grey matter of the anterior horn of the cord, or in the grey matter of 
 the anterior horn itself, or in the peripheral nerve-fibres leading from 
 this to the muscles. In the first two cases the reaction of degeneration 
 would be absent, although the muscles, if the lesion was of long standing, 
 would be atrophied to some extent; in the last two there would be acute 
 atrophy of the muscles, and the reaction of degeneration would be 
 obtained. 
 
 Trophic Nerves. — There is no question that nerves exert a very 
 important inlluence upon the nutrition of the parts supplied by 
 them, in influencing the specific function of those parts. So that 
 in this sense all nerves arc trophic nerves. The fact that the proper 
 nutrition of nerve-fibres and striated muscular fibres is dependent 
 on their connection with nerve-cells has been by some writers 
 generalized into the doctrine that all tissues are provided with 
 ' trophic ' nerves, which, apart from any influence of functional 
 activity, regulate the nutrition of the organs they supply. But the 
 evidence for this view, when weighed in the balance, is found 
 wanting; and it may be said that up to the present no unequivocal 
 proof, experimental or clinical, has ever been given of the existence of 
 specific trophic fibres, anatomically distinct from other efferent or 
 aff'erent nerves. 
 
 It is true that in various diseases and injuries of the nervous .system 
 nutritive changes in the skin, and sometimes in the bones and joints, 
 are apt to appear. But it is very difficult in such cases to disentangle 
 the effects produced by accidental injuries acting on structures whose 
 normal sensibility is lost or lessened, or whose circulation is deranged, 
 from true trophic changes. The most that can be said is that there is 
 some evidence that the power of the skin to resist injur)^ and the 
 capacity of recovering from it, are diminished by interference with its 
 nerve-supply, so that a large sore may result from a trifling lesion, and 
 healing may be slow and difficult. Experimentally it has been found 
 that division of the trigeminus nerve within the skull is sometimes 
 followed by cloudiness of the cornea, going on to ulceration, and ulti- 
 mately inflammation and destruction of the eyeball. Ulcers also form 
 on the lips and on the mucous membrane of the mouth and gums; and 
 the nasal mucous membrane on the side corresponding to the divided 
 nerve becomes inflamed. But in this case the sensibility of the eye is 
 lost, and reflex closure of the eyelids ceases to prevent the entrance of 
 foreign bodies. The animal is no longer aware of the contact of particle.s 
 of dust or bits of straw or accumulated secretion with the conjunctiva, 
 and makes no effort to remove them. The lips, being also without 
 sensation, are hurt by the teeth, particularly- as the muscles of mastica- 
 tion on the side of the divided nerve are paralyzed, and decomposed 
 food, collecting in the mouth, and inhaled dust in the nose, will tend 
 still further to irritate the mucous membranes. There is thus no more 
 need to assume the loss of unknown trophic influences in order to 
 explain the occurrence of the ulcerative changes than there is to 
 explain the production of ordinary^ bed-sores, bunions or corns on parts 
 peculiarly liable to pressure. And, as a matter of fact, if the eye be 
 
8o6 NERVE 
 
 artificially protected, after section of the trigeminal nerve, the 
 ophtlialmia either does not occur or is much delayed. 
 
 In man, too, a case has been recorded in which both the fifth and 
 the third nerves were paralyzed. The eye was still shielded by the 
 contraction of the orbicularis oculi supplied by the seventh nerve, as 
 well as by the drooping of the upper eyelid that accompanies paralysis 
 of the third. It remained perfectly sound for many months, till at 
 length the tumour at the base of the brain which had affected the other 
 nerves involved the seventh too. The eye was now no longer com- 
 pletely closed; inflammation came on, and vision was soon permanently 
 lost (Shaw). In another case a patient lived for seven years with 
 complete paralysis of the fifth nerve, yet the eye remained free from 
 disease and sight was unimpaired (Gowers). 
 
 The so-called ' trophic ' effects following division of both vagi we 
 have already discussed (p. 286) so far as they are concerned with the 
 respiratory system. The degenerative changes sometimes seen in the 
 heart are perhaps due to its being overworked in the absence of nervous 
 restraint on its functional activity. The nutritive alterations in 
 muscles and salivary glands after section of motor and secretory nerves 
 seem to depend in part on functional and vaso-motor changes. In the 
 paralyzed muscles nutrition is not only interfered with in consequence 
 of their inactivity, as would be the case even if the paralysis wers due 
 to a lesion above the level of the anterior cornual cells, but the already 
 poorly nourished fibres are continually pressed upon by the capillaries, 
 which are dilated owing to the division of the vaso-motor nerves. The 
 degeneration may also be in part ascribed to the loss of a reflex tonic 
 influence exerted on the muscles by the spinal cord, through the 
 ordinary motor nerves (p. 917). When all allowance has been made for 
 these factors, the rapid and characteristic degeneration of the striated 
 muscles, after their connection with the central nervous system is 
 severed, is still inexplicable, except on the assumption that their 
 nutrition is specially related to the integrity of their efferent nerves. 
 In other words, it is necessary to suppose, not, indeed, that distinct 
 trophic nerves exist for the muscles, but that an influence or impulses, 
 which can be termed trophic or nutritive, do normally pass out to them 
 from the spinal cord along their motor nerves. 
 
 Section of the cervical sympathetic in young rabbits and dogs increases 
 the growth of the ear and of the hair on the same side. But it is 
 impossible to separate these consequences from the vaso-motor paral- 
 ysis; and the same is true of the hypertrophy following section of the 
 vaso-motor nerves of the cock's comb and of the nerves of the bones. 
 After section of the superior laryngeal the vocal cord on the side of the 
 section is at once rendered motionless, and remains so, but the muscles, 
 notwithstanding their inaction, do not degenerate. And Mott and 
 Sherrington have found that, although section of the posterior roots in 
 monkeys is followed after a time (three weeks to three months) by 
 ulceration over certain portions of the foot, no corresponding lesions 
 occur in the hand. They believe, therefore, that the lesions are not due 
 to the withdrawal of a reflex trophic tone, but are accidental injuries 
 in positions specially exposed to mechanical or microbic insults. 
 
 One of the best examples of interference with the proper nutrition of 
 a part produced by a lesion in the nerves supplying it is an eruption 
 (herpes zoster), limited to the skin supplied by the nerve-fibres coming 
 from one or more spinal ganglia, and depending on an (infectious) 
 inflammatory change in the ganglia. It has been suggested that the 
 Vehicles are formed either because the pa.ssage of afferent impulses 
 normally concerned in the nutrition of the skin is interfered with or 
 
ci..issrrh'.\ Tin\' nr ni:rvi:s 
 
 807 
 
 because the skin is boiul)ar(lcd by antidromic (p. t8i) impulses dis- 
 charged irom tlie inflamed gmglia. But an alternative liypothcsis is 
 that a toxine spreads out along the nerves from the ganglia, just as 
 in traumatic tetanus the toxine is known tf) pass in the opposite direc- 
 tion along the nerves from the scat of injury to the central nervous 
 system. 
 
 Classification of Nerves. — Omitting the group of ' trophic ' nerves, 
 and tlie even more problematical ' thermogenic ' fibres (which some 
 have supposed to preside over the production of heat, and therefore 
 to' assist in the regulation of the temperature of the body, but of 
 whose existence as distinct and specific nerve-fibres with no other 
 function there is not the slightest proof), peripheral nerves may be 
 classified as follows: 
 
 Centripetal , 
 or afferent ^ 
 fibres. 
 
 I. Nerves of special sensation . „' 
 
 f Smell. 
 I Tas 
 
 aste. 
 
 2. Nerves of general sensation 
 
 3.* Possibly nerves other than 
 those included under i 
 
 and 2, concerned 
 reflex changes in 
 
 in 
 
 I Hearing. 
 I Sight. 
 Touch (light touch). 
 Pressure (perhaps in- 
 cludmg the nerves of 
 muscular sense). 
 Warmth— Cold. 
 ^ Pain. 
 
 ' Calibre of small arteries 
 (pressor, depressor). 
 Action of heart. 
 Respiratory movements. 
 Visceral movements. 
 Glandular secretion. 
 Ordinary skeletal 
 muscles. 
 ' Skeletal muscles 
 Visceral 
 
 Motor nerves for Vascular , , ( Vaso-constrictor 
 
 I Cardio-augmentor. 
 Erector muscles of hairs (pilo-motor 
 fibres). 
 f Visceral muscles 
 
 2. Inhibitory nerves for - f Vaso-dilator. 
 [ Vascular ,, -.' Cardio-inhibi- 
 
 3. Secretory nerves [ tory. 
 
 * It is not known whether the afferent portion of a reflex arc is always com- 
 posed of fibres included, in the first two categories, although undoubtedly in 
 some cases it is. 
 
 Centrifugal 
 
 or efferent 
 
 fibres. 
 
 PRACTICAL EXERCISES ON CHAPTERS XIII. AND XIV. 
 
 I, Difference of Make and Break Shocks from an Induction Machine. 
 
 — Connect a Daniell or other cell B (p. 724) with the two upper binding- 
 screws of the primary coil P, and interpose a spring kej^ K in the circuit. 
 Connect a pair of electrodes with the binding-screw's of the secondary 
 cod (Fig. 283). 
 
8o8 
 
 Ml'SCLE AND NIIRVE 
 
 Electrode s cnn he very simply made by pushing copper wires through 
 two glass tubes, filling the ends of the tubes with sealing-wax and 
 binding thcni together with waxed thread. The projecting points may 
 be filed, and the nerve laid directly on them, or they may be tipped with 
 small pieces of platinum wire soldered on. 
 
 (a) Push the secondary away from the primary, until no shock can 
 be felt on the tongue when the current from the battery is made or 
 broken with the key. Then bring the secondary gradually up towards 
 the primary, testing at every new position whether the shock is per- 
 cejitible. It will be felt first at break. If the secondary is pushed still 
 further up, a shock will be felt both at make and at l)reak. From this 
 we learn that for sensory nerves the break shock is stronger than the 
 make. The same can easily be demonstrated for motor nerves and 
 foi muscle. 
 
 (b) Smoke a drum and arrange a myograph, as shown in Fig. 287. 
 But omit the brass piece F, and do not connect the primary through 
 the drum, as there sliown, but connect it as in Fig. 283. Pith a frog 
 (brain and cord), and make a muscle-nerve preparation. 
 
 To make a Muscle-Nerve Preparation. — Hold the frog by the hind legs 
 back upwards; the front part of the body will hang down, making an 
 angle with the posterior 
 portion. With strong 
 scissors divide the back- 
 bone anterior to this 
 angle, and cut away all 
 the front portion of the 
 body, which \vill fall 
 down of its own weight. 
 Make a circular incision 
 at the level of the tendo 
 Achillis, and another at 
 the lower end of tiie 
 femur, through the skin. 
 The sciatic nerve must 
 now be dis.sected out, as 
 follows : Remove the 
 skin from the thigh , and, 
 holding the leg in the 
 left hand, slit up the fascia which connects the external and internal 
 groups of muscles on the back of the thigh. Complete the separa- 
 tion with the two thumbs. Cut through the iliac bone, taking 
 care that the blade of the scissors is well pressed against the bone, 
 otherwise there is danger of severing the sciatic plexus. Now divide 
 in the middle line the part of the spinal column which remains above 
 the urostyle. A piece of bone is thus obtained by means of which the 
 nerve can be manipulated without injury. Seize this piece of bone with 
 the forceps, and carefully free the sciatic plexus and nerve from their 
 attachments right down to the gastrocnemius muscle, taking care not 
 to drag upon the nerve. The muscles of the thigh will contract, as the 
 branches going to them are cut. This is an instance of mechanical 
 stimulation. Now pass a thread under the tendo Achillis, tie it, and 
 divide the tendon below it. Strip up the tube of skin that covers the 
 gastrocnemius, as if the finger of a glove were being taken ofif. Tear 
 through the loo.se connective tissue between the muscle and the bones 
 of the leg, and divide the latter with scissors just below the knee. Cut 
 across the thigh at its middle. 
 
 Fix the preparation on the cork plate of the myograph by a pin passed 
 
 Fig. 283. — Arrangement of Coil for Single Shocks. 
 
PRACTICAL Kxr.ncisES 
 
 809 
 
 through the cartilaginous lower end of the fcniur, and attach the 
 thread to the upright arm of the lever by one of the holes in it. Hang 
 not far from the axis by means of a hook a small leaden weight (5 to 
 10 grammes) on the arm of the lever which carries the writing-point, 
 and move the myograph plate or the muscle-nerve preparation until 
 this arm is just horizontal. Fasten the electrodes from the secondary 
 coil on the cork plate with an indiarubbcr band ; lay the nerve on them ; 
 and cover both muscle and nerve with an arch of blotting-paper 
 moistened with physiological salt .solution, taking care that the blotting- 
 paper does not touch the thread. Or put the preparation in a moist 
 chamber* (Fig. 322, p. 843). Muscle troughs of various kinds may also 
 
 Fig. 284. — Lucas's Muscle Trough. A, trough made of hard rubbsr; B, a hard rubber 
 boss with a hole drilled in it to receive the pin which fastens the gastrocnemius 
 preparation; H, H, electrodes cased in hard rubber except at the ends, which 
 in the trough carry platinum wires; C, a brass plate mounted on one side of the 
 trough, carrying a lever with a vertical arm F ending in a hook, which is attached 
 by a loop of thread to the tendon of the preparation; G, the writing arm of the 
 lever; K, M, holes in G for loading the muscle. C can be slid horizontally by 
 means of the slots in it, and clamped by the screw E. I, tube for running off 
 the solution. 
 
 be used, which permit immersion of a muscle (or nerve) in Ringer's 
 solution. A convenient form is shown in Fig. 284, but a trough suffi- 
 cient for the purposes of the student can be easily impi"ovised in any 
 laboratory. Adjust the v.'riting-point to the drum. Begin with such 
 a distance between the coils that a break contraction is just obtained 
 on opening the key in the primary circuit, but no make contraction. 
 The lever will trace a vertical line on the stationary drum. Read off 
 on the scale of the induction machine the distance between the coils, 
 and mark this on the drum. Now allow the drum to move a little, still 
 keeping the writing-point in contact with it ; then push up the secondary 
 coil I centimetre nearer the primary, and close the key. If there is a 
 
 * Porter's moist chamber is found in many laboratories, and is very con- 
 venient. It consists of a porcelain plate around which runs a groove. A bell- 
 shaped glass cover, which can be lifted off at will, rests in the groove. The 
 femur of the muscle-nerve preparation is fixed in a small clamp, composed 
 of a split screw on which moves a nut. By means of the nut the clamp is 
 tightened on the femur. The gastrocnemius hangs vertically down, the thread 
 on the tendo Achillis passing through a hole in the porcelain plate to a lever 
 separately supported on the same stand as the moist chamber. A piece of 
 wet blotting-paper fixed inside the cover keeps the air in the chamber saturated. 
 
8io MUSCLE AND NERVE 
 
 contraction, let the drum move a little before opening the key again, 
 so that the lines corresponding to make and break may be separated 
 from each other. If there is still no contraction at make, go on moving 
 the secondary up, a centimetre (or less) at a time, till a make con- 
 traction appears. When the coils are still further approximated, the 
 make may become equal in height to the break contraction, both being 
 maximal — i.e., as great as the muscle can give with any single shock 
 (Fig. 2 85)- 
 
 {c) Attach a thin insulated copper wire to each terminal of the 
 secondary'. Loop the bared end of one of the wires through the tendo 
 
 Fig. 285. — Contractions caused by Make and Break Shocks from an Induction 
 Machine. M, make, B, break, contractions. The numbers give the distance 
 between the primary and secondary coils in centimetres. 
 
 Achillis, and coil the other round the pin in the femur, so that the shocks 
 will pass through the whole length of the muscle. Repeat the experi- 
 ment of (b), with direct stimulation of the muscle. 
 
 2. Stimulation of Nerve and Muscle by the Voltaic Current. — (a) Con- 
 nect a Daniell cell through a kev with a pair of electrodes on which the 
 nerve of a muscle-nerve preparation lies. Observe that the muscle con- 
 tracts when the current is closed or broken, but not during its passage. 
 
 286. Simple Rheocord arranged to send a Twig of a Current through a .Muscle 
 or Nerve. B, battery; R, rheocord wire (German silver); S, slider formed of 
 a short piece of thick indiarubber tubing filled .vith mercury; K, spring key; 
 NV, W, wires connected with electrodes. 
 
 Connect the cell with a simple rheocord, as shown in Fig. 280, so that 
 a twig of the current of any desired strength may be sent through the 
 nerve. As the strength of the current is decreased by moving the 
 slider S, it will be found that it first becomes impossible to obtain a 
 contraction at break. The current must be still further reduced before 
 the make contraction disappears, for the closing of a galvanic stream 
 is a stronger stimulus than the breaking of it. The break or make con- 
 
PRACTICAL EXEIiCISES 8ii 
 
 traction obtained by stimulating a ncive with an induction macliinc 
 must not be confused with the break or make contraction caused by the 
 voltaic current. In the case of the induction machine, the break or 
 make applies merely to what is done in the primary circuit, not to what 
 happens to the current actually passing through the nerve. The 
 current induced in the secondary at make of the primary circuit is, of 
 course, both made and broken in the nerve — made when it begins to 
 flow, broken when the flow is over; the shock induced at break of the 
 primary is also made and broken in the nerve. And although make and 
 break of the actual stimulating current come very close together, the 
 real make, here, too, is a stronger stimulus than the real break. 
 
 (6) Repeat {a) with the muscle directly connected to the cell by thin 
 copper wires, or, better, unpolarizable electrodes (p. 73 1)- 
 
 3. Ciliary Motion. — Cut away the lower jaw of the same frog, and 
 place a small piece of cork moistened with physiological salt solution 
 (o'75 per cent.) on the ciliated surface of the mucous membrane covering 
 the roof of the mouth. It will be moved by the cilia down towards the 
 gullet. Lay a small rule, divided into millimetres, over the mucous 
 membrane, and measure with a stop-watch the time the piece of cork 
 takes to travel over 10 millimetres. Then pour salt solution heated to 
 30° C. on the ciliary surface, rapidly swab with blotting-paper, and 
 repeat the observation. The piece of cork will now be moved more 
 quickly than before, unless the salt solution has been so hot as to injure 
 the cilia. 
 
 4. Direct Excitability of Muscle — Action of Curara. — Pith the brain 
 of a frog, and prevent bleeding by inserting a piece of match. Expose 
 the sciatic nerve in the thigh on one side. Carefully separate it, for a 
 length of half an inch, from the tissues in which it lies. Pass a strong 
 thread under the nerve, and tie it tightly round the limb, excluding 
 the nerve. Now inject into the dorsal or ventral lymph-sac a few drops 
 of a I per cent, curara solution. As soon as paralysis is complete, make 
 two muscle-nerve preparations, isolating the sciatic nerves right up to 
 the vertebral column. Lay their upper ends on electrodes and stimu- 
 late; the muscle of the ligatured limb will contract. This proves that 
 the nerve-trunks are not paralyzed by curara, since the poison has been 
 circulating in them above the ligature. The muscle of the leg which 
 was not ligatured will contract if it be stimulated directly, although 
 stimulation of its nerve has no effect. The ordinary contractile sub- 
 stance of the muscular fibres, accordingly, is not paralj-zed. The seat 
 of paralysis must therefore be some structure or substance physiologic- 
 ally intermediate between the nerve-trunk and the general contractile 
 substance of the muscular fibres (p. 738). 
 
 3. Graphic Record of a Single Muscular Contraction or Twitch. — Pith 
 a frog (brain and cord), make a muscle-nerve preparation, and arrange 
 it on the myograph plate, as in i {b). Lay the nerve on electrodes 
 connected with the secondary coil of an induction machine arranged 
 for single shocks. Introduce a short-circuiting key (Fig. 240, p. 732) 
 between the electrodes and the secondary coil, and a spring key in the 
 primary circuit. Close the short-circuiting key, and then press down 
 the spring key with the finger. Let the drum off (fast speed) ; the 
 writing-point will trace a horizontal abscissa line. Open the short- 
 circuiting key, and then remove the finger from the spring key. The 
 nerve receives an opening shock, and the muscle traces a curve. Now 
 adjust the writing-point of an electrical tuning-fork (Fig. 2S7), vibrating, 
 say, 100 times a second, to the drum, and take a time-tracing below the 
 muscle-curve. Stop the drum, or take off the writing-point, the 
 moment the time-tracing has completed one circumference of the drum, 
 
8l3 
 
 MUSCLE AND NLIiVE 
 
 so Ihat the trace may not run over on itself. Cut off the drum-paper, 
 write on it a brief description of the experiment, with the time-vahie of 
 
 
 
 .1^ c 
 
 S 3-5 
 
 o-^ 
 
 c > 
 
 3-5JJ «-- s o 
 
 I. v^* O. U _ « >. = 
 
 • aj «•£ rtf " . 
 
 ; S " 3--X Q. >, ' 
 
 ■"CS— o, "^icu 
 i o ^ c-a c-5 S.a' 
 
 "- o '^ c-a 5-5 S.a' 
 
 
 4) U C 
 
 a " ^ 
 
 
 = 2 0-5 n S o ~ E 
 c a- ■"- Vj; 5 £ c 
 — i) O 0. '• " - ^ 
 
 ■S =>-° 5 e-SeS 
 <iiS'^ 5 §==!■= 
 
 .2 u " o-l-.--- * 
 
 E ^■■^ ox u c i •" 
 = a=>i:H - «■- c"" 
 
 = 3 - £^- °^ = 2 
 
 "03 EH Ji-S oH S 
 iZ 
 
 each vibration of the fork, the date, and the name of the maker of the 
 tracing, and then varnish it. An exactly similar tracing can be obtained 
 by directly stimulating the muscle (curarized or not). 
 
PRACTICAL EXERCISES 813 
 
 o. Influence of Temperature on the Muscle-Curve. — Pith a frog (brain 
 and cord), make a muscle-nerve j)rcparalion, and arrange it on a 
 myograph. Lay the nerve on electrodes connected through a short- 
 circuiting key with the secondary coil of an induction machine, or 
 connect the muscle directly with the key by thin copper wires. Take 
 a Diiniell cell, connect one pole through a simple key with one of the 
 upper binding-screws of the primary coil, and the other pole with the 
 metal of the drum. A wire, insulated from the drum, but clamped on 
 the vertical part of its su})port, and with its bare end projecting so as 
 to make contact with a strip of brass fastened on the spindle, is con- 
 nected with the other upper terminal of the primary (Fig. 28/). At 
 each revolution of tlie drum the primary circuit is made and broken 
 once as the strip of brass brushes the projecting end of the wire. The 
 object of this ■arrangement is to ensure that when the writing-point of 
 the myograph le\-er has been once adjusted to the drum, successive 
 stimuli will cause contractions, the curves of which all rise from the 
 same point. Close the key in the primary, set the drum off (fast speed), 
 open the short-circuiting key, and as soon as the muscle has contracted 
 once, close it again. Now stop the drum, mark with a pencil the 
 position of the feet of the stand carrying the myograph plate, take the 
 writing-point off the drum, and surround the muscle with pounded ice 
 or snow. After a couple of minutes brush away any ice which could 
 hinder the movement of the muscle, rapidly replace the stand in exactly 
 its original position, with the writing-point on the drum, and take 
 another tracing. Again take off the writing-point, and remove all 
 unmelted ice or snow. With a fine-pointed pipette irrigate the muscle 
 with physiological salt sohation at 30° C, and quickly take another 
 tracing. Then put on a time-tracing with the electrical tuning-fork. 
 Fig. 255, p. 748, shows a series of curves obtained in this way. 
 
 7. Influence of Load on the Muscle- Curve. — Arrange everything as 
 in 6. Take a tracing first with the lever alone, then with a weight oi 
 10 grammes, then with 50, 100, 200, and 500 grammes (Fig. 254, p. 748). 
 
 8. Influence of Fatigue on the Muscle- Curve. — Arrange as in 7, but 
 leave on the same weight (say 10 grammes) all the time. Place the 
 nerve on. the electrodes. Leave the short-circuiting key open. The 
 nerve will be stimulated at each revolution of the drum, and the writing- 
 point will trace a series of curves, which become lower, and especially 
 longer, as the preparation is fatigued. Two or four curves can be 
 taken at the same time, if both ends of one or of two brass slips be 
 arranged so as to make contact with the projecting wire at an interval 
 of a semicircumference or quadrant of the drum (Fig. 287). (For 
 specimen curve, see Fig. 288, p. 814.) 
 
 9. Seat of Exhaustion in Fatigue of the Muscle-Nerve Preparation for 
 Indirect Stimulation. — When the nerve of a muscle-nerve preparation 
 has been stimulated until contraction no longer occurs, the muscle can, 
 under ordinary conditions, be made to contract by direct stimulation. 
 The seat of exhaustion is, therefore, not the general contractile sub- 
 stance of the muscular fibres themselves. To determine whether it is 
 the nerve-fibres or some structure or substance intermediate between 
 them and the ordinary contractile substance of the muscle, perform 
 the following experiments : 
 
 (a) Pith a frog; make two muscle-nerve preparations; arrange them 
 both on a mj-ograph plate, which has two levers connected with it. 
 Attach each of the muscles to a lever in the usual wa}', and lay botli 
 nerves side by side on the same pair of electrodes. Cover with moist 
 blotting-paper. The electrodes are connected with the secondary of an 
 induction machine arranged for tetanus. With a camel's hair brush 
 
Si4 
 
 MUSCLE ASD NERVE 
 
 moisten one of the nerves between the electrodes and the muscle with a 
 mixture ot eiju.il jxirts of ether and akohol, diluted with twice its volume 
 of water, to abolish the conductivity. Or put the mixtinc in a small 
 bottle, in which dips a piece of filter-paper. The projecting end of the 
 filter-paper is pointed, and the nerve is laid on the point. As soon as 
 it is possible to stimulate the nerves without obtaining contraction in 
 this muscle, proceed to tetanize both nerves till the contracting muscle 
 is exhausted. If the other muscle begins to twitch during the stimu- 
 lation, more of the ether mixture must be painted on the nerve. As 
 soon as th« stimulation ceases to cause contraction in the non-etherized 
 preparation, wash off the mixture from the other nerve with physio- 
 logical salt solution, and soon contraction may be seen to take place in 
 
 l"ig. 288. — Fatigue Curve of Skeletal Muscle: Gastrocnemius of Frog. Indirei t 
 stimulation; taken with arrangement shown in Fig. 287 (p. S12). Time-tracing. 
 J J^ of a second. 
 
 the muscle of this preparation. This shows that the nerve-trunk is still 
 excitable. Now, both nerves have been equally stimulated, and there- 
 fore the exhaustion in the non-etherized preparation was not due to 
 fatigue of the nerve-fibres, but of something between them and the 
 contractile substance of the muscle. 
 
 10. Influence of Veratrine on Muscular Contraction. — Arrange a 
 drum as in Fig. 287. Pith a frog (brain only), expose the sciatic nerve 
 in one thigh, and isolate it for ^ inch from the surrounding tissues. 
 Pass under it a strong thread, and ligature everything except the nerve. 
 Now inject into the dorsal or ventral lymph-sac a few drops of o-i per 
 cent, solution of sulphate of veratrine. In a few minutes make two 
 muscle-nerve preparations from the posterior limbs. First put the 
 preparation from the unligatured limb on the myograph plate. Lay 
 
pr.mth .11. i-.xr.RcisES 815 
 
 tlie nerve on electrodes connected Ihrougli a sliort-circuiting key with 
 the secondary of an induclion machine arranged as in Fig. 287. Put 
 the writing-point on tiie drum and set it oil (fast speed). Open the 
 short-circuiting key till tlic nerve has been once stimulated, then close 
 it again. Tiie curve obtained differs from a normal curve, in that 
 the period of descent (relaxation) is exceedingly prolonged. Now 
 connect the preparation from the ligatured limb with the lever, and 
 take a tracing of a single contniction. Put on a time-tracing with the 
 electrical tuning-fork (see Figs. 264, 265, p. 735). 
 
 II. Measurement of the Latent Period of Muscular Contraction. — 
 (i) For this the drum must traxel at a faster speed than usual. It 
 is most con\cnient to use a drum rotated very rapidly by a cord 
 attached to a falling weight or by the recoil of a stretched rubber band 
 or spring. The arrangement for automatic stimulation described in 
 Experiment b (p. 813) may be employed. Or an electro-magnetic signal 
 may be connected in the primary circuit of the induction coil so that 
 when the primary is closed or opened the writing-point of the signal 
 moves. Arrange the writing-point of the signal on the drum in the 
 same vertical line as the writing-point of the muscle lever, and in the 
 same line place the writing-point of a vibrating electric tuning-fork. 
 The coil is adjusted for single opening shocks as in Experiment 5 
 (p. 811). Pith a frog, and make a muscle-nerve preparation. Arrange 
 it on the myograph plate. The muscle, or the nerve very near the 
 muscle, is to be excited by a single opening shock while the drum is 
 moving. When the curve has been traced, the latent period is got by 
 drawing a vertical line through the point at which the curve just begins 
 to rise from the abscissa line, and another through the signal mark. 
 The number of vibrations of the tuning-fork included between these 
 two verticals gives the latent period. 
 
 Or (2) use the spring myograph (Fig. 231, p. 746), raising it on blocks 
 of wood. Smoke the glass plate over a paraffin f!ame, or cover it with 
 paper, and smoke the paper. Connect the knock-over kev of the myo- 
 graph with the primary circuit of an induction coil. Arrange a muscle- 
 ner\'e preparation on the myograph plate. Place electrodes below the 
 nerve as near the muscle as possible, and connect by a short-circuiting 
 key with the secondary. Bring the writing-point in contact with the 
 smoked surface of the spring myograph, so as to get the proper pressure. 
 See that the writing-point of the tuning-fork is in the right position for 
 tracing time. Then push up the plate so as to compress the spring, 
 till the rod connected with the frame which carries the plate is held by 
 the catch. 
 
 With the short-circuiting key closed, press the release and allow an 
 abscissa line to be traced. Again shove back the frame till it is caught. 
 Push home the rod by means of which the prongs of the tuning-fork are 
 separated, and rotate it through 90°. Close the knock-over key, open 
 the short-circuiting key, shoot the plate again, and a muscle-curve and 
 time-tracing will be recorded. Again close the short-circuiting key, 
 withdraw the writing-point of the tuning-fork, push back the plate, 
 close the trigger key, then open the short-circuiting key, and. holding 
 the travelling frame with the hand, allow it just to open the knock- 
 over and stimulate the nerve. The writing-point now records a vertical 
 line (or, rather, an arc of a circle), which marks on the tracing the 
 moment of stimulation. The latent period is obtained by drawing a 
 parallel line (or arc) through the point of the muscle-curve where it just 
 begins to diverge from the abscissa line. The value of the portion of the 
 time-tracing between these two lines can be readily determined, and 
 is the latent period. 
 
8i6 AJLSCLH AND Mih'VE 
 
 12. Summation of Stimuli. — Arrange two knock-over keys on tho 
 spring nivograph at sucli a distance from each other that the plate 
 travels fn;ni one to the other in a time less than the latent period. 
 Connect each key with the primary circuit of a separate induction coil 
 having a couple of Daniells in it. Join two of the binding-screws of 
 the secondaries together; connect the other two through a short- 
 circuiting key with electrodes, on which the nerve of a muscle-nerve 
 preparation is arranged. Push up the secondaries till the break shocks 
 obtained on opening the two knock-over keys are maximal. Then 
 shoot the plate as described in ii, first with one trigger key closed, and 
 then with both. The curves obtained should be of the same height in 
 the two cases, as a second maximal stimulus falling within the latent 
 period is ignored by the nerve or muscle. Repeat the experiment with 
 submaximal stimuli — i.e., with such a distance of the coils that opening 
 of either trigger key does not cause as strong a contraction as is caused 
 when the coils are closer. The cur\e will now be higher when the two 
 shocks are thrown in successively than when the nerve is only once 
 stimulated. This shows that (submaximal) stimuli can be summed in 
 the nerve. The same could be demonstrated for muscle (p. 756). 
 
 13. Superposition of Contractions. — Smoke a drum arranged for auto- 
 matic stimulation as in Fig. 287. Adjust the brass points with a 
 distance of. say, i centimetre between them, so that a second stimulus 
 may be thrown into the nerve at an interval greater than the latent 
 period of muscle. Put two Daniells in the primary circuit. Lay the 
 nerve of a muscle-nerve preparation on electrodes connected through a 
 short-circuiting key with the secondary. Allow the drum to revolve 
 (fast speed) ; open the short-circuiting key till both brass points have 
 passed the projecting wire, then close it. Now bend back the second 
 brass point, and take a tracing in which the first curve is allowed to 
 complete itself. This will not rise as high as the second curve obtained 
 when the two stimuli were thrown in. Repeat the experiment with 
 varying intervals between the brass points — that is, between the two 
 successive stimuli. Put on a time-tracing with the electrical tuning- 
 fork. (For specimen curve, see Fig. 260, p. 756.) 
 
 14. Composition of Tetanus. — {a) Adjust a muscle-nerve preparation 
 on a myograph plate, the nerve being laid on electrodes connected 
 through a short-circuiting key with the secondary of an induction 
 machine, the primary circuit of which contains a Daniell cell and is 
 arranged for an interrupted current (Fig. 93, p. 200). The lever should 
 be shorter than that used for the previous experiments, or the thread 
 should be tied in a hole farther from the axis of rotation, so as to give 
 less magnification of the contraction. Set the Neef's hammer going, 
 let the drum revolve (slow speed), and open the key in the secondary. 
 The writing-point at once rises, and traces a horizontal or perhaps 
 slightly-ascending line. Close the short-circuiting key, and the lever 
 sinks down again to the abscissa line. If it does not quite return, it 
 should be loaded with a small weight. This is an example of complete 
 tetanus. 
 
 {b) Connect the spring shown in Fig. 289 with one of the upper 
 terminals of the primarj- coil, and the mercury cup with the other. 
 Fasten the end of the spring in one of the notches in the upright piece 
 of wood by means of a wedge, so that its whole length can be made to 
 vibrate. Let the drum off, set the spring vibrating by depressing it 
 with the finger, then open the key in the secondary. The muscle is 
 thrown into incomplete tetanus, and the writing-point traces a wavy 
 curve at a higher level than the abscissa line. Close the short-circuiting 
 key, and the lever falls to the horizontal. Repeat the experiment with 
 
PRACrtCAL EXERCISES 
 
 817 
 
 the spring fastened, so that only }. \, J. i of its length is free to vibraic. 
 
 The rate of interruption of tlie primary circuit increases in proi^ortion 
 
 to the shortening of 
 tlie spring, and the 
 tetanus becomes more 
 and more complete, 
 till ultimately the 
 writing- point marks 
 an unbroken straight 
 line. Put on a time- 
 tracing by means of 
 an electro - magnetic 
 marker connected 
 with a metronome 
 beating seconds or 
 half-seconds (Fig. 88, 
 p. 195). (For speci- 
 men curves, see Fig. 
 267, p. 757-) 
 
 15. Contraction of 
 
 Smooth Muscles — 
 
 Spontaneous 
 
 Fig. 289 —Arrangement for Tetanus. A, upright with 
 notches, in which the spring S is fastened (shown in 
 section); C, horizontal board to which A is attached, 
 and in a groove in which the mercury-cup E slides. 
 The primary coil P is connected with E, and through 
 a simple key,.K, with the battery B, the other pole 
 of which is connected with the end of the spring. 
 The wires from the secondary coil, P', go to a short- 
 circuiting key, K', from which the wires F go off to 
 the electrodes. 
 
 Rhythmical Contrac- 
 tions. — Immerse in 
 oxygenated Ringer's 
 solution a ring of 
 CESophagus obtained 
 inunediately after death from a cat, or, still better, from a chicken. Or 
 a segment of rabbit's intestine may be employed as described on p. 45O. 
 Use the arrangement 
 described on p. -}56. In 
 the case of the ca t's oeso- 
 phagus the ring should 
 be taken from the lower 
 half of the oesophagus, 
 since the upper portion 
 contains purely striated 
 muscle. Obtain tracings 
 of the rhythmical con- 
 tractions on a slowly- 
 moving drum (Fig. 290). 
 (2) Fix one end of 
 a piece of cat's oeso- 
 phagus, 2 to 5 centi- 
 metres long, to a muscle- 
 cla rap in a moist 
 chamber, and the other 
 end to a lever writing 
 on a drum. Connect 
 thin copper wires from 
 the secondary coil of an 
 inductorium with the 
 two ends of the piece 
 of oesophagus. Take 
 tracings to show [a] the curve of a single contraction caused by a single 
 make or break shock, with estimation of the latent period, as in Experi- 
 ment II, p. 815; (6) summation, as in Experiment 12, p. 8r6; {c) genesis 
 
 52 
 
 Fig. 290. 
 
 -Rhythmical Contractions of CEsophagus of 
 Chicken (Botazzi). 
 
Sid 
 
 MUSCLE AND NERVE 
 
 of tetanus, as in Experiment 14, p. 816; {d) the relations between 
 strength of r-timuhis and amount of contraction. For this hist experi- 
 ment the (Iriun should be stationary while the contraction is being 
 recorded, and should be allowed to move a little between successive 
 contractions. Begin with the secondary at such a distance from the 
 primary that a contraction is just caused by a break shock. Then 
 gradually increase the strength of the stimulus (always using the break) 
 till miximum contraction is obtained. The gradual increase in the 
 response is very clearly seen with the oesophageal preparation (Waller). 
 
 For further exjx'rimcnts on the contraction of smooth muscle, see 
 pp. 66 and 457. 
 
 16. Velocity of the Nerve-Impulse. — Use the spring myograph 
 (Fig. 251. p. 74f)) or a very rapidly rotating drum. IMake a muscle- 
 nerve preparation from a large frog (preferably a bull-frog), so that the 
 sciatic nerve may be as long as possible. Connect the knock-over key 
 with the primary circuit of an induction machine, which should contain 
 
 Fig. 291. .■\rrangcmont for Measurinp; th*^ \Vlocity of the Nerve-Impulse. A. travel 
 ling plate of spring myograph; M, mubcle lying on a myograph plate; N, nerve 
 lying on two pairs of electrodes, E and E'; C, Pohl's ( oinimitator without cross- 
 wires; K, knock-over key of si)ring myograph (only the binding-screws shown); 
 K', simple key in primary circuit; B, battery; P, primary coil; S. secondary coil. 
 
 a single Danicll cell. Arrange two pairs of fine electrodes under the 
 nerve on the myograph plate, one near the muscle, the other at the 
 central end. Connect the electrodes with a Fold's commutator (with- 
 out cross-wires), the side-cups of which are joined to the terminals of 
 the secondary coil, as shown in Fig. 291. By tilting the bridge of the 
 commutator the nerve may be stimulated at either point. Great care 
 mu.st be taken to keep the nerve in a moist atmosphere by means of wet 
 blotting-paper or a moist chamber; but at the same time it must not 
 lie in a pool of salt solution, as twigs of the stimidating current would 
 in this case spread down the nerve; and we could never be sure that 
 the apparent was always the real point of stimulation. The writing- 
 points of the lever and tuning-fork having been adjusted to the smoked 
 plate, as in 11 (p. 815), the bridge of the Ptjhl's commutator is arranged 
 for stimulation o[ the distal point of the nerve, the plate is shot with 
 the short-circuiting key in the secondary closed, and an abscissa line 
 and time-curve traced. Then the writing-point of the fork is removed 
 and the plate again shot with the key in the secondary open, and a 
 
PRACTICAL EXERCISES 8i9 
 
 mupclc-curvc is obtained. The commutator is now arranged for stimu- 
 lation of the central end of the nerve, and another mu.scle-curve taken. 
 Vertical lines are drawn through the points where the two curves just 
 begin to separate out from the abscissa line. The interval between 
 these lines corresponds to the time taken by the nerve-impulse to travel 
 along the nerve from the central to the distal pair of electrodes. Its 
 value in time is given by the tracing of the tuning-fork. The length of 
 the nerve between the two pairs of electrodes is now carefully measured 
 with a scale divided in millimetres, and the velocity calculated (p. 793). 
 17. Chemistry of Muscle. — Mince up some muscle from the hind-legs 
 of a dog or rabbit (used in some of the other experiments), of which 
 the bloodvessels have been washed out by injecting 0*9 per cent, salt 
 solution through a cannula tied into the abdominal aorta until the 
 washings arc no longer tinged with blood. To some of the minced 
 muicle add twentv times its bulk of distilled water, to another portion 
 ten times its bulk of a 5 per cent, solution of magnesium sulphate. 
 Let stand, with frequent stirring, for twenty-four hours. Then strain 
 through several folds of linen, press out the residue, and filter through 
 paper, (i) With the filtrate of the watery extract make the following 
 observations : 
 
 (a) Reactio)!. — To litmus-paper acid. 
 
 (b) Determine the temperatures at which coagulation of the various 
 proteins in the extract takes place, according to the method described 
 on p. 9.* Put some of the watery extract in the test-tube, and heat 
 the bath, stirring the water in the beakers occasionally with a feather. 
 Note at what temperature a coagulum first forms. It will be about 
 47° C. Filter this off, and again heat; another coagulum will form at 
 56* to 58°. Filter, and heat the filtrate; a third slight coagulum may- 
 be formed at 60° to 65° C, but this represents merely a residue of the 
 myosinogen which was left in solution at the previous heating. A 
 fourth precipitate (of serum-albumin) will come down at 70° to 73°. 
 Saturate some of the water\' extract with magnesium sulphate; a large 
 precipitate will be formed, showing the presence of a considerable 
 amount of globulin. Filter off the precipitate and heat the filtrate; 
 coagulation will again occur at very much the same temperatures as 
 before, although the total amount of precipitate will be less. Note in 
 particular that there is still some precipitate at 47° to 50°. Paramyo- 
 sinogen possesses some of the characters of both globulins and albumins, 
 for it is partially but not entirely precipitated by saturation with 
 magnesium sulphate, and is not precipitated b}- sodium chloride. 
 
 (2) (a) Test the reaction of the magnesium sulphate extract. It 
 will usually be faintly acid to litmus. 
 
 {b) Heat some of it. Precipitates will be obtained at the same tem- 
 peratures as in (i) {b). but those at 47" to 50° and 56° to 58° will be 
 more abundant. Of the two, that at 47° to 50° will usually be the 
 larger when time is given for it to come down and the heating is gradual. 
 
 {c) Dilute some of the magnesium sulphate extract with three times, 
 another portion with four times, and another with five times, its volume 
 of water in a test-tube, and put in a bath at 40° C. Coagulation or 
 
 * It should be remembered that the temperature of heat-coagulation of 
 any substance is by no means an absolute constant. It depends on the 
 reaction, the proportion and kind of neutral salts present, perhaps on the 
 strength of the protein solution and the manner of heating. A solution oi 
 egg-albumin, e.g., can be coagulated at a temperature much below 70° when 
 it is heated for a week. Small differences in the temperature of heat-coagula- 
 tion, unless supported by well-marked chemical reactions, are not enough 
 to characterize protein substances as chemical individuals. 
 
820 MUSCLE AND NERVE 
 
 precipitation will occur in one or all of these test-tubes. To another 
 test-tube of the extract diluted in the proportion which has given the 
 best ' muscle-clot ' add a few drops of a dilute solution of potassium 
 oxalate, and place in a bath at 40°. Coagulation occurs as before. 
 Filter off the clot from all the test-tubes. The filtrate is the ' muscle- 
 serum,' and yields a precipitate of serum-albumin at 70* to 73° C. 
 
 (3) Myosiyiogen, like other globulins, is insoluble in distilled water, 
 but soluble in weak saline solutions. Saturation with neutral salts like 
 sodium chloride and magnesium sulphate precipitates mycsinogen, but 
 not albumin, from its solutions; .saturation with ammonium sulphate 
 precipitates both. Verify the following reactions of myosinogen, using 
 the original magnesium sulphate extract of the muscle: 
 
 (a) Dropped into water, it is precipitated in flakes, which can be 
 redissolved by a weak solution of a neutral salt (say 5 per cent, mag- 
 nesium sulphate). 
 
 (6) When a solution of myosinogen is dialyzed, it is after a time pre- 
 cipitated on the inside of the dialyzer as the salts pass out. 
 
 [c) If a piece of rock-salt is suspended in a solution, the myosin 
 gradually gathers upon it, diffusion of the salt out through the precipi- 
 tated myosin always keeping a saturated layer around it. 
 
 {d) Saturate a solution containing myosinogen with crystals of 
 magnesium sulphate, stirring or shaking at frequent intervals. The 
 myosinogen is precipitated. 
 
 {e) Without adding any salt, simply shake a myosinogen solution 
 vigorously; a certain amount of the myosinogen will be precipitated 
 and the solution will become turbid. This reaction can also be ob- 
 tained with solutions of other proteins, such as albumins (Ramsden). 
 
 Extracts qualitatively similar to those obtained from the muscles 
 of a freshly-killed animal can be got from muscles that have entered 
 into rigor, but the quantity of the various proteins going into solution 
 is less. 
 
 18. Reaction of Muscle in Rest, Activity, and Rigor Mortis. ^(a) Take 
 a frog's muscle, cut it across, and press a piece of red litmus-paper on 
 the cut end; it is turned blue. Yellow turmeric paper is not affected. 
 {b) Immerse another muscle in physiological salt solution (0*75 per 
 cent, for frog's tissues) at 40° to 42° C. It becomes rigid. The reaction 
 becomes acid to litmus-paper, and also turns brown turmeric paper 
 yellow. 
 
 (c) Plunge another muscle into boiling physiological salt solution. 
 It becomes harder than in (6). 
 
 (d) Stimulate another muscle with an interrupted current from an 
 induction machine (Fig. 93, p. 200), till it no longer contracts. The 
 reaction is now acid to litmus-paper. Brown turmeric paper may also 
 be turned yellow. 
 
 {e) To demonstrate the formation of lactic acid in muscle in heat 
 rigor or fatigue, perform the following experiment : Pith a frog, and 
 afterwards leave it for half an hour at rest, so that the lactic acid pro- 
 duced in the movements connected with the pithing operation may 
 disappear from the muscles. See that the circulation in the hind-limbs 
 is not interfered with by pressure or flexion. Then remove both hind- 
 limbs. Carefully, but rapidly, remove the muscles of one from the 
 bones with as little manipulation as possible. Immediately place them 
 in a small mortar cooled in ice, and containing some sand and 20 or 
 30 c.c. of ice-cold 95 per cent, alcohol, and quickly grind them up. 
 Produce heat rigor (p. 777) of the muscles of the other hind-limb, or 
 fatigue them with induction-shocks, and then grind them up imder 
 alcohol in the same way. Filter the alcoholic extracts, and then 
 
PRACTICAL EXERCISES 821 
 
 evaporate them to dryness on the water-bath. Rub up the residues 
 with a few c.c. of hot water. Add to each aqueous extract a small 
 quantity (say a decigramme) of finely powdered charcoal. Then heat 
 each extract to boiling in a test-tube, and filter. Evaporate the 
 filtrates to dryness, and apply 
 
 Hopkins's Reaction for Lactic Acid. — The reagents required are (i) a 
 very tiilute alcoholic solution of tliiophene (C4H4S) (10 to 20 drops in 
 100 c.c); (2) a saturated solution of copper sulphate; and (3) ordinary 
 strong sulphuric acid. 
 
 Have ready a glass beaker containing water briskly boiling. Place 
 about 5 c.c. of strong sulphuric acid in a test-tube, with i drop of the 
 copper sulphate solution.* Add to the mixture a few drops of the 
 solution to be tested, and shake well.f 
 
 (In the case of the muscle extracts the dry residues arc dissolved in 
 the 5 c.c. of strong sulphuric acid, the acid transferred to test-tubes, 
 and the test proceeded with by the addition of the copper sulphate 
 solution, etc.) 
 
 Now place the test-tube in the boiling water for one to two minutes. 
 Then cool it well under the cold-water tap. and add 2 or 3 drops of 
 the thiophene solution from a pipette. Replace the tube in the boiling 
 water, and immediately observe the colour. If lactic acid is present, 
 the liquid rapidly takes on a bright cherry-red colour, which is only 
 permanent if the test-tube be cooled immediately after its appearance. 
 The tube should always be cooled as described, before addition of the 
 thiophene, as the gradual appearance of the colour on re-warming 
 makes the test more delicate. 
 
 (The extract of the resting limb generally gives a negative, that of 
 the other a strongly positive, reaction.) 
 
 * The copper sulphate is added to hasten the oxidation that follows. 
 
 •{• For practice use a i per cent, alcoholic solution of lactic acid. The test 
 cannot be applied directly to material which chars with the strong sulphuric 
 acid used. In this case preliminar}^ extraction of the lactic acid is necessary. 
 Alcohol should be used as the solvent, or if ether is employed it must first be 
 well washetl to remo\'e aldehvde-yielding products, since the colour-change is 
 due to an aldehyde reaction with thiophene. 
 
CHAPTER XV 
 ELECTRO-PHYSIOLOGY 
 
 A LITTLE more than a hundred years ago the foundation both of electro- 
 physiology' and of the vast science of voltaic electricity was laid by a 
 chance observation of a professor of anatomy in an Italian garden. It 
 is indeed true that long before this electrical fishes were not only 
 popularly known, but the shock of the torpedo had been to a certain 
 extent scientifically studied. But it was with the disco\ cry of Galvani 
 of Bologna that the epoch of fruitful work in electro-physiology began. 
 Engaged in experiments on the effect of static and atmospheric elec- 
 tricity in stimulating animal tissues, he happened one day to notice 
 that some frogs' legs, suspended by copper hooks on an iron railing, 
 twitched whenever the wind brought them into contact with one of 
 the bars (p. 842). He concluded that electrical charges were developed 
 in the animal tissues themselves, and discharged when the circuit was 
 completed. Volta, professor of physics at Pavia, fixing his attention on 
 the fact that in Galvani's experiment the metallic part of the circuit 
 was composed of two metals, maintained that the contact of these was 
 the real origin of the current, and that the tissues served merely as 
 moist conductors to complete the circuit ; and after a controversy lasting 
 for more than a decade, he finally clinched liis argument by constructing 
 the voltaic pile, a series of copper and zinc discs, every two pairs of 
 which were separated by a disc of wet cloth, or paper moistened with salt 
 solution. The pile yielded a continuous current of electricity. ' So,' 
 said Volta, ' it is clear that the tissue in Galvani's experiment only acts 
 the part of the cloth.' Galvani, however, had shown in the meantime 
 that contraction without metals could be obtained by dropping the nerve 
 of a preparation on to the muscle (p. 842) ; and it soon began to be recog- 
 nized that both Galvani and Volta were in part right, that the tissues 
 produce electricity, and that the contact of different metals does so 
 too. Although it is curious to note how completely the growth of 
 that science of which Volta's discovery was the germ has overshadowed 
 the parent tree planted by the hand of Galvani, yet animal electricity 
 has been deeply studied by a large number of observ-ers, and many 
 interesting and important facts have been brought to light. 
 
 Since it is in muscle and nerve that the phenomena of electro- 
 physiology are seen in their simplest expression, and have been 
 chiefly studied, we shall develop the fundamental laws with reference 
 to muscle and nerve alone, and afterwards apply them to other 
 excitable tissues. 
 
 I. All points of an uninjured resting muscle or nerve are approxi- 
 mately at the same potential {or i so- electric). In other words, if any 
 
 822 
 
DEMARCATION CURRENT 
 
 823 
 
 two points are connected with a galvanometer by means of un- 
 polarizable clcctrodos, little or no current is indicated. (Although 
 it is scarcely possible to isolate a muscle without its showing some 
 current, the more carefully the isolation is performed, the feebler 
 is the current; and between two points of the inactive, uninjured 
 ventricle of the frog's heart no electrical difference has been found. 
 Frogs' nerves kept ten to twenty hours after excision in physiological 
 salt solution to which a little calcium salt and frog's blood have 
 been added, are absolutely iso-electric.) 
 
 2. Any uninjured point of a resting muscle or nerve is at a different 
 potential from any injured point. The difference of potential is such 
 that a current will pass through the galvanometer from uninjured to 
 injured point and through the tissue from injured to uninjured point 
 (current of rest, or demarcation current, or injury response) (Fig. 292). 
 
 3. Any unexcjted point of a muscle or nerve is at a different potential 
 from any excited point, and any less excited point is at a different 
 
 Fig. 292. — A, uninjured, B, injured, 
 portion of nerve; G, galvanometer. 
 The large arrows show direction of 
 demarcation current or current of 
 rest, the small arrows direction of 
 negative variation or action current. 
 
 Fig. 293. — Diagram of Currents of 
 Rest in a Regular Muscle, or Muscle 
 Cylinder. E, equator. The dotted 
 lines join points at the same po- 
 tential, between which there is no 
 current. 
 
 potential from any more excited point. The difference of potential 
 is such that a current will pass through the galvanometer to the 
 excited from the unexcited or less excited point (action current, 
 01 negative variation, or excitatory electrical response). 
 
 It has been customary in physiological writings to speak of the 
 electrical change in injured or active tissue as a negative one, because 
 when the tissue is led off to a galvanometer the current passes from 
 the galvanometer to the injured or excited portion of the tissue. 
 It may be called with greater precision ' galvanometrically negative.' 
 It is in this sense that we shall employ the term. 
 
 The best object for experiments on the demarcation current is a 
 straight-fibred muscle like the frog's sartorius. If this muscle be taken, 
 and the ends cut off perpendicularly to the surface, a muscle-prism or 
 muscle-cylinder is obtained (Fig. 2qi). The strongest current is got 
 when one electrode is placed on the middle of either cross-section, and 
 the other on the ' equator ' — that is, on a line passing roimd the longi- 
 tudinal surface midway between the ends. The direction of this 
 current is from the cross-section towards the equator in the muscle. 
 If the electrodes are placed on symmetrical points on each side of the 
 equator, there is no current. 
 
824 ELFXTRO-PHYSIOLOGY 
 
 Current of Action, or Negative Variation. — When a muscle or 
 nerve is excited, an electrical change sweeps over it in the form of 
 a wave. Suppose two points, A and B (Fig. 294), on the longi- 
 tudinal surface of a muscle to be connected with a capillary electro- 
 meter (p. 729), the movements of the mercury being photographed 
 on a travelling surface — for example, a pendulum carrying a sensitive 
 plate. Let the muscle be excited at the end, so that the wave of 
 excitation will be propagated in the direction of the arrow. The 
 wave will reach A first, and while it has not yet reached B, A wall 
 
 Fig. 29 1 . — iJiagram to illustrate Propagation of the Electrical Change along aa 
 Active Muscle or Nerve. Suppose AB to be a horizontal bar representing the 
 muscle or nerve. Let C be a curved piece of wood representing the curve of the 
 electrical change at any point. Let W, W be two glass cylinders connected by 
 a flexible tube, the whole being filled with water. Suppose the rims of the 
 cylinders originally to touch AB at the points A and B, and let them be movable 
 only in the vertical direction. The level of the water being the same in both, 
 there is no tendency for it to flow from one to the other. This represents the resting 
 state of the tissue when A and B are symmetrical points. Now let C be moved 
 along the bar at a uniform rate. The cylinder W, being free to move down, but 
 not horizontally, will be displaced by C, and, if it is kept always in contact with 
 its curved margin, will, after describing the curve of the electrical variation, 
 come again to rest in its old position at A. B will do the same when C reaches 
 it. But since C reaches A before B, the level of the water in B will at first be 
 higher than that in A, and water will flow from B to A as the current Hows 
 through the galvanometer. This will correspond to the time during which the 
 point of the tissue represented by A would be gaivanometrically negative t.) a 
 point represented by B. Later on, when C has reached the position shown by 
 the dotted lines, the level of the water in .•K will be higher than that in B, and a 
 flow will take place in the opposite direction to the first flow. This corresponds 
 to a second phase of the electrical variation. 
 
 become negative to B. If there is a resting difference of potential 
 between A and B, this will be altered, the new and transitory differ- 
 ence adding its«-lf algebraically to the old. When the wave reaches 
 B, it may already have passed over A altogether, and B now be- 
 coming negative to A, there will be a movement of the meniscus 
 of the electrometer in the opposite direction. This is called the 
 
NEGATIVE VARIATION 825 
 
 dipliasic current of action. If the wave has not passed over A before 
 it reaches B, as would in general be the case in an actual experiment, 
 there will be first a period during which A is relatively negative to 
 B (first pliase) ; this will end as soon as B has become iso-electric 
 with A, and will be succeeded by a period during which B is rela- 
 tively negative to A (second phase). Since the wave takes time to 
 reach its maximum, it is evident that a well-marked first phase will 
 be favoured when the interval between its arrival at A and at B is 
 long, for in this case A will have a chance of becoming strongly 
 negative while B is still normal. Similarly, if A has again become 
 normal, or nearly normal, before the maximum negative change has 
 passed over B, a strong second phase will be favoured. The heart- 
 muscle, accordingly, where the wave of contraction, and its accom- 
 panying electrical change, move with comparative slowness, is 
 better suited for showing a well-marked diphasic variation than 
 skeletal muscle, and still better suited than nerve. In the gastroc- 
 
 Fig. 205. — Photuf^raphic Electrometer Curves from Sartorius Muscle (Sanderson). 
 The darkly-shaded curv'e represents the diphasic variation of the uninjured 
 muscle; the lightly-shaded curve the monophasic variation of the muscle after 
 injury of one end. The toothed curve at the top is the time-tracing registered by 
 photographing the prong of a tuning-fork vibrating five hundred times a second. 
 
 nemius muscle of the frog, when excited through its nerve, the elec- 
 trical response begins about y^Vo second, and the change of form of 
 the muscle about yxfvo second, after the stimulation. It is believed 
 that in a muscle directly excited the electrical change begins in less 
 than jjy^jj second, and the mechanical change in iu\x> second (Burdon 
 Sanderson, Figs. 295-300). 
 
 When one electrode is placed on an injured part, the wave of action 
 and of electrical change chminishesas it reaches the injured tissue; 
 and if the tissue is killed at this part, it diminishes to zero; so that 
 here the second phase may be greatly weakened or may disappear 
 altogether, and we then have what is called a monophasic variation. 
 
 In this case the current of action can be demonstrated, even for a 
 single excitation, but .still better for a tetanus, with an ordinary galvan- 
 ometer, which in general is not quick enough to analyze a diphasic 
 variation with equal phases, and gives, therefore, only their algebraic 
 sum — that is, zero. When the muscle or nerve is tetanized, the action 
 current appears, while stimulation is kept up, as a permanent deflection 
 representing the ' sum ' of the separate eftects. It is in the opposite 
 direction to the current ot rest, since the injured tissue, being less 
 
Pz6 
 
 ELECTRO-PHYSIOLOGY 
 
 affected by the excitation, and therefore undcrg.oing a smaller negative 
 change than the uninjured, becomes relatively to the latter less nega- 
 tive. Appearing as a diminution or reversal of the current of rest, it was 
 called the negative variation. The term negative is not used here in 
 its electrical, but in its algebraic, sense, and merely as indicating the 
 direction of the current with reference to that of the demarcation 
 current. It is in this sense that ' negative variation ' and the converse 
 term, ' positive variation,' are used (pp. 838, 8jc)) in speaking of the 
 electrical changes produced in glands and in the retina by stimulation. 
 
 jn^j-yryr^j^ 
 
 Fig. 2q6. — 'Spike' (Diphasic Variation) of Uninjured 
 Gastrocnemius (Sanderson). 
 
 A photographed on slow, B on fast-moving, plate. 
 
 Fig. 297. — Variation of In- 
 jured Gastrocnemius (San- 
 derson). A 'spike' fol- 
 lowed by a ' hump.' 
 
 Fig. 298. — Variation of Injured Gas- 
 trocnemius (Sanderson). The plate 
 was moving ten times faster than in 
 Fig. 297. 
 
 Fig. 299. — Variation of Uninjured 
 Muscle excited Eighty-Four Times 
 a Second (Sanderson). 
 
 pjg 300. — Curve of an Injured Muscle excited Sixty Times a Second (Sanderson). 
 
NEGATIVE VARIATION 827 
 
 When the current of rest is compensated by a branch of an external 
 current just sufficient to balance it and bring the galvanometer image 
 back to zero (Fig. 234, p. 727), the action current appears alone in un- 
 diminished strength. This shows that the latter is not due to a change 
 of electrical resistance during excitation, since such a change would 
 equally alYect current of rest and compensating current, and they would 
 still balance each other. The action current is really due to a change 
 of potential, which can be measured by determining what electro- 
 motive force is just required to balance it, and which may actually 
 exceed that of the current of rest. Thus, Sanderson and Gotch obtained 
 an average of 0-08 of a Daniell cell (the electromotive force of the 
 Daniell would be about a volt) as the electromotive force of the action 
 current due to a single indirect excitation of a vigorous frog's gastroc- 
 nemius, and about 0-04 Daniell as that of the current of rest. The 
 electromotive force of the current of rest in the rabbit's nerve was 
 found by du Bois-Reymond to be 0-026; Gotch and Horsley found the 
 average for the cat o-oi, and for the monkey only 0*005. 
 
 That the fusion of the successive variations of a tetanized muscle, 
 as seen with an ordinary galvanometer, is only apparent has been 
 shown by means of the capillary electrometer or the string galvanometer. 
 Even with a frequency of stimulation far beyond what is necessary for 
 complete tetanus, each stimulus is answered by a movement of the 
 meniscus (Figs. 299, 300). In nerve, also, each of two successive 
 stimuli causes its appropriate electrical change when they are separated 
 by an interval longer than a certain small fraction of a second. The 
 precise interval at which the second stimulus ceases to be effective 
 depends on the temperature of the nerve, being markedly increased by 
 cold (Gotch and Burch) . 
 
 The rate of propagation of the electrical change in muscle is the 
 same as that of the mechanical change, and in nerve the same as that 
 of the nervous impulse. The velocity of propagation of the diphasic 
 variation along a fresh sartorius at 14° C. was in one experiment 
 2-8 metres, in another at 18° C, 3*5 metres (Sanderson). (See p. 759.) 
 Lucas has pointed out that in strict accuracy what is observed is merely 
 that the time interval separating contraction at one point of the muscle 
 from contraction at another is equal to the time interval separating 
 the electrical changes which occur at the same points. The facts 
 observed do not formally prove that either the contraction or the elec- 
 trical disturbance is propagated at all. So far as they go, some other 
 perfectly distinct change may be propagated, which at all points of the 
 fibre at which it arrives sets up both the contraction and the electrical 
 change. Such direct evidence, however, as we possess goes to show 
 that it is the electrical disturbance which is the propagated one, and 
 that this evokes the contractile disturbance. 
 
 There is ample evidence that the excitatory electrical response 
 is a normal physiological phenomenon. In human skeletal muscles 
 the current of action has been demonstrated by connecting a gal- 
 vanometer with ring electrodes passing round the forearm, and 
 throwing the muscles into contraction. A diphasic variation is thus 
 obtained; and the electrical change travels with a velocity of as 
 much as twelve metres per second, which is greater than the velocity 
 in frogs' muscles. Electromotive changes are likewise associated 
 with the beat of the heart. Action currents have also been detected 
 in the phrenic nerves of living animals accompanying the respiratory 
 
828 
 
 ELECTRO-PHYSIOLOG Y 
 
 discharge (Reid and Macdonald), in the vagi accompanvnng the 
 movements of the lungs, in the oesophagus during swallowing, in 
 the cutaneous sensory nerves in response to the ' adequate ' stimulus 
 of pressure (Steinach), in the retina in response to the adequate 
 stimulus of light, in glands during secretion, in the central nervous 
 s^'stem during the passage of impulses along its conducting paths. 
 Some of these will be further considered a little later on. 
 
 As to the interpretation of the facts we have been describing, 
 and which are summed up in the three propositions on p. S2i, two 
 chief doctrines long divided the physiological world: (i) the theory of 
 du Bois-Revmond, the pioneer of electro-physiolog}-, and (2) the theory 
 of Hermann. It was believed by du Bois-Reymond that the current 
 of rest seen in injured tissues is of deep physiological import, and that 
 the electrical difference which gives 
 rise to it is not developed by the 
 lesion as such, but only unmasked 
 when the electrical balance is upset 
 by injury. He looked upon the 
 muscle or nerve as built up of elec- 
 tromotive particles, with definite 
 positive and negative surfaces ar- 
 ranged in a regular manner in a sort 
 of ground-substance which is elec- 
 trically indifferent. The ' negative 
 variation' he supposed to depend en 
 an actual diminution of previously 
 existing electromotive forces; and 
 from this conception arose its his- 
 toric name. Hermann and his school 
 assumed that the uninjured muscle 
 or nerve is ' streamless,' not because 
 equal and opposite electromotive 
 forces exactly balance each other in 
 the substance of the tissue, but be- 
 cause electromotive forces are absent 
 until they are called into existence 
 (by chemical changes) at the boun- 
 dary, or plane of demarcation, be- 
 tween sound and injured tissue. For this reason du Bois-Reymond 's 
 current of rest is called in the terminology of Hermann the ' demarca- 
 tion ' current. 
 
 The newer theories, such as Macdonald's, have sought to take account 
 of the recent developments of physical chemistn,'. and it is unquestion- 
 able that it is here the real explanation is to be found. There is little 
 doubt that the electrical phenomena of the tissues are connected with 
 the existence in them of membranes, envelopes, or sheaths, physiological 
 if not always anatomical, which are relati\ely impermeable to certain 
 ions. When such a sheath is injured, these ions, carrying with them 
 their electrical charges, may be supposed to migrate with abnormal 
 freedom through the injured part. A new distribution of electricity is 
 thus established in the tissue, and differences of potential depending 
 uiKjn differences in the concentration of the ions at different points are 
 set up. Bernstein and Tschermak. from an investigation of the thermo- 
 d\-namic relations of bio-electrical currents, have come to the conclusior 
 that they are analogous to the currents produced by so-called concentra- 
 
 Fig 301. — Upper Curve, Record ul iLe 
 Electrical Changes in the Vagtis 
 N'er\'e (so-called ' Electrovagogram '), 
 taken with the String Galvanometer. 
 The small waves on it are s\-nchronous 
 with the heart-beats, while the large 
 waves are s>-nchronous with the respi- 
 ratory movements, the mechanical 
 record of which constitutes the 
 second curve (ascent, inspiratioi.). 
 The lowest curve is a mechanical 
 record of the pulse (Einthoven). 
 
THEORIES OF DEMARCATION AND ACTION CURRENTS 829 
 
 tion cells — i.e.. arrangements of solutions of electrolytes of different 
 concentration in contact with each other. Since the development of 
 the new electrical condition depends upon the fundamental structure 
 of the tissue, these modern views lead us back to du Bois-Reymond's 
 doctrine of a pre-existing electrical equilibrium connected with the 
 essential physiological properties of muscle or nerve. But instead of 
 his electromotive elements and their definite arrangement, we have 
 the ions and their dciinite relation to the semi-pormcable membranes. 
 
 Relation between the Action Current and Functional Activity. — 
 Although the negative variation is so general an accompaniment of 
 excitation, and is even within tolerably wide limits, in muscle and nerve 
 at least, pretty nearly proportional to the strength of the stimulus, it 
 is at present impossible to say definitely what the chemical or physical 
 changes are which underlie it. Unquestionably the electrical changes 
 are closely related to the excitatory process and to the functional 
 activity of the tissues. In the case of nerve some writers, indeed, 
 assume that the redistribution of potential associated with the excited 
 state is identical with the nervous impulse, but the common view is 
 that the negative variation is an accompaniment of some other change 
 which constitutes the propagated disturbance. There is at present no 
 clear experimental evidence sufficient to decide the question. From 
 time to time attempts have been made to show that the two processes 
 can be dissociated, but none of the experiments so far reported are 
 really crucial. 
 
 Like the demarcation current, the action current and the excitation 
 which accompanies it may be due to changes in the permeability of 
 membranes or changes in the concentration of certain ions. 
 
 Although the electromotive changes caused by excitation are much 
 more transient than those caused by injury, everything suggests that 
 there must be some deep analogy between the two conditions. Some 
 have supposed that what may be called a subdued and more or less 
 permanent excitation exists in the neighbourhood of the injured tissue, 
 an excitation which, like some other forms, does not spread, and that 
 this explains the similarity of electrical condition in activity and injury. 
 
 It is, of course, clear that energy must be transformed to produce an 
 electromotive force capable of doing work. It may be assumed that 
 this energy is ultimately derived from the stock of chemical energy in 
 the tissue-substance. But whether in the final transformation the 
 electrical phenomena are the expression of chemical changes or of 
 physical (osmotic) changes, or of both, we do not know. In the case of 
 muscle it is possible that the liberation cf lactic acid, which there are 
 several reasons for regarding as essentially concerned in the initiation 
 of the mechanical change, is associated in some way with the appearance 
 of tlie negative variation. It is known that the latter, although it 
 begins before the contraction, and very rapidly reaches its maximum, 
 declines more gradually, so that it overlaps the mechanical change of 
 form. This is particularly well seen in veratrinized muscles (p. 755), in 
 which the electrical variation, like the contraction, is greatly prolonged 
 (Garten). 
 
 Polarization of Muscle and Nerve. — We have already spoken of 
 electrical excitation and of the changes of excitabihty caused by 
 the passage of a constant current (p. 785). We are now to see that 
 these physiological effects are accompanied by, and indeed very 
 closely related to, more physical changes which the galvanometer 
 or electrometer reveals to us. Since these throw light on the 
 
Sjo electro-ph ysiolog y 
 
 physical, and therefore ultimately on the physiological, structure of 
 the tissues, they have been deeply studied, especially in nerve. 
 There is no question that they depend upon the presence in the 
 tissues of membranes presenting a relatively great resistance to the 
 passage of ions. When a current is passed by means of unpoJarizable 
 electrodes (Fig. 238, p. 731) through a muscle or nerve for several 
 seconds, and the tissue connected to the galvanometer immediately 
 after this polarizing current is opened, a deflection is seen indicating 
 a current (negative polarization current) in the opposite direction. 
 
 This (negative) polarization, like the polarization of the electrodes 
 seen after passage of a current through any ordinary electrolytic con- 
 ductor, dilute sulphuric acid, e.g., depends on the liberation of ions 
 (p. 429) at the kathode and anode. It is seen not only in muscle, nerve, 
 and other animal tissues, but also in vegetable structures, and indeed, 
 to a certain extent, in unorganized porous bodies soaked with electro- 
 lytes. In muscle and nerve, however, it is particularly well marked; 
 and although it is not bound up with the life of tiie tissue, and may be 
 obtained when this has become c]uite inexcitable, it is nevertheless 
 dependent on the preservation of the normal structure, for a boiled 
 muscle shows but little negative polarization. 
 
 When the polarizing current is strong, and its time of closure short, 
 we obtain, on connecting the tissue with the galvanometer after opening 
 the current, not a negative, but a positive deflection, indicating a 
 current in the same direction as that of the polarizing stream. This is 
 really an action stream, due to the opening excitation set up at the 
 anode (p. 741). It is only obtained when the tissue is living, and is far 
 more strongly marked in the anodic than in the kathodic region. 
 
 Suppose that the nerve in Fig. 302 is stimulated by the opening of 
 the battery B, and that, immediately after, the nerve is connected with 
 the galvanometer G by the electrodes E, Ej. Suppose, further, that 
 the shaded region near the anode remains more excited for a short time 
 than the rest of the nerve, and we have seen (p. 787) that after the 
 opening of a strong current there is a delect of conductivity, especially 
 in the neighbourhocd of the anode, which would tend to localize excita- 
 tion. An action current will pass through the galvanometer from Ej 
 to E, and through the nerve in the same direction as the original stimu- 
 lating stream. Under certain conditions a state of continuous excita- 
 tion in the ancdic region of a nerve is shown by a tetanus of its muscle 
 (Hitler's tetanus, p. 741, and Fig. 303). 
 
 Electrotonic Currents. — If a current be passed from the battery 
 through a medullated nerve (Fig 304) in the direction indicated by 
 the arrows, while a galvanometer is connected with either of the 
 extrapolar areas, as shown in the figure, a current will pass through 
 the galvanometer, in the same direction in the nerve as the polar- 
 izing current, so long as the latter continues to flow. 
 
 These currents are called electrotonic (in the kathodic region katelectro- 
 lonic , in the anodic, anelectrotonic). The exact mode of their produc- 
 tion is obscure. Similar currents can be detected in artificial models 
 consisting of a good conducting core and a badiv conducting envelope; 
 for example, a platinum wire in a ghiss tube filled with saturated zinc 
 sulphate solution, or a zinc wire covered with cotton-wool soaked in 
 salt solution. In such models it appears to be essential that there 
 
ELECTROTOKIC CVRRESTS 
 
 83t 
 
 should be polarization (separation of ions) at the i)Oiinclary between 
 the core anrl the sheath — i.e., between the wire and the liquid, where 
 the current passes from the one to the other. 
 
 A current led into the sheath tries, so to speak, to pass mostly by 
 the good ccnductiiiy wire. if this is not pohirizable - if it is, e.s,., a 
 
 Fig, 30J. — Diagram to show Dis- 
 tribution of ' Positive Polar- 
 zation ' after opening Polar- 
 izing Current. B, battery; 
 G, galvanometer. The dark 
 shading signifies that the ex- 
 citation to which the current 
 causing the positive deflection 
 after the opcTiing of the polar- 
 izing current is due is greatest 
 in the immediate neighbour- 
 hood of the anode, and fades 
 away in the intrapolar region. 
 ■+■ indicates the anode, and 
 — the kathode of the polariz- 
 ing current. 
 
 Fig. 303.— Ritter's Tetanus. 
 A strong voltaic current 
 was passed for some time 
 through the nerve of a 
 muscle - nerve preparation. 
 On opening the circuit, the 
 muscle gave one strong con- 
 traction, and then entered 
 into irregular tetanus, which 
 continued for four minutes. 
 (Only the first part of the 
 tracing is reproduced.) 
 
 zinc wire surrounded by saturated zinc sulphate solution — there is 
 little or no spreading of the current outside the electrodes: it passes at 
 once into the core, and so on to the other electrode. If, howe\er, there 
 is polarization when the current passes from the liquid into the wire, 
 as is the case in the platinum-zinc sulphate or the zinc -sodium chloride 
 
 combinations, the stream 
 spreads longitudinally in 
 the sheath, since the 
 polarization introduces a 
 virtual resistance at the 
 surface of the wire, in 
 comparison with which 
 the difference in resis- 
 tance of an oblique and a 
 direct transverse path 
 through the liquid becomes small. It has been supposed that in 
 medullated nerve a similar polarization takes place at the boundary 
 between some part of the nerve-fibre which may be called a core, and 
 another part which may be called a sheath — for instance, between the 
 axis-cylinder and the medullary sheath, or between the latter and the 
 neurilemma. It is known that the electrical resistance of nerve in the 
 
 ^€H ,-f-^"k, . ,^>. 
 
 Fig. 304. — Diagram showing Direction of the Extra- 
 polar Electrotonic Currents, -f is the anode 
 and - the kathode of the polarizing current. 
 
832 ELECTRO-PHYSIOLOGY 
 
 transverse direction is much greater (five to seven times)* than the 
 longitudinal resistance. Since a rapidly-established polarization would, 
 by the ordinary methods of measurement, appear as a resistance, this 
 has been adduced as evidence of the great capacity of nerve for polar- 
 ization by a current passing across the fibres. It is, however, probable, 
 from what we know of the high electrical resistance of the physiological 
 envelopes of such cells as the red blood-corpuscles (p. 26), that the 
 great transverse resistance of nerve, and indeed the electrotonic currents, 
 are due in part, if not wholly, to the true resistance of one or more of 
 its envelopes (perhaps the medullary sheath). Examples of such 
 differences of resistance even in the fluid constituents of one and the 
 same animal structure are not wanting. For instance, the specific 
 resistance of the yolk of a hen's egg may be three times greater than 
 that of the white. 
 
 The electrotonic currents cannot spread beyond a ligature; they are 
 stopped by anything which destroys the structure of the tissue; they 
 are affected by various reagents. But this does not prove that they 
 are other than physical in origin, for what destroys the structure of 
 the tissue or modifies its molecular condition may destroy or diminish 
 its capacity for polarization, or alter its electrical resistance. 
 
 There are, however, certain facts which indicate that physiological 
 factors, as well as physical, are concerned. While the currents obtained 
 from core-models show a general resemblance to the electrotonic currents 
 of medullated nerve, there is one significant difference: in the former the 
 katelectrotonic and anelectrotonic currents arc of equal intensity; in 
 the latter the anelectrotonic preponderates. The most probable eX' 
 planation is that the anelectrotonic current of medullated nerve is made 
 up of two distinct electrical effects, one physiological in nature, the other 
 dependent merely on the structure and physical properties of the fibres, 
 while the katelectrotonic current is wholly physical. It is in favour of 
 this hypothesis that under the infironce of ether, which abolishes the 
 physiological functions of nerve, the anelectrotonic current diminishes 
 till it becomes equal to the kateletrotonic. Non-medullated nerves, in 
 which the conditions for physical electrotonus, if present at all, are only 
 feebly developed, and which exhibit no katelectrotonic current, or only 
 a very weak one, show an anelectrotonic current, which is abolished by 
 ether, and seems to represent the physiological portion of the anelectro- 
 tonic current of medullated nerve. 
 
 A nerve may be stimulated by an electrotonic current produced 
 in nerve-fibres lying in contact with it. A well-known illustration 
 of this is the experiment known as the paradoxical contraction 
 (Practical Exercises, p. 84-I). 
 
 The current of action of a nerve can also stimulate another nerve 
 when the excitability of both is greater than normal, as is the case 
 in the nerves of frogs kept in the cold. This comes under the head 
 of secondary contraction. But the best-known form of secondary 
 contraction is where a nerve, placed on a muscle so as to touch it in 
 two points (Fig. 305), is stimulated by the action-current of the 
 muscle, and causes its own muscle to contract. A secondary tetanus 
 
 * Since a part of the current is conducted by the connective tissue and 
 other structures lying between the nerve-ftbres, and the long;itudinaI and 
 transverse resistance of these tissues may be supposed equal, the disproportion 
 between the longitudinal and transverse resistance of the nerve fibres them- 
 selves is probably much greater than this. 
 
ELECTROTONIC CURRENTS 
 
 833 
 
 can be obtained in this way by dropping a nerve on an artificially 
 tetanized muscle. The beat of the heart causes usually only a 
 single secondary contraction when the sciatic nerve of a frog is 
 allowed to fall on it (p. 203). But when the diphasic variation is 
 well marked, as it is in an uninjured heart, there may be a secondary 
 contraction for each phase — 
 i.e., two for each heart-beat. 
 Excitation of one muscle may in 
 the same way cause secondary 
 contraction of another with 
 which it is in close contact. 
 
 I 
 
 
 Fig. 305. — Secondary Coutrax:- 
 tioa. The nerve of muscle M 
 touches muscle M' at a and h. 
 Stimulation of the nerve of M' 
 at S causes contraction of M. 
 
 Fig. 306. — : ; r^' rd from Rab- 
 
 bit's Heart {(j'.trh). the lieart was ex- 
 posed and beating in situ. Contacts, one 
 on base of right ventricle, the other on 
 right apex. The commencement of the 
 beat is on the left-hand edge of the dark 
 line V. The length of the dark line shows 
 the duration of the beat. Upward move- 
 ment signifies relative negativity (activity) 
 of the part at or near the base contact. 
 Time-trace at tou, one-fifth second. 
 
 The electromotive phenomena of the heart and of the central ner- 
 vous system are naturally included under those of muscle and nerve. 
 
 Heart. — Records of the electrical changes obtained with the 
 capillary electrometer or string galvanometer from the exposed 
 ventricles vary in certain details with the position of the two 
 contacts. When one contact is on the base of the ventricles (in the 
 rabbit) near the auriculo-ventricular groove, and the other on the 
 apex (Fig. 306), for each beat of the ventricle the electrometer record 
 shows (i) a sharp rise, indicating relative negativity (activity) of 
 the base ; (2) an equally sharp fall, indicating relative negativity at 
 the apex; (3) a slower but marked rise, indicating an increase or a 
 fresh development of relative negativity at the base; (4) a more 
 rapid fall, which returns first slowly, then quickly, until (i) follows 
 again (Gotch). The time between the beginning and the top of 
 rise (i) I's believed to correspond to the time of transmission of the 
 
 53 
 
834 
 
 ELECT RO-PH YSIOLOG Y 
 
 active state from the base to the apex. The rate of propagation 
 on the rabbit's ventricle varies from i to 3 metres a second, accord- 
 ing to the rate of the heart-beat. Such observations have been inter- 
 preted as indicating that the excitation, with its accompanying 
 electrical change, begins at the base, then develops in the region of 
 the apex, and finally involves the poition of the ventricles near the 
 aorta and pulmonary artery, possibly extending even into the roots 
 of these vessels. The full explanation of this seemingly erratic 
 course of the excitation wave is doubtless dependent upon a full 
 knowledge of the course and connections of the conducting system. 
 
 Fig. 307. — Electrometer Record from Tortoise Heart (Gotck). Out contact upon 
 the sinus, the other on the ape.x oi the '.entricle. One complete beat shown. 
 Upward movement signifies relative negativity of the sinus contact. The dark 
 line A shows the auricular effect, and the dark line V the ventricular effect. 
 Time-trace at top, one-&fth second. 
 
 and this we do not possess as yet. The fact that the ventricle is 
 originally developed from a tube with a venous and an arterial end, 
 and that this tube later on becomes bent upon itself so that the two 
 ends (the auricular or venous and the aortic or arterial) lie together 
 at the base of the ventricle, probably affords the clue. It should 
 be mentioned, however, that this explanation of the second rise of 
 the ventricular ciu"ve (the T-wave, according to Einthoven's nomen- 
 clature. Fig. 313) is by no means universally accepted. Einthoven, 
 who has worked with the string galvanometer, believes that be- 
 tween the first (R) and the second (T) ventricular waves the whole 
 of the ventricle is in contraction, and that there is no difference of 
 
ELECTRO-CA RDIOGRA M 
 
 «35 
 
 1 
 
 Fig. 308. — Electro-Cardiograms from Man 
 (Capillary Electrometer) (Einthoven and 
 Lint). Obtained from the same individual 
 at rest (upper curve), and immediately after 
 vigorous muscular exercise (lower curve). 
 The elevations A, C, D, indicate negativity 
 of base to ape.x; the notches B and C^, nega- 
 tivity of apex to base. 
 
 potential at this time between its various parts. The T-wave he 
 considers to be produced, when it is present, merely because the 
 
 excitated state does not dis- 
 appear simultaneously over 
 the whole ventricle. 
 
 In the ventricle of the 
 frog and tortoise the same 
 order of development of the 
 negative change is seen, the 
 base first becoming rela- 
 tively negative, then the 
 apex, and then the neigh- 
 bourhood of the origin of 
 the aorta (Fig. 307). 
 
 Under certain conditions 
 the action current of the heart 
 may stimulate the phrenic 
 nerves, causing the dia- 
 phragm to contract sjTichro- 
 nously with the heart. 
 
 The Human Electro- Cardi- 
 ogram. — An electrical change 
 accompanies each beat of the human heart. Waller first showed how 
 this may be demonstrated by means of the capillary electrometer. 
 
 Einthoven and 
 Lint then investi- 
 gated the pheno- 
 menon on a large 
 numberof persons. 
 From the photo- 
 graphic records of 
 the movements of 
 the meniscus they 
 constructed the 
 true electro - car- 
 diographic curves* 
 (Fig. 309;, which 
 express the actual 
 changes in the po- 
 tential difference 
 between the two 
 points led ofif. 
 They distinguished 
 in every one of 
 these constructed 
 electro-cardio- 
 grams five points 
 or cusps, three of 
 which indicate re- 
 lative negativity 
 
 Fig. 309, — Constructed Elec- 
 tro-Cardiograms from Man 
 (EinthovenandLint). Time 
 is laid off along the hori- 
 zontal, and electromotive 
 force along the vertical axis, 
 the same space being allot- 
 ted to ten millivolts (i.e., 
 Y^ volt) as to one second. 
 
 Fig. 310. — Illustrating the 
 Position of Favourable and 
 Unfavourable Leads for 
 the Human Electro- 
 Cardiogram (Waller). 
 
 * In all accurate work with the capillary electrometer such curves must be 
 obtained by construction from the direct photographic records, which do not 
 themselves give an absolutely true picture of the variations. 
 
836 
 
 ELECT RO-PH YSIOLOG Y 
 
 of tlie base of the heart to the apex, and two negativity of the apex to 
 the base. The capillary electrometer hns now been superseded by the 
 string galvanometer (p. '726) for the investigation of the human electro- 
 cardiogram (Figs. 311-315). But a sample of the records obtained by 
 the former method (Fig. 308), witli the corresponding constructed 
 
 Fig. 311. — Human Electro-Cardiogram 
 (String Galvanometer) (Einthoven). 
 Led off from the two hands, i mm. 
 of the abscissa corresponds to 00 1 
 second. 
 
 Fig. 312. — Human Electro-Cardio- 
 gram (String (ialvanoraeter) 
 (Einthoven). Led off from right 
 hand and left foot. 
 
 0,1 Sec 
 
 FJ§- 313- — Schematic Representation of Electro-Cardiogram (String Galvanometer) 
 (Einthoven). Five points are lettered at which the curve changes sign. P cor- 
 responds to the auricular contraction; the other four are included in the ven- 
 tricular cycle. 
 
 Fig. 314.— Electro-Cardiogram from Man (String Galvanometer) (Lewis). From a 
 case of paroxysmal tachycardia. The heart-rate was 200 a minute. The upper 
 notched line is the time-trace in one-fifth seconds. 
 
 electro -cardiograms, (Fig. 309) is reproduced for their historical interest. 
 In their main features it is obvious that they agree with the records 
 obtained by the string galvanometer. The electro-cardiograms are 
 distinctly affected by exercise and by the position of the body, and very 
 markedly in disease. The galvanometer may be connected with the two 
 
ELECTRO-CA R DIOCRA M 
 
 837 
 
 liands, or, bettor, wilh the ri},'lit hand and the loft foot. Tlic two feet 
 arc the most unfavourable oombination. The reason is obvious from 
 the (lireetion of the long axis of the heart, which determines the 
 direction of the lines of flow of currents due to differences of potential 
 between base and apex (I'Mg. },\o). 
 
 Relation of the Waves of the Electro-Cardiogram to the Mechanical 
 Events in the Cardiac Cycle. Tlioro is ovidonco that the excitation pro- 
 cess with its associated electrical change spreads over the auricle from the 
 sinus mxle, followed at each point by the mechanical change or contrac- 
 tion, in such a manner that the portions nearer the node begin to relax 
 before the more distal units have finished contracting. When a tracing 
 of the approximation of two distant points of the auricle is taken, 
 the total shortening represents the algebraic sum of the contractions 
 and relaxations of all the muscular units between the two points. 
 
 '^^^m^J' 
 
 Fig- 315— Upper curve, pressure in right auricle. Second curve from top, right 
 auricular myogram; the down-stroke corresponds to contraction. Third curve, 
 ventricular sounds. Bottom curve, electrocardiogram, lead // (left hind and 
 right fore leg) (Wiggers). 
 
 Electrical effects obtained by leading off from the heart in any particu- 
 lar way must also be more or less complex resultants of the changes at 
 different points. Certain general relations, however, have been estab- 
 lished between the mechanical events and the electro-cardiogram. In 
 Fig; 31.5 are shown simultaneous records of the contraction of the 
 auricle (auricular myogram), the intra-auricular pressure, the heart 
 sounds and the electro-cardiogram (Wiggers). The first electrical 
 variation, commencing at i, is seen to precede the rise of pressure in 
 the auricle, 2, by a definite interval (about 002 sec), and the onset of 
 the mechanical shortening ,3, by a somewhat greater interval (o-o^ sec). 
 The length of these intervals is, of course, not precisely the same in 
 different experiments. 
 
 The relation of the beginning of the rise of intra-auricular pressure 
 and of the beginning of the mechanical systole of the auricles to the 
 
838 ELECTRO-PHYSIOLOGY 
 
 P wave of the electro-cardiogram (the wave specially associated with 
 the passage of excitation over the auricle) is also slightly variable. 
 Roughly, the apex of the P wave may be taken as mdicating the onset 
 of the auricular systole. The relation l^etwcen the end of the auricular 
 systole, 4, and the electro-cardiogram, is still more variable, but in 
 general it falls not far from the summit of the R wave (a wave specially 
 associated with the passage of the excitation over the ventricle). This 
 shows that the auricular systole still continues at a time when the ex- 
 citation process has already made considerable progress in the ventricle. 
 The mechanical contraction of the ventricle, as shown in Fig. 315, bv 
 the position of the vibrations corresponding to the first sound, follows 
 very promptly the completion of the auricular svstole. 
 
 Central Nervous System. — It was discovered by du Bois-Rej-mond 
 that the spmal cord, like a nerve, shows a current of rest between longi- 
 tudinal surface and cross-section, and that a current of action is caused 
 by excitation. Setschenow stated that when the medulla oblongata 
 of the frog was connected with a galvanometer, spontaneous variations 
 occurred which he supposed due to periodic functional changes in its 
 grey matter. Gotch and Horsley have made experiments on the spinal 
 cords of cats and monkeys. Leading off from an isolated portion of 
 the dorsal cord to the capillary electrometer, and stimulating the 
 ' motor ' region of the cortex cerebri, they obtained a persistent nega- 
 tive variation followed by a series of intermittent variations. This 
 agrees remarkably with the muscular contractions in an epileptiform 
 convulsion started bv a similar excitation of the cortex, which consist 
 of a tonic spasm followed by clonic or phasic (interrupted) contractions. 
 By means of the galvanometer, the same observers have made in- 
 vestigations on the paths by which impulses set up at different points 
 travel along the cord. To these we shall have to refer again (p. 893). 
 
 Electrical Phenomena of Glands. — These have been studied with any 
 care chiefly in the submaxillary gland and in the skin, although the 
 liver, kidney, spleen, and other organs also 
 show currents when injured. In the sub- 
 maxillary gland the hilus is galvanometrically 
 positive to any point on the external surface 
 of the gland : a current passes from hilus to 
 surface through the galvanometer, and from 
 surface to hilus through the gland (Fig. 316). 
 Fig. 316. — Current of Sub- When the chorda tvmpani is stimulated with 
 maxillary Gland. rapidly - succeeding shocks of moderate 
 
 strength, there is a positive variation — i.e.. the 
 hilus becomes still more positive to the surface. This variation can 
 be abolished by a small dose of atropine. 
 
 Skin Currents. — So far as has been investigated, the integument of all 
 animals shows a permanent current passing in the skin from the external 
 surface inwards. This is feebler in skin which possesses no glands. In 
 skin containing glands the current is chiefly, but not altogether, secre- 
 tory. As such, it is affected by influences which affect secretion, a 
 positive variation being caused by excitation of secretorv nerves — e.g., 
 in the pad of the cat's foot by stimulation of the sciatic. The deflection 
 obtained when a finger of each liand is led off to the galvanometer, 
 which was at one time looked upon as a proof of the existence of currents 
 of rest in intact muscles, is due to a secretion current. 
 
 Of more doubtful origin is the current of ciliated mucous membrane, 
 which has the same direction as that of the skin of the frog and the 
 mucous membrane of the stomach of the frog and the rabbit — viz., from 
 ciliated to under surface through the tissue, or from ciliated surface to 
 cross-section, if that is the way in which it is led off. The current is 
 
ELECTROMOTIVE PHr:\OMi:XA OF THE EYE 
 
 830 
 
 strengthened by induction shocks, by heating, and in general by influ- 
 ences which increase the activity of the cilia. Some circumstances 
 point to tlie gobiet-cells in the membrane as the source of the current; 
 but, on the whole, the balance of evidence is in favour of the cilia V)cing 
 the chief factor (Engelmann), although the mucin-sccreting cells may 
 be concerned, too. Klectrical changes associated with secretion have 
 been observed in the frog's tongue on excitation of the glosso-pharyngeal 
 nerve. 
 
 Eye-Currents. — If two unpolarizable electrodes connected with a 
 galvanometer are placed on the excised eye of a frog or rabbit, one on 
 the cornea and the other on the cut optic nerve, or on the posterior 
 surface of the eyeball, it is found that a current passes in the eye from 
 optic nerve to cornea, the fundus of the eye being therefore negative 
 as regards the cornea (Fig. 317). The current has the same direction 
 if the anterior electrode is placed on the an- 
 terior surface of the retina itself, the front of 
 the eyeball being cut away, or if one electrode 
 is in contact with the anterior and the other 
 with the posterior surface of the isolate, d 
 retina. There is nothing of special interest in 
 this; but the important point is that if light be 
 now allowed to fall upon the eye, or upon the 
 isolated retina, characteristic electrical changes 
 are caused. These are spoken of as the photo- 
 electric reaction, and are best studied by means 
 of the string galvanometer. The features of 
 the curve representing the photo-electric reaction vary with the duration 
 and intensity of the illumination and with the previous condition of tlie 
 eye as regards illumination. A careful analysis of the curves obtained 
 under different conditions supports the hypothesis that there occur in 
 the eye three separate processes, which may for convenience be con- 
 sidered to depend upon the existence in the retina of three separate 
 photo-chemical substances. When light of moderate intensity is 
 allowed to act upon an eye which has not shortly before been exposed 
 
 3 17. — E ye -Current . 
 
 Pig, 318.— Photo-Electric Reaction of Frog's Eye (Einthoven and Jolly). The 
 duration of the flash (of green light) wasooi second. The eye had been pre- 
 viously in the dark, i millimetre of the abscissa corresponds to 05 second, 
 I millimetre of the ordinate to 10 microvolts. Curve to be read from left to right. 
 
 to strong light, a form of curve is obtained which seems to represent 
 the combined reaction of the three substances (Einthoven and Jolly) 
 (Fig. 318). After a latent period a small preliminary negative deflec- 
 tion A is observed (downward movement of the string). This is at once 
 
840 
 
 ELECTROPHYSIOLOGY 
 
 followed by a mivch larger upward movement (positive variation) in 
 the same direction as the resting effect, the fundujp becoming relatively 
 more negative to the cornea than before. After the peak B has been 
 reached, the curve sinks first rapidly, then more gradually, but soon 
 mounts again, and reaches a second maximum C, vhich is higher than B 
 (second positive variation). Finally, the curve descends to its original 
 level.* The photo-electric reaction is substantially the same in all 
 vertebrate eyes hitherto investigated. In the cephalopcd retina, too, 
 the only imj)ortant electrical change on illumination is in the same 
 direction as the resting effect. 
 
 The reaction depends upon the retina alone, nnd does not occur 
 when it is removed. Blenching of the visual purple docs not much 
 affect it, so that it is not connected with chemical changes in this 
 substance. Its seat must be the layer of rods find cones, since in the 
 
 Fig. 319. — Diagram showing iJircction of Shock in Gyninotus. 
 
 cephalopods the structure called the retina contains only this layer, the 
 other layers of the vertebrate retina being represented in the optic nerve 
 and ganglion (Beck). Of the spectral colours, yellow light causes the 
 largest variation; blue, the least; but white light is more powerful than 
 either (Dewar and McKendrick). (For' visual purple,' seeC hap. XVIII.) 
 Electric Fishes. — Except lightning, the shocks of these fishes were 
 probably the first manifestations of electricity observed by man. The 
 Torpedo, or electrical ray, of the coasts of Europe was known to the 
 Crocks and Romans. It is mentioned in the writings of Aristotle and 
 
 Pliny, and had the honour of 
 being described in verse 1,500 
 years before Faraday made the 
 first really exact investigation 
 of the shock of the Gymnotus, 
 or electric eel, of South America. 
 Another of the electric fishes, 
 Malapterurus clectricus, al- 
 though found in many of the 
 African rivers, the Nile in par- 
 ticular, and known forages, was 
 scarcely investigated till fifty 
 years ago. 
 
 In all these fishes there is a 
 special bilateral organ immediately under the skin, called the electrical 
 organ. It is in this that the shock is developed. It consists of a 
 series of plates arranged parallel to each other. To one side of each 
 plate a branch of the electrical nerve supplying each lateral half of 
 
 * In the figure the last portioD of the curve while it is still slowly descending 
 has not been reproduced. 
 
 320. — Diag.-am showing Direction of 
 Shock in Malapterurus. 
 
ELECTRIC FISHES 841 
 
 the organ is tlistrilnitcd, so that each half of the organ represents a 
 battery of many cells arranged in series. 
 
 In C.ymnotus the plates are vertical, and at right angles to the long 
 axis of the fish, and the nerves are distributed to their posterior surface ; 
 the shock passes in the animal from tail to head. In Malapterurus, 
 although the direction of the plates is the same, and the nerve-supply 
 is also to the posterior surface, the shock passes from head to tail. 
 
 In Torpedo, the plates or septa dividing the vertical hexagonal prisms 
 of which each lateral half of the organ consists are horizontal ; the nerve- 
 supply is to the lower or ventral surface ; and the shock passes from belly 
 to back through the organ. In all electric fishes the discharge is dis- 
 continuous; an active fish may give as many as 200 shocks per second. 
 
 The electrical nerve of Malapterurus is peculiar. It consists of a 
 single gigantic nerve-fibre on each side, arising from a giant nerve-cell. 
 The fibre has an enormously thick siieath, the axis-cylinder forming a 
 relatively small part of the whole; and the branches which supply the 
 plates of the organ are divisions of this single axis-cylinder. 
 
 The electromotive force of the shock of the Gymnotus may be very 
 considerable; and even Torpedo and Malapterurus are quite able to 
 kill other fish, their enemies or their prey. Indeed, Gotch has esti- 
 mated the electromotive force of i cm. of the organ of Torpedo at 
 5 volts. Schonlein finds that the electromotive force of the whole 
 organ may be equal to that of 31 Daniell cells, or 0-08 volt for each 
 plate, and it is one of the most interesting questions in the whole of 
 electro-physiol'jgy, how they are pro- 
 tected from their own currents . There 
 is no doubt that the current density 
 inside the fish must be at least as 
 great as in any part of the water sur- 
 rounding it, and probably much 
 greater. The central nervous system 
 and the great nerves must be struck 
 by strong shocks, yet the fish itself is Fig. 321.— Diagram showing Uirec- 
 not injured; nay, more, the young in tion of Shock in Torpedo, 
 
 the uterus of the viviparous Torpedo 
 
 are unharmed. The only explanation seems to be that the tissues of 
 electric fishes are far less excitable to electrical stimuli than the tissues of 
 other animals; and this is found to be the case when their muscles or 
 nerves are tested with galvanic or induction currents. It requires ex- 
 tremely strong currents to stimulate them ; and the electrical nerves are 
 more easily excited mechanically, as by ligaturing or pinching, than elec- 
 trically. In general, too, the shock is more readily called forth by reflex 
 mechanical stimulation of the skin than by electrical stimulation. But 
 that the organ itself is excitable by electricity has been shown by Gotch. 
 He proved that in Torpedo a current passed in the normal direction 
 of the shock is strengthened, and a current passed in the opposite 
 direction weakened, by the development of an action current in the 
 direction of the shock. And, indeed, a single excitation of the electrical 
 nerve is followed by a series of electrical oscillations in the organ, which 
 gradually die away. The latent period of a single shock is about 
 oJo second. The skate must be included in the list of electric fishes. 
 Although its organ is relatively small, and its electromotive force rela- 
 tively feeble, yet it is in all respects a complete electrical organ. It 
 is situated on either side of the vertebral column in the tail. The 
 plates or discs are placed transversely and in vertical planes. The 
 nerves enter tlieir anterior surfaces; the shock passes in the organ from 
 anterior to posterior end. Gotch and Sanderson have estimated the 
 maximum electromotive force of a length of i cm. of the electrical 
 organ of the skate at about half a volt. 
 
842 ELECT RO-PH YSIOLOG Y 
 
 WTiether the electrical organ is the homologue of muscle or of nerve- 
 ending, or whether it is related to either, has Ix^cn much discussed. 
 Our surest guide in a question of this sort is the study of development; 
 and researches along this line have shown that there are two kinds oi 
 electrical organ, one being modified muscle (as in Gymnotus, Torpedo, 
 and the skate) ; the other transformed skin-glands (as in Malapterurus). 
 The scantv blood-supply of the electrical organs in comparison with that 
 of muscle is noteworthy. In no case do bloodvessels enter the substance 
 of the plates. 
 
 PRACTICAL EXERCISES ON CHAPTER XV. 
 
 1. Galvani's Experiment. — Pith a frog (brain and cord). Cut through 
 the backbone above the urostyle. and clear away the anterior portion 
 of the body and the viscera. Pass a copper hook beneath the two 
 sciatic plexuses, and hang the legs bj- the hook on an iron tripod. If 
 the tripod has been painted, the paint must be scraped away where the 
 hook is in contact with it. Now tilt the tripod so that the legs come 
 in contact with one of the iron feet. Whenever this happens, the 
 circuit for the current set up by the contact of the copper and iron is 
 completed, the nerves are stimulated, and the muscles contract (p, 822). 
 
 2. Make a muscle-nerve preparation from the same frog. Crush the 
 muscle near the tendo AchilMs. so as to cause a strong demarcation 
 current. Cut off the end of the sciatic nerve. Then lift the nerve 
 with a small brush or thin glass rod, and let its cross-section fall on or 
 near the injured part of the muscle. Everj-time the nerve touches the 
 muscle a part of the demarcation current passes through it, stimulates 
 the nerve, and causes contraction of the muscle (p. 822). 
 
 3. Secondary Contraction. — Make two muscle-nerve preparations. 
 Lay the cross-section of one of the sciatic nerves on the muscle of the 
 other preparation (Fig. 305. P. 833^. Place under the nerve near its 
 cut end a small piece of glazed paper or of glass rod, and let the longi- 
 tudinal surface of the nerve come in contact with the muscle beyond 
 this. Lay the nerve of the other preparation on electrodes connected 
 with an induction machine arranged for single shocks, with a Daniell 
 cell and a spring key in the primary- circuit (Fig. 283, p. 808). On 
 closing or opening the key both muscles contract. Arrange the induc- 
 tion machine for an interrupted current. When it is thrown into one 
 nerve, both muscles are tetanized; the nerve lying on the muscle whose 
 nerve is directly stimulated is excited by the action current of the muscle. 
 
 4. Demarcation Current and Current of Action with Capillary Elec- 
 trometer. — (a) Study the construction of the capillan,- electrometer 
 (Fig. 235, p. 729). Raise the glass reservoir by the rack and pinion 
 screw, so as to bring the meniscus of the mercury' into the field. Place 
 two moistened fingers on the binding-icrews of the electrometer, of)en 
 the small key connecting them, and notice that the mercury- moves, a 
 difference of potential between the two binding-screws being caused 
 by the moistened fingers. 
 
 (b) Demarcation Current. — Set up a pair of unpolarizable electrodes 
 (Fig. 238. p. 731). Fill the glass tubes about one-third full of kaolin 
 mixed with physiological salt solution till it can be easily moulded. 
 To do this, make a piece of the clay into a little roll, which will slip down 
 the tube. Then with a match push it down until it forms a firm plug. 
 Next put some saturated zinc sulphate solution in the tubes, above the 
 clay, with a fine-pointed pipette. Fasten the tubes in the holder fixed 
 in the moist chamber (Fig. 322). Now amalgamate the small pieces of 
 zinc wire (p. 197) which are to be connected with the binding-screws of 
 the chamber. (Or use Porter's ' boot ' electrodes. These are made of 
 unglazed potter's clay. In use the leg of the boot is half-filled with 
 
PRACTICAL EXERCISES 
 
 843 
 
 saturated zinc sulphate solution, into which dips a thick amalgamated 
 zmc wire, in the toot ot the boot is a hollow (or well) which is filled 
 with physiological salt solution and serves to keep the feet well moist- 
 ened with the salt solution. The nerve is laid on the feet of the boots. 
 When not in use the boots should be kept in physiological salt solution.) 
 The zincs are now placed in the tubes, dipping into the zinc sulphate. 
 A piece of clay or blotting-paper moistened with physiological salt solu- 
 tion is laid across the electrodes to complete the circuit between their 
 points, and they are connected with the electrometer to test whether 
 they have been properly set up. There ought tc be little, if any, move- 
 ment of the mercury on opening the side-key of the electrometer. If the 
 movement is large, ___^==* 
 
 the electrodes are 
 'polarized,' and must 
 be set up again. The 
 second pair of bind- 
 ing - screws in the 
 chamber are con- 
 nected with a pair of 
 platinum -pointed 
 electrodes on the one 
 side, and on the other, 
 through a short-cir- 
 cuiting key, with the 
 secondary coil of an 
 induction machine ar- 
 ranged for tetanus. 
 
 Next pith a frog 
 (cord and brain), and 
 make a muscle-nerve 
 preparation. Injure 
 the muscle near the 
 tendo Achillis. Lay 
 the injured part over 
 one unpolarizable 
 electrode, and an un- 
 injured part over the 
 other. Put a wet sponge in the chamber to keep the air moist, and place 
 the glass lid on it. Focus the meniscus of the mercury, and open the 
 key of the electrometer; the mercury will move, perhaps right out of the 
 field. Note the direction of movement, and, remembering that the 
 real direction is the opposite of the apparent direction, and that when 
 the mercury in the capillary tube is connected with a part of the muscle 
 which is relatively positive to that connected with the sulphuric acid, 
 the movement is from capillary to acid, determine which is the galvano- 
 metrically positive and which the negative portion of the muscle (p. 823) . 
 
 (c) Action Current. — Now, without disturbing its position on the 
 electrodes, fasten the muscle to the cork or paraffin plate in the moist 
 chamber by pins thrust through the lower end of the femur and the 
 tendo Achillis. Lay the nerve on the platinum electrodes. Open the 
 key of the electrometer, and let the meniscus come to rest. This 
 happens very quickly, as the capillary electrometer has but little inertia. 
 If the meniscus has shot out of the field, it must be brought back by 
 raising or lowering the reservoir. Stimulate the nerve by opening the 
 key in the secondary circuit ; the meniscus moves in the direction oppo- 
 site to its former movement. 
 
 {d) Repeat {b) and (c) with the nerve alone, laying an injured part 
 (crushed, cut, or overheated) on one electrode, and an uninjured part 
 on the other. Of course, the nerve does not need to be pinned. 
 
 B' B 
 
 Fig. 322. — Moist Chamber. E, unpolarizable electrodes 
 supported in the cork C; M, muscle stretched over the 
 electrodes and kept in position by the pins A, B, stuck 
 in the cork plate P; B, binding-screws connected with 
 galvanometer or capillary electrometer. The othei 
 pair of binding-screws serves to connect a pair of 
 stimulating electrodes inside the chamber with the 
 secondary coil of an induction machine. 
 
844 ELECTRO- PH YSIOLOG Y 
 
 Clean the iinpolarizablc electrodes, and be sure to lower the reservoir 
 of the elcclronicttr ; otherwise the mercury ma}' reach the point of the 
 capillary tube and run out. 
 
 In 4 a galvanometer (p. 72G) may be used with advantage by 
 students, if one is available, instead of the electrometer, the un- 
 polarizable electrodes being connected to it through a short-circuit- 
 ing key. The spot of light is brought to the middle of the scale by 
 moving the control-magnet; or if a telescope -reading is being used, the 
 zero of the scale is brought by the same means to coincide with the 
 vertical hair-line of the telescope. The short-circuiting key is then 
 opened. 
 
 5. Action Current of Heart. — Pith a frog (brain and cord). Excise 
 the heart, and lay the base on one unpolarizable electrode, and the 
 apex on the other, having a sufficiently large pad of clay on the tips of 
 the electrodes to insure contact during the movements of the heart, or 
 having little cups hollowed in the clay and filled with physiological salt 
 solution, into which the organ dips. Connect the electrodes with the 
 capillary electrometer and open its key. At each beat of the heart the 
 mercurj^ will move (p. H^s). 
 
 6. Electrotonus.^Set up two pairs of unpolarizable electrodes in the 
 moist chamber. Connect two of them with a capillary electrometer 
 (or galvanometer), and two with a battery of three or four small Daniell 
 cells, as in Fig, 304. Lay a frog's nerve on the electrodes. When the 
 key in the battery circuit is closed, the mercury (or the needle of the 
 galvanometer) moves in such a direction as to indicate that in the extra- 
 polar regions parts of the nerve nearer to the 
 anode are relatively positive to parts more re- 
 mote, and parts nearer to the kathode are rela- 
 tively negative to parts more remote. The 
 direction of movement of the mercury (or gal- 
 vanometer needle) must be made out first for one 
 direction of the polarizing current. Then the 
 latter must be reversed, and the movement of 
 the mercury (or needle) on closing it again noted 
 (P 830). 
 
 7. Paradoxical Contraction. — Pith a frog (brain 
 and cord). Dissect out the sciatic nerve down to 
 the point where it splits into two divisions, one 
 for the gastrocnemius b, and the other for the 
 peroneal muscles a. Divide the peroneal branch 
 as low down as possible, and make a muscle-nerve 
 preparation in the usual way. Lay the central 
 3^3- — Paradoxical end of the peroneal nerve on electrodes con- 
 Contraction, nected through a simple key with a battery of two 
 Daniell cells. When the peroneal nerve is stimu- 
 lated, the gastrocnemius muscle contracts. This result is not due to the 
 current of action, for it is not obtained with mechanical stimulation 
 of the nerve. But it is not the result of an escape of current, for if the 
 peroneal nerve be ligatured between the point of stimulation and the 
 bifurcation, no contraction is obtained. The contraction is really due 
 to a part of the electrotonic current set up in the peroneal nerve passing 
 tlxrough the fibres for the gastrocnemius, where they lie side by side 
 in the trunk of the sciatic. 
 
 8. Alterations in Excitability (and Conductivity) produced in Nerve 
 by the Passage of a Voltaic Current through it. — Set up two pairs of 
 unpolarizable electrodes in the moist chamber. Connect a batter)' of 
 two or three Daniell cells, arranged in series through a simple key 
 
PRACTICAL EXERCISES 845 
 
 with the side-cups of a Pohl's commutator with cross-wires in. Con- 
 nect the commutator to one pair of the unpolarizable electrodes (' the 
 polarizing electrodes '), as in Fig. 324. The other pair of unpolarizable 
 electrodes (' the stimulating electrodes ') are to be connected through a 
 short-circuiting key with the secondary of an induction machine 
 arranged for tetanus. A single Daniell is put in the primary coil. 
 Pith a frog (brain and cord), make a muscle-nerve preparation, pin 
 the lower end of the femur to the cork plate in the moist chamber, 
 attach the thread on the tendo Achillis to the lever connected with the 
 chamber through the hole in the glass provided for this purpose, and 
 arrange the nerve on the electrodes so that the stimulating pair is 
 between the muscle and the polarizing pair. By moving the secondary, 
 seek out such a strength of stimulus as just suffices to cause a weak 
 tetanus when the polarizing current is not closed. Set the drum off 
 (slow speed), and take a tracing of the contraction. Then close the 
 polarizing current with a Pohl's commutator so arranged that the 
 anode is next the stimulating electrodes — i.e., the current ascending in 
 the nerve. Again open the short-circuiting key in the secondary; the 
 contraction will now be weaker than before, or no contraction at all 
 may be obtained. Allow the preparation two minutes to recover, 
 
 Fig. 3-4- — Arrangement for showing Changes of Excitability produced by the Voltaic 
 Current. M, muscle; N, nerve; Ej. Eg. electrodes connected with secondary 
 coilS; E3, E4, unpolarizable electrodes connected with Pohl's commutator (with 
 cross-wires) C; B', 'polarizing' battery; B, 'stimulating' battery in primary 
 circuit P; K, K", simple keys; K', short-circuiting key. 
 
 then stimulate again, as a control, without closing the polarizing 
 current. If the contraction is of the same height as at first, close the 
 polarizing current with the bridge of the commutator reversed, so 
 that the kathode is now next the stimulating electrodes. On stimu- 
 lating, the contraction will now be increased in height. (See Figs. 273, 
 274. P- 786.) 
 
 9. Pfliiger's Formula of Contraction (p. 788). — To demonstrate this, 
 connect two unpolarizable electrodes, through a spring key and a 
 commutator, with a simple rheocord (Fig. 286, p. 810), so as to lead 
 off a twig of a current from a Daniell cell. The unpolarizable elec- 
 trodes are placed in a moist chamber. A muscle-nerve preparation 
 is arranged with the nerve on the electrodes and the muscle attached 
 to a lever. The effects of make and break of a weak current, assending 
 and descending, can be worked out with the simple rheocord. The 
 effects of a medium current will probably be obtained wath a single 
 Daniell connected directly with the electrodes through a key. The 
 effects of a strong current will be got when three or four Daniells are 
 connected with the electrodes. Care must be taken to keep the prepara- 
 tion in a moist atmosphere, and more than one preparation may be 
 needed to verify the whole formula. 
 
846 ELECTRO-PHYSIOLOGY 
 
 10. Formula of Contraction for (Human) Nerves in Situ. — Connect 
 eight or ten drv nils in sirii-s * ("oniai t oiu- trriinii.tl ot llir battt-ry 
 to a Kirye phitc electrode, and the oilier lo a sin. ill electrode, butli 
 covered with cotton, flannel, or sponge, moistened with salt soluti n 
 Include in the circuit a simple key for making or breaking the current, 
 and a commutator for changing its direction at will. Leave the key 
 open. Place the large electrode behind the shoulder (or on the back 
 of the neck), and the small electrode over the ulnar nerve at the elbow 
 between the internal condyle and the olecranon. Arrange the com- 
 mutator so that the small electrode shall be the kathode. Close, and 
 then open the key. If no contraction occurs at closing, the battery 
 is too weak, and more cells must be added. If contraction occurs at 
 closing, but not at opening, reverse the commutator, making the small 
 electrode the anode, and observe whether contraction now occurs at 
 closing, at opening, or at both. Note also the relative strength of the 
 various contractions. If the current is ' weak,' the only contraction 
 will be a closing one when the kathode is over the nerve. If the current 
 is of ' medium ' strength, a closing kathodic contraction and both 
 opening and closing anodic contractions will be obtained. With ' strong ' 
 currents contractions will occur at closing and at op)ening, whether the 
 kathode or the anode is over the nerve. The contractions will vary 
 in strength, as described on p. 789. To work out the different cases 
 of the formula summarized in the table, the number of cells must be 
 increased or diminished. 
 
 Weak Currents. 
 
 Medium Currents. 
 
 Strong Curr«nts. 
 
 KCC 
 
 KCC 
 ACC 
 AOC 
 
 KCC 
 ACC 
 AOC 
 KOC 
 
 The abbreviations KCC, ACC, are used respectively for kathodic 
 closing contraction and anodic closing contraction; KOC, AOC, for 
 kathodic opening contraction and anodic opening contraction. KCC 
 is stronger than KOC, and ACC tlian AOC. KCC is stronger than 
 ACC, and AOC than KOC. Therefore, as the strength of the current 
 is increased, in the case of normal tissues, KCC is first obtained, then 
 ACC, then AOC. and finally KOC. 
 
 II. Ritter's Tetanus. — Lay the nerve of a muscle-nerve preparation 
 on a pair of unpolarizable electrodes connected through a simple key 
 with a battery of three or four small Daniells. Connect the muscle 
 with a lever. Pass an ascending current (anode next the muscle) for 
 a few minutes through the nerve, and let the writing-point trace on 
 a slowly-moving drum. When the current is closed there may be a 
 single momentary twitch, or the muscle may remain somewhat con- 
 tracted (galvanotonus) as long as the current is allowed to pass, or it 
 may continue to contract spasmodically (' closing tetanus '). When 
 the current is opened the muscle will contract once, and then immedi- 
 ately relax, or there may be a more or less continued tetanus (Ritter's 
 or ' opening tetanus '). If opening tetanus is obtained, divide the 
 nerve between the electrodes: the tetanus continues. Divide it be- 
 tween the anode and the muscle: the tetanus at once disappears. This 
 shows that the seat of the excitation which causes the tetanus is in 
 the neighbourhood of the anode (p. 831). 
 
 ♦ If the laboratory possesses a batteiy (with rheostat), such as is used by 
 neurologists, the experiment is more conveniently performed with this. 
 
CHAPTER XVI 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 In other divisions of our subject we have been able to follow to a 
 greater or less extent the processes which take place in the organs 
 described. The chemistry and the physics of these processes have 
 bulked more largely in our pages than the anatomy and histology 
 of the tissues themselves. In dealing with the central nervous 
 system, we must adopt a method the very reverse of this. Its ana- 
 tomical arrangement is excessively intricate. The events which 
 take place in that tangle of fibre, cell, and fibril are, on the other 
 hand, almost unknown. So that in the description of the physiology 
 of the central nervous system we can as yet do little more than 
 trace the paths by which impulses may pass between one portion 
 of the system and another, and from the anatomical connections 
 deduce, with more or less probability, the nature of the physiological 
 nexus which its parts form with each other and the rest of the body. 
 And here it may be well to remark that, although for convenience 
 of treatment we have considered the general properties of nerves 
 in a separate chapter, there is not only no fundamental distinction 
 between the central nervous system and the outrunners which 
 connect it with the periphery, but obviously a central nervous 
 system would be meaningless and useless without afferent nerves 
 to carry information to it from the outside, and efferent nerves along 
 which its commands may be conducted to the peripheral organs. 
 
 Section I. — Structure of the Central Nervous System — 
 Histological Elements. 
 
 In unravelling the complex structure of the central nervous 
 system, we avail ourselves of information derived (i) from its gross 
 anatomy; (2) from its microscopical anatomy; (3) from its develop- 
 ment; (4) from what we may call, although the term is open to the 
 criticism of cross-division, its physiological and pathological 
 anatomy. 
 
 Certain tracts of white or grey matter are differentiated from each 
 other by the size of their fibres or cells. For example, the postero- 
 midian column of the spinal cord has small fibres, the direct cere- 
 
 847 
 
848 THE CENTRAL NERVOUS SYSTEM 
 
 bellar tract large fibres; the large pyramidal cells (giant cells or cells 
 of Betz), in what we shall afterwards have to distinguish as the ' motor 
 area ' (p. 950) of the cerebral cortex, are the cells of origin of fibres of 
 the pyramidal tract subserving the volitional movements of the limbs 
 and trunk. The pyramidal cells of the ' face area ' are comparatively 
 small. In general, an efferent or motor nerve-cell is larger the longer 
 its axon is — e.g.. tlie largest of all the pyramidal cells in the ' motor ' 
 region are found in the portion known as the ' leg area,' from which 
 the pyramidal fibres have to pass all the way down the cord to the 
 segments from which the spinal nerves going to the lower limbs arise. 
 
 The recent work of Brodman and of Campbell has shown that the 
 cerebral cortex may be histologically differentiated into regions which 
 correspond to a great extent to the various functional regions mapped 
 out by physiological methods (p. 958). 
 
 The study of development enables us not only to determine the 
 homology, the morphological rank, of the various parts of the brain 
 and cord, but also, by comparison of animals of different grades of 
 organization, sometimes to decide the probable function and physio- 
 logical importance of a strand of nerve-fibres or a column of nerve- 
 cells. It is of special value in helping us to differentiate the various 
 areas of grey matter on the surface of the brain, and to trace the various 
 tracts or paths into which the white matter of the central nervous 
 system may be divided. For the medullary sheath is not developed 
 at the same time in all the tracts, and a strand of nerve-fibres in which 
 it is wanting — e.g.. the pyramidal tract (p. 878), which is the last of 
 the spinal tracts to become myelinated — is readily distinguished under 
 the microscope. 
 
 Then, again — and this is what we propose to include under the 
 fourth head — experimental ph3-siology and clinical and pathological 
 observation throw light not only on the functions, but also en the 
 structure, of the central nervous system. For instance, complete or 
 partial sectioH, or destruction by disease, of the white fibres of the 
 cord or brain, or of the nerve-roots, or removal of portions of the grey 
 matter, is followed by degeneration in definite tracts. And since, as 
 we have already seen, degeneration of a nerve-fibre is caused when it 
 is cut off from the cell of which it is a process, the amount and dis- 
 tribution of such degeneration teaches us the extent and position of 
 the central connections of the given tract. Con\ersely, the cells in 
 which a tract of nerve-fibres arises may sometimes be identified by 
 the alterations in the chromatin (p. 859) and other changes which occur 
 in them after section of their axons. Particularly in young animals, 
 removal of a peripheral organ — an eye or a limb — or section of its 
 nerves, may be followed by atrophy of portions of the central nervous 
 system immediately related to it. 
 
 ' Softening ' of a definite portion of the white or grey matter may 
 also in certain cases be caused by depriving it of its blood-supply by 
 the injection of artificial emboli, and the resulting degenerations may 
 then be studied. For instance, fine particles like lycopodium spores 
 are injected into the abdominal aorta between the origins of the renal 
 and inferior mesenteric arteries. They are prevented by clamps from 
 entering these ves.sels, and, passing through the lumbar arteries, stick 
 in the branches of the anterior spinal artery, and cause softening 
 mainly of the grey matter of the lumbar portion of the cord. When 
 the abdominal aorta of a rabbit is temporarily compressed (for about 
 an hour) below the origin of the renal arteries, the grey matter of the 
 corresponding portion of the cord is so seriously injured that it and 
 the fibres that arise from it degenerate, while the fibres whose cells of 
 
DEVELOPMENT 
 
 449 
 
 3-25. — Formation of the Neural 
 Canal at an Early Stage (Beard). 
 
 6rif];iri arc not situated in this part of the grey matter are not affected, 
 or at least completely recover. 
 
 C'ertain tracts may also be marked out by means of the electrical 
 variation, which gives token of 
 the passage of nervous impulses 
 along them when portions of the 
 central nervous system or peri- 
 pheral nerves are stimulateej 
 (Horslcy and Gotch). 
 
 Development of the Central 
 Nervous System. — ^Vcry early iu 
 development (Fig. 325) the keel 
 of the vertebrate embryo is laid 
 down as a groove or gutter in tho 
 ectoderm of the blastodermic area 
 (Chap. XIX.). The walls of this 
 ' medullary ' or ' neural ' groove 
 grow inwards, and at length there 
 is formed, by their coalescence, the ' neural canal ' (Fig. 326), which 
 expands at its anterior end to form four cerebral vesicles ^Fig. 327). 
 Thus there is a continuous tunnel from 
 end to end of the primary cerebro -spinal 
 axis; and this persists as the central 
 canal of the spinal cord and the ven- 
 tricles of the brain, whose ciliated 
 epithelium represents the ectodermic 
 lining of the primitive neural canal. In 
 the adult portions of the canal may 
 become obliterated from an overgrowth 
 of the lining cells, and the cilia are, if 
 present at all, less distinct than in the 
 child, and far less distinct than in the 
 lower animals. From the wall of this 
 canal is formed the cerebro-spinal axis, 
 in which developing nerve-cells or neuro- 
 
 
 ~4G 
 
 y 
 
 ^JijQ,-' 
 
 :■ ."'in- 
 
 l^\ 
 
 Fig. 326. — Neural Canal at a Later 
 Stage (Beard). C. neural canal; 
 G, posterior spinal ganglion. 
 
 Fig. 327. — Diagram to illustrate 
 the Formation of the Cerebral 
 Vesicles. A. i indicates the 
 cavity of the secondary fore- 
 brain, which eventually becomes 
 the lateral ventricles. In B the 
 secondary fore-brain has grown 
 backwards so as to overlap the 
 other vesicles. I, first cerebral 
 vesicle (primary fore-brain or 
 'tween brain) ; II, second cerebral 
 vesicle (mid-brain); III, third 
 cerebral vesicle (hind-brain); IV, 
 fourth cerebral vesicle (after- 
 brain). 
 
 blasts soon become differentiated from the supporting cells or spongio- 
 blasts, and wander outwards from the neighbourhood of the central canal 
 (Fig. 338) till their further progress is checked by the barrier of the mar- 
 
 54 
 
850 THE CENTRAL NERVOUS SYSTEM 
 
 ginal veil, a closely-woven network or thicket, into which the processes of 
 the spongioblasts break up at the outside of the primitive ccrcbro-spinal 
 axis. Although the neuroblasts themselves are unable to penetrate 
 the marginal veil, the axis-cylinder processes of some of them do so, 
 and form the motor roots of the spinal nerves. The neuroblasts from 
 which the fibres of the white columns of the cord are dc\xloped are 
 apparently unable to send their axons through the marginal veil. 
 They are accordingly forced to assume a longitudinal direction, and 
 in this way the central grey matter becomes covered with a sheath of 
 longitudinal white fibres. For a time only motor nerve-cells and the 
 fibres connected with them are developed in the cerebro-spinal axis. 
 The ganglia on the posterior roots arise from a series of ectodermic 
 thickenings or sprouts from the neural crest which runs along the dorsal 
 aspect of the neural canal. These sprouts contain the neuroblasts 
 which develop into the spinal ganglion cells with the posterior root- 
 fibres. From each pole of each neuroblast a process grows out, one 
 towards the periphery, which forms a peripheral nerve-fibre, the other 
 centrally to connect the cell with the cord. From the after-brain (or 
 myelencephalon) is developed the medulla oblongata or spinal bulb, 
 from the hind-brain (or metencephalon) the cerebellum and pons, 
 from the mid-brain (or mesencephalon) the corpora quadrigemina and 
 crura cerebri. The fore-brain, or primary fore-brain (thalamencepha- 
 lon), gives rise of itself only to the third ventricle and optic thalamus; 
 but a secondary fore-brain (telencephalon) buds off from it and soon 
 divides into two chambers, from the roof of which the cerebral hemi- 
 spheres, and from the floor the corpora .striata, are derived. Their 
 cavities persist as the lateral ventricles, which communicate with the 
 third ventricle by the foramen of Monro. The olfactory tracts are 
 formed as buds from the secondary fore-brain. 
 
 To complete the story of the development of the brain, it may be 
 added that the retina is really an expansion of its nervous substance. 
 A hollow process, the 'optic vesicle, buds out on each side from the 
 primary fore-brain. A button of ectoderm, which afterwards becomes 
 the lens, grows against the vesicle and indents it so that it becomes 
 cup-shaped, the inner concave surface of the cup representing the 
 retina proper, the outer convex surface the choroidal epithelium. The 
 stalk becomes the optic nerve. 
 
 Histological Elements of the Central Nervous System. — The central 
 nervous system is built up (i) of true nervous elements, (2) of sup- 
 porting tissue. The nervous elements have usually been described as 
 consisting of nerve-fibres and nerve-cells, but the antithesis of a time- 
 honoured distinction must not lead us to forget that the essential 
 part of a nerve-fibre, the axis-cylinder, is a process of a nerve-cell, 
 and the medullary sheath a structure whose integrity is intimately 
 related to that of the axis-cylinder.* In strictness, the term ' nerve- 
 cell ' ought to include not only the cell-body, but all its processes, out 
 to their last ramifications. But the habit of speaking of the position 
 of the cell-bodyt as that of the nerve-cell is so ingrained, that it seems 
 better to continue the use of the latter term in its old signification, and 
 to speak of the cell and branches together as a neuron (also spelled 
 neurone). 
 
 * While the medullary sheath, like the axis-cylinder, seems to be as regards 
 its nutrition under the control of the nerve-cell, and must therefore be looked 
 upon as an integral portion of the neuron, although not essential for its de- 
 velopment, the neurilemma in respect both of its nutrition and iits develop- 
 ment appears to be an independent structure. 
 
 \ Foster and Sherrinpton call the cell-body the perikaryon. 
 
HISTOLOGICAL ELEMENTS 
 
 851 
 
 The Neurons.— A typical ncrvc-cell (Figs. 328, 330, 33-i) is a knot of 
 granular protoplasm, containing a large nucleus, inside of which lies 
 a highly refractive nucleolus. A centrosome and attraction sphere 
 (p. 5) have also been found in some nerve-cells, though not as yet 
 demonstrated in all. Pigment may also be present, especially in old 
 age. By certain methods of staining it may be shown that fibrils 
 (neuro-fibril.s) run through the protoplasm of the cell, forming a felt- 
 work in it, and entering the dendrites on the one hand and the axis- 
 cylinder process on the other (Figs. 328, 331, 335)- In the axis- 
 cylinaers of nerve-fibres the fibrils (Fig. 329) appear to preserve their 
 
 identity down to the distribution of 
 the fibre. In the ground substance 
 between the fibrils lie round, an- 
 gular, or spindle-shaped bodies 
 (Nissl's bodies) which stain with 
 basic dyes (Fig. 340).* These bodies 
 vary in appearance in different 
 kinds of nerve-cells, and in the 
 same nerve-cell under different con- 
 ditions. According to Macallum, 
 they contain organically combined 
 iron. In a multipolar cell, like those 
 
 -Anterior Horn Cell from Man 
 showing Fibrils (Bethe). 
 
 Fig. 329. — MeduUated Nerve- 
 Fibre showing Fibrils of Axis- 
 Cylinder (Bethe). The fibrils are 
 seen passing, without interrup- 
 tion, across a node of Ranvier. 
 
 in the anterior horn of the spinal cord, several processes — it may be five 
 or six, or even more — pass off from the cell-body (Frontispiece). The 
 most complete pictures of them are given by preparations impregnated 
 according to the method of Golgif (Figs. 330, 333). One of the pro- 
 
 * In Nissl's method the sections are stained in a solution of methylene blue, 
 and decolourized in aniliu-alcohol. 
 
 t The method depends upon the deposition of mercury, or silver, in or 
 around the cell-bodies and their processes in tissues which have been hardened 
 in bichromate of potassium and then soaked in a solution of mercuric chloride 
 or silver nitrate. In Pal's improvement of Golgi's method a solution of sodic 
 sulphide follows the mercuric chloride. 
 
852 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 cesses of most nerve-cells is distinguished from the rest by the fact 
 that it maintains its original diameter for a comparatively great 
 distance from the cell, and gives off comparatively few branches. 
 This process, which in favourable preparations can be traced on till it 
 becomes the axis-cylinder of a nerve-fibre, is called the axis-cylinder 
 process, or more shortly the axon. The few slender brai ches that come 
 off from it, usually at right angles, are called collaterals. The collaterals 
 consist essentially of one or more fibrils of the axon. Both the main 
 thread of the axon and the collaterals end by breaking up into an 
 arborescent system of fibrils or telodendrion . The telodendrions vary 
 greatly in appearance from simple end -brushes to far-branching 
 thickets, or such special end-organs as motor plates (Fig. 335) or 
 muscular spindles. The rest of the processes of the cell, which are 
 termed dendrites or protoplasmic processes, very rapidly diminish in 
 diameter, as they pass away from the cell by breaking up into 
 
 Fig. 3 JO. — Multipolar Nerve-Cell: Golgi Preparation (Barker, after Kolliker). 
 n, axon; c, collaterals. 
 
 fibrils like the branches of a tree. The Nissl bodies extend for some 
 distance into the dendrites, but not into the axon. The dendrites 
 of some cells, especially the pyramidal cells of the cerebral, and 
 the Purkinje's cells of the cerebellar cortex, have small swellings, 
 the so-called lateral buds or gemmtiles, on their course. Their signifi- 
 cance is unknown. The dendrites terminate at a little distance from 
 the cell, where they come into relation with the end -arborizations of 
 the axons of other neurons. In this way two or more neurons are 
 linked together to form a nervous path. According to the view most 
 commonly held (neuron hypothesis), the relation is not one of actual 
 anatomical continuity, but the processes come so close together that 
 nerve impulses are able to pass across from the terminal brush of the 
 axon of one nervous element to the dendrites or cell-body of another. 
 This kind of junction is called a synapse. 
 
 It has been suggested that the contact may be rendered more or less 
 close through amoeboid movements of the dendrites, and that in this 
 
HISTOLOGICAL ELEMENTS 
 
 85^ 
 
 way the nervous impulse may be switched like a railway-train from 
 one path to another. But there is no experimental basis for this some- 
 what crude, if fascinating, hypothesis. Sherrington has suggested 
 that the presence of a ' membrane ' at the synapse may limit the con- 
 duction and determine its direction. Some membranes, such as frog's 
 skin, are known to possess a so-called irreciprocal permeability for 
 certain substances, permitting them to pass more easily in one direc- 
 tion than the other, and it is conceivable that a membrane at the 
 synapse might have a similar action in respect to the movement of ions 
 concerned in the propagation of the nervous excitation. Whatever 
 
 Fig. 331— Nerve-Cells of Hirudo (Schafer. 
 after Apathy). A, vinipolar motor cell; 
 a, network of neuro-fibrils near the sur- 
 face of the cell; b. near the nucleus n; 
 c, afferent, d, efferent neuro-fibril. B, bi- 
 polar sensory cell a with its nucleus n ; 
 cu, cuticle; ep, epidermis cells between 
 which a neuro-fibril passes up from its 
 branched ending near the surface of the 
 skin to the nerve-cell, where it forms a 
 network, which gives off a fibril passing 
 towards the central nervous system. 
 
 Fig. 332.— Large Pyramidal Cell of 
 Cerebral Cortex (Barker, after Bech- 
 terew). a, axon; b, dendrite. 
 
 the nature of the relation between two superposed neurons may be, it 
 does not permit the conduction of nerve-impulses indiscriminately' in 
 both directions. For instance, stimulation of the central end of the 
 posterior root of a spinal nerve causes an electrical response (p. 824) 
 in the anterior root of the same segment, while no electrical change is 
 produced in the posterior root by stimulation of the anterior. We shall 
 see later on (p. 872) that some of the fibres of the posterior root and 
 their collaterals end by arborizing around the dendrites of the cells 01 
 the anterior horn. The excitation is, therefore, able to pass from the 
 
854 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 telodcndrions of the posterior root-fibres through the dendrites of the 
 anterior horn cells towards their cell-bodies, but not in the opposite 
 
 Fig. 333- — • — e shows the development of the pyramidal nerve-cells of the cerebral 
 cortex in a typical mammal; a, neuroblast with commencing axon; b, dendrites 
 appearing; d, commencing collaterals. A — D shows the different degree of com- 
 plexity in the fully-developed pyramidal cells in different vertebrates: A, frog; 
 B, lizard; C. rat; D, man (Donaldson, after Ram6n y Cajal). 
 
 direction, and in general the direction of conduction is from the den- 
 drites towards the cell-body. 
 
 Some investigators believe that the fibrils already spoken of as 
 forming a felt-work in the protoplasm of the nerve-cell may run right 
 
 Fig. 334— Cells from the Gasserian Ganglion of a Developing Guinea-Pig. 
 originally bipolar cells are seen changing into cells apparently unipolar, 
 same process occurs in the cells of the spinal ganglia (Van Gehuchten). 
 
 The 
 The 
 
 through from one cell to another, thus constituting an actual anatomical 
 connection between the neurons, and that .such a connection may be 
 established also by fibrils which do not enter the cells at all, but run in 
 the intercellular substance of the grey matter. Such a continuity of 
 
// IS TO I. OG I CA L EL EM EN TS 
 
 fibrils from cell to cell has 
 been demonstrated in some 
 of the invertebrates — e.g., 
 in annelids (Fig. 331) — 
 where previously the best 
 examples of strictly iso- 
 lated neurons were sup- 
 posed to be found (Apathy)- 
 The supporters of the 
 theory of continuity look 
 upon the cell-body as 
 merely necessary for the 
 nutrition of the nerve-net, 
 but deny that it is neces- 
 sary for the conduction of 
 nerve-impulses. If this is 
 the case, it is obvious that 
 the neurons can no longer 
 be considered as functional 
 units in which the law of 
 isolated conduction of 
 nerve-impulses (p. 793) 
 holds good. Nor is it by 
 any means so easy to un- 
 derstand as on the neuron 
 hypothesis such facts as the 
 strict limitation of Wal- 
 lerian degeneration to the 
 boundaries of the neurons 
 directly affected, or the 
 strict limitation of the 
 silver reduction in Golgi 
 preparations to single neu- 
 rons. It is, of course, true 
 that the simplicity and 
 order introduced by the 
 neuron hypothesis into our 
 conceptions of the nervous 
 conduction paths by no 
 means prove its accuracy. 
 Yet they are reasons for 
 not lightly abandoning it, 
 and it has recently been 
 corroborated by important 
 new evidence on the growth 
 of nerve-cells on artificial 
 media outside of the body 
 (p. 802; Fig. 337. P- 8.57)- 
 Varieties of Neurons. — 
 Nearly all the nerve-cells 
 of the cerebro-spinal axis 
 agree with the cells of the 
 anterior horn in the posses- 
 sion of an axon and one or 
 more dendrites, although 
 sometimes the dendrites 
 are scanty in number and 
 
 Pig ^35. — Scheme of Lower Motor Neuron 
 (Barker), a, h, axon-hilljck (the portion of the 
 cell from which the axon comes off), containing 
 no Nissl bodies, and showing fibrillation; ax, 
 axis-cylinder or axon; m, medullary sheath, 
 outside of which is the neurilemma; c, cell- 
 substance (cytoplasm), showing Nissl bodies in 
 a lighter ground substance; d, protoplasmic 
 processes or dendrites containing Nissl bodies; 
 n, nucleus; «', nucleolus; n, R, node of Rauvier; 
 s.f. side fibril; n of n, nucleus of the neurilemma; 
 tel., motor end-plate; m', striped muscle-fibre; 
 s. I , incisure. 
 
856 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 insignificant in size. In the cerebral cortex the typical cells are ol 
 pyramidal shape. From the base comes off the axon, and from the 
 angles dendritic processes, a particularly massive dendrite proceeding 
 from the apex of the pyramid towards the surface of the brain. 
 
 Sometimes an axon, instead of ending in an arborization which 
 comes into relation with the dendrites of another nerve-cell, or, as is 
 more frequently the case, with the dendrites of more than one cell, 
 breaks up into a sort of basket-work of fibrils surrounding the cell- 
 body. The cells of Purkinje, for instance, in the cerebellum are sur- 
 rounded by such pericellular baskets {L'ig. 336). The cells of the spinal 
 ganglia have two axons, which in the embryo arise one from each end 
 of the bipolar cell, but in the adult, in all vertebrates except some 
 fishes, are connected to the cell by a single process (Fig. 334)- It has 
 been commonly held that the unipolar cell with a single T-shaped 
 
 process is developed from a bipolar cell, 
 which grows towards one side, so that the 
 two processes come together and fuse. 
 Such observations as that of Harrison on 
 the bifurcation of the growing end of the 
 main process of isolated nerve-cells culti- 
 vated in vitro suggest an alternative and 
 a simpler explanation — viz., that the 
 T-shaped process is derived from the 
 splitting of a single chief process. If this 
 be the case, one of the original processes 
 at the poles probably undergoes a retarded 
 development or disappears, since the great 
 majority of the spinal ganglion cells with 
 the T-shaped process appear to have no 
 dendrites. Another kind of cell which 
 seems undoubtedly to be of nervous nature 
 is the ' granule-cell.' Granule-cells are 
 much smaller than the ner\-e-cells we ha\'e 
 been describing. Their processes are much 
 less easily followed, but all appear to give 
 off an axon and several dendrites. They 
 contain a relatively large nucleus (5 to 8 /.t 
 in diameter), with only a mere fringe of 
 cell-substance. The nucleus, unlike that 
 of a large nerve-cell, stains deeply with 
 haematoxylin. Some parts of the grey 
 matter are crowded with these granule-cells — e.g., the nuclear layer 
 of the cerebellum and the substantia gelatinosa, or substance of 
 Rolando, which caps the posterior horn in the cord. In other parts 
 they are more thinly scattered, but probably they are as widely diflused 
 as the large nerve-cells proper, and no extensive area of the grey matter 
 is wholly without them. 
 
 Although there are several varieties of granules (Hill), they all 
 agree in this, that their axons run a comparatively short course, and 
 never, or rarely, pass beyond the grey matter. Another kind of neuron 
 which is also confined to the grey matter, and is typically seen in the 
 cortex of the cerebrum and cerebellum, presents the peculiarity of an 
 axon which branches into an intricate network immediately after 
 commg off from the cell (cell of Golgi's second type). Unlike the long 
 axon of the typical large nerve-cell, the axis-cylinder process of this 
 Golgi cell remains unmcdullated. 
 
 The sympathetic ganglion cells are developed from immature neuro- 
 
 Fig. 336. — Pericellular Baskets 
 (Schafer, after Cajal). Two 
 cells of Purkinje from the 
 cerebellum are seen sur- 
 rounded by end ramifications 
 forming a basket-work, b, de- 
 rived from the branching of 
 axons of small nerve-cells in 
 the molecular layer; a, axon. 
 
HISTOLOGICAL ELEMENTS 
 
 8S7 
 
 blasts that migrate, in the course of development, from the rudiments 
 of the s[)inal ganglia, and gatliering in clumps form the ganglia of the 
 sympathetic cliain (His). They agree in general with the cells of the 
 cerebro-spinal axis in jjossessing an axon and one or more, commonly 
 several, dendrites, although a few of them are devoid of dendrites. 
 The great majority of the axons remain unmedullated, but a few 
 acquire a very fine medullary sheath. 
 
 The epithelium lining the central canal of the cord and the ventricles 
 of the brain has also been considered by some as of nervous nature. 
 The fact that the deep ends of the cells are continued into processes 
 which pierce far into the grey substance has been supposed to lend 
 weight to this opinion, but there is no good ground for it. 
 
 Growth of Neurons. — The growth of a neuron from origin to com- 
 pletion is a comparatively slow process in the higher animals. Early 
 in foetal life (about the third or fourth week in man) certain round 
 germinal cells make their appearance amid the columnar ectodermic 
 cells surrounding the neural canal. From their division are formed, 
 in the first months of embryonic life, the primitive nerve-cells or 
 neuroblasts. These soon elongate and push out processes, first the 
 
 Fig. 33,7. — Isolated nerve-cells from the spinal cord of a tadpole growing in clotted 
 Ivmph. A, B, C, are cells in different stages of growth. The lower view of C 
 was drawn under the microscope 4I hours later than the upper (Harrison). 
 
 axon or axons, and then the dendrites (Fig. 333). The formation of 
 the axons from the nerve-cell is most clearly followed in isolated 
 cultures (Fig. 337). As development goes on, the cell-body grows 
 larger, and the processes longer and more richly branched. The axon 
 and its collaterals, when it has any, in the case of the great majority of 
 the nervous elements of the brain and cord, ultimately acquire a 
 medullary sheath, although, as we have said, the time at which medul- 
 lation is completed varies in different groups of elements, and in some 
 nervous tracts it is even wanting at birth. At birth, too, the branches 
 of many of the cells are less numerous, and the connections between 
 different nervous elements therefore less intimate than they will after- 
 wards become. For many years the processes, and particularly the 
 axons, continue not only to grow longer, but to grow thicker as well. 
 The cell-body also enlarges, and the quantity of material in it that 
 stains with basic dyes increases. In the growing (lumbar) spinal 
 ganglia of the white rat the increase in volume of the largest cell- 
 bodies is very closely correlated with the increase in area of the cross- 
 section of the nerve-fibres growing out of them. The cross-section 
 of the axis-cylinder is, and remains, almost exactly equal to the area 
 
SjS 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 of the medullar}' sheath (Dofialdson). Even after puberty is reached 
 the anatomical organization of the nervous system may still continue 
 to advance, although at an ever-slackening rate, and the finishing 
 touches may only be given to its architecture in adult life. In old 
 age the nervous elements decay as the body does. The cell- 
 body diminishes in size ; the stainable material lessens in amount ; 
 vacuoles form in the protoplasm and pigment accumulates; the nucleus 
 shrinks; the nucleolus is obscured or may di.sappear altogether. At 
 the same time the processes of the cell, and especially the dendrites, 
 tend to atrophv (Fig- 339)- 
 
 Nutrition of the Neuron. — We have already seen that when an axon 
 is cut off from its cell-body, it and its medullary sheath, when it 
 possesses one, undergo a rapid degeneration. It was long supposed 
 
 Fig. 338. — Section 
 through Half of Neural 
 Tube (Barker, after 
 His). The pear- 
 shaped neuroblasts are 
 seen migrating out- 
 wards. The axons of 
 some of them are seen 
 pushing their way out 
 through the marginal 
 veil as the anterior 
 root of a spinal nerve. 
 
 Ii^ 
 
 Fig. 339. — I. spinal ganglion cells of a still-bom male 
 child; 2, of a man ninety-two years old ( x 250) 
 — N, nuclei; 3, nerve-cells from the antennary 
 ganglion of a honey-bee just emerged in the per- 
 fect form ; 4. of an old honey-bee. The nucleus is 
 black in the figure. In 3 it is very large, in 4 it 
 is shrunken and the cell-substance contains 
 vacuoles (Hodge). 
 
 that no change took place in the nerve-cell. The researches of recent 
 years have shown that not only does loss of the specific function and 
 trophic influence of the cell-body affect the nutrition of the axon, but 
 loss of function of the axon reacts on the cell-body. In many cases 
 at least, when a nerve-fibre is divided from its cell, characteristic 
 changes are produced in the latter and in its dendritic processes, and 
 they are scarcely less rapid, although usually less profound, and far 
 more transient than the degeneration in the peripheral portion of the 
 nerve-fibre. The cell-body and the nucleus swell. Many of the Nissl 
 bodies (Fig. 340) disintegrate, and are reduced to a finely granular 
 condition. After a time much of the disintegrated chromatic sub- 
 stance disappears altogether. The nucleus may be displaced to one 
 
HISTOLOGICAL ELEMENTS 
 
 859 
 
 side of the cell. Certain changes in the neurofibrils of the cell may 
 accompany the changes in the chromatin. In rabbits after division 
 of the facial nerve the alterations in its nucleus of origin have been 
 found to reach a maximum in about three weeks, after which there is a 
 tendency to recovery on the part of the majority of the cells, even when 
 regeneration of the nerve has been prevented by cutting out a portion 
 of it. Some of the cells may completely atrophy and disappear. 
 Similar changes have been found by Warrington in the motor cells ol 
 the anterior horn after section of the posterior (dorsal) spinal roots. 
 Since in this case no anatomical injury has been inflicted on the motor 
 neurons, it has been surmised that the cause of the alterations is the 
 loss of impulses which normally reach them along their dendrites. In 
 short, we may say. with Marinesco, that the functional and anatomical 
 integrity of the neuron depends on the integrity of all its constituent 
 parts, and of the neurons which carry to it functional excitations — i.e., 
 excitations connected with its proper physiological work. The neuron, 
 in fact, lives by its function, or, in common language, by doing its 
 work. Yet the anatomical tokens of mere disuse, as in the motor cells 
 
 
 
 
 
 
 Fig. 340. — Cells from the Nuclei of the Oculo-Motor Nerves of the Cat Thirteen Days 
 alter Division of the Root-Fibres on one Side: Nissl's Stain (Barker, after Flatau). 
 a, normal cell from side on which the roots were not cut; b, cell from side operated 
 upon. Only a few Nissl bodies are present in b, and the nucleus is displaced to 
 one side of the cell. 
 
 of the anterior horn after division of the cord at a higher level, are less 
 distinct than those which follow section of the axon. Therefore it 
 must be concluded that the latter, although not indispensable for the 
 nutrition of the cell as the cell is for the axon, exerts an influence upon 
 it. Similar changes in the chromatin may also be produced in nerve- 
 cells by a period of anaemia, in extensive superficial burns, in tetanus 
 caused by the injection of bacterial cultures, in acute alcoholic poisoning, 
 in fatigue, and in other ways. According to Wright, the inhalation 
 of ether or chloroform (in dogs) so alters the chromatic substance 
 that it loses its affinity for aniline dyes. In long-continued anaesthesia 
 the nucleus is also affected, while the nucleolus is the last part of the 
 cell to suffer. A greater alteration occurs in the cells in the three hours 
 between the sixth and ninth hours of anaesthesia than in the five hours 
 between the first and sixth. Although the changes are transitory, the 
 cells, after a narcosis of nine hours, being practically normal in Jorty- 
 eight hours, they indicate that the duration of safe surgical anaesthesia 
 has a limit measured by hours. 
 
 It is probable that the alterations in the chromatic substance should 
 
Rfio 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 not be looked upon as the token of any specific lesion; they are the 
 common structural response of the cell to injurious influences of the 
 most varied nature. 
 
 Grey and White Matter. — Nerve-cells are the most distinctive his- 
 tological feature of tlie grey nervous substance. Sown thickly in the 
 cerebral cortex, the basal ganglia, the floor of the fourth ventricle, and 
 the cervical and lumbar enlargements of the cord, they are scattered 
 more sparingly wherever the grey matter extends. They also occur 
 in the spinal ganglia, and their cerebral homologues (such as the Gas- 
 serian ganglion), in the ganglia of the sympathetic system, and the 
 sporadic ganglia in general. But wide as is their distribution, and 
 great as is the size of the individual cells, some of which have a diameter 
 of 140/Z, or even more, they yet make up but a small portion of the whole 
 of the central nervous substance, the total weight of the 9,000 millions of 
 nerve-cell bodies in the human brain being less than 27 grammes 
 (Donaldson). And although it is not to be wondered at that objects 
 so notable when \ iewed under the microscope should have struck the 
 
 imagination of physiologists, it is probable 
 that the \-ery high powers which it is so 
 common to attribute exclusively to them 
 are. in part at least, shared with the network 
 or feltwork formed by their processes. 
 
 The grey matter, in addition to this ex- 
 ceeding!}' delicate feltwork of non-medullated 
 fibres and filaments representing the den- 
 drites and such axons and collaterals as 
 terminate within itself, contains also, as may 
 be seen in preparations stained by Weigert's 
 method,* great numbers of exceedingly fine 
 medullated fibres, many of which are the 
 collaterals of fibres that are passing out to the 
 white matter. 
 
 Only medullated nerve-fibres are met with 
 in the white matter of the cerebro-spinal axis. 
 They are commonly stated to be devoid of a 
 neurilemma (or neurolemma), and in the sense 
 that there is no continuous separate mem- 
 branous sheath corresponding to the sheath 
 of Schwann of the peripheral medullated 
 fibres this is correct. Sheath cells, however, 
 are present, and form a reticulum around each fibre in the meshes 
 of which myelin is contained. In diameter the medullated fibres of 
 the white matter vary from 2 /* to 20 /i. In Malapterums electricus 
 the fibre in the cord which supplies the electrical organ is of immense 
 size; and in the anterior column of many fishes may also be seen a 
 single gigantic fibre on each side with a diameter of nearly 100 jx. It 
 cannot be said that any relation between the functions of neurons 
 and the calibre of their axons has been definitely established. Many 
 afferent fibres, it is true, are small — this is notably the case with the 
 fibres of the posterior column, and many motor fibres are large. But 
 the di.stinction can by no means be generalized, for the fibres of the 
 direct cerebellar tract (p. 866), which certainly are afferent, are amongst 
 the largest in the spinal cord ; and the vaso-motor fibres, which pass from 
 the cord by the anterior (ventral) roots (Fig. 341) into the sympathetic, 
 are smaller than the fibres of the posterior column. Even the motor 
 * Weigert's is a special method of staining the medullary sheath with 
 hematoxylin. 
 
 Fig. 341. — Transverse Section 
 of a Bundle of Nerve- 
 Fibres from the Anterior 
 (Ventral) Root of the First 
 Coccygeal Nerve of the Cat 
 (Dale). The great differ- 
 ence in the diameter of the 
 fibres is well shown. The 
 small fibres are vaso-motor. 
 
HISTOLOGICAL ELEMENTS 86i 
 
 nerve-fibres of striated muscles vary considerably in diameter, those of 
 the tongue, e.g., being smaller than those of the mus'jles of the limbs. 
 Further, the mcdullated fibres of the brain are, without reference to 
 function, in general finer than the fibres of the cord. As a rule the 
 fibres whose course is the longest arc the thickest, but the rule is often 
 broken. For example, the average diameter of the fibres going to the 
 thigh of the frog is greater than that of the fibres going to the lower 
 part of the limb (Dunn). The cause of these differences in the size of 
 nerve-fibres is quite unknown. It is more likely to be morphological 
 than ph\-siological. 
 
 Supporting Tissue. — The protective membranes of the central nervous 
 system consist of ordinar^^ connective tissue derived from the meso- 
 derm. The supporting framework which interpenetrates the nervous 
 substance consists of a peculiar form of tissue derived from the ecto- 
 derm, and called neuroglia. The whole cerebro-spinal axis is wrapped 
 in four concentric sheaths. Next the walls of the bony hollow in which 
 it lies is the dura mater. Next the nervous substance itself, following 
 the convolutions of the brain and the fissures of the cord, and giving 
 off bloodvessels to both, is the pia mater. Between the dura and 
 the pia, separated from ;he latter by a jacket of cerebro-spinal fluid, 
 is the double layer of the arachnoid. The comparatively coarse septa 
 that run into the nervous substance as if coming off from the pia mater 
 are the main beams in the scaffolding of non-nervous material with 
 which that substance is interwoven, and by which it is supported. 
 The interstices are filled in by a thick-set feltwork of interlacing neurog- 
 lia fibres, which lie close against the small glia cells. In preparations 
 impregnated by the Golgi method many of the neuroglia fibres appear 
 to be processes running out from the attenuated cell-body like the 
 arms of a microscopic crab or spider. But this is a deceptive appear- 
 ance, as has been shown by means of special methods in which the 
 neuroglia fibres are alone stained {Weigert, Huber, etc.). They 
 generally lie in close contact with, or embedded in, the protoplasm 
 of the neuroglia cells, from which they have become differentiated 
 structurally and chemically, but sometimes they may detach themselves 
 entirely from the cells and lie free in the intervening tissue. The 
 neuroglia is present in greatest abundance in the grey matter immedi- 
 ately surrounding the central canal of the cord and the ventricles of 
 the brain (the ependyma, as it is called), from which long neuroglia 
 fibres pass out radially, giving off branches on their course, and ending 
 in little knobs or enlargements attached to the pia mater. 
 
 Section II. — General Arrangement of the Grey and White 
 Matter in the Central Nervous System. 
 
 (i) Around the central canal, as we have seen, a tube of grey 
 matter sheathed with white fibres is developed. This tube, from 
 oi)tic thalamus to conus medullaris, may be conveniently referred to 
 as the central grey axis or stem, which, in the lowest vertebrates — e.g., 
 fishes — is much the most important part of the central nervous 
 system . 
 
 (2) On the outer surface of the anterior portion of the neural 
 axis, but not in the part corresponding to the spinal cord, is laid 
 down a second sheet or mantle of cortical grey matter. Between 
 
862 THE CENTRAL NERVOUS SYSTEM 
 
 this and the primitive grey stem are interposed (a) the sheath of 
 white fibres that clothes the latter, and connects its various parts, 
 and (6) a new development of white matter (corona radiata, cere- 
 bellar peduncles), which serves to bring the cortex into relation 
 with the primitive axis, and through it with the rest of the body. 
 
 Although there are histological and developmental differences 
 between the cerebral and the cerebellar cortex, we may, for some 
 purposes, classify them together as cortical formations. Anl we 
 may also include under this head the corpora striata, which, although 
 for descriptive purposes generally grouped with the optic thalami 
 and the other clumps of grey matter at the base of the brain, as the 
 basal ganglia, are to be regarded as cortical in character. As we 
 mount in the vertebrate scale the cortex formation of the secondary 
 fore-brain and hind-brain acquires prominence. 
 
 In other words, the grey matter developed in the roof of the cerebral 
 vesicles I. and III. (Fig. 327) (the grey matter of the cerebral and cere- 
 bellar cortex) comes to overshadow the superficial grey matter hitherto 
 present only in the roof of vesicle II. (in the corpora bigemina). And 
 this cortex formation becomes larger in amount, and, in the case of 
 the cerebral grey matter, more richly convoluted, the higher we ascend, 
 until it reaches its culmination in man. As the anterior cerebral 
 vesicles develop, they spread continually backward, until at length the 
 cerebral hemispheres cover over, and almost completely surround, the 
 primary- fore-brain and the mid- and hind-brains, so that the anterior 
 portion of the primitive stem comes, as it were, to be invaginated into 
 the second wider tube of cortical grey matter. This development of 
 the cortical grey substance is accompanied with a corresponding 
 development of nerve-fibres, for an isolated nerve-cell (apart, of course, 
 from possible embryonic rudiments which have not undergone com- 
 plete development) is no more conceivable than a railway-station the 
 track from which leads nowhere in particular, or a harbour on the top 
 of a hill. 
 
 But it is to be particularly observed that the new formation does 
 not supplant the old, but works through and directs it. The neuro- 
 blasts of the cortex do not throw out their axons to make direct junc- 
 tion with muscles and sensory surfaces. Such junction the cortex 
 finds already established between the primitive cerebro-spinal axis and 
 the peripherJ^ It joints itself on by nerve-fibres to the cells of the 
 central stem; and we have reason to believe that no single axon in an 
 ordinary spinal or cranial nerve* runs all the way from the periphery 
 to the cortex, and no axon of a cortical nerve-cell all the way from the 
 cortex to the periphery, but that the connection is made by a cliain 
 of at least two neurons, the cell-body of one of which is situate in this 
 primitive grey tube. 
 
 The fibres from the cortex of each cerebral hemisphere (corona 
 radiata), radiating out like a fan below the grey matter, are gathered 
 together into a compact leash as they sweep down through the isthmus 
 of the brain in the internal capsule, to join the crura cerebri. The 
 cortex of each cerebellar hemisphere, and the ribbed pouch of grey 
 
 * The olfactory and possibly to some extent the optic nerves are exceptions 
 to this statement. Their relation to the cortex, as is ea,sily under.stood from 
 the manner of their development (p. 850), is different from that of the other 
 nerves. 
 
GREY AND WHITE MA ITER IN THE SPINAL CORD 
 
 863 
 
 matter, known as tlic corpus dentatum, which is buried in its white 
 core, arc also connected l)y strands of fibres with the central stem and 
 the cerebral mantle. The restiform body or inferior peduncle brings 
 the cerebellum into communication with the spinal cord. The superior 
 peduncle by one path, and the middle peduncle by another, connect it 
 with the cerebral cortex. A great transverse commissure, the corpus 
 callosum, unites the cerebral hemispheres across the middle line, while 
 transverse fibres, that break through the middle lobe or worm, form 
 a similar though far less massive junction between the two hemispheres 
 of the cerebellum. 
 
 The fibres of the nervous system may be divided into (i) fibres 
 connecting the peripheral organs with nerve-cells in the central grey 
 axis; (2) fibres connecting nerve-cells in this central axis with cells 
 in the external or cortical grey tube; and (3) fibres linking cortex 
 with cortex, or central ganglia with each other. In the third group 
 are included {a) fibres which connect portions of the cortex on the 
 same side (association fibres) ; {b) fibres which connect portions on 
 opposite sides of the middle line (commissural fibres) ; (c) fibres which 
 connect the central grey matter at different levels — e.g., the proprio- 
 spinal or endogenous fibres of the cord. Our first task is, therefore, 
 to trace the peripheral nerves to their cells of origin or centres of 
 reception* in the nervous stem. And although there is reason to 
 believe that the, whole of the peripheral nerves, cerebral and spinal 
 (with the exception of the olfactory and optic, which are rather 
 portions of the brain than true peripheral nerves), form a morpho- 
 logical series, it will be well to begin with the spinal nerves, since 
 their motor and sensory fibres are gathered into different and definite 
 roots, whose course within the cord is, in general, more easily traced 
 than the course of the cerebral root-bundles within the brain. 
 
 Section III. — Arrangement of the Grey and White Matter 
 IN THE Spinal Cord. 
 
 The grey matter of the spinal cord is arranged on each side in a 
 great unbroken column of roughly crescentic section, joined with 
 its fellow across the middle line by a grey bar or bridge, which 
 springs from the convexity of the crescent, and is pierced from end 
 to end by the central canal. The anterior horn of the crescent, 
 although it varies in shape at different levels of the cord, is, in 
 general, broad and massive, in comparison with the slender and 
 tapering posterior horn. In the lower cervical and upper dorsal 
 region a moulding or projection, forming a lateral horn, springs 
 from the fluted outer side of the grey substance. Within the grey 
 matter nerve-cells are found, sometimes so regularly arranged that 
 they form veritable cellular or vesicular strands. Of these the best 
 
 * The centre or nucleus of reception of a nerve contains the nerve-cells 
 around which its axons terminate; the nucleus of origin of a nerve contains 
 the cells from which its axons arise. 
 
864 
 
 Thin CENTRAL NERVOUS SYSTEM 
 
 marked are — (i) The tract or tracts made up by the cells of the 
 anterior horn (Fig. 342), which practically run from end to end of the 
 cord, swell out in the cervical and lumbar enlargements, where the 
 cells arc very numerous and of great size (70 /j, to 140 jj, in diameter), 
 and contract to a thin thread in the thoracic region, where they are 
 relatively few, scattered, and small. In the enlargements there 
 are several groups of these cells corresponding with the segments 
 
 of the limbs, the movements 
 \ / of the hand, forearm, and 
 
 upper arm being each repre- 
 sented by a group in the 
 cervical, and those of the foot, 
 leg, and thigh by groups in 
 the lumbar swelling. In the 
 rest of the cord only two 
 well-marked groups of cells 
 are present in the anterior 
 horn, a mesial and a lateral. 
 (2) Clarke's column, whose 
 cells, mostly of good size and 
 somewhat rounded in outline, 
 are situated at the inner side 
 of the root of the posterior 
 horn just where it joins on to 
 the grey cross-bar. It gradu- 
 ally increases in size from 
 above downwards, usually 
 appearing first at the level of 
 the seventh or eighth cervical 
 nerve, attaining its maximum 
 development at the eleventh 
 or twelfth dorsal and dis- 
 appearing altogether, as a 
 continuous strand, at the level 
 of the second or third lumbar 
 nerves. Scattered nerve-cells, 
 however, constituting the so- 
 called cervical and sacral nuclei of Stilling, are frequently found 
 occupying the same po.sition towards the upper and lower ends of 
 the cord, and may be looked upon as isolated portions of Clarke's 
 column. (3) A tract of small cells called the intermedia-lateral 
 tract, lateral cell column, or lateral horn, situated at the outer edge 
 of the grey matter, about midway between the anterior and pos- 
 terior horns. It is best marked in the thoracic region, up to about 
 the second thoracic segment, although in the corresponding situa- 
 tion there are scattered cells in the lumbar swelling and the cervical 
 
 StilUr)gs CerULCol 
 r?ucleus 
 - CeruLCoi 
 Lnlargewevt 
 
 lateral Cell- column 
 Ccolurnn of^ p)e enter - 
 medio -lateral tract) 
 
 Stclliops dorsal 
 
 nucleus orClark&'5 
 Column 
 
 Ce]h aj 1he. drilkrior 
 Cornu 
 
 Scattered ceils of' 
 
 iKttermedio-lc^era^ 
 tract 
 
 lurnhdr Enlargement 
 
 StilUno's Sacral 
 nuec&us 
 
 Fig. 342. — Diagram of Grey Tracts of Cord. 
 
GREY AND WHITE MATTER IN THE SPINAL CORD S65 
 
 cord. There is reason to believe that the axons of cells of the inter- 
 medio-lateral tract, which pass out as small medullated fibres in 
 the anterior roots, form tiie preganglionic segments of the efferent 
 vascular and visceral nerves (p. 185)- (4) The cells of the posterior 
 horn, which, although numerous, are smaller than those of the 
 anterior horn. Throughout the whole cord, however, two small 
 groups of cells may be distinguished, one on the lateral side of the 
 horn, about its middle, and the other on the mesial side, a little 
 in front of — i.e., ventral to — the edges of the substance of Rolando. 
 Both of these groups are broken up by the passage through them 
 of bundles of fibres which form a network, and they are therefore 
 called respectively the group of the lateral and the group of the 
 posterior reticular formation. 
 
 The white matter of the cord is anatomically divided by the 
 position of the nerve-roots and the anterior and posterior fissures 
 
 Fig. 343. — Diagrammatic Section of the Spinal Cord in the Cervical and Lumbar 
 Enlargements, to show Tracts of Fibres (Starr), i, antero-median column; 
 2, antero-lateral column; 3, ascending antero-lateral or Gowers' tract; 4, mar- 
 ginal tract (ground bundle, consisting of short endogenous fibres); 5, lateral or 
 crossed pyramidal tract; 6, direct cerebellar tract; 7, tract of Lissauer; 8, ex- 
 ternal portion, and 9, root zone, of Burdach's column; ro, comma tract; 11, pos- 
 terior commissural tract; 12, Goll's column; 13, septo-marginal tract. 
 
 into three columns on each side : the anterior, lateral, and posterior 
 columns. The first two, since they are not separated by a perfectly 
 definite boundary, are often grouped together as the antero-lateral 
 column. In the cervical region it may be seen with the microscope 
 that the posterior white column is almost bisected by a septum 
 running in from the pia mater towards the grey commissure. The 
 inner half is called the postero- median column, or column of Goll ; 
 the outer half the postero-external column, or column of Burdach 
 (Fig. 343). No localization of any of the other conducting paths 
 in the cord is possible by gross anatomical examination; but by 
 means of the developmental method and the method of degenera- 
 tion the columns of Goll and Burdach can be followed throughout 
 the cord, and several similar areas can be mapped out. We shall 
 only mention those that are physiologically the most important. 
 
 55 
 
866 THE CENTRAL NERVOUS SYSTEM 
 
 WluMi the spinal cord is divided, and the animal allowed to survive 
 for a time, certain tracts arc picked out by the degeneration of their 
 fibres, although in every degenerated tract some fibres remain un- 
 affected. We luay distinguish the tracts that degenerate above 
 the lesion (ascending degeneration) from those that degenerate 
 below the lesion (descending degeneration). 
 
 Ascending Tracts. — Above the lesion degeneration is found both 
 in the posterior and the antero-lateral columns. Immediately 
 above the section nearly the w^hole of the posterior column is in- 
 volved. Higher up the degeneration clears away from Burdach's 
 tract, and, shifting inwards, comes to occupy a position in the 
 column of Goll. In the antero-lateral column two degenerated 
 regions are seen, both at the surface of the cord, one a compact, 
 sickle-shaped area extending forwards from the neighbourhood of 
 the line of entrance of the posterior roots, and the other an area of 
 scattered degeneration, embracing many intact fibres, and complet- 
 ing the outer boundary of the column almost to the anterior median 
 fissure. The compact area is called the dorsal or direct cerebellar 
 tract, or tract ofFlechsig {or the fasciculus cerebello-spinalis) , the diffuse 
 area the antero-lateral ascending tract, or tract of Gowers, or ventral 
 cerebellar tract (or the fasciculus antero-lateralis snperficialis).* The 
 dorsal cerebellar tract is distinguished by the large size of its fibres. 
 It is only distinct in the dorsal and cervical regions of the cord. The 
 tract of Lissauer, or posterior marginal zone, is another small ascend- 
 ing tract at the outer side of the tip of the posterior horn. It is 
 made up of fine fibres from the posterior roots which soon pass into 
 the posterior column., 
 
 Descending Tracts. — When the cord is divided, say, in the upper 
 dorsal or cervical region, the following tracts degenerate below the 
 lesion : 
 
 (i) A small group of fibres close to the antero-median fissure, 
 which has received the name of the direct pyramidal tract — pyramidal 
 1 ecause higher up in the medulla oblongata it forms part of the 
 pyramid; direct, because it does not cross over at the decussation of 
 the pyramids, but continues down on the same side. In the stan- 
 dard anatomical nomenclature it is termed the fasciculus cercbro- 
 spinalis anterior. The direct pyramidal tract is only present in man 
 and the higher apes. 
 
 (2) A tract of degenerated fibres in the posterior part of the 
 lateral column. This is the lateral or crossed pyramidal tract (or the 
 fasciculus cerebro-spiualis lateral is), and is much larger than the direct. 
 In the medulla it also lies within the pyramid, but, unlike the direct 
 pyramidal tract, it crosses to the opposite side of the cord at the 
 decussation. The pyramidal tracts are also called corticospinal to 
 indicate their origin and termination. 
 
 ♦ Some WTiters employ the terms dorsal and ventral s/>imo cerebellar 
 tracts. 
 
GREY AND WHITE MATTER IN THE SPINAL CORD 867 
 
 {},\ A tract of scattered degeneration lying along the margin of the 
 cord in the anterior portion of the antero-lattTal column, and partly 
 overlajiping the tract of (iowers. It is called the antcro-lateral 
 descend i Hi:, tract, or tract of Loewcnthal, or the vestibulo-spinal tract. 
 
 (4) The prcpyramidal (or rubrospinal) tract, or M onakoxv' s tract 
 (also called the fasciculus intermcdio-lateralis), \ymg immediately in 
 front of the crossed pyramidal tract. 
 
 (5) A small, comma-shaped island of degeneration {comma tract) 
 can be followed downwards for a short distance in the middle o! 
 Burdach's column. It is only 
 
 and 
 
 D. C 
 
 D.P 
 
 V.B 
 
 seen in the cervical 
 upper thoracic regions. 
 
 Less well known descending 
 tracts are^ - 
 
 (6) The olivo - spinal and 
 thalamico - spinal tracts (or 
 Helweg's bundle) in the antero- 
 lateral column opposite the 
 head of the anterior horn. 
 This tract docs not pass down 
 beyond the lower cervical re- 
 gion. The olivo-spinal tract 
 appears to consist of fibres 
 running down from the olivary 
 body into the cord, while the 
 thalamico-spinal tract is made 
 up of descending fibres origina- 
 ting in the optic thalamus. 
 This is an important tract in 
 the lower vertebrates, but not 
 in man. 
 
 (7) The tract of Marie in the 
 anterior column is chiefly a 
 continuation into the cord of 
 
 the posterior longitudinal bundle, one of the conspicuous tracts of the 
 brain-stem or upper portion of the cerebro-spinal axis (p. 885). It 
 contains both ascending and descending fibres. 
 
 When we have deducted the long ascending and descending tracts 
 which have been described, there still remains in the antero-lateral 
 column a balance of white matter unaccounted for. This white 
 substance, which does not degenerate for any great distance either 
 above or below a lesion, is called the antero-lateral ground-bundle, 
 and lies chiefly in the form of an incomplete ring around the grey 
 matter. For descriptive purposes it is sometimes distinguished as 
 the anterior ground-bundle (or fasciculus anterior proprius) in the 
 anterior column, and the lateral ground-bundle (or fasciculus lateralis 
 proprius) in the lateral column. It is believed to consist of fibres 
 (endogenous or proprio-spinal fibres) which run only a comparatively 
 short course in the cord, and serve to connect nerve-cells at different 
 levels. Some of these endogenous fibres are ascending, others 
 
 Fig. 344. — Scheme of Cross-Section of Spinal 
 Cord (Donaldson, after Lenhossek). On the 
 left side only the afferent fibres are shown; 
 the efferent fibres and the spinal cells on the 
 right side. D.R., posterior (dorsal) root; 
 V.R.x anterior (ventral) root; C.P., crossed 
 pyramidal fibres; C, direct cerebellar tract; 
 A.L., antero-lateral tract; D.C., posterior 
 columns. 
 
868 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 descending. The sepio-marginal bundle consists also largely of fibres 
 which begin and end in the cord (proprio-spinal fibres). Some endog- 
 
 Figr 345.— Medulla Oblongata, Pons and 
 • Corpora Quadrigemina (Dorsal or Pos- 
 terior View) (Sappey). i, corpora 
 quadrigemina; 2, nates; 3, testes; 
 4, anterior brachium uniting the nates 
 to the lateral geniculate body; 5. pos- 
 terior brachium uniting the testes to 
 the internal geniculate body 6; 7, pos- 
 terior commissure; 8, pineal gland 
 pulled forward to show nates; 9, su 
 perior peduncle of the cerebellum; 10 
 II, 12, valve of Vieussens; 13, troch 
 lear nerve; 14, lateral sulcus; 15, fillet 
 16, superior, 17, middle, and 18, in 
 ferior, peduncle of the cerebellum 
 19, floor of fourth ventricle; 20, audi 
 tory nerve; 21, spinal cord; 22, postero 
 median column, continued in the me 
 dulla as the funiculus gracilis; 23, the 
 clava, the continuation of the funiculus 
 gracilis. 
 
 Fig. 346. — Medulla Oblongata, Pons 
 and Crura Cerebri (Ventral or .in- 
 terior View). I, infundibuluin; 
 2, tuber cinereum; 3, corpus mam- 
 millare; 4, cerebral peduncle or crus 
 cerebri; 5, pons; 6, middle peduncle 
 of cerebellum; 7, pyramid; 8, decus- 
 sation of pyramids; 9, olive; 10, tu- 
 bercle of Rolando ; 11, e.\ternal 
 arcuate fibres; 12, upper end of cord; 
 13, ligamentum denticulatum; 14, 
 dura mater of cord; 15, optic tract; 
 16, chiasraa; 17, third nerve; 18, 
 fourth nerve; 19, fifth nerve; 30, 
 sixth nerve; 21, seventh nerve; 22. 
 eighth nerve; 23, nerve of VVrisberg 
 (portio intermedia), which unites 
 with the facial; 24, glosso-pharyn- 
 geal nerve; 25, vagus; 26, spinal 
 accessory; 27, hypoglossal; 28, 29, 
 30, first, second, and third pairs of 
 cervical spinal nerves. 
 
 enous fibres may also be intermingled with the fibres of certain of 
 the long tracts, both in the antero-lateral and posterior columns, and 
 
GREY AND WHITE MATTER IN CEREBROSPINAL AXIS 860 
 
 Sherrington has shown (in Xhv do^) lli;i.t long proprio-spinal fibres 
 passing down in the lateral colunm connect the upper with the lower 
 parts of the cord (p. 908). 
 
 The next question which arises is: How are the long tracts con- 
 nected below — i.e., with the periphery — and above — i.e., with the 
 higher parts of the central nervous system ? The answer to this 
 question, partly derived from clinical records and partly from 
 experimental results, is in the case of some of the tracts unexpectedly 
 full and minute, though meagre in regard to others. But to render 
 it intelligible it is necessary, first of all, to describe briefly — 
 
 Section IV. — Arrangement of Grey and White Matter 
 IN the Upper Portion of the Cerebro-Spinal Axis. 
 
 In the medulla oblongata the grey and white matter of the spinal 
 cord is rearranged, and, in addition, new strands of fibres and new 
 nuclei of grey substance make their appearance. Of these nuclei the 
 most conspicuous is the 
 dentate nucleus of the in- 
 ferior olive, which, covered 
 by a crust of white fibres, 
 appears as a projection on 
 the antero-latcral surface 
 of the medulla. In front 
 of the olive, between it 
 and the continuation of 
 the anterior median fis- 
 sure, is another projec- 
 tion, the pyramid, which 
 looks like a prolongation 
 of the anterior column of 
 the cord, but is made up 
 of very different consti- 
 tuents. Dorsal to the 
 olive is the restiform body 
 or inferior peduncle of the 
 cerebellum, and behind 
 the restiform body lie two pjg. 347._Medulla Oblongata and Cerebellum, with 
 thin columns, \\\e funicn- Fourth Ventricle (Hirschfeld). i, mesial groove 
 Itis cuneatus. which con- of floor of ventricle running down to the calamus 
 tinues the postero-exter- scriptorius; 2, stria3 acustica-; 3, inferior peduncle 
 nal column of the cord, of the cerebellum; 4, clava; 5, superior peduncle 
 a.nd the funic itlus gracilis, crossing the inferior and passing to its internal 
 which continues the pos- side; 7. 7. lateral sulcus; 8, corpora quadrigemina. 
 tero-internal column. In 
 
 these funiculi are contained collections of small or medium-sized nerve- 
 cells termed respectively the nucleus cuneatus and the nucleus gracilis. 
 The rearrangement of the constituents of the cord is due mainly to two 
 causes: (i) The opening up of the central canal to form the fourth 
 ventricle, and the folding out, on either side, of the grey matter which 
 lies posterior to it in the cord; (2) the breaking up of the grey matter 
 of the anterior horn by strands of fibres as they sweep through it from 
 the lateral pyramidal tract to take up a position in the p^Tamid of the 
 opposite side (decussation of the pyramids), and a little higher up by 
 
870 THE CENTRAL NERVOUS SYSTEM 
 
 fibres passing across the middle line from the gracile and cuncate nuclei 
 (sensory decussation or decussation of the fillet). The mosaic of grey 
 and white matter formed in the medulla by the interlacing of longi- 
 tudinal and transverse fibres with each other and with tlie relics of the 
 anterior horn, is called the reticular formation (formatio reticularis). 
 It occupies the anterior and lateral portions of the bulb behind the 
 pyramids and olivary bodies, and is continued upwards in the dorsal 
 portion of the pons and crura cerebri, and downwards for a little way 
 into the upper part of the cervical cord. 
 
 The cercbro-spinal axis passes up from the medulla through the pons, 
 encircled and traversed by the transverse pontine fibres derived from 
 the middle cerebellar peduncle or commissure, which enclose every- 
 where between them numerous collections of nerve-cells {nuclei ponti's). 
 Enlarged by the accession of many of these fibres which come from the 
 cortex of the cerebellum on the opposite side, as well as of fibres from the 
 nuclei of the cranial nerves that take origin in this neighbourhood (fifth 
 and eighth), the central nervous stem bifurcates above the pons into the 
 two divergent crura cerebri. From each crus a great sheet of fibres 
 passes up betrween the optic thalamus and the caudate nucleus of the 
 corpus striatum on the one hand, and the globus pallidus of the lenticular 
 nucleus on the other, as the internal capsule, from which they are dis- 
 persed, in the corona radiata, to the cerebral cortex. Both in the upper 
 part of the pons and in the crus a ventral portion, or crusta, containing 
 the fibres of the pyramidal tract, and a dorsal portion, or tegmentum, 
 can be distinguished, the line of separation being marked in the crus by 
 a collection of grey matter, called from its usual, though not invariable, 
 colour the substantia nigra (Fig. 352), A portion of the tegmentum is 
 continued below the optic thalamus. 
 
 Section V. — Connections of the Long Paths of the Cord. 
 
 Coming back now to our question as to the connections of the long 
 tracts of the cord, let us consider, first of all, 
 
 The Connections of the Postero-Median and Poster©- External 
 Columns. — When a single posterior root is divided, say, in the dorsal 
 region, between the cord and the ganglion, its fibres, as we have 
 already seen (p. 797), degenerate above the section. Since the cell- 
 bodies of these neurons lie in the ganglion, if a series of microscopic 
 sections of the spinal cord be made, well-marked degeneration will 
 be found at the level of entrance of the root on the same side of the 
 cord, while below that level there will be only a few degenerated 
 fibres in the comma tract. Immediately above the plane of the 
 divided root the degeneration will be confined to Burdach's column 
 and to its external border. Higher up it will be found in the internal 
 portion of Burdach's and the external rim of Goll's column. Still 
 higher up the degenerated fibres will be confined to the postero- 
 median column ; the postero-external will be free from degeneration. 
 
 When a number of consecutive posterior roots are cut, the whole 
 of the postero-external column in the sections immediately above 
 the highest of the divided roots will be found occupied by degene- 
 rated fibres, while Goll's column may be free from degeneration, or 
 
CONNECTIONS OF THE LONG PATHS OF THF CORD 
 
 871 
 
 f—yr^ 
 
 degenerated only at its outer border. Higher up degeneration will 
 be found to have involved tiie whole of the postero-median column, 
 and to liave cleared away altogether from the postero-external. 
 Tlie degeneration in the column of (ioll may be traced along the 
 whole length of the cord to the medulla, although the number of 
 degenerated fibres diminishes as we pass upward. The explanation 
 of these appearances is as follows: It may be 
 seen in preparations of the cord impregnated by 
 Golgi's method that the fibres of the posterior 
 roots soon after their entrance into the cord 
 divide into two processes, one of which runs up 
 and the other down in the posterior column, or 
 in the adjoining portion of the posterior horn. 
 From both of these collaterals are given off at 
 intervals to the grey matter. The descending 
 branches run downwards only for a short dis- 
 tance, and the degeneration in the comma tract 
 seen after section 
 of the cord is due 
 to the division of 
 these branches. 
 Many of the as- 
 cending branches 
 pass up for a short 
 distance in the 
 postero-external 
 column, sweeping 
 obliquely through 
 it to gain the tract 
 of Goll. In this 
 tract some of them 
 run right on to 
 the medulla ob- 
 longata, to end by 
 arborizing among 
 the cells of the 
 nucleus gracilis. 
 Other fibres, both 
 of Goll's and of 
 Burdach's tract, 
 end at various 
 levels in the cord, 
 their collaterals, and ultimately the main branches themselves, 
 coming into relation with nerve-cells in the grey matter. When the 
 cervical posterior roots are cut, many of the degenerated fibres 
 remain in Burdach's column up to the medulla, where they terminate 
 
 ^-^ 
 
 Fig. 348.— Diagrams 
 of Degeneration at 
 Difierent Levels in 
 the Cord after Sec- 
 tion of a Number of 
 Posterior Roots of 
 Nerves forming the 
 Lumbo-Sacral Plex- 
 us (Mott). 
 
 Fig. 349. — Branching of Posterior 
 Root-Fibres in Cord (Donald- 
 son, after Cajal). Collaterals, 
 Col, are seen coming off from 
 the two main branches of the 
 root -fibres. DR, and ending in 
 arborizations. CC, cells in the 
 grey matter of the cord, whose 
 axons also give off collaterals. 
 
872 THE CENTRAL NERVOUS SYSTEM 
 
 in the nucleus cuneatus. In the posterior cohimn, then, the 
 numerous fibres of the posterior roots which do not end in the spinal 
 cord are arranged in layers, the fibres from the lower roots being 
 nearest the median fissure (in the postero-median column), and those 
 from the higher roots farthest away from it (in the postero-extemal 
 column. Thus, in a section througli the upper cervical region Goll's 
 column is almost entirely composed of fibres from the posterior limb, 
 while the column of Burdach consists of fibres from the anterior 
 limb. Other collaterals from the posterior root-fibres, and many 
 of the main root-fibres themselves, run into the anterior horn and 
 terminate in arborizations around its cells; some pass into the 
 posterior horn, and doubtless come into relation with its scattered 
 cells and, in the dorsal region, with the cells of Clarke's column. 
 Some of the posterior root-fibres and their collaterals also form 
 synapses with the cells of the intermedio-lateral tract. Other 
 collaterals and probably some axons cross the middle line in the 
 anterior and posterior commissures and end in the grey matter of the 
 opposite side. 
 
 Connections of the Direct or Dorsal Cerebellar Tract. — Since the 
 dorsal or direct cerebellar tract does not degenerate after section of 
 the posterior nerve-roots, but does degenerate above the level of the 
 lesion after section of the spinal cord, the nerve-cells from which its 
 axons arise must be situated somewhere or other in the cord. Now, 
 it has been observed that the vesicular column of Clarke first becomes 
 prominent in the lower dorsal region, and that in this same region 
 the direct cerebellar tract begins. Atrophy of the cells of Clarke's 
 column has sometimes in disease been shown to accompany de- 
 generation of the direct cerebellar fibres. After an experimental 
 lesion of these fibres in animals, some of the cells of the vesicular 
 column show the changes in the Nissl bodies and the other changes 
 which we have already described as occurring in nerve-cells whose 
 axons have been cut. After two or three months these cells may 
 be found almost completely atrophied (Schafer). Finally, axis- 
 cylinder processes have been seen sweeping out from Clarke's 
 column into the direct cerebellar tract (Mott). The evidence, then, 
 is complete that the cells of origin of this tract are in Clarke's column. 
 Clarke's cells are surrounded by arborizations, some of which, as 
 previously stated, represent the terminations of posterior root-fibres 
 and of their collaterals. The neurons whose axons run in the dorsal 
 cerebellar tract arc therefore the second link in an afferent path. 
 The direct cerebellar tract runs right up to the cerebellum through 
 the restiform body, without crossing and without being further 
 interrupted by nerve-cells. The restiform body ends parti v in the 
 dentate nucleus of the cerebellum, partly in the vermis, and among 
 the fibres which end in the vermis are those of the direct cerebellar 
 tract. In the dorsal cerebellar tract there is a definite stratification 
 
CONNECTIONS OF THE LOSG PATHS OF THE CORD 
 
 873 
 
 of the fibres: the fibres from the lowest segments of the cord lie 
 outermost; beneath these come fibres from the lowest thoracic seg- 
 ments, then fibres from the higher thoracic segments; and, internal 
 to all, fibres from the topmost thoracic and lowest cervical segments. 
 
 Connections of the Antero-Lateral Ascending Tract. — According to 
 Schafcr. tlic axons of this tract arc prf)bably connected with cells 
 situated in the middle and posterior parts of the grey crescent, mainly 
 
 Fig. 350. — Transverse Section of Medulla 
 Oblongata at the Level of the Decussa- 
 tion of the Fillet (Halliburton, after 
 Schwalbe). a.m.f, anterior, and p.m./, 
 posterior, median fissure; /.a and f.a^, 
 external arcuate fibres; f.a', internal 
 arcuate fibres becoming external; n.a.r, 
 nuclei of arcuate fibres; py, pyramid; 
 o, 0', lower end of nucleus of olive; /.r, 
 formatio reticularis; n.l, lateral nucleus; 
 n.g, nucleus gracilis; f.g, funiculus gra- 
 cUis; n.c, nucleus cuneatus; n.c', external 
 cuneate nucleus; /.c, funiculus cuneatus; 
 g, substance of Rolando; c.c, central canal 
 surroundedby grey matter; n. A'7, nucleus 
 of spinal accessory; n.XII, of hypoglos- 
 sal; a.V, ascending root of fifth nerve; 
 s.d, the decussation of the fillet, or 
 superior decussation. 
 
 Fig. 351 — Transverse Section of Medulla 
 Oblongata at about the Middle of the 
 Olive (Sch.valbe). f.l.a, anterior median 
 fissure; n.a.r, arcuate nucleus; p., pyra- 
 mid; n.XII, h\'poglossal nucleus; XII, 
 root bundle of hypoglossal ner\-e coming 
 off from the surface ; at 6 it rims between 
 the pyramid and the dentate nucleus of 
 the olive, 0; f.a.e, external arcuate fibres; 
 n.l, lateral nucleus; a, arcuate fibres going 
 to restiform body c.r, partly through the 
 substantia gelatinosa g, partly superficial 
 to the ascending root of the fifth nerve 
 a.V; X, root-bundle of vagus; n.X , n.X', 
 two portions of vagus nucleus; f.r, for- 
 matio reticularis: n.g, nucleus gracilis; 
 n.c, nucleus cuneatus; n.t, nucleus of the 
 funiculus teres; n.am, nucleus ambiguus; 
 f, raphe; 0', 0", accessory olivary nucleus; 
 p.o.l, peduncle of the olive. 
 
 on the opposite side of the cord . although also on the same side. None of 
 the fibres of the tract can come directly from the posterior nerve-roots, 
 since no degeneration is seen in it on section of the roots alone. 
 
 The antero-lateral ascending tract passes up through the medulla, 
 where some of its fibres perhaps form synapses with the cells of the 
 
'74 
 
 THE CENTRAL \ERVOUS SYSTEM 
 
 lateral nucleus, a collection of grey matter in the lateral portion of the 
 spinal bulb. But its main strand runs on unbraken through the 
 medulla, in front of the rcstiform body, and behind the olive, and after 
 reaching the upper part of the pons bends back over and in company 
 with the superior peduncle as the ventral spino-cerebcUar bundle, to 
 end in the worm of the cerebellum (Fig. 363). 
 
 A few fibres of Gowers' tract may pass by the middle peduncle to the 
 opposite cerebellar hemisphere, bome of its fibres do not go to the 
 cerebellum at all. One group can be followed to the corpora quadri- 
 gemina {spiyio-tectal fibres), and another by way of the tegmentum of the 
 crus cerebri to the optic thalamus {spino-thalamic fibrss). 
 
 Through the relay of the gracile and cuncate nuclei, the postero- 
 internal and postero-external columns of the cord are further con- 
 nected on the one hand with the cerebrum, and on the other with the 
 cerebellum. The cells of the nuclei give oft fibres (internal arcuate 
 fibres) which, sweeping in wide arches across the mesial raphe to the 
 
 opposite side, take up 
 a position behind the 
 pyramid in the tract of 
 the filld, a bundle of 
 fibres which becomes 
 more compact, and 
 therefore more distinct, 
 as it passes brainwards. 
 Receiving fibres from 
 other sources on its 
 way, and also giving 
 off fibres, it runs up- 
 wards through the dor- 
 sal or tegmental portion 
 of the pons. In the mid- 
 brain it divides into 
 two portions, the lateral 
 fillet, also called the 
 lower fillet or fillet of Reil, and the intermediate, also called the upper 
 fillet. The lateral fillet contains mainly fibres arising in the cochlear 
 nucleus of the auditory never, and ends in grey matter of the pos- 
 terior corpus quadrigeminum, and partly in the mesial geniculate 
 body. It appears to be a path for the conduction of auditory 
 impulses. The intermediate fillet contains chiefly the fibres that 
 come off from the gracile and cuneate nuclei, but is enlarged by the 
 accession of fibres from the sensory nuclei of the cranial nerves. It 
 terminates in the lateral nucleus of the optic thalamus by forming 
 synapses with nerve-cells, whose axons, passing through the posterior 
 limb of the internal capsule and the corona radiata, continue the 
 afferent path to the cerebral cortex. 
 
 Not all of the axons from the cells of the cranial sensory nuclei run 
 
 Fig- 35-- — Diagrammatic Transverse Section of 
 Crura Cerebri and Aqueduct of Sylvius, a, an- 
 terior corpora quadrigemina 6, aqueduct; c, red 
 nucleus; d, fillet; e, substantia nigra;/, pyramidal 
 tract in the crusta of the crura cerebri: g,, fibres 
 from frontal lobe of cerebrum; h, fibres from tem- 
 poro-occipital lobe ; i, posterior longitudinal bundle. 
 
CONNECTIOSS OF THE LONG PATHS OF THE CORD 873 
 
 in the fillet. Many of them occupy a position in the reticular forma- 
 tion of the tegmentum dorsal to the tillet as they pass through the 
 pons and mid-brain to end in the thalamus and the region below it 
 (sub-thalamic region). From the sensory nucleus 0^ the fifth nerve 
 a separate bundle of fibres ascends to the thalamus, in the tegmen- 
 tum of the mid-brain lateral to the posterior longitudinal bundle. 
 Connections of the Pyramidal Tracts. — When the cortex in and in 
 front of the fissure of Rolando is destroyed by disease in man, or 
 removed by operation in animals, it is found that in a short time 
 degeneration has taken place in the fibres of the corona radiata which 
 pass off from this area. The degeneration can be followed down 
 through the genu and the anterior two-thirds of the posterior limb 
 of the internal capsule r 
 
 (Fig- 353) and the 
 crusta of the cerebral 
 peduncle of the corre- 
 sponding side into the 
 medulla oblongata. 
 Below the decussation 
 of the pyramids it is 
 found that the degene- 
 ration has involved the 
 two pyramidal tracts, 
 and only these — the 
 crossed pyramidal 
 tract on the side oppo- 
 site the cortical lesion, 
 the direct pyramidal 
 tract on the same side 
 — and that the cross- 
 section of the two de- 
 generated tracts goes 
 on continually dimin- 
 ishing as we pass down the cord. (We overlook for the moment, in 
 the interest of simplicity of statem.ent, the fact that some degenerated 
 fibres are found in the crossed pyramidal tract on the same side as the 
 lesion.) This is proof positive that the cell-bodies of the neurons whose 
 axons run in these tracts are situated in the cerebral cortex. They 
 have indeed been identified with certain of the large pyramidal cells 
 (the so-called giant cells or cells of Betz) in the cortex of the " motor ' 
 region in front of the Rolandic fissure (p. 950). For after division 
 of the motor pyramidal fibres in the upper cervical region of the cord 
 (in monkeys) changes in the chromatin (so-called chromatolysis) and 
 atrophy of these large cells occur. The same has been found to be 
 true in man in cases where the cord was injured by fracture of the 
 spine in such a way as to interrupt the tract (as well as other tracts) 
 
 MID. BRAIN 
 Fig. 353. — Pyramidal Path (after Gowers). Degenera- 
 tion after destruction of the ' motor ' area of the 
 right cerebral hemisphere. The degenerated areas 
 are indicated by the shading. 
 
876 THE CENTRAL NERVOUS SYSTEM 
 
 couiplcU'ly and permanently, without entailing death for a consider- 
 able time (Holmes and May). The fact that after destruction of the 
 cortex or the path in its course the degeneration below th<; lesion does 
 not spread to the anterior roots shows that at least one relay of 
 nerve-cells intervenes between the pyramidal fibres and the root- 
 ftbres. The results both of normal and morbid histology enable us 
 to identify the cells of the anterior horn as the cells of origin of the 
 axons of the anterior root- fibres. For 
 
 (i) Axis-cylinder processes have been actually observed passing out 
 from certain of the so-called motor cells of the anterior horn to become 
 the axis-cylinders of the anterior root. 
 
 (2) In the pathological condition known as anterior poliomyelitis, 
 the cells of the anterior horn degenerate, and so do the anterior roots 
 of the affected region, the motor fibres of the spinal nerves, and the 
 muscles supplied lay them. 
 
 (3) As already mentioned (p. 858), comparatively transient but 
 decided changes occur in the anterior horn cells on section of the corre- 
 sponding anterior roots. 
 
 (4) An enumeration* has been made in a small animal (frog) of the 
 cells of the anterior horn and of the anterior rcot-fibres, and it has been 
 found that the numbers agree in a remarkable manner. From all this 
 it cannot be doubted that most, at any rate, of the cells of the anterior 
 horn are connected with fibres of the anterior root. But since the 
 number of fibres in the pyramidal tracts (about 80,000 in each half of 
 the human cord) falls far short of the number of fibres in the anterior 
 roots (not less than 200,000 in man on each side), it is necessary to 
 suppose either that one pyramidal fibre may be connected with several 
 cells or that all the anterior root-fibres are not in functional connection 
 with the pyramidal tract. 
 
 There is no reason to assume any such connection in the case of the 
 fine meduUated root-fibres arising in the lateral horn and going to the 
 visceral and vascular muscles. 
 
 While there is no doubt that anterior root-fibres and pyramidal 
 fibres of the brain and cord form segments of the same nervous path, 
 the connection between the pyramidal fibres and the cells of the 
 anterior horn has not yet been anatomically demonstrated. Many of 
 the pyramidal fibres pass into the grey matter between the anterior 
 and posterior horns or near the base of the posterior horn. The 
 anterior horn cells are surrounded by arborizations. Some of these 
 are probably the terminations of axons whose cell-bodies are situated 
 in the posterior horn, others the terminations of posterior root-fibres 
 or their collaterals. Many of them very likely represent the end 
 arborizations of pyramidal fibres or their collaterals. Some ob- 
 servers, however, suppose that the pyramidal fibres do not come into 
 immediate relation with the anterior horn cells, but that another 
 neuron is intercalated between them and the cells. 
 
 The pyramidal fibres are unquestionably paths for voluntary 
 motor impulses passing down from the cortex to the cord. But 
 
 • Such enumerations can be made with great accuracy from photographs 
 of sections of the nerves (Hardesty, Dale). (See Fig. 341, p. 860.) 
 
CONNECTIONS OF THI-l LONG J'.iriJS OF THE CORD 877 
 
 they are not the only cortico-spinal efferent paths, and in many 
 animals they are not even the most important paths for voluntary 
 movements. It is the more skilled and delicate movements which 
 the pyramidal tract subserves in man, and it is these movements 
 which arc permanently lost when the tract is destroyed. The size 
 of the path is proportioned to the degree of development of the 
 brain. Thus, it is larger in the monkey than in the dog, larger in the 
 anthropoid apes than in the lower monkeys, and larger in man than 
 
 Fig- 354- — Paths from Cortex in Corona Radiata (Starr). A, tract from frontal con 
 volutions to nuclei of pons and so to cerebellum; B, motor pyramidal tracts 
 C, afferent tract for tactile sensations {represented in the diagram as separated 
 from B by an interval for the sake of clearness); D, visual tract; E, auditory 
 tract; F, G, H, superior, middle, and inferior cerebellar peduncles; J, fibres 
 from the auditory nucleus to the posterior corpus quadrigeminum ; K, decussa- 
 tion of the pyramids in the bulb; FY, fourth ventricle. The roman numerals 
 indicate the cranial nerves. 
 
 in even the highest of the apes. In the lower mammals it is exceed- 
 ingly small. While in man the pyramidal tracts constitute nearly 
 12 per cent, of the total cross-section of the cord, they make up 
 little more than i per cent, in the mouse, 3 per cent, in the 
 guinea-pig, 5 per cent, in the rabbit, and nearly 8 per cent, in the cat. 
 In some mammals, as the rat, mouse, guinea-pig, and squirrel, the 
 pyramidal tracts lie, not in the antero-lateral, but in the posterior 
 columns. In vertebrates below the mammals the pyramidal system 
 does not exist as a collection of neurons which send their axons with- 
 
R78 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 out interruption down from the cortex to the cord. In liirds, e.f^., 
 after the removal of a hemisphere, the degeneration does not extend 
 below the mid-brain (Boyce). 
 
 Section VI. — Paths from and to the Cortex. 
 
 Thus far we have been able to map out two great paths from 
 the cerebral cortex to the periphery — one efferent, the other afferent, 
 (i) The great efferent or motor pyramidal path, which, starting in 
 the cortex in front of the fissure of Rolando, where its axons give off 
 numerous collaterals to the grey matter soon after emerging from 
 the cells, and sweeping down the broad fan of the corona radiata, 
 
 passes through the narrow 
 isthmus of the internal cap- 
 sule into the crusta of the 
 crus cerebri, and thence into 
 the pons (Figs. 354, 355). At 
 this level, the fibres destined 
 to make connection with the 
 motor nuclei of the cranial 
 nerves in the grey matter 
 underlying the aqueduct of 
 Sylvius and the fourth ven- 
 tricle terminate. Most of 
 these fibres decussate to make 
 physiological connection with 
 nuclei on the opposite side, 
 but some join nuclei on the 
 same side. The question 
 whether they arborize di- 
 rectly around the cells of the 
 motor nuclei or make junc- 
 tion with them through 
 another intercalated neuron 
 is precisely in the same 
 position as the corresponding 
 question for the spinal pyra- 
 midal path (p. 876). On their 
 way through the pons they send off collaterals to the nuclei 
 pontis, as they do higher up to the grey matter of the basal 
 ganglia of the cerebrum and the substantia nigra, and the path 
 may be continued to the motor nuclei by axons arising here. 
 There is no proof, however, that this is the case. The rest of 
 the pyramidal fibres run on into the pyramid of the bulb, 
 where the greater part (usually about 90 per cent.) of the fibres 
 decussate, appearing in the c^Tvical cord as the massive crossed 
 
 Fig. 355. — Motor Pyramidal Tracts (Diagram- 
 matic) (Halliburton, after Gowers). The 
 convolutions are supposed to be cut in 
 vertical transverse section, the internal 
 capsule, I, C, and the crus in horizontal 
 section. O, TH, optic thalamus; CN, cau- 
 date nucleus; L2 and L3, middle and ex- 
 ternal portions of lenticular nucleus; f,a, I. 
 fibres from the face, arm. and leg areas of 
 the cortex respectively; E, S, Sylvian fis- 
 sure. The genu or knee of the internal 
 capsule is indicated by the asterisk. 
 
PATHS FROM AND TO THE CORTEX 
 
 879 
 
 pyiiiinuhil liiicl ot the o[)p()sitc side. A few (usually about 10 per 
 cent.) reniiiin on tlie same side as the slender direct pyramidal tract. 
 The size of this tract varies much in different individuals, and it 
 is occasionally absent. Its breadth constantly diminishes as it 
 proceeds down the cord, and it disappears before the middle of the 
 thoracic region is reached, its fibres continually decussating across 
 the anterior white commissure and plunging into the opposite 
 anterior horn. They 
 either end among its 
 cells, or, passing through 
 it, reinforce the crossed 
 pyramidal tract. The 
 fibres of t his crosse d t ract 
 are, in their turn, con- 
 tinually passing off into 
 the grey matter to make 
 connection (p. 876) with 
 the cells of the anterior 
 horn, whose axis-cylin- 
 der processes enter the 
 anterior roots of the 
 spinal nerves. The losses 
 which it suffers as it 
 descends the cord may 
 be in some slight degree 
 compensated by the bi- 
 furcation of some of its 
 fibres (geminal fibres), 
 but ultimately the whole 
 tract forms synapses 
 with cells in the grey 
 matter, and dwindles 
 away as the lumbar re- 
 gion is reached(Fig. 343). 
 A certain number of the 
 pyramidal fibres do not 
 decussate either in the 
 bulb or in the cord. 
 These are called homo- 
 lateral fibres. They run 
 down in the lateral py- 
 ramidal tract, and are 
 represented by the fibres 
 that degenerate in that 
 tract after a lesion in the ' motor ' area of the same side (p. 875)- 
 This would explain the escape in hemiplegia (parah'sis of one side 
 
 Fig. 356. — Horizontal Section through the Right 
 Hemisphere to show the Constituents of the 
 Internal Capsule (von Monakow). A, knee of 
 corpus callosum : B, anterior, B', posterior, horn of 
 lateral ventricle; C, knee of internal capsule; 
 S. sensory fibres; V, visual tract; AH, Amnion's 
 horn; Calc, calcarine fissure; T, first, T', second, 
 temporal convolution; OR, optic radiation; Aud, 
 auditory tract ; D, retrolenticular region of internal 
 capsule; lo. lenticulo-optic division of internal 
 capsule; CI, claustrum; op., operculum; I, island 
 of Rcil; E, external capsule; Is, lenticulo-striate 
 division of internal capsule; F, fibres from frc-ntal 
 lobe; F', inferior part of third frontal convolution; 
 Tk, optic thalamus; Put, putamen. 
 
88o THE CENTRAL NERVOUS SYSTEM 
 
 fiSrpiJlsCAlIoSum,. 
 
 ?-^^L^(sU5ff. 
 
 ^Lt.ntkuliLi-Ngckus 
 
 
 
 'P'tjiTAf'fcflcrcItJs 
 
 6mo-Ccirri(il fibrd 
 
 Crosstd Sensory Fibres 
 /pAin. Hti.t& Cold\ 
 ITouch & Pressure/ 
 
 —foferlorOUw 
 
 5f)ino-Cer€belUr 
 Tracts 
 
 (Co-ordinfiitton & 
 Muscular Tont 
 
 De£(> ftftuafe Fibres 
 
 Dorsal Column (direct) 
 /stnst of posifion '\ 
 \ ' " moi/tmcnf/ 
 
 S^nd.lGan^li'on _. 
 Sf>iri&.l Nerve Jl:< 
 
 Fig. 337. — Ascending Nerve Tracts (after Holmes), 
 
PATHS FROM AND TO THE CORTEX 881 
 
 of the botly) of those muscles which are accustomed to work with 
 the corresponding muscles on the opposite side — e.g., the respiratory 
 muscles, these being innervated to some extent from both cerebral 
 hemispheres. 
 
 (2) A great afferent or sensory path by which some at least of the 
 impulses carried up through the posterior roots of the spinal nerves, 
 after passing through various relay's of nerve-cells, reach the cortex 
 of the cerebellum ; or the upper portions of the central grey tube, the 
 corpora quadrigemina and optic thalamus; or, finally (through the 
 tegmentum and the posterior limb of the internal capsule behind the 
 motor fibres), the cerebral cortex itself. 
 
 The efferent pyramidal path from the cortex to the periphery is 
 broken by at most two relays of nerve-cells — those intercalated cells 
 to which reference has already been made (p. 876), if they really 
 exist, and the motor cells of the anterior horn. The afferent path to 
 the cerebral cortex is interrupted by at least three relays with axons 
 of considerable length. One of the cells is situated in the ganglion 
 on the posterior root, another in the medulla oblongata, a third in the 
 optic thalamus ; and on some of the routes another, or even more than 
 one, is intercalated between the medulla and the cortex (Fig. 357). 
 
 The Internal Capsule. — We have already recognized the pyramidal 
 tract and the afferent tegmental path as constituents of the internal 
 capsule. The cranial fibres of the pyramidal tract occupy mainly 
 the genu or knee, the spinal fibres the posterior limb as far back as 
 the posterior border of the lenticular nucleus (Fig. 356). 
 
 The fibres from the various motor areas are to a certain extent 
 arranged in order in the capsule, those for the eyes and head lying 
 farthest forward, those for the leg farthest back, while the fibres 
 going to the face, arm and trunk occupy intermediate positions. 
 The separation, however, is far from complete, the fibres of neigh- 
 bouring regions being considerably intermixed (Hoche). As the 
 tracts pass downwards the intermingling becomes continually 
 greater (Simpson and Jolly) (Figs. 358, 359)- The afferent fibres 
 from the thalamus to the cortex, which we have described as the 
 last segment of the afferent tegmental path, lie in the posterior part 
 of the posterior limb. But here again there is no absolutely sharp 
 line of demarcation. Some motor fibres are intermingled with the 
 sensory in the posterior part of the capsule, for lesions of this region 
 produce a certain degree of paralysis as well as anaesthesia on the 
 opposite side of the body. A pure capsular hemiansesthesia — that 
 is, a loss of sensation on the opposite side due to a lesion in the 
 internal capsule and unaccompanied by motor defect — does not 
 appear to exist. Accordingly the common statement that the efferent 
 (motor) path occupies the anterior two-thirds, and the afferent 
 (sensory) path the posterior third of the posterior limb of the 
 internal capsule, while true in a general sense, is not strictly correct. 
 
 56 
 
8S2 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 The destination of the afferent fibres of the internal capsule has 
 not been definitely settled. There is no doubt that they pass up to 
 the convolutions around the fissure of Rolando (central convolu- 
 tions), and there is reason to believe that some of them terminate in 
 the * motor ' region in front of that fissure, although many of the 
 fibres concerned in tactile sensations seem to end in the ascending 
 parietal convolution. 
 
 But we have not yet exhausted the constituents of the internal 
 
 capsule. Two great cones of fibres 
 sweep down into it, one from the 
 frontal, the other from the occipital 
 and temporal portions of the cerebral 
 c6rtex. The first passes through its 
 anterior limb, the second behind the 
 sensory path in its posterior limb. 
 The cells of origin of the frontal fibres 
 are known, and those of the occipital 
 and temporal fibres are supposed, to 
 be situated in the cortex. They are 
 therefore efferent fibres as regards 
 the cortex (cortifugal). Running on 
 through the crust a of the cerebral 
 peduncle (Fig. 352), the frontal tract 
 
 Fig- 358. — Pyramidal Tract in In- 
 ternal Capsule (Simpson and 
 Jolly). Horizontal section 
 through right cerebral hemi- 
 sphere, cutting fibres of internal 
 capsule transversely at an upper 
 level a little- below the upper 
 surface of the lenticular nucleus. 
 The extent of the degeneration 
 following destruction of the 
 whole of the right ' motor ' cor- 
 te.x, except the ' head and eyes ' 
 area (in one of the lower mon- 
 keys), is shown. Note over- 
 lapping of fibres from face, arm, 
 and leg areas, as shown by ex- 
 periments in which one or other 
 of these areas was alone re- 
 moved. 
 
 internal, the occipito-temporal external, they end in the grey 
 matter of the pons, and serve as one segment of an extensiv-e 
 connection between the cerebral and the cerebellar cortex of the 
 opposite side, the other segment being formed by neurons whose 
 cell-bodies are situated in the pons, and whose axons, crossing 
 
 Fig- 359- — Pyramidal Tract in Internal 
 Capsule at Lower Level (Simpson and 
 Jolly). CN', head of caudate nucleus: 
 OT, optic thalamus; CI, claustrum. 
 
PATHS FROM AND TO THE CORTEX 
 
 ftfl:? 
 
 the middle line, pursue their cours(! through the middle cerebellar 
 peduncle, to terminate in the superficial grey matttT of the cere- 
 bellum. It is evident that thi> junction of the cerebral cortex with 
 this pontine grey matter, through and into which so many nerve- 
 tracts pass, multiplies the number of possible routes by which 
 impulses may travel between one part of the brain and another. 
 The corpus callosum forms a mighty link between the two cerebral 
 hemispheres. And intertwined in the corona radiata with the 
 callosal fibres are other systems, of which it is especially necessary 
 to mention the afferent {cortipetal) fibres that join the optic thalamus 
 with nearly every part of the cerebral cortex. Such fibres pass from 
 the cells of the grey matter of the thalamus to the frontal and parietal 
 
 Fig. 300. — Association Fibres (after Starr). Cerebral hemisphere seen from the side 
 A, A, association fibres between adjacent convolutions; B, between frontal and 
 occipital lobes; C, cinguluui, connecting frontal and toniporosphenoidal lobes; 
 D, uncinate fasciculus between frontal and temporal regions; E, inferior longi- 
 tudinal bundle between occipital and temporo-sphenoidal lobes; O.T., optic 
 thalamus; C.N., caudate nucleus. 
 
 regions through the anterior border of the internal capsule in front of 
 the frontal fibres previously described as running in the anterior 
 limb of the capsule to the pons; and from the thalamus to the occi- 
 pital region through the extreme posterior border of the internal 
 capsule, behind the occipital fibres that proceed to the pons. The 
 fibres that connect the thalamus with the occipital cortex are 
 spoken of as the optic radiation. Some of the fibres of the optic 
 radiation, however, proceed, not from the thalamus, but from the 
 anterior corpus quadrigeminum and the lateral geniculate body. 
 The thalamus is also connected with the cortex of the temporal lobe, 
 udth the cerebellum, and through the fillet with the posterior part of 
 the tegmental system, the medulla oblongata and the spinal cord 
 (p. 874). Fibres also pass from the inner and deeper part of the 
 thalamus to the lenticular nucleus of the corpus striatum. The 
 
884 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 thalamus must be regarded as a great sensory centre througli which 
 afferent impulses stream on their way to all parts of the cortex. 
 
 The fibres which connect the cerebral cortex with lower levels of 
 the central nervous system are sometimes grouped together as 
 projection fibres in contradistinction to the commissural and associa- 
 tion fibres. A large proportion of the fibres of the corona radiata are 
 projection fibres, including efferent groups (pj-ramidal tract, fronto 
 
 pontine fibres, temporo- 
 pontine fibres) and afferent 
 groups (the fillet system, 
 thalamo-cortical fibres from 
 the grey matter of the 
 thalamus to the cortex, in- 
 cluding the optic radiation). 
 
 Section VII. — Connections 
 OF Brain Stem with Cord 
 — Connections of Cere- 
 bellum. 
 
 Connections of the Vestibulo- 
 spinal or Antero-Lateral De- 
 scending Tract. — The main 
 origin of these fibres is the 
 nucleus of Deiters, a collection 
 of large multipolar nerve-cells 
 in the floor of the fourth ven- 
 tricle near the inner auditory 
 nucleus. This nucleus consti- 
 tutes an important intermedi- 
 ate station between the cere- 
 bellum and the cord. Its 
 cells give off axons which paiss 
 into the posterior longitudinal 
 bundle of the bulb and pons, 
 mostly to the bundle of the 
 same side, but partly into that 
 of the opposite side. Here the 
 fibres bifurcate into an ascend- 
 ing branch, which passes up to 
 the oculo-motor nucleus, and a 
 descending (vestibulo - spinal) 
 branch, which passes down- 
 wards to the spinal cord and 
 enters the antero-latera! de- 
 
 Fis;. 361. — Fibres connecting Frontal and 
 
 Temporo-Occipital Lobes with Cerebellum, 
 etc. (Diagram) (after Gowcrs). Fr, frontal, 
 Oc, occipitallobc; interrupted lines indicate 
 fibres (TOC) connecting cerebellum and 
 temporo-occipital cortex, and fronto-cere- 
 bellar fibres (FC). On left side the position 
 of these two groups of fibres and of motor 
 (p^Tamidal) tract, PY, in the crus, is indi- 
 cated by letters. The p>Tamidal tract is 
 seen on the right passing down from the 
 Rolandic area through posterior limb of 
 internal capsule IC (the genu or knee of 
 which is indicated by asterisk) to decussate 
 in the bulb. AF, ascending frontal convolu- 
 tion: AP, ascending parietal convolution; 
 FR, fissure of Rolando; IPF, intraparietal 
 fissure; PCF, precentral fissure; Ipt, crossed 
 pyramidal, apt, direct pyramidal tract. 
 
 scending tract. The fibres of 
 this tract ultimately pass into the anterior horn, where most of them 
 end by arborizing amongst the cells of the horn. Higher up corre- 
 sponding fibres from the posterior longitudinal bundle arborize in the 
 cr.'.nial motor nuclei. 
 
 Connections of the Rubro-Spinal Tract. — These fibres, as the name 
 gi\cn to the bundle implies, originate in the red nucleus and run down 
 into the cord. A little distance from their cells of origin they cross the 
 
CONNECTIONS OF CEREBELLUM 
 
 88 = 
 
 median line, and then pass down first in the tegmentum, and below that 
 in the lateral column of the bulb and cord. On their way they come 
 into relation with the motor nuclei of the cranial nerves, and in the 
 cord with the cells of the anterior horn. It is obvious that in contrast 
 to the projection fibres the fibres of the rubro-spinal, vt;stibulo-si)inal, 
 olivo-spinal, and thalamico-spinal tracts (p. 867) and the posterior 
 longitudinal bundle connect the brain stem or cerebral axis with the 
 cord, or different levels of the brain stem with each other. 
 
 Connections of the Grey Matter of the Cerebellum with the Periphery 
 and other Parts of the Central Nervous System. — Numerous as are the 
 nervous ties of the cerebral cortex, those of the grey matter of the 
 cerebellum are, in proportion to its mass, still more extensive, particu- 
 larly as regards afferent fibres, and perhaps not less important. 
 
 Speaking broadly, we may say that the restiform body or inferior 
 peduncle connects chiefly the dentate nucleus and the grey matter of 
 the worm with the spinal cord and medulla oblongata, and through 
 them with the periphery. The fibres which it receives from the direct 
 
 S Auc^ 
 
 Fig. 362. — Direct Sensory Cerebellar 
 Path of Edinger. D, Deiters' 
 nucleus; v, median nucleus of 
 auditory nerve; /, nucleus of the 
 roof; g. nucleus globosus. 
 
 Fig. 363- — Diagram of Dorsal and Ventral Spino 
 Cerebellar Tracts entering Cerebellum (^Iott). 
 P.C.Q., posterior corpora quadrigemina; s.v., 
 superior vermis of cerebellimi; d.a.c, v.a.c, 
 dorsal and ventral ascending cerebellar tracts. 
 
 cerebellar tract (dorsal spino-cerebellar tract) of its own side it carries 
 to the worm. These fibres occupy the outer portion of the peduncle. 
 The fibres which reach the restiform body from the olivary nucleus of 
 the opposite, and alro in smaller numbers from that of the same side, 
 run mainly to the hemisphere. All these fibres are afferent in relation 
 to the cerebellum (cerebello-petal). An uncrossed afferent connection 
 also exists between the cerebellum and the vestibular branch of the 
 auditory nerve, through certain of its nuclei of reception, and also 
 between it and the nuclei of other cranial nerves, such ai the trigeminus 
 and the vagus. The fibres pass up in the inner portion of the inferior 
 peduncle (direct sensory cerebellar path of Edinger, Fig. 362) to the 
 nucleus of the roof (nucleus tecti) and nucleus globosus. Some efferent 
 fibres (cerebellofugal) also run down from the cerebellum in the inferior 
 peduncle, including fibres from the nucleus tecti of the opposite side 
 which are on their way to the medulla oblongata. 
 
886 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 The middle peduncle is in the main a link between the cerebellar 
 cortex and the cerebral cortex of the opposite side, through the relay 
 of the pontine grey matter. Most of the fibres in it are afferent in rela- 
 tion to the cerebellum, their cells of origin being situated in the nuclei 
 of the pons, and sending their axons across the middle line to end in the 
 cerebellar cortex. 
 
 The superior peduncle connects chiefly the dentate nucleus of one 
 side with the cortex of the opposite cerebral hemisphere through the 
 red nucleus of the tegmentum of the crus cerebri and the optic thalamus 
 on the opposite side. The great majority, or perhaps all, of its fibres 
 are efferent fibres as regards the cerebellum — i.e., their cells of origin lie 
 in the dentate nucleus. Running upwards and forwards in the superior 
 
 peduncle towards the mid- 
 brain they cross the middle 
 line below the corpora 
 quadrigemina, and then 
 bifurcate into ascending 
 and descending branches. 
 The ascending branches end 
 mainly in connection with 
 cells in the red nucleus, but 
 some of them pass on to 
 the optic thalamus, with 
 which cells of the red 
 nucleus are also connected. 
 The thalamus, as we have 
 seen, is in its turn exten- 
 sively connected with the 
 cerebral cortex and the 
 red nucleus (by the efferent 
 tract of Monakow) with the 
 grey matter uf the cord. 
 The descending branches 
 of the fibres of the superior 
 peduncle, entering the re- 
 ticular formation of the 
 pons, pass down, it is said, 
 to make connection with 
 the motor nuclei of the 
 cranial and spinal nerves.. 
 The tract of Gowers, as 
 previously stated, comes 
 into relation with the su- 
 perior peduncle, passing 
 backwards along its mesial border to the worm. Since the cortex of the 
 cerebellum is linked to the dentate nucleus, the superior peduncle affords 
 an indirect connection betrween it and the cerebral cortex. Through 
 the restiform body afferent impulses pass up to the cerebellum. From 
 the cerebellum they may proceed to the cerebrum. So that the path by 
 the restiform body, dentate nucleus, and superior peduncle may form an 
 alternative route for afferent impressions ascending from the periphery to 
 the great brain — a path broken by at least four relays of nerve-cells. 
 The cerebellar hemisphere may be connected by an efferent path through 
 the nucleus of Deiters and the descending antero-lateral tract with the 
 motor roots of the same side. Another efferent path (from the dentate 
 nucleus) may be constituted by the fibres of the superior peduncle and 
 Monakow's bundle. 
 
 Fig. 364. — Paths of Middle Cerebellar Peduncle 
 (Mingazzini). The scheme indicates the afferent 
 and efferent paths which run through the middle 
 cerebellar peduncle, connecting cerebellum with 
 opposite side of cerebrum, a, fibre coming from 
 a cell in the nuclei pontis and going to the cere- 
 bellar cortex; 6, fibre from a cell in cortex of 
 opposite cerebral hemisphere making connection 
 in the pons with a (a and b together constitute 
 an afferent path to the cerebellum); c, a fibre 
 springing fiom a Purkinje's cell in the cerebellar 
 cortex and making connection in the pons with 
 a cell d, which sends its axon to the cerebral 
 cortex of the opposite side, c and d constitute 
 an efferent path from cerebellum to opposite 
 cerebral hemisphere; e, f, represent a path 
 coming from the cerebellar cortex, which crosses 
 the middle line in the pons, and then ascends 
 till it loses itself in the forraatio reticularis. 
 
FUNCTIONS OF CENTRAL NERVOUS SYSTEM 887 
 
 We have purposely omitted to enumerate other paths by which 
 the various tracts of grey matter in the brain are brought into com- 
 munication with each other, and our knowledge of such connections 
 is no doubt far from complete. When we add that not only are the 
 cerebral hemispheres united by many ties to the subordinate portions 
 of the cerebro-spinal axis and to each other, but that cortical areas 
 of one and the same hemisphere are in communication by short 
 connecting loops of ' association ' fibres (Fig. 360), it will be seen that 
 the linkage of the various parts of the central nervous system is 
 extremely complex; that an excitation, blocked out from one path, 
 may have the choice of many alternative routes; and that the ap- 
 parent simplicity and isolation of the pyramidal tracts must not be 
 allowed too far to govern our views of the possibilities open to a 
 nervous impulse once it has been set going in the labyrinth of the 
 nervous network. Nor is it only by the main channel of the axis- 
 cylinder that nervous impulses can be conducted, they can also pass 
 along the collaterals. And the actual route taken by a given impulse 
 is determined not only by anatomical relations, but also by molec- 
 ular conditions, particularly in the terminal fibrils of the axons, 
 collaterals and dendrites, and in the substance, if such a substance 
 there be, which intervenes between the end arborizations of a neuron 
 and the dendrites or cell-bodies of the neurons with which they lie in 
 contact. So that a road open at one moment may be closed at 
 another. (See p. 902.) W'e ma}' suppose that the greater the number 
 of connections between the cells of the central nervous system, the 
 greater is the complexity of the processes which may be carried on 
 within it. And, indeed, comparison of the brains of different animals 
 shows that it is not so much by excess in the number of nerve-cells 
 as by the increased complexity of linkage, that a highly-developed 
 brain differs from a brain of lower type; the higher the brain, the 
 more richly branched are the dendrites and the terminations of the 
 axons and their collaterals, and, therefore, the greater is the numbei 
 of possible paths between one nerve-cell and another. 
 
 Section VIII. — Functions of the Central Nervous System — 
 (i) The Spinal Cord (including the Medulla Oblongata). 
 
 Much of our knowledge of the functions of the central nervous 
 system and of its divisions has been gained by the removal or 
 destruction of more or less extensive tracts of nervous substance, or 
 the cutting off of connection between one part and another. But it 
 is well to warn the reader at the very outset that in no other part of 
 physiology is such caution required in making deductions as to the 
 working of the intact mechanism from the phenomena which mani- 
 fest themselves after such lesions. 
 
888 THE CENTRAL NERVOUS SYSTEM 
 
 In tlie first place, every operation of any magnitude on the brain or 
 cord is immediately followed by a depression of the functional power of 
 the ner\()us tissue distal to the lesion, a depression which may extend 
 far from the actual seat of injury and manifest itself by various phe- 
 nomena, which arc grouped together under the name of ' shock,' better 
 termed spinal or cerebro-spinal shock, to distinguish it from the cardio- 
 vascular or surgical shock already mentioned (p. 192). Thus, when the 
 spinal cord of a dog is divided, e.g., in the dorsal region, all power, all 
 vitality-, one might almost say, seems to be for ever gone from the 
 portion of the body below the level of the section. The legs hang limp 
 and useless. Pinching or tickling them calls forth no reflex movements. 
 The vaso-motor tone is destroyed, and the vessels gorged with blood. 
 The urine accumulates, overfills the paralyzed bladder, and continually 
 dribbles away from it. The sphincter of the anus has lost its tone, and 
 the faeces escape involuntarily. And if w^e were to continue our observa- 
 tions only for a short time, a few hours or days, we should be apt to 
 appraise at a very low value the functions of that part of the cord 
 which still remains in connection with the paralyzed extremities. But 
 these symptoms are essentially temporary'. They are the immediate 
 results of the section; they are not permanent ' deficiency ' phenomena. 
 And if we wait for a time, we shall find that this torpor of the lower 
 dorsal and lumbar cord is far from giving a true picture of its poten- 
 tialities; that, cut off as it is from the influence of the brain, it is still 
 endowed with marvellous powers. If we wait long enough, we shall 
 see that, although voluntaiy motion never retiims, reflex movements 
 of the hind-limbs, complex and co-ordinated to a high deg-ree, are readily 
 induced. A few months after transection of the cord it is easy to show 
 that, although the dog cannot use the hind limbs for continuous pro- 
 gression, the machinen,' for executing the appropriate movements exists 
 in the cord. When, for example, the animal is held in the proper 
 position and given a slight push forwards, it may take two or three steps 
 before its legs give way. The regulation of the movements necessary 
 for the maintenance of "equilibrium cannot be achieved when the control 
 of the higher centres is eliminated. In water, where the problem of 
 the maintenance of the normal position is solved by the mechanical 
 properties of the medium, the dog can use the hind-legs in swimming. 
 The tone of the resting muscles below the lesion is even somewhat 
 greater than normal. Vaso-motor tone also comes back. The 
 functions of defaecation and micturition are normally performed. 
 Erection of the penis and ejaculation of the semen take place in a dog. 
 A man with complete paralysis below the loins and destitute of all 
 sensation in the paralyzed region has been known to become a father 
 (Brachet). Pregnancy carried on to labour at full term has been 
 observed in a bitch whose cord was completely divided above the 
 lumbar enlargement. The severity and duration of spinal shock are 
 greater in the monkey than in the dog, in man than in the monkey, and 
 in the whole mammalian group than in the lower vertebrates. The 
 mechanism of its production has been much discussed, and will be 
 referred to on another page (p. 912). 
 
 We cannot doubt that the spinal cord takes an important share in 
 the recovery of function after shock. But here again it would be 
 erroneous to conclude that everything is due to the cord. For Goltz 
 and Ewald have been able to keep dogs alive for long periods after 
 preliminary section of the cord in the cervical region and subsequent 
 removal of large portions of it. They find th.^t even after destruction 
 of the lumbar and sacral regions of the cord the external sphincter of 
 the anus, striped and even voluntary muscle though it be, regains its 
 
FUNCTIONS OF THE SPINAL CORD 8^ 
 
 tone, allhougli it is temporarily lost after tlic first cervical section. 
 The bladder ultimately recovers the power of emptying itself spon- 
 taneously and at regular intervals. A pregnant bitch in which the 
 lumbar enlargement and the whole cord below it to the cauda equina 
 had been removed, and therefore all the nerve-roots supplying fibres 
 to the uterus cut, whelped in a normal manner, and the corresponding 
 mammary glands behaved exactly as the rest. Digestion went on as 
 usual when practically nothing of the cord except its cervical portion 
 was left. Certain vaso-motor phenomena were also observed which 
 suggest that the sympathetic system, independently of the cerebro- 
 spinal system, is itself possessed of regulative powers (p. 183). 
 
 Secondly, we must not run into the opposite error, and assume, 
 without proof, that all the functions which the brain or cord is capable 
 of manifesting under abnormal circumstances are actually exercised by 
 either when, under ordinary conditions, it is working along with and 
 guiding, or being guided by, the other. For example, in many animals 
 certain of the reflex powers of the cord are, if not increased, at all events 
 more freely exercised when the controlling influence of the higher centres 
 has been cut off than when the central nervous system is intact. 
 
 Thirdly, there is another class of phenomena which we must make 
 allowance for, and perhaps more frequently in the case of pathological 
 lesions in man than in experimental lesions in the lower animals. This 
 is the class of ' irritative ' phenomena. The irritation set up by a blood- 
 clot or a collection of pus, or in any other way, in a wound of the grey 
 or white matter, may cause a stimulation of nervous tracts by which, 
 for a time, the ' deficiency ' effects of the lesion may be masked. 
 
 In the fourth place, we must not hastily conclude that, when no 
 obvious deficiency seems to follow the removal of a portion of the central 
 nervous system, the function of that portion must necessarily be of 
 such a nature as to give rise to no objective sigiis. For there is reason 
 to believe that, to a certain extent, the function of one part may, in its 
 absence, be vicariously performed by another. 
 
 Bearing in mind the cautions we have just been emphasizing, we 
 may broadly distinguish between the functions of the cord (including 
 the bulb) and those of the brain proper by saying that the cord is 
 essentially the seat of reflex actions, the brain the seat of automatic 
 actions and conscious processes. But neither of these conceptions 
 is entirely correct. Both err by defect and by excess. The brain, 
 it is true, is pre-eminently automatic. The movements which are 
 started in the grey matter of the cerebral cortex are pre-eminently 
 voluntary (p. 946), but we cannot deny to the brain the possession of 
 reflex powers as well. The movements in which the only nerve 
 centres concerned are those of the spinal cord are above all reflex 
 (p- 897)- But some of its centres, and especially those lying in the 
 medulla oblongata — e.g., the respirator^' centre — are, much as they 
 are influenced bj'' afferent impulses, capable of discharging auto- 
 matic impulses too. And while consciousness is certainly bound up 
 with integrity of the brain, and in all the higher mammals is asso- 
 ciated with cerebral activity alone, it has been plausibly maintained 
 that the spinal cord, even of such an animal as the frog, may also be 
 endowed with something which might be called a kind of hushed 
 consciousness. Whether this be so or not for the frog, with its 
 
Sgo 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 distinct though relatively ill-developed cere',jral hemispheres, it 
 would seem by no means unlikely in the case of fishes and animals 
 below them, which are practically devoid of a cerebral cortex 
 altogether. 
 
 The functions of the spinal cord may be classified thus: 
 
 1. The conduction of impulses set up elsewhere — either in the 
 
 brain or at the periphery. 
 
 2. The modification of impulses set up elsewhere (reflex action). 
 
 3. The origination of impulses (?). 
 
 Ce/ebral 
 
 Fibre for 
 Head ^ 
 
 z)e cassation 
 of Pyramids " 
 
 Ft,6re ofDtrect t . 
 
 Pi/ramidal tract 
 
 JVerue - Cells ^- _ - .'igf^ 
 of Ant Horn -^-^^^^^"^^i 
 Terminal ArSonsotton. VX-^C 
 qfoPj/fomdaL Fibre. , /^.JjgiC 
 around cell of 
 Ant //orn 
 
 (yncrossed Tibr^ 
 Spioat 
 
 Anterior 
 
 Boot 
 
 Fibres 
 
 Fig- 365- — Some Possible Paths of Efferent Impulses in the Central Nervous System 
 (Schematic). Details are omitted from the scheme. For instance, each pyra- 
 midal fibre is represented as arborizing around one anterior cornual cell only, 
 and no collaterals are shown. The hypothetical intercalated neurons between 
 the pyramidal fibres and the anterior horn cells (p. 876) are not shown. 
 
 I. Conduction of Nervous Impulses by the Cord. — The old con- 
 troversy as to whether the white fibres of the spinal cord are directly 
 excitable has long been settled in the affirmative. 
 
 The inquiry was complicated by the presence of the spinal roots, 
 which, since the experiments of Charles Bell, have been known to be 
 capable of excitation by artificial stimuli. But at length the difficulty 
 was overcome in this way: The posterior (dorsal) portion of several 
 
FUNCTIONS OF THE SPINAL CORD SQI 
 
 segments of the cord with the attached posterior roots and the grey 
 matter was excised. Long strands of the white matter of the anterior 
 (ventral) portion of the cord were isolated, and laid on electrodes, and 
 contractions of muscles were seen to follow stimulation, even when the 
 anterior roots nearest the stimulating electrodes had been cut, and every 
 precaution taken to avoid escape of current on to the distant anterior 
 roots of the nerves supplying the muscles. Indeed, apart from direct 
 experimental evidence, the fact that the white fibres of the brain are 
 universally admitted to be excitable by artificial means would be of 
 itself almost sufficient to decide the question, for we know of no essential 
 difference between the cerebral and the spinal fibres. But the con- 
 ditions must rarely occur under which direct stimulation of white fibres 
 in their course is possible in the intact body ; and the only impulses with 
 which we need concern ourselves here are those that reach the con- 
 ducting paths from grey matter in the cord itself or in the brain, or from 
 the peripheral organs. 
 
 What sort of impulses do the various tracts of the spinal cord 
 conduct ? For the dorsal or posterior roots this question was first 
 fully answered by Magendie; for the ventral or anterior roots, 
 although with a certain degree of ambiguity, by Sir Charles Bell. 
 Bell observed that when, in an animal just killed, he mechanically 
 stimulated the anterior roots, muscular contractions were obtained 
 at each touch of the forceps. He concluded that the anterior roots 
 are motor and sensory, while the posterior roots are ' vegetative ' — 
 i.e., connected with the functions of the viscera, the so-called 
 ' vegetative ' organs. But although he is often credited with the 
 discov-ry of the functions of the posterior roots as well, he was not 
 the first to make the decisive experiment necessary to show that they 
 are the conductors of sensory impulses. It was after Magendie's 
 discovery that only a portion of the nerves are sensitive, and that 
 there are nerves ' which are like tendons, aponeuroses, or cartilages 
 in insensibility,' that Bell formulated the law that the anterior roots 
 are purely motor, the posterior purely sensory. This law, often 
 termed Bell's Law, is more correctly denominated the Magendie- 
 Bell Law. 
 
 When the posterior roots are divided, loss of sensation occurs in 
 the region to which they are distributed. If only one root is cut, 
 the loss of sensation is never complete in any part of the skin ; and 
 Sherrington has found that the cutaneous areas of distribution of 
 consecutive nerve-roots are not perfectly independent, but to some 
 extent overlap. Stimulation of the peripheral end of the divided 
 posterior root has no effect. Stimulation of the central end gives 
 rise, if the animal be conscious, to evidences of pain, and other signs 
 of the passage of afferent impulses — e.g., a rise in blood-pressure. 
 The latter may also be observed when the animal is anaesthetized. 
 
 Referred Pain. — The posterior roots contain sensory fibres not only 
 for the skin, but also for the deeper structures and the viscera. The 
 afferent fibres reach the viscera by the sympathetic, the vagus, and the 
 pelvic nerves or nervi erigentes. Clinical observations have thrown 
 
892 THE CENTRAL NERVOUS SYSTEM 
 
 much light upon the distribution of the visceral fibres and their rela- 
 tion to the cutaneous sensory nerves. It has long been known that 
 in disease of an internal organ the pain is often referred to some super- 
 ficial piirt. It has now been demonstrated that each organ is related 
 to a more or legs definite region, or more than one region, of the skin. 
 In disease of the organ there is in this area increased excitability 
 (hyperalgesia) or tenderness to slight mechanical stimuli, and often 
 also increased excitability for heat or cold, and the reflexes elicited by 
 stimulation are exaggerated (Head, Dana). 
 
 The bond of connection appears to be the origin from the same spinal 
 segments of the autonomic* sensory fibres of any viscus and the sensory 
 supply of the correspcnding cutaneous area. The common anatomical 
 origin seems to carry with it a physiological correlation, either because 
 the irritation of the visceral fibres spreads in the cord to the somatic 
 afferent fibres which enter the corresponding segments, or because of 
 some action higher up in the cerebral centres, the nature of which will 
 be best considered along with the general topic of the localization of 
 sensor}^ impressions (Chapter XVIII.). 
 
 Recurrent Sensibility. — Although muscular contraction is the 
 most conspicuous event that follows stimulation of the peripheral end 
 of an anterior nerve-root, it is by no means the only one. It is 
 frequently observed, though not in all kinds of animals, that here, 
 too, pain is caused. That this pain is not due to the muscular con- 
 traction is proved by the fact that it can still be elicited when the 
 nerve-trunk is divided between the junction of the roots and the 
 periphery. The real explanation of the phenomenon is that certain 
 fibres from the posterior roots (' recurrent fibres,' see footnote on 
 p. 797) bend up for some distance into the anterior roots, and then 
 turn round again and pursue their course to their peripheral dis- 
 tribution in the mixed nerve, or run on in the motor roots to supply 
 the sheath surrounding them (nervi nervorum), and even the mem- 
 branes of the spinal cord. 
 
 The afferent impulses that enter tlje cord along the posterior roots 
 have the choice of many paths by which they may reach the brain. 
 The following are a few of the routes whicli they may follow: 
 
 (i) They may pass directly up through the postero-median column. 
 If they take this route, their course will be first interrupted by nerve- 
 cells in the gracile or cuneate nuclei in the medulla oblongata. Thence 
 they may find their way across the middle line b)' the arcuate fibres of 
 the upper or sensory decussation, and, sweeping along the fillet and the 
 sensory path in the hinder part of the posterior limb of the internal 
 capsule, finally arrive at the cerebral cortex. Between the gracile and 
 cuneate nuclei and the cortex they pass through nerve-cells in the optic 
 thalamus. 
 
 (2) They may pass up by the direct cerebellar tract and restiform 
 body to the grey matter of the cerebellar worm. If they take this 
 route their course will be interrupted very soon after their entrance into 
 
 * Langley uses the term autonomic nervous system to include the nerve 
 supply of heart muscle, all unstriated muscle, and all gland cells ia the body. 
 It embraces, in addition to the sympathetic, cranial autonomic fibres in 
 several of the cranial nerves and sacral autonomic fibres in the nervi erigentes 
 (see Chapter XVII.). 
 
FUNCTIONS OF THE SPINAL CORD 893 
 
 the cord in the cells of Clarke's column. Since the supcrhcial grey 
 matter of the vermis is connected by association fibres with the dentate 
 nucleus, and the dentate nucleus by the superior peduncle with the oppo- 
 site cerebral hemisphere, this is also a possible path to the great brain. 
 
 (3) They may reach the antero-latcral ascending tract of the same 
 side through its cells of origin in the spinal grey matter, and, passing 
 through the medulla and pons to the superior peduncle of the cere- 
 bellum, enter the grey matter of the superior worm. 
 
 (4) They may cross the middle line, after entering the cord, through 
 axons or collaterals (p. 872) which run in the anterior and also in the 
 posterior commissure, enter one of the ascending tracts on the other 
 side — e.g., the tract of Gowers — and continue without further decus- 
 sation up to their central destination. 
 
 (5) They may spread from neuron to neuron in the tangle of the grey 
 matter itself, and pass out again at a different level into one of the 
 white tracts on the same or on the opposite side of the cord. 
 
 Efferent impulses from the brain may travel — 
 
 (i) Through the direct or crossed pyramidal tract. 
 
 (2) From one side of the cerebral cortex to the other, and then down 
 the pyramidal tracts corresponding to that side (?). 
 
 (3) From the frontal part of the cerebral cortex, through the anterior 
 limb of the internal capsule to the grey matter in the pons, and thence 
 to the cerebellum by its middle peduncle. 
 
 (4) From the occipital or temporal cortex, in the hinder rim of the 
 internal capsule, to the pontine grey matter, and through the middle 
 peduncle to the cerebellum. From the cerebellum they may possibly 
 pass down to the nucleus of Deiters and thence along the antero-lateral 
 descending tract tx) the anterior horn of the cord, and indirectly to the 
 periphery. 
 
 All the paths enumerated, as well as others to which it would be 
 tedious to formally refer, and which the ingenuity of the reader may 
 profitably be employed in constructing for himself, from the data 
 already given, are to be looked upon as possible channels for the 
 passage of impulses between the brain and the periphery. But it 
 must be distinctly pointed out that what is certain is in this case 
 much more limited than what is possible. Among the efferent paths 
 it is certain that the pyramidal tracts are conductors of voluntary 
 motor impulses, and that in most individuals the great majority of 
 such impulses decussate in the medulla oblongata, only a small 
 minority in the cord. For a lesion involving the pyramidal tract 
 above the decussation of the pyramids causes paralysis of the oppo- 
 site side of the body, a lesion below the decussation paralj^sis of the 
 same side. It is certain that when one pyramidal tract has been 
 destroyed, in many animals at least, the resulting paralysis is soon 
 recovered from, at any rate to a great extent, and it is possible that 
 in this case the motor cortex on the side of the lesion has placed itself 
 again in communication with the paralyzed muscles through its 
 commissural connections with the opposite hemisphere. This, 
 however, is not the only alternative, for, as already pointed out, the 
 pyramidal tracts are not the only cortico-spinal paths which can 
 
894 THE CENTRAL NERVOUS SYSTEM 
 
 subserve volitional movements, and division of the anterior portion 
 of the antero-lateral column may cause deeper and more permanent 
 paralysis than division of the pyramidal tract. 
 
 In the dog total section of the pyramids is not followed by com- 
 plete paralysis of voluntary movements, and stimulation of the 
 cortical motor areas can still ehcit characteristic movements. It is 
 obvious that impulses emanating from the cortex can reach the 
 motor nuclei of the cord by other routes than the long pyramidal 
 fibres, possibly by paths with several segments, of which, for 
 example, the rubro-spinal tract (p. 867) may be one. Just as an 
 important business house may find it useful or indispensable to 
 supplement or replace the common telegraph service by private wires 
 in the interest of more prompt and satisfactory communication with 
 its principal correspondents, while still utilizing the ordinary channels 
 to some extent, so the higher brains may be supposed to have 
 developed more and more the direct service of the pyramidal tract 
 to tighten the grip of the cortex upon the motor nuclei of the cerebro- 
 spinal axis, while still availing themselves, although in diminishing 
 degree as their evolution proceeds, of the more primitive indirect 
 paths. 
 
 Decussation of the Sensory Paths. — On the other hand, it is certain 
 that pathological or traumatic lesions, apparently involving the 
 destruction of one lateral half of the cord in man and experimental 
 iemisections in some mammals, are followed by symptoms which 
 suggest that some kinds of sensory impulses decussate chiefly in the 
 spinal cord — viz., diminution or loss of sensibility to pain and to 
 changes of temperature on the opposite side below the level of the 
 lesion, with little or no impairment, and often increase of sensibility 
 (hyperesthesia) on the same side. Tactile sensibility is lost on the 
 side of the lesion, and likewise the muscular sense. 
 
 The first general description of this symptom-complex was given by 
 Brown-Sequard. On the basis of clinical observations in man, he 
 came to the conclusion that unilateral lesions of the cord, equivalent 
 approximately to a semisection, are associated with muscular paralysis 
 below the level of the lesion on the. same side, and loss of cutaneous 
 sensibility on the opposite side, while on the side of the lesions there 
 may be an augmentation of sensibility. He interpreted these facts as 
 meaning that the sensory path decussates soon after its entrance into 
 the cord. The sensory path from the left side is therefore spared by a 
 lesion of the left side of the cord, but interrupted by a lesion of the 
 right side of the cord. The left and right motor paths, having already 
 decussated in the bulb, are cut by lesions in the left and right halves of 
 the cord respectively. Long afterwards Brown-Scquard saw cause to 
 retract this interpretation of the facts observed by him, but the majority 
 of subsequent observers have considered his original hypothesis more 
 satisfactory' than his later ones. While it may be true that in man it has 
 not been rigidly demonstrated that the symptoms are associated with 
 a clean-out lesion precisely limited to one-half of the cord, clinical 
 observation has on the whole tended to confirm the view that an 
 
FUNCTIONS OF THE SPINAL CORD 895 
 
 important portion of tlic sensory path decussates in the cord. But it 
 is a curious circumstance that experimental physiologists have for tlie 
 most part obtained contradictory results. Thus Mott, working with 
 monkeys, found that the different kinds of sensation, far from being 
 abolished, are as a rule impaired in a smaller degree on the side opposite 
 to the semisection than on the same side, while Ferrier and Turner 
 obtained on the whole a contrary result, and one that corresponded 
 closely with Brown-Scquard's original description. The discovery that 
 no ascending degeneration, or only a trifling amount, is to be found on 
 the opposite side of the cord, either after semisection or after division 
 of posterior roots, does not of itself enable us to decide the question. 
 For while this latter fact shows that few or none of the afferent fibres 
 cross the middle line to enter the long conducting paths before being 
 interrupted by nerve-cells, it by no means proves that afferent impulses 
 do not decussate in the cord. The long paths of the posterior column, 
 indeed, do not decussate below the level of the bulb. The dorsal and 
 ventral spino-cerebellar tracts are also, in the main at least, uncrossed 
 spinal paths. A portion of the afferent impulses must therefore be 
 carried up to the cerebrum and the cerebellum without decussating in 
 the cord. But nobody can tell how massive a link between the two 
 halves of the cord may be formed by the grey matter and the endogenous 
 fibres of the white columns and their collaterals. We know that some 
 afferent impulses do decussate far below the level of the medulla. For, 
 (i) A part of the action current (p. 838) crosses the middle line and 
 ascends in the opposite half of the cord when the central end of one 
 sciatic is stimulated (Gatch and Horsley). (2) Crossed reflex move- 
 ments are possible; and when excitation ot the central end of the sciatic 
 is followed by contraction of the muscles of the opposite fore-limb, the 
 afferent impulses must either decussate in the lumbar cord, and then 
 run up on the opposite side to the level of the brachial plexus, or must 
 ascend on the same side and cross over somewhere between the plane 
 of the sciatic and the brachial nerve-roots. The only other hypothesis 
 on which crossed reflex action can be explained — but a hypothesis for 
 which there is not a tittle of evidence — is that the afferent impulse 
 always acts on the few motor cells whose axis-cylinder processes pass 
 over to the opposite side, and there enter anterior nerve-roots. But 
 while, for these reasons, it cannot be denied that some afferent impulses 
 decussate in the cord, it would be an error to conclude that all do so in 
 any animal, or that all animals are in this respect alike. It is indeed 
 extremely probable that in different species of animals, and even in 
 individuals of the same species, there are considerable differences in 
 the extent of the sensory decussation in the cord, just as there are in the 
 extent of the motor decussation in the bulb. In some animals the 
 greater part of the sensory path may decussate in the cord : in others the 
 greater part may decussate in the bulb, or higher up. The lack of 
 agreement in the experimental results may be due partly to this cause. 
 When it is further remembered how difficult it sometimes is to interpret 
 the account which a man gives of his sensations, and to recognize 
 precisely the degree and nature of sensory defects produced by disease 
 in the human subject, it will not be thought surprising that experi- 
 ments on animals, from the time of Galen onwards, should have yielded 
 evidence which, although perhaps now at length tending to a definite 
 result, is still unfinished and in part confhcting. 
 
 If, leaving them out of account, not as valueless but as still 
 difficult of interpretation, we attempt to draw any general conclusion 
 
896 THE CENTRAL NERVOUS SYSTEM 
 
 from the clinical observations which, however imperfect, are in such 
 questions our surest guide, it can only be this, that in man some 
 of the sensory impulses, and particularly those connected with the 
 cutaneous sensations of pain and temperature, decussate, in part at 
 least, in the cord. But there is also evidence that tactile afferent im- 
 pulses, including those coming from the muscles and related to the 
 muscular sense, and, it may be, some of the impulses associated with 
 pain, decussate, not in the cord, but in the bulb. 
 
 The Paths for Different Kinds of Sensory Impressions. — If this is the 
 state of our knowledge where the problem is merely to determine the 
 crossing-place of afferent impulses which are certainly known to cross, 
 it is only to be expected that we should be still more in the dark as 
 regards the routes by which different kinds of afferent impulses thread 
 their way through the maze of conducting paths in the neural axis to 
 reach their planes of decussation and gain the ' sensory crossway ' in 
 the internal capsule. Some authors have indeed cut the Gordian knot 
 by assuming that any kind of sensory impression may travel up any 
 afferent path. Direct stimulation of a naked nerve-trunk, it has been 
 argued in favour of this view, gives rise to a sensation of pain; stimula- 
 tion of the skin in which the end-organs of the nerve lie gives rise to a 
 sensation of touch or a sensation of temperature, according as the 
 stimulus is a mild mechanical or a thermal one, the contact of a feather 
 or of a hot test-tube. Why, it has been asked, should we imagine that 
 the difference in the result of stimulation depends on a difference in the 
 . nerve-fibres excited, and not on a difference in the kind of impulses set 
 up in the same nerve-fibres ? This is a question which we shall have 
 again to discuss. But apropos of our present problem, we may 
 say that there is very clear proof from the pathological side that a 
 limited lesion in the conducting paths of the central nervous system 
 may be associated with defect or total loss of one kind of sensation , while 
 all the other kinds remain intact. And there seems no other tenable 
 hypothesis than that in such cases the pathological change has picked 
 out a particular group of fibres, either collected into a single strand or 
 scattered among unaltered fibres of different function. For example, 
 in syringo-myelia, a condition in which cavities are formed in the grey 
 matter of the cord secondary to a new gro\\i;h of the neuroglia surround- 
 ing the central canal, a frequent symptom is the loss in a certain region 
 of sensibility to pain and to changes of temperature, while tactile 
 sensibility is unaffected (dissociation of sensations). Again, in loco- 
 motor ataxia, a disease in which inco-ordination of movement and 
 derangement cf the mechanism of equilibration are prominent symptoms, 
 degeneration in the posterior column of the cord is a most constant 
 lesion. And there is strong evidence that afferent impulses from 
 muscles and tendons, which either give rise to impressions belonging to 
 the group of tactile sensations, or produce no effect in consciousness, and 
 which, according to the most widely accepted doctrine, serve as the 
 basis of the muscular sense, and play an important part in the main- 
 tenance of equilibrium (p. 941), pass up in the posterior column. It 
 may also conduct tactile impressions from the skin. A case has been 
 observed where a man received a stab which di\ided the whole of one 
 side of the cord and the posterior column of the other side. Sensibility 
 to touch was lost on both sides of the body below the level of the injun,-. 
 sensibility to pain only on the side opposite to the main lesion. In 
 another case, in which' some small syphilitic tumours (gummata) iu 
 
FUNCTIONS OF THE SPINAL CORD 807 
 
 the lateral column on the left side caused marked degeneration in the 
 left direct cerebellar tract, the tract of Gowers, and the crossed pyram- 
 idal tract, without affecting the posterior columns, tactile sensibility 
 was only slightly impaired in the opposite leg, while the sensibility for 
 pain and temperature was much enfeebled. In the left leg, which was 
 paralyzed, there was slight hyperassthesia. These observations indicate 
 that impressions of pain and temperature pass up in the antero-lateral 
 column, either in the tract of Gowers, or in the direct cerebellar tract, or 
 in botli (Dejerine and Thomas). 
 
 But it does not follow that they cannot ascend by other p>aths as 
 well. It appears, indeed, that the grey matter of the cord, or, rather, 
 short endogenous fibres arranged in series in the antero-lateral column 
 so as to connect the grey matter at different levels, constitute such a 
 path, and that impulses which give rise to pain can be propagated along 
 a cord in which hardly a vestige of white substance remains uncut. In 
 man the path for pain and temperature impressions along these short 
 endogenous fibres seems to be mainly or entirely a crossed path. The 
 afferent paths for such vaso-motor reflexes as are elicited by stimulation 
 of the central end of the sciatic ascend in the lateral column, and the 
 impulses largely cross the middle line in the cord. The posterior 
 columns have nothing to do with the conductioxi of painful impressions, 
 for division of them causes not anaesthesia, but rather hyperaesthesia, 
 while if they are left intact, and the rest of the cord, including the grey 
 matter, divided, the animal is insensitive to pain below the level of the 
 lesion. Just as man differs from lower animals in the completeness 
 with which certain of the sensory impressions decussate in the cord, so 
 differences exist in the degree of localization of the different kinds of 
 impressions in particular tracts. One of the outstanding differences is 
 that in animals it seems to be easier for a still intact path to be substi- 
 tuted for a severed path as a conductor of impulses which normally 
 traverse the latter. The rapiditj' with which sensation is restored 
 below the lesion after semisection of the cord in animals is an illustration 
 of this. Another difference, which can be explained in the same way, is 
 that a sharply-marked dissociation of sensations — retention of tactile 
 sensibility, for example, with loss of sensibility to pain or to pain and 
 temperature changes — either cannot be produced experimentally in 
 animals, or is very difi&cult to realize. 
 
 The impulses which descend the cord give token of their arrival at the 
 periphery by causing either contraction of voluntary muscles, or con- 
 traction of the smooth muscular fibres of arteries, or secretion in glands. 
 They all pass down in the antero-lateral column, but the path of the 
 voluntary impulses in the pyramidal tracts is the best known and most 
 sharply defined. 
 
 2. Modification of Impulses set up elsewhere (Reflex Action). — 
 The spinal cord, although it is a conductor of nervous impulses 
 originating elsewhere, is by no means a mere conductor. Many of 
 the impulses which fall into the cord are interrupted in its grey 
 matter. Some of the efferent impulses proceeding from the brain 
 are perhaps modified in the cord, and then transmit ted to the muscles. 
 Some of the afferent impulses are modified, and then transmitted to 
 the brain ; some are mo(H fied, and deflected alt ogel her into an efferent 
 path. These last are the impulses which give rise to reflex effects. 
 A reflex action has sometimes been defined as an action carried out 
 in the absence of consciousness: not necessarily, however, in the 
 
 57 
 
89S THE CENTJi-AL NERVOUS SYSTEM 
 
 absence of general consciousness, but in the absence of consciousness 
 of the particular act itself. But the term is now more correctly 
 used so as to embrace all kinds of actions which are not directly 
 voluntary, whether the individual is conscious of them or not. For 
 example, when the sole of rhe foot is tickled, the leg is irresistibly 
 and involuntarily drawn up by reflex contraction of its muscles; yet 
 the person is perfectly cognizant both of the movement and of the 
 sensation which accompanies the afferent impulse. Many reflex 
 actions usually associated with sensations proceed normally when 
 consciousness is entirely in abeyance; during sleep most of the 
 ordinary reflexes can be elicited. 
 
 Anatomical Basis of Reflex Action. — Since the essence of reflex action 
 
 is that the arrival of afferent impulses in the spinal cord or brain causes 
 the discharge of efferent impulses, there must be some connection 
 between the incoming and the outgoing nerve-fibres. In unicellular 
 animals, such as amoeba, there is no differentiation of any special 
 nervous or conducting path. A stimulus applied at one point may 
 cause contraction anywhere. Even in the lowest multicellular animals 
 or metazoa — e.g., in the sponges — there is no special nervous tissue. 
 In some species of hydra, however, many of the surface or ectodermic 
 cells (p. 6) possess deeply-placed contractile or muscular processes, 
 and stimulation of the surface cells is followed by contraction of these 
 processes. We may imagine that the first l:>eginnings of an actual 
 nervous system may have arisen by a further differentiation of such 
 an ectodermic cell into a receptive portion at the surface, a deeper con- 
 tractile portion, and an intermediate strand of protoplasm connecting 
 the two, and capable of conducting the excitation from surface to 
 muscular process. In such a reflex arc the nervous link would consist 
 only of the conducting strand analogous to the nerve fibre joining the 
 receptive or sensory .element to the contractile element, and the dis- 
 tinction between afferent and efferent fibre would not exist. When 
 development has gone a step further, and the neuro-muscular process 
 is interrupted by a second epithelial cell transformed into a nerve-cell, 
 the afferent fibre enters one pole and the efferent fibre leaves the other 
 pole of the same cell. It is this condition which we actually find when 
 the nervous system first emerges in the animal scale as an unmistakably 
 differentiated structure — namely, in the Coelcnterates in such forms as 
 the jellyfishes. Here the three types of cell, receptive or sensory cell, 
 reactive or central cell, and motor or contractile cell, arc connected 
 together by conducting paths or nerve-fibres. In a simple reflex action 
 three events can be distinguished : stimulation of a receiving mechanism, 
 conduction of the excitation, and the consequent reaction or end -effect. 
 'I"he receiving mechanism or receptor may consist of ordinary sensory 
 nerve-endings in the skin, or of special sense-endings, as in the retina 
 or internal ear. The conducting mechanism or conductor in all except 
 the very simp'.est nervous systems is made up of at least two neurons, 
 one the afferent portion of the reflex arc connected with the receptor, 
 the other the efferent portion of the arc, connected with the organ, 
 sometimes termed the effector organ — a muscle, e.g., or a gland — which 
 accomplishes the end-effect. The transference of the excitation from 
 the afferent to the efferent neuron takes place across the intervening 
 synapre. The simple isolated reflex arc, as thus described, although 
 a convenient abstraction, corresponds but little to anything which 
 actually exists in one of the higher animals. With increasing com- 
 
FUNCTIONS OF THE SPINAL CORD 899 
 
 plexity of organization the nervous impulse passing up an afferent 
 fibre is in general otfcrccl, instead of a single efferent path, a choice of 
 many potential routes when it reaches the spinal coril. We have 
 previously (p. 872) described the course taken by the fibres of the 
 posterior roots on entering the cord. It is obvious tluit through the 
 main fibres and their collaterals an extensive connection — partly direct, 
 partly by the link of intermediate neurons — is established with the 
 motor cells on both sides of the cord. But the facts of physiology 
 demonstrate an even ampler connection than the mere anatomical 
 study of the distribution of the root-fibres would suggest. Indeed, the 
 phenomena of strychnine-poisoning seem to show that every afferent 
 fibre is potentially connected with the motor mechanisms of the whole 
 cord, or at least with a very large proportion of them. For in a frog under 
 the influence of this, drug, stimulation of the smallest portion of the skin 
 will cause violent and general convulsions, which are unaffected by de- 
 struction of the brain, but cease at once on destruction of the cord (p. 904)- 
 
 In an unpoisoned reflex frog — that is, a frog in wliich interference 
 with the single spinal reflexes has been prevented by section of the bulb 
 or destruction of the brain — the movements resulting from stimulation 
 of a given receptive area are by contrast surprisingly limited, localized, 
 and constant. Thus, a harmful stimulus of a certain intensity applied 
 to a toe will elicit time after time a raising of the leg — in other words, 
 an excitation of muscles whose motor nerves arise from cells in the same 
 region of the cord into which the afferent fibres from the receptive skin 
 area enter. The localization of the reflex is in this case without doubt 
 dependent upon the fact that the connections of the afferent fibres with 
 the group of efferent neurons in question are more direct and more 
 intimate than with any other group. This anatomical isolation of a 
 given reflex arc is never complete, but so far as it goes it may be 
 assumed to be constant and incapable of variation. Under normal 
 conditions the anatomical isolation is always supplemented by a 
 physiological isolation , which is susceptible of variation in the direction 
 either of increase or of diminution. 
 
 It is therefore a question of great interest how the isolated con- 
 duction of the impulses in a given reflex arc, in so far as it depends upon 
 the physiological condition of the arc and of its connections, is normally 
 achieved. The best answer which can at present be given is that it is 
 not equally easy for a reflex excitation to pass across all the synapses 
 which are potentially open to it, and that a lowering of the resistance 
 of the synapses in the favoured path is probably quite as important a 
 factor in the isolation as an increase of the resistance in those which 
 are to be barred. Following the path of least resistance, the excitation 
 traverses the synapse or synapses which it is easiest for it to break 
 through. What property of the synapse is associated with resistance 
 to the passage of the impulse is unknown. But it is a variable property, 
 and when a general reduction in the resistance is produced, as by strych- 
 nine or tetanus toxin, an excitation impressed upon a single afferent 
 path may force a great many synapses normally impervious to it. 
 
 While it is convenient in a preliminary survey to speak of the resist- 
 ance to spreading of the excitation in the cord being diminished by 
 strychnine or by tetanus toxin, we shall see presently that more than 
 this is involved (p. 903). 
 
 Principle of the Common Path. — In considering the architecture 
 of the cerebro-spinal nervous system as a basis of reflex action, one 
 feature is of such importance as to deserve special mention. The 
 
900 THE CENTRAL NERVOUS SYSTEM 
 
 afferent neurons, running from the receptive surfaces to the centres, 
 constitute eucli for its own receptive point-a ' private ' path which 
 can only be used by impulses arising at that point, and not by 
 impulses arising at any other point. Through its central connec- 
 tions an afferent neuron from a single point may be put into com- 
 munication with numerous efferent neurons, and thus with numerous 
 and distant effector organs (muscles or glands). Conversely, the 
 efferent portion of a single reflex arc can convey reflex excitations 
 originating in numerous and distant receptive fields. It is the sole 
 path which all efferent impulses — let them originate where they may 
 — must use to reach the end-organ in question. It is therefore not a 
 private but a public path, and may be termed in this relation the 
 final common path (Sherrington). 
 
 The existence of the common path is of great importance in under- 
 standing the manner in which reflexes are compounded together, a 
 problem absolutely fundamental in nervous co-ordination. One 
 consequence of the existence of a common path is that when, among 
 the receptors which may use it, two are simultaneously stimulated 
 which, when separately excited, produce opposite effects upon the 
 effector organ, only one of the effects is produced. In other words, 
 impulses which produce the two opposed effects can be successively, 
 but cannot be simultaneously, sent along the common path. Thus, 
 ■' excitation of the central end of the afferent root of the eighth or 
 seventh cervical nerve of the monkey evokes reflexly in the same 
 individual animal sometimes flexion at the elbow, sometimes ex- 
 tension. If the excitation be preceded by excitation of the first 
 thoracic root, the result is usually extension ; if by excitation of the 
 sixth cervical root, it is usually flexion. Yet though the same root 
 may thus be made to evoke reflex contraction of the flexors or of the 
 extensors, it does not evoke contraction in both flexors and extensors 
 in the same reflex response. . . . The flexor-reflex, when it occurs, 
 seems, therefore, to exclude the extensor- re flex, and vice versa. 
 Either the one or the other results, but not the two together ' 
 (Sherrington). It is obvious that this is an advantageous arrange- 
 ment. An algebraical summation of the opposed effects by the 
 common path would result in a useless action which was neither 
 effective flexion nor effective extension, a compromise and not a 
 co-ordination. The conditions which determine which of two or 
 more competing reflexes shall obtain possession of the final common 
 path are considered on p. 9<^2. 
 
 Role of the Receptor in Reflex Action.— The role of the receptor in 
 the reflex arc is above all to sift out from the various kinds of im- 
 pressions impinging upon the receiving surface the particular kind 
 to which the appropriate response is the reflex action in question. 
 As w^ill be pointed out in greater detail in the study of the special 
 senses, each kind of afferent end-organ has become adapted to a 
 
FUNCTIONS OF THE SPINAL CORD 901 
 
 special, or, as it is termed, an ' adequate ' stimulus, so that it is 
 easily affected by this, and with difficulty or not at all by other 
 modes of stimulation. Thus, light is the adequate stimulus of the 
 end-organ of the optic nerve, heat that of the end-organs of the 
 nerves by which we perceive the sensation of warmth, mechanical 
 pressure that of the nerves by which we perceive the sensation of 
 pressure. Other kinds of stimuli are either entirely inactive or much 
 less effective in evoking tlie particular sensory response. There is 
 every reason to believe that the receptor in the reflex arc occupies the 
 same position in regard to adequate stimuli as it does when it func- 
 tions as a sense-organ. 
 
 Sherrington has shown that the different kinds of nerve-endings 
 in one and the same area of the skin (in the dog) must be assumed to 
 possess totally different spinal connections, since the movements 
 elicited by stimuli suitable for one form of nerve-ending are quite 
 different from those elicited by stimuli suitable for another. 
 
 The ' extensor-thrust ' is a reflex obtained in the hind-leg of the 
 dog. and characterized by a brief, strong extension at the hip, knee, 
 and ankle. It is only ehcited by a certain kind of mechanical stimu- 
 lation, best in the spinal dog — i.e., in a dog whose brain has been 
 desti-oyed or severed from the cord some time before — by pushing the 
 tip of the finger between the plantar cushion and the pads of the toes. 
 The stimulus is similar to that which normally liberates the reaction 
 — namely, the pressure of the ground on the sole of the foot during 
 locomotion. The reflex cannot be obtained by electrical stimula- 
 tion or by any kind of direct stimulation of afferent nerve-trunks. 
 The same is true of the pinna-reflex in the cat — i.e., the backward 
 crumpling of the ear ehcited by squeezing or tickling its tip. The 
 scratch-reflex,* a scratching movement of the hind-foot, is much 
 more easily elicited in the spinal dog by mechanical stimulation 
 (rubbing, tickling, or tapping) applied to the skin of the back behind 
 the shoulder than by electrical stimulation, which often fails to 
 evoke it at all. The puzzhng fact that, according to surgical ex- 
 perience, many of the internal organs — e.g., the ureters and bile- 
 ducts — can be handled, cut, and sutured without pain, while the 
 passage of a renal calculus or a gall-stone may cause excruciating 
 agony, becomes explicable in view of the apparently slight difference 
 which sometimes distinguishes an adequate from an inadequate 
 stimulus. Thus Sherrington has shown that very distinct reflex 
 eftects — e.g., a rise of blood-pressure — can be obtained by sudden 
 distension of the bile-duct by the injection of salt solution into its 
 lumen. Distension is here the adequate form of mechanical stimu- 
 lation, and it is the form induced by the passage of a calculus, while 
 nerve-cutting, although a mechanical stimulus,is not an adequate one. 
 
 * The scratch-reflex is very easily obtained in cats during resuscitation 
 after a period of cerebral anaemia. 
 
902 THE CENTRAL NERVOUS SYSTEM 
 
 Characteristic Properties of the Reflex Arc. — Conchiction in reflex 
 arcs shows certain pecuHarities when compared with the conduction 
 in nerve-trunks already studied (p. 781): (i) The direction of the 
 reflex conduction cannot be reversed. There is an absolute block 
 on the passage of impulses backwards through a synapse. (2) The 
 velocity of conduction over the whole reflex arc is much smaller 
 than over a nerve-trunk of equal length. Both of these differences 
 depend mainly on the fact that the impulses must be transmitted 
 from one neuron to another, and very likely on a fundamental 
 property of the synapse. The delay or ' lost time ' in the discharge 
 of the efferent impulses which constitute the reflex response to the 
 excitation of an afferent path increases with the complexity of the 
 response — ^that is, with the number of neurons and tlierefore of 
 synapses involved in it. (3) The reflex arc is easily fatigued, easily 
 affected by deprivation of oxygen and by drugs, in comparison with 
 the nerve-trunk. This difference is due to the portion of the arc 
 in the grey matter, including the synapse or synapses. Fatigue 
 expresses itself by an increase in the degree of block or resistance to 
 the passage of impulses along the arc. (4) The reflex end-effect may 
 much outlast the stimulus — in other words, a marked ' after-dis- 
 charge ' is characteristic of reflexes. The more intense the stimulus 
 which liberates the end-effect, the greater is the duration of the after- 
 discharge. For example, the ' crossed extension reflex ' (extension 
 at the knee, ankle, and hip, produced in the spinal dog by stimula- 
 tion of the skin of the opposite or contralateral hind-limb), when 
 provoked by a stimulus of more than a certain intensity, may outlast 
 the stimulation by ten or fifteen seconds, and the after-discharge 
 may be stronger than any other part of the reflex (Sherrington). 
 (5) A succession of impulses may easily pass along a reflex arc when 
 one of the series would fail to pass (temporal summation). This 
 does not occur in a nerve-trunk. The first stimulus, though itself 
 unable to produce the reflex effect, facilitates the action of succeeding 
 stimuli, so that summation of the impulses occurs in the cord 
 (Stirling). A stimulus — e.g., a make-induction shock, far too weak 
 to produce the scratch-reflex when applied once only to a point of 
 that area of skin from which the reflex is normally elicited — has been 
 seen to cause the reflex after more than forty shocks had been 
 delivered at the rate of eighteen per second. The facilitation of the 
 passage of an impulse by the previous passage of impulses along the 
 same reflex path recalls a somewhat similar phenomenon already 
 alluded to in connection with the conduction of the propagated 
 disturbance in nerve-fibres (p. 791), although in the case of the reflex 
 arc the effect, it may be supposed, is exerted upon the fields of 
 conjunction, including the synapses, between the different neurons. 
 There is reason to believe that summation in the reflex arc is mainly 
 achieved by the removal of block or resistance. The phenomenon of 
 
FUNCTIONS OF THE SPINAL CORD 903 
 
 facilitation is probably of great importance in the acquirement of 
 new reactions and in rendering these acquisitions stable. It is prob- 
 ably one of the main physiological foundations of habit, and there- 
 fore of education. In this connection it is important to note that 
 the very same repetition of stimuli which leads to facilitation leads 
 to fatigue when the stimuli are applied in too rapid succession, 
 (6) The rhythm and intensity of the reflex end-effect correspond 
 much less closely with the rhythm and intensity of the stimulus than 
 in nerve-trunks. (7) The phenomena of refractory period (p. 155), 
 inhibition and ' shock,' are much more conspicuous in the reflex arc 
 than in nerve-trunks. 
 
 Inhibition in Reflex Action. — Special emphasis must be laid upon 
 the part plaved b\- inhibition in reflex actions. For the proper 
 carrying out of many reflex movements it is necessary not only that 
 the appropriate effector organ, the appropriate muscle, or group of 
 muscles, should be caused to contract at the proper time, but that 
 their contraction, or that of other muscles, should be diminished or 
 abolished by inhibition, or even rendered for a certain period im- 
 practicable by the establishment somewhere in the reflex arc of a 
 refractory state, which is itself a phenomenon of inhibition. There is 
 good evidence that this is a central inhibition — i.e., it depends on 
 some process occurring in the spinal portion of the reflex arc. 
 
 As an example of the numerous class of reflexes in which the 
 excitation of certain muscles is accompanied by the inhibition of 
 their antagonists (reciprocal inhibition), we may take the ' flexion 
 reflex,' the flexion at the knee, hip, and ankle of the hind-limb 
 readily elicited in the spinal dog by ' nocuous ' or harmfui stimuli 
 (such as a prick, a strong squeeze, chemical agents, or excessive 
 heat), or by electrical stimuh applied to the skin of the limb or of 
 any afferent nerve of the limb. 
 
 Sherrington has shown that when the legs of the animal are so 
 prepared that only the flexors can act on one knee, and only the 
 extensors on the other, stimulation of symmetrical points on the 
 two sides in the area of skin (receptive field) from which the flexion 
 reflex can be evoked causes contraction (excitation) of the flexors and 
 simultaneous relaxation (inhibition) of the tone of the extensors. The 
 same is true when corresponding afferent nerve-twigs are stimulated ^ 
 on the two sides. From this it is inferred that each of the nerve- fibres 
 from the receptive field of the reflex divides in the cord into two sets 
 of end-branches {e.g., collaterals) — a set which produces excitation 
 when it is stimulated, and another set which produces inhibition. 
 
 Reversal of Reflexes. — The difference in action is specific in the 
 sense that no mere change in the kind or intensity of stimulation 
 affects it. Yet there are facts which show that the specificity is not 
 absolutely immutable, and that a change of conditions in the spinal 
 cord may permit excitation of a given group of muscles to be pro- 
 
904 THE CENTRAL NERVOUS SYSTEM 
 
 duced by the stimulation of an aft'ercnt path which is primarily 
 inhibitory for them. One of the most striking illustrations of this 
 possibility is seen in the action of strychnine. Stimulation of the 
 internal saphenous nerve below the knee — say in a dog after removal 
 of the cerebrum — is known always to produce inhibition of tl.e 
 portion of the quadricei)s extensor whose contraction causes the 
 knee-jerk. 
 
 If now the animal be poisoned by a small dose of strychnine, 
 stimulation of the nerve causes no longer reflex relaxation, but reflex 
 contraction of the muscle. This fact indicates that the essential 
 action of strychnine is something different from a mere reduction of 
 the resistance to the spread of impulses in the cord (Sherrington). 
 Tetanus toxin produces a similar effect, though more slowly. 
 
 The reversal of the depressor reflex on the blood-pressure has been 
 previously alluded to (p. i88). A different type of reversal, and one 
 of most interest in connection with the co-ordination of reflexes, is 
 illustrated by such observations as the following: The extensor 
 thrust is only obtained by the adequate form of stimulation de- 
 scribed on p. 901, when the hind-limb is in a condition of flexion. 
 When the leg is passively extended at the time when the stimulus is 
 applied, the response is not the extensor thrust, but flexion of the 
 leg and thigh (direct flexion reflex). The passive assumption of a 
 condition of flexion at the knee and thigh appears, accordingly, to 
 favour the extensor reaction (Sherrington). The observations of 
 Magnus have shown that such relations are general; for example, 
 the reaction is usually extension when the opposite posterior limb 
 is flexed at the time of stimulation, and flexion when the opposite 
 leg is extended. In the spinal cat, stimulation applied to the tail, 
 especially near the root, elicits always a stroke towards the side on 
 which at the time of stimulation the muscles are extended. The 
 phenomenon is dependent upon the integrity of the afferent nerves 
 of the passively extended or flexed muscles whose position influences 
 the reflex, and of the afferent nerves of the tendons and fascia re- 
 lated to them. The condition of the reflex centres is in some way 
 influenced by impulses conducted along those afferent paths. 
 
 Not only is the tone of the extensors diminished or abolished 
 during the activity of the flexors, but the contraction of the knee 
 extensors evolved by striking the patellar tendon, which is called 
 the knee-jerk, either fails to appear, or appears but feebly, when the 
 flexion reflex is simultaneously elicited, even when the mechanical 
 antagonism of the flexor contraction has been eliminated by pre- 
 viously detaching the flexors from the knee. 
 
 The Knee-jerk. — This is sometimes termed a pseudo-reflex. For 
 certain authorities believe that the mechanism by which it is pro- 
 duced is different from that concerned in tlie reflex blinking of the 
 eyelid, or the reflex retraction of the testicle, or the drawing-up of 
 
FUNCTIOiWS 01- THE SPINAL CORD 905 
 
 the foot wiien tlie sole is tickled. The knee-jerk is obtained in 
 undiminished strength when the nerves of the ligamentum patellae 
 have been divided. It is therefore not a reflex movement caused by 
 stimulation of afferent nerves coming from the tendon, and the name 
 ' tendon-reflex ' is clearly a misnomer. But that it is related in some 
 way or other to afferent impulses is certain, for division of the 
 posterior roots that enter into the anterior crural nerve abolishes 
 the knee-jerk. The phenomenon, according to these authors who 
 deny that it is a true reflex, comes under the head of what is called 
 myotatic irritabilit}' — that is, it depends on mechanical stimulation 
 of the slightly-stretched muscle by the pull of the tendon when it is 
 struck. It is necessary for this stimulation that the muscle should 
 be to a certain extent tonically contracted. So that when the 
 afferent fibres are interrupted, or the grey matter of the cord dis- 
 organized, and the reflex tone abolished, the knee-jerk disappears. 
 The strongest objection to considering it an ordinary reflex is the 
 shortness of the interval which elapses between the tap and the jerk, 
 which, according to some observers, is not much greater than the 
 latent period of the quadriceps muscle for direct electrical stimula 
 tion, as measured under the ordinary conditions of its contraction. 
 There is no doubt that the interval is very brief, although somewhat 
 conflicting results have been obtained by different observers for the 
 corrected latency — that is, the period between stimulus and response 
 minus the latent period of the muscle. In man this period seems 
 to be about 002 second. In a dog with divided spinal cord the 
 interval was found to be 0014 to 002 second (Applegarth) ; in the 
 rabbit only 0008 to 0005 second (Waller and Gotch). Recent 
 observations in which the electrical response of the muscle as re- 
 corded by the string galvanometer was employed instead of the 
 contraction have 3aelded results not very different from those 
 obtained by the older methods, ooii to 0-015 second according to 
 Synder. Taking account of the newer observations on the velocity 
 of the nervous impulse (p. 793), it would appear that the interval is 
 not really too short to prevent the knee-jerk from being classified 
 as a true reflex contraction, although a very brief one.* The rein- 
 forcement of the knee-jerk is referred to under another heading 
 (p. 911). It is admitted that, in addition to the direct stimu- 
 lation of the muscle on the same side, the tendon-tap may cause 
 also a true reflex knee-jerk on the opposite side, the interval between 
 tap and contraction being about ^ second. 
 
 Spread or Irradiation of Reflex Action. — As the strength of the 
 stimulus which has been evoking a gi\en reflex movement is in- 
 creased, the reflex effect becomes more and more extensive, spreading 
 out or irradiating in various directions. If, for example, the reflex 
 
 * There is really now no good reason for regarding the knee-jerk as anj^hing 
 else than a true reflex. The term pseudo-reflex and other terms implj-ing 
 that the knee-jerk is not a reflex should therefore be dropped. 
 
9o6 THE CENTRAL NERVOUS SYSTEM 
 
 in question is tlie flexion reflex elicited by stimulation of the plantar 
 surface of the hind-foot in the spinal animal, increase of the stimulus 
 will cause, in addition to flexion of the same hind-foot, extension of 
 the opposite hind-limb, then in the homonymous fore-limb {i.e., the 
 limb on the same side) extension at the elbow and retraction at the 
 shoulder, then certain definite movements, the details of which need 
 not detain us here, in the opposite fore-limb, and ultimately also 
 definite movements of the head and tail (Sherrington). Obviously 
 there is a certain orderliness in the spread of the reflexes; they 
 follow a certain regular march; the irradiation in the tangle of the 
 spinal paths is not an indiscriminate one. The same fact emerges 
 quite as clearly when other reflexes are studied in a similar way; and 
 certain laws or rules which define the spread of the impulses in spinal 
 reflexes have been deduced. For descriptive purposes, in dealing 
 with reflex action, it is convenient to consider each lateral half of 
 the cord as divisible into regions each related on the one hand to a 
 certain area of the receptive surface (skin), and on the other to 
 certain muscles. Such regions are those of the neck, including the 
 pinna (cervical), the fore-limb (brachial), the trunk (thoracic), the 
 hind-limb (crural), and the tail (caudal). According to their rela- 
 tion to these regions the spinal reflexes can be classified as ' short ' 
 or ' long.' The short spinal reflexes are those in which the muscular 
 response takes place in the same region as the application of the 
 stimulus. The long reflexes are those evoked when the stimulus is 
 applied to the receptive field of one region, and the response occurs 
 in the musculature of another region. For the short reflexes 
 Sherrington has given a number of rules, which may be stated as 
 follows: (i) The closer together their spinal segments, the easier is 
 it for stimulation of a given efferent root to excite reflex contractions 
 of muscles supplied by a given afferent root. (2) For each afferent 
 root there exists in its own spinal segment (of course, on its own side 
 of the cord) a reflex motor path of as low a threshold {i.e., as easily 
 set into action) and of as high potency {i.e., producing as great a 
 reflex effect) as any open to it anywhere. It has been shown that 
 the afferent nerves of a skeletal muscle are derived from the spinal 
 ganglion corresponding to the segment of the cord containing its 
 motor cells. (3) Motor mechanisms for the skeletal musculature 
 lying in the same region of the cord, and in the selfsame spinal 
 segment, show markedly unequal accessibility to the local afferent 
 channels as judged by the reflex contractions produced. For 
 example, the reflex contraction of the flexors of the knee on the 
 stimulated side, and of the extensors of the opposite knee, is in 
 many animals much more easily elicited than contraction of the 
 extensors of the homonymous and the flexors of the contralateral 
 {i.e., opposite) side. This, however, is not because the last-named 
 extensors and flexors are really incapable of being reflexly affected 
 through the afferent fibres of the corresponding spinal segments, but 
 
FUNCTIONS OF THE SPINAL CORD 907 
 
 because the reflex effect produced by them is in tliis case not con- 
 traction, but inhibition. (4) The groups of motor cells contempor- 
 aneously discharged by spinal reflex action innervate synergic 
 muscles (muscles which act in the same direction in effecting a 
 harmonious movement), and not antergic muscles (which antagonize 
 each other). 
 
 This disproves the old idea that the movements, caused by ex- 
 citation of an efferent spinal root, are co-ordinated synergic move- 
 ments, since at many joints the flexors and extensors both receive 
 motor fibres from one and the same root, and stimulation of the 
 root must simultaneously excite antagonistic muscles. ' The 
 collection of fibres in a motor spinal root does not represent a reflex 
 figure — i.e., a number of simple reflexes occurring simultaneously — 
 nor does the receptive field of a reflex correspond with the distribu- 
 tion of an afferent root.' 
 
 (5) It follows from (i), (2), and (4) that the spinal reflex move- 
 ment which can be elicited in and from any one spinal region will 
 exhibit much uniformity even when the exciting stimulus is applied 
 at different and distant points within the receptive field. The 
 flexion reflex of the hind-limb, e.g., will have the same general char- 
 acter — i.e., flexion of each of the three main joints — whatever part 
 of the surface of the limb is stimulated. Yet the flexion movement 
 will be strongest at the joint whose flexors are innervated by motor 
 cells situated in a spinal segment near the entrance of the afferent 
 fibres from the stimulated skin area. 
 
 For the long spinal reflexes it is less easy to deduce definite rules, 
 for they can be less easily and constantly evoked than the short 
 reflexes. The so-called laws of spread formulated by Pfliiger for 
 the long spinal reflexes, and based mainly on observations made 
 in the brainless frog and on clinical records in cases of spinal lesion 
 in man, need not be stated here. For Sherrington has shown that 
 they require serious modification. Especially is this true of Pfliiger's 
 fourth law, that the reflex irradiation spreads always more easily 
 up in the direction of the medulla oblongata, so that stimulation of 
 a fore-limb does not cause reflex contraction of a hind-limb, although 
 excitation of a hind-limb may cause movement of one or both fore- 
 limbs. This law does not hold in the mammal. As a rule, indeed, 
 irradiation takes place more easily down than up the cord. Excita- 
 tion of the skin of the pinna easily causes reflex movements of the 
 limbs, while the reverse is rare. Reflex movements of the hind- 
 limb in the spinal animal are more easily evoked by stimulation of 
 the fore-limb than movements of the fore-limb by stimulation of 
 the hind. It is easier for the irradiation to cross the cord from 
 hind-limb to hind-limb than to pass up from hind- to fore-limb; 
 but it is often easier for irradiation to occur down the cord from 
 fore- to hind-Hmb than across the cord from one fore-limb to the 
 other. Afferent channels from the skin of the shoulder, through 
 
9o8 THE CENTRAL NERVOUS SYSTEM 
 
 which the scratch-reflex is discharged (in the dog), are freely con- 
 nected with efferent paths to the muscles of the hip, knee, and ankle 
 by an uncrossed path descending the lateral column (Sherrington). 
 In cats, after temporary occlusion of the cerebral circulation, which 
 throws the brain out of gear, it is easy to elicit movements of the 
 hind-legs by pinching the fore-paws or the skin of the upper part 
 of the body. The scratch-reflex can also be very readily evoked, 
 and in great intensity, by stimulating the pinna, and is not confined 
 to the side stimulated. In anaemia of the brain and (cervical) cord 
 and subsequent resuscitation, homolateral reflexes {i.e., on the 
 same side as the stimulus) are submerged later and emerge sooner 
 than contralateral refle.xes whose centres lie in the area which was 
 rendered ansemic (Pike, (iuthrie, and Stewart). 
 
 Co-Ordination of Reflexes. — The co-ordination or orderly combina- 
 tion of muscular actions for the production of appropriate and har- 
 monious movements is one of the most important functions of the 
 central nervous system. Both the brain and the cord take a share 
 in this co-ordination. The role of the brain \\'ill be considered later 
 on, but it is essential to recognize now that many of the movements 
 which the brain directs represent spinal reflexes already synthesized, 
 compounded, or co-ordinated in a very high degree. This is the 
 reason why, in the spinal animal, the inexperienced observer may 
 sometimes be startled by the apparently ' purposive character ' of 
 a reflex movement— the scratch-reflex in the dog or cat, e.g., or the 
 extensive reflex movements of the hind-legs of a brainless frog 
 when the skin is pinched or painted with dilute acid, so plainly 
 directed to the seat of irritation. When a drop of acid is applied 
 to the flank of such a frog, it will attempt to wipe it off with the 
 foot which is situated most conveniently. If this foot be held, it 
 will use the other. These reactions are necessarily purposive in 
 character, since they have been evolved with reference to the ad- 
 vantage of the organism as a whole. They are the sort of complex 
 reactions which the intact animal would have had to improvise 
 by the combination of a considerable number of simple movements 
 when it was executing such defensive reactions, with the conscious 
 purpose of escaping from the irritant, w-ere they not already present 
 as purposive reflexes in the ready-made condition. 
 
 In the combining of reflexes we may distinguish between simul- 
 taneous combination — i.e., the combination of reflex actions taking 
 place at the same time — and successive combination — i.e., the 
 combination of reflexes in such a way that they follow each other 
 in an orderly sequence. The facts already mentioned in speaking 
 of irradiation afford a partial explanation of the co-ordination of 
 reflexes by simultaneous combination. The movements are orderly 
 and harmonious because the spread of the reflexes is not indis- 
 criminate, but follows a definite ' march,' determined partly by the 
 
FUNCTIONS OP THE SPINAL CORD O09 
 
 anatomical relations of afferent and efferent paths, partly by the 
 varying resistance of the synapses or other structures whose proper- 
 ties lix the threshold value of the excitation by which an arc can be 
 forced. In general it is not enough that the channel of the final 
 common paths (p. 899) to the muscles whose contraction produces 
 the reflex movement should be thus open to the afferent arcs that 
 elicit the movement; they must be closed to other afferent arcs 
 which might disturb the reflex. Not only so: there is evidence 
 that very frequently the final common paths are, so to say, more 
 widely opened to the afferent arcs in question by the ' reinforcing ' 
 or ' facilitating ' influence of allied, though it may be distant, 
 afferent arcs, which are simultaneously excited (p. 911). Further, 
 the final common paths to antagonistic muscles must also be 
 temporarily closed. The closing of these central connections, or 
 rather the raising of their threshold sufficiently to bar the impulses 
 from passing through the door, is an inhibitory phenomenon. Ex- 
 citation of the desired movements and inhibition of antagonistic 
 movements go hand-in-hand in the simultaneous combination of 
 reflexes. It is obvious that if a movement is to be efficiently exe- 
 cuted, it cannot be the result of a compromise between competing 
 reflexes. A segment of a limb can be either flexed or extended, but 
 cannot at the same time undergo both flexion and extension. In 
 the interests of an effective movement, one or the other must give 
 way utterly. The reflex which eventually prevails makes a clear 
 field for itself by inhibiting all other reflexes which do not co-operate 
 with it. For example, if the receptive area of skin from which the 
 scratch reflex is elicited be stimulated and a painful stimulation be 
 at the same time applied to the foot, we do not obtain a mixed 
 scratch and flexion reflex, which would result in a confused and 
 ineffective combination of movements, but a pure scratch or flexion 
 reflex, as a rule the latter. 
 
 The successive combination of reflexes is well illustrated by the 
 contraction of the oesophagus in deglutition. First one portion of 
 the tube and then the next below are involved in the reflex action. 
 The combination consists in the orderly sequence. The manner in 
 which this is secured in this class of reflex action has been lumin- 
 ously discussed by Sherrington,* but details cannot be given here. 
 While only aUied reflexes — i.e., such as mutually reinforce and 
 therefore harmonize with each other — can be simultaneously com- 
 bined, and antagonistic reflexes cannot, both allied and antagonistic 
 reflexes can be successively combined. An example of the succes- 
 sive combination of allied reflexes is the series of scratch reflexes 
 caused by a parasite travelling across the receptive field of the 
 reflex. An example of the successive combination of antagonistic 
 
 * ' Integrative Action of the Nervous System,' to which work the advanced 
 student is referred. 
 
 / 
 
910 THE CENT.^AL NERVOUS SYSTEM 
 
 reflexes is afforded when either the scratch reflex or the flexion 
 reflex is induced and caused to interrupt the other while it is pro- 
 ceeding. The transition — e.g., from flexion to scratch reflex — is 
 made without any period of confusion. Thus, if the scratch reflex 
 has been induced and is being executed, and the foot is then pain- 
 fully stimulated, the scratch reflex immediately ceases, and the 
 flexor reflex takes its place. When the flexor reflex has termin- 
 ated, the scratch reflex may be resumed. The same holds good for 
 other antagonistic reflexes. In many cases the avoidance of con- 
 fusion is due to the inhibition of the first reflex, or often to inhibition 
 of the set of muscles which were active in the first reflex combined 
 with excitation of their antagonists (so-called interference). It is 
 obvious that this is an adaptation of great importance. 
 
 Influence of the Brain on the Spinal Reflexes. — The spinal reflexes 
 can be influenced by impulses descending from the higher centres. 
 For (a) it is a matter of common experience that a reflex movement 
 may be to a certain extent controlled, or prevented altogether by an 
 effort of the will, and it is worthy of remark that only movements 
 which can be voluntarily produced can be voluntarily inhibited. 
 (b) Long-continued muscular contractions may be caused in animals 
 after removal of the cerebral hemispheres by stimulation of afferent 
 nerves — for example, by scratching the mucous membrane of the 
 mouth in a ' brainless ' frog or Necturus. (c) By stimulation of 
 certain of the higher centres reflex movements which would other- 
 wise be elicited may be suppressed or greatly delayed. If the 
 cerebral hemispheres are removed from a frog, and one leg of the 
 animal dipped into dilute acid, a certain interval, the (uncorrected) 
 reflex time, will elapse before the foot is drawn up (p. 996). If, 
 now, a crystal of common salt be applied to the optic lobes, or 
 corpora bigemina, or the upper part of the spinal cord, and theexperi- 
 ment repeated, it will be found either that the interval is much 
 lengthened or that the reflex disappears altogether. Stimulation 
 of the optic lobes relaxes the reflex sexual embrace of the male frog 
 when it is present. From such experiments it has been concluded 
 that centres which can inhibit the spinal reflexes are situated in the 
 thalamus, the corpora bigemina and the medulla oblongata of the 
 frog. In mammals, also, there is evidence of the existence of 
 mechanisms in the brain, the excitation of which diminishes the 
 reflex excitability of the cord. For example, stimulation of the 
 frontal convolutions in the dog causes a diminution in the height 
 of reflex contractions of the limbs. Strong stimulation of an 
 afferent nerve may abolish or delay a reflex movement which is 
 being elicited through other receptors, (d) If such inhibitory 
 mechanisms exist, it is to be supposed that elimination of the brain 
 will render it easier to elicit reflexes from the cord. Experiment 
 shows that this is actually the case. An animal like a frog responds 
 
t-UNCTIONS Of THE SPINAL CORD gii 
 
 to stimuli by retlcx movements more readily after the medulla 
 oblongata has been divided from the spinal cord or the brain re- 
 moved. In the dog the scratch reflex is elicited more easily after 
 removal of the cerebral cortex or its elimination by cerebral 
 anaemia. In the guinea-pig, after extirpation of the cortex of one 
 hemisphere, the scratch reflex is more readily evoked on the side 
 of the lesion (Brown). 
 
 That the brain exerts more than a merely inhibitory influence on 
 the production of reflex movements is suggested by many facts. 
 The knee-jerk, for example, is increased or ' reinforced ' if an instant 
 before the tendon is struck the patient makes a voluntary movement 
 or is acted on by a sensory stimulus (Bowditch and Warren). In 
 health it varies in strength with many circumstances which affect 
 the activity of the central nervous system as a whole (Lombard, 
 etc.). It often disppears in pathological lesions, situated high up 
 in the cord in man, and is markedly impaired after high section of 
 the cord in dogs. In hemiplegia (paralysis of one side of the body, 
 caused by disease in the brain) the cutaneous reflexes on the para- 
 lyzed side may sometimes be absent for years. Some observers 
 have even gone so far as to say that under normal conditions the 
 so-called spinal reflexes are really cerebral — in other words, that 
 the afferent impulses run up to the brain and there discharge efferent 
 impulses, which pass down to the motor cells of the anterior horn 
 and cause their discharge. It may be admitted that there is no 
 physiological ground for supposing that the afferent impulses which 
 have to do with the reflex contraction of the muscles of the leg 
 when the sole is tickled, stop short at the motor cells of those spinal 
 segments from which the efferent nerves come off, while the af* 
 ferent impulses which have to do with the sensation of tickling pass 
 up to the brain. The probability is that under ordinary circum- 
 stances such afferent impulses pass up the cord in long afferent 
 paths, as well as directly towards the motor cells along those fibres 
 of the posterior roots and their collaterals which bend forward into 
 the anterior horn at the level of their entrance into the cord. And 
 the only question is whether, as a matter of fact, the spinal motor 
 cells are most easily discharged by the impulses that reach them 
 directly, or by the impulses that come do\yn to them by the round- 
 about way of the brain, and the efferent fibres that connect it with 
 the cord. It is evident that the answer to this question need not 
 be the same for all kinds of animals. It may well be that in the 
 higher animals, in which the cortex has undergone a relatively great 
 development, the spinal motor mechanisms are more easily dis- 
 charged from above than from below, while in lower animals the 
 opposite may be the case. When the cord is cut off from the brain 
 the afferent impulses may overflow more easily into the spinal motor 
 cells since their alternative path is blocked. In the frog, where 
 
512 THE CENTRAL NERVOUS SYSTEM 
 
 there is already a beaten track between the posterior root-fibrea 
 and the cells of the anterior horn, this overflow may be established 
 immediately after section of the cord, and may of itself lead to an 
 exaggeration of the reflexes. In animals like the dog a longer time 
 may be necessary before the unaccustomed route from the end 
 arborizations of the afferent axons and their collaterals to the 
 dendrites or the bodies of the motor cells becomes natural and easy; 
 in man a still longer interval may be required. Moore and Oertel 
 have made a careful comparative study of reflex action after com- 
 plete section of the cord in the cervical or upper dorsal region, and 
 conclude that the spinal reflexes in the higher animals are far more 
 dependent on the upper portions of the central nervous system than 
 in the frog. 
 
 Spinal Shock. — The phenomena of spinal shock and its varying 
 severity in different animals may be accounted for by the rupture of 
 the paths normally used in the reflexes. The theory that the shock is 
 due to an inhibition set up by the mechanical injury is untenable. For 
 shock affects only the portion of the central nervous system distal (or 
 aboral) to the lesion. Wlien a dog is allowed to live after transection 
 of the cord in the lower cervical region till shock has been recovered 
 from, a second transection distal to the first is followed by only slight 
 and very transient depression of the reflex power, although the direct 
 effect of the second injury ought, of course, to be as great as that of the 
 first. Finally, according to Sherrington, the condition of the spinal 
 reflex arcs in shock diflers from the condition caused by inhibition, and 
 resembles rather a general spinal fatigue in which conduction along the 
 arc and especially across the synapses is difficult and uncertain. This 
 condition is supposed to be due to the loss of a ' tonic ' influence of 
 higher centres, assumed to be necessary for the maintenance of the 
 normal conductivity of the arc. These cranial centres, if they exist, or, 
 at least, the most efficient of them, must be assumed to be situated 
 distal to the cerebral cortex, probably in the pons or mid-brain. For 
 section just behind the pons causes much more severe shock than 
 removal of the cerebral hemispheres. 
 
 Peripheral Reflex Centres. — The question whether any reflex centres 
 exist outside cf the spinal cord and brain, and especially in the sympa- 
 thetic ganglia, has been the subject of a lengthy controversy. That 
 the spinal ganglia cannot act as reflex centres is generally acknowledged, 
 and it is not difficult to see that, for anatomical reasons, this must be so. 
 A reflex arc must, so far as we know, in all highly-organized animals 
 include at least two neurons. There is no proof that an afferent 
 impulse can ascend an axon to a cell-body and there excite an efferent 
 impulse, which, descending the same axon in a separate set of fibrils, 
 gives rise to a reflex contraction, or a reflex secretion. Now, the cells 
 of a spinal gangUon represent the original neuroblasts from which the 
 posterior root-fibres grew out as processes towards the cord on the one 
 side and the periphery on the other. A sensory fibre passing into the 
 ganglion makes connection with a cell by a T-shaped junction and 
 passes on its course again. No afferent fibres run from tlie nerve-trunk 
 into the ganglion, to end in arborizations around the ganglion cells, 
 and no efferent fibres arise from ncrvc-cells in the ganglion to pass out 
 into the trunk. For although a shghtly greater number of mcduUatcd 
 fibres of small calibre is found in a spinal nerve-trunk immediately 
 
FUNCTIONS OF THE SPINAL CORD yij 
 
 distal to the junction of the roots than in both roots taken together, this 
 appears to be due to tlie passago into tlic nerve (from tlie grey ramus 
 communicans) of mcdullated fibres which end in the bloodvessels or 
 other tissue of the ganglion (Dale). Here it is evident that there is no 
 possibility of a complete reflex arc. Indeed, it is not certain that the 
 normal afferent impulses pass through the bodies of the spinal ganglion 
 cells at all. For (i) a negative variation can be observed in the j)osterior 
 roots above the ganglia on stimulation of the trunk of a fr g's sciatic 
 nerve more than two days after the death of the animal, when the 
 ganglion cells may be supposed to have completely lost their vitality. 
 and when no reflex negative variation can be detected in the central 
 stump of a severed anterior root on excitation of the sciatic or the 
 corresponding posterior root. Such a reflex action current is normally 
 obtainable from a fresh preparation. (2) When the blood-supply of the 
 posterior root-fibres and the ganglion is cut off without killing the frog, 
 the nerve impulse is still conducted by the fibres, as is shown by the 
 reflex movements elicited on stimulation of the central end of the sciatic, 
 at a time when the nerve-cells show marked histological alterations. 
 
 (3) Prolonged excitation of the posterior roots or the mixed nerve causes 
 no noticeable microscopical changes in the ganglion cells (Stcinach).* 
 
 (4) The application of nicotine to a spinal ganglion does not hinder the 
 passage of impulses through the corresponding afferent fibres. If it 
 acts on spinal ganglion cells as it does on sympathetic ganglion cells 
 (p. 182), this must be because the impulses do not require to traverse 
 the ganglion. 
 
 Axon-Reflexes. — In the ordinary sympathetic ganglia, f also, it is 
 doubtful whether the anatomical foundation for a reflex arc exists, and 
 the most careful physiological experiments have failed to connect them 
 with any reflex function. Sokownin, indeed, observed that stimulation 
 of the central end of the hypogastric nerve caused contractions of the 
 bladder, and he considered these movements to be reflex, the centre 
 being the inferior mesenteric ganglion. Langley and Anderson have 
 also found that when all the nervous connections of the inferior 
 mesenteric ganglion, except the hypogastric nerves, are cut, stimulation 
 of the central end of one hypogastric causes contraction of the bladder, 
 the efferent path being the other hypogastric. In addition, they have 
 observed an apparent reflex excitation of the nerves which supply the 
 erector muscles of the hairs (pilo-motor nerves) through other sympa- 
 thetic ganglia. They believe, however, that in neither case is the action 
 truly reflex, but that it is caused by stimulation of the central ends of 
 motor fibres, which come off from the spinal cord, and in passing through 
 the ganglion give off collateral branches to some of its cells. In the 
 case of the inferior mesenteric ganglion the spinal fibres passing down 
 in the left hypogastric would send branches to arborize around ganglion 
 cells which give origin to fibres of the right hypogastric, and vice versa. 
 When the central end of the left hypogastric is stimulated the excitation 
 is conducted up the spinal fibres, and so reaches their branches, and, 
 through the ganglion cells, the sympathetic fibres of the right hypogastric, 
 which convey it to the muscles of the bladder (see sartorius or gracilis ex- 
 periment of Kiihne, p. 792) . Other examples of such axon-reflexes exist. 
 
 * Hodge obtained changes. In such experiments it is necessary that thf 
 ganglion should not be directly excited by electrotonic currents or escape of 
 the stimulating current. 
 
 t The ganglion cells of Auerbach's and Meissner's plexus in the intestine 
 are not of ordinary sympathetic type, and, as has been previously pointed 
 out, it is probable that they, or some of them, are true reflex centres for the 
 stomach and intestines. 
 
 58 
 
914 THE CESTRAL NERVOUS SYSTEM 
 
 Reflex Time. — W'lien a reflex movement is evoked, a measurable 
 period ela})ses between the application of the stimulus and the 
 commencement of the movement. This inter\'al may be called the 
 uncorrected reflex time or the latent period of the reflex. A part of 
 the interval is taken up in the transmission of the afferent impulse 
 to the reflex centre, a part in the transmission of the efferent impulse 
 to the muscles, a part represents the latent period of muscular 
 contraction, and the remainder is the time spent in the centre, or 
 the true reflex time. Ordinarily this time, though absolutely short, 
 is relatively so great that the total latent period of a reflex is much 
 longer than when a similar length of nerve-trunk is interposed be- 
 tween the point of application of the stimulus and the muscle. 
 When the conjunctiva or eyelid is stimulated on one side both eye- 
 lids blink. This is a typical reflex action reduced to its simplest 
 expression, and the true reflex time is correspondingly short — only 
 about ^\j second (50 <r*). An additional yj^ second (10 a) is con- 
 sumed in the passage of the afferent impulse along the fifth ner\'e 
 to the medulla oblongata, of the efferent impulse from the medulla 
 to the orbicularis palpebrarum along the seventh nerve, and in the 
 latent period of the muscle. \\'hen a naked ner\'e, like the sciatic, 
 is stimulated, the true reflex time is reduced to j^ to -^ second. As 
 estimated by Tiirck's method (p. 996), the uncorrected reflex time 
 is greatly lengthened, it ma}- be to several, or even many, seconds. 
 For here it is evident that the time taken by the acid to soak 
 through the skin and reach the nen'e-endings in strength sufficient 
 to stimulate them is included. But even when the peripheral 
 factors remain constant, the central factor may var\'. With strong 
 stimulation, eg., the reflex time is shorter than with weak stimula- 
 tion. With weak stimuli the latent period of the flexion reflex in 
 the dog is usually 60 cr or 120 a-- It may even be as long as 200 a. 
 With strong stimuli it may be as little as 30 a- Even 22 a has been 
 seen, which is little more than for ner\^e-trunk conduction. Fatigue 
 of the nerve-centres delays the passage of impulses through them; 
 and strychnine, while it increases the excitability of the cord, also 
 lengthens the reflex time. 
 
 Reflexes in Disease. — In order that a reflex action may take place, 
 the reflex arc— afferent nerve, central mechanism, and efferent nerve — 
 must be complete; and, in fact, a whole series of simple reflex move- 
 ments exists, the suppression, diminution, or exaggeration of which 
 can be used in diagnosis as tests of the condition of the reflex arc. It 
 is customary to divide these into superficial reflexes, elicited from 
 receptive fields on the surface of the body [extero-ceptive fields), and deep 
 reflexes, elicited from receptors in the depth of the organism (proprio- 
 ceptive fields), especially in the muscles and the tendons and joints con- 
 nected with them. The extero-ceptive reflexes are normally excited 
 by extraneous stimuli acting on the surface from the environment. 
 Ihe proprio-ceptive reflexes arc normally excited by changes (muscular 
 
 • <r = oooi second. 
 
FUNCTIONS OF THE SPINAL CORD 
 
 915 
 
 contractions) occurring in the body itself, which changes arc in turn 
 i.sually initiated by excitation of surface receptors by the environment. 
 Examples of superficial reflexes are the plantar reflex (the dra\ving-up 
 of the foot when the sole is tickled), the cremasteric reflex (retraction of 
 the testicle when the skin on tlic inside of the thigh just below Poupart's 
 ligament is stroked, especially in boys), the gluteal, abdominal , epigastric, 
 and interscapular reflexes (contraction of the muscles in those regions 
 when the skin covering them is tickled). The behaviour of the toes, 
 especially of the great toe, is of considerable diagnostic importance. 
 Normally, on tickling the sole, the toes 
 are flexed towards the planta ; but 
 when a lesion of the pyramidal tract 
 exists, as in hemiplegia, there is dorsal 
 instead of plantar flexion, most marked 
 in the case of the great, toe, and the 
 toe moves more slowly than in the 
 healthy person (Babinski'ssign). This 
 is an instance of reversal of a reflex 
 owing to the elimination of the in- 
 fluence of the cortex. In an epileptic 
 fit there is said to be a temporary 
 reversal of the same reflex, indicating 
 probably that the cortex is temporarily 
 eliminated in consequence of fatigue 
 due to intense and prolonged discharge. 
 In children during the first few months 
 of life stimulation of the sole causes 
 normally a dorsal flexion of the big toe, 
 this reversal of the normal reaction of 
 the adult persisting until the pyra- 
 midal path has attained functional 
 completion (p. 848). During sleep 
 the reversed reaction (dorsal flexion) 
 is still obtained for a time. Examples 
 of deep reflexes are the knee-jerk (a 
 sudden extension of the leg by the 
 rectus femoris and vastus medialis 
 components of the quadriceps muscle 
 when the ligaraentum patellae is sharply 
 struck), the heel-jerk or foot-jerk (a 
 movement of the foot caused in most 
 healthy persons, though not in all, by 
 tapping the tendo Achillis), and the 
 periosteal radial reflex (a movement 
 of flexion and slight pronation of the 
 forearm and hand elicited by tapping 
 the lower end of the radius). The 
 jaw-jerk (a movement of the lower jaw when, with the mouth open, 
 the chin is smartly tapped) and ankle-clonus (a series of spasmodic 
 movements of the foot, brought about by flexing it shar])ly on the leg) 
 are phenomena of the same class, which can be elicited only in 
 disease. Any condition which impairs the conducting power of the 
 afferent or efferent fibres of the reflex are necessarily diminishes or 
 abolishes the reflex movement, even if the central connections are 
 intact. E.g., in locomotor ataxia the disappearance of the knee-jerk 
 is one of the most important diagnostic signs. This disease involves 
 the posterior roots and the fibres that continue them in the posterior 
 
 'rttersea/tu/ur 
 
 Epicfastric 
 
 .^hdcmittnl 
 
 kneg-jerh 
 
 AnkU-Clonui 
 Plantar- 
 
 Fig. 366. — Diagram of Refle.K Centres 
 in Cord (after Hill). 
 
 [2 Cremaster 
 
5i6 THF CFNTRAL NERVOUS SYSTEM 
 
 column. The anterior nerve-roots are perfectly healthy. The grey 
 matter of the cord — at least, in the earlier stages of the disease 
 —is unaffected. The weak link in the chain is the afferent path. 
 Where the presence of the knee-jerk is doubtful, it is necessary to search 
 for the most favourable position of the limb for eliciting it before deter- 
 mining that it is absent. The patient may be made to clasp his hands 
 tightly at the moment of the tap to reinforce the jerk (p. gii). In 
 anterior poliomyelitis (p. 876) the afferent link is intact, but the other 
 two are broken, and the reflexes also disappear. Certain lesions which 
 partially cut off the spinal cord from the higher centres without affecting 
 the integrity of the spinal reflex arcs increase the strength of reflex 
 movements and the facility with which they are called forth. In 
 primary spastic paraplegia (a paralysis of the legs and the lower portion 
 of the body), which is associated with degenerative changes in the lateral 
 columns, the deep reflexes are all exaggerated. But according to the 
 best authorities, a lesion amounting to total transection of the cord in 
 man abolishes all reflexes below the lesion. In the monkey the knee- 
 jerk may be tried for in vain for weeks after section of the cord in the 
 middle of the thoracic region, whereas in the rabbit it can be obtained 
 ten to fifteen minutes after the transection. The position of the centres 
 in the cord for the various reflex movements is shown in Fig. 366. 
 
 3. The Origination of Impulses in the Spinal Cord (Automatism). — 
 An action known to be caused or conditioned by afferent impulses 
 is called a reflex action. There is some evidence that the reflex 
 centres are continually in a state of activity, and are not simply 
 roused to activity by the arrival of the afferent impulses, which 
 discharge the reflex. Their condition, when not discharging, seems 
 to represent a state of balance between excitatory and inhibitory 
 influences, a so-called ' innervation equilibrium,' which can be up- 
 set in one direction or the other, according to the intensity of the 
 antagonistic influences. A ph\^siological action is termed auto- 
 matic when it depends upon a nervous outflow which seems to be 
 spontaneous, in the sense that it is not brought about by any evi- 
 dent reflex mechanism, or, in other words, is not discharged by 
 afferent impulses falling into the centre where it arises, although it 
 may be determined by substances in the blood. Automatic actions 
 being thus defined in a negative manner by the defect of a quality, 
 there is always a possibility that some day or other it may be de- 
 monstrated that any given action which at present seems automatic 
 in its origin depends on afferent impulses hitherto unnoticed. As 
 a matter of fact, the supposed proofs of spinal automatism have in 
 more than one case vanished with the advance of knowledge, and as 
 the domain of purely automatic action has been narrowed, that of 
 reflex action has extended, until the controversy as to the boun- 
 daries between the two seems not unlikely to be ended by the ab- 
 sorption of the automatic in the reflex. And as we seem almost 
 driven to conclude that from the anatomical standpoint the ner\'ous 
 system is essentially a vast collection of looped conducting paths, 
 each with an afferent portion, an efferent portion, and connections 
 between them formed by the end arborizations of the axons and 
 
FUNCTrONS OF THE SPINAL CORD 917 
 
 tlicii" collattiiils, till' dendrites and the cell-bodies, so it may be 
 that no strict physiological automatism really exists either in cord 
 or brain, that every form of physiological activity — muscular move- 
 ment, secretion, intellectual labour, consciousness itself — would 
 cease if all afferent impulses were cut off from the nervous centres. 
 Assuredly no neuron is entirely isolated from other neurons. The 
 more the nervous system is investigated, the deeper grows the con- 
 viction of its essential solidarity, the more clearly it displays itself 
 as a single mechanism, the most distant parts of which are intricately 
 knit together. But there are certain groups of actions so widely 
 separated from the most typical reflex actions that, provisionally 
 at least, they may be distinguished as automatic. Such are the 
 voluntary movements, and certain involuntary movements, like 
 the beat of the heart. And we may proceed to inquire whether the 
 spinal cord has any power of originating movements or other actions 
 of this high degree of automatism. 
 
 Muscular Tone or Tonus — Postural Reflexes. — It is generally 
 stated that so long as a muscle is connected with the spinal segment 
 from which its nerves arise, it is never completely relaxed ; its fibres 
 are in a condition of slight tonic contraction, and retract when cut. 
 This tonus has been clearly demonstrated for some muscles, though 
 not for all. If a frog whose brain has been destroyed is suspended 
 so that the legs hang down, and one sciatic neive is cut, the corre- 
 sponding limb may be observed to elongate a little as compared 
 with the other, owing to a slight relaxation of the flexors. At one 
 time this tone of the muscles was supposed to be due to the continual 
 automatic discharge of feeble impulses from the grey matter of the 
 cord along the motor nerves. But it has been proved that if the 
 posterior roots of the limb be cut, its tone is completely lost, although 
 the anterior roots are intact. So that the tone of the skeletal 
 muscles in this classical experiment depends on the passage of 
 afferent impulses to the cord, and must be removed from the group 
 of automatic actions and included in the reflexes. The subject is 
 considered here and not with the ordinary reflexes, partly to em- 
 phasize by a notable example the gradual abridgement of the sup- 
 posed automatic ftmctions of the cord, which has been already 
 referred to, but partly because these reflexes have certain peculiari- 
 ties which distinguish them from the reflexes manifested by move- 
 ments. It has since been shown that this reflex tonus of skeletal 
 muscle is a postural reflex — i.e., a reflex contraction of muscles asso- 
 ciated with the maintenance of the posture of a part or of the animal 
 as a whole. It can be readily demonstrated in the decerebrate 
 mammal that the tonus of the extensor muscles of the limbs is a 
 reflex sustained through the afferent fibres of the muscles themselves, 
 including those from the tendons and the neighbouring joints (the 
 proprioceptive system) and not througli the cutaneous nerves. It 
 
yl8 TMK CENTRAL XERVOUS SVSTliM 
 
 is obviously in accord witJi the interpretation ol the tonus as a 
 postural reflex that in the mammal the extensor limb muscles should 
 exhibit the phenomenon and the flexors not, while in the frog it is 
 the reverse. For it is the extensors which are concerned in the re- 
 flex standing posture so characteristic of the mammal, while the 
 flexors of the iiind limbs are especially concerned in the squatting 
 posture so characteristic of the frog. 
 
 The postural reflexes differ in no essential way from the reflexes 
 previously studied, except that they are directed to the maintenance 
 of posture and not to the production of movement. Reflex postural 
 tonus has cilso been demonstrated for other groups of skeletal muscles, 
 of which the most important are the neck muscles concerned in the 
 position of the head. The reflexes in this instance originate not only 
 through the afferent fibres of the muscles themselves, but also from the 
 otic labyrinth, in discussing the functions of which the subject must be 
 returned to. But it may still be mentioned here, and it shows how 
 intricate is the correlation of the postural reflexes to one another, 
 that not only docs the labyrinth influence the postural contraction of 
 the extensors of the limbs directly — i.e., through afferent fibres from 
 the labyrinth itself, but also indirectly through the changes produced 
 in the posture of the head and neck — i.e., through the afferent fibres 
 of the neck muscles (Magnus and de Kleijn). Even when the head of 
 a normal rabbit is passively moved so that its position relatively to the 
 body is altered, the postural tonus of the muscles of the extremities 
 and even of some of the muscles of the trunk, especially those connected 
 with the lumbar vertebrae, is definitely affected. 
 
 A remarkable property of a muscle which exhibits postural reflex 
 tonus is that its tension remains approximately unaltered, even when 
 its length is greatly changed by placing the joint on which it acts in 
 different postures. Within a wide range it is able to counterbalance 
 just the same extending force whatever the length of the active muscle 
 may be (Practical Exercises, p. looo). This property is dependent upon 
 the integrity of the reflex arcs. A muscle which is not under the 
 influence of its nerve centre reveals no trace of this pecidiarity, which, 
 however, is possessed by the smooth muscle of viscera — e.g., the urinary 
 bladder and the stomach. It has been shown that these hollow organs 
 can hold very different quantities of liquid without any great change 
 of tension. With a larger volume of contents, indeed, the tension 
 may be even less than with a smaller volume. It is oljvious that this 
 property must play an important part in regulating the pressure 
 within such viscera, so that in the case of the bladder —<?./;'., the pres- 
 sure may not rise prematurely to the point at which the desire to 
 micturate is aroused. The adjustment of the tonus of these smooth 
 muscles docs not depend altogether upon the central nervous system, for 
 it is still exhibited, although not so amply, by the excised living stomach. 
 
 Other characteristics of the reflex postural contraction are the long 
 periods for which it usually endures without apparent fatigue, and 
 what is probably associated with this relative unfatiguability, the 
 slight expenditure of energy by which it is maintained (Roaf). 
 
 It is probable that the tone of such visceral muscles as the sphincters 
 of the anus and bladder has a reflex element analogous to postural 
 contraction, and possible that the same is true of the tone of the smooth 
 muscular fibres of the bloodvessels on which the maintenance of the 
 mean blood-pressure so largely depends (p. 185). 
 
FUNCTIONS OF THF SPINAx. CORD 9i9 
 
 Trophic Tone.- - The degenerative changes that occur in muscles, 
 nerves, and other tissues when their connection with the central 
 nervous system is interrupted have been already referred to (p. 804). 
 It is possible to explain these changes in some cases without the 
 assumption that tonic impulses are constantly passing out from the 
 brain and cord to control the nutrition of the pcriplieral organs; 
 and we have seen that there is no real evidence of the existence of 
 specific trophic fibres. But the degeneration of muscles after sec- 
 tion of their motor nerves is difficult to understand, except on the 
 hypothesis that impulses from the cells of the anterior horn influence 
 their nutrition. The only question is whether these are the im- 
 pulses to which muscular tone is due, and therefore reflex, or dif- 
 ferent in nature and automatically discharged. Now, degeneration 
 of a muscle is not usually caused, or at least not lor a long time, by 
 interruption of its afferent nerve-fibres, as in locomotor ataxia, or 
 after section of the posterior nerve-roots (Mott and Sherrington). 
 We can hardly suppose that in any case the trophic influence of the 
 cells of the spinal or sympathetic ganglia to which all other reflex 
 powers have been denied, is of reflex nature. And there is, indeed, 
 more evidence in favour of trophic tone being an automatic action 
 of the cord than for any of the other tonic functions hitherto con- 
 sidered. 
 
 The evidence for respiratory automatism upon which the spinal 
 cord has been chiefly credited with true automatic action has pre- 
 viously been given (p. 284). 
 
 The ' Centres ' of the Cord and Bulb. — We have frequently used the 
 word ' centre ' in describing the functions of the spinal cord, but the 
 term, although a convenient one, is apt to convey the idea that our 
 knowledge is far more minute and precise than it really is. When we 
 say that a centre for a given physiological action exists in a definite 
 portion of the spinal cord, all that is meant is that the action can be 
 called out experimentally, or can normally go on, so long as this portion 
 of the cord and the nerves coming to it and leaving it are intact, and 
 that destruction of the ' centre ' abolishes the action. For example, a 
 part of the medulla oblongata on each side of the middle line in the 
 floor of the fourth ventricle above the calamus scriptorius is so related 
 to the function of respiration that when it is destroyed the animal ceases 
 to breathe. But this respiratory centre — the ' noeud vital ' of Flourens 
 ■ — docs not correspond in position with any definite collection of grey 
 matter, although it includes the nuclei of origin of several cranial nerves, 
 and forms an important point of departure for efferent, and of arrival 
 for afferent, fibres connected with the respirator}- act. Its destruction 
 involves the cutting off of the impulses constantlv travelling up the 
 vagus to modify the respiratory rhythm, and of the impulses constantly 
 passing down the cord to the phrenics and the intercostal nerves. And 
 just as the traffic of a wide region can be paralyzed at a single blow, by 
 severing tlie lines in the neighbourhood of a great railway junction, or 
 more laboriously, though not less effectually, by separate section of the 
 same tracks at a radius of a hundred miles, so destruction of the 
 respiratory centre accomplishes by a single puncture what can be also 
 
920 THE CENTRAL NERVOUS SYSTEM 
 
 performed by section of all the respiratory nerves at a distance from 
 the medulla oblongata. But while nobody speaks of the destruction of 
 a ' centre ' when a reflex action is abolished by division oi the peripheral 
 nerves concerned in it, there is a tendency, when the same effect is 
 brought about by a lesion in the brain or cord, to invoke that mysterious 
 name, and to forget that the cerebro-spinal axis is at least as much a 
 stretch of conducting paths as a collection of discharging nervous 
 mechanisms. 
 
 It is, perhaps, a profitless task to enumerate all the so-called centres 
 in the bulb and cord. In addition to the great vasomotor, respiratory, 
 cardio-inhibitory and cardio-augmentor centres in the bulb, which 
 perhaps, have more right than the rest to be regarded as distinct 
 physiological mechanisms, if not as definitely bounded anatomical 
 areas, there have been distinguished ano-spinal, vesico-spinal, and 
 genito-spinal centres in the lumbar cord, a cilio-spinal centre for r lila- 
 tatioji_of_jthe_pupiLiii the cervical cord, and in the medulla centres for 
 sneezing, for coughing, for sweating, "for sucking, for masticating, for 
 swallowing, for salivating, for vomiting, for the production of general 
 convulsions, for closure of the eyes, for the secretion of tears, and even a 
 ' diabetes ' or ' sugar ' regulating centre (p. 547). It has been recently 
 shown that in the cat a region of the dorsal cord between the last 
 cervical and the third dorsal segments is capable of sustaining the 
 spontaneous liberation of epinephrin from the adrenal glands after the 
 cord has been divided higher up. 
 
 Section IX. — The Crani.^l Nerves. 
 
 Unlike the spinal nerves, which arise at not very unequal intervals 
 from the cord, the nuclei of the cranial nerves, with the exception 
 of the olfactory and optic, are crowded together in the inch or two 
 of grey matter of the primitive neural axis in tlie immediate neigh- 
 bourhood of the fourth ventricle and the Sylvian aqueduct. Of 
 these nuclei some are the end nuclei or ' nuclei of reception ' of 
 sensory fibres — that is to say, collections of nerve-cells around 
 which the sensory fibres break up into terminal arborizations. Such 
 are the sensory nuclei of the fifth, the nuclei of the eighth, and the 
 sensory nuclei of the glossopharyngeal and vagus nerves (Figs, ^by, 
 368). The nuclei of origin of the motor fibres lie, upon the whole, 
 in two longitudinal rows — a median tow, which consists of the 
 nuclei of the third and fourth nerves in the floor of the aqueduct, 
 and those of the sixth and twelfth nerves in the floor of the fourth 
 ventricle; and a lateral row comprising the motor nuclei of the fifth, 
 seventh, tenth, and eleventh nerves. The clumps of grey matter 
 which make up these nuclei ma\' be considered as liomologous with 
 the grey matter of the ventral or anterior (including the lateral) 
 horn of the spinal cord ; and the motor fibres of the nerves themselves 
 as homologous with the anterior spinal roots. Without going 
 further into the thorny subject of the homologies of the cranial and 
 spinal nerves, we may point out that while all the spinal mrv 
 contain both efferent and afferent fibres, some of the cranial nciv 
 
TIIF. CRANIAL MiRVES 
 
 Q2I 
 
 arc pnrrly efferent, sonu' purely afferent, and otliers mixed. So 
 that if we are to look upon tl.c motor nerves as the homologues of 
 
 the ventral roots, the dorsal 
 (posterior) root- fibres cor- 
 rtsponding to them must be 
 represented in tlie other 
 cranial nerves. Thus, the 
 sensory portion of the mixed 
 fifth nerve, and the purely 
 afferent auditory nerve, must 
 be supposed to contain 
 fibres corresponding to seve- 
 ral dorsal roots. 
 
 Fig. 367. — Nuclei 'A Cranial Nerves (Toldt). 
 Motor red, sensory blue. The numbers 
 correspond to the cranial nerves. 
 
 The first or olfac- 
 tory nerve consists 
 of fine fibres, each 
 of which is a process 
 of an olfactory cell 
 (Fig. 369). The ol- 
 factory cells, which 
 are really peripheral 
 nerve-cells, lie among 
 the epithelial cells in 
 the olfactory region 
 of the Schneiderian 
 membrane, the com- 
 mon lining of the 
 nostrils. Each olfac- 
 tory cell gives off two 
 processes, a short 
 
 9 
 10 
 
 Fig- 368.— Nuclei and Roots of Cranial 
 Nerves (Toldt). Lateral view. Motor 
 red, sensory blue. 
 
 one, representing a dendrite, which runs out to the surface of the mucous 
 membrane, and a longer but more slender process, representing an axon, 
 
922 
 
 THE CENTRAL KEliVOVS SYSTEM 
 
 wliicli as a fibre of tlic olfactory nerve pierces the cribriform plate of the 
 ethmoid bone, and plunges into the olfactory bulb. 
 
 In the olfactory bulb at least four layers can be distinguished — (i) on 
 the surface, beneath the pia mater, the layer of entering oliactory 
 nerve-fibres; (2) the layer of olfactory glomeruli, peculiar structures, each 
 of which is made up of an intricate basket-like arboiization formed by 
 an olfactory nervo-fibre, or, it may be, more than one, and a brush-like 
 arborization belonging to a dendrite of one of the mitral cells of the next 
 layer; (3) the molecular or mitral layer, which contains a number of 
 large nerve-cells called, from their most common shape, mitral cells, 
 along with smaller nerve-cells (' granules ') and neuroglia ; (4) the nuclear 
 layer, containing numerous small nerve-cells or ' granules ' intermingled 
 with white fibres. The mitral cells give off axons, which pass through 
 the fourth layer, and then as fibres of the olfactory tract to the grey 
 matter of the hippocampal region of the brain. The course of the 
 impulses from the olfactory mucous membrane to the brain is lihown in 
 F^u- 369- The olfactory tract, as it runs back, divides into portions 
 
 Fig- 369- — Scheme of the Olfactory Nervous 
 Apparatus (Cajal). A. olfactory cells; B. glomeruli; 
 C, mitral cells; D, olfact(^ry granule cell; E, lateral 
 root of olfactory tract; F, cortex of brain in the 
 region of the uncinate gyrus; a, small cell of mitral 
 layer; b, brush of dendrite of a mitral cell ending in a 
 glomerulus; c, thorns or spines on the processes of an olfactory granule; e, collateral 
 coming off from the axon of a mitral cell; /, collaterals ending in the molecular layer 
 of the uncinate gyrus; g, pyramidal cells of the cortex; h, supporting epithelial cells 
 of the olfactory mucous membrane. 
 
 called its ' roots.' Of these the lateral is the most important, and it 
 terminates in the hippocampal and uncinate gyri of the same side. 
 Fibres of the olfactory tract arc also connected either directly or through 
 the relay of another neuron with the opposite side of the brain, especially 
 the opposite uncinate gyrus. The anterior commissure contains 
 numerous fibre*;, which connect the hippocampal regions of the two 
 sides. Other central comiections of the olfactory tract exist, but some 
 are imperfectly known. The name ' rhinencephalon ' is given to the 
 portions of the brain concerned with the sense of smell. Disturbances 
 of smell sensation may be caused by lesions in any part of the rhinen- 
 cephalon, and also by changes in the olfactory mucous membrane and 
 olfactory fibres; but the symptoms do not obtrude themselves, and are 
 doubtless often overlooked. Excessive stimulation of the olfactory 
 nerve by exposure to a strong odour has been said to cause complete 
 and permanent loss of smell. 
 
 The second or optic nerve (ontains mainly afferent fibres, which 
 arise from the ganglion cells of the retina, and teruiinatc by forming 
 synapses with nerve-cells in llic lateral or external grniculate body, the 
 
TUi: CRA>!IAL NERVES 
 
 92.^ 
 
 Corp. 
 
 pulvinar ^or posterior portion) of the optic thalamus, and tlie anterior 
 corpus quiuliigcminum. Jn young animals all these structures undergo 
 atrophy after extirpation of the eyeball. The visual path is continued 
 from the pulvinar and the external corpus geniculatum by the axons 
 of these nerve-cells, which proceed in the optic radiation (p. 883) to the 
 occipital cortex. The fibres which pass from the retina to the anterior 
 corpus quadrigeminum are distinguished by their small size, and 
 probably constitute the path of the impulses which cause contraction 
 of the piipil when light falls on the retina. The reflex arc is schematic- 
 ally shown in Fig. 370, where optic nerve-fibres are represented as 
 forming synapses with cells in the anterior corpus quadrigeminum 
 whose axons pass to the nucleus of the third nerve ami arbcrize around 
 
 some of its celts (Figs. 354, 3^6, 
 and 370). At the chiasma the 
 fibres of the optic nerve de- 
 cussate, partially in man and 
 some mammals, as the rabbit, 
 dog, cat, and monkey, com- 
 pletely in animals whose visual 
 field is entirely independent for 
 the two eyes, as in fishes and 
 birds. In man the fibres for 
 the nasal halves of both retinae 
 cross the middle line at the 
 chiasma, those for the temporal 
 halves do not. This does not 
 mean, however, that exactly 
 half of the optic nerve-fibres 
 decussate. The number of un- 
 crossed fibres is smaller than 
 that of crossed. The chiasma 
 also contains fibres in its pos- 
 terior portion, which extend 
 from one optic tract to the 
 other, but are not connected 
 with the retinae or the optic 
 nerves. They are commissural 
 fibres which connect the two 
 mesial geniculate bodies across 
 the middle line, and are called 
 Gudden's commissure. A suffi- 
 ciently extensive lesion involv- 
 ing the occipital cortex on one 
 side, or the posterior portion 
 of the optic thalamus, or the 
 optic tract, causes hemianopia* or defect of the visual field on the 
 side opposite to the lesion, with blindness of the corresponding halves 
 of the two retinae. Thus, a lesion equivalent to complete section of the 
 right optic tract would cause blindness of the nasal half of the left, and 
 of the temporal half of the right eye, and the left half of the field of 
 vision would be blotted out — the patient would be unable, with his eyes 
 directed forwards, to see an object at his left. Such a complete 
 hemianopia is much rarer in disease of the cortex than in disease of the 
 * The terms ' hemiopia,' ' hemianopia,' ' hemianopsia,' are used with refer- 
 ence sometimes to the blind side of the retinae, but ordinarily to the half of the 
 visual field which is deficient We shall always use the word ' hemianopia ' 
 in the latter sense. 
 
 Nerue 
 
 Fig 370. — Scheme of the Visual Path (after 
 Schafer). 
 
924 rW£ CENTRAL NERVOUS SYSTEM 
 
 optic tract. A lesion — e.g., a tumour of the pituitarv body —involving 
 the whole of the optic nerve in front of the chiasma, would cause com- 
 plete blindness in the corresponding eye. Sometimes in disease of the 
 optic nerve vision is not totally destroyed in the eye to which it belongs, 
 but the field is narrowed by a circumference of blindness. In this case 
 the pathological change involves the circumferential fibres of the nerve. 
 When the chiasma is affected by disease, a very frequent symptom is 
 bitemporal hemianopia. blindness of the nasal halves of the retinip. with 
 loss of the outer or temporal half of each field of vision. The optic nerve 
 and tract contain a few efferent fibres for the retina, whose cell-bodies 
 have not vet been ccrtainlv located. 
 
 The third nerve, or ocuio-motor, arises from an elongated nucleus, 
 or a scries of nuclei, containing large nerve-cells in the fioor of the 
 Sj'lvian aqueduct below the anterior corpora quadrigemina. The root- 
 bundles coming off from the most anterior of the nuclei carry fibres that 
 innervate the ciliary muscle, and thus have to do with the mechanism 
 of accommodation, and also fibres that innervate the sphincter muscle of 
 the iris, and thus cause contraction of the pupil when light falls on the 
 retina. Both groups of fibres terminate by arborescing around sympa- 
 thetic cells in the ciliary ganglion, from which the path to the (unstriated) 
 ciliary and sphincter muscles is continued by post-ganglionic fibres. 
 Farther back in the oculo-motor nucleus arise the motor fibres for four 
 of the extrinsic muscles of the eyeball and the elevator of the upper 
 eyelid. In the dog these fibres come off in the following order, from 
 before backwards; internal rectus, superior rectus, levator palpebra' 
 superioris, inferior rectus, inferior oblique. Most of the fibres of the 
 third nerve arise from nerve-cells on their own side of the middle line, 
 but a certain number decussate to enter the nerve of the opposite side. 
 
 Complete paralysis of the third nerve causes loss of the power of 
 accommodation of the corresponding eye, dilatation of the pupil by the 
 unopposed action of the sympathetic fibres, diminution of the power of 
 mov'ng the eyeball, ptosis, or drooping of the upper iid, external squint, 
 and consequent diplopia, or double vision. 
 
 The fourth or trochlear nerve arises from the posterior part of the 
 same tract of grey matter which gives origin to the third nerve. It 
 supplies the superior oblique muscle. Paralysis of the nerve causes 
 internal squint when an object below the horizontal plane is looked at, 
 owing to the unopposed action of the inferior rectus. There is also 
 diplopia on looking down. Unlike the other cranial nerves, the two 
 trochlear nerves decussate completely after they emerge from their 
 nuclei of origin. 
 
 The fifth or trigeminus nerve appears on the surface of the pons as a 
 large sensory root and a smaller motor root. Its deep origin is more 
 extensive than that of any of the other cerebral nerves, stretching a-s it 
 does from the level of the anterior corpus quadrigeminum above to the 
 upper part of the spinal cord below. Its scnsorv root, in fact, seems to 
 include the sensory divisions of several motor cranial nerves. 
 
 The motor root arises partly from a nucleus {principal motor nucleus) 
 in the floor of the fourth ventricle below the pons, partlv from large 
 round nerve-cells lying at the side of the grey matter bounding the 
 aqueduct of Sylvius all the way from the anterior quadrigcminate body 
 to the point at which the motor root is given off [accessory or superior 
 motor nucleus). 
 
 The fibres of the sensory root have their cells of origin in the Gasserian 
 ganglion, whence they pass into the pons. Here thev bifurcate into 
 ascending and descending branches. The ascending branches end in 
 the principal sensory micleus, a collection of grey matter at the side of 
 
THE CRANIA I. NEliVES 
 
 925 
 
 the principal motor nucleus. The descending branches, turning down- 
 wards into the mcthilla oblongat;i, terminate in a long tract of scattered 
 cells, constituting with the fibres the so-called spinal root, and extending 
 frorn the level of the second cervical nerve through the medulla oblon- 
 gata and the pons, where it is continued into the principal sensory nucleus. 
 The attcrent path is continued by the axons 
 of cells of the sensory nuclei (or nuclei of 
 reception) of the nerve, many of which cross 
 the middle line and enter the intermediate 
 fillet of the opposite side, and also the 
 special ascending bundle going to the thala- 
 mus. Some of the axons do not decussate, 
 but ascend in the fillet of the same side. 
 
 TV. »p. n. V. 
 
 371. — Scheme of Motor and Sensory Neurons of Trigeminus (Gehuchten). 
 G. s. G., Gasserian ganglion; Nu. m. m. n. V., nucleus of the descending root; 
 A^M. m. pr. n. V., chief motor nucleus of the fifth nerve; Rad. desc. mes. n. V.. 
 accessory motor nucleus, sometimes called the descending root; Tr. sp. n. V ., 
 tractus spinalis, or spinal root of the fifth. 
 
 The motor fibres of the fifth nerve supply the muscles of mastication 
 and the tensor tympani. The sensory fibres confer common sensation 
 on the face, conjunctiva, the mucous membranes of the mouth and nose, 
 and the structures contained in them, and, according to Gowers, special 
 sensation, through branches given off to the facial and glosso-pharyngeal 
 nerves, on the organs of taste.* Complete paralysis of the nerve causes 
 
 * It should be stated that some physiologists believe that the glosso-pharyu- 
 geal is the nerve of taste, and that none of the taste fibres go to the sensory 
 nuclei of the fifth nerve. The majority hold that the glosso-pharyngeal 
 supplies the posterior third, and the chorda tympani and lingual the anterior 
 two-thirds of the tongue with gustatory fibres. The removal of the Gasserian 
 ganglion and the adjacent portion of the fifth nerve for severe and persistent 
 neuralgia, has afforded opportunities to test this question. But, unfortunately 
 the results described by various observers do not agree, some finding that 
 taste is unimpaired, others that it is abolished. Gowers states that the gus- 
 taJ:ory sensations may persist for some time after the operation, although 
 ultimately (in two or three weeks) they disappear. It has been shown by 
 Harris that when alcohol is injected into the third division of the fifth nerve 
 at the foramen ovale or into the Gasserian ganglion, immediate loss of taste 
 develops in a very large proportion of cases in the anterior half of the tongue 
 on that side. Taste fibres are therefore certainly present in the fifth nerve 
 at this level. 
 
926 THE CENTRAL NERVOUS SYSTEM 
 
 loss of movement in the muscles of mastication, sometimes impaired 
 hearing, and loss of common sensation in the area supplied by it. Lose 
 or impairment of taste in the corresponding half of the tongue is also 
 often seen in disease involving the sensory root, althf)ugh not in 
 affections of the trunk of the nerve, since the taste fibres leave it near 
 its origin (Cowers). Both taste and touch are lost in the monkey in the 
 anterior two-thirds of the tongue after intracranial section of the 
 trigeminus (Sherrington). 
 
 Vaso-motor changes are occasionally, and ' trophic ' changes fre- 
 cjuently, observed in disease of the fifth nerve. The trophic disturbance 
 is most conspicuous in the eyeball (ulceration of the cornea, going on, 
 it may be, to complete disorganization of the eye). These effects are 
 partly due to the loss of sensation in the eye, with the consequent risk of 
 damage from without, and the unregarded presence of foreign bodies 
 and accumulation of secretion within the lids (p. 805). 
 
 The sixth or abducens nerve takes origin from a nucleus in the floor 
 of the fourth ventricle at the level of the posterior portion of the pons. 
 It supplies the external rectus muscle of the eyeball. Paralysis of it 
 causes internal squint. It is generally described as a purely motor 
 nerve, but this is incorrect. It has been shown that the sixth, as we'll 
 as the third and fourth, cranial nerves contain a considerable number 
 of afferent fibres, whose receptive nerve-endings are situated in the 
 recti and ublicjui muscles and their tendons. 
 
 Xhe motor fibres of the seventh or facial nerve arise from a nucleus 
 in the reticular formation of the medulla oblongata, and running up 
 some distance into the pons. They supply the muscles of the face ; and 
 when these are greatly developed, as in the trunk of the elephant, the 
 nerve reaches very large proportions. Since the fibres which connect 
 the cerebral cortex with the nucleus decussate about the middle of the 
 pons, a lesion above this level which causes hemiplegia paralyzes the 
 face on the same side as the rest of the body — i.e., on the side opposite 
 the lesion. But the paralysis is confined to the muscles of the lower 
 portion of the face, and affects especially the muscles about the mouth. 
 Sometimes the pyramidal tract and the facial nerve, or nucleus, are 
 involved in a common lesion. In this case paralysis of the face is on 
 the side of the lesion, and is total, while the rest of the body is para- 
 lyzed on the opposite side. Paralysis of the seventh nerve is more 
 common than that of any other nerve in the body. It is often caused 
 by an inflammator}- process in the nerve itself (neuritis). The symp- 
 toms of complete facial palsy are very characteristic. The face and 
 forehead on the paralyzed side are smooth, motionless, and devoid of 
 expression. The eve remains open even in sleep, owing to paralysis 
 of the orbicularis palpebrarum. A smile becomes a grimace. An 
 attempt to wink with both eyes results in a grotesque contortion. The 
 mouth appears like a diagonal slit in the face, its angle being drawn 
 up on the sound side, and the patient cannot bring the lips sufficiently 
 close together to be able to blow out a candle or to whistle. Liquids 
 escape from the mouth, and food collects between the paralyzed buc- 
 cinator and the teeth. The labial consonants are not properly pro- 
 nounced. Taste may be lost in the anterior two-thirds of the tongue 
 when the nerve is injured above the exit of the gustatory fibres in the 
 chorda tympani, but not when the lesion is in the nucleus of origin, or 
 anywhere above it. Hearing is sometimes impaired because the 
 auditory and facial nerves, lying close together for part of their course, 
 are apt to suffer together, but perhaps also because the stapedius 
 muscle is supplied by the seventh. 
 
THE CRAKJAL NERVES 
 
 927 
 
 The seventh nerve is not purely motor. From the cells of a ganglion 
 on it corresponding to a spinal ganglion (the geniculate ganglion) 
 afferent fibres arise, which pass in the pays intermedia or nerve of 
 VVrisberg into the pons between the seventh and eighth nerves, and 
 there bifurcate into nscending and descending branches, like other 
 afferent fibres originating in ganglia of the spinal type. The descend- 
 ing brandies enter the fasciculus solitarius, and end by arborizing 
 around nerve-cells in the upper part of that bundle. The peripheral 
 axons of the nerve-cells in the geniculate ganglion enter the large super- 
 ficial petrosal nerve and the chorda tympani, in which they, or some 
 of them, perhaps represent taste fibres. 
 
 The eighth or auditory nerve enters the medulla oblongata by two 
 roots (a dorsal and a ventral), one of which passes in on each side of 
 
 vin 
 
 Fig- 372-— Scheme of Path of Auditory Impulses (.Lewandowsky). Sp, ganglion 
 spirale; G, accessory nucleus; T, acoustic tubercle; Tr, trapezium; H, Heid's 
 fibres; St, striae acustics; tr, trapezoid nucleus; Os, upper olive; LI, lateral fillet, 
 with its nucleus, nL; P, commissure of the lateral fillets; Qp, posterior corpora 
 quadrigemina, with Cq, their commissure, and Bq, the brachia; Gm, mesial or 
 internal geniculate body; R, cerebral cortex. 
 
 the restiform body. The cells of origin, both of the dorsal and of the 
 ventral root, are situated in the internal ear, the former in the ganglion 
 spirale, or ganglion of Ccrti, which is embedded in the bony spiral of 
 the cochlea, the latter in the ganglion vestibulare, or ganglion"of Scarpa, 
 which lies in the vestibule. These cells correspond to the ganglion 
 cells on the posterior root of a spinal nerve, but, unlike them, they 
 remain, even in mammals, bipolar throughout life. Their centra'l 
 processes form the axons of the eighth nerve. Their peripheral pro- 
 cesses are distributed in the case of the dorsal root to the organ of 
 Corti, in the case of the ventral root to the semicircular canals and the 
 vestibule. For this reason the dorsal root is often called the cochlear 
 division, and the ventral root the vestibular division of the auditorv 
 
928 THE CENTRAL NEKVOVS SYSTEM 
 
 nerve. Ana the cochlear and vestibular roots arc pliysiologically 
 as well as anatomically distinct. For the cochlea subserves the 
 function of hearing, tlie semicircular canals and vestibule the function 
 of equilibration. As they enter the medulla oblongata, the fibres of 
 the dorsal root bifurcate. Of the two branches, one is considerably 
 thicker than the other. Many of the thicker brandies terminate by 
 arborizing around the cells of the accessory auditory nucleus, whose 
 position is indicated by a swelling on the ventral surface of the resti- 
 form body at the junction of the dorsal and ventral roots; but some 
 pass over the restiform body to end in another nucleus (lateral nucleus), 
 also indicated by a swelling (tuberculum acusticum) lying over the 
 restiform bod}'. The nerve-cells of the acces-sory nucleus and the 
 acoustic tubercle, therefore, constitute nuclei of reception for the 
 dorsal root-fibres. The more slender branches of the coclilear root- 
 fibres run downwards for some distance before breaking up into fibrils. 
 
 The path to the higher parts of the brain is continued by the axons 
 of nerve-cells in the accessory nucleus and the acoustic tubercle. The 
 fibres from the accessory nucleus pass into the trapezium, a mass of 
 transverse fibres lying in the pons behind the pyramidal fibres. In 
 their course through the trapezium some of the fibres terminate around 
 the cells of the nucleus of the trapezium, others run into the superior 
 olive of the same side, and end there ; but most of them cross the middle 
 line, and enter the trapezoid nucleus and superior olive of the opposite 
 side, where many of them terminate. Others, however, run through 
 those nuclei and pass into the lateral fillet, to end in its nucleus or in 
 the posterior corpora quadrigemina. The path of the fibres which 
 terminate in the nuclei of the trapezium, superior olive, and lateral 
 fillet, is continued by another relay of fibres, which link them also to 
 the posterior corpora quadrigemina. The axons of the cells of the 
 acoustic tubercle enter for the most part the sirics acusticcB, a series of 
 prominent strands that run transversely across the floor of the fourth 
 ventricle. Passing across the raphe, they join the fibres from the 
 accessory nucleus on their way to the superior olive, and accompany 
 them into the lateral fillet, which terminates in the grey matter of the 
 posterior corpus quadrigeminum. We must assume, from clinical and 
 experimental data, that the dorsal root is ultimately connected with 
 the first or first and second temporo-sphenoidal convolutions on the 
 opposite side. From the posterior corpora quadrigemina the auditory 
 path to the convolutions seems to run in the brachium to the internal 
 or mesial geniculate body, whence it is continued in the posterior 
 extremity of the internal capsule. 
 
 The fibres of the ventral root of the eighth nerve, better termed the 
 vestibular nerve, after entering the medulla oblongata, pass to a 
 nucleus called the principal nucleus of the vestibular division. Here 
 each bifurcates into a descending and an ascending branch. The 
 descending branches running down in tlie medulla terminate at dif- 
 ferent levels around cells in the principal nucleus, and the grey matter 
 continued down from it {descending vestibular nucleus). The ascending 
 branches run up on the inner side of the restiform body towards the 
 nucleus of the roof [nucleus tecti) in the cerebellar worm. On their 
 course they enter into relation through their collaterals with the nuclei 
 of Deiters and Bechterew. The nucleus of Deiters, as already stated, 
 sends fibres into the posterior longitudinal bundle. Through ascend- 
 ing branches of these fibres a communication is established with the 
 nuclei of the third and sixth nerves, and through descending branches 
 that pass into the antero-lateral descending tract of the cord with the 
 anterior horn cells. It is obvious that through these connections 
 
THE CRANIAL NERVES 929 
 
 which link the vestibule with the cerebellum, the nuclei of the motor 
 nerves of the eyeball and the motor cells of thj cord, the nucleus of 
 Deiters has an important relation to the co-ordination of those move- 
 ments mainly concerned in equilibration. Nothing is known of the 
 connections of the vestibular nerve with the cerebrum. Two promi- 
 nent symptoms may be associated with disease of the auditory nerve — 
 {a) disturbance or loss of hearing; {b) loss or impaii-ment of equilibration. 
 
 The ninth or glosso-pharyngeal nerve comprises both sensory and 
 motor libres — sensory for the posterior third of the tongue and the 
 mucous membrane of the back of the mouth, motor for the middle 
 constrictor of the pharynx and the stylo-pharyngeus. It also conta,ins 
 the nerves of taste for the posterior third of tiic tongue. The efferent 
 libres arise from a nucleus {moior nucleus of the glosso-pharyngeal) a 
 little posterior to the facial nucleus. The afferent fibres take origin 
 from unipolar cells in ganglia of spinal type connected with the nerve 
 (ganglion petrosum and ganglion superius). Entering the medulla, 
 oblongata, the central processes of these cells bifurcate into ascending 
 and descending branches. Their peripheral processes pursue their 
 course as the axons of sensory fibres to the structures to which the 
 nerve is distributed. The ascending branches terminate in a nucleus 
 {prmcipal nucleus of the glosso-pharyngeal) beneath the floor of the 
 fourth ventricle. The descending branches, as well as similar branches 
 from the pars intermedia of the seventh nerve and from the afferent 
 fibres of the vagus, form a bundle called the fasciculus solitarius (some- 
 times termed the descending root of the facial, vagus, and glosso-pharyn- 
 geal). It can be traced to the lower boundary of the spinal bulb. 
 Along the mesial border of the fasciculus solitarius are strung out the 
 somewhat scattered nerve-cells [descending nucleus of facial, vagus, ami 
 glosso-pharyngeal), around which the descending branches arborize. 
 At its upper end the grey matter of the fasciculus solitarius is con- 
 tinuous with the principal nuclei of the glosso-pharyngeal and vagus. 
 
 The tenth nerve, or vagus, also contains both motor and sensory 
 fibres. The efferent fibres arise partly from the nucleus ambiguus or 
 ventral nucleus of the vagus, a collection of large nerve-cells situated in 
 the reticular formation, and extending from a point a little below the 
 facial nucleus to a point a little above the lower limit of the medulla 
 oblongata, where it becomes continuous with the column of cells from 
 which the spinal fibres of the eleventh nerve take origin. A second 
 nucleus of origin for efferent vagus fibres is constituted by the upper 
 part of the dorsal accessory-vagus nucleus, a collection of rather small 
 cells extending from a little below the lower margin of the pons to 
 nearly the level of the first cervical nerve. 
 
 The affei-ent fibres of the vagus arise from unipolar cells in ganglia 
 connected with the nerve (ganglion jugulare, ganglion nodosum). In 
 tile medulla oblongata they bifurcate, like other fibres coming off from 
 the cells of ganglia of spinal type. The ascending branches, which are 
 short, terminate in the upper sensory or principal nucleus, and the 
 descending branches, which are long, in the cells of the fasciculus soli- 
 tarius, just as in the case of the glosso-pharyngeus. 
 
 The motor fibres of the vagus are partly derived from the accessory, 
 whose internal branch joins the vagus not far from its origin. The 
 distribution of the nerve is more extensive than that of any other in 
 the body. The oesophagus receives both motor and sensory branches 
 from the oesophageal plexus. I'he pharyngeal branch of the vagus is 
 the chief motor nerve of the pharynx and soft palate (including the 
 tensor palati). The superior laryngeal branch is the nerve of common 
 sensation for the larynx abo\e the vocal cords, and the motor nerve 
 
 59 
 
930 THE CENTRAL NERVOUS SYSTEM 
 
 of the crico-thyroid muscle. The inferior or recurrent laryngeal sup- 
 plies the rest of the laryngeal muscles, and tlie sensory fibres for the 
 mucous membrane of the trachea and the larynx below the glottis. 
 The superior laryngeal contains afferent fibres, stimulation of which 
 gives rise to coughing, slows respiration, or stops it in expiration. 
 Reflex movements of deglutition are also caused. The vagus supplies 
 the lungs both with motor and sensory filaments through the pulmonary 
 plexus. The motor fibres when stimulated cause constriction of the 
 bronchi; excitation of the afferent fibres causes reflex changes in the 
 rate or depth of respiration. The cardiac branches contain inhibitory 
 fibres probably derived from the spinal accessory, and depressor fibres 
 which pass up in the vagus trunk (dog), or as a separate nerve to join 
 the vagus or its superior laryngeal branch or both (rabbit). The gastric 
 and intestinal branches contain both motor and sensory nerves for the 
 stomach and intestines. The sensory are probably large medullated 
 fibres (7 /* to 9 m). The afferent vagus fibres from the stomach carry 
 up impulses v/hich excite the action of vomiting. Lesions of the vagus, 
 its nuclei of origin, or its branches, are associated with many interest- 
 ing forms of paralysis and other symptoms. Paralysis of the pharynx 
 is generally caused by disease of the nucleus in tlie medulla. From its 
 anatomical relation to the nuclei of the glosso-pharj'-ngeal and hypo- 
 glossal, it will be easily understood that these nerves are often involved 
 in localized central lesions along with the vagus. But the fact that in 
 progressive bulbar palsy (glosso-labio-laryngeal paralysis) — a condition 
 characterized by progressive paralysis and atrophy of the muscles of 
 the tongue, lips, larynx, and pharynx — the orbicularis oris and other 
 muscles of the mouth and chin are paralyzed, while the rest of the 
 muscles supplied by the facial remain intact, might seem to indicate 
 that in system diseases it is not so much anatomical groups of nerve- 
 cells which are liable to simultaneous degeneration and failure, as 
 physiological groups normally associated in particular functions. Such 
 functional groups of cells, occupied with the same kinds of labour at 
 the same times and under the same conditions, might be supposed to 
 take on a similar bias or tendency to degeneration — a tendency not 
 indicated, it may be, by any structural peculiarity, but traced deep in 
 the molecular activity of the cells. There is no foundation for the 
 view that the lips are involved in progressive bulbar palsy because the 
 fibres of the facial which supply them arise from the hypoglossal 
 nucleus, any more than for the idea that the upper part of the face 
 escapes becau.se its motor fibres, wliile reaching it in the seventh nerve, 
 really arise from the oculo-motor nucleus (Bruce). Difficulty in swal- 
 lowing is the chief symptom of pharyngeal paralysis. The sjanptoms 
 of laryngeal paralysis have been already described under ' Voice ' 
 (p. 316). Tachycardia, or a permanent increase in the rate of the 
 heart, has been stated to occur in certain cases of paralysis of the 
 vagus, caused by disease or accidental interference; and a persistent 
 slowing of the respiration has been occasionally attributed to the same 
 cause. But it is difficult to reconcile many of these cases with experi- 
 mental results, for in most of them the lesion only involved one vagus; 
 and in animals section of one vagus has no permanent effect on the 
 rate of the heart or of the respiratory movements. 
 
 Destruction of the nerve near its origin has been sometimes found 
 associated with disappearance of the food-appetites, hunger and thirst, 
 and it has been assumed that this was due to loss of afferent impulses 
 from the stomach. But clinical testimony is by no means unanimous 
 on this puint, and experiments on animals show that other factors are 
 involved in these sensations (see Chapter XVIII.). 
 
FUNCTIONS OF THE BRAIN 931 
 
 The eleventh or spinal-accessory nerve contains only efferent fibres. 
 The cells of origin of its spinal portion lie in the lateral horn of the 
 cord, from about the level of the first to the fifth or sixtJx cervical 
 nerves. The bulbar portion, sometimes called the bulbar accessory, 
 arises from the lower two-thirds of the dorsal accessory-vagus nucleus, 
 from about the level of the first cervical nerve up to the level of the 
 tip of the calamus scriptorius. The accessory portion of the nucleus 
 lies behind and to the side of — i.e., dorso-lateral to — the central canal; 
 the upper or vagus portion is more laterally placed in the floor of the 
 fourth ventricle. Soon after the junction of its bulbar and spinal 
 portions, the nerve divides into two branches, an internal and an 
 external. The external branch, containing the spinal fibres, passes out 
 to supply the trapezius and sterno-mastoid muscles with motor fibres. 
 The internal branch, containing the bulbar fibres, passes bodily into 
 the vagus. 
 
 The twelfth or hypoglossal nerve is exclusively an efferent nerve. 
 Its nucleus of origin is an elongated collection of large nerve-cells ex- 
 tending throughout approximately the lower two-thirds of the bulb 
 close to the median line and parallel to it. It contains the motor 
 supply of the intrinsic and extrinsic muscles of the tongue and of the 
 thyro- and genio-hyoid. Paralysis of it causes deficient movement of 
 the corresponding half of the tongue. When the tongue is put out, it 
 deviates towards the paralyzed side, being pushed over by the un- 
 paralyzed genio-hycglossus of the opposite side, which is thrown into 
 action in protruding the tongue. 
 
 Section X. — Functions of the Central Nervous System — 
 
 (2) The Brain. 
 
 The paths by which the various parts of the central nervous 
 system are connected with each other and with the periphery have 
 been already described, and we have completed the examination of 
 the functions of the spinal cord and medulla oblongata. The 
 events that take place in the upper part of the central nervous 
 stem and in the cortex of the cerebellum and cerebrum now claim 
 our attention. 
 
 From very early times the brain has been popularly believed to be 
 the seat of all that we mean by consciousness — sensation, ideation, 
 emotion, volition. And he who loves to trace the roots of things back 
 into the past may see, if he choose, running through the whole texture 
 of the older speculations a belief that the brain does not act as a whole, 
 but is divided into mechanisms, each with its special work — a fore- 
 shadowing, often in grotesque outlines, of the doctrine of localization 
 so widely held to-day. But until comparatively recent times, cerebral 
 physiology remained a kind of scientific terra incognita ; and no notable 
 additions were made for a thousand years to the doctrines of Galen. 
 Even to-day the utmost limit of our knowledge is reached when in 
 certain cases we have connected a particular movement or sensation 
 with a more or less sharply-defined anatomical area. How the cere- 
 bral processes that lead to sensations and movements, to emotions and 
 intellectual acts, arise and die out; what molecular changes are asso- 
 ciated with them; above all, how the molecular changes are translated 
 into consciousness — how, for example, it is that a series of nerve- 
 impulses from the optic radiation flickering across the labyrinth of the 
 
932 THE CENTRAL NERVOUS SYSTEM 
 
 occipital cortex sliould light up there a visual sensation — these are 
 questions tc wliich we can as yet give no answer, and the answers to 
 some of which must for ever remain hidden from us. 
 
 Functions of the Upper Part of the Central Stem and Basal Ganglia. 
 
 — Tlie function of tlie pons is .sufficiently indicated by its name. The 
 grey matter so plentifully scattered, especially in its ventral portion, 
 may exercise a not unimportant influence on the impulses that traverse 
 it. But on the whole its main office is to provide a bridge along which 
 impulses may travel between other portions of the nervous system. 
 We have already seen that many of its transverse fibres arising from 
 the cells of the pontine grey matter, and then crossing the middle line 
 to the opposite middle peduncle, arc the cerebellar segments of com- 
 missural arcs connecting the cerebral with the opposite cerebellar 
 hemispheres. The cerebral segments of these arcs are the cortico- 
 pontine fibres originating in the prefrontal, temporal, and occipital 
 portions of the cerebral cortex, and passing through the corona radiata, 
 internal capsule, and crura cerebri, to end in the nuclei-pontis. Many 
 fibres and collaterals of the pyramidal tract also terminate here. On 
 the dorsal aspect of the pons in the floor of the fourth ventricle are the 
 nuclei of origin (or reception) of the fifth, sixth, and seventh cranial 
 nerves. Various reflex centres are situated in this region — e.g., that 
 for the closure of the eyelids, when the conjunctiva is stimulated. 
 
 The posterior corpora qiiadrigemina and internal geniculate bodies are 
 connected with the cochlear division of the auditory nerves, and form 
 important stations on the auditory path to the cortex. 
 
 The anterior corpora quudrigemina and the lateral corpora geniculata 
 are connected with the optic tracts. Their development is arrested 
 after extirpation of the eyeball in young animals, and they may there- 
 fore be assumed to be concerned in vision, although the size of their 
 homologues, the optic lobes or corpora bigemina, in animals below the 
 rank of mammals (birds, reptiles, amphibians), does not seem to be 
 related to the development of the organs of sight. Proteus and the 
 Hag-fish, e.g., have large optic lobes, rudimentary eyes and optic tracts. 
 The optic nerve, the anterior corpus quadrigeminum, the nucleus of the 
 oculo-motor nerve in the wall of the Sjdvian aqueduct, and' the fibres 
 which it carries to the iris, form a reflex arc for the contraction of the 
 pupil to light, as represented in Fig. 370, p. 923. 
 
 The functions of the optic thalami have not been fully defined either 
 by experiment or pathological observation, except in so far as they can 
 be deduced from their connections. Lying as they do in the isthmus 
 of the brain, begirt by the great motor and sensory paths, it is to be 
 expected that lesions of the thalami should affect also the internal 
 capsule, and give rise to the symptoms of motor and sensory paralysis. 
 But it is questionable^ whether any definite defect of motor power or 
 common sensation has ever been unequivocally associated with a lesion 
 restricted to the thalami. The most constant features of the so-called 
 thalamic syndrome (or symptom-complex) are partial loss of sensibility, 
 especially to tactile impressions, and of the muscular sense on the 
 opposite side, with some degree of inco-ordination and disorder, though 
 little, if any, actual paralysis of voluntary movements. These phe- 
 nomena are accounted for by the extensive connections of the thalami. 
 Each of the thalamic nuclei is linked with a definite cortical region in 
 such a way that destruction of the cortical area in young animals or 
 human beings leads to degeneration of the corresponding nucleus. 
 Some of the fibres connecting the cortex (and the corpus striatum) 
 with the thalamus end in the thalamic grey matter, and are therefore 
 efiferent with respect to the cortex (corticofugal). It is, however, the 
 
FUNCTIONS OF THE BRAIN 933 
 
 afferent paths to the cortex with which the thalami are specially related 
 as centres of relay. The fibres of the upper fillet carrying afferent im- 
 pulses up from the opposite posterior column of the cord to the cere- 
 brum end in the grey matter of the thalamus, as docs the central path 
 of the afferent fibres of the opposite fifth nerve. The posterior portion 
 of the thalamus, or pulvinar, forms part of the central visual apparatus; 
 for (rt) it is found to be undeveloped in animals from which the eyeballs 
 have been removed soon after birth ; (b) a portion of the optic tract is 
 certainly connected with it; (c) in some cases of atrophy of the occipital 
 cortex, which, as we shall see, is undoubtedly a central area for visual 
 sensations, atrophy of the pulvinar has also been noticed; {d) a lesion 
 of the pulvinar may give rise to hemianopia (p. 923). 
 
 Haemorrhage into the caudate cr lenticular nucleus of the corpus 
 striatum often causes hemiplegia, but this is frequently due to implica- 
 tion of the internal capsule. It is said, however, that lesions presumably 
 confined to the lenticular nucleus cause paralj'^sis or paresis of the limbs 
 or face, which is less severe than that produced by lesions in the internal 
 capsule. Experimental lesions in dogs and rabbits are stated to be 
 followed by disturbances of the heat-regulating mechanism and rise of 
 temperature. 
 
 Certain structures belonging to the primary fore-brain which have 
 now lost some or all of their functional importance may nevertheless be 
 mentioned as milestones in the march of development. The pineal 
 body is made up of the vestiges of the unpaired mesial eye of such 
 animals as the ancient labyrinthodonts, which resembled the eye of 
 invertebrates in having the retinal rods directed towards the cavity 
 instead of towards the circumference of the eyeball. In many living 
 forms, especially in certain lizards, this pineal or parietal eye is found 
 in a more perfect condition, though covered by a thin membrane. The 
 ganglia habennlcB, two small collections of nerve-cells, one of which is 
 situated at the posterior part of each thalamus, are supposed by some 
 authorities to represent the optic ganglia of this cyclopean eye. They 
 are less prominent in man than in many of the lower animals. The 
 infu-ndibidum is probably what remains cf the gullet of the ancestors 
 of the vertebrates. The pituitary body is in a different category. It 
 is now known that, far from being a useless vestigial remnant, it has a 
 highly important function (p. 667). It consists of two portions, the 
 anterior lobe, or hypophysis, derived from the buccal cavity, the pos- 
 terior lobe, or infundibular body, from the primary fore-brain. 
 
 Functions of the Cerebellum. — The elaborate pattern of the arbor 
 vitae, the appearance given by the branched laminae in a section 
 of the cerebellum, excited the speculation of the old anatomists. 
 A structure so mar\'ellous must be matched, they thought, with 
 functions as unique. At a time when the discoveries of Galvani 
 and Volta were fresh, and the world ran mad on electricity, the 
 hypothesis of Rolando, that ' nerve-force ' was generated by the 
 lamellae of the cerebellum as electrical energy is generated by the 
 plates of the voltaic pile, ridiculous as it now appears, was not 
 unnatural. The speculation of Gall, who connected the cerebellum 
 with the development of sexual emotions and the action of the 
 generative mechanisms, was based on no fact. It has been definitely 
 disproved by the observations of Luciani, who found that a bitch 
 deprived of its cerebellum showed all the phenomena of heat or 
 
934 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 ' nit,' was impregnated, whelped at full term in an entirely normal 
 manner, and manifested the maternal instincts in their full intensity. 
 Flourens put foru'ardthe doctrine that the cerebellum is an organ 
 concerned in the co-ordination of movements, and especially the 
 maintenance of equilibrium, supporting his conclusions by an 
 elaborate series of experiments. Notwithstanding the very large 
 amount of experimental and clinical study which has been devoted 
 to the cerebellum since the time of Flourens, our actual knowledge 
 
 Fig. 373- — Cerebellar Cortex: Section in Direc- 
 tion ol Lamina (Cajal). a, Purkinje's cell; 
 b, granule cell in inner layer; c, dendrite of 
 a granule cell; d, axon of a granule passing 
 into the molecular layer, where it bifur- 
 cates into two fine longitudinal branches 
 (Golgi's method). 
 
 I'ig- 374 — Cerel^ellar Cortex : 
 Section across a Lamina 
 (Cajal). a, Purkinje's cell; 
 the numerous dots in the 
 molecular layer represent 
 cross-sections of the bifur- 
 cated axons of the granule 
 cells (Golgi's method). 
 
 of its functions had not until recently greatly advanced beyond the 
 point then reached. Some of the more modern authorities restrict 
 its influence entirely to the actions on which equilibration depends ; 
 others extend it to all volitional movements. Luciani looks upon 
 it as ' an organ which by processes that do not awaken conscious- 
 ness exerts a continual strengthening (reinforcing) action upon the 
 activity of all other nerve-centres.' Sherrington conceives of the 
 cerebellum as the head ganglion of the proprio-ceptive system — 
 i.e., of the system of neurons whose receptors he not on the surface. 
 
r UNCTIONS Ol- Tin: BRAIN 935 
 
 bill in the ckcpcr parts of the body (labyrinth of car, muscles, 
 tendons, joints, viscera, etc.) (p. 914)- After removal of the whole 
 cerebellum (in the dog or monkey), there is at first rigidity and tonic 
 spasm of cerl;).in muscles, which contribute to the difficulty of co- 
 ordinating their movements. When this stage has passed, the 
 muscles all over the body, but especially those of the loins and hind- 
 limbs, and those which fix the head, are weaker than normal (as- 
 thenia), are deficient in tone (atonia), and contract with a peculiar 
 want of steadiness (Luciani). When one lateral half of the cere- 
 bellum is removed, the symptoms affect especially the muscles on 
 the same side. In extensive lesions of the cerebellum in man what 
 has been noticed is a marked in;d)ility to maintain the upright 
 posture, giddiness, a staggering gait, twitching movements of the 
 eyes (nystagmus), tremor accompanying voluntary movements — 
 in a word, a general breakdown of the co-ordinating machinery 
 (asynergy or asynergia), and especially of the part of it concerned 
 in the movements necessary for locomotion, and for the maintenance 
 of the equilibrium of the body— the so-called cerebellar ataxia. 
 There is no sensory paralysis and none of voluntary movement 
 such as lesions of the cerebral cortex produce, nor is there any 
 psychical disturbance. In cases of congenital defect of the cere- 
 bellum, the power of walking, and even of standing, may be late in 
 being acquired, and imperfect. But it is remarkable what great 
 deficiencies in the cerebellar substance are often compensated for 
 when established early in life, so that even cases of marked atrophy 
 or lack of development have sometimes been recognized for the 
 first time at the necropsy. 
 
 The connections of the cerebellum with other parts of the central 
 nervous system and with the periphery corroborate the direct 
 results of experiment. For, in addition to the visual impressions, 
 the most important afferent impulses concerned in equilibration are 
 those from the semicircular canals and vestibule of the internal ear, 
 the muscles, tendons, joints, etc., and certain portions of the skin, 
 such as that of the soles of the feet. And the cerebellum, as we have 
 seen (p. 885), is linked with all of these, and has besides an extensive 
 crossed connection through the middle and superior peduncles with 
 the opposite cerebral hemisphere. The importance and extent of 
 this crossed connection with the great brain is illustrated by the facts 
 that in disease atrophy or deficient development of one cerebellar 
 hemisphere is associated with a similar condition of the opposite 
 cerebral hemisphere, and that a lesion in one-half of the cerebellum 
 affects chiefly the co-ordination of the movements of the same side 
 of the body— that is to say, of the side connected with the opposite 
 cerebral hemisphere. 
 
 We do not as yet know the full significance of this extraordinarily 
 free communication of the grey matter of the cerebellum with every 
 part of the central nervous svstem. But it is evident that by the broad 
 
936 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 highway of the rcstiform body, or the cross-country routes from cere- 
 bral cortex to cerebellum, impulses may reach it from every quarter; 
 while impulses passing out from it along its peduncles may influence 
 the motor discharge either indirectly through the Rolandic cortex and 
 the pyramidal tract, or more directly through the antero-lateral de- 
 scending spinal path that brings it into relation with the nuclei of 
 origin of the motor nerves. It is an organ so connected that is suited 
 to take cognizance of the multitudes of afferent impressions concerned 
 in the co-ordination of movements and the maintenance of equilibrium, 
 and to regulate the outflow of efferent impulses in correspondence with 
 the inflow of aitcrcnt. 
 
 Sherrington points out that all the modern theories of cerebellar 
 function harmonize with his conception of the cerebellum as the head 
 ganglion of the proprio-ceptive system (p. 934). The most influential 
 of the proprJo-ceptivc organs being the labynnth, the central organ of 
 the whole proprio-ceptive mechanism is built up over the central con- 
 nections of the labyrinth. Thither converge connecting (internuncial) 
 paths from the central endings of proprio-ceptive neurons in all seg- 
 ments of the body (from joints, muscles, tendons, ligaments, viscera, 
 etc.). Thus a central organ is developed, which varies in size and 
 complexity in 
 different kinds of 
 animals accord- 
 ing to the com- 
 plexity of their 
 habitual move- 
 ments. 
 
 Fig- 375- — The Semicircular Ca-ials (Diagrammatic) (after 
 Ewald). H, horizontal or external; S, superior; P, pos- 
 terior. The two horizontal canals lie in the same plane. 
 The plane of the superior vertical canal of one side is 
 parallel to the plane of the posterior vertical canal of the 
 opposite side. 
 
 Afferent Im- 
 pulses concerned 
 in Equilibration 
 and Orientation. 
 — This is a con- 
 venient place to 
 consider a little 
 more in detail 
 the nature and 
 
 peripheral sources of some of the most important afferent impressions 
 concerned in equilibration and orientation. 
 
 (i) Afferent Impulses from the Semicircular Canals. — The semi- 
 circular canals are three in number, and lie nearly in three mutually 
 rectangular planes: the external canal in the horizontal plane, the 
 superior canal in a vertical longitudinal plane, and the posterior canal 
 in a vertical transverse plane. Each canal bulges out at one end into 
 a swelling, or am])ulla, which opens into the utricular division of the 
 vestibule (Figs, 375, 455). The other extremities of the superior and 
 posterior canals join together, and have a common aperture into the 
 utricle, but the undilatcd end of the external or horizontal canal opens 
 separately. The utricle and the semicircular canals are thus connected 
 by five distinct orifices. The greater part of the internal surface of 
 the membranous canals, utricle and saccule, is lined by a single layer 
 of flattened epithelium. But at or.e part of each ampulla projects a 
 transverse ridge, the crista acustica, covered not with squamous, but 
 with long columnar epithelium. Hair-like processes (auditory hairs) 
 
FUNCTIONS OF THE BRAIN 
 
 937 
 
 arc borne by some of the columnar cells, between which lie more 
 elongated fibrc-likc supporting cells. The hairs project into a mucus- 
 like mass, sometimes containing otoconia, or crystals of calcium car- 
 bonate. The ampullae, like the rest of the membranous labyrinth, is 
 filled with a watery fluid called endolymph. The utricle and saccule 
 have each a somewhat similar but broader elevation, the macula 
 acustica, covered with epithelium and hair-cells of the same character, 
 and the hairs project into a similar mass in which otoconia are con- 
 stantly present. In some animals, as fishes, the calcareous matter in 
 the utricle and saccule forms masses of considerable size {otoliths). 
 Fibres of the auditory nerve end in arborizations around the bodies 
 of the hair-cells of the macular and cristse acusticse. We have already 
 seen that it is the ventral or vestibular division of the nerve which is 
 especially related to the vestibule (p. 927). 
 
 There is very strong evidLUce that the semicircular canals are con- 
 cerned, not in hearing, but in equilibration. A pigeon from which 
 the membranous canals have been removed still hears perfectly 
 well so long as the cochlea is intact, but exhibits the most profound 
 disturbance of equilibrium. If 
 the horizontal canal is destroyed 
 or divided, the pigeon moves its 
 head continually from side to side 
 around a vertical axis ; if the 
 superior canal is divided, the 
 head moves up and down around 
 a horizontal axis. The power of 
 co-ordination of movements is 
 diminished, but not to the same 
 extent in all kinds of animals. 
 Thrown into the air, the pigeon is 
 helpless ; it cannot fly ; but a goose 
 with divided semicircular canals 
 can still swim. The condition is 
 only temporary, even when the 
 injury involves the three canals 
 on one side ; but if the canals on 
 both sides are destroyed, recovery Fig. 376. —Dog Twenty -two Months 
 is tardy, and often incomplete. p^^-r't,"' "**' ''''""'"' 
 In mammals the loss of co-ordina- 
 tion is less than in birds, although at first the animal is unable to 
 walk propcrlv, easily falls over to the injured side, and goes con- 
 tinually in a circle turning towards the side of the lesion. Move- 
 ments of the eyes, the direction of which depends on the canal 
 destroyed, take to a large extent the place of movements of 
 the head. Torsion of the head towards the side of the injury is, 
 however, pronounced and permanent (\Mlson and Pike^ (Fig. 376). 
 Speaking generally, the eyes are deviated to the side of the lesion, 
 and exhibit the phenomenon of nystagmus. 
 
938 THE CENTRAL NERVOUS SYSTEM 
 
 I'his is composed of two phases, a slow movement towar.ls the injured 
 side and a quick jerk back towards the uninjured side. The nystag- 
 mus is synchronous in both eyes, and is constantly present for some 
 clays after the operation. There is reason to believe that the slow 
 deviation is due to excitation arising in the labyrinth and conveyed 
 through the vestibular nuclei to the oculomotor nuclei by way of the 
 posterior longitudinal bundle. The slow movement can still be ob- 
 tained after removal of the cerebral cortex. The quick return jerk is 
 different in its origin, since it is abolished by the removal of the cere- 
 bral hemisphere on the side to which the eyes are moved in the slow 
 deviation — i.e., the side of the cerebrum from which the efferent im- 
 pulses concerned in pulling the eyes back to the primary position of 
 equilibrium arise. 
 
 In speaking of the postural reflexes it was stated that evidence 
 had been obtained of the widespread influence of the labyrinth on 
 the tonus of the skeletal muscles. The effects on the postural tonus 
 of the limb muscles were separated into two components, one due 
 to the labyrinth directly, and the other to impulses passing along 
 the afferent nerves of the neck muscles whose postural tonus is 
 itself affected from the labyrinth. These phenomena have been 
 demonstrated especially b}^ Magnus and his pupils, in mammals 
 like the rabbit, cat, and dog, and to a certain extent in man. They 
 studied the effects of excitation of the labyrinth as well as the 
 effects of its extirpation. To excite the labyrinth they emploj^ed 
 such ' adequate ' stimuli as are generated when the position of the 
 head is altered with reference to the vertical. Without going into the 
 details of this elaborate work, it may be said that it has placed in 
 a clear light the manner in which the posture of the head and of 
 the neck reacts upon the postural contractions of the limbs. The 
 strange attitudes so often seen after injury or disease of the laby- 
 rinth are to a great extent the consequences of the abnormal 
 postures assumed by the neck. 
 
 In the frog, in which no direct influence of destruction of the labyrinth 
 on the tonus of the extremities has been established, the effects of the 
 altered neck posture on the postural tonus of the limbs have also been 
 clearly demonstrated. On the injured side the extremities, especially 
 the anterior limb, arc flexed and adducted, the extremities of the other 
 side extended and abducted; the head and vertebral column are ro- 
 tated to the injured side (Ewald). All that is necessary to abolish the 
 difference in the posture of the limbs on the two sides is to divide the 
 posterior roots of the spinal nerves supplying the neck muscles 
 
 (I'ig- 377)- 
 
 The effects of destructive lesions of the labyrinth have their 
 counterpart in the phenomena caused by stimulation ; excitation of a 
 posterior canal, for example, in the pigeon causes movements of the 
 head from side to side. 
 
 Lee's results in fishes are, on the whole, of similar tenor. Mechan- 
 ical stimulation of the ampullfe in the dogfish, by pressing on them 
 with a blunt needle, calls forth characteristic movements of the 
 
FUNCTIONS or THE BRAIN gjg 
 
 eyes and fins, and electrical stimulation of the auditory nerve 
 causes movements compounded of the separate movements obtained 
 by stimulation of the ampullae one by one. Lee concludes that the 
 semicircular canals are the sense-organs for dynamical equilibrium 
 {i.e., equilibrium of an animal in motion), and the utricle and saccule 
 for statical equilibrium {i.e., equilibrium of an animal at rest). 
 
 The evidence from all sources points strongly to the conclusion 
 that afferent impulses are actually set up in the fibres of the auditory 
 nerve, through the hair-cells, by alterations of picssure or by stream- 
 ing movements of the cndolymph when the position of the head is 
 changed. Rotation of the head to the right may be supposed to 
 cause the cndolymph in the right external canal, in virtue of its 
 inertia, to lag behind the movement, and to press upon the anterior 
 surface of the ampulla. The disorders of movement after lesions of 
 the canals may be explained as the result of the withdrawal of 
 certain of these afferent impulses, and the consequent overthrow of 
 
 
 
 Fig- 377- — '^> ^'^^^ after Extirpation of the Left Labyrinth, showing the Difference 
 in the Posture of the Limbs on the Two Sides. B, the Same Frog after Section 
 of the Posterior Roots of the Second Pair of Spinal Nerves. The head and 
 vertebral column remain rotated toward the side of the lesion, but the legs are 
 now held symmetrically. 
 
 that equipoise of excitation necessary for the maintenance of equi- 
 librium. An experiment of Kreidl on a crustacean (palaemon) has 
 made it probable that the otoliths by their weight may mechani- 
 cally affect the hair-cells, and so increase their sensitiveness to 
 changes of position. This animal has the peculiarity that in moult- 
 ing the inner lining of the otocysts, in which the otoliths lie and 
 which open to the exterior, are shed along mth the otoliths. When 
 moulting is over, the animal by means of its claws conveys fine 
 sand grains into the otocysts, where they function as otoliths. 
 Kreidl placed the animal after moulting upon finely powdered iron, 
 
940 THE CENTRAL NERVOUS SYSTEM 
 
 some of wliich was conveyed into the otocyst instead of sand. It 
 was now found possible to obtain definite reactions from the animal 
 in the presence of a magnet, which, of course, tended to attract the 
 ferruginous otoliths, and so to alter their position with reference 
 to the hairs. The way in wliich the animal changed its position in 
 response to the magnet could be satisfactorily accounted for on the 
 hypothesis that normally the contact of the otoliths with the hairs 
 is altered under the influence of gravity when such changes of posi- 
 tion occur. Even in man there is evidence of the existence of some 
 mechanism not depending on the muscular sense or on impressions 
 passing up the channels of ordinary or special sensation, by which 
 orientation (the determination of the position of tlie body in space) 
 is rendered possible. For a man lying perfectly still, witli eyes shut, 
 on a horizontal table wliich is made to rotate uniformly, can not 
 only judge whether, but also in what direction, and approximately 
 through what angle, he is moved. The phenomena of pathology 
 afford weighty additional testimony in favour of the equilibratory 
 function of the semicircular canals. For many cases of vertigo are 
 associated with changes in the internal ear (Meniere's disease). 
 And while nearly every normal individual becomes dizzy when 
 rapidly rotated, 35 per cent, of deaf-mutes are entirely unaffected 
 (James), and the proportion seems to be much higher among con- 
 genital deaf-mutes. Kreidl and Bruck, too, have found that ab- 
 normalities of locomotion and equilibration are much more common 
 in deaf-and-dumb children than in others. Now, in these cases 
 the defect is usually in the internal ear. 
 
 Summary. — We must conclude, then, that the co-ordination of 
 muscular movements necessary for equilibrium is achieved in some 
 centre or centres to which afferent impulses pass from the internal ear 
 by the vestibular branch of the auditory nerve, and from ivhich efferent 
 impulses pass out to the muscles. If this centre or one of these centres 
 is situated in the cerebellum, the efferent path is, as already suggested, 
 partly an indirect one {perhaps by commissural fibres to the Rolandic 
 area, arid then out along the Pyramidal tract), or more probably to 
 lower centres, which control such massive co-ordinated movements as 
 those concerned in walking and the maintenance of the normal attitude, 
 and thence out along certain tracts that connect the thalamus to the 
 spinal cord (/>. 88b). 
 
 The influence of the labyrinth on the eye nio\ements through its 
 connection with the oculomotor nuclei in the mid-brain has been 
 previously mentioned as a factor in the phenomena whicii follow 
 its destruction or stimulation. It would, however, be erroneous to 
 assume that either the cerebellum or the labyrinth is essential to the 
 crude maintenance of that postural muscular tonus which is the reflex 
 foundation of the act of standing, l-'or in the dog and cat the posture 
 persists after removal of the fore-brain, the mid-brain back to the 
 
FUNCTIONS 01- THE BRAIN 94I 
 
 hinder edge of the posterior corpora quadrigemina and the labyrinth, 
 being supported partly through spinal centres and partly through 
 prc-spinal centres mainly in the region of the pons, but partly in the 
 bulb (Sherrington) . But it is none the less true that the act of standing 
 is aided and regulated in important xvays by centres in the mid-brain 
 and cerebellum through afferent impulses originating in the labyrinth 
 and elsexi'hcre — e.g., in the muscles. 
 
 Ewald has made an observation which illustrates the peculiar 
 relation of the semicircular canals to the muscular system — namely, 
 that the labyrinth (in rabbits), influences the course of rigor mortis 
 in the striped muscles. Rigor does not come on so soon on the side 
 from which tlic labyrinth has been removed. 
 
 (2) Afferent Impressions from the Muscles.— Muscles are richly 
 supplied with afferent fibres, for about half of the fibres in the nerves 
 of skeletal muscles degenerate after section of the posterior roots 
 beyond the ganglia (Sherrington). Various kinds of impressions 
 may pass up these nerves : («) Impressions giving rise to pain, as in 
 muscular cramp and in experimental excitation of even the finest 
 muscular ner\'e-filament ; {b) impulses causing a rise of blood-pres- 
 sure ; (c) impulses which are not associated with a distinct impres- 
 sion in consciousness, but which enable us to localize the position 
 of the limbs, head, eyes, and other parts of the body; (d) impulses 
 which inform us as to the extent arid force of muscular contraction, 
 and seem to underlie the so-called muscular sense. It is the last 
 two kinds — if, indeed, they are distinct — which must be concerned 
 in equilibration. In locomotor ataxia such impressions are blocked 
 by degeneration in a part of the afferent path (p. 915), and disorders 
 of equilibrium are the result. 
 
 (3) Afferent Impressions from the Skin. — Of the various kinds of 
 impulses that arise in the nerve-endings of the skin, only those of 
 touch and pressure seem to be concerned in the maintenance of 
 equilibrium. When the soles of the feet are rendered insensitive by 
 local anaesthesia or by cold, and the person is directed to close his 
 eyes, he staggers and sways from side to side. The disturbance of 
 equilibrium in locomotor ataxia must be partly attributed to the 
 loss of these tactile sensations, for numbness of the feet is a frequent 
 symptom, and the patient asserts that he does not feel the ground. 
 An interesting illustration of the importance of afferent impubcs 
 from the skin in the maintenance of equihbrium is afforded by the 
 behaviour of a frog deprived of its cerebral hemispheres. Such a 
 frog will balance itself on the edge of a board like a normal animal, 
 but if the skin be removed from the hind-legs, it will fall like a lo^'. 
 
 Localization of Function in the Cerebellum. — In birds and lower 
 vertebrates the cerebellum is only represented by the worm. Yet in 
 many of these animals the same characteristic disturbances follow its 
 removal as in the higher animals where the cerebellar hemispheres have 
 become so prominent. Indeed, it was mainly on the pigeon that 
 
942 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 Flourens made his classical experiments. At first the pigeon can 
 neither fly nor feed itself. When it attempts to walk, extensor spasms 
 of the legs come on, and it falls, wildly struggling and apparently 
 panic-stricken, to the ground. The power of flight is soon regained, 
 but for a long time the animal is unable to perch, the legs and talons 
 stiffening in rigid extension as it attempts to alight. 
 
 In the higher animals stimulation of certain parts of the worm and 
 lateral lobe causes conjugate movements of the eyes towards the same 
 side, both eyes being turned to the right— eg-., when the cerebellum is 
 stimulated to the right of the middle line. Inhibition of movement 
 can also be elicited from the organ. Excitation of the cerebellar cortex 
 
 for some distance 
 
 -.. / LcK \ Ls 
 
 Lans 
 
 outwartls from the 
 line of junction of 
 the superior worm 
 with the lateral lobe 
 in animals which 
 exhibit tonic con- 
 traction of extensor 
 muscles after ex- 
 cision of the cere- 
 bral hemispheres 
 (decerebrate rigid- 
 ity or acerebral 
 tonus, as it is called) 
 causes immediate 
 relaxation of the 
 rigid muscles of the 
 neck, tail, and espe- 
 cially the anterior 
 limb, particularly 
 on the same side. 
 The relaxation of 
 the extensors may 
 be accompanied by 
 contraction of the 
 antagonistic flexors 
 — for example, relaxation of the triceps and contraction of the biceps 
 (Horsley and Lowenthal). But this can scarcely be considered a re- 
 action specific to the cerebellum. For Sherrington, who finds that 
 the tonus or spasm is largely due to centripetal impulses coming from 
 the rigid limb, has been able to inhibit it by stimulation of various 
 other regions, including the portion of the cerebral cortex in front of 
 the fissure of Rolando (p. 955). 
 
 The confusion which so long reigned in regard to cerebellar 
 localization has in great measure been cleared up by recent physio- 
 logical work following on a more accurate anatomical mapping of the 
 lobes and lobules of the cerebellum in accordance with their genetic 
 relations (Elliott Smith, Bolk) (Figs. 378, 379). The classical descrip- 
 tion of the mammalian cerebellum as consisting of a median lobe or 
 vermis and two hemispheres has been abandoned. by the modern 
 investigators in this field. They divide the organ into two chief 
 lobes, an anterior and a posterior, separated by the deep and constant 
 primary fissure. 
 
 Fig. 378. — Scheme of Dog's Cerebellum (Dorsal View), ac- 
 cording to the Anatomical Dixision of Bolk (after van 
 Rynberk). La, lobus anterior, which is separated from 
 the larger posterior lobe by the deep primary fissure 
 (sulcus priniarius), Spr, Ls, lobulus simplex; Si, sulcus 
 intercruralis; C^, crus primum; C^, crus secundum; 
 L.ans, lobulus ansiformis; Lp, lobulus paramedianus; 
 Lmp, lobulus medianus posterior; Fv, formatio vermi- 
 cularis (pars tonsillaris); Sp, sulcus paramedianus. 
 
FUNCTIONS OF THE BRAIN 
 
 943 
 
 Followiiif,' tliis scheme, van Rynberk has obtained satisfactory 
 evidence of hjcahzation of function. Thus the loljuhis simplex con- 
 stitutes a centre for tlie neck muscles, and the elimination of its 
 influence by excision leads to movements of the head (so-called head 
 nystagmus). The anterior extremity is represented by a centre in 
 the crus primum, and the posterior extremity by a centre in the cms 
 secundum, of the ansiform lobule of its own side, and injury in the 
 region of these centres is associated with abnormal movements of the 
 corresponding fore and hind foot respectively. Extirpation of a 
 lobulus paramedianus causes rolling movements of the body around 
 its long axis or bending of the body to one side, and this centre is 
 connected with the muscles of the trunk. A general scheme of the 
 localizations in the mammalian cerebellum is given in Fig. 379. 
 
 Ftacc 
 
 
 Fig. oyg. — Bolk's Scheme of the Mammalian Cerebellum. On the right half, certain 
 localizations are indicated (Mills after Von Bechterew). 
 
 It must be remarked that the areas connected with the co- 
 ordination (synergia) of the muscles concerned in particular move- 
 ments cannot be so sharply localized on the surface of the cere- 
 bellum as the areas connected with the discharge of the movements 
 can be localized on the surface of the cerebrum. It is stili an open 
 question whether in the function of these centres only the cortex 
 of the lobules is concerned, or in addition the corresponding por- 
 tions of the central nuclei of the eerebellum. These observations 
 are supported by other facts. For example, microscopical studies 
 have shown that definite regions of the cerebellar cortex are especially 
 connected with definite levels of the spinal cord. Further, the 
 lobulation of the cerebellum in mammals keeps pace with the in- 
 crease in complexity of the voluntary motor apparatus of the whole 
 body, and the variations in the degree of development of definite 
 lobules are related to the variations in the anatomical and physio- 
 
944 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 logical development of the corresponding groups of muscles. All 
 this fits in well with the idea that the cerebellum is a great reflex 
 mechanism standing in intimate relation on the one hand to numer- 
 ous afferent paths (skin, muscles, labyrinth, etc.), and on the other 
 
 to the voluntary muscles. It is 
 the precise nature of the influence 
 exerted by it upon the latter 
 which is in doubt, whether an 
 augmenting sthenic influence, as 
 Luciani supposes, or a co-ordinat- 
 ing influence, asFlourens assumed, 
 or a combination of these. 
 
 Progress has recently been made 
 in utilizing the results of experi- 
 mental and clinical study of the 
 cerebellum for the localization of 
 circumscribed cerebellar lesions in 
 man (Barany). 
 
 The centres for the limbs are 
 situated in the cortex of the hemi- 
 spheres, those for the right ex- 
 tremities in the right semilunar 
 
 Fig. 380. — Localizations on the Infero- 
 latcral Aspect of the Human Cere- 
 bellum (Barany). X , is a centre for 
 the tonus of the muscles abducting 
 the right arm ; O, a centre for the 
 tonus of the muscles concerned in 
 adduction of the right hand ; + , a 
 
 centre for the tonus of the muscles (superior and inferior) and digas- 
 
 adducting the right arm; ±, a centre t^ic lobuleS ; thoSC for the left 
 
 for the tonus of the muscles adducting 
 the right hip. N.V, N.VI, N.VIl, 
 N.IX, N.XII, are cranial nerves. 
 
 extremities in the corresponding 
 positions on the left cerebellar 
 hemisphere. 
 
 Forced Movements.— Wc have incidentally mentioned that in fishes 
 mjuncs to the semicircular canals may give rise to movements which 
 seem to be beyond the control of the animal, and which have conse- 
 quently received the name of 
 ' forced movements.' It may 
 be added that when the in- 
 ternal ear of a Necturus (one 
 of the tailed amphibia) is 
 destroyed on one side, rapid 
 movements of rotation around 
 a longitvidinal axis arc ob- 
 served. The animal spins 
 round and round apparently 
 without voluntary control, 
 purpose, or fatigue. The di- 
 rection of rotation is towards 
 the side of the lesion, the 
 observer being supposed to 
 look down upon the animal as 
 it lies in its normal position. 
 After a time it becomes quiescent; but the forced movements can be 
 again produced by pinching or exciting it in other ways. Similar 
 rolling movements, and in the same direction, have been observed in 
 
 Fig. 381 — Localizations on Posterior Aspect 
 of Human Cerebellum (Barany). '^, a centre 
 for the tonus of the muscles concerned in 
 the movements of the right arm downwards; 
 X , same as in Fig. 380. 
 
FUNCTIONS OF THE DRAIN 945 
 
 niainnials after extirpation of one labyrinth. They arc elicited with 
 special eas? in the rabbit. In this animal it has been shown by study- 
 ing the movements by the aid of the cinematograph that the rolling 
 movements are really movements of progression (running and spring- 
 ing), which, on account of the changes in the position of the head and 
 neck, and in the tonus of the muscles, lead to a spiral rotation of the 
 body, in which the forward movement is small in proportion to the 
 rotation. 
 
 In man, too, during the passage of a galvanic current through the 
 head by electrodes applied just behind the ears, a tendency to move 
 the head towards the anode is experienced. The person may resist 
 the tendency; but if the current be strong enough his resistance will be 
 overcome ; he will execute a forced movement. When the head turns 
 towards the anode the eyes move in the same direction, and then under- 
 go jerking movements towards the kathode. There is at the same 
 time a feeling of vertigo. Complex as such an experiment is, involving 
 as it docs stimulation of so many structures within the cranium, there 
 is reason to believe that it is the excitation of the semicircular canals, or 
 their cerebellar connections, that is responsible for these forced move- 
 ments. For when the experiment is performed on a pigeon, forced 
 movements are caused so long as the membranous canals are intact, 
 but not after they have been destroyed (Ewald). The observation of 
 Rawitz, that the peculiar rotatory movements of the so-called Japanese 
 dancing mice are associated with marked anatomical peculiarities in 
 the labyrinth, is another fact in favour of the connection of the canals 
 with the maintenance of equilibrium and the sense of rotation. So is 
 the relation between the degree of development of the canals in different 
 species of birds and the degree of agility in the co-ordination of then 
 movements (Laudenbach). 
 
 But forced movements may also follow injuries (especially unilateral) 
 to many portions of the brain — e.g., the pons, crus cerebri, posterior 
 corpora quadrigemina, corpus striatum, even the cerebral cortex, and 
 above all the cerebellum. The movements are of the most various 
 kinds. The animal may run round and round in a circle (circus move- 
 ment) ; or, with the tip of its tail as centre and the length of its body 
 as radius, it may describe a circle with its head, as the hand of a clock 
 does (clock-hand movement) ; or it may rush forward, turning end- 
 less somersaults as it goes. Intervals of rest alternate with paroxysms 
 of excitement, and the latter may be brought on by stimulation. In 
 man forced movements associated with vertigo have been sometimes 
 seen in cases of tumour of the cerebellum — e.g., involuntary rotation 
 of the body in tumour of the middle peduncle. No entirely satisfac- 
 tory explanation of these forced movements has been given. They are 
 evidently connected with disturbance of the mechanism of co-ordina- 
 tion, leading to a loss of proportion in the amount of the motor dis- 
 charge to muscles or groups of muscles accu.stomed to act together in 
 executing definite movements. For instance, in circus movements the 
 muscles of the outer side of the body contract more powerfully than 
 those of the inner side, and the animal is therefore constrained to trace 
 a circle instead of a straight line, the excess of contraction on the outer 
 side being analogous to the acceleration along the radius in the case 
 of a point moving in a circle. 
 
 In connection with the consideration of the mechanism of equilibra- 
 tion, a short account of the muscular actions concerned in the main- 
 tenance of the erect posture so characteristic of man, and of those 
 concerned in locomotion, is subjoined here: 
 
 Standing. — In the upright posture the body is supported chiefly by 
 
 60 
 
946 THE CENTRAL NERVOUS SYSTEM 
 
 non-muscular structures, the bones and ligaments. But muscles also 
 play an essential part, for it is only peculiarly-gifted individuals, like 
 sorne of the fishermen of the North Sea, who can go to sleep on their 
 feet, and a dead body cannot be made to stand erect. The condition 
 of equilibrium is that the perpendicular dropped from the centre of 
 gi-avity to the ground should fall within the base of support — that is, 
 within the area enclosed by the outer borders of the feet and lines 
 joining the toes and heels respectively. The centre of gravity alters 
 its position with the position of the body, which tends to fall whenever 
 the perpendicular cuts the ground beyond the base of support. 
 
 In the comfortable and natural erect position tlic centre of gravity 
 of the head is a little in front of the vertical plane passing through the 
 occipital condjdcs, and as much as 4 centimetres in front of the vertical 
 plane passing through the ankle-joints. A certain degree of contrac- 
 tion of the muscles of the nape of the neck is required to balance it. 
 When these muscles are relaxed, as in sleep, the head must fall forward, 
 and this is the reason why Homer or any lesser individual nods. In 
 animals which go upon all-fours none of the weight of the head bears 
 directly upon the occipito-atloid articulation; its support by muscular 
 action alone would be an intolerable fatigue, and the ligamentum 
 nuchae is specially strengthened to hold it up. 
 
 The vertebral column is kept erect by the ligaments and muscles 
 of the back. The centre of gravity of the trunk lies almost vertically 
 over the horizontal line joining the two acetabula, but the centre of 
 gravity of the whole body is about the level of the third sacral vertebra, 
 and a little more than 4 centimetres in front of the vertical plane 
 passing through the ankle-joints. E(iuilibrium is maintained by con- 
 traction of the muscles of the back and of the legs. By means of the 
 muscular sense, and the tactile sensations set up by the pressure of the 
 .soles on the ground, alterations in the position of the centre of gravity, 
 and consequent deviations of the perpendicular passing through it, 
 are detected, and adjustment of the amount of contraction of this or 
 the other muscular group is promptly made. 
 
 In standing at ' attention ' the heels are close together, the legs and 
 back straightened to the utmost, and the head erect; the weight falls 
 equally upon both legs, but the advantage may be more than counter- 
 balanced by the muscular exertion associated with this more orna- 
 mental than useful position. In ' standing at case,' practically the 
 wliolc weight is supported by one leg, the ]jerpcndicular from the 
 centre of gravity passing through the knee and ankle-joint. The 
 centre of gravity is brought o\ er the supporting leg by llcxure of the 
 body to the corresponding side, and comparatively little muscular 
 effort is required. The other foot rests lightly on the ground, the 
 weight of the leg itself being almost balanced by the atmospheric 
 pressure acting upon the air-tight and air-free cavity of the hip-joint. 
 The light touch of this foot varies slightly from time to time, so as to 
 maintain equilibrium. 
 
 When the head or arms are moved, or the body swaj-ed, the centre 
 of gravity is correspondingly displaced, and it is by such movements 
 that tight-rope dancers continue to keep the perpendicular passing 
 through it always within the narrow base of support. 
 
 In sitting, the base of support is larger than in standing, and the 
 equilibrium therefore more stable. The easiest posture in sitting 
 without support to the back or feet is that in which the perpendicular 
 from the centre of gravity passes through the horizontal line joining 
 the two tubcra ischii. 
 
 Locomotion. — In walking, the legs are alternately swung forward 
 
FUNCTIONS OF THE BRAIN 947 
 
 and rested on the ground, With most persons the swinging foot tirst 
 strikes the ground by the heel; then the sole comes down, tlie heel 
 rises, the leg is extended, and, with a parting pusli from the toe, the 
 leg again swings free. By this manoeuvre the body is raised vertically, 
 tilted to the opposite side, and also pushed in advance. 
 
 The forward swing of the leg is only slightly, if at all, due to mus- 
 cular action; it is more like the oscillation of a pendnlum displaced 
 behind its position of equilibrium, and swinging through that position, 
 and in front of it, under the influence of gravity. For this reason the 
 natural pace of a tall man is longer and slower than that of a short 
 man; but it may be modified by voluntary effort, as when a rank of 
 soldiers of different height keeps step. The lateral swing of the body 
 is illustrated bj' the everyday experience that two persons knock 
 against each other when they try to walk close together without 
 keeping step. In step both swing their bodies to the same side at 
 the same moment, and there is no jarring. Even in the fastest walk- 
 ing on le\el ground there is a short time during whi< h both feet touch 
 the ground together, the one leg not beginning its swing until the 
 other foot has begun to be set down. In running, on the other hand, 
 there is an interval during which the body is completely in the air, 
 while in walldng uphill or in carrying a load the one foot is not raised 
 until the other has been firmly planted. 
 
 Functions of the Cerebral Cortex.— When an animal, Hke a frog, 
 is deprived of its cerebral hemispheres, the power of automatic 
 voluntary movement appears to be definitively and entirely lost. 
 The animal, as soon as the effects of the anaesthetic and the shock 
 of the operation have passed away, draws up its legs, erects its head, 
 and assumes the characteristic position of the normal frog at rest. 
 So close maybe the resemblance, that if all external signs of the opera- 
 tion have been concealed, it may not be possible for a casual ob- 
 server to tell merely bj^ inspection which is the intact and which the 
 ' brainless ' frog. The latter will jump if it be touched or othenvise 
 stimulated. It will croak if its flanks be stroked or gently squeezed 
 together. It will swim if thrown into water. If placed on its back, 
 it will promptly recover its normal position. But it will do all 
 theve things as a machine would do them, without purpose, without 
 regard to its environment, with a kind of ' fatal ' regularity. 
 Every time it is stimulated it will jump, every time its flanks are 
 squeezed it will croak, and, in the absence of all stimulation, it will 
 sit still till it withers to a mummy, even by the side of the water 
 that might for a while preserve it. 
 
 A Necturus, without its cerebral hemispheres, will, like the frog, 
 refuse to lie on its back. On stimulation it move's its feet or tail, 
 or its whole body; but if not interfered with, it lies for an indefinite 
 time in the same position. Its giUs are seen to execute rhythmic 
 movements, which never stop, and rarely slacken, except for an 
 instant, when some part of the skin, particularly in the region of 
 the head, is mechanically or electrically stimulated. The normal 
 Necturus, on the other hand, hes for long periods with its gills at 
 
948 THE CENTRAL NERVOUS SYSTEM 
 
 perfect rest, and w Ijcn stimulated, moves for a considerable distance. 
 Alter a time — two months or more — it is true the brainless frog, 
 if it be kept alive, as may be done by careful attention, will recover 
 a certain portion of the powers which it has lost by removal of the 
 cerebral hemispheres; and, indeed, the longer it lives, the nearer it 
 approximates to the condition of a normal frog. A brainless frog 
 has been seen to catch flies and to bury itself as winter drew on. 
 A fish even three days after the destruction of its cerebrum has been 
 seen to dart upon a worm, seize it before it had time to sink to the 
 bottom of the aquarium, and swallow it. Even in the pigeon the 
 loss of the hemispheres, which at first induces a state of profound 
 and seemingly permanent lethargy, is to a great extent compensated 
 for, as time passes on, by the unfolding in the lower centres of 
 capabilities previously dormant or suppressed. A brainless pigeon 
 has been known to come at the whistle of the attendant and follow 
 him through the whole house. 
 
 In the mammal the removal of the whole or the greater part of 
 the cerebral hemispheres at a single operation is uniformly and 
 speedily fatal; even rabbits or rats, which bear the operation best, 
 survive but a few hours. During those hours they manifest 
 phenomena similar to those observed in the bird and the frog. In 
 the dog the entire cortex has been removed piecemeal by successive 
 operations. In this case, of course, the change in the condition of 
 the animal is more gradually produced, and an opportunity is 
 afforded for a certain recovery of function in the intervals between 
 the operations. On the whole, however, as might be expected, 
 from its greater intellectual development, recovery is more imperfect 
 in the dog than in the bird, much more imperfect than in the frog. 
 But even in the dog wonderful resources Ue hidden in the grey 
 matter of the central neural axis, and are called forth by degrees 
 to replace the lost powers of the cerebral cortex. It is true that a 
 brainless dog is a less efficient animal than a brainless fish, or even 
 than a brainless frog; but in favourable cases, even in the dog, the 
 mo\ements of walking may still be carried out with tolerable pre- 
 cision in the absence of the cerebral hemispheres. The animal can 
 swallow food pushed well back into the mouth, although it cannot 
 feed itself. Stupid and listless as it is compared with the normal 
 dog, it seems to be by no means devoid of the power of experiencing 
 sensations as the result of impressions from without, or of carrying 
 on mental operations of a low intellectual grade. Goltz had a dog 
 which lived more than a year and a half practically without its 
 cerebral hemispheres, and another which lived thirteen weeks. 
 He believes that they had lost understanding, reflection, and 
 memor}', but not sensation, special or general, nor emotions and 
 voluntary power. Their condition may be best described as one of 
 general imbecility. Hunger and thirst are present. They experi- 
 
FUNCTIONS OF THE BRAIN 949 
 
 enco sitisfaction when fed, become angry when attacked, see a very 
 brit'ht light, avoid obstacles, hear loud sounds, such as those pro- 
 duct d by a fog-horn, and can be awakened by them. They are not 
 completely deprived of sensations of taste and touch. But it ought 
 to be remembered that the interpretation of the objective signs of 
 sensation in animals is beset with difficulties; and although every- 
 body admits the accuracy of Goltz's description of what is to be 
 seen, his interpretation of the facts has been severely criticized, 
 particularly by H. Munk. 
 
 Difficult as it is to keep dogs alive after removal of the greater 
 part of the cerebrum, the problem is far more difficult in monkeys. 
 In some recent experiments, however, in which the hemispheres 
 were removed by two successive operations from Macaque monkeys, 
 one of the animals survived for as long as twenty-six days the ex- 
 cision of the second hemisphere, and others lived a week. The 
 movements of the extremities were much affected. The animals 
 seemed to be in a sleepy condition with the eyelids closed, and most 
 of them made no movements which could be interpreted as voluntary 
 movements during tlie first days after loss of the second hemisphere. 
 Sounds caused the appropriate reflex movements of the ears. The 
 pupil was constricted by light. The animals cried in the usual 
 manner when subjected to painful stimuli, but the ordinary facial 
 accompaniments of pain were absent. 
 
 In man the destruction of considerable masses of brain-substance, 
 particularly if gradual, is not necessarily fatal. How great a loss 
 is compatible with life cannot be exactly stated. It depends to a 
 large extent on the position of the lesion. But it is possible that 
 one cerebral hemisphere may be rendered functionally useless 
 without immediately putting a term to existence. In the foetus, 
 however, no portion of the great brain is absolutely indispensable for 
 life and movement. An anencephalous foetus (in whicli the brain has 
 remained undeveloped) may be bom alive, and live for a short time. 
 
 We see, then, that homologous organs are not necessarily, nor 
 indeed usually, of the same physiological value in different kinds of 
 animals. A loss which perhaps hardly narrows the range of the 
 psychical, and certainly restricts only to a slight extent the phj'sical 
 powers of a fish, impairs in a marked degree the voluntary move- 
 ments of a dog, still more those of a monkey, in addition to cutting 
 off from it a great part of its intellectual life, and is in man incom- 
 patible with life altogether. It would be easy, however, to exag- 
 gerate the difference in the importance of the cerebrum to the higher 
 and the lower animals. After all, it remains a striking fact that 
 monkeys and dogs can live in the absence of the cerebral hemispheres, 
 and to the remnant of the central nervous system which enables such 
 highly organized animals to support life must still be regarded as a 
 very wonderful and complex mechanism. Perhaps, indeed, it is 
 not too much to say that the real lesson of these experiments on the 
 
950 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 extirpation of the cerebrum is not so much tlie supreme importance 
 of tlie h('misi)hcrcs of the great brain in the l)iglicr animals as the 
 manifold and fundamental functions which still reside in the basal 
 ganglia. The cerebral cortex seems to have taken over and exten- 
 sively developed and adapted some of those primitive powers of 
 lower portions of the nervous axis, but without depriving the older 
 formations of the capacity for reassuming them in some degree when 
 the cortex has been destro3'ed. 
 
 The results of the removal of the entire cerebral hemispheres help 
 us to fix their position as a whole in the physiological hierarchy. A 
 more minute analysis shows us that the cerebral cortex itself is not 
 homogeneous in function, that certain regions of it have been set 
 
 aside for special labours. 
 
 :,C.//, 
 
 Our knowledge of this 
 localization of function in 
 tlie cerebral cortex has been 
 derived partly from clinical, 
 coupled with pathological 
 observations on man, and 
 partly from the results of 
 the removal or stimulation 
 of definite areas in animals. 
 In addition, the study of 
 tlie development of the 
 myehn sheath, and especi- 
 ally in recent years the 
 minute study of the hist- 
 ology of the various regions, 
 lia\e aided materially in 
 niapi)ing out the cortex. 
 
 It is a fact which might 
 appear strange and almost 
 inexplicable did the history 
 of science not constantly 
 present us with the Hke, that 
 fifty years ago the universal 
 opinion among physiologists, 
 ,, ^ ^, , , . . , pathologists, and physicians 
 
 was that the cerebral cortex is mexcitable to artificial stimuli that 
 no visible response can be obtained from it. The great names of 
 Flourens and iMagendie stood sponsors for this error, and repressed 
 research. In 1870, however, Ilitzig and Fritsch showed that not only 
 was It possible to elicit muscular contractions by stimulation of the 
 cortex of the brain in the dog with voltaic currents, but that the 
 excitable area occupied a definite region in the neighbourhood of the 
 crucial sulcus or sulcus centralis, which runs out over the convexity of 
 the hemispheres nearly at right angles to the longitudinal fissure In 
 this region they were further able to isolate several distinct areas 
 stimulation of which was followed by movements respectively of the 
 head, face, neck, hind-leg, and fore-leg (Fig. 382). This was the 
 
 Fig. 382. — Motor Areas of Dog's Brain, n, neck ; 
 /./., fore-limb; h.L, hind-liinb; /, tail;/, face; 
 C.S., crucial sulcus; e.m., eye movements; p, 
 dilatation of the pupil in both eyes, but espe- 
 cially in the opposite eye. All the areas are 
 marked in the figure only on the left side 
 except the eye areas, whose position, to avoid 
 confusion, is indicated on the right hemi- 
 sphere. 
 
FUNCTIONS OF THE BRAIN 
 
 95» 
 
 starting-point of a long series of researches by Ferrier, Munk, Horsley, 
 Soliafer, Heidcnhain, and many others, on the brains of monkeys as 
 well as dogs — researches which liavc formed the basis of an exact 
 cortical localization in the brain of man, and have enriched surgery 
 with a new province. In these later experiments the interrupted cur- 
 rent from an induction machine has been found the most suitable form 
 of stimulus (see Practical Exercises, p. looi), especially when one elec- 
 trode only is placed on the cortex and the other on some indifferent 
 part of the body — e.g., in the rectum (unipolar stimulation), a pro- 
 cedure which permits of finer 
 
 localization than when both 
 electrodes are applied to the 
 brain (bipolar stimulation). 
 
 ' Motor ' Areas.* — These 
 have been localized 
 with great care (both by 
 stiiniilation and by removal 
 of portions of the cortex) 
 in the brains of the higher 
 apes (gorilla, orang, and 
 chimpanzee) by Sherrington 
 and Griinbaum, and there 
 can be no doubt that the 
 results, in their general 
 outlines at least, can be 
 applied to the human brain. 
 These observers employed 
 the so-called unipolar 
 method of stimulation. 
 
 The ' motor ' region in- 
 cludes the whole length of 
 and the whole of the free 
 width of the precentral 
 or ascending frontal con- 
 volution, and dips down to 
 the bottom of the central 
 sulcus (fissure of Rolando 
 in man), but does not 
 extend behind the sulcus. It extends also into the depth of all the 
 fissures, so that the hidden part of the excitable area probably 
 equals, perhaps exceeds, the part which is free on the surface of the 
 hemisphere. The anterior limit of the ' motor ' field is not quite 
 
 * Since the so-called ' motor ' area, as is now well known, is really sensori- 
 motor, and a region having to do purely with the discharge of motor impulses 
 does not exist, it would be better to call it the sensori-motor, or, follo\\'ing 
 Bastian's suggestion, the kinaesthetic area. Probably, however, the altera- 
 tion of a term so long sanctioned by custom in physiological writings would 
 lead to confusion. Accordingly, in what follow^s the word 'mjtor' will be 
 retained, but to show that it is used in a special sense it will be enclosed in 
 quotation marks. 
 
 F'g- 383. — Dog's Brain with Lesion. A portion 
 of the cortex indicated by the shaded area 
 was destroyed by cauterization. The symp- 
 toms were complete blindness of the opposite 
 eye (in this case the right); weakness of the 
 muscles of the limbs and of the neck on the 
 right side; slight weakness of the limbs on the 
 left side. When the animal walked, there was 
 a tendency to turn to the left in a circle. In 
 eating or drinking, the head was turned to the 
 left, so that the mouth was oblique, and the 
 right angle of the mouth was lower than the 
 left. The tail movements were normal, and 
 there was no deviation of the tail to one side. 
 
952 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 sharp, but sliadis off soincvvliat gradually into inexcitable cortex. 
 The sulci in this region cannot be considered to represent physio- 
 logical boundaries, and they vary so much in these higher brains, 
 that they can easily prove fallacious landmarks. On the mesial 
 surface of the hemispliere the ' motor ' area does not extend quite 
 to the calloso-marginal fissure. 
 
 Within this area are localized movements of the leg and arm and 
 their various joints, of the head, face, mouth, tongue, ear, nostril, 
 and vocal cords, of the neck, chest, and abdominal wall, of the pelvic 
 floor, and the anal and vaginal orifices. 
 
 Anus $ vayina.. 
 ^oes ^ SaUt 
 
 Anhl^e 
 Kne^ 
 
 "^.^^^ 
 
 Shouider 
 Eihqv/ 
 WrlsC 
 
 Fin£er3 
 
 (f thumb ,.__ 
 
 Abdomen 
 
 Cheat 
 
 Ofjd.W. 
 
 Opening 
 ofj&w. 
 
 Sulcus cerUraUa. 
 
 Voca.i '; 
 
 cords. fiaaiictiCion 
 
 CSS.<f«/. 
 
 Fig. 384. 
 
 -' Motor ' Area of Cortex of Chirtapanzee (Griinbaum and Sherrington). 
 Lateral aspect of the hemisphere. 
 
 The arrangement of the various regions follows very closely the 
 order of the cranio-spinal nerves, which supply them, but the organs 
 whose nerves come off lowest down arc represented highest up in 
 the ' motor ' area. Figs. 3.'^4, 385 will make this clear. In the frontal 
 region, isolated from the motor ' area by a strait of inexcitable 
 cortex, lies an area the stimulation of which causes conjugate devia- 
 tion of the eyes. But the reaction differs from that obtained on 
 excitation of the ' motor ' area proper in front of the Rolandic fissure. 
 
 It is to be particularly noted (i) that within the larger areas, such 
 as those of the arm and leg, smaller foci can be mapped off which 
 are related to movements of the separate joints — thus, in the leg 
 area, the hip, knee, and ankle-joints, and the great toe, are repre- 
 
FUNCTIONS OF THE BRAIN 
 
 953 
 
 sented by separate and special centres; (2) that stimulation of any 
 one of these areas leads, not to contraction of individual muscles, 
 but to contraction of muscular groups which have to do with the 
 execution of definite movements. 
 
 Sul<: calloso 
 marg- 
 
 Stiic.pariito 
 uccip 
 
 StUc Central ^^"■'^^^^g'^'^ 
 
 Sulc prccenCr.mary 
 
 SuJbc.calcarin 
 
 CS S del. 
 
 Fig, 
 
 385. — 'Motor' Area on Mesial Surface of Hemisphere: Brain of a Cliimpanzee 
 {Troglodytes Niger) (Griiubaum and Sherrington). Left hemisphere: mesial sur- 
 face. The extent of the ' motor ' area on the free surface of the hemisphere is 
 indicated by the black stippling. On the stippled area ' LEG ' indicates that 
 the movements of the lower limb are represented in all the regions of the ' motor ' 
 area visible from this aspect. The muiuter subdivisions m this area overlap 
 each other so much that no attempt is made to distinguish them in the diagram. 
 ' Anus and vagina ' indicates the position from which perineal movements can 
 be primarily elicited. Sulc. central. = central fissure; Sulc. calcarin. = calcarine 
 fissure; Stilc. parieto occ/^. =parieto-occipital fissure; Sm/c. calloso warg.^calloso- 
 marginal fissure; Sttlc. precentr. niarg. = precentral marginal fissure. The single 
 italic letters mark spots whence, occasionally and irregularly, movements of the 
 toot and leg (//), of the shoulder and chest (s), and of the thumb and fingers [h), 
 have been evoked by strong faradization. The shaded area marked 'EYES' 
 indicates a field of free surface of cortex which, imder faradization, yields con- 
 jugate movements of the eyeballs. The conditions under which these reactions 
 are obtained separates them from those characterizing the ' motor ' area. 
 
 Th^ Stability of the Reactions obtained by Stimulating Cortical Points. 
 
 — The question whether stimulation of a ' motor ' area, or point invariably 
 causes the same movements, when it causes any movements at all, has 
 been recently investigated by Graham Brown and Sherrington. They 
 observed the contractions of two isolated antagonistic muscles acting 
 on the elbow-joint (in monkeys) after elimination of all the other 
 muscles of the arm and shoulder by section of their ' motor ' nerves, when 
 a point on the area of the cortex in which the movements of the elbow 
 are represented was excited by the unipolar method. They find that 
 a cortical point which has given flexion at the elbow, sometimes on 
 
954 THE CENTRAL NERVOUS SYbThM 
 
 investigation the next day, may give the opposite result of extension oi 
 the elbow. Even within shopt intervals reversal of the reaction elicited 
 from one and the same point may be seen. They do not question at all 
 the general regularity of the results which such cortical points give 
 when investigated by suitable methods after sufficient intervals of rest, 
 and on which the current statements as to the reactions elicited from 
 the various ' motor ' areas arc based. But they see in the influence of 
 transient excitation either of the point itsek or of other more distant 
 points in modifying or reversing the reaction an indication that one 
 of the functions of the cortex may be the carrying out of such phe- 
 nomena of reversal, a function which may play some part in the 
 co-ordination of voluntary movements. In this connection it may be 
 remarked that a phenomenon analogous to the ' facilitation ' already 
 described for the reflex arc is also exhibited by the motor cortex. 
 If a motor reaction — e.g., the movement of flexion at the elbow, as 
 studied in a pair of isolated antagonistic muscles in monkeys, is elicited 
 by stimulation of the appropriate cortical area, and a second cortical 
 stimulation is made to follow the first, the reaction evoked by the 
 second stimulus is greater than that following the first, providccl that 
 the interval of time between the two is not too long. If the first stimu- 
 lus is so chosen that it is just below the strength necessary to evoke a 
 movement, a second or third stimulus, which also by itself would fail 
 to cause a reaction, may do so. Not only so, but stimulation of one 
 cortical point, say in the area which gives flexion of the elbow, may 
 raise the excitability of neighbouring points in that area (so-called 
 ' secondary facilitation '), so that a stimulus which previously did not 
 ehcit the flexion movement from these points may now do so. 
 
 Inhibition from the Cortex. — Contraction is not the only effect on 
 the muscles which can be elicited by stimulating the cortex. Cor- 
 tical inhibition of tonus and of active contraction is just as char- 
 acteristic, though not so obvious a result. There is abundant evi- 
 dence of reciprocal innervation of volitional movements from the 
 cortex. When, e.g., the part of the arm area whicli presides over 
 extension of the elbow is stimulated (in the monkey), it can be shown 
 that the biceps relaxes as the triceps contracts. In like manner, 
 stimulation of the appropriate part of the leg area will cause along 
 with contraction of the extensors of the hip relaxation of such flexors 
 as the psoasiliacns and the tensor fascia femoris. Such observations 
 are most easily made when, in a certain stage of narcosis, the limbs, 
 instead of hanging limp, assume a position of tonic flexion, especially 
 at the elbow and hip. Under other conditions the position of tonic 
 extension of a joint may be assumed, and then it can be shown that 
 excitation of the appropriate focus for flexion of that joifit will 
 cause simultaneous contraction of the flexors and relaxation of the 
 extensors. 
 
 The observer cannot fail to be struck with the general resem- 
 blance between these cortical reactions and their co-ordination and 
 the co-ordinated bulbo-spinal reflex movements previously studied. 
 There are, however, certain differences which place the cortical 
 reactions upon a higher level. One of the most important is the 
 part played by visual, auditory, and pure ' touch ' stimuli in eliciting 
 
FUNCTIONS OF THE BRAIN 955 
 
 cortical motor responses — e.g., ' the closure of the hand, pricking 
 of the ear, opening of the eyes, and turning of the head in the 
 direction of the gaze ' (Shernngton). The facility of response to 
 stimuli acting from a distance tiirough the distance-receptors, such 
 as those of tlie retina and labyrinth, is one of the great characteristics 
 of the cerebrum as an organ concerned in movements, and helps 
 to place tlie ' motor ' cortex at the helm, since these distance- 
 receptors control more than others the skeletal musculature as a 
 whole. Spinal reflex movements are mainly such as are elicited 
 by harmful (nocuous) stimuli (protective reflexes), or through the 
 sexual skin nerves, or from the visceral afferent fibres, or such as 
 are concerned in the chief movements of locomotion. 
 
 Decerebrate Rigidity is a phenomenon closely related to the in- 
 hibitory function of the cerebral cortex. It is a condition of pro- 
 longed s])asm of certain groups of skeletal muscles (especially the 
 retractor muscles of the head and neck, the elevators of the jaw 
 and tail, and the extensors of the elbow, knee, shoulder, and hip), 
 supervening on removal of the cerebral hemispheres by transection 
 anywhere in the mid-brain or in the posterior part of the thalamus, 
 and favoured by suspending the animal in the vertical posture. 
 If the afferent roots belonging to one of the rigid limbs are severed, 
 it at once becomes flaccid, while the other limbs remain rigid. The 
 tonus is therefore reflex through the local afferent nerves, and, to 
 be more precise, through those that supply the deep structures 
 (joints, muscles, etc.). The centre must be situated somewhere 
 between cerebrum and spinal bulb, since section of the bulb 
 abolishes the rigidity. It is not apparently in the cerebellum. It 
 is noteworthy that the muscles mainly involved in decerebrate 
 rigidity are those which are much more easily inhibited than excited 
 from the ' motor ' cortex, and also in the local spinal reflexes. After 
 removal of the cerebrum, the mechanism which maintains their 
 tonic contraction has free play. Sherrington points out that this 
 mechanism sustains the steady muscular tension necessary to pre- 
 serve against the force of gravity the attitude or posture of the body. 
 According to him, decerebrate rigidity is simply 'reflex standing.' 
 When the transient spinal reflex or the transient cortical effect 
 breaks in upon this tonic contraction — e.g., in locomotion — ^inhibi- 
 tion of the contracted extensors accompanies contraction of the 
 flexors (see also p. 942). 
 
 Removal of a single ' motor ' region leads to paralysis of the 
 corresponding limb, or part of a limb, on the opposite side. For 
 example, after extirpation of the hand area the hand is for a few 
 days practically useless and apparently powerless. In a few weeks, 
 however, it recovers remarkably, so that it is once more used in 
 climbing or in conveying food to the mouth. It is an important 
 question in what way this recovery is brought about. If the whole 
 
956 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 of the corresponding area in the opposite hemisphere is now re- 
 moved, a similar paralysis occurs in the other hand, but the hand 
 whose ' motor ' area was first extirpated remains entirely unaffected 
 by the second lesion. On the contrary, the first hand is used more 
 freely and more adroitly than before the second operation, probably 
 because the animal needs to use it more. The second hand recovers 
 eventually, like the first. If when this has taken place the remain- 
 ing part of the arm area from which the hand area was first excised 
 be removed, neither hand is apparently affected, although there is 
 severe paralysis of the shoulder and slighter paralysis of the elbow 
 on the side opposite to the lesion, which is again largely recovered 
 from. The recovery of the hand movement cannot therefore be 
 attributed to the taking on of the function of the corresponding 
 
 Fig. 386. — Cerebral Cortex Man (seen from Above). The front of the brain is towards 
 the left. The dotted line shows the position of the fissure of Rolando, as fixed 
 by Thane's rule (p. 963). 
 
 ' motor ' area either by the opposite hand area or by the adjacent 
 ' motor ' cortex of the same hemisphere. According to some 
 authorities, the recovery is due to the representation of the upper 
 limb in the post-central gyrus (ascending parietal convolution in 
 man) acting through fibres that descend from this g>Tus to the 
 optic thalamus, and thence through the rubro-spinal tract, which 
 runs to the spinal cord (p. 8^-7). 
 
 Removal of the whole of the ' motor ' cortex of one hemisphere, 
 in such animals as this operation has been performed on, causes 
 paralysis of movement on the opposite side of the body. The 
 paralysis is less marked in the case of bilateral muscles that habitu- 
 alh' act together than in the case of those which ordinarily act alone. 
 Thus the muscles of respiration and the muscles of the trunk in 
 
FUNCTIONS OF THE BRAIN 957 
 
 general are, although perhaps weakened, never completely para- 
 lyzed. This is an indication that each member of such functional 
 pairs of muscles is innervated from both hemispheres; and this 
 physiological deduction is supported by the anatomical fact already 
 referred to, that after removal of the ' motor ' cortex, or injury to 
 the pyramidal tracts in the internal capsule or crus, some degener- 
 ated fibres (homolateial fibres) are found in the crossed pyramidal 
 tract on the side of the lesion (p. 875)- 
 
 In the dog after a time the paralysis may more or less completely 
 disappear. In the monkey restoration is less complete. 
 
 Some interesting observations have been made on a monkey, 
 which was carefully watched for eleven years after the removal by 
 two operations of the cortex of the greater portion of the frontal 
 and parietal lobes on the left side. The character of the animal 
 which had been studied for months before the operations, was en- 
 tirely unaffected. All its traits remained unaltered. There was no 
 loss of memory or intelHgence. On the other hand, disturbances 
 of movement on tlie right side were very noticeable up till its death. 
 It learned again to use the right limbs in locomotion ; but, although 
 they were not markedly weaker than those of the left side, their 
 movements had a certain clumsiness, which was associated with a 
 permanent diminution in the sensibility of the skin of these limbs. 
 ^Muscular sensibility was also lessened. In acts requiring the use only 
 of one hand, the right was never willingly employed, and it evidently 
 cost the animal a great effort to use it in such movements, but by 
 special training it learnt again to give the right hand when asked 
 for it, and to make use of it for other purposes. The movements 
 with which the ' motor ' areas are concerned are essentially skilled 
 movements, and we may suppose that it is more difficult for a 
 monkey to educate again a centre for such complex and elaborate 
 mancEuvres as are performed by its hand than for a dog to regain 
 normal control of the comparatively simple movements of its paw. 
 In man in cases of hemiplegia, when the patient lives for some time, 
 a certain amount of recovery usually takes place, especially in young 
 persons, in the paralyzed leg, but much less in the paralyzed arm. 
 
 In the lower monkeys the ' motor ' area was formerly stated to 
 extend behind the sulcus centralis into what in man would be called 
 the ascending parietal convolution (post-central gyrus), and also to 
 be more extensively represented on the mesial surface of the hemi- 
 sphere than in the higher apes. Such observations, however, require 
 to be reinterpreted in view of the results of Sherrington and Griin- 
 baum, especially as they were carried out by the bipolar method of 
 stimulation, with both electrodes on the cortex. This method does 
 not admit of such strict locahzation of the stimulus as the unipolai 
 method. The most recent work with the unipolar method has 
 
958 THE CENTRAL NERVOUS SYSTEM 
 
 indicated that in the lower apes also excitation of the gyrus post- 
 centralis does not cause movements (C. and O. Vogt). 
 
 It is in the light of the results obtained in monkeys, and by the 
 aid of histological, embry ©logical, clinical, and pathological ob- 
 servations, that the ' motor ' areas in man have to a great extent 
 been mapped out. 
 
 'Jhe histological differentiation of the various cortical regions recently 
 demonstrated by Brodmann and by Campbell are of especial interest 
 (Figs. 387-391). It has long been customary to divide the cortex into 
 layers, although the number and the boundaries of these layers are 
 somewhat arbitrarily fixed. Brodmann distinguishes six layers: (i) A 
 zonal or peripheral layer, containing many nerve-fibres and neuroglia 
 cells, but few nerve-cells; (2) a layer containing ' granules ' and small 
 pyramidal cells {external granular layer) ; (3) a layer of medium and 
 large pyramidal cells {pyramidal layer); (4) a laj'cr of small irregular 
 
 iirr-- 
 
 \. 
 
 ^:U. 
 
 Pig. 387. — Ctll-Lamination of Gyrus Postcentralis (Campbell). A, just behind 
 upper end cf fissure of Rolando; B, from the posterior edge of the gyrus (inter- 
 mediate postcentral area of Campbell). 
 
 cells {internal granular or stellate layer) ; (3)- a 'ganglionic' layer, con- 
 taining the largest pyramidal cells ideep large pyramids); (6) a layer 
 {lamina miilliformis) of spindle-shaped or polymorphous cells. These 
 layers vary in their structural details, and especially in their relative 
 devcloi>mcnt in animals of different rank in the mammalian scale, in 
 one and the same animal at diflercnt periods in its embryonic and 
 extra-uterine growth, and also in different parts of the cortex in an 
 adult animal of given species. The. region in front of the central 
 sulcus (fissure of Rolando), e.g., is characterized by the presence of the 
 giant pyramids of Betz, which give origin to the pyramidal fibres 
 going to the trunk and limbs (Fig. 388). More than forty years ago 
 
FUNCTIONS OF THE BRAIN 
 
 950 
 
 Bctz.when first describing these large pyramidal cells, suggested thatthey 
 were related to some motor function, and this view was a few years later 
 more clearly developed by Lewis, the real pioneer in cortical localization 
 by the histological method. He mapped out the motor area in man 
 by this method, and his results differ surprisingly little from those of 
 Campbell obtained by a much more elaborate technique. He pointed 
 out that areas containing the giant pyramids corresponded with a 
 number of the areas defined as motor areas by the experimental 
 physiologists by means of electrical excitation. Definite proof of 
 the connection of the Betz cells with the pyramidal fibres was not 
 obtained till much later. Some of the facts which have established 
 such a connection are alluded to on a previous page (p. S73). Other 
 characters than the size, shape and distribution of the nerve cells 
 
 <r 
 
 .■ y 
 
 V b' 
 
 
 :v. 
 
 .^1 
 
 Fig- 3S8 — Cell-Lamination of Gyrus 
 Preccntralis (Campb-U). From the 
 portion of the gyrus immediately 
 in front of the central sulcus (Camp- 
 bell's precentral area in Figs. 390, 
 391)- 
 
 Fif- 389. — Cell-Lamination of Gyrus 
 Precentralis (Campbell). From an- 
 terior part of the gyrus (Campbell's 
 intermediate precentral area in Figs. 
 390, 391)' 
 
 have also proved of value in differentiating histologically the various 
 regions of the cortex — for example, the differences in the diameter 
 and the number of the medullated nerve fibres which run verti- 
 cally into and out of the grey matter. Although the method has 
 yielded valuable and suggestive results, it would be misleading to 
 state that the agreement with the experimental and pathological 
 findings is anything more than a general one. Discrepancies in 
 detail are not lacking, and this might be expected. Histological dif- 
 ferences, after all, are only rough criteria for the differentiation of 
 function. 
 
 Although the results are less definite, the work of Flechsig on the 
 time of development of the medullary sheath of the fibres in the various 
 cerebral convolutions has also contributed to our knowledge of localiza- 
 
96o 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 tvo-ptydua 
 
 Te*P»" 
 
 Fig. 390. — Structurally DLSerentiated Cortical Area? (Campbell). External surface 
 of hemisphere (human brain). 
 
 Vino- 
 
 Fig. 391. — Structurally Differentiated Cortical Areas fCan>jl»iI; Mesial surface of 
 hemispheie (humar* brain). 
 
FUNCTIONS OF THE BRAIN 
 
 961 
 
 tion in the cortex. In the dev^elopment of a neuron four stages can be 
 distinguished : (i) Oils witliout processes; [z) the appearance of pro- 
 cesses, first tlie axon and tiien the dendrites; (3) the formation of col- 
 
 Fig. 3<52. — Flechsig's Developmental Zones (after Flechsig). Outer surface of human 
 cerebral hemisphere. Primary zones (i-io), darkly shaded; intermediate zones 
 (11-31), less deeply shaded; terminal zones {32-36), unshaded. 
 
 laterals; (4) myelination or the formation of the medullary sheath 
 (Fig. 3J3. P- 854). 
 
 Myelination occurs in the cerebral convolutions in a regular order. 
 In some areas the fibres miy be meduUated three months before birth, 
 
 Fig. 393- — Flechsig's Developmental Zones (after Flechsig). Inner surface of human 
 cerebral hemisphere. 
 
 in others not till six months later. For instance, the Rolandic and 
 olfactor}'- regions, the calcarine portion of the occipital lobe associated 
 with vision, and the portion of the temporal lobe associated with 
 hearing, are plentifully provided with meduUated fibres a short time 
 after birth, at any rate before the first month, whereas the remaining 
 regions of the cortex are completely, or almost completely, free from 
 
<j^i THE CENTRAL NERVOUS SYSTEM 
 
 such fibres. In this way Flechsig has distinguished thirty-six cortical 
 fields (Figs. 392, 393). which he divides according to the time of ^ 
 myehnation into three groups: 
 
 1. Primary fields, ten in number, which are well provided with mye- 
 linated fibres at birth. They include the cortical centres for the 
 various sensations and also the ' motor ' area. They are connected 
 especially with the so-called projection fibres. Thus, the cutaneous 
 and muscular sense is assumed to be represented in field i, the sense 
 of smell in field 2, of vision in 4, and of hearing in 5. From field i 
 arise the fibres of the pyramidal tract, chiefly from the ascending 
 frontal convolution, while the sensory fibres from the skin and muscles 
 end mainly in the ascending parietal. This is an illustration of what 
 Flechsig considers a general rule for these primary fields — viz., that 
 each primordial sensory region is connected both with an afferent 
 (cortici-petal) and witli an efferent (cortici-fugal) tract. From the 
 visual area (4), e.g., arises a tract which proceeds mainly to the anterior 
 corpus quadrigeminum. 
 
 2. Terminal fields (32 to 36 in the figures) which become myelinated 
 late, the process not beginning until at least a month after birth. 
 
 3. Intermediate fields (11 to 31) which become myelinated earlier 
 than the terminal, but later than the primary. They and the terminal 
 fields constitute par excellence association centres, which furnish fibres 
 (association fibres) connecting the centres represented in the primary 
 fields — e.g., such fibres as must be continually conveying impressions 
 from the visual centre to the ' motor ' cortex when the hand is sketching 
 a landscape. It may also be considered a function of these association 
 centres to store up the memories of previous sense impressions. Flech- 
 sig divides the association centres represented in the terminal fields 
 into — (i) The great anterior association centre in the frontal lobe in 
 front of the ' motor ' area; (2) the great posterior association centre in 
 the parieto-temporal region; (3) the smaller middle or insular associa- 
 tion centre, which coincides with the island of Reil. an area which, 
 according to Sherrington and Griinbaum, is totally ' inexcitable ' as 
 regards the production of movement in the anthropoid apes. These 
 association centres are foci, from which issue and to which come the 
 long association paths. The reader must bear in mind that Flechsig's 
 conclusions as to the functions of his very numerous areas are in niany 
 cases hypothetical, and can only be accepted when corroborated by 
 other methods. We are far from being able at present to subdivide 
 the functions of the cortex so minutely as is suggested by his map. 
 
 Clinical and Pathological Observations in man agree, upon the 
 whole, with wonderful precision with the results of experiments on 
 animals; and, indeed, before any experimental proof of the minute 
 and elaborate subdivision of the cortex had been obtained, Broca 
 had already, from the phenomena of the sick-bed and the post- 
 mortem room, located a centre for speech in the left inferior frontal 
 convolution (but see p. 971), and Hughlings Jackson had associated 
 pathological lesions of the Rolandic area with certain cases of epi- 
 leptiform convulsions. 
 
 An extensive haemorrhage involving the Rolandic area of the 
 cerebral cortex, or an embolus blocking the middle cerebral artery, 
 causes paralysis of the opposite side of the body. An embolus of a 
 branch of the middle cerebral artery causes paralysis of the muscles. 
 
FUNCTIONS Of THE BRAIN 963 
 
 or rather movements, represente'd in the area supphed by it. A 
 tumour causes symptoms of irritation, motor or sensory — convul- 
 sions beginning in, or sensations referred to, the parts represented 
 in the regions on which it presses. In connection with the locahza- 
 tion of lesions in the ' motor' area of the cortex, and operative 
 interference for their cure, the cortex has been frequently stimulated 
 in man. There is no doubt that the ' motor ' region corresponds 
 closely in position to that of the higher apes. It does not include 
 the postcentral gyrus, for stimulation of this convolution with such 
 strengths of current as are permissible evokes no movements, while 
 movements are readily elicited from the precentral gyrus (Horsley, 
 etc.). In exposing the ' motor ' region, or any particular part of it, 
 the exact position of the fissure of Rolando becomes important; and 
 Thane has given the following simple method for fixing it: The 
 point midway between the point of the nose and the occipital pro- 
 tuberance is fixed by measuring the distance with a tape. The 
 upper end of the fissure of Rolando lies half an inch bebind this 
 middle point. The fissure makes an angle of 67° with the longi- 
 tudinal fissure (Fig. 386). The minor fissures are so inconstant as 
 to afford no safe guidance in the locahzation of a given area. This 
 must be delimited by stimulation. 
 
 Sensory Functions of the Rolandic Area. — There are many proofs 
 that the ' motor ' region is not a purely motor, but a sensori-motor, 
 or kincBsthetic, area. Histological and embryological studies on the 
 course of the sensory paths, as already pointed out, support this 
 conclusion. It has also been mentioned that, according to Goltz's 
 observations (p. 948), removal of the Rolandic cortex causes defects 
 of sensation as well as of movement. In man, in connection with 
 operations on the brain, still better evidence has been obtained. 
 In two cases Gushing was able to elicit tactile sensations by electrical 
 stimulation of the gyrus postcentralis (ascending parietal convolu- 
 tion), and the sense of muscular movement by electrical stimulation 
 of the gyrus precentralis. In a very careful study of a case in which 
 he removed the upper limb area of the right hemisphere in a boy 
 for violent convulsive movements of the whole of the left arm, 
 Horsley came to the conclusion that the precentral gyrus in man 
 is the seat of representation of (i) slight tactile sensation (after the 
 operation appreciation of the lightest tactile stimuli was lost); 
 (2) topognosis — i.e., appreciation of the localization in space of the 
 point touched; (3) muscular sense; (4) stereognosis, or the power of 
 recognizing the form of objects touched and handled; (5) pain — 
 e.g., that caused by a pin-prick; (6) volitional movement. The 
 postcentral gyrus in man appears to be the seat of a similar sensory 
 representation, but as its relation to the efferent impulses concerned 
 in volitional movements is less decided than that of the precentral 
 gyrus, so its relation to afferent impulses, both from the skin and the 
 
964 THE CENTRAL NERVOUS SYSTEM 
 
 deeper structures, is better markfid. From the tield of experiment 
 further evidence of the sensori-motor nature of the ' motor ' region 
 is forthcoming. 
 
 (i) It has been found that if the posterior roots of the nerves 
 supplying one of the Hmbs be cut in a monkey, all the most delicate 
 and skilled movements of the limb are either greatly impaired or 
 totally abolished (Mott and Sherrington). The limb is not used for 
 progression or for climbing, but hangs limp, and apparently help- 
 less, by the side of the animal. That this condition is not due to 
 any loss of functional power by the peripheral portion of the motor 
 path may be assumed, since the anterior roots remain intact. That 
 it is not due to any want of capacity on the part of the ' motor ' 
 centres to discharge impulses when stimulated may be shown by 
 exciting the cortical area of the limb — either electrically or by 
 inducing epileptic convulsions by intravenous injection of absinthe 
 — when movements of the affected limb take place just as readily 
 as movements of the sound limb. The cause of the impairment of 
 voluntary motion, then, can only be the loss of the afferent impulses 
 which normally pass up to the brain, and presumably to the ' motor 
 cortex. When only one sensory nerve-root is cut, no defect of move- 
 ment can be seen; and this is evidently in accordance \sith the fact 
 previously mentioned (p. 891), that complete anjesthesia of even the 
 smallest patch of skin is never caused by section of a single posterior 
 root. And that it is the loss of impulses from the skin which plays 
 the chief part is shown by the fact that after division of the posterior 
 roots supplying the muscles of the hand or foot, which only partially 
 interferes with the sensory supply of the skin, joints, sheaths of 
 tendons, etc., movement is unimpaired; while section of the nerve- 
 roots supplying the skin, those of the muscles being left intact, causes 
 extreme loss of motor power. 
 
 (2) If a strength of stimulus be sought which will just fail to 
 cause contraction of the muscular group related to a given motor 
 area, and a sensory nerve, or, better, a sensory surface (best of all, 
 the skin over the corresponding muscles), be now stimulated, con- 
 traction may occur — that is to say, the excitability of the motor 
 centres may be increased. This shows that the ' motor ' region is 
 en rapport not only with efferent, but also with afferent fibres, that 
 it receives impulses as well as discharges them. 
 
 The same experiment is a proof that the results of excitation of the 
 motor cortex are due to stimulation of the grey matter, and not, as 
 might be objected, of the white fibres of the corona radiata. It is 
 undoubtedly possible to excite these fibres by electrodes directly 
 applied to the motor cortex, but in the latter case the current has to 
 be made stronger than is sufficient to excite the grey matter alone. 
 Further evidence is afforded by the following facts: [a) The ' period 
 of delay ' — that is, the period which elapses between stimulation and 
 contraction — is greater by nearly 50 per cent, when the cortex is stimu- 
 
FUNCTIONS OF THE ISRAIN 
 
 965 
 
 latcd tlum when the white hbres are directly excited. (6) Morphine 
 greatly increases the period of delay for stimluation of the cortex, and 
 at the same time renders the resulting contractions more prolonged 
 than normal, wliile the results of direct stimulation 01 the white fibres 
 are much less, if at all, affected, (c) Stimulation of the grey matter, 
 when separated from the subjacent white matter by the knife, but left 
 in position, is without effect unless the strength of stimulus be increased, 
 although twigs of the current ought, of course, to pass into the corona 
 radiata as easily as before. 
 Perfectly definite movements LI" RF 
 
 can. however, be excited or 
 inhibited by stimulating de- 
 finite spots in the corona radi- 
 ata, and even in the internal 
 capsule. This simply means 
 that in these positions the 
 fibres representing these move- 
 ments are not yet intermingled 
 with fibres representing other 
 movements. 
 
 Sensory Areas — ^Visual Cen- 
 tres. — In the occpital lobe in 
 animals an area of consider- 
 able extent has been found, 
 destruction of which causes 
 hemianopia (p. 923). Thus, 
 if the right occipital cortex is 
 destroyed, the right halves 
 of the two retinae are para- 
 lyzed, and the left half of the 
 field of vision is a blank. 
 There is conjugate deviation 
 of the head and eyes to the 
 5ame side as the lesion — in 
 other words, the animal turns 
 its head and eyes to the right. 
 Destruction of this region on 
 both sides causes complete 
 blindness. When the same 
 region is stimulated, the eyes 
 and head are turned to the 
 left — that is, there is conju- 
 
 Fig. 394. — Diagram oi Relations of Occipital 
 Cortex to the Retinae. RO, LO, right and 
 left occipital cortex; RE, LE, right and left 
 retina; C, optic chiasma; RF, LF, right and 
 left visual fields. The continuous lines 
 passing back from the retinae to the occi- 
 pital cortex represent the crossed, the 
 broken lines the uncrossed, fibres of the 
 optic nerves and tracts. For the sake of 
 simplicity the intermediate stations on the 
 visual path in the anterior corpora quadri- 
 gemina, lateral geniculate bodies, and pul- 
 vinar are not represented in the diagram. 
 For these connections, see Fig. 370, p. 923 
 
 gate deviation to the opposite 
 side. In the higher monkeys the eye movements can be elicited only 
 from the extreme posterior apex of the occipital lobe and from its 
 calcarine region, and then not easily. The movements differ from 
 those produced by stimulation of the area for eye movements in the 
 frontal lobe. They are not so certain, their latent period is longer, 
 and a stronger stimulus is required to evoke them. It cannot be 
 
966 THE CENTRAL MERVOUS SYSTEM 
 
 doubted tliat the occipital region is concerned in vision, and it is a 
 very natural suggestion that the movements are the result of visual 
 sensations in the excited occipital cortex. The right occipital lobe 
 is concerned with vision in the right halves of the two retina (Figs. 
 370 and 3_)4)- Now, under normal conditions, a visual image would 
 be cast on the two right retinal halves by an object placed towards 
 the left of the field. The movements of the head and eyes to the 
 left may therefore be plausibly explained as an attempt to look at, 
 and a rotation towards, the supposed object. 
 
 The pathological evidence is very clear that disease of the occipital 
 lobe, especially of the cuneus, a triangular area on its mesial surface, 
 causes hemianopia in man. A limited lesion may even be associated 
 with an incomplete hemianopia, and cases have been recorded in which 
 colour hemianopia (blindness of the corresponding halves of the two 
 retinae for coloured objects) co-existed with normal vision for white 
 light. The precise limits of the occipital visual area are still disputed. 
 It probably occupies, in addition to the cuneus, the lingual lobule and 
 a portion of the external aspect of the occipital lobe. The question of 
 the projection of the retina upon the visual cortex — i.e., the question 
 whether each retinal area is represented in a definite cortical area — 
 has given rise to much debate. The representation of the fovea cen- 
 tralis, the area of most distinct vision, has aroused especial interest. 
 It has been asserted that a circumscribed area in the region of the cal- 
 carine fissure is the centre for the fovea (Henschen). But it is totally 
 opposed to this view that extensive lesions of the occipital cortex, even 
 on both sides, do not, except in rare cases, cause total blindness in the 
 foveal region, although peripheral vision is destroyed. On the other 
 hand, in no case has a purely cortical lesion been found associated with 
 blindness confined to the fovea (Monakow). The fibres of the optic 
 radiation which are on the path from the fovea are accordingly dis- 
 tributed diffusely to the visual cortex. Sometimes dimness of vision in 
 the whole of the opposite eye (crossed amblyopia), and not hemianopia, 
 is caused by a lesion of the occipital cortex. It seems impossible to 
 explain this and other facts without postulating the existence of more 
 than one visual centre; and it has been supposed that in the angular 
 gyrus and the neighbouring region a higher visual centre exists which 
 is connected with the lower occipital centres for the two halves of the 
 opposite e^-e. Thus, the right angular gyrus would be in connection 
 with the part of the right occipital cortex which has to do with vision 
 in the nasal half of the left eye, and with the part of the left occipital 
 cortex which has to do with vision in the temporal half of that eye. 
 This higher centre, which perhaps functions as a storehouse of visual 
 memories, probably corresponds to the structurally differentiated area 
 (visuo-psychic area of Campbell), as the lower centre corresponds to 
 his structurally differentiated visuo-sensory area (Figs. 391, 392)- 
 
 Auditory Centre. — On the outer surface of the temporo-sphenoidal 
 lobe, mainly in the first temporal convolution, lies an area asso- 
 ciated with the sense of hearing. Stimulation in the region of the 
 hrst temporal convolution may cause the animal to prick up its ears 
 on the opposite side. Destruction of this area on both sides is 
 followed by complete and irremediable loss of hearing. If it is 
 destroyed only on one side, there is partial deafness of the opposite 
 
FUNCTIONS OF THE BRAIN 
 
 967 
 
 ear, and also to sonic extent of the ear on the same side. This is 
 grathuiHy recovered from. If it is destroyed on the left side there 
 is also tlie pecuHar condition called ' word-deafness,' which will be 
 referred to directly (p. 972). In deaf-mutes the first temporal 
 convolution may be atrophied. There is evidence that the posterior 
 corpora quadrigemina and the mesial geniculate body form an in- 
 ferior relay on the route between the fibres of the auditory nerve 
 and the temporal cortex. There are indications that within the 
 auditory area so-called ' musical centres ' exist — that is, an orderly 
 
 SYLVIA 
 FISSURE 
 
 Fig. 395. — Lateral View oi Left Hemisphere with Sensory Areas: Man. 
 of the brain is towards the left. 
 
 The front 
 
 arrangement of the cell-bodies of the neurons that have to do with 
 the perception of pitch, so that a limited lesion may cause deafness 
 to notes of a particular pitch when it is situated on one part of the 
 area, and deafness to notes of a different pitch when it is situated 
 elsewhere (Larionow). 
 
 Centre for Smell. — As to the position of the centre for smell, direct 
 experiment on animals cannot teach us much, for if the outward 
 tokens of visual and auditory sensations are dubious and fluctuating, 
 still more is this the case with the signs of sensations of smell. A 
 
968 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 further source of fallacy is the fact that other sensations tlian those 
 of smell are caused by stimulation of the mucous membrane of the 
 nose. Substances like ammonia, for example, affect entirely the 
 endings of the trigeminus, which is the nerve of common sensation 
 for the nostrils. Pathological and clinical evidence would be of great 
 value, but it is as yet scanty, and of itself indecisive. Some cases 
 of epilepsy have been reported in which the attack was heralded by 
 smells for which there was no objective cause. At necropsy the un- 
 cinate gyrus was found diseased. So far as it goes, such evidence 
 supports the view derived from the anatomical connections of the 
 olfactory tracts, that the centre for smell is situated in the uncinate 
 gyrus on the mesial aspect of the temporal lobe, for the olfactory 
 track may be traced into this region. In animals with a very acute 
 sense of smell, this gyrus is magnified into a veritable lobe, called 
 from its shape the pyriform lobe; from its supposed function, the 
 
 Fig. 396. 
 
 -Sensory Areas of Mesial Surface of Human Brain. The front of the brain 
 is towards the right. 
 
 rhinencephalon. The centre for taste is supposed to be situated in 
 the same region as the centre for smell (in the hippocampal convolu- 
 tion posterior to the uncinate gyrus). 
 
 Ordinary and Tactile Sensations, including the muscular sense, 
 have been located in the Rolandic area (p. 963) ; and there are good 
 grounds for believing that afferent fibres from the joints, the muscles 
 and their accessory structures and the skin terminate here in arboriza- 
 tions which come into contact either with the motor pyramidal 
 cells, or with intermediate cells which link them to the pysamidal 
 cells. 
 
 Our knowledge of the localization of this group of sensations is still 
 unsatisfactory, largely because it has hitherto lx>en necessary to rely 
 almost exclusively upon extirpation experiments, and it is difficult 
 to determine in animals the existence of a local defect of sensation due 
 to a limited cortical lesion. .\ promising new method, the application 
 of strychnine to limited regions of the cortex, seems likely to aid in 
 illuminating this dark corner of cerebral physiology (de Barenne). 
 Changes in cutaneous and deep sensibility of the fore-lnnbs of the cat 
 
FUNCTIONS 01- Till-: lih'AlN 
 
 969 
 
 arc produced— c.i7.. by applying stryclininc to a zone including the 
 gyrus signu.idcus anterior, the frontal part of the gyrus siginoueus 
 posterior, the frontal part of the gvrus suprasylvius and the iniddlc 
 third of the gyrus cctosylvius anterior. The zone for the head almost 
 completely overlaps the fore-limb zone. The zone for the hind-limb 
 occupies the frontal half of the gvrus marginalis. 
 
 As regards the cutaneous sensibilitv localized in these zones, both 
 sides of the body seem to be represented in the cortex of one hemi- 
 sphere, but the opposite side the most. The disturbances of deep 
 sensibility caused by the application of strychnine to the cortex of one 
 hemisphere are confined to the bones, tendons, and muscles of the 
 opposite side of the body. The remainder of the region of the cortex 
 
 \,aiiiv^J^'^- 
 
 lag con. o.f 
 
 C/i"os£eflL 
 Sy nx^xXo-n-uiXoLo qy 
 
 Fig. 397. — Zones for Cutaneous and Deep Sensibility on the Convexity of the Left 
 Cerebral Hemisphere of the Cat (Dusser de Barenne). The chief gyri and sulci 
 are indicated, s.cr., Crucial sulcus; F.S., fissure of Sylvius; a, the 'compensa- 
 tory ansate fissure ' of Campbell. 
 
 which responds to strychnine by sensory changes is called by de 
 Barenne, the zone of ' crossed symptomatology,' because the altered 
 or increased sensitivity of the skin is manifested in the fore-limb of the 
 same side, and the hind-limb of the opposite side. He suggests that 
 the sensory mechanism in this area may be related to the movements 
 of progression. In so far as these sensory zones overlap the motor area 
 a common sensori-motor cortical zone may be said to exist. 
 
 Aphasia. — Words are, at bottom, arbitrarv signs by which certain 
 ideas are expressed. The power of intelligent communication by spoken 
 or written language may be lost: (i) by paralysis of the muscles of 
 articulation or the muscles which guide" the pen; (2) by inability to 
 hear or sec the spoken or written word — i.e., by deafness" or blindness; 
 (3) by inability to comprehend the meaning of spoken or written lan- 
 guage, although sensations of hearing and sight mav not be abolished 
 
97<» THE CENTRAL NERVOUS SYSTEM 
 
 — that is to say, by inability to interpret the auditory or visual symb )ls 
 by which ideas are conveyed; (4) by inability to clothe ideas in words, 
 althougli the words may be present in the patient's consciousness, and 
 the ideas conveyed by speech or writing may be comprehended. 
 Neither (i) nor {2) is considered to constitute the condition of aphasia; 
 (3) represents what is called amnesia, or sensory aphasia : (4) is aphasia 
 in the ordinary restricted sense, or motor aphasia. 
 
 Motor aphasia may be divided into two varieties — subcortical or pure 
 motor aphasia, and cortical, or Broca's aphasia. In t^e subcortical 
 type the patient understands speech and writing perfectly, and is able 
 to write normally; but he cannot speak spontaneously or read aloud, 
 or repeat words when requested to do so. He may know quite well 
 what to reply in answer to a question, but the words necessary to 
 express his meaning do not come to him. In Broca's type of aphasia, 
 which is the most common, the patient may understand spoken 
 and written words — often imperfectly, it is true — but he is unable to 
 speak spontaneously, to repeat words spoken to him, and to read aloud. 
 Unlike the person suffering from the subcortical type of motor aphasia, he 
 has difficulty in reading by the eye without articulation, and in writing 
 spontaneously or to dictation. There is often or always some intellectual 
 deficiency. The gradations in the loss of the expressive factor in speech 
 may be infinite. A patient may sometimes sing a song without a single 
 slip in words or measure, and yet be unable to speak or write it. In a 
 case recorded by Larionow an aphasic could speak only one syllable, 
 ' tan,' but could sing the ' Marseillaise.' In certain cases the change 
 is confined to loso of the power of spontaneous speech, and the patient 
 may be able to read intelligently. Sometimes he can express his ideas 
 in speech, but not in writing (agraphia). Sometimes the loss is restricted 
 to certain sets of ideas. For example, a boy was injured by falling on 
 his head. Typical symptoms of motor aphasia developed, but the 
 power of dealing with ideas of number was not interfered with, and 
 the boy continued to learn arithmetic as if nothing had happened. 
 Proper names and nouns are more easily lost than adjectives and verbs. 
 Motor aphasia is generally accompanied by paralysis, frequently 
 transient, of voluntary movement on the right side, sometimes amount- 
 ing to complete hemiplegia, but more often involving the right arm alone. 
 This association is generally explained by the proximity of the inlerior 
 frontal convolution to the motor area of the arm, and their common 
 blood-supply. It has already been stated that since Broca it has been 
 generally assumed that in most persons the inferior frontal convolution 
 on the left side is concerned in the expression of ideas in spoken or 
 written language. It is even said that oratorical powers have been 
 found associated with marked development of this convolution (as in the 
 case of Gambetta, the French statesman). It is the cortical or Broca's 
 type of motor aphasia which has been supposed to be associated with a 
 lesion in the left inferior frontal convolution. The portion of the con- 
 volution concerned is the posterior extremity, where it borders on the 
 fissure of Sylvius, and it either completely coincides with or largely 
 overlaps the centre for the movements of the tongue, lips, and larynx 
 concerned in articulation. The failure, however, does not lie in the 
 articulatory mechanism. The patient uses the same muscles of articu- 
 lation, without any marked impairment of function, for chewing and 
 swallowing his food. It is only when the corresponding area in the 
 right inferior frontal convolution, or the path from it to the internal 
 capsule, is also destroyed, that articulation is greatly and permanently 
 interfered with. 
 
 The question obviously presents itself whj'' it is that motor aphasia is 
 
FUNCTIONS OF THE BRAIN 971 
 
 commonly due to a lesion in the left hemisphere alone. The answer to 
 this question is supposed to be partly supplied by the important and 
 curious observation that in left-handed individuals damage to the right 
 inferior frontal convolution may cause aphasia. In the right-handed 
 man the motor areas of the left hemisphere may be supposed to be more 
 highly educated than those of the right hemisphere. The movements 
 of the right side which they initiate or control are stronger and more 
 delicate and precise than those of the left side. It is only necessary to 
 assume that this processs of specialization, of selective training, has 
 been carried on to a still greater extent in the left frontal convolution, 
 that in most men the speech-centre there has taken upon itself the whole, 
 or the greater part, of the labour of clothing ideas in words, leaving to 
 the right centre only its primitive but undeveloped powers. In left- 
 handed persons the speech-centre on the right side may be supposed to 
 share in the general functional development of the right hemisphere. 
 That great capabilities are lying dormant in the right speech-centre of 
 the ordinary right-handed individual is indicated by the fact that after 
 complete destruction of the left inferior frontal convolution the power 
 of speech may be to a considerable extent, though slowly and laboriously 
 regained; and it is said that this second accumulation may be swept 
 away, and without remedy, by a second lesion in the right inferior frontal 
 convolution. But frail is the tenure of life in a person who has twice 
 suffered from such a lesion ; and we do not know whether recovery might 
 not take place to some extent even after destruction of both inferior 
 frontal convolutions, if the patient only lived long enough. 
 
 Recently ]\Iarie has reopened the whole question of the relation of 
 aphasia to lesions of the inferior frontal convolution. He believes that 
 the so-called Broca's area has nothing to do with aphasia in the proper 
 sense of the term — i.e., it is not a cortical area concerned in ' internal ' 
 speech processes, or in which motor or kinaesthetic ' speech memories ' 
 are stored — but simply a ' motor ' area for the movements of articula- 
 tion. He maintains that there is but one form of true aphasia — the 
 aphasia of Wernicke — which has for its basis a lesion of the so-called 
 zone of Wernicke (the supramarginal and angular gyri, and the posterior 
 portions of the first and second temporal convolutions) . This, according 
 to him, is the true speech-centre. The symptom-complex known as 
 Broca's aphasia, which everybody admits to exist as a distinctly charac- 
 terized clinical condition, is due, he says, to a double lesion. One lesion 
 causes aphemia (loss of the power of co-ordinating the movements 
 needed in the articulation of words without actual paralysis of the 
 muscles), and the other the disturbance of internal speech, and the 
 difficulty of reading and of writing, which constitute the true aphasia. 
 According to Marie, the lesion which causes the aphemia is not even 
 situated in Broca's convolution, but somewhere in a rather badly de- 
 fined region, which he denominates the lenticular zone, since it includes 
 the lenticular as well as the caudate nucleus, in addition to the external 
 and internal capsules and the cortex of the island of Reil. It would be 
 out of place to enter more minutely here upon such controversial 
 matters. The conclusion which emerges most definitely from the dis- 
 cussion is that Broca's localization was based upon a very narrow 
 foundation, and must probably be modified. 
 
 It is generally recognized that in almost all cases of aphasia in which 
 the brain has been studied after death, some lesion of association fibres 
 has been present, and not merely a cortical lesion. Interference with the 
 association fibres causes confusion in the processes of association which 
 are so important in mental activity', and defects of intelligence are there- 
 fore commonly observed in aphsisia. 
 
972 THK CENTRAL NERVOUS SYSTEM 
 
 A so-called temporary' aphasia may occur without any structural 
 change in the speech-centre — for exajnpie, during an attack of migraine. 
 In children it may even be caused by some comparatively slight irrita- 
 tion in the digestive tract, such as that due to the presence of a tape- 
 worm. 
 
 In the anthropoid apes no evidence of the existence of any ' speech- 
 centre,' even distantly foreshadowing the human, has been obtained 
 by stimulating tlic inferior frontal convolution on either side. No move- 
 ments, and particularly no movements connected with vocalization, are 
 elicited. 
 
 Sensory Aphasia. — In typical motor aphasia spoken and written 
 words convey to the patient their ordinary meaning. They call up in 
 his mind the usual sequence of ideas, but the chain is broken at the 
 speech-centre, and the outgoing ideas cannot be clothed in words. The 
 expressive factor in speech is deranged. In sensory- aphasia the percep- 
 tive factor in speech is deranged. In ordinary sensory aphasia [Wer- 
 nicke's, or cortical sensory aphasia) the patient cannot understand 
 spoken or written language, but, far from being unable to speak, he 
 often babbles incessantly. He may string together a series of words, 
 each correctly articulated, but having no meaning, or may utter a jargon 
 not composed of known words at all. Instead of the words which he 
 desires to use to express his meaning, he may use others having a 
 similar sound {paraphasia). Damage to two regions of the brain has 
 been found associated with this condition: (i) the middle part of the 
 first and second temporal convolutions, (2) inferior parietal convolu- 
 tions and the angular g>'rus in the neighbourhood of the occipital visual 
 centre. When the temporal region is alone affected, it is the spoken 
 word that is missed, the written that is understood {word-deafness). 
 When, as occasionally happens, the lesion is confined to the occipital 
 region, spoken language is perfectly understood, written language not 
 at all {word-blindness) . It is the left hemisphere wh'ch is affected in 
 right-handed persons, the right hemisphere in left-handed persons. 
 Sensory, like motor aphasia, may exist in any degree of completeness, 
 from absolute word-deafness or word-blindness, in which no spoken or 
 printed word calls up any mental image, to a condition not amounting 
 to much more than a marked absence of mind or unusual obtuseness. 
 Motor and sensory aphasia may be present together. In well-marked 
 cortical word-deafness speech is always interfered with to some extent. 
 In so-called pure word-deafness (subcortical sensory aphasia) the patient 
 may be perfectly capable of rational speech. He may talk to himself 
 or on a set topic with fluency and sense, may write intelligently, and 
 understand what he reads ; but he may be unable to understand a single 
 word spoken to him, or to repeat words when asked to do so. 
 
 Cortical Epilepsy. — Disturbed action of the motor centres may take 
 the form either of depression or of increased excitability. The former 
 will be associated with partial or complete paralysis of the movements 
 represented in the area, the latter by abnormally intense or prolonged 
 discharge leading to the condition called cortical epilepsy — that is. 
 epileptic attacks associated with cortical lesions. Among these are the 
 cases of so-called Jacksonian epilepsy — a condition characterized by the 
 fact that the seizure does not begin by general, but by local, convulsions. 
 They may remain confined to a single limb, or to one side of the face, or 
 to one side of the body. So long as the convulsions are not general, 
 consciousness need not be lost. Or a seizure beginning as Jacksonian 
 may spread so as to involve the whole body, in which case the symptoms 
 become identical with those of ordinary ep'lep.«^y, including the loss of 
 consciousness. It has been found possible in some cases to localize the 
 
FrSCTIONS OF THE BRATN 973 
 
 position of the lesion from the part of the body in which the lit, or the 
 aura (the sensation or group of sensations peculiar to each case, which 
 precedes and announces the ati:ack) begins. For example, if the con- 
 vulsions commence with a twitching of the right thumb and extend over 
 the arm, or if the aura consists of sensations beginning in the thumb, 
 there is a strong presumption that the seat of the lesion is the part of the 
 arm-area known as the ' thumb-centre ' in the left cerebral hemisphere. 
 It is the seat of the convulsion at its commencement, not the regions to 
 which it may afterwards spread, that is important in diagnosing the 
 position of the lesion. For just as strong or long-continued electrical 
 stimulation of a given ' centre ' of the ' motor ' cortex may give rise to 
 contractions of muscles associated with other ' centres,' so the excita- 
 tion set up by localized disease may spread far and wide from its 
 original focus, involving area after area of the ' motor ' region first in 
 the one hemisphere and then in the other. The part of the body to 
 which a sensory aura is referred is as significant an indication of the 
 seat of the discharging lesion as is the part of the body which first begins 
 to twitch. This is one of the proofs that the ' motor ' region is not a 
 purely motor area. Disturbed action of the sensory areas on the cortex 
 may, as in the case of the motor regions, take the form either of de- 
 ficiency or of excitation. Excitation expresses itself by hallucinations, 
 the person having the impression of a sight, a sound, a smell or taste, or 
 one or other of the cutaneous sensations in the absence of the related 
 objects. 
 
 Seat of Intellectual Processes — ^Association Areas. — When we 
 have deducted from the cortex of the hemisphere the vi^hole Rolandic 
 region and the sensory centres, there still remains a large territory 
 unaccounted for. Considerable portions of the occipital, parietal, 
 and temporal lobes, nearly the whole of the island of Reil and the 
 greater part of the frontal lobe anterior to the ascending frontal 
 convolution are ' silent areas,' and respond to stimulation by neither 
 motor nor sensory sign. They correspond to the association 
 centres previously referred to. They are connected with the 
 sensory and motor areas and with each other, but are not directly 
 connected by projection fibres with the lower parts of the central 
 nervous system, as the motor area, for example, is by the pyramidal 
 path. By a process of exclusion it has been supposed that, in addi- 
 tion to, or partly in virtue of, their associative function, they are 
 the seat of intellectual and psychical operations. It is supposed 
 that the sensations aroused in the various sensory areas by the 
 impulses received from the sense organs are linked in the associa- 
 tion areas into complex perceptions. For instance, when an 
 orange is taken into the hand, the visual sensation of a yellow body, 
 the tactile sensation of a smooth round body, and perhaps the 
 olfactory sensation characteristic of an orange, are collected from 
 the sensor}^ areas, connected and combined, or synthesized in an 
 association area to the concept of an orange. Somewhere in the 
 association areas it is to be supposed is stored the memory of past 
 experiences. The intellectual function has been more particularh' 
 assigned to the frontal lobes, and with great probability, although 
 
974 THF. CENTRAL NERVOUS SYSTEM 
 
 we have little real knowledge to guide us to a decision. Extensive 
 destruction and' loss of substance of the prefrontal region may 
 sometimes occur without any marked symptoms. But usually 
 there is restriction of mental power, or it may be loss of moral 
 restraint. Thus in the famous ' American crowbar case,' an iron 
 bar completely transfixed the left frontal lobe of a man engaged 
 in blasting. Although stunned for the moment, he was able in 
 an hour to climb a long flight of stairs, and to answer the inquiries 
 of the surgeon. Finally, he recovered, and lived for nearly thirteen 
 years without either sensory or motor deficiency, except that he 
 suffered occasionally^ from epileptic convulsions. But his intellect 
 was impaired; he became fitful and vacillating, profane in his 
 language and inefficient in his work, although previously decent in 
 conversation and a diligent and capable workman. 
 
 Flechsig supposes that his great anterior association centre in the 
 frontal lobe is concerned in the retention of the memory of all conscious 
 bodily experiences, especially those connected with voluntary acts. 
 The great posterior association centre he imagines to be engaged in the 
 formation and collection of ideas of external objects and of the ' word 
 pictures ' which represent them, and with the preparation of speech in 
 respect of the thoughts to be expresseji and the form of expression, the 
 office of the Broca's area (but see p. 971) being to execute the mechanical 
 part of the process by transforming these thoughts into actual spoken 
 words. This posterior association centre may be looked upon as the 
 seat of intellect in the narrower sense, as the anterior is of will and feeling. 
 
 The experiments of Franz on the relation of the cerebral association 
 areas, and especially the frontal area, to certain acquired habits are of 
 interest. Cats were allowed to acquire certain habits involving simple 
 mental processes, and then it was seen how these were affected by 
 cortical lesions. After bilateral extirpation of the frontal lobes (the 
 area anterior to the crucial sulcus) newly-formed, but not long-standing, 
 habits are lost. This cannot be due to shock, since other brain lesions 
 are not followed by loss of the habits. Extirpation of one frontal area 
 usually causes a partial loss of newly-acquired habits, or, rather, a slow- 
 ing of the association process leading to unusual delay in the execution 
 of the movements connected with the habit. Habits once lost after 
 removal of the frontal lobes may be releamed. 
 
 The influence of psychical events upon bodily functions is well known 
 and has been more than once illustrated in preceding pages. The con- 
 verse question of the influence of bodily states upon psychical e\•ent^ 
 has also been raised, especially in connection with the genesis of emotion. 
 Some psychologists assume that the bodily changes associated with such 
 emotions as grief, fear, rage, or love, are not evoked as a consequence ol 
 the emotions, but that the bodily changes follow directly the perception 
 of the exciting fact — e.g., a spectacle which causes fear or rage, ' and 
 that our feeling of the same changes as they occur is the ernotion ' 
 (James). Sherrington, however, has shown that in dogs in which, by 
 transection of the vagi and the spinal cord, all sensation of viscera, skin, 
 and muscles behind the level of the shoulder was eliminated, no obvious 
 emotional defect was caused. Notwithstanding the immense abridg- 
 ment of the field of sensation, anger, joy, fear, disgust (as on being 
 offered dog's flesh, which most dogs refuse to eat), were as marked as 
 ever, and were evoked by the same objects as before the operation 
 
FUNCTIONS OF THE BRAIN 975 
 
 When the afferent field is still more restricted, as in the head of a dog 
 grafted on the circulation of another dog by anastomosis of the blood- 
 vessels, with precautions to avoid interruption of the blood-flow, not 
 only docs the respiratory centre continue to discharge itself with a 
 regular rhythm, but cortical volitional movements persist (Guthrie, 
 Pike, and Stewart), and, so far as can be judged, sense perception, 
 emotional, and even intellectual, processes continue. In one case the 
 picture represented by the engrafted head was essentially the same as 
 that presented by the head of the ' host ' for over two hours. In a 
 transplanted head from a younger dog in which the circulation had 
 been interrupted for twenty-nine minutes, a remarkable return of 
 cerebral function was observed (Guthrie). 
 
 Conditioned or Conditional Reflexes. — This is perhaps the place to 
 refer briefly to certain phases of brain function which have been illus- 
 trated by the work of Pawlow, already alluded to in Chapter VI, on 
 the so-called psychical secretions. This study has led him to formulate 
 some novel views of the higher nervous activities. He has shown, for 
 instance, that if food is presented to an animal, and at the same time 
 the skin of the foot i^: stimulated electrically, the psychical secretion 
 of saliva, which the mere sight or smell of the food brings about, be- 
 comes, when the experiment has been repeated for a sufficient number 
 of times, associated with the electrical stimulus. It is then no longer 
 necessary to offer the food in order to elicit the secretion ; all that is re- 
 quired is to stimulate the foot. Even the nature of the stimulus may 
 be altered, cutting or burning the foot being substituted for the electri- 
 cal excitation ; the secretion is still obtained. Pawlow has termed such 
 reactions conditioned or conditional reflexes, because, unlike the 
 ordinary spinal and bulbar reflexes which are always obtainable and 
 are therefore spoken of as unconditioned reflexes, the conditioned re- 
 flexes depend upon the establishment of certain conditions, such as the 
 associated influence of some stimulation of the sense organs or of psy- 
 chical excitation. He concludes from his extensive studies on this 
 subject that an important function of the central nervous system, and 
 especially of the cerebrum, in addition to its power of integrating or 
 correlating nerve impulses, is that of dispersing impulses, producing new 
 types of activity and new reflexes. 
 
 Localization of Function in the Central Nervous System. — Let 
 us now consider a little more closely the real meaning of this 
 localization of function. Scattered all over the grey matter of 
 the primitive neural axis, and, as we have seen, over the grey mantle 
 of the brain as well, are numerous ' centres ' which seem to be 
 related in a special way to special mechanisms, sensory, secretory, 
 or motor. The question may fitly be asked whether those centres 
 are really distinct from each other in quality of structure or action, 
 or whether they owe their peculiar properties solely to differences 
 in situation and anatomical connection. It is clear at the outset 
 that the nature of the work in which a centre is engaged must be 
 largely determined by its connections. The kind of activity which 
 goes on in the vaso-motor centre in the bulb, for example, may 
 in no essential respect differ from that which goes on in the respira- 
 tory centre. The calibre of the bloodvessels will alter in response 
 to a change of activity in the one because it is anatomically con- 
 
q76 TUl'- Cr.MTKAL NERVOUS SYSTEM 
 
 nected with the muscular coat of the bloodvessels. Tiie rate or 
 depth of the respiratory movements will alter in response to a change 
 of activity in the other, because it is connected witli muscles which 
 can act u})()n the chest-walls. 
 
 Experiments on the anastomosis of nerves afford a very interest- 
 ing illustration of the (kti-rniining influence of their peripheral con- 
 nections on the function of nerve-fibres. It has, in fact, been 
 shown that the central end of any efferent somatic fibre — i.e., any 
 fibre running from the central nervous system and ending in 
 striated muscle — can make functional connection with the peri- 
 pheral end of any other efferent fibre of the same class, whatever 
 be the normal actions produced by the two fibres. Advantage has 
 been taken of this in surgery. For instance, in a case of severe 
 facial (motor) tic the facial nerve was divided, and its peripheral 
 end united with a portion of the fibres of the spinal accessory. The 
 voluntary movements of the face, after regeneration had occurred, 
 were normally carried out through impulses descending the spinal 
 accessory. In cases of local paralysis, due to destruction of anterior 
 horn-cclis (anterior poliomyelitis), restoration of movement has also 
 been obtained by connecting the motor nerve of the paralyzed muscles 
 to a portion of a nerve coming off from an uninjured region of the 
 cord. But the possibilities of this procedure have been exaggerated 
 
 By such operations it has been possible to transpose motor areas 
 on the cerebral cortex associated with the flexion and extension 
 of a particular joint, so that the part of the cortex which originally 
 caused flexion after the nerve anastomosis causes extension, and 
 vice versa. When the nerves supplying a group of muscles of the 
 dog's fore-limb are eliminated, the nerves of the antagonistic group 
 may be used to supply both groups, and co-ordinated movements 
 may be restored, although this does not occur so rapidly as when 
 the nerves supplying the two groups are simply cut and cross- 
 sutured (Kennedy). However, the limitations of this method 
 ought to be recognized. Before any anastomosis of nerves can be 
 made, good fibres must first be destroyed. Under favourable cir- 
 cumstances these may all regenerate and find their way to the struc- 
 tures they are intended to innervate. When regeneration is com- 
 plete, the number of fibres capable of functioning will at best be the 
 same as before the operation, and may easily be considerably less. 
 The benefit, whatever it is, will be associated solely with the re- 
 distribution of the fibres. There is reason to think that the closer 
 to the cell of origin a nerve is injured or divided, the less is the chance 
 of restoration, and Feiss has found that after lesions in the cord 
 or the spinal roots neither the anatomical pattern of the affected 
 nerves nor their functional power is much affected by subsequent 
 nerve anastomosis. 
 
 The central end of any efferent somatic fibre can also make 
 
FVXcTioxs or Tin- /5/?.i/.v 077 
 
 functional union with tlic peripheral end of any of the efferent fibres 
 which run from the central nervous system and end in ganglion 
 cells (pre-ganglionic fibres), and the central end of any pre-gan- 
 glionic fibre can do the same with the peripheral end of any efferent 
 somatic fibre (Langley and Anderson). For instance, Langley 
 divided (in cats) the vagus nerve and the cervical sympathetic. 
 The peripheral end of the former degenerated, of course, below the 
 section, and the peripheral (cephalic) end of the latter degenerated 
 above the section, up to the terminations of its axons in the 
 supsrior cervical ganglion. The central end of the cut vagus was 
 subsequently sutured to the peripheral end of the cut sympathetic. 
 After a time the vagus-fibres grew along the course of the degener- 
 ated sympathetic up to the ganglion, where some of them formed 
 arborizations around the ganglion cells. It was now found that 
 stimulation of the vagus produced the effects usually caused by 
 stimulation of the cervical sympathetic — for example, dilatation 
 of the pupil and constriction of the bloodvessels of the head and 
 neck. From these experiments it follows that the functions of the 
 various groups of fibres in the cervical sympathetic do not depend 
 on anything pecuHar to the fibres; any fibre which can make con- 
 nection with one of the ganglion cells that send axons to the 
 dilator muscle of the iris will, when stimulated, act as a pupillo- 
 dilator fibre, just as well as a cervical sympathetic fibre. Other 
 instances of the same law have already been given in connection 
 with the regeneration of nerves (p. 800). 
 
 Functional union does not take place between efferent somatic 
 fibres (or pre-ganglionic fibres) and post-ganglionic fibres — i.e., 
 fibres arising in peripheral ganglia, and ending in smooth muscle 
 and glandular tissue; e.g., the cervical s3-mpathetic after excision 
 of the superior cervical ganglion does not unite with the fibres 
 leaving the anterior end of the ganghon in such a way that stimula- 
 tion of it can produce any of the effects normally produced through 
 these fibres. No proof has been given that afferent fibres can unite 
 with efferent fibres or efferent with afferent. 
 
 Afferent fibres of one nerve can unite with afferent fibres of 
 another nerve, but there is not sufficient evidence to show whether 
 fibres concerned in one sensation can unite with fibres concerned 
 in another. 
 
 The localization of function in the cerebral cortex has been likened to 
 the localization of industries in the multiplex commercial life of the 
 modem world. The barbarian household in which cloth is woven and 
 worked into garments; sandals, or moccasins cobbled together; rough 
 pottery baked in the kitchen fire, and all the rude furniture of the lodge 
 fashioned by the hands which built it, and which rest beneath its roof at 
 night — this state of things where centralization has not yet begun, it 
 has been said, is a picture of what goes on in the undeveloped brains of 
 the frog, the pigeon, and the rabbit. The ' diffusion ' of industries 
 which is characteristic of a primitive state has given place among the 
 
 62 
 
978 THE CKSTRAL NERVOUS SYSTEM 
 
 most highly civilized men to extreme centralization and concentra- 
 tion. Manchester spins cotton and Liverpool ships it. Chicago handles 
 wheat and pork that ha\'e been produced on the prairies of Alinnesota 
 and Illinois. Amsterdam cuts diamonds. Munich brews beer. Lyons 
 weaves silk. New York and London are centres of finance. This, it is 
 said, is the picture of the highly specialized brain of a monkey or a man. 
 But ingenious and alluring though such analogies are, they do not rest 
 upon a sufficient basis of fact. Indeed, the more deeply the structure 
 and function of the central nervous system are studied, the more clearly 
 does its essential solidarity appear, the more clearly does it emerge as an 
 organized co-ordinated system, not an aggregate of separate mechanisms 
 jumbled together for convenience of storage in the protected cranio- 
 spinal cavity. 
 
 It has never been shown — nor is it likely that the proof will soon be 
 forthcoming — that there is any difference whatever in the physical, 
 chemical, or psychical processes which go on in the various centres of 
 the ' motor ' cortex. It may be supposed, indeed, that the so-called 
 sensory areas of the cortex differ more widely in their internal activity 
 from the ' motor ' areas than the latter do among themselves, and that 
 the activity of the anterior portion of the brain, the portion which has 
 been credited par excellence with pyschical functions, differs in kind, not 
 merely in degree, from that of all the rest. But, as we have just seen, 
 even the ' motor ' areas have sensory functions. A cast-iron physiology 
 may explain this by the assumption of ' sensory ' as well as ' motor ' 
 cells in the Rolandic area, and may find support for such an assumption 
 in the well-known fact that the large pyramidal cells whose axons form 
 the pyramidal tract make up but a small proportion of the total number 
 of pyramidal cells in this region, which, besides, contains numerous cells 
 of Golgis second type (p. 856)- And although it may be true that the 
 tactile sensations constituting the so-called body-sense are represented 
 mainly not in the motor region itself, but in the adjacent gyrus post- 
 centralis posterior, to the Rolandic fissure (p. 951), there is nothing to 
 contradict the supposition that the discharge of energy- from the most 
 circumscribed motor area or element may be accomi>anied with con- 
 sciousness. And, indeed, some writers have supposed that such a 
 consciousness of, or even conscious measurement of, the discharge 
 from the ' motor ' areas is the basis of the muscular sense (Bain, 
 Wundt). 
 
 So far, at least, as the ' motor ' region and the grey matter imme- 
 diately around the neural canal are concerned, the analogy of an 
 electrical switch-board connected with machines of various kinds might 
 be more correct. Touch one key or another, and an engine is set in 
 motion to grind corn, or to saw wood, or to light a town. The difference 
 in result lies not in any difference of material or workmanship in the 
 switches, but solely in the difference in their connections. 
 
 Grey matter in the upper part of the precentral convolution is excited, 
 ?.nd the muscles of the leg contract. Grey matter on the lower part of 
 the convolution is excited, and there are movements of the face and 
 mouth. Grey matter in the medulla oblongata is excited, and the 
 salivary glands pour forth a thin, watery fluid, poor in proteins, and 
 containing an amylolytic ferment. Another portion of grey (?) matter 
 in the medulla is thrown into activity, and the pancreatic ducts 
 become flushed with a thicker secretion, relatively rich in proteins and in 
 ferments which act on proteins, starch, and fat. Here, too, there is a 
 variety in result according as one or another nervous switch is closed ; 
 here, too, the variety is due. not to essential differences in the structure 
 of the acti\ ity or the nervous centres, but to their connection, by nervous 
 
FUNCTIONS OF THE BRAIN 970 
 
 paths, with pcripchral organs ol different kinds. There is, indeed, a 
 specialization, a localization, of function, but the localization is at the 
 peripherv', the specialization is in the peripheral organs. 
 
 It may be asked whether, if this is the case for the peripheral organs 
 of efferent nerves, the converse does not hold true for the afferent nerves 
 — in other words, whether the localization here is not at the centre. And 
 that there is in some degree a central localization of sensation may be 
 considered proved by the well-known clinical fact, already referred to, 
 that sensations of various kinds may be produced by pathological 
 changes in the cortex. For example, a tumour involving the upper part 
 of the temporal lobe may give rise to epileptiform convulsions preceded 
 by an auditory aura, a sound, it may be, resembling the ringing of bells; 
 a tumour involving the occipital region may cause a visual aura, and so 
 on. Central sensory localization is the fundamental idea of the old 
 doctrine of the specific energy of nerves, which, in modem phraseology, 
 expresses the fact that excitation of the central end of a sensory nerve 
 by various kinds of stimuli causes always — or at least very often — the 
 particular kind of sensation appropriate to the nerve. The observation 
 so frequently made in surgery before the days of anaesthetics, that when 
 the optic nerve was cut in removing the eyeball the patient experienced 
 the sensation of a flash of light, * was long looked upon as the strongest 
 prop of the law of specfic energy, and well illustrates the meaning of the 
 term. Here a mechanical excitation of the optic fibres in their course 
 gives rise to the same sensation as excitation of the retina by the 
 natural or homologous or adequate stimulus of light. Since a similar 
 mechanical stimulus applied to the auditory nerve gives rise to a sensa- 
 tion of sound, and, applied to the trigeminal nerve, to a sensation of pain, 
 many physiologists have assumed that the impulses set up in the 
 auditory nerve when sound impinges on the tympanic membrane do not 
 differ essentially from those set up in the optic nerve when a ray of light 
 falls upon the retina, or from those set up in the fifth nerve by the irri- 
 tation of a carious tooth, or from those set up in certain fibres of the 
 cutaneous nerves when a warm body comes in contact with the skin. 
 Since the results in consciousness are very different, this assumption has 
 necessitated the further conclusion that somewhere or other in the 
 central nervous system there exist organs that are differently affected 
 by the same kinds of afferent impulses — in other words, that senson,' 
 localization is at the centre. On this view, the viscual areas in the cortex 
 respond to all kinds of stimuli by visual sensations ; the auditory areas 
 by sensations of sound, and so on. 
 
 But while it cannot be doubted that special sensory regions exist in 
 the grey matter of the brain, where the afferent paths concerned in the 
 different kinds of sensation end, it has not been proved that the nerve- 
 impulses which travel up the various paths are absolutely similar until 
 they have reached the centres, and there suddenly become, or produce, 
 sensations absolutely different. There is, indeed, evidence of a certain 
 amount of sensory specialization at the periphery. For example, when 
 an ordinary nerve-trunk is touched, the resultant sensation is not one 
 of touch. If there is any sensation at all, it is one of pain. Heating 
 or cooling a naked nerve-trunk gives rise to no sensations of tempera- 
 ture. When the ulnar nerve is artificially cooled at the elbow, the first 
 effect is severe pain in the parts of the hand supplied by the nerve. The 
 pain disappears somewhat abruptly as cooling goes on, and is succeeded 
 by gradual loss of all sensation in the ulnar area of the hand ; but the 
 cooling of the nerve-trunk does not give rise to any sensation of cold 
 (Weir Mitchell). Stimulation of the receptors or end -organs is normally 
 
 * It is said that this is not always the cas«. 
 
986 THE CENTRAL NERVOUS SYSTEM 
 
 essential in order that sensations of touch and temperature should be 
 experienced, .\lthough as previously stated, one great function of 
 the receptor is to lower the threshold of the adequate stimulus, 
 and thus to render the afferent neuron more easily excited by an 
 adequate stimulus than by any other, it may also serve to impress a 
 particular rhythm or other character upon the nerve impulse, so that the 
 afferent impulses may be to some extent differentiated before they reach 
 their centres. One reason, then, why excitation of the temporal cortex 
 by impulses falling into it along the auditory nerve-fibres causes a sensa- 
 tion different from that caused by impulses reaching the occipital cortex 
 through the fibres of the optic nerve may be a difference in the nature of 
 the impulses. If this were the only reason, it would follow that were it 
 possible to physiologically connect the fibres of the optic radiation with 
 the temporal cortex, and those of the temporal radiation with the 
 occipital cortex, sights and sounds would still be perceived and dis- 
 criminated in a norr.ial manner, although now the integrity of the 
 occipital lobe would be bound up with the perception of sound, the 
 integrity of the temporal lobe with visual sensation. This state of 
 affairs would correspond to complete specialization for sensation in the 
 peripheral organs, complete absence of specialization in the centres. On 
 the other hand, it is conceivable that, after such an ideal experiment, 
 sound-waves falling on the auditors^ apparatus might cause visual 
 sensations, and luminous impressions falling on the retina sensations of 
 sound. This would correspond to complete specialization of sensation 
 in the centres, complete absence of specialization at the periphery. A 
 third possibility would be that the ' tran.sposed ' centres, responding at 
 first feebly or not at all to the new impulses, might, by slow degrees, 
 become more and more excitable to them. This would correspond to a 
 peripheral specialization, combined with a tendency to development oi 
 central specialization. And, indeed, it is not easy to conceive in what 
 way, except as the result of differences in the nature of impulses coming 
 from the periphery', specialization of sensor^^ areas in the central nervous 
 system could have at first arisen. 
 
 Degree of Localization in Different Animals. — Before leaving this 
 subject, two points ought to be made clear: (i) The degree of 
 localization of function in the cortex goes hand in hand with the 
 general development of the brain. In man and the monkej-, the 
 motor localization is more elaborate than in the dog — that is to 
 say, a greater number of movements can be associated with definite 
 cortical areas. In the rabbit, whose ' motor ' centres have been 
 particularly studied in recent years by Mann and ]\Ii]ls, localization 
 is still less advanced than in the dog. Towards the bottom of the 
 mammalian group certain ' motor ' areas can still be demonstrated, 
 though they are rather ill-defined, for instance in the hedgehog 
 (Mann), opossum (Cunningham), and ornithorhynchus (Martin). 
 In general the movements of the anterior limb are easier to obtain 
 than those of the posterior. In birds Mills found no evidence of the 
 existence of any ' motor ' centres. 
 
 (2) Areas of the same name (homologous areas) in different groups 
 of animals do not necessarily have the same function — that is, in 
 the case of the ' motor ' areas, are not necessarily associated with 
 the same movements. Taking the position of the centre for the 
 
FUNCTIONS or Till-: BRAIN 981 
 
 orbicularis oculi as a test, Ziehen has come to tJie conclusion that 
 in the anthropoid apes and in man this centre has been pushed 
 forward by the encroachment of the centres behind it, and especially 
 of the visual centre, the arm centre, and the speech centre, which 
 have undergone a great functional development. 
 
 Acquisition of Co-ordination of Voluntary Movements. — The co-ordina- 
 tion of movements has already been alhidcd to in connection with the 
 spinal reflexes. No fundamental distinction can be drawn between the 
 co-ordination of reflex and of voluntary movements, but the conscious 
 and often long-continued efforts necessary to acquire mastery over the 
 latter lends to their co-ordination a special interest. The new-born child 
 brings with it into the world a certain endowment of co-ordinative 
 powers; it has inherited, for example, from a long line of mammalian 
 ancestors the power of performing those movements of the cheeks, lips, 
 and tongue, on which sucking depends; perhaps from a long, though 
 somewhat shadowy, race of arboreal ancestors the power of clinging 
 with hands and feet, and thus suspending itself in the air. Many move- 
 ments, such as walking and the co-ordinated muscular contractions 
 involved in standing, and even in sitting, which, once acquired, appear 
 so natural and spontaneous, have to be learnt by painful effort in the 
 hard school of (infantile) experience, and this despite the fact that in 
 these movements the \-oluntarv co-ordination mechanism makes use to 
 a great extent of a motor machinery already existing in the cord and 
 capable of discharging well co-ordinated reflexes.* In addition to such 
 fundamental movements, most people consciously learn, and are 
 willing to confess that they have learnt, to execute a considerable 
 number of co-ordinated movements with the arms, and especially with 
 the fingers. Some part even of the extreme dexterity of jaws, tongue, 
 and teeth displayed by a hungry school-boy, in a minor degree, perhaps, 
 by a hungry mouse, is the result of the much practice, entailing at first 
 some conscious effort, which maketh perfect. The exquisite co-ordina- 
 tion of the muscles of the eyeball, which we shall afterwards have to 
 speak of, and the no less wonderful balance of eft'ort and resistance, of 
 power put forth and work to be done, of which we have already had 
 glimpses in studying the mechanism of voice and speech, become to a 
 s^reat extent the common property of all fully-developed persons. But 
 the technique of the finished singer or musician, of the swordsman or 
 acrobat, and even the operative skill of the surgeon, are in large part the 
 outcome of a special and acquired agility of mind or bod ■, in virtue of 
 w^hich highly-complicated co-ordinated movements are promptly deter- 
 mined on and immediately executed. 
 
 With such special and elaborate movements it is impossible to occupy 
 ourselves in a book like this. Their number may be almost indefinitely 
 
 * The question, how much is ' learned ' in an act such as walking, and 
 how much is already present at birth in the form of a co-ordinated mechanism 
 in the nervous system, is not easy to answer, and indeed the answer may be 
 different for different animals. It has been shown that even the unborn 
 foetus of the cat, when shelled out of the uterus into saline solution without 
 interference with the circulation through the umbihcal cord, can be made to 
 execute unmistakable movements of progression under the influence of 
 asphyxia, produced by pressure upon the cord. It may also execute such 
 movements spontaneously. Graham Brown, to whom we owe these facts, 
 concludes thai the co-ordination of the mechanism concerned in walking is 
 already developed during intra-uterine life, and is not ' learned' after birth. 
 
0R2 THE CENTRAL NERVOUS SYSTEM 
 
 extended, and their nature almost infinitely varied, by the needs and 
 training of special trades and professions, it will be sufficient for our 
 purpose to sketch in a few words the mechanism of one or two of the 
 most common and fundamental co-ordinations of muscular effort, 
 passing over the rest with the general statement that the more refined 
 and complex movements are in general brought about, not by the abrupt 
 contraction of crude anatomical groups of muscles, but by the contrac- 
 tion of portions of muscles, perhaps even single fibres or small bundles 
 of fibres, while the rest remain relaxed. The excitation may gradually 
 wax and wane as the different stages of the movement require. Antago- 
 nistic muscles may be called into play to balance and tone down a con- 
 traction which might otherwise be too abrupt. 
 
 Many interesting illustrations of this process of ' give and take ' 
 between opposing muscles have been reported, especially by Sherring- 
 ton. Some have been already alluded to in discussing reflex move- 
 ments (p. 903). One or two additional observations may be given here. 
 In the cortex cerebri, as we shall see (pp. 95 1, 965), there is an area in 
 the frontal region, and another in the occipital region, stimulation of 
 which gives rise to conjugate deviation of the eyes — that is, rotation of 
 both eyes — to the opposite side. Sherrington divided the third and 
 fourth cranial nerves in monkeys — say on the left side. The externai 
 rectus, which is supplied by the sixth nerve, caused now by its unopposed 
 contraction external squint of the left eye. When either of the cortical 
 areas referred to, or even the subjacent portion of the corona radiata, 
 was stimulated on the left side, both eyes moved towards the right, the 
 left eye, however, only reaching the middle line— that is, the position in 
 which it looked straight forward. The same thing was observed when 
 the animal, after complete recovery from the operation, was caused to 
 voluntarily turn its eyes to the right by the sight of food. Here an 
 inhibitory influence must have descended the fibres of the abducens, the 
 only nervous path connected with the extrinsic muscles of the left eye, 
 and the relaxation of the left externa) rectus must have kept accurate 
 step with the contraction of the right internal rectus. Hering has made 
 an exhaustive analysis of the co-ordinated movements concerned in 
 opening and closing the hand in monkeys. These movements can be 
 produced by stimulation of the cortex or the internal capsule, but not 
 by stimulation of the anterior spinal roots. When the hand is opened 
 the muscles that open it are excited, and those which close it are in- 
 hibited from the cortex. 
 
 Reaction Time. — Just as in a reflex act a certain measureable 
 time (reflex time) is taken up by the changes that occur in the lower 
 nervous centres, so we may assume that in all psychical processes 
 the element of time is involved. And, indeed, when the interval 
 that elapses between the application of a stimulus and the signal 
 which announces that it has been felt {reaction time) is measured, 
 it is found that for the cerebral processes associated with the per- 
 ception of the simplest sensation and the production of the simplest 
 voluntary contraction it is longer than the time which the spinal 
 centres require for the elaboration of even complex and co-ordinated 
 reflex movements. Suppose, e.g., that the stimulus is an induction 
 shock applied to a given point of the skin, and that the signal is the 
 closing of the circuit of an electro-magnet, then, if both events are 
 
FATIGUE AND SLEEP— HYPXOSIS 9S3 
 
 automatically recorded on a revolving drum, the interval can be 
 readily determined. It is evident that this includes, not only the 
 time actually consumed in the central processes, but also the time 
 required for the afferent impulse to reach the brain, and the efferent 
 impulse the hand, along with the latent period of the muscles. The 
 time taken up in these three events can be approximately calculated, 
 and when it is subtracted, the remainder represents the reduced or 
 corrected reaction time — that is, the interval actually spent in the 
 centres themselves. This is by no means a constant. It is in- 
 fluenced not only by the degree of complexity of the psychical acts 
 involved, and the mental attitude of the person (whether he expects 
 the stimulus or is taken by surprise, whether he has to choose 
 between several possible kinds of stimuli and respond to only one, 
 etc.), but it varies also for different kinds of sensation, for the same 
 sensation at different times, and, as is recognized in the personal 
 equation of astronomers, in different individuals. For sensations 
 of touch and pain it may be taken as one-ninth to one-fifth, for 
 hearing one-eighth to one-sixth, and for sight one-eighth to one- 
 fifth of a second. So that the proverbial quickness of thought is 
 by no means great, even in comparison with that of such a gross 
 process as the contraction of a muscle (one-tenth of a second). 
 Nor is it the case that the man ' of quick apprehension ' has always 
 a short reaction time, or the dullard always a long one, although in 
 all kinds of persons practice will reduce it. 
 
 Section XI. — Fatigue and Sleep — Hypnosis. 
 
 Sleep and Fatigue. — Certain gland-cells, certain muscular fibres, 
 and the epithelial cells of ciliated membranes, never rest, and 
 perhaps hardly ever even slacken their activity. But in most 
 organs periods of action alternate at more or less frequent inter- 
 vals with periods of relative repose. In all the higher animals 
 the central nervous system enters once at least in the twenty-four 
 hours into the condition of rest which we call sleep. What the 
 cause of this regular periodicity is we do not know. It is 
 accompanied by changes in the microscopical appearance of the 
 nerve-cells. Thus, Hodge found differences between the cells of 
 certain portions of the cerebral cortex in birds, and of certain 
 ganglia in the honey-bee after a long day of work and after a 
 night's rest. Mann, Lugaro, and other observ^ers, found similar 
 dift'erences in the cells of the cerebral cortex and the anterior 
 horn, and Dolley in the Purkinje's cells of the cerebellum in 
 dogs fatigued by muscular exercise as compared with rested dogs 
 (Fig. 398). 
 
9^4 
 
 THE CF.XTRAL NERVOJrS SYSTEM 
 
 According to Dolloy, tlicrc is, as a result of coiuimied activity', at 
 first a steady increase of the basic chromatic material. This increase 
 affects first the extra-nuclear chromatin, the Nissl substance, which, 
 according to the most modern view, is really nuclear substance distri- 
 buted through the cytoplasm and functions as such (C.oldschmidt). 
 The size and number of the granules are increased, and some of the 
 chromatic material is diffused throughout the cyto})lasm, as indicated 
 by diffuse staining. Then the intranuclear chromatin also undergoes 
 an increase, and the size of the cell is increased too. In moderate 
 activity the change goes no farther. At this stage the cell is hyper- 
 chromatic — i.e., as compared with a normal resting cell it contains an 
 
 ei 
 
 
 Pig 3gg — Effect of Fatigue on Nerve-Cells (Barker, after Mann). Two motor 
 cells from kunbar cord of dog fixed in sublimate and stained with toluidiu 
 blue, a, from rested dog; i, pale nucleus; 2, dark Nissl spindles ; 3, bundles 
 of nerve' fibriW. b, from fatigued dog; 4, dark shrivelled nucleus; 5, pale 
 spindles. 
 
 excess of chromatin. The production of chromatin ha\ing reached the 
 maximum of whicli the nucleus is capable, and functional activity, 
 which entails the using up of the extranuclear chromatin, still continu- 
 ing, the total chromatin content begins t(j diminish, first in the nucleus, 
 through the passage of its chromatin into the cytoplasm to recruit the 
 Nissl substance, then in the cytoplasm as well. Accompanying the 
 disappearance of the chromatic material there is diminution in the size 
 of both cell and nucleus, but especially of the nucleus, so that the normal 
 j)roportion between volume of celland volume of nucleus (nucleus- 
 plasma relation of Hertwig) is disturl)cd in favour of the cytoplasm. 
 Both cell and nucleus become irregular in outline or crenated. Later 
 
FATTGVF. AND SLEEP— HVrSOSTS 983 
 
 on, and, it would seem, rallier abniptly, swelling of the nucleus and, 
 after sonic time, of the cytoplasm occurs. This is due to oedema, 
 and may be taken to indicate an upset of their normal osmotic relations. 
 The earlier occurrence of a>dema in the nucleus leads to another change 
 in the nucleus-plasma relation, which is now disturbed in favour of the 
 nucleus. In the measure in which fatigue progresses the extranuclear 
 chromatic material continues U-> be used up, and, in spite of its replenish- 
 ment from the nucleus, it almost or entirely vanishes from the cyto- 
 plasm. Then follows what is perhaps a ' last effort ' on the part of the 
 nucleus to supply the cytoplasm, in the form of a discharge of chro- 
 matic substance, which" first masses itself around the outside of the 
 nuclear membrane, and tliencc gradually diffuses into the cytoplasm. 
 With the using up of this supply all the basic chromatic material of 
 the cell, except that in the karyosome (nucleolus) , is exhausted. Finally, 
 this too is yielded up to the cytoplasm, and with its consumption there 
 remains a totally exhausted cell, devoid of basic chromatin and incap- 
 able of recuperation. 
 
 According to Pugnet, even in extreme fatigue, as when dogs were 
 caused to run forty to nearly sixty miles in a special apparatus, the 
 changes varied greatly in degree in different cortical cells, from mere 
 diminution of the chromatic substance to complete disappearance of it. 
 and such disintegration of the cell as must have precluded its recovery, 
 had the animal been allowed to live. Many, and indeed most, of the 
 cortical cells were quite unaffected. Histological alterations may also 
 be caused in sympathetic ganglion cells by prolonged artificial stimula- 
 tion of the nerves connected with the ganglia. Experiments on fatigue 
 changes in the cells of the spinal ganglia after electrical excitation of the 
 posterior root-fibres are less decisive, some observers having obtained 
 positive, others negative, results (p. 913). 
 
 Theories of the Causation of Sleep. — (i) Some have suggested that sleep 
 is induced by the using up of substances necessary for the functional 
 activity of the neurons — e.g., the stored -up or intramolecular oxygen — 
 or by the action of the waste products of the tissues, and especially lactic 
 acid, when they accumulate beyond a certain amount in the blood, or in 
 the nervous elements themselves. 
 
 (2) Others have looked for an explanation to vascular changes in the 
 brain, but so far are the possible causes of such changes from being 
 understood, that it is even yet a question whether in sleep the brain is 
 congested or anaemic. Certain writers have settled this question by the 
 summary statement that when the brain rests the quantity of blood in 
 it must be supposed to be diminished, as in other resting organs. But 
 this is a fallacious argument. For when the whole body rests, as it does 
 in sleep, it has as much blood in it as when it works ; in sleep, therefore, 
 if some resting organs have less blood than in waking life, other resting 
 organs must have more ; and it is the province of experiment to decide 
 which are congested and which anaemic. In coma, a pathological con- 
 dition which in some respects has analogies to profound and long- 
 continued sleep, the brain is congested, and the proper elements of the 
 nervous tissue presumably compressed. And artificial pressure (applied 
 by means of a distensible bag introduced through a trephine hole into 
 the cranial cavity) may cause not only unconsciousness, but absolute 
 anaesthesia. But it is possible that this artificial increase of intra- 
 cranial pressure may produce its effects by rendering the brain anaemic, 
 and it has been actually observed that the retinal vessels, as seen with 
 the ophthalmoscope, and the vessels of the pia mater exposed to direct 
 observation in man by disease of the bones of the skull, or in animals by 
 operation, shrink during sleep. Statements to the contrary may be due 
 
986 THE CENTRAL NERVOUS SYSTEM 
 
 to neglecting the influence of difference of position in tHc sleeping and 
 waking states. In sleeping children the fontanelle sinks in, an indica- 
 tion that the intracranial pressure is reduced. Observations witli the 
 plethysmograph have shown that the arm swells in sleep, and shrinks 
 when the sleeper awakes, or even when lie is subjected to sensorj^ stimuli 
 not sufficient to arouse him — e.g., a tune played by a musical-box 
 (Howell). The tone of the vaso-motor centre is therefore diminished, 
 and the arterial pressure falls during sleep. But a fall of general arterial 
 pressure is usually accompanied by a diminution of the quantity of 
 blood passing through the brain. So that the balance of evidence is in 
 favour of the view that sleep is associated iviih a certain degree of cerebral 
 auamia. 
 
 As to the nature of the relation between the two conditions, it has 
 been suggested that the anaemia is produced by fatigue of the vaso- 
 motor centre, which causes it to relax its grip upon the periplieral blood- 
 vessels, and that the condition of the cortical ner\c-cells which we call 
 sleep is directly produced by the lack of blood. But there does not 
 appear to be any good reason for believing that the vaso-motor centre 
 is more susceptible of fatigue than the higher cerebral centres. On the 
 contrary', it is probable that the bulbar centres are less delicately 
 organized and more resistant than the higher centres. In any case, if 
 the cerebral nerve-cells ' go to sleep ' because their blood-supply is 
 diminished, ought we not to look for a similar cause for diminished 
 activity of the vaso-motor centre ? Or if the answer is made that the 
 activity' of the vaso-motor cells is directly lessened by fatigue, or by the 
 cessation of external stimuli, why should not this be the case also for the 
 cortical cells ? It can be shoxs-n by means of the sphygmomanometer 
 (p. 114) that the fall of arterial pressure is not essentially connected with 
 sleep, but is produced by the bodily rest and waiTnth which accompany 
 it. Further, even a great diminution in the supply of blood going to the 
 brain is not necessarily followed by sleep. For example, both carotid.'; 
 and both vertebral arteries may frequently be tied in dogs at the same 
 time without producing any symptoms, the anastomosis of the superior 
 intercostal arteries with the aiiterior spinal artery providing a sufficient 
 channel for the blood absolutely required by the'brain. Monkeys after 
 ligation of both carotids may be most alert and active. To produce 
 sopor in animals the cortical "circulation must be reduced almost to the 
 vanishing-point, and to a far greater degree than e\er occurs in sleep 
 (Hill). We must, therefore, conclude that although sleep is normally 
 associated with some anesmia of the hrain, it is not directly caused by it. 
 The cortical centres go to sleep because they are ' tired,' or because the 
 stimuli which usually excite them have ceased, and not because their 
 blood-supply is diminished. 
 
 (3) The idea that the dendrites are contractile, and by pulling them- 
 selves in, and thus breaking certain nervous chains, cause sleep, is a 
 mere theon.-, unsupported by any real evidence. The same is true of 
 the notion that the fibrils of "the neuroglia insinuate themselves into the 
 ' joints,' by which one neuron comes into contact with another, and, 
 acting as insulating material, block the nerve-impulses. 
 
 In general, the depth of sleep, as measured by the intensity of sound 
 needed to awaken the sleeper, increases rapidly in the first hour, falls 
 abruptly in the second, and then slowly creeps down to its minimum, 
 which it reaches just before the person awakens. As to the amount of 
 sleep required, no precise rules can be laid down. It varies with age, 
 occupation, and perhaps climate. An infant, whose main business is to 
 grow, spends, or ought to spend, if mothers were wise and feeding-bottles 
 clean, the greater part of its time in sleep. The man, whose main 
 
FATIGUE AND SLEEP—HYPNOSIS 987 
 
 business it is to work witli his hands or brain, requires his full tale of 
 eight liours' sleep, but not usually more. The dry and exliilarating air 
 of some of the inland portions of North America, and perhaps the plains 
 of Victoria and New South Wales, incites, and possibly enables a new- 
 comer to live for a considerable period with less than his ordinary 
 amount of sleep. Idiosyncrasy, and perhaps to a still greater extent 
 "habit, have also a marked influence. The great Napoleon, in his 
 heyday, never slept more than four or five hours in the twenty-four. 
 Five or six hours or less was the usual allowance of Frederick of Prussia 
 throughout the greater part of his long and active life. 
 
 Hypnosis is a condition in some respects allied to natural slumber; 
 but instead of the activity of the whole brain — or perhaps we should 
 rather say, the whole activity of the brain — being in abeyance, the 
 susceptibility to external impressions remains as great as in waking life, 
 or may be even increased, while the critical faculty, which normally 
 sits in judgment on them, is lulled to sleep. The condition can be 
 induced in many ways — by asking the subject to look fixedly at a bright 
 object, by closing his eyes, by occupying his attention, by a sudden loud 
 sound or a flash of light, etc. The essential condition is that the person 
 should have the idea of going to sleep, and that he should surrender his 
 will to the operator. In the hypnotic condition the subject is extremely 
 open to suggestions made by the operator with whom he is en rapport. 
 He adopts and acts upon them without criticism. If, for example, the 
 hypnotizer raises the subject's arm above his head, and suggests that he 
 cannot bring it dowTi again, it stays fixed in that position for a long time 
 without any appearance of fatigue; or the whole body may be thrown, 
 on a mere hint, into some unnatural pose, in which it remains rigid 
 as a statue. Suggested hemiplegia or hemianaesthesia, or paralysis of 
 motion and sensation together or apart in limited areas, can also be 
 realized ; and surgical operations have been actually performed on 
 hypnotized persons without any appearance of suffering. If, on the 
 other hand, the operator suggests that the subject is undergoing intense 
 pain, he will instantly take his cue, writhing his body, pressing his hands 
 upon his head or breast, and in all respects behaving as if the suggestion 
 were in accord with the facts. If he is told that he is blind or deaf, he 
 will act as if this were the case. If it is suggested that a person actually' 
 present is in Timbuctoo. the subject will entirely ignore him, will leave 
 him out if told to count the persons in the room, or try to walk through 
 him if asked to move in that direction. What is even more curious is 
 that the organic functions of the body are also liable to be influenced by 
 suggestion. A postage-stamp was placed on the skin of a hypnotized 
 person, and it was suggested that it would raise a blister. Next day a 
 blister was actually found beneath it. The letter K, embroidered on a 
 piece of cloth, was suggested to be red-hot. The left shoulder was then 
 ' branded ' with it, and on the right shoulder appeared a facsimile of the 
 K as if burnt with a hot iron. The secretions can be increased or 
 diminished, subcutaneous haemorrhages, veritable stigmata,* can be 
 caused, and many of the ' miracles ' of Lourdes and other shrines, ancient 
 and modem, repeated or surpassed by the aid of hypnotic suggestion. 
 Hypnotism has also been practically employed in the treatment of 
 various diseases, and particularly in functional derangements of the 
 
 * I.e., bleeding spots on the skin generally corresponding to the wounds 
 of Christ. In the well-known case of Louise Latour, which excited great 
 interest in France in 1868, blisters first appeared; they burst, and then there 
 was bleeding from the true skin. The probable explanation is that she con- 
 centrated her attention on these parts of her body and so influenced them, 
 perhaps by causing congestion through the vaso-motor centre. 
 
q88 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 nervous system. But care and judgment are necessary' on the part of 
 the operator, and although as a rule there is no difficulty in putting an 
 end to the condition by a suitable suggestion, it is said that in rare 
 instances grave mischances have occurred . There seems to be no ground 
 for the opinion that women are more easily hypnotized than men. Out 
 of more than a thousand persons, Liebault found only seventeen abso- 
 lutely refractory. 
 
 Section XII. — Size of Brain and Intelligence — Circulation 
 IN and Resuscitation of Central Nervous System after 
 Anemia — Chemistry of Nervous Activity — Cerebro-spinal 
 Fluid. 
 
 Relation of Size of Brain to Intelligence. — While it is the case 
 
 that some men of great ability have liad remarkably heavy and 
 richly convoluted brains, it would seem that in general neither great 
 size nor any other obvious anatomical peculiarity of the cerebrum 
 is constantly associated vi^ith exceptional intellectual power. In 
 the animal kingdom, as a whole, there is undoubtedly some relation 
 between the status of a group and the average brain development 
 within the group. But that this is a relation which is complicated 
 by other circumstances than the mere degree of intelligence is 
 sufficiently shown by the fact that a mouse has more brain, in pro- 
 portion to its size, than a man, and thirteen times more than a horse ; 
 while both in the rabbit and sheep the ratio of brain-weight to body- 
 weight is nearly twice as great as in the horse, in the dog only half 
 as great as in the cat, and not very much more than in the donkey. 
 The following tables, too, which illustrate the weight of the brain 
 in man at different ages, show that, although we might give ' the 
 infant phenomenon ' an anatomical basis, we should greatly over- 
 rate the intellectual acuteness of the average baby if we were to 
 measure it by the ratio of brain to body-weight alone. 
 
 
 Age. 
 
 Brain-weight. 
 
 
 
 Age. 
 
 Brain-weight. 
 
 
 I year 
 
 885 grm. 
 
 
 8 
 
 years 
 
 1,045 grm. 
 
 
 2 years 
 
 909 .- 
 
 
 10 
 
 • > 
 
 1. 315 .. 
 
 
 3 .. 
 
 1,071 ,, 
 
 
 II 
 
 
 1,168 ,, 
 
 
 4 ., 
 
 1,099 .. 
 
 
 12 
 
 
 1.286 ., 
 
 
 5 
 
 1,033 .. 
 
 
 13 
 
 
 1.505 .. 
 
 
 6 ,, 
 
 1. 147 .. 
 
 
 14 
 
 
 1-336 ,. 
 
 
 7 .. 
 
 1,201 ,, 
 
 
 15 
 
 
 1,414 •. 
 
 — BiSCHOFF. 
 
 
 Brain-weight — 
 
 Brain-weight — 
 
 
 
 Brain-weighl- 
 
 Brain-weight— 
 
 Age. 
 10-19 
 
 Men. 
 
 Women. 
 
 Age. 
 
 Men. 
 
 Women. 
 
 . . 1,411 grm. 
 
 . . 1,219 grm. 
 
 50 
 
 -59 
 
 .. 1,389 grm 
 
 . .. 1,239 grm. 
 
 20-29 
 
 .. 1,419 .. 
 
 . . 1,260 ,, 
 
 60 
 
 -69 
 
 . . 1,292 ,, 
 
 .. 1,219 ,. 
 
 30-39 
 
 .. 1,424 .. 
 
 . . 1,272 ,, 
 
 70 
 
 -79 
 
 .. 1,254 .. 
 
 .. 1,129 ,. 
 
 40-49 
 
 . . 1,406 ,, 
 
 . . 1,272 ,, 
 
 80- 
 
 -90 
 
 . . 1,303 .. 
 
 898 .. 
 — HUSCHKE. 
 
THE CEREBRAL CIRCULATION fjho 
 
 In sumo small l)ir(.l^ \.\w ratio is as high as i : 12, in large birds 
 as low as i : i,2ou ; in certain fishes a gramme of brain has to serve 
 for over 5 kilos of body. As a rule, especially within a given species, 
 the brain is proportionally of greater size in small than in large 
 animals. It is to be supposed that quality as well as quantity of 
 brain substance is a potent factor in determining the degree of 
 mental capacity. 
 
 The Cerebral Circulation. — The arrangement of the cerebral blood- 
 vessels has certain peculiarities which it is of importance to remember 
 in connection with the study of the diseases of the brain, many of which 
 are caused by lesions in the vascular system — haemorrhage, or embolism. 
 I'our great arterial trunks carry blood to the brain, two internal carotids 
 and two vertebrals. The vertebrals unite at the base of the skull to 
 form the single mesial basilar artery, which, running forward in a groove 
 in the occipital bone, splits into the two posterior cerebral arteries. 
 Each carotid, passing in through the carotid foramen, divides into a 
 middle and an anterior cerebral artery; the latter runs forward in the 
 great longitudinal fissure, the former lies in the fissure of Sylvius. A 
 communicating branch joins the middle and posterior cerebrals on each 
 side, and a short loop connects the two anterior cerebrals in front. In 
 this way a hexagon is formed at the base of the brain, the so-called 
 circle of Willis. While the anastomosis between the large arteries is 
 thus very free, the opposite is true of their branches. All the arteries 
 in the substance of the brain and cord are ' end-arteries ' — that is to 
 say, each terminates within its area of distribution without sending 
 communicating branches to make junction with its neighbours. The 
 consequence of these two anatomical facts is: (i) that interference with 
 the blood-supply of the brain between the heart and the circle of Willis 
 does not readily produce symptoms of cerebral aneemia; (2) that the 
 blocking of any of the arteries which arise from the circle or any of their 
 branches leads to destruction of the area supplied by it. Nearly all 
 dogs recover after ligation in one operation of both carotids and both 
 vertebral arteries. In monkeys both carotids may, as a rule, be safely 
 tied, and one carotid in man. If, in addition to the two carotids, one 
 vertebral be ligated at the same time in the monkey, sopor results, and 
 this is generally followed by extensor rigidity, coma, and death in 
 twenty-four hours. In one case a monkev survived this triple ligation, 
 but became demented. The motor paralysis and rigidity were much 
 greater than in the dog. In the condition of partial anaemia the cortex 
 is more excitable than normal, but the excitability disappears at once 
 when the anaemia is rendered complete (Hill). 
 
 The basal ganglia are fed by twigs from the circle of Willis and the 
 beginning of the posterior, middle, and anterior cerebral arteries. Of 
 these the most important are the lenticulo-striate and lenticulo-optic 
 branches of the middle cerebral, which are given off near its origin, and 
 run through the lenticular nucleus into the internal capsule, and thence 
 to the caudate nucleus and optic thalamus respectivel3^ The chief part 
 of the blood from the circle of Willis is carried by the three great cerebral 
 arteries over the cortex of the brain. The white matter, with the 
 exception of that in the immediate neighbourhood of the basal ganglia, 
 is nourished by straight arteries which penetrate the cortex. The 
 middle cerebral supplies the whole of the parietal as well as that portion 
 of the frontal lobe which lies immediately in front of the fissure of 
 Rolando and the upper part of the temporal lobe. The rest of the 
 
990 THE CENTRAL NERVOUS SYSTEM 
 
 frontal lobe is supplied by the anterior cerebral, and the occipital lobe, 
 with the lower part of the temporal lobe, by the posterior cerebral. 
 The medulla oblongata, cerebellum, and pons are fed from the vertc- 
 brals and the basilar artery- before the circle of Willis has been formed. 
 
 Resuscitation of the Central Nervous System after Total Anaemia. 
 — Complete temporary anaemia of the brain and upper cervical 
 cord can be produced in most cats by passing temporary ligatures 
 around the innominate artery and left subclavian proximal to 
 the origin of the vertebral artery. Artificial respiration is main- 
 tained through a tube passed through the glottis. The eye reflexes 
 disappear very quickly, and a period of high blood-pressure imme- 
 diately follows the occlusion. A fall of pressure succeeds, due to 
 vagus inhibition of the heart, and this is followed by a second rise 
 after the vagus centre succumbs to the anaemia. Respiration stops 
 temporarily (in twenty to sixty seconds) after occlusion; then 
 follows a series of strong gasps, and finally cessation of all respiratory 
 movements. The blood-pressure slowly falls to a level which is then 
 maintained approximately constant for the remainder of the occlu- 
 sion period. The anterior part of the cord and the encephalon lose 
 all function ; no reflexes can be elicited from this part of the central 
 nervous system. The intra-ocular tension is much reduced, and the 
 cornea is characteristically wrinkled. 
 
 When the cerebral circulation is restored by releasing the vessels, 
 the general arterial pressure soon begins to rise if the period of 
 occlusion has not overstepped the limit of successful cardio-vascular 
 resuscitation. The respiration returns suddenly, the time of 
 return depending on the length of the occlusion and on other factors. 
 The respiratory rate, at first slow, soon becomes normal, and then 
 more rapid than normal. The eye-reflexes reappear more gradu- 
 ally; the intra-ocular tension increases, and the shrunken cornea 
 becomes smooth and hard. The anterior part of the cord recovers 
 its functions gradually; the reflexes connected with it return, first 
 the homonymous, then the crossed. A short period of quiet follows ; 
 then spasms of the skeletal muscles appear, gradually increase in 
 severity and extent, and terminate in (a) death, (J) partial, or 
 (c) complete recovery. In partial recovery, disturbances of loco- 
 motion, such as walking in a circle, paralysis, apparent dementia 
 or loss of intelligence, and loss of sight or hearing, may be observed. 
 Voluntary movements of the head, neck, shoulders, and fore-limbs 
 have been seen eight minutes after release from an occlusion of six 
 minutes. Blindness has been observed without loss of the pupillary 
 light reflex. In this case the visual cortex would seem to have 
 suffered more than the lower centres, an illustration of a general 
 rule. Complete recoverv is rare after total anaemia lasting as much 
 as fifteen minutes, and has not been observed after an anaemia of 
 twenty minutes. Ten to fifteen minutes of total anaemia represent 
 
CHEMISTRY OF NERVOUS ACTIVITY Q^l 
 
 the limit beyond which recovery of the brain, and therefore successful 
 resuscitation of the animal, cannot be expected. 
 
 Chemistryof Nervous Activity.- -Of this we are practically ignorant. 
 The percentage composition of the sohds and the percentage of 
 water in the brains of three persons of different ages are ex- 
 hibited in the following table (W. Koch) : 
 
 
 Child 6 Weeks 
 (Brain 640 Grms.). 
 
 Child 2 Years 
 (Brain 1,100 Grms.). 
 
 Adult 19 \'ears 
 (Brain 1,670 Grms.). j 
 
 Whole Uraiii. 
 
 Grey. 
 
 White. 
 
 Whole 
 Brain.* 
 
 Grey. 
 
 White. 
 
 Whole 
 Brain, t 
 
 37-1 
 
 6-7 
 4-1 
 
 27-3 
 12-7 
 
 0-3 
 117 
 
 1 Proteins 
 
 1 Extractives . . 
 
 Ash 
 
 Lecithins and 
 kephalins . . 
 
 Cerebrins 
 
 Lipoid S as SO4 
 
 Cholestcrint 
 
 46-6 
 I2'0 
 
 8-3 
 
 24-2 
 69 
 
 O-I 
 
 1-9 
 
 48-4 
 lO-O 
 
 5-8 
 
 247 
 8-6 
 o-i 
 
 2-4 
 
 31-9 
 5-9 
 3-2 
 
 26-3 
 17-2 
 
 0-5 
 15.0 
 
 40-1 
 8-0 
 
 4-5 
 25-5 
 
 12-9 
 
 0-3 
 87 
 
 47-1 
 
 9-5 
 5-9 
 
 237 
 8-8 
 
 O-I 
 
 4-9 
 
 27-1 
 
 3-9 
 
 2-4 
 
 3I-0 
 1 6-6 
 
 0-5 
 18.5 
 
 Water . . 
 
 8878 
 
 84-49 
 
 76-45 
 
 80-47 
 
 83-17 
 
 69-67 
 
 76-42 
 
 The next table shows the variations in the content of water, 
 soHds, and protein in different parts of the nervous system (Halli- 
 burton) : 
 
 
 Water. 
 
 Solids. 
 
 Percentage of Pro- 
 teins in Solids. 
 
 Cerebral grey matter 
 Cerebral white matter 
 Cerebellum 
 " Spinal cord as a whole . 
 Cervical cord 
 Dorsal cord 
 Lumbar cord 
 Sciatic nerves 
 
 
 • 
 
 83-5 
 69-9 
 
 79-8 
 71-6 
 
 72-5 
 69-8 
 72-6 
 65-1 
 
 16-5 
 30-1 
 
 20-2 
 28-4 
 
 27-5 
 30-2 
 27-4 
 
 34-9 
 
 51 
 
 33 
 42 
 31 
 31 
 
 28 
 
 33 
 29 
 
 The grey matter of the cerebrum in the adult contains 8i to 
 86 per cent, of water, the white matter 68 to 72 per cent., the 
 brain as a whole 81 per cent., the spinal cord 68 to 76 per cent., 
 and the peripheral nerves 57 to 64 per cent. In the foetus more 
 water is present (92 per cent, in the grey and 87 per cent, in the 
 white matter). 
 
 The superior richness of the grey matter in proteins and the 
 preponderance of water in it are the chief chemical peculiarities 
 which distinguish it from the white matter. That it should have 
 * CalculatL'd. t Calculated by difference. 
 
,j()2 Tin: CESTRAL MiRVOUS SYSTLM 
 
 a high pidtiin content is easily understood, for tlie protoplasmic 
 structures, the nerve-ccUs, are situated in the grey matter. But 
 that the most important functions should have their seat in a tissue 
 containing only 14 to 19 per cent, of solids is surprising, and should 
 warn us that the water is no less significant a constituent of living 
 matter than the solids, and that it is not the mass of the solid 
 substances in a tissue wliich is the essential thing, but the whole 
 colloid complex, which cannot be constituted without the water. 
 
 Fresh nervous tissues are alkaline to Utmus, but become acid 
 soon after death. No change of reaction has been detected during 
 activity. 
 
 That o.xygen is used up during cerebral activity is certain, and 
 when the brain is coloured with methylene blue, b\- injecting it 
 into the circulation, any spot of it which is stimulated loses the 
 blue colour, the pigment being reduced. But if the animal is so 
 deeply narcotized that it does not respond to stimulation, the change 
 of colour does not occur. 
 
 ChoUn (p. 366), a substance which can be derived from lecithin, 
 is believed to represent one of the waste products of nervous activity. 
 Exceedingly small traces of it are present in normal cerebro-spinal 
 fluid, and in certain diseased conditions of the brain, as in general 
 paralysis, the quantity is said to be notably increased, indicating 
 an increased decomposition of lecithin. The fatty acid constituent 
 of lecithin is liberated in degenerating nerve, giving rise to the 
 reaction with osmic acid (p. 797). Some writers assert that this 
 increase in the cholin can be used as a test to distinguish organic 
 nervous disease from that which is purely functional. But the 
 matter is in dispute. 
 
 Cerebro-spinal Fluid. — The cerebro-spinal fluid, which fills the 
 ventricles of the brain and the central canal of the cord, is con- 
 tinuous with that contained in the subarachnoid space through the 
 foramen of Magendie, an opening in the piece of pia mater that helps 
 to roof in the fourth ventricle. It is secreted in part by the cubical 
 cells covering the choroid plexus, a fold of pia mater which i)rojects 
 into each lateral ventricle. Extracts of choroid plexus, when in- 
 jected intravenously, increase the rate of secretion. 
 
 This action is dependent upon the presence of sonu' sul^stance in 
 the choroid plexus, wliich, however, is not a specific product of the 
 activity of the plexus, since extracts of the brain produce the same 
 efifect. It may therefore be some product of the metabolism of the 
 brain which passes to the choroid plexus and stimulates secretion 
 by the epithelium. The substance is removed from the fluid by 
 filtration through a Chamberland filter, and is therefore probably 
 of high molecular weight. It is probable that variations in the rate 
 of secretion of the cerebro-spinal fluid In' the choroid plexus are more 
 infiuential in governing the intracranial pressure than variations in 
 
C EREB RO-SPINA L l-I. UID 
 
 995 
 
 the arterial and venous pressures. The idea that the cranial contents 
 constitute a fixed quantity, without the power of contraction or 
 expansion, can no longer be maintained (Dixon and Halliburton). 
 A graphic record of the rate of secretion of the cerebro-spinal fluid 
 in the dog may be obtained by inserting a hollow needle through the 
 occipito-atlantoid ligament into the great subarachnoid cistern, 
 and allowing the liquid to fall upon a drop-counter writing on a 
 drum (Mg. J()<)). It is not always possible, ho\ve\'er, to be certain 
 by this method that the rate at which the fluid escapes represents 
 
 "\ ■....^-^■ 
 
 
 Fig. 399. — Influence of Extract of the Posterior Lobe of the Pituitary upon the Flow 
 of Cerebro-Spinal Fluid through a Hollow Needle inserted into the Cisterna 
 Magna through the Occipito-Atlantoid Ligament in a Dog. The animal was 
 anaesthetized by a constant method, insufflation of ether into the trachea. The 
 uppermost curve is respiration; the next, drops of cerebro-spinal fluid; the next, 
 arterial blood pressure; the fourth, signal line showing the point at which 50 mg. 
 of a dried extract of posterior lobe was injected into a vein. The signal line is 
 also the zero of blood pressure. The bottom trace is the time in seconds {Weed 
 and Gushing). 
 
 accurately the rate at which it is formed. A more exact method 
 appears to be the introduction of the needle into the third ventricle 
 (Fig. 400). 
 
 Cerebro-spinal fluid can easily be obtained in man by lumbar 
 puncture with a hypodermic needle sufficiently long to enter the 
 subarachnoid space in the spinal canal. The point usually selected 
 for the puncture is between the fourth and fifth lumbar vertebrae. 
 The normal pressure of the fluid is such that it trickles out by drops, 
 but in disease it is sometimes so high that it spurts out in a steady 
 stream. An examination of the fluid. especiaUy for leucocytes or 
 bacteria, is of great diagnostic value in certain conditions. Nor- 
 mally it is a thin, clear, watery fluid, faintly alkaline in reaction 
 
 63 
 
994 
 
 THE CENTRAL NERVOUS SYSTEM 
 
 to litmus, and with a specific ;,'ravity of about 1004 to 1007. It 
 contains tin- ordinan- salts, but more potassium than sodium, unhkc 
 other bodv fluids; a ver\' small amount of protein (globulin) — 
 usually about 01 per cent. — and a little dextrose (Xawratzki). 
 Its composition is e\idently different from that of ordinan,' lymph. 
 Only a few Ivmphocvtes are present in health, but in some diseases 
 (as in general paralysis of the insane, tabes, and cerebro-spinal 
 syphilis) a marked increase occurs. In acute cerebro-spinal menin- 
 gitis numerous polymorphonuclear leucocytes are found, which are 
 absent from the normal fluid. 
 
 The depression of the freezing-point (A) usually lies between 
 060° and 0-65° C. In a case of hydrocephalus it was 065° C. 
 Normally, cerebro-spinal fluid is somewhat hypertonic to the blood- 
 
 Fig. 400. — Sagittal Section of Dog's Skull. ?h' Aving the Needle introduced into Third 
 Ventricle to tap Cerebro-Spinal Fluid (Weed and Cashing). 
 
 serum. In injury of the cribriform plate of the ethmoid bone and 
 also in some cases where there is no traumatic injury, the fluid 
 escapes from the nose, and the rate of its formation can thus be 
 ascertained. In one case it was found to be as much as 2 c.c. to 
 nearly 4 c.c. in ten minutes. 
 
 PRACTIC.\I. EXERCISES OX CHAPTER XVT. 
 
 I. Section and Stimulation of the Spinal Nerve-Roots in the Frog. — (a) 
 Select a large fn.g [a. bull- frog, il possible Pith the brain. Fasten 
 the frog, belly down, on a plate of cork. Make an incision in the middle 
 line over the spinous processes of the lowest three or four vertebrae, 
 separate the muscles frtmi the vertebra! arches, and with strong scissors 
 o jen the spinal canal, taking care not to injure the cord by passing the 
 bla-lc of the scissors too deeply. Extend the opening upwards till tvvo 
 
PRACTICAL EXERCISES 995 
 
 or three posterior roots come into view. Pass fine silk ligatures under 
 two of them, tic, and divide one root central to the ligature, the other 
 peripheral to it. Stimulate the central end, and reflex movements will 
 occur. Stimulate the peripheral end; no effect is produced. Now cut 
 away the expo.sed posterior roots and isolate and ligature two of the 
 anterior roots, which arc smaller than the posterior. Stimulate the 
 central end of one : there is no effect. Stimulation of the peripheral end 
 of the other causes contractions of the corresponding muscles. 
 
 [b) Stimulation of the roots may be repeated on the mammal, using 
 the dog employed for the experiment on the motor areas (p. 100 1); 
 Place lue auiiiial, belly down, and insert a good-sized block of wood 
 between it and the board at the level of the lumbar vertebra; of the 
 spine. Divide the skin and muscles on either side of this region till the 
 laminae of the vertebrae are exposed. Snip through them with strong 
 forceps, and open the spinal canal, exposing a length of cord correspond- 
 ing to three or four vertebrae. Ligate and stimulate the roots as in {a). 
 
 2. Reflex Action in the ' Spinal ' Frog. — Pith the brain of a frog, 
 destroying it down to the posterior third of the medulla oblongata, 
 (i) Note the position of the limbs immediately after the operation, and 
 again thirty to fortj- minutes later. Its hind-legs possess tone, and are 
 drawn up against the flanks. The animal can still execute certain 
 co-ordinated movements — e.g., pulling away its leg if a toe is pinched. 
 The power of maintaining equilibrium is lost. If placed on its back, it 
 lies there. When thrown into water it sinks usually without any 
 attempt at swimming. Verify the following facts, using mechanical 
 stimulation (pinching the toes or skin of the leg) : (a) If the stimulus 
 provokes muscular movements only on one side of the body, this is 
 usually on the same side as the stimulated point, {b) When the stimulus 
 causes reflex moA-ements on both sides of the body, the stronger con- 
 tractions are on the side to which the stimulus was applied. 
 
 Determine whether it is easier to obtain movement of a portion of the 
 body innervated from a region of the cord above the level of the stimu- 
 lated nerv^es or below that level. 
 
 (2) With electrical stimuli (using a coil arranged for single shocks de- 
 termine if reflex movements are elicited by a single induced shock ap- 
 plied to the skin. Verify the fact that a series of shocks is more efficient, 
 the effects of the separate stimuli being summated in the reflex centres. 
 
 (3) To test the effect of thermal stimuli, dip the leg into a beaker of 
 warm water. Vary the temperature of the water, using a series of 
 beakers with water at io°C., I5°C., 20°C., etc., above the temperature of 
 the room. Place the leg for a moment in each, and determine which is the 
 most efficient stimulus. Immediately on withdrawing the leg from each 
 of the hot-water beakers immerse it in a beaker of water at room tem- 
 perature. Finally, dip the leg into a beaker of cold water, and heat it 
 gradually to a temperature at which a reflex was previously obtained. 
 Probably it will not be elicited by the gradual warming. 
 
 (4) ' Purposive ' Movements. — Touch the skin of one thigh with blot- 
 ting-paper soaked in strong acetic acid. The leg is drawn up, and the 
 foot moved as if to get rid of the irritant. If the leg is held, the other 
 is brought into action. Immerse the frog in water to wash away the acid . 
 
 (5) Spread {Irradiation) of Reflexes. — Gently stimulate a toe or a small 
 spot on the flank with weak induction shocks or weak mechanical 
 stimuli, and note the reflex effect obtained. Then go on gradually 
 increasing the strength of stimulation without increasing the area of 
 the field stimulated, and observe the extent and order of spread of the 
 reflex movements. 
 
 3. Reflex Time. — Pass a hook through the jaws. Holding the frog by 
 
996 THE CENTRAL NERVOUS SYSTEM 
 
 the hook, dip one leg into a dilute solution of sulphuric acid (02 to 
 05 per cent), and note with the stop-watch the interval which elapses 
 before the frog draws up its leg (Tiirck's method of determining the 
 reflex time). Wasli the acid off with water. 
 
 Determine how the reflex time varies with the strength of the stimulus. 
 This can be done by using various strengths of acid. The reflex time 
 will be shorter the stronger the stimulus up to a certain point. Compare 
 the reflex time of movements on the same side of the body as the point 
 pf application of tin- stimulus and on the opposite side. 
 
 4. Inhibition of the Reflexes. — (i) Destroy the cerebrum of a frog. 
 Dip one leg into dilute sulphuric acid as in 3, and estimate the reflex 
 time. Then apply a crystal of common salt to the upper part of the 
 spinal cord. If the opening made for pithing the frog is not large enough 
 to enable the cord to be clearly seen, enlarge it. Again dip the leg in 
 the dilute acid. It will either not be drawn up at all, or the interval will 
 be distinctly longer than before. 
 
 (2) Expose the viscera, including the heart, taking care not to injure 
 the cardiac nerves. Tap the intestines sharply with the handle of a 
 scalpel many times in succession. The heart is inhibited. 
 
 (3) Tie strings tightly around both fore-legs of a normal frog. Place 
 the animal on its back; it does not turn over. The hind-legs may be 
 pulled about in various ways without the frog turning over into its 
 normal position. The reactions concerned in the maintenance of 
 equilibrium are inhibited. Remove the strings. The animal cannot 
 be made to lie on its back except by force. 
 
 5. Spinal Cord and Muscular Tonus. — Destroy the brain of a frog. 
 Isolate the gastrocnemius, and cut away the bone below the knee. 
 Isolate the sciatic nerve without injuring it. Remove the muscles from 
 the femur, cut the bone and fix it in a clamp for graphic recording. 
 Connect the tendon with a lever, weighted with 5 to 10 grammes. Take 
 a base line. Destroy the spinal cord, or cut the sciatic and again take 
 a base line. The Jength of the muscle is slightly altered. 
 
 6. Spinal Cord and Tonus of the Bloodvessels. — Destroy the brain of 
 a frog. Arrange the web of the foot on the stage of a microscope, and 
 note the calibre of the bloodvessels in the field. Destroy the cord, and 
 observe the change in their calibre. They will dilate. 
 
 7. Action of Strychnine. — Pith a frog (brain only). Inject into one of 
 the lymph-sacs thice or four drops of a o'l per cent, solution of strych- 
 nine. In a few minutes general spasms come on, which have inter- 
 missions, but are excited by the slightest stimulus. The extensor 
 muscles of the trunk and limbs overcome the flexors. Destroy the 
 spinal cord; the spasms at once cease, and cannot again be excited. 
 
 8. Mammalian Spinal Preparation (Sherrington).* — Deeply anaes- 
 thetize a cat with ether. Insert a cannula into the trachea (p. 202), and 
 continue the anaesthesia through this. Expose and ligate both common 
 carotids. Make a transverse incision through the skin over the occiput, 
 and extend it laterally behind the ears. Pull back the skin so as to 
 exf)Ose the neck muscles at the level of the axis vertebra. Feel for the 
 
 • A similar preparation can be used for certain experiments on the circu- 
 lation (Crile, Guthrie). For these, as well as for the study of many reflexes, 
 a good preparation is obtained by occlusion of the cerebral blood-supply in cats 
 (without decapitation). Even a human "spinal preparation' is capable of 
 executing reflex movements, llie Turkomans are stated to have decapitated 
 their prisoners and immediately placed on the neck a hot metal plate, which 
 sealed up the cut vessels. The (reflex) movements, which are described as very 
 lively were then watched with an interest, it is to be supposed, not wholly 
 scientific. 
 
PRACTICAL EXERCISES 997 
 
 ends of the transverse processes of the atlas, and divide tlic muscles 
 down to the bone just behind these processes. Now start artificial 
 respiration (p. 202), or sooner if necessary- Notch the spinous process 
 of the axis with bone forceps. Pass a strong thick hgature by a sharp- 
 ended aneurism needle close under the body of the axis, and tic it tightly 
 in the groove left by the incis-on behind the transverse processes of the 
 atlas and the notch made in the spinous process of the axis. This com- 
 presses the vertebral arteries where they pass from transverse process 
 of axis to transverse process of atlas. Pass a second strong ligature 
 under the trachea at the level of the cricoid cartilage and include in it 
 the whole neck, except the trachea, but at present only tie a single loop 
 on it. Now decapitate the animal with a large knife (an amputating 
 knife) passed from the ventral aspect of the neck through the occipito- 
 atlantal space, severing the cord just behind its junction with the bulb. 
 At the moment of decapitation tighten the ligature round the neck and 
 complete the Itnot. Destroy the head. If there is oozing of blood from 
 the vertebral canal, arrest it by raising the neck somewhat above the 
 level of the body. The carcass must be kept warm by placing it on a 
 metal box or table containing hot water, and the air used for artificial 
 respiration must also be warmed, as by passing it through a coil of 
 rubber tubing immersed in a water-bath which is kept hot. Stitch the 
 skin-flaps together so as to cover the cut end of the spinal cord and the 
 other structures cut in decapitation. By this procedure the spinal cord 
 is usually severed about 4 millimetres behind the point of the calamus 
 scriptorius. Although the blood-pressure remains low, reflexes employ- 
 ing the skeletal muscles can be fairly well elicited for hours. Study on 
 the preparation the reflexes described in the text (pp. Qoi, 904) — e.g., the 
 flexion reflex of the hind and fore limb, as elicited from the skin, or one 
 of the afferent nerves of the limb — the crossed extension reflex of hind 
 and fore limb, the scratch reflex. 
 
 (i) Scratch Reflex. — -(a) Evoke the reflex by rubbing the skin of the 
 neck behind the pinna. The scratching movements are in the hind-leg 
 of the same side. Record them on a drum, on which is also written a 
 time-tracing in seconds. The record can be obtained by tying a piece 
 of tape, not too tightly, round the foot, leg, or thigh, and connecting 
 this by a thread with a lever. The thread is passed over a pulley below 
 the lever, so that its pull may be exerted at right angles to the axis of 
 rotation of the lever. The lever is attached to a light spring or a rubber 
 band, which is stretched when it moves in one direction, and in recoiling 
 brings it back again to its position of rest at the end of the contraction. 
 If the reflex is not easily evoked, it can be facilitated by producing a 
 slight degree of asphyxia by temporarily clamping the respiration tube. 
 Some time must elapse after the decapitation before a fair scratch reflex 
 can be expected. It is usually sufficiently well marked within an hour. 
 
 {b) WTiile the reflex is occurring, stimulate w^th an interrupted current 
 the central stump of the popliteal nerve of the opposite hind-limb. 
 The scratch reflex may be cut short by inhibition. Also, during the 
 stimulation of this nerve the reflex may be incapable of being elicited 
 till the excitation of the inhibitory afferent nerve is stopped. 
 
 (2) Flexion Reflex.— {a) Stimulate with a weak interrupted current 
 the skin of some part of the hind-limb — say one of the toes. The flexion 
 reflex of the hind-limb on the same side may be evoked — i.e., a flexion 
 movement at the knee, hip, and ankle. Record the movements of one 
 of the joints or of flexor muscles after severing them from their insertion. 
 
 (6) Stimulate with a weak interrupted (faradic) current the central 
 stump of one of the nerves of a hind-limb — say the peroneal nerve. 
 The flexion reflex of the same limb may be elicited. Record the move- 
 
998 I HI-: CENTRAL NERVOUS SYSTEM . 
 
 merits. Now produce temporary asphyxia by clampinq; the respiration 
 tube, and repeat the stinuilation at half-minute intervals. The reflex 
 will be increased by the asphyxia. Do not interrupt the respiration for 
 more than two or three minutes, and immcchatciy start it if the heart, 
 which can be felt through the chest, begins to weaken. 
 
 (3) Ehcit the knee-jerk, as described in the text (p. 90.}). It is 
 generally exaggerated. 
 
 (4) By the unipolar method (p. 031) stimulate with a i)oint electrode 
 one lateral half of the cross-section of the cervical cord exposed in 
 decapitation. The large electrode is placed on a shaved part of a fore- 
 arm. Various effects may be eUcited according to the point of the 
 cross-section stimulated — e.g., stepping and scratch movements of the 
 hind-limbs. Other facts mentioned in the text in regard to spinal 
 reflexes can l)e verified on this ]irrparation. 
 
 q. Decerebrate Cat Preparation (Miller and Sherrington). — This 
 preparation, which must be made by the demonstrator, differs from 
 the spinal preparation described in 8, in that the plane of the section 
 is considerably higher, passing through the posterior part of the mid- 
 brain ' entering the posterior colliculi (posterior corpora quadrigemina) 
 near their hinder end and emerging about a millimetre anterior to the 
 front edge of the pons.' Many reactions can be conveniently studied 
 on this preparation, some of which cannot be oV)taincd with t:he spinal 
 preparation. The respiratory movements usually go on without inter- 
 ruption, and reflexes whose centres are situated in the bulb, such as 
 the swallowing reflex, can be elicited. The circulation is well main- 
 tained, and the preparation can be used for a number of the experi- 
 ments given after Chapters III. and IV. 
 
 Under deep anaesthesia (chloroform and ether), the carotids are 
 temporarily clamped opposite the uppermost tracheal cartilage, and 
 the cat is then placed on the decerebrator (Fig. 401) in the prone posi- 
 tion, with its neck on the upper edge of the neck-block. 
 
 The interparietal suture is exposed by an incision through the scalp 
 from beyond the coronal in front to the lambdoid ridge and supraocci- 
 pital protuberance behind. A distance of 30 millimetres is then 
 measured off from the coronal suture backward along the interparietal 
 and the point is marked by notching the longitudinal median ridge of 
 bone. The head is placed between the prongs of the yoke with the 
 tongue-guard of the yoke-plate inside the mouth above the tongue, 
 which it protects. The chin lies in the hollow of the yoke under the 
 yoke-plate, the lower canines covered by the plate. The pelvis lies 
 on the pelvic platform, P, the hind limbs hanging freely. The head 
 is pushed down, the tongue guard in the mouth, until the embayed end 
 of the yoke-plate on either side of the tongue-guard meets the anterior 
 edge of the coronoid process of the lower jaw. The hook attached 
 to the leather cord is fixed in a loop of string previously tied trans- 
 versely through the upper lip, and the snout is drawn firmly down by 
 the cord, securing the head in position. The cord is fastened to a 
 cleet on the under surface of the neck-block. The nose-piece is now 
 slid up so as to engage and support in its notch the apex of the muzzle, 
 and is fixed by the screw-clamp. A knife consisting of a planing-blade 
 mounted in a wooden handle is used for the decercbration.* 
 
 * The blade is 12-5 centimetres wide, 9 centimetres high, and 4 millimetres 
 thick. It is bevelled on one face, the bevelled edge being 2 centimetres deep. 
 The cutting edge docs net extend the whole width of the blade, but stops short 
 at 1-5 centimetres from each lateral edge. The mid-width of the blade is 
 m;irked bv an engraved line on thr front of the knife. 
 
PRACTICAL EXERClSr-:S 90^ 
 
 The operator, standinfj; on the loll side of the animal, applies the mid- 
 point of the siiarp edge of the blade, bevelled side forward, to the 
 point notchefl in the interparietal ridge, the width of the blade being 
 kept truly at right angles to the median plane of the head. The knife 
 thus held in the left hand is kept vertical, or nearly so, and is directed 
 so that the plane of the blade if continued downward through the 
 
 Fig. 401. — Cat Decerebrator (Miller and Sherrington). N, wooden neck-block, 
 mounted firmly on a strong base-board. N is inclined at 22° to the vertical 
 and supported by two stout wooden props meeting it somewhat below its top 
 at an angle of 44°. The top edge of the neck-block (cut at right angles to the 
 face of the block) is therefore at an angle of 22° to the horizontal. V, yoke a 
 Y-shaped fork of wood with one of the prongs projecting 6 centimetres beyond 
 the top of the neck-block, the other prong truncated nearly to its base. A 
 Y-shaped steel plate (the yoke-plate) is screwed to Y. It is shaped somewhat 
 like the wooden yoke, but its two side prongs are of equal length, and between 
 them projects a shorter prong, T. the tongue-guard. S is a T-shaped wooden 
 nose-piece, adjustably attached to the front of the steel-covered yoke. In the 
 upper boi-der of the cross-piece of the T, is a V-shaped notch. A slot in the stem 
 of the T allows the T-block to be slid up or down on the fteel yoke-plate, and 
 it can be fixed at any position by a thumb-screw. C, a leather cord passing 
 through a hole piercing neck-block, yoke and yoke-plate. The top end of the 
 cord, issuing from the hole in the mid-line of the yoke-plate, carries a short 
 strong hook. The point of the notch in the nose-piece slides up to and slightly 
 beyond this hole. P, a light single-pillared platform, somewhat saddle-shaped 
 at the top, which can be slid on the baseboard nearer to or farther from the 
 neck-block. 
 
 head would meet a horizontal line engraved on the side-prongs of the 
 yoke-plate. This line is at the level of the free end of the tongue- 
 guard. A light blow is then struck with a mallet on the top of the 
 handle of the knife, sufficient to engage the edge in the skull in the 
 proper direction — i.e., toward the horizontal line on the metal plate. 
 Then with a couple of heavier blows the head is severed in the desired 
 plane, 
 
looo THE CESTRAL NERVOUS SYSTEM 
 
 The ]ircparation is then removed from the apparatus, the neck being 
 hcUl laterally behind the wings of the atlas to control the vertebral 
 arteries. It is placed on the experiment table with the neck well raised 
 by a string passed through the skin over the occiput, to restrain any 
 haemorrhage. Some cotton is packed across the cut surface of the mid- 
 brain. Bleeding soon ceases, and in two or three minutes one carotid 
 can be undamped, arteries in the masseteric regions being tied if neces- 
 sary. In two minutes more the clamp can be removed from the other 
 carotid. 
 
 TO. With the preparation described in q, study the swallowing reflex, 
 evoked — e.g., by the application of water by drops to the pre-epiglotti- 
 dcan sinus between the base of the tf)nguc and the epiglottis, or by 
 allowing water to drop into the pharynx. Dilute alcohol (one part of 
 ethyl alcohol added to four parts of water) is even more effective 
 than water; oil much less effective. 
 
 II. Reflex Postural Tonus (Decerebrate Rigidity). — Study the dis- 
 tribution of the tonus in the decerebrate cat prepared as in g —e.g., 
 in the extensor muscle of the knee (the vasto-crureus), the gastrocne- 
 mius, semimembranosus, triceps, supraspinatus, etc. Isolate the knee 
 extensor by paralvzing all the other muscles of both hind limbs by nerve 
 section. The vasto-crurcus still maintains its postural reflex contrac- 
 tion. To observe the right vasto-crureus place the animal on its left 
 side. Begin with the knee nearly at full extension and determine what 
 weight, attached to the tibia and pulling it backward by a cord fastened 
 over a pulley — i.e., tending to flex the knee — is just counteracted by 
 the postural action of the muscle. Now forcibly flex the knee nearly 
 to the full, bending it steadily and not too quickly, so that thc^ move- 
 ment occupies a couple of seconds. Apart from a slight partial return 
 towards extension, and this not always, the limb remains in the new- 
 position. Although the length of the vasto-crureus is now greater 
 than before, the weight needed to counterbalance its pull is practically 
 the same. That is to say, the muscle has assumed a new postural 
 length wnthout any sensible change of tension. This is the so-called 
 ' lengthening reaction ' of the posturally contracted muscle. The 
 ' shortening reaction ' can be obtained by repeating the observations 
 in the reverse order — i.e., starting with the knee in nearly full flexion 
 (Sherrington » . 
 
 12. Reflexes in Man. — Study systematically on a fellow-student 
 and on youi^elf the chief reflexes described in the text (p. 914), 
 especially — 
 
 The Knee-jerk. — (i) Elicit the jerk in the usual way by striking the 
 ligamentum patellae and observe its height. Then cause the patient to 
 make a strong voluntary movement (squeezing the hands together or 
 clenching the jaws) at the moment when the tendon is struck, and note 
 whether the height is increased by ' reinforcement.' 
 
 (2) Attach a suitable recording apparatus to the foot of a person 
 sitting with his legs over the edge of a table, and record the jerks 
 elicited by taps made as uniform in strength as possible. A small 
 hammer worked by an electro-magnet or a spring might be employed 
 for this purpose. Compare the records obtained when the jerk is 
 elicited while the person is squeezing his hands together with those 
 previously obtained. The influence of mental activity, especially of ex- 
 citement or irritation (opportunities of studying such physical states 
 occasionally ofter themselves in physiological "laboratories) in increasing 
 the height of the knec-jork may also be verified (Lombard). 
 
 13. Excision of Cerebral Hemispheres in the Frog (Fig. 402). — 
 Anaesthetize a frog lightly by putting it under a bell-jar or tumbler 
 
PRA C TIC A L l-XERCISHS 
 
 with a small piece of cotton-wool soaked in ether. Put very little ether 
 on the cotton, and leave the frog only a very short time under the 
 
 bell-jar. Ihcn, holding it in a cloth, make an 
 
 incision through the skin over the skull in the 
 
 mesial line. With scissors open the cranium 
 
 about the position of a line drawn at a tangent 
 
 to the posterior borders of the two tympanic 
 
 membranes. Remove the roof of the skull in 
 
 front o{ this line with forceps, scoop out the 
 
 cerebral hemispheres, eind sew up the wound. 
 
 As soon as the animal has recovered from the 
 
 ether, the phenomena described at p. 947 should 
 
 be verified. The frog will swim w^hen thrown 
 
 into water, will refuse to lie on its back, and 
 
 will not fall if the board on which it lies be 
 
 gradually slanted. Let the frog live for a 
 
 day, keeping it in a moist atmosphere ; then 
 
 expose the brain again, determine the reflex 
 
 time by Tiirck's method ; apply a crystal of 
 
 common salt to the optic lobes, and repeat the 
 
 observation. The reflex movements will be 
 
 completely inhibited or delayed. Remove the 
 
 salt, wash with physiologi'^.al salt solution, 
 
 excise the optic lobes, and see whether the 
 
 frog will now swim. 
 
 14. Excision of the Cerebral Hemispheres in 
 
 a Pigeon. — l-'eed a pigeon for two or three days 
 
 on drj^ food, etherize it by holding a piece of 
 
 cotton-wool sprinkled with ether over its beak, 
 
 or inject into the rectum | gramme chloral 
 
 hydrate. The pigeon being wrapped up in a 
 
 cloth, and the head held steady by an assis- 
 tant, the feathers are clipped off the head, an 
 
 incision made in the middle line through the 
 
 skin, and the flaps reflected so as to expose 
 
 the skull. Cut through the bones with scissors, 
 
 and make a sufficiently large opening to bring the cerebral hemispheres 
 into view. They are now rapidly divided from the corpora bigemina 
 and lifted out with the handle of a scalpel. The bleeding is very free, but 
 may be partially controlled by stuffing the cavity with the vegetable 
 fibre known as Pengavar Djambi, which should be removed in a few 
 minutes, the wound cleansed with iodoform gauze wrung out of physio- 
 logical salt solution at 50° C, and sewed up. Study the phenomena 
 described on p. 948. 
 
 15- Stimulation of the Motor Areas in the Dog. — (a) Study a hardened 
 brain of a dog, noting especially the crucial sulcus (Fig. 382, p. 950), the 
 convolutions in relation to it, and the areas mapped out around it by 
 Hitzig and Fritsch and others, (b) Inject morphine under the skin of 
 a dog. Set up an induction-coil arranged for tetanus, with a single 
 Daniell in the primary circuit. Connect a pair of fine but not sharp- 
 pointed electrodes through a short-circuiting key with the secondary. 
 Fasten the dog on the holder, belly down , and put a large pad under the 
 neck to support the head. Clip the hair over the scalp. Feel for the 
 condyles of the lower jaw, and join them bj- a string across the top of the 
 head. Connect the outer canthi of the eyes by another thread. The 
 crucial sulcus lies a little behind the mid-point between these two lines. 
 Now give the dog ether, make a mesial incision through the skin down 
 
 Fig. 402. — Brain of Frog 
 (after Steiner). «, cere- 
 bral hemispheres ; h, 
 position of optic thala- 
 mi; c, optic lobes; d, 
 cerebellum; e, medulla 
 oblonptata ; .4, upper 
 end of spinal cord. 
 
roo2 THE CENTRAL NERVOUS SYSTEM 
 
 to the bone, and reflect the flaps on either side. Detach as murh of the 
 temporal muscle from the bone as is necessary to get room for two 
 trephine holes, the internal borders of which must be not less than 
 ^ inch from the middle line, so as to avoid wounding the longitudinal 
 sinus. Carefully work the trephine through the skull, taking care not 
 to press heavily on it at the last. Raise up the two pieces of bone with 
 forceps, connect the holes with bone forceps, and enlarge the opening as 
 much as may be necessary to reach all the ' motor ' areas. At this 
 stage only enough ether should be given to prevent suffering. Now 
 unbind the hind- and fore-limbs on the side opposite to that on which 
 the brain has been exposed, apply blunt electrodes successively to the 
 areas for the fore- and hind-limbs, and stimulate.* The ' unipolar ' 
 method of stimulation (p. 951) may also be employed. Contraction of 
 the corresponding groups of muscles will be seen if the narcosis is not 
 too deep. Movements of the head, neck, and eyelids may also be calhd 
 forth by stimulating the ' motor ' areas for these regions. Stimulation 
 in front of the crucial sulcus may also cause great dilatation of the pupil, 
 the iris almost disappearing. The dilatation takes place most promptly 
 and is greatest on the opposite side, but the pupil on the same side is 
 also widened. Even after section of both vago-sympathetic nerves in 
 the neck, a slow and slight dilatation, greatest perhaps on the same side, 
 mav be caused by cortical stimulation. Repeat the whole experiment 
 on the opposite side of the brain. In the course of his observations the 
 student will perhaps have the opportunity of seeing general epileptiform 
 convulsions set up by a localized excitation. They begin in the group 
 of muscles represented in the portion of the cortex directly stimulated. 
 After the convulsions have been sufficiently studied, they should be 
 again induced, and the stimulated ' motor ' area rapidly excised during 
 their course. In some cases this will be followed by immediate cessation 
 of the spasms, {c) The same animal can be used for stimulation of the 
 spinal nerve-roots, as described in Experiment i (p. 995). 
 
 • it is not necessary to remove the dura mater. 
 
CHAPTER XVII 
 
 THE AUTONOMIC NERVOUS SYSTEM (THE SYMPATHETIC 
 AND ALLIED NERVES) 
 
 The efferent fibres of the body can be divided into two classes: 
 (i) Those which supply multinuclear striated muscle (skeletal 
 muscle); (2) those which supply other structures (smooth muscle, 
 heart muscle, glands). The second group is called ' autonomic,' 
 to indicate that it possesses a certain independence of the central 
 nervous system, although this independence is far from absolute. 
 The autonomic fibres arise from four regions of the central nervous 
 system : (i) The mid-brain; (2) the bulb; (3) the thoracic and upper 
 lumbar cord; (4) the sacral portion of the cord. All autonomic 
 fibres after issuing from the central nervous system end sooner or 
 later by forming synapses around nerve-cells of sympathetic type, 
 by whose axons the path is continued to the peripheral distribution. 
 The autonomic path accordingly comprises two neurons, the fibre 
 which arises from the brain or cord being termed the ' pregang- 
 lionic,' and that which arises from the sympathetic ganglion the 
 ' postganglionic ' fibre. 
 
 The autonomic fibres originating in the mid-brain emerge in the 
 oculo-motor nerve, and form synapses with cells in the ciliary 
 ganglion, which in turn send fibres to the ciliary muscle and the 
 constrictor muscle of the iris (pp. 923, 1024), The bulbar autonomic 
 fibres emerge in the seventh, ninth, and tenth cranial nerves. Those 
 in the vagus include inhibitory fibres for the heart muscle, motor and 
 inhibitory fibres for the smooth muscle of the alimentary canal from 
 the oesophagus to the descending colon, and for the muscles of the 
 trachea and lungs, and secretory fibres for the gastric glands and 
 the pancreas. The sympathetic ganglion cells with which these 
 preganglionic fibres form synapses have not always been definitely 
 located, but lie near or in the tissue supplied (p. 181). The auto- 
 nomic fibres in the seventh and ninth nerves supply the mucous 
 membranes of the mouth and nose with vaso-dilator and secretory 
 fibres. The preganglionic portion of the path terminates in such 
 ganglia as the submaxillary and subhngual (p. 391) and the spheno- 
 palatine and otic ganglia. 
 
 1003 
 
I004 
 
 THE AUTONOMIC NERVOUS SYSTEM 
 
 \Mief- 
 ' Brain 
 
 ' £u/6 
 
 The part of the autonomic system which originates in the middle 
 region of the spinal cord (in the cat from the first thoracic to the 
 fourth or fifth lumbar nerves) is the sympathetic proper. The 
 course of the fibres has already been described in connection with 
 the vaso-motor nerves (p. i8i). Among the fibres may be men- 
 tioned the dilators of the pupil, the augmentors 
 of the heart, motor (viscero-motor) and inhibi- 
 tory fibres for the smooth muscle of the alimen- 
 tarv canal, sweat-secretory, pilo-motor and vaso- 
 constrictor fibres. The preganglionic fibres issue 
 from the cord in the anterior roots, and leave 
 the corresponding spinal nerve in the white 
 ramus communicans, which connects it with the 
 corresponding ganglion of the lateral sympa- 
 thetic chain. A fibre may either end in this 
 ganglion by forming a synapse, or it may run up 
 or down in the chain for some distance before 
 terminating. Some of the preganglionic fibres, 
 particularly the vaso-constrictors for the ab- 
 dominal and pelvic viscera, do not end in the 
 lateral chain at all, but, issuing from it still as 
 medullated fibres, terminate in one of the pre- 
 vertebral ganglia — e.g., coeliac ganglion, inferior 
 mesenteric ganglion — from which postganglionic 
 fibres proceed to the viscera, as previously 
 described (p. 332). The postganglionic fibres 
 arising from cells of the lateral ganglia return 
 as non- medullated fibres in grey rami com- 
 municating to the spinal nerves, and are dis- 
 tributed with them to the head, limbs, and the 
 superficial parts of the trunk. 
 
 The autonomic fibres arising from the sacral 
 region of the cord emerge as preganglionic fibres 
 in the anterior roots of the second to the fourth 
 sacral nerves, from which they pass to the pelvic 
 nerve (nervus erigens) (pp. 181. 332). They 
 comprise vaso-dilator fibres for the rectum, anus, 
 and external genitals, motor (viscero-motor) 
 fibres for the smooth muscle of the descending 
 colon, rectum, and anus, inhibitory fibres for 
 the smooth muscle of the anus, and the 
 muscles of the external genitals, motor fibres for the bladder, etc. 
 The preganglionic fibres terminate by forming synapses with 
 sympathetic ganglion cells in the pelvic plexus, or in the neighbour- 
 hood of the organs which they supply. From these ganglion cells 
 the postganglionic fibres arise. 
 
 ■Sacra i 
 
 Fig. 403.— Diagram 
 showiag the Cen- 
 tral Origin of the 
 Autonomic Fibres 
 (Langley). 
 
FUNCTIONS Of THE AUTONOMIC SYSTEM 
 
 1005 
 
 Action of Nicotin and Adrenalin on the Autonomic System. — 
 The action of nicotin upon the sympathetic ganghon cells, or the 
 link between them and the preganglionic fibres, which has been 
 taken advantage of in tracing the course of the autonomic fibres, 
 has already been described (p. 182). The special relation of adrena- 
 lin or epinephrin to the sympathetic, although not to the rest of the 
 autonomic system, has also been alluded to (p. 655). 
 
 Functions of the Autonomic System. — The functions of the auto- 
 nomic nerves are sufficiently defined by the enumeration of the 
 peripheral organs with which they are connected. It is obvious 
 that they preside over functions for the most part withdrawn from 
 the control of the will, the so-called vegetative functions, like the 
 heart-beat, the tone of the bloodvessels, the movements of the 
 alimentary canal and of the uterus, the erection of the hairs, and 
 the secretion of sweat. It is no doubt advantageous that these 
 functions should be withdrawn from voluntary control, and this 
 withdrawal is, we may assume, secured either by the absence of 
 anatomical connections betw'een the regions of the cortex connected 
 with voluntary movements and the ganglion cells in the cerebro- 
 spinal axis from which the preganglionic fibres arise, or by the 
 existence of a high threshold of resistance in such paths as exist. 
 There is no anatomical or physiological reason why autonomic 
 fibres should not carry impulses which would elicit voluntary move- 
 ments were such impulses once shunted on to an autonomic path, 
 and certain autonomic fibres do innervate structures which are 
 under voluntary control— <?.^., the fibres to the ciliary muscle of 
 the eye and those to the urinary bladder. The power of voluntarily 
 accelerating the heart possessed by some individuals (p. 172) is 
 a further instance showing that the general rule is broken by ex- 
 ceptions. 
 
CHAPTER XVIII 
 
 THE SENSES 
 
 Hitherto we have been considering from a purely objective standpoint 
 the organs that compose the body, and their work. The student has 
 been assumed to be in the little world — the ' microcosm ' — of organiza- 
 tion which he has been studying, but not of it. He has listened to the 
 sounds of the heart, seen its contraction, felt it hardening under his 
 fingers; but we have not inquired as to the meaning or the mechanism 
 of this hearing, seeing, and feeling. We have now to recognize that all 
 our knowledge of external things comes to us by the channels of the 
 senses, and, like the light that falls through coloured windows on the floor 
 of a church, is tinged, and perhaps distorted, in the act of reaching us. 
 
 The Senses in General. — ^The old and orthodox enumeration of 
 ' the five senses ' of sight, hearing, touch, taste, and smell, must 
 be augmented by at least two more, the senses of pressure and 
 temperature. The so-called temperature sensations are themselves 
 divisible into two groups of quite distinctive quality, sensations of 
 warmth and sensations of cold. The power of appreciating the 
 amount of a muscular effort ; the power of localizing the various 
 portions of the body in space ; the sensations of pain, tickling, itching, 
 hunger, and thirst; the sensations accompanying the generative 
 act, etc., can certainly be no longer lumped together in the omnium 
 gatherum of ' common sensibility.' They are more appropriately 
 regarded as separate senses subserved by special nerves, and 
 perhaps connected with definite centres. In the development of 
 a simple sensation we may distinguish three stages: the stimulation 
 of a peripheral end-organ, the propagation of the impulses thus set 
 up along an afferent nerve, and their reception and elaboration in 
 a central organ. 
 
 We do not know in what manner a series of transverse vibrations in 
 the ether when it falls upon the eye, or a series of longitudinal vibrations 
 in the air when it strikes the ear, excites a sensation of light or sound. 
 We can trace the ray of light through the refractive media of the eyeball, 
 see it focussed on the retina, lead off the current of action set up in that 
 membrane, which, doubtless, gives token of the passage of nervous 
 impulses into and up the optic nerve. We can even follow the nervous 
 impulses to a definite portion of the cortex of the occipital lobe, and 
 determine that if this is removed no sensation of sight will result from 
 
 1 006 
 
THE SENSES IN GENERAL 1007 
 
 any excitation of retina or optic nerve. And it is fair to conclude lliat 
 in some manner this part of the cerebral cortex is essential to the pro- 
 duction of visual sensations. But in wliat way the chemical or physical 
 processes in the axis-cylinders or nerve-cells are related to the psychical 
 change, the interruption of the smooth and unregarded flow of conscious- 
 ness which we call a sensation of light, we do not know. To our 
 reasoning, and even to our imagination, there is a great gulf fixed between 
 the physical stimulus and its psychical consequence; they seem incom- 
 mensurable quantities; the transition from light to sensation of light is 
 certain, but unthinkable. 
 
 Each kind of peripheral end-organ is peculiarly suited to respond 
 to a certain kind of stimulus. The law of ' adequate ' or ' homol- 
 ogous ' stimuli is an expression of this fact. The ' adequate ' 
 stimuli of the organs of special sense may be divided into (1) vibra- 
 tions set up at a distance without the actual contact of the object 
 — e.g., light, sound, radiant heat; (2) changes produced by the 
 contact of the object — e.g., in the production of sensations of taste, 
 touch, pressure, alteration of temperature (by conduction). Mid- 
 way between (i) and (2) lies the adequate stimulus of the olfactory 
 end-organs, which are excited by material particles given off from 
 the odoriferous body and borne by the air into the upper part of 
 the nostrils. 
 
 The end-organs of the special senses all agree in consisting essentially 
 of modified ectodermic cells, but they occupy areas by no means pro- 
 portioned to their importance and to the amount of information we 
 acquire through them. The extent of surface which can be affected by 
 light in a man is not more than 20 sq. cm. ; the endings of both nerves of 
 liearing taken together do not at most expand to more than 5 sq. cm.; 
 the olfactony' portion of the mucous membrane of the nose has an area of 
 not more than 10 sq. cm.; the sensations of taste are ministered to by 
 an area of less than 50 sq. cm. ; the end-organs of the senses of pressure, 
 touch, and temperature are distributed over a surface reckoned by 
 square metres. As the physiological status of the sensory end-organs 
 rises, their anatomical distribution tends to shrink. The organs of com- 
 paratively coarse and common sensations are widely spread, inter- 
 mingled with each other, and seated in tissues whose primary function 
 may not be sensory at all. Even the nerve-endings of the sense of taste 
 are not confined to one definite and circumscribed patch, but scattered 
 over the tongue and palate ; and both tongue and palate are at least as 
 much concerned in mastication and deglutition as in taste. The 
 olfactory portion of the nasal mucous membrane, although a continuous 
 area with fairly distinct boundaries, is still a part of the general lining 
 of the nostril. The epithelial surfaces which minister to the supreme 
 sensations of sight and hearing — the retina and the sensitive structures 
 of the cochlea — are the most sequestered of all the sensory areas, as the 
 organs of which they form a part are, of all the organs of sense, the most 
 highlv specialized in function, and anatomically the most limited. But 
 although hidden in protected hollows, they are endowed, either in virtue 
 of their own movements or of those of the head, with the power of 
 receiving impressions from every side, and their actual size is thus in- 
 definitely multiplied. 
 
LOo8 THE SENSES 
 
 Section I. — Vision. 
 
 Physical Introduction. — Physically, a ray of light is a series of dis- 
 turbances or vibrations in the luminiferous ether, which radiates out 
 from a luminous body in what is practically a straight line. The ether 
 is supposed to fill all space, including the interstices between the mole- 
 cules of matter and the atoms of which those molecules are composed. 
 Suppose a bar of iron to be gradually heated in a dark room. In the 
 cold iron the molecules are moving on the average at a relatively slow 
 rate, and the waves set up in the ether by their vibrations are compara- 
 tively long. Now. the long ethereal vibrations do not excite the retina, 
 because it is only fitted to respond to the impact of the shorter waves ; 
 and, indeed, the long waves are largely absorbed by the water>' media 
 of the eye. As the temperature of the iron bar is increased, the mole- 
 cules begin to move more quickly, and waves of smaller and smaller 
 length, of greater and greater frequency, are set up, until at last some 
 of them are just able to stimulate the retina, and the iron begins to glow 
 a dull red. As the heating goes on the molecules move more quickly 
 still, and, in addition to waves which cause the sensation of red, shorter 
 waves that give the sensation of yellow appear. Finally, when a high 
 temperature has been reached, the very shortest vibrations which can 
 
 affect the eye at all mingle with the medium 
 and long waves, and the sensation is one of 
 intense white light. 
 
 We have said that a ray of light travels 
 
 in a straight line, and the direction of the 
 
 straight line does not change as long as the 
 
 medium is homogeneous. But when a ray 
 
 reaches the boundary of the medium through. 
 
 which it is passing, a part of it is in general 
 
 turned back or reflected. If the second 
 
 medium is transparent (water or glass, e.g.). 
 
 the greater part of the ray passes on through 
 
 it, a smaller portion is reflected. If the 
 
 404.— Reflection from a second medium is opaque, the ray does not 
 
 Plane Mirror. penetrate it for any great distance; if it is 
 
 a piece of polished metal, e.g., nearly the 
 
 whole of the light is reflected ; if it is a layer of lampblack, ver^- little 
 
 of the light is reflected, most of it is absorbed. 
 
 Reflection. — The first law of reflection is that the reflected ray. the ray 
 which falls upon the reflecting surface {incident ray), and the normal to the 
 surface, are in one plane. The second law is that the reflected ray makes 
 with the perpendicular [normal) to the reflecting surface the same angle 
 as the incident ray. A corollary to this is that a ray perpendicular to 
 the surface is reflected along its own path. 
 
 Reflection from a Plane Mirror. — Let a ray of light coming from the 
 point P (.Fig. 404) meet the surface DE at B, making an angle PBA with 
 the normal to the surface. The reflected ray BC will make an equal 
 angle ABC with the normal ; and the eye at C will see the image of P 
 as if it were placed at P', the point where the prolongation of BC cuts 
 the straight line drawn from P perpendicular to DE. This is the posi- 
 tion of an ordinary looking-glass image. 
 
 Reflection from a Concave Spherical Mirror. — A spherical surface may 
 be supposed to be made up of an infinite number of infinitely small plane 
 surfaces. The normal to each of these plane surfaces is the radius of 
 the sphere, and the reflected ray makes with the radius at the point of 
 
VISION 
 
 too^ 
 
 incidence the same angle as the incident ray. Let D (Fig. 405) be the 
 middle point of the mirror, and C its centre of curvature — i.e., the 
 centre of the sphere of which it is a segment. Then CD is the principal 
 axis, and any other line through C which cuts the mirror is a secondary 
 axis. When the mirror is a small portion of a sphere, rays parallel to 
 the principal axis are focussed at the principal focus F midway between 
 C and D; rays parallel to any secondary axis are focussed in a point 
 
 405. — Reflectio.i trom a Concave 
 Spherical Mirror. 
 
 Fi,'. 406. — Formation of Real Inverted 
 Image by a Concave Spherical Mirror. 
 
 lying on that axis ; and rays diverging from a point on any axis arc 
 focussed in a point on the same axis. 
 
 These facts afford a simple construction for finding the position of 
 the image of an object formed by a concave mirror. Let AB be the 
 object (Fig. 406). Then the image of A is the point in which all Ta.ys 
 proceeding from A and falling on the mirror, including rays parallel to 
 the principal axis, are focussed. But the ray AE, parallel to the prin- 
 cipal axis, passes after reflection through the principal focus F, there- 
 fore the image of A must lie on the straight line EF. If any secondary 
 axis ACD be drawn, the 
 image of A must lie on 
 ACD. It must therefore 
 be the point of intersec- 
 tion, a, of EF and ACD. 
 Similarly, the image of B 
 must be the point of inter- 
 section, b, of GF and BCH. 
 The image ab of an object 
 AB farther from the mirror 
 than the principal focus 
 is real and inverted. The 
 Purkinje -Sanson image re- 
 flected from the concave 
 anterior surface of the 
 vitreous humour (Fig. 421) 
 is an example. 
 
 After reflection from a convex mirror, rays of light always diverge, and 
 only erect, virtual images are formed — i.e., images which do not really 
 exist in space, but which, from the direction of the rays of light we. judge 
 to exist. The position of the image of an object AB (Fig. 407) niay be 
 found by a construction similar to that for reflection from a concave 
 mirror. The image of a flame reflected from the anterior surface of the 
 cornea or lens is erect and virtual. It diminishes in size with increase 
 in the curvature or convexity' of the reflecting surface (Fig. 421). 
 
 Refraction. — A ray of light passing from one medium into another 
 has its velocity-, and consequently its direction, altered. It is said to 
 
 64 
 
 407. — Formatic ;i of Image by a Convex 
 Mirror. 
 
THE SENSES 
 
 be refracted. The first law of refraction is that the refracted ray is in 
 the same plane as the incident ray and the nornuil to the surface. The 
 second law is that the sine of the angle of incidence has a constant ratio 
 (for any given pair of media) to the sine of the angle of refraction. The 
 angle of incidence is the angle which the ray makes with the normal 
 to the surface, separating the two media; the angle of refraction is the 
 angle made with the normal in the second medium. This ratio is called 
 the index of refraction between the two media. For purposes of com- 
 parison, the refractive index of a substance is usually taken as the ratio 
 of the sine of the angle of incidence to the sine of the angle of refraction 
 of a ray passing from air into the substance. 
 
 When a ray strikes a surface at right angles, it passes through without 
 suffering refraction. When a ray passes from a less dense to a denser 
 medium {e.g., from air to water), it is bent towards the perpendicular. 
 
 
 Fi^. 40'. — Refraction at a Plane Surface 
 AB is the incident; BD, the refracted 
 ray; CB, the normal to the surface. 
 When the ray passes from air into 
 another medium, the refractive index of 
 
 the latter is the fraction - — — . 
 
 Fig. 403. — Refraction by a Medium 
 bounded by Parallel Planes, P and 
 P'. The ray ABDE issues parallel 
 to its original direction; CB, FD, 
 normals to P and P'; a. angle of 
 incidence; B,f, angles of refraction. 
 
 When it passes from a more dense to a less dense medium (as from 
 water to air), it is bent away from the perpendicular. 
 
 When a ray passes across a medium bounded by parallel planes, it 
 issues parallel to itself; in other words, it undergoes no refraction 
 (Fig. 409). 
 
 Refraction and Dispersion by a Prism. — The beam of light is bent 
 towards the normal N as it ])asses across BA and away from the normal 
 N' as it passes across BC (Fig. .\io) ; at both surfaces it is bent towards 
 the base of the prism AC. At the same time the light suftcrs dispersion 
 — that is, the rays of shorter wave-length are more refracted than those 
 of greater wave-length. The deviation of any given ray is measured by 
 the angle which the refracted ray makes witli its original direction. 
 The amount of dispersion produced by a prism is measured by the 
 difference in the deviation of the extreme rays of the spectrum. The 
 dispersion produced by a given substance is proportional to the differ- 
 ence of its refractive indices for the extreme rnys. 
 
 Refraction by a Biconvex Lens. — A straight line ABC passing tlirough 
 the centres of curvature of the two surfaces of the lens is called the 
 principal axis. A point C lying on the principal axis between the 
 
VISION 
 
 loii 
 
 two centres of curvature, and possessing the property that rays passing 
 through it do not suffer refraction, is called the optical centre of the 
 lens. Any straight line, D("E, passing through the ojHical centre, is a 
 secondary axis. Rays of light proceeding from a point in the principal 
 axis arc focussed in a point on that axis. When the rays proceed from 
 an infinitely distant point in the principal axis — i.e., when they are 
 parallel to it^they arc focussed in F, the principal focus. Similarly 
 rays parallel to, or 
 proceeding from, a 
 point in a secondary 
 axis are focussed in 
 a point on that axis; 
 but if the focus is to 
 be sharp, the angle 
 between the secon- 
 dary and the princi- 
 pal axis must not be 
 so large as is indi- 
 cated in Fig. 411. 
 
 Formation of Im- 
 age by Biconvex Lens 
 (Fig. 412).— Let AB 
 be the object; then 
 if AHD be the path 
 of a ray from A parallel to the prmcipal axis, the image of A will be the 
 intersection of the straight line DF and the secondary' axis passing 
 through A. Similarly, the image of B will be the intersection of GF 
 and the secondary axis BC. Where AB is farther from the lens than 
 the principal focus, the image ab is real and inverted. This is the case 
 with the image of an external object formed on the retina. When the 
 object is nearer than the principal focus, the image is virtual and direct. 
 
 Fig. 410. —Refraction and Dispersion by a Prism. 
 
 411. — Refraction 
 Biconvex Lens. 
 
 — Formation of Image by 
 Biconvex Leas. 
 
 The image formed by the objective of a microscope when the object is in 
 focus is real and inverted ; the ocular forms a virtual erect image of this 
 real image. 
 
 Refraction by a Biconcave Lens (Fig. 413). — Parallel rays are rendered 
 divergent by the lens ; there is no real focus ; but if the rays are pro- 
 longed backwards they meet ui the virtual focus F, from which they 
 appear to come when received by the eye through the lens. 
 
 Formation of Image by Biconcave Lens (Fig. 414). — Let AB be the 
 object. Let AHDI be the path of a ray from any point A of the object 
 
I012 
 
 THE SENSES 
 
 parallel to the principal axis. Produce DI backwards (dotted line); 
 it will pass through the principal focus F. 'J hrou^h A draw the second- 
 ary axis AC. The image of A must lie both on A(" and on IDh'—i.e.. 
 it must be the intersection, a. of these straight lines. Similarly, the 
 image of B is b, the intersection of KGF and BC. The image is virtual 
 and erect. 
 
 Absorption. — No substance is perfectly transparent; in addition to 
 what is reflected, some light is always absorbed. In other words, in 
 
 Fig. 4 1 3. — Refraction by 
 a Biconcave Lens. 
 
 Fig. 414. — Formation of Image by Biconcave Lens. 
 
 passing through a body some of the light is transformed into heat, a 
 portion of the energy of the short, luminous waves going to increase the 
 vibrations of the molecules of the medium, just as a wave passing under 
 a row of barges or fishing-boats set them swinging and pitching, and so 
 imparts to them a certain amount of energy, which is ultimately changed 
 into heat by friction against the water, and against each other, and by 
 
 the straining and rubbing of 
 the chains at their points of 
 attachment. Some bodies ab- 
 sorb all the rays in the pro- 
 portion in which they occur in 
 white hght ; whether looked at 
 or looked tlu-ough, they appear 
 colourless or white. Other 
 substances absorb certain rays 
 by preference, and the amount 
 oi absorption is proportional 
 to the thickness of the layer. 
 The colours of most natural 
 bodies are clue to this selective 
 absorption. Even when looked 
 at in reflected light, they are 
 seen by rays that have pene- 
 trated a certain way into th6 
 substance and have then been 
 
 <o" 
 
 
 Fig. 415.— Diagram to show Connection of Body reflected; and, of course, a 
 Colour with Selective Absorption. smaller number of the rays 
 
 which the body specially ab- 
 sorbs are reflected than of the rays which it readily transmits, for more 
 of the latter than of the former reach any given depth. This is called 
 ' body colour' ; and such substances have the same colour when seen by 
 reflected and by transmitted light. The colour of haemoglobin is due 
 to the absorption of the violet and many of the yellow and green rays, 
 as is shown by the position of the absorption bands in its spectrum (p. 51 )• 
 In Fig. 4 1 5 the violet rays are represented as being totally absorbed before 
 passing through the substance. Some of the green rays are reflected, some 
 
VISION 
 
 1013 
 
 transmitted, some absorbed. The red rays are supposed to be mostly 
 reflected and transmitted, only to a slight extent absorbed. The colour 
 of such a substance, botii wlun looked at and when looked through, 
 would therefore be that due to a mixture of red light with a smaller 
 quantity of green. Then there is another class of substances which owe 
 their colour to selective rejection. Certain rays only are reflected from 
 their surface, and the light transmitted through a thin layer is com- 
 plementary to the reflected light— that is, the reflected and transmitted 
 rays together would make up white light. These bodies have what is 
 called ' surface colour.' and include metals, various aniline dyes, and 
 other substances. 
 
 Comparative. — Many invertebrate animals possess rudimentary sense- 
 organs, by means of which they may receive certain luminous impres- 
 sions. It is true that the mere sensation of light is not in itself sufficient 
 for the exact appreciation of the form and situation of surrounding objects. 
 But even the closure of the eyelids does not prevent a person of normal 
 eyesight from distinguishing differences in the intensity of illumination. 
 
 Cornea 
 
 ..diiiary Afusclc 
 
 Fovea ^ CentmlisS. 
 
 -Jclemtc 
 
 ---Retina 
 Optic Nen/& 
 
 Fig. 416. — Diagrammatic Horizontal Section of the Left Eye. 
 
 And it is possible that many of the humbler animals may, through the 
 pigment spots which are often called eyes, or perhaps, as in the earth- 
 worm, by means of end -organs more generally diffused in the skin, 
 attain to some such dim consciousness of light and shadow as will enable 
 them to avoid an obstacle or an enemy, to seek the sunny side of a 
 boulder or the obscurity of an overhanghig ledge of rock. But the 
 indispensable condition of distinct vision is that an image of each part 
 of an object should be formed upon a separate portion of the receiving 
 or sensitive surface. This condition is, to a certain exentt, fulfilled by 
 the compound eyes of some of the higher invertebrates (insects, e.g.). 
 Here rays from one point of the object pass through one of the funnel- 
 shaped elements of the compound eye, and rays from another point 
 
IOI4 
 
 THE SENSES 
 
 Rod* 
 
 Cones. 
 
 through another. Rays striking obliquely on the facets are stopped 
 by the opaque partitions between them. In the Cephalopods we find 
 that this compound type of eye has already been abandoned ; the smgle 
 system of curved refracting surfaces so characteristic of the vertebrate 
 eye has made its appearance; and the formation of a clean-cut image 
 of the object on the retina, with the excitation of a sharply-bounded area 
 of that membrane, follows as a geometrical consequence from the theor>' 
 of lenses. 
 
 We have to consider (i) the mechanism by which an image is 
 formed on the retina, and (2) the events that follow the formation 
 of such an image and their relations to the stimulus that calls them 
 forth. 
 
 Structure of the Eye. — The eye may be described with sufficient 
 accuracy as a spherical shell, transparent in front, but opaque over 
 
 the posterior five-sixths of its 
 surface, and filled up with a 
 series of transparent liquids 
 and solids. The sheU consists 
 of three layers concentrically 
 arranged, like the coats of an 
 onion: (i) An external tough, 
 fibrous coat, the sclerotic, the 
 anterior portion of which 
 appears as the white of the eye. 
 In front this external layer is 
 completed by the transparent 
 cornea. (2) A vascular layer, 
 the choroid, which, in the re- 
 stricted sense of the term, ends 
 in front in a series of folds or 
 plaits, the cilian,- processes. The 
 choroid contains a greater or 
 smaller quantity of the black 
 pigment melanin. The cilian,- 
 processes abut on the outer 
 boundary of the iris, which 
 may be looked upon as an 
 anterior continuation of the 
 choroidal or middle coat of the 
 eyeball. Betvveen the comeo- 
 
 .. -. sclerotic junction and the an- 
 
 Fig. 417.— Diagram of Structure of Retina terior portion of the choroid is 
 
 (after Cajal). H, layer of nerve-fibres; G, 
 layer of ganglion cells; F, internal mole- 
 cular layer; E, internal nuclear layer; 
 C, external molecular layer; B. external 
 nuclear layer; external limiting membrane ; 
 A , laver of rods and cones. 
 
 interposed a ring of unstriped 
 muscular fibres, the ciliary 
 muscle. (3) The inner or sen- 
 sitive coat, termed the retina 
 (Fig. 417). This covers the 
 choroid as a delicate mem- 
 brane, extending to the ciliary processes, where it ends in a 
 toothed margin, the ora serrata. The optic nerve forms a kind of 
 stalk to which the eyeball is attached. Its point of entrance at 
 the optic disc is a little nearer the median line than the antero-posterior 
 axis which nearlv passes through the centre of a small depression, 
 the fovea centralis, situated in the middle of the macula lutea, or 
 yellow spot. From the optic disc ^metimes called the optic 
 
VISION 
 
 1015 
 
 papilla) tho optic nerve spreads over the retina as a laj'er of non- 
 meduUated fibres, separated from the interior of the eyeball only 
 by the internal liniitinf,' nu-nibrane. 'Ihis so-called membrane is formed 
 by the expanded fei-t of the fibres of Miiller, which run like a scaffolding 
 or framework through nearly the whole thickness of the retina, ter- 
 minating at the outer limiting membrane. External to the layer of 
 nerve-fibres is the stratum of large ganglion cells, whose axons they 
 are; next to this the inner molecular layer, or inner synapse layer, 
 made up largely of the branching dendrites of these cells. The fifth 
 layer is the inner granular or nuclear layer, containing many fusiform 
 (bipolar) ' granule ' cells which send out axons into the fourth, and 
 dendrites into the sixth, or outer molecular layer, and are thus con- 
 nected with the ganglion cells of the third layer on the one hand, and 
 with the terminations of the rod and cone fibres of the seventh or outer 
 nuclear layer on the other. The arborizations of the axons of these 
 bipolar cells are situate at different 
 levels in the internal molecular 
 layer. The bipolar cells connected 
 with the rod fibres send their axons 
 right through the internal, mole- 
 cular layer to arborize around the 
 bodies of the ganglion cells, whereas 
 the axons of the bipolar cells con- 
 nected with the cone fibres ramify 
 about the middle of the layer 
 (Fig. 417). The seventh stratum 
 receives its name from the large 
 number of nuclei which it contain?. 
 These belong to structures con- 
 tinuous with the rods and cones 
 of the ninth layer, which is divided 
 from the seventh by the exterral 
 limiting membrane. Each rod is 
 prolonged into the external nuckar 
 layer as a fine fibre, which has on 
 its course a swelling containing a 
 nucleus, and terminates (in mam- 
 mals) in a fine knob in the external 
 molecular layer among the den- 
 drites of the bipolar cells. Each 
 cone of the rod and cone layer is 
 
 directly prolonged into a nucleated enlargement in the external nuclear 
 layer. From this enlargement a fibre (cone fibre) , of considerably greater 
 calibre (in mammals) than the rod fibre, passes into the external mole- 
 cular layer, where it forms an arborization, which comes into relation 
 with the arborization of the dendrites of a bipolar cells. At the fovea 
 centralis the rods are entirely absent, and the other layers of the retina 
 greatly thinned ; over the optic disc neither rods nor cones are present. 
 The disc is pierced by the retinal bloodvessels (Fig. 418). 
 
 External to the rods and cones is a sheet of pigmented epithelial cells 
 of hexagonal shape, belonging to the choroid, but remaining attached 
 to the retina when the latter is separated, and therefore often reckoned 
 as its most external layer. 
 
 A little behind the cornea and anterior to the retina is the lens, en- 
 closed in a capsule, and attached to the choroid by the suspensory 
 ligament, or zonule of Zinn. The iris hangs down in front of the lens 
 like a diaphragm, with a central hole, the pupil. Incorporated in the 
 
 Fig. 418. — Retinal Bloodvessels (Henle). 
 The arteria centralis is seen issuing 
 from the optic dies and branching over 
 the retina. The shaded area in the 
 middle of the figure represents the 
 yellow spot with the fovea centralis in 
 its centre. 
 
roi6 THE SENSES 
 
 stroma or framework of Ihc iris arc two arrangements of smooth mus- 
 cular fibres, wliich confer on it the power of adjusting the size of the 
 pupil. One of these — the sphincter pupilla} — consists of a well-defined 
 band of concentric fibres surrounding the margin of the pupil. The 
 other — the dilator pupilla: — is less sharply differentiated. It is repre- 
 sented by radial bundles of elongated, spindle-shaped cells running in 
 from the ciliary border of the iris towards the pupil. Between the iris 
 and the posterior surface of the cornea is the anterior chamber of the 
 eye. filled with the aqueous humour. Between the iris and the anterior 
 surface of the lens lies the posterior chamber, which is rather a potenial 
 than an actual cavity. The space between the lens and the retina is 
 accurately occupied by an almost structureless semi-fluid mass, the 
 vitreous humour, enclosed by the delicate hyaloid membrane, which in 
 front is reflected over the folds of the ciliary processes, and blends with 
 the suspensory ligament of the lens. The attachment of the suspensory 
 ligament is rendered firmer by the connection of this part of the hyaloid 
 membrane to a circular fibrous portion of the vitreous. Around the 
 edge of the lens is left a space, the canal of Petit. 
 
 Chemistry of the Refractive Media. — Ihe aqueous humour is a per- 
 fectly colourless, watery liquid, of slightly alkaline reaction to litmus. 
 The specific gravity is about 1008, and the total solids about i per 
 cent. Of the solids the inorganic salts (mainly sodium chloride) con- 
 stitute much the largest portion. A very small amount of protein 
 (o'Oi to 0-04 per cent.) is present, also a little dextrose (0-05 per cent.), 
 and minute traces of urea and other substances. The liquid of the 
 vitreous humour has a very similar composition, except that it contains 
 a mucin-like body, hyalomucoid, to the amount of o-o6 to o-i per cent. 
 A similar mucin-like substance is present in the cornea. The freezing- 
 point of both liquids is a little lower than that of blood-serum, A being 
 ibout 0'6°. 
 
 The lens is far richer in solids than the aqueous and vitreous humours 
 with which it is in contact (30 to 35 per cent of solids, 60 to 65 per cent, 
 of water). The salts, with small quantities of lecithin and cholesterin, 
 make up about i per cent. ; the balance of the solids consists of proteins. 
 The physical alterations, with production of turbidity, which occur in 
 the lens, and presumably in its proteins, when water enters or leaves 
 it in too great amount through imbibition or osmosis, are of importance 
 in connection with the etiology of cataract. The anatomical and 
 physiological integrity of its capsule is a prime factor in the maintenance 
 of that high degree of transparency which is necessary for the function 
 of the lens. Cataract can be experimentally induced by injuring the 
 capsule. In like manner the cornea is protected against injurious 
 changes in its water-content (normally about 80 per cent.) and conse- 
 quent turbidity by the epithelium, which separates it from the tears, 
 and the endotlieliuni, wliich separates it from the aqueous humour. 
 
 Secretion of the Intra-ocular Liquids. — The aqueous humour is 
 secreted by the uveal epithelium covering the ciliary- processes, and 
 to some extent by that covering the iris. As it is continually secreted, 
 so it is continually absorbed, the absorbed constituents finding their 
 w:;v eventually into the vein or venous sinus called the canal of Schlemm 
 and the bloodvessels of the iris and ciliary processes. The source of 
 the liquid of the vitreous body is also the uvea. While the intra-ocular 
 liquids differ from ordinary lymph, there is no reason to doubt that they 
 are secretions which contribute to the nutrition of those transparent 
 .structures of the eye which are not, and, on account of their function, 
 cannot be supplied with bloodvessels. Their most obvious use is tc 
 
VISION 1017 
 
 maintain the proper intra-ocular pressure on which the geometrical 
 figure of the eyeball, and therefore its efficiency as an optical instrument, 
 depend. 1 he balance between secretion and absorption is accurately 
 adjusted in health, but in disciise it may be upset, as in glaucoma, where 
 the intra-ocuhir tension is so much increased as to interfere with the 
 circulation, and injuriously affect the nutrition and function of the retina. 
 Experimentally, occlusion of all the arteries supplying the head causes 
 a rapid fall of tension, and the cornea becomes wrinkled and slack to 
 the touch. On restoring the circulation after not too long an interval, 
 the tension gradually returns to normal, and then becomes markedly 
 hypernormal, even when the general arterial pressure is still low. This 
 is probably due to the crippling of the elements which secrete and 
 absorb the intra-ocular fluids, or of the capillar^' walls, so that a proper 
 adjustment can no longer be attained, as happens in a tissue rendered 
 oeaematous by temporary' ana-mia. Where asphyxia of the eyeball is 
 avoided or is brief the intra-ocular pressure varies directly as the blood- 
 pressure in the ocular vessels within a wide range (Henderson and Starling) . 
 
 Retraction in the Eye — Formation of the Retinal Image. — The 
 
 amount of refraction which a ray of hght undergoes at a curved 
 surface depends upon two factors — the radius of curvature of the 
 surface, and the difference between the refractive indices of the 
 media from which the ray comes and into which it passes. The 
 smaller the radius of curvature, and the greater the difference ol 
 refractive index, the more is the ray bent from its original direction. 
 A ray of light passing into the eye meets first the approximately 
 spherical anterior surface of the cornea, covered with a thin layer 
 of tears. Since the refractive index of the tears is much greater 
 than that of air, the ray is strongly refracted here. The anterior 
 and posterior surfaces of the cornea being practically parallel, and 
 the refractive indices of the tears and aqueous humour being nearly 
 equal, but little refraction takes place in the cornea itself. At the 
 anterior and posterior surfaces of the lens the ray is again refracted, 
 since the refractive index of the aqueous and vitreous humours is 
 less than that of the lens. The following tables show the radii of 
 curvature of the refracting surfaces and the refractive indices of 
 the dioptric media, as well as some other data which are of use in 
 studying the problems of refraction in the eye : 
 
 In accommodation for 
 
 Far Vision. Near Vision. 
 
 rComea - - - - 7-8 mm. 7-8 mm. 
 Radius of curvature of J Anterior surface of lens - lO'O ,, 6*o ,, 
 
 I, Posterior surface of lens - 6-o ,, 5-5 ,, 
 
 Anterior surface of cornea and an- 
 terior surface of lens . . . 2-6 ,, 3-2 ,, 
 Anterior surface of cornea and pos- 
 terior surface of lens 
 Anterior and posterior surface of lens 
 .Posterior surface of lens and retina 
 Antero-posterior diameter of eye along the axis 
 
 Distance 
 between 
 
 7-6 ,. 
 
 7-6 
 
 4-0 ., 
 
 4-4 
 
 14-6 ,. 
 
 14-6 
 
 22-2 ,, 
 
 22-2 
 
loi8 
 
 THE SENSES 
 
 Refractive Indices — 
 
 Air i-ooo 
 
 Cornea - - ^'377 
 
 Aqueous humour ------- i"3365 
 
 Vitreous humour ------- 1-3365 
 
 Lens (total refractive index) ----- 1-437 
 
 Water . - - - 1-335 
 
 It will be seen that the refractive indices of the aqueous and vitreous 
 humours are nearly the same as that of water. That of the lens 
 differs for its various layers, the central core having a higher re- 
 fractive index (1-411) than the more superficial portions (1-388). 
 Although such calculations are open to error, it has been computed 
 that the lens acts as a homogeneous lens of 
 the same curvatures, and with a refractive 
 index of 1-437 would do. This is called the 
 total refractive index of the lens.. The 
 apparent paradox that it is greater than the 
 refractive index even of the core is explained 
 by the consideration that the core taken by 
 itself has a greater curvature than the entire 
 lens, and therefore causes a greater amount of 
 refraction in proportion to its refractive index. 
 The optical problems connected with the 
 formation of the retinal image are complicated 
 by the existence in the eye of several media, 
 with different refractive indices, bounded by 
 surfaces of different and, in certain cases, of 
 variable curvature. For many purposes, how- 
 ever, the matter can be greatly simplified, and 
 a close enough approximation yet arrived at, 
 by considering a single homogeneous medium, 
 of definite refractive index, and bounded in 
 front by a spherical surface of definite curva- 
 ture, to replace the transparent solids and 
 The principal focus being supposed to lie 
 position of the nodal point — i.e., the point 
 
 reduced ' 
 
 Fig. 419. — The Reduced 
 Eye. S. the single 
 spherical refracting 
 surface, 2-2 mm. be- 
 hind the anterior sur- 
 face of the cornea; N, 
 the nodal point, 5 mm. 
 behind S ; F, the 
 principal focus (on the 
 retina), 20 mm. behind 
 S. The cornea and 
 lens are put in in 
 dotted lines in the 
 position which they 
 occupy in the normal 
 eye. 
 
 liquids of the eye. 
 
 on the retina, the 
 
 through which rays pass without refraction — of such a 
 
 or ' schematic ' or ' simplified ' eye, and other constants, are shown 
 
 in the following table. The single refracting surface would be 
 
 situated behind the cornea and in front of the lens, at a rather 
 
 smaller distance from the anterior surface of the latter than from 
 
 the anterior surface of the former. The nodal point would be less 
 
 than half a millimetre in front of the posterior surface of the lens 
 
 (Fig. 419). The refractive index of the single transparent medium 
 
 would be a little greater than that of water. 
 
VISION luig 
 
 Reduced Eye — 
 
 Radius of curvature of the single refracting surface - 5-1 mm. 
 
 Index of refraction of the single refracting medium - - I'iS* 
 Antero-posterior diameter of reduced eye (distance of 
 
 principal focus from the single refracting surface) - 20-0 
 
 Distance of the single refracting surface behind the 
 
 anterior surface of the cornea - - - - - 2-2 
 Distance of the nodal point of the reduced eye from 
 
 |its anterior surface - - - - - - -5'0 
 
 Distance of the nodal point from the principal focus 
 
 (retina) - - - - - - - - - -15-0 
 
 Knowing the position of the centre of curvature of the single 
 ideal refracting surface — i.e., the nodal point of the reduced eye 
 — all that is necessary in order to determine the position of the 
 image of an object on the retina is to draw straight lines from its 
 circumference through the nodal point. Each of these lines cuts 
 the refracting surface at right angles, and therefore passes through 
 without any devi- 
 ation. The retinal 
 image is accord- 
 ingly inverted and 
 its size is propor- 
 tional to the solid 
 angle contained 
 between the lines 
 
 , , Fig. 420. — Figure to show how the Visual Angle and 
 
 boimdary of the sjze of Retinal image varies with the Distance of 
 
 object to the nodal an Object of Given Size. P'or the distant position 
 
 DOint or the eaual °^ ^^ *^^ visual angle is a, for the near position 
 
 ^ , ' , . 1, (dotted lines) B. 
 
 angle contamed by 
 
 the prolongations of the same lines towards the retina. This angle 
 is called the visual angle, and evidently varies directly as the size 
 of the object, and inversely as its distance. Thus the visual angle 
 under which the moon is seen is much larger than that under which 
 we view any of the fixed stars, because the comparative nearness of 
 the earth's satellite more than makes up for its relatively small size. 
 
 The dimensions of the retinal image of an object are easily calculated 
 
 when the size of the object and its distance are known. For let AB 
 
 in Fig. 420 represent one diameter of an object, A'B' the image of this 
 
 diameter, and let AB', BA', be straight lines passing through the nodal 
 
 point. Then AB and A'B' may be considered as parallel lines, and 
 
 the triangles of which they form the bases, and the nodal point the 
 
 common apex, as similar triangles. Accordingly, if D is the distance 
 
 of the nodal point from A, and d its distance from B', we have 
 
 AR A'B' 
 — -= — — . Now, d may approximately be taken as 15 mm. Suppose, 
 
 then, that the size of the moon's image on the retina is required. Here 
 0=238,000 miles, and AB (the diameter of the moon) ^2,160 miles. 
 
 ♦ Or a httle more than that of the aqueous humour. 
 
1020 THE SENSES 
 
 -ri J. 2,i6o A'B' , , I A'B' , , . , .,„- ,^, 
 
 Thus we get — „ = , or (say) — = , from which A B (the 
 
 ° 238,000 15 ^ •" no 15 ^ 
 
 diameter of the retinal image) = — ^, or about 1 mm. 
 
 ^ ' no ^ 
 
 A ship's mast 120 feet high, seen at a distance of 25 miles, will throw 
 
 on the retina an image whose height is ., - x 15 mm., i.e., 
 
 ° * 25 miles -* 
 
 120 feet I , ^ 
 
 — -n 7—7x15 mm., or x is mm., equal to 0*013 mm., or 
 
 5,280x25 feet -^ 1,100 -» T 
 
 13 ^ in size. This is not much larger than a red blood-corpuscle, and 
 
 only four times the diameter of a cone in the fovea centralis, where the 
 
 cones are most slender. In this calculation the effect of aberration 
 
 (p. 1027) in enlarging the image has been neglected. This effect is, of 
 
 course, proportionately greater for small and distant than for large and 
 
 near objects; and it is doubtful whether the smallest possible image 
 
 can be confined to an area of the retina of the size of a single cone. 
 
 Accommodation. — A lens adjusted to focus upon a screen the 
 rays coming from a luminous point at a given distance will not be 
 in the proper position for focussing rays from a point which is 
 nearer or more remote. Now, it is evident that a normal eye 
 possesses a great range of vision. The image of a mountain at a 
 distance of 30 miles, and of a printed page at a distance of 30 cm., 
 can be focussed with equal sharpness upon the retina. In an 
 opera-glass or a telescope accommodation is brought about by 
 altering the relative position of the lenses ; in a photographic camera 
 and in the eyes of fishes and cephalopods, by altering the distance 
 between lens and sensitive surface; in the eye of man, by altering 
 the curvature, and therefore the refractive power of the lens. That 
 the cornea is not alone concerned in accommodation, as was at one 
 time widely held, is shown by the fact that under water the power 
 of accommodation is not wholly lost. Now, the refractive index 
 of the cornea being practically the same as that of water, no changes 
 of curvature in it could affect refraction under these circumstances. 
 That the sole effective change is in the lens can be most easily 
 and decisively shown by studying the behaviour of the mirror 
 images of a luminous object reflected from the bounding surfaces 
 of the various refractive media when the degree of accommodation 
 of the eye is altered. Three images are clearly recognized: the 
 brightest an erect virtual image, from the anterior (convex) surface 
 of the cornea; an erect virtual image, larger, but less bright, from 
 the anterior (convex) surface of the lens; and a small inverted real 
 image from the (concave) posterior boundary of the lens (Purkinje- 
 Sanson images). The second image is intermediate in position 
 between the other two. It is possible with special care to make 
 out a fourth image; but since it is reflected from the posterior 
 surface of the cornea, at which only a slight change in the refractive 
 index occurs, it is less brilliant than the first three. When the eye 
 is accommodated for near vision, as in focussing the ivory point of 
 
VISION 
 
 the phakoscope (Practical Exercises), the corneal image is unchanged 
 in size, brightness, and position. The middle image diminishes 
 in size, comes forward, and moves nearer to the corneal image. 
 This shows that the curvature of the anterior surface of the lens 
 has been increased — that is to say, its radius of curvature diminished 
 — for the size of the image of an object reflected from a convex 
 mirror varies directly as the radius of curvature. A slight change 
 takes place in the image from the posterior surface of the lens, 
 indicating a small increase of its curvature too. By means of a 
 method founded on the observation of the changes in these images, 
 and a special instrument called an ophthalmometer which allows 
 of their measurement, Helmholtz 
 has calculated that during maxi- 
 mum accommodation, the radius 
 of curvature of the anterior surface 
 of the lens is only 6 mm., as com- 
 pared with 10 mm. when the eye 
 is directed to a distant object and 
 there is no accommodation. When 
 the lens has been removed for 
 cataract, fairly distinct vision may 
 still be obtained by compensating 
 for its loss by convex spectacles 
 of suitable refractive power (lo 
 diopters* for distant vision, and 
 15 diopters for the distance at 
 which a book is usually held), but 
 no power of accommodation re- 
 mains. The person does indeed 
 contract the pupil in regarding a 
 near object, just as happens in the 
 intact eye; the most divergent 
 rays are thus cut off and the image 
 made somewhat sharper, and there 
 may appear to be some faculty of 
 accommodation left. But the loss 
 of the whole iris by operation does 
 not affect accommodation in the least; the iris, therefore, takes 
 no part in it. That no change in the antero-posterior diameter 
 of the eyeball, caused by its deformation by the contraction of the 
 ^extrinsic muscles, can have any share in accommodation, as has 
 
 * A diopter (i D.) is the unit of refractive power generally adopted in 
 measuring the strength of lenses, and corresponds to a lens of i metre focal 
 length. A lens of 2 diopters (2 D.) has a focal length of h metre, a lens of 
 4 diopters (4 D.) a focal length of \ metre, and so on. The diverging power 
 of concave lenses is similarly expressed in diopters with the negative sign 
 prefixed. Thus, a concave lens of i metre focal length has a strength of — i D.. 
 and will just neutralize a convex lens of i D. 
 
 Fig. 421. — Purkinje - Sanson Images. 
 A, in the absence of accommoda- 
 tion; B, during accommodation for 
 a near object. The upper pair of 
 circles enclose the images as seen 
 when the light falls on the eye 
 through a double slit on a pair of 
 prisms: the lower pair show the 
 images seen when the slit is single 
 and triangular in shape. 
 
I022 THE SENSES 
 
 been suggested, is clearly proved by the fact that atropine, which 
 does not affect the action of these muscles, paralyzes the mechanism 
 of accommodation. To the consideration of that mechanism we 
 now turn. 
 
 The Mechanism of Accommodation. — While everybody is agreed 
 that the main factor in accommodation is the alteration in the 
 curvature of the lens, there is by no means the same unanimity 
 as to the manner in which this is brought about. Helmholtz's 
 explanation, which has long been the most popular, is as follows: 
 In the unaccommodated eye the suspensory ligament and the 
 capsule of the lens are tense and taut, the anterior surface of the 
 lens is flattened by their pressure, and parallel rays (or, what is the 
 same thing, rays from a distant object) are focussed on the retina 
 without any sense of effort. In accommodation for a near object, 
 the meridional or antero-posterior fibres of the ciliary muscle by 
 their contraction pull forward the choroid and relax the suspensory 
 ligament. The elasticity of the lens at once causes it to bulge 
 forwards till it is again checked by the tension of the capsule. 
 
 The explanation of Helmholtz, although widely adopted in the text- 
 books, has not escaped question in the archives. Tscheming has put 
 forward the view that when the ciliary muscle contracts, the suspensory 
 ligament is pulled backwards and outwards. Its tension is thus in- 
 creased, and the soft external layers of the lens are in consequence 
 moulded upon the harder nucleus, so as to increase the curvature 
 especially around the anterior pole. And Schoen, reviving a similar 
 theory originated fifty years ago by Mannhardt, believes that the 
 ciliary muscle, in contracting, exerts pressure on the anterior portion 
 of the lens, and so increases its curvature. He likens the process to the 
 bulging of an indiarubber ball when it is held in both hands and com- 
 pressed by the fingers a little behind one of the poles. It will be ob- 
 served that in both of these theories the suspensory ligament is supposed 
 to be stretched during accommodation, not relaxed as Helmholtz sup- 
 posed. While they have certain advantages over the theory of Helm- 
 holtz, particularly in taking account of the presence of radial and circular 
 as well as meridional fibres in the ciliary muscle, they do not agree so 
 well with such experimental tests as have been applied, and therefore 
 Helmholtz's explanation must still be regarded as the best. 
 
 It is supported by the observation of Hess that when the ciliary 
 muscle has been very strongly contracted by eserinc the lens can he 
 observed to move about with each slight movement of the eye. The 
 suspensory ligament must therefore be slackened by the contraction of 
 the ciliary muscle. ,VVhen atropine is applied the movability of the 
 lens soon disappears, owing to paralysis of the ciliary muscle. These 
 facts were first estabUshed in patients after iridectomy, but ha\e also 
 been demonstrated in the normal eye. Ev^en under the influence of 
 gravity alone, without any movements of the eye, the lens sinks about 
 i^ to ^ ram. in strong accommodation. An additional proof that the 
 suspensory ligament is perfectly slack during accommodation is derived 
 from the result of simultaneous measurements in animals of the pressure 
 in the anterior chamber and in the vitreous. Even in strong accommo- 
 dation no alteration occurs, although even slight contact with the outer 
 surface of the eyeball or contraction of the external eye muscles causes 
 
VISION 1023 
 
 a distinct cflcct. In two cavities separated by a slack membrane no 
 differences of pressure would be expected. 
 
 Anderson Stuart lays stress upon tlie function of those fibres of the 
 suspensory ligament wliicli are attached to the vitreous body, and are 
 put under tension by the contraction of the ciliary muscle, in anchoring 
 tlic Icus during strong accommodation. He believes that the liquid 
 contents of the hyaloid canal move from its anterior to its posterior end 
 in accommodation, and in the opposite direction when accommodation 
 is relaxed, and that this movement tends to prevent strains in the 
 vitreous. 
 
 In cephalopods and fishes, which are normally short-sighted, accom- 
 modation for objects at a distance is effected by a movement of the lens 
 towards the retina. In the fish's eye this is accomplished by the con- 
 traction of a special muscle, the retractor lentis. In amphibia and most 
 snakes the lens is mo\ed towards the cornea and away from the retina 
 by changes of intra-ocular pressure (Beer). 
 
 Innervation of the Ciliary Muscle and the Muscles of the Iris. — The 
 ciliary muscle and the sphincter pupilla: are supplied by autonomic 
 fibres (p. 1004), reaching them through the short ciliary nerves arising 
 from the ciliary ganglion (Fig. 422). The preganglionic fibres take 
 origin from cells in the anterior part of the oculo-motor nucleus in the 
 mid-brain. Passing to the orbit in the third nerve, they reach the 
 ciliary ganglion, and end there by forming synapses with some of its 
 cells. The axons of these cells continue the path as post-ganglionic 
 fibres in the short ciliary nerves. The dilator pupillse is supplied by the 
 long ciliary nerves coming from the ophthalmic branch of the fifth 
 nerve. 
 
 The preganglionic dilator fibres pass out by the anterior roots of the 
 first three thoracic nerves (dog, cat, rabbit), accompanied by vaso- 
 constrictor fibres for the iris. Reaching the sympathetic chain through 
 the corresponding rami communicantes, they traverse the first thoracic 
 ganglion, the annulus of Vieussens, the inferior cervical ganglion, and 
 the cervical sympathetic. They end by arborizing around some of the 
 cells of the superior cervical ganglion, whose axons eventually arrive. at 
 the Gasserian ganglion, and running along the ophthalmic division of 
 the trigeminal to the eye, reach the iris by its long ciliary branches. 
 
 The exact origin of the dilator path in the brain has not been defi- 
 nitely settled.. Some place it in the mid-brain, others in the bulb. 
 There must be at least one neuron on the path central to the spinal 
 neuron whose axon emerges from the cord as a preganglionic fibre. 
 The lower cervical and upper thoracic portion of the spinal cord has 
 received the name of the cilio-spinal region from its relation to the 
 pupillo-dilator fibres. It must not be looked upon as a centre in any 
 proper sense of the term, but rather as the pathway by which these 
 fibres pass down from the bulb, and where they may accordingly be 
 tapped by stimulation. 
 
 Stimulation of certain areas on the cortex of the frontal lobe of the 
 cerebrum (p. 1002) causes slight dilatation of the pupil even after the 
 sympathetic has been divided. This is due to inhibition of the pupillo- 
 constrictor fibres in the third nerve. 
 
 Changes in the Pupil during Accommodation. — It has been aheady 
 mentioned that along with the alteration in the curvature of the 
 lens a change in the diameter of the pupil takes place in accommo- 
 dation. When a distant object is looked at, the pupil becomes 
 larger; when a near object is looked at, it becomes smaller. Narrow- 
 
I024 
 
 THE SENSES 
 
 ing of the pupil is thus associated with contraction of the ciHary 
 muscle, and widening of the pupil witli its relaxation. 
 
 This physiolcgical correlation has its anatomical counterpart; for the 
 third nerve supplies both the iris and the ciHary muscle. Stimulation 
 of the nerve within the cranium causes contraction of the pupil, while 
 stimulation of certain portions of its nucleus in the floor of the third 
 ventricle and the Sylvian aqueduct or of the short ciliary nerves 
 (Fig. 4.22), which receive branches from the third nerve, or of the 
 ganglion itself, is followed by that change in the anterior surface of the 
 lens which constitutes accommodaticn (Hcnscn and \'oclckers). This 
 can be observed either through a window in the sclerotic in a dog or by 
 following the movements of a needle thrust into the eyeball. Bv 
 carefully localized stimulation near the junction of the aqueduct with 
 
 e?c 
 
 Fig. 422. — Scheme of Innervation of CiUar>' 
 and Iris Muscles (after Schultz). i. ciliary 
 ganglion; 2. oculo-motor nucleus; 3. spinal cell, 
 from which comes off the preganglionic fibre on 
 the pupillo-dilator path, which forms a synapse 
 with 4. a cell in the superior cervical ganglion. 
 The axon of 4 is shown passing (as an interrupted 
 line) through the Gasserian ganglion into the 
 ophthalmic division (Oph.) of the fifth nerve, V. 
 aad thence in a long ciliary nerve. 5, to the dilator of the iris. 8. From i axons 
 are shown passing by short ciliary nerves to the ciliary muscle, 6. and the constrictor 
 pupillje, 7; 9, cell of origin (in mid-brain ?) of fibre which constitutes the central 
 neuron of the pupillo-dilator path; 10. optic nerve; III. third nerve; V. fifth nerve 
 with Gasserian ganglion. 
 
 the third ventricle, it is possible to bring about the forward bulging of 
 the lens without any change in the iris : but the normal and voluntary- 
 act of accommodation cannot be disjoined from the corresponding 
 alterations in the size of the pupil. Inward rotation of the eyes accom- 
 panies contraction of the pupil in accommodation, and the question 
 may be raised whether the pupillary- change is associated with the action 
 of the extrinsic muscles of the eyeball which cause convergence or with 
 the action of the intrinsic muscles which determine the changes in the 
 curvature of the lens. It is usually considered to be associated with 
 both. In any case, accual convergence is not necessary- for the reaction, 
 since it may still be obtained on accommodation when convergence is 
 impossible on account of paralysis of the internal recti. 
 
VISION 1025 
 
 Changes in the Pupil produced by Light. — It is not only by 
 accommodation that the size of the pupil may be affected. In 
 the dark it dilates, at hrst rapidly, then gradually, and it main- 
 tains the width it has reached for several hours. This has been 
 shown by taking photographs of the eye with the magnesium flash- 
 light. In this way the width of the pupil is recorded before it has 
 time to alter. Or a longer exposure to ultra-violet light, which 
 affects the pupil but little, may be employed. When ordinary 
 light falls upon the retina the pupil contracts, and the amount of 
 contraction is roughly proportional to the intensity of the light. 
 Contraction of the pupil to light is brought about by a reflex 
 mechanism, of which the optic nerve forms the afferent and the 
 oculo-motor the efferent path, while the centre is situated in the 
 floor of the aqueduct of Sylvius. The relation of this centre to 
 that which controls the changes in the pupil during accommodation 
 has not as yet been sufficiently elucidated; but this we do know, 
 that one of the paths may be interrupted by disease, while the other 
 is intact. For in tabes (locomotor ataxia), and in dementia para- 
 lytica (general paralysis), the light-reflex sometimes disappears, 
 while the constriction of the pupil in accommodation and conver- 
 gence still takes place (Argyll-Robertson pupil). Artificial stimula- 
 lion of the optic nerve has the same effect on the pupil as the 
 ' adequate ' stimulus of light; and in many animals (including man), 
 though not in those whose optic nerves completely decussate, there 
 is a consensual light-reflex — i.e., both pupils contract when one 
 retina or optic nerve is excited. This should be remembered in 
 using the pupil-reaction as a test of the condition of the retina. 
 For although the absence of contraction may show that the retina 
 of the eye on which the light is allowed to fall is insensible (unless 
 there is some physical hindrance to its passage, such as opacity 
 of the lens or cataract), the occurrence of contraction does not 
 exclude insensibility of the retina unless the other eye has been 
 protected from the light. 
 
 Stimulation of the cervical sympathetic causes marked dilata- 
 tion of the pupil, even when the third nerve is excited at the same 
 time. The pupillo-dilator fibres do not act by constricting the 
 bloodvessels of the iris. For dilatation of the pupil can be caused 
 in a bloodless animal by stimulating the sympathetic. And even 
 when the circulation is going on, a short stimulation of the sympa- 
 thetic causes dilatation of the pupil without vaso-constriction, 
 while with longer excitation the dilatation of the pupil begins before 
 the narrowing of the bloodvessels. Nor does it seem possible to 
 accept the view that the sympathetic fibres are inhibitory for the 
 sphincter muscle of the iris. They act directly upon dilator muscu- 
 lar fibres. It has, indeed, long been known that in the iris of the 
 otter and of birds a radial dilator muscle exists; and it has been 
 
 65 
 
1026 THE SE>!SES 
 
 shown by Langley and Anderson that in the ins of the rabbit, cat, 
 and dog, the presence of radially arranged contractile substance, 
 different it may be in some respects from ordinary smooth muscle, 
 must be assumed. Both the constrictor and the dilator muscles 
 of the iris are normally in a condition of greater or less tonic con- 
 traction, so that the size of the pupil at any given moment depends 
 on the play of two nicely balanced forces. Reflex dilatation of the 
 pupil through the sympathetic fibres is caused in man by painful 
 stimulation of the skin, by dyspnoea, by muscular exertion, and 
 in some individuals even by tickling of the palms. In animals the 
 stimulation of naked sensory nerves has the same effect. The ' start- 
 ing of the eyeballs from their sockets,' which the records of torture so 
 often note, is due to a similar reflex excitation of the sympathetic 
 fibres supplying the smooth muscle of the orbits and eyelids. 
 
 Action of Drugs on the Function of the Intrinsic Eye Muscles. — The 
 
 local application of atropine causes tempc)rar3' paralysis of accommoda- 
 tion and dilatation of the pupil. When the third nerve is divided, the 
 pupil dilates; it dilates still more when atropine is administered after 
 the operation. Dropped into one eye in small quantity, atropine only 
 produces a local effect ; the pupil of the other eye remains of normal 
 size, or somewhat constricted on account of the greater reflex stimula- 
 tion of its third nerve by the greater quantity of light now entering the 
 widelv-dilated pupil of the atropinized eye. Even in the excised eye 
 the effect of the drug is the same. Introduced into the blood atropine 
 causes both pupils to dilate. Its action is to paralyze the endings of 
 the oculo-motor fibres to the sphincter pupillae and ciliary muscle. 
 Other mydriatic, or pupil-dilating drugs, are cocaine, daturine. and 
 hyoscvamine. Physostigmine or eserine. pilocarpine , and muscarine are 
 the chief miotics, or pupil-constricting substances. They also cause 
 spasm of the ciliary muscle, and inability^ to accommodate for distant 
 objects. They act' by stimulating the structures (nerve-endings) (see 
 pp. 182, 739) which atropine paralyzes. The work of the mydriatics 
 can be undone by the miotics. Thus the dilatation produced by atro- 
 pine is removed by pilocarpine. 
 
 Functions of the Iris. — In vision the iris performs two chief 
 functions: (i) It regulates the quantity of light allowed to fall 
 upon the retina. The larger the aperture of a lens, the greater is 
 its collecting power, the more light does it gather in its focus. In 
 the eye, the area of the pupil determines the breadth of the pencil 
 of light that falls upon the lens. If this area was invariable, the 
 retina would either be ' dark from excess of light ' in liright sunshine, 
 or dark from defect of light in dull weather or at dusk. In ordei 
 that the iris may act as an efficient diaphragm it must be pig- 
 mented, and it is the pigment in it which gives the colour to the 
 normal eye. The vision of albinos, in whose eyes this pigment is 
 wanting, is often, though not invariably, deficient in sharpness. 
 There is always intolerance of bright light ; and the same is true 
 in the condition known as irideremia, or congenital absence or 
 defect of the iris. 
 
VISION 
 
 1027 
 
 (2) Another, and pcrliaps equally inii)()iiant, function of tlie iris 
 is to cut off the more divergent rays of a pencil of light falling upon 
 the eye, and thus to increase the sharpness of the image. This 
 leads us to the consideration of certain defects in the dioptric 
 arrangements of the eye. 
 
 Defects of the Eye as an Optical Instrument. — (i) Spherical Aberra- 
 tion.— It is a property of a sphcrii ,il rcl'nictiug surface that rays of 
 liglit passing through the peripheral portions arc more strongly reirai.tcd 
 than rays passing near the principal axis. Hence a luminous point 
 is not focussed accurately in a single ix)int by a spherical lens ; the image 
 is surrounded by fainter circles of light, the so-called circles of diffusion 
 representing the rays which have not yet come to a focus, or having been 
 already focussed have crossed and arc now diverging. In the eye this 
 spherical aberration is partly corrected by the interposition of the iris, 
 which cuts off the more peripheral rays, especially in accommodation 
 for a near object, when they are most divergent. In addition, the 
 anterior surfaces of the cornea and lens are not segments of spheres, but 
 of ellipsoids, so that the curvature diminishes somewhat with the dis- 
 tance from the optic axis, 
 and, therefore, the re- 
 fracting power as we pass 
 away from the axis does 
 not increase so rapidly 
 as it would do if the 
 surfaces were truly 
 spherical. Further, the 
 refractive index of the 
 peripheral parts of the 
 lens is less than that of 
 its central portions. 
 
 (2) Chromatic Aberra- 
 tion. — All the rays of the 
 spectrum do not travel 
 with the same velocity 
 through a lens, and are, 
 therefore, unequally refracted by it, the short violet rays being focussed 
 nearer the lens than the long red rays. It was at one time supposed that 
 this chromatic aberration, as it is called, is compensated in the eye; and 
 it is said that this mistake gave the first hint that Newton's dictum as 
 to the proportionality between deviation and dispersion was erroneous, 
 and led to the discovery of achromatic lenses. But in reality the eye 
 is not an achromatic combination ; and the violet rays are focussed 
 about J mm. in front of the red. Thus, in Fig. 424 the white light 
 passing through the lens is broken up into its constituents: the violet 
 focus is at V, and the red at R, behind it. A screen placed at R would 
 show not a point image, but a central point surrounded by concentric 
 circles of the spectral colours, with violet outside. If the screen was 
 placed at V, the centre would be violet and the red would be external. 
 For this reason it is impossible to focus at the same time and with perfect 
 sharpness objects of different colours; a red light on a railway track 
 appears nearer than a blue light, partly perhaps for the reason that it is 
 necessary to accommodate more strongly for the red than for the blue, 
 and we associate stronger accommodation with shorter distance of the 
 object, although other data are also involved in such a visual judgment. 
 When we look at a white gas-fiame through a cobalt glass, which allows 
 only red and violet to pass, we see either a red fiame, surrounded by a 
 
 Fig. 423. — Spherical Aberration. Rays passing 
 through the more peripheral parts of a biconvex 
 lens L are brought to a focus F nearer the lens than 
 F', the focus of rays passing through the central 
 portions of the lens. 
 
1028 
 
 THE SENSES 
 
 violet ring, or a violet flame surrounded by a red ring, according as we 
 focus for the red or for the viokt rays. But the dispersive power of 
 the eye is so small, and the capacity of rapidly altering its accommoda- 
 tion so great, that no practical inconvenience results from the lack of 
 achromatism, which, however, may be easily demonstrated by looking 
 at a pattern such as that in Fig. 425 at a distance too small for exact 
 accommodation. 
 
 It is also reckoned among the optical imperfections of the eye (3) that 
 the curved surfaces of the cornea and lens do not form a ' centred ' system 
 — that is to say, their apices and their centres of curvature do not all 
 lie in the same straight line; (4) that the pupil is eccentric, being 
 situated not exactly opposite the middle of the lens and cornea, but 
 nearer the nasal side, and that in consequence the optic axis, or straight 
 line joining the centres of curvature of the lens and cornea, does not 
 coincide with the visual axis, or straight line joining the fovea centralis 
 with the centre of the pupil, which is also the straight line joining the 
 centre of the pupil and any point to which the eye is directed in \'ision. 
 The angle between the optic and visual axis is about 5° (Fig. 416). 
 
 Fi;^. 424. — ^Chromatic Aberration. The violet 
 rays are brought to a focus V nearer the lens 
 than R, the focus of the red rays. 
 
 Fig. 425. — To show Dispersion in 
 Eye (v. Bezold). View the 
 figure from a distance too small 
 for accommodation. Approach 
 the eye towards it; the white 
 rings appear bluish owing to 
 circles of dispersion falling on 
 them — i.e., circles of light of 
 different colours due to the 
 decomposition of white light 
 into its spectral constituents by 
 the media of the eye. A little 
 closer, and the black rings be- 
 come white or yellowish -white. 
 
 (5) Muscae volitantes, the curious bead- 
 like or fibrillar forms that so often flit 
 in the visual field when one is looking 
 through a microscope, are the token that 
 the refractive media of the eye arc not 
 perfectly transparent at all parts ; they seem to be due to floating opacities 
 in the vitreous humour, probably the remains of the embr^'onic cells from 
 which the vitreous body was developed. (6) Lastly, it may be men- 
 tioned that slight irregularities in the curvature of the lens exist in all 
 eyes, so that a point of light, like a star or a distant street-lamp, is not 
 seen as a point, but as a point surrounded by rays (irregular astigma- 
 tism). In bringing this review of the imperfections of the dioptric 
 media of the normal eye to a close, it may be well to explain that what 
 are defects from the point of view of the student of pure optics are not 
 necessarily defects from tlie freer standpoint of the physiologist, who 
 surveys the mechanism of vision as a whole, the relations of its various 
 parts to one another and to the needs of the organism it has to serve, 
 the long series of developmental changes through which it has come 
 to be what it is, and the possibilities, so far as we can limit them, that 
 were open to evolution in the making of an eye. The optician may 
 perhaps assert, and with justice, that he could easily have made a better 
 lens than Nature has furnished, but the physiologist will not readily 
 admit that he could have made as good an eye. 
 
VISION 
 
 1029 
 
 While the defects hitherto mentioned are shared in greater or 
 less degree by every normal eye, there are certain other defects 
 which either occur in such a comparatively siriail numlx-r of eyes, 
 or lead to such grave disturbances of vision when they do occur, 
 that they must be reckoned as abnormal conditi(jns. In the normal 
 or emmetropic eye, parallel rays — and for this purpose all rays 
 coming from an object at a distance greater than 65 metres may be 
 considered paralK'l — are brought to a focus on the retina without 
 any effort of accommodation. The distance at which objects can 
 be distinctly seen is only limited by their size, the clearness of the 
 atmosphere, and the curvature of the earth; in other words, the 
 punchtm remotnm, or far-point of vision, the most distant point at 
 which it is possible to see with distinctness, is practically at an 
 infinite distance. When accommodation is paralyzed by atropine, 
 only remote objects can be clearly seen. On the other hand, the 
 normal eye, or, to be more precise, the normal eye of a middle-aged 
 
 Fig. 426. — Refraction in the (Xormal) Emmetropic Eye. The image V oi a distant 
 point P falls on the retina when the eye is not accommodated. To save space, 
 P is placed much too near the eye in Figs. 426, 427. 
 
 adult, can be adjusted for an object at a distance of not more than 
 12 cm. (or 5 inches). Nearer than this it is not possible to see 
 distinctly; this point is accordingly called the punctuni proximum 
 or near-point. The range of accommodation for distinct vision 
 in the enmietropic eye is from 12 cm. to infinity. 
 
 Myopia, or short-sightedness, is generally due to the excessive 
 length of the antero-posterior diameter of the eyeball in relation 
 to the converging power of the cornea and the lens. Even in 
 the absence of accommodation, parallel rays are not focussed on 
 the retina, but in front of it; and in order that a sharp image may 
 be formed on the retina the object must be so near that the rays 
 proceeding from it to the eye are sensibly divergent — that is to 
 say, it must be at least nearer than 65 metres — but as a rule an 
 object at a distance of more than 2 to 3 metres cannot be distinctly 
 seen. With the strongest accommodation the near-point may be 
 as little as 3 cm. from the eye. The range of vision in the myopic 
 
I030 
 
 THE SENSES 
 
 eye is therefore very small. The defect may be corrected by con- 
 cave glasses, which render the rays more divergent. It is to be 
 noted that many cases of internal squint in children are connected 
 with myopia, the eyes necessarily rotating inwards as they are made 
 to fix an abnormally near object. The treatment both of the squint 
 and the myopia in these cases is the use of concave spectacles 
 (Fig. 427). Myopia, although a condition that shows a distinct 
 
 Fig. 427. — Myopic Eye. The image P' of a distant point P falls in front of the retina 
 even without accommodation. By means of a concave le.is L the image may be 
 made to fall on the retina (dotted lines). 
 
 hereditar\' tendency, is rarely present at birth; the elongation of the 
 antero-posterior diameter of the eyeball develops gradually as the 
 child grows. 
 
 In hypermetropia, or long-sightedness, the eye is, as a rule, too 
 short in relation to its converging power; and with the lens in the 
 position of rest, parallel rays would be focussed behind the retina. 
 Accordingly, the hypermetropic eye must accommodate even for 
 
 Fig. 428. — Hypermetropic Eye. The image P' of a point P falls beliind the retina 
 in the unaccommodated eye. By means of a convex lens L it may be focussed 
 on the retina without accommodation (dotted lines). 
 
 distant objects, while even with maximum accommodation an 
 object cannot be distinctly seen unless it is farther away than the 
 near-point of the emmetropic eye. The far-point of distinct vision 
 is at the same distance as in the emmetropic eye — viz., at infinity — 
 the near-point is farther from the eye. The defect is corrected by 
 convex glasses (Fig. 428). Hypermetropia, unlike myopia, is 
 present at birth. 
 
VISION 1031 
 
 Presbyopia, or llie long-sightedness of old age, is not to be con- 
 founded with hypermetropia. It is essentially due to failure in 
 the power of accommodation, chiefly through weakness of the 
 ciliary muscle, but partly owing to increased rigidity and loss of 
 elasticity of the lens. Images of distant objects are still formed 
 on the retina of the unaccommodated eye with perfect sharpness — 
 i.e., the far-point of vision is not affected. But the eye is unable 
 to accommodate sufficiently for the rays diverging from an object 
 at the ordinary near-point ; in other words, the near-point is farther 
 away than normal. Convex glasses are again the remedy. 
 
 The near-point of distinct vision can be fixed in various ways — 
 among others, by means of Scheiner's experiment (Practical 
 Exercises, p. 1103). Two pin-holes are pricked in a card at a dis- 
 tance less than the diameter of the pupil. A needle viewed through 
 the holes appears single when it is accommodated for, double if it 
 is out of focus. The near-point of vision is the nearest point at 
 which the needle can still, by the strongest effort of accommoda- 
 tion, be seen single. 
 
 Astigmatism. — It has been mentioned that slight differences of 
 curvature along different meridians of the refracting surfaces exist 
 in all eyes. But in some cases the difference in two meridians at 
 right angles to each other is so great as to amount to a serious 
 defect of vision. To this condition the name of ' astigmatism ' or 
 ' regular astigmatism ' has been given. It is usually due to an 
 excess of curvature in the vertical meridians of the cornea, less fre- 
 quently in the horizontal meridians; occasionally the defect is in 
 the lens. Rays proceeding from a point are not focussed in a point, 
 but along two lines, a horizontal and a vertical, the horizontal 
 linear focus being in front of the other when the vertical curvature 
 is too great, behind it when the horizontal curvature is excessive. 
 The two limbs of a cross or the two hands of a clock when they are 
 at right angles to each other cannot be seen distinctly at the same 
 time, although they can be successively focussed. The condition 
 may be corrected by glasses which are segments of cylinders cut 
 parallel to the axis (Practical Exercises, p. 1105). 
 
 The Ophthalmoscope. — The pupil of the normal eye is dark, and 
 the interior of the eye invisible, without special means of illu- 
 minating it. But this is not because all the light that falls upon the 
 fundus is absorbed by the pigment of the choroid, for even the pupil 
 of an albino appears dark when the eye is covered by a piece of 
 black cloth with a hole in front of the pupil. The explanation is 
 as follows : 
 
 Let the rays from a luminous point, P, be focussed by the lens, 
 L, at P' (Fig. 429). It is plain that rays proceeding from F will 
 exactlv retrace the path of those from P and be focussed at P. 
 Now, the eye receives rays from all directions, and, when it is 
 
1032 
 
 THE SENSES 
 
 sufficiently well illuminated, sends rays out in all directions. The 
 moment, however, that the observing eye is placed in front of the 
 observed eye, the latter ceases to receive light from the part of the 
 field occupied by the pupil of the former, and therefore ceases to 
 reflect light into it. 
 
 This difficulty is avoided by the use of an ophthalmoscopic 
 mirror. The original, and theoretically the most perfect, form of 
 
 such a mirror is a plate, 
 or several superposed 
 plates, of glass, from which 
 a beam of light from a 
 laterally placed candle or 
 lamp is reflected into the 
 observed eye, and through 
 Fig. 429. which the eye of the ob- 
 
 server looks (Fig . 430). 
 But the illumination thus obtained is comparatively faint; and a 
 concave mirror is now generally used. In the centre is a small 
 hole or a small unsilvered portion of the mirror for the observer's 
 eye. In the direct method of examination (Fig. 432), the mirror 
 is held close to the observed eye, and an erect virtual image of 
 
 I-ig. 430. — Figure to illustrate the Principle of the Ophthalmoscope. Rays of light 
 from a point are reflected by a glass plate M (several plates together in Helm- 
 holtz's original forin) into the observed eye E*. Their focus would fall, as shown 
 in the figure, at P, a little behind the retina of E^. The portion of the retina 
 AB is therefore illuminated by diffusion circles; and the rays from a point of 
 it I"" will, if El is emmetropic and unaccommodated, issue parallel from F.^ and 
 be brought to a focus at F* on the retina of the (emmetropic and unaccommo- 
 dated) observing eye E. 
 
 the fundus is seen. When the eye of the observer and of the 
 patient are both emmetropic, and both eyes are unaccommodated, 
 the rays of light proceeding from a point of the retina of the 
 observed eye are rendered parallel by its dioptric media, and are 
 again brought to a focus on the observer's retina. 
 
 If the observed eye is myopic, the rays of light coming from 
 
VISION 
 
 1033 
 
 a point of the retina leave the eye, even when it is unaccommo- 
 datecl, as a convergent pencil; and the emmetropic non-accom- 
 modated eye of the observer must have a concave lens placed 
 before it in order that the fundus may be distinctly seen. 
 
 When the observed eye is hyper- 
 metropic, the rays emerging from the 
 unaccommodated eye are divergent, 
 and a convex lens, the strength of 
 which is proportional to the amount 
 of hypermetropia, must be placed 
 before the observer's unaccommo- 
 dated eye if he is to see the fundus 
 distinctly. By accommodating, the 
 observer can see the fundus clearly 
 without a convex lens. 
 
 By this method errors of refraction 
 in the eye may be detected and 
 measured. The observer must always 
 keep his eye unaccommodated, and 
 if it is not emmetropic, he must 
 know the amount of his short- or 
 long-sightedness — i.e., the strength 
 and sign of the lens needed to correct 
 his defect of refraction, and must 
 
 allow for this in calculating the defect of his patient. Non- 
 accommodation of the eye of the latter can always be secured by 
 the use of atropine. 
 
 Fig 43>- 
 
 May's Electric Ophthal- 
 moscope. 
 
 Fig. 432. — Direct Method of using the Ophthalmoscope. Light falling on the per- 
 forated concave mirror M passes into the observed eye E' ; and, both E' and the 
 observing eye E being supposed emmetropic and unaccommodated, an erect 
 virtual image of the illuminated retina of E' is seen by E. 
 
 By the direct method of ophthalmoscopic examination, only a 
 small portion of the retina can be seen at a time, and this is highly 
 magnified. A larger, though less magnified, view can be got by 
 the indirect method. The observed eye is illuminated as before, 
 
1034 THE SENSES 
 
 but the mirror and the observer's eye are at a greater distance 
 (Fig. 435). Here the rays from a considerable portion of the 
 retina are brought to a focus by a convex lens held near the eye 
 of the patient, so as to form a real and inverted aerial image of the 
 
 Fig. 433. — Use of the Ophthalmoscope (Direct Method) for testing Errors of Re- 
 fraction in Myopic Eye. Rays issuing from a point of the retina of E', the 
 observed (myopic and unaccommodated) eye, pass out, not parallel, but con- 
 vergent. They will therefore be focussed in front of the retina of the observing 
 (unaccommodated) eye E if the latter is emmetropic. By introducing a concave 
 lens L of suitable strength, however, a clear view of the retina of E' will be 
 obtained, and the strength of this lens is the measure of the amount of myopia. 
 
 retina. This image is viewed by the observer at his ordinary visual 
 distance. It is not necessary in this method that the observed 
 
 eye should be non-accommodated, although it is convenient as in 
 
 Eig. 4.34. Testing Errors of Refraction in Hypermetropic Eye. Rays from a point 
 of the retina of E', the observed eye, issue divergent, and are focussed behind 
 the retina of the observing (unaccommodated and emmetropic) eye E. The 
 strength of the convex lens L, which must be introduced in front of E to give 
 clear vision of the retina of E', measures the degree of hypermetropia. 
 
 the direct method to cause dilatation of the pupil by atropine, which 
 also relaxes the accommodation (Practical Exercises, p. II08). 
 
 Skiascopy. — To a great extent the oplithalmoscopic method of 
 measuring errors of refraction has been replaced by the more modern 
 
VISION 
 
 »035 
 
 method of skiascopy (shadow test). It depends upon the following 
 observation: When one throws light from a little distance with a 
 concave mirror into an observed eye and then rotates the mirror 
 slowly aroimd the long axis of the liandle, one sees that the pupil, 
 which at hrst was completely illuminated, becomes dark from one 
 side as if covered by a shadow. This shadow will move in the same 
 direction in which the mirror is rotated or in the opposite direction, 
 accorchng to whether the observer is farther from the observed eye 
 than its far-point, or between the eye and the far-point. If the 
 observer is exactly at tiie far-point, no direction of movement of 
 the shadow can be made out, but the pupil in its whole extent is 
 
 Fig. 435. — Indirect Method of using the Ophthalmoscope. The rays of light issuing 
 from E', the observed eye, are focussed by the biconvex lens L, and a real inverted 
 image of a portion of the retina of E', magnified four or five times, is formed in 
 the air between the lens and the observing eye E. This image is viewed by E 
 at the ordinary distance of distinct vision (10 to 12 inches). (The exaggeration 
 of the size of the mirror makes it appear as if some of the rays from the lamp 
 passed through the lens before being reflected from the mirror. This would not 
 be the case in an actual observation.) 
 
 either illuminated or altogether dark. In this way the distance 
 of the far-point of a myopic eye can be easily determined by a 
 metre rule, and from this the degree of myopia. If the far-point 
 is either too near, as in strong myopia, or too distant, as in weak 
 myopia and emmetropia, or behind the observed eye, as in hyper- 
 metropia, it can be brought to a convenient distance by interposing 
 suitable lenses. The observer then determines the far-point exactly 
 by moving his eye nearer to or farther from the observed eye, 
 or, keeping his own eye fixed, by bringing the far-point of the 
 observed eye to coincide with it by inserting lenses (Practical 
 Exercises, pp. 1109, iiio). 
 
1036 
 
 THE SENSES 
 
 The phenomenon depends upon the interruption wliich the liglit pro- 
 ceeding from the observed retina experiences first at the margin of the 
 pupil of the observed eye, and then at the margin of the hole in the 
 mirror or of the observer's pupih When the mirror is rotated, an illu- 
 minated point of the observed retina will move in the opposite direction 
 over the retina.* The light proceeding from this point when the 
 observed eye is emmetropic is so refracted by the lens and cornea that 
 it leaves the eye as a bundle of parallel rays in the direction of the 
 image of the source of light (L') (Fig. 43^). If the image of the flame 
 reflected by the mirror is situated on the principal axis of the observer's 
 eye, and if the pupils of observed and observer are of equal size, all 
 the rays coming from the observed retina will fall on the observer's 
 retina, and therefore the whole pupil of the observed eye will appear 
 light. If the mirror is now rotated so that the image of the source of 
 light moves away from the principal axis, and the illuminating rays are 
 no longer in that axis, the illuminated point will move in the opposite 
 direction from the principal axis, and the light returning from the pupil 
 of the observed eye will again issue in the direction of the image of the 
 
 Fig. 436. — Path of Rays in Skiascopy (Snellen). U, observed eye; Be, eye of ob- 
 server; Sp, mirror; /., source of light; /-', image of the source of light; A, A', 
 principal axis; P. I", pupils. 
 
 source of light. It can then happen that none of the rays hit the 
 observer's pupil, and the observed pupil will appear entirely dark. Or 
 the direction of the rays may be such tliat a portion of them enters the 
 observer's pupil, the rest being interrupted by its border. In this case 
 the part of the observed pupil from which rays enter the observer's 
 pupil will appear light, while the rest is dark. From Fig. 436 it can be 
 seen that the light part of the observed pupil is on the opposite side of 
 the principal axis from the image of the source of light. If, therefbrc, 
 the image of the source of light moves to the riglit (by rotation of a 
 concave mirror to the right, or rotation of a plane mirror to the left) 
 the skiascopic appearance in the observed pupil moves to the left — i.e., 
 in the opposite direction to the image of the source of light. 
 
 If the observed pupil is myopic — i.e., if its far-point is between the 
 observer and the observed eye, rotation of the mirror so far from the 
 jirincipal axis that only a part of the rays issuing from the observed 
 pupil enter the observer's eye, will cause the pupil to appear light only 
 
 • When a concave mirror is rotated to the right, the inverted real mirror 
 image also moves to the right, and the illuminated point to the left. When 
 a plane mirror is rotated to the right, the virtual mirror image moves to tho 
 left, and the illuminated point on the retina therefore to the right. 
 
VISION 
 
 to37 
 
 on oaie side, and on account of the crossing of the rays this illuminated 
 portion will be on the same side of the principal axis as the image ol 
 the source of light (Fig. 437). When the image of the source of light is 
 moved to the right the light area of the observed pupil will also move 
 to the right — i.e.. with rotation of a concave mirror in the same direction 
 as the image of the source of light, and with rotation of a plane mirror 
 in the opposite direction (Snellen). 
 
 A method of photographing the retina in the living eye has also been 
 employed as a means of investigating the fundus. 
 
 Single Vision with Both Eyes — Diplopia. — Scheiner's experiment shows 
 that it is possible to have double vision, or diplopia, with a single eye 
 when two separate images of the same object fall upon different parts 
 of the retina. In vision with both eyes, or binocular vision, an image 
 of every object looked at is, of course, formed on each retina, and we 
 have to inquire how it is that as a rule these images are blended in 
 consciousness so as to produce the perception of a single object; and 
 
 A- 
 
 Fig- 437-- 
 
 -Path of Rays in Skiascopy (Myopic Eye) (Snellen). PR, far -point ol 
 observed eye. The otber references are as in Fig. 436. 
 
 how it is that under certain conditions this blending does not take 
 place, and diplopia results. Two chief theories have been invoked in 
 the attempt to answer these questions: (i) the theory of identical 
 points, (2) the theory of projection. 
 
 In regard to the second theory, we shall merely say that it assumes 
 that in some way or other the retina, or, rather, the retino-cerebral 
 apparatus, has the power of appreciating not only the shape and size 
 of an image, but also the direction of the rays of light which form it, 
 and that the position of the object is arrived at by a process of mental 
 projection of the image into space along these directive lines. Where 
 the directive lines of the two eyes cut each other, the two images coin- 
 cide, and the object is seen single in the position of the point of inter- 
 section. The first theory we shall examine in some detail. 
 
 The Theory of Identical Points. — This theory assumes that every 
 point of one retina ' corresponds ' to a definite point of the other retina, 
 and that in virtue of this correspondence, either by an inborn necessity 
 or from experience, the mind refers simultaneous impressions upon two 
 corresponding or identical points to a single point in external space. 
 If we imagine the two retinas in the position which the eyes occupy 
 when fixing an infinitely distant object — that is, with the visual axes 
 parallel — to be superposed, with fovea over fovea, ever)-' point of the 
 one retina will be covered by the corresponding point of the other 
 retina, so that identical points could be pricked through with a needle. 
 
,oj8 THE SENSES 
 
 But since the actual centre of the retina docs not corrcsjKind with the 
 fovea centralis ^Fig. 416J. but lies nearer tlie nasal side, the nasal edge 
 of the left retina will overlap the temporal edge of the right, and the 
 nasal edge of the right will overlap the temporal edge of the left; so 
 that a part of each retina has no corresponding points in the other. 
 
 The adherents of this theorj^ claim, and with justice, that a small 
 object so situated that its image must be formed on corresponding 
 points of the two retinae does, as a rule, appear single, and, what is even 
 more striking, that a phosphene, or luminous ring produced by pressing 
 the blunt end of a pencil or the finger-nail on a point of the globe of one 
 eye (which Newton compared to the circles on a peacock's tail), is not 
 doubled by pressure over the corresponding point of the other eye. 
 although two circles are seen when pressure is made upon points which 
 do not correspond. If in rotating the eyes one eye is prevented by 
 pressure with the finger from following the movement of the other, 
 there is double vision. When strabismus or squinting is produced by 
 paralysis of the third (p. 924) or the sixth cranial nerve (p. g2t)), it is 
 accompanied by diplopia, until in course of time the mind icams to 
 disregard one of the images. In some cases of squint the double images 
 are never completely suppressed, but a new abnormal form of visual 
 localization is developed, which, however, ver\' seldom pemiits any 
 accurate judgment of depth. In strabismus it is obvious that the two 
 images of an object cannot fall on corresponding points. 
 
 But it is also a fact that, under certain conditions, images situated 
 on corresponding points may not, and that images not situated on 
 corresponding points may, give rise to a single impression. For ex- 
 ample, if one of the closed ej'es be held slightly out of its ordinary' 
 position by the finger, pressure on identical points of the two eyes gives 
 rise to two separate phosphenes. And some of the phenomena of stere- 
 oscopic vision (p. 1039) show clearly that images falling on points not 
 strictly corresponding may give a single impression; while we do not 
 habitually see double, although it is certain that the images of multi- 
 tudes of objects are constantly falling on points of the retinae not ana- 
 tomically ' identical.'* 
 
 The question therefore arises. How is it that we do not see these 
 double images? This is one of the difficulties of the theory- of identical 
 points. The following is a partial explanation: (i) The images of 
 objects in the portion of the field most distinctly seen — that is, the 
 portion in the immediate neighbourhood of the intersection of the 
 visual lines, or the part to which the gaze is directed — are formed on 
 identical points; and by rapid movements the eyes fix successively 
 different parts of the field of view. (2) Vision grows less distinct as 
 we pass out from the centre of the retina, and we are accustomed to 
 neglect the blurred peripheral images in comparison with those formed 
 
 • In every fixed position of the eyes, the objects whose images fall on 
 corresponding points will be arranged on certain definite lines or surfaces 
 which varv with the direction of the visual axis and to which the name of 
 horopter, or point-horopter, has been gi\cn. I"or most eyes when directed 
 to the horizon — that is, with the visual axes parallel — the horopter is practi- 
 callv the horizontal plane of the ground, so that all objects within the field 
 of vision, and resting on the ground, fall upon corresponding points, and are 
 seen single. When the eyes are directed to a point at such a distance that 
 the lines of vision are sensibly convergent, the horopter consists (i) of a 
 straight line dra^^'n through the fixing-point and at right angles to a plane 
 passing through the fixing-point and the two visual lines (visual plane) ; (2) of 
 a circle passing through the fixing-point and the nodal points of the two eyes 
 (the famous horopteric circle of Miiller). 
 
VISION 
 
 16.^0 
 
 on the fovea. (3) When the images of an object do not fall on identical 
 points, one of the points on which they flo fail may be occupied with 
 the images of other objects, some of which may be so boldly marked 
 as to enter into conflict with the extra image and to suppress it. 
 (4) Lastly, the physiological ' identical po'v.t ' is not a geometrical 
 j)oint, but an area which increases in size in xm more peripheral zones 
 of the retina, and can also be increased by practice; and images which 
 lie wholly or in chief part within two corresponding areas practically 
 coincide. 
 
 Stereoscopic Vision. — ^Although the retinal image is a projection of 
 external objects on a surface, we perceive not only the length and 
 breadth, but iilso the depth or solidity of the things we look at. When 
 we look directly at the front of a build- 
 ing, the impression as to its form is the 
 same whether one or both eyes be used, 
 although with a single eye its distance 
 cannot be judged so accumtely. But 
 when we view the building from such a 
 position that one of the corners is visible, 
 we obtain a more correct impression of 
 its depth with the two eyes. This is 
 partly due to the fact that to fix points 
 at different distances from the eyes the 
 visual lines must be made to converge 
 more or less, and of the amount of this 
 convergence we are conscious through 
 the contraction of the muscles which 
 regulate it. But there is another element 
 involved. When the two eyes look at a 
 uniformly -coloured plane surface, the 
 retinal image is precisely the same in 
 both. But when the two eyes are 
 directed to a solid object (say a book 
 lying on a table) the picture formed on 
 the left retina differs slightly from that 
 formed on the right, for the left eye sees 
 more of the left side of the book, and 
 the right eye more of the right side. 
 
 That there is a close connection be- 
 tween uniformity of retinal images and 
 impression of a plane surface on the one 
 hand, and difference of retinal images and 
 impression of solidity on the other, is 
 proved by the facts of stereoscopy. It 
 is evident that if an exact picture of the solid object as it is seen by 
 each eye can be thrown on the retina, the impression produced will 
 be the same, whether these images are really formed by the object 
 or not. Now, two such pictures can be produced with a near approach 
 to accuracy by photographing the object from the point of \iew of 
 each eye. It only remains to cast the image of each picture on the 
 corresponding retina, while the eyes are converged tc the same extent 
 as would be the case if they were viewing the actual object. This is 
 accomplished by means of a stereoscope (Fig. 438). 
 
 It is found that the resultant impression is that of the solid object. 
 It is impossible to reconcile this with the doctrine of strictly identical 
 geometrical points. A pair of identical pictures gives with the stere- 
 oscope not the impression of a solid, but of a plane surface. If the 
 
 Fig. 438. — Brewster's Stereoscope. 
 p and TT are prisms, with their re- 
 fracting angles turned towards 
 each other. The prisms refract 
 the rays coming from the points 
 c, 7 of the pictures ab and a^ so 
 that they appear to come from a 
 single point q. Similarly, the 
 points a and <t> appear to be situ- 
 ated at/, and the points b and /3, 
 at a. 
 
ro40 THE SENSES 
 
 relative position of any two points differs in the two pictures, the 
 blended picture has a corresponding point in relief. So great is the 
 delicacy of this test that a good and a bad banknote will not blend 
 under the stereoscope to a flat surface, and the method may be actually 
 used for the detection of forgery. 
 
 When the pictures are interchanged in the stereoscope so that the 
 image which ought to be formed on the right retina falls on the left, and 
 that which is intended for the left eye falls on the right, what were 
 projections before become hollows, and what were hollows stand out 
 in relief. The pseudoscope of Wheatstone is an arrangement by which 
 each eye sees an object by reflection, so that the images which would be 
 formed on the two retinae, if the object were looked at directly, are inter- 
 changed, with the same reversal of our judgments of relief. 
 
 Visual Judgments.^ — We say judgments of relief; for what we call 
 seeing is essentially an act that involves intellectual processes. As the 
 retina is anatomically and developmentally a projection of the brain 
 pushed out to catch the waves of light which beat in upon the organism 
 from every side, so, physiologically, retina, optic nerve, and visual 
 nervous centre are bound together in an indissoluble chain. W^e 
 cannot say that the retina sees, we cannot say that the optic nerve 
 sees — the optic nerve in itself is blind — we cannot say that the \-isual 
 centre sees. The ethereal waves falling on the retina set up impulses 
 in it which ascend the optic nerve; certain portions of the brain are 
 stirred to action, and the resulting sensations of light springing up, we 
 know not where, are elaborated, we know not how (by processes of 
 which we have not the faintest guess), into the perception of what we 
 call external objects — trees, houses, men, parts of our own bodies, and 
 into judgments of the relations of these things among themselves, of 
 their distance and movements. 
 
 A child leams to see, as it learns to speak, by a process, often un- 
 conscious or subconscious, of ' putting two and two together.' The 
 musical sounds united and terminated by noises which make up the 
 spoken word ' apple ' are gradually associated in its mind with the 
 visual sensation of a red or green object, the tactile sensation of a 
 smooth and round object, and the gustatory and olfactor^^ sensations 
 which we call the taste or flavour of an apple. And as it is by ex- 
 perience that the child leams to label this bundle of sensations with a 
 spoken, and afterwards with a written, name, so it is by experience 
 that it learns to group the single sensations together, and to make the 
 induction that if the hand be stretched out to a certain distance and in 
 a certain direction — i.e, if various muscular movements, also associated 
 with sensations, be made — the tactile sensation of grasping a smooth 
 round body will be felt, and that if the further muscular movements 
 involved in conveying it to the mouth be carried out, a sensation agree- 
 able to the youthful palate will follow. At length the child comes to 
 believe, and, unless he happens to be specially instructed, carries his 
 belief with him to his grave, that when he looks at an apple he sees a 
 round, smooth, tolerably hard body, of definite size and colour; while 
 in reality all that the sense of sight can inform him of is the difference 
 in the intensity and colour of the light falling on his retina when he 
 turns his head in a particular direction. 
 
 An interesting illustration of the role of experience in shaping 
 our visual judgments is found in the sensations of persons born 
 blind and relieved in after-life by operation. A boy between 
 thirteen and fourteen years of age, operated on by Cheselden, 
 
VISION 
 
 1041 
 
 thouglit all the objects he looked at touched his eyes. He forgot 
 which was the dog and wliieli the cat, but catching the cat (which 
 he knew by feeling), lie looked at her steadfastly and said, " So, 
 puss, I shall know you another time." Pictures seemed to him only 
 parti-coloured planes; but all at once, two months after the opera- 
 tion, he discovered they represented solids.' Nunnely, perhaps 
 renuMubeiing the dictum of Diderot, that ' to prepare and interro- 
 
 Fig. 439. — Illusion of Parallel Lines (Hering). 
 
 gate a person born blind would not have been an occupation un- 
 worthy of the united talents of Newton, Des Cartes, Locke, and 
 Leibnitz,' made an elaborate investigation in the case of a boy nine 
 years old, on whom he operated for congenital cataract of both eyes, 
 and, what is of special importance, instituted a set of careful 
 experiments and interrogations before the operation, so as to gain 
 data for comparison. Objects (cubes and spheres) which before 
 the operation he could easily recognize by touch were shown hiim 
 afterwards, but al- 
 
 
 xmxmxmxm 
 
 though ' he could at 
 once perceive a differ- 
 ence in their shapes, 
 he could not in the 
 least say which was 
 the cube and which 
 the sphere.' It took 
 several days, and the 
 objects had to be 
 placed many times in 
 his hands before he 
 could tell them by 
 
 the eye. ' He said everything touched his eyes, and walked most 
 carefully about, with his hands held out before him to prevent 
 things hurting his eyes by touching them.' 
 
 Many other illustrations might be given of the fact that ' seeing ' 
 is largely an act of reasoning from data which may sometimes 
 mislead. Thus in Figs. 439 and 440 the long horizontal lines are 
 really parallel, but do not appear so owing to the confusion of 
 judgment produced bv the short sloping lines. In Fig. 441 the 
 spaces covered by A, B, and C are equal squares, but A appears 
 
 66 
 
 Fig. 4(o. — Illusion of Parallel Lines (Zollner). 
 
I042 
 
 THE SENSES 
 
 <" > 
 
 taller than H, and C smaller than either A or B. In the same 
 figure the lines D and E are of the same length, but E seems con- 
 sitlerablv longer than D. 
 
 Illusions of movement are among the most interesting optical 
 illusions. If two similar objects are momentarily shown to the 
 eye in rapid succession and at points in space not separated by too 
 great a distance, the illusion is produced that the first object has 
 moved to the position of the second. Such illusions are the basis 
 of the so-called ' moving pictures ' shown by the cinematograph. 
 A series of instantaneous photographs of a movement are taken, 
 recording the successive positions assumed by the moving body. 
 When these are thrown on the retina in the same order and in rapid 
 succession, an illusion of the original movement is produced. 
 
 The apparent size and form of an object is intimately related to 
 the size, form, and sharpness of its image on the retina. We are, 
 
 therefore, able to dis- 
 A t C criminate with great 
 
 precision the un- 
 stimulated from the 
 excited portions of 
 that membrane, es- 
 peciallv in the fovea 
 centralis, and also 
 the degree of excita- 
 tion of neighbouring 
 excited parts. But 
 instead of localizing the image on the retina as we localize on the 
 skin the pressure of an object in contact with it, we project the 
 retinal image into space, and see everything outside the eye. 
 
 In vision, in fact, we have no conception of the existence of either 
 retina or retinal image; and even the shadows of objects within the 
 eye — for instance, an opacity or a foreign body in any of the refractive 
 media — are referred to points outside it. Generally opacities in the 
 vitreous humour are movable, in the lens not. 
 
 Purkinje's Figures. — As was first pointed out by Purkinje, the 
 shadows of the bloodvessels in the retina itself, and even of the 
 corpuscles circulating in them, although neglected in ordinary 
 vision, may be recognized under suitable conditions, a conclusive 
 proof that the sensitive layer must lie behind the vessels. 
 
 If a beam of sunlight is concentrated on the sclerotic as far as possible 
 from the margin of the cornea, and the eye directed to a dark ground, 
 the network of retinal bloodvessels will stand out on it. Another 
 method is to look at a dark ground while a lighted candle, held at one 
 side of the eve at a distance from the visual line, is moved .slightly to 
 and fro. In the first method, a point of the sclerotic behind the lens 
 is illuminated, and rays passing from it across the interior of the eyeball 
 in every direction cast shadows of the vessels of the retina on its sensi- 
 
 -< 
 
 Fig. 441. — Illusions of Space-Perception. 
 
VISION 
 
 1043 
 
 tive layer. In the second metliod, the image of the flame formed on 
 the retina by rays falling obliquely through the pupil becomes in the 
 general darkness itself a source of light, by interrupting the rays from 
 which the retinal vessels form sliadows. The distance of the sensitive 
 from the vascular layer may be approximately calculated by measuring 
 the amount by which the shadows change their position, wlien the 
 position of the illuminated point of the sclerotic is altered. The nearer 
 a vessel lies to the sensitive layer, the smaller must be the angle through 
 wiiich the apparent position of its shadow moves for a given move- 
 ment of the spot of light. In this way it has been calculated that the 
 sensitive layer is about o-z to 0-3 mm. behind the .stratum which con- 
 tains the bloodvessels. 
 This corresponds suffi- 
 ciently well with the 
 position of the layer of 
 rods and cones, which all 
 other evidence shows to 
 be the portion of the 
 retina actually stimulated 
 by light. The shadows of 
 the blood -corpuscles in 
 the retinal vessels may be 
 rendered visible by look- 
 ing at a bright and uni- 
 formly illuminated ground, 
 like the milk glass shade 
 of a lamp or the blue skv, 
 and moving the slightly 
 separated fingers or a 
 perforated card rapidly 
 before the eye. From the 
 rate of their apparent 
 movement, Vierordt cal- 
 culated the velocity of the 
 blood in the retinal capil- 
 laries at o*5 to 0'9 mm. 
 per second. One reason 
 why the shadows of these 
 intra-retinal structures do 
 not appear in ordinary 
 vision seems to be their small size. The retinal vessels are in reality 
 only vascular threads; the thickest branch of the central vein is not 
 .js mm. in diameter. The apex of the cone of complete shadow 
 fumbra) cast by a disc of this size, at a distance of 20 mm. from a pupil 
 4 mm. wide, would lie only 1 mm. behind the disc — that is to say, the 
 umbra of the retinal vessels would not reach the layer of the rods and 
 cones at all, and only the penumbra, or region of relative darkness, 
 would fall upon it. 
 
 When the eyes, after being closed for some time, are suddenly opened, 
 the branches of the retinal vessels may be seen for a moment. This is 
 especially the case after sleep; and a good view of the phenomenon 
 may be obtained by looking at a white pillow or the ceiling immediatelv 
 on awaking. If the eyes are kept open for a few seconds, the branch- 
 ing pattern fades away; if they are only allowed to remain open for 
 an instant, it may be seen many times in succession. The main vessels 
 appear to radiate out from a central point. But their actual junction 
 there is not seen, since it lies in the optic disc or blind spot. 
 
 Fig. 442. — Method of rendering the Retinal Blood- 
 vessels visible by concentrating a Beam of Light 
 on the Sclerotic. From the brightly-illuminated 
 point of the sclerotic, a, rays issue, and a shadow 
 of a vessel, v, is cast at a'. It is referred to an 
 external point, a", in the direction of the straight 
 line joining a' with the nodal point. When the 
 light is shifted so as to be focussed at b, the 
 shadow cast at b' is referred to b" — i.e., it appears 
 to move in the same direction as the illuminated 
 point of the sclerotic. 
 
I044 
 
 THE SENSES 
 
 The Blind Spot. — The fibres of tlie optic nerve are insensible to 
 light; light only stimulates them through their end-organs. This 
 can be proved by directing by means of an ophthalmoscope a beam 
 of light upon the optic disc, where the true retinal layers do not 
 exist. The person experimented on has no sensation of light when 
 the beam falls entirely upon the disc; when its direction is shifted 
 so that it impinges upon any other portion of the retina, a sensation 
 of light is at once experienced. The blind spot is not recognized 
 in ordinary vision, for (i) the two optic discs do not correspond. 
 
 The left disc has its corre- 
 sponding points on a sensitive 
 part of the right retina, and 
 the right disc on a sensitive 
 part of the left retina; and the 
 consequence is that in binoc- 
 ular vision the objects whose 
 images are formed on the cor- 
 responding points fill up the 
 blind spots. (2) The optic 
 disc does not lie in the line of 
 direct, and therefore distinct, 
 vision. The eye is constantly 
 moving so as to bring the 
 surrounding objects succes- 
 sively on the fovea centralis; 
 and the gap which the blind 
 spot makes in the visual field 
 of a single eye is thus more 
 easily neglected. In any case 
 we ought not to see it as a 
 dark spot, for darkness is only associated with the absence of 
 excitation in parts of the retina capable of being excited by light. 
 There is no more reason why the optic discs should appear dark 
 than there is for our having a sensation of darkness behind us when 
 we are looking straight in front. And since the experience of our 
 other senses — the sense of touch, for example — tells us that the 
 objects we look at do not in general have a gap in the position corre- 
 sponding to the part of the image that falls on the blind spot, we 
 see, so to speak, across the spot. 
 
 By Mariotte's experiment, however, the existence of the blind spot 
 can not only be demonstrated, but its size determined and its bounaaries 
 mapped out. Let the left eye be closed, and fix with the right the small 
 cross; then, if the eye be moved towards or away from the paper, keeping 
 the cross fixed all the time, a position will be found in whicli the while 
 disc disappears altogether. In this position its image falls on the 
 blind spot (Fig. 444). 
 
 Fig- 443- — Method of rendering the Blood- 
 vessels of the Retina visible by Oblique 
 Illumination through the Cornea. Light 
 from a candle at a illuminates a', and 
 rays proceeding from «' cast a shadow of 
 the bloodvessel, v, at a", which is referred 
 to a'". When a is moved to b, the 
 shadow on the retina moves to 6*, and 
 the shadow in the visual field of the illu- 
 minated eye to b'". 
 
VISION 
 
 1045 
 
 Relation of the Rods and Cones to Vision. — We have more than 
 once referred to the rods and cones us the sensitive layer of the 
 retina. It is now necessary to develop a little more the evidence 
 in favour of this statement. And at the outset, since the sensitive 
 layer has been shown to lie behind the plane of the retinal blood- 
 vessels, the only competitors of the rods and cones are the external 
 nuclear layer and the pigmented epithelium. The nuclear layer 
 may be at once excluded as a separate mechanism, since, as we have 
 seen (p. 1015), the portions of the rod and cone elements in it are 
 continuous with the portions in the layer of the rods and cones 
 proper. In the fovea centralis, where vision is most distinct, the 
 nuclear layer becomes very thin and inconspicuous. 
 
 The layer of pigmented hexagonal cells, or at. least their pigment, 
 cannot be essential to vision, for albino rats, rabbits, and men, in 
 whose eyes pigment is absent, can see. In man and most mammals 
 there are cones, but no rods in the yellow spot and fovea centralis; 
 the relative proportion of rods increases as we pass out from the 
 fovea towards the ora serrata. But this does not enable us to 
 
 Fig. 444, — Mariotte's Experiment. 
 
 analyze the bacillary layer into sensitive cones and non-sensitive 
 rods, for on the rim of the retina, which is still sensitive to light, 
 there are only rods; in the bat and mole there are said to be no 
 cones even in the yellow spot, in the rabbit very few. Reptiles 
 possess only cones over the whole retinal surface, and birds, true 
 to their reptilian affinities, have every\vhere more cones than rods, 
 as have also fishes. 
 
 One of the difficulties in the way of understanding how a ray of 
 light can set up an excitation in a rod or cones is the transparency 
 of these structures. An absolutely transparent substance — that 
 is, a substance which would allow light to traverse it without the 
 least absorption — would, after the passage of a ray, remain in 
 precisely the same state as before; its condition could not be 
 altered by the passage of the light unless some of the energy of the 
 ethereal vibrations was transferred to it. But an absolutely trans- 
 parent body does not exist in Nature; and it is not necessary to 
 suppose that all the energy required to stimulate the end-organs 
 of the optic nerve comes from the luminous vibrations. These 
 may, and probably do, act by setting free energy stored up in the 
 
I046 THE SENSES 
 
 retina, just as the touch of a child's hand could be made to fire a 
 mine, or launch a ship, or flood a province. Some have looked upon 
 the transverse lamellae into which the outer members of the rods 
 and cones can be made to split as an arrangement for reflecting 
 back the light to the inner members, and have compared them 
 to a pile of plates of glass, which, transparent as it is, is a most 
 efficient reflector. It is even possible, although here we are already 
 treading the thin air of pure speculation, that the light may be 
 polarized in the process of reflection, and that the rods and cones 
 may be less transparent to light polarized in certain planes than to 
 unpolarized light. 
 
 As to the nature of the transformation undergone by the ethereal 
 vibrations in the rods and cones, various theories have been formu- 
 lated. Some have supposed that the absorbed light-waves are 
 transformed into long heat-waves, and that the endings of the optic 
 nerve are thus excited by thermal stimuli. This hypothesis has so 
 little evidence in its favour that it is perhaps an unjustifiable waste 
 of time even to mention it. It is ruled out of court b}' the mere fact 
 that the long radiations of the ultra red, filtered from luminous ra3's 
 by being passed through a solution of iodine, and focussed on the 
 eye by a lens of rock-salt, produce not the slightest sensation of 
 light, although they are by no means all absorbed in their passage 
 through the dioptric media. Again, it has been suggested that the 
 energy of the waves of light is first transformed into electrical energy, 
 and that the visual stimulus is really electrical. In support of 
 this view it has been urged that the passage of a voltaic current 
 through the eye causes sensations of light, and that light, un- 
 doubtedly, causes (p. 839) an electrical change in the retina and 
 optic nerve. But, as has more than once been pointed out, an 
 electrical change is the token and accompaniment of the activity 
 of the excitable tissues in general; and all that the currents of 
 action of the retina show is that light excites the retina — a proposi- 
 tion which nobody who can see requires an objective proof of, and 
 which does not carry us very far towards the solution of the 
 problem how that excitation is brought about. Then there is 
 the photo-mechanical theory, according to which the pigmented 
 epithelial cells of the retina, altering their shape and volume under 
 the stimulus of light, press upon the rods and cones, and thus 
 mechanically stimulate them. Lastly, there is the photo-chemical 
 theory, which supposes that some chemical change produced in the 
 rods and cones under the influence of light sets up impulses in them 
 which ascend the optic nerve. This is the most probable of all the 
 theories, notwithstanding the fact that the discovery by Boll of 
 the famous visual purple or rhodopsin, wliich at first seemed likely 
 to place it upon a sure foundation, has lost its significance in this 
 regard. But although the visual purple is not a photo-chemical 
 
VISION io»7 
 
 substance throut^h which the retinal elements are excited by 
 luminous stimuli, it seems to fulhl an important function in adapt- 
 ing the retina — i.e., rendering it more sensitive — for vision in dim 
 light. In any case, its discovery is in itself so interesting and so 
 suggestive as a basis for future work, that a short account of the 
 properties of the substance cannot be omitted here. 
 
 Visual Purple. — If the eye of a frog or rabbit, which has been kept 
 in the dark, be cut out in a dimly-lighted chamber or in a chamber 
 illuminated only by red light, and the retina removed, it is seen, when 
 viewed in ordinary light, to be of a beautiful red or purple colour. 
 Exposed to bright light, the colour soon fades, passing through red and 
 orange to yellou-, and then disappearing altogether. The yellow colour 
 is due to the formation of another pigment, visual yellow; the preceding 
 stages are due to the intermixture of this v-isual yellow with the un- 
 changed visual purple in ciifterent proportions. With the microscope 
 it may be seen that the pigment is entirely confined to the outer segment 
 of the rods, where it exists in most vertebrate animals. It may be ex- 
 tracted by a watery solution of bile-salts, and the properties of the 
 pigment in solution are very much the same 
 as its properties in situ ; light bleaches the 
 solution as it does the retina. Examined w\\\\ 
 the spectroscope, the solution shows no definite 
 bands, but only a general absorption, which is 
 very slight in the red, and reaches its ma.xi- 
 mum in the yello%\T,sh-green. In accordance 
 with this, it is found that of all kinds of mono- 
 chromatic light the yellowish -green rays bleach 
 the purple most rapidly, the red rays most 
 slowly. 
 
 If a portion of the retina is kept dark while 
 
 the rest is exposed to light, onlv the latter p- ^^^ n,.f^^^,^ d-,-* 
 • -Li u J 4 J i! Jl\^ • r i^ig- 445- — Optogram. Part 
 
 portion is bleached. And when the image of ^f retina of rabbit, the 
 an object possessing weU-marked contrasts of eye of which had been 
 light and shadow [e.g., a glass plate with strips directed to an illumin- 
 of black paper pasted on it at intervals, or a ated plate of glass cov- 
 window with dark bars) is allowed to fall on an ered with strips of black 
 eye otherwise protected from light, the pattern paper, 
 of the object is picked out on the retina in 
 
 purple and white. A veritable photograph or ' optogram ' may thus be 
 formed even on the retina of a living rabbit; and if the eye be rapidly 
 excised, the picture may be ' fixed ' by a solution of alum, and thus 
 rendered permanent. 
 
 These facts certainly suggest that light falling on the retina may 
 cause in some sensitive substance or substances chemical changes, 
 the products of which stimulate the endings of the optic nerve, 
 and set up the impulses that result in visual sensations. 
 
 The visual purple cannot itself be such a substance, for it is 
 absent from the cones of all animals and the rods of some. Frogs 
 and rabbits can undoubtedly see at a time when, by continued 
 exposure to bright sunlight, the purple must have been completely 
 bleached. And although the alleged absence of the pigment in 
 the eye of the bat might seem to afford a ready explanation of the 
 
1048 THE SENSES 
 
 proverbial ' blindness ' of that animal, such a hasty deduction 
 would be at once corrected by the fact that birds with as sharp 
 vision as the pigeon are equally devoid of visual purple, while in 
 other nocturnal animals, like the owl, it is plentifully found. The 
 most probable hypothesis of the function of the visual purple is 
 indeed that which attributes to it the property, in virtue of its 
 capacity for regeneration in the dark, of adapting the eye for night 
 or twilight vision — in other words, of increasing the sensitiveness 
 of the retina for faint light, especially of the shorter wave-lengths. 
 If this is the case, it is precisely in nocturnal animals that we should 
 expect to find it in large amount; and recently visual purple has 
 been obtained from more than one species of bat (Trendelenburg). 
 The fact that central vision (p. 1058) in which the rodless fovea is 
 concerned is but little, if at all, susceptible of dark-adaptation, 
 while peripheral vision shows a marked capacity of adaptation, 
 agrees well with this hypothesis. We shall see later that there is 
 some evidence that it is the mere perception of luminous impressions 
 as such and of their intensity, without any distinction of quality 
 or colour, with which the rods have to do. They are, then, on the 
 hypothesis under discussion, elements concerned in achromatic 
 sensations under conditions of feeble illumination (twilight vision). 
 The cones are supposed on this theory to be more highly developed 
 elements than the rods, their function being connected, especially 
 with the perception of colour, but also with the perception of 
 achromatic sensations under daylight conditions. 
 
 The pigmented retinal epithelium is undoubtedly sensitive to light, 
 and has important relations to the formation of the visual purple! 
 When the eye is exposed to light, black pigment migrates along the 
 processes of the epithelial cells between the rods, even as far as the 
 external limiting membrane. In the dark the pigment moves back 
 again, and gathers around the outer portions of the rods, where the 
 visual purple is being regenerated. That the central nervous system 
 is not concerned in the pigment migration, or at least that it is not 
 indispensable for it, has been shown in the larvsr of Amblystoma. one 
 of the tailed amphibia. Optic cups were transplanted to various parts 
 of the body, where they flcvclopcd to form more or less perfect eyes. 
 The forward movement of the pigment in these transplanted eyes when 
 exposed to light was fully as great as in the normal eyes. Contraction 
 of the cones was also observed in them just as in the normal eyes. In 
 the eye exposed to the light, the cones, whose expanded length is 23^ 
 shortened by more than ^fi (Laurens and Williams). The precise mean- 
 ing of the changes in the pigmented cells is obscure. 
 
 The pigmented epithelium is known to be concerned in the regenera- 
 tion of the visual purple. When a frog is curarizcd, oedema occurs 
 between the retina and the choroid, so that the former membrane is 
 separated from the hexagonal epithelium. If the frog is now exposed 
 to sunlight till the visual purple is bleached, and the retina then taken 
 out and placed in the dark, no regeneration of the purple takes place. 
 When the same experiment is repeated on a non-curarized frog, the 
 visual purple is restored in the dark, and may be seen under the micro- 
 scope in the rods. The only difference in the two experiments is that 
 in the latter the pigmented epithelium adheres to the retina, and it 
 
VISION 1049 
 
 must therefore have a hand in the regeneration of the jngment. Evcr 
 thc visual pin-ple of a retina from which the epitliehum has been de- 
 tached will, after being bleached, be restored if the retina is simply laid 
 again on the ejiithelial surface. And it docs not seem to be the black 
 pignient of the hexagonal cells which is the agent in this restoration, 
 for it takes place in the pigment-free retina' of albiiKj rabbits or rats. 
 Even a retina isolated from the pigmented epithelium, and then 
 bleached, may, to a certain extent, develop new visual purple in the 
 dark. This is even true when it has been kept in the dark in a saturated 
 solution of sodium chloride, and is then, after washing with physio- 
 logical salt solution, bleached by light. Here the regeneration of the 
 pigment cannot be the result of vital processes, but must be due to 
 chemical changes in products formed from the original pigment by the 
 action of light. No such regeneration takes place in a retina which, 
 after having been bleached m situ, is removed without the pigmented 
 epithelium and placed in the dark; and the only probable explanation 
 of the difference is that in this case the photo-chemical substances 
 from which visual purple can be formed have been absorbed into the 
 circulation, and have so escaped. 
 
 The inner segments of the cones of certain animals (birds, reptiles, 
 amphibia, and some fishes) contain globules of various colours, ranging 
 over almost the whole spectrum, and including, besides, the non-spectral 
 colour, purple. The globules are composed chiefly of fat with the 
 pigments (chromophanes, as they have been called) dissolved in it. 
 The function of these globules is unknown. They cannot be concerned 
 in colour vision, or, at least, they cannot be essential to it, for in the 
 human retina they do not exist. 
 
 The yellow pigment of the macula lutea does not belong to the layer 
 of rods and cones; it only exists in the external molecular layer and the 
 layers in front of it; in the fovea centralis it is absent. 
 
 Time necessary for Excitation of the Retina by Light — Fusion of 
 Stimuli. — Whatever the exact nature of retinal excitation may be, 
 it is called forth by exceedingly slight stimuli. A lightning flash, 
 
 although it may last only th of a second, lasts long enough 
 
 ° ■^ -^ 1,000,000 ° ° 
 
 to be seen. A beam of light thrown from a rotating mirror on the 
 
 eye stimulates when it only acts for ^ th of a second. The 
 
 •^ ^ 8,000,000 
 
 minimum stimulus in the form of green light corresponds, as we have 
 
 already seen (p. 784), to a quantity of work equivalent to no more 
 
 than — 8 erg — that is, about — jg gramme-millimetre, or — ^ milli- 
 gramme-millimetre, which is the work done by th of a 
 
 ° . •' 10,000,000 
 
 milligramme in falling through a millimetre; and it cannot be doubted 
 that a portion even of this Lilliputian bombardment is wasted as heat. 
 So quickly, too, is the stimulus followed by the response that no latent 
 period has as yet ever been measured. It is certain, however, that 
 there is a latent period, as surely as there is a latent period in the 
 excitation of a naked nerve-trunk, although this also has never been 
 experimentally detected. The analogies, in fact, between a muscular 
 contraction and a retinal excitation are numerous and close. Like the 
 muscle, the retina seems to possess a store of explosive material wdiich 
 the stimulus serves only to fire off. The retina, like the muscle, is 
 exhausted by its activity, and recovers during rest. Like the muscle 
 curve, the curve of retinal excitation rises not abruptly, but with a 
 measurable slowness to its height, and when stimulation is stopped, 
 
I050 THE SENSES 
 
 takes a sensible time to fall again, the retinal impression outlasting the 
 luminous stimulus by about one-eighth of a second. With compara- 
 tively slow intermittent stimuli the retinal, like the muscle curve, 
 flickers up and down. When the rate of stimulation is increased, the 
 steady contraction of the tetanized muscle is analogous to the fusion 
 of the individual stimuli by the tetanized retina (or retino-cerebral 
 apparatus) into a continuous sensation of light, such, e.g-, as the bright 
 ' trail ' of a falling star, or the fiery circle traced in the air when a fire- 
 brand is rapidly whirled round. But the maximum retinal excitation 
 which a stimulus of given strength can call forth depends much more 
 closely upon the time during which the stimulus acts than the maximum 
 contraction does upon the length of the muscular stimulus. 
 
 As the strength of the light increases in geometrical progression, the 
 time during which it must act in order to produce its maximum effect 
 decreases approximately in arithmetical progression (Exner). For light 
 of moderate intensity this time is about ^ second. Since for complete 
 fusion the stimuli must follow^ each other at a much more rapid rate 
 than four in the second, the intensity of the resultant sensation is 
 always less when a succession of similar stimuli are fused than when one 
 of the stimuli is allowed to produce its maximum effect. 
 
 If the time of each stimulus is equal to the interval during which 
 there is no stimulation, the sensation, when complete fusion has been 
 reached, is the same as would be produced by a constant light of half 
 the strength employed. And, in general, if m be the proportion of the 
 time during which the eye is stimulated by a light of intensity /, and n 
 the proportion of the time during which it is not stimulated, the resultant 
 impression is the same as that which wonld be produced by an un- 
 
 I/. This is Talbot's law, which 
 
 may be expressed without the aid of symbols thus: When a light of 
 given intensity is allowed to act on the eye at intervals so short that the 
 impressions are completely fused, the resultant 
 sensation is independent of the absolute length of 
 each flash, and is proportional only to the fraction 
 of the whole time which is occupied by flashes and 
 to the intensity of the light. Talbot's law may be 
 readily demonstrated by means of a rotating disc 
 with alternate white and black sectors (Fig. 
 4271, so arranged that the same proportion of the 
 circumference of each of the three concentric 
 zones is black. 
 
 When the rotation is sufficiently rapid to give 
 
 Fig. 446.— Disc for de- complete fusion (say 20 to 30 times a second), 
 
 monstrating Talbot's the whole disc appears equally bright. However 
 
 law, much the rate of rotation is now increased, no 
 
 further change occurs. It has been sho^vn that 
 
 even for stimuli as short as the nTjffJijTRi'th of a second, repeated at 
 
 intervals of yigth second, Talbot's law holds good. So that not only 
 
 does a flash so inconceivably brief affect the retina, but it sets up 
 
 changes which last for a measurable time. For intense stimuli Talbot's 
 
 law ceases to be true : the field appears brighter than it should be 
 
 (Griinbaum). 
 
 Two chief theories have been proposed to account for the fusion of 
 intermittent retinal stimuli: (i) The persistence theory, according to 
 which the excitatory process in the retina remains for a short time at 
 the maximum reached when the light ceases to act. Steady fusion is 
 supposed to be obtained when the interval between successive stimuli 
 does not exceed this time. (2) The theory of Fick, who maintains that 
 
VISION 1051 
 
 as sr>on as the light is withdrawn the retinal excitation begins to sink, 
 at first rapidly, then more gradually. As the rate of stimulation is 
 increased the time allowed for the decline of the excitation is, of course, 
 correspondingly shortened, and ultimately the oscillations become so 
 small that a continuous smooth sensation results. I'ick's theory 
 appears to explain the phenomena best. 
 
 The experiments of Charpentier have shown that the retina when 
 stimulated has a natural tendency to enter into oscillations at the rate 
 of about 36 in the second, so that the effect of a flash of light when it 
 falls on a retinal area is not a single excitation which rises smoothly to 
 its maximum and then declines smoothly to zero, but a series of swings 
 which die away like the vibrations of an elastic body. This may be 
 demonstrated by slowly rotating a well-illuminated disc, one quadrant 
 of which is white and the rest black, while the eye is kept fixed on the 
 centre. A black band, or rather sector, running out from centre to 
 circumference, will be seen in the white quadrant a little behind the 
 border of it which first passes the eye. This band may be succeeded by 
 one or more fainter black bands placed at regular intervals in the white 
 portion of the disc. The explanation is this. At the moment when the 
 image of the advancing edge of the white quadrant falls upon the 
 retinr. it is excited, and we get the sensation of white. Then comes a 
 swing in the opposite direction which gives rise to the first black band, 
 and succeeding swings cause the other bands. The period of the oscil- 
 latory process can be calculated from the speed of the disc, and the 
 distance of the first band from the edge of the white quadrant. The 
 well-known fact that a single flash of lightning, or other intense stimulus, 
 may appear .j.s two flashes, finds its explanation in these retinal oscilla- 
 tions. 
 
 Colour Vision. — Besides differences in the distance, size, shape, 
 and brightness of objects, the eye recognizes differences in their 
 colour; and we have now to consider the physical and physiological 
 differences on which these depend. 
 
 Colours may differ from each other — ^(i) In tone or hue, e.g., red, 
 yellow, green. (2) In degree of saturation or fulness or purity, i.e., in 
 the degree in which they are free from admixture with white light, e.g., 
 a ' pale ' or ' light ' blue is a blue mixed with much white light, a ' deep ' 
 or ' full ' blue with kttle or none. {3) In brightness or intensity, i.e., in 
 the amount of the light coming from unit area of the coloured object. 
 Thus, a ' dark ' red cloth sends comparatively little light to the eye, a 
 ' bright ' red cloth sends a great deal. 
 
 When a beam of sunlight falls into the eye, a sensation of ' white 
 light ' results. When a prism is placed before the eye, the sensation 
 is entirely different ; we see a spectrum running up from red through 
 green to violet, with a multitude of intermediate shades, the eye 
 being able to distinguish in the solar spectrum at least one thousand 
 different hues (Aubert). What, then, has happened ? Physically, 
 nothing more has taken place than a rearrangement of the rays 
 in the beam of white light. A few of them may have been lost by 
 reflection, but upon the whole the beam is made up of exactly the 
 same constituents as before; only the rays are now arranged in the 
 precise order of their refrangibility, the more refrangible, which are 
 also those of shortest wave-length, being displaced more towards the 
 base of the prism than the longer and less refrangible rays. In- 
 
I052 THE SENSES 
 
 stead of the long and short rays falling together on the same ele- 
 ments of the retina, as they did in the absence of the prism, they 
 now fall, if proper precautions have been taken to secure a pure 
 spectrum, in regular order from one side to the other of the portion 
 of retma on which the image is termed. The physical condition, 
 then, of our sensations of the prismatic colours is, that rays of 
 approximately the same wave-length should fall unmixed with 
 other rays upon the retinal elements. Rays of a wave-length of 
 760 /iijj,* to 650 /x/A give the sensation of red; from 650 jufi to 590 ^/t, 
 the sensation of orange; from 430 fjju to 400 jbijn, the sensation of 
 violet, and so on. When rays of all these wave-lengths fall together, 
 in the proportion in which they are present in sunlight, upon the 
 same part of the retina, the resultant physiological effect is very 
 different ; we are no longer able to distinguish red, blue, green, etc. ; 
 we receive the single sensation of white light. The sensation is a 
 simple one; in consciousness we have no hint that it has a multiple 
 physical cause. 
 
 But we find further that it is not necessary for the sensation of 
 white light that waves of every length present in the solar spectrum 
 should be mixed. If rays of wave-lengths 675 jliju (which acting 
 alone produce the sensation of red) be mixed in certain proportions 
 — i.e., be allowed to fall on the same part of the retina — with rays 
 of wave-length 496 /xju (which give the sensation of bluish-green), 
 the resultant sensation is also that of white light. And an in- 
 definite number of sets can be combined, two and two, so as to give 
 the same sensation of white. Such colours are called comple- 
 mentary. The following are pairs of complementary colours: 
 
 Red and bluish-green. Yellow and ultramarine-blue. 
 
 Orange and cyan-blue. f Greenish-yellow and violet. 
 
 The green of the spectrum has no simple complementary colour; 
 purple, a colour not present in the spectrum, but obtained by 
 mixing light from the two spectral extremes — i.e., by mixing red 
 and violet — may be considered complementary to it. Suppose now 
 that one of a pair of complementary colours is added to the other 
 in greater intensity than is required to give white, the resultant 
 sensation is a colour which has a certain amount of resemblance both 
 to white and to the colour present in excess. Thus, if the two 
 colours are orange and blue, and the blue is present in greater in- 
 tensity than is necessary to give white, the resultant colour is a 
 whitish or pale blue, or, to use the technical phrase, an unsaturated 
 blue. The more nearly the intensity of the blue rays in the mixed 
 light approaches the proportion necessary to give white, the less 
 saturated is the resultant colour; the greater the excess of blue, 
 the more nearly does the resultant sensation approach that of the 
 saturated blue of the spectrum. But any non-saturated spectral 
 
 * /*//. is a symbol representing one-millionth of a millimetre, 
 t Cyan-blue is a greenish-blue. 
 
VISION 1053 
 
 colour produced by the mixture of two complementary colours may 
 be equally well produced by the mixture of the corresponding 
 spectral colour with a certain quantity of ordinary white light. 
 And it is found that when two spectral colours which are not com- 
 plementary are mixed together the resultant is not white, but a 
 colour which may be matched by some spectral colour lying between 
 the two (or by purple), either without addition or plus a larger or 
 smaller quantity of ordinary white light. From all this it follows 
 that the retina may be excited by an infinite nurriber of different 
 physical stimuH, and yet the resultant sensation may be the same. 
 This leads straight to the conclusion that somewhere or other in 
 the retino-cerebral apparatus simplification, or synthesis, of im- 
 pressions must take place; and we have to inquire what the simplest 
 assumptions are which will explain all the phenomena. Now, it is 
 not possible, from two spectral colours alone, to produce a sensation 
 corresponding to all the others. By mixing three standard spectral 
 colours, however, in various proportions, we can produce not only 
 the sensation of white light, but that of every colour of the spectrum 
 (and of purple). These statements are based on demonstrated facts 
 obtained by very numerous experiments on colour mixtures. The 
 hypotheses framed to explain the facts are to be carefully dis- 
 criminated from the facts themselves. 
 
 Primary Colours. — The simplest assumption we can make, then, 
 is that there are three standard sensations, and that either the 
 retina itself can respond by no more than three distinct modes of 
 excitation to the multiplex stimuli of the luminous vibrations, or 
 that complex impulses set up in the retina are reduced to simplicity 
 because the central apparatus is capable of responding by only 
 three distinct kinds of sensation. Which three sensations we select 
 as fundamental or primary is, to a certain extent, arbitrary. Fick 
 chose red, green, and blue; most commonly red, green, and violet 
 are accepted as the primary colours. Red, yellow, and blue, 
 although so long considered the primary colours, from data yielded 
 by the mixture of pigments, will not do; for no possible combination 
 of them will produce either a pure green or white light. 
 
 The Young-Helmholtz Theory, — The theory which has been most 
 widely accepted is that of Young, generally called, on account of 
 its adoption and extension by Helmholtz, the Young-Helmholtz 
 theory. Red, green, and violet are taken as the fundamental or 
 elementary colour sensations. In its more modern form it assumes 
 that in the retina, or in the retino-cerebral apparatus, there are 
 three kinds of elements — (i) a substance or a component chiefly 
 affected by light of comparatively long wave-length (red), to a less 
 extent by light of medium wave-length (green), and to a still less 
 extent by the shortest visible waves (violet) ; (2) a component mainly 
 affected by medium, but also to a certain extent by long and short 
 waves; (3) a component chiefly affected by the short vibrations, 
 
I054 
 
 THE SENSES 
 
 less by tlic iiicdiuiii, and still less ])y the hn\^ waves. The curves 
 in Fig. 44(7 illustrat<> tlusc relations. 
 
 The theory explains as follows the phenomena of colour- rrwxture 
 referred to above. When all the rays of the spectrum act upon 
 tlie retina together, the three components are about equally affected, 
 and this equal effect is supposed to be the condition of the sensation 
 of white light. When the green of the spectrum alone falls on the 
 retina, tlu; 'green ' component is strongly excited, the other two 
 
 Fig. 447. — Curves of Excitability of Primary Sensations from Observations on 
 Colour Mixtures (Konig). The numbers give wave-leugths of the spectrum in 
 millionths of a millimetre. 
 
 only slightly; this is the relation between the amount of excitation 
 in the three components which is associated with a sensation of 
 spectral green. When two complementary colours, such as red and 
 bluish-green, fall together on the same portion of the retina, the 
 three components are excited in the relative proportions associated 
 with the sensation of white light. 
 
 The colour triangle is a graphic method of representing various facts 
 in colour-mixture (Fig. 44^). 
 
 The chief points to be noted are tlie following: (i) On the curve 
 
 tlic spectral colours are 
 
 CtjanBlue 
 
 Green 
 
 Xeilour 
 
 A)ran(/f 
 
 arranged at such dis- 
 tances that the angle con- 
 tained between straight 
 lines drawn from the 
 point marked ' white,' 
 and intersecting the 
 curve at the positions 
 corresponding to any two 
 colours is proportional to 
 their difference in tone. 
 (2) The distance of any 
 point of the curve from 
 the point marked 'white' 
 is proportional to the stimulation intensity of the colour corresponding 
 to it.' (if the stimulatii'Ti intensities of all tlie colours be represented by 
 
 Purple 
 
 Fig. 448. — Colour Triangle. 
 
VISION 1035 
 
 proportiDnal \vcMp;hts lyiiif; at the corresponding^ points on tlu; curve, the 
 point 'white ' will be the centre of gravity of the system.) (3) The position 
 of a colour proiUiced by the mixture of any pair of spectral colours is 
 found by joiuiiig the corresjjonding points by a straight line. The mixed 
 colour lies on tiiis line at distances from tlie two points inversely proi)or- 
 tional to tile stimulation intensity of the two colours — i.e., it lies in the 
 centre of gravity of the weiglits rejiresenting tlie twocolours. (4) It is a 
 particular case of (3) that the complementary colours are situated at 
 the jHjints where straight lines lirawn llirough ' white ' intersect the 
 curve, since the point marked ' white ' is the centre of gravity corre- 
 sponding to a pair of colours only when it lies on the straight line 
 joining them. Thus tlie orange and yellow lying between the red and 
 green are mixtures of the red and green sensations in different propor- 
 tions; tile cyan-blue anil indigo-blue are mixtures of the green and 
 violet sensations. Tlie purj>les, representctl by a broken line, are not 
 present in the spectrum, and are mixtures of red and violet. 
 
 It is a point of great theoretical interest that on the Young-Helm- 
 holtz theory the pure spectral colours, although physically saturaued 
 [i.e., due to ethereal vibrations of a definite wave-length for each 
 colour), ought not to be physiologically saturated, since they all affect 
 the three components, although in different degrees. In other words, 
 the red, let us say, of the spectrum ought not to be the purest or fullest 
 red which it is possible to perceive. Now, it is found that this is really 
 the case. If, for example, we look first at the bluish-green, and then 
 at the red of the spectrum, the sensation of red is fuller or more saturated 
 than if we had looked at the red directly. Similarly, if we look first at 
 a small bluish-green square on a black ground, and then at a red ground, 
 we see a more fully saturated square in the middle of the latter. The 
 explanation, on the Young-Helmholtz theory, is that the ' green ' 
 component, being fatigued before the eye is turned upon the red, the 
 latter colour no longer affects it, or afifects it less than it would other- 
 wise do, and tlierefore the excitation is almost entirely confined to the 
 red component in the area fatigued for green. This brings us to the 
 subject of retinal fatigue, and the related phenomena of after-images 
 and contrast. 
 
 After-images. — We have seen that the retinal excitation always takes 
 time to die away after the stimulus is removed. If a white object is 
 looked at, especially when the eye is fresh, for a time not long enough 
 to cause fatigue, and the eye is then closed, an image of the object 
 remains for a short time, diminishing in brightness at first rapidly', then 
 more slowly. This is a positive after-image, and by careful observa- 
 tion it may, under certain conditions, be seen that the positive after- 
 image of a white object, of a slit illuminated by sunlight, for example, 
 undergoes changes of colour as it fades, passing through greenish-blue, 
 indigo, violet, or rose, to dirty orange. On the Young-Helmholtz 
 theory this is explained by the supposition that the excitation does 
 not decline with the same rapidity in the three hypothetical components. 
 If the object is looked at for a longer time, or if the eye is fatigued, a 
 dark or negative image may be seen upon the faintly-illuminated ground 
 of the closed eyes; but negative after-images may be more easily 
 obtained when the eye, after being made to fix a small white object on 
 a black ground, is suddenly turned upon a white or neutral tint surface. 
 
 Here Helmholtz supposed the portion of the retina on which the 
 image of the object is formed to be more or less fatigued. And this 
 fatigue will extend to all three kinds of fibres; so that white light of a 
 given intensity will now cause less excitation in this part than in the 
 rest of the retina. It is easy to understana that the negative after- 
 image of a coloured object will be seen, upon a white ground, in the 
 
I056 THE SENSES 
 
 complementary colour, for the components chiefly excited by the latter 
 will have been least fatigued. The negative atter-images seen when 
 the eye, after receiving the positive impression, is turned upon a coloured 
 ground, vary with the colour of the object and ground in a manner which 
 has been cxjjlained as due to fatigue of one or other component. It 
 is difficult, however, to reconcile the fatigue hypothesis of the after- 
 image with all the facts. Hering supposes that the retina is not 
 passively fatigued, but that a metabolic change is set up in it which is 
 of the opposite kind to that caused by the original excitation (see 
 P-,i057)- 
 
 J he phenomena of negative after-images are often included together 
 as examples of successive contrast, the name implying mutual in- 
 fluences of the portions of the retina (or retino-cerebral apparatus) 
 successively stimulated. We have now to consider simultaneous 
 contrast, often spoken of simply as contrast. 
 
 Contrast. — A small white disc in a black field appears whiter, and a 
 small black disc in a white field darker, than a large surface of exactly 
 the same objective brightness. A disc with alternate sectors of white 
 and black, so arranged that the proportion of white to black increases 
 in each zone from centre to circumference, when set in rotation, ought, 
 by Talbot's law, to show sharply marked and uniform rings, of which 
 each is brighter than that internal to it. But each zone appears 
 brightest at its inner edge, where it borders on a zone darker than itself, 
 and darkest at its outer edge, where it borders on a brighter zone. A 
 plausible explanation of this is based on the assumption that in the 
 neighbourhood of an excited area of the retina, as well as within the 
 area itself, the excitability is diminished; and the same explanation has 
 been extended to the contrast phenomena of coloured objects. A small 
 piece of grey paper, e.g., is placed on a green sheet. The grey patch 
 appears in the complementary colour of the ground — viz., pink or 
 rose-red (Meyer). The red colour is much stronger if the whole is 
 covered with translucent tracing-paper. Here we may suppose that 
 the fatigue of the substance or component chiefly affected by the ground 
 colour spreads into the portion of the retina occupied by the image oi 
 the grey paper; the white light coming from the latter, therefore, 
 affects mainly the component connected with the sensation of the com- 
 plementary colour. 
 
 The curious phenomenon of coloured shadows is also an illustration 
 of contrast. 'Ihey may be produced in various ways. For example, 
 when a lamp is lit in a room in the twilight, before it has yet grown 
 too dark, the shadows cast by opaque objects on a white wmdow-blind 
 are coloured blue. The yellow light of the lamp overpowers the feeble 
 daylight which passes through the blind, and the general ground is 
 yellowish ; but wherever a shadow is thrown it appears of a bluish tint 
 in contrast to the yellow ground. Here the only illumination the eye 
 receives from the region occupied by the shadow is the feeble daylight. 
 Falling upon an area in which the component chiefly affected by vellow 
 rays is more or less fatigued, it causes a sensation of the complementary 
 colour. As darkness comes on, the shadows become black, for now 
 practically no light at all comes from them. 
 
 Helmholtz looked upon simultaneous contrast as a result of false 
 judgment, and not of a change of excitability in parts of the retina 
 bordering on the actually excited parts. For the sake of perspective, 
 it \\ill be worth while to apply this theory by way of illustrating it, to 
 the explanation of the case of contrast we have just been considering, 
 from the other point of view, in Meyer's experiment. Helmholtz's ex- 
 planation of this experiment is as follows: When a coloured surface is 
 
VISION 1057 
 
 covered with translucent paper, Uie latter appears as a coloured covering 
 spread over the field. 1 he mind does not recognize that at the grey 
 patch there is any breach of continuity in this covering; it is therefore 
 assumed that the greenish veil extends over this spot too. Now, the 
 grey seen through the translucent white paper is objectively white — i.e., 
 sends to the eye the vibrations which together would give the sensation 
 of white light. But with a green veil in front of it, this could only 
 happen if the really grey patch was the colour complementary to green 
 — that is, rose-red. The mind, therefore, judges falsely that the patch 
 is red. Hering has severely criticized this theory of Helmholtz as to 
 false judgments; and the weight of evidence certainly seems to be in 
 favour of the view that simultaneous, like successive, contrast is due 
 to the influence of one portion of the retina, or retino-cerebral apparatus, 
 on another. 
 
 Hering's Theory of Colotir Vision. — The Young-Helmholtz theory 
 of colour vision has not met with universal acceptance. The best- 
 known rival theory is that of Hering, who takes his stand upon the 
 fact that certain visual sensations (red, yellow, green, blue, white, 
 black) do appear to us to be fundamentally distinct from each other, 
 while all the rest are obviously mixtures of these. Accepting these 
 six as primary sensations, he assumes the existence in the visual 
 nervous apparatus of substances of three different kinds, which may 
 be called the black-white, the green-red, and the blue-yellow. Like 
 all other constituents of the body, these substances are broken down 
 and built up again — in other words, undergo disassimilation and 
 assimilation, destructive and constructive metabolism. The sensa- 
 tions of black, of green, and of blue he supposes to be associated with 
 the constructive, and the sensations of white, of red, and of \ellow 
 with the destructive, processes in the three substances. The black- 
 white substance is used up under the influence of all the rays of the 
 spectrum, but in different degrees; the smaller the quantity of hght 
 falling on the retina, the more rapidly is it restored, and the more 
 intense is the sensation of black. The green-red substance is built 
 up by green rays, broken down by red. The blue-yellow substance 
 is destroyed by yellow rays, restored by blue. A prominent dif- 
 ference between this and the Young-Helmholtz theory, and, so far 
 as it goes, an advantage, is that Hering's theory attempts to assign 
 a direct objective cause for the visual sensations of white, black, 
 and yellow, as well as for red, green, and blue, instead of making 
 the sensations depend upon the magnitude of the stimulation pro- 
 cess. When any of the visual substances are consumed at one part 
 of the retina, they are supposed to be more rapidly built up in the 
 surrounding parts, and in this way many of the phenomena of 
 simultaneous contrast receive an easy and natural explanation. The 
 same is true of the simpler phenomena of after-images or successive 
 contrast. But in applying the theory to the more complicated 
 phenomena difficulties soon emerge, which, to say the least, are not 
 
 less formidable thein those connected with the Young-Helmholtz 
 
 67 
 
1038 
 
 THE SENSES 
 
 theory. Neither theory, in short, can be considered more than a 
 partially successful attempt to grapple with a very complex mass of 
 facts. Each, however, has been fruitful in leading to the discovery 
 of new facts — a great merit in a scientific hypothesis. 
 
 Sensibility of Different Parts of the Retina — Perimetry. — The 
 perception of colours, like the perception of white light, is not 
 equally distinct over the whole retina. We have repeatedly had 
 occasion to refer to the fovea centralis as the region of most distinct 
 vision; but it would be a mistake to suppose that it is therefore 
 necessarily more sensitive than the rest of the retina. As a matter 
 of fact, when the minimum intensity of white light which will cause 
 an impression at all is determined for each portion of the retina, it 
 
 is found that the fovea 
 centralis requires a some- 
 what stronger stimulus 
 than the zone immedi- 
 ately surrounding it. Ob- 
 jects only a little brighter 
 than the general ground 
 on which they lie — e.g., 
 verj^ faint stars — are best 
 seen when the eye is 
 directed a little to one 
 side. This has been attri- 
 buted to the absence of 
 visual purple from the 
 fovea, in accordance with 
 the theory previously 
 alluded to that the visual 
 purple acts as a mechan- 
 ism which ' adapts ' the 
 retina for the perception 
 of light of var\ing inten- 
 sity. But, with this ex- 
 ception, the sensibility of 
 the retina diminishes steadily from centre to periphery, both for 
 white and for coloured light. 
 
 When the eye is fixed, and the visual field — that is, the whole 
 space from which light can reach the retina in the given position, or, 
 what comes to the same thing, the projection of the visual field on 
 the retina by straight lines passing through the nodal point — 
 explored by means of a perimeter (Figs. 44^, 450), it is found that, 
 under ordinary conditions, a white object is seen over a wider field 
 than any coloured object, a blue object over a wider field than a 
 red, and a red over a wider field than a green object. The exact 
 shape, as well as size, of the visual field also differs somewhat for 
 
 Fig. 449. — Priestley Smith's Perimeter. A", rest 
 for chin ; 0, position of eye ; Ob, object, white or 
 coloured, which slides on the graduated arc B ; 
 /, point fixed by the eye. 
 
VISION 
 
 1059 
 
 different colours. In disease of the retina, or of the visual path 
 between it and the cortex, or of the visual cortex itself, the abridg- 
 ment of the field for white and for monochromatic light as mapped 
 out bv observations with the perimeter is often of value in diagnosis. 
 Although it has been shown by Aubert and others that monochro- 
 matic light of considerable intensity can bo perceived over the whole 
 retina, yet it may be said that the retinal rim is even then relatively 
 and, under ordinary conditions, absolutely colour-blind. This and 
 
 xn 
 
 Fig. 450. — Perimetric Chart of Right Eye (after Hirschberg). The numbers repre- 
 sent degrees of the visual field measured on the graduated arc of the perimeter. 
 w, boundary of field for white object ; b, for blue ; r, for red ; g, for green ; m, blind 
 spot; M, medial, and L, lateral side of the field of vision. The Roman immbers 
 represent twelve meridians of the retina, each making an angle of 30° with 
 the next. They fix the 'longitude ' of any point in the fieid. The concentric 
 circles indicated by Arabic numbers represent angular distances from the 
 fixation point in the planes of these meridians. They give the ' latitude ' of any 
 point. 
 
 other facts have given rise to the theory (p. 1047) that the rods, which 
 are alone present at the ora serrata, are concerned in achromatic 
 vision (under conditions of dark adaptation), the cones in colour 
 vision as well as in achromatic vision (under daylight conditions). 
 
 This brings us to the subject of colour-blindness, a phenomenon 
 of great interest in its theoretical as well as in its practical bearings. 
 
 Colour-Blindness. — A considerable number of persons (about 
 4 per cent, of all males, but only one-tenth of this proportion of 
 
io6o THE SENSES 
 
 females) are deikient in the power of distinguisliing between certain 
 colours. They are said to be colour-blind; but the term must not 
 be taken to signify that they are absolutely devoid of colour-sensa- 
 tions. A very small minority of the colour-blind appear to have 
 but one sensation of colour tone, everything appearing as white, 
 grey, or black (total colour-blindness, sometimes called mono- 
 chromatic vision). All colours are confused by them, but differences 
 of brightness are correctly appreciated. Probably the totally 
 colour-blind person receives somewhat the same impressions from 
 a coloured picture as the normal person does from a reproduction 
 of the same picture in black-and-white. There are close resemblances 
 between the vision of the totally colour-blind eye and that of the 
 normal eye adapted by resting in the dark for twilight vision. The 
 fovea is relatively, and in some cases absolutely,_ insensitive to 
 light, while the peripheral portion of the retina is normal, or nearly 
 normal, in this regard. This is the foundation of the theory that in 
 total colour-blindness the cones are devoid of their normal func- 
 tions, and that the hypothetical mechanism for twilight vision (the 
 rods) is functioning alone. In another condition (night-blindness, 
 or hcmeralopia) it is sometimes assumed that the other mechanism 
 (that of the cones) which is adapted for daylight vision, and has 
 little power of dark-adaptation, is alone acting. But it cannot be 
 said that this has been proved. 
 
 The rest of the colour-blind are dichromatic — i.e., their colour 
 reactions seem to correspond only to two of the fundamental colour 
 sensations of the normal person and their combinations, in addition 
 to white. Of the dichromates a very few confuse blue with yellow. 
 The great majority are unable to distinguish between red and green. 
 The condition will be most easily understood by considering some 
 of the extraordinary mistakes which may be made by the colour- 
 blind, without necessarily leading them to suspect that there is any- 
 thing abnormal in their vision. Thus, to quote the words of a 
 distinguished writer on this subject, himself a sufferer from the 
 deliciency: ' A naval officer purchases red breeches to match his 
 blue uniform; a tailor repairs a black article of dress with crimson 
 cloth; a painter colours trees red, the sky pink, and human cheeks 
 blue.' The shoemaker, Harris, the discoverer of colour-blindness, 
 picked up a stocking, and was surprised to hear other people 
 describe it as a red stocking; it seemed to him only a stocking. 
 The celebrated Dalton was twenty-six years of age before he knew 
 that he was colour-blind. He matched samples of red, pink, 
 orange, and brown silk with green of different shades; blue both 
 with pink and with violet ; lilac with grey. 
 
 When the condition of vision in dichromates is tested by means of 
 the spectrum, it is found that they fall into two classes: (i) A class 
 (of green-blind) by whom the whole of the spectrum from red to yellow is 
 described as yellow of different degrees of brightness (intensity) ; the green 
 
VISION loOi 
 
 appears as a pale yellow with a grey or wiiite band in its midst; while 
 the violet end is seen as different shades of blue. (2) A class of (red- 
 blind) whose whole spectrum, from rod to green, is seen as green of 
 different intensities, the extreme red being entirely invisible. The 
 violet end is blue, as in (i), and there is a band of white or grey near 
 the blue end of the green. 
 
 Sir John Hcrschcll explained Dalton's peculiarity of vision on the 
 hypothesis that hv only possessed two, instead of three, primary 
 sensations. 
 
 On the Young-flelmholtz theory, the missing sensation is supposed 
 to be either red or green. At the intersection of the curves that repre- 
 sent the violet and green sensations (Fig. 447), the red-blind individual 
 will see what he describes as white — viz., the sensation produced by 
 tlie stimulation of the only two components he possesses. Similarly, 
 at the intersection of the red and violet curves the green-blind person 
 will see what is wiiite to him. 
 
 Those who have attempted to explain colour-blindness on Hering's 
 theorj' have usually assumed that the colour-blind possess the blue- 
 yellow, but lack the green-red visual substance. So that on this theory 
 there should be no difference between red-blindness and green-blind- 
 ness. But V. Kries, in a study of twenty cases of congenital partial 
 colour-blindness, brings forward strong evidence that the red-green 
 blind can be divided, as regards the comparison of red (lithium) and 
 orange (sodium) light, into two sharply-separated groups— a result 
 which is, so far as it goes, in favour of the Young-Helmholtz theory, 
 and against the theory of Hering. 
 
 The observations of Burch on temporary colour-blindness produced 
 by placing the eye behind a transparent coloured screen and focussing 
 a beam of strong sunlight on it, lend additional support to the former 
 theory. Thus, if a spectrum is looked at after green-blindness has been 
 induced by exposure of the eye to green light, the red portion of the 
 specti"um seems to pass into the blue, and no intermediate green band 
 is seen. If the eye is exposed to yellow light it becomes temporarily 
 blind not only for yellow, but also for red and green. This is in favour 
 of the assumption of the Young-Helmholtz theory that the sensation 
 of yellow is caused when the retinal eletnents concerned in the production 
 of the sensations of red and green are simultaneously stimulated. It is, 
 however, equally difficult to reconcile some of the phenomena of colour- 
 blindness with the Young-Helmholtz theory. Anomalies and defects 
 of colour-sensation are common accompaniments of pathological lesions 
 of the visual apparatus, and can be produced by various drugs, as by 
 abuse of tobacco. But colour-blindness, in its true sense, is con- 
 genital, often hereditary; the colour-blind are ' bom, not made.' And 
 although the condition cannot be cured, it is of great importance that 
 it should be recognized in the case of persons occupying positions such 
 as those of engine-drivers, railway-guards, and sailors, in which coloured 
 lights have to be distinguished. For, while it is true that the sensations 
 which red and green lights give the colour-blind are far from baing 
 identical (Pole) under favourable conditions, it is precisely when the 
 conditions are unfavourable — as in a fog or a snow-storm — that the 
 capacity of distinguishing them becomes invaluable (Practical Ex- 
 ercises, p. 1 1 12). 
 
 Irradiation. — The phenomenon known as irradiation was first 
 described by Kepler, who gave as an example the appearance known 
 as the 'new moon in the old moon's arms,' where the crescent of the 
 new moon seems to overlap and embrace the unilluminated portion of the 
 lunar disc. A white circle on a black ground (Fig. 451) appears, in 
 
,o62 THE SENSES 
 
 a good lig'it, to be larger tlian an exactly equal black circle on a white 
 ground. The explanation is as follows: Owing to the aberration of the 
 refractive media of the eye (p. 1027), all the rays proceeding from the 
 luminous object are not brought accurately to a focus on the retina, 
 and the image is surrounded by dilfusion circles (p. 1028) which encroach 
 upon the unilluminated boundary. Physically these represent a 
 weaker illumination than that of the image proper, and therefore the 
 latter ought to stand out in its real size as a brightei area surrounded by 
 weaker haloes. That this is not the case, and that the image is pro- 
 jected in its full brightness for a certain distance over its dark boundary, 
 is due to the fact that the eye does not recognize verj' small differences 
 of, brightness. Wlien the accommodation is not perfect, the diffusion 
 circles are, of course, much \\dder, and irradiation is better marked when 
 the object is a little out of focus. 
 
 The Movements of the Eyes. — That the eyes may be efhcient 
 instruments of«'vision, it is necessary that they should have the 
 power, of moving independently of the head. An eye which could 
 not move, though certainly better than an eye which could not see, 
 
 would \^et be as imperfect after 
 its kind as a ship which could 
 / ^^^ \ run before the \vind, but could 
 not lack. The mere fact that 
 the angle between the visual 
 axes must be adapted to the 
 distance of the object looked at 
 renders this obvious; and the 
 beauty of the intrinsic mechan- 
 ism of the eyeball has its fitting complement in the precision, 
 delicacy, and range of movement conferred upon it by its extrinsic 
 muscles. 
 
 Not only are movements of convergence and divergence of the 
 eyeballs necessary in accommodating for objects at different dis- 
 tances, but without compensatory movements of the eyes it would 
 be impossible to avoid diplopia with every movement of the head; 
 for the images of an object fixed in one position of the head would 
 not continue to fall on corresponding points of the retinse in another 
 position. 
 
 All the complicated movements of the eyeball may be looked 
 upon as rotatioris round axes passing through a single point, which 
 to a near approximation always remains fixed, and is situated about 
 177 mm. behind the centre of the eye. 
 
 The position which the eyeballs take up when the gaze is directed to 
 the horizon, or to any distant point at the level of the eyes, is called 
 the primary position. ' Here the visual axes are parallel, and the plane 
 passing through them horizontal. WTiile the head remains fixed in this 
 position, the eyeballs can rotate up or down around a horizontal axis, 
 or from side to side around a vertical axis; or upwards and inwards, 
 downwards and outwards, downwards and inwards, and upwards and 
 outwards around oblique axes, which always lie in the same plane as 
 the vertical and horizontal axes of rotation— i.e., in the vertical plane 
 
VISION 
 
 ro03 
 
 passing through the fixed centre of rotation. These facts, spoken of 
 collectively as Listing's law, and first detliicpd by him from theoretical 
 considerai^ions, were afterwanls proved experimentally by MelmJioltz 
 and Donders. It necessarily follows from i.isting's law (and this is, 
 indeed, another way of stating it) that in moving from the primary posi- 
 tion into any other, there is no rotation of tiie eyeball round the visual 
 axis — no wheel-movement, as it is called. 
 
 A true rotation of the eye round the visual axis does, however, occur 
 when the eyes are converged as in accommodation for a near object, 
 each eyeball rotating towards the temporal side. This is especially the 
 case when the eyes are at the same time converged and directed down- 
 wards; and the rotation may amount to as much as 5°. When the 
 head is rolled from side to side, while the eyes are kept fixed on an 
 object, a slight compensatory rotation of the eyeballs takes place 
 against the direction of rotation of the head. The amount of rotation 
 of the eyes is relatively greater for small than for large movements of 
 the head (eye 5° for head 20°; eye 10° for head 80° — Kiister). 
 
 The Extrinsic Muscles of the Eyes. — The eyeball is acted upon by 
 six nuiscles arranged in three pairs, whicli may be considered, 
 rouglily speaking, as antagonistic sets. These are the internal and 
 external recti, the superior and 
 inferior recti, and the superior 
 and inferior obliqui. 
 
 Although the movements of the 
 eye have been very fully studied, 
 and are, upon the whole, well 
 understood, our knowledge of the 
 manner in which any given move- 
 ment is brought about, and of the 
 exact action of the muscles which 
 take part in it, is by no means 
 as copious and precise. From 
 the nature of the case, the greater 
 part of what we do know has 
 been inferred from the anatomical 
 relations of the muscles as re- 
 vealed by dissection in the dead 
 body rather than gained from actual observation of the living eye. 
 A plane, called the plane of traction, is supposed to pass through the 
 middle points of the origin and insertion of the muscle whose action 
 is to be investigated, and through the centre of rotation of the 
 eyeball. A straight line drawn at right angles to this plane through 
 the centre of rotation is evidently the axis round which the muscle 
 when it contracts will cause the eye to rotate, provided thai the 
 fibres of the muscle are symmetrically distributed on each side of 
 the plane of traction. The axes of rotation of the antagonistic 
 pairs almost, but not completely, coincide with each other. The 
 common axis of the external and internal recti practically coincides 
 with the vertical axis of the eyeball (Fig. 452) in the primary posi- 
 
 int 
 
 B sup 
 H in/ 
 
 Fig. 452.— Horizontal Section of Left 
 Eye. Arrows show direction of 
 pull of the muscles. The axis of 
 rotation of the external and internal 
 recti would pass through the inter- 
 section of a and /3 at right angles 
 to the plane of the paper. 
 
io64 THE SENSES 
 
 tion. The eye is turned towards the temple when the external 
 rectus alone contracts, towards the nose when the internal rectus 
 alone contracts. The common axis of the superior and inferior 
 recti, 13, lies in the horizontal visual plane in the primary position, 
 but makes an angle of about 20" with the transverse axis, its inner 
 end being tilted forwards. The consequence is that contraction 
 of the superior rectus turns the eye up, and contraction of the 
 inferior rectus turns it down, but both movements are also com- 
 bined with a slight inward rotation. The common axis of the 
 oblique muscles, a, makes an angle of 60'' with the transverse axis, 
 the outer end of it being the most anterior. The direction of traction 
 of the superior oblique is, of course, given not by the line joining 
 its bony origin and its insertion, but by the direction of the portion 
 reflected over the pulley. When the superior oblique contracts 
 alone, the eyeball is rotated outwards and downwards; the inferior 
 oblique causes an outward and upward rotation. None of the 
 common axes of rotation of the pairs of muscles, except that of the 
 external and internal recti, lies in Listing's plane. Now, as we have 
 seen that every movement which the eye, supposed to be originally 
 in the primary position, can execute may be considered as a rota- 
 tion round an axis in this plane, it is clear that every movement, 
 except truly transverse rotation, must be brought about by more 
 than one pair of muscles. For vertical rotation, the inward pull of 
 the superior rectus is antagonized by a simultaneous outward pull 
 of the inferior oblique; for downward rotation, the inferior rectus 
 and superior oblique act together. In oblique movements, a muscle 
 of each of the three pairs is concerned. The effect on the eyeball 
 of simultaneous contraction of certain pairs of muscles may be 
 summarized thus: 
 
 External rectus (outward) + internal rectus (inward) = none. 
 
 Superior rectus (upward and inward) + inferior oblique (upward and 
 outward) = upward. 
 
 Inferior rectus (do%\Tiward and inward) + superior oblique (downward 
 and outward) = downward. 
 
 Section IL — He.\ring. 
 
 The transverse vibrations of the ether fall upon all parts of the surface 
 of the body, but only find nerve-endings capable of giving the sensa- 
 tion of light in the little discs, which we call the retinae. So the much 
 longer and slower longitudinal waves of condensation and rarefaction 
 which are being constantly originated in the air or imparted to it by 
 solid or liquid bodies that have been themselves set vibrating fall upon 
 all parts of the surface, but only produce the sensation of sound when 
 they strike upon the tiny mechanism of the internal ear. 
 
 But just as the etliereal vibrations, and especially those of greater 
 wave-length, are able to excite certain end-organs in the skin which 
 have to do with the sensation of temperature, so the sound-waves, 
 when sufficiently large, are aJso capable of stimulating certain cutaneous 
 
HEARING 
 
 1-165 
 
 nerves and of givuig rise to a sensation of intermittent pressure or tliriU. 
 This is readily perceived when the finger is immersed in a vessel ol 
 water into which dips a tube connected with a source of sound, or when 
 a vibrating bell or tuning-fork is touched. So far as we know, what 
 takes place in the ear is essentially similar — that is to say, a mechanical 
 stimulation of the ends of the auditory nerve, but a stimulation which 
 acts through, and is gratluated and controlled by, a special intermediate 
 mechanism. 
 
 As the visual apparatus consists of a sensitive surface, the retina, 
 vvhich contains the end-organs of the optic nerve and of dioptric 
 arrangements which receive and focus the rays of light, the auditory 
 apparatus consists of the sensitive end-organs of the cochlear divi- 
 sion of the eighth nerve and of a mechanism which receives the 
 sound-waves and communicates them to these. 
 
 Physiological Anatomy of the Ear. — At the bottom of the external 
 auditory meatus lies the membrana tympani, a nearly circular mem- 
 brane set like a drum-skin in a 
 ring of bone, and separating the 
 meatus from the tympanum or 
 middle ear. Its external surface 
 looks obliquely do%vnwards, and 
 at the same time somewhat for- 
 wards, so that if prolonged the 
 membranes of the two ears would 
 cut each other in front of, and also 
 below, the horizontal line passing 
 through the centre of each (Figs. 
 
 453.454)- 
 
 Ihe tympanum contains a 
 chain of little bones stretching 
 right across it from outer to inner 
 wall. Of these the malleus, or 
 hammer, is the most external. 
 Its manubrium, or handle, is in- 
 serted into the membrana tym- 
 pani, which is not stretched taut 
 within its bony ring, but bulges 
 inwards at the centre, where the 
 handle of the malleus is attached. 
 The stapes, or stirrup, is the most 
 internal of the chain of ossicles, 
 and is inserted bj' its foot-plate 
 into a small oval opening — the 
 foramen ovale — on the inner wall of the tympanic cavity. A mem- 
 branous ring — the orbicular membrane — surrounds the foot of the 
 stapes, helping to fill up the foramen and attaching the bone to its 
 edges. The inner surface of the foot of the stapes is in contact with 
 the perilymph of the internal ear. The incus, or anvil, forms a link 
 between the malleus and the stapes. The auditor>^ ossicles, as well as 
 the whole cavity of the tympanum, are covered by pavement epithelium. 
 
 The tympanum is not an absolutely closed chamber; it has one 
 channel of communication with the external air — the Eustachian tube 
 — which opens into the phary-nx. By the action of the cilia lining this 
 tube the scanty secretion of the middle ear is moved towards its 
 phar>Tigeal opeiiing, which, usually closed, is opened when a swallowing 
 
 Fig. 453.— The Ear. in, external meatus; 
 /, head of malleus; 0, short process of 
 malleus; g, handle of malleus; h, incus; 
 i, foot of stapes in oval foramen; e, tym- 
 panic membrane. 
 
to66 
 
 THE SENSES 
 
 movement occurs. Its function is to keep the pressure in the middle 
 ear approximately tliat oi the atmosphere. In a balloon ascent an 
 excess of pressure is establislicd on the internal surface of the tympanic 
 membrane. In the air-lock of a caisson wlien the air is being com- 
 pressed the excess of pressure is on the external surface of the membrane. 
 The feeling of uncomfortable tension is relieved in both cases by swallow- 
 ing movements which allow the pressure in the tympanum to adjust 
 itself to that in the pharynx. In catarrh of the naso-pharynx the 
 orifice may be occluded, and this is accompanied by impairment of 
 hearing and a disagreeable sensation of tension in the ear, owing to 
 absorption and consequent rarefaction of the air in the tympanum. 
 
 The patient instinc- 
 tively makes efforts 
 
 . which increase the pha- 
 
 :„ ryngeal pressure from 
 
 -- time to time so as to 
 
 1 open the tube. 
 
 The loosely - jointed 
 chain of ossicles is 
 steadied and its move- 
 ments directed by liga- 
 ments and by the ten- 
 sion of its terminal mem- 
 branes. It forms a kind 
 of bent lever by which 
 tlie oscillations of the 
 membrana tympani are 
 transferred to the mem- 
 brane covering the oval 
 foramen, and at the 
 same time reduced in 
 size. Two slender 
 muscles, the tensor tym- 
 pani and stapedius, con- 
 tained in the tympanic 
 
 Fig. 454— Tympanum of Left Ear. showing the ^^^1^^' ^^.f. ^^^° ^°"" 
 Ossicles (Mon-is). i. superior, and 4. external. ^^Cted with and may 
 ligament of malleus; 2. head; 7. short process, and ^^ upon the ossicles. 
 10, manubrium or handle, of malleus; 5, long process -"^"^ former lies in a 
 of incus, terminating in 9, the os otbicufare ; 6. base, groove above the Eusta- 
 and H. head.of stapee; II. EusfftcBlan tube; 12. ex- chian tube, and its 
 ternal auditory meatus; 13. membrana tympani; tendon, passing round a 
 3, upper, and 14, lower, part of t'/mpanum. kind of osseous pulley 
 
 (processus cochleari- 
 formis), is inserted into the handle of the malleus; the stapedius is 
 lodged in a hollow of the inner bony wall of the tympanum. Its 
 tendon is attached to the neck of the stapes near its articulation with 
 the incus. This inner wall is pierced not only by the oval foramen, 
 but also by a round opening, the fenestra rotunda, which is dosed by 
 a membrane to which the name of secondary membrana tympani is 
 sometimes given. 
 
 The internal ear consists of the bony labyrinth, a series of curiously 
 excavated and communicating spaces in the substance of the petrous 
 portion of the temporal bone, filled \vith a liquid called the perilymph, 
 in which, anchored bv strands of connective tissue, floats a correspond- 
 ing series of membranous canals (the membranous labyrinth), filled 
 with a liquid called endolymph. The labyrinth of the internal ear is 
 
HEARING 
 
 1067 
 
 divided into three well-marked parts: the cochlea, the vestibule, and 
 the semicircular canals (I'ig. 455). Ihe cochlea, the most anterior of 
 the three, consists of a convoluted lube which coils round a central 
 pillar, tlie columella or modiolus, like a spiral staircase. The lamina 
 spiralis projects from the modiolus and divides the tube into an upper 
 compartment, the scala vcstibuli, antl a lower, the scala tympani 
 (Fig. 456). The part of the lamina next the modiolus is of bone, but it 
 is completed at its outer edge by a membiane, the lamina spiralis mem- 
 branacea, or basUar membrane. The scala tympani abuts on the 
 fenestra rotunda, and its perilymph is only separated from the air of 
 the tympanic cavity by the membrane which closes tliat opening. 
 At the apex of the cochlea the lamina spiralis is incomplete, ending in 
 a crescentic border, so that the scala tympani and the scala vestibuli 
 here communicate by a small opening, the helicotrema. The scala 
 vestibuli communicates with the vestibule, and Ihe vestibule with the 
 semicircular canals, so that the perilvmph of the entire labyrinth forms 
 a continuous sheet separated from the cavity of the middle ear by tiie 
 
 — 9 
 
 Fig- 455- — Diagram of Right (Membranous Labyrinth (after lestut). i, utricle; 
 2, 3, 4, superior, posterior, and horizontal semicircular canals; 5, saccule; 
 6, ductus endolymphaticus arising by two branches, 7, 7'; 8, saccus endo- 
 lymphaticus; 9, canalis cocdilearis (canal of the cochlea) ending at 9', and 9'; 
 10, canalis reuniens. 
 
 structures that fill up the round and oval foramina. In the mem- 
 branous labyrinth, and in it alone, are contained the end-organs of the 
 auditory nerve. The membranous portion of the cochlea is a small 
 canal of triangidar section, cut off from the scala vestibuli by the mem- 
 brane of Reissner, which stretches from near the edge of the bony 
 spiral lamina to the outer wall (Fig. 457), to which it is attached by the 
 spiral ligament. The canal has received the name of the scala media, 
 or canal of the cochlea. The membrane of Reissner forms its roof. 
 Its floor is composed (i) of the projecting edge of the spiral lamina, 
 called the limbus, and (2) of the basilar membrane. The most con- 
 spicuous constituent of the basilar membrane is a layer of stiff, parallel, 
 transparent fibres arranged radially — i.e., in the direction from limbus 
 to spiral ligament. They are embedded in a homogeneous material. 
 Below the cochlear canal ends blindly, but communicates by a side- 
 channel with the portion of the membranous vestibule called the sac- 
 cule, which in its turn communicates wdth the utricle by the Y-shaped 
 origin of the ductus endolymphaticus. Into the utricle open the three 
 
io68 
 
 THE SENSES 
 
 semicircular canals, the endolymph of which has, therefore, free com- 
 inunicatioii with that of the vestibule and cochlea. But although the 
 semicircular canals and vestibule belong anatomically to the internal 
 ear, and arc supplied by branches of the auditory nerve, we have no 
 positive proof that in the higlicr animals, at least, they are in any way 
 concerned in hearing; and since experiment has assigned them a 
 definite function of another kind (p. 936), vve shall not consider them 
 
 /r.v. 
 
 Fig. 45r>. — Longitudinal Section through the Cochlea of a Cat (Schafer, after Sobotta) 
 X 25. c/c, canal or duct of cochlea ;sci;,scalavestibuli;sc/,scalatympani;ii', bony 
 wall of cochlea; C, organ of Corti ; mi?, Reissner's membrane ; », fibres of cochlear 
 nerve; gsp, ganglion spirale; str.v., stria vascularis. 
 
 further in this connection. The scala media contains the organ of Corti, 
 which (Fig. 458) consists of a series of modified epithelial cells planted 
 upon the basilar membrane. The epithelial cells are of three kinds: 
 (1) supporting epithelial cells; (2) the pillars or rods of Corti, in two 
 series (inner and outer), sloped against each other like tlie rafters of a 
 roof, and covering in a vault or tunnel which runs along the whole of 
 the scala media from tlie base to the apex of the cochlea; (3) the hair- 
 cells, around which the fibres of the auditory nerve arborize. These 
 last are columnar epithelial cells, surmounted by hairs. They are 
 
HEARING 
 
 io6q 
 
 arranged in several rows, one row lying just internal to the inner line 
 of pillars, and several rows external to the outer line of pillars. Be- 
 tween the outer hair-cells arc supporting cells {cells of Deiters). A thin 
 membrane, the reticular lamina or membrana reticularis, composed of 
 tiddle-shaped rings or phalanges, covers the hair-cells, and through 
 openings in it the hairs project. A thicker membrane, the membrana 
 tectoria, springing from the edge of the osseous spiral lamina near the 
 attachment of Reissner's membrane, forms a kind of canopy over both 
 pillars and hair-cells. The outer wall of the canal of the cochlea is 
 clad by cubical epithelium covering a membrane richly supplied with 
 bloodvessels [stria vascularis). The fact that the hair-cells of Corti's 
 organ are connected with the fibres of the cochlear division of the 
 
 Fig. 457. -Vertical Section of the First Turn of the Cochlea (after Retzius). D.C 
 canal of cochlea; tC, tunnel of Corti; h.m. basilar membrane; h.i, h.e, internal 
 and external hair-cells; Mt, membrana tectoria; s.sp, spiral groove; str.v, stria 
 vascularis; sp.l, spiral lamina; n, fibres of the cochlear nerve; /, limbus lamindB 
 spiralis; R, Reissner's membrane; s.v, scala vestibuli; s.t, scala tympani; l.sp, 
 spiral ligament. 
 
 auditory nerve, and its elaborate structure, suggest that it must play 
 a peculiar part in auditory sensation. Comparative anatomy shows 
 us that the cochlea is the most highly developed portion of the internal 
 ear, the last to appear in its evolution, and the most specialized. It 
 is absent in fishes, which possess only a vestibule and one to three semi- 
 circular canals. It first acquires importance in reptiles, but attains 
 its highest development in mammals; and there is every reason to 
 believe that it is the terminal apparatus of the sense of hearing. 
 
 Functions of the Auditory Ossicles. — The anatomical arrange 
 ments of the middle ear suggest that the tympanic membrane and 
 the chain of ossicles have the function of transmitting the sound- 
 waves to the liquids of the labyrinth ; and observation and experi- 
 
T070 
 
 THE SENSES 
 
 ment fully confirm this idea. Tracings of the movements of thj 
 ossicles have been obtained by attaching very small levers to them, 
 and their movements have been directly observed with the micro- 
 scope. Even in man it may be shown, by viewing the membrane 
 through a series of slits in a rapidly-revolving disc (stroboscope), 
 that it vibrates when sound-waves fall on it. 
 
 When the handle of the malleus moves inwards, rotating around 
 an axis which may be supposed to pass through its neck, its head 
 moves in the opposite direction. The joint between that bone and 
 the incus is thus locked, on account of the shape of the articular 
 surfaces. The long process of the incus, constituting the second 
 
 458. — Organ of Corti (Barker, after Retzius). mb, basilar membrane; tb. its 
 tympanal covering; vs. bloodvessel (vas spirale): re, medullated distal processes 
 of bipolar nerve-cells in the ganglion spirale, passing in to arborize around the 
 hair-cells; iS, epithelial cells continuous with the epithelium of the sulcus 
 spiralis internus; p, inner pillar of Corti, with its basal cell, b ; p', outer pillar 
 with its basal cell, b' ; i, 2, 3, supporting cells of Deiters, whose processes run up 
 to be attached to the lamina reticularis, r : H, Hensen's supporting cells; C, cells 
 of Claudius; /, internal hair-cell with its liairs. i' (the upper part of the hair-cell 
 is concealed by the head of the inner pillar of Corti): c, external hair-cell: c', hairs 
 of three external hair-cells; n, n^. to n*. cross-sections of the spiral strand of 
 cochlear nerve-fibres. 
 
 portion of the bent lever, passes inwards, carrying with it the stapes, 
 which is attached to it by an almost rigid joint, and the stapes is 
 pressed into the oval foramen. Since the long process of the incus 
 is about one-third shorter than the handle of the malleus, the ex- 
 cursion of the point of the former is correspondingly smaller than 
 that of the latter, but at the same time more powerful. When the 
 tympanic membrane passes outwards, the handle of the malleus 
 and foot of the stapes do the same. But the joint now unlocks, and 
 excessive outward movement of the stapes, which might result in 
 its being torn from its orbicular attachment, is prevented. The 
 ossicles vibrate en masse. It is only to a trifling extent that sound 
 
HEARING 1071 
 
 can he cDnducti'd tliiou{^'li them to the hibyrinth as a molecular 
 vibration; for when they are anchylosed, and the foot of the stapes 
 fixed immovably in the foramen ovale, as sometimes occurs in 
 disease, hearing is greatly impaired. 
 
 Of course, every vibration of the tympanic membrane must cause 
 a corresponding condensation and rarefaction of the air in the 
 middle ear; and this may act on the membrane closing the fenestra 
 rotunda, and set up oscillations in the perilymph of the scala tym- 
 pani. That this is a possible method of conduction of sound is 
 shown by the fact that, even after closure of the oval foramen, a 
 slight power of hearing may remain. But under ordinary con- 
 ditions by far the most important part of the conduction takes 
 place via the ossicles. And when it is remembered that the tym- 
 panic membrane is about thirty times larger than that which fills 
 the oval foramen, it will be seen that the force acting on unit area 
 of the foot of the stapes may be much greater than that acting on 
 unit area of the membrana tympani, and that the mode of trans- 
 mission by the ossicles is a very advantageous method of trans- 
 forming the feeble but comparatively large excursions of the tym- 
 panic membrane into the smaller but more powerful movements of 
 the stapes. The average excursion of the membrane of the oval 
 foramen does not at most amount to more than o 04 millimetre. 
 Even the so-called cranial conduction of sound when a tuning-fork 
 is held between the teeth or put in contact with the head, which 
 was at one time supposed to be due solely to direct transmission 
 of the vibrations through the bones of the skull to the liquids of 
 the labyrinth or the end-organs of the auditory nerve, has been 
 shown to take place, in great part, through the membrana tympani 
 and ossicles; the vibrations travel through the bones to the tym- 
 panic membrane, and set it oscillating. So that this test, when 
 appHed to distinguish deafness caused by disease of the middle ear 
 from deafness due to disease of the labyrinth or the central nervous 
 system, may easily mislead, although it enables us to say whether 
 the auditory meatus is blocked — by wax, e.g. — beyond the tym- 
 panic membrane. 
 
 A membrane like a drum-head has a note of its own, which it gives 
 out when struck, and it vibrates more readily to this note than to any 
 other. It would evidently be a serious disadvantage if the tympanic 
 membrane, whose office it is to receive all kinds of vibrations, and 
 respond to all, had a marked fundamental tone which would be con- 
 tinually obtruding itself among other notes. The difficulty is obviated 
 by the damping action of the ossicles and the liquids of the labyrinth 
 on the movements of the membrane, which in addition is not stretched, 
 but lies slacldy in its bony frame, so that when the handle of the malleus 
 is detached from it, it retains its shape and position. 
 
 The tensor tympani, when it contracts, pulls inwards the handle of 
 the malleus, and thus increases the tension of the tympanic membrane. 
 The precise object of this is obscure. It has been suggested that damp- 
 
I072 THE SENSES 
 
 ing of the movements of the auditory ossicles is thus secured. Another 
 theory is that the increased tension of the membrane renders it more 
 capable of responding to higher tones, and that the muscle thus acts as 
 a kind of accommodating mechanism. But Hensen has observed that 
 the tensor only contracts at the beginning of a sound, and relaxes again 
 when the sound is continued ; and this is difficult to reconcile with either 
 of these hypotheses. The muscle is normally excited refiexly through 
 the vibrations of the membrana tympani, but some individuals have 
 the power of throwing it into voluntary contraction, which is accom- 
 panied by a feeling of pressure in the ear, and a harsh sound. The 
 function of the stapedius is unknown. Its contraction would tend to 
 press the posterior end of the foot-plate of the stapes deeper into the 
 foramen ovale, and cause the anterior end to move in the opposite 
 direction ; but it is not easy to see how this would affect the action of 
 the auditory mechanism. 
 
 The tensor tympani is supplied by the fifth nerve through a branch 
 from the otic ganglion; the stapedius is supplied by the seventh. 
 Paralysis of the fifth nerve may be accompanied with difficulty of 
 hearing, especially for faint sounds. WTien the seventh nerve is 
 paralyzed, increased sensitiveness to loud sounds has been observed. 
 
 We have already recognized tlie organ of Corti, particularly the 
 hair-cells, as a sensory epithelium which constitutes the terminal 
 apparatus of the cochlear nerve. The adequate stimulus of the 
 auditory receptors is the periodic changes of pressure in the endo- 
 lymph. But there are various opinions as to how these vibrations 
 are transmitted to the hair-cells, and as to how the vibrations of 
 the hair-cells are translated into nerve impulses in the auditory 
 fibres. The pillars of Corti, the basilar membrane, and the mem- 
 brana tectoria, have in turn been regarded as the structures im- 
 mediately set into vibration by the changes in the endolymph. 
 The case for the tectorial membrane is perhaps the most plausible, 
 for its position renders it most capable of acting on thi; hairs. 
 Others have supposed that the hairs of the hair-cells are directl}' 
 affected by the endolymph. Some, despairing of further analysis, 
 content themselves with the conclusion that the organ of Corti 
 vibrates as a whole. Some of these theories will be again referred 
 to in considering what is the greatest problem of the physiology of 
 hearing, viz. : 
 
 The Perception of Pitch — Analysis of Complex Sounds.— As the 
 eye, or, ratlier, the retina plus the brain, can perceive colour, so the 
 labyrinth plus the brain can perceive pitch. The colour-sensation 
 produced by ethereal waves of definite frequency depends on that 
 frequency; and upon the frequency of the aerial vibrations depends 
 also the pitch of a musical note. But there is this difference be- 
 tween the eye and the ear: that while the sensation produced by a 
 mixture of rays of light of diticrent wave-len,utli is always a simple 
 sensation — that is, a sensation which we do not perceive to be built 
 up of a number of sensations, which, in other words, we do not 
 analyze — the ear can perceive at the same time, and distinguish 
 
HEARING 1*^73 
 
 from eacli other, the components of a compU'X sound. When a 
 number of notes of different pitch are souncU'd together at the 
 same distance from tlie ear the disturbance which reaches the mem- 
 brana tympani is the physical resultant of all the disturbances pro- 
 duced by the individual notes, and it strikes upon the membrane as 
 a single wave. ' A single curve describes all that the ear can possibly 
 hear as the result of the most compHcated musical performance. 
 ... In the complicated sound the variations of the pressure of the 
 air are more abrupt, more sudden, less smooth, and less distinctly 
 periodic than they are in softer, purer, and simpler sound. But the 
 superposition of the dit^erent effects is really a marvel of marvels ' 
 (Kelvin). The ear or brain must, therefore, possess the power of 
 resolving the complex vibrations into their constituents, else we 
 should have a mixed or blended sensation, and not a sensation in 
 which it is possible to distinguish the constituents of which it is 
 made up. Several hypotheses have been proposed to explain this 
 physiological analysis of sound, on the assumption that the analysis 
 takes place in the labyrinth. The most important, in spite of certain 
 defects, is still that of Helmholtz. 
 
 Helmholtz attempted to explain the perception of pitch on the 
 assumption that in the internal ear there exists a series of resonators, 
 each of which is fitted to respond by sympathetic vibration to a 
 particular note, while the others are una^ected; just as when a note 
 is sung before an open piano it is taken up by the string which is 
 attuned to the same pitch and ignored by the rest. Let us sup- 
 pose that a given fibre of the auditory nerve ends in an organ which 
 is only set vibrating by waves impinging on it at the rate of lOO a 
 second, and that the end-organ of another fibre is only influenced 
 by waves wnth a frequency of 200 a second. Then, on the doctrine 
 of ' specific energy ' (according to which the sensation caused by 
 stimulation of a nerve depends not on the particular kind of stimu- 
 lus but on the anatomical connection of the nerve with certain 
 nerve centres), in whatever wa^' the first fibre is excited, a sensation 
 corresponding to a note with a pitch of 100 a second will be per- 
 ceived. Whenever the second fibre is excited, the sensation will be 
 that of a note of 200 a second, or the octave of the first. If both 
 fibres are excited at the same time the two notes will be heard 
 together. Now, Hensen actually observed that in the auditory 
 organs of some crustaceans, the hair-like processes of certain 
 epithelial cells can be set swinging by waves of sound, and, further, 
 that they do not all vibrate to the same note unless the sound is 
 very loud. In the lobster there are between four and five hundred 
 of these hairs, varying in length from 14 fx to 740 [i; and in some 
 insects, such as the locust, similar hairs, also graduated in length, 
 exist. 
 
 To gain an anatomical basis for his theory, Helmholtz supposed 
 first of ail that the pillars of Corti were the vibrating structures, 
 
 68 
 
1074 THE SENSES 
 
 and that, diroctly or through the hair-cells, their mechanical vibra- 
 tions were translated into impulses in the auditory nerve-fibres. 
 But apart from the fact that their number is too small (about 3,000) 
 to allow us to assign one rod to each perceptible difference of pitch, 
 and their dimensions too similar to permit of the requisite range 
 of vibration frequency, it was pointed out that birds do not possess 
 pillars of Corti — a fact which was decisive against the assumption 
 of Helmholtz, since nobody denies to singing-birds the power of 
 appreciating pitch. Helmholtz accordingly, choosing between the 
 remaining possibilities, gave up the pillars of Corti, and adopting 
 a suggestion of Hensen, substituted the radial fibres of the basilar 
 membrane as his hypothetical resonators. These are more ade- 
 quate to the task imposed on them, since their range of length is 
 far greater (41 ju at the base to 495 jli at the apex of the cochlea — 
 Hensen); and the elaborate structure of Corti's organ certainly 
 suggests that some one or other of its elements may be endowed 
 with such a function. Experimentally, too, it has been shown 
 that destruction of the apex of the cochlea causes loss of appreciation 
 of low notes, and destruction of the base loss of appreciation of high 
 notes, which agrees with Helmholtz's view. But while the theory 
 of peripheral analysis of pitch tends upon the whole to be strength- 
 ened as evidence gathers, it is possible that the analysis is accom- 
 plished in some other way than by sympathetic resonance. 
 
 Ewald has developed a theory according to which each note causes 
 the basilar membrane to vibrate throughout its whole extent in such 
 a way that stationary waves are Droduced in it, like the Chladni's 
 figures seen on a metal plate strewed with sand when it is set into 
 vibration. The pattern of the movement, the ' sound-picture,' will be 
 different for each tone, since the interval between the waves will be 
 different. The hair-cells and auditory fibres of particular parts of the 
 organ of Corti will therefore be stimulated by the pressure of the mem- 
 brane, or escape stimulation, according to the position of the stationary 
 waves with reference to them for each note. In this way each sound- 
 picture will be printed, so to speak, upon the sensitive terminal appa- 
 ratus of the auditory nerve, as a letter is printed upon a piece of paper 
 by a type. The corrcsj^onding excitation pattern — i.e., the particular 
 distribution of cochlear fibres stimulated — is supposed to be associated 
 in consciousness \\dth the appreciation of the pitch of the particular 
 note. Ewald has endeavoured to suj)port his theory by showing that 
 fine membranes of the dimensions of the basilar membrane do yield 
 very distinct sound-pictures for different simple tones as well as for 
 complex tones. These can be observed with the microscope and photo- 
 graphed (Fig. 459). 
 
 One of the best-known theories of central analj'sis may be con- 
 veniently labelled the 'telephone theory,' in accordance with the simile 
 used by Rutherford. He supposed that the organ of Corti (or at any 
 rate the hair-cells) is set into vibration as a whole by all audible sounds, 
 and that its vibrations are translated into impulses in the auditory 
 nerve, which are the physiological counter])art of \h^ aerial waves 
 and the waves of increased and diminished pressure in the liquids 
 of the labyrinth to which they give rise. Thus, a sound of 100 
 vibrations a second would start 100 impulses a second in the auditory 
 
SMELL AND TASTE 1075 
 
 nerve; a loud sound would set up impulses more intense than a 
 feeble sound; and a camplox wave, which is the resultant of several 
 sounds of difterent vibration-frequency, would also in some way or 
 other stamp the iin])ress of its /o/m on the auditory excitation wave; 
 just as in a telephone every wave in the air causes a swing of the 
 vibr \ting plate, and thus sets up a current of 
 corresponding intensity and duration in the 
 wires. This theory evidently abandons the 
 doctrine of specilic energy for the particular 
 case of the analysis of pitch, for it assumes 
 that differences of auditory sensation are 
 related to differences in the nature of the im- 
 pulses travelling up the auditory nerve, and 
 not merely to diiferences in the anatomical 
 connections (peripheral and central) of the 
 auditor v nerve-fibres. It is unsatisfactory 
 because it takes no account of the remarkable 
 and suggestive structure of the telephone plate 
 — i.e., of the organ of Corti — and gives no hint 
 of how the analysis is accomplished in the 
 central organ. 
 
 The range of hearing is very great. The 
 highest audible tone corresponds to 30,000 to 
 40,000 vibrations a second, the lowest to about pig. 459.— Photograph of a 
 30. Between these limits as many as 6,000 Sound-Picture (Ewald). 
 variations of pitch can be perceived. 
 
 Wien has elaborately investigated the question how the sensitive- 
 ness of the ear varies for tones of different pitch . A tone of 50 vibrations 
 a second, in order to be just heard, must have an intensity corre- 
 sponding to about 100 million times as much energy as is needed for a 
 tone of 2,000 vibrations. It is only on the extraordinary sensibility 
 of the ear for the range of tones used in ordinary speech that the 
 possibility of understanding speech depends when the circumstances 
 are unfavourable — e.g., at a great distance, or in the presence of much 
 stronger accompanying noises. 
 
 Section III. — Smell and Taste. 
 
 Smell was defined by Kant as ' taste at a distance '; and it is 
 obvious that these two senses not only form a natural group when 
 the quality of the sensations is considered, but are closely associated 
 in their physiological action, especially in connection with the 
 perception of the flavour of the food. Their intimate relation is 
 further indicated by the fact that the cortical areas in which smdl 
 and taste are represented lie close together or overlap each other 
 on the gyrus hippocampi and uncus (p. 968). The olfactory end- 
 organs in the mucous membrane of the upper part of the nostrils, 
 the so-called regio olfactoria, have been already described (p. 921). 
 In cases of anosmia, in which the olfactory nerve is absent or 
 paralyzed, smell is abolished; but substances such as ammonia and 
 acetic acid, which stimulate the ordinary sensory nerves (nasal 
 branch of fifth) of the olfactory mucous membrane, are still per- 
 ceived, though not distinguished from each other. In fact, the 
 so-called pungent odour of these substances is no more a true smell 
 
I076 THE SENSES 
 
 than the sense of smarting they produce when their vapour comes 
 in contact with a sensory surface hke the conjunctiva, or a piece 
 of skin devoid of epidermis. 
 
 It was at one time behevcd tliat odoriferous particles could not 
 be appreciated unless they were borne by the air into the nostrils; 
 but this appears not to be the case, for the smell of substances 
 dissolved in physiological salt solution is distinctly perceived when 
 the nostrils are filled with the liquid; and fish, as every line-fisher- 
 man knows, have no difficult}- in finding a bait in the dark. The 
 odoriferous substances, even when air-borne, are dissolved in the 
 nasal secretion before they can affect the olfactory end-organs, and 
 it may be due to the peculiarities of this solvent that it is so difftcult 
 to imitate a normal stimulation of the olfactory organs by solutions 
 experimentally introduced into the nose (Parker). 
 
 The substances which can affect the olfactory mucous membrane 
 can be divided into four groups : 
 
 1. Those which act only on the olfactory nerves, the odours proper. 
 
 2. Substances which act at the same time on olfactory nerves, and on 
 
 nerves of common sensation (tactile nerves) — e.g., acetic acid. 
 
 3. Substances which act at the same time on the gustatory nerves. 
 
 4. Substances which act only on the nerves of common sen- 
 
 sation (tactile nerves) — e.g., carbon dioxide. 
 Zwaardemaker has classified the pure odours as follows : 
 
 (1) Ethereal odours, as those of fruits; (2) aromatic odours, as of 
 camphor or bitter almonds; (3) fragrant odours, as of flowers; (4) am- 
 brosial odours, as of amber or musk; (5) garlic odours, as of onion, 
 garlic, asafoetida; (6) empyrcumatic, or burning odours, as of burnt 
 coffee or tobacco smoke; (7) caprylic or goat odours, as of sweat; 
 (8) repulsive odours, as the odour of the disease oza?na; (9) nauseating 
 odours, as of faeces or putrefying material. 
 
 The most interesting form of inadequate stimulation is electrical 
 excitation of the olfactory mucous membrane, which causes a sensation 
 like the smell of phosphorus. The sensation is experienced at the 
 kathode on closure and the anode on opening. As to the manner in 
 which the multitiidinous adequate stimuli excite the olfactory nerves, 
 we can only suppose that they act as chemical stimuli. Smell and 
 taste are pre-eminently the ' chemical ' senses, as sight and hearing are 
 pre-eminently ' physical ' senses. But little is known of the relation 
 between the chemical constitution or physical properties of substances 
 and the quality of the odoriferous sensation which they excite, although 
 Haycraft has pointed out some interesting relations between the atomic 
 weights of certain elements and their power of exciting odours. The 
 number of distinct odours which can be perceived is so great that it is 
 scarcely conceivable that each is subserved by special olfactory fibres. 
 Marked changes occur in disease, and all odours need not be affected 
 to the same extent. Some may be almost normally perceived, while 
 relative or complete loss of smell exists as regards others. These and 
 other facts have given rise to the idea that there are several groups of 
 olfactory fibres, each concerned in the appreciation of a particular 
 odour or group of odours. Yet it has not proved possible to reduce them 
 to a limited number of fundamental odours and their combinations. 
 
 Acviteness of smell may be measured by arrangements called olfac- 
 tometers. Zwaardemaker's olfactometer consists of a piece of india- 
 rubber tubing fitted inside a glass tube, through which air is drawn 
 
SMELL AND TASTE 1077 
 
 into the nostrils. Another glass tube just fitting the rubber tube is 
 pushed inside it, so as to cover a portion of it. The minimum amount 
 of surface of the indiarubber tube which must be left exposed so that 
 the smell of the rubber may be perceived is a measure of the acutcness 
 of smell. To investigate other odours tubes of the corresponding 
 odorous substances can be constructed. 
 
 Taste. — The sense of taste is not so strictly localized as the sense 
 of smell. The tip and sides of the tongue, its root, the neighbour- 
 ing portions of the soft palate, and a strip in the centre of the dorsum, 
 are certainly endowed with the sense of taste; but the exact hmits of 
 the sensitive areas have not been defined, and, indeed, vary in 
 different individuals. 
 
 The nerves of taste are the glosso-pharyngeal, which innervates the 
 posterior part of the tongue, and the lingual, which supplies its tip 
 (see p. 925). The end-organs of the gustatory nerves are the taste- 
 buds or taste-bulbs, which stud the fungiform and circumvallate 
 papillae, and are most characteristically seen in the moats surrounding 
 the latter. They are barrel-like bodies, the staves of the barrel being 
 representctl by supporting cells; each bud encloses a number of gusta- 
 tory cells with fine processes at their free ends projecting through the 
 superficial end of the barrel. They are surrounded by the end arboriza- 
 tions of the fibres of the gustatory nerves. Taste-buds are also found 
 on the posterior surface of the epiglottis and in the larynx. It has 
 been suggested that these form the afferent end-organs of a reflex 
 apparatus which guards the glottis against the entrance of food in 
 deglutition (Wilson). Epithelial buds, different from the olfactory 
 elements, also occur in the olfactory region of the nasal mucous mem- 
 brane. It is possible that the so-called nasal taste — e.g., the sweet 
 taste caused by chloroform when aspirated in not too small an amount 
 through the nose — depends upon these buds. 
 
 As to the properties in virtue of which sapid substances are 
 enabled to stimulate the gustatory nerve-endings, we know that 
 they must be soluble in the hquids of the mouth, and there our 
 knowledge ends. An attempt has been made by various authors 
 to connect the taste of such bodies with their chemical composition, 
 but researches of this kind have not hitherto yielded much fruit. 
 The number of distinct qualities of taste sensation is considerable, 
 but by no means so great as the number of qualities of olfactory 
 sensations, and they are more easily reduced to a few primary or 
 fundamental sensations. Sapid substances have generally been 
 divided into four classes as regards the fundamental sensations pro- 
 duced by them — viz.: (i) Sweet, (2) acid, (3) bitter, (4) saHne. 
 All taste sensations seem to be combinations of these, or combina- 
 tions of one or more of them with olfactory sensations, or with sensa- 
 tions due to excitation of the ordinary sensory nerves of the tongue. 
 
 Sweet and acid tastes are best appreciated by the tip, and bitter 
 tastes by the base, of the tongue. Differences have been detected 
 between individual papilhe in their power of reaction to sapid sub- 
 stances which produce one or other of the fundamental sensation*. 
 Of 125 fungiform papillae tested with solutions of tartaric acid, sugar, 
 and quinine, 27 gave no sensation of taste. Tartaric acid evoked 
 
I078 THE SENSES 
 
 its acid tasti- in 91 of the remaining 98, sugar its sweet taste in 79, 
 and (jxiinine its bitter taste in 71 ; 12 reacted only to tartaric acid, 
 and 3 only to sugar (Ohrwall). Such facts indicate, althcmgh they 
 do not definitely prove, the existence of specific receptors for each 
 of the fundamental taste sensations — i.e., gustatory end-organs, 
 which are easily excited by an adequate stimulus (acid, e.g., in the 
 case of an ' acid' taste-bud), with difficulty or not at all by an in- 
 adequate stimulus. 
 
 The form of inadequate stimulation most investigated is that pro- 
 duced when a constant current is passed through the tongue. An acid 
 taste is experienced at the positive, and an alkaUnc or bitter taste at the 
 negative pole; and this is the case even wlicn the current is conducted 
 to and from the tongue by unpolarizable combinations, which prevent the 
 deposition of electrolytic products on the mucous membrane (p. 731). 
 The sensations are due to stimulation of the gustatory end-organs and 
 not of the nerve-trunks. 
 
 Normal lymph, which bathes these end-organs, does not excite any 
 sensation of taste, but when the composition of the blood is altered in 
 di-sease or by the introduction of foreign substances, tastes of various 
 kinds may be perceived. Sometimes this may be due to the stimula- 
 tion of substances excreted in the saliva; but in other cases it seems 
 that, without passing beyond the blood and lymph, foreign substances 
 may excite the gustatorv nerves. 
 
 Flavour embraces a group of mixed sensations in which smell and 
 taste are both concerned, as is shown by the common observation that 
 a person suffering from a cold in the head, which blunts his sense of 
 smell, loses the proper flavour of his food, and that some nauseous 
 medicines do not taste so badly when the nostrils are held. 
 
 In common speech, the two sensations are frequently confounded 
 with each other and with tactile sensations. Thus the ' bouquet ' of 
 wines, which most people imagine to be a sensation of taste, is in 
 reality a sensation of smell; the astringent ' taste ' of tannic acid is not 
 a taste at all, but a tactile sensation ; the ' hot ' taste of mustard is no 
 more a true sensation of taste than the sensation produced by the same 
 substance when applied in the form of a mustard poultice to the skin. 
 
 As already remarked, the substances which affect the olfactory end- 
 organs in air-breathing animals, like those which affect the gustatory 
 end-organs, must eventually go into solution before causing stimulation. 
 The most striking distinction between the two senses is the astonishingly 
 small concentration in which substances can elicit sensations of smell, 
 as compared with sensations of taste. Thus ethyl alcohol is a stimulus 
 for both smell and taste, but it can be recognized by smell in a dilution 
 24,000 times greater than the dilution necessary for taste (Parker). 
 
 Section IV. — Cutaneous and Intern.xl Sensations. 
 Under the sens? of touch it was at one time usual to include a 
 group of sensations which differ in quality — and that in some in- 
 stances to as great an extent as any of the sensations which are 
 universally considered as separate^ and distinct — but agree in this, 
 that the end-organs by which they are perceived are all situated in 
 the skin, the mucous membranes, or the subcutaneous tissue. 
 They are more correctly designated ' cutaneous sensations.' Such 
 are the common tactile sensations — including pressure, tickling, 
 and itching — and the sensations of temperature, or, more correctly, 
 
CUTANEOUS AND INTERNAL SENSATIONS 
 
 to79 
 
 of change of tcnipmature, or of warmth and cold. The sensation 
 of pain, although it cannot be absolutely separated from these, ought 
 not to be grouped along with them. It is called forth by the stimula- 
 tion of afferent nerve-iibres in their course; and it may originate, 
 under certain conditions, in internal organs which are devoid of 
 tactile sensibility, and the functional activity of which in their 
 normal state gives rise to no special sensation at all. The peculiar 
 sensation associated with voluntary muscular effort, to which the 
 name of the muscular sense has been given, also deserves a separate 
 place; for although it may in part depend on tactile sensations set 
 up through the medium of end-organs situated in muscle, tendon, 
 or the structures which enter into the formation 
 of the joints, other elements are, in all proba- 
 bility, involved. 
 
 The simplest form of tactile sensation is that 
 of mere contact, as when the skin is lightly 
 touched with the blunt end of a pencil. This 
 soon deepens into the sensation of pressure 
 the contact is made closer; and eventually the 
 sense of pressure merges into a feeling of pain. 
 Most physiologists agree that in the skin itself 
 four fundamental qualities of sensation are re- 
 presented — 'touch in the restricted sense (the 
 sensation elicited by hght contact), warmth, 
 cold, and pain. Pressure is mainly a sensation 
 connected with the stimulation of structures 
 deeper than the skin — e.g., the sensation of 
 contact is abolished in cicatrices where the 
 true skin has been destroyed, while sensibility 
 to pressure persists — although the sensation of 
 light pressure may be to some extent re- 
 presented in the skin itself in association 
 with touch. In a somewhat diagrammatic 
 sense it may be said that the surface of the skin is divided into a 
 great number of very small areas, each of which is related especially 
 to one or other of the four fundamental sensations. Areas con- 
 cerned in one sensation are everywhere mingled with areas con- 
 cerned in the others. By appropriate methods it has been found 
 possible to determine the existence on the skin of the trunk and 
 limbs of not less than 30,000 ' warm-spots,' which always react to 
 stimulation by a sensation of warmth; 250,000 ' cold-spots,' which 
 react by a sensation of cold; and half a million touch-spots, whose 
 specific reaction is a sensation of touch. It is more difficult to 
 locahze definitely bounded ' pain-spots,' partly because of the very 
 rich supply of pain-fibres to the '^kin. Yet there is reason to beheve 
 that pain, like touch, warmth, and cold, is subserved by separate 
 
 Fig. 460. — Tactile Cor- 
 puscle from Skin of 
 Finger (Smirnow). 
 (Golgi preparation.) 
 The winding and in- 
 tersecting black lines 
 are the non-medul- 
 lated endings of the 
 one or more nerve- 
 fibres that enter the 
 corpuscle. 
 
loSo THE SENSES 
 
 receptors. The simplest assumption wliicli will satislactorilv 
 account for the distribution of the four fundamental cutaneous 
 sensations is that the skin is supplied with four kinds of nerve- 
 fibres, anatomically as well as functionally distinct. Some fibres 
 minister to the sensation of cold, (others to that of waniith. others 
 to that of touch, and others still to pain. And just as stimulation 
 of the optic ner\c gives rise to a sensation of light, so stimulation 
 of any one of the cutaneous n( rves gives rise to the specific sensa- 
 tion proper to the group to which it belongs. The existence of 
 different forms of sensory end-organs in the skin and other tissues 
 (tactile or touch-corpuscles, corpuscles of Pacini, end-bulbs of 
 Krause, etc.) points in the same direction. The end-organs of the 
 touch sensations are believed to be the ring-like arrangements of 
 non-medullated nerve-fibres encircling the hair-follicles, and in 
 parts of the skin devoid of hairs the corpuscles of Meissner (v. Frey) 
 
 Touch-spots can easily be demonstrated by touching the skin lightly 
 with some small object such as a hair. The most exact quantitative 
 observations have been made by means of v. Frey's hair aesthesiometer. 
 This consists of a handle in which hairs of different diameter can be 
 fixed. The area of the cross section of each hair is measured under the 
 microscope, and the pressure necessary to bend it is determined by 
 pressing it upon the scale-pan of a balance. The pressure in milli- 
 grammes, divided by the cross section in square millimeters, gives the 
 pressure per square millimetre, which, according to v. Frey, permits 
 hairs to be chosen so as to give a uniform intensity of stimulation or 
 a variable intensity, according to the object of the investigation. Many 
 observers, however, believe that it is more accurate to take no account 
 of the pressure per unit of area, but to graduate the hairs according to 
 the total pressure needed to bend them. When touch-spots ascer- 
 tained in this way are excited, by an inadequate stimulus — e.g., an 
 alternating current of minimal strength, applied by the unipolar 
 method through the head of a pin as an electrode — they still respond 
 by their characteristic or specific reaction — namely, a sensation of 
 touch — in the case supposed, a vibrating sensation like that caused by 
 a tuning-fork in contact with the skin. In the spaces between the 
 touch-spots the sensation produced by the same strength of current, or 
 even by a weaker current, is not one of touch, but a painful pricking 
 sensation which has no vibratory character, but is permanent as long 
 as the current lasts. 
 
 The spots most sensitive to touch lie close to the hairs on their 
 ' windward ' side — i.e., on the side awav from which they slope. The 
 minimum pressure necessary to evoke a sensation of contact is not the 
 same for every portion of the skin. The forehead and palm of the 
 hand are most sensitive. According to Lombard the cutaneous pres- 
 sure and tickle sensations called out by delicate mechanical stimuli 
 (hairs, etc.), do not arise from the same spots. 
 
 If two points of the skin are touched at the same time there is a 
 double sensation when the distance between the points exceeds a cer- 
 tain minimum, which varies for different parts of the sensitive surface. 
 
 Practice increases the acuity of touch for the two points test. Even 
 in a few hours it mav be temporarilv quadrupled on some parts of the 
 skin. Since at the same time it is increased m the corresponding part 
 of the opposite side of the body, it is argued that the modification takes 
 place in the central nervous system, not in the end-organs themselves. 
 
CUTANEOUS AND INTERNAL SENSATIONS 
 
 •1081 
 
 Few of the internal organs are supplied with tactile nerves. The 
 mucous membrane of the alimentary- canal from the upper end of the 
 oesophagus to the junction of the rectum with the anal canal is in- 
 sensitive to tactile stimulation (Hertz). The movements of a tape- 
 worm in the intestines are not recognized as tactile sensations, nor the 
 movements of the alimentary canal during digestion, nor the rubbing 
 of one muscle on another during its contraction. 
 
 
 Number of Touch- 
 Spots per Sq. Cm. 
 
 Mean Threshold Value 
 . Grammes 
 
 in 7; r; 
 
 bq. Mm. 
 
 Wrist (ventral surface) 
 Wrist (dorsal surface) ... 
 Forearm . - . - - 
 Elbow ------ 
 
 Upper arm - - - - - 
 
 Foot (dorsal surface) - - - 
 Leg (ventral surface) - 
 Thigh (ventral surface) 
 Breast- . - - . - 
 Back 
 
 28 
 28 
 16 
 12 
 10 
 23 
 5 
 14 
 21 
 26 
 
 I«I 
 
 I'2 
 1*2 
 
 1-3 
 1*4 
 
 I'2 
 2'I 
 
 1-3 
 
 2-7 
 
 4-3 
 
 (Ktesow). 
 
 Pressure is only perceived when it affects two neighbouring areas to 
 a different degree. Thus, the atmospheric pressure, bearing uniformly 
 on the whole surface of the body, causes no scrsation; we are so entirely 
 unconscious of it that it needed the inspiration of genius to discover 
 it, and the persistence of genius to force the discovery on the world. 
 When the finger is dipped in a trough of mercury at its own temperature, 
 no sensation is perceived except a feeling of constriction at the surface 
 of the liquid. The perception of light pressure and of the form and size 
 of objects in contact with the skin is believed to be due to the touch- 
 spots. Deep pressure, however, is appreciated, not by the skin, but 
 through sensory end-organs in deeper structures — probably, e.g., 
 Pacini's corpuscles and the muscle-spindles (Fig. 471, p. 1096). 
 
 
 Distance at which Two Points 
 
 
 can be distinctly felt, in Mm. 
 
 Point of tongue - 
 
 I "I 
 
 Palmar surface of third 
 
 
 phalanx of finger 
 
 2-2 
 
 Dorsal surface of third 
 
 
 phalanx of finger 
 
 6-7 
 
 Tip of nose - - - 
 
 6-7 
 
 Back - - - - 
 
 II-2 
 
 Eyelids - - _ 
 
 II-2 
 
 Skin over sacrum 
 
 40-5 
 
 Upper arm - - - 
 
 67-6 
 
 Sensations of Warmth and Cold. — When a body colder or hotter 
 than the skin is placed on it, or when heat is in any other way 
 
1082 
 
 THE SENSES 
 
 withdrawn from or imparted to the cutaneous tissues with sufficit-nl 
 abrujitnoss, a sensation of cold or warmth is experienced. And 
 when two portions of the skin at different temperatures are put in 
 contact, we feel that, relatively to one another, one is warm and 
 the other cold. But it is worthy of remark that it is only difference 
 
 of temperature (or, perhaps, rather the 
 rate at which heat is being gained or 
 lost by the skin), and not absolute 
 height, which we are able to estimate 
 by our sensations. Thus, a hand which 
 has been working in ice-cold water will 
 feel water at io° C. as warm ; whereas it 
 would appear cold to a warm hand. 
 
 Blix, Goldscheider, and others have 
 shown that the whole skin is not en- 
 dowed with the capacity of distin- 
 guishing temperature, but that the 
 temperature sensations are confined 
 to minute areas scattered over the 
 cutaneous surface. The great majority 
 of these are ' cold ' spots — i.e., respond 
 to stimulation only by a sensation of 
 cold — while a smaller number are 
 * warm ' spots, and respond only by a 
 sensation of warmth (Fig. 461). These 
 spots can be mapped out by bringing 
 into contact with the skin small pieces 
 of wire at a temperature a few degrees 
 above or below that of the skin. With 
 such mild stimuli a response can 
 generally be obtained only from one 
 kind of spot — that is, the cold wire 
 stimulates only the cold and not the 
 warm spots, and vice versa-— hut with 
 much more intense thermal stimuli — 
 say, temperatures of 45° to 50° C. — 
 not only do the warm spots respond 
 with the appropriate sensation, but 
 the cold spots respond with a sensation 
 of cold. This is well seen when a 
 beam of sunlight is focussed succes- 
 sively on a warm and a cold spot. Inadequate stimuli (mechanical 
 and electrical) also evoke the specific response of warmth from 
 warm spots, and of cold from cold spots. 
 
 When the hand is put into water at the temperature of the skin, 
 and the water slowly heated, the warm spots are at first alone stimu- 
 
 Fig. 461. — 'Warm' and 'Cold' 
 Areas on Skin (Goldscheider). 
 The areas are mapped out on 
 the palm of the left hand. In 
 the upper figure the relative 
 sensitiveness to warmth is 
 represented by the depth of the 
 shading, the black areas being 
 most sensitive, then the lined 
 areas, then the dotted, and 
 last of all the white areas. In 
 the lower figure the relative 
 sensitiveness to cold stimuli is 
 shown in the same way. 
 
CUTANEOUS A\D INTERNAL SENSATIONS 1083 
 
 lated, and the sensations of lukewarm and then of warm are experi- 
 enced. When the temperature of the water reaches 45° C., the 
 quahty of t he sensation changes to ' hot . ' At a still higher tempera- 
 ture the sensation becomes painful or burning. The most probable 
 explanation of these facts is mentioned below (p. 1084). 
 
 It is not only of physiological interest, but of practical importance, 
 that most mucous membranes are in comparison with the skin but 
 slightly sensitive to changes of temperature. Only towards the ends 
 of the alimentary canal, in the mouth, pharynx, oesophagus, and anal 
 canal, is it possible to elicit warmth or cold sensations. There is some 
 difference of opinion whether a blunted sensibility appears in the 
 stomach also. The uterus, too, is quite insensible to moderate heat; 
 and hot liquids may be injected into its cavity at a temperature higher 
 than that which can be borne by the hand, without causing inconveni- 
 ence — a fact which finds its application in the practice of g^-naecologv 
 and obstetrics. It is. indeed, obvious that in the greater number of 
 the internal organs the conditions necessary for stimulation of tem- 
 perature nerves, even if such were present, could hardly ever exist. 
 
 It has already been mentioned that changes of external temperature 
 exert a remarkable influence on the intensity- of metabolism (p. 693), 
 and it has been supposed that this is brought about by afferent impulses 
 travelling up the cutaneous nerves. We have also seen that for certain 
 kinds of stimuli the excitability of nerve-fibres is increased by cooling 
 (p. 784). It is possible that this is the case for the fibres in the skin 
 which are concerned in the regulation of the production of heat, and it 
 has been suggested that this fact may have a bearing on the reflex 
 regulation of temperature (Lorrain Smith) . 
 
 Pain Sensations. — \\'hile the cold and the warmth spots are irregu- 
 larly distributed over the skin in more or less compact groups, and 
 the touch sensations are intimately associated wath the hair follicles, 
 the pain spots are more uniformly spread, and at the same time set 
 closer together. In parts of the body where but one of these 
 elementary forms of general sensibility is present, as in the central 
 parts of the cornea and in the dentine and pulp of the teeth, it is 
 always pain. 
 
 In certain situations pain and temperature sensibihty are found 
 together, but not touch — e.g., at the margin of the cornea and on 
 the conjunctiva. 
 
 In general, the skin is far more sensitive to pain than the deeper 
 structures. The most painful part of an operation is generally the 
 stitching of the wound. The cutting of healthy muscle causes no 
 pain. In an operation in which an artificial connection was estab- 
 lished between the stomach and the small intestine (gastro-enter- 
 ostomy), and in which no anaesthetic was administered, the only 
 pain of which the patient complained was produced by the incision 
 in the skin (Senn). This, however, does not prove that the 
 abdominal viscera are devoid of pain nerves, for it has been showTi 
 in animals that exposure of the intestines, etc., as in laparotomv, 
 leads to a rapid depression (exhaustion ?) of the sensibility for pain 
 
io84 THE SENSES 
 
 (Kast and Mdtzei). In the intact animal and human being painful 
 impressions can unquestioneibly be excited in tlie viscera by adequate 
 stinmli (p. 9<Ji). Thus, the spasmodic contraction of tlie intestines 
 and stomach causes the intense pain of cohc and gastralgia. Labour 
 is an example of a strictly physiological function which is the 
 occasion of severe pain. It would appear from the observations 
 of Hertz that the only immediate cause of true visceral pain, as 
 distinguished from referred pain (p. 891) is distension acting on the 
 muscular coat of hollow organs and on the fibrous capsule of solid 
 organs. The sensation of pain in the alimentary canal is due to a 
 more rapid or a greater distension than that which constitutes the 
 adequate stimulus for the sensation of fulness. Visceral sensi- 
 bility seems to be exaggerated in such conditions as hypochondri- 
 asis, neurasthenia, and anaemia. Tissues normally insensible, or, 
 rather, but slightly sensible, to pain may become acutely painful 
 when inflamed. 
 
 The question has been raised whether the sensation of pain can 
 be caused by excessive stimulation of the nerves of common tactile 
 sensibility, or of the nerves that subserve the sensations of coolness 
 and warmth. It is true that when the skin is lightly touched in 
 the region of a touch-spot with a small object at its own temperature 
 the sensation is one of pure touch. As the pressure is increased, a 
 sensation of pressure, quite distinct from that of contact, may be 
 felt ; and if the pressure is stiU further increased, a sensation of pain 
 may be elicited. It seems to be quite clearly made out that the 
 pressure sensation in this case is due not to excessive stimulation 
 of the touch-nerves, but to stimulation of the specific pressure- 
 nerves when the threshold is reached. The most natural explana- 
 tion of the pain sensation is that it, too, is due to excitation of the 
 nervous apparatus for pain. Similarly (as was stated on p. 1082), 
 if the skin is raised to higher and higher temperatures, the response 
 is at first a pure sensation of warmth, increasing in intensity without 
 changing its quality. When a certain temperature (about 45° C) 
 is exceeded, the sensation changes to ' hot,' either because a pain 
 element is now added to the pure thermal sensation, or because the 
 cold spots are now stimulated as well as the warm spots, and mingle 
 their specific response (cold sensation) with that of the warm spots. 
 Further increase of the temperature will cause distinct pain, the 
 sensation assuming a burning character. When a cold spot is 
 tested with decreasing temperatures, an analogous series of sensa- 
 tions is run through, the pure sensation of coolness eventually giving 
 place to cold, intense cold, and finally pain. Here, also, it is simplest 
 to assume that the pain sensation is caused not by excessive stimu- 
 lation of warm or cold spots, but by excitation of the specific pain- 
 spots. In any case, there is no doubt that afferent ' pain ' fibres 
 exist which are anatomically distinct from the fibres of tactile and 
 
CUTANEOUS AND INTERNAL SENSATIONS 1085 
 
 of temperature sensations. For the conducting paths in the spinal 
 cord are not the same for tactile and for painful impression*;. And 
 in certain cases of disease sensibility to pain may be lost, while 
 tactile sensations are still perceived ; or, on the other hand, pain may 
 be felt in cases where tactile sensibility is abolished. Loss of tem- 
 perature sensation, however, is usually accompanied by loss of 
 sensibility to pain. When a nerve is compressed, the sensibility 
 of the tract supplied by it disappears for cold sooner than for 
 warmth. 
 
 Pain has been defined as ' the prayer of a nerve for pure blood.' The 
 idea is not only true as poetry, but, with certain deductions and limita- 
 tions, true as physiology; that is to say, pain, as a rule, is a sign 
 that something has gone wrong with the bodily machinery; freedom 
 from pain is the normal state of the healthy body. Physiologically, 
 pain acts as a danger-signal. It points out the seat of the mischief, 
 and even, in certain cases, by compelling rest, favours the process of 
 repair. Thus, the surgeon has sometimes looked upon pain as ' Nature's 
 splint.' But, as a matter of fact, a certain amount of pain occurring 
 at intervals is not incompatible with high health; and probably nobody, 
 even when accidents and indiscretions of all kinds are avoided, is en- 
 tirely free from pain for any considerable time. Sometimes, indeed, 
 the mere fixing of the attention on a particular part of the body is 
 suJB&cient to bring out or to detect a slight sensation of pain in it; and 
 it is matter of common experience that a dull continuous pain, like that 
 of some forms of toothache, is aggravated by thinking of it, and relieved 
 when the attention is diverted. 
 
 As to the sensations of tickling and itching, it is enough to say 
 that physiologists are not agreed whether they represent specific 
 sensibilities subserved by special nerves distinct from those of touch 
 and pain, or merely modifications or mixtures of these sensations. 
 
 Phenomena observed after Section of Cutaneous Nerves. — ^The 
 innervation of the skin can be explored not only by appropriate 
 stimulation of the normal skin, but by study of the defects or altera- 
 tions of sensibility which follow section of a cutaneous nerve, and 
 which may be observed at different stages in its regeneration. In 
 recent years this has proved a fruitful method, especially in experi- 
 ments made by skilled observers in whom one or more cutaneous 
 nerves were intentionally divided. 
 
 An extensive investigation was made by Trotter and Davies. 
 They divided at different times, extending over more than a 
 year, no fewer than seven of their own <;utaneous nerves, in- 
 cluding the internal saphenous at the knee, the great auricular, 
 three divisions or branches of the internal cutaneous of the arm 
 just below the elbow, and a branch of the middle cutaneous of 
 the thigh. The operations were purposely done at such intervals 
 as would allow the experience gained in investigating one area 
 to be applied to others. About a quarter of an inch was cut out 
 of each nerve, and the ends then sutured together. ' In each 
 
io86 
 
 THE SENSES 
 
 case the area of skin supplied by the nerve showed defcc^ts in seven 
 distinct functions: four sensory — namely, sensibihty to touch, cold, 
 heat, pain — and three motor — namely, vaso-motor, pilo-motor, 
 sudo-motor (sweat -secretory). The sensory changes showed a 
 central area of profound loss, an area of moderate extent surrounding 
 
 
 Stpokinc oi/nim 
 
 Fig. 46i:. — .\reas of Altered Sensibility produced by Section of all Three Branches 
 of the Internal Cutaneous Nerve of the Left Forearm (Trotter and Davies). 
 (Reduced by Two-thirds.) The thick lines show the areas of anaesthesia to the 
 brush. The thick continuous lines enclose the areas of the anterior and posterior 
 branches. The thick broken line and heavy shading mark the area of the in- 
 crease in anffisthesia which followed section of the middle branch. The thin 
 lines show the areas of minimal hypoa;sthesia — i.e., the ' stroking outline.' The 
 complete oval outline is the ' stroking outline ' which followed section of the pos- 
 terior branch. The large addition to the oval on the right of the diagram shows the 
 increase in the ' stroking outline ' which followed section of the anterior branch. 
 The thin broken line and fine shading show the additions to the ' stroking out- 
 line ' produced by division of the middle branch. 
 
 this of partial loss, and a large area in which a qualitative change 
 could be alone detected.' The maximal extent of change, and 
 therefore the outer boundary of this third area, can be mapped out 
 by getting the subject to determine by light, stroking touches the 
 area which feels in any way unnatural when he touches it himself. 
 The most common feeling is that the skin has become smoother at 
 
CUTANEOUS AND INTERNAL SENSATIONS 
 
 IO&7 
 
 llu! bijundary as the stroking linger crosses it, coming from the 
 normal skin. This area is always much larger than the area in- 
 cluded in it, in which by quantitative methods — e.g., the use of a 
 very fine camel's-hair brush, or more exactly by the v. Frey hairs — 
 the sensibility to touch can be shf)wn to be diminished (region of 
 hypotcsthesia to touch) (Fig. 4^-)- 
 
 For a variable distance within the ' stroking outline ' the hypo- 
 
 
 Fig. 463. — Middle Cutaneous: Left Thigh (Trotter and Uavies) (reduced by One- 
 third Linear). Twenty-six days after section. Results of examination with 
 V. Frey hairs. Touch spots marked • responded to hair of 280 milligrammes' 
 pressure; those marked o to hair of 800 milligrammes; and those marked + to 
 liair of 2,280 milligrammes. The continuous line marks the limit within which 
 there was anaesthesia to the camel's-hair brusli. 
 
 aesthesia for tactile stimuli is so slight that it cannot be detected 
 with the brush or udth cotton-wool, or even with the v. Frey hairs. 
 Like those of normal skin, 90 per cent, of its hair-bulbs respond to 
 a hair exerting a pressure of 70 milligrammes, and the remaining 
 10 per cent, to hairs exerting a pressure of 140 or 280 milligrammes. 
 Inside this zone of minimal hypoaesthesia the defect of sensibility 
 
io88 
 
 THE SENSES 
 
 rapidly increases as we pass inwards, each line of hair bulbs re- 
 quiring a heavier pressure than the lin«' external to it, till at 
 last 3I or 4 grammes' pressure is needed to cause a sensation of 
 touch, and inside of this line of hairs the skin does not respond 
 at all (Fig. 463). 
 
 For thermal sensibility there is also a region of complete anaes- 
 thesia and a region of partial anaesthesia. The best way of out- 
 
 *. • • * • J • •*• • • 
 
 •• » . • • • •• •«• 
 
 • •••••••• 
 
 Fig. 464.— Middle Cutaneous: Left Thigh (Trotter and Davies). Twenty-one da>'S 
 after section. Results of examination with temperature of o" C. On spots 
 marked • stimulus was felt as cold; on spots marked o it was felt as cool. The 
 blank area is that of thermal anaesthesia. The continuous outline marks the 
 limit within which there was anaesthesia to the camel's-hair brush. 
 
 lining these is the use of a temperature of 0° C. as the stimulus 
 (Fig. 464). 
 
 Outside the zone of complete thermal anaesthesia there is a region 
 in which temperature sensations are distinctly elicited, but do not 
 possess the normal intensity, the temperature of 0° C, for example, 
 being felt only as cool, and not as cold. The outer limit of this 
 region is the line at which the temperature of 0° C. is first felt as 
 
CUTANEOUS AND INTERNAL SENSATIONS 
 
 1089 
 
 we work inwards from the normal skin to yield the sensation of 
 cool instead of cold. Similarly, the outer limit of thcrmo-hypo- 
 aesthesia can be determined by using a high temperature (50° C ). 
 It is the line at which the sensation of hot yielded by the normal 
 skin gives place to the sensation of warm. The two boundaries 
 correspond closely when allowance is made for the separate grouping 
 of cold and warmth spots on the normal skin. 
 
 •V 
 
 Fig. 465. — Middle Cutaneous (External Branch): Left Thigh (Trotter and Davies). 
 Twenty-three da\-s after section. Results of examination with algometer (an 
 arrangement by which a needle is pressed against the skin by a hair whose 
 pressure value has been determined). Spots marked • reacted by sensation of 
 pain to pressure of i,86o milligrammes (normal threshold); spots marked o re- 
 quired 2,280 milligrammes. The continuous line marks the area within which 
 there was anaesthesia to the camel's-hair brush. 
 
 The investigation of the sensibility of the skin areas for painful 
 stimuli is complicated by the fact that during a certain period; 
 from about the second to the sixth week after division of the nerve, 
 hyperalgesia (increased sensitiveness to painfuJ impressions) may 
 appear. This, however, does not seem to be a consequence of any 
 sensory loss, but rather a complication due to an irritative change. 
 When this is taken account of, it is found that the defect of sensi- 
 bility to pain after nerve section resembles the defects of sensi- 
 
 69 
 
lo^d THE SENSES 
 
 bility to touch and temperature, showing a central area of absolute 
 anaesthesia surrounded by a zone of ])artial loss, which is slight 
 towards the outer boundary, but increases as we pass inwards 
 (Fig. 4^)5)- 
 
 After section of a nerve function is recovered only as a result of 
 regeneration. This is true of all the sensory functions of the skin 
 and of the pilo-motor and sudo-motor functions. Vaso-motor tone 
 in the affected area is restored much sooner than the other functions. 
 This rapid recovery probably depends upon a local compensatory 
 mechanism, and not upon regeneration of the vaso-motor fibres. 
 Recovery of all the functions dependent upon regeneration begins 
 about the same time, and this recovery progresses over the area at 
 about the same rate for all, although the rate at which they progress 
 towards normal acuitj^ is different. 
 
 Sensibility to touch probably appears a little earlier than sensi- 
 bility to cold and pain. Yet the recovery of touch does not progress 
 so fast, and for awhile a given zone of the recovering area remains 
 hypoaesthetic (less sensitive than normal) to touch, while to cold 
 and pain it soon becomes even hypersensitive. The most remark- 
 able peculiarities of a recovering area are : (i) This qualitative 
 change, in virtue of which cold, pain, and the pain element of heat 
 are intensified, while touch is little altered, although more difficult 
 to elicit ; (2) the reference of sensations, not to the point stimulated, 
 but to distant parts of the area. 
 
 'When a spot which has developed this peripheral reference is 
 touched, one of two possibilities may occur: either the touch is 
 felt locally, and is referred as well, or nothing is felt locally, and 
 the touch is felt in the area of peripheral reference. The region 
 in which the referred touch is felt is always at the edge of the most 
 peripheral part of the anaesthesia,' perhaps more than a foot awaj' 
 from the spot actually touched. The peripheral reference of cold 
 is even more striking, particularly in the remarkable intensity of 
 the referred sensation. 
 
 Peripheral reference occurs also with pain. ' The referred pain 
 shows three well-marked qualities: it is, proportionately to the 
 stimulus, very intense ; it does not reproduce a normal sensation 
 with the exactitude found in the case of touch or cold, but has a 
 special quality of strangeness and unpleasantness, such as no pin- 
 prick on normal skin can give; finally, it produces an almost irre- 
 sistible desire on the part of the subject to rub or scratch the region 
 in which it is felt.' As recovery proceeds the local sensory response 
 becomes more distinct, and the abnormal quality of both local and 
 referred sensations fades. But ' while peripheral reference is the 
 earliest phenomenon of recovery, it persists until recovery is so far 
 advanced that hypoaesthesia is scarcely detectable by any quanti- 
 tative methods.' 
 
CUTANEOUS A\D INTERNAL SENSATIONS 1091 
 
 The work of Heatl, who was the pioneer in this method of investiga- 
 tion, must also be mentioned. He found that when tlie median nerve 
 was divided in his own arm, recovery of sensation began with the 
 restoration of scnsibihty to pain and to extreme degrees of heat and 
 cold; but the hand stiUremained for a time as insensitive as before to 
 such stimuH as sUght toucli. In the parts which had regained their 
 sensibiUty to severe stimuh, hke pricking and extremes of heat and cold, 
 the sensation radiated widely, was referred to remote parts, and could not 
 be accurately localized. This form of sensibility I lead calls protohathic. 
 As the nerve recovered further, a second form of sensibility appeared, 
 associated with accurate localization of cutaneous stimuli and dis- 
 crimination of two compass pcjints. Light touch and moderate degrees 
 of heat and cold could now be again ap])rcciatcd. This form of sensi- 
 bilit\- he terms epicrHic. \ third form of sensibility {deep sensibility) 
 was investigated after complete division of the radial and external 
 cutaneous nerves at the elbow. The radial half of the arm and back 
 of the hand became totally insensitive to cutaneous stimuli, but re- 
 tained their sensibility to pressure or to any stimulus which deformed 
 the subcutaneous structures, as well as their power of localization of 
 such stimuli. The afferent fibres upon which this deep sensibility 
 depends must run with the motor nerves. According to Head, the 
 other two forms of sensibility (protopathic and epicritic) also depend 
 on two separate systems of nerves, of which the protopathic is the older 
 in the phvlogenetic sense, and has a wider distribution. It is assumed 
 that the protopathic fibres regenerate more easily and speedily than the 
 epicritic or than the motor nerves of voluntary muscle. The proto- 
 pathic fibres are supposed by Head to exert a trophic influence. A 
 part deprived of its nerve-supply is liable to injuries, and the sores so 
 produced heal slowly. But as soon as ' protopathic ' sensibility returns 
 to the part, they heal rapidly, even in the absence of all epicritic sensa- 
 tion. The intestine is described as possessing 'protopathic,' but not 
 ' epicritic,' sensibility — i.e., it reacts to extremes of heat and cold, but 
 not to moderate heat and cold or light touch. 
 
 Quite recently an elaborate study of the loss and return of the 
 skin sensations alter section of a cutaneous nerve has been made by 
 Boring. His work is distinguished from that of all previous ob- 
 servers by the fact that he brought to his task the training of a 
 professional psychologist, and that he studied in detail for fifteen 
 months the area of skin with whose innervation he intended to 
 interfere. Section of the nerve chosen (the anterior branch of the 
 internal cutaneous nerve in the forearm) caused amesthesia and 
 hypoKsthesia of a relatively small area of skin (on the volar aspect 
 of the forearm near the wrist), so that it was possible to make an 
 intensive study of it, and the observations were continued for more 
 than 1,000 days after the operation. Points on the affected area 
 were identified by reference to a series of points tattooed on the 
 skin represented by crosses in Fig. 466. 
 
 The sensations studied, in addition to those of warmth and cold, 
 were the four qualities which appear upon mechanical stimulation 
 of the skin: Contact, cutaneous pressure, subcutaneous or deep 
 pressure and pain. Boring uses the terms ' tickle-contact,' ' pene- 
 trating pressure,' ' dull pressure,' and ' sharpness ' for these quali- 
 
togl 
 
 THE SENSES 
 
 ties. Th(^ localization of the sensations and the power of discrimi- 
 nating iwo points were also investigated. 
 
 Tiie general tendency during recovery was from anaesthesia or 
 h\ pcoicsthesia through decreasing degrees of hypoiesthesia to normal. 
 \\'armth and cold, however, passed from hypoiesthesia through a 
 stage of h\T)ercesthcsia on their way to normal. Pain, pressure, and 
 cold approached nonnality at about the same rate, but in compari- 
 son with these the return of warmth sensation was much delayed 
 
 Fig. 466.— Volar Aspect of Left Forearm, showing Affected Region in Outline. 
 The larger area was that marked off by the subject with the camel's hair 
 brush as insensiti%-e. The inclosed smaller area is that which was marked ofi 
 when the e.xpcrimenter manipulated the brush, and the subject with closed 
 eyes reported when he felt anything at all. This smaller area was taken as 
 the region of greatest change in sensitivity, and the experiments on localization 
 and the discrimination of two points were mainly made within this area. The 
 dotted Une shows the approximate course of the nerve, divided at S. The 
 horizontal and vertical lines dividing the area into small squares were impressed 
 by a rubber stamp on the skin, to facilitate identification of points. The 
 position of each point stimulated was fixed with reference to these rectilinear 
 co-ordinates, the tattooed point represented by the Maltese cross behig taken 
 as the origin, and the distances in mm. measured in the central (C), peri- 
 pheral (P), radial (R), and ulnar (U) directions (Boring). 
 
 For all four the distribution of sensitivity over the skin was irregular 
 and patchy, and no definite boundaries could be drawn. In general, 
 however, immediately after division of the nerve the central zone 
 of the affected area was practi ally anaesthetic as regards cutaneous 
 sensation. This was surrounded by a zone of decreased sensiti\ity. 
 In the return of sensibihty the outer zone preceded the inner. 
 No new modes or quahties of sensation were observed at any time, 
 although ' a number of unusual sensory complexes, which might be 
 described by an untrained observer as new sensations, were noted. 
 
CUTANEOUS AND INTERNAL SENSATIONS 1003 
 
 . , . The most striking single experience was the intense algesic cold, 
 whicli occurred when the skin was hyperasthetic to cold.' Deep 
 sensibility to pressure and pain was not altered. Localization 
 of pressures (of 20 gm.) and discrimination of two pressures (two- 
 point chscrimination) remained unaffected. 
 
 This stuJy on the vshole confirms that of Trotter and Davies. How- 
 ever, the larger outer or third area defined by the so-called ' stroking 
 outline ' of Trotter and Davies is probably not an area of sensory 
 abnormality at all, but merely an area in which a physical change in 
 the skin, due, e.g., to some interference with the action of the sweat 
 glands, IS appreciated by the stroking finger. This follows from the 
 fact that it can be mapped out approximately by an observer who 
 strokes it with his own finger without asking the subject to report his 
 sensations. The results of Boring's investigation are quite opposed to 
 the most essential of Head's conclusions. No evidence was found in 
 favour of Head's distinction between epicritic and protopathic sensi- 
 bility, and weighty evidence against it. There does not seem to be 
 any real necessity in the observed facts for introducing so revolutionary 
 a conception of the nervous system. Nor is it possible to uphold the 
 distinction in any thoroughgoing fashion for all structures. For in- 
 stance, in abdominal operations performed under local anaesthesia it 
 has been seen that the parietal peritoneum is quite insensitive to touch, 
 pressure, and temperature stimuli, including extreme temperatures 
 (Ramstrom), while pain is caused ,by traction on it. Its sensibility 
 is therefore neither purely epicritic nor purely protopathic in Head's 
 sense. In like manner the mucous membrane of the mouth, in which 
 sensibility only to touch and temperature is present, conforms entirely 
 to neither type. Its sensibility is not alone epicritic, since it responds 
 to extreme temperatures, nor is it purely protopathic, since a pin-prick 
 prodiices no painful sensation. These terms and the theory associated 
 with them should be dropped. 
 
 Localization of Cutaneous Sensations. — We not only perceive the 
 quality and estimate the intensity of sensations of touch, warmth, cold 
 pain, etc., but are able, more or less accurately, to localize the part of 
 the body from which the sensory impressions come. In other words, 
 two impressions from different parts of the tx)dy, although identical 
 in quality and intensity, are nevertheless stamped with a distinctive 
 something, which may be called the local sign. This power of localiza- 
 tion is not equal for all portions of the body nor for all kinds of sensa- 
 tions. It is best developed for touch (in the restricted sense), and all 
 the varieties of common sensation are better localized on the skin than 
 in any of the deeper structures. The precise mechanism of the localiza- 
 tion IS unknown. But we must suppose that each peripheral area is 
 ' represented ' in the brain, so that the arrival of afferent impulses from 
 it affects particularly the related cerebral area. The brain, therefore, 
 so to speak, associates excitation of a given cerebral area with stimula- 
 tion of the corresponding peripheral area, and thus not only recognizes 
 the quality and quantity of the resultant sensation, but also localizes 
 it; just as a waiter who watches the bell-indicator not only learns how 
 a bell has been rung, whether once or twice, peremptorilv or languidly, 
 but also in which room it has been rung. If, to pursue the illustration 
 a little farther, he is aware that two rooms are connected with one 
 bell, but that one of the rooms is scarcely ever occupied, he associates 
 the ringing of the bell with a summons from the other room even when 
 it happens to be rung from the usually vacant room. In like manner 
 
1094 
 
 THE SENSES 
 
 the brain seems to connect the arrival of sensory impulses from the 
 internal organs, which have few sensory fibres, and tliese perhaps not 
 often stimulated, with excitation in a related cutaneous region, from 
 which it is constantly receiving sensory impressions. The fact already 
 mentioned (p. 802), that in disease of internal organs the pain is re- 
 terrcd to some portion ot the skin, mav be thus explained. 
 
 An attempt has been made to explain certain illusions of touch 
 on the theory that just as an object is recognized as single by the eye 
 when its images fall on corresponding points of the two retina? (p. 1037). 
 so an object is recognized as single by tl,e fingers when it comes into 
 contact witii corresponding points or rather areas of the skin. These 
 are the areas which experience has taught us are in contact with an 
 object when it is held in the natural way. When now a single object is 
 made, by placing the fingers in an unnatural position, to touch areas 
 which could ordinarily be touched at the same time only by two or 
 by three objects, we experience the sensation of contact with two or with 
 three objects. 
 
 Fig. 467. — Illusion of Touch of 
 Aristotle. A small oljject placed 
 between the index and middle 
 fingers, crossed as shown, is felt 
 as two objects (Wassenaar). 
 
 
 y 
 
 ..->. /■ 
 
 A 
 
 
 
 Fig. 468. — An Object placed in contact with 
 the Index, Middle and Ring Fingers, 
 crossed as shown, is fdt as three objects 
 (Wassenaar). 
 
 It is through the localization of touch sensations that the size and 
 form of objects in contact with the skin are percoi\ed in the absence 
 of other tlian the cutaneous sensations, and especially in the absence 
 of visual and muscular sensations (stcreognosis). 
 
 Muscular Sensations (Muscular Sense), etc. — Sometimes, although 
 rather loosely, grouped together as muscular sensations, arc a number 
 of forms of .sensation of which our knowledge is much less accurate 
 than it is in the case of the fundamental skin sensations. Among 
 these may be mentioned especially (i) the sensations by which the 
 position in space of the body as a whole or of particular parts is recog- 
 nized in the absence of visual sensations; (j) the sensations associated 
 with movements, passive as well as active: (3) the sensations associated 
 
CUTAXEOUS AXD IXTERXAL SEXSATIOS'S 
 
 1093 
 
 with resistance to movement. In none of these groups are we dcahng 
 with purely muscular sensations; cutaneous tactile sensations and 
 pressure sensations elicited from other structures than muscles are 
 also involved. 
 
 Voluntary muscular movements arc accompanied with a peculiar 
 sensatioii of ettort, graduated according to the strength of the con- 
 traction, and affording data from which a judgment as to its amount 
 and direction may be formed. 
 
 It has been shown, however, that when pressure sensations are elimi- 
 nated or reduced to a minimum by enclosing the arm, held horizontally, 
 in a rigid apparatus suc'a as that shown in Fig. ^dq, the moments of 
 rotation of a weight* fastened at ditferent distances from the shoulder 
 can be discriminated with great exactness. The sensation of effort is 
 therefore an independent sensation (v. Frey). 
 
 ^^f'^ 
 
 'J'"L\^.^x W " 
 
 Fig. 469.— Apparatus for Arm for Testing Muscle Sense. At the right is shown a lead 
 weight which can be placed on either of the hoops of the apparatus (v. Frey). 
 
 Some writers have supposed that this so-called muscular sense does 
 not depend upon afferent impulses at all, but that the nervous centres 
 from which the voluntary impulses depart take cognizance, retain a 
 record, so to speak, of the quantity of outgoing nervous force that the 
 effort which we feel in lifting a heavy weight is an effort of the cells 
 of the motor centres from which the groups of muscles are innervated, 
 and not of the muscles themselves. 
 
 But although this feeling of central effort or outflow (we can hardly say 
 of central fatigue) may be a factor, it cannot be doubted that the braiii 
 is kept in touch with the contracting muscle by impulses of various 
 kinds which reach it by different afferent channels. 
 
 The corpuscles of Pacini, which exist in considerable numbers in the 
 neighbourhood of joints and ligaments, and in the periosteum of bones, 
 
 ^C*'^J<^1f''^'^^^^*~^^T:'>f-^^>£7'::^ 
 
 F'g. iyo. — Nerve-Ending in Tendon near the Insertion of the Muscular 
 Fibres (Golgi). 
 
 would seem well fitted to play the part of end-organs for the tactile 
 sensations causetl by the movements of flexion, extension, or rotation 
 of one bone on another, which form so large a portion of all voluntary 
 
 * With the arm horizontal the moment is the product of the weight by its 
 distance from the shoulder joint (see p. 749). 
 
1 096 
 
 THE SENSES 
 
 muscular movements. And it has been stated that paralysis of these 
 bodies in the limbs of a cat by section of the ner\cs going to them 
 causes a characteristic uncertainty of movement which suggests that 
 something necessary to normal co-ordinati<jn has been taken away. 
 Tendons also possess afferent ner\'e-fibres, which terminate by breaking 
 up into reticulated end-plates (Fig. 470). We have already seen that 
 the skeletal muscles possess numerous afferent fibres (p. 941). Some 
 of these must be nerves of ordinary sensation. For. although when a 
 muscle is laid ba- » in man and stimulated electrically, the sensation 
 docs not in general amount to actual pain, it is capable, under the 
 influence of strong .stimuli, of taking on a painful character. And 
 nobody who has felt the severe and sometimes almost intolerable pain 
 of muscular cramp would be likely to deny the existence of sensory 
 muscular nerves. But after deducting these, we must assume that a 
 
 m.'n.h 
 
 Fig. 448. — Muscle Spindle (after Ruffini). c, sheath of the spindle ; n.tr., trunk 
 of nerve, which sends fibres through the sheath into the spindle, where they 
 form endings (pr.e., s.e., pl.e.) of various kinds; m.n.b., bundle of motor fibres. 
 
 large proportion of the afferent nerves of muscle have other functions, 
 and among them may be the conveyance of impulses connected with 
 the muscular sense. The muscle-spmdles or neuro-muscular spindles 
 (Fig. 471), peculiar structures which occur in large number in most 
 of the skeletal muscles, and have been carefully studied by Huber, 
 Sihler, Ruffini, and other observers, are the terminations of many of 
 the sensory fibres. They are long narrow bodies, with a thick sheath 
 of connective tissue enclosing fine striped muscular fibres. Medul- 
 lated nerve-fibres enter the spindle, and there, dividing into branches 
 and losing their medullary sheath, form endings of various kinds around . 
 and between the muscular fibres. It is possible tliat in contraction 
 of the muscles the nerve-fibres in the spindles are compressed, and thus 
 mechanically stimulated. 
 
 In the spinal cord these impulses are conducted up through the 
 posterior colimin; and, although less is known as to the paths they 
 follow in the higher parts of the central nervous system, it is certain 
 that there is some afferent bond of connection between the cortical 
 motor areas and the muscles which they control (p. 963). 
 
 Tactile sensations set up in the skin or mucous membrane lying 
 over contracting muscles may also help the nervous motor mechanism 
 in appreciating and regulating the amount of contraction; but the fact 
 that, in anaesthesia of the mucous membrane covering the vocal cords 
 produced by cocaine, the voice is not at all impaired, shows that mus- 
 cular contractions of extreme nicety can be carried on without any 
 such aid. 
 
 Sensations of Hunger and Thirst. — These are representatives of 
 the group of interior sensations. As Tiedemann pointed out long 
 
CUTANEOUS AND INTERNAL SENSATIONS 1097 
 
 ago. at least two elements are iincjlved in the somewliat va;,Mi<' 
 sensation oi hunger: the local sensation of emptiness in the stomach, 
 and the general sensations of malaise, depression, and weakness. 
 There is some evidence that the general sensations are — in part at, 
 least — dependent upon the state of the stomach. But it would 
 appear that — at any rate, during prolonged deprivation of food — a 
 general condition of the tissues may exist which can arouse in con- 
 sciousness the sensation of hunger, even after the stomach has been 
 amply filled. Thus a patient with a fistula in the upper part of 
 the small intestine constantly suffered from hunger in spite of the 
 enormous quantities of food consumed. The stomach always felt 
 full, but as most of the food escaped from the fistula, the tissues 
 continued to be starved, and the general sensation of hunger re- 
 mained (Hertz). In diabetes the same thing may be observed. 
 On the other hand, it was noted by Carlson and one of his pupils 
 that after a fast of five days practically all of the mental depression 
 and some of the feeling of weakness disappeared during the first 
 meal. He therefore concluded that the depression of the central 
 ner\''ous system was essentially a reflex condition, depending prob- 
 ably on afferent impulses from the digestive tract, rather than a 
 result of deficiency of nutrient material in the blood. Complete 
 recovery from the bodily weakness, however, did not take place 
 till the second or third day after breaking the fast. 
 
 Fig. 472. — Commencement of Gastric Hunger Contractions (the Large Elevations 
 in a Man. At X she belt was tightened and the hunger contractions inhibited. 
 To be read from left to right (Carlson and Lewis). 
 
 An important factor in the local sensations associated with 
 hunger is the strong periodical contractions of the empty stomach, 
 which have been shown to coincide with the hunger pains (Cannon 
 and Washburn). 
 
 Carlson was able in observations on a man with a permanent 
 gastric fistula to confirm this coincidence Even when the empty 
 stomach was artificially caused to contract by distending it with a 
 
1098 
 
 THE SENSES 
 
 balloon, the man experienced a typical hun^'cr jKiin. During his 
 own h\e (lays' fast Carlson recorded these contractions by means 
 of a small balloon attached to a rubber tube, which was swallowrd 
 and allowed to remain in the stomach. The tube was connected 
 to a recording apparatus. It was found possible to go to sleep 
 witli the balloon in the stomach, and to obtain a record all thnni-di 
 
 Fig. 473. — Gastric Hunger Contractions in a Man at a More Advanced and Intense 
 Stage than in Fig. 472. Tightening of the belt at x did not stop the con- 
 tractions which ran the usual course to their termination. To be read from 
 left to right (Carlson and Lewis). 
 
 the night. After the first day of starvation the hunger sensation 
 referred to the epigastrium was almost continuous, and did not 
 wholly disappear during the intervals between the periods of 
 vigorous gastric contractions. This feeble continuous hunger sen- 
 sation was obviously associated with the increased tonus and the 
 more or less continuous, although weak, rhythmical contractions 
 that correspond to the periods of relative quiescence of the empty 
 stomach during prolonged starvation. The precise manner in which 
 the hunger contractions of the stomach arouse the pangs or pains 
 of hunger remains in doubt. Since the sensation has a specific 
 character, it is to be supposed that it is subserved by a special 
 sensory apparatus with receptors in the stomach. The vagi do not 
 seem to be concerned. But thegastriccontracticjns duringdigestion of 
 a meal notoriously do not cause such sensations, and tln'refore it has 
 been suggested that the nervous mechanism associated with the 
 local sensation of hunger becomes more and more excitable in the 
 absence of food, until at last the threshold is reached at which the 
 stimulus connected with the hunger contractions becomes effective. 
 It comes to the same thing to say that the presence of food in some 
 way inhibits the discharge which leads to the sensation. This, 
 
CUTAXEOrS AXD IXTERXAL SEXSATIOXS 1099 
 
 however, is only another way of saying that the true explanation is 
 still to seek. 
 
 Carlson was unable to confirm the common statement that 
 hunger disappears after the third day of staivation, although there 
 was certainly some decrease in the sensation of hunger, and especi- 
 ally in appetite, on the fourth and fifth days. As has been often 
 sliown.the deprivation of food for long periods, or even till death, 
 when water is allowed, is not associated with acute suffering. 
 
 Appetite is distinguished from hunger by those observers who 
 have studied the question most precisely, but of the physiological 
 basis of the sensations that constitute appetite we know even less 
 than we do of the physiological basis of hunger. The taking of 
 food blunts the appetite, as it stills hunger. Fasting evokes both. 
 Yet during a prolonged fast, appetite, the desire for food and the 
 pleasure in the thought or at the sight of it, may disappear, or be 
 much lessened, while the hunger pangs are still sharp. The smell 
 and taste of agreeable food and the mental representations of these 
 sensations are elements in appetite, and even the associations con- 
 nected with the time and place of a customary meal and with those 
 who share it. But there is a gastric element as well: the mere 
 filling of the stomach apart from the passage of nutrient material 
 into the blood helps to satisfy the appetite; the emptying of the 
 stomach in the course of digestion seems of itself to take a part in 
 restoring the appetite for the next meal. To what extent, if at all, 
 the gastric element in the sensation of appetite is dependent upon 
 the same mechanism as the gastric element in hunger is unknown. 
 Some have supposed that the same stimulation which, when its inten- 
 sity' is sufficiently increased, cau.ses gastric hunger pains, causes in smaller 
 intensity a milder hunger sensation, which is the gastric factor in 
 appetite. According to Carlson, a factor in appetite is the memor^^ 
 process of removal of hunger pangs by feeding, and he assumes that 
 the revival of such memories in consciousness depends upon the con- 
 dition of the alimentary canal, and is inhibited when the stream of 
 afferent impulses from the viscera is altered by changes in the motility 
 or secretory activity of the gastro-intestinal tract. He believes that 
 the secretion of the so-called appetite gastric juice, in man at least, 
 although clearlv demonstrated on a case of gastric fistula during 
 mastication of palatable food, does not possess the great importance 
 attributed to it bv Pawlow (p. 404), since normally there is a continuous 
 secretion of gastric juice in the absence of food in the stomach and of 
 psychical stimulation, and this is sufficient to initiate gastric digestion, 
 and therefore to insure a sufficient gastric secretion. The vagi do not 
 seem to contain fibres concerned in the sensations of hunger or appetite. 
 After section of these nerves, dogs, when they survive some time, eat 
 ravenously, although the food is often regurgitated. 
 
 Thirst. — This is a sensation, referred chiefly to the pharynx, and 
 certain of the sensory nerve fibres of this region, supphed by the 
 
iioo TTfE SENSES 
 
 glosso-pharvnfjeal norv^, may be assumed to be specificallv related 
 to it. I'luler ordinary conditions the sensation is elicited through 
 the afferent nerves of the pharynx when the mucous membrane 
 becomes dry, as when dry or salt food is eaten, or dry and dusty 
 air inhaled, and local moistening of the area in question gives 
 temporary relief, e\'en when no water is swallowed. When water 
 is long withheld, the water-content of all the tissues sinks, and a 
 more intense and distressing thirst, which cannot be allayed in any 
 way except by the ingestion of water, ensues. Probably in this 
 case afferent impulses originating in many organs, and conditioned 
 in some way by the abnormally low water-content of the blood and 
 tissues, as well as a more direct action of the loss of water upon the 
 (imknown) centre in which the sensation is represented, are re- 
 sponsible. 
 
 Relation of Stimulus to Sensation. — It i.s impossible to measure 
 sensation in terms of stimuhis. All that we can do is to compare 
 differences in the intensity of stimuli and differences in the resultant 
 sensations, or, in other words, to compare stimuli together and to com- 
 pare sensations together. And when we determine the amount by 
 which a given stimuhis must be increased or diminished in order that 
 there may be a just perceptible increase or diminution in the sensation, 
 it is found that (with certain limitations) the two are connected by a 
 simple law: Whatever the absolute strength of a stimuhis of given kind 
 may be, it must be increased by the same fraction of its amount in order 
 that a difference in the sensation may he perceived (sometimes called 
 Weber's laiv). Thus, a light of the strength of one standard candle 
 must be increased by ,^,jth candle, a light of lo candles bv ,'^'o, and in 
 light of ICO candles by a candle, in order that the eye may perceive 
 that an increase has taken place, just as the weight neces.sary to turn 
 a balance increases with the amount alreadv in the pans. The fractiou 
 varies for the different senses. It is about ^}-,^^ for light, ^ for sound. 
 But it would appear that Weber's law does not hold for the pressure 
 sense, nor for the other senses above and below certain limits. Fechner, 
 making various assumptions, has thrown Weber's law into the form 
 
 y=k _S — ^ where y is the intensity of .sensation, x the intensity of 
 
 stimulation, x„ the smallest intensity of stimulus which can be perceived 
 (liminal intensity), and k, a constant. This so-called psycho-physical 
 law of Fechner states that the sensation varies as the logarithm of the 
 stimulus. But Fechner's law has been subjected to serious criticism, 
 and the subject cannot be further pursued here. 
 
pTdCTTc AT. r.xr.nrT'^F<; noi 
 
 PRACTICAL KXERCISES ON CHAPTER XVIII. 
 VISION. 
 
 I. Dissection of the Eye. — I he stiuleiit may profitably refresh his 
 niemorv on the .uiatomy of the eye by dissecting a fresh eye — that of 
 a large animal like an ox is preferable, but the eye of a sheep or dog 
 may also be used. The eye is removed from the orbit by cutting 
 tlirough the conjunctiva where it is reflected on to the eyelids, care- 
 fully severing the extrinsic muscles and scooping the eyeball out of the 
 mass of loose connective tissue and fat in which it is embedded, and 
 which serves as a cushion to protect it from injmy during its move- 
 ments. Observe the transparent cornea in front, blending at its pos- 
 terior border with the opaque sclerotic, which is covered by a layer of 
 conjunctiva reflected from the lids. On clearing the fat cautiously 
 away, the tentlinous insertions of the external or extrinsic muscles of 
 the eyeball into the anterior part of the sclerotic will be seen. Identify 
 the \arious muscles (p. 1063). 
 
 Immerse the eye in water in a small glass dish, with the cornea 
 uppermost. The interior can now be seen, because the refractive 
 index of the cornea being nearly the same as that of water, the light is 
 only very slightly refracted there. The same effect is produced when 
 a cover-slip is placed over the cornea in the air; a plane surface being 
 substituted for the curved anterior surface of the cornea, its refraction 
 is abolished. Observe in the fundus of the eye the optic disc, eccentric- 
 ally placed in the retina, and the retinal vessels radiating out from it. 
 A portion of the fundus shows brilliant iridescent colours in many 
 animals (the tapetum lucidum). This portion is abruptly bounded by 
 a line a little above the optic disc. The appearance is due to a peculiar 
 arrangement of the connective-tissue (including elastic) fibres in this 
 part of the choroid. 
 
 Pinch up with forceps a small portion of the sclerotic a little posterior 
 to its junction with the cornea, and clip it away with fine, blunt- 
 pointed scissors, being careful not to penetrate the choroid layer, which 
 lies immediately beneath the sclerotic. Extend the incision through 
 the sclerotic backwards, and then transversely, and peel off strips of 
 the sclerotic from behind forwards. The lower surface of the sclerotic 
 (the so-called lamina fusca) is dark, owing to the presence in it of the 
 same pigment which is so abundant in the choroid coat. Go on re- 
 moving the sclerotic piecemeal until a considerable area of the dark 
 choroid layer is exposed with the ciliary nerves passing forward on its 
 surface towards the iris. One or other of the long ciliary arteries may 
 also be seen coursing between the sclerotic and choroid if the sclerotic 
 happens to have been removed at its position. On the anterior part of 
 the choroid may be observed some pale fibres passing backwards from 
 the comeo-sclerotic junction. They are the meridional fibres of the 
 ciliary muscle (p. 1022). 
 
 The eye being immersed in water, remove cautiously with the forceps 
 and scissors the portion of the choroid exposed. The retina is now seen 
 as a pale membrane, transparent when quite fresh, but becoming whitish 
 soon after death. Cut through sclerotic, choroid, and retina about half- 
 way round the eyeball, a little posterior to the comeo-sclerotic junction. 
 The vitreous humour will bulge out. Since its refractive index is 
 nearly the same as that of water, it is scarcely observed when im- 
 mersed, and the interior of the eye can be easily seen through it. 
 
 The optic disc can now be again studied, with the stump of the optic 
 
tio2 THE SENSES 
 
 nerve entering it and llie retinal vessels piercing the disc. In the 
 centre of the retina is the yellow spot. 
 
 In the anterior portion of the eyeball note the crystalline lens, and 
 at its circumference the radiating folds of the choroid called the ciliary 
 processes. Closely covering the ciliary- processes, the anterior border 
 of the retina forms the ora serrata, a plaited arrangement like an old- 
 time ruff. 
 
 Now complete the separation of the anterior and posterior portions 
 of the eyeball. Remove the vitreous humour, noting that it is attached 
 to the ciliary processes and the posterior surface of the capsule of the 
 lens by its enveloping membrane, the hyaloid membrane. With 
 scissors snip through the corneo-sclerotic junction at one point down 
 to the border of the lens, and observe the suspensory ligament passing 
 from the ciliary body chiefly towards the anterior surface of the lens, 
 where it blends with the lens capsule. Open the anterior chamber of 
 the eye by an incision through the cornea in front of its junction 
 with the sclerotic. It is filled with the clear, watery, aqueous humour. 
 Xote the pigmented iris projecting in front of the lens. 
 
 Remove the sclerotic and cornea for some distance along their line 
 Df junction, using gentle pressure with the edge of a fine knife to separate 
 the junction from the attached border of the iris. The ciliary muscle, 
 forming a pale, narrow ring around the eye at the corneo-sclerotic 
 junction will be thus exposed. Its external surface is closely adherent 
 to the sclerotic, and its internal blends with the ciliary body. The 
 circumference of the iris is attached at its anterior border. Posteriorly 
 it passes into the choroid. 
 
 Take out the lens and observe the curvature of its anterior and 
 posterior surfaces. Determine which has the greater curvature. In 
 the excised eye the lens will, of course, be in the condition of relaxed 
 accommodation . 
 
 2. Formation of Inverted Image on the Retina. — Fix the eye of an ox 
 or of a dog or rabbit, after careful removal of part of the posterior 
 surface of the sclerotic, in one end of a blackened tube, with the cornea 
 in front. A tube made by rolling up a piece of thick brown paper will 
 do. Place a candle in front of the eye. Look through the other end 
 of the tube, and observe the inverted image of the candle formed on 
 the retina. Move the candle until the image is as sharp as possible. 
 Now bring between the candle and the eye a concave lens. The image 
 becomes blurred, the candle must be put farther away to render it 
 distinct, and perhaps no position of the candle can be found which will 
 give a sharp image. If the lens is convex, the candle must be brought 
 nearer, and a sharp image can always be formed by bringing it near 
 enough. If both a convex and a concave glass be placed in front of 
 the eye, they will partially or whollv neutralize each other. Instead 
 of the candle a window may be looked at. If the eye of an albino 
 rabbit can be obtained, it is not necessary to remove a part of the 
 sclerotic. 
 
 3. Helmholtz's Phakoscope (Fig. 474). — This instrument is em- 
 ployed in studying the changes that take place in the curvature of the 
 lens during accommodation. It is to be used in a dark room. A candle 
 is placed in front of the two prisms P, P'. The observer looks through 
 the hole B; the observed eye is placed at a hole opposite the hole A. 
 The candle or the observed eye is moved till the observer sees three 
 pairs of images, one pair, the brightest of all, reflected from the anterior 
 surface of the cornea; another, the largest of the three, but dim, re- 
 flected from the anterior surface of the lens; and a third pair, the 
 smallest of all, reflected from the posterior surface of the lens (Fig. 421, 
 
PRACTICAL EXERCISES 
 
 tioi 
 
 Fig. 474. — Phakoscope. 
 
 p. 102 1). I'hc last two pairs can, of course, only be seen within the pupil 
 The observed eye is now focussed first for a distant object (it is enough 
 that the person should simply leave his eye at rest, or imagine he is 
 looking far away), and then for a near object (an ivory pin at A). 
 During accommodation for a near object no change takes place in the 
 size, brightness, or position of the first or third pair of images; there- 
 fore the cornea and the posterior surface of the lens are not altered. 
 The middle images become smaller, somewhat brighter, approach each 
 other, and also come nearer to the corneal images. This proves (a) that 
 the anterior surface of the lens undergoes a change ; (b) that the 
 change is increase of curvature (diminution of the radius of curvature), 
 for the virtual image reflected from a convex mirror is smaller the 
 smaller is its radius of curvature. (The third pair of images really 
 
 undergo a slight change, such 
 as would be caused by a small 
 increase in the curvature of 
 the posterior surface of the 
 lens ; but the student need 
 not attempt to make this 
 out.) 
 
 4. Scheiner's Experiment, — 
 Two small holes are pricked 
 with a needle in a card, the 
 distance between them being 
 less than the diameter of the 
 pupil. The card is nailed on 
 a wooden holder, and a needle 
 stuck into a piece of wood is looked at with one eye through the holes. 
 When the eye is accommodated for the needle, it appears single; when 
 it is accommodated for a more distant object, or not accommodated at 
 all, the needle appears double. The two images approach each other 
 when the needle is moved away from the eye, and separate out from 
 each other when it is moved towards the eye. When the eye is ac- 
 commodated for a point nearer than the needle, the image is also 
 double ; the images approach each other when the needle is brought 
 closer to the eye, and move away from each other when it is moved 
 away from the eye. If while the needle is in focus one of the holes be 
 stopped by the finger, the image is not affected. When the eye is 
 focussed for a greater distance than that of the needle, stopping one 
 of the holes causes the image on the other side of the field of vision 
 to disappear; if the eye is focussed for a smaller distance, the image 
 on the same side as the blocked hole disappears (Fig. 475). To de- 
 termine the near-point of distinct vision (p. 1029) the card may be 
 mounted vertically on a cork, and this fastened by a rubber band to 
 the end of a foot-rule. Mo\-e a needle, also inserted vertically into a 
 cork, along the rule, beginning at the end farthest from the eye, until 
 with the strongest effort of accommodation it is seen double. Then 
 push it back slightly to the point at which, again with maximum 
 accommodation, it is just seen single. Repeat the measurement with 
 a needle mounted horizontally. If regular astigmatism is present, 
 the distances will not be the same. Most eyes have slight regular 
 astigmatism. 
 
 In myopic persons the far-point of distinct vision can also be de- 
 termined by Scheiner's experiment. The needle being left on a shelf 
 at the level of the eye, the person walks away from it backwards, re- 
 garding it all the time through the perforated card, till it is no longer 
 seen single. 
 
1104 
 
 THE SENSES 
 
 5. Kuhne's Artificial Eye. — This is an elongated box provided with 
 a glass k'vs to rei)nsrnt the tiystalline, and a ground-glass plate to 
 represent the retina. The box is filled with water to which a little 
 eosin has been added. The water must be perfectly clear. If the 
 tap-water is turbid it should be filtered or allowed to settle, or dis- 
 tilled water should be used. A beam of sunlight or electric light, or, 
 
 in case these are not available, a beam from an oil stereopticon, is made 
 
 to pass through the box. Many of the facts of vision can be illustrated 
 
 by means of this piece of apparatus. The modification of it introduced 
 
 by Lyon is ver^^ convenient. 
 
 (a) Let the rays of light pass through an arrow-shaped slit in a piece 
 
 of cardboard. An inverted image of the arrow is formed on the retina. 
 
 Move the retina nearer to or farther from the lens to make the image 
 
 sharp. In the eye of man and of most animals, accommodation is 
 
 not brought about by a change in the distance of retina and lens, but 
 
 by a change of curvature in the lens. 
 
 {b) Remove the lens. The focus is now far behind the retina. This 
 
 illustrates the state of matters after the lens has been removed for 
 
 cataract. The arrow 
 
 can again be sharply 
 
 focussed on the retina 
 
 by putting a convex 
 
 lens in front of the 
 
 artificial eye. But 
 
 this must be much 
 
 weaker than the lens 
 
 which has been re- 
 moved, for if the 
 
 latter be placed in 
 
 front of the eye, the 
 
 image is formed a 
 
 little behind the 
 
 cornea. 
 
 (c) Replace the lens. 
 
 Move the retina so 
 
 far back that the 
 
 image is focussed in 
 
 front of it. This is 
 
 the condition in the 
 
 myopic eye. Put a 
 
 weak concave lens in 
 
 front of the eye; the image now falls more nearly on the retina. ]Move 
 
 the retina forward so that the focus is behind it. This corresponds 
 
 to the hypermetropic eye. Put a weak convex lens in front of the 
 
 eye to correct the defect. 
 
 {d) Observe that a plate with a hole in it, placed in front of the eye, 
 renders an indistinctly focussed image somewhat sharper by cutting 
 off the more divergent peripheral rays. 
 
 {e) Fill with water the chamber in front of the curved glass that repre- 
 sents the cornea. The focus is now behind the back of the eye alto- 
 gether. Refraction by the cornea is here abolished, as is the case in 
 vision under water. An additional lens inside the eye, or a weaker 
 one in front of it, corrects the defect. Fishes have a much more nearly 
 spherical lens than land animals, and a flat cornea. 
 
 (/) Fill the hollow cylindrical lens with water, and place it in front of 
 the artificial eye. The eye is now astigmatic. A point of light is 
 focussed on the' retina, not as a point, but as a line. The vertical and 
 
 Fig. 475. — Scheiiier's E.xperiinent. In the lower figvire 
 the eye is focussed for a point farther away than the 
 needle, in the upper for a nearer point. The con- 
 tinuous lines represent ra>-s from the needle, the inter* 
 rupted lines rays from the point in focus. 
 
PRACTICAL EXERCISES 
 
 1 105 
 
 horizontal limbs of a cross cut out of a piece (jf cardboard aud placed 
 in the path of the beam f)f lij^'ht cannot be both focussed at the same 
 time. 
 
 6. Astigmatism (Regular). — (i) Look at a figure showing a number 
 of lines radiating horizontally, vertically, and in intermediate directions 
 from a common centre. Fir.st fix the figure at such a distance tliat one 
 can comfortably accommodate. If astigmatism is present, all the lines 
 cannot be seen with etjual di.slinctness at the same time, iDut they can 
 
 all be successively accommodated for. 
 Next, bring the figure to the near- 
 point of distinct vision for the hori- 
 zontal and neighbouring lines. Prob- 
 ably the vertit al lines will be blurred 
 antl cannot be made as distinct as the 
 horizontal by any effort of accom- 
 modation. If the eye is distinctly 
 astigmatic, the diffe<ence will be 
 marked. 
 
 (2) Use the Ophthalmometer. — A 
 convenient form is shown in Figs. 476 
 and 477. 
 
 Raise or lower the chin-rest till the 
 upper bar of the head-rest is just 
 above the patient's eyebrows, his head 
 being exactly vertical. The eye not 
 to be examined is covered with the 
 blind. The patient looks steadily into 
 the opening of the tube with his eye 
 wide open. The height of the instru- 
 ment having been adjusted, a clear 
 image of the mires is obtained by 
 focussing. The tube is then turned 
 horizontally slightly to right or left 
 until the two images of the mires are 
 close together and equally distinct. 
 Rotate the outer tube (Fig. 477, d) 
 until the long meridian lines of the 
 images are exactly in line with each 
 other. If there is no astigmatism, 
 this will be seen at all axial posi- 
 tions ; if there is astigmatism, at only 
 two positions. An axis having thus 
 been obtained, the graduated disc 
 (Fig. 476, A) on either side of the 
 tube is rotated until the shorter lines 
 or spurs of the images also unite, 
 forming a perfect cross with the longer ones (Fig. 478), and the adjust- 
 able pointer on the left-hand disc is made to coincide with the stationary 
 one and a reading taken. Now rotate d through 90 degrees; the long 
 axial lines of the images will be in alignment without further adjustment. 
 But if the eye is astigmatic, the short lines will not (Fig. 479). By. 
 rotating A, the short lines are made to coincide, so that a perfect cross 
 is again formed, and the graduation is read. The difference between 
 this and the previous reading — i.e., the difference betw-een the two 
 pointers — gives the difference in the curvature of the cornea in the two 
 meridians. The images of circles which form the outer portion of the 
 mires are oval in ordinary astigmatism. 
 
 70 
 
 Fig. 476. — Ophthalmometer, as seen 
 from behind the Patient. B, blind 
 for covering the eye not being ex- 
 amined; H, chin-rest; A, A, gradu- 
 ated discs on which radii of cur\'a- 
 ture of the cornea in various meri- 
 dians are read off or their equivalent 
 in diopters; E, eye-piece of telescope; 
 C, milled head for raising and lower- 
 ing chin-rest ; F, milled head for 
 adjusting height of the ophthalmo- 
 meter, and G for moving it horizon- 
 tally back and forth; «. graduated 
 disc fur giving the rotation of the 
 outer tube of the telescope and the 
 black disc «. In u are seen the two 
 illuminated mires. 
 
iio6 
 
 THE SENSES 
 
 J. Spherical Aberration.^C'losc one eye, and bring a small object 
 (a pin or tlie point of a pencil) towards the other eye till it becomes 
 blurred. Interpose between the object and the eye a card perforated 
 by a small hole. The object becomes more distinct owing to the 
 cutting oil of the peripheral rays (p. 1027). 
 
 8. Chromatic Aberration. — Look at Fig. 424 (p. 1028) from a distance 
 too small for perfect accommodation, and verify the facts given in 
 tl^ description of the figure. 
 
 Fh 
 
 4yy. — Vertical Section of Ophthalmometer. d, outer tube of the telescope 
 rotating in sleeve or collar s (supported by stanflard /, which is swivelled in 
 tubular support, g); k, diaphragm; 10, eye-piece with lenses a and 6; »i, a station- 
 ary disc, borne on collar s, graduated to indicate angle of rotation of «, a black 
 concave disc rcjtating with tube d, and having fixed in it two illuminated figures 
 (or mires), w. w, whose images reflected from the cornea are observed ; (' is a pointer 
 carried on the tube d which shows on the graduated arc the amount of rotation; 
 12, 12, hemispherical shells containing small incandescent lamps for illuminating 
 the translucent mires. The lamps are connected with wires running in the 
 hollow stem t:fis the inner tube of the telescope carrying tlie double prism, //, It. 
 By means of the rack 0, projecting through the slot »t, and engaged by the pinion 
 p,/ is moved back and forth in the outer tube, thus approximating or separating 
 the corneal images of the mires. On the axis of p is a milled head for turning it, 
 and two duplicate discs graduated with a scale showing the radii of curvature 
 of the cornea in millimetres, and another scale showing their equivalent in 
 diopters. 
 
 g. Measurement of the Extent of the Field of Vision. — Use the peri- 
 meter shown in Fig. 449 (p. 1058). 
 
 (i) For White Light. — Fix In the holder, Ob, on the gradual ed arc, 
 a small piece of white paper, and put one of the charts supplied with 
 the instrument at the back of the wheel which revolves w'ith the arc. 
 The observations can be recorded on this chart. The patient rests his 
 chin on K and adjusts one eye against O. This eye is kept fixed on 
 the mark at /during the whole period of observation, and the other eye 
 
PRACTICAL EXr.IiCISES 
 
 H07 
 
 is covered. The arc is placed in a definite position, and the white 
 object gradually moved from the end of the arc until the person an- 
 nounces that he can just see it. The angle at whicli this occurs is read 
 off and recorded on the chart. The arc is then rotated into a new 
 positit)n and the observation repeated. A line is drawn througli all 
 the points thus obtained, and this constitutes the boundary of the 
 field of vision (Fig. 450). 
 
 If the position of each point is inserted on the chart, a point above 
 the horizontal plane passing through the visual axis being placed 
 
 Fig. 478. 
 
 Fig. 479 . 
 
 below it, and a point to the right of the vertical plane being moved to 
 the left, we obtain a map of the sensitive portion of the retina. Usually 
 perimeters are arranged to do this automatically. 
 
 (2) Repeat the mapping of the field, using coloured papers (red, 
 green, and blue) instead of white. 
 
 10. Mapping the Blind Spot. — Make a black cross on a piece of white 
 paper attached to the wall, the centre of the cross being at the height 
 of the eye in the erect position. Stand about 12 inches from the wall, 
 
 the chin supported on 
 a projecting piece of 
 wood. Fix the centre 
 ot the cross with one 
 eye, the other being 
 closed, and move over 
 the paper a pencil 
 covered, except at the 
 point, with white 
 paper, until the point 
 j ust disappears . Alake 
 a mark on the paper 
 at this point , and repeat 
 the observation for all 
 diameters of the field. 
 The blind spot is thus 
 marked out (Fig. 480*. 
 Its shape is not the same in all eyes (Fig. 481). Its size and distance 
 from the fovea centralis can be calculated from the construction given 
 in Fig. 420 (p. loiq). 
 
 11. The Macula Lutea, or Yellow Spot. — (i) After closing the eyes 
 for a minute or two, look with one eye through a strong solution of 
 chrome alum in a clear glass bottle with parallel sides. Hold the bottle 
 between the eye and a white screen or a white cloud. An oval rose- 
 coloured spot will be seen in a greenish field. The pigment of the 
 yellow spot absorbs the bh.e and green rays. 
 
 Fig. •♦80, — Map of Blind Spot (reduced by One-half). 
 Right eye. Distance of eye from paper 12 inches. 
 
iio8 THE SENSES 
 
 (2) Keep the eye closed for a short time. J hen direct it to a surface 
 ilhiminated by a weak bhie light. A dark blue or almost black spot 
 (Alaxwcll's spot), corrcsixjiuling to the macula, is i-ecn in the visual 
 field, owing to the absorption of the blue rays. 
 
 Fig. 461. — Composite picture of Blind S]M,t (n.jt rrjuci-d). The- Mind spot of tlie 
 right eye was mapj)ed by 31 men, the eye being always at a distance of 12 inches 
 from the paper. The maps were then superposed. The amount of white at 
 any point of the figure is intended to correspond to the number of maps which 
 overlapped at that point. Although the mechanical process of reproduction 
 gives rather an imperfect view of the composite rna]), the area in the centre of 
 the figure where the white is most continuous, and which represents the shape 
 of the majority of the blind spots, evidently bears a general resemblance to the 
 outline in Fig. 480. 
 
 12. Ophthalmoscope — (i) Human Eye (p. T031). — Let A be the ob- 
 server, and B the iK-rson whose eye is to be examined. A and B 
 are seated facing each other. Suppose that the right eye of B is to 
 be examined. Close to the left ear of B is a lamp on a level with his 
 eyes: the room is otherwise dark. For a clinical examination, the pupil 
 should be dilated by putting into the eye a drop of a 0-5 per cent. 
 
PRACTICAL EXERCISES nog 
 
 solution of atropine sulphate, but lliib is not indispensable for the 
 experiment. 
 
 (a) Direct Method. — A takes the mirror in his right hand, and, 
 holding it close to his own eye, looks through the central hole, and 
 throws a beam of light into B's eye. A red glare, the so-called ' reflex ' 
 from the choroidal vessels, is now seen. A then brings the mirror 
 to within 2 or 3 inches of B's eye, keeping his own eye always at the 
 aperture. A and B both relax their accommodation, as if they were 
 looking away to a distance. If both eyes are emmetropic, the retinal 
 vessels will be seen. B should now look away past the little finger of 
 A's right hand. This causes slight inward rotation of B's eye, and 
 brings into \iew the white optic disc with the central artery and vein 
 of the retina crossing it. 
 
 (6) Indirect Method. — A takes the mirror in his right hand to ex- 
 amine B's right eye, places his own eye behind the aperture as before 
 at a distance of about 18 inches from B, and throws a beam of light 
 into B's eye. Then A takes a small biconvex lens in his left hand, and 
 places it 2 or 3 inches in front of B's eye, keeping it steady by resting 
 his little finger on B's temple. A now moves the mirror until he sees 
 the optic disc. 
 
 (2) Examine a rabbit's eye by the direct and indirect method. 
 Dilate the pupil by a drop or two of atropine solution. 
 
 For practice, before doing (i) and (2) the student should examine 
 an artificial ' eye ' by both methods, so as to get a clear view of what 
 represents the retina. A substitute for the artificial eye may be made 
 by unscrewing the lower lens of the eyepiece of a microscope, and 
 fastening in its place a piece of paper with some printed matter on it. 
 The letters must be made out with the ophthalmoscope. 
 
 The opportunitj' should also be taken to observe the eye of an 
 anaesthetized animal by the simple cover-glass method mentioned 
 in I (p. iioi). Around cover-glass is slipped under both eyelids and so 
 held in position on the cornea. The fundus of the eye can now be 
 clearly seen, including the optic disc and retinal, vessels. The instilla- 
 tion of a little cocaine into the eye of a rabbit will produce local an- 
 aesthesia sufficient to permit the experiment. 
 
 13. Skiascopy or Retinoscopy. — The simplest method is as follows: 
 The observer places himsclt at a distance of a metre from the observed 
 eye, which he illuminates by a beam reflected from a concave ophthal- 
 moscopic mirror held in front of his eye. The accommodation of the 
 observed eye is relaxed. If, now, when the mirror is rotated no direc- 
 tion of movement of the shadow or the light area (p. 1035) can be made 
 out, the pupil becoming all at once dark throughout its whole extent 
 when the mirror is rotated in one direction, and all at once light 
 throughout its whole extent when the mirror is rotated in the opposite 
 direction, the observer is in the far-point of the observed eye. Since 
 the far-point is at the distance of a metre, there is in this case myopia 
 amounting to one diopter. If, however, the light area moves in the 
 same direction as the rotation of the concave mirror, the far-point of 
 the observed eve lies between the observer and the observed eye, so 
 that the myopia amounts to more than one diopter. The precise 
 degree of myopia can be estimated by interposing biconcave lenses of 
 different strength until the far-point is made just i metre. 
 
 If the light area mo\es in the opposite direction to the rotation 
 of th? mirror, the far-point is more than a metre distant, and therefore 
 the oDserved eye is emmetiopic or hypermetiopic, or myopic to a degree 
 less than a diopter. The lens, convex or concave, can now be sought 
 out which will just bring the far-point to a metre, and from the strength 
 
IIIO 
 
 THE SENSES 
 
 of it, minus one diopter, the refraction can be estimated. Suppose, 
 for instance, that a convex lens of two diopters is required, then hyper- 
 metropia of one diopter exists. 
 
 In order to facilitate the introduction of the various lenses, instru- 
 
 Fig 
 
 ^ii2. Geneva Retinoscope and Ophthalmoscope. A, frame of instrument; 
 
 B, retinoscope attachment; C, ophthalmoscope attachment; D, base; i, mirror 
 handle; 2, clip to hold the proper lens to correct the abnormality of refraction 
 of observer or patient when viewing the retina with the ophthalmoscope; 3. scale 
 indicating the meridian of handle and pointer; 4, ring in which mirror cup rotates; 
 6, mirror; 7, mirror spring for reflecting the light to a given point; 8, screws for 
 adjusting mirror; 9, screw for holding light and ring 4 in position; 10, handle 
 for swinging A from side to side; 13, opening iu iris diaphragm, controlled by 
 handle 14; 15. lamp hood; 17, knurled handle for rotating disc containing the 
 full diopter lenses; 18, handle for rotating the disc containing the fractional 
 lenses (white numbers indicate plus lenses, and red minus lenses) ; 20, opening 
 through which observer looks when adjusting the retinf)Scope to the patient's 
 eye; 21, pinion for advancing or retracting instrument; 24. bracket ring of 
 retinoscope attachment B, which is slipped over ring 25 when putting retinoscope 
 attachment into place; 28, clips for ' fogging' lenses through which the patient 
 looks to relax accommodation; 29, opening through which the pupil is viewed in 
 retinoscopy; 30, opening containing clip in which extra lenses may be inserted 
 when required, or the defect is over 8 diopters; 32, patient's eye-cup; 33. ring of 
 ophthalmoscope attachment C, which telescopes over 25; 34. ophthalmoscope 
 tube; 35, binding-screw which holds the instrument in a fixed position when 
 retinoscope is being used ; 37, rack to raise and lower the instrument ; 40, handle 
 controlling height of chin-rest 44; 46, forehead-rest. 
 
 ments called skiascopes or retinoscopes may be used, one of wliich is 
 shown in Fip. 482. 
 
 14. Pupillo-dilator and Constrictor Fibres. — [a) Set up an induction 
 machine arranged for tetanus, and connect a pair of electrodes through 
 
PRACTICAL nXERCTSES tin 
 
 a short-ciicuiting key with the secondary. Etherize a cat by putting 
 U into a larf;c vessel with a lid, sli]:)ping into the vessel a piece of cotton- 
 wool soaked with ether, and waiting till the movements of the animal 
 inside the vessel have ceased. Then quickly put the cat on a holder 
 and maintain an;csthesia with ether. Expose the vago-sympathetic 
 in the neck (pp. 203, 212); the carotid is taken as the guide to it. 
 Ligature the nerve and cut below the ligature. On stimulating the 
 upper (cephalic) end, the pupil of Die corresponding eye dilates. 
 
 Carefully separate the sympathetic from the vagus, and repeat the 
 observation on the former. 'Jhe result on the pupil is the same. 
 
 [b) Observe in the eye of a fellow-student, or, by means of a looking- 
 glass, in your own eye, that when light falls on one eye both pupils 
 contract. 
 
 {c) Observe that when the eye is accommodated for a near object the 
 pupil contracts, and that it dilates when a distant object is looked at. 
 
 15. Colour-Mixing. — [a) Arrange a red and a bluish-green disc on 
 one of the steel discs of the colour-mixing apparatus shown in Fig. 483, 
 so that a part of each is seen. On another arrange a violet and a yellow 
 disc, and on the third an orange and a blue disc. By adjustment of 
 the proportions of the two colours a uniform grey can be obtained 
 from each of these combinations (complementary- colours) when the 
 discs are rapidly rotated. 
 
 {h) Mix two colours that are not complementary^ — e.g., blue and red — 
 grey or white cannot be obtained by any adjustment of proportions; 
 the result is always a mixed colour, the precise hue depending on the 
 amount of each ingredient. 
 
 (c) Take papers of any three colours from widely-separated parts of 
 the spectrum — e.g., blue, green, and red — and arrange them on one 
 of the rotating discs. By varying the proportions, white (grey) can be 
 produced, and any other coloured paper fastened on another of the 
 rotating discs can be matched by adding white to the three colours. 
 
 16. After-images — (i) Positive. — (a) Rest the eyes for two or three 
 minutes by closing them, or by going into a dark room. Then look for 
 an instant at a bright object, a window or an incandescent lamp, and 
 at once close the eyes again. A bright positive after-image of the 
 object looked at will be seen. 
 
 [b) Look at an incandescent lamp through a coloured glass as in (a). 
 The positive after-image will appear in the same colour as the glass. 
 
 (2) Negative After-image. — {a) Look at an incandescent lamp for 
 thirty seconds, and then direct the eyes to a white surface. The 
 after-image of the filament will appear dark. 
 
 (6) Look at the lamp through a coloured glass for thirty or forty 
 seconds, and then close the eye of look at a white ground. The after- 
 image of the filament will appear in the complementary colour of the glass . 
 If the glass was red, for instance, the after-image will be greenish. 
 
 [c) Look at a white square on a dark ground for thirty seconds, 
 then quickly cover the field with white paper. A dark square will be 
 seen on the white ground. 
 
 [d) Repeat (c) with coloured squares. The after-image of the 
 square will be in the complementar\' colour. 
 
 Contrast. — Perform Meyer's experiment (p. 1056). 
 
 17. Retinal Fatigue. — Fix the eye steadily on a portion of a printed 
 page a considerable distance away. Note that the print soon be- 
 comes blurred. Wink the eye; the short rest causes a notable recovery 
 of the retina. 
 
 18. Visual Acuity. — Draw on a white card a series of vertical black 
 lines I millimetre thick, and separated from each other by a distance 
 
ma 
 
 THE SENSES 
 
 of a millimetre. Set ihc card up in a good liplil, and walk backwards 
 from it till the individual lines just fail to be dis< riniinated. Measure 
 the distance from the card at which this occurs, and calculate the size 
 of the retinal image (p. 1019). 
 
 10. Colour-Blindness. — Spread out Holmgren's coloured wools on 
 a sheet of white lilter-paper in a good liglit. Do not mention the 
 colours of any of the wools, but (i) ask the ])erson who is being tested 
 to pick out ail the wools which seem to him to m;itch a pale pure green 
 wool (neither yellow green nor blue green), whiili is handed to him. 
 He is not to make an exact match, but to pii k out the skeins which 
 
 Fig. 483. — Apparatus for Colour-.Mixing. 
 
 seem to have the same colour. If he makes any mistakes, by selecting, 
 e.g., in addition to the green skeins, any v)f the ' confusion colours,' 
 such as grey, greyish-yellow, or blue wools, there is some defect of 
 colour discrimination. Jo determine whether the person is red or green 
 blind, tests (2) and (^) are then made. (2) (live him a medium purple 
 (magenta) wool, and ask him to pick out mat( li*-s for it. If he is red- 
 blind, he will select as mat( lies to it only blues and violets, as well as 
 other purples. If he is green-blind, he will select only greens and 
 greys. (3) The third test is a red wool. In selecting matches for this, 
 the red-blind will choose (with reds) greens, greys, or browns less bright 
 
PRACTICAL EXERCISES IH3 
 
 than llic lest. The Rrccn-blind will choose (with reds) greens, greys, 
 or browns which arc brighter than the test. 
 
 It must bo remembered that the results of tests with the coloured 
 wools need not be precisely the same as those with coloured lights, 
 and that when there is a discrepancy between the two the test with 
 the coloured liglits should be accepted; for it is usually the normal 
 perception and discrimination of coloured lights which has practical 
 importance. 
 
 zo. Talbot's Law. — Rotate a disc one sector of which is black and the 
 rest wdiite, or a disc like that in Fig. 446 (p. 1050). A uniform shade is 
 produced as soon as a speed of about 25 revolutions a second has been 
 attained, and this is not altered by further increase in the speed. 
 
 21. Purkinje's Figures. — (a) Concentrate a beam of sunlight by a 
 lens on the sclerotic at a point as far as possible from the corneal ma.rgin, 
 passing the beam through a parallel-sided glass trough filled with a 
 solution of alum to sift out the long heat-rays. The eye is turned 
 towards a dark ground. The field of vision takes on a bronzed appear- 
 ance, and the retinal bloodvessels stand out on it as a dark network, 
 which appears to move in the same direction as the spot of light on the 
 sclerotic. A portion of the field corresponding to the yellow spot ii 
 devoid of shadows (p. 1043). 
 
 (6) Direct the eyes to a dark ground while a flame held at the side of 
 the eye, and at a distance from the visual line, is moved slightly to and 
 fro. A picture of branching bloodvessels appears. This experiment 
 is performed in a dark room. 
 
 (c) Immediately on awaking look at a white ceiling for an instant; 
 a pattern of branched bloodvessels is seen. If the eye be at once closed, 
 and then opened with a blinking movement, this may be observed again 
 and again. Ultimately the appearance fades away. 
 
 HEARING, TASTE, SMELL, TOUCH, ETC. 
 
 22. Monochord. — Study by means of the monochord, a stretched 
 string witli a movable stop, the relation between the pitch of the note 
 given out by a vibrating string, and its length and tension. 
 
 23. Beats. — Cause two tuning-forks of nearly equal pitch to vibrate at 
 the same time. Make out the beats, and count their number per second. 
 
 24. Sympathetic Vibration. — Take three tuning-forks mounted on 
 resonators. Let two of them be of the same pitch. Strike one of 
 these; the other is thrown into sympathetic vibration, and continues 
 to give out a note after the first is quickly stopped by touching it. 
 The third fork is unaffected. 
 
 25. Determine by means of Galton's whistle the pitch of the highest 
 audible tone. 
 
 26. Cranial Conduction of Sound. — When a tuning-fork is held 
 between the teeth, a part of the sound passes out of the ear from the 
 vibrating membrana tympani; if one ear is closed, the sound is heard 
 better in this than in the open ear. If the tuning-fork is held between 
 the teeth, till, with both ears open, it becomes inaudible, it will be 
 heard for a short time if one or both ears be stopped ; and when in this 
 position the sound again becomes inappreciable, it can still be caught 
 if the handle be introduced into the auditory meatus. 
 
 27. Taste. — (i) Apply to the tongue by means of a camel's-hair 
 brush a solution of quinine (i to i.ooo), sodium chloride (i to 200), 
 cane-sugar (i to 50). and sulphuric acid (i to i.ooo). Determine at 
 what part of the tongue the strongest sensations are elicited by each. 
 
Ill J THE SENSES 
 
 (2) Prepare a series of solutions of sulphuric acid of gradually in- 
 
 M 
 creasing strength, beginning with a solution (a two-thousandth 
 
 gramme-molecular solution) (p. 426;. Put into the mouth, after 
 previous rinsing with distilled water, 4 or 5 c.c. of one of the solutions 
 of the acid, beginning with the weakest, and determine at what con- 
 centration of the H ions the acid taste first appears, rinsing out the 
 mouth after each observation. Repeat the experiment with solutions 
 of hydrochloric acid, and determine whether the threshold value is the 
 same. 
 
 A similar comparison of the necessary concentration of the OH 
 ions can be made with solutions of sodium hydroxide and potassium 
 hydroxide. 
 
 (3) Connect two short pieces of platinum wire with the copper wire 
 from the poles of a Daniell or dry cell. Apply one platinum wire to 
 the inner surface of the lip and the other to the' tip of the tongue. 
 Reverse the poles. Note the difference in the sensation according to 
 whether the anode or the kathode is on the tongue. 
 
 28. Smell. — (i) Pass a current tlirough the olfactory mucous mem- 
 brane by connecting one electrode with the forehead and the other 
 by means of a small piece of sponge or cotton-wool soaked in physio- 
 logical salt solution with one nostril. An odour like that of phosphorus 
 will be perceived. 
 
 (2) To distinguish between Taste and Smell. — Use a solution of clove- 
 oil in water which can just be distinguished from w^ater when it is placed 
 on the tongue by means of a camel's-hair brush. Close the nostrils, 
 and determine whether the clove-oil can now be detected. 
 
 29. Touch and Pressure. — (i) Prepare a number of hair aesthesio- 
 meters by fastening hairs of different thicknesses to small wooden 
 handles about 3 inches long by means of sealing-wax. Hairs as straight 
 as possible should be chosen, or straight portions of hairs. The hair is 
 to be fastened on one end of the piece of wood at right angles to the 
 long axis of the handle, so that about an inch of the hair projects to 
 one side. Determine the pressure value of each hair by pressing it 
 down upon the scale of a balance till it is slightly bent, and observing 
 the greatest weight in the other scale which it will lift. Mark the 
 number in milligrammes on the handle. In this way, when a hair is 
 placed at right angles to a point of the skin, and pressure exerted on 
 it till it begins to bend, the intensity of the touch stimulus — i.e., the 
 pressure exerted on the skin — is definitely measured, and by using 
 hairs of different pressure values the threshold value of the stimulus 
 for any touch area — i.e.. the pressure which just gives the sensation 
 of light touch — can be determined (p. 1081). 
 
 (a) Using the back of the hand, note how light a touch of the aesthesi- 
 ometer applied to the end of a hair suffices to elicit a sensation of touch, 
 eis compared with a part free from hairs. The hairs diminish the 
 threshold of the stimulation by acting as le\ers. whose short arm 
 presses against the nerve-endings surrounding the hair-follicles, while 
 the stimulating weight acts on the long arm. When the skin is shaved 
 the threshold is always raised. 
 
 (b) Shave an area on the back of the hand, and make out the relation 
 of the touch-spots to the hair follicles. Each hair has an especially 
 sensitive touch-spot just on the ' windward ' side of the follicle (p. 1080). 
 Using aesthesiometers of different pressure \alues, determine the 
 threshold value for the shaved area. Outline an area of a square 
 centimetre on the skin, and determine the number of touch-spots, 
 using first a hair of the threshold value, and then going over the area 
 
PRACTICAL EXERCISES 1115 
 
 again with a hair of a decidedly higher pressure value. The threshold 
 value for many parts of the hairy skin is obtained with a hair which 
 bends at 70 milligrammes. Repeat the determinations for other skin 
 areas, such as the back of the upper arm, the palm of the hand, the 
 anterior surface of the leg, the chest, the back, and the cheek, forehead, 
 and lips. 
 
 It is well that the subject should be blindfolded during the ex- 
 amination of the skin areas. He should understand by preliminary 
 practice what the sensation of light touch is, the perception of which 
 he is to indicate. With strong aesthesiometer hairs the pricking sen- 
 sation due to stimulation of pain-spots must be discriminated from 
 touch sensation. When the two sensations are elicited together, the 
 touch sensation is momentary, and the subject must be alert to detect 
 it immediately on stimulation. The pain sensation develops more 
 slowly, but lasts longer and becomes much more conspicuous than the 
 touch sensation, which accordingly is apt to be submerged by it in 
 consciousness. 
 
 (2) Touch the skin with a blunt point (at or about skin temperature). 
 With light contact the sensation is that of simple touch. On in- 
 creasing the pressure, the quite distinct sensation of deep pressure is 
 perceived. 
 
 (3) Touch a portion of skin with a camel's-hair brush of ordinary 
 size, pressing on it till the hairs of the brush begin to bend. The first 
 sensation of simple contact gives place to a sensation of pressure. Re- 
 peat with a camel's-hair brush of the finest hairs half a centimetre in 
 length, cut away till its cross section is only half a millimetre in diameter 
 at the base. Probably a pure sensation of touch, without any pressure 
 element, will be obtained when the brush is applied so as just to bend 
 the hairs. 
 
 (4) Find the least distance apart at which the points of the aesthesi- 
 ometer compasses can be recognized as two when applied to the back of 
 the hand, the forearm, upper arm, forehead, finger-tips, or tip of the 
 tongue. Both points of the compasses must be placed on the skin 
 at the same time, and the same pressure applied to both. The subject 
 must not see the points. 
 
 (5) Time Discrimination of Touch. — Touch the prong of a vibrating 
 tuning-fork lightly with the tip of the finger. The taps of the prong 
 on the skin do not blend into a continuous sensation even when the 
 fork vibrates several hundred times per second. 
 
 30. Temperature Sensations. — For the investigation of these, pieces 
 of thick copper wire, filed at one end to a blunt point, and fixed by 
 the other in a small wooden handle, may be used. They can be heated 
 in a sand-bath or in a beaker of water to the desired temperature, or 
 cooled in cold water or in ice. Or a metal tube drawn out at one end, 
 through which water at the required temperature can be passed before 
 use, may be employed. Another device is a metal cylinder ending in 
 a point, and filled with water at the given temperature. 
 
 (i) On the dorsal side of the hand outline an area of skin with a 
 pen or a coloured pencil. Divide this into areas of 4 square milli- 
 metres. Go over the area with a wire or cylinder at a temperature of 
 about 40° C, and determine the extent and position of the spots which 
 on contact yield a sensation of warmth, marking them on the skin by 
 ink-dots, or mapping them on ruled paper. Then repeat the ex- 
 ploration with points at a temperature of about 15° C, and map the 
 spots which yield a sensation of coolness. Now note whether a warm 
 spot touched with a pomt at 15" C. or a cold spot touched with a point 
 at 40° C, yields any temperature sensation. 
 
trifi THE SENSES 
 
 (2) Touch the skin with a test-tube containing water at 50° C, and 
 again with a test-tube containing ice. Do the sensations differ in any 
 way from those of pure warmtli and coohiess ? Repeat (i) with 
 teni])eratuics of 50° and 0°, and note wlictlicr there is any difierence 
 in the quaUty of the sensations yickled by tlie warm and cold spots. 
 When a cokl spot is touched with a point at a temperature of 50°, or 
 a warm spot with a point at a temperature of 0°, is any sensation 
 obtained ? If so, what ? 
 
 (3) Apply successively to one and the same j)ortion of the skin test- 
 tubes containing water at 50°, 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 
 5°, and 0° (ice), and determine the sensations excited in each case. 
 The contact should only be momentary, so as not to cause extensive 
 and lasting change of temperature of the skin. Note that there is a 
 certain range of temperature above and below that of the skin within 
 which no sensation of heat or cold is given. 
 
 (4) Take three beakers of water at 20°, 30°, and 40° C. respectively. 
 Place a finger of one hand in the coldest beaker, a finger of the other 
 hand in the warmest, until no definite temperature sensations are felt 
 by either finger. Plunge both fingers into the beaker at 30° C, and 
 temperature sensations will be perceived. 
 
 (5) Teyyiperature Discriminalion. — Find the least perceptible differ- 
 ence in temperature between two beakers of water at about 0° C. 
 Repeat the experiment with two beakers of water at about 30° C, and 
 again with two beakers of water at about 55° C. Use the same hand. 
 Expose the same amount of surface to the water. 
 
 (6) Compare the acuteness of the temperature sensations of the 
 skin and the mucous membrane of the mouth, touching a given portion 
 of skin and then a portion of mucous membrane with tubes containing 
 water at various temperatures. 
 
 31. Pain. — (i) Using a pin, explore a cutaneous area to determine 
 whether every point of the skin yields the painful sensation of pricking. 
 Especially compare the result of stimulating the region in the imme- 
 diate neighbourhood of the hairs with the spaces between hairs. Dis- 
 criminate the touch sensation given by the light contact of the pin-point 
 from the painful impression caused when the pressure is increased. 
 Note that the touch element is moie evanescent than the pain element. 
 
 (2) With strong v. Frey hairs determine the pressure at which the 
 sensation of touch passes into that of pain. 
 
 (3) Compare the .sensibility to pin-pricks of the mu( ous membrane 
 within the mouth with that of the skin. 
 
 32. Having determined the systolic blood-pressure in one arm of 
 a fellow-student (p. 113), release the pressure in tlie cutl. then raise 
 the hand in the air so as to empty the arm of blood, and while it 
 is still raised, get up a pressure in the cuff equal to the systolic })rcssurc. 
 Lower the hand and maintain this pressure by squeezing the bulb occa- 
 sionally. Be careful not to increase the pressure above the systolic 
 pressure. There is no disadvantage in letting it drop 5 to 10 milli- 
 metres below systolic pressure from time to time. Now compare the 
 acuity of the sensations of contact, pre.ssuie, warmth, cold, and pain 
 in the anicmic and the normal hand, always on symmetrically placed 
 areas of the two hands. Repeat the comparison at intervals till a 
 definite difference is found, and note the sensation for which the acuity 
 first diminishes. Do not prolong the experiment unduly. If the sub- 
 ject experiences discomfort, the pressure in the armlet is to be at once 
 released. 
 
CHAPTER XIX 
 REPRODUCTION 
 
 Regeneration of Tissues,- In lower forms of animals and in all 
 or most })lants, the power of regeneration is much greater than in 
 the higher animals and in man. A ninvt can reproduce an am- 
 putated toe, and every tissue — skin, muscle, nerves, bone — will be in 
 its place. After extraction of the crystaUine lens in triton larvae, 
 a new lens is formed from the iris epithelium. Artificial mouths 
 surrounded by tentacles can be formed in Cerianthus, an animal 
 belonging to the same group as the sea-anemones, merely by 
 making a cut in the body-wall and preveuting it from closing. In 
 an Ascidian, too {Cynone intestinalis) , artificial openings in the 
 bianchial sac, surrounded by numerous pigmented points similar 
 to the eye-spots around the natural mouth and anus, have been 
 produced (Loeb). A classical example of regeneration in inverte- 
 brates is that of the rays of starfishes after amputation. According 
 to some observers, this massive regeneration, as well as other in- 
 stances of the regeneration of complicated organs in invertebrates, 
 depends, in some degree at any rate, upon the nervous system. 
 
 Even in the higher animals regeneration of tissues is a common 
 phenomenon. Since cells are constantly dying within the body, 
 they must be constantly reproduced. In some tissues the process 
 by which this is accomplished is more evident, and therefore better 
 known, than in others. The most highly-organized tissues are 
 with difficulty repaired, or not at all. The epidermis is always 
 wearing away at its surface, and is being constantly replaced by the 
 multiplication of the cells of the stratum Malpighii. In the corneous 
 layer we have only dead cells; in the Malpighian layer we have every 
 histological gradation from squames to columns, and every physio- 
 logical gradation from cells which are about to die to cells that have 
 just been born. The corpuscles of the blood undoubtedly arise at 
 first, and are recruited throughout hfe, by the proliferation of 
 mother-cells. The gravid utenis grows by the formation of new 
 fibres from the old, and by the enlargement of both old and new. 
 A severed muscle is generally united only by connective or scar 
 tissue, but under favourable conditions a complete muscular 
 
 H17 
 
1 1 1 8 RE PROD UCTION 
 
 ' splice ' may be formed. A broken bone is regenerated by the 
 proliferation of cells of the periosteum, which become bone- 
 corpuscles. Gland cells — e.g., liver cells — are also, under certain 
 circumstances, capable of regeneration. Some of the most striking 
 instances of new formation of glandular tissues ha\'e already been 
 mentioned in connection with tlie growth of grafts of certain of the 
 endocrine organs {e.g., thyroid, adrenal cortex), when a physio- 
 logical insuthciency has been created by removal of the greater 
 portion of the organ (p. 648). There is no evidence that the influence 
 of the nervous system is a factor. It is doubtful whether there is any 
 new fonuation of nerve-cells in the adult organism, but peripheral 
 nerve-filires which have been destrcjyed by accident or operation 
 are readily regenerated, and the end-organs of efferent nerves may 
 share in this regeneration. 
 
 Thus, in a sense, reproduction is constantly going on within the 
 bodies even of the higher animals. But since the whole organism 
 eventually dies, as well as its constituent cells, a reproduction of the 
 whole, a regeneration en masse, is required. 
 
 A cell of the stratum Malpighii can only, so far as we know, 
 reproduce a similar cell, and this is characteristic of cells that have 
 undergone a certain amount of differentiation, especially in the 
 higher animals. The fertilized ovum, on the other hand, has the 
 power of reproducing not only ova like itself, but the counterparts 
 of every cell in the body. And this is only the highest development 
 of a power which is in a smaller degree inherent in other cells in 
 lower forms. Plants and the lowest animals are far lees dependent 
 upon reproduction by means of special cells. A piece of a Hydra 
 separated off artificially or by simple fission becomes a complete 
 Hydra, as was shown by Trembley a century and a half ago. A 
 cutting from a branch, a root, a tuber, or even a leaf of a plant, may 
 reproduce the whole plant. It is as if each cell in these lowly forms 
 carried within it the plan of the complete organism, from which it 
 built up the perfect plant or animal. 
 
 Reproduction in the Higher Animals. — ^In regard to the secretions 
 of the reproductive glands, all that is necessary to be said here is 
 that, unhke other secretions, their essential constituents are living 
 cells. The spermatozoa in the male have, indeed, diverged far from 
 the primitive type. Certain cells (spermocytes) in the tubules of the 
 testicle divide, each forming two daughter spermocytes. Each of 
 the daughter spermocytes in turn divides, so that four cells (sperma- 
 tids) are formed from each spermocyte. In the final division which 
 produces the spermatids a reduction of the chromosomes (p. 1122) 
 occurs, so that the spermatid possesses only one-half the number 
 characteristic of the somatic cells of the species. The spermatids 
 elongate and become spermatozoa, the head of the latter repre- 
 senting the nucleus of the former; and it is this nucleus (with the 
 
REPRODUCTION IN THE HIGH I. U ANIMALS 1119 
 
 middle pirce originally containing the male centrosome and attrac- 
 tion sphere, p. 5) wliich is tlie t-ssuntial contribution of the male to the 
 reproductive process. The tail of the spermatozoon is simply, from 
 the physiological point of view, a motile arrangement, whose function 
 it is to carry the nucleus of the male element, freighted with all that 
 the father can transmit to the offspring, into the neighbourhood of 
 the female reproductive element or ovum. After the spermatozoon 
 has penetrated the ovum its tail disappears, being probably 
 absorbed. The function of the accessory reproductive glands, the 
 prostate, the seminal vesicles, and Cowper's gland, are not well 
 understood. But the spermatozoa in the act of ejaculation are 
 mi.xed with the secretions of these glands, and therefore it is to be 
 supposed that they are of importance. When the prostate and the 
 seminal vesicles are removed in white rats, the female is no longer 
 fertilized, although the sexual power of the male is unaltered. The 
 testes apparently dexelop spermatozoa in the nomial manner, but 
 for some reason they either do reach the ovum or do not react 
 with it normally if they do reach it. When the testes are re- 
 moved from a young animal, the development of the prostate is 
 interfered with; in an adult animal the gland atrophies. 
 
 The ovum also begins as a typical cell with nucleus (germinal 
 vesicle), nucleolus (germinal spot), centrosome and attraction sphere, 
 and it forms, by its repeated subdivision, all the cells of the foetal 
 body. But, except in some {parthenogenetic) forms, it never 
 awakens to this reproductive activity till fecundation has occurred; 
 and fecundation essentially consists in the union of the male with the 
 female element, or rather in the union of the male and female nuclei. 
 
 From time to time a ripe Graafian foUicle, overdistended by its 
 hquor folliculi, bursts on the surface of the ovary and discharges an 
 ovum. It is probable that in the majority of mammals {e.g., the 
 cow, mare, sow, sheep, and bitch) ovulation, or the discharge of 
 the ovum, occurs spontaneously during oestrus (period of heat). 
 In others {e.g., the rabbit, ferret, and cat), it seems only to take place 
 as a result of copulation. Whether sexual intercourse has any in- 
 fluence upon ovulation in women can hardly be considered as settled. 
 The common opinion is that most ova are discharged spontaneously 
 at the time of the menstrual period, but some \vriters take the view 
 that the discharge bears no relation to menstruation. Only one 
 ovum seems to be shed each month. It was foimerly believed that 
 the fra\'ed or fimbriated end of the Fallopian tube, rising up finger- 
 like from the dilatation of its bloodvessels, grasps the ovum. But 
 it is more than doubtful whether this occurs. It is more probable 
 that the ovum is first discharged into the pelvic cavity, and 
 is guided to the orifice of the Fallopian tube, not necessarily 
 that of its own side, by the movements of the cilia around the 
 orifice, and then passed slowly along the tube by the downward 
 
1120 REPRODUCTION 
 
 lashing cilia which line it. Probably the ovum takes as a rule eight 
 or ten days to reach the uterus, and it is during this time that 
 fertilization takes place. If not impregnated, it soon perishes amid 
 the secretions of the utenjs — how soon has been matter of discussion, 
 and can hardly be considered as settled. If, however, impregnation 
 (Kcurs, the o\ um penetrating the superiicial e])ithelium into the 
 subepithelial connective tissue becomes hxed in one of the crypts or 
 pouches of the uterine mucous membrane {decidna serolina), which 
 grows round it as the decidna reflexa. The Graafian follicle, after 
 the discharge of the ovum, fills up with blood, and a cellular struc- 
 ture, the corpus luteum, is developed in its interior from cells in 
 the wall of the follicle. In the absence of iniprt gnation the corpus 
 luteum begins to disappear before the next menstrual period, and is 
 spoken of as a false corpus luteum. But when pregnancy occurs, it 
 continues to grow till the fourth or fifth month of pregnancy, and is 
 called a true corpus luteum. 
 
 Menstruation, — In the mature female, from puberty, the age at 
 which the reproductive power begins (thirteenth to fifteenth year), 
 on till the time of the menopause (fortieth to fiftieth year), at which 
 it ceases, an ovum — or it may be in some cases more than one — is 
 discharged at regular intervals of about four weeks. This discharge 
 is accompanied by certain constitutional symptoms and local signs 
 that last for a \'ariable number of days. The temperature of the 
 body diminishes somewhat, rarely more thi.n i° F., and there is 
 also a slight fall in the pulse-rate. The genit;i I organs are congested, 
 and a quantity of blood, which varies in diilerent individuals, but 
 is usually not over 50 c.c, is shed. If more than 60 c.c. is lost, the 
 fiow is copious. Over 100 c.c. it is abnormally great (G. Hoppa- 
 Seyler). At the same time, the whole or a portion of the mucous 
 membrane of the uterus is cast off. 
 
 As to the physiological meaning of this menstruation, as it is 
 called, opinion is divided. Two chief theories have been proposed 
 to account for it, both of which agree in considering the phenomenon 
 to be connected with a preparation of the uterus for the reception 
 of the ovum. But according to the theory of Pfliiger, the mucous 
 membrane is stripped off (by a process analogous to the ' f eshening ' 
 or paring of the indurated edges of a wound by the surgeon, in 
 order that nnion may occur when they are brought together) on 
 the chance, so to speak, that an impregnated ovum may arrive. On the 
 alternative theory, this change takes place because the ovum has not 
 been impregnated, and the bed prepared for it not being required, 
 the swollen and congested uterine mucous membrane undergoes 
 degeneration, and is in part cast off (Keichert, Williams, etc.). 
 However this may be, it is now pretty generally agreed that the 
 degenerative process involves only the superficial portion of the 
 mucosa, and not its whole thickness. 
 
MENSTRUATION tt2t 
 
 The process of menstruation, and the nutrition of the genital 
 organs, espcciallv the uterus, are intimately dependent upon the 
 ovaries. There is good evidence that the influence is exerted through 
 an internal secretion formed by some portion of the ovarian sub 
 stance. When, for instance, the ovaries of young animals (guinea- 
 pigs) are removed from tlieir normal situation and transplanted to 
 a distant part of the body, the external genitals, vagina, and uterus 
 undergo the normal development instead of being arrested in their 
 growth, as is the case when the ovaries are removed altogether. The 
 removal of the ovaries in adult animals leads to tibrous degeneration 
 of uterus and Fallopian tubes. On the other hand, removal of the 
 items has no effect on the development of the ovaries in a young 
 animal, and does not cause degeneration of the ovaries of an adult 
 animal. In monkeys, in which a menstrual flow comparable to that 
 in the human female occurs, it was found that menstruation took 
 place after the ovaries had been transplanted from their original seat, 
 and the flow stopped when the transplanted ovaries were removed. 
 The view has been put forward that the important part of the ovary 
 for these functions is the corpus luteum, which is considered to be 
 a gland with an internal secretion (Born). This secretion seems 
 to be connected with the implantation of the ovum and the sub- 
 sequent growth of both ovum and uterus. According to Fraenkel, 
 the absence of the corpus luteum prevents implantation. The 
 experiments of Marshall and Jolly also indicate that the corpus 
 luteum forms some substance, which exerts an action on the uterine 
 mucosa, during the earher stages of pregnancy. When the ovum 
 has not been fertilized the corpus luteum brings about menstruation. 
 Where fertiHzation has occurred it prepares the uterus for the im- 
 plantation of the ovum. It is generally considered that as regards 
 their origin there is no difference between the true and the false 
 corpora lutea. 
 
 The mode of origin of the corpus luteum has given rise to much 
 discussion. Two chief views have been put forward: (i) That it is 
 a structure derived from certain large epithelium-like cells (theca 
 cells) in the connective-tissue wall (theca) of the discharged folUcle 
 (v. Baer, et al.) ; (2) that it is developed from the folHcuIar epitheHum 
 (membrana granulosa) (Sobotta, et al.). The first view seems to be 
 best established. The theca cells multiply and grow into the cavity 
 of the discharged folhcle. Their yellowish colour is due to the 
 presence in them of lipoid droplets. 
 
 The influence of the ovary on the formation of the decidua has 
 been illustrated in a very interesting way by the investigations of 
 L. Loeb on the artificial production of deciduomata. He has shown 
 that if a number of incisions are made into the uterus of a rabbit or 
 guinea-pig within a certain interval after the oestral period (period of 
 heat), a structure with the histological characters of the decidua 
 
 71 
 
1122 REPRODUCTION 
 
 develops at each wound. Impregnation does not appear to be a 
 necessary factor, nor even contact of tlic o\uni with the uterine 
 mucous membrane. On the other hand, ovulation, the discharge of 
 an ovum or ova, or at any rate the condition of the ovary associated 
 with this discharge, seems to be indispensable. For extirpation of 
 the ovaries in a large number of guinea-pigs prevented the formation 
 of deciduomata from wounds of the uterus made at the most favour- 
 able period after copulation. Tlie uterus then appears to have an 
 inherent power of responding to such a stimulus as a mechanical 
 injury by the production of a decidual structure, but only under the 
 influence of the ovary. The ovarian factor is probably not nervous 
 but chemical, some specific substance which acts on the uterus 
 being liberated periodically in connection with the sexual rhythm. 
 Development of the Ovum. — Before fecundation, and apparently 
 as a preparation for it, the ovum is the seat of remarkable changes, 
 similar upon the whole to those seen in the mitotic or indirect 
 division of ordinary cells.* They have been most fully studied in 
 the eggs of certain invertebrate animals. 
 
 The di\ision of the cell is initiated by changes in the centrosome and 
 attraction sphere. The centrosome divides into two daughter centro- 
 somes. These take up a position one at each pole of the nucleus. 
 Each daughter centrosome is surrounded by a system of radiating lines 
 or filaments, which are less conspicuous than the chromatin filaments 
 of the nucleus, since they do not stain as these do. Meanwhile the 
 nuclear membrane and the nucleoli disappear, or at any rate become 
 indistinguishable from the rest of the chromatin skein. The skein 
 breaks up into chromosomes, the number of which is constant for a given 
 species, but is not the same in all species of animals. 
 
 The daughter centrosomes or astrospheres are united by. meridional 
 achromatic fibres, which form a spindle running through the nucleus 
 from one pole to the other. The chromosomes arrange themselves at 
 right angles (equatorially) to the spindle, and then each chromosome 
 divides longitudinally into two. The halves of the chromosomes now 
 pass toward their respective centrosomes, being perhaps guided by the 
 fibres of the spindle. It results from this that two daughter nuclei are 
 formed, each with the same number of chromosomes as the original 
 nucleus, although with only half the amount of chromatin. The cyto- 
 plasm divides also, so that the parent cell is now represented by two 
 daughter cells. In ordinary cell division the two daughter cells are of 
 equal size, but in the division of the ovum which occurs before fertiliza- 
 tion the two resulting cells are verv unequal. The large cell continues 
 to be kno\\Ti as the ovum; the small one is the first polar body. After 
 extrusion of the first polar body the ovum again divides unequally. A 
 new spindle forms, and a second polar body, again much the smaller of 
 the two daughter cells, is cast off. There is a difference, howeve*, 
 between the process of division which gives rise to the first and that 
 which gives rise to the second polar body. In the case of the latter a 
 so-called reduction-division occurs; the chromosomes do not split longi- 
 tudinally, but half of the original number pass into each daughter 
 nucleus. As to the significance of these changes there has been much 
 discussion. It is agreed that the result of the process is the expulsion 
 * For figures illustrating the changes, bee any good textbook of Histology. 
 
DEVELOPMENT Of THE OVUM 1123 
 
 of a portion of the chnjnialiii, the ovum lunv possessing only half the 
 original nnmber of chromosomes, although nearly all the origmal 
 cytoplasm. In fertilization the original number is restored by the male 
 element when it arrives and penetrates the ovum. For in the final cell 
 division by which the mature spermatozoon is formed the chromosomes 
 of its nucleus arc also, after two divisions essentially similar to those 
 occurring in maturation of the ovum, reduced to half the normal number. 
 The two reduced nuclei in the fertilized ovum are spoken of as the 
 male and female pronuclei. By their union a single nucleus is formed 
 with the number of chromosomes normal to the species. 
 
 An enormous amount of interesting work has been done with the 
 view of iUustrating the connection of the compHcated phenomena 
 described with the structure of the ovum. Only a bare reference 
 to one or two of the experiments is possible here. Driesch and 
 Hertvvig find that the nucleus can be made artificially to change its 
 place with reference to the yolk, without hindering the development 
 of a normal animal. Lilhe has shown that centrifugalization of the 
 eggs of annelids, although it markedly alters the distribution of the 
 yolk and other substances, does not affect the form of cleavage. 
 The polar bodies appear in the position which they would normally 
 occupy. In other words, no redistribution of the granules or nucleus 
 affects the polarity of the egg, which therefore is a function or 
 property of the ground substance of the protoplasm. The whole 
 of the protoplasm, however, is not necessary for complete develop- 
 ment. Even in Amphioxus, the lowest of the vertebrates, the 
 eggs have been broken up by shaking, and a complete animal 
 evolved from as little as one-eighth of an ovum. If the separation 
 was incomplete a kind of Siamese twins, or even triplets, could be 
 obtained (Wilson and Mathews). Nor is it always indispensable 
 that both pronuclei should be present. 
 
 Parthenogenesis. — Attempts have been made to separate the 
 constituents of spermatozoa which are essential to fertilization. 
 From the sperm of a sea-urchin a substance can be extracted by 
 strongly hypotonic salt solutions, containing ether, which acts as a 
 powerful fertilizing, agglutinating, and cytolyzing agent upon the 
 eggs. It is soluble in dilute acid, and is probably identical with a 
 fertihzing agent called oocytase present in blood-serum (Robertson). 
 Whatever it is that the spermatozoon suppHes, the process of 
 fertilization can in certain forms be started artificially in the absence 
 of spermatozoa or any of their constituents. The studies of Loeb 
 and his pupils on artificially induced parthenogenesis are of special 
 importance. When the unfertiHzed eggs of the sea-urchin are 
 exposed for one or two minutes to 50 c.c. of sea-water, to which 
 3 or 4 c.c. of decinormal acetic acid has been added, the majority of 
 the eggs form the membrane characteristic of the entrance of the 
 spermatozoon. When these eggs are afterwards exposed for thirty 
 to forty minutes to 100 c.c. of sea-water, to which 14 or 15 c.c. of a 
 strong solution of sodium chloride (two and a half times the strength 
 
11.-4 REPRODUCTION 
 
 of a normal solution, or about 14-6 per cent.) has been added, those 
 of the eggs which have formed membranes develop into swimming 
 larvas that rise to the surface. These larvas develop into perfect 
 sea-urcliin larvas or ' plutei ' as fast as the larvas of eggs fertilized 
 with sperm. It has lately been shown that pricking oi tiie unfer- 
 tilized egg of a frog with a needle suffices to induce normal develop- 
 ment of the egg (Bataillon). These parthenogenetic frogs have been 
 successfully reared, and apparently are all males (Loeb). These 
 observations have an important bearing on the question of the deter- 
 mination of sex. In the frog it would seem that the eggs are all 
 alike, since in the absence of a spermatozoon only one sex (the male) 
 is developed. The male frog is hetero-gametic for sex — i.e., there 
 are two kinds of spermatozoa, one with and the other without a sex 
 chromosome. If a spermatozoon of the former type enters an egg, 
 a female is produced. If a spermatozoon of the latter type, or no 
 spermatozoon at all, enters an egg, a male is produced. 
 
 It is impossible to enter here into a discussion of the factors which 
 determine sex. While due weight must be given to such morphological 
 distinctions as sex chromosomes in the gametes (or sexual reproductive 
 elements), evidence has been adduced that the fundamental factor may 
 be chemical and metabolic pecularities in the gametes. In pigeonse .g., 
 — in which the female is the hetero-gametic sex, producing two kinds 
 of eggs — it has been shown that the egg which is to develop a female 
 is characterized by a lower metabolism, a lower percentage of water 
 and a higher total content of fat and phosphorus or of phosphatides, 
 than the egg which is to develop a male. There are indications that by 
 changing these chemical conditions sex can be to some extent controlled 
 (Whitman, Riddle). 
 
 The facts of parthenogenesis show that it is not absolutely neces- 
 sary for development that the ovum should have the normal number 
 of chromosomes restored. It can develop with half the number, the 
 chromosomes of the female pronucleus being sufficient for growth, 
 although, of course, in this case for a growth uninfluenced by the 
 properties of the male element. In like maimer it is stated that 
 portions of the maturated ovum devoid of a nucleus can undergo 
 development if penetrated by a spermatozoon, the chromosomes of 
 the male pronucleus being sufficient for growth. 
 
 Formation of the Embryo.- — Not till all these c\ tnts have taken place 
 — extrusion of the two polar bodies, or maturation ; penetration of the 
 spermatozoon, and blending of its head (the male pronucleus) with the 
 remnant of the nucleus of the ovum (female pronucleus), or fecundation 
 — not till then does the ovum begin the process of repeated division by 
 which the whole body is reproduced. The fused or segmentation nucleus 
 divides into two, each containing the normal number of chromosomes 
 derived from the splitting of those contributed by both the male and 
 female elements. It is believed that the division takes place in such a 
 way that both male and female chromosomes are represented in each 
 nucleus. The cytoplasm being also cleft by a corresponding furrow. 
 
FORMATIOX OF THE EMBRYO 1125 
 
 two complete nucleated cells make their appearance. These divide in 
 turn, till at length (in the mammal) the embryo is represented by a 
 hollow sphere or vesicle, with a cellular crust. During division the 
 upper or outer cells have always been larger than the inner and lower, 
 and have multiplied more rapidly; and thus it comes about that the 
 hollow sphere of large cells encloses a mass of smaller cells, along with 
 remnants of broken-do\\-n yolk and of fluid derived by absorption from 
 the contents of the uterus. The smaller cells continue to multiply and 
 arrange themselves as a lining to the sphere already formed, so that in a 
 short time it becomes double, and we have already differentiated two of 
 the primary' embryonic layers — the ectoderm, also called the epiblast, or 
 superficial, and the endoderm, also called the hypoblast, or deep layer. 
 The whole sphere is called the blastoderm, or the blastodermic vesicle. 
 
 WTiile this inner shell of endodermic cells is gradually creeping on to 
 completion, there appears at a part where it is already fully formed a 
 small opaque whitish disc, the germinal area or embryonal shield. This 
 represents the stocks on which the framework of the embr^'O is to be laid 
 down. The area elongates; at its posterior end appears a thickened 
 line, the primitive streak, soon furrowed by a longitudinal groove, the 
 primitive groove, that marks the direction in which the long axis of the 
 future embr\'0 ^-ill lie, but is not itself a permanent line in the building, 
 and ultimately vanishes. The appearance of the primitive streak is the 
 signal that a rapid proliferation of the cells of the germinal area, and 
 especially of the ectoderm, has begun ; and this goes on until a third layer 
 is formed, intermediate in position to the original two, and therefore 
 named the mesoderm. WTiile this is pushing its way over the germinal 
 area and into the rest of the blastodermic vesicle, the ectoderm in front 
 of the primitive streak rises up in two lateral ridges, enclosing between 
 them the medullary groove. The medullary groove is the beginning of 
 the cerebro-spinal axis; its walls first come to overhang the furrow, and 
 then to coalesce; and the medullary groove has now become the neural 
 canal. Immediately under it the mesoderm forms a rod of cells, the 
 notochord, which is the forerunner of the vertebral column ; around this 
 the bodies of the vertebrae are afterwards de\'eloped from cubical masses 
 of mesodermic cells, arranged in pairs alon.-; the notochord, and called 
 the protovertehrcB. The rest of the mesoderm, running out on each side 
 from the proto vertebrae, splits into two layers, an upper or somatic layer, 
 which unites with the ectoderm, forming with it the somatopleure, and 
 a lower or splanchnic layer, which unites with the endoderm to form 
 the splanchnopleure. Between the somatopleure and the splanchno- 
 pleure is a space called the coelom, or pleuro-peritoneal cavity (Fig. 485). 
 The layer of ectoderm which envelops the whole (termed the tropho- 
 blast, from its nutritive function), in conjunction with the underlying 
 mesoderm, represents the prechorion, the early stage of the chorion. 
 
 Up to the present, apart from the enclosure of the neural canal, all this 
 formative activitv is buried beneath the surface of the blastoderm, and 
 has not showed itself bv any external token ; the embryo still appears as 
 a portion of the germinal area, and lies in its plane. But now a pocket, 
 or crease, or moat, beginning at the head as the head-fold, then pushing 
 under the tail, gradually creeps round and undermines the whole 
 embryo, which is raised above the general level, and, as it were, scooped 
 out from the rest of the blastoderm; till at length it lies on the latter, 
 something like an upturned canoe, enclosing a tube, complete in front 
 and behind, but still open in the middle, where it communicates with 
 the interior of the yolk- vesicle. Since this tube has been formed by the 
 tucking in of the three ancestral layers of the blastoderm, it follows that 
 it is lined by endoderm, supported externally by the splanchnic sheet 
 
1 1 26 REPRODUCTION 
 
 of mesoderm. So that now tlit- body consists of a dorsal tube ithe 
 neural canal), essentially of ectodermic origin, a ventral tube (the 
 alimentar\' canal), essentially of endodermic origin, and between the 
 two a massive double layer of mesodcrmic tissue, which contributes 
 supporting elements to both. At this point it mav be well to emphasize 
 the fact that this embr\ological distinction of the three primitive layers 
 has a deep and fundamental meaning, and corresponds to a physiological 
 distinction that endures throughout life. The endoderm, the lowest 
 layer in position, may also be described as the lowest in the physiological 
 hierarchy. It furnishes the epithelial lining of the alimentary canal 
 from the beginning of the oesophagus to near the end of the rectum, as 
 well as the epitlielium of the organs which arise from diverticula of the 
 primitive intestine — viz., the digestive glands (with the exception of the 
 salivary glands), the lungs, and the passages leading to them, the 
 thyroid, and the greater part of the thymus gland in its primitive con- 
 dition before th? lymphoid tissue derived from the mesoderm has as 
 yet grown into it. According to some authorities, the notochord is also 
 derived from the endoderm. 
 
 Upon the whole, it may be said that the tissues of endodermic 
 origin are essentially concerned in chemical labours, in the absorption 
 of food material ?nd excretion of waste products. The mesodermic 
 tissues are essentially concerned in mechanical labour; they are the 
 tissues of movement and of passive support. The ectodermic tissues 
 are at the top of the pyramid ; they govern the rest. 
 
 From the mesoderm arise the muscles, the entire vascular system, 
 with its blood- and lymph -corpuscles, the bones and connective tissues; 
 and the Wolffian body and its appendages, which are the predecessors 
 of the genital glands and ducts, and of the chief portion of the renal 
 apparatus. 
 
 The ectoderm forms the epidermis and its appendages, the epithelial 
 end-organs of the nerves of special sense, and the nervous system, 
 cerebro-spinal and sympathetic. The salivan,- glands and the raucous 
 lining of the mouth and anus are developed from the ectoderm, which 
 is indented to meet the intestinal canal and give it access to the exterior 
 at either end. 
 
 It is not possible here to trace in detail the development of all the 
 organs of the embr\-o. Its nutrition and metabolism not only dis- 
 tinctly belong to the physiological domain, but, carried on as they are 
 under conditions that seem so strange, and even so bizarre, to one 
 acquainted onlv with adult physiology, are calculated to throw light 
 on the metabolic processes of the fully-developed body. And they 
 cannot be understood without reference to the peculiarities of the 
 vascular svstem in foetal life. These we shall accordingly describe, but 
 for further details as to the anatomy of the embr\'o the student is 
 referred to some standard anatomical textbook, such as Quain's 
 ' Anatomv.' 
 
 Development of the Connections between the Embryo and the 
 Uterus. — In the first period of its development the ovum, nc-stling in 
 the pouch formed by the decidua serotina and reflexa, Is fed from the 
 maternal blood and tissues directly, without the mediation of foetal 
 bloodvessels, through the finger-like processes or villi with which its 
 external layer, the zona pellucida, becomes studded. At the earliest 
 stage at which a human oxnim has been studied after implantation it is 
 already enveloped by a thick ectodermic covering (the trophoblastic 
 envelop>e), consisting of two layers of cells, one unquestionably of foetal 
 origin, the so-called cells of Langhans, and the other the SNTicytium, the 
 origin of which is assigned by some authorities to the ovum, by other» 
 
FORMATION OF THE EMBRYO 
 
 1127 
 
 to the maternal tissues The trophoblastic covering is everywhere in 
 contact with the maternal blood, w-liich, pushing its way into tlie tropho- 
 blast at intervals, divides it into columns. Later on the foetal mesoderm 
 grows into these, and so the primary chorionic villi are formed. It is 
 not till after the first three weeks that bloodvessels make their way into 
 these villi, although the mesoderm of the foetus begins to enter the villi 
 about the end of the first, or the beginning of the second, week. The; 
 scanty yolk of the human 
 
 line of union 
 
 -prechorion 
 embryo 
 -^ — amnion 
 
 -somatopleure 
 •coetom 
 
 splanchnopieure 
 
 Fig. 4S'. — Showing the Folds of the Somatopleure 
 in a Bird's Ovum uniting over the Embryo 
 and becoming demarcated into Amnion and 
 Prechorion (Keith). 
 
 ovum IS totally inade- 
 quate to supply it with 
 nutriment for the time 
 that elapses before the 
 bloodvessels are devel- 
 oped, and food sub- 
 stances must be obtained 
 from the maternal liquids 
 by imbibition, osmosis, 
 diffusion, or filtration, 
 aided, perhaps, by more 
 special absorptive pro- 
 cesses on the part of the 
 foetal tissues. Soon the 
 heart appears as a tube 
 (at first double), formed 
 by cells belonging to the 
 splanchnic layer of the 
 mesoderm. It begins to 
 pulsate in the chick as 
 early as the middle of the 
 second day, although it as 
 
 yet contains neither nerve-cells nor fuUy-formed muscular fibres. In 
 the mammal pulsation is late in making its appearance, in man about 
 the beginning of the third week. A bloodvessel grows out from the 
 anterior end of the heart and divides into two primitive aortic arches, 
 from each of which a vessel (omphalo-mesenteric cr vitelline artery) runs 
 out in the mesoderm covering the umbilical vesicle, or yolk-sac. The 
 blood is returned to the heart by the vitelline veins coursing in on the 
 walls of the vitelline duct. In this way the store of nutriment in the 
 umbilical vesicle of the chick, which is the only solid or liquid food it 
 receives or needs during the whole period of development, is tapped, 
 and a regular channel of supply established. Oxygen is at the same 
 time absorbed through the porous shell; but later on this respiratory 
 function is taken over by the second or allantoic circulation. In the 
 mammal the circulation on the umbilical vesicle is of much less conse- 
 quence, for the quantity of material left over after the formation of the 
 blastoderm is exceedingly small; it is only with a few days' provision 
 in its haversack that the embryo starts out on its developmental march. 
 And the vitelline vessels deriving their further supply of food and 
 oxygen from the tissues of the mother in contact with the ON-um cease 
 to be of use as soon as the second and more perfect placental circulation 
 is established, and soon shrivel up and disappear, as the umbilical 
 vesicle shrinks. 
 
 The second circulation of the embryo is developed in connection with 
 a remarkable offshoot from the hind-gut called the allantois, which, 
 before the fifth day in the chick and during the second week in man, 
 pushes its way out between the somatic and splanchnic layers of the 
 mesoderm — i.e., in the pleuro-peritoneal cavity — and grows through the 
 
II28 
 
 liEPRODUCTIOS 
 
 umbilicus, carr\ing bl<;odvessels along with it in its mesodcrmic layer. 
 Still earlier, and, indeed, while the embryo is beinf,' separated off from 
 
 and raised above 
 the level of the rest 
 of the blastoderm 
 by the deepening 
 nf the ditch around 
 it, the further 
 banks of this fur- 
 row, formed of 
 ectoderm and 
 somatic mesoderm, 
 have risen up on 
 every side, and, 
 growing over the 
 back of the em- 
 bryo, have finally 
 coalesced and en- 
 closed it in a 
 double- walled 
 pouch (Fig. 4851. 
 The superficial 
 layer of the pouch 
 is called the false 
 amnion ; it soon 
 blends with the 
 tufted chorion or 
 common outer 
 envelope of the 
 o\-um. The inner 
 layer jjersists as 
 the true amnion ; a 
 liquid, the ammotic 
 fluid, 16 secreted in the cavity which it encloses; and the embryo, loosely 
 anchored for the rest of its intra-uterine life by the umbilical cord alone, 
 floats freely within it. The amniotic fluid acts as a water-jacket or 
 cushion, to break the force of the inevitable shocks and jars transmitted 
 from the mother to the foetus and from the foetus to the mother. To 
 some extent, in addition, it may serve as a nutritive fluid, for substances 
 can pass from the blood of the mother into the amniotic fluid, and the 
 amniotic fluid can be swallowed by the fcjetus. This is shown by the 
 fact that sodium sulphindigotate, when injected into the maternal 
 circulation, is found in the amniotic fluid and in the alimentary canal 
 of the foetus, although not in any of the foetal tissues. Fine lanugo 
 hairs from the foetal skin have also been found in the meconium. 
 
 The precise origin and manner of formation of the amniotic fluid 
 have not been puttied. It is probably in the main a maternal secretion 
 or transudation. But something is contributed by the foetus in tlie 
 form of renal, and perhaps of skin, secretions. The fluid is poor in 
 solids. Its maximum content of protein, reached during the first half 
 of pregnancy, is only 0-7 per cent. Later on it diminishes, and at full 
 term is only one-tenth of this amount. The specific gravity is 1006 to 
 1009. Its osmotic concentration, as measured by the depression of the 
 freezing-point, is less than that of the mother's blood-serum. 
 
 The allantois, growing out at the umbilicus, in the manner described, 
 insinuates itself between the true and false amnion, and soon blends 
 with the latter. For a time the secretion of the primitive kidneys 
 continues to be poured into the cavity of the allantois, so that it serves 
 
 Fig. 435 — Diagram to illustrate Formation of Amnion and 
 Allantois. A, cavity of true amnion; F, F', folds about 
 to coalesce and complete the amniotic cavity; m, meso- 
 dcrmic layer of amnion; B, allantois; I, intestinal cavity 
 of embryo; Y, yolk-sac; h. endodermic layer; e, ecto- 
 dermic layer of embryo. The embryo is the shaded por- 
 tion in the middle of the figure. E is placed over the 
 head region. Xo attempt is made to delineate its actual 
 form. The mesoderm is represented by the interrupted 
 line. 
 
NUTRITION OF THE EMBRYO 1129 
 
 in pa'-t as an excretory organ, while in the bird it also performs the 
 function of respiration ; anil in the mammal brjth food anu oxygon arc 
 carried by its vessels to the f<i;tus during the greater part of intra- 
 uterine life. But later on the outgrowth atrophies and disappears, all 
 except its origin from the alimentary canal, wriich dilates and persists 
 as the urinary bladder, and its bloodvessels, which grow in the form, of 
 tufts or loops into the chorionic villi. The vessels are fed by two 
 umbilical arteries which arise from the hypogastric arteries and run out 
 at the umbilicus on the allantois. The blood is returned by an umbilical 
 vein, whose further course we shall have soon to trace. The shrivelled 
 stalk of the allantois, projecting through the umbilicus, takes part, with 
 its bloodvessels, in the formation of the umbilical cord, which contains 
 also the remains of the yolk-sac and is clothed externally by a layer of 
 the amnion. Continuous with the umbilical cord, and stretching from 
 the umbilicus to the urinary- bladder, is a portion of the allantois which 
 is represented in extra-uterine life by a thin cord-like structure, the 
 urachus. The vascular tufts of the chorion, which at first cover the 
 whole surface of the ovum and suck up food and oxygen from decidua 
 serotina and reflexa alike, disappear in the region of the reflexa, hyper- 
 trophv all over the serotina — that is, where the o\'um is in actual contact 
 with the uterine wall— and this part of the chorion is now distinguished 
 as the chorion frondosum. The giant villi of the chorion frondosum 
 push their way into the thickened decidua serotina, and ultimately 
 penetrate into the great capillaries or sinuses of the uterine mucous 
 membrane. At the same time the tissue of the villi external to the 
 vessels becomes reduced to a mere film, so that, except for a thin cover- 
 ing of decidual cells, the foetal vessels are bathed in maternal blood. 
 By this interweaving of decidua and chorion frondosum is formed the 
 placenta, which for the rest of intra-uterine life acts as the great 
 respiratory, alimentary, and excretory organ of the foetus. 
 
 Exchange of Materials in the Placenta. — ^The maternal blood, as 
 it streams through the colossal capillaries of the decidua, gives up 
 to the foetal blood oxygen and food substances and receives from it 
 carbon dioxide and in all probability lurea. It is true that the blood 
 in the uterine sinuses is not itself fully oxygenated; it is not bright 
 red arterial blood. But it yet contains more oxygen, and oxygen at 
 a higher partial pressure (p. 247 ), than the purest blood of the fcetus, 
 and is, therefore, able to part with some of the surplus to the dark 
 stream of oxygen-impoverished blood brought by the umbilical 
 arteries to the placenta. Thus, it has been found that while the 
 blood of the umbilical artery of the foetus of a sheep had 47 volumes 
 per cent, of carbon dioxide, and only 23 of oxygen, that of the 
 umbilical veins had 6*3 volumes of oxygen, and only 40 5 of carbon 
 dioxide (Zuntz and Cohnstein). In the exchange of gases between 
 the placental and the foetal blood the same general features present 
 themselves as in the external and internal respiration of the mother, 
 with this difference, that the exchange of oxygen is neither between 
 air and haemoglobin, as in the lungs, nor between hemoglobin and 
 tissue elements, as in the organs; but between maternal and foetal 
 haemoglobin, of course, through the mediation of the maternal and 
 fcetal plasma. There is no reason to suppose that the mechanism 
 
1I30 REPRODUCTION 
 
 of the exchange is essentially different from that of the more famiUat 
 forms of respiration. Diffusion of the gases from places of higher 
 to places of lower tension unquestionably plays an important 
 part. But this does not exclude the possibility of a more active 
 process of some other kind, although there is at present no direct 
 evidence of such a gaseous secretion as has been previously discussed 
 in connection with pulmonary respiration (p. 262). The presence of 
 oxydases in the placenta does not throw any light on the question. 
 For there is no proof that they act in transferring oxygen from the 
 one circulation to the other, and oxydases are found in the most 
 diverse tissues. Their significance for the combustion processes of 
 the body has already been alluded to (p. 271 ). 
 
 Salts soluble in water, including not only those necessary for 
 nutrition, like sodium chloride, but many foreign salts, pass readily 
 from the placenta to the foetus, and in general more easily the lower 
 their molecular weight. Such salts as potassium iodide, e.g., when 
 injected into the maternal circulation, appear in the foetus in a very 
 short time. On the other hand, colloidal solutions — e.g., of silver 
 or silicic acid — do not pass over at all. It is of practical importance 
 that substances like chloroform, ether, and other narcotics, and alka- 
 loids likemorphine and scopolamine, when administered in obstetrical 
 practice, may find their way from the mother to the child, although 
 more slowly and more capriciously than the salts. While diffusion 
 and osmosis assuredly take part in the passage of materials from the 
 placenta to the foetus, there is no more reason to conclude that the 
 whole exchange, even for the salts, depends upon such simple physical 
 processes than there is in the case of the exchange between any one 
 of the maternal tissues and the maternal blood. The essential 
 similarity of placental and intestinal absorption, to take one instance, 
 is seen in the mechanism by which the foetus gains the iron required 
 for the development of its haemoglobin. The haemoglobin of the 
 mother appears to be the most important source of this iron. 
 Erythrocytes in all stages of decomposition can be found in con- 
 tact with the chorionic villi, and even in the epithelium covering 
 the villi. These corpuscles come partly from extravasations in 
 the maternal portion of the placenta, but it is possible that the 
 villi also possess the power of haemolyzing intact corpu3cles in the 
 circulatm'^ placental blood. Iron can be demonstrated by micro- 
 chemical reactions in the epithelial cells of the chorionic villi as fine 
 granules, which increase in size towards the base of the cells. As we 
 pass deeper into the villus towards its central bloodvessel, the 
 granules again diminish in size. The picture is very like that seen 
 in the absorption of iron from the intestine. And if the micro- 
 chemical picture is practically the same, the process by which the 
 iron is absorbed is not likely to be fundamentally different in the 
 two cases (p. 447). 
 
NUTRITION OF THE EMBRYO 1131 
 
 The same is true of the passage of fat acfoss the placenta. Fat 
 can always be demonstrated microchcniieally in the chorionic villi. 
 The most superficial layer of tin; villi is free from visible fat droplets. 
 They increase in numl)er towards the base of the epithelial cells. 
 As in the case of the intestine, these appearances agree well with 
 the view that the fat is split before being absorbed by the villi, and 
 undergoes resynthesis in the epithelium. That, as a matter of fact, 
 fat passes from the mother to the foetus is shown by the observation 
 that when pregnant guinea-pigs were fed with a foreign fat (from 
 cocoanuts), the characteristic fatty acid (lauric acid) was found in 
 the foetus. This, however, does not exclude the possibility that the 
 foetus may form fat in its own tissues from carbo-hydrates, and 
 perhaps from proteins, as it is destined to do in extra-uterine life. 
 
 Among the carbo-hydrates the passage of dextrose from the 
 maternal to the foetal blood has been experimentally demonstrated 
 A specially interesting proof is afforded in cases where the mother 
 suffers from diabetes mellitus. In one case in which the mother, 
 during diabetic coma, was delivered of a stillborn child, the blood 
 of the child contained 2-2 per cent, of sugar, its urine 5-24 per cent., 
 and the amniotic fluid 047 per cent. The blood of the mother had 
 a sugar content of o-8 per cent., and her urine a content of 6-94 per 
 cent. The sugar of the maternal blood is not the only source of the 
 carbo-hydrates of the foetus. The glycogen store of the placenta is 
 to be regarded as a second source, which is rendered available on 
 conversion into dextrose by the placental diastatic ferment. This 
 store of easily available food material is especially important in the 
 early stages of development of the ovum before a circulation has 
 been established in the villi. In the youngest ova investigated the 
 decidual covering has been found rich in glycogen. 
 
 While it is to be supposed that the products of the hydrolytic 
 decomposition of proteins can be absorbed by the foetal blood in its 
 passage through the placenta, to be synthesized to the appropriate 
 tissue proteins in the foetal organs, there is evidence that certain 
 proteins can be taken up without change. In this connection it 
 must be remembered that the mother is much more closely related 
 to the foetus as regards her protein composition than any ordinary 
 protein food can be to an animal in extra-uterine life. In some 
 respects, indeed, the foetus may be considered, especially, perhaps, 
 in the first stages of its development, as a part of the mother, an 
 additional, although very complex, organ rather than an independent 
 organism. 
 
 The blood of the umbilical artery, although far from the level of 
 the ordinary arterial blood of the mother as regards its gaseous 
 content, is yet the best the foetus ever gets; and by a series of con- 
 trivances it is assured that this best should go first to the most 
 important parts — the liver, the heart, and the head — ^while the legs 
 
II ?2 REPRODUCTION 
 
 and most of tlic abdominal organs have to put up with an inferior 
 supply. This is brought about mainly by the existence ot three 
 short-cuts for the blood, which disappear in the adult circulation, the 
 ductus venosus, the ductus arteriosus, and the foramen ovale. 
 
 The blood of the umbilical vein, rich in oxygen for foetal blood, 
 passes partly through the circulation of the liver, but a part takes 
 the route of the ductus venosus, and empties itself into the inferior 
 vena cava. The latter gathers up the more or less vitiated blood 
 from the inferior extremities and the renal and hepatic veins, and 
 pours its mixed, but still fairly oxygenated, contents into the right 
 auricle. By means of the Eustachian valve, the jet coming from 
 the mouth of the inferior vena cava is directed into the left auricle 
 through the foramen ovale in the inter-auricular septum. There 
 it is joined by the trickle of blood which is creeping through the 
 unexpanded lungs. The left ventricle propels its contents through 
 the aorta, and thus a large part of this comparatively pure or 
 second-best blood is sent to the head and upper extremities. It 
 returns in a vitiated state by the superior vena cava into the right 
 auricle, and owing to the position of the Eustachian valve and the 
 direction of the current, it flows now, not through the foramen ovale, 
 but into the right ventricle. Thence it is driven through the pul- 
 monary artery, but only a small quantity of it finds its way through 
 the lungs; the main stream is short-circuited through the ductus 
 arteriosus, and mingles with the contents of the thoracic aorta 
 below the origin of the cephalic and brachial vessels. 
 
 We may now give something more of precision to the statements 
 that different parts of the body receive blood of different quality; 
 and it -is possible roughly to divide the organs in this respect into 
 four categories: (i) The liver, which partakes both of the best and 
 the worst, the purified blood of the umbihcal veins and the vitiated 
 blood of the intestines and spleen; (2) the heart, head, and upper 
 limbs, which receive the blood from the inferior extremities and 
 kidneys, mixed with the pure blood of the venous duct; (3) the 
 legs, trunk, intestines, and kidneys, which are fed chiefly by the 
 off-scourings of the cephalic end, mitigated, however, by a pro- 
 portion of mixed blood from the inferior cava; (4) the lungs, which 
 receive only a feeble stream of unmixed venous blood. 
 
 These peculiarities of the embryonic circulation are in obvious 
 correspondence with the physiological events taking place in the 
 foetal body. The liver is not only the greatest gland in the embryo, 
 as it continues to be in the adult, but its activity seems to dwarl 
 that of all the other glands put together, and is in striking contrast 
 with the functional toipor of the lungs. From the third month of 
 intra-uterine life the secretion of bile begins and the intestines 
 gradually fill with meconium, of which the principal constituent is 
 bile. Accordingly the liver is most lavishly suppHed with blood, 
 
NUTRITION OF THE EMBRYO 1133 
 
 while the lunfjs are stinted. And since the hver has, as we have 
 already learnt, other and, in the adult at least, even more important 
 labours than excretion, a large portion of the blood it receives 
 is of the best quality: it enters the gland comparatively rich in 
 oxygen, and passes out comparatively poor; while the lungs, which 
 have to be nourished only for their own sake, and are of no use 
 whatever till the child is born and respiration has begun, must be 
 content with the poorest fare — with the crumbs that fall from the 
 table of foetal nutrition. The full-fed cephalic end of the embryo 
 grows far more rapidly than the half-starved inferior extremities, 
 and the head of the new-born child is large in proportion to the rest 
 of the body. 
 
 Metabolism of the Embryo. — ^There are some other points in the 
 physiology of intra-uterine life which call for remark; and, to sum 
 up in a few w^ords the grand distinction between foetal and adull 
 life, we may say that growth is the keynote of the former, worK 
 (functional activity) of the latter. Thus, the muscles at an early 
 period in their development, long before anj' glycogen can be 
 found in the liver, become the seat of an accumulation of glycogen, 
 which, since it cannot be used up in contraction as in the adult 
 muscles, seems to be intimately connected with their own growth, 
 and perhaps also with the growth of other tissues. It is true 
 that the foetal tissues as a whole, including the muscles, are not 
 richer, as used to be taught, but poorer in glycogen than adult 
 tissues, and therefore the old doctrine that the foetal glycogen fulfils 
 a special ' formative ' function in the development of the tissues, 
 has lost its experimental basis. Nevertheless, there is a paral- 
 lelism between the growth of the foetus and its glycogen content. 
 In cases where the growth of the foetus has been spontaneously 
 arrested, the percentage amount of glycogen in its organs has been 
 found to be diminished out of proportion to the diminution in weight. 
 A similar retardation of development can be produced by repeatedly 
 injecting phloridzin into the mother, and thus reducing the glycogen 
 store of the foetus (Lochead and Cramer). Probably, then, the foetal 
 glycogen assists the growth of the embryo, which is known to be 
 accompanied by an intense carbo-hydrate metabolism, by furnishing 
 a store of easily oxidized material for the nutrition of the developing 
 tissues. When the muscles have been formed, their glycogen is 
 still consumed in growth, and their functional powers lie dormant, 
 but for the infrequent and feeble movements, generally regarded as 
 reflex, but possibly to some extent originated in the cerebral cortex, 
 which give the mother the sensation of ' quickening.' It is only 
 late in development that the embryonic liver takes on its glycogenic 
 function. In the earlier stages it is entirely free from gljxogen. ' It 
 is an interesting illustration of that exact adaptation of means to 
 ends which so constantly impresses the investigator of the animal 
 
H34 REPRODUCTinS 
 
 mechanism tliat the kimcnt which converts glycogen into dextrose 
 (glycogenasc) is a'so either entirely absent from the Hver early in 
 gestation, or present only in traces; anrl that astheglycogen-forming 
 and glycogen-storing functions of the organ increase in importance, it 
 becomes richer in glycogenoh'tic ferment. It cannot be doubted that 
 the glj'cogen found in the placenta is also deposited there in the 
 interest of the rapidly growing foetal tissues, perhaps as a kind of 
 current account on which they can operate at any moment of 
 emergency, when the more distant maternal reserves cannot be 
 drawn upon in time. The glycogen is formed in the placenta, prob- 
 ably from the dextrose of the maternal blood. By means of a 
 glycogen-splitting ferment, which can be extracted by glycerin from 
 the placenta, the glycogen appears to be reconverted into dextrose 
 for absorption by the foetus. In the earlier period of gestation the 
 placenta seems to perform vicariously the glycogenic function of the 
 liver, and as the glycogen content of the liver increases in the later 
 stages of intra-uterine life, that of the placenta diminishes pro- 
 portionally. 
 
 The excretory glands of the embryo, except the liver, scarcely 
 awaken to activity during foetal life. Urine may indeed be some- 
 times found in the bladder at birth, but it is often absent. It is a 
 dilute urine, with a molecular concentration only about half as great 
 as that of the blood, and although a portion of the amniotic fluid, 
 which contains traces of urea and salts, in addition to small quantities 
 of albumin, may be secreted by the renal tubules, and find its way 
 through the still open urachus into the amniotic sac, this contribution 
 cannot imply more than a slight degree of glandular action. Under 
 certain experimental conditions, however, it can be largely increased. 
 Thus, extirpation of the kidneys in a pregnant animal causes an 
 increase in the amount of amniotic fluid (hydramnios) through the 
 stimulation of the foetal kidneys to increased activity by the passage 
 of the unexcreted urinary constituents of the mother's blood into 
 that of the foetus. After the injection of phloridzin into the foetus 
 sugar has been found in abundance in the amniotic fluid, although 
 the injection of that drug into the mother caused no such effect. On 
 the other hand, after injection of sodium sulphindigotate into the 
 circulation of the foetus in the sheep, the foetal kidneys contained 
 particles of the pigment, while the amniotic fluid remained un- 
 coloured. Long before full term the sebaceous glands have 
 begun their work by the secretion of the vernix caseosa, an 
 oily material which covers the skin and serves to protect it 
 from the continual irritation of the fluid in which the embryo 
 floats. 
 
 The nervous system is even less active than the glandular tissues, 
 and nut more active than the muscles. There is evidently no scope 
 for the exercise of the special senses. Psychical activity of every 
 
NUTRITIOX 01' THE EMDRVO I135 
 
 kind must he at its lowrsi i-bb. Consciousness, if it exists at all, 
 must be dull and mulHcd. And if motor impulses are discharged 
 from the cortex, the psychical accompaniments of such discharge are 
 doubtless widely different from those which we associate with 
 voluntary effort. 
 
 It is a remarkable fact that this functional calm, broken only by 
 the beat of the heart, is accompanied by a relatively intense 
 metabolism of the same order of magnitude as that of the adult. 
 In the hen's egg at all stages of development the consumption of 
 oxygen and production of heat (per kilogramme and hour) are the 
 same as in the adult hen. The oxygen consumption and carbon 
 dioxide production of pregnant guinea-pigs were determined before 
 and during compression of the umbilical cord of a foetus, and a dis- 
 tinct diminution was observed when the respiratory exchange of the 
 foetus was eliminated. From the results of a number of observations 
 it was calculated that the carbon dioxide produced by the mother 
 was 462 c.c, and by the foetus 509 c.c. per kilogramme of body- 
 weight per hour (Bohr and Hasselbach). A similar comparison 
 betweeai women before and during pregnancy never showed any 
 diminution in the respiratory exchange reckoned on the unit of body- 
 weight in the pregnant condition. In one case, indeed, and that 
 the most exactly observed, there was an increase in pregnancy. 
 Now, in the pregnant woman a considerable part of the increase of 
 body-weight is due to the amniotic fluid, in which, of course, meta- 
 bolism does not go on. It is evident, then, that in the human foetus 
 also the intensity of metabolism is at any rate not of a lesser order of 
 magnitude than in the mother, in spite of the much smaller amount 
 of muscular contraction taking place. The heat production of mother 
 and child together has been directly estimated in several cases in a 
 respiration calorimeter provided with a bed just before parturition 
 and just after it. After parturition the heat production of the 
 mother was also separately determined. From the difference it was 
 concluded that the heat production of the child per kilogramme 
 of body-weight per hour is approximately two and a half times 
 that of the mother under the same conditions. (Carpenter and 
 Murlin.) 
 
 The foetal heart beats at the rate of about 140 tiilies a minute at 
 full term.* The blood-pressure in the umbilical artery of the 
 mature embryo (sheep) varies from 60 to So mm. of mercury; 
 but at the beginning of the aorta it will be more. The pressure in 
 
 * It has not been finally determined whether the rate of the heart varies 
 with the size or, what probably comes to the same thing, with the sex of the 
 fcBtus. As we have seen, the variation of the rate in the adult with the size 
 of the body is associated with a corresponding variation in the metabohsm 
 and heat-loss, which are proportionally greater in a small than in a large 
 animal. If this is a causal connection we should not expect that in the 
 cmhrvo in utevo. where the conditions as regards heat-loss arc entirely different, 
 ?uch a relation should cxi.st, at any rate within the same species. 
 
1136 REPRODUCTION 
 
 the pulmonary trunk must be about equal to that in the aorta, since 
 the comparatively short and easy circuit through the lungs does 
 not as yet exist ; and in accordance with this equality of pressure 
 (of work to be done) is the equality of thickness (of working power) 
 in the walls of the two sides of the heart. 
 
 Suppose, now, that the embryo contains 60 grammes of blood for 
 every kilo of body- weight, and that the whole of the blood passes 
 through the circulation in twenty seconds. Then in twenty-four 
 hours 2592 kilos of blood will be forced through the heart for every 
 kilo of body-weight against a pressure of, say, 80 mm. of mercury, 
 or I metre of blood. This is equivalent, in round numbers, to 260 
 kilogramme-metres of work, or 06 calories. Now, taking the total 
 heat-production of the heart at three times the equivalent of its 
 mechanical work, we get i-8 calories per kilo of body- weight in 
 twenty-four hours (see p. 676), or about ^^ of the heat-production 
 of a resting adult. 
 
 Such movements of the skeletal muscles as occur cannot account 
 for any large proportion of the total metabolism, since they are 
 executed in a medium (the amniotic fluid) of nearly the same specific 
 gravity as that of the body, and therefore require the expenditure of 
 a very limited amount of energy. The ordinary functional activity 
 of the embryo, then, is quite incapable of accounting for the intensity 
 of the foetal metabolic processes. Still less can it be due to an active 
 combustion in the tissues to compensate for a rapid loss of heat, 
 for the foetus lies sheltered in the uterus as in a thermostat at its 
 own temperature, and can lose practically no heat unless its tempera- 
 ture be kept a little above that of the maternal blood. The only 
 remaining explanation of the magnitude of the foetal metabolism 
 is that the growth processes are associated with a large amount of 
 oxidation (and cleavage). 
 
 Notwithstanding the intensity of metabolism in the embryo, not 
 only is even the purest blood, as has already been stated, far from 
 saturated with oxygen, but the relative proportion of haemoglobin, 
 the oxygen-carrier, is less than in the adult ; and although constantly 
 increasing in amount from the moment of its first appearance, it is 
 still somewhat deficient, even at full term, but leaps sharply up at 
 birth. At an early period of development the embr\'o also contains 
 much more water than the adult ; the specific gravity of its tissues 
 increases as development goes on. 
 
 The remarkable vitality of the foetus, and its resistance to 
 asphyxia, are related not to the feebleness of its metabolism, but to 
 the comparatively slight excitability and high endurance of ner\'ous 
 centres like the respiratory, vaso-motor, and cardio-inhibitorj-. 
 Even when totally deprived of oxygen, as by pressure on the um- 
 . bilical cord during delivery, the child does not perish in the two or 
 
PARTURITION 1137 
 
 three minutes which deride the fate of the asphyxiated adult ; nor are 
 the convulsions, rise of blood-pressure, and slowing of the heart-beat 
 associated with asphyxia in the latter, so n^adily induced, nor 
 })remature and fatal efforts at respiration easily excited in utero. 
 But although in such a case the enil)ryo behaves as a separate 
 organism, governed by its own laws, there are circumstances in 
 which it becomes merely a part of the mother and participates in her 
 fate. Thus, the stream of oxygen which normally passes from the 
 maternal to the foetal blood is turned back if asphyxia threatens 
 the mother; the blood of the umbilical arteries, instead of being 
 purified in the placenta, loses the little oxygen it holds to the 
 blood of the uterine sinuses, and the tissues of the embryo are 
 impoverished to support the metabolism of the maternal organs. 
 In the same way, the phenomena of starvation have taught us 
 that the nutrition of the organism is not subject to the rules of 
 red tape. In normal circumstances the flow of nutriment follows 
 definite lines: the blood feeds the tissues through its intermediary, 
 the lymph, and recoups itself from the contents of the alimentary 
 canal. But when the normal sources of nutrient material fail, the 
 body falls back upon its stores. The organs immediately necessary 
 to life are kept, as far as possible, on full diet; organs of secondary 
 importance have to be content with half-rations; organs less im- 
 portant still are drawn upon for supplies. 
 
 Parturition. — The period of gestation is abruptly closed about 
 280 days after the last menstruation, usually in what would have 
 been the tenth intermenstrual period had menstruation been occur- 
 ring. There is necessarily a considerable variation in the time when 
 reckoned in this way, since the cessation of the menses merely an- 
 nounces that conception has occurred some time after the last 
 period. It may even be disputed whether the fertilized ovum 
 corresponds to the last menstruation or to the first absent 
 period. Parturition, or the expulsion of the foetus, is accom- 
 plished by periodical contractions, the ' pains ' of labour, at first 
 confined to the uterus. Soon the os uteri begins to soften and 
 dilate, the walls of the vagina become congested, and its secretions 
 are augmented. The uterine contractions increase in frequency 
 and force, and are now accompanied by reflex contractions of the 
 abdominal muscles, and, if the woman is not anaesthetized, also by 
 voluntary contractions of these and of other muscles, which can 
 increase the intra-abdominal pressure. The uterine contractions 
 can be initiated and modified by impulses coming from the central 
 nervous system by way of the extrinsic nerves of the organ. It is 
 known, e.g., that the gravid uterus can be excited to contraction by 
 the stimulation of various sensory nerves. Powerful mental impres- 
 sions, such as fright, may bring on premature labour. Conversely, 
 sudden cessation of labouj- pains during parturition is not uncom- 
 
 72 
 
1 138 REPRODUCTION 
 
 inoiily obs rvcd t<» be produced by emotional disturbances — for 
 instance, llie entrance of a stranger into the room. Yet the con- 
 tract ic)n> of the uterus are not essentially dependent upon extrinsic 
 impulses. For not only do rhythmical contractions occur, but the 
 whole process of parturition has been seen to take place in a uterus 
 whose nerves have all been cut. Even the excised uterus may be 
 kept alive for as long as forty-eight hours, and may go on executing 
 periodical contractions when its bloodvessels are perfused with such 
 an artificial fluid as Locke's solution, or, indeed, when it is simply 
 immersed in the oxygenated solution (Kurdinowski) (Practical 
 Exercises, p. 1147)- 
 
 It is a question of great interest how the uterine contractions are 
 started so abruptly at full term after so long a period of quiescence. 
 It can hardly be that the increasing mechanical distension of the 
 uterus, tolerated for so many months, should suddenly, in an hour, 
 become intolerable. For if the foetus dies before full term it is 
 expelled without reference to the bulk which the uterus has reached. 
 It is more likely that some chemical change associated \vith the 
 completion of intra-uterine development, a change which leads, 
 perhaps, to the production of some specific substance in the placenta 
 or the foetus, is the determining event. The placenta is a structure 
 whose function is strictlv limited to the term of intra-uterine develop- 
 ment. The foetus is to Hve on, and so is the mother. Ma\' it not 
 be that the placenta or essential elements in it are timed to die, or 
 to begin to die, at full term, and that in their death or degeneration 
 the substance or substances are produced which start, and later 
 sustain, the uterine contractions ? And ma}' not the contractions of 
 the uterus, by exciting its afferent nerves, or through the pressure 
 of the foetus the afferent nerves of the vagina, in turn evoke the 
 associated reflex contractions of the abdominal walls ? These are 
 questions which have been asked, but not as yet satisfactorily 
 answered. It has also been suggested that a hormone formed in the 
 mammary gland at full term stimulates the uterus and thus brings 
 on labour. 
 
 At birth, great changes take place in the fcetal circulation, and these 
 are intimately connected with the commencement of the respiratory 
 activity of the lungs. The causes of the first respiration are: (i) The 
 increasing venosity of the blood circulating in the bulb, which stimu- 
 lates the respiratory centre when the umbilical cord has been cut o: 
 tied and the placental circulation thus interfered with; (2) the stimula- 
 tion of the skin by the air, which, as we ha\e seen, acts reflexlj- upon the 
 respiratory centre. That both of these factors may be involved is 
 shown by the fact that either compression of the umbilical cord alone, 
 or exposure of the foetus by opening the uterus of an animal wthout 
 interference with the circulation, has been observed to be followed 
 by attempts at breathing. Once distended, the lungs never again 
 completely collapse — ^not even after death, nor when the chest is 
 opened. The aspiration caused by the elevation of the chest-walls in 
 
MILK 1 1 39 
 
 inspiration (for the respiration of the newborn child is mainly costal) 
 SUCKS blood into the thorax, and expands the vessels of the lungs for 
 its reception ; and in the measure in which the blood passing through the 
 pulmonary trunk finds an easy way through the lungs, tlie quantity 
 which takes the route of the ductus arteriosus diminishes. Ihe pul- 
 monary veins, and consequently the left auricle, are better filled ; and 
 the increasing pressure on this side of the septum tends to oppose the 
 passage of the blood through the foramen ovale, to approximate its 
 valve, and to close its orifice. 
 
 By the second or third day the ductus arteriosus has usually become 
 obliterated. The umbilical arteries and veins and the ductus venosus 
 become impervious so(>n after the intcrruptioia of the placental circula- 
 tion. The vein and venous duct remain in the adult as the round 
 ligament of the liver, the arteries as the lateral ligaments of the bladder. 
 
 Although from birth onwards the young mammal obtains its 
 oxygen and gets rid of its carbon dioxide through its own pulmonary 
 surface instead of through the placenta, it still lives, as regards its 
 food proper, on the tissues of the mother, and that in as literal a 
 sense as when it drew its supplies directly from the maternal blood. 
 
 Milk. — ^The milk secreted during the first few days of each lacta- 
 tion, the colostrum, as it is called, indeed may represent in part the 
 fragments of cells lining the alveoli of the mammary glands, which 
 have undergone a fatty change and been bodily broken down. The 
 colostrum corpuscles are leucocytes filled with fat globules taken up 
 from the contents of the alveoli. The chief chemical difference 
 between colostrum and ordinary milk is the greater richness of the 
 former in protein. It has been supposed that it is of special impor- 
 tance for the nutrition of the suckling, perhaps in virtue of the 
 enzymes contained in it, and it is said that young animals bear 
 artificial feeding much better if they have been allowed to suckle the 
 mother for the colostrum. 
 
 In addition to the fat, which w^hen milk is allowed to stand rises to 
 the top as cream, milk contains a considerable quantity of caseinogen, 
 to whose coagulation, under the influence of the lactic acid produced 
 from the lactose, or milk-sugar, by certain bacteria, spontaneous 
 curdling is due. Another protein, lact-albumin (Halliburton), a large 
 amount of water, and some inorganic salts, are the most important of its 
 remaining constituents. Recently the presence of small amounts of 
 phosphatides intimatelv associated with the protein constituents, and 
 possibly combined with them as ' lecith-albumins ' has been shown 
 (Osborne and Wakeman ) . The molecular concentration (p. 426) of milk, 
 as measured by its freezing-point, is almost exactly the same as that of 
 blood-serum. Its electrical conductivity varies extremely, since it 
 depends on the quantity of fat present, the fat globules, like the blood- 
 corpuscles, being practically non-conductors. The hydrogen-ion con- 
 centration of fresh cow's milk has been found to vary from o-i8 . lo-^N 
 (Ph=6'75*) too'25 . io-«N(Ph=6'6o) in the great majority of specimens. 
 
 * Instead of expressing the hydrogen-ion concentration as a fraction of a 
 normal solution, it is more convenient for many purposes to take as a measure 
 of the concentration the logarithm of this number, omitting the negative sign, 
 represented by the symbol Pg . 
 
II40 
 
 REPRODUCTION 
 
 This is distinctly greater than the hydrogen-ion concentration of blood. 
 — 6mo -8(1'h =7*-2) to 2-iu -*(P,, =7-7). During the course of rennin 
 action there is no change in the hydrogen-ion contentration of milk 
 (Milroy). 
 
 The inorganic composition of milk is particularly interesting when 
 compared with that of the blood on the one hand and that of the 
 suckling on the other. Thus, 100 grammes of ash from each source 
 gave the following values for the rabbit (Abderhalden) : 
 
 Rabbits (14 Days 
 Old;. 
 
 K2O 
 
 Nap 
 CaO 
 
 Ci 
 
 10-84 
 5-9<J 
 
 35-0^ 
 2-\g 
 0-23 
 
 41-94 
 4-94 
 
 Rabbit's Milk. 
 
 Rabbit's Blood. 
 
 io-o6 
 
 -^3-75 
 
 7-92 
 
 31-38 
 
 35-(^5 
 
 0-81 
 
 2 -20 
 
 O-O4 
 
 0-08 
 
 (j-93 
 
 39-86 
 
 11-11 
 
 .5-4- 
 
 32-()6 
 
 Rabbit's Blood- 
 Scruni. 
 
 319 
 
 54-7^ 
 1-42 
 0-56 
 
 O-OO 
 
 2-98 
 
 47-83 
 
 The richness of the milk (and of the suckling) in calcium, phos- 
 phorus, and magnesium, as compared with the serum, is to be especially 
 remarked. This is, of course, essential for the development of the 
 bones. Whereas sodium predominates greatly over potassium in the 
 serum, the opposite is the case in the milk (and the suckling). This is 
 connected with the development of the tissue cells, which are richer in 
 potassium than in sodium. The high chlorine content of the serum is 
 in sharp contrast with the relative poverty of the milk in that element, 
 which preponderates in the tissue liquids and is relatively scanty in the 
 cells. 
 
 In addition to substances susceptible of chemical analysis, milk 
 contains enzymes like those present in blood-serum, including 
 oxydases and various hydrolytic ferments (proteolytic, diastatic, 
 and perhaps lipolytic). It is now universally acknowledged that 
 mother's milk is superior for the feeding of the infant to any 
 artifif'ial substitut'^, and one factor in this superiority may be the 
 presence of ferments specifically adapted for the digestion of the 
 human suckling. More important is the practical sterility of the 
 human milk and the necessarily finer adaptation of its quantitative 
 and qualitative composition, particularly the closer relationship of 
 its proteins with those of the child. In addition, there is some 
 evidence that the maternal milk contains immune bodies (anti- 
 bodies) which may increase the resistance of the suckling to 
 infections. 
 
 However this may be, there is no question that much of the high 
 infant mortality associated with the industrial conditions of our 
 great cities could be prevented if breast-feeding were carried out by 
 every mother physically capable of it. 
 
 As to the manner in which milk is secreted, there is no doubt 
 that its chief constituents are formed in the gland-cells. Caseinogen 
 
CULTIVATION 01- TISSUES 1141 
 
 and lactose do not exist in the blood or lynipli. The former is 
 probably produced by an alteration in one or other of the serum 
 proteins, the latter by a change in the dextrose of the blood. The 
 fat of the milk may come partly from the fat of the blood, but it 
 may also be formed in the gland-celh from proteins, and carbo- 
 hydrates. The precise manner in which the fat globules are extruded 
 from the cells into the lumen of the alveoli is not clear, but there is 
 no good ground for believing that the cells or their free ends break 
 up bodily in the process. 
 
 Little is known as to the influence of the nervous system on the 
 secretion of milk, and no definite secretory fibres have as yet been 
 clearly demonstrated, although the fact that marked changes may 
 be produced in the milk of nursing women as the result of emotional 
 disturbances indicates that such nerves do exist. There is reason 
 to suppose that the stimulus for growth and development of the 
 mammary glands may be distinct from the stimulus which causes 
 increased secretion. Some observers lean to the opinion that milk 
 secretion is governed in an important degree by hormones carried 
 to the glands in the blood. The effect of pituitrin has already been 
 alluded to (p. 669. ). 
 
 Pregnancy is accompanied with vascular dilatation and hyper- 
 trophy of the mammary glands, but the mechanism by which these 
 changes are produced is unknown. It is probable that they depend 
 upon some internal secretion of the ovary or some other of the 
 organs of reproduction. Pregnancy is not an absolutely indispens- 
 able condition, and therefore it would seem that the exciting 
 substance, if any specific substance exists, is not a product of the 
 foetus or of the placenta. Intravenous injection of extract of 
 placenta is said to cause an increase in the flow of milk in goats, and 
 the deduction has been drawn that some ' internal secretion ' of 
 the placenta may be responsible for initiating the activity of the 
 mammary gland at the time of parturition. But precisely similar 
 phenomena are occasionally seen in animals which have not been 
 impregnated and even in men. Himiboldt relates the case of an 
 Indian father, who so well understood the responsibihties of pater- 
 nity, and was so capable of lulfiUing them, that he suckled his child 
 for five months on the death of the mother. Virgin bitches are 
 frequently known to produce milk, occasionally even in quantity 
 sufficient to rear pups, the flow occurring about the time when they 
 would have whelped had they conceived during the pre\'ious oestrus. 
 Bitches which after copulation have ' missed ' having pups have 
 been known to produce so much milk, beginning at the time they 
 were due to whelp, that they were able to rear litters of puppies 
 belonging to other bitches. Mules, which are themselves sterile, 
 may have enough milk to suckle a foal. The nipples of certain 
 monkeys become swollen and congested at each menstruation 
 
1142 REPRODUCTION 
 
 (Heapc), and in women some development of the mammary glands 
 is often associated witli the menstrnal ]XTiod. The stimnlus to the 
 development of the gland in these cases appears to be some change 
 correlated with a-strus, and cannot be a change correlated with 
 pregnancy. 
 
 Cultivation of Tissues outside of the Body.— Closely related to the 
 marvellous power of growth of the fertilized ovum in the favourable 
 nidus of the pregnant uterus, although, of course, incomparably 
 inferior, is the power of growth and reproduction of isolated tissue 
 cells in a suitable medium outside of the body. An instance of this 
 has already been described in the case of nerve-cells (pp. 803, 857). 
 Many other tissues have been successfully cultivated in sterile 
 coagulated lymph or blood-plasma. Connective-tissue cells grow 
 very easily, and can apparently be preserved indefinitely in the 
 living state. A strain of these cells, originally obtained from a 
 fragment of the heart of an embryo chick which had been pulsating 
 in vitro for 104 days, has been seen to proliferate rapidly outside of 
 the organism for more than sixteen months, and after more than 
 190 passages into fresh media. At the end of this time the rate of 
 proliferation of the connective-tissue cells was even greater than 
 that of fresh connective tissue taken from an embryo eight days old. 
 Extracts of tissues and tissue juices under certain conditions acceler- 
 ate the growth of connective tissue from three to forty times, the 
 growth being measured by the increase in area of the minute pieces 
 of tissue. This activating power is especially marked in extracts 
 of embryos, of adult spleen, and of certain sarcomas. This is 
 noteworthy as the great characteristic of malignant tumours is 
 their indefinite power of growth. The activating substance is 
 unable to pass through a Chamberland filter (Carrel). Cultures of 
 adult tissue have a smaller power of persistent growth. In the 
 majority of cases growth in plasma without the addition of a 
 ; timulating tissue extract ceases after three or four generations 
 (Walton). 
 
 The time of survival of tissues at low temperatures under con- 
 chtions which do not encourage growth is also a matter of consider- 
 able interest, both from the physiological and the practical point of 
 view, since living sterile tissue is required for a number of surgical 
 operations — for example, skin for grafting. Skin has been suc- 
 cessfully grafted after being kept two to seven weeks in cold storage, 
 but after a longer period there were many failures. Embryonic 
 chick and rat tissues Uve longest at about ()° C, but not more than 
 twenty days under the most favourable conditions, according to 
 Lambert. 
 
 Transplantation of Tissues. —Besides the growth and regeneration 
 of tissues or organs, the simple displacement of them from their 
 normal situation and their implantation in a new en\ironment have 
 
TRANSPLANTATION OF TISSUES 1143 
 
 been studii'd. Normally, a migration of tissue elements is only 
 witnessed in the adult in the case of cells moving with the circulating 
 liquids, or endowed with the power of amoeboid movement. Under 
 pathological conditions fragments of tissue, such as tumour cells, 
 may be carried by the blood or lymph to distant parts, and, settling 
 there, may undergo development (forniing metastases). In the 
 embryo the slow migration of ti>sue elements is a process which 
 is responsible for some of the anatomical pecularities of the adult. 
 The migration of the ovum from the ovary is the starting-point of 
 the process of reproduction. The artificial displacement of tissues 
 within the body of one and the same animal (auto-transplantation 
 or autografting) can be successfully accomplished in the case of 
 most normal organs and tissues, and also i n the case of most tumours. 
 Instances have already been given in speaking of the endocrine 
 functions of the ovary, thyroid, spleen, thymus, etc. (Chap. XL). 
 A small piece of tissue or sometimes a small organ is simply inserted 
 in its new situation without provision for the immediate establish- 
 ment of a circulation. Necrosis of the central portion occurs, but 
 the peripheral zone soon becomes vascular, the graft ' takes ' and 
 under suitable physiological conditions grows. Hctero-transplan- 
 tation, or grafting between animals of different species, does not 
 succeed. Homoeo-transplantation, or grafting from one animal to 
 another of the same species, is in the case of normal tissues success- 
 ful only in rather rare instances. In most cases, although some 
 of the homoeo-grafted tissue may remain alive for some time, or 
 even begin to grow, its growth is soon checked, and it is eventually 
 absorbed. Certain tumours, however, can be readily grafted from 
 one animal to another of the same species, and can live and grow in 
 the new environment. 
 
 The difference in the fate of auto- and homa30grafts illustrates in a 
 striking way the important chemical and metabolic differences which 
 exist, not only between different species, but between individuals of the 
 same species. In general, a piece of tissue from a rabbit is treated as 
 an ' unclean ' thing, which must eventually be cast out, not onlv when 
 it is introduced into the body of a dog, but when it is introduced into the 
 body of another rabbit. It is unable to adapt itself to its new en- 
 vironment, and soon perishes. But a bit of thyroid, of adrenal cortex, 
 or of uterus, may easily settle down as a successful colonist in very out- 
 landish places witliin the body of the animal to which it belongs. An 
 invasion of lymphocytes, and an ingrowth of fibroblasts, causing develop- 
 ment of bands of connective tissue, have beenregarded by some observers 
 as the immediate causes of the failure of homoeografts to grow. It is 
 fully as probable, however, that the lymphocytes gather around and 
 invade the graft, and that the connective tissue trabecular appear in it, 
 because it has already been injured by the antibodies of the host, or, if 
 not by specific antibodies, then simply by exposure to the more or less 
 altered metabolic conditions, which it is unable to face successfully. 
 The difference between the autograft and the homoeograft has not yet 
 been sufi&ciently taken account of by surgeons, e.g., in connection with 
 
"44 
 
 REPRODUCTION 
 
 transfusion of blood. They have slowly learnt that in this case hetero- 
 grafting (for wc can truly call transfusion the grafting of the fluid 
 tissue blood) is not permissible, and nobody now allows sheep's blood 
 to pass into the veins of a man. But the danger to the host of repeated 
 and massive homcEO-transfusions is only beginning to be recognized 
 by the men who have the power to ' bind and to loose ' veins and arteries. 
 
 Some normal organs, e.g., the ovary, arc mf)re readily homoeograftcd 
 than others. Guthrie has shown that hens whose ovaries have been 
 interchanged are capable of laying eggs. When the hens were im- 
 pregnated and the eggs hatched out the colour characters of the resulting 
 offspring seemed to have been infiuonced, not c)nly by the hen to which 
 the o\ary originally belonged, but also by the hen to which it had been 
 transferred. 
 
 Young have also been obtained from guinea-pigs, whose (jv-aries had 
 been replaced by ovaries from other guinea-pigs. Eighteen months 
 after interchange of the ovaries in two sister puppies, it was shown by 
 histological examination that the engrafted ovaries contained numerous 
 normal Graafian follicles, as well as corpora lutea. Statements arc on 
 record of successful ovarian homoeografts even in women. 
 
 Another point of great interest in connection with homtjeograf ti ng 
 is that a small number of indi\iduals of a species may constitute more 
 favourable hosts than the great majority for a tissue from anotlicr 
 
 Fig. 486.— Method of Transplantation (of both Kidneys) in Mass (after Guthrie) 
 Segments of the mferior vena cava and abdominal aorta are removed with the 
 kidneys and renal vessels, and interposed in the course of the vena cava and aorta 
 of another animal, according to the method of Carrel and Guthrie. 
 
 Individual of the same species. For instance, a rabbit's thyroid 
 cannot as a rule be successfully grafted into another rabbit, even 
 when thyroid deficiency has been caused bv removal of the greater 
 part of the thyroid from the host. But if a large nuutbcr of rabbits 
 are tried one will occasionally be found in which thyroid hom-ieo- 
 
TRANSPLANTATION 01- TISSUES 
 
 «I43 
 
 grafts succeed (Marine and Manlcy). It is not as yet known what 
 the circumstances are whicli so niud.f\' the u^ual ad\ ir>e condi- 
 tions that a homoeograft can take, grow and permanently burvive. 
 
 Fig. 487. —Suturing Bloodvessels: Prcliuiiuary l-'ixation of Ends of Divided Vessels 
 (after Gutiuie). Three fixing ligatures are placed at equidistant points on the 
 circumference of the cut ends, each ligature being passed through corresponding 
 points of the two vessels. The ends of the vessels are approximated by drawing 
 on the ligatures, which are then tied, and the margins of the vessels sewed together 
 by continuous stitches in the intervals between the fixing ligatures, as in Fig. .t88. 
 (Carrel's method). 
 
 But there is reason to beheve that the solution of this problem would 
 be a long step towards answering the immensely important practical 
 question what the conditions are wliich permit the development 
 of malignant tumours. 
 
 Fig. 488. — Suturing Bloodvessels: Method of approximating Edges aid putting in 
 Continuous Suture (after Guthrie). The needles are very imt ca nbric sewing- 
 needles, and the threads single strands of Chinese twist silk ur human hair. 
 Needles and threads are sterilized in paraflin-oil. (Method of Carrel and Guthrie.) 
 
 Transplantation of organs may also be done with anastomosis of 
 bloodxessels. The main vessels of the engrafted organ are sutured 
 to suitable arteries and veins in the ' host,' so that the circulation 
 is at once effective. Consequently there is practically no hmit to 
 the size of the grafts. The kidney, spleen, and even a limb, have 
 
1146 REPRODUCTION 
 
 been transpUiiiU'd in this way from one clog to another. Although 
 from the operative point of view successful, the homoeo-transplants 
 do not permanently survive. Reimplantation of organs, however, 
 in one and the same animal with suturing of the bloodvessels has 
 often been successfully performed. Such organs as the kidney live 
 and function after reimplantation, and the operation is now a 
 recognized physiological method of insuring that an organ has been 
 completely disconnected from the central nervous system, since even 
 the nerves running in with the bloodvessels must have been cut. 
 It has been shown that a reimplanted kidney suffices to maintain a 
 dog in complete health for an indefinite period after tlie removal 
 of the other kidney. 
 
 In the case of structures like the large bloodvc-sels, which 
 perform mainly a passive mechanical function, homoeo-transplanta- 
 tion succeeds. Segments of arteries preserved in cold storage 
 for a few days or even weeks, and even portions of arteries fixed by 
 formaldehyde, have been transplanted so as to take the place of 
 segments removed from arteries of living animals, and have con- 
 tinued to function perfectly for long periods. Portions of veins 
 have also been used to fill up gaps in arteries. Even heteroplastic 
 vascular grafts have been found to succeed, portions of dog's 
 arteries, e.g., grafted into a cat, and portions of rabbit's, cat's, or 
 human arteries grafted into a dog. Doubtless the favourable result 
 is largely due to the fact tliat the mechanical function of the large 
 arteries can be discharged e\en by a dead tube of the requisite 
 strength, and with the smooth interior presented by a dead endo- 
 thelial lining (Carrel, Guthrie). 
 
 Parabiosis. — Not only may an organ or a portion of tissue from 
 one individual be engrafted on another, but two individuals may be 
 so united that a greater or smaller degree of piiysiological in- 
 timacy is produced between them. Occasionally, as in the famous 
 Siamese twans, an anomaly of development results in such close 
 anatomical union of the circulatory and other systems that in 
 certain respects the two individuals constitute almost a single 
 organism, and cannot be separated by surgical interference. A 
 less intimate union can be established c.xperimcntallv by opening 
 the peritoneal cavities of the two animals, and suturing the skin 
 and connective tissue together so as to permit of permanent 
 communication. Pairs of animals living in this condition (so- 
 called parabiosis) have been utilized for the study of certain 
 questions in immunity. White rats have been kept alive in para- 
 biosis for as long as thirty-four days in order to test the question 
 whether destructive antibodies for cancer are present in the circula- 
 tion (Rous), since it has been shown that circulating antibodies easily 
 pass from one to the other of such a pair of animals (Ehrlich). 
 
PRACTICAL /:A'/.7i'( /.S7:S 1 147 
 
 Cm- of each pair of rats liad a j^iowiiif,' tumour prtxluccd by 
 traii^]ilantation, while the other liacl been proved resi>taut to the 
 same type of tumour. No evidence of the passage of an antibody 
 was found in this case. 
 
 PRACTICAL EXERCISES. 
 
 I . Contractions of Isolated Uterine Rings. — Kill a female adult 
 rabbit by strikinj^ it at the back of the neck, A rabbit which is not 
 pregnant, or only at the beginning of pregnancy, shoukl be selected. 
 Open the abdomen, and carefully remove the uterus. While separating 
 the organ from the broad ligament and vagina, support the horns o{ 
 the uterus on soft threads Ligature the vagina before cutting through 
 
 Fig. 489. — Contractions of Rabbit's Uterus Ring. At 41 Ringer's solution was 
 replaced by adrenalin solutinn, 1:1,000,000. Time-trace, half-minutes. 
 
 it, and cut below the hgature, which can then be used to manipulate 
 the uterus. Do not pinch the uterus with forceps, and handle it as 
 little as possible. At once place it in Ringer's or Tyrode's solution* 
 (p. 200), kept at body temperature (38° C.) in a small beaker immersed 
 in a water-bath, as in the experiment on the contraction of isolated 
 intestine (p. 452). Cut a ring of tissue about i-J- centimetres in width 
 from one of the horns. Tie a loop with a iine silk thread at each end 
 of a diameter of the ring, pinching up a little of the external coat to do 
 so with fine forceps. Make the arrangements necessary for recording 
 contractions of the circular fibres of the ring while it is immersed in a glass 
 cylinder in the bath, as in Experiment i , p. 452 . Connect another segment 
 
 * Tyrode's solution contains o'S gm. NaCl, 0-02 gm KCl o-o" gm CaCl 
 o-oi gm. MgClg, o 005 gm. NaHaPO^ o-i gm. NaHCOj and o-i gnf. dextros^e 
 in too CO. of water. 
 
1148 
 
 REPRODUCTION 
 
 longitudinally to a lever as in that experiment, and make all the arrange- 
 ments mentioned there. After a longer or shorter interval spontaneous 
 rhythmical contractions of the uterus ring commence. As soon as they 
 are well established, and while the contractions are being recorded on a 
 very slow drum, replace the Ringer's solution by serum, defibrinated 
 blood, blood prevented from coagulating by citrate solution (p. 66), or 
 hirudin, or bv plasma, and note the effect. The serum or plasma may 
 be diluted to 'a known amount with Ringer's or Tyro*!''- -"Int-on hrfnro 
 
 i'ig 
 
 ^QQ _At II Ringer's solution was replaced by citrate plasma. M 39 RiiiRer s 
 station was replaced by hirudin plasma ; at 41 by the corresponding hirudin 
 
 application to the segment. Wash away the serum or plasma thor- 
 oughly with Ringer's solution. Replace the Ringer's solution by 
 adrenalin solution (i : 10,000,000). Note whether the tone of the ring 
 (as shown by its permanent shortening) or the rate and strength of the 
 contractions arc increased. While a tracing is being taken repeat the 
 observation, adding a larger propcjrtion of adrenalin. Determine in 
 what concentration a distinct effect is produced. A sufficient number ot 
 uterus rings can be obtained from one animal for a considerable number 
 of experiments. 
 
PRACTICAL EXERCISES 
 
 IM9 
 
 2. Comparison of Changes of Tone Produced in Uterus Segments by 
 Different Concentrations of Adrenalin. l\)r this \\\v uterus of a virghi 
 rabbit (full-grown or nearly so), is best, as it is advantageous that the 
 spontaneous contractions should be absent or feeble. Starting always 
 with the segment* in Ringer's or Tyrode's solution replace the solution 
 by adrenalin in different dilutions (i : 10,000,000, i : 50,000,000. 
 I : r, 000, 000. etc.), washing off the adrenalin thoroughly with the 
 Ringer's solution. Compare the effect of serum or defibrinated blood 
 obtained from the rabbit itself or from some other laboratory animal 
 with that of a known solution of adrenalin. 
 
 If blood collected from the adrenal veins of an animal is available it 
 should be compared with blood from the same animal taken from the 
 
 Fig. 491. — Action on Rabbit's Uterus Segment of Blood Specimens from the Adrenal 
 Veins (of a Dog) with Different Concentrations of Epinephrin, and Comparison 
 with Adrenalin added t(j Blood. At 28 Ringer's solution was replaced by the 
 second adrenal specimen ; at 29 by the third adrenal specimen; at 30 by the fourth 
 adrenal specimen; at 31 by the fifth adrenal specimen ; at 37 by the sixth adrmal 
 specimen; at 41 by jugular vein blood. All bloods diluted with 15 volumes 
 Ringer's solution. .\t 34 adrenalin in jugular blood (i : 2,000,000); at 35 adrena- 
 lin in jugular blood (i : 3,000,000); at 36 adrenalin in jugular blood (i : 4,000,000) 
 replaced Ringer's solution. The adrenalin bloods after being made up to the 
 concentrations mentioned, were diluted with 15 volumes of Ringer's sohuion 
 bef'ire application to the segment. (Reduced to one-half.) 
 
 general circulation (jugular vein or carotid artery). The tone-increasing 
 power of tlie adrenal vein blood will be greater than that of the in- 
 different blood, because both the serum and the epinephrin will act in 
 the same sense (Fig. 491). 
 
 3. Partition of Adrenalin between Serum and Corpiiscles. — Add to 
 100 c.c. of dog's blood 0-5 c.c. of the i : 1,000 solution of adrenalin. 
 Centrifuge a portion of the mixture to obtain clear serum. Centrifuge 
 another portion of the dog's blood to which adrenalin has not been 
 added. Test on rabbit's uterus segments and also on intestine seg- 
 
 * It is best to arrange the segment to record the longitudinal shortening. 
 
II50 
 
 REPRODUCTION 
 
 ments (p. 453) the defibrinated blood, the serum and the- sediment of 
 corpuscles from the original blood and from the blood tf. which arlrcnalin 
 was added. The adrenalin action of the serliment will be much less 
 than that ol the serum or of the blood (Fig. 492). 
 
 Fig 492- — Action of Adrenadin Defibrinated Blood, Sernjn and Sediment on Rabbit's 
 Uterus Segments. At 42 Ringer's solution was replaced by adrenalin blood 
 serum (i part in 6 parts of Ringer's solution) ; at 43 by the same serum (i in ii); 
 at 44 by the same serum (i in 16); at 52 by the same serum (i in 24); at 51 
 Ringer's solution was replaced by adrenalin blood (i in 24); at 53 by adrenalin 
 blood sediment (i in 6); at 54 by the adrenalin blood sediment (i in 24); at 55 by 
 the ordinary defibrinated blood (i in (">); at 56 by the ordinary defibrinated blood 
 (i ui 24). (Reduced to one-half.) 
 
APPENDIX A 
 
 C "MPARISON OF METRICAL WITH KNGLISK MEASURES. 
 
 Measures of Length. 
 
 I millimetre = 0'03937 inch. 
 I centimetre =0-39371 ,. 
 I decimetre = 3-93708 inches. 
 I metre = 39*37079 ,, 
 
 I inch = 25-3995 millimetres. 
 
 Measures of Weight. 
 
 I gramme = 15-432349 grains. 
 
 I kilogramme = 2-2046213 pounds. 
 
 I ounce = 28-3495 grammes. 
 
 I pound =453-5926 
 
 Measures of Volume. 
 
 I cubic centimetre= 0-061027 cubic inch. 
 
 I litre (1,000 cubic centimetres) =61-027052 cubic inches. 
 
 = 1-760773 English or 2-11 
 American pints. 
 
 = 0-22009668 gallon. 
 
 I cubic inch = 16-3861759 cubic centimetres. 
 
 I cubic foot = 28-31531 19 cubic decimetres (or litres). 
 
 I pint =0-567932 litre. 
 
 I gallon = 4-5434579 litres. 
 
 Measures of Work. 
 
 I kilogrammetre = about 7-24 foot-pounds. 
 
 I foot-pound =0-1381 kilogrammetre. 
 
 I (kilo)calorie of heat = 425-3 kilogrammetres of work. 
 
 Temperature Scales. — To convert degrees Fahrenheit into degrees 
 Cen^^'grade, subtract 32, and multiply the remainder by ?,. To convert 
 degrees C. into degrees F., multiply by i. and add 32 to the result. 
 
APPENDIX B 
 BIBLIOGRAPHY. 
 
 CHAPTER I. 
 
 INTRODUCTION. 
 
 Colloids. — Bechold. Die Kolloide in Biologic unci Mpdizin, Dresden, 191 a. 
 Van Bemmelen, Die Absorption {colloids). Dresden, 1910. Botazzi, 
 Archivio di Fis., IQ09, 7, 579- Bixton and Rahe, Hofmeister's Beit., 
 1908, 11, 479. Field and Teac.tte, J. Exp. Med., 1907, 9, 222 {electric 
 charge of native proteins and agglutinins). Hardy, J. Phys., 1905-6, 33, 
 251 (colloidal solution). Heard, J. Phys., 1912, 45, 27. Hober. 
 Hofmeister's Beit., 1908, 11, 64 {neutral salt actions). Paili, Hofmeister's 
 Beit., 1906, 7, 531 ; 3, 225. Robertson (T. B.), Die physikalische Chemie 
 der Proteine, Dresden, 1912. Schryver, Proc. Roy. Soc, 1910, B 83, 
 96. Wai.pole, J. Phys., 191 3- 47, P- xiv. 
 
 Coagulation of Proteins. — Buglia, Arch. Internat. de Phy.^iol., 1910. 10, 
 224. Chick and Martin, J. Phys., 1910, 40, 404; 1911, 43, i ; 1912. 45, 
 61, 261. Mirray IC). Bioch. j., 1906, 1, 167. Ramsden, Proc. Roy. 
 Soc, 1903, B 72, I5'» (surface lay.'rs of solutions and suspensions — 
 mechanical coagulation). Sutherland, J. Phys., 1911, 42, p. vii. 
 
 Structure and Aggregate State of Protoplasm.— Chambers, Am. J. Ph^-s.. 
 1917, 43, I. Jensen, PHUger's Arch., 1901, 87, .^'jI- Hardy, J. Phys., 
 
 1899, 24, 158, 2o-». Kite, Am. J. Phys., 1913, 32, 14''). Mathews. Biol. 
 Bull., 1906, 11, 141. Rhi'mbler, Z. f. allg. Phys., 1902. 1, 279. SchXfer, 
 Qu. J. Exp. Phys., 1910, 3, 285. Schenck, i^fluger's Arch., 1900, 
 81, 584. Macallum (A. B.), J. Phys., 1905, 32, 95 [distribution of K in 
 cells). 
 
 Reaction of Protoplasm. — Barratt, Brit. Med. J., June 18, 1904, p. 1413. 
 Henderson iL. J.) and Black (O. P.), Am. J. Phys., 1907, 18, 250. 
 
 Protoplasmic Movement. — Jensen, Ergeb. d. Phvsiol. (Bioph.), 1902, i. 
 Kuhne, Z. f. Biol.. 1897, 35, 43; ^t-. 1898, 36, 4^5- Schenck, Pfluger's 
 Arch., 1S07, 66, 241 (oxvgen and protoplasmic movement) . 
 
 Differentiation and Specificity of Starches. — Reichert (E. T.), Carnegie 
 
 Instit. Pub., 1013 (Washington). 
 
 Nucleus Plasma Relation.— Howard (W. T.), J. Exp. Med.. 1908. 10, 207. 
 
 Combinations of Proteins and Inorganic Substances.— Loeb (J.), Am. J. Phvs., 
 
 1900, 3, ^27 {wn-protem compounds). Rohertson (T. B.). Ergeb. d. 
 Physiol., 1910, 216. Mann (G.), Chemistry of the Proteids, London, 
 1906. Pauli and Handowsky, Hofmeister's Beit., 190S, 11, 415. 
 
 Plant Proteins. — Osborne (T. B.), Ergeb. d. Phys., 1910, 47; Science, 1908, 
 28. 4 1 - 
 
 1 1 52 
 
THE CIRLVLATISG LHjllDS Oi JUL liOUY 1153 
 
 CHAPTER II. 
 
 Till-: CIRCULATING LIQUIDS OF THE BODY. 
 
 BuCKMASTER (G. A.), The Morphology of Normal and Pathological Blood, 
 London, 1906. 
 
 Erythrocytes. — DiiiixjEN, Virchow's Arch., i9oi,165, 282 (envelope). Meyer. 
 Arch. Int. Med., 1914, 14, 94 [colour index). Albrecht, Zentr. f. Phys., 
 1905, 19, 19 [envelope). Meves, Anat. Anzrig., 23, 212 (structure). 
 Peskind, Am. J. Phys., 1903, 8, 414 [action of acids and acid salts). 
 L6HNEK, .Arch. Mikros. Anat., 1907, 71, 129 (' membrane ' of). Rous 
 and Turner, J. E.\p. Med., 1916, 23, 219, 239 [livnig erythrocytes in vitro). 
 Schaeer. Anat. An/eig., 1905, 26 (structure). Weber and Suchard, 
 Arch, do Plij-s., iSSo, 12, 521 (rouleaux). Stewart (G. N.), Am. J. 
 Phys., i9o_', 8, iiH (envelope of Xecturus corpuscles). 
 
 Blood Formation and Regeneration. — Foot, J. Exp. Med., 1913, 17, 43 
 (boue-)iiayrow in vitto). IIall and Eubank, ib., 1896, 1, 656. Noll, 
 Ergeb. d. Phys. (Bioch.), 1903, 433. Malassez, Arch, de Phys., 1882, 
 I. Pearce (R. M.) et al., J. Exp. Med., 1912, 16, 758, 7G9, 780 (spleen). 
 Seemann, Ergeb. d. Phys. (Bioch.), 1904, 12. Woolley, J. Lab. Clin. 
 Med., 1916, 1, 347 (in foetus). Opie, J. Exp. Med., 1905, 7, 759- See- 
 mann, Ergt'h. d. Phys. (Bioch.), 1904, 30. 
 
 Blood at High Altitudes. — Abderhalden, Z. f. Biol., 1902, 43, 125,443; 
 Pfliiger's Arch., 1905, 110, 95. Burker, ib.. 1904, 105, 480. Jaquet, 
 Arch. Exp. Path. Pharm., 1900, 45, i. Schneider and Havens, Am. J. 
 Phys., 1915, 36, 380. Henocque, Arch, de Phys., 1889, 710. Gaule, 
 Pfliiger's Arch., 1902, 89, 119. Guillemard and Moog, J. Phys. Path. 
 Gen., 1907. 9, 17; ib., 1910, 12, 869. 
 
 Destruction of Erythrocytes in the Body. — Bain, J. Phys., 1903, 29, 352 
 (yCle of liver and spleen). Findlay, ib., 1910, 40, 445 (hcsmolysis in the 
 liver ?). Kyes, Internal. Monatsch. Anat. Phys., 1914, 31, 543 [in birds). 
 Rous and Robertson, J. Exp. Med., 1917, 25, 651, 665. 
 
 Variation in Number of Erythrocytes. — Boothby and Perry, Am. J. Phys., 
 1915, 37, 378. Hawk, jh., 1904, 10, 384 (effect of exercise). Btjrker, 
 Pfluger's Arch., 1905, 107, 42O (technique). Downs and Eddy, Am. J. 
 Phys., 1917,43,415 (influence of secretin). HASSELBALCHandHEVERDAHL, 
 Skand. Arch. Phys., 1908, 20, 289 [some physical causes of variation). 
 Ward, Am. J. Phj-s., 1904, 11, 394. Wheels (J. J.) and Sutton (J. E.), 
 Am. J. Phys., 1915, 39, 31 (blood counts in frog, turtle and mammals). 
 (For influence of .\drenahn see Chapter XI.) 
 
 Permeability of Erythrocytes. — De Boer, J. Phys., 1917, 51, 211 {influence 
 of respiration on exchange (f SO^ between corpjtscles and plasma). Ham- 
 burger, Osmotischer Druck und lonenlehre; Bioch. Z., 1915, 71, 464 
 [influence of osmotic pressure and the permeability problem) ; Z. f. Phy^ikal. 
 Ch., 1909, 69, 663 (for Ca ions). Ho-^er, Pfluger's Arch., 1904, 102, 196; 
 Oppenheimer's Handb. d. Bioch., 1908, 2, i. Masing, Pfliiger's Arch., 
 1913, 149, 227 (glucose). Manwaring and Kusama, Soc. Exp. Biol. 
 Med., 1916, 13, 173 (for protein). Rohonyi, Kolloid. Chem. Bcihefte, 
 I9i^>, 8, 337, 377 (Phy.siol. Abstracts, 1917, 2, 178, 179). Spiro and 
 Henderson, Bioch. Z., 1908. 15, 114 [influence of CO2). 
 
 Osmotic Relations of Erythrocytes.— Bang, Bioch. Z., 1909, 16, 255. 
 EvKMAN, Pfluger's .\rch., 1897. 68, 58 [permeability). Hedin, ib., 68, 
 229 (permeability). Hober, ib., 1904, 102, 196 (ion-permeabilitv). 
 Gryns, ib., 1896, 63, 86; ib., 1905. 109, 289. Hamburger, Z. f. Biol., 
 1897, 35, 252, 289 (respiratory exchange and volume of erythrocytes). 
 KoRANYi and Bence, Pfluger's Arch., 1905, 110, 532 (action of CO^. 
 Koeppe, ib., 1897, 67, 189. Moore and Roaf, Bioch. J., 1907, 3, 55. 
 Scott (F. H.), J. Phys., 1915, 50, 128. Stewart (G. N.), J. Phys.. 
 1900-1, 26, 470. 
 
 73 
 
ir5f BIBLIOGR \IHY 
 
 Resistance of Erytlirocytes.— Chalilr aiul Chaki.et, J. Phys. Paili. Gen., 
 lyii. 13, j-^i [fffact of splenectomy). Hamburgkr (H. J.), %b., 1900, 2, 
 889. Hii.L (L. v.), Arch. Int. Med., 1915, 16, 8o<j {m the aiiceinias, etc.). 
 Mussru and Kkumbh.xar, J. Am. Med. Ass., 1916, 67, 1^91- 
 
 Hfiemolysis.— Akriiicnil'.s, Bioch. Z., 1908, 11, 161; ICrgcl). d. Phys., 1908, 
 .j8o. B.\siiFORD. Arch, de Pharmacodyn., 8, loi ; 9, -151 (bloodiiumunity). 
 13aumgarti:n, Bioch. Z., 1908, 11, 21 (osmological theory). Boruet, 
 Ann. Instit. Pasteur, 1900, 14, 257; Bordet and Gay, ib.. 1908, 22 
 (hccmolytic sera). Eiiiu.icn, Proc. Roy. Soc, 1906, B66; Bcrl. Khn. Woch. 
 (nunicrous papers from 1899 onwards). Flexnkr and Noguchi, J. Exp. 
 ]\led., 6, 277; Kyes, Berl. Khn. Woch., 1903, Nos. 42, 43; Bioch. Z.. 
 1907, 4, 99; J. Infect. Dis., 1910, 7, 181; Mitchell and Keichert, 
 Sniithson. Contrib., 1886, 9 {venom hcrtnolysis). Guthrie (C. C), Am. 
 J. Phys., 1905, 8, 441; J. Lab. CHn. Med., 19x7, 3, 87; Githrie and Lee, 
 Soc. Hxp. Biol. Med., 1914, 11, 149 (lahing by hypertonic solutions). 
 JoBLiNQ antl Bull, J. Exp. Med., 191 3, 17, f>i {relation oj immune serum 
 lipase to hcenwlysis). Kraus and Levaditi, Handb. d. 'lech. u. Method, 
 d. Immunilatsforschung, 1, 57; 2, 903. McPhedran, J. Exp. Med., 
 1913. 18, 527 {acids and hcemolysis). Manwaring, Brit. Med. J., 1906, 
 2, 1342; J. Inf. Dis., 1907, 4 {physical chemistry of hcemolytic serum); 
 J. Biol. Ch., 1907, 3, 387 {qtiantitative methods). Meltzer and Welch, 
 J. Phys., 1884-5, 5» -55 {shaking). Noguchi, Bioch. Z., 1907, 6, 185. 
 Traube, Bioch. Z., 1908, 10, 371; Pfluger's Arch., 1904, 105, 541, 559 
 {lipoids and hemolysis). Peskind (S.), Am. J. Phys., 1904, 12, 184 
 {ether laking). Roaf, Q. J. Exp. Phys., 1912, 5, 132 {taking by alkali, 
 hypotonic NaCl, heat). Stewart (G. N.), J. Pharm. Exp. Ther., 1909, 
 1, 49 {mechanism of hemolysis) ; Am. J. Phys., 1902, 8, 103 {nucleated 
 corpuscles) ; ib., 1903, 9, 72 {iujluence of cold) ; ib., 1904, 11, 250; 12, 3O3 
 {htrmolysinogenic and agglutininogenic action of laked corpuscles) ; J . Med. 
 Res., 1902, 8, 268; J. Phys., 1900-1, 26, 470. Wassermann, Immune 
 Sera (translated by Bolduan). 
 
 Cytolysins. — Lambert, J. Exp. Med., 1913, 19, 277. Taylor, J. Biol. Ch., 
 
 ivoy, 5, 311. 
 
 Leucocytes. — Busch and Van Bergen, J. Med. Res., 1902, 8, 408; ib., 1903. 
 10, 230 {differential count in dog and cat). Deetjen, Arch. f. Phys., 1906 
 401 (division of human leucocytes in vitro). Evans (F. A.), Arch. Int. 
 Med., 1916, 18, 692 {mononuclear). Hardy and Wesbrook, J. Phys., 
 1895, 18, 490. Hamburger (H. J.), Arch. f. Phys.. 1902, Supp. Bd.. 
 119 {permeability of leucocytes). Kanthack and Hardy, J. Phys., 
 1894-5, 17, 81 {wandering cells of mammalia). Howe and Hawk. Am. J. 
 Phys., 1912, 30, 174 {differential count during fasting). Ehrlich and 
 Lazarus, The Histology of Blood, Normal and Pathological. Ross 
 (H. C), J. Phys., 190S, 37, 327 {dectth of leucocyte.':). Walker (C. E.), 
 Proc. Roy. Soc. (Lond.), 1906, B78, 53 ; ib., 1907, 79, 491, 495 {life history). 
 
 Blood-Platelets. — Brown (W. H.), J. Exp. Med., 1913. 18, 273 {histogenesis). 
 I'.iJKKKK, Pfliiger's Arch., 1904, 102, 3O {in coagulation). Bunting, J. Exp. 
 Med., 1909, 11, 541. Bayne-Jones, Am. J. Phys., 1912, 30, 74 {pro- 
 thrombin and thromboplastin). Deetjen, Z. f. Physiol. Ch., 1900, 63, i. 
 Duke, Arch. Int. ]\Ied., 1913, 11, 100; J. Am. Med. Ass., 1913, 65, 1600 
 {cause of variations in platelet count). J^mmel (V. E.), J. Med. Res., 1917, 
 37, 67 {erythrocytic origin). Lee and Minot, J. Am. Med. Ass., Apr. 21, 
 1917, 1211 {significance). — Le Sourd and Pagniez, J. I'hys. Path. G6n., 
 1909, 11, I {in coagulation); ib., 1912, 14, 1167 {in regeneration of blood). 
 Minot, Arch. Int. Med., 1917, 19, 1062 {in purpura, etc.). Zucker and 
 Stewart, Zentrall). f. Phys., 1913, 27, 85 {platelets and the vasoconstrictor 
 property of serum). Kemp and Calhoun, Am. J. Ph/s., 1901, 5, iv. 
 Wright (J. H.) and :\1inot, J. ]:xp. Med., HJ17, 26, :-,<)!). Zucker (T. V.), 
 Soc. Exp. Biol. Med., 1914, 11, Oo {platelets and clotting). 
 
 Viscosity of Blood.— Bukton-Opitz, J. Exp. Med., 1906, 8, 50, 240; J. Phys., 
 1901-5. 32,385; J. Am. Med. Ass., 1911, &7, 353) ^^"^- J- l'l»ys.. I9M. 35, 
 
Tin: CIRCULATING LIQUIDS Of THE BOhY 1155 
 
 .51. 265. Denning and Watson, Proc. Roy. Soc, 190O, B 78, 328. 
 lltTRTnin, 1900. PflUgcr's Arrh , 82, .115. Sxydkr and Todd. Am. 
 J. riiys.. loii, 28, 161. 
 
 Reaction of Blood.- Aullk, Am. J. Phys., 1907, 19, i. Cllli:n, J. Biol. 
 C\\ . iwi;. 30, itHj. llASSiiLBALCif and Li'ndsc;aari>. Skand. Arch. Phys., 
 191.:. 27, 13; Bioch. Z., 1012, 38, 77: ib., 41, .147 [effect of CO.,). Milroy, 
 Q. J. Kxp. Phys.. 1015. 8, mi; J. Pliys., 1917. 51, 259. McClendon. 
 J. Biol. Ch.. 1916, 24, 519; ib., 25, <)<»9 [method). Parsons (T. R.), J. 
 Phys., 1917. 51, 440. Scott (R. V.). J. Lab. Clin. iMed., 1916, 1, 6o« 
 {dissociation curve as index of H-ion concentration). Peters. Am. J. 
 Phys., 1917. 43, 113 (COo). Levy. Rowntree and Marriott, Arch. 
 Inf. ^Ied., 1915, 16, 389. Robertson, J. Biol. Ch., 1909, 7, 351 • 
 
 Regulation of Reaction. — Henderson (L. J.) and Black (O. F.), Am. J. 
 IMivs., igo>s, 21, .|2o. Henderson, ib., 21, 173, 427; ib., 1907. 18, 250; 
 ICrgeb. d. Phys., 1909, 254; J. Biol. Ch., 1909,7,29. Mooke and Bxglanu, 
 Bioch. J., 1909, 5, 32. McClendon et al., J. Biol. Chom.. igi?- 31, 
 519. Kop.ertson, ib., 1909, 6, 313. 
 
 Relative Volume of Corpuscles and Plasma.— Bleibtreu. Pfliiger's Arch.- 
 iSi).'. 51, 151; ib., us.>5, 60, 405. ('API'S, J. Med. Res., 1903, 10, 367 
 [volume index). Fraenckel (P.), Z. 1". Klin. Med., 1904, 52, 470 ; Stewart 
 (G. N.), J. Phys., 1899, 24, 356 [electrical resistance method). Hedin, 
 Pflu-;er's Arch., 1895, 60, 36o;"Koeppe, ib.. 1905, 107, 187 [hematocrit). 
 Larrabee, J. Med. Res., 1911, 24, 15 [volume index). 
 
 Electrical Conductivity of Blood. — Brunings, Pfliiger's Arch., 1903, 100. 
 303. H6iu:r, Physikal. Chem. d. Zelle. Hamburger, Osmotischer 
 bruck. Frank, Am. J. Phys., 1905, 14, 466 [during coagulation). 
 Oker-Blom, Pfluger's Arch., 1900, 81, 167. Stewart (G. N.), J. Phys., 
 1S99, 24, 211. Wilson (T. P.), Am. j. Phys., 1905, 13, 139; Bioch. J., 
 1907, 2, 377 [in coagulation). 
 
 Blood-Coagulation. — Arthus, J. Phys. Path. Gen., 1901, 3, 887 [fluoride); 
 ib., 1902, 4, I, 281; Arch, dc Phys., 1890, 22, 79. Collinvvood and 
 MacMahon, J. Phys., 1912, 45, 119. Cramer and Pringle, Q. J. Exp. 
 Phys., 191 3, 6, I ; J. Phys., 191 2, 45, p. xi. Delezennk, J. Phys. Path. Gen., 
 1897, 333, 347 [bird's blood). Howell, Am. J. Phys., 1911, 29, 187 
 [antithrombin); ib., 1914, 35, 143 [ultramicroscope); ib., 1916. 40, 526. 
 Loeb (L.). Hofmeister's licit.. 1907, 9, 185. Loeb and Fleischer, Bioch. 
 Z., 1910, 28, 169 [coaguiins). Mellanby, J. Phys., 1908, 38, 28. Pick 
 and Spiro, Z. Physiol. Ch., 1900, 31, 235 [proteoses). Morawitz, Ergeb. 
 d. Phys., 1905, 307; Deut^ch. Arch. Klin. Med., 1903-4, pp. i, 215, 432. 
 Reichert, J. Exp. Med., 1905, 7, 173 [second coagulation). Rettger, 
 Am. J. Phys., 1909, 24, 406. Dastre and Floresco, Arch, de Phys., 
 1896, 402. Stuebel, Pfluger's Arch., 1914, 156, 361 [ultramicroscope). 
 
 Coagulation Time. — ^ .Addis, Q. J. Exp. Phys., 1908, 1, 305. Burker, Pfluger's 
 Arch., 1913, 149, 318. Cannon and Gray, Am. J. Phys., 1914, 34, 232. 
 Cannon and Mendenhall, ib., 1914. 34, 243 [adrenalin effect). Simpson 
 and Rasmussen, O. J. Exp. Phys., iqK). 10, 159. 
 
 Calcium and Coagulation.— Arthus, Arch, de Phys., 1896, 47; ib., 1897, 219. 
 Austin and Pepper, .\rch. Int. Med., 1913, 11, 305. Addis, Q. J. Exp. 
 Med., 1909, 2, 149. Beard, J. Phys., 191 7, 51, 294. Hess, Soc. Exp. 
 Biol. Med., 1916. 13, 59. Goddard, Am. J. Phys., 1914, 35, 333. 
 Morawitz, Hofmeister's Beit., 1904, 4, 381. Rich, Am. J. Phys., 1917, 
 43,371- 
 
 Anticoagulants. — Franz (F.), Arch. Exp. Path. Pliarm., 1903, 49, 342 [hirudin). 
 Havcraet, ib., 1884, 18, 209 [leech extract). Lee and Vincent, J. Med. 
 Res., 1915, 32, 445 [anaphylaxis and leech extract). Mellanby (J.), 
 J. Phys., H)09. 38, 441 [venoms). Minot, Am. J. Phj's., 1915, 39, 131 
 [chloroform). Pringle and Tait, J. Phys., 1910, 40, p. x.xxv. ; ib., 1911, 
 42, p. xxxviii. Shattuck, .Vrch. Int. Med., 1917. 20, 167 (protein 
 intoxication). 
 
IT56 BIBLIOGRAPHY 
 
 Proteoses and Blood-Coagulation. — Arthus and HuniiR, Arcli. de Phys., 1896, 
 857. Dastkk ami Fi.oresco, ih., 1897, 210. Dki-Kzknne, ib., 1895, 8, 
 635; ib., 1898, 50S [relation of liver). Gley and Pachon, ib., 1896,715 
 [iiver). Pick and Spiro, Z. Physiol. Cii., 1900, 31, .^},5. Schmidt- 
 MuLHEiM, Arch. f. Phys., 1880, 33. 
 
 Fibrin, Fibrinogen. — Howell, Am. J. Phys., lyiO, 40, 526 [fibrin-gel and 
 theories 0/ f^d- formation). MoRAWnz, Oppcnhcimcr'.s Handb. d. Bioch., 
 ii.,2, ')o. 
 
 Origin of Fibrinogen. — Goodpasture, Am. J. Phys., 1914, 33, 70. Mathews 
 (\. P.), lb., 1899, 3, 53. Meek, ib., 1912, 30, 161 [liver). Opie, Barker 
 and Dochez, J. Kxp. Med., 1911, 13, 162. Whipple, Am. J. Phys., 
 igi.). 33, 50- 
 
 Thrombin, etc.— Coi.linwoou and MacMahon, J. Phys., 1913-14, 47, 4 1 
 (tlnoDibin and antithrombin). Gasser, Am. J. Phys., 1917. 42, 378 
 [significance of protliyo)nbin and thrombin in serum). Howell, Am. J. 
 Phys., 1914, 35, 474 [firothronibin). Drinker (C. K. and K. R.), ib., 
 1916, 41, 5 [prothrombin from bone-marrow). MiNOT and Denny, Arch. 
 Int. Med., 1916, 17, loi [prothrombin and antithrombin factors in coagit- 
 latiou). Rich, Am. J. Phys., 1917, 43, 549 [nwtathrombin). Mellanby 
 (J.), J. IMiys., 1917, 51, 390 {rate of formation from prothrombin). 
 
 Antithrombin.— Denny and Minot, Am. J. Phys., 1915, 38, 233. Hess, 
 J. JCxp. Med., u)i.5, 21, 338. 
 
 Thromboplastic Substances in Coagulation. — Howell, Am. J. Phys., 1912, 
 31, I. MacRae and Sciinac k, Hi., i'ji3. 32, 211 [action in clotting). 
 McLean, ib., i9i(), 41, ^30; ib., i<)i7, 43, 586 [crphalin). 
 
 Intravascular Coagulation. Davis, Am. J. Phj's., 191 1, 29, 160. Halli- 
 burton and Brodi];, J. Phys., 1894, 17, 135. Mudge, Proc. Roy. See. 
 (Lend.), 1907, B 79, 103. Pickering, J. Phys., 1896, 20, 310 [albinos). 
 Wright (A. E.), J. Phys., 1891, 12, 184. 
 
 Coagulation in Invertebrates. — Alsberg and Clark, J. Biol. Ch., 1908, 6, 323 
 [limuliis). L()i;b (L.), Bioch. Z., 1910, 24, 478. Tait, Q. J. E.\p. Phys., 
 1 910, 3, I. 
 
 Blood-Proteins. — Briggs, J. Biol. Ch., 1915, 20, 7. Cullen and Van Slyke, 
 Soc. Exp. Biol. Med., 1916, 13, 197 (methods). Epstein, J. Exp. Med., 
 1913, 17, 444. PoRGEs and Spiro, Hofmcister's Beit., 1903, 3, 277 
 [globulins). Robertson, J. Biol. Ch., 1912, 13, 325. Thompson, ib.. 
 1915, 20, I- Wells, ib., 1913, 15, 37. Woolsey, ib., 1913, 14, 433. 
 Hammarsten, Ergeb. d. PhysT (Bioch.), 1902, 330. Mellanby (J.), ). 
 Phys., i.)07-8, 36,288. 
 
 Blood-Lipoids. — Bloor, J. Biol. Ch., 1916, 25, 577 [man). Brown (E. W.), 
 Am. J. Phys., 1899, 2, 306 [cholesterol in birds). Joslin, Bloor and 
 Gray, J. Am. Med. Ass., 1917, 69, 375; Seo, Arch. Exp. Path. Pharm., 
 1909, 61, I {diabetes). 
 
 Cholesterol in Blood.— Bloor, J. Biol. Ch., 1916, 24, 227; ib., 1917, 29, 437. 
 CsuNKA, ib., 1916, 24, 431. Gorham and Mveks, Arch. Int. Med., 1917, 
 20, 399. Weston And Kent, J. Med. Res., 1912, 26, 531. 
 
 Blood-Fat. — Bloor, J. Bioi. Ch., 1914, 19, i. Terroine, J. Phys. Path.G6n., 
 191 4, 16, 212. 
 
 Serum Ferments. — Bronfenbrenner and Scott, Soc. Exp. Biol. Med., 
 
 1915, 12, 137. Jobling, Petersen and Eggstein, J. Lab. Clin. Med., 
 
 1916, 1, 172; J. Exp. Med., 1915, 22, 129, 5O8. Sloan, Am. J. Phys.. 
 1915, 39, 9. Carlson and Luckhardt, Am. J. Phys., 1908, 23, 148. 
 Gould and Carlson, ib.. 1911, 29, 163 ; Otten and Galloway, ib., 1910, 
 26, 347 [relation of pancreas to serum diastase). King, ib., 1914, 35, 301. 
 Van uek 1£rve, ib., 1911, 29, 182 [diastatic enzymes in serum). 
 
 Vasoconstrictor Property 0! Serum. — .Atkinson and Fitzpatrick. Soc. Exp. 
 r.iol. Med., H)iJ., 9, 4u. Ci shny and Gi'NN, J. Pharm. Exp. Ther., 
 1913, 5, I [action of serum on perfused heart). O'Connor (J. M.), Arch. 
 
THE CIRCULATISC. LIQUIDS 01' illl. IIODY Ii57 
 
 Hxp. i'iitli. Pharni., 191 2. 67, i«J5. Stkwart (H. A.) and Harvly 
 (S. C). J. Exp. Mod., igi.j, 16, 103. Stewart (G. N.) and Zuckkr, 
 J. Iixp. Med.. 1913, 17, 152. Tatum, J. Pharm. Exp. Ther., 191 .J, 4, 115. 
 
 Anaphylactic or Protein Shock. — Anderson and Schultz, Soc. Exp. Biol, 
 .\li il , i<»ii). 7, ^j. Ai'i;k and Robinson, J. Exp. Med., 1913, 18, 450, 
 55b. Eisi-NBRiiY and Pearce, J. Pharm. ICxp. Tlu>r., 191 2, 4, 21. 
 joHLiNr., Petkrskn and Ec.gstein, J. Exp. Med., 1913. 22, 401 {ferment 
 actions). Manwakinc; and Crowe, J. Immnnitv, K^iy! 2, 517; Voegtun 
 and Bernheim, J. Ph;irm. Exp. Thcr., 191 1, 2, 507; Weil, J. Inununity, 
 1<)17, 2, 323 {relation of liver to). Weil, ib., 1917, 2, 429 {the vasomotor 
 (leptes.sion in). 
 
 HsBmoglobin and Derivatives. — Barcroet and Hill, J. Phys., iqio, 39, 411 
 {nature of oxyhannoglobin, molecular weight). Huener and Gansser, 
 Arch. f. Phys., 1907, 209 {molecular weight). Eischer (H.), ICrgeb. d. 
 Phys., I9i(), 185, 791 {blood and bile pigments). Hai.dane, J. Phys., 
 1900-1, 26, 497 {colorimetric deiermination); ib., 189S, 22, 298 {methcemo- 
 globin). Hartley, J. Phys., 1907, 36, 62 {sulphhcEmoglobin) . Alsberg 
 and Clark, J. Biol. Ch., 1910, 8, i; Alsberg, //;., 1915, 23, 495 {hcsmo- 
 cyanin). Menzies, J. Phys., 1895, 17, 402 {mcthcvmoglobin). Milroy 
 (J. A.), J. Phys., 1909, 38, 3^4 {hcrmochromogen); ib., 1909, 38, 392; 
 Menzies, ib., 1914, 49, p. iv. {hcematin). Laidlaw, ib., 1904, 31, 464 
 {synthesis of hcematin). Keichert, Am. J. Phys., 1903, 9, 97. Reichert 
 and Brown, Soc. Exp. Biol. Med., 1907-8, 5, 66; Proc. Am. Phil. Soc. 
 (Philadelphia), 1908, 47, 298. Frieboes, Pfliiger's Arch., 1903, 98, 434 
 {hcemoglobin crystals). 
 
 Quantity of Blood. — Douglas, J. Phys., 1905-G, 33, 493; ib., 1910, 40, 472. 
 Haldane and Smith, J. Phys., 1899-1900, 26, 331; Smith (J. Lorrain), 
 ib., p. vi. (CO method). Drever (G.), Ray and Walker, Skand. Arch. 
 Phys., 191 3, 28, 290. Keith, Rowntree and Geraghty, Arch. Int. 
 Med., 1913. 16, 547. Plesch, Z. Exp. Path. Ther., 1909, 6, 380. Zuntz 
 and Plesch, Bioch. Z., 1908, 11, 47. 
 
 Vividiffusion. — Abel, Rowntree and Turner, J. Pharm. Exp. Ther., 1914, 
 5, 275. Rohde (A.), J. Biol. Ch., 1915, 21, 325 {ammonia of the circulating 
 blood) . 
 
 Lymph. — Carlson, Greer and Luckhardt, Am. J. Phys., 1908, 22, 91 
 {chlorides). Carlson, Woelfel and Powell, ib., 1911, 28, 176 (local 
 hcBmodynamic action of tissue metabolites). Green (J. R.), ib., 1910, 
 26, 68; Rous, J. Exp. Med., 1908, 10, 537 {leucocytes). Davis and 
 Petersen, J. Exp. Med., 1917, 26, 693 {ferments). Howell, Am. J. 
 Ph^-s., 1914. 35, 483; LussKY, ib., 25, 334 {coagulation). Hughes and 
 Carlson, Am. J. Phys., 1908, 21, 236 {hcsmolytic action). Luckhardt, 
 ib., 1910, 25, 345 {conductivity compared ivith serum). 
 
 Chyle.— Hall (W. S.), J. Am. Med. Ass., 1910, 55, 388. Hamill, J. Phys., 
 1906-7, 35, 131. Paton (D. Noel), J. Phys., 1890, 11, iii. Sollmann, 
 Am. J. Phj-s., 1907, 17, 487. 
 
 CHAPTER III. 
 
 THE CIRCULATION OF THE BLOOD AND LYMPH. 
 
 Carlson, Biol. Bull., 1903,8,123 {comparative physiology of invertebrate heart). 
 MacWilliam, J. Phys., 1885, 6, 192 {heart of eel); ib., 1888, 9, 107 
 {rhythm of mammalian heart). Nukada (S.), Die Automatic und Koordi- 
 nation dos Herzcns, Tokyo, 191 7 {limulus heart). Roy and Adami, 
 Phil. Trans. Roy. Soc, 1892, 183, 199 [physiology and pathology of heart). 
 Tigerstedt, Kreislauf. Wiggers, The Circulation in Health and Disease, 
 1915- 
 
1 1 58 BIBLIOGRAPHY 
 
 Cardiac Cycle. -r>ACHMANN, Am. J. Phys., 1910, 41, 309 {intei auricular 
 nitaval). Wiggers, ib.. 1016, 40, 218 Uiuricular myogram); ib., igi6, 
 42, i-ii (events of auricular systole). Havcraft and Paterson, J. Phys., 
 1895-0, 19, 496 {changes in heart's shape and position); ib., -zbz (papillary 
 muscles). Tunnicliffe, ib., 189O, 20, 51 (diastole). 
 
 Heart Sounds. — Battaerd. Heart, 1915, 6, 121 {graphic researches). Bridg- 
 -MAX, Heart, 1915, 6, 41. Einthoven, Pfliiger's Arch., 1907, 120, 31. 
 Sewall, Pliila. Montlily Med. J., Sep., 1899 (papillary muscles). Thwer, 
 Arch. Int. Med., 1909, 4, 297 (third heart-sound). Wiggers and Dean, 
 A7n. [. Phy.s., 1917, 42, 476 (nature of time relations). 
 
 Registration of Heart Sounds.— Ckehore and Meaka, J. Exp. Med., 1911, 
 13, 016 (micrograph). Junthoven, Pfliiger's Arch., 1907, 117, 461. 
 HoLowiNSKi, Arch, de Phys., 1896, 823. Hurthle. Pfliiger's Arch., 
 1893. 60, 263. Weis-s (O.), Phono-kardiogrammc (Jena, 1909). Wiggers 
 and Dean, Am. J. Med. Sci., 1917, 153, 666. 
 
 Heart Rate. — Bainbridge, J. Phys., 1915, 50, 65 {influence of venous filling on 
 rate). Buchanan (F.), ib., 1910, 40, p. xlii (i'n hibernation); ib., 1908, 
 37, p. Ixxix (in mouse); Sci. Progress, July, 1910 (in vertebrates). Loeb 
 and EwALD, Bioch. Z., 1913, 58, 177 (heart-rate as function of the 
 temperature). 
 
 Function of Pericardium. — Barnard (H. L.), J. Phys., 1898, 22, p. xliiii. 
 Kixo (V.), ib., 1915. 50, I. 
 
 Endocardiac Pressure: Auricle. — Wiggers, Am. J. Phys., 1914, 33, 13. 
 ZwAH-WKxr.rKG and Ac.ne\v, Heart, 1912, 3, 343. 
 
 Endocardiac Pressure: Ventricle.— Frank (O.), /. f. Biol., 1S97, 35, 478. 
 Fkan9ois-1'r.\nk, Arcli. de Phys., 1890, 22, ^95; ib., 189^. 25, 8^ 
 Porter. J. ICxp. Med., 1S96, 1, 296. Tigerstedt, Skand. Arch. Phvs., 
 1912, 28, 37: ib.. 191.), 31, 241. Wiggers, Am. J. Phys., 1914, 33, 382. 
 
 Coronary Circulation. — Barbour and Prince, J. Exp. Med., 1915, 21, 330 
 (epinephrin). Guthrie and Pike, Science, 1906, 24, 52 (coronary pressure 
 and action of heart). Hyde, Am. J. Phys., 1, 213 (dilation of ventricles 
 and coronary flow). Langendorff, Pfliiger's Arch., 1899, .78, 423 
 (isolated heart). Magrath and Kennedy, J. Exp. ISIed., 1897, 2, 13 
 (coronary circulation and ventricular beat). Markwalder and Starling, 
 J. Phys., 1913, 47, 273. Miller and Matthews, Arch. Int. Med., 1909, 
 
 3, 476 (obstruction of left coronary). Porter, J. Exp. Med., 1895, 1» 46 
 (closure of coronaries); Am. J. Phys., 1, 145 (influence of beat on coronary 
 
 flow) . 
 
 PULSE. 
 
 Arterial Pulse. — Dawson (P. M.), Am. J. Phys., 1917. 42, 613 {pulse velocitv). 
 Frank (O.), Z. f. Biol., 1899, 37, 483 (mathematical); ib., 1905, 46, 441. 
 Hewlett, Arch. Int. Med., 1914. 14, 609 (reflection of primary wave). 
 Hill, Barnard and Sequeira, J. Phys., 1897, 21, 147 (effect of venous 
 pressure). Hoorweg, Pfliiger's Arch., 1905. 110, 598 (peri phcral reflection), 
 HOrthle, Pfliiger's Arch., 1890, 47, 17 (origin of secondary tvaves). 
 Lewis (T.), J. Phys., T906, 34, 414. Lohman, Pfliiger's Arch., 1904, 103, 
 632 (dicrotic wave). MacWilliam, Kesson and Melvin, Heart, 1913, 
 
 4, 393 (conduction of pulse wave). Tigerstedt, Ergeb. d. Phys., 1909, 593. 
 Wiggers, J. Am. Med. Ass., 1915, 64, 1483 (contour of normal pulse). 
 
 Venous Pulse. — Cushny and Grosh, J. Am. Med. Ass., 1907, 49, 1254. 
 Ewing, Am. J. Phys., 1914. 33, 158. Eyster, J. Exp. Med., 1911, 14, 
 594; ib., 1910, 12, 257. FREDiiRiCQ, Zcntralb. f. Phys., 1908, 22, 297. 
 McQueen and Falconer, J. Phys., 1914. 48, 292 (' C ' wave). Morrow, 
 Brit. Med. J., Oct. 27, and Dec. 22, 1906; Pfliiger's Arch., 1900, 79, 
 442 (velocity). Wiggers, J. Am. Med. Ass., 1915. 64, 1483. 
 
 Cardiopneumatic Movements. — Harris, J. Phys., 1903, 32, 495- Haycraft, 
 il'-. 1S91, 12, \2(<. Meltzer, Am. J. Phys., 1S98, 1, 117. Stewart 
 (G. X.), Arch. 1'. Phys., 1912, 4O0. 
 
THE CIRCULATION OF THE BLOOD AND LYMI'lI 115O 
 
 BLOOD-PRESSURE. 
 
 Arterial Blood-Pressure. - Hkooks, Heart, loio, 2, 5 {tmcings from quiescent 
 tininial). C.\.Mi'nj-i.r. (H.), J. Phys., 1898-9, 23, 301 {/ylnce of chief resist- 
 ance to jlow). Dawson. Am. J. Phys., 1906, 15, "^14 {pycssure at diff^renl 
 points of aitcrial tree). Frank (O.). Z. f. iiiol.. 1907. 50, -'81 (elastic 
 membranes). Hukthi.e, Pfliiger'-s Arch., 1903, 110, 421; //'., 191^, 147, 
 509 (pressure and velocity). MacCraken and Wernkss. J. Pharm., 
 E.\p. Thcrap., 191 7. 9, 305 (overcoming clotting). Pilcher, Am. J. Phys., 
 1915. 38, 209 (membrane manometer curves). Riddle and Matthews, 
 Am. J. I'hys., 1907, 19, 108 (birds). VVicgers, it., 1914, 33, i (pressure 
 curve in pulmonary artery). Wood (H. C), ib., 1899, 2, 352 (traube 
 ivaves). WooLEY, J. Lab. Clin. Med., 1915. 1, 203 (CO^andblood-prcssure). 
 
 Action of Proteoses on Blood-Pressure (and Coagulation). — Chittenden, 
 Mendel and IIicndkkson, Am. j. Phys., 1890, 3, r |2. Pearce (R. M.) 
 and EisENHREY, Arch. Int. i\Icd., 1910, 6, 218. Thompson, J. Phys., 
 1896, 20, 455; 1899, 24, 374. Underbill, Am. J. Phys., 1903, 9, 343. 
 Zunz, Arch. Int. dc Phj's., 1911, 11, 73. See also under Chapter II. 
 (proteoses and coagulation). 
 
 Arterial Blood-Pressure in Man. — Borach and Marks, Arch. Int. Med., 1913, 
 11, 485; ib., 191 4.. 13, 648. Elliott (B. L.), Am. J. Phys., 191 7, 42, 290 
 (effect of occlusion of bloodvessels). Erlanger and Hooker, Johns 
 Hopkins Hosp. Rep., 1904, 12, 145. Hill and Rowlands, Heart, 191 2, 
 
 3, 219. Lombard, Am. J. Phys., 191 2, 29, zt,5 (skin). McCurdy, Am. 
 J. Phys., 1 90 1, 5, 95 (exercise). Muller (F.), Harvey Lecture, New York, 
 1907. RoLLESTON, Heart, 1912, 4, 83 (in aortic incompetence) . Taussig, 
 Arch. Int. Med., 1913, 11, 342. 
 
 Measurement of Blood-Pressure in Man. — Frank (O.), Tigerstedt's Handbuch 
 d. physiol. Mcthodik, 2, Abth. 4, 216. INIacleod, J. Lab. Clin. Med., 
 1913, 1, 62, 13S (r^sumi-). 
 
 Auscultatory Method. — Brooks and Luckhardt, Am. J. Phys., 1916, 40, 49. 
 Erlanger, ib., 40, 83. Foley, Coblentz and Snyder, ib., 40, :'54. 
 Hill (L.), Heart, 1909, 1, 73. Hooker and Southworth, Arch. Int. 
 Med., 1914. 13, 384. Kilgore, Arch. Int. Med., 1915, 16, 927. Mac- 
 William and Melvin, Heart, 1914, 5, 153. Warfield, Arch. Int. Med., 
 1912, 10, 23S. Wiggers, J. Am. Med. Ass., 1915, 64, 1485 (segment 
 capsules, optical record). 
 
 Oscillatory Method. — Erlanger, Johns Hopkins Hosp. Rep., 1904, 12, 53; 
 
 Am. J. Phys., 1908, 21, p. xxiv. Kilgore, Arch. Int. Med., 1915, 16, 893. 
 Venous Pressure. — Burton-Opitz, Am. J. Phys., 1903, 9, 198. Hooker, ib., 
 
 1014, 35, 73; ib., 1916, 40, 43. V. Recklinghausen, Arch. Exp. Path. 
 
 Pharm., 1906, 55, 470. Sewall, J. Am. ^Nlcd. Ass., 1906, 47, 1279. 
 
 RATE OF PERIPHERAL BLOOD-FLOW. 
 
 Burton-Opitz, Am. J. Phys., 1914, 36, 64 (carotid); Quart. J. Exp. Phys., 
 
 1910, 3, 297; ib., 1911, 4, 93; ib-, 191 2, 5, 83 (hcpxtic artery); ib.. 191 1, 
 
 4, 113; ib., 1912, 5, 189; ib., 1912, 5, 309 (portal vein). Brodie and 
 Russell, J. Phys., 1905, 32, p. xlvii. 
 
 Blood-Flow in Man. — Edmunds, Am. J. Phys., 1907, 18, 129 (influence of 
 drugs on velocity). Frank (O.), Z. f. Biol., 189S, 37, i (velocity. Pilot's 
 tubes). Hewlett and Van Zwaluwenburg, Heart, 1909,1,87 (arm); 
 Am. J. Med. Sci., 1913. 145, 636; Arch. Int. Med., igir, 8, 591. Hough 
 and Ballantyne, J. Bost. Soc. Med. Sci., June, 1899 (skin, influence of 
 temperature). Macleod, J. Lt.b. Clin. Mod., 1916, 1, 359 (resumi). 
 MACLEOD and Pearce, Am. J. Phys., 1914, 35, 87 (liver). Matas, J. Am. 
 Med. Ass., 1914, 63, 1441 (collateral circulation). Shields, J. Exp. Med., 
 1896, 1, 71 (effect ojf odours and mental work). Stewart (G. N.), Heart] 
 
 1911, 3, 33 (hands); Am. J. Phys., 1911, 28, 190 (forced breathing); Arch! 
 Int. :Med., 1912, 9, 706 (pressures on upper arm); J. Exp. Med., 1913, 
 
ll6o BIBLIOGRAPHY 
 
 18, 354 (fcut)', i^-< 18, 1 1.5 [anamias); ib., 1915, 22, 694 [collaleral circu- 
 lation after ligation of innominate). V. Kries, Z. Exp. Path. Thcrap., 191 1, 
 9, (33 (arteries in ina)i). 
 
 Rate of Blood-Flow in Veins.— I'ikton-Opitz, Am. J. Phys.. 1903, 7, 4351 
 /7'., PHiiger's Arch., 1907, 121, 150 [sirotmihr); ib., 1908, 121, 156. 
 
 Circulation Time. — Hering, Vierordt, Vierordt's Physiologic, 1871, p. 147. 
 L.\Nt.LOis and Desbouis, J. Phys. Path. Gen., 1912, 14, 282, 1113 (pul- 
 monary). Stewart (G. N.), J. Phys., 1893, 15, i [electrical and methylene 
 blue methods). 
 
 Heart Output. — Bornstein (A.), Z. Exp. Path. Tlier., 1911, 9, 382 [gaso- 
 metric method in man). Cowl, Arch. f. Phys., 1900, 564 [ROntgen cardio- 
 graphs in man). D.^wson and Gorh.^m, J. Exp. Med., 1908, 10, 484 
 (pulse pressure as index). Gesell (R.), Am. J. Phys., 1915, 38, 404. 
 Henderson (Y.) and Barringer, Am. J. Phys., 1913, 31, 2SS (conditions 
 determining output). Henderson (Y.) and Prince, ib., 1914, 35, 106 
 (the oxygen pulse and the systolic discharge). Knowlton and Starling, 
 J. Phys., 191 2, 44, 206 (influence of temperature and blood-pressure on 
 performance of isolated heart). Murlin and Greer, Am. J. Phys., 1914, 
 33, 253 (relation of heart-rate to respiratory metabolism). Krogh and 
 Lindhard, Skand. Arch. Phys., 1912, 27, 100 (gasometric methodin man). 
 Krogh, ib., 27, 126, 227. Patterson, Piper and Starling, J. Phys., 
 1914, 48, 465 (output depends on inflozv). Plesch, Z. Exp. Path. Ther., 
 1909, 6, 380 (in man). Stewart (G. N.), J. Phys., 1898, 22, 159 (dog). 
 Tigerstedt, Skand. Arch. Phys., 1907, 19, 1; ib., 1909, 22, 115 (dog). 
 Wolf, Arch. Int. Med., 1911, 8, 463 (cat, influence of temperature). 
 
 Pulmonary Circulation.^ — Puhner and Starling, J. Phys., 191 3, 47, 286. 
 Plesch, Z. f. Exp. Path. Ther., 1913, 13, 165. Tigerstedt, Ergeb. d. 
 Phys. (Bioph.). 190^, 52S; Skand. Arch. Phys., 1907, 19, 231. Wiggers, 
 Am. J. Phys., I9i2,36, 23;;. Wood (H. C.), Am. J. Phys., 1902, 6, 283; 
 J. Exp. Med., 1911, 14, 320. 
 
 ORIGIN OF HEARTBEAT. 
 
 Sino-Auricular Node. — Cohn, Kessel and Mason, Heart, 1912, 3, 311, 341. 
 EvsTER and Meek, Arch. Int. Med., 1916. 18, 775 (conduction of excitation 
 from sino-auricular node). Flack, J. Phys., 19x0, 41, 64. Lewis and 
 Oppenheimer (B. S. and A.), 'Heart, 1910, 2, 147 (location of pacemaker). 
 Macleod, J. Lab. Qin. I\Ied., 1916, 1, 263 (origin and spread of impulse 
 — resumi). Meek and Eyster, Am. J. Phys., 1914. 34,368 (location of 
 pacemaker); Heart, 1914, 5, 119. 227; Am. J. Phys., 191 7. 42, 611; Am. 
 J. Phys., 1916, 39, 291. Schlomovitz and Chase, Am. J. Phys., 1915, 
 41, 112 (pacemaker in turtle's heart). Moorhouse, ib., 1912. 30, 358; 
 ib., 1913, 31, 421. Oppenheimer (B. S. and A.), J. E.xp. Med.. 1912, 
 16, 613 (nerves in sino-auricular node). Sansum, Am. J. Phys., 1912, 30, 
 41 1 (extra systoles caused by stimulation of node). 
 
 Cause 0! Heart Beat. — Carlson, Am. J. Phys., 1904. 12, ''?• 471 (Umulus). 
 Carlson and Meek, ib., 1908, 21, 1 (embryonic heart rhythm in limulus). 
 Cyon, Pfliiger's Arch., 1906, 113, m. Dale (D.) and Thacker, J. 
 Phys., 1914, 47, 493 (H-ion concentration). Erlanger, Harvey Lecture, 
 New York, 1912-13. Greene (C. W.), Am. J. Thys., 1899, 2, 82 
 (blood salts). Hering, Pfliiger's Arch., 1907. 116, 143. Kronecker, 
 Z. f. Biol., 1896, 34, 529. — Langendorff, Ergeb. d. Phys., 1902, 317; 
 ib., 1905. 764. Lake, J. Phys., 191G, 50, 364 (growth of heart tissue in 
 vitro). Martin (E. G.), Am. J. Phy.s., 191 2, 30, 182 (ventricular tonus 
 and causation of beat); Am. J. Phys., 1913, 32, 1O5 (blood salts). Porter 
 (W. T.), J. Phys., 1S07, 2, 3"i. 
 
 Extra Contraction and Compensatory Pause.- Carlson, Am. J. Phys., 1908,. 
 21, 19 (limulus); ih.. 1907, 18, 71 (mechanism of refractory period); 
 ib., 1906, 16, 67 (excitation of heart during different phases of beat). Cushny. 
 Heart, 1012, 3, 257 (stimulation of isolated ventricle). Cushny and 
 
THE CIRCULATION OF THE BLOOD A\D LYMPH 1161 
 
 Matthews, J. Phys., 1897, 81, 213 {effects of electrical stimulation of 
 mammalian heart). Hirschfelder and Eyst?;r, Am. J. Phvs., 1907, 
 18, 212. Langendorff, Ergeb. d. Phys. (Bioph.). igo2, 282 {physio- 
 lof^iial properties of heart muscle). Mtti-LER (Fr.), Harvey Lecture, New 
 York, 1907 (extra systoles). Schultz (\V. H.), Am. J. Phys.. 1908, 22, 
 133 (refractory period). Wenkebach, Arch. f. Phys., 1903, 57 (compen- 
 satory pause) . WooDWORTH (R. S.), Am. J. Phys., 1902, 8, 213 (refractory 
 period and compensatory pause). 
 Heart Muscle Strips. — Erlanger, Am. J. Phys., 1910, 27, 87 (auricle). 
 Martin (E. G.), ib., igo.), 11, 103 (terrapin ventricle). 
 
 CONDUCTION OF CARDIAC EXCITATION AND CONTRACTION. 
 
 Atrio - Ventricular Conduction System : Auriculo - Ventricular Bundle. — 
 
 Barker and Hir.schfelder, Arch. Int. Med., n;o(7, 4, I9^^ Carlson, 
 
 Am. J. Phys., 1908, 21, n (liinultis). Cohn, Heart, 1909, 1, lO; [auricido- 
 
 nodal junction). Clllis and Dixon, J. Phys., 1911, 42, I5'>. Engel- 
 
 MANN, Pfliiger's Arch., 1894, 56, 149; 1895, 61, 275; 1890, 62, 543. 
 
 Erlanger, Am. J. Phys., 1909, 24, 375; Arch., Int. Med., 1913, 11, 334; 
 
 ib., 191 2, 30, 395 (physiology of Purkinje tissue). pREDfiRicQ, .\rch. Int. 
 
 de Phys., 1912, 11, 405, 478. Gault, Am. J. Phys., 191 7, 43, 22 
 
 (turtle, influence of vagus and sympathetic). Hering, PjSugcr's Arch., 
 
 1905, 108, 267:107, 99- Howell, J. Am. Med. Ass., 1906, 46,Nos. 22,23. 
 
 Keith, Lancet, Mar. 5, 1904. Kent, J. Phys., 1893, 14, 233; Quart. J. 
 
 Exp. Phys., 1913, 7, 193; Proc. Roy. Soc, "1914, B 87, 198. Laurens, 
 
 Am. J. Phys., 1916-17, 42, 89, 513 (ttirlle). Lewis, White and Meakins, 
 
 Heart, 1914, 5, 289. Lewis, ib., 1913, 5, 21 (ratein dog's auricle). Prince 
 
 and Ceraci, Heart, 1915, 6, 167. Saltzmax, Skand. Arch. Phys., 
 
 1908, 20, 233 (papillary muscles). Tawara, "Das Reizleitungssystem 
 
 des Saiigethierherzens," Jena, 1906; Zentralbl. f. Phys., I905, 19, 70. 
 
 White and Kerr, Heart, 1917, 6, 207 (whale). Wilson (J. G.), Proc. 
 
 Roy. Soc, 1909, B 81, 151 (nerves of atrio-ventricular bundle). 
 
 Heart-Block. — Bachmann, Arch. Int. Med., 1909, 4, 238 (strophanthin). 
 
 Buchanan (F.), J. Phys., 42, p. xix (dissociation of auricles and ventricles 
 
 in hibernation). Christian, Arch. Int. Med., 1915, 16, 341 {digitalis). 
 
 Erlanger, J. Exp. Med., 1905, 7, 676; ib., 1906, 8, 8. Erlanger and 
 
 Blackman, Heart, 1910, 1, 177. Eyster and Meek, Arch. Int. Med., 
 
 1917, 19, 117 (sino-aiiricular and sino-ventricular block). Eyster and 
 
 Evans, ib., 1915, 16, 832. Carrey, Am. J. Phys., 1912, 30, 283 (com- 
 
 ptvssion of cardiac nerves of limulus). Gesell, ib., 1916, 40, 2(>7. 
 
 Fibrillation in Heart. — Garrey, Am. J. Phys., 1908, 21, 283 (influence of 
 
 cardiac nerves on); ib., 1914, 33, 397. Gunn (J. A.), Heart, 1915, 5, i 
 
 (rate). Levy (A. G.), J. Phys., 1914, 49, 54. MacWilliam, J. Phys., 
 
 1887, 8, 296. Porter, Am. J. Phys., 1898, 1, 71 (recovery of heart from). 
 
 Influence of Temperature on the Heart. — Carlson, Am. J. Phys., 1906, 15, 
 
 207. Evans (C. L.), J. Phys., 1917. 51, 91 (mechanism of acceleration by 
 
 warmth and adrenalin). L.\ngendorff, Ergeb. d. Phys., (Biophys.), 
 
 1903, 517. Stewart (G. N.), J. Phys., 1892, 13, 119 (heat standstill). 
 
 Isolated Mammalian Heart. — Barcroft and Dixon, J. Phys., 1906-7, 35, 
 
 182 (gaseous metabolism). Cushny and Gunn, J. Pharm. Exp. Therap., 
 
 1913, 5, I ; Manwaring, Meinhard and Denhart, Soc. Exp. Biol. Med., 
 
 1916, 13, 173 (effect of serum). Evans (C. L.). J. Phys., 1914, 47, 407 
 
 (effect of glucose on gaseous metabolism). Guthrie and Pike, Am. J. 
 
 Phys., 1907, 18, 14 (relation of activity to pressure in coronary). Gorham 
 
 and Morrison, ib., 1910, 25, 419 (action of blood proteins). Langendorff, 
 
 Pfliiger's Arch., 1895, 61, 291; ib., 1897, 66, 2,55; ib., 1898, 70, 473. 
 
 Locke and Rosenheim, J. Phys., 1907, 36, 205 (consumption of dextrose). 
 
 Neukirch and Rona, Pfluger's Arch., 191 2. 148, 285 (consumption of 
 
 sugars by). Porter (W. T.), Am. J. Phys., 1898, 1, 511. Waller and 
 
 Reid, Phil. Trans. (Roy. Soc, Lond.), 1887, B 178, 215 (action of excised 
 
 heart) . 
 
ir(,i BIBLIOGRAPHY 
 
 RELATION OF SALTS TO HEART ACTION. 
 
 Benedict (S. R.), Am. J. I'hys., 1908, 22, 16; Carlson, ib., 16, 221; Eggers 
 (H. E.), ib., 1907, 18, 6.{ {non-electfolytes). Botazzi, Arch, dc Physiol., 
 1896, 882 (potassium). Burkidgk, (.j. J. ]''xp. Phys., 1915, 8, 303 (NaCl) ; 
 ib., 8, 331 (Ca salts and alkalies). Clark (A. J.), J. Phys., 1913-14, 47, 
 66 [ions and lipoids). Howell, Am. J. Phys., 1901, 6, i8r (Na. K and 
 Ca). Langendorit, Ivrgeb. d. Phys. (Bioch.), 1902, 312 [chemical con- 
 ditions of heart-beat). Lingle (D. }.), Am. J. Phys., 1900, 4, 265 {non- 
 electrolyt(^s) ; ib., 1902, 8, 73 {{NaCl); ib., 1905. 14, 433. Loeb (J.), Am. 
 J. Phys., 1900, 3, 383; i'lUiger's Arch., 1900, 80, 229 {Ca and K). 
 Mines, J. Phys., 1913, 46, 188 {electrolytes); ib., 1911. 42, 309. Martin 
 (E. G.), Am. J. Phys., 1913, 32, 165 {blood salts). Maxwell and Hill, 
 Am. J. Phys., 1902, 7, 409 {Ca and free oxygen). Ringer (S.), J. Phys., 
 1895, 18, 425 (antagonism bet'ween Ca salts and Na, K, and NH^ salts). 
 Waller (M. D.), J. Phys., 1914, 48, p. xlvi (electrolyte concentrations 
 and frequency). 
 
 COo and Heart. — Bayliss, J. Phj^s., 1900-1, 26, p. xxxii. Cathcart and 
 " Clark, ib., 1913, 47, 393- Jerusalem and Starling, ib., 1910, 40, 279. 
 Ketcham, King and Hooker, Am. J. Phys., 1912, 31, 64. 
 
 Resuscitation of Heart. — Ckile and Dolley, J. Exp. Med., 1906, 8, 713 (after 
 anaesthetics and asphyxia). Erlanger, ib., 1912, 16, 452 (sinus stitnii- 
 lation as a factor). Gunn (J. A.) and Martin (P. A.), J. Pharm. Exp. 
 Ther., 1915, 7, 31 [intraspinal medication and massage). Kemp and 
 Gardner, Medical News, 83, 184 (after chloroform). Kuliabko, Pfluger's 
 Arch., 1903, 97, 539- Langendorff, Ergeb. d. Phys., 1905, 769. Pike, 
 Guthrie and Stewart, J. Exp. Med., 1908, 10, 371. 
 
 Heart Nerves (Cardio-Regulative Nerves).— Carlson, Ergeb. d. Phys., 1909, 
 
 ^71 (comparative physiology of heart nerves and heart ganglia in inverte- 
 brates). Clark (G. H.), Heart, 1913, 4, 379 (influence of temperature). 
 CoHN, J. Exp. Med., 1912, 16, 732 (differences between the ttco vagi in dog). 
 CuLLis and Tribe, J. Phys., 1913, 46, 141 (distribution of nerves in heart). 
 Cyon, Die Nerven dcs Herzens (BcrHn) ; Lcs Ncrfs du Ca?ur, Paris, 1905. 
 DoGiEL and Archangelsky, Pfliiger's Arch., 1906, 113, i. Engelmann, 
 Arch. f. Phys., 1900, 315; ib., 1902, Supp. Bd., i, 103, 443 (effects of vagus 
 on rate, force, etc.). Garrey, Am. J. Phys., 1912, 30, 451 (effects of vagi 
 in heart-block); ib., 1911, 28, 33 (turtle). Gaskell, J. Phys.. 1883, 4, 43 
 (tortoise); Phil. Trans. (Roy. See, Lend.), 1882, 993 (frog). Harrington 
 (D. W.), Am. J. Phys., 1898, 1, 383 (guinea pig). Hough (T.), /. Phys., 
 1895, 18, 161 (escape of heart from vagus inhibition). Hunt (R.), J. Exp. 
 Med., 1897, 2, 151; Am. J. Phys., 1899, 2, 395 (relation of accelerator to 
 inhibitory nerves). Langendorff, Ergeb. d. Phys. (Bioph.), 1902, 263 
 (heart muscle and intracardial innervation). Lewis (T.), Heart, 191 4, 5, 
 247 (vagal stimulation and antrio-ventricular rhythm). Meek and Eyster, 
 Am. J. Phys., 1912, 30, 271 (electrical changes in heart during vagus 
 stimulation). Paton (D. N.), J. Phys., 1912, 45, 106 (birds). Schlomo- 
 viTZ, Eyster and Meek, Am. J. Phys., 1915, 37, 177 (relation of nodal 
 tissue to inhibitory nerves). Sewell and Donaldson (F.), J. Phys., 1880- 
 82, 3, 357 (influence of intracardiac pressure on vagus action). Stewart 
 (G. N.), J. Phys., 1892. 13, 59) Z. f. Biol., 1913, 59, 5U (influence of 
 temperature of heart on activity of heart nerves); Am. J. Phys., 1909, 2% 
 341 (tortoise vagus). Wiggers, Am. J. Phys., 1916, 42, 133 (influence 
 of vagus on "fractionate " contraction of right auricle). 
 
 Accelerators. — Cyon, Pfliiger's Arch., 1906. 113, 111. FKioiiRicQ (H.). 
 Arch. Intcrnat. de Phys., 1913, 13, 115. Hering (H. E.), Pfluger s 
 Arch., 1903, 107, 125 (direct action on mammalian ventricle). 
 
 Action of Accelerated on Quiescent Heart. — Carlson, Am. J. Phys., 1904, 
 12, 35 (molluscs). Hering, Pfliiger's Arch., 1906, 115, 354 (mammals). 
 Stewart (G. X.), J. Phys., 1892, 13, S3, 90 (amphibia). 
 
Tlir: CIRCUL.IIIOS Ol- the DLOOD A.\D lymph 1163 
 
 Voluntary Acceleration of Heart. 1"avi 1.1. ;incl White. Heart, 19.7, 6, 175- 
 \'an 1)K \'i;i i>i;, I'lln-ns Anli., i8<)7, 66, 2^2. 
 
 Cardio-Inhibitory Centre and Reflexes. Hainbridcie, J. Phys., 1914, 48, 
 ^32. Eyster and Hooker, Am. J. Phys., 1908, 21, 373; Filehne ;i:ul 
 BiBERFiELU, Pfliigcr's Arch., 1909. 128, 443 {rffcci of increased blond- 
 pressure). Hooker, Am. J. Phys., 1908, 19, 417 [reflex acceleration 
 independently of cardio-inhibitory centre ?). Miller and liowMAN, Am. 
 J. Phys., 1915, 39, 149. Wertheimer and IMeyer, Arch, dc Phys., 1890, 
 284 {influence of deglutition on hearl-rhytlnn). 
 
 Relation 0! Salts to Inhibition.— Brine (B. U.). Am. J. Phys., 191 7 44, 171; 
 l^uRRiU(;i:, ]. Phvs., 1917, 51, .J.5 ((^ " ""<^ -^^')- Ho<;an and Ormono, Am. 
 J. Phys., 191.:, 3d, 105 (Ca). Howell, ib., 1906, 15, 280 (salts of blood). 
 Howell and Duke, ib.. 1908, 21, 51 [output of K in inhibition) ; ib., 1908, 
 23, 1 74 [accelerators and Ca, K and N metabolism of isolated heart) ; J . Phys., 
 1906-7, 35, 131 [isolated mammalian heart). Langendorff and Hueck, 
 Pflugcr's Arch., 1903, 96, 473 [Ca)- Loeb (J.), J. Biol. Ch., 1906, 1, 
 427 [Mg and Ca on contractions of jellyfish). Martin (E. G.), Am. J. 
 Phys., 1904, 11, 370 (^^'C/). 
 
 VASOMOTOR NERVES. 
 
 BowDiTCH and Warren, J. Phys., 7, 416 [of limbs). Drinker (C. K. and 
 K. R.), Am. J. Phys., 1916, 40, 514 [of bone-niarroiv) . Gaskell (W. H.), 
 J. Phys., 1878-9, 1, 262 [vasomotors of muscles). Langley, J. Phys., 
 189I, 12, S45. 375 [course of sweat and vasomotor fibres of cat' s foot) ; ib., 
 iQii! 41, .483 [frog's foot). 
 
 Vasomotors o£ Intestine.— Bunch (J. L.), J. Phys., 1899, 24, 72. Burton- 
 Opitz, Am. ]. Phys., 191 5, 35, 203 [duodenum) . Hallion and Fran^ois- 
 Franck, J. "Phys. Path. Gen., 1896, 478, 493. 
 
 Vasomotors of Lungs.— Brodie and Dixon, J. Phys., 1904, 30, 476. 
 Francois-Franck, Arch, de Phys., 1S96, 178. Jackson, J. Pharm. Exp. 
 Thcr.,' 1913, 4, 291. Krogh, Zentralbl. f. Physiol., 20, 802 [tortoise). 
 Langlois and Desbouis, J. Phys. Path. Gen., 1912, 14,282. Plumier, 
 ib., 1904, 655. Tigerstedt, Ergeb. d. Phys. (Bioph.), 1903, 571. 
 Tribe (E. M.), J. Phys., 1914, 48, 154. Wiggers, J. Pharm. Exp. Ther., 
 1909, 1, 341- 
 
 Cerebral Vasomotors. — Baylis.s and Hill, J. Phys., 1S95, 18, 334- Dixon 
 and Halliburton, Q. J. Exp. Phys., 1910, 3, 315- Gulland (G. L.), 
 J. Phys., 1895, 18, 361; Huber (G. C), J. Comp. Neurol., 1899, 9, i; 
 Hunter (W.), J. Phys., igoo-i, 26, 465 [histological). Hill and Macleod, 
 ib. 26, 394- Jensen, Pfliiger's Arch., 1904. 103, 171, 196. Wiggers, 
 Aril. J.' Phys., 1905, 14, ^5^:ib., 1907, 20, 206; ib., 1908, 21, 454; J. Phys., 
 1914. 48, 109. 
 
 Vasomotors of Heart.— Brodie and Cullis, J. Phys., 1911, 43, 313- Dogiel 
 and Archangelsky, Pfliiger's Arch., 1907, 116, 482. Porter, Am. 
 J. Phys., 1912, 29, p- x^xi [method). Wiggers, ib., 1909. 24, 391. 
 
 Vasomotors of Veins (Veno-Motors).— Bancroft, Am. J. Phys., 1898, 1, 477 
 [hind limb). Bayliss and Starling, J. Phys., 1894, 17, 120; Burton- 
 Opitz, Q. J. Exp. Phys., 1913, 7, 57: Am. J. Phys., 1914, 36, 325; 
 Edmunds (C. W.), J. Pharm. Exp. Ther., 191 5, 6, 5'^9 [portal vein). 
 Francois-Franck and Hallion, Arch, de Phys., 1897, 434 [liver). 
 Henderson (Y.), Am. J. Phys., igiq, ^2, 5^9 ['"eno-pressor mechanism). 
 
 Vasomotor Mechanism.— Asher, Ergeb. d. Phys. (Biophys.), 1902, 346. 
 Bayliss, ib., 1906, 319. Cotton, Slade and Lewis, Heart, 1917, 6, 227 
 [contractile power of capillaries). Edwards (D. J.), Am. J. Phys., 1916, 
 35 15 [compensatory phenomena during splanchnic stimulation). Hooker, 
 Am. J. Phys., 1911, 28, 361 (chemical regulation of vascular tone). Porter 
 and Newburgh, ib., 1914, 35, i [in pneumonia) . Porter and Turner, 
 ib., 1915, 39, 236 {vasotonic and vascreflex mechanism). 
 
M64 BIBLIUL.RAI'IIY 
 
 Vasomotor Centres. Mathison, J. Phys., loii, 42, 283; Portlr (W. T.), 
 Am. J. J'hys.. 1913, 31, p. xxix {functional relation of nerve cells in); ib., 
 19^5. 36, 418 (vasotonic and vasorcjlcx centre). Poktkk and Ci.akk, ib., 
 1908, 21, p XV [difference between bulbar and spinal vasomotor cells). 
 PoRTF.R and Storey, ib., 1907, 18, 181 (effect of injuries of brain). 
 Kanson, ib., 191 6, 42, i (chief vasoconstrictor centre). Sollmann and 
 PiLCHER, ib., 1910, 26, 233 (effect of sciatic stimulation and ctirara). 
 
 Vasodilators. — Bayliss, J. Phys., 1900, 26, 173; ib., 190.', 28, 27O (hind limb. 
 antidrfliiiic impulses). Bernard (Cl.), Liquidcs do ror^anisnie, 2, 269 
 (chorda). Carlson (A. J.), Am. J. Phy.s., 1907, 19, 408; McLean (!•'. C), 
 ib., 22, 279 (vasodilators to submaxillary in cat's cervical sympathetic). 
 EcKiiARD, Bcitra2;c, 3, 125; 4, (>9 (mervi erigentes). Kendall and 
 LucHsiNGER, Pfliigi'i-'s Arcli., 1876, 13, 197 (difference between dilators 
 and constrictors after nerve section). 
 
 Depressor. — Bayliss, J. Phy.s., 1908, 37, 264. Cyon, Plliiger's Arch., 1901, 
 84, 304. Porter and Beyer, Am. J. Phys., 1900, 4, 283. Ranson 
 and BiLLiNc.sLEY, Am. J. Phy.s., 1916, 42, 9. Sewall and Steiner, 
 J. Phys., 1885, 6, 162. Sollmann and I'ilchkr, Am. J. Phys., 1912, 
 30, 369 (response of vasomotor centre to). Tigerstedt, Skand. Arch. 
 Phys., 1908, 20, 330. TsciiiRwiNSKY, Zentralb. f. Phys., 9, 777; 10,65. 
 
 Vasomotor Reflexes. — Henderson (V. E.) and Loewi (O.), Arch. Exp. Path. 
 Pharm., 1903, 53, 56 (vasodilator excitation). Hunt, J. Phys., 1895, 18, 
 381 (fall of blood-pressure on stimulation of afferent nerves). Langley, 
 J. Phys., 191 2, 45, 239 (effect of strychnine). Martin and Lacey, Am. 
 J. Phys., 1914, 33, 212 (vasomotor reflex thresholds). Martin and 
 Mendenhall, ib., 1915, 38, 98 (vasodilator response to sensory stimulation). 
 Martin and Stiles, ib., 1916, 40, 194 (vasomotor summations). Porter, 
 ib., 1907, 20, 399 (uniform stimuli with blood-pressure at different levels); 
 ib., 1910, 27, 276 (relations of afferent impulses to vasomotor centres). 
 Porter and Marks, ib., 1908. 21, 460 (effect of hcsmorrhage). Porter 
 and Richardson, ib., 1908, 23, 131. Stewart (G. N.), Heart, igii, 3, 
 76; Stewart and Laffer, Arch. Int. Med., 1913, 11, 365; Stewart and 
 Walker, ib., 11, 383 (elicited by loarmth and cold in man). Vincent and 
 Cameron, Q. J. Exp. Phys., 1915, 9, 45. 
 
 Influence of Asphyxia on Circulation. — Hill and Flack, J. Phys., 1908, 37, 
 77 (on circulation and respiration). MacVVilliam, J. Phys., 1901-2, 27, 
 337 (asphyxia and cardiac failure). Mathison, (7;., igii, 42, 283 (medul- 
 lary centres); ib., 1910, 41, 416. Sollmann and Pilcher, Am. J. Phys., 
 191 1, 29, 100 [reaction of vasomotor centre to asphyxia). 
 
 Pressor Amines. — Abelous andBAROiER, Compt. Rend. Sec. do Biol., ^hlr.I7, 
 1906; Dale and Dixon, J. Phys., 1909, 39, 25 (formed in putrefaction). 
 Baehr and Pick, Arch. Exp. Path. Pharm., 1916, 80, 161 (point of attack). 
 Bain (W.), Q. J. Exp. Phys., 1914, 8, 229 (pressor bases in urine). Dale 
 and Laidlaw, J. Phys., 1911, 43, 182; Laidlaw, Bioch. J., 1911, 6, 141 
 (action). Walpole, J. Phys., 1909, 38, 2.^3. 
 
 Depressor Amine ("Vasodilation"). — Barger and Dale, J. Phys., 1911, 
 41, 499; Mellanby and Twort, ib., 191 2, 45, 53 (in intestine wall). 
 
 Intracranial Pressure. — Gushing (H.). Johns Hopkins Hosp. Bull.. Sep., 1901. 
 IvYSTER, Burrows and Essick, J. Exp. Med., 1909, 11, 489. 
 
 Influence of Gravity on Circulation. — Hill (L.), J. Phys., 1S93, 18, 13. Hill 
 and Barnard, ib., 1897, 21, 323. SALATiii, Compt. Rend., 1877, 85, 445. 
 
 SHOCK. 
 
 Bainbridge and Bullen, Lancet (London), 191 7, 2, 51. Bayliss (W. M.), 
 Arch. Med. Beiges, 191 7. 70, 793 (Physiol. Abstracts, 1918. 2, 625) (treat- 
 inent by intravenous injections). Erlanger and Wooovatt, J. Am. Med. 
 Ass., 1917, 69, 1410; Erlanger, C^esell, Gasser and Elliott, ib., 1917, 
 69, 2089. Guthrie, ib., 1917, 69, 1394- Henderson (V.), Am. J. Phys., 
 
RESPIRATION 1165 
 
 1908, 21, 126; 16., 1900, 23, 345: ih.. If 10. 27, 15-2: Henderson and 
 ScARHROi t;n, ib., lyio. 26, ^ho (acapnia and shock). Henderson, 
 t6.. 1910, 25, 310. 385; Henderson, Prince and Haggard. J. Am. Med. 
 Ass.. H)i7. 69, 965. Janeway and Jackson, Soc. Exp. Biol. Med., 1915. 
 12, i<)3; J. Am.. Sled. Ass.. Oct. 16. 1915. 371. Lvon and Swartz. Soc. 
 Kxp. Biol. Med., 1910, 7, I39- Meltzer. Arch. Int. Med., 1908, 1, 571, 
 Morrison and Hooker, Am. J. Phys., 1915. 37, «<'> Pike and Coomus. 
 J. Am. Med. Ass., 191 7, 68, 1892. " Porter, Bost. Med. Surg. J., 191 7. 
 177, 320. Porter, Marks and Swift, Am. J. Phys., 1907, 20, 44^• 
 Porter and Quinby. Am. J. Phys., 1908. 20, 500. Seelig and Joseph, 
 J . Lab. Clin. Med., 1916, 1, 283. Simonds, J. Am. Med. Ass., 191 7, 69, 883. 
 
 Transfusion.— BoTAzzi and Japelli. Bioch. Z., 190S, 11, 331 {physico-chemical 
 properties of blood and lymph after). Carlson and Ginsburg, Am. J. 
 Phys.. 1015. 36, 280 (influence on hyperglyceemia of pancreatic diabetes). 
 Crile (C. \V.), Soc. Exp. Biol. Med., 1906, 4, 6. Haskins (H. D.), J. 
 Biol. Ch., 1907, 3, 321 (effect on N metabolism). Ottenberg and 
 Thalhimer, J. Med. Res., 1915, 33, 213. Rabens, Am. J. Phys.. 1914, 
 36, 294 (influence on kidneys). 
 
 Lymph Hearts. — Abel and Tunner, J. Pharm. Exp. Ther.. 1914, 6, Oi 
 (action after cardiectomy). Laxgendorff, Pfliiger's Arch.. 1906, 115, 
 533. Moore (A.), Am. J. Phys.. 1901, 5, 87 (influence of ions); ib., 5, 
 196 (spinal centres). Priestley (J.), J. Phys., 1878-9, 1, I, 19 [older 
 literature). Tschermak, Pfluger's Arch., 1907. 119, 165 (spinal in- 
 nervation). 
 
 Channels in Liver Cells communicating with Blood Capillaries. — Schafer, 
 Anat. Anzeig.. 190J, 21, 18. Herring and Simpson, Proc. Roy. Soc, 
 1906, B 78, 455- 
 
 CHAPTER IV. 
 
 RESPIRATION. 
 
 Blood in Lungs. — Kino. J. Phys.. 1917, 51, 154- 
 
 Respiratory Movements. — Baglioni. Ergeb. d. Phys., 1911, 526. Eyster, 
 Austrian and Kingsley, Am. J. Phys.. 1907. 18, 413 (temporary occlusion 
 of aorta). Fitz (G. W.), J. Exp. Med., 1896. 1, 677. DU Bois-Reymond 
 (R.), Ergeb. d. Phys. (Bioph.). 1902, 377 (mechanics of respiration). 
 Guthrie and Pike. Am. J. Phys., 1906, 16, 475; 1907. 20, 45 (effect of 
 change in blood-pressure on) . Lundsgaard and Van Slyke, J. Exp. Med., 
 1918. 27, 65 (lung volume). 
 
 Temperature of Expired Air. — Loewy and Gerhartz, Pfluger's Arch., 1914, 
 155, 231 
 
 Artificial Respiration and Resuscitation. —Schafer. Lancet, May 30, 1903; 
 Trans. Roy. Med.-Chir. Soc, London, 1904, 86; Proc. Roy. Soc. (Edin.), 
 1904, 25, 39 (in the apparently drowned). Stewart (G. N.) and Pike 
 (F. H.), Am. J. Ph\'s., 1907, 19, 328 (resuscitation of respiratory and other 
 bulbar centres, n-ith reference to their atitowatism). 
 
 Respiratory Dead Space. — Douglas and Haldane, J. Phys., 1912, 46, 235. 
 Haldane (J. S.). Am. J. Phys., 1915, 38, 20. Henderson (Y.) et al.. 
 Am. J. Phys., 1915, 38, i. Krogh (A.) and Lindhard (J.), J. Phys.. 
 iqi7, 51, 59; ib., 191 3, 47, 30. Pearce (R. G.) and Hoover (D. H.), 
 Am. J. Phys., 191 7- 44, 391- 
 
 Alveolar Air. — Hough (T.), Am. J. Phys.. 191 2, 30, iS (alveolar air in muscular 
 exercise). Haldane and Priestley. J. Phys.. 1905. 32, 225. Henderson 
 (Y.) and Morriss (\V. H.), J. Biol. Ch.^ 1917, 31, 217. Krogh and 
 Lindhard, J. Phys., 1914, 47, 43i- Macleod (J. J. R.), J. Lab. Clin. 
 Med., 1916, 1, ^22 (clinical method for determination of CO2 in alveolar air). 
 Pearce (R. G.). Am. J. Phys., 1917, 44, 369. Van Slyke, Stillman 
 and CuLLEN, J. Biol. Ch., 1917, 30, 401 (alveolar CO^ and plasma bicar- 
 bonate) . 
 
Ii66 lillil.IOGRAl'HY 
 
 Respjiatory Gaseous Exchange. — Benedict and IIomans. Am. J, Phys., 
 inii, 28, -■'». lii.NKnicT [V. G.), ib., 1^09, 24, .;-}5 {a/? para I us). Bene- 
 dict .lud lOMi'KiNb, Boston ftled. Surg. J., i<jio, 174, 857, 8»jS, 939 
 (apparatus for clinical use). Carpenter, Carnegie Inslit. Pub., No. 216, 
 lyij {methods in man). Jaquet, Ergcb. d. Pliy.s, (Bioch.), 1902, 457. 
 Pembrey, J. Phy.s., 1901, 27, 66 {marmot). * Wolf and Hele, J. Phys., 
 1914, 48, 1-8 {decerebrate animal). 
 
 Respiratory Quotient. — Benedict, Emmes and Riche, Am. J. Phys. 1911, 
 27, i'A?, [influence of preceding diet on). Lusk, Arch. Int. Med., 1915, 15, 
 939 {diabetes). 
 
 BLOOD GASES. 
 
 Barcroft, J. Phys., 1908, 37, 12; Barcroft and Higgins, ib., 1911, 42, 
 512; Barcroft and Koukrt.s, ib., 1910, 39, 429 {differential method). 
 BucKMASTEK, J. Phys., 1917, 51, 164 {relations of CO^ in blood). Buck- 
 master and Gardner, J. Phj^s., 1910, 40, 373 {gas" pumps); ib., 1910, 
 41, 60 {gases of arterial and venous blood); ib., 1912, 43, 401 {nitrogen). 
 Cooke and B.\rcroft, J. Phys., 1914, 47, p- xxxv [percentage saturation 
 of O2 in arterial blood in man). Friedman (E. D.) and Jackson (H. C), 
 Arch. Int. Med., 1917, 19, 767 (CO2 of blood and alveolar air in obstructed 
 respiration). Haldank. J. Phys." 1898, 22, 465 {analysis). Krogh. 
 Skand. Arch. Phys., 1908, 20, 259 {microtonometer). Murlin, Edelmann 
 and Kramer, J. Biol. Ch., 191 3, 16, 79 {after clamping abdominal aorta 
 and inferior cava). Peters (J. P.), Am. J. Phys., 1917, 43, 113 (CO2 
 acidosis and cardiac dyspnoea). Rasmussen, Am. J. Phys., 1915, 39, 
 20; ib., 1916, 41, 162 [blood gases in hibernation). 
 Oxygen Tension of Arterial Blood. — Haldane and Smith, (J. L.), J. Phys.. 
 1890, 20, 497. Kkogh, Skand. Arch. Phys., 1910, 23, 252. Osborne 
 (\V. A.), J. Phys., 1907, 36, 48. Scott (R. W.), Am. J. Phys., 1917, 44, 
 196 {decerebrate cat). 
 CO2 Tension. — Boothby and Sandford, Am. J. Phys., 1916, 40, 547 {venous 
 blood, rest and work). Christiansen, Douglas and Haldane, J. Phys., 
 1914, 48, 244. Henderson (Y.) and Prince, J. Biol. Ch., 1917, 32, 325 
 {venous blood). 
 Oxygen Dissociation Curves (oi Blood and Oxyheemoglobin) . — Barcroft and 
 I'amis, J. Pliys., ii)Oi), 39, 14,^ I-Sakcroft and ORi'.Ki.r, ib., 1910, 41, 
 355 (influence of lactic acid). liAKCROFT, ib.. 1911, 42, 44 [altitude). 
 Barcroft and Kinc;, ib., 1907, 39, 374 {tempi ralure). Bohr, Hassel- 
 balch and KKOc;n, Skand. Arch. Phys., 190O, 16, 402 {influence of CO^)- 
 Douglas and Haldane (J. S. and J. B. S.), J. Phys.. 1912, 44, 275 
 {combination of Hb with CO^ and Oo)- Hufner, Arch. f. Phj's., 1901, 
 Supp. Bd., 187 {dissociation of oxylicBmoglobin). Mathison, J. Phys., 
 
 1911, 43, 347 {influence of acids on reduction of arterial blood). 
 
 Oxygen Capacity of Blood.— Barcroft and Burn, J. Phys., 1913, 45, 49.^ 
 Burn, ib.. 1913. 45, 482. Douglas, ib., 1910, 39, 453 [efter hcemorrhage) ; 
 ib., 1910, 40, 472 [total O2 capacity and blood volume at different altitudes). 
 Haldane, ib., 25, 295 [ferricyanide method). Hufner, Arch. f. Phys., 
 1894, 130; ib., 1903, 217 {O^-capacity of blood pigment). I'kters, J. Phys., 
 
 1912, 44, 131. 
 
 Carbon Monoxide. — GuiiiANT, Arch, dc Phys., 1898, 315. 434 (absorption). 
 Haldane, J. Phys., 18, 201, 430 (action). Nasmith and Graham, ib., 
 35, 32 (poisoning). Nkloux. J. Phys. Path. Gen., 1914, 6, 145, 164 
 (absorption). 
 
 Chemical Regulation of Respiration.— Bayliss and Starling, Ergeb. d. 
 Phys., 1906, 6O9. Campi'-ell, Douglas, Haldane and Hobson, J. 
 Phys., 1913, 46, 301. Gasser and Loevenhart, J. Pharm. E.\p. Ther., 
 1914, 5, 239 (decreased O^. Gordon and Haldane, J. Phys., 1909, 
 38, 420. Haldane and "Poulton, ib.. 1008, 37, y)o (O^-defuiency). 
 Haldane and Priestley, ib., 1905, 32, 225. Hough. Am. j. Phys., 
 
RESPIRA riOyj I167 
 
 1911, 28, .K>o (hreaihing a confined volume of air). Hill and Flack, 
 J. Phys., 1908, 37, 77 (excess of COn und uuuit of O.^). Peters, Am. J. 
 I'hys.. i>)i7, 44, >S4 (H-ion comoilrolion of blood). ijcoTT (R. W.), Am. 
 J. riiys., 11)17, 44, T<)("> {COo and H-ion concentiation in decerebrate cat). 
 
 Nervous Mechanism of Respiration. — Barry, J. Phys., i<ji.?, 46, 473 (afferent 
 niiprcisuois). Bokl:it.\ii, Jirgcb. d. Phys. (Biophys.), 1902, 403. 
 Deason and Kobb, Am. J. Phys., 1911, 28, 57 (paths in cord). Gad, 
 Arch. 1. Phys., 1880. i. Gruber, Am. J. Phys., 1917, 42, 450. Nice, 
 Am. J. Phys., 1914, 33, -304 (thresholds for respiratory reflex). Frohlich. 
 Pfliiger's Arch., 1906, 113, 433 (elimination of vagus without stimulation). 
 Haldane and Mavrogordato, J. Phys., ii)i<^>, 50, p. xh (vagus regulation) . 
 LoKWv (A.), Pfliiger's Arch., 1888, 42, .^73. Lewandowsky, Arch. 1. 
 Phys., 189G, 195. Meltzek, Arch. f. Plus., 1892, 340. Nicolaide.s, 
 Arch. f. Phys., 1907, 68. Porter (\V. T".), J. Phys., 1S94-5, 17, 455 
 (phrenic path). Porter and Turner, Am. J. Phys., 1913, 32, 95 (reflex 
 respiratory movements). Stewart (G. N.), ib., 1907, 20, 407. Stewart 
 and Pike, //;., 1907, 19, 328; ib., 20, 61 (resuscitation (f nervous respira- 
 tory Dit'chanisni). 
 
 Respiratory Centre. — Baglioni, Ergeb. d. Phys., 191 1, 58S (automatism of). 
 Boruttau, lb.. 1904, 89. Brown (T. G.), J. Phys., 1914, 48, p. xxxii 
 (a respiratory tract in mid-brain). Hooker, J. Pharm. Exp. Ther., 1913, 
 4, 443 (perfusion in frog). Laqueur and VerzAr, Pfliiger's Arch., 191 2. 
 143, 395 (specific action of CO^, on). Loewy, ib., 1888, 42, 245 (repetition 
 of Marckwald's experiments on paraffin injection [Z. f. Biol., 1890 26, 
 259]). 
 
 Bronchi. — Abbott, J. Med. Res., 1912, 26, 513. Dixon and Brodie, J. Phys., 
 1903, 29, 97; Dixon and Ransom, J. Phys., 1912, 45, 413 (innervation). 
 DU Bois-Reyaiond (R.), Ergeb. d. Phys. (Bioph.), 1902, 396 (alterations 
 in calibre). Henderson (V. E.) and Taylor, J. Pharm. Exp. Ther., 
 
 1910, 2, 153 (secretion). Jackson, ib., 1914, 6, 479 (drugs). 
 Dyspncea. — Athanasiu and Carvallo, Arch. d. Phys., 1898, 95 (heat dyspnoea). 
 
 Lewis, Ryffel, Wolf, Cotton and Barcroft, Heart, 1915, 5, 45 
 (dvspncea in cardiac and renal patients). Moorhouse, Am. J. Phj's., 
 
 1 91 1, 28, 223 (lieat dyspnoea). 
 
 Apncea. — Bqothby, J. Phys., 1912, 45, 328. FoA., Arch. di. Fis., 1911, 9, 
 453. Githens and Meltzer, See. Exp. Biol. Med., 1914, 12, 64. 
 :\iiLROY, Q. J. Exp. Phys., 1913, 6, 373. Mosso, Arch. Ital. do Biol., 
 40, I. Pembrey and Pitts, j. Phys., 1899, 24, 305 (respiration in 
 hibernation). Scarbrough and Henderson, Am. J. Phys., 1910, 25, 
 p. xiii. 
 
 Cheyne-Stokes Respiration.— Barbour, J. Pharm. Exp. Ther., 1914, 5, 393 
 (morphine). Clark (A. J.) and Hamill, ib., 357 (circulatory changes in). 
 Douglas, J. Phys., 1910, 40, 454 (at high attiiudes). Eyster, J. Exp. 
 Med., 1906, 8, 5G5. Fulton, Heart, 1915, 6, 77. Gordon and Haldane, 
 J. Phys., 1909, 38, 401. Mackenzie and Cushny, ib.. 1907, 36, p. xiii. 
 Pembrey, Beddard and French, ib., 1906, 34, p. vi. Pembrey and 
 Allen, J. Ph3'-s., 1905, 32, p. xviii. Pollock, Arch. Int. Med., 1912, 
 9, 406. 
 
 Mechanism of Gas Exchange in Lungs. — Boothby and Berry, Am. J. Phys., 
 1913, 37, 433; Christiansen and Haldane, J. Phys., 1914, 48, 273 
 (influence of distension of lungs). Dixon and Ransom, J. Pharm. Exp. 
 Ther., 1914, 5, 539 (effect of altered vascular conditions in lungs) . Douglas 
 and Haldane, J. Phys., 1912, 44, 305 (causes of O2 absorption in lungs). 
 Evans and Starling, J. Phys., 1913, 46, 413 (oxidation in lungs). 
 Haldane and Lorrain Smith, ib., 189S, 22, 231, 307. Hartridge, 
 ib., T912, 45, 170 (O2 secretion ?). Krogh (M.), ib., 1915, 49, 271 (diffusion 
 throvgh lungs). 
 
 Swim Bladder. — Baglioni, Z. allg. Phys., 1970, 11, 145. Jafcer, Pflflger's 
 Arc'-i., 1903, 94, 65. 
 
1 1 68 BIBLIOGRAPHY 
 
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 Gaseous Metabolism of Organs. — Barcroft and Brodie. J. Phj^., 1903. 32, 
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 1907, 19, 199 {oxidizing power of cupric acetate solutions). McClendon, 
 J. Biol. Ch., 1915. 21, 275 {oxidizing power of oxyhesmoglobin and 
 erythrocytes). Uxderhill and Closson. Am. J. Phys., 1905, 13, 35S 
 {methylene blue, etc.). Usui. Pfliiger's Arch., 1912. 147, 100 {measure- 
 ment of tissue oxidations in vitro). 
 
 Oxidiling Ferments. — Abel^us and Biarn£s, Arch, de Phys., 1896, 311; 
 ib., I8<j8, 664; ib., 1897, 277. Battelli and Stern, Ergeb. d. Phys.. 
 1910. 10, 531; ib., 1912. 12, 96. 197. Bertrand. Arch, de Phj-s., 1896. 
 23 (laccase). Bunzel. J. Biol. Ch., 1916, 24, 91 {mode of action) ; ib., 1916, 
 28, ii5 {relation to H-ion concentration); ib., 24, 103 {plants). Kastle. 
 Hyg. Lab. Bull., No. 59, Dec, 1909. Kastle and Porch, J. Biol. Ch., 
 
 1908, 4, 301 {peroxidase reaction of milk). Lillie, J. Biol. Ch., 1913, 15, 
 237 {formation of indophenol at nuclear and plasma membranes of frogs' 
 blood-corpuscles). Loevenhart and Grove. J. Pharm. Exp. Ther.. 1911, 
 3, loi. Moore and Whitley, Bioch. J.. 1909, 4, 136. Reed, J. Biol. 
 Ch., 1915, 22, 99 (r6le in respiration); ib., 1916, 27, 299 {relation to H-ion 
 concenitation). 
 
 Catalases. — Amberg and Winternitz. J. Biol. Ch., 1911, 10, 295 {sea-urchin 
 eggs). Arkin, Am. J. Phys.. 1917, 42, 603. Battelli and Stern, Ergeb. 
 d. Physiol., 1910, 5?i. Burge, Am. J. Phys.. 191 7, 43, 545'. 44, 75, 290; 
 ib., 1916, 41, isi {>i"iscles). Burge. Kennedy and Neill, Am. J. 
 Phys., 1917, 43, 433 {effect of thyroid feeding). Evans. Bioch. J.. 1907. 
 2, 133 {blood). LoEW, Pfliiger's Arch.. 1909, 128, 560; U. S. Dept. Agric. 
 Rep., No. 68. 1901. Mendel and Leavenworth, .\m. J. Phys.. 1908, 
 21, 85 {tissues). Shaffer, Am. J. Phys., 1905, 14, 299. Winternitz 
 and Meloy, J. Exp. Med.. 1908, 10, 759 {blood). Winternitz and 
 Pratt, J. Exp. Med., 1910, 12, i, 115 {blood). Winternitz and Rogers. 
 ib.. 1910, 12, 12, 755 {eggs). 
 
RESPlkATtON 1109 
 
 Reductases. — Harris (D. l-".). J. Biol. Ch.. i«ji5, 22, 533. Harris and 
 
 Cki ir.inoN, ih., 21. '■."> : 20, 170; Bioch. J., 1914, 8, 585. 
 Bioluminescence (Phosphorescence).— Harvey, Am. J. Phys., 1915, 37, 230; 
 
 ib.. 1916, 41,44'), 454; 'b-. 1917.42, 318; J. Biol. Ch., 1917. 31, 311. 
 
 Kastle and McDermott, Am. J. Phys., 1910, 27, 122. Moore, Bioch. 
 
 J., 1908, 4, I. 
 
 COMPRESSED AND RAREFIED AIR. 
 
 Caisson Illness. — Boycott and Damant, J. Phys., 1907-8, 36, p. xiv. Ham 
 and Hill, ib., 1905-6, 33, pp v, vi, vii. Hill and Macleod, ib., 1903, 
 29, 382, 492. Hill and Greenwood, Proc. Roy. Soc, 1906, B 77, 442; 
 1907, B 79, 21, 284; 1908, B 80, 12. TwoRT and Hill, J. Phys., 1910, 
 41, p. \-. 
 
 Effects of Atmospheres Rich in Oxygen. — Benedict and Higgins, Am. J. 
 Phys., 191 1, 28, I (effect of O.^-yich mixtures on man). Bullott, J. Phys., 
 1904. 31, 359 {action of O^ at low and high pressure on the cornea). Hill 
 and Macleod, Proc. KoyT Soc, B 70, 455, 465 {effects of an atmosphere of 
 O2 on respiratory exchange and circulation in mouse and frog). Hill and 
 Flack, J. Phys., 1910, 40, 347 {effect of oxygen inhalation on muscular 
 work). Karsner, J. Exp. Med., 1916, 23, 149. Karsner and Ash, 
 J. Lab. Clin. Med., 1917, 2, 254. Lorrain Smith, J. Phys., 1899, 24, 19 
 {pathological effect of increased O^ tension). Mosso, Arch, de Phys. et 
 Path., 1878, 10, 76 {action of compressed air) . 
 
 Influence of High Altitudes. — Barcroft, J. Phys., 1911, 42, 44; ib., 1913, 
 46, p. XXX. Bartlett, Am. J. Phys., 1904, 10, 149. Boycott and 
 Haldane, J. Phys., 1908, 37, 355 {low atmospheric pressures) . Cohnheim, 
 Ergeb. d. Phys. (Bioch.), 1903, 612. Douglas, Haldane, Henderson 
 and Schneider, Proc. Roy. Soc. (Lond.), 1913, B 85. Durig and 
 Zuntz, Arch. f. Phys., 1904, Supp. Bd., 417. Hueppe, Pfliiger's Arch., 
 1903, 95, 447. Mosso and Marro, Arch. Ital. Biol., 1903, 39, 387. 
 Schneider et al.. Am. J. Phys., 1908, 23, 90; ib., 1914, 34, 29; ib., 1916, 
 40, 380 {circulation). Tissot, J. de Phys. Path. Gen., 1910, 12,520; ib., 
 1911, 13, 75 {mountain sickness). Ward, J. Phys., 1908, 37, 378. Zuntz 
 and V. ScHRorTER, Arch. f. Phj's., 1902, Supp. Bd., 430, 436 {balloon). 
 
 Influence of Respiration on Circulation. — Golla and Symes, J. Phys., 1916, 
 50, p. xxxii {cerebrospinal pressure and respiratory movements). Hender- 
 son and Barringer, Am. J. Phys., 1913, 31, 399 {respiration and heart 
 output). Snyder, Am. J. Phys., 1915, 1^7, 104 {causes of respiratory 
 change in heart rate) . 3 
 
 Respiratory Waves in Blood -Pressure. — Erlanger and Festerling, J. Exp. 
 Med., 1912, 15, 370. Lewis (T.). J. Phys., 1908, 37, 213, 233. Snyder, 
 Am. J. Phys., 1915, 36, 430. Wiggers, Am. J. Phys., 1911, 35, 124 {in 
 pulmonary artery). 
 
 Cutaneous Respiration. — Barratt, J. Phys., 1897, 21, 192 {CO^and H^O); 
 ib., 24, II {varnished skin). Bohr, Skand. Arch. Phys., 1900, 10, 74 
 {frog). Reid and Hambley, J. Phys., 1895, 18, 411 (C"6.^ in frog). 
 
 CHAPTER V. 
 
 VOICE AND SPEECH. 
 
 Fleeming Jenkin and Ewing, Trans. Roy. Soc. (Edin.), 1879, 28, 745 {vowe 
 sounds). GRiJrzNER, Ergeb. d. Physiol. (Bioph.), 1902, 466 {voice and 
 speech). Hermann, Pfliijer's Arch., 1901, 83, i, S3 {consonants); ib., 86, 
 92 {vowel sounds). McKendrick, Trans. Roy. Soc. (Edin.), 37, Pt. 4. 
 Meyer, The Organs of Speech. Paulsen, Pfliiger's Arch., 1895, 61, 
 407 {the singing voice of children); ib., 1899, 74, 570 {pitch of the voice). 
 Russell (J. S. R.), Proc. Roy. Soc, 1892, 102 {innervation of glottis). 
 . Scripture, Study of Speech Curves, Carnegie Instit. Pub., Wasliington, 
 1906. 
 
 74 
 
1170 BlBLlOGh'.U HY 
 
 CHAPTER VI. 
 D I G E S IM O N . 
 
 MOVEMENTS OF ALIMENTARY CANAL. 
 
 Cannon, Mechanical I'actois of Digestion, New York, 1911; J.A.ISl.A., 1903, 
 40, 749- 
 
 Deglutition. — Botazzi, J. Phys., iSgg, 25, 157 (nerves). Cannon, Am. J. 
 Pliys., 1907, 19, 436 {oesophageal peristalsis after vagototiiy). Cannon 
 and MusEK, ib., i8y8, 1, 435. Kahn, Arch. f. Phys., 1903, Supp. Band., 
 386 (nerves); ib., 1906, 355, 362. Kaiser, Arch. Ncerland do. Phys., 
 191 7, 1, 148. Meltzer, J. Exp. Med., 1897, 2, 453; See. Exp. Biol. Med., 
 1906, S, 52 (reflexes); Brit. Med. J., Dec. 22, 1906 (vagus reflexes); Soc. 
 Exp. Biol. Med., 1907, 4, 35 (secondary peristalsis of cesophagus). Miller 
 and Sherrington, Q. J. Exp. Phys., 1913-16, 9, 147 (reflex deglutition 
 in decerebrate animal). Stiles, Am. J. Phys., 1901, 5, 338 (rhythmic 
 activity of cesophagus). Stuart (T. P. Anderson), J. Phys., 1907, 35, 
 44G (epiglottis). 
 
 Stomach Movements.— Auer (J.), Am. J. Phys., 1908, 23, 165 (rabbit). 
 Cannon (\V. B.), ib., 1911, 29, 250 (nature of gastric peristalsis); ib., 29, 
 2G7 (receptive relaxation). Carlson, ib., 1912, 31, 151; ib., 1913, 32, 
 245 (enifty stomach of man). Hertz, Q. J. Med., 1910, 3, 373 (man). 
 RofX and Balthazard, Arch, de Physiol., 1897, 85 (x-rays). 
 
 Innervation of Stomacb. — Auer (J.), Am. J. Phys., 1910, 25, 334- Brune- 
 MKiER and Carlson, /6., 1913, 36, 191 (reflexes from intestinal mucosa to 
 stomach). Cannon, ib., 190O, 17, 429. Lamgley. J. Phys., 1898-9, 
 23, 407 {inhiliitorv fibres in vagu.i). .AIay (W. P.), J. Phys., 1904, 31, 260. 
 Rogers, Atn. J. Phy->., 191 7. 42, 605 (y.^flex control of gastric vagus tone). 
 
 Sensibility of Stomach. — Carlson and Braaflaadt, Am. J. Phys., 1915, 36, 
 153. Hertz, Cook and Schlesinger, J. Phys., 1908, 37, 481 (stomach 
 and intestines). Miller, J. Phys., 1910, 41, 409. 
 
 Pylorus Control. — Boldyreik, Pfluger's Arcli., 1907, 121, 13. Cannon, 
 Am. J. Phys., 1904, 12, 387; ib., 1907, 20, 283; ib.. 1908, 23, 105 (acid 
 control). Cathcart, J. Phys., 1911, 42, 433. Morse, Am. J. Phys.. 
 1916, 41, 439 (acid control). Hedblom and Cannon, Am. J. Med. Sci., 
 (Xt., 1909. 
 
 Movements of Intestines. — Alvarez, Am. J. Phys., 1914, 35, 177; ib., 1915, 
 37, 207 (rhythm of segments from different parts of intestine); J. Am. Med. 
 Ass., 1913, 65, 383. Bayliss and Starling, J. Phys., 1900, 26, 107, 123. 
 Cannon, Am. J. Phys., 1902, 6, 251; 1911, 29, 2;^ii; 1912. 30, 114 (tonus 
 and anti peristalsis); J. Am. Med. Ass., 1912, 59, i (large intestine); Arch. 
 Int. Med., 1911, 8, 417 (importance of tonus). Elliott and Barclay- 
 Smith, J. Phys., 1904, 31, 272; Hertz and Newton, J. Phys., 1913-14, 
 47, 57; Lyman, Am. J. Phys., 1913. 32, Gi (colon). Hambleton, Am. 
 J. Phvs., 1914, 34, 44O (movements of villi). Hertz, J. Phys., 1913, 47, 
 54 (il'eo-colic sphincter). Magnus, Pllii^er's Arch., 1904. 102, 123, 349; 
 ib., 103, 513, 523; ib., 1906, 111, 152 (surviving intestine). Meltzer 
 and AiKR. .\m. j. Phys., 1907, 20, 239 (peristaltic rush). 
 
 Innervation of Intestine.— Bunch, J. Phys., 1898, 22, 337; 'b-. 1899, 25, 22. 
 Cannon, Am. J. Phys., 1906, 17, 429. Langley and Magnus, J. Phys., 
 1903-6, 33, 34- 
 
 Defsecation.- Charles, Brit. Med. J., Sept. 30, 1899; Frankl-Hochwart and 
 liOHi.icH, Pfiiger's Arch., 1900, 81, 420 (tonus and iiinrrvntion of anal 
 .sf^liinclcrs). Hertz, Sensibility of llic Alimentary Canal. 191 1. 
 
 Vomiting: Emetics. — Brooks and Luckhardt, Am. J. Phys., 1915, 36, 
 104 (blood-pressure during vomiting). Eggleston and Hatcher. J. Pharm. 
 Exp. Ther., 1913. 7, 225. Magnus, Ergeb. d. Physiol., 1903. 643. 
 Miller (F. K.), "Pr.ii^'er's Arch., 1912, 143, i; Am. J. Phys., 1915. 38, 
 240 (cardiac inhibition during vomiting). 
 
DIGESTION iijt 
 
 CHEMICAL PHENOMENA OF DIGESTION. 
 
 BoLUVRKFF, O. J. I xp IMiys , Km". 10, 17', * . Kii n \s oou and Saunders, 
 J. I'hys.. i8i)|, 16, .(41 (f>roto:.0(in digestion). London, Z. Physiol. Ch., 
 1005. 46, ,1^1; ib.. 1906, 47, 3O8 {prolein digeslioti); ib., 1907. 61, 241; 
 ib.. 190S. 58, .512 (caiboliydrate digestion). Pawi.ow, Work of the 
 Digestive Gliimis, London, 1910; Ergeb. d. Physiol. (Bioch.), 1902, 
 2.\h (l^h.ysiologicul surgery of digestive canal). Shaw, Am. J. Phys., 
 lui ^ 31, ■\},9 {in birds— chick). 
 
 Catalysis, Catalysers. -Bredig, Anorganische Fermeutc; Bioch. Z., 1907, 
 6, ^bi;. liicRc; and Gies, J. Biol. Ch.. 1906, 2, 489 {ions and catalysis). 
 Brown (O. H.). Am. J. Phys., 1905. 13, 427. Euler. Z. f. Physiol. Ch., 
 1905, 45, 4-!o. Kasti.e and Loevknmart, Am. Clicm. J., 1903, 29, 397, 
 503. LoEVENHART, Am. J. Phys., 1903, 13, 171 {H.2p,^. Neilson and 
 Terry, Am. J. Phys., 1905, 14, 248. Dakin, J. Biol. Ch., 1909, 7, 49 
 {catalytic action of amino-acids, etc.). T.wlor, ib., 7, 49; ib., 1910, 8, 503. 
 
 ENZYMES OR FERMENTS. 
 
 Armstrong (H. E. and E. i".), Proc. Ivoy. Soc. (Lond.), 1907, B 79, 360 
 {nature of enzymes). Armstrong and Ormerod, ib., B 78, 376 {lipase). 
 Bayliss, Nature of Enzyme Action, 1908; J. Phys, 1913. 46, 236; ib., 
 1915, 50, 85 {enzyme action). Bearn and Cramer, Bioch. J., 1907, 2, 
 174 {zymoids). Bredig, Ergcb. d. Phys. (Bioch.), 1902, 134. Bunzel, 
 J . liioi. Ch., 1915. 20, 697 (alfalfa laccase). Buchner, Arch. f. Phys., 1906, 
 548 [in micro-oi'ganisms). Croft Hill, Brit. Med. J., June '20, 1903 
 {reversibility of maltase action). Cole (S. W.), J. Phys., 1904, 30, 281; 
 Mathews and Glenn, J. Biol. Ch., 1911, 9, 29; Osborne (W. A.), Z. f. 
 Physiol. Ch., 1899, 28, 399 {invertase). Falk (K. G.), J. Biol. Ch., 1917, 
 28, 389; Van Slvke and Cullen, J. Biol. Ch., 1914. 19, 141 {mode of 
 action of urease and of enzymes in general). Fischer (E.), Ber. Deutsch. 
 Chem. Ges., 28, 1429; Zcntralb. Physiol., 10, 117 {configuration and 
 enzyme action). Euler, Ergeb. d. Phys., 1907, 239 {synthesis by ferments) ; 
 ib.. 187 {chemistry). jNIutch, J. Phj's., 1912, 44, 176 {histozym). 
 MiCHAELis and Eiirenreich, Bioch. Z., 1908, 9, 283 {adsorption analysis 
 of ferments). Pavy and Bywaters, J. Phj's., 1910, 41, 168. Peters, 
 J. Biol. Ch., 1908, 5, 367 {adsorption of diastase and catalase). Porter 
 (A. E.), Q. J. Exp. Phj^s., 1910, 3, 375 {inactivation of enzymes). Oppen- 
 HEIMER, Ferments and their Actions, translated by Mitchell. Sorenson, 
 Bioch. Z., 1907, 7, 45; ib., 1909, 22, 352. 
 
 Action of Substances on Ferments. — Bierry, J. Phys. Path. Gen., 1912, 14, 
 253 (electrolytes in diastatic actions). Cole (S. W.), J. Phys., 1904, 30, 202 
 (acid on saliva). Morse, J. Biol. Ch., 1915, 22, 125 (halogens). Neilson 
 and Brown, Am. J. Phys., 1904, 10, 225, 335 (ions). Quinan, J. Biol. 
 Ch., 1909, 6, 53 (hydroxyl-ion concentration and diastatic^hydrolysis). 
 
 Enzyme Syntheses. — Bradley and Kellersberger, J. Biol. Ch., 1912, 13, 
 425 (diastase and starch). Bradley, ib., 1912, 13, 431 (lactase of mammary 
 gland). TAYLtiR (A. E.), ib., 1908, 3, 87 (trypsin and protein). 
 
 Proteolytic Enzymes.— Cathcart, J. Phys., 1905, 32, 299 (spleen enzyme)- 
 Dakin, ib., 1903, 30, 84 (kidney enzyme). Effront, Biochemical Cataly- 
 sis in Life and Industry, Proteolytic Enzymes (translated by Prescott), 
 1917- Frankel, J, Biol. Ch., 1916, 26, 31 (action on purified proteins)'. 
 Hedin, J. Phys., 1904,30, 155, 195. LEVENEandSTOOKEY, Am. J.Phys., 
 1904. 12, I (interaction of). Kober, J. Biol. Ch., 1911, 10, 9 (method)'. 
 Opie and Barker, J. Exp. Med., 1907, 9, 207 (leucoprotease). Shackles 
 and Meltzer, Am. J. Phys., 1909. 25, 81 (effect of shaking). Roaf, Bioch. 
 J., 1908, 3, 188 (colorimetric method). Sloan, Am. J. Phys., 1917, 48, 
 568 (origin of proteolytic ferments). 
 
 Lipases.— Arthus, J. Phys. Path. Gen., 1902, 4, 56, 455 (lipase of blood). 
 BoLDYREFF, Z. Physiol. Ch., 190O-7, 50, 394 (lipase of intestinal juice). 
 Bradley, J. Biol. Ch., 1910, 8, 251 (lipase reactions). Connstein, 
 
tl72 BIBLIOGRAPHY 
 
 Krgcb. d. riiys. (Bioch.). 1904, 194. Falk, J. Biol. Oh.. 1917. 31, 07- 
 Hull and Ki;i;i'on, J. Bi(jl. Cli., 191 7. 32, 1^7 {gailric lipase). I.okven- 
 HAKT, J. Biol. Ch., 1906, 2, 391; KosKNHiiiM, J. Phys., 1910, 40, p. xiv 
 (co-cnzyme of lipase). Loevenhart, J. Biol. Ch., 1906, 2, 427 (identity 
 of lipases) ; Am. J. Plays., 1902, 6, 331 [lipase and fat metabolism). London, 
 Z. f. Phys. Ch., 1906-7, 60, 125. Jobling, Eggstkin and Pktersen, 
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 An'iiJerments. — Bayliss, J. Phys., 1912, 43, 455 [anti-emulsin) . Cathcakt, 
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 [tape-worm). 
 
 SALIVARY DIGESTION. 
 Cannon and Day, Am. J. Phj-s., 190:;, 9, 396 [in slotnach). Maxwell. 
 
 Bioch. J., 1915, 9, 323 [salivary and gastric digestion). 
 Diastase in Saliva. — Carlson and Ryan, Am. J. Phys., 1908, 22, i [cat). 
 Evans, J. I'hys., 1912, 44, 191 [amylo-clastic action of saliva). Chitten- 
 den and KicHARDS, Am. J. Phys., i8g8, 1, 461 [iiian). Mendel and 
 Undekhill, J. Biol. Ch., 1907, 3, 135 [dog). Palmer, Am. J. Phys., 
 1916, 41, 483 [ox). Seymour, Am. J. Phys., 1917, 43, 577 [horse). 
 Secretion oJ Saliva. — Asher and Cutter, Z. f . Biol., 1900. 40, 535. Barcroft, 
 J. Phys., 1900, 25, 479 [movement of ivater in secretion). Bunch, J. Phys. 
 1907, 36, I [changes in volume of submaxillary during activity). Carlson 
 and McLean, Am. J. Phys., 1908, 20, 457 (Og supply and secretion). 
 Carlson, Greer and Becht, Am. J. Phys., 1907, 20, 180 [blood-supply 
 and character of saliva). Carlson and Crittenden, ib., 1910, 26, 169; 
 Kyan (J. G.), ib., 1909, 24, 234 [ptyalin concentration). Demoor, Arch. 
 Intcrnat. de Phys., 1913, 13, 187. Grunbaum (O. F. F.), J. Phys., 
 189S, 22, 385 {resistance to secretion and percentage of salts). Hender- 
 son (V. E.), J. Pharm. Exp. Ther., 1910, 2, i [action of drugs). L.\ngley, 
 J. Phys., 1885, 6, 71, ib., 1888, 9, 55; ib.. 1890, 11, 123 [paralytic secre- 
 tion); 1916, 50, p. xxvi [trophic secretory fibres). Japelli, Z. f. Biol., 
 1906, 48, 398 [physico-chemical conditions). Latimer and Warren, 
 J. Exp. Med., 1897,' 2, 465 [zymogen of ptyalin). Mathews (.\. P.), Am. 
 J. Phys., 1901, 4, 482 [atropiti). Pawlow, Ergeb. d. Physiol.. 1904, 
 177 [psychical secretion); Arch. Internat. de Phj-s.. 1904, 1, 119. 
 Wi.rthi;imi:r and Battez, J. Phys. Path. Gen., 1914, 6, 438. 
 Salivary Glands and Gastric Juice. — Hemmeter, Bioch. Z.. 1908, 11, 238. 
 Swanson, Am. J. Phys., 1917. 43, 205. Hyde, Z. f.'Biol., 1897, 35, 459 
 [Octopus macropus). 
 
 GASTRIC DIGESTION. 
 Gastric Juice. — Carlson, Am. J. Phys., 1915. 37, 50 [secretion in man). 
 Carlson, Hagar and Rogers, ib.. 1915, 38, 248 [chemistry of normal 
 human gastric juice). Cohnheim and Soetheer, Z. f. Physiol. Ch., 1902-3, 
 37, 467; Gmelin, Pfliigcr's Arch.. 1904, 103, 618 [secretion of new-borti). 
 Edkins, J. Phys., 1906, 34, 133; Edkins and Tweedy, ib.. 1909, 38, 263 
 [chemical mechanism of gastric secretion). Hamburger (W. W.), J.Exp. 
 Med., 191 1. 14, 535 [pepsin and so-called antipepsin). Harvey (B. C. H.), 
 Am. J. Anat., 1907, 6, 207 [gastric glands). Porter (A. E.), J. Phys., 
 191 T, 42, 389 [pepsin and rennet are independent). Rogers, ]^\HE, 
 Eawcett and Hackett, Am. J. Phys., 1916, 39, 345 [effect of organ ex- 
 tracts on gastric secretion). 
 
DIGESTION 1 1 73 
 
 Quantitative Relations o! Pepsin Action.— Huppert (and SftcHTz). Pfliiger's 
 Arch., lyoo, 80, 470. Neilson and Bonnot, Arcli. Int. Med., 1913. 
 11, 305. SpRir.cs, Z. f. Physiol. Ch., igoi, 36, 4O5. 
 
 HCl of Gastric Juice.- I'leio, J. Phys. Path. G<Sn., 1908, 10, toog {reactions 
 for). LusK and I'erris, Am. J. Pliy.s., 1898, 1, 277 (inversion of cane 
 sugar by). Pai.mi k, Bioch. J.. 1906, 1, 398 (in carcinoma). SjSjVisT. 
 Skand. Arch. Phys., 18^3, 5, 277. Weinland, Z. f. Biol.. 1910, 65, 58 
 (in shar/i). Widdicombe (J. H.), J. Phys., 1902, 28, 175 (digestion of 
 cane sugar). 
 
 Acidity of Gastric Juice. — Mf.nten, J. Biol. Ch., 191 5, 22, 341 (in wan). 
 Michaelis and Da\id.soiin, Z. Exp. Path. Ther.. 1910, 8, 398. Tan-gl, 
 Ptliigcr's Arch., I90(j, 115, 64. 
 
 Formation of HCl of Gastric Juice. — Bensley and Harvey, Trans. Chicago 
 Path. Soc, igi^ 9, -:-'i. Bergeim, Soc. Exp. Biol. Med., 1914, 12, 21. 
 Benrath and Sach.s, Pfliiger's Arch., 1905, 109, 466. Koeppe, PflUgcr's 
 Arch., 1896, 62, 567. Liebermann, Pfliiger's Arch., 1891, 60, 25. 
 Osborne (T. B.), Am. J. Phys., 1901, 5, 180. Monti, Archivio di Fisiol., 
 
 1913, 11, 155 (function of the delomorphic cells), von Rhorer, Pfluger's 
 Arch., 1905, 110, 416. Wesener, ib., 1899, 77, 483. 
 
 Acidity of Gastric Contents. — Fowler, Bergeim and Hawk, Soc. Exp. 
 Biol. Med., 1916, 13, 58 (indicators). JNIcClendon, Am. J. Phys., 1915, 
 38, 191 (adults and infants, acidity in stomach and duodenum) . Moore, 
 Alexander, Kelly and Roaf, Bioch. J., 1906, 1, 274. 
 
 Protein Digestion in Stomach. — Tobler, Z. f. Physiol. Ch., 1905, 45, 185. 
 ZuNz (E.), Ergcb. d. Phys., 1906, 622, 663. Chittenden, Mendel 
 and Jackson, Am. J. Phys., 1898, 1, 164 (action of alcohol on digestion). 
 
 Proteoses, Albumoses. — Chittenden and Hartwell, J. Phys., 1891. 12, 12. 
 Haslam, ib., 1907, 36, 164 (deutero-albuinose) . Kuhne and Chittenden, 
 Z. f. Biol., 18S4, 20, II, 409. 
 
 Digestion of Nucleins. — Amberg and Jones, J. Biol. Ch., 191 1. 10, 81. 
 Levene and Medigreceanu, ib., 9, 375. 
 
 Chymase (Rennin). — Bang, Z. f. Physiol. Ch., 1904-5, 43, 358. Bosworth, 
 J. Biol. Ch., 1913, 15, 231 ; ib., 1914, 19, 397. Burge, Am. J. Phys., 1912, 
 29, 330. Edmunds, J. Phys.. 1896, 19, 466. Fuld., Ergeb. d. Physiol. 
 (Bioch.), 1902, 468. Hawk, Am. J. Phys., 1903, 10, 37. Kent, J. Phys., 
 1911, 43, p. xxiv. Leary and Sheib, J. Biol. Ch., 1917, 28, 393. Locke, 
 J. Exp. Med., 1897, 2, 493. Loevenhart, Z. f. Physiol. Ch., 1904, 41, 
 177. Mellanby, J. Phvs., 1912, 45, 345. Pawlow and Parastschak, 
 Z. f. Phj^siol. Ch., 1904, 42, 415. Porter (A. E.), J. Phys., 1911, 42, 389. 
 Taylor (A. E.), J. Biol. Ch., 1908, 5, 399- Warren (J. W.), J. Exp. 
 Med., 1897, 2, 475. 
 
 PANCREATIC JUICE. 
 
 Bayliss and Starling, J. Phys.. 1904, 30, 61. Boldyreff, Q. J. Exp. Phys., 
 
 1914, 8, 1 ; Jb., 1916, 10, 175 ; Ergeb. d. Physiol., 1911, 121, 156. Bradley, 
 J. Biol. Ch., 1909, 6, 133 (hitman). De Zilwa, J. Phys., 1904, 31, 230 
 (composition). Fischer (E.) and Abderhalden, Z. f. Physiol. Ch., 1907, 
 61, 264 (action on polypeptides). Welker and Falls, J. Biol. Ch., 1917, 
 32, 509 (influence of pancreatic digestion on non-colloidal N-content of 
 S(riim). 
 
 Enzymes of Pancreas. — Bayliss, J. Phys., 1907, 36, 221 (causes of rise of 
 electrical conductivity in trypsin action). Edkins, ib., 1891, 12, 218 
 (action on casein). Hedin (S. G.), ib., 1905, 32, 468; ib., 1906, 34, 370 
 (trypsin action). Magnus, Z. f. Physiol. Ch., 1906, 48, 376 (synthetic bile 
 acids and pancreatic fat-splitting). M.\Ys (K.). ib., 1907, 61, 182. 
 Mellanby and Worley. J. Phys., 1913, 47, 338 (trypsin, trypsinogen, 
 enterokinase); ib., 1913, 46, 159 (Ca and generation of trypsin from tryp- 
 sinogen). Robertson (T. B.), J. Biol. Ch., 1908, 5, 31 (r6le of alkali i:i 
 hydrolysis of proteins by trypsin). Terroine and Schaeffer, J. Phys. 
 
"74 
 
 BIBLIOGRAPHY 
 
 Path. Gen., 1910. 12,884, 065 (trypsin anderepsin). Terroine, ib., 1911, 
 
 13, 837 (saponifying ferments); ib.. 1913, 15, 1125, 1148 (digestion and 
 absorption of fat). Tekroine and Weill, ib., H)i2, 14, 437 (starch 
 digestion). Vernon, J. Piiys., xqoi, 26, 405 (trypsin); ib.. 1910, 47, 325 
 (liVpsinogcn autocatalysis); ib., 27, 174 (pancreatic rennin and diastase); 
 ib', iyo2, 28, 448 (zyiiiogens); ib., 1904, 30, 330. Zunz, Arch. Internat. 
 Physiol., 191 1, 13, 191 (action on proteins and proteoses). Rachford, 
 J. Phys., 1^99, 25, 165 (influence of bile); Am J. Phys., 1899, 2, 483. 
 
 Secretion of Pancreatic Juice. — Von Anrep, J. Phys.. 1914, 49, i; ib., 1916, 
 50, 421 (vagus). C.A.MUS and Gley, Arch. Internat. Phys., 1913, 13, 102 
 (pilocarpin) . Herring and Simpson, Q. J. IC.xp. Phy.s.. 1909. 2, 100 
 (secretory pressure). May (O.), J. Phys., 1904. 30, 400 (secretion and 
 blood supply). Rogers, Rahe, Fawcett and Hackett, Am. J. Phys., 
 1916, 40, 12 (effect of organ extracts). Werthkimer and Boulet, Arch. 
 Internat. Phys., 191 2, 12, 247. 
 
 Secretin.- — Bayliss and Starling, Ergeb. d. Physiol., 1906, G70; ib., 693 
 (chemical nature of hormones); J. Phys., 1903. 28, 325; ib., 29, 174. 
 Bainbridge and Beddard, ]5ioch. J., 1906, 1, 429; Evans. J. Phys., 
 191 2, 44, 461 (secretin and diabetes). Delezenne, J. Phys. Path. Gen., 
 1912, 521, 540. Dixon and IIamill, J. Phys., 1909, 38, 314. HiooN, 
 Arch. Internat. Phys., 1912, 12, 485. Wertheimer and Lepage, 
 J. Phys. Path. Gen., 1901, 3, O89, 708. 
 
 Adaptation in the Digestive Juices. — Bayliss and Starling, Ergeb. d. Physiol., 
 lyoO, 681; J. Phys., 1904, 30, O4. Plimmer (R. H. A.), J. Phys., iyo6, 
 84, 93; i^-' 1906, 35, 20 (adaptation of pancreas to lactose). 
 
 BILE. 
 
 Chemistry oJ Bile. — Brand, Pfliiger's Arch., 1902, 90, 491; Rosenbloom, 
 J. Biol. Ch., 1913, 14, 241 (human bile). Fischer (H.), Ergeb. d. Phj's., 
 1916, 185 (bile and blood pigment). Heynsius and Campbell, Pfliiger's 
 Arch'., 1871, 4, 497; Haycraft and Scofield, Z. f. Physiol. Ch., 1890, 
 
 14, 73; Stewart (G. N.), Studies Physiol. Lab., Univ. Manchester, 1891, 
 201 (bile- pigment spectra). Hammarsten, Ergeb. d. Physiol., 1905. 1. 
 Okada, J. Phys.. 1915, 60, 114 (reaction). Gardner and Knox, J. Phys., 
 1907, 36, p. ix (cholesterol in bile). Hammarsten, Z. f. PhysioJ. Ch.. 
 1904-5, 43, 127; Lewis, Bioch. J., 1908, 3, 119; Schryver, J. Phys., 1912, 
 44, 2O5 (bile-salts). Sellards, J. Exp. Med., 1909, 11, 786 (reaction with 
 blood-serum). 
 
 Bile and Bile-Pigment Formation.— Whipple and Hooper, Am. J. Phys., 
 1916, 40, 332; ib., 191 7, 42, 256, 544; ib., 191 7. 43, 258, 275, 290; J. Exp. 
 Med., 1913, 17, 612 (from hemoglobin mitside the liver). 
 
 Bile and Bile Pigment Secretion.— Barbera, Arch. Ital. Biol., 1902, 38, 447. 
 liAYLiss and Starling, Ergeb. d. Physiol., 1906, 677. DovoN and 
 Di-FOURT, Arch, de Phvs., 1896, 587; ib.. 1897, 562. Dastre, ib., 1890, 
 800. Eiger, Z. f. Biol., 191 5, 66, 229 (vagus influence). Hooper and 
 Whipple, Am. J. Phys., 1917, 42, 264, 280 (influence of bile). Okada, 
 J. Phys., 19x5, 49, 457. Pfaff and Balch, J. Exp. Med., 1897, 8, 49- 
 Pugliese, Arch. Ital. Biol., 1902, 38, 257. Simpson (S.), Soc. Exp. Biol. 
 Med., 1910, 7, 8. 
 
 Eck's Fistula. — Bernheim and Voegtlin, J. Pharm. Exp. Ther., 1909, 1, 463. 
 Carrel and Guthrie, Compt. Rend. Soc. Biol., June 30, 1906, 1104 
 (simple method). Hawk, Am. J. Phys., 1908, 21, 259. Herrick (F. C), 
 J. Exp. Med., 1905, 7, 751- Sweet, J. Exp. Med., 1905. 7, 163. 
 
 Absorption of Bile, Icterus.— Harley, Proc. Roy. Soc. 1892, (paths). 
 Harold, Pepper and 1'erry, J. Exp. Med., 1915, 22, 675. Herring 
 and Simpson, Proc. Roy. Soc, 1907, B 79, 517 (secretory pressure and 
 absmption). Pearce (R. M.) et al., J. Exp. Med., 1912, 16, 758, 769. 
 7S0 (hemolytic jaundice and the spleen). Sutherland, Bioch. J., 1906. 
 1, 364. Voegtlin and Bernheim, J. Pharm. Exp. Ther., 191 1, 2, 455- 
 
DIGESTIOX 1175 
 
 Wertheimer and Lepage, Arch, de Phys., 1897. y>i (paths of absorp- 
 tion); ib., 1S08. 334: J. I'hys. Path. Gen.. 1899, 1, 259. Whipple and 
 Hooper, J. E.\p. Med., i>,ni. 17, 593 ; 191O, 23, 137. Whipple and Kino, 
 ib.. 1911, 13, 115. 
 
 Toxicity of Bile. -Krothingham and Minot, J. Med. Kcs., 1912. 27, 79- 
 Kaks.nkk iiiul EisENisREY, lb., 1912, 26, 357 (antibodies). King and 
 Stewart (H. A.), J. Exp. Med., 1909, 11, 573. Meltzek and Salant, 
 ib., 1906, 8, 127. Tatum, J. Biol. Ch., 191O, 27, 243 (itijhtencc on autolysis). 
 
 Bile Circulation. — Stadelmann, Z. f. Biol., 1897. 34, i. Wektheimkk, Arch. 
 dc riiys., iS()2, 577. 
 
 Innervation of Gall-BIadder.— Bainbridge and Dale, J. Phys.. 1905. 33, 138. 
 Fkeicsk, Johns llopk. Hosp. Bid!., 16, June, 1905. LiEBand McWhorter, 
 Soc. Exp. Biol. Med., 1913, 12, 102. 
 
 Bile and Bile-Salts in Digestion. — Chittenden and Albro, Ain. J. Pliys., 
 189S, 1, 307 [iuflnoicc on pancreatic proteolysis). De Jonge, Arch. 
 Neerland. Physiol., 1917, 1, 182. Kingsbury, J. Biol. Ch., 1917, 29, 
 367. Loevenhart and Sol'der, ib., 1906-7, 2, 415. Pfluger (E.), 
 Pfliiger's Arch., 1902, 90, i. Kachi-ord, J. Phys., 1891, 12, 93. 
 
 INTESTINAL JUICE. 
 
 Bayliss and Starling, Ergeb. d. Physiol., 1906, 678 (chemical reflexes). 
 Hamburger and Hekma, J. Phys. Path. Gen., 1902, 4, 805; ib., 1904, 6, 
 40 (man). Mendel, Pfliiger's Arch., 1896, 63, 425 (paralytic secretion). 
 Mosenthal, j. Exp. yied., 191 1. 13, 319. Pregl, Pfliiger's Arch., 1895, 
 61, 359 (sheep). Salaskin, Z. Physiol. Ch., 1902, 35, 419 (dog). 
 
 Ferments. — Blood (A. P.), J. Biol. Ch., 1910, 8, 215; Cohnheim, Z. Physiol. 
 Ch., igo6, 47, 286; 1902, 35, 134; 36, 13, 244; Reed and Stahl, J. Biol. 
 Ch., 1911, 10, 109; Vernon, J. Phys., 1905, 33, 81 (erepsin). Hamill, 
 J. Phys., 1905-6, 33, 476; Mellanby and Woolley, ib., 1912, 45, 370 
 (enterokinase) . 
 
 Reaction of Intestinal Contents. — McClendon, Shedlov and Thomson, 
 J. Biol. Ch., 1917, 36, 269 (ileum). Moore and Bergin, Am. J. Phys., 
 1900, 3, 316. 
 
 Digestibility of Foods.— Bryant and Milner, Am. J. Phys.. 1903. 10, 81 
 (vegetables). Frank. J. Biol. Ch., 191 1, 9, 463 (egg-white). Langworthy 
 and Holmes, U. S. D_'pt. Agric. Bull., 1917. 505, 507; Langworthy, ib., 
 
 1915, 310; Smith, Miller and Hawk, J. Biol. Ch., 1915, 23, 505 (fats). 
 RocKwooD, J. Biol. Ch., 1910, 8, 327 (flour). 
 
 Bacteria of Alimentary Canal. — BALowaN, J. Ciol. Ch., 1909, 7, 37. Gushing 
 and Livingood, Johns Hopkins Hosp. Rep., 9, 543. Gerhardt, Ergeb. 
 d. Physiol. (Bioch.), 1904, 107. Herter, Harvey Lect., Xew York, 
 Nov. 3, 1906. Herter and Kendall, J. Biol. Ch., 1909, 6, 499;. 16., 
 
 1909, 7, 203 (influence of diet on intestinal flora). Kendall, J. Med. Res., 
 191 1, 25, 117. KiANiziN, J. Phys. Path. Gen., 191 1, 13, 689; J. Phys., 
 
 1916, 50, 391; XuTTALL and Thierfelder, Arch. f. Physiol., 1895, 559; 
 Schottelius, Arch. f. Hygiene, 34 (aseptic digestion). 
 
 Fseces. — Ellis and Gardner, Proc. Roy. Soc, 191 2, B 86, 13 (excretion of 
 cholesterol). 
 
 CHAPTER VIL 
 
 ABSORPTION. 
 
 Adsorption. — Barrett and Edie, Bioch. J., 1907, 2, 44.V Bayliss, ib., 1906, 
 1, 175. Hedin, ib., 1907, 2, 112 (of enzymes). Hofmann, Zentr. f. Phys., 
 
 1910, 24, 805. Michaelis and Rona, Bioch. Z., 1908, 15, i9*i- Robert- 
 son, J. Biol. Ch., 1908, 4, 35. Van Slyke, ib., 190S, 4, 259. 
 
 Diffusion.— Denis (W.), Am. J. Phvs., 1906, 17, 35 (siiUs of blood). Flexner 
 and Xoguchi, Soc. Exp. Biol. Med., 1906, 3, 66. Hedin, Pfluger's Arch., 
 1899, 78, 205. Hober, ib., 1898, 71, 624 {in intestinal absorption); ib., 
 
1 1 76 BIBLIOGRAPHY 
 
 1899, 74, 225. Mkyer, Hofmeistcr's Beit., 1906, 7, 393. Rkid (W.). 
 J. Phys., 1897, 21, 85; Mines, ib.. 191 1, 42, p. x.wiii {nnthod). Voigt- 
 LAN'DER, Z. f. Physikal. Ch., 1889, 3, 3 if). 
 Imbibition. — Fi.scher and Moore, Am. J. Phys., 1907, 20, 330. Henderson, 
 I'almer and Bixiir. J. Phariii. Exp. Thcr., 1914, 5, ^ (9 (H-ion concen- 
 liation). OsTWALU (W.), l^lliiger's Arch., 1905, 108, 5O3 ; 109, 277; ib., 
 
 KloO, 111, 5S1. 
 
 Surface Tension. — Beard and Cramer, Proc. Roy. Soc, 1915, B 88, 575 (and 
 fenuent action). Cramer, v'^., B 88, 584 [and cell metabolism). Macallum 
 (A. B.), Ergeb. d. Physiol., 1911, 11,598; Proc. Roy. Soc, 1913, B 86, 527. 
 Traube, Pfliiger's Arch., 1904, 105, 559 (surface tension and vital pheno- 
 mena) . 
 
 Mechanism of Absorption. — Munk, Ergeb. d. Phys. (Bioch.), 1902, 296. 
 Overton, Nagel's Ilandb. d. Physiol,, Bd. ii., 2, 744. Scott and Denis, 
 Am. J. Phys., 1913, 32, i (dog-fish). Hamburger, Arch. f. Phys., 1896, 
 302, 42S (i)itya-inlestinal and intra-abdominal pressure and absorption). 
 
 Absorption from Intestine.— Brodie and Vogt, J. Phys., 1910, 40, 133 (gaseous 
 exchange of intestine and absorption). Brodie, Cl'llis and Halliburton, 
 ib.. 1910, 40, 173. CoHNHEiM, Z. f. Biol., 1896, 33, 9; ib., 37, 443 ; 38, 419; 
 39, 167. Dakin, J. Biol. Ch., 1908, 4, 437 (isomeric substances) . Hanzlik 
 and Collins, J. Pharm. Exp. Ther., 1913, 5, 185 (alcohol). London et 
 AL., Z. f. Physiol. Ch., 1906, 49, 324, 328. Wallace and Cushny. Am. 
 J. Phys., 1S98, 1, 411. Reach, Pfliiger's Arch., 1901, 86, 247 (compara- 
 tive absorption in large and small intestine). Reid, J. Phys., 1898, 22, 
 p. Ivi.; ib., 1900-1, 26, 436 (nerves and absorption); ib., 1896,26, 298. 
 Heidenhain, Pfliiger's Arch., 1894, 56, 579 (serum). Ravenel and 
 Hammer, J. Med. Res., 1911, 24, 513 (bacteria). Coleman and Gephart, 
 Arch. Int. Med., 1915, 15, 882 (in fever). 
 
 Absorption from Peritoneum. — Adler and Meltzer, J. Exp. Med., 1896, 1, 
 4S2. Buxton, J. i\Ied. Res., 1907, 16, 17. Fleisher and Loeb, 
 J. Exp. Med., 1910, 12, 2S8, 4S7, 510. Meltzer, J. Phys., 189S, 22, 196. 
 Shipley and CuNNiNCiHAM, Am. j. Phj's., 1916, 40, 75. Starling, J. Phys., 
 1898, 22, p. xxiv. Wells and Mendel, Am. J. Phys., 1907, 18, 156. 
 
 Absorption from Connective Tissue. — Hamburger, Bioch. Z., 1907, 3, 359. 
 MELTZERand Auer, J. Exp. Med., 1905, 7, 59; 1911, 13, 328 (intramusculat 
 tissue). Starling, J. Phys., 1895-6, 19, 312. 
 
 Absorption by Skin (Frog). — Maxwell, Am. J. Phys., 1913, 32, 2S6. 
 
 Absorption of Fat. — Bloor, J. Biol. Ch., 1912, 11, 429; 1913, 15, 105; 1913, 
 16, 517; 1915. 23, 317. Harley, J. Phys., 1S95, 18, i (effect of pancrea- 
 tectomy). Greene and Skaer, Am. J. Phys., 1913, 32, 358. Greene, 
 ib., 1912, 30, 278 (salmon). Mendel and Baumann, J. Biol. Ch., 1915, 
 22, 165 (fro)n stomach). McClure, Vincent and Pratt, Am. J. Phys., 
 1917, 42, 596 (pancreatectomy); J. Exp. Med., 1917, 25, 381. Moore and 
 Rockwood, J. Phj's., 1897, 21, 58. Munk, Zentr. f. Phys., 13, 657; 14, 
 121, 153, 409; 16, 297. Plant, Am. J. Phys., 1908-9, 23, 65. PflItger 
 (E.), Pfliiger's Arch., 1900, 82, 303; 1902, 88, 299, 431. Mendel, Am. J. 
 Phys., 1909, 24, 493 (stained fat) ; J. Biol. Ch., 1912, 13, 71. Whitehead, 
 Am. J. Phys., 1909, 24, 294; ib., 1910, 25, p. xxviii (stained fat). 
 
 Absorption of Cholesterol.— Corper, J. Exp. Med., 1915, 21, 179. Eraser 
 and Gardner, Proc. Roy. Soc, 1909, B 81, 230. Lehman, J. Biol. Ch., 
 1913, 16, 495- Mueller, J. Biol. Ch., 1916. 27, 463. 
 
 Absorption of Proteins. — Cathcart and Leathes, J. Phys., 1905-6, 33, 462. 
 Cohnheim, Z. f. Physiol. Ch., 1902, 35, 396, 416 (octopods); ib., 1906, 
 49, 64. FoLiN and Denis, J. Biol. Ch., 1913, 14, 453; ib., 1912, 12, 253 
 (large intestine). Mendel, Am. J. Phys., 1899, 2. 137 (paths). Munk. 
 Zentralb. f. Phys., 1907, 11, 585 (paths). Reid, J. Phys., 1895-6, 19, 240 
 (peptones). Nolf, J. Phys. Path. G6n., 1907, 9, 9-5. 957- Salaskin, 
 Z. f. Physiol. Ch., 1907, 51, 167 (stomach). Folin and Lyman, J. Biol. 
 Ch., 1912, 13, 389 (stomach); ib., 1912, 12, 259. London, Z. f. Physiol. 
 Ch., 1909, 62, 448. 
 
FORMATION OF LYMPH 1177 
 
 Albumoscs in Tissues and Blood. — Abel. Pincoffs and Rouillkr, Am. J. 
 
 Phys., 191 7, 44, 3^0. liMnuiiN and Knoop, Hofmeister's Beit., 1903, 3, 
 
 120. Langstein. ib.. 3, 373. Schumm, 16., 1904. 4, 453. 
 Absorption of Sugars. Hfino>f, Arch, de Pharmacod., 1900, 7, 163. MUNK, 
 
 Arch. f. Phys., ivSgo. 370 {paths for sugar, protein, fat). Reach. Arch. 
 
 E.vp. Path. Pliarni., 47, ^31 (i>y rectum). Reid. J. Phys., 1901. 26, 427; 
 
 190J, 28, 241. RoiiMANN and Nacano. Pfluger's Arch., 1903. 95, 533. 
 Absorption 0! Iron. — Ahuerhalden. Z. f. Biol., 1900,39,113, rgv Bunge, 
 
 Z. f. Physiol. Ch.. 1898. 25, 36. Hall (W. S.). .\rch. f. Phys., 1896. 
 
 49; ib., 1894, 435. Meyer, Ergeb. d. Phys.. 1906, 698. Sattler, Arch. 
 
 Hxp. Path. Pharm., 1905, 52, 320. 
 
 CHAPTER VHI. 
 
 FORMATION OF LYMPH. 
 
 Lymphatic System. — Job, Anat. Record, 1915, 9. JMacCallum (W. G.), Arch, 
 f. Anat. (u. Physiol.), 1902, 273 {relation of lymphatics to connective tissue). 
 Sabin (F. R.), Ergeb. d. Anat. u. Entwick., 1913; Am. J. Anat., 1904, 
 3, 183 {origin of lymphatic system). 
 
 Lymph Formation. — Asher and Barbera, Z. f. Biol., 1898. 36, 154. Asher 
 and BuscH, Z. f. Biol., 1900, 40, 333. Asher, Z. f. Biol., 1899, 37, 261. 
 Asher and Gies, Z. f. Biol., 1900, 40, 180. Baixbridge, J. Phys., 1906, 
 34, 275 {post-mortem); J. Phys., 1900-1, 26, 79 {submaxillary gland); 
 ib., 28, 204 {liver); ib., 32, i {pancreas). Brande and Carlson, Am. J. 
 Phys., 19, 221 {lymphagogues and agglutinins in serum and lymph). 
 Cuttat-Galizka, Z. f. Biol., 191 1, 56, 309 {post-mortem). Cohnstein, 
 Pfluger's Arch., 1895, 59, 350, 508; ib., 1895, 62, 58; Arch. f. Phys., 1896, 
 379. Carlsox, Greer and Becht, Am. J. Phys., 1907, 19, 360 {salivary 
 glands); ib., 22, 104 {lymphagogue action of lymph). Dixon (R. L.), J. 
 Exp. Med., igi2, 16, 139. Ellinger, Ergeb. d. Phys. (Bioch.). 1902, 
 355. Hamburger (H. J.), Arch. f. Phys., 1S95, 364 {risuine of Heiden- 
 hain'sview);ib., 1897, 132. Japelli, Z.f. Biol., 1910,53,319. Lazarus- 
 Barlow, J. Phys., 1895-6, 19, 418 {osmosis and filtration). Leathes, 
 J. Phys., 19, I. Mendel and Hooker, Am. J. Phys., 1902, 7, 380 
 (strawberry extract). Mendel, J. Phys., 19, 227. ^Iuller, Pfliiger's 
 Arch., 1908, 122, 455 {Tannenberg bodies). Opie, J. Exp. Med., 1912, 
 16, 831 {lymph formation and oedema of liver). Pugliesi, Arch. Ital. 
 Biol., 1902, 38, 422. Scott (F. H.), J. Phj-s., 1915-16, 50, 159; Scott, 
 HERM.A.N and Snell, Am. J. Phys., 1917, 44, 313; Scott, Am. J. Phys., 
 1917, 44, 29S. Sihler, J. Exp. Med., 1900, 5, 493. Starling, J. Phj-s., 
 1894-5, 17, 30; Wertheimer, J. Ph^'s. Path. Gen., 1906, 8, 806 {work of 
 glands and lymph formation). Y.a.nagama, J. Pharm. Exp. Ther., 1916 
 9, 75- 
 
 (Edema. — Bolton, Proc. Roy. Soc, 1907, B 79, 267 {by obstruction of vence 
 cavcB and portal). Fischer (M), CEdema, 1910. Fleisher, Hoyt and 
 LoEB (L.), J. Exp. Med., 1909, 11, 291. Lazarus-Barlow, Pliil. Trans. 
 Roy. Soc, 1894, 185, 779 {accompanying passive congestion). Meltzer, 
 Amer. Medicine, 1904, 8- Miller (J. L.) and Matthews (S. A.), Arch'. 
 Int. Med., 1909, 4, 356 {pulmonary). Moore (A. R.), Pfluger's Arch. 
 191 2, 147, 28; Am. J. Phys., 1915, 37, 220. Pearce (R. M.), Arch. 
 Int. Med., 1909, 3, 422. Woolley, J. Lab. Clin. Med., 1916, 1, 267 
 {nervous influences and). 
 
 CHAPTER IX 
 EXCRETION. 
 
 COMPOSITION OF URINE. 
 
 BoucHEZ, J. Phys. Path. Gen., 1912, 14, 46, 74. Camerer, Z. f. Biol., 
 1904, 45, i; FoLiN, Am. J. Phys.. 1905. 13, 45, 66 {normal urines). 
 Cathcart, Bioch. Z., 1907, 6, 109 {in starvation). 
 
1 1 78 BIBLIOGRAPHY 
 
 Total Nitrogen Excretion in Normal Persons. — BARRi.sr.tR (T. B. and B. S.), 
 Am. J. Phys., mio, 27, ii9- 
 
 Urea in Urine. — Marshall, J. Biol. Ch., 1913, 14, 283 ; ib., 15, 495; Van Slyke 
 uiul C'l'LLKN, ib., 1914, 19, 211. Van Slykk, ib., 1916, 24, 117 {deter- 
 }iii nation by urease method). 
 
 Ammonia in Urine. — Folin and Bell, J. Biol. Ch., 1917, 29, 329 [colorimeiric 
 itttcnm nation). Folin and Macallum, ib., 1912, 11, 323 {determination). 
 
 Acidity of Urine. — Henderson (L. J.) and Palmer, J. Biol. Ch., 1912, 13, 
 3>is; "''■, 14, 81. Henderson and Spiro, Bioch. Z., 1908, 15, 105. 
 
 Phenols. — Dubin, J. Biol. Ch., 1916, 26, f>9 (physiology of). Folin and Denis, 
 '''■. 5f'7 {relative excretion of, by Sidneys and iittesiine). 
 
 Uric Acid Excretion. Benedict and Hitchcock, J. Biol. Ch., 1915, 20, C19; 
 Folin and Denis, ib., 1912, 13, 363, 469 (colorimeiric estimation of uric 
 acid in xirine). Hanzlik and Hawk, ib., 1908, 5, 355 (normal men). 
 Leathes, J. Phys., iyo6, 35, 125 (diurnal and nocturnal variations). 
 Mendel and Brown, J. Am. .Med. Ass., 1907, 49,, 89*) (rate in man). 
 Mendel and Stehle, J. Biol. Ch., 1915, 22, 215 (role of digestive glands in 
 excretion of endogenous). Rockwood, Am. J. Phys., 1904, 12, 38 
 {endogenous). Wells (H. G.), J. Biol. Ch., 1916, 26, 319 (acciimtilalion 
 in tissues in suppression of urine). 
 
 Alkaptonuria. — Dakin, J. Biol. Ch., 1911, 9, 151. Garrod and Hartley, 
 J. Phys., 1907,36, 136. Garrod and Hele, ib., 1905-6, 33, 198. Garrod 
 and Clarke, Bioch. J., 1907, 2, 217. R a wold and Warren, J. Biol. 
 Ch,, 1909, 7, 465. ScHULZ, 1-rgeb. d. Physiol. (Bioch.), 1903, 180. 
 
 Bile-Salts in Urine. ^ — Allen, J. Biol. Ch., 191 5, 22, 505 (Hay's surface tension 
 method). Grtjnbaum, J. Phys., 1904, 30, p- xxvi. 
 
 Bile-Pigments in Urine. — Hammarsten, Skand. Arch. Phj's., 9, 313. Jolles 
 (A.), ib., 10, 338; Pfliiger's Arch., 1899, 75, 446. Munk, Arch. f. Phys., 
 1898, 361. ScHULz, Ergcb. d. Physiol. (Bioch), 1903, 174. 
 
 Proteinuria. — Cameron and Wells, Arch. Int. Med., 1915, 15, 74; Cloetta, 
 Arch. Exp. Path. Pharm., 1S99, 42, 453 (origin of the proteins). Folin 
 and Denis, J. Biol. Ch., 1914, 18, 273; Marshall, Banks and Graves, 
 Arch. Int. Med., 1916, 18, 250 (estimation of the proteins). Sikes, J. Phys., 
 1905-6, 33, loi (the globulin of" albuminous " urine). 
 
 Amino-Acids in Urine. — Benedict and Murlin, J. Biol. Ch., 191 3, 16, 365 
 (determination of amino-acid nitrogen). Forssner, Z. f. Physiol. Ch., 
 1906, 47, 15- Hall (I. W.), Bioch. J., 1906, 1, 241. Levene and Van 
 Slyke, J. Biol. Ch., 1912, 12, 301; Van Slyke, ib., 1913, 16, 125 (estima- 
 tion). Mutch, J. Phys., 1914, 49, p. ii- 
 
 Pentosuria. — Levene and La Forge, J. Biol. Ch., 1913, 16, 4S1 ; ib., 1915, 18, 
 319 (note on a case). Neuberg, Ergcb. d. Physiol. (Bioch.), 1904, 373 
 (physiology of pentoses and glycuronic acid). 
 
 Heematoporphyrin in Urine. — Garrod, J. Phys., 1892, 13, 598; ib.. 1894, 15, 
 108; ib., 1894-5, 17, 349. Schulz, Ergeb. d. Physiol.. 1903, 162. 
 
 SECRETION OF URINE. 
 
 CusHNY, The Secretion of Urine, London, 191 7; J. Phys., 1901-2, 27, 429; 
 J. Phys., 1917, 51, 36 (excretion of urea and sugar). Bainrridge and 
 Bedd.\rd, Bioch. J., 1906, 1, 255 (secretion by renal tubules in frog). 
 Bainbridge, Mrnzies and Collins, J. Phys., 1914, 48, 233 (urine forma- 
 tion in frog). Barcroft and Straub, ib., 1910, 41, 145. Barcroft and 
 Piper, ib.. 1915, 49, p. xiii (in decerebrate animals). Beddard, ib., 1902, 
 28, 20 (ligation of renal arteries in frog). Boyd, ib., 1902, 28, 76 (extirpa- 
 tion of renal medulla). Brodie and Cullis, ib., 1906, 34, 224. Brodie 
 and Mackenzie (J. J.), Proc. Roy. Soc, 191 4. B 87, 594 {changes in 
 glomentli and tubules accompanying activity). Brodie, ib., 87, 571 
 (glomerular function). Cow (D.), J. Phys., 19x4. 48, i- Cullis (C.), 
 J. Phys., 1906, 34, 250; ib., 1908, 37, P- xvi (frog). Folin and Denis, 
 
EXCRETION 1 1 79 
 
 J. Biol. Ch., 1915, 22, 321 {selective activity of human kidney). Haskins, 
 Am. J. Phys., 1904, 10, 302; Hatcher and Sollmann, ib., 1903, 8, 139 
 (in sttll-hiniger). von I'ukth, Ergeb. d. Physiol. (Hioch.). 1902, 395 
 {urine secntton of loivvr animals). Knowlton (F. P.), J. Phys., 191 1, 
 43, 219 {influence of colloids). Isaacs (R.), Am. J. Phy.s., 1917, 45, 71 
 {reaction of kidney colloids and renal function). Lindemann, Z. f. Biol., 
 1901, 42, 161 {elimination of glomeruli). Gesell, Am. J. Phys., 1913, 
 32, 70. Hooker, ib., 1910, 27, 24 {relation of pulse pressure to renal 
 secretion). Macallim and Benson, J. Biol. Ch., 1909. 6, 87 {composition 
 of dilute renal e.xcrctions). Magnus, Arch. Exp. Path. Pharm., 1901, 45, 
 201 (in plethora). Quinby, Am. J. Phys., 1917, 42, 593; J. Exp. iMt-d., 
 1910, 23, 535 (denervated kidney). Richards and Plant, Am. J. Phys., 
 1017, 42, 592 (blood-pressure and urine formation). Sollmann, Am. J. 
 Phys., 1902, 8, 155. Sollmann and Brown, J. Exp. Med., 6, 207 
 (injection of egg-albumin, etc.). Sollmann, Am. J. Phys., 1905, 9, 425 
 (chlorides of urine). De SotJZA, J. Phys., 1900, 26, 139 (effects of venous 
 obstruction). Spiro and Vogt, Ergeb. d. Physiol. (Bioch.), 1902. 414. 
 Spiko, Arch. Exp. Path. Pharm., 1898, 41, 148 (action of artificial concen- 
 tration of the blood). Sharpe, Am. J. Phys., 1912, 31, 75 (in birds). 
 Starling, J. Phys., 1S99, 24, 317 (glomerular function). Underhill, 
 Wells and Goldschmidt, J. Exp. Med., 1913. 18, 347 (renal secretion 
 during tartrate nephritis). 
 Perfusion of Excised Kidneys. — Richards and Plant, J. Pharm. Exp. Ther., 
 
 1915. 7, 4S5. Sollmann (T.), Am. J. Phys., 1905, 13, 241; ib., 1907, 
 19. -53'. '*-. 1908, 21, 37. WiLLiATkis, ib.. 1907, 19, 252. 
 
 Excretion of Pigment by the Kidney. — Carter (W. S.), J. Am. Med. Ass., 
 Nov. 21, 1903, p. 1248. GuKWiTSCH, Pfluger's Arch., 1902,91, 71. Hober 
 and Kempner, Bioch. Z., 1908, 11, 105. Hober and Konigsberg, 
 Pfliiger's Arch., 1905, 108, 323. Shaffer (G. D.), Am. J. Ph3's., 1908, 
 22, 355- Sobieranski, Pfluger's Arch., 1903, 98, 135. 
 
 Acid Secretion of Kidney. — Cushny, J. Ph^'s., 1904, 31, 188. Dreser, 
 Hofmeister's Beit., 1905, 6, 178. Henderson and Palmer, J. Biol. Ch., 
 1914.17,305. Henderson (L. J.), i6., 1911, 9, 403. Trevan, J. Phys., 
 
 1916, 50, 265. 
 
 Reabsorption from Kidney. — Addis and Shevky, Am. J. Phys., 191 7, 43, 
 363 (return of urea from kidney to blood). Henderson (V. E.), J. Phys., 
 1905-6, 33, 175- 
 
 Saline, Diuresis. — Cushny, J. Phys., 1902, 28, 431. Sollmann, Am. J. Phj^s., 
 1903, 9, 454. Thompson (W. H.), J. Phys., 1899-1900, 25, 487. Win- 
 field, ib., 1912, 45, 182 (osinotic pressure of blood and urine during diuresis 
 by Ringer's fluid). Yagi and Kuroda, ib., 1915, 49, 162. 
 
 Tests of Renal Function. — Mosenthal, J. Am. Med. Ass., 1916, 67, 933; 
 Arch. Int. Med., 1915, 16, 733. Pepper and Austin, Am. J. Med. Sci., 
 1913, 145, 254. Rowntree and Geraghty, J. Pharm. Exp. Ther., 1910, 
 1, 579; Arch. Int. Med., 1912, 9, 284 (phenolsul phone phthalein test). 
 
 Urea Excretion. — Ambard, J. Phys. Path. Gen., 1910, 12, 209; Ambard and 
 Weill, ib., 1912, 14, 753 ; McLean. J. Exp. Med., 1915, 22, 212 (numerical 
 laws of renal secretion of urea and NaCl). Addis and Watanabe, J. Biol. 
 Ch., 1916, 24, 203;i6., 27, 249;i6., 1917,29, 381. 399 (rate of urea excretion) . 
 Mendel and Lewis, J. Biol. Ch., 1913. 16, 19, 37, 55 (rate of nitrogen 
 excretion as influenced by diet factors). 
 
 Nephrectomy, etc. — Herter and Wakeman, J. Exp. Med., 1899, 4, 177. 
 Jackson and Saiki, Arch. Int. Med., 1912, 9, 79. MacNider, J. Med. 
 Res., 1911,24,425 (ligationof one branch of renal artery). Pilcher (J.D.). 
 J. Biol. Ch.. 1913, 14, 3S9 (K-excretio*i after ligation of branches of renal 
 arteries). 
 
 Innervation of Kidney. — Asher and Pearce, Z. f. Biol., 1913, 63, 83 ; Zentralb. 
 f. Physiol.. 1913, 27, 584 (secretory fibres). Burton-Opitz, Am. J. Phys., 
 1916. 40, 437; J. Exp. Med., 191 1, 13, 308. Burton-Opitz and Lucas, 
 
II60 BIBLIOGRAPHY 
 
 Pfluger's Arch., 1909, 127, 143, 148. Bradford (J. R), J. Phys., 1889. 
 10, 358 (vasomotors). JosT (W.), Z. f. Biol., 1914. 64, 441. De Souz.\, 
 J. Phys., 1900, 26, 139- 
 
 Innervation of Bladder.— B.\rrington, Q. T. Kxp. Phys., 1913. 9, -o. 
 l-^LMOTT, J. Phys., 1905-0, 33, p. xxix. Knowlton. ib., it^ii, 43, 'ii 
 F.xc.GE, ib., 190V 28, 304. L.\NGLEY. ib., 1901-2, 27, -5-:; ib.. 1910. 40, 
 p. Ixii; ib., 1911, 43, 125. Ott, Zentralb. f. Physiol., 189.5. 335 (centre). 
 Stewart (C. C), Am. J. Phy.s., 1899, 2, 182; ib.. 1900, 3, i. Waddell, 
 J. Pliarm. Exp. Ther., 191 7, 10, 243 (drugs). 
 
 Excretion by Skin. — Benedict (F. G.). J. Biol. Ch., 1905, 1, 263 (nitrogenous 
 matter). Schwenkenbecher and Spitta, Arch. Exp. Path. Pharm., 
 1907, 56, 2S4 (.VaC7 and A). Taylor (A. E.), J. Biol. Ch., 191 1, 9, 21 
 (nitrogen, sulphur, phosphorus). 
 
 Sweat. — Biggs, J. Med. Res., 1911, 24, 285; Camerer, Z. f. Biol., 1901, 41, 
 271 (chemistry of sweat). O'Connor (J. M.), J. Phys., 1915, 49, 113 (in- 
 fluence of temperature on sweat secretion). Wende and Bvsch, J. Am. 
 Med. Ass., 1909, 53, 207 (localized facial sweating following olfactory 
 stimuli) . 
 
 CHAPTER X. 
 
 METABOLISM, NUTRITION AND DIETETICS. 
 
 LusK The Science of Nutrition. Schryver, Bioch. J., 1906. 1, 123 (chemical 
 dynamics of animal nutrition). 
 
 CARBOHYDRATE METABOLISM. 
 
 Dakin and Dldlev, J. Biol. Ch., 1913, 14, 555. Johannson, Skand. Arch. 
 Phys., 1908, 21, I. Woodyatt, Harvey Lecture, New York, 1915-16 
 (intermediate carbohydrate metabolism). 
 
 Dextrose. — Davis. Am. J. Phys., 191 7. 43, 514 (intravenous injection). 
 Macleod, J. Lab. Clin. Med.. 1917,2,112 (utilization). Kleiner, J. Exp. 
 Med., 1911, 14, 274 (excretion in stomach and intestine). Janney and 
 CsONKA, J. Biol. Ch., 1915, 22, 203 (glucose formation from body proteins). 
 Mathews (A. P.), J. Biol. Ch.. 1909, 6, 3 (spontaneous oxidation of sugars). 
 LusK, Am. J. Phys., 1908, 22, 174. Ringer, J. Biol. Ch., 1912, 12, 511; 
 Stiles and Lusk,' Am. J. Phys., 1903, 9, 380 (formation from amino-acids). 
 Macleod and Fllk, Am. J. Phys., 191 7. 42, 193 (retention of dextrose by 
 liver and muscles). 
 
 Glycogen. — Botazzi and d'Errico, Pfluger's Arch., 1906, 115, 159 (physico- 
 chemical experiments). Cremer, Ergeb. d. Phys. (Bioch.), 1902, 803 
 (physiology of glycogen). Huber and Macleod. Am. J. Phys., 1917, 42, 
 619; Macleod, Soc. Exp. Biol. Med., 191 7. 14, 124; Kalkmann, Compt. 
 Rend. Soc. Biol., 1895, 317 (glycogen in bloodvessels of liver). Langstein, 
 Ergeb. d. Phys. (Bioch.), 1904. 453 (formation of carbohydrate from protein). 
 Lusk, Am. J. Phys., 1911. 27, 427 (cold baths and glycogen content). 
 Macleod and Pearce, Am. J. Phys., 1911, 27, 341: ^f>-- 1915. 88, 425 
 {sugar-retaining power and glycogen content of liver). Pfluger (E.). 
 Pfluger's Arch., 1902, 91, 119; ifc., 1903. 96, i (monograph on glycogen): 
 ib., 1903, 93, 165 (directions for estimation); ib., 1904. 103, 169 (abbreviated 
 method). Rusk, Soc. Exp. Biol. Med., 1912, 12, 21 (comparison of 
 chemical and microchemical methods). 
 
 Glycogenesis. — Epstein and Baehr. J. Biol. Chem., 1916, 24, 17 (influence 
 ofphlorhiziyi). Hatcher and Wolf, ib.. 1907. 3, 25 (formation of glycogen 
 in muscle). Macleod, Soc. Exp. Biol. Med., 1916, 13, 169 (influence of 
 alkali). McGuigan, J. Pharm. Exp. Ther., 1916, 8, 407 (influence of 
 atropin and pilocarpin). McDanell and Underbill, J. Biol. Ch.. 
 191 7, 29, 255 (relation of diet to glycogen content of liver). Pfluger (E.). 
 Pfluger's Arch., 1907. 120, 2^1 (in starvation) 
 
METABOLISM. KUTRinON AND DIETETICS ii8t 
 
 Glycogenolysis. — Bang, Bioch. Z., 1913, 49, 40, 81 ; Macleod and Ruh, Am. J. 
 Phys., 1908. 22, 397 (splanchnic stimulation). Macleou, ib., 22, 3 73 
 {glycogenolytic fibres in splanchnic ?). Macleod and Pearce, 16., 1911, 2i8, 
 403 (glycogenase). Neilson and Terrv, ib.. 1905, 14, 105. Paw, J. 
 Phys.. 1898, 22, 391. Paton (D. N.), J. Phys., 1899, 24, 36 {sugar 
 formation in liver). Taylor, J. Biol. Ch., 1908, 5, 315- 
 
 Blood-Sugar Content Methods.— Fitz (R.), Arch. Int. Med., 1914, 14, 133 
 (Bang and Btiliund ,net)iods compared). Lewis and Benedict (S. R.), 
 J. Biol. Chein.. 1915 20, 61. Macleod, J. Lab. Clin. Med., 1916, 1, 445 
 {rtsumi). McGuiGAN and Ross, J. Biol. Ch., 191 7. 31, 533 (Benedict 
 and Bertrand methods compared). Morris, J. Lab. Clin. Med., 191 6, 1, 
 208, 252. Myers and Bailey, J. Biol. Ch., 1916, 24, 147. Pearce, ib., 
 1915, 22, 525. Scott (E. L). Am. J. Phys., 1914, 34, 271. Shaffer, 
 J. Biol. Ch.. 1914, 19, 285, 297. 
 
 Blood-Sugar Content. — Epstein and Aschner, J. Biol. Ch., 1916. 25, 151. 
 {psychic and sensory stimuli). Graham, J. Phys., 1916, 50, 285. 
 Kramer and Coffin, J. Biol. Ch., 1916, 25, 423 (psychic and sensory 
 stimuli). Macleod and Wedd, ib., 1914, 18, 447 (in hepatic vein). 
 McGuigan, Am. J. Phys., 1916, 39, 4S0. Lee and Scott, ib.. 1917, 40, 
 486. Macleod, ib., 1909, 23, 278 (asphyxia). Macleod and Pearce, 
 ib., 1915, 38, 415. McDanell and Underhill, J. Biol. Ch., 1917, 29, 
 227, 233, 265 (alkali). RoNA and Michaelis, Bioch. Z.. 1908, 14, 476; 
 ib., 1909, 16, 60 (partition between corpuscles and plasma) Ross and 
 McGuigan, J. Biol. Ch., 1915, 22, 407 (ether ancssthesia). 
 
 Glycolysis. — Cohnheim, Z. Physiol. Ch., 1903. 39, 336; ib., 1904, 42, 401; ib., 
 1905. 43, 547; ib.. 190O. 47, 253; TucKETT, J. Phys., 1910, 41, 89; Claus 
 and Embden, Hofmeister's Beit., 1905. 5, 214; ib., 1906, 6, 343; Levene 
 and Meyer, J. Biol. Ch.. 1911. 9, 97; ib.. 1912, 11, 347; McGuigan, Am. 
 J. Phys., 1908, 21, 351 (muscle and pancreas). Levene and Meyer, J. 
 Biol. Ch., 1912, 11, 353 (action of tissues on glucose); ib., 1912, 11, 361 
 (leucocytes) . 
 
 Blood Glycolysis. — Arthus, Arch. dePhys.. 1891, 425. Lupine, J. Biol. Ch.. 
 1913. 16, 559. ;\LvcLEOD, J. Biol. Ch.. 1913, 15, 497- Macleod and 
 Pearce, Am. J. Phys., 1914, 33, 378. Pavy and Siau, J. Phys., 1901-2, 
 27, 451. AL-vckenzie (G. M.), J. Exp. Med.. 1915. 22, 757. 
 
 HYPERGLTCSIMIAS AND GLYCOSURIAS. 
 
 Brown (O. H.), Am. J. Phys., 1904, 10, 378 (effect of Ca on glycosuria). 
 Edie. Bioch. J., 1906. r, 455 (excess of CO^ in air). Henderson and 
 Underhill, Am. J. Phys., 1911, 28, 275 (acapnia and glycosuria). 
 Macleod, Harvey Lecture, New York, February 14, 1914. McGuigan 
 and Brooks, Am. J. Phys., 1907. 18, 256. Pavy and Godden, J. Phys., 
 1911, 43, 199- 
 
 Salt Glycosuria.— Burnett. J. Biol. Ch.. 1908, 5, 35i- Fischer (M.), 
 Pfluger's Arch., 1905, 106, 80; 109, i; Univ. of Calif. Pub., Dec. 24, 
 1903; ib., Feb. 15, 1904. McDanell and Underhill, J. Biol. Ch., 191 7, 
 29, 273. Underhill and Kleiner, ib.. 1908, 4, 395. 
 
 Adrenalin Glycosuria. — Blum, Pfluger's Arch.. 1902, 90, 617. Herter and 
 Wakeman, Virchow's Arch., 169, 479- McDanell and Underhill, 
 J. Biol. Ch., 1917, 29, 245. Macleod and Pearce, Am. J. Phy.s., 1912, 
 29, 419 (adrenals and sugar production by liver). Peters and Geyelin, 
 J. Biol. Ch., 1917, 31, 471- Paton (D. N.), J. Phys., 1903, 29, 286; ib., 
 1905. 32, 59. PoLLAK, Arch. Exp. Path. Pharm., 1909, 61, 149- Under- 
 hill and Closson, Am. J. Phys.. IQ06. 17, 4-- Vosburgh and Richards, 
 Am. J. Phys., 1903, 9, 35. 
 
 Relation of Adrenals to Experimental Hyperglycwmias. — Kahn. Pfluger's 
 Arch., 191 1. 140, 209; 16., 191-i, 144, 251, 396; ib., 1912, 146, 576; 
 Schwarz, Pflijger s Arch., 1910, 134, 259; Wertheimer and Battez, 
 
1182 BIBLIOGRAPHY 
 
 Aixh. Inlcrn.a. dc Phys.. 1910, 9, 140, 363; Nism, Arch. I-xp. Path. 
 Pharm., lyog, 61, i^O (puncture hyperglycamia). SxtwARi and KoooFF, 
 Am. J. Phys., 1917. 44, 543 [asphyxia and ancBsthcsia). 
 
 Puncture 6 ycosuria. — Bernard, L<'9ons sur le sysl6me nerveux, t. 1, 440. 
 Hlkii \Ki>. Z. f. Biol., 1903. 44, 407. 
 
 Alimentary Hyperglyceemia and Glycosuria. —Bailey, Soo. Exp. Biol. Med., 
 igi'), 13, 153. HoiMhisTEK, Arch. Jixp. Path. Pharm., 1S89, 25, 240 
 (assiintlalion linuts for sugars). Miura, Z. f. Biol., 1898, 34, 281. Taylor 
 (A. E.) and Hulton, J. Biol. Ch., 1916, 25, 173; Wilder and Sansum, 
 Arch. Int. Med.. 1917, 19, 311 [sugar tolerance). 
 
 Emotional Hyperglycamia and Glycosuria. — Cannon, Shohl and Wright, 
 Am. J. Pliys., 191 1, 29, .:So. Eolin, Denis and Smillie, J. Biol. Chem., 
 1914, 17, 519- Lnderhill, ib., 191 7, 29, 279. 
 
 Ether Glycosuria. — King, Movle and Haupt, J. Exp. Med., 1912. 16, 178. 
 Grube, Pfifiger's Arch., 1911, 138, 601. Ross and Hawk, Arch. Int. 
 Med., 1914, 14, 779. Seelig, Arch. Exp. Path. Pharm., 1905, 52, 4S1. 
 
 Pblorhizin Diabetes. — Cathcart and Taylor, J. Phys., 1910, 41, 276. 
 Levene, ib., 1894, 17, 259. Pavy. Brodie and Siau, ib., 1903, 29, 467. 
 Underhill, J. Biol. Ch., 1912. 13, 15 [niec/ianism of). Dakin and 
 Dudley, J. Biol. Ch.. 1914, 17, 451 {/ate of alanin). Lusk, Am. 
 J. Med. Sci., 1917, 153, 40 [intermediary tiielabolisiii); Am. J. Phys., 
 1908, 22, 17} [sugar production from glutamic acid). M vndel and Lusk. 
 Am. J. Ph\'s., 1903, 10, 47 [respiration experiments). McDermott and 
 Lusk, ib., 1900, 3, 139 [phosphorus poisoning and phlorhizin). Reilly, 
 Nolan and Lusk, ib., 1898, 1, 395. Stiles and Lusk, ib., 1903, 10, 67 
 {action of phlorhizin). Ringer, J. Biol. Ch., 1914, 17, 107 [theory of 
 diabetes, acidosis). Woodyatt and Sansum. J. Biol. Ch., 1915, 21, i 
 [narcotics in); ib., 1916, 24, 23 [determination of utilizable carbohydrates in 
 foods) . 
 
 Pancreatic Diabetes. — Carlson and Drennan. Am. J. Phys.. 191 1, 28, 391; 
 Carlson and Ginsburg, ib.. 1915, 36, 217; Carlson, Orr and Jones, 
 J. Biol. Ch.. 1914, 17, 19 [influence of pregnancy). Auer and Kleiner, 
 Soc. Exp. Biol. Med., 1917, 14, 151 [coagulation of pancreas in situ). 
 Epstein, J. Biol. Chem., 1916, ^, Homans, J. Med. Res., 1915, 33, i; 
 Thiroloix, Arch, de Phys., 1892, 24, 716 [diabetes after partial pancrea- 
 tectomy). Evans (C. L.), J. Phys., 191 2, 44, 461 [fate of secretin in). 
 Hbdon, Arch. Internat. de Phys., 1911, 11, 195; ib., 1913, 13, 4; J. de 
 Phys. Path. Gen.. 1912, 14, 907. Minkowski, Pfliiger's Arch., 1906, 
 111, 13; Arch. Exp. Path. Pharm., 1905, 63, 331. Murlin and Kramer, 
 J. Biol. Ch.. 1916. 27, 517 [influence of alkali). Murlin and Sweet, 
 ib., 191'j, 28, 261 [influence of gastrectomy). Underhill and Fine, ib., 
 
 1911, 10, 271 [inhibition of pancreatic diabetes). Scott (E. L.), Am. J. 
 Phys., 1912, 29, 306 [influence of pancreatic extract). Tuckett, J. Phys., 
 1910, 41, 88. \\r)oiJVATT. J. Biol. Chem., 1915, 20, 129. 
 
 Sugar Consumption in Diabetic Tissues. -Clark (A. H.). J. Exp. Med., 191 7, 
 26, 721 [surviving heart and pancreas in sugar metabolism). Cruickshank, 
 J. Phj-s., 1913, 47, I [glycogen in normal and diabetic animals). Cruick- 
 shank and Patterson, ib., 1914, 47, 381; Maclean and Smedley, ib.. 
 
 1912, 45, 470; Patterson and Starling, ib., 1913. 47, 137; Knowlton 
 and Starling, ib., 191 2, 45, 146 (sugar consumption in diabetic heart). 
 Hoagland and Mansfield, J . Biol. Ch., 191 7. 31, 501 (muscle) . Murlin, 
 J. Biol. Ch., 1913. 15, 365 [respiratory exchange in depancreatized animal). 
 Macleod and Pearce, Am. J. Phys.. 191 3, 32, 184 [normal and depan- 
 created eviscerated dogs). Milne and Peters, J. Med. Res., 1912, 26, 415 
 [glycolytic power of blood and tissues in diabetic organism). Myers and 
 Killian, Am. J. Phys., 191 7, 42, 582 [diastatic activity of blood in diabetes). 
 Starling, Evans and Lovatt, J. Phys., 1914, 49, 67 (respiratory exchange 
 in diabetic heart). Stewart (H. A.), J. Exp. Med., 1910, 12, 59 (perfused 
 human heart). 
 
METABOLISM, KUlRlllUS A.\D DILTETILS il8j 
 
 Diabetes Mellitus.— Allkn. Studies concerning Glyco.siuia and Diabetes. 
 Boslrn i<)i3; Host. Mi-d. Surg. J.. i<)i.5. 173, ■J^^^, Am. J. ^^cd. Sri.. 1915. 
 150, 480; J. Am. M''d. Ass., njK), 66, 15^3. C.\.mmiiji.i:, Lancet (London). 
 Oct. o, 11)17. 5JJ. Dakin and Kansom, J. liiol. Ch., i()o'). 2, 305; 
 FosiER (N. 13.). J. Uiol. Cii., iyo6, 2, 297; BAiNUKim.ic and Bkddaru, 
 Bioch. J., 190O, 1, 429 [trealnient with secretin). Greknwalu, J . Biol. Ch., 
 1014. 18, 113 (glucose from citric acid); ib., 1913. 16, 375 (glucose from 
 propionic acid). Baer and Blum, Arch. M.\p. Patii. Pliarin.. 190O. 65, 
 87; ih., 1907. 56, 9.2; ib., 1910. 62, 129 (decomposition of fatty acids in). 
 Benkdict (V. G.) and Joslin, Carnvgic Instit., Pub. ' 138, 1910 
 (metabolism in diabetes mellitus). Bai.nbriuc;k and Bkddakij, Bioch. 
 J.. 1907. 2, 89 (diastatic ferments in). Gkphart, Ai n, Du Jiois and 
 LusK, Arch. Int. Med., 1917. 19, 908 (metabolism). Jannev. .\rch. Int. 
 Med., 1916, 18, 584 (sugar from protein). Joslin, Arcii. Int. Mod., 1915, 
 16, 693 (carbohydrate utilization). Macleod (J. J. R.). Diabetes: Its 
 Patholosical Physiology, London, 1913; J. Am. Med. Ass., 1910, 55, -2133 
 (experimental diabetes and diabetes mellitus). Lusk, Arch. Int. Med., 
 
 1909, 3, I (metabolism in). Moorhouse, Patterson and Stephenson. 
 Bioch. J., 1915, 9, 171 (metabolism in experimental diabetes). Mosse. 
 J. de Phys. Path. Gen., 1901, 3, 792; 4, 128 (potatoes in). Mlrlin and 
 Graver, J. Biol. Ch., igiO, 28, 289 (sodium carbonate action), von 
 NooRDEN. Diabetes Mellitus, its Pathological Chemistry and Treatment. 
 Woodyatt, J. Am. Med. Ass., 1916, 66, 1910 (acidosis). Magnus-Levy, 
 Arch. Exp. Path. Pharm., 1901,45, 389 (acidosis). Opie. J. Iv\p. Med.. 
 1900, 5, 527 (islets). Cecil, J. Exp. Med., 1909, 11, 266; Rennie and 
 Eraser, Bioch. J., 1906, 2, 7 (islets). Pavy, Physiology of the Carbo- 
 hydrates; Lancet (London), Nov. 21, 28 and Dec. 12, 1908. Moore, 
 Edie and Abram, Bioch. J., 1906, 1, 446. Ringer, FRANKELand Jones, 
 J. Biol. Ch., 1913, 14, 525; ib., 14, 539; 1914, 18, 81 (sugar formation in 
 diabetic organism). 
 
 Diabetes Insipidus. — Christie and Stewart. Arch. Int. Med., 191 7. 20, 10. 
 FiTZ, ib.. 1914, 14, 706. Herrick (J. B.), ib., 1912, 10, i. ;Matthews 
 (S. A.), ib., 1915. 15, 451. 
 
 Diabetic Coma. — Beddard, Pembrey and Spriggs, J. Phys., 1904. 31, 
 p. xliv. ; ib., 1908, 37, p. xxxix. Magnus-Levy, Arch. Exp. Path. Pharm., 
 1S99, 42, 149. PouLTON, J..Phys., 1915, 50, i. 
 
 Acidosis. — FiTZ and Van Slyke, J. Biol. Ch., 191 7, 30, 389. Van Slyke, 
 ib., 191 7, 30, 289. Stillman and Van Slyke. J. Biol. Ch., 1917, 30, 457 
 (diabetes). Woolley, J. Lab. Clin. Med., 1916. 1, 712 (restimi). Palmer 
 and Van Slyke, J. Biol. Ch., 191 7, 32, 499 (alkali retention and alkali 
 reserve) . 
 
 Acidosis and Respiration. — Macleod, J. Lab. Clin. Med., 1915, 1, 197 (methods). 
 
 Kennaway. Pembrey and Poulton, J. Phys., 1913-14, 47, p- x. 
 
 Peabody. Arch. Int. Med., 1914, 14, 236; ib., 1915, 16, 955. Peters, Am. 
 
 J. Phys., 1917. 43, 113- 
 Acidosis, Experimental. — Fitz. Alsberg and Henderson, Am. J. Phys., 
 
 1907. 18, II > Hirschfelder, J. Am. Med. Ass., 1916, 67, 1891. 
 
 Acidosis in Nephritis. — Bostock. Z. Physiol. Ch., 1913, 84, 468. Goto, J. 
 E.xp. Med., 191 7, 25, '^93. Marriott and Howland, Arch. Int. Med., 
 iiji'>. 18, 708. SziLi, Pfliigcr's Arch., 1909, 130, 134. 
 
 Acetone Bodies. — Folin, J. Biol. Ch., 1907, 3, i 77; Folin and Denis, ib., 1914, 
 18, 203; Rothera, J. Phys., 1908, 37, 491; Scott-Wilson, J. Phys., 
 191 1, 42, 444 (estimation in urine). Embden and Marx. Hofmeister's 
 Beit.. 1908, 11, 318 (acetone formation in liver). 
 
 Aceto-Acetic Acid, Formation and Decomposition in Body.^DAKiN and 
 Dudley, J. Biol. Ch., 1913, 16, 313 \\ akeman and Dakin. J. Biol. Ch., 
 
 1910. 8, 103. Embden et al., Hofmeister's Beit., 1908, 11, T,2y, Bioch. 
 Z., 1908, 13, 262. Wilder, J. Biol. Ch., 191 7, 31, 59. 
 
1184 BIBLIOGRAPHY 
 
 Ozybutyric Acid.— Dakin, J. Biol. Cii., 1910, 8, 97 [formation in body from 
 acelo-acelic acid). Wakeman and Dakin, ib., 1909, 6, 373 (decomposition 
 
 by liver enzymes). 
 
 Glyoxal in Intermediary Metabolism. — Dakin ;in<l Dldlp;y, J. Biol. Ch., 1914. 
 18, J'»; il'.. i.^ij, K, |j?; ;',., 15, ^63; lb., 16, 505 (glyoxalase). 
 
 Pyruvic Acid in Intermediary Metabolism. — Daki.n and Janney. J. Biol. Ch.. 
 1913. 15, I 77 {relations to glucose). Levene and Meyer, ib., 1914, 17, 443 
 (action of leucocytes and kidney tissue on). Ringer (A. I.), ib., 191 3, 16, 
 145 (intermediary metabolism of alanin); ib., 1914, 17, 281 (fate of pyruvic 
 
 acid) . 
 
 Glycuronic Acid. — Xeuberg, Ergeb. d. Phys. (Bioch.), 1904, 373. Austin, 
 J. Med. Res., 1905, 14, 181 (production in dog). 
 
 METABOLISM OF FAT. 
 
 Bloor, J. Biol. Ch.. 1916, 24, 447. Dakin, ib., 1908. 4, 419; ib.. 6, 173, 303; 
 ib., 1909, 6, 203, 221, 235 (oxidation of phenyl derivatives of fatty acids). 
 Dakin and Dcdley, ib., 1913, 14, 155; Dakin and Wakeman, tb., 1911, 
 9, 329 (intermediary metabolism). Fischer (M.), Fats and Fatty De- 
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 tion of branched chain fatty acids). Lyman, J. Biol. Ch., 191 7, 32, il 
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 I (decomposition of fatty acids). Murlin and Lusk, J. Biol. Ch., 1915, 
 22, 13 [influence of fat on heat production). 
 
 Fat Formation. — Leathes, Ergeb. d. Phys., 1909, 8, 356; Moore (B.), Proc. 
 Roy. Soc. (Lond.), B 72, 134; Taylor, Univ. Calif. Publ., 1904 (synthesis 
 of fat in body). McClendon, J. Biol. Ch., 1915. 21, 269 [from protein). 
 Pfluger (E.), Pflugcr's Arch., 1899, 77, 521 (against Voit on fat formation 
 from protein). Morgiiis and Pratt, Am. J. Phys., 1913, 32, 200; 
 RuBNER, Z.f. Biol., 1886, 22,272 [from carbohydrate) . Pembrev, J. Phys., 
 1901-2, 27, 407 [respiratory exchange during fat deposition). Rosenfeld, 
 Ergeb. d. Phys. (Bioch.), 1902, 651 ; ib., 1903, 50. Smedley (L), J. Phys., 
 191 2, 45, p. XXV. (synthesis of fatty acids from carbohydrate). Ruttan 
 and Marshall, J. Biol. Ch., 191 7, 29, 319 (adipocere). 
 
 Migration of Fat. — Mendel and Daniels, J. Biol. Ch., 1912, 13, 71 [stained 
 fat). KRAUssandSoMMER, Hofmeistcr'sBeit., 1902, 2,86; Wells (H. G.), 
 Z. Phys. Ch., 1905, 45, 412 (in phosphorus poisoning). 
 
 Liver and Fats. — Corper and Mottram, J. Phys., 1912, 45, 363; ib., 1915, 49, 
 157; lb., 1914, 49, 23 (fatty acids in liver in pregnancy and lactation). 
 Jackson and Pearce, J. Exp. Med., 1907, 9, 578 (fats and lipoids in liver 
 necrosis). Leathes, Lancet (Lond.), Feb. 27. 1909; Arch. Exp. Path. 
 Pharm. Supp. Bd., 1908, 327. Raper, J. Biol. Ch., 1913, 14, 177. 
 Paton (D. N.), J. Phys., 1895-6, 19, 167. 
 
 Obesity. — Croftan (A. C), J. Am. Med. Ass., 1906, Sept. 15, 820 [dietetics of). 
 FoLiN and Denis, J. Biol. Ch., 1915, 21, 183 (starvation and obesity with 
 reference to acidosis), von Willebrand, Skand. Arch. Phys., 1908, 20, 
 152 [metabolism in). 
 
 Phosphatides. — Hatai, Am. J- Phys., 1903, 10, 57 (lecithin and growth). 
 McCollim, Halpin and Dreschek, J. Biol. Ch., 1912, 13, 219 (synthesis 
 of lecithin in hen). NerkinG, Bioch. Z., 1908. 10, 193 [distribution of 
 lecithin in the body). 
 
 Lipoids, Lipins. — Bang, Ergeb. d. Phys., 1907, 136; ib.. 1909. 463 [cell lipoids). 
 Hanes J. Exp. Med.. 1912, 16, 312 [lipoid metabolism in chick). Mac- 
 Arthur and Luckett, J. Biol Ch., 1915. 20, 161 (lipins in nutrition). 
 McCollu.m and Davis, J. Biol. Ch., 1913, 15, 167 [necessity of lipins in 
 growth) . 
 
MLIAUOIISM, SllUlllOS ASP I)H:ILT1CS il8s 
 
 METABOLISM OF PROTEINS. 
 
 CATHCARTundClKi;, N lii.uli I i.ii ;.7, I [Kil< <if /■niliinciiltibalisni): }. Pliys.. 
 I90>), 39, >ii (inlliii»icf of nuho/iyiiiiile and fat). I-olin, Am. J. Thys., 
 I9i>3. 13, 117 (<* llnory of protein ntetahotisni). Kolin and Mokris, 
 J. liiol. Cli.. IM13. 14, 309 {normal, in rat). Haskins (H. U), J. I^iol. Ch., 
 1900, 2, -:i7 {effect nf diet and diitrt-tics). Hawk and Chamhkri.ain. Am. 
 J. Phys., 1904, 10, J<i9 (after ingislion of protein). Kochkr. J. liiol. Ch., 
 1910, 26, 571 (sparinf; action of carholtydrate). Jannkv, J. Riijl. Ch., 
 1913. 20, 3-:i (relation of proteins to glucose). Lan<;stein, ICrgcb. d. 
 Phys. (Hioch.), 1902, 03 (formation of carbohydrate from protein). Mhndel, 
 ICr^ol). d. Phys., 191 1, 41S (theories of protein nietalxdism). McCollum 
 iuul HoAciLAND, J. Hiol. Ch., 1913. 16, .:99, 317 (effects of fat and acids on 
 endogenous S'-inelaholisni). Paton (D. X.). j. I'hys., 1905-6, 33, i (I'olin's 
 theory). ( )sti:kbkri; and WobK, Bioch. Z., 1907, 5, 304. 
 
 Nitrogen Estimation. — Dakin and Didlkv, J. Biol. Ch., 1914. 17, ^73; 
 Krr^cniiK .uul Stki'del, Z. Phys. Ch., 1903. 39, 12 (Kjeldahl method). 
 FoLiN and Denis, J. Biol. Ch., 1910, 26, 473 (urine); ib.. 26, 491 (non- 
 protein nitrogen of blood) (by Xcsslericatwn). Peakck (K. C). J. Lab. 
 Clin. Mi'd., I ')!(). 2, I i<> (revieio). 
 
 Non-Protein Nitrogen in Blood. — Folin and Denis, J. Biol. Ch., 191O, 26, 
 491. Foster (X. B.), Arch. Int. .Med., 1913. 15, 35<i. Pepper and 
 Austin, J. Biol. Ch., 1915, 22, Si. Greenwalu, J. Biol. Ch., 1916, 21, 
 61. Welker and Falls, ib.. 1910. 25, 5O7. Taylor and Hulton, 
 ib., 1913, 22, 63. 
 
 Amino-Acids. Dakin, J. Biol. Ch., 1905, 1, 171; ib.. 1908, 4, 63; Denis, 
 J. liiul- Ch., 1911, 9, j!b5 ; ib., 1911, 10, 73 (oxidation of aniino-acid's).. 
 Folin, J . Am. Med. Ass., 191 7, 69, 1209 (resume). Abderhaloen et al., 
 Z. Phys. Ch., 1906, 47, 391; lb.. 48, 357; //'., 51, 311, 323 (decomposition 
 of amino-acids in the body). Hardinc; and Maclean, J. Biol. Ch., 1916, 
 25, 337 {ninhydrin reaction). Folin and Denis, J. Biol. Ch., 1912, 12: 
 141 ; Wishart (M. B.), ib., 1915, 20, 533 (amino-acids in blood and tissues). 
 Harding and Maclean, ib., 1916. 24, 503; Van Slyke, ib., 1912. 12, 
 273; ib., 1913. 16, 121; ib., 1913, 23, 407 (amino-acids, amino-nitrogen, 
 estimation of). Osborne and Jones, Am. J. Phys., 1910, 26, 212 
 (amino-acids in proteins). Osborne and Mendel, J. Biol. Ch., 1914, 17, 
 325 (amino-acids in nutrition and growth). Van Slyke, Arch. Int. Med., 
 IQ17, 19, 56 (amino-acids in physiology and pathology, resumi). Van 
 Slyke and Meyer, J. Biol. Ch., 1912. 12, 399; ib., 1913, 16, 197, 231 
 (amino-acid nitrogen of blood). Gyoroy and Zunz, J. Biol. Ch., 1913, 
 21, 511 (amino-acid nitrogen in blood). 
 
 Intermediary Metabolism of Amino-Acids. — Dakin, J. Biol. Ch., 1913, 14, 
 3JI. Greenwald, J. Biol. C'h.. im<), 25, Si ; Lusk, Z. Physiol. Ch., 1910, 
 66, 106; KiNGER, J. Biol. Ch.. 1912, 12, 223 (production of dextrose from 
 amino acids). Janney, J. Biol. Ch., 1913, 22, 191 ; Csonka, J. Biol. Ch., 
 1913, 20, 339 (rate of metabolism of amino-acids). Levene and Meyer, 
 Am. J. Phys., 1909, 25, 214 (elimination of nitrogen, etc., after administra- 
 tion of some amino-acids). Macleod, J. Lab. Clin. Med., 1915, 1, 112 
 (resume). Lusk, J. Am. Chem. Soc. 1910, 32, 671 (fate of amino-acids in 
 organism). Matthews (S. A.) and Nelson, J. Biol. Ch., 1914, 19, 229 
 (fate in muscular tissue). Wakeman and Dakin, ib.. 1911, 9, 139. Van 
 Slyke and Meyer, J. Biol. Ch., 1913, 16, 213; Woelfel, Am. J. Phys., 
 iqij. 29, p. xxxviii (locus of transformation of absorbed amino-acids). 
 
 Arginine Metabolism.— Dakin, J. Biol. Ch., 1907, 3, 433; Kossel and Dakin, 
 Z. Physiol. Ch., 1904, 41, 321 (arginase). Thompson, J. Phys., 1903, 82, 
 137; ib., 1905-6, 33, 106; ib.. 1917, 51, III, 347- 
 
 Tryptophane. — Hopkins and Cole, J. Phys.. 1903, 29, 431 (constitution). 
 WiiLCocK and Hopkins, J. Phys., 1906 35, 88 (m nutrition). Dakin, 
 J. Biol. Ch., 1906, 2, 289; Hopkins and Cole, Proc. Roy. Soc. (Lond.), 
 
 75 
 
Iib(* BlBLlOGliAPHY 
 
 1901, n 68, 23 [glyoxylic acid teacttou for). L'M'EKHILL, Vale Univ. 
 l^iL-^h. iiri) PhVMology of Aniiuo-acjds. 
 Cystiu. Cystein. — .Mathhws and Walkkk, J. Biol. Ch.. lyoy, 6, 21, 29, 289. 
 ^it<) [iffontunecnis oxidation of cystein). Kotheka. J. Phys., I905, 32, 175; 
 Lewis (H. B.). J- BioI.Ch., 1917,31, 3O3 (cystxn and metabolism) . Abder- 
 HALDEN and ScHiTTENHELM. Z. Physiol. Ch., 1903. 45, 468; Garrod and 
 Hurtley, J. Phys., lyoO, 34, 217. Alsberg and Folin, Am. J. Phys., 
 1905, 14, 34; Hele, J. Phys., 1909, 39, 52; Simon, Z. Physiol. Ch., 1905, 
 45, 357, Williams and Wolf. J. Biol. Ch., 1909, 6, 337; Wolf and 
 Shaffer, J. Biol.Ch., iqoH, ^, .^T^g (protein metabolism in cystinuria) . 
 Hippuric Acid Synthesis. — Epstein and Bookman, J. Biol. Ch.. 191 1, 10, 
 ^33 ; (^.. H(i 2. 13, 117;/^., 1 91 4, 17, 455 [formation of glycocoll in the body). 
 KiNt.sBiRY and Bell, ib., 1915, 20, 73 (in tartrate nephritis); ib., 1915. 
 21, 297 [after nephrectomy). Lewis (h. B.), ib.. 1914, 17, 503 (on glyco- 
 coU-free diet) ; ib., 1914, 18, 223 [after benzoate in ma7i). PARKERand Lusk. 
 Am. J. Phys., 1900, 3, 402; Kinger, J. Biol. Ch., 1911, 10, 327 (maximum 
 production). Kaiziss and Dl bin. J. Biol. Ch., 1913, 21, 331. 
 Lactic Acid in Intermediary Metabolism — Asher and Jackson, Z. f. Biol., 
 i\ioi. 41, 393 Levkne and Mevkk, J. Biol. Ch., 1913. 14, 149. 551 
 (lactic acid from carbohydrates). Macleod and Hoover (D. H.), Am. 
 J. Phys., 191 7, 42, 460 (lactic acid prodtution in blood after injection of 
 aikali). Macleod and Wedd, J. Biol. Ch., 1914. 18, 447 [sugar and lactic 
 acid in liver blood). Mandel and Lusk, Am. J. Phys., 1906, 16, 129; 
 Ryffel, J. Phys., 1909, 39, p. xxix (lactic acid formation in man). 
 Urea in Blood. — Folin and Denis, J. Biol. Ch., 191 2, 11, 527; ib., 1916, 26, 
 305. Lewis and Karr. ib., 1916. 28, 17- McLean and Selling, ib.. 
 1914. 19, 31. Marshall, ib., 1913, 15, 487. 
 Ammonia in Blood. — ^Fiske and Karsner. J. Biol. Ch., 1914. 18, 381 (destruc- 
 tive lesions of liver and reduced ammonia in blood). Folin and Denis, 
 ib., 1912. 11, 161. 527. Jacobson (C.), ib.. 1914, 18, 133; Am. J. Phys . 
 1910. 26, 407. Salaskin et al.. Z. Physiol. Ch., 1902. 35, 246. 552. 
 Taylor and Ringer, J. Biol. Ch., 1913, 14, 407 (ammonia in protein 
 metabolism). 
 Urea Formation. — Bostock (G. D.), Bioch. J., 191 1, 6, 388 (deamidization). 
 Djyon and Dufox'RT. Arch, de Phys.. 1898. 322 [ligation of hepatic artery 
 and portal vei.i). Fiske and Karsner, J. Biol. Ch., 191 3, 16, 399 [per- 
 fusion of liver with ammonium carbonate and with glycocoll). Fiske and 
 Summer, ib., 1914. 18, 285; Jansen, ib., 1913, 21, 557; Salaskin. Z. f. 
 Physiol. Ch., 1898, 25, 128 (from amino-acids in liver). Folin andDENis, 
 J. Biol. Ch.. 1912, 12, 141. HoAGLAND and Mansfield, ib., 191 7, 31, 
 487 (muscular tissue and urea formation). Macleod and Haskins, 
 16.. 1906, 1, 319 [carbamates) . Matthews and Miller, ib. 1913. 15, 87 
 (liver circulation and nitrogen metabolism). Halsey, Z. Physiol. Ch., 1898, 
 25, 325 (prjcursors of urea). Jacoby (M.). Ergeb. d. Phys. (Bioch.), 
 1902, 332. Taylor and Lewis. J. Biol. Ch., 1915. 22, 17 (predominance 
 of liver). Wakeman and Dakin. J. Biol. Ch., 1911. 9, 327 (relationship 
 hetiv&en urea and ammonium salts). Van Slyke. Cullen and McLean, 
 Soc. Exp. Biol. Med., 1915. 12, 93 (liver). 
 Purin Metabolism. — AcKROVoand Hopkins, Bioch. J., 1916. 10, 551 (arginin 
 and hislidin as possible precursors of purins). Burian and Schur, 
 Pfliiger's Arch., 1900, 80, 241; ib., 1901, 87, 239; ib., 1903, 94, 273 (tn 
 man). Hunter (A.), J. Biol. Ch., 1914. 18, 107; Hunter and Givens, 
 ib., 1912, 13, 371; lb., 1914, 17, 37 [monkey). Hunter. Givens and 
 GuioN, ib., 1914, 18, 387 (marsupials, rodents and carnivora) . Kennaway. 
 J. Phys.. 1908. 38, I (effect of muscular work). Macleod and Haskins. 
 J. Biol. Ch.. 190G, 2, 231 (man). Wells (H. G.). J. Biol. Ch.. 1909. 7, 
 171 (monkey); J. Lab. Clin. Med., 1916. 1, 164. 
 Poiin Enzymes. — Jones (W.), Z. Physiol. Ch., 1905, 45, 84 iguanase in spleen). 
 Caldwell and Wells, J. Biol. Ch., 1914, 18, 137: ''' 19, 2-9. Long. 
 ib.. 191 \. 15, 449 (adenase). Rohde and Jones, ib., 1909, 7, 237. 
 
MliT.lIiOl.lSM. MTh'iriOS' AMJ DUiTI'.TICS 1187 
 
 Allantoiu. — Huntek (A.). J. Biol. Ch . KJ17. 28, 3<»'j (in hlood). Givens, 
 ('' . I'M J. 18, ji; Mkndel and Whitk. Am. J. Phys.. iwo^. 12, 85 
 (fni'i/iicliun in the body). 
 
 Uric Acid in Blood, -liiiNKDicT {S. K.), J. Biol. Ch., 1915, 20, 533 (ox and 
 chickiu). Dknis, J. Biol. Ch., 1915, 23, 147 (effect of ingested purins). 
 I'INE and CiiALE, J. Pharm. iCxp. 'Ihcr., 1914, 6, 219; I-olin and Denis, 
 J. Biol. Ch., 1913. 14, 29 (uric acid, urea and non-prolein nitrogen in 
 blood). FoLiN and Denis, Arch. Int. Med., 1915, 16, },i. Slemons and 
 BoGERT, J. Biol. Ch., i«>i7, 32, 03 (maternal and fcetal blood). 
 
 Uric Acid Metabolism. Cathcakt and Leathes. Prcic. Roy. See. (Lond.), 
 IQ07, H 79, 341 [relation between uric acid output and heat production). 
 Ckoftan, I'tliiger's Arch., 1908, 121, 377. Benedict (S. R.). J. Lab. 
 Clin. -Med.. 1916, 2, i. Raiziss, Duuin and Rin(;er. J. Biol. Ch.. 1914, 
 19, 473 (endogenous). Wiener, Ergeb. d. Phys. (Bioch.), 1902, 555; 
 ;/'.. 11)03. 377 [in pathology). 
 
 Uric Acid Formation.^ — Cathcakt, Kennaway and Leathes, Q. J. Med., 1908, 
 1, 410; Stehle, Soc. Exp. Biol. Med., 1915, 12, 148 (origiri of endogenous). 
 Jerome, J. Phys., 1898, 22, 146 (influence of diet). Milroy (T. H.), 
 J. Phys.. 1903, 30, 47 (in birds). Plimmer, Dick and Lieb, ib., 1909,39, 
 98 (origin). Taylor and Ross, J. Biol. Ch., 1914, 18, 519 (influence of 
 protein intake). 
 
 Uricolysis. — Fine (M. S.), J. Biol. Ch., 1915, 23, 471 (non-destructibiliiy of 
 uric acid in man). Schittenhelm, Z. Physiol. Ch., 1905, 45, 161 (urico- 
 lytic ferments). Taylor and Adolph, J. Biol. Ch., 1914,18,521. Taylor 
 and Rose, J. Biol. Ch., 1913, 14, 419; Wiechowski, Arch. Exp, Path. 
 Pharm., 1909, 60, 185 (in man). 
 
 Metabolism of Nucleins. — Abderhalden and Schittenhelm, Z. f. Physiol- 
 Ch., 1906, 47, 452 (formation and decomposition ofmichic acids in the body). 
 Jones (W.), J. Biol. Ch., 1908, 5, i (identity of nucleic acids of thymus, 
 spleen and pancreas) . Jones and Austrian, Z. Physiol. Ch., 1906, 48, 
 no; Schittenhelm and Schmid, Z. Physiol. Ch., 1906-7, 50, 30 (ferments 
 of nuclein metabolism). Jones (W.), J. Biol. Ch., 1911, 9, 169 (des 
 amidases). Jones, ib-, 1911, 9, 129; Levene and La Forge, ib., 1912, 
 13, 507; Levene and Medigreceanu, ib., 1911, 9, 65, 389 (nucleases). 
 McCollum, Am. J. Phys., 1909, 25, 120 (nuclein synthesis in the body). 
 Milroy and Malcolm, J. Phys., 1898-9, 23, 217 (metabolism of nucleins) ; 
 ib., 1899, 25, 105 (in leucocythcBmia). Sweet and Levene. J. Exp. Med., 
 1907, 9, 229 (nuclein metabolism with Eck's fistula). Givens and Hunter, 
 J. Biol. Ch., 1913. 23, 299 (sodium nucleate). 
 
 Creatin and Creatinin Metabolism. — Folin, J. Biol. Ch., 1914, 17, 469 (deter- 
 mination in urine); ib., 19x4, 17, 47.5 (determination in blood, milk, and 
 tissues). Folin and Denis. i6., igi:{. 17, ^8j (content of blood); ib., 1914, 
 17, 493 (in relation to metabolism). Foster (N. B.) and Fisher, ib.. 
 191 1, 9, 359 (with Eck's fistula). Mellanby (E.), J. Phys., 1907-8, 36, 
 447. Mendel and Rose, J. Biol. Ch., 1911,10,213 (rdle of carbohydrates)'. 
 Graham and Poulton, J. Phys., 1914, 48,p.liii (in starvation). Shaffer, 
 Am. J. Phys., 1908, 23, i {in health and disease) ; J. Bil. Ch., 1914, 18, 
 525. TowLES and Voegtlin, J. Biol. Ch., 1911, 10, 479 (function of 
 liver). Wolf, ib., 1911, 10, 473. 
 
 Creatinin. — Benedict and Myers, Am. J. Phys., 1907, 18, 377; Tracy and 
 Clark, J. Biol. Ch., 1914, 19, 115 (elimination in woman). Amberg and 
 Morrill, J. Biol. Ch., 1907, 3, 311 (in new-born infant). Levene and 
 Kristellar. Am. J. Phys.. 1909, 24, 45 (factors regulating output in man). 
 Myers and Fine, J. Biol. Ch., 1914, 17, 65; ib.. 1915, 21, 383; Scott 
 (E. L.) and Spohn, Am. J. Phys., 191 7, 42, 600 (in muscles). Palmer, 
 J. Biol. Ch., 1914, 19, 239 (basal metabolism and creatinin elimination). 
 Ringer and Raiziss, J. Biol. Ch., 1914, 19, 487 (excretion of creatinin ivith 
 creatin-free diet). Rockwood and Van Epps, Am. J. Phys., 1907, 19 
 97 (influence of drugs on elimination of creatinin). 
 
1 1 88 Illlil.KX.RAl'llY 
 
 Creatin: CreatiD Content of Muscle. — Brown and Cathcart, Bioch. J., i90y, 
 4, 420 [work). Dknis. J. Biol. Ch., 1916, 26, 379. Folin and Blckman, 
 J. Biol. Oil., u>i.i, 17, |«3 MiNOKL and KosE. ih.. utix. 10, 255; 
 Mykrs and Fink, /7^.,iyi ^ 13, 2S3 [starvation); ib., lyij, 14, 9. 1 homi'- 
 SON, J . Phys., i9i(), 50, p liii (excitation of motor nerve). 
 
 Creatin: Creatin Estimation. -Baumann and Hinks, J. Biol. Ch.. 191O, 24, 
 .431). li.M .MA.NN aiul 1n*.valdsen, ib.. 19K), 26, 195. Benedict (S. K.), 
 ib.. 191 4. 18, iMi J.vNNEYand Blatherwick, ib., 1915,21, 5O7. Kose, 
 ib., 1912, 12, 73. Walpole, J. Phys., 1911, 42, 301. 
 
 Creatin: Creatinuria. Dhms and Minot, J. Biol. Ch., 1917, 31, 561 {normal 
 adults). Foi.iN and Denis, ib.. 191 2, 11, 253 (children). Kral'se and 
 Cramer, (j. J. Exp. Phys., 1910, 3, 289; tb., 1911, 4, 293 (m women). 
 Rose, J. Biol. Ch., 1917, 32, i (women). McCrvdden and Sargent, 
 ib., 1916, 24, 423. Taylor (A. E.), ib., 1915, 21, 663. 
 
 Creatin : Creatin Metabolism. — Balmann and Marker, J. Biol. Ch., 1915, 22, 
 49 (origni uj cifutin). Benedict (S. K.) and Osterberg, ib.. 1914, 18, 
 195 (origin of urinary creatin). AIcCollcm and Steenbock, ib., 1912, 
 13, 209 (growing pig). Myers and Fine, ib., 1915, 21, 377 (file of creatin 
 administered to )nan). Paton and Mackie, J. Phys., 1912, 45, 115 
 (liver). Koss, Dimmitt and Cheetham. J. Biol. Ch., 191O, 26, 339 {pro- 
 tein feeding and creatin elimination in fasting man). Kowe, Am. J. Phys., 
 1912. 31, i'><( (creatin-splitting enzyme). Twort and Mellanby, J. 
 Phys., 1912, 44, 43 (creattn-destroying bacilli in intestine). 
 
 Autolysis. — BosTocK, Bioch. J., 1912, 6- Bradley, J. Biol. Ch., 1916, 25, 
 joi. Bradley and Taylor, ib., 25, 261 (effect of reaction); ib., 191 7, 
 29, 281 (effect of bile). Jackson (H. C), J. Exp. Med., 1909, 11, 55. 
 Dochez, J. Exp. Med., 1910, 12, 666 (liver). Jacoby, Ergeb. d. Phys. 
 (Bioch.), 1902, 213. Levene, Am. J. Phys., 1904, 11, 437; ib., 1904, 12, 
 276. Lane-Clay'ton and Schryver, J. Phys., 1904, 31, 169. Benson 
 and Wells, J. Biol. Ch., 1910, 8, 61; Stewart (G. X.). J. Exp. Med., 
 1899, 4, 235. (aittolysis studied by physico.-chemical methods). Mendel 
 and Leavenworth. Am. J. Phys., 1908, 21, 69 (embryo). Morse, J. Biol. 
 Ch., 1916. 24, 163 ; 191 7. 30, 197 (reaction) ; 1917. 31, 303 (spleen) ; Am. J. 
 Phys., 1915, 36, 143 (in involution); J. Lab. Clin. Med.. 1917, 2, 506 
 (resume). Tatvm, j. Biol. Ch., 1916, 27, 243. Schryver, Bioch. J.. 
 1906, 1, 123. Schryver, J. Phys.. 1905, 32, 150; Wells and Benson, 
 J. Biol. Ch.. 11)07, 3, 35 (influence (f thyroid). 
 
 Protein Metabolism after Removal of Portions of Intestine. — Carrel, Meyer 
 and Levene, Am. J. Phys., 1910, 25, 439; »'' . 26, 369. Erlanger and 
 Hewlett, ib.. 1902, 6, i- Levin, ^Manson and Levene, ib., 1909, 25, 
 231. Underhill, ib.. 1911, 27, 366. 
 
 Assimilation of Protein.^ — Abderhalden, Funk and London, Z. Physiol. Ch., 
 i<>o7. 51, 2()<). Pkin(,i-k and Cramer, J. Phys., 1908, 37, 158. 
 
 Parenterally Introduced Substances. — Austin and Eisenbrey, Arch. Int 
 Med., 1912, 10, 305 (utilization of serum). Michaelis and Rona, Pfliiger's 
 Arch., 1907, 121, 163 (protein). Hogan, J. Biol. Ch.. igi4. 18, 4S3: 
 Kuriyama, ib., 1916, 25, 521; Am. J. Phys., 191 7. 43, 343; Mendel and 
 Kleiner, Am. J. Phys., 1910, 26, 396 (utilization of sucrose). 
 
 INORGANIC SALTS. 
 
 Calcium. — Bergeim, Stewart and Hawk, J. Exp. Med., 1914. 20, 225 (Ca 
 metabolism after thyroparathyroidectomy). Lyman. J. Biol. Ch., 1013. 21, 
 531 (estimation in urine and fcBces) ; ib., 191 7. 29, i<)9: ''' . 30, i (in blood). 
 Malcolm (J.), J. Phys., 1903, 32, 183 (Ca and Mg relationship). Mendel 
 and Benedict (S. R.1. Am. j. Phys., 1909. 25, i}, (Ca r.xcretion). Nelson 
 and Williams, J. Biol. Ch., 1916, 28, 231 (Ca in urine and faces). Patter- 
 son, Bioch., j. 1908, 3, 39 (Ca metabolism). 
 
METABOLISM. i\'UTHllIO\ A.\U DIETETICS 1189 
 
 Phosphorus. — Hart. McCollum and Filler. Am. J. Phys., i<)oy. 23, ^4'' 
 \toif of inorganic I' in nutrition). Lisk Am. J. I'hys.. 1907, 19, \*>i 
 (infiuence on tueluhnlisni). Nasmiih and Fiulkk, J. I'hy.s., iyo,s. 37, -7^- 
 Paton. DiNLop. Ckawforu and ArrcjiisoN. J. Phys., ibyu, 26, J«^ 
 (P metaholism). Scott (F. H.). ib.. lyoO-j, 86, iiy (histo-chemical 
 methods for detection). Weber, Ergeb. d. Phys. (Bioch.). 1904. 284 
 (infiuence on metaholism). 
 
 Iron.— Abdekhaluen. Z. f. Biol.. 1900, 39, 487; Kinkel, Pflijger's Arch., 
 1895. 61. 595 (blood -formation). Di'bin and Pearce. J. Exp. Med.. 
 1917. 26, 075 (distribution in anccmia). Macalli.m (A. B.). J. Phys.. 
 1897. 22, y^ {micro-chemical reaction). Stock.man, J. Phys.. 1895, 18, 
 484 (in fond). Stockman and Gkeu;. ib., iSij-, 21, 35. 
 
 Metabolism, Qaantitative Data.— Benedict and Hom. J. Biol. Ch., Kjij. 
 20, ^u (vegetarians). Benedict and Smith, ib.. njij. 20, -:43 (athletes). 
 DiNLoi'. J. Phys., i8yO, 20, 82 (action of acids). Goodhouv, Bardswell 
 and Chapman, J. Phys., lyoj. 28, ^57 (ordinary and forced diets). Krim- 
 HACHEK, Ergcb. d. Phys.. lyoo. 74O. Pflugek (E.), Pfluger's Arch.. 1899. 
 77, 4-5 (influence of quantity and kind of food). Rubner. Gesetze des 
 Energieverbrauchs. Speck. Ergeb. d. Phys. (Bioch.), 1403. i. Weber. 
 ib.. 1904. 21^ (influence of various substances on metabolism). Zuntz. 
 Pfliiger's Arch., 1903. 95, 192; Arch. f. Phys., 1895. 378 (work and 
 metahnlisni). 
 
 Basal Metabolism. — Alb and Di Bois, Arch. Int. Med., 191 7, 19, 840 (dwarfs 
 and legless men) ; ib.. 1917, 19, 823 (old men). Benedict, Emmes, Roth 
 and Smith, J. Biol. Ch., 1914, 18, 139. Benedict and Emmes. ib., 1915. 
 20, 253 (men and women). Gephart and Du Bois. Arch. Int. Med., 
 1915, 15, 836 (effects of food). Means, J. Med. Res., 1915, 32, 121; Arch. 
 Int. Med., 1916, 17, 704 (obesity). 
 
 DIETETICS. 
 
 Benedict (F. G.), Am. J. Phys., iyo6. 16, 409. McCay, The Protein Element 
 in Nutrition. Chittenden, The Nutrition of Man, N. Y.. 1907; Physio- 
 logical Economy in Nutrition, 1905. Macleod. J. Lab. Clin. Med., 
 191 7, 2, 743 (resume, economic readjustment of dietaries). Mendel, 
 Changes in Food Supply and their Relation to Nutrition. Vale Univ. 
 Press, 1916. Knigt, Pratt and Langworthy, U.S. Dept. Agric. 
 Bull., 22i3, 1910 (dietary studies in public institutions). Pembrey and 
 Parker, J. Phys., 1907-8, 36, p. xlix (food of the soldier). Voit (C), 
 Physiologie des Stofiwechsels, 1881 . Wilson and Rathbun. J . Am. Med. 
 Ass., 191b, 66, 1 760 (dietary at .V. Y. Municipal Sanitarium). Siven. Skand. 
 Arch. Phys.. igoi, 11, 308; Caspari, Arch. f. Phys., 1901, ^2^ (minimum 
 protein requirement). Taylor (A. E.), Univ. of Calif. Pub., July 30, 
 1904 (ash-free diet). Rlbner, Z. f. Biol., 1901. 42, 261 (energy value of 
 food of human beings). Little and Harris, Bioch. J., 1907, 2, 230 
 (vegetarians). 
 
 Inanition. — Benedict, N. Y. Med. J., Sept. 11. 1907; Proc. Nat. Acad. Sci., 
 1915, 1,228. Cathcart and Fawcett. J. Phys., 1907, 36, 27. Givens. 
 See. Exp. Biol. Med.. 191 7, 14, 149 (Ca and Mg metabolism). Greene. 
 Ani. J. Phys., 191 7, 42, Ooy (changes in composition of muscle). Hoover 
 and Sollmann, J. PIxp. Med.. 1897. 2, 405 (hypnosis). Howe, Mattill 
 and Hawk, J. Biol. Ch., 1912, 11, 103. Kalfmann, Z. f. Biol., 1901, 
 41, 75. Lewis (H. B.), J. Biol. Ch., 1916. 26, 61 (S and N elimination). 
 Meyers, J. Med. Res., 191 7, 36, 51 (morphological changes). Sherwin and 
 H.\WK, J. Biol. Ch., 1912, 11, 169 (putrefaction in intestine). Voit, Z. f. 
 Biol., 1901, 41, 1O7, 502 ; ib.. 1905. 46, 167 (diminution in weight of organs). 
 Weber, Ergeb. d. Phys. (Bioch.), 1902, 702. Woelfel, J. Biol. Ch., 
 1909, 6, 189 (transfer of protein). 
 Milk and the Suckling. — Abderhalden. Z. Physiol. Ch.. 1898-y. 26, 498 
 (ash of suckling tnd ash of milk). Camerer. Z. f. Biol., 1900, 39, ^7 
 (physiology of suckling). Langstein, Ergeb. d. Phys., 1905, 851 (energy 
 
Iiyo blBLlOGUAPllY 
 
 halawc oj suckling). Oppenheimer, Z. f. Biol., imoi, 42, 1(7 (food 
 requireiucnt and hodv surface of suckling). Kihner and Heubner, 
 Z. f. Biol., i8.)8, 36,' I (feeding of suckling). Sikes (A. W.), J. Phys.. 
 i')o»i, 34, .}04 (Ca and P of Ininian milk). 
 Influence of Diet on Growth and Nutrition. — Gardner and Laider, Proc. 
 Roy. See, 1914. B87, 22(r. Mikli-ek, J. Biol. Ch.. 1913. 21, -'3 (cholesterol 
 and growth). Mendel, Krgeb. d. Physiol , mK), 102; Harvey Lecture, 
 New York, 1914-15. McCollum, Simmonds and Vn/., J. Biol. Ch., 
 1916. 27, 33 (fat-soluble A and water-soluble li and the growth-promoting 
 properties of milk). Mendel and Osborne, J. Lab. Clin. Med., 191b, 
 1, 211 (resume). McCollim and Davis, J. Biol. Ch., 1915, 23, 231 
 (essential factors in diet during growth). O.sborne and Mendel, J. Biol. 
 Ch., 1912, 12, Si (growth on fat -free food) ; ib.. 12, 473 (gliadin in nutrition) ; 
 ib., 13, ~ii (maintenance experiments with isolated proteins); ih., 1914, 
 
 18, 95 (suspension of growth) ; ib.. 1915, 20, 331 (comparative value of 
 certain proteins in growth, and the problem nf the protein minimum) ; ib., 
 1913, 23, 439 (resumption of growth) ; ib., 191b, 25, 1 (amino-acid minimum 
 
 for maintenance and growth). Robertson (T. B.), J. Biol. Ch., 1916, 25, 
 (133 (cholesterol and growth); ib.. 25, t>.\~ (lecithin). Watson (C), Lancet 
 (Lond.). July 21, 1906, 145; Dec. 8, 1585 (excessive meat); Proc. Roy. 
 Soc. (Edin.), 1905-6, 26, 87 (varying diets). Watson and Hunter, 
 J. Phys., 1906, 34, III. 
 
 Vitamines, Accessory Factors in Dietaries.^-DRUMMOND and Halliburton, 
 J. Phys., 1917, 51, 235 (nutritive value of margarine and butter substitutes). 
 Funk (C.), Ergeb. d. Phys., 1913. 124; J. Biol. Ch., 1916, 25, 409 (exclusive 
 diet of oats) ; J . Phys., 1913, 46, i 73 (chemistry of vitamine from yeast and 
 rice polishings); Funk and Macallum, J. Biol. Ch.. 1916, 27, 51 (lard 
 and butter-fat in growth); ib., 1915, 23, 413 (nature of growth- promoting 
 substances). Hopkins (F. G.), J. Phys., 1912, 44, 425. McCollum, 
 Simmonds and Fitz, Am. J. Phys., 1916, 41, 361 (fat-soluble A). Osborne 
 and Mendel, J. Biol. Ch., 1916, 24, 37 (butter-fat) . 
 
 Polyneuritis, Beriberi.— Funk and Douglas, J. Phys., 1914, 47, 475 (relation 
 of beriberi to endocrine glands). McCollum and Kennedy, J. Biol. Ch., 
 1916, 24, 491 ; ib., 1912, 45, 73- Steenbock, Am. J. Phys., 191 7, 42, 610 
 (antineuritic substances from egg-yolk). 
 
 Pellagra.^ — Chittenden and Underbill, Am. J. Phys., 1917. 44, 13. McCol- 
 lum and Simmonds, J. Biol. Ch., 1917, 32, 181. Vedder, Arch. Int. 
 Med., 191O, 18, 137- 
 
 Experimental Scurvy. — Jackson (L.) and Moore (J- J.). J- Infect. Dis., X916, 
 
 19, 478. — McCollum and Fitz, J. Biol. Ch., '^91 7, 31, 229. 
 
 CHAPTER XI. 
 
 INTERNAL SECRETION. 
 
 Biedl, Innere Sekretion. Schafer, The Endocrine Organs, 1916. Vincent 
 (S.), Internal secretion of the ductless gland.s, Ergeb. d. Phys., 1910, 
 451; ib.. 1911, 218. KojiMA (M.), Q. J. Exp. Phys., 1917. 11, 255 
 (relations between endocrine glands). Mann (F. C), Am. J. Phys., 191G, 
 41, 173 (ductless glands and hibernation). 
 
 PANCREAS. 
 Islets. — Bensley, Am. J. Anat., 1911-12, 12, 297. Cecil, J. Exp. Med., X912, 
 16, I. Homans, Proc. Roy. Soc, 1913, B 86, 73; J. Med. Res., 1914 
 30, 49- Milne and Peters, J. Med. Res., 1912, 26, 405 (atrophy of 
 pancreas after occlusion of duct). MacCallum (W. G ), Johns Hopkins 
 Hosp. Bull., Sep. 19, 1909. Pratt and Murphy, J. ICxp. Med., 1913. 17, 
 232 (transplantation of pancreas in spleen). Vincent and Thompson, 
 |. Phys., 1900, 34, p. xxvii. DeWitt, J. Exp. Med., 190') 8, 193. 
 
/.V/7.7v'.V.lL SLCJiLTlO.V Ilgt 
 
 Internal Secretion of Pancreas. Drennan. Am. J. IMiys , i<jii, 28, 396 
 {presence of. m Uood). Hbdon. Arch. Intornat. de P'liys., lyn. 13, 255 
 (pancreatic diabetes). (For additional references sec Chapter X.) 
 
 SEXUAL ORGANS. 
 Bayliss and Starlinc. Ergeb. d. I'hys., lyoo, 684 [chemical correlations of 
 sexual organs). Carmichael and Marshall, I. Phys., njoH, 36, 431 
 (compensatory hypertrophy of ovary). Dixon (\V. K.), J. Phys., 1900-1. 
 26, ^44 (action of orchilic extracts): ib., 1900. 25, 350; Rosenheim, ib., 
 191 7. 51, p. vi (spermine). Hanes, J . Exp. Med., 191 1, 13, 338 ; Steinach, 
 Pfluger's Arch., 1912, 144, 71 (interstitial cells of I.rydig and internal 
 secretion of testicle). Lipschutz, J. Phys., 191 7. 51, 283. Loewy, 
 Ergeb. d. Phys. (Bioch.), 1903, 130. Marshall and Jolly, Q. J. Exp'. 
 Phys., 1908, 1, 115 {heteroplastic transplantation of ovaries). Oliver 
 {]■)• J- Phys., 1912, 44, 3.5,5 (internal secretion of ovary). Wheelon and 
 Shipley, Am. J. Phys., 191O, 39, 394 (effects of testicular transplants on 
 vasomotor irritability). 
 
 Castration.— Henderson (J.), J. Phys., 1904, 31, 222 (castration and the 
 thymus). Livin(.ston, Am. J. Phys., iqit>, 40, 153 (effect on pituitary). 
 Marshall and Hammond, J. Phys., 1914. 48, 171 (effect on horn growth). 
 McCrudden. J. Biol. Ch.. 1901). 7, 185 (effect on metabolism). Morc;an. 
 See. Exp. Biol. Med., 1915, 13, 31 (ejfect on feathers). Simpson and 
 Marshall, Q. J. Exp. Phys., 1908, 1, 257 (stimulation of nervi erigentes 
 after castration). 
 
 THYMUS. 
 
 GooDALL, J. Phys., 1905, 32, 191 (effect of castration). Hewer, J. Phys., 1914, 
 47, 479 (effect of thymus feeding on reproductive organs). Marine and 
 Manley, J. Lab. Clin. Med., 191 7, 3, 48 (grafting ; relation of thymus to 
 sexual maturity). Paton, J. Phys., 1905, 32, 2S (thymectomy and growth 
 of sexual organs); ib., 191 1, 42, 267 (relation of thymus and sexual organs 
 to growth). Paton and Goodall, ib., 1904, 31, 49. Pappenheimer, 
 J. Exp. Med., 1914, 19, 319; ib., 1914, 20, 477; Park (E. A.), ib., 1917, 25^ 
 129; Vincent (S.), J. Phys., 1904, 30, p. xvi. (results of extirpation). 
 Seemann, Ergeb. d. Phys. (Bioch.), 1904, 45. Vincent (S.), ib., 1911, 
 303- 
 
 PARATHYROID. 
 
 Arthus and Schafermann, J. Phys. Path. Gen., 1910, 177 (parathyroidectomy 
 and Ca salts in rabbit). Camis, J. Phys., 1909, 39, 73 ; Meigham. J. Phys.. 
 1917, 51 (action of giianidin on muscle). Cooke (J. V.), J. Exp. Med.! 
 
 1910. 12, 45 (<^"« and Mg excretion) ; i6., 191 1, 13, 439 (N metabolism after 
 parathyroidectomy). Halsted. Am. J. Med. Sci.. 1907, 134, i; J. Exp. 
 Med., 1909. 11» 175; >b-. 1912, 15, 205 (grafts). Hoskins and Wheelon, 
 Am. J. Phys., 1914. 34, 2b^^ (vasomotor irritability after parathyroidectomy). 
 Joseph and Meltzer. J. Pharm. Exp. Ther.. igii, 2, 361 (action of NaCl 
 after parathyroidectomy). Koch (W. P.), J. Biol. Ch., 1912, 12, 313 
 (methyl guanidin in urine); ib., 1913, 15, 43 (toxic bases in urine after 
 parathyroidectomy); J. Lab. Clin. Med., 1916, 1, 299 (physiology of para- 
 thyroid). Marine (D.), Soc. Exp. Biol. Med.. 1914. H, 117 (hyperplasia 
 in fowls). Paton et al.. Q. J. Exp. Phys., 1917, 10. Thompson (F. D.). 
 Phil. Trans. Koy. Soc. (Lond.). 1910. \\ 201, 91 (thyroid and parathyroid 
 in vertebrates) . \Vil.son, Stearns. Thornton and Jannev, J. Biol. Ch., 
 1015. 23, 123 (excretion of acids and ammonia after parathyroidectomy). 
 
 Parathsrroid Tetany. — Carlson, Am. J. Phys., 191 2, 30, 309 (digestive tract in). 
 Carlson ;;nd Jackson, ib.. 191 1, 28, 133 (nature of tetany). Greenwald, 
 J. Biol. Ch., 191b, 25, 223. Haskins and Gerstenberger, J. Exp. Med., 
 
 191 1, 13, 314 (Ca metabolism in infantile tetany). Keeton, Am. J. Phys., 
 1914, 33, 25 (secretion of gastric juice during the tetany). MacCallum 
 (W. G.), Med. News, Oct. 31, 1903; ih.. 1^03. 86, 625 (gastric and duodenal 
 dilatation in); Soc. Exp. Biol. Med., 1912, 9, 2^ (seat of action in tetany). 
 
1192 BJULJUURAPHY 
 
 MacCalli M ami \oi:(.tlin, J. Exp. Mod.. 1909. 11, 118 {Ca in); J. 
 Pharm. Exp. Ther.. lyii, 2, 421 {influence of various sails tn). Mac- 
 Calli'm and V'o<;ei.. J. Exp. Med., uii .^ 18, 018. MacCallvm. Lambert 
 and VoGKL. J. Exp. Med.. 1914. 20, 149 (retuoval of L a from the blood by 
 dialysis). Marine (]).), ib.. 191.}, 19, 89. Stoland, Am. J. Phys., 1914. 
 33, -^83 (influence of the tetany on liver and pancreas). Underhill and 
 Blatherwkk. J. Hiol. Ch.. 1914, 19, 119 (influence of dextrose and Ca 
 lactate on blood-sugar and tetany). 
 
 THYROID. 
 
 AsHER, Pfluger's Arch., k^ii, 139, 5()i (history and methods). Bayliss and 
 Starling, Ergeb. d. Phys., 1900, 683 (chemical correlations of thyroid). 
 V. EiJRTH. ib.. 1909. 9, 5^4; Oswald, Pfliigcr's Arch., i9i(). 164, 500 
 {thyroid and the circulation). Vincent (S.), Ergcb. d. Phys., 1911, in; 
 Vincent and Jolly, J. Phys., 190b, 34, 295 (functions of thyroid and 
 parathyroid) . 
 
 Results of Thyroidectomy. — Gley, Arch, do Phys., 1893, 467 (rabbit); ib., 
 ji-ih (dog). 1 Iai.phnny and Gi'NN, Q. J. Exp. Phys.. 1911. 4, 237 (monkey). 
 HosKlNS and Morris, Soc. Exp. Biol.. Med, 191 7. 14, 74 (amphibia). 
 Palmer, Am. J. Phys.. 1917. 42, 572 (pig)- Simpson. (). J. Exp. Phys., 
 
 1913, 6, 119 (sheep). Smith (J. L.), J. Phys.. 1894, 16, 378 (heat regula- 
 tion). Tatim (A. L.). J. Exp. Med., 1913. 17, i>3<> (experimental cretinism). 
 
 Morphological Changes in Thyroid. — Halsted (\V. S.). Trans. Ass. Amer. 
 Physicians. 19x3; If)hns Hopkins Hosp. Rep.. 1896. 1 (compensatory 
 hypertrophy). Marine (D.), J. Exp. Med., 1914, 19, 37O (involution of 
 active hyperplasia in brook trout). Marine and Lenhart. Arch. Int. 
 Med., 1909, 4, 253, 440; Marine and Willl-^ms, ib., 1908, 1, 349 (relation 
 of iodine to thyroid structure). \V.\tson (C), J. Phys., 1905, 32, p. xvi; 
 io., 1906, 34, p- xxix ; ib.. 1907, 36, p. i (changes in, on meat diet). 
 
 Influence of Thyroid on Metabolism. — Carlson and Jacobson. Am. J. Phys,, 
 1910, 25, 403; Jacobson (C). J. Biol. Ch.. 1914. 17, 133 (blood-ammonia 
 after thyroidectomy). Cramer and Krai^se, Proc. Roy. Soc, 1913, B 86, 
 550 (carbohydrate metabolism and the thyroid). Hinter (.\.), Q. J. Exp. 
 Phys., 1914, 8, 23 (thyro-parathyroidectomy and A' metabolism in sheep). 
 King (J. H.), J. Exp. Med., 1909, 11, 6O5 ; Underhill and Hilditch, Am. 
 J. Phys., 1909, 25, 66; Kuriyama. Am. J. Phys., 191 7, 43, 481 (carbo- 
 hydrate metabolism after thyroidectomy). McCtrdy (J.), J. Exp. Med., 
 1909, 11, 798 (thyroidectomy and alimentary glycosuria). 
 
 Thyroid Feeding. — Carlson, Rooks and McKie, Am. J. Phys., 1912. 30, 129 
 (attempts to produce hyperthyroidism). Cramer and McCall, O. J. I-lxp. 
 Phvs., 191 7. 11, 59 (effect on gaseous metabolism). Ci'nningham (H. H.|, 
 J. Exp. Med., 1898, 3, 147 (experimental thvroidism). Guderxatsch, 
 Am. J. Phys., 1913. 36, 370 (in rats). Hewitt (J. A.), Q. J. Exp. Phys.. 
 
 1914, 8, 113. 297 (influence of small amounts of thyroid and anterior lobe of 
 pituitary on metabolism). Kuriyama. J. Biol. Ch., 191 7. 33, 193 (storage 
 and moiiilization nf I ivri glycogen in). 
 
 Active Constituents of Thyroid.— Baimann. Z. f. Physiol Ch.. 1895-6. 21, 
 ;i9 (thyroidin). Caldwell, Am. J. Phys., 1912, 30, 42 (intravenous 
 injection of thyroid pressure liquid). Carlson and Woelfel, ib.. 1910. 
 26, ^^ (internal secretion of thyroid). 1'\\wcett. Rogers, RAHEand Beebe, 
 lb.. i<»t4. 36, 113; Eenger, J. Biol. Ch.. i()i2. 11, 4^59: ili.. 12, r,^ (active 
 principle in thyroid and suprarenal before and after birth). Graham (A^, 
 J. Exp. Med., 1916. 24, 343; Lenhart, ib., 1915. 22, 739; Rogoff and 
 Marine, J. Pharm. Exp. Ther., 1916, 9, 57 (relation of effect on tadpoles 
 to amount of iodine). Giderna tsch. Arch. Entwick. Niech. d. Org.. 
 1912-13, 35, 437; Am. J. Anat., 1913. 15, 431 (effect on tadpoles). Hi'NT 
 and Seidell, J. Pharm. Exp. Ther., i<)io. 2, 15 (thyreotropic iodine 
 compounds). Hunt (U.). J. Biol. Ch.. 1905. 1, .vV. Lussky (H. O.). 
 Am. J. Phys., 1912, 30, 63 (acelo-nilrile test). Kendall, J. Biol. Ch., 
 
IM KhWAL SliCJUiTJON ii'J3 
 
 I«ii3 20, .501 (product of (ilUalme hydrolysis of thyroid). Koch (F. C). 
 J. Hiol. C\\.. i<»i |, U)i (nutitre of the lodine-containing lonif^le.x lu thyreo- 
 f;lol>ulin). Marixk. il>.. i'»i s, 22, 31 7 ((» t'/T'o absorption of K I hv thyroid). 
 Marink ;iiul I'kiss. J. I'hjiriu. JCxp. Ther., n»t3, 7, 537 Uihsorption of Kl 
 by perfused thyroid). Makink and !<()(. okk, ib.. i<)i<>. 9, 1 Untie required 
 for elaboration of the iodme-ioutaining substance). Mousk (M), J- Biol. 
 Ch.. IQ14. 19, .JJI (the principle accelerating involution m tadpoles). 
 Oswald. Arch. Jixp. P.ith. Pharm., lyog, 60, 115 (iodolhyrin). Pick 
 and riNELEs. Z. Kxp. Path. Ther., 190Q, 7, 518.' Kocioj-i- (J. M), J. 
 Pharm. Exp. TIut., 191 7, 10, 199 (tadpole method for standardization 
 of thyroid prepnyations. 
 
 Iodine Content of Thyroid. -Aldrich, Am. J. Phys., 1912, 31, r^S- Fenger, 
 J. Biol. Ch., i.)i.;, 14, 397 (/ and P in fecial thyroids). Hunter (A.), 
 lb.. 1910, 7, .1-11 (estimation). Hinter and Si.mp.son, ib., IQI3, 20, 119 
 (influence of diet of marine algcr). W'atis, Am. J. Phys., 1913, 38, 35O 
 (iodine co)itrnt and bloodfloiv through thyroid). 
 
 Innervation of Thyroid. — Secretory Nerves ? — Asher and Plack, Z. f. Biol.. 
 1911. 56, 83. BuRGET. Am. j. Phys., 1917, 44, 4q-:. Cannon, Bingep. 
 and Pnz, ib.. 1914, 36, 363. Levy, ib.. i<)i(). 41, iM-- Manley and 
 Marine, Soc. Exp. Biol. Med., 1915, 12, 2.01. IMarine, Rogoff and 
 Stewart, Am. J. Phys., 1918, 45, 2b8. Kahe, Rogers, Fa wcett and 
 Beebe, (7)., 19K). 34, 72. 
 
 Vasomotors of Thyroid. — Fran^ois-Franck and Hallion, J. de Phys. 
 Path. Gen., 1908, 10, 442. Stewart (G N.), J. Phys., 1893. 15, 79- 
 
 Thyroid Grafts. — Hesselberg (C), J. Exp. Med.. 1913. 21, i'm ian'o- and 
 homoco-grafls in guinea pig). Manley and Marine, J. Am. Med. Ass., 
 1916, 67, 260. 
 
 ADRENALS. 
 
 Epinephrin (Adrenalin, Suprarenin). — Abel (J. J.). Am. J. Phys., 1901, 5, 
 p. v; lb.. 1903, 8, p. xxix ; Alurich, ib.. 190 1, 5, 437; ib.. 7, 3391 v. FiJrth, 
 Hofmeistcr's Beit., 1902, 1, 243: Takamine. J. Phys., 1901-2, 27, P- xxix 
 (isolation). Abel and Macht, J. Pharm. Exp. Ther., 1912, 3, 327, 334 
 (in toad's venom). Embden and v. Fijrth, Hofmeister's Beit., 1904, 4, 
 421. Weiss and Harris, Pfluger's Arch., 1904, 103, 510 (destruction 
 in the body). Ewins and Laidlaw, J. Phys., 1910, 40, 275 (formation). 
 Funk, J. Phys., 1911, 43, p. iv; Greer and Wells, Arch. Int. Med., 
 1909, 4, 2qi (absent in hvpernephroma). 
 
 Action of Suprarenal Estract and Adrenalin. — Aler and Gates, J. Exp. 
 Med.. 1917, 26, 201: Jackson. J. Pharm. Exp. Ther.. 1912, 4, 59 (on 
 lungs). Bainbridge and Trevan, J. Phys., 1917, 51, 460 (on liver). 
 Barbour and Kleiner, J. Pharm. Exp. Ther., 1915, 7, 341 ion vagus). 
 Barcroft and Piper, J. Phys., 1912, 44, 339 (on gaseous metabolism of 
 submaxillarv). Botazzi, D'Enrico and Japelli, Bioch. Z., 1908, 7, 431 
 (on saliva and urine secretion). Brown (E. D.). J. Pharm. Exp. Ther., 
 1916, 8, 195. BuRKET. Am. J. Phys., 191 2, 30, 382 (on blood-pressure). 
 Cannon and Gray, Am. J. Phys., 1914. 34, 2}i: Grabfield, Am. J. 
 Phys.. 191(5, 42, 4'} (on coagulation). Cannon and Nice, ib.. 1913. 32, 44; 
 Gruber, 77)., 1914. 33, 333; ib., 1917. 43, 330 (on muscular fatigue). 
 Cannon and Lyman, (7*., 1913. 17, 37'i; Hoskins and ^IcClure, ib.. 1912, 
 30, 192; Moore and Purinton, Pfluger's Arch., 1900, 81, 483; Am. J. 
 Phys.. 1900, 3, p. XV (depressor action of minimal doses). Cushny, J. 
 Phys., 1908, 37, 130: it>.. 1909, 38, 239 (adrenalin isomers). Evans and 
 Ogawa, ib.. 191 4, 47, 44'> (on gaseous metabolism of heart). Edmunds, 
 Am. J. Phys.. 18, 129 (on blood-velocity). Elliott, J. Phys., 1903. 
 32, 401. F^LEISHER and Loeb. J. Exp. Med.. 1910, 12, 288 (on absorption). 
 GiTHENs, J. Exp. Med., 191 7, 25, !t,27i. Golla and Symes, J. Pharm. 
 Exp. Ther., 1913, 5, 87 (on bronchioles). Gunn. C_). J. Exp. Phys., 1913, 
 7, 75 (f'" heart). Gunn and Chavasse, Proc. Roy. Soc, 1913, (on veins). 
 Harold, Xierenstein and Roaf, J. Phys.. 1910, 41, 308. Hartmann 
 
1194 BIBLIOGRAPHY 
 
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 GuNNiN(i aiui Berry, Am. J. Phys., lyiO, 41, 513 {on circulation in limb). 
 HosKiN.s and .McClire. Arch. Int. Med., 191 2, 10, 343 (blood- pressure). 
 HosKiNS, Am. J. Phys., 1915, 36, 4^3 (adrenals and syrtipathetic irrita- 
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 McGuiGAN and Mostrom, J. Pharm. Exp. Ther., 1913, 4, 277; Magnus, 
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 Oliver and Schafer, J. Phys., 1895, 18, 230. Park, J. Exp. Med., 
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 Determination o! Epinephrin. — Folin, Cannon and Deni.s, J. Biol. Ch,, 
 1912, 13, 477; Seidell, ib., 1913, 15, 197 (colorimetrtc). Elliott, 
 J. Phys., 191 2, 44, 374 (pithed cat) ; ib., 1913, 46, p. xv. 
 
 Epinephrin Content of Adrenals.^ — Elliott, J. Phys., 191 2, 44, 374 McCord, 
 J. Biol. Ch., 1915, 23, 435 (foettts). Ritchie and Bruce, Q. J. Exp. Phys., 
 
 191 1, 4, 127 (effect of diphtheria ioxine). Seidell and Eenger, U. S. 
 Hyg. Lab. Bull., 100, 1914, p. 57. Stewart and Rogoff, J. Exp. Med., 
 
 1916, 24, 709. 
 
 Epinephrin in Blood (and Tests for). — Barbour and Prince, J. Exp. Med., 
 1915, 21, 330; Barbour, ib.. 1912, 15, 403; Janeway and Park, ib., 
 
 1912, 16, 541 ; Park, ib., 1912, 16, 532 (coronary artery test). Dale and 
 Laidlaw, J. Phys., 1912, 45, i ; J. Pharm. Exp. Ther., 1912, 4, 75 (guinea 
 pig uterus test). Jackson (D. E.), Am. J. Phys., 1909, 23, 226 (disappear- 
 ance after injection). Lawen, Arch. Exp. Path. Pharm., 1904, 51, 415 
 (frog perfusion test). Meyer, Z. f. Biol., 1906, 48, 352; Park and Jane- 
 way, Soc. Exp. Biol. Med., 191 2, 9, 31 (artery ring test). Schultz (W. H.), 
 J. Pharm. Exp. Ther., 1909, 1, 291 (critique of tests). Stewart (G. N.), 
 J. Exp. Med., 1911, 14, 377 (biological tests — rabbit intestine and uterus 
 segments); ib., 1912, 15, 347 (absence of detectable epinephrin in venous 
 blood); ib., 1912, 16, 302 (comparison of plasma and serum on intestine 
 segments). Stewart and Rogoff, J. Pharm. Exp. Ther., 1917. 9, 393 
 (partition between corpuscles and plasma). Stewart and Zixker, J. 
 Exp. Med., 1913, 17, 152, 174 (artery ring, frog perfusion, rabbit intestine 
 and uterus coynpared). Trendelenburg, Arch. Exp. Path. Pharm., 
 1913.79, 134- 
 
 Epinephrin Secretion and Adrenallnnervation. — Asher. Z. f. Biol., 1912, 58, 
 274; Pfluger's Arch., 1917, 166, 372. Cannon, Aub and Binger, J. 
 Pharm. Exp. Ther.. 1912, 3, 379 (nicotine). Dreyer. Am. J. Phys., 1899, 
 3, 203. Elliott, J. Phys., 1912, 44, 374; ib., 1913, 46, 283 (innervation); 
 ib., 1914, 49, 38 (some results of excision of adrenals). Hoskins and 
 McPeek, J. Am. Med. Ass., 1913, 60, 1777 (massage of adrenals). Joseph 
 and Meltzer, .\m. J. Phvs., ii)i2, 29. p. xxxiv (splanchnic stimulation). 
 O'Connor, Arch. Exp. Path. Pharm., 1912. 67, 193: 'b.. 68, 383. 
 Stewart, Rogoff and Gibson, J. Pharm. K\p. Ther., 1910, 8, 203 
 (splanchnic stimulation). Stewart and Rogoif, ib.. 191b, 8, 479 
 (spontaneous liberation); ib.. 1917. 10, 49 (asphyxia); J. Exp. Med., 191 7, 
 26, 637 (effect of sensory stimulation) ; ib., 191 7. 26, 613 (spinal centre for 
 epinephrin secretion); J. Pharm. Exp. Ther., 191 7, 10, i (indispensa- 
 bility of epinephrin ?); Am. J. Phys., 191 7. 44, 149 (relation of liberation 
 of epinephrin and adrenal blood- flow). 
 
 Adrenals and Metabolism.— Edmunds. J. Pharm. Exp. Ther.. 191 1, 2, 359; 
 Mann, Arch. Int. Med., 1915, 16, 781 ; Pemberton and Sweet, ib., 1912, 
 
INTERNAL SECRETION iuj5 
 
 10, 169 {relation to pancreas). Li'sK ;iiul KiCHE, tb., l<n\. 13, 673; 
 KiNUKK, I V.\\< Med Ki'.o. 12, 103 (diahetfs). 
 
 Disseminated Chromaffin Tissue. Hikui. and WiEshi.. PHiiKer's Arch., ujoz. 
 91, 434. tii.K ami Macleou, Am. J. Phys., i<;i(i, 40, n. Gaskell 
 (J. F.), J. Phys., i<>iJ. 44, 59 (distribution of medullary tissue in petro- 
 myzon). 
 
 PITUITARY. 
 
 Blair Bell. Q. j. Ilxp. Phys . 191 7, 11, 77 [fxperuuental operatums). Cu.shin<". 
 (H.). The pituitary body and its disorders, I'hiladelphia. iqi2: Johns 
 Hopkins Hosp. Bull., 1910, 21, 1^7 (experi}tietital hypnphysectomy). 
 V. Cyon, Pfliiger's Arch., 1900. 81, .;'>7; J- Phys. Path. Gen., 1909, il, 
 J59. GoETscH (E.), Q. J. Med., 1914, 7, 173 (review). Herring (P. T.). 
 y. J. Exp. Phys.. 1908. 1, 111 (histology); ib.. 1913, 6, 73 {comparative 
 anatomy and physiology): ib., 1914, 8, 267 (activity of pars intermedia and 
 pars nervosa); ib.. 1914, 8, .245 (origin of active material of posterior lobe). 
 Pai'lesco, J. Phys. Path. Gen., 1907, 9, 441. Schaker. Proc. Roy. 
 Soc. 1909, B81, 442 (functions). Simpson and Hunter, Q J. E.\p. Phys., 
 1910, 8, i.:i {relation bettveen thyroid and pituitary). Vince.nt (S.), 
 Ergeb. d. Phys., iqii, 3ot>; Practitioner, Jan., 1915 (general review). 
 
 Influence on Growth and Metabolism, .\lurich. Am. J. Phys., 191J, 31, 
 94 (feeding to rats). Bi.nedict ;ind Homans, J. Med. Res., 1912, 25, 409 
 (metabolism after hypophysectomy). Gushing and Goetsch, J. Exp. 
 Med., 1915, 22, 25 (hibernation and the pituitary). Malcol.vi (J.), J. 
 Phys., 1903, 30, 270. Maxwell. Univ. of Calif. Pub.. 1916, 5, 5; Pearl 
 (R.), J. Biol. Ch., 1916, 24, 123 (feeding pituitary to fowl). Miller and 
 Lewis. Arch. Int. Med., 1912, 9, 601 (glycosuria after injection of extracts). 
 Robertson (T. B.), J. Biol. Ch., 1916, 24, 397, 409; Robertson and 
 Delprat, ih., 191 7, 31, 567; Schmidt, J. Lab. Clin. Med., 1917. 2, 719 
 (tethelin). Schafer (E. A.), Q. J. Exp. Phys., 1912, 5, 203 (effect of 
 ovarian, pituitary, and thyroid tissue on growth of rats). Wulzen (R.), 
 Am. J. Phys., 1914, 34, 127 (growth in birds). 
 
 Action of Extracts. — Addis and Barnett, Soc. Exp. Biol. Med., 1916, 14, 49 
 (on urea secretion by kidney). Auer and Meltzer, J. Pharm. Exp. Ther.. 
 1913, 4, 359 (pituitrin on depressor action of vagus). Dale, Bioch. J., 
 
 1909, 4, 427. Hamburger (W. W.), Am. J. Phys., 1904, H, 282; ib., 
 
 1910, 26, 1 78 (anterior lobe). Howell, J. Exp. Med., 1898,3, 245 (posterior 
 lobe). HosKiNs and Means. J. Pharm. Exp. Ther., 191 3, 4,435 (pituitrin 
 diuresis). Kin(. and Stoland, Am. J. Phys., 1913, 32, 405 (action on 
 renal activity). Xice, Rock and Courtright, Am. J. Phys., 1914, 35, 
 194 (on respiration). Paton and Watson, J. Phys.. 1912, 44, 413 {on 
 circulation of bird). Pilcher and Sollmann, J. Pharm. Exp. Ther., 
 191 5, 6, 405 (on vasomotor centre). Schafer and Herring, Phil. Trans. 
 Roy. Soc. (Lond.), 1906, B 199, i (on kidney). Waddell, Am. J. Phys., 
 i<»i6, 41, 529 {on frog's cesophagus). 
 
 Formation and Secretion (?) of Active Substance.— Carlson and Martin, 
 Am. J. Phys., 1911, 29, 64 (question of infundibular secretion in cerebro- 
 spinal fluid). Cow (D.). J. Phys., 1915, 49, 367. Fencer, J. Biol. Ch.. 
 1915, 21, 283; ib., 1916, 25, 417 (composition and activity of pituitary). 
 Keeton and Becht. Am. J. Phys., 1915, 29, 109 (stimulation of pituitary). 
 McCord, J. Biol. Ch.. 191 5. 23, 435 (active substance in fcetus). Rabens 
 and LiFSCHlTZ, Am. J. Phys.. 191 4, 36, 47 (innervation). Weed and 
 Gushing, ib.. 191,5 36, 77 (effect of pituitary extract on its secretion). 
 (For action of pituitary extract on milk secretion, see Chapter XIX.) 
 
 SPLEEN. 
 
 Splenectomy.^ — Goldschmidt and Margot, J. Exp. Med., 1913, 22, 319; 
 Mendel and Gibson, .\m. J. Phys., 1907. 18, 201 (.V metabolism in man). 
 RicHET, J. Phys. Path. Gen., 1912, 14, 089; ib., 1913, 15, 579 {effects on 
 nutrition). 
 
1196 BlliUOGRAPHY 
 
 Blood Changes after Splenectomy. —KARsNiiR and Pkarck, J. Kxp. Med., 
 lyi-:, 16, 7<->»j. PiiARCE, AisriN and MirssER. ib.. n)ii. 16, 758 (hanio- 
 lylic jaundice). Orr, J. Lab. Clin. Med.. 1917, 2, 093. 
 
 Spleen and Blood Formation. Do.nhauskr, J. Kxp. Med., kjoH, 10, 559. 
 MoKKis, ///., nil |. 20, 3 7<». Paton, CiuLLAND and Fowler, J. Phys., 
 i')o;, 28, ."^-: Si KMANN. Ergeb. d. Phy.s. (Bioch.), 1904, 30. 
 
 Spleen and Haemolysis. — Levin, J. Med. Res., 8, iio. Krumbhaar and 
 Mus.sER, J. Kxp. Med., 1916, 23, 07. Krumbhaar. ib.. 1914, 20, 108. 
 Paton and Goodall, j. Phys., 1903. 29, 411. Pearce, Austin and 
 Krumbhaar, [. Exp. Med., 1912, 16, S'^v Pearce and Peet, J. Exp. 
 Med., 1013. 18, l-M. 
 
 Relation of Spleen to Pancreas. — Herzen, J. Phys. Path. Gen.. 1902, 4, 625; 
 
 Pfliiger's Arch., 1901, 84, 115. Mendel and Kettger, Am. J. Phys., 
 
 1902, 7, 387- 
 Spleen Innervation. — Langley, J. Phys., 1896, 20, 223. bcHiFER and 
 
 .MUOKK. lb.. 20, I. 
 
 Spleen Grafts. — Manley and Marine, J. Exp. Med., 191 7, 25, 619; See. Exp. 
 Biol. .Med., IQ17. 14, 123. 
 
 Effects of Reduction of Kidney Substance. — Bainbridge and Beddard, 
 Proc. Koy. Soc, H)<J7, \i 79, 73- Barrington. Heart, 1915, 6, 163. 
 Bradford (J. K.), J. Phys., 189S-M. 23, 415. Kar.sner, Bunker and 
 Grabfield, J. Exp., Med. 1915, 22, 344. Pearce (R. M.), ib., 1908, 
 10, ()32. Sampson and Pearce, ;//.. i()«h. 10, 743. 
 
 Effect of Kidney Extracts on Blood-Pressure.— Pearce (1^ M.), J. Exp. Med.. 
 i90tj, 11, 430; Arch. Int. Med., 1912, 9, 3'j2. Tigerstedt and Bergman, 
 Skand. Arch. Phys., 189S, 8, 223 {pressor substance in kidney extracts). 
 
 Pineal Body. — v. Cyon, Pfliiger's Arch., 1903, 98, 327. Dandy, J. Exp. Med., 
 1915, 22, 237 {extirpation). Fenger, J. Am. Med. Ass., 1916, 17, 183O 
 {composition and activity). Horrax, Arch. Int. Med., 1916, 17, 607- 
 McCoRD, J. Am. Med. Ass., 1915, 65, 517. Jordan and Eyster, Am. J 
 Phys., 1911, 29, 113 {extracts). Orr and Scott, See. Exp. Biol. Med., 
 1012, 9, O.f {extracts). 
 
 Salivary Glands (Removal). — Schafer and Moore, J. Phys., 19, p. xiii. 
 
 Organ Extracts. - Broun and Joseph, J. Phys., i<jo6. 34, 282. Campbell 
 (J. A.), (). J. Ex]). Phys., 1911, 4, I {on bloodvessels). Kawcett, Rahe, 
 Hackett and Ro(,ers, Am. J. Phys., 1915, 39, 154 {on smooth muscle). 
 Joseph (D. R.), ]. Exp. Med., i<)07, 9, 606 {on blood-pressure). Miller 
 (J. L. and E. M.)", J. Phys., 1911, 43, 242. 
 
 Bone-Marrow Extracts. — Brown and Guthrie, Am. J. Phys., 1905, 14, 328; 
 Brown and Josicph, ib., 1906, 16, no. 
 
 Extracts of Nervous Tissue. — Halliburton, J. Phys., iqoo-i, 26, 229. 
 Osborne and Vincicn 1 , ib., 1899-1900, 25, 283. Schafer and Moore, ib., 
 189O, 20, I. Schafer and Vincent, 25, 87. Vincent and Cramer, ib., 
 1904, 30, 143. 
 
 CHAPTER XII. 
 
 ANIMAL HEAT. 
 
 Calorimetric Observations. — Atwater, lugcb. d. Phys. (iiioch.). 1904, 41^8. 
 Benedict, and Carpenter, Carnegie Instil. Pub., 123, i<>io (respiration 
 calorimeters for man); ib., Pub. 128, 1910 {mctaliolism of normal men). 
 Du Bois, J. Am. Med. .\ss., 1914, 63, 827, 830 {total cnrrpy requirement 
 in disease); Arch. Int. Med.. 1916, 17, 887 {children). dWrsonval, Arch, 
 de Phys., 1890, ()io, 781. Hill (.\. V.), J. Phys., 191 1, 43, 379 {cold- 
 blooded animals); ill.. 1912-13, 45, 2()i {micro-calorimeter). Hill (A. V. 
 and A. M.), ib., IQ13, 46, 81 {warm-blooded animals). Langworthy and 
 MiLNER, yparbook, U.S. Dept. Agric, 1910 (respiration calorimeter). 
 Lefevre j. Phys. Path. Gen., 1900, 2, 259. Lusk, Arch. Int. Med., 
 
AM MAI. HEAT 1 197 
 
 IMI3, 16, 7i»3 (respiration calorimeter for study of disfase) ; J. Biol. Cli., iyi2. 
 13, -7 (ingestion of dextrose and fat). McCri'UUEN and LisK, J. Biol. 
 Cli.. iMiJ. 13, 447- Macdonald (J. S.). J. Phys.. lyij, 44, p. iv (man). 
 Mi'KLiN ami HooBLEK, Am. J. Dis. Childn-n, It^i3, 9, 91 (infants). 
 MuRLiN anil LusK, J. Biol. Ch., 191 3. 22, 13 (ingestion of fat). Pkauody, 
 Meyer and Du Bois. Arch. Int. Med., 19K), 17, 980 (hasal metabolism 
 in cardio-renal disease). KicuE and Sooekstrom, Arch. Int. Med.. 
 1913. 15, 903. Williams, J. Biol. Ch., lyi.*, 12, J17 (small calorimeter). 
 Williams, Kichk and Li'sk. (/>., 1912, 12, 349 (ingestion of meat). 
 
 Specific Dynamic Action of Foodstuffs. — Lusk. J. Biol. Ch., 1915. 20, 555. 
 
 Surface Area.- Benkdu r (!•. C). \m. J. IMivs-, 1916, 41, 275. Du Bois 
 iD. Hiul 1-:. F.), Arch. Int. Med., 1913, 15, .S()8; ib., 1910, 17, 80^ 
 
 Surface Area and Metabolism (Heat Production). I^e.neukt (F. G.), Am. J. 
 Phys.. mil), 41, .i'U. C.icpilxkt and Dr Hois. .\rch. Int. Med., 1916, 
 17, 00.'. Mi;.\Ns I J. 111. J. Biol. Ch., H)i3, 21, ^''3. 
 
 Heat Production in Various Organs (and Functions). — Bayliss and Hill (L.). 
 J. Phys., iiS<j4, 16, 331 [salivury glands). Chauveat, Arch, de Phys., 
 1887, 2.49 (thermodynamics of muscular work). Herlitzka, Archivio di 
 Fis.. 1912, 10, 301; Snyder, Am. J. Phys., 1917, 44, 421 (heart). Hill 
 (A. v.), J. Phys., 1912, 43, 433; Rolleston (H. D.), ib., 1890, 11, 208; 
 Stewart (G. N.), ib.. iSyi, 12, 409 (nerve). Mosso (A.), Proc. Roy. Soc, 
 1892, B 51, 83 (brain). Reichert (E. T.), Am. J. Phys., 1900, 4, 397 
 (digestion). Reid (W.), J. Phys., 1893, 18, p. xx.xi (glands). Vernon, 
 ib.. 1894, 17, 277 (relation of respiratory exchange to temperature). 
 
 Effect of Various Conditions on Heat Production and Loss (Climate). — Lee, 
 
 Edmi'nds, et al., Soc. E.xp. Biol. Med.. 1913, 12, 72 (humidity, etc.). 
 Lefevre, Arch, de Phys., 1898, 683 (death by cold) ; J . de Phys. Path. G^n., 
 1903. 5, 783 (radiation). Macleod (J. J. R.), Am. J. Phys., 1907, 18, 
 I (humidity). Masje, Virchovv's Arch., 1887, 107; Stewart (G. N.), 
 Studies, Phj'siol. Lab. Univ. Manchester, 1891, 1, loi (loss by radiation). 
 McClure and S.^uer, Am. J. Dis. Children, 1913, 9, 490 (effect of clothing). 
 Osborne (W. A.), J. Phys., 1910-11, 41, 343; ib.. 1913, 49, 133 (climate). 
 Pembrey and Pitts, J. Phys., 1899, 303 (hibernating animals). Rubner, 
 Arch. f. Hygiene, 1891. 11, 208; Nature, May 28, 1891, 666 (dry and 
 moist air); Die Gesetze des Energieverbrauchs, 1902. Waller (A. D.). 
 J. Phys., 1893, 14, p. XXV (calorimetry by surface thermometric and 
 hygrometric data) . 
 
 Varnishing the Skin. — BabXk, Pfliiger's .\rch., 1903, 108, 389. LAULAxifi, 
 Arch, de Phys., 1897, 302. Stewart (G. N.), Studies, Physiol. Lab. 
 Univ. Manchester, 1891, 1, 122. Winternitz, Arch. Exp. Path. Pharm., 
 1894, 33, 286. 
 
 Effect of Cold (Hibernation). — Cameron and Brownlee, Q. J. Exp. Phys.. 
 1913, 7, 113; Cameron (A. T.), ib., 1913, 8, 341; Harris, J. Phys., 1910. 
 40, p. liii (on frog). Merzbacher, Ergeb. d. Phys. (Bioph.), 1904, 214 
 (general physiology of hibernation). Simpson (S.), Soc. Exp. Biol. Med., 
 191 3. 10, 180 (hibernation and external temperature). Simpson and 
 Herring. J. Phys., 1903. 32, 303 (cold narcosis) . 
 
 Heat Paralysis. — Becht, Am. J. Phys., 1908, 22, 456 (heat paralysis in nerve 
 tissue). Cameron and Brownlee, Q. J. Exp. Phys., 1915, 9, 247 (death 
 temperature in frog). Eve, J. Phys., 1900-1, 26, 119 (superior cervical 
 sympathetic ganglion). Halliburton, Q. J. Exp. Physiol., 1915-16, 
 9, 193 (death temperature of nerve). Mayer, Am. J. Phys., 1917, 44, 581. 
 
 Body Temperature. — Damant (G. C. C), J. Phys., 1906, 35, p. v (goat). 
 F'ROTniNc.HAMand MiNOT, Am. J. Phys., 1912, 30, 430 (rabbit). Lazarus- 
 Barlow. Lancet (London), 1893, Oct. 26 (mouth). Pembrey and Xicol, 
 J. Phys., 1898-9, 23, 386 (deep and surface temperatures). Simpson (S.), 
 Proc. Roy. Soc. (Edin.). 1912, 32 (i). no (seasonal changes); ib., 1907-8' 
 28 (2), 661 (fishes). Woodhead (G. S.), J. Phys., 1898-9, ^, p. xv (rest and 
 ivork. in horse). Young (W. J.), ib., 1913, 49, 202 (Europeans in tropics). 
 
ii.>8 BIIiI.I()(,RAl'H\ 
 
 Diurnal Variation of Body Temperature. — Benedict (F. G.). Am. J. Phys.. 
 l^>t>^. 11, 145- JouANSsu.N, Sk.iiul. Arch, i'hys., lSm-**. 8, >> > SiMpsnv 
 (S.), J. Phys., 1902, 28, p. xxi [monkey). Si.mpson ;inii G.XLbKAliii. 
 ib.. 1905, 33, 225 {nocturnal birds, etc.). Toulouse arnl PifcKos, J. Phys. 
 Path. G<jn., 1907, 9, 425 {inversion of dAily routine). 
 
 Temperature Topography. — Heidenhain and K6rner, PHuger's Arch., 1871. 
 4, .t.t!^ (*'S^'t tind h-ft ventricles). Kunkel (A.). Deutscli. Med. Zc-it., 1887; 
 Stewart (G. N.). Studies, Physiol. Lab. Iniv. Manchester, 1, 1891, 104 
 (surface temperatures in man). Lefevrk, Arch, de Phys., 1898, 254 {ther- 
 mal topography iti cooling by baths). Kancken and Tic.erstedt, Skand. 
 Arch. Phys., 1909, 21, 80 {stomach). 
 
 Thermotaxis. — BabXk, Pfliiger's Arch., 1902, 89, 154 {new-born). Boycott 
 and Haldane, J. Phys., 1905-6, 33, p. xii {high external temperature). 
 Chauveau, Compt. Rend., 136 (13), p. 792; ib. (14), pp. 847, 852 {animal 
 thermostat) ; Zentralb. f. Phys., 1903, 17, 391. Colosanti, Pfliiger's Arch., 
 1871), 14, 92. Hale White, Lancet (London), 1897 (June 19, 26; July 3, 
 10). HXri, Pfliiger's Arch., 1909, 130, 90 {chemical regulation in mam- 
 mals). Johansson. Skand. Arch. Phys., 1904, 16, 88. LEFivRE, J. 
 Phys. Path, Gen., 1901, 3, p. i. Pembrey and Hale White, J. Phys., 
 189.5-6, 19, 477 {hibernation). Pembrey, Gordon and Warren, ib.. 
 1894-5, 17» 331 {chick before and after hatching). Pembrey, ib., 1895, 
 18, 363 {young animals). Richet, Arch, de Phys., 1893, 25, 312 {shive:-ing) 
 
 Heat Centres. — Aronsohn, Virchow's Arch., 169, 505; Aronsohn and 
 Citron, Z. Exp. Path. Ther., 1910, 8, 13 {puncture fever). Barbour and 
 Wing, J. Pharm. Exp. Ther., 1913, 5, 105 {application of drugs to centres) ; 
 Barbour and Prince, ib.. 1914, 6, i ; Cloetta and Waser, Arch. Exp. 
 Path. Pharm., 1914, 77, 16 {local heating of centres). Kennaway and 
 Pembrey, J. Phys., 191 2, 45, 82 {effect of section of spinal cord on tem- 
 perature and metabolism). Means, Aub and Du Bois, Arch. Int. Med., 
 191 7, 19, 832 {effect of caffein on heat puncture). Ott (L), J. Nerv. Ment. 
 Dis., N. Y., 1884. Pembrey, Brit. Med. J., 1897 (2), 883. Reichert, 
 Univ. Pann. Med. Mag., Mar., 1893, Feb.. 1894; J. Am. Med. Ass., 1902, 
 38, 143. Sachs and Green, Am. j. Phys.. 1917, 42, 6o^ Hale White 
 J. Phys.. 1890, 11, i; lb., 1891, 12, 233.' 
 Fever. — Babak, Pfliiger's Arch., 1904, 102, 320. Burnett and Martin. 
 Soc. Exp. Biol. Med., 1916, 13, 141. Carpenter and Benedict, Am. 
 J. Phys., 1909, 24, 203. Coleman and Du Bois, Arch. Int. Med., 1914, 
 14, 168 {high-caloric diet in typhoid). Leathes, J. Phys.. 1907, 35, 205 
 {nitrogen, creatin, and uric acid excretion). Loewi, Ergeb. d. Phys. 
 (Bioch.), 1904, 339. Mandel, Am. J. Phys., 1907. 20, 439 {xanthin); 
 ib., 1904, 10, 452 {alloxuric bases in aseptic fever). Ott and Collmar, 
 J. Phys., 1887, 8, 216 {pyrexial agents); Ott and Scott. J. Exp. Med., 
 1907, 9, 671 {metabolism). Rosenthal, Zentralb. f. Phys., 1888, 635; 
 Deutsch. Med. Woch.. 1888, No. 8. Sharpe and Simon, J. Exp. Med., 
 1914, 20, 282 {nitrogen excretion). Stewart (G. N.), ib., 1913, 18, 372 
 {bloodflow in extremities in fever). 
 
 CHAPTER XIII. 
 
 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES. 
 
 Cilia. — LiLLiE (R. S.), Am. J. Phys., 1901. 5, 5^. '^o-^. 7, 25: 1906, 16, 89 
 {influence of ions). Maxwell, j6.. 1905.13,154- Meyer, Soc. Exp. Biol. 
 Med., 1909, 7, 13. Parker. Am. J. Phys., 1905. 13, i: 14, i. Pitfter, 
 Ergeb. d. Phys. (Bicrph.), 1903, i. Schafer, Anat. Anzeig., 1904. 24, 
 Xos. iM and 20; 1905, 26, 517- 
 
 Smooth Muscle. -BoTAZZi, Pfliiger's Arch.. 1906, 113, 136. Botazzi and 
 (.iKUNBAUM. ]. Phys., 1899, 24, 51 (cesophagus of toad and auricle of 
 tortoise). Grutzner, Ergeb. d. Phys., 1904. 12. Lewis (M. R. and 
 W. H.), Am. J. Phvs.. igi7, 44, 57 {smooth muscle cells in cultures). 
 
THE I'liySI()JA)GY or THE COSTRALTll.i: TISSUES II.J9 
 
 LiNc.LU (D. J.). Am. J. Fhys.. igio. 28, 3O1 (tone in smooth mvsrle), 
 iliiiL.s Am. J. Phys.. igi-j. 29, 317 {tttuyoscopic study of living ■.iinxiHt 
 muscle). Stewakt" (C. C), ih., U)Oo, 4, 1S5 (cat's blad,der). WuouwuRTii, 
 lb.. iSoo. 3, .'<). 
 General PhysioIoRical Properties of (Diaphragm) Muscle. — Lee. Guknther 
 ,nicl Mi'Mi'MN , .\m J I'hys., Kji'), 40, ( i') Hotazzi, Rend. Acud. dei 
 Liiuci, n)i3 [mittiiititis papers). 
 Elasticity 0! Animal Tissues. - Haycraft, J. I'hy.s., 1904. 31, 39^- 
 Muscle Contraction Theories. -Bernstein. PfltiKcr's Arch., 1909,128, 136; 
 '/'.. 1413. 162, 1. Hkki, (\V.). tb.. 1913, 149, 195 [Zuntz's theory). 
 Enoelmann, Arch. I. I'hys., 1907, 25 (contractility and double refraction). 
 Burnett (T. C), J. Biol. Ch.. 1907. 2, 193 (influence of temperature on 
 contractility, and its relation to chemical reaction velocity). Ewalu, 
 Pfluger's Arch., 1S87, 41, ^13 (volume unaltered in contraction) . Garrey, 
 Am. J. Phys.. 1903, 13, 1H6 (t7vitchinf;s produced by salt solutions). 
 Lanc.ley, J". Phys., 1907-S, 36, 347; h»".S, 37, i(>5. 285; 1909, 39, .;35 
 (receptive substances). Lombard and Aishott, Am. J. Phys., 1907. 20, 
 I (contraction of individual muscles of frog's thigh). Lucas (K.), J. Phys., 
 1905-b, 33, 125 (graduation of activity in skeletal muscle); ib., 1904. 30, 
 443 (influence of tension). McDougall. J. Anat. and Phys., 1897, 31, 
 410; ib., 1898, 32, 187. Macdonald (J. S.), J. Phys., 1908, 37, p. xxv. 
 Meigs, Am. J. Phys., 1905, 14, 138. Schafer, Q. J. Exp. Phys., 1910, 
 3,63. 
 Action of Substances on Muscle -Permeability of Cells. — Asher, Bioch. Z., 
 190S, 14, I. Carliek, Brit. Med. J., Sept. 16, 1911 (various salts). 
 Hamburger (H. J.), Bioch. Z., 1908, 11, 443; Osmotischer Druck, etc. 
 Harvey (E. N.), J. Exp. Zool.. 1911, 10, 507; Am. J. Phys., 1913, 31, 
 335- Joseph and Meltzer. Am. J. Phys.. 1911, 29, i (A'a and Ca). 
 Kite, ib., 1915, 37, 282 (permeability of internal cytoplasm). Lillie 
 (R. S.), ib., 191 1. 28, 197 (relation of stimulation and conduction to per- 
 meability changes). Locke (F. S.), Pfliiger's Arch., 1893, 54, 501 (NaCl 
 solutions): J. Exp. Med., 1893, 1. ^3° (ether). Loeb (J.), see J. Biol. Ch., 
 23 to 32, for numerous papers. Mathews and Loniifellovv, J. Pharm. 
 Exp. Ther., 1910, 2, 201 (dyes). McClkndon, Am. J. Phys., 1912, 29, 
 302 (increased permeability of muscle to ions during contraction) ; ib., 1915, 
 38, 173 (ancssthetics and permeability). Meigs and Atwood, ib., 1916, 
 40, 31 (KCl). MiLLiKiN and Stiles. Am. J. Phys., 1905, 14, 359 (Na or 
 Li ions). Mines and Dale (D.), J. Phys., 191 1. 42. p. xxix (acids). 
 Osterhout. J. Biol. Ch.. 1914, 19, 335, 493 (effect of alkali and acid). 
 Overton, Ergeb. d. Phys. (Bioch.), 1902, 749 (anilin dyes); Pfluger's 
 Arch., 1902, 92, 115 (osmotic properties of muscle); ib.. 92, 340; ib., 1904, 
 105, 170 (.Vfl or Li ions in contraction). Roaf. Bioch. J.. 1906. 1, 88 
 (tadpole). Robertson (T. B.). J. Biol. Ch., 1908, 4, i. Stiles, Am. J. 
 Phys.. 1903, 8, 269 (Ca and K on smooth muscle tone). Zoethout, ib., 
 1902, 7, 199 (K and Ca on striated muscle) ; ib., 1904, 10, 373 (electrolytes), 
 
 EXCITATORY PROCESS IN MUSCLE (AND NERVE). 
 
 Biedermann, Ergeb. d. Phys. (Bioph.), 1902, 121; ib.. lyog, 26 (the excitable 
 tissues). Erlanger and Garrey, Am. J. Phys., H)i4, 35, 377; Martin 
 (E. G.j, Am. J. Phys., 1908, 22, 6i, 116; ib.. 191 1, 28, 49; 1910, 27, 226 
 (faradic stimulation) ; Measurement of Induction Shocks, New York, 
 1912. Hill (A. V.), J. Phys., 1910, 40, 170. Lapicque, J. Phys. Path. 
 Gen., 1903, 6, 843, 991; ib., 1907. 9, 368, O19; ib., 1909,11, 1009, 1035; 
 tb., 1910, 12, t)oi, 624; ib.. 1911, 13, 42. Lillie (R. S.), Am. J. Phys., 
 1916, 41, 126. Lucas (K.), J. Phys., 1908, 37, 459 (rate of development 
 of excitation); ib., 1907, 36, 253; ib.. 1910, 40, 223; ib.. 1909, 39, 331 
 (refractory period); ih.. 1908, 37, P- xxx (Nernst's Theory applied); Proc. 
 Roy. Soc. (Lond.), 191 2, B 85, 493 (process of excitation in nerve and 
 muscle). Lucas and Mines, J. Phys., 1907-8, 36, 334 (temperature). 
 
I200 iubliography 
 
 Nkrnst, PfliiRcr's Arcli., i<)o8. 122, ^75- Pfiulkr (H), Pflugcr's Arch.. 
 1883, 31, 119 i/«Ji' "/ contraction). Pratt, Am. J. IMiys.. 1417. 43, 159 
 {excitation of microscopic areas). Weuensky, PfluKcr's Arch., 1904, 
 100, 5- WooLLEY, J. Phys., lyoi, 37, i-^- {temperature coefficient of 
 conduction). Zoethout, Am. J. Phys., 1902, 7, 3^o {contact irritability). 
 
 Threshold Stimuh. — Graufielu and Martin, Am. J. Phys., 191 3, 31, 300. 
 Gruber, ib., 1915, 37, -259 {cervical sympathetic). M.\rtin, Grace and 
 McGuiRE, J. Pharm. Exp. Ther., 1915, 6, 527 {influence of drugs). Men- 
 denhall, .\m. J. Phys.. m\\. 36, 57 (aittonnmic). 
 Relations of Salts and Ions to Muscular Contraction. — Burridge, J. Phys., 
 191 1, 42, 339 {potassiii}n). GiENTHKK, Am. J. Phys., 1905, 14, 73 
 (AX/, XaCi and CaCl.,). Locke, J. Phys., 1905, 32, p. xxii (K and Na 
 action on indirect excilahility). Zoethout, Am. J. Phys., 1909, 23, 374 
 {.\'aCl and CaCLt influence on l\' -concentration). 
 •All or None' in Muscular Contraction.^ — Eisenherger, Am. J. Phys., 1917, 
 45, 44 {yninimal contraction). Lucas (K.), J. Phys., 1909, 38, 113. 
 Pratt, Am. J. Phys., 1917, 44, 517. 
 Summation. — Adrian and Lucas, J. Phys., 1912, 44, (j8 {of propagated dis- 
 turbance in nerve and muscle). Lucas (K.), ifc., 1910, 39,4'ji {of inadequate 
 stimuli). Mines (G. K.), (6., 1913, 46, i {of contractions). 
 Staircase Phenomenon (' Treppe'). -Lie (F. S.), Am. J. Phys., 1907, 18, 
 
 j()7. Lee and Harvey, Soc. Exp. Biol. ^f<^d., 1910, 7, 135- 
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 18O; ib., 95, 484 ; ib.. 1904, 103, 291. Kronecker and Stirling, J. Phys.. 
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 Tonus Rhythms in Striated Muscle. — Cannon and Gruber, Am. J. Phys.. 
 191b, 42, >•) Samojloff, Arch. f. Phys., 1907, 145. Storey, Am. J. 
 Phys,, 1904, 12, 75. Wedensky, Arch, de Phys., 1891. 23, 59- 
 Voluntary Contraction. — Cleghorx and Stewart (C. C), Am. J. Phys., 1901, 
 5, 281 {inhibition lime). FoA,, Z. f. AUg. Phys., 191 1, 13, 35 {rhythm of 
 motor impulses). Haycraft, J. Phys.. 1890. 11, 352; ib.. 1898, 23, i 
 (rapid voluntary movements). Harris, J. Phys., 1894-5. 17, 315 {time 
 relations in man). Griffiths, ib., i888. 9, 39 {rhythm). Lombard 
 (W. P.), J. Phys., 1892, 13, I. 
 Fatigue. — Burridge, J. Phys., 1910, 41, 285 {chemical factors). Crider and 
 KoBiNsoN, Am. J. Phys., 1916. 41, 37t' if^'og's muscle). Forbes (A.). 
 Am. J. Phys., 1912, 31, 102 (reflex fatigue). Franz (S. L), ib., 1900, 4, 
 348. Gruber, ib., 1913, 32, 221. 438. Lee (F. S.), ib.. 1907, 20, 170 
 (fatigue substances); J. Am. ?»Ied. Ass.. May 19, 1906. Lee and Arono- 
 viTCH, Soc. Exp. Biol. Med., 1917, 14, 153 {fatigue toxin?). Lee and 
 ElvERiNGHAM, Am. J. Phys., 1909, 24, 384 {pseudo-fatigue of cord). 
 Lombard (W. P.), J. Phys., 1893, 14, 97- Pipkr. Arch. f. Phys., 1909. 
 491. Ryan and Agnew, Am. J. Phys., 191 7. 42, 5W Storey, Am 
 J. Phys.. 1903, 8, 355- Schenck, Pfluger's Arch., 1900. 82, 3S4. Wood- 
 worth. Am. J. Phys., 1901, 5, p. iv. 
 Ergograph, Ergometer. Benedict and Emmes, Am. J. Phys., 1915, 38, 52. 
 Hall (\V. S.). ib.. 1902, 6, p. xxiii. Houcm (T.), ib., 1901, 5, 240; ib., 
 1902, 7, 76. Lombard, ib., 1902, 6, p. xxiv. Martin (C. J.) J. Phys., 
 1914. 48, p. XV. 
 Lactic Acid and Muscular Work.— Feldman and Hill (L.), J. Phys., 191 1. 
 42, 43-9 {influence of oxygen). Fletcher, ib., 1911, 43, 286; ib., 1911-12, 
 45, 28O; ib., 1913, 47, 3f)i- Fletcher and Hopkins, ib., 1906-7, 35, 247. 
 Hill (A. V.), ib., 1914, 48, p. ix {oxida:ive removal). Kwanjitsuji, ib., 
 1916, 60, T,i2 {isolated heart). Roaf. ib., 1914, 48, 380. Winfield and 
 Hopkins, ib.. 191 5, 50, p. v {influence of pancreatic extracts). 
 Source of Energy of Muscular Contraction.— DuNLOP, Paton, Stockman and 
 Macadam J. Phys., 1898, 22, 08 (muscular exercise and metabolism). 
 Frentzel Pfluger's Arch., 1897, 68, 191- Krummacher. Z. f. Biol., 
 
ini. PllVSlOLOGY or the COSriiACltLE TISSUES liol 
 
 iSyo, 33, io8; Pettenkofer and \oit, ih.. 1866, 2, 538 (protein metab- 
 olism not increased). Pflui;er (E.). Pfluger's Arch.. 1891, 50, 98. 
 SEEf.EN, Arch. f. Phys.. i8yO. 383, 4O5. Shaffer, Am. J. IMiys., 1908. 
 22, m5 {diminished muscular activity and protein metabolism). Speck, 
 Arch. f. Phys., 1895. 4O3. 
 
 ENERGY TRANSFORMATIONS IN MUSCULAR WORK. 
 
 Anderson and Lisk, J. Biol. Ch., 1917. 32, 4^1 (diet and body condition and 
 heat production in muscular work). Benedict and Cathcart, Carneg. 
 Instil. •Pixh.. 191 3. Benedict and Murschacser, Carneg. Pub., No. 231, 
 1915 (horizontal walking). Bkoca and Kichet. Arch, de Phys., 1898, 
 JJ3. Berg, dv Bois-Keymond (R.) and Zlnz. Arch. f. Phys. Supp. 
 Bd., 1904, 20 (bicycling). Chauveau, Arch, de Phys., 1897, 229. 261. 
 JoHANNsoN, Skand. Arch., Phys., 1901, 11, 273 ; ib.. 1903, 14, 60 (CO., out- 
 put). Lee and Scott, Am. J. Phys., 1916, 40, 486 (action of temperature 
 and huutidity on working power of muscles). Macdonald (J. S.), J. Phys.. 
 1914, 48, p. xxxiii (efficiency in man). Reach (F.), Bioch. Z., 1908, 14, 
 43°- 
 
 Heat Production in Muscular Contraction. — Blix, Skand. Arch. Phys., 1902, 
 12, 52. Evans and Hill. J. Phys.. 1914, 49, 10 (relation of length to 
 tension and heat production). Frank (O.), Ergeb. d. Phys., 1904, 348 
 (thermodynamics of nim^.ilar contraction). Hill (A. V.), J. Phys., 1911, 
 42, I (position of heat production in the sequence); ib., 1912, 44, 46O; ib.. 
 1913, 47, 305; ib.. 1913, 46, 435 (mechanical efficiency); ib., 1910. 40, 389 
 (contracture and tonus). Peters, J. Phys., 1913, 47, 243 (in fatigue and 
 relation to lactic acid); ib., 1913, 46, 28 (recovery processes). Snyder, 
 Am. J. Phys., 1914, 35, 340 (smooth muscle). Weizsacker, J. Phys., 1914, 
 48, 396. 
 
 Eff^ts of Muscular Exercise. — Barach, Arch. Int. Med., 1910, 5, 382 {severe 
 exertion, Marathon race). Cook and Pembrey, J. Phys., 1913, 45, 429. 
 Gasser and Meek, Am. J. Phys., 191 4. 34, 48 (mechanism of heart accelera- 
 tion). Hill (L.) and Flack, J. Phys., 1910, 40, 347 (O2. inhalation). 
 Hough, Am. Phys. Educ. Rev.. April, 1909. Hyde, Root and Curl, 
 Am. J. Phys., 191 7, 43, 371 (athlete and non-athlete). Krogh and Lind- 
 hard, J. Phys., 1913, 47, 112 (regulation of respiration and circulation 
 in work). Lowsley, Am. J. Phys., 1911, 27, 446 (blood-pressure and 
 heart-rate). Martin, Gruber and Lanman, Am. J. Phys., 1914, 35, 211 
 (body temperature and pulse-rate). Schneider and Havens, ib., 1915, 36, 
 239 (blood changes) . 
 
 Denervated and Regenerating Muscle. — Langley, 1917- 51, 377. 
 
 Rigor Mortis. — Folin (O.), Am. J. Phys., 1903, 9, 374 (cold rigor). Latham. 
 Bioch. J., 1908, 3, 193 (lactic acid and CO., formation). Joseph and 
 Meltzer, J. Exp. Med., 1909, 11, 10. 314; Am. J. Phys., 1909, 25, 113; 
 MacWilliam, J. Phys., 1901-2, 27, 33(> (rigor of heart). Meltzer and 
 Auer, J. Exp. Med., 190S, 10, 45 (influence of Ca and Mg). Winter- 
 stein. Pfluger's Arch., 1907. 126, 225. 
 
 Heat Rigor. — Burridge and Scott. J. Phys., 1912, 44, p. iii. Fletcher and 
 Brown, ib., 1914, 48, 177 (CO2 production). Vernon, ib., 1899, 24, 239. 
 Vrooman, Bioch. J., 1907, 2, 363. 
 
 Water Rigor. — Brooks (C), Am. J. Phys.. 1906, 17, 218 (conduction ana 
 contraction in). Meigs, J. Phys., 1909, 39, 3S5. 
 
 CHEMISTRY OF MUSCLE. 
 
 Botazzi (F.). Bioch. Bull., 1913, 2, 379 (physical chemistry of muscle-plasma). 
 BoTAZZi and Quagliariello, Arch. Internat. Phys., 191 2. 12, 234, 289, 
 409 (proteins) ; Arch. Ital. deBiol., 19x3. 60, 255. Halliburton. J. Phys.. 
 1887. 8, 133 ; Biochemistry of Muscle and Nerve, von Furth. Ergeb. d. 
 Ph^'^. (Bioch.), 1902, no; ib., 1903, 575; Arch. Exp. Path. Pharm., 1895, 
 
 76 
 
120 J hlBLlOORAPHV 
 
 36, -31. jANNbv, J. Biol. Cli., 1910, 25, 177, 1S5 {total pyoieim). Lee, 
 Scott and Colvin, Am. J. Phys., kjiO, 40, 176. Mek.s. Am. J. Phys., 
 1909,24, 1. i-j"/ {protein Lixigidatiori (indheat shortening). MKK.sand Ryan, 
 J. Biol. Ch., i»)iJ, 11, 401 [ash of smooth muscle). ObBORNK and Zobel, 
 J. Phys., 1903. 29, I (sugars). Ransom (F.), J. Phys., 1910, 40, i [enzymes). 
 Saiki, J. Biol. Ch., 1908, 4, 483. Stewart and Sollmann, J. Phys., 
 1899, 24, 4^7 [proteins). Urano, Z. f. Biol., 1908, 51, 483 [salts). 
 Vincent (S.) and Lewis, J. Phys., 1901, 26, 445 [proteins and heat 
 shortening) . 
 
 CHAPTER XIV. 
 NERVE. 
 
 The Nerye Impulse or Propagated Disturbance. — Bramwell and Llcas, 
 J. Phys., 1911, 42, 495 (refractory period and propagated disturbance). 
 Mathews (A. P.), Science, 1902. 15, 492; ib.. 1903, 17, 729; Maxwell 
 (S. S.), J. Biol. Ch., 1907, 3, 359; Strong, J. Phys., 1899-1900, 25, 427; 
 Sutherland, Am. J. Phys., 1905, 14, 112; ib., 1906, 17, 297; ib., 1909, 
 23, 113 (theories). 
 
 Chemistry 0! Nerve. — Alcock and Lynch, J. Phys., 1907, 38, 93; ib., 1910, 
 39, 402 (saits). Halliburton, Ergeb. d. Phys., 1903. 24. Macallum 
 (A. B.), Proc. Roy. Soc, 1906, B 77, 163. Macdonald (J. S.), J. Phys., 
 1907, 36, pp. iii, xvi (chlorides). Tashiro, Am. J. Phys. 1913, 32, 107, 
 137; Tashiro and Adams, Am. J. Phys., 1914, 34, 405 ; J. Biol. Ch., 1914, 
 18, 329; Waller (A. D.), J. Phys., 1896, 19, p. i {CO., production in nerve). 
 Tkornlk. I'fluger's Arch., 1914, 156, 253 (O.^ requirement of nerves). 
 
 Fatigue of Nerve. —Brodie and Halliburton, J. Phys., 1903. 28, 181 (non- 
 medullated). Scott (F. H.), J. Phys., 1906, 34, 145. Tait (J.) and Gunn 
 (J. A.), Q. J. Exp. Phys., 1908, 1, 191 (vohi mbini zed nerve) . Tait, J. Phys., 
 T906, 34, p. xxxv. (cooli)ig and fatigue). 
 
 Excitation and Conduction in Nerve. —Adrian, J. Phys., i9i4. 47, 460; 
 lb., 1913. 46, 3<S4 (all-or-Hone principle); ib., 191b, 50, 345 (recovery). 
 BiEDERMANN. Ergob. d. Phys. (Bioph.), 1902, 141. Cardot, J. Phys. 
 Path. Gen., 1912, 14, 737. Gau and Sawyer, Arch. f. Phys., 1889, 350 
 (CO2 and alcohol). Gruber, Am. J. Phys., 1913, 31, 413 (nerve block). 
 Lan'oley, J. Phys., 1901, 27, 226; Proc. Roy. Soc. 190O, B 78, 170 {nerve 
 endings). Lillie (R. S.), Am. J. Phys., i<)i3. 37, 348. Lucas (K.), 
 J. Phys., 1911, 43, 4f> [transference of impulse from nerve to muscle); ib., 
 
 1913, 46, 470 (alcohol). Li'CAS (K.), Conduction of the Nervous Impulse 
 (revised by E. D. .\drian), London, 1917. Meek and Leeper. Am. J. 
 Phys., 191 1, 27, 308 [pressure). Mayer, Am. J. Phys.. igib. 39, 375; 
 ib., 1917. 42, 469. Symes (\V. L.), J. Phys., 191 7, 51, p. xix [survival 
 of mammalian nerve). Waller, J. Phys., 1917, 18, p xlv (ancBsthetics). 
 Wedensky, Pfliiger's Arch., 1900, 82, 134 [fundamental properties of 
 nerves under certain poisons). 
 
 Temperature and Excitability of Nerve, .\drian, J. Phys., 1914. 48, 453 
 (temperature coefficient of refraclnrv period). Boycott, ib.. 190J, 27, 488. 
 GoicH and Macdonald, //;., 189(1, 20, 247. Tait, Q. J . Exp. Phys., iqio. 
 3, 221 [refractory phase and electrical change); ib., 1909, 2, 157 [refractory 
 phase in yohimbini::ed nerve). 
 
 Electrotonus.— LoEB (J.), Pfliiger's Arch., 1907,116, 193; Univ. of Cj,lif.Pub. 
 1905, 3, 9. Hermann and Tschitschkin, Pfliiger's Arch., 1899. 78, 
 ^3 (inexcitabilitv of kathode with certain current strengths). Pfluc;er (E). 
 Electrotonus. "Stewart (G. N.), J. Phys.. 1888. 9, 2b; ib., 1889, 10, 
 458 (depression of conductivity at kathode as compared with anode ivith 
 certain current strengths). Werigo (B.). Pfliiger's Arch., 1901, 84, 547 
 (depressive action at ka'hode). 
 
 ' Chemical ' Stimulation of Nerves. — Guthrie and Lee, Soc. Exp. Biol. Med., 
 
 1914. 11, !.('> (sensory). Gr^tzner, Pfliiger's Arch., 1894, 58, 69. 
 
NERVE 
 
 1203 
 
 Mathews (A. P.). Am J. J'liys., lyo.j, 11, 435; t^., 1.J05, 14, ^oj. Lillil. 
 Soc. Exp. Biol. Med . u>io, 7, lyo. Loku and Ivwalu, J. Biol. Ch., 1916, 
 28, 377. Si'iniiRi.AND. Am. J. Phys., ii>o(>, 17, 20b. 
 Velocity of Nerve Impulse. Adrian, J. Phys., 1914, 48, 43. Carlson, Ami. 
 I I'hys i>io-\. 10, 401. Hermann, PHiiger's Arch., 1002, 91, 189. 
 Jenkins and Caki.son, J. Comp. Neurol.. 1903, 13, 239; Am. J. Phys., 
 
 1903. 8, 231. LiM.iE, Am. J. Phys., 1914, 34, 414. Lucas (K.), J. Phys.. 
 1908. 37, 112; Snvder (C. D.), Am. J. Phys., 1908, 22, 179 (tenipeyature 
 coefficient 0/ velocity of nerve conduction); ib., 191 1, 28, i()7 {temperature 
 coefficients of velocities of various physiological actions). McClendon, 
 J. Biol. Ch.. 1917. 82, 275 (effect of stretching). Nicolai, Pfliiger's Arch., 
 1901. 86, <>5 {olfactory nerve of pike). Piper, ib., 1908, 124, 59; ib., 1909. 
 127, 4 74 {in vuin). 
 
 Degeneration 0! Nerves. — I-'eiss and Cramer, Proc. Roy. Soc, 1912-13, B 86, 
 119. Langley, J. Phys., 1909, 38, 304 (nerve endings). Tuckett. 
 J. Phys.. 1896. 19, 2'>7 (non-medullated fibres). — Van Gehuchten, Le 
 Nevraxe, i<)o^ 1, i. 263 ; ib., 1905, 7, 203. 
 
 Regeneration of Nerve. -Baer, Dawson and Marshall, J. Exp. Med.. 1899. 
 
 4, 29 [dorsal root-fibres in cord). Bethe, Pfliiger's Arch.. 1907, 116, 385! 
 Bruce and Dawson, Trans. Roy. Soc, J-:dinburgh, 1913, 48, 697. Cajal, 
 Compt. Rend. Soc. de Biol., 1903, 420 {against autoregeneration). Clark 
 (E)., J. Comp. Neurol., 1914, 24, Oi. Feiss. Q. J. Exp. Phys., 1913, 7, 
 31. Harrison (R.), Anat. Record., Dec, 1908; Ingebrigtsen, J. Exp. 
 Med., 1913, 17, 182; ib., 1913, 18, 412 (in vitro). Head, Brit. Med. J.. 
 May 27, 1903. Huber, J. Lab. Clin. Med., 1917. 2,837 (operative treat- 
 ment of peripheral nerves); Am. J. Phys.. 1900. 3, 339 (degeneration and 
 regeneration of nerve endings in nniscle). Langley and Anderson, J. 
 Phys., 1904, 31, 418 (on autogenetic regeneration); ib., 31, 365 (union of 
 different kinds of fibres). Langley, J. Phys., 1900, 26, 417 (preganglionic 
 fibres); ib., 1898, 22, 213; Kilvington and Osborne, J. Phys., 1906, 34, 
 267 (postganglionic fibres). Meek, Am. J. Phys.. 1910. 26, 367; 1911, 
 28, 352 (myenteric nerves). Mott, Halliburton and Edmunds, Proc 
 Roy. Soc, 1906, B 78, 239, 329, (no autoregeneration). Osborne and 
 Kilvington, J. Phys., 1908. 37, i; ib., 1909. 38, 268 (axon bifurcation); 
 Brain, 1910, 33, 261 (central nervous response to peripheral nervous dis- 
 tortion). ScaiFER and Feiss, Q. J. Exp. Phys., 1916, 9, 329 (cervical 
 sympathetic and vagus). Tuckett, J. Phys., 1903, 29, 303 (vagus). 
 
 Anastomosis of Nerves. — Budgett and Green, Am. J. Phys., 1900, 3, 115 
 (vagus and hypoglossal). Cunningham, ib., 1898, 1, 239. Erlanger, 
 ib., 1903, 13, 372 (spinal nerve and vagus). Feiss, Q. J. Exp. Phys., 1912, 
 
 5, I, 399- Howell and Huber. J. Phys., 1892^ 13, 333. Kennedy! 
 Proc. Roy. Soc, 1914, B 87, 331 (nerve anastomosis). LANtiLEY, J. Phys., 
 
 1904, 31, 363 (phrenic and cervical sympathetic); ib., 1898, 23, 240 (vagus 
 and cervical sympathetic). Langley and Anderson, J. Phys., 1904, 30, 
 439 (union of a cervical nerve with superior cervical ganglion). 
 
 Trophic Nerves. — Bikeles and Jasninski, Zentralbl. f. Phys., 12, 343. 
 Jacobson (C). Am. J. Phys., 1910, 26, 413. ]Marinesco and Serieux, 
 Arch, de Phys., 1893. 26, 453- Turner (W. A.), Brit. Med. J., Nov. 23 
 1895. 
 
 CHAPTER XV. 
 ELECTRO-PHYSIOLOGY. 
 
 Biedermann, Elecktrophysiologie ; Ergeb. d. Phys. (Bioph.), 1902, 120; ib., 
 1903, 103. Du Bois-Reymond, I'ntersuch. iibcr thierische Elektricitat. 
 
 Relation of Permeability of Cell Envelopes to Ions and Electrical Phenomena 
 of Tissues.— Bernstein, Pfliiger's Arch., 1902, 92, 321. Br^nings, ib., 
 1903. 98, 241; 100, 367. Hober, ib.. 1903, 106, 399- Lillie (R. S.), 
 Am. J. Phys., 1914, 34, 414; t6., 1913,37, 34^; ib., 1916, 41, 126 (conditions 
 
I204 BIBLIOGRAPHY 
 
 of physiological coudiicliun in iiiilable tis:>itis). Macuonalu (J. S.), 
 Thompson Vates Lub. Kep., I'niv.. Liverpool, njo-', 4, ^i,?. Nernst, 
 Go.tingcM- Xachrichte Math. Phys. Kl., 1899, llvli 1 (resume in Hojer's 
 Physikal. Cheni. tl. Zell. u. Gewcb. 3rd Edit., lyii, 454 ) (theory oj stimu- 
 lation). Stewart (G. N.), J. Bost. Soc. Med. Sci., June 3, 1897; J- Phys.. 
 iS(»'). 24, JiJ. 
 
 Electrolytes and Cells.- Ckoziek, Am. I. Phys., lyiO, 39, 297 {sensory stimu- 
 lation). LoHB and Cattell, J. Biol. Ch., 1915. 23, 41 {diffusion of 
 potassium). Loeb (J.), Am. J. Phys., lyoj, 6, 411; Pflii^er's Arch., 
 1902, 88, OS; ib., 1902, 91, 248; ib. ,'igo^, 107, 25 j; Bioch. Z., 1907, 6, 
 351 ; Mathews (A. P.), Am. J. Phys., 1904, 12, 419 (' toxic and antitoxic ' 
 effects of ions). 
 
 Current of Injury (Demarcation Current, Resting Current). — Bernstein and 
 
 TbCHERMAK, PUiiger's Arch., 1904, 103, 07. Bernstein, ib.. 1906, 113, 
 605. Bru.n'ings, ib.. 1904, 101, 201. Cybulski, Arch. Internal, de F'hys.. 
 
 1912, 11, 418. Hexze, Pfliiger's Arch., 1902, 92, 451- Hermann, Z. f. 
 Biol., 1912, 58, 281. Hardy, J. Phys., 1913, 47, 108. Ho3er, Pfliiger's 
 Arch., 1909, 126, 331; ib.. 1910, 136, 333; Stewart (G. N.), Am. J. 
 Phys., 1903, 9, 75 {effect of saponin on resting current of muscle and nerve). 
 Loeb and Beutner, Science, 1912, 35, 912; Bioch. Z., 1912, 44, 303; ib., 
 1914. 59, 195- Macdonald (J. S.), Proc. Roy. Soc, 1900, B 67, 310, 315, 
 325; SowTON and Macdonald, ib.. B 71, 282, 472 {nerve). Mathews 
 (A. P.), Am. J. Phys., 1903, 8, 294 {electrical polarity in hydroids). 
 
 Action Current of Muscle. — Bernstein, Pfluger's Arch., 1902, 89, 289 {relation 
 to work). Buchanan, J. Phys., 1901-2, 27, 95 {persistent contractions). 
 HoFFM.\NN, Arch. f. Phys.. 1909, 341 {voluntary contraction). Ll'c.\s (K.), 
 J. Phys., 1909, 39, 207 {relation to propagation of excitation). Sanderson 
 (J. B.), J. Phys., 1898-9, 23, i^5- Snyder, Am. J. Phys., 1913, 32, 336 
 {twitch) . 
 
 Action Cujrrent of Nerves. — Bernstein, Pfluger's Arch., 1897, 67, 349- 
 Alcock and Sekmann, Pfluger's Arch., 1903. 108, 426; J. Phys., 1905, 32, 
 p. XXX ; Lewandowsky, Pfluger's Arch., 1898, 73, 288 (vagus in respira- 
 tion). Macdonald (J. S.), J. Phys., 1899, 24, p. xxvi {vagus). Mac- 
 don.\ld and Keid, J. Phys., 1898, 23, 100 {phrenic). Waller and 
 Sowton, Proc. Roy. Soc, Oct. 31, 1903; J. IMiys., 189S, 22, 1 {effect of 
 poisons on). Wedensky, J. de Phys. Path. Gen., 1903,5, 1042 {telephone). 
 
 Polarization of Nerves. — Du Bois-Reymond, Sitzungsber. d. Kgl. Preuss. 
 
 Akad., 1883, 1 {secondary electromotive phenomena). Herm.\nn. Pfluger's 
 Arch., 1879, 19, 416; ib.. 1881, 26, 246; ib., 1884, 33, 103; Handbuch. 
 d. Physiologie, Band 2, 1878. Lapicque and Petetin, j. Phys. Path. 
 Gen., 1910, 12, 696. Locke (F. S.), J. Exp. Med., 1896. 1, 630 {effect 
 of ether). Schwartz, Pfluger's Arch., 1911, 138, 487. Stewart (G. N.), 
 Proc Roy. Soc (Edin.), Jan. 21, 1889; J. Phys., 1889. 10, 458. Waller 
 (A. D.), J. Phys., 1895, 19, p. vii; ib.. 20, p. xi; ib.. 21, p- vi; ib.. 22, p. i 
 (electrotonic currents). 
 
 String Galvanometer. — ^Einthoven, Pfluger's Arch., 1909, 130, 287. Samo- 
 JLOFF, Arch. f. Phys., 1910, 477. Snyder, Am. J. Phys., 1913. 32, 329 
 {use of). Williams (H. B.), Am. J. Phys., 1916, 40, 230 {protection 
 against external electrical disturbances). 
 
 Action Current of Heart (Electrocardiogram). — Dale and Mines, J. Phys., 
 
 1913, 46, 319 {nerve stimulation). Fkaser, J. Exp. Med., 1915. 22, 292. 
 GoTCH, Heart, 1910, 1, 235. Jolly, (,). J. Exp. Phys., 1915, 9, 9. Meek 
 and Eyster, Am. J. Phys., 1912, 30, 271 {vagus stimulation); ib.. 1912. 
 31, 31. Mines, J. Phys.', 1914, 47, 419 {vagus). Pike (F. H.), Am. J. 
 Phys., 1916, 40, 433 {stimulation of phrenic by). Sanderson and Page, 
 Proc. Roy. Soc, 1878, 401. Symes, J. Phys., 1905, 32, p. Ixxi {heart- 
 nerve stimulation). Waller. Phil. Trans. Roy. Soc, 1889, B 189. 
 Wiggers, Arch. Int. Med., 1917, 20, 93. 
 
ELECTRO-PHYSIOLOGY 1205 
 
 Human Electrocardiogram. Barker (L. F.), Johns Hopk. Hosp. Bull.. 1910, 
 }^6 (ifsiinie). Hi i.L, J. Phys.. 1911, 43, p. v; Fahr (G.), Heart, 1912,4, 
 147 (electro- and phono-cardiograms) . Einthovkn et al., Pfliiger's Arch., 
 1900. 80, 139: lb-. 1903, 99, 47^; ib.. 1913, 149, 48, 05; ib., 1913, 150, 
 EYSTERanil Mei:k. Arch. Int. Mod., 191 3. 11, 204; Forbes and H apple ye, 
 Am. J. Phys.. 11(17. 42, 228 (effect of temperature). Goddard, Arch. Int. 
 Med., 1915, 16, 033. Krl'mbhaar and Jenks, Heart, 1917, 6, 189 
 (children). Lewis (T.), Heart, 1910, 2, 23. HoniNsoN (Canby), J. 
 Exp. Med., 1912. 16, 291: Arch. Int. Med., i9i(>. 18, 830. Waller, 
 Lancet, 1913. May 24 and 31 (general review): .^rch. d. Pliys, 1890, 22, 
 14ft; J. Phvs., 11)14, 48, pp. x\ii, xl. \Villl\ms, Am. J. Phys., 1914, 
 35. 2QJ. 
 
 Gland Currents.— Bradford (J. R.), J. Phys., iSSS. 9, 287 (submaxillary gland). 
 Cannon and Cattell, Am. J. Phys., 1916, 41, 74. Gesell, ib.. 1917, 42, 
 
 Eye Currents.— Day, Am. J. Phys., 1915, 38, 369. Einthoven and Jolly, 
 (). J . JIxp. Phys.. 190S, 1, 373. GorcH. J. Phys., 1903, 29, 388; ib., 1904, 
 31, I. Jolly, Q. J. Exp. Phys., 1909, 2, 363. Trendelenblrg, Ergeb. 
 d. Phys., 191 1, 21. Waller, Q. J. Exp. Phys., 1909. 2, 401. 
 
 Electric Fishes.- Du Bois-Reymond, Ges. Abhand., 2, 001 (Malapterurus) ; 
 Sitz. d. Berl. .\kad., March 13, 1883 ; July it), 1885 (torpedo). Gotch and 
 Birch, Phil. Trans. Roy.Soc, 1896, B1S7, 3 .{J (Malapterurus) . Sander- 
 son and Gotch, J. Phys., 1888, 9, 137 (skate). 
 
 Galvanotropism. — Abbott and Life. .\m. J. Phys., 1908, 22, 202 (bacteria). 
 Bancroft (F. W.). l.'niv. Calif. Pub., 1904, 1905, 1906 (paramoecium). 
 Dale (H. H.). J. Phys., 1900-1. 26, 291 ; Garrey (W. E.), Am. J. Phys., 
 1900, 3, 291 : Pearl (R.), Am. J. Phys.. 1900. 4, 96 (infusoria). Hadley 
 (P. B.), ib., 1907, 19, ^9 (lobster larvcB). Loeb and Budgett, Pfluger's 
 Arch., 1897. 65, 518 (theory). Miller (F. R.), J. Phys., 1906-7, 35, 215 
 (crayfish). Moore and Goodspeed, Univ. Calif. Pub., 191 1. Moore 
 and Kellogg, Biol. Bull., iqK) 30, 131. 
 
 CHAPTER XVI. 
 THE CENTRAL NERVOUS SYSTEM. 
 
 Von Bechterew, Funktionen der Xervencentra, Jena, 191 1. Do.valdson 
 (H. H.), The Rat, 191 5 (statistical data). Van Gehuchten, Anatomie 
 du Systeme Xerveux. Schafer and Symington, Quain's Anatomy. 3, 
 Pt. I (numerous references). Sherrington, Integrative Action of the 
 Xervous System, Xew York, 1906. Van Rijnberk, Arch. Xeerland. de 
 Phys., 191 7, 1, 198 (organization of nervous system). 
 
 Nerve-Cells. — Donaldson (H. H.). J. Comp. Xeurol., 1899, 9, 141; Am. J. 
 Phys., 1900, 4, p. vi (size of cell body and axon). Gomez and Pike, J. Exp. 
 Med., 1909, 11, 25; TucKETT, J. Phys., 1905, 33, 77 (effects of ancemia). 
 KiLviNGTON, J. Phys., 1903, 28, 426 (snake venom). Stewart (C. C), 
 J. Exp. Med., 1896, 1, 623 (alcohol poisoning). Warrington, J. Phys., 
 1898-9, 23, 112; 24, 464; 1 899-1900, 25, 462 (alterations after section of 
 nerve fibres). 
 
 Spinal Ganglia.— Kramer (S. P.), J. Exp. Med., 1907, 9, 314 (function). 
 Steinach. Pflii.c^er's .\rch.. 1809, 78, 291 (centripetal conduction). 
 
 Enumeration of Fibres in Spinal Roots. — Dale, J. Phys., 1899, 25, 198 (dorsal 
 roots, cat). Dvnn, J. Comp. Xeurol., 1909, 19, 6S5; Hardesty, ib.. 1899, 
 9, 64. Ingbert, 16., 1903, 13, 53; ib., 1904, 14, 209 (man). Hatai, ib.', 
 13, 177 ('" growing rats). 
 
 Paths in Central Nervous System. — BRowN-StguARo, Arch, de Phy^., 1889, 
 484 (sensory). Brice (X.), O. J. Exp. Ph^'s.. 1910, 3, 391 (Ci07ver's tract). 
 Eraser (E. H.), J. Phys., 1901-2, 27, 37-; 1902, 28, }C>C-> (Monakow's 
 bundle). Ranson and Billingsley, Am. J. Phys., 1916, 40, 571; 
 
I206 BIBLIOGRAPHY 
 
 Ranson and Von Hess, ib.. 191 5, 38, 1^8 [pain and affitent vasomotor 
 paths). ScHAFER, Q. J. Exp. I*tiy.s., lyio. 3, 355 [paths for volitional 
 impulses). Simpson and Jolly, Proc. Roy. Soc. (Edin.), 1906-7, 27, 
 281 (degenerations after lesions of motor cortex in monkeys). 
 
 SPINAL CORD. 
 
 Donaldson and Davis, J. Comp. N'eurul., 1903, 13, 19 {area of cross-sections). 
 
 Fkiedenthal, Arch. f. Phys., 1905, 127; Goltz and Ewald, Pfluger's 
 
 Arch., ibgO, 63, 362 (exciston of part of cord). Sherrington, J. Phys., 
 
 1897, 21, 209; Dale, ib., 1901-2 '27, 30° {efferent fibres in dorsal roots). 
 
 Sherrington, ib., 27, 360 {spirial roots and dissociative aneesthesia). 
 
 Trendelenburg, Ergeb. d. Phys., 1910, 454 [comparative physiology 
 
 of cord) . 
 Spinal Preparation. — Guthrie (C. C), Z. biol. Tech. Meth., 1911, 2, 138 
 
 {}}ia»i»ial and bird). Roaf and Sherringto.n, Q. J. Exp. Phys., 1910, 
 
 3, 209. Sherrington, J. Phys., 1909, 38, 375 [cat). 
 
 Decerebrate Preparation. — Brown (T. G.), Q. J. Exp. Phys., 1914, 7, 293, 
 345 [reflexes). Forbes and Sherrington, Am. J. Phys., 191 4, 35, 367 
 [acoustic reflexes). Miller and Sherrington, Q. J. Exp. Phys., 1916, 
 9, 147 [decerebrator) . Weed, Am. J. Phys., 1917, 48, 131 [reactions in 
 decerebrate kittens) . 
 
 Reflexes. -Baglioni, Z. f. Allg. Phys., 1912, 40, 160 [cutaneous reflexes). 
 Brown (T. G.), Ergeb. d. Phys., 1913, 279; Q. J. Exp. Phys., 1914, 8, 
 "^ob' 193 [progression). Brooks, Am. J. Phys., 1910, 27, 212 [effect of 
 lesions of dorsal roots). Forbes and Gregg, Am. J. Phys.,1915, 39, 172 
 [strength of stimulus and reflex response) ; ib., 1915, 37, 118 [flexion reflex). 
 Langley, J. Phys.. 1900, 25, 3t)4 {axon reflexes). Mayhew, J. Exp. Med., 
 1897, 2, 35 [time of reflex winking). Moore and Oertel. Am. J. Phys., 
 1900, 3, 45 [reflexes after high section of cord). Pamlow, Ergeb. d. Phj-s., 
 1911, 345 [conditioned reflexes). Porter (E. L.), .\m. J. Phys., 1913. 
 31, 223 [reflex arc in asphyxia) ; ib., 191 7, 43, 497 [variations in irritability 
 of reflex arc). Sherrington and Laslett, J. Phys.. 1903, 29, 58 [inter- 
 connection of spinal segments). Sherrington, Ergeb. d. Phys., 1905. 
 797 [co-ordination of reflexes, common path); J. Phys., 1904, 30, 37 [spinal 
 reflex and quality of cutaneous stimulus); ib., 1910, 40, 28 [flexion reflex, 
 crossed extension reflex); ib., 1900, 34, i ; Q. J. Exp. Phys., 1910, 3, 213 
 [scratch reflex); Proc. Roy. Soc, 1907, B' 79, 337; 1908, 80, 53; 1909. 
 81, 249; 1913, 86, 219 (reciprocal innervation of antagonistic muscles). 
 Simpson and Herring. J. Phys., 1905. 32, 305 [cold narcosis and reflexes). 
 
 Knee-Jerk. — Bowditch and Warren, J. Phys., 1890, 11, 25. Franz, Am. 
 J. Insanity, 1909, 65, 471. Jolly, Q. J. Exp. Phj's.. 191 1, 4, 07. 
 Lombard, J. Phys., 1889. 10, 122. Sherrington, J. Phys., 1892. 13, 
 669 [posterior roots concerned). Snyder, Am. J. Phys., 1910, 26, 474. 
 Stewart (P.). J. Phys.. 1898. 22, oi. Waller, ib., 1890, 11, 384. 
 
 Reversal of Reflexes. — Brown (T. G.), Ergeb. d. Phys., 191 3, 430. Knowl- 
 TON and Moore, Am. J. Phys., 1917. 44, 490 (reversal of reciprocal inhibi- 
 tion in earth-worm). Sherrington and Sowton, J. Ph\-s., 1911, 42, 
 383 [chloroform and reversal) ; Proc. Roy. Soc, 1911, B 83, 435. 
 
 Inhibition in Nervous Reactions. — BRowN-SfiQUARO, Arch, de Phys.. 1889, 
 21, 751. Hering. Ergeb. d. Phys. (Bioph.). 1902, 50V Forbes (A.), 
 Q. J. Exp. Phys., 191 2, 5, 149 [reflex inhibition). McDoug.^ll, Brain, 
 1903, 102 (2), p. 153. Pawlow, Richet's Livre Jubilaire, 1912. 325. 
 Yerkes, J. Comp. Neurol., 1904, 14, 124 [frog). Sherrington, J. Phj-s., 
 
 1907, 36, 185 [effect of strychnin); ib., 1913. 47, 196; Q. J. Exp. Phys.. 
 
 1908, 1, 67 (combination of excitation with inhibition). 
 
 Spinal Shock.— Pike (F. H.), 1912. Am. J. Phys., 1912, 30, 436; Q. J. Exp. 
 Phys . iyi3, 7, i- Porter and Mihlberg, Am. J. Phys., 1900, 4, 334 
 (inhibition after injury of cord?). 
 
THE CENTRAL NERVOUS SYSTEM 1207 
 
 CEREBELLUM. 
 
 Herrick (C. J.). J. Comp. Xeurol., 1895, 6, 66 (histogenesis) ; ib., 1914, 24, 
 I {S'ecturus). Luciani, Ergcb. d. Phys. (Bioph.), 1904, 259. Wilson 
 and Pike. Am. J. Phys.. 1916. 41, 571 {lesions). 
 
 Localization. — BakX.ny. Wicn. Klin. Woch., 191 2, No. 52. Black, J. Lab. 
 C~lin. Med., iqK), 1, 407 (risti)ne). Bradley, J. Anat. and Phys., I903, 
 37, -i-!! (fissures). Lkwandowsky, Arch. f. Phys,, 1903, 129. Meyers, 
 J. .\m. Mfd. .\ss.. i9i<>, 67, 1745. Mills and \Veisenbir(;. ih., 1914, 
 Nov. 21. I Si 3. \an Kynhekk, Ergcb. d. Phys., 1908, 653. 
 
 Labyrinth and Equilibration. — Alexander and Kreidl, Pfliiger's Arch., 
 1902, 89, 473 {galvanic reaction in deaf vmtes). Beritoff, Q. J. Exp. 
 Phys., 11)10. 9, ig9 [labyrinthine reflexes in decerebrate preparation). Bak- 
 Any, Z. f. Sinnesphysiol., 1906, 41 (2), 37. Cyon, Pfltiger's Arch., 1900. 
 79, 211 ; Arch. f. Phys., 1897. 29 (vestibule and space perception). Ewald 
 (J. K.), Pfliiger's Arch., 1896, 521 (labyrinth and rigor). Fisher and 
 Muller, Am. J. Phys.. 1916, #1, 267 (cats). Golla, Proc. Koy. Soc. 
 Med., 1912, 5, 123. Hensen, Pfluger"s Arch., 1899, 74, 22 (statocysts). 
 Kreidl, Ergeb. d. Phys., 1906, 572 (vestibular apparatus). Lee (F. S.), 
 Am. J. Phys., 1898, 1, 128 (ear and lateral line in fishes). Lyon (E. P.), 
 ib., 1900. 3, 86; 4, 77 (compensatory movements in fishes). Maxwell, 
 (S. S.), ib., 1912. 29, 367. Mills and Jones, J. Am. Med. Ass., 1916, 
 67, 1296. Parker, Bull. I'.S. Bur. Fisheries, 1909, 29, 45 (influence 
 of eyes, ears, etc.. on movements of dog fish). Prince, Am. J. Phys., 1917, 
 42, 308 {kittens). Wilson and Pike, Phil. Trans. Roy. Soc' (Lond.), 
 1 91 2, B203, 127; Arch. Int. Med., 191 4, 14, 911. 'S'erkes. Am. J. Phys., 
 1907. 10, p. xviii. ZoTH, Pfliiger's Arch., 1901, 86, 147 (ear of dancing 
 »wuse) . 
 
 Postural Reflexes, Decerebrate Rigidity. — Brown (T. G.), J. Phys., 191 5, 49, 
 180 (plastic flexor tonus in monkey). Cobb, Bailey, and Holtz, .\m. J. 
 Phys., 191 7, 44, 239 (extensor rigidity). Frohlich and Sherrington, 
 J. Phys.. 1903, 28, 14 (path of inhibitory impulses). Maonvs and de 
 Kleijn, Pfluger's Arch., 1913, 164, 163, 178; ib.. 1915, 160, 429 (postural 
 reflexes); ib., 1914,159, 2i8(frog). Mills (C. K.), J. Am. Med. Ass., 1916, 
 67, 1485 (problems of cerebral tone) . Roaf, Q. J. Exp. Phys., 1913, 5, 31 
 {CO2 output in decerebrate rigidity). Sherrington, Brain, 1913, 38, 191 
 (postural activity of muscle and nerve); O. J. ]*-xp. Phvs.. 1909, 2, 109. 
 J. Phys., 1898, 22, 319 (decerebrate rigidity and reflex co-ordination of 
 movements). Van Kijnberk. Arch. Neerland. de Phys., 1917, 1, 762 
 (muscular tonus and decerebrate rigidity). Weed. J. Phys., 1914, 48, 205. 
 
 Muscular Tonus. — Burnett (T. C), Soc. Exp. Biol. Med., 1915, 12, 177 
 [skeletal muscle). Hooker, Am. J. Phys., 1912, 31, 47 (influence of 
 CO.y and O^ on tone in bloodvessels and alimentary canal). Lingle (D. J.), 
 Am"*. J. Phys., 1910, 26, 361 {plain muscle). Mott and Sherrington, 
 Proc. Koy. Soc, 1895, 57, 481 (influence of sensory nerves on movements 
 and nutrition of limbs). Sherrington, J. Phys., 1894-5, 17. -JH (nerves 
 of muscles). 
 
 Co-ordination of Movements. — Beevor, Ergeb. d. Phys., 1909, 326. Dv Bois- 
 Kevmond ( K.). Arch. f. Phys., Supp. Bd., 1900, '327; ib., 1902, Supp. Bd.. 
 27. Hering and Sherrington, Pfluger's Arch., 1897, 68, 211 {inhibition 
 of voluntary muscles from corte.x:). M.\gnl's, ib.. 1909, 130, 219, 2^^; ib., 
 191a, 134, 545; Sherrington, Proc. Koy. Soc, 1905, B 76, 160, 269 
 (reciprocal innervation). 
 
 Basal Ganglia and Mid-Brain. - -Brown (T. g.), J. Phys., 1915, 49, 195, 208 
 (is progression learnt ?). Herrick (C. J.), J. Comp. Xeurol.. 1917, 28, 
 215 (mid-brain and thalamus of Xccturus). 
 
 CEREBRUM. 
 
 Baglioni, Zentralb. f. Phys., 1901, 14, 97; Maxwell (S.S.), J. Biol.Ch., 1907, 
 2, 183 (chemical stimulation), von Bechterew, Arch. f. Phj-s., 1902, 
 264 (cortical secretory centres); ib., 1905, 297 (urine and sweat centres)'; 
 
t2o8 BIDfJOGRAPHY 
 
 ib., 1005. 5-25 (injluencc of cortex on sexual glands). Brown (T. G.), Q. J. 
 Exp. Pliys., 1910, 3, 1,^9 {removal of cortex of one hemisphere); J. Phys., 
 1914, 48, pp. XXX, xxxiii (post-central gyrus). Campbkll, Hrit. Med. J.. 
 Feb. 6, 1904 (histological differentiation, summary). Flechsk;, Lancet, 
 Oct. 19, igoi, 1027; Vogt., J. Phys. Path. Gtin., 1900, 525 (myelination). 
 Fran(;:ois-Franck and Pitres, Arch, de Phys., 1885, 7, My (exciiahility). 
 Franz (S. I.), Psychol. ]iull., 191 1, 8, m ; ib., 1914, 11, 131 ; ib.. 1916, 13, 
 149 (review and summary); J. Am. IVlcd. Ass., 190O, 47, M^M (association 
 areas in monlieys). Golt/:, PHiiger's Arch., 189J, 51, 370; ih., 1899, 76, 
 411 (brain extirpations, monkey). Hkrrick (C. J.), J. Animal Behav., 
 1913, 3, 222 (origin of cerebral cortex). Holmks (G.), J. Phys., 1901, 27, 
 I (histology of Goltz's 'brainless dog'). Karpi.us and Kreidl, Arch. f. 
 Phys., 1914, 155 (extirpation of hemispheres in monkeys), von Monakow, 
 Krgeh. d. Phys. (Bioph.), 1902, 534; ib., 1904, 100 (localization). Mott, 
 ScHi'STKR and Hai.libiirton, Proc. Roy. Soc, 1910, B 82, 124 (cortical 
 lamination). Rollett, Pfliiger's Arch., 1900, 79, 303; 80, O38 (historical, 
 especially on Gall's doctrines). 
 
 Frontal Lobes. Bolton, Brain, 26, 215. Franz, Am. J. Phys., 1902, 8, i 
 (frontal lobes and sensori-motor habits); Arch, of Psychol., Mar., 1907, 
 No. 2 (functions) . Herrick (C. J.), Science, 1910, 31, 7 (intelligence and its 
 organs). McDougall, Brain, 1901, 24, 577 (seat of psycho-physical 
 processes) . 
 
 Motor Areas. — von Bechterew, Arch. f. Phys., 1899, Supp. Bd., 543 (man); 
 lb., 1900, 22 (sensory functions of motor area). Brown and Sherrington, 
 J. Phj's., 1911, 4S, 209 (baboon); ib.. 1913, 46, p. xxii (recovery after 
 lesions). Brown (T. G.), Q. J. Exp. Phys., 1915, 9, 82. loi, 117, 131 
 (^facilitation ' in motor cortex in monkey). Ci'nnin<;ham, J. Phys., 1898. 
 22, 2(14 (opossum). Franz (S. I.), Psychol. Monographs. April, 1915. 
 Gru.nraum and Sherrington, Proc. Roy. Soc, 190 1, B 69, 206; ib.. 72, 
 152 (higher apes). Hitzig, Brit. Med. J., Dec. i, 1900. Levton and 
 Sherrington, Q. J. Exp. Phys., 1917, 11, 135 (excitable cortex of chim- 
 panzee, orang-utan and gorilla). Russell (J. R.), J. Phys., 1894-5, 17, 
 378 (eye-movements). Simpson and Kin<;, y. J. Exp. Phys., 1911, 4, 
 53 (sheep). ScHAEER, J. Phys., 1898-9, 23, 310 (sensory function). 
 Ziehen, .\rch. f. Phys.. 1899, 138 (relation between position and function 
 in motor region). 
 
 Sensory Localization in Cerebral Cortex.^ — Dusser de Barenne (J. G.), 
 (.). J. Exp. Phys., 1910. 9, 333; Arch. Neerland. de Phys., 1916, 1, 15. 
 von Bechterew, Arch. f. Phys., 1905, 53; 1912, t,},; Black, J. Comp. 
 Neurol., 1913, 23, 193; Hitzig, Arch. f. Psychiat., 35, 383; Sharkey, 
 Lancet, May 22, 1897, 1399; Vitzou, Arch, de Phys., 1893, ^7^ (visual 
 centres). Franz, Am. j. Phys., 191 1, 28, 308 (occipital lobes). Larionow, 
 Pfliigcr's Arch., 1899, 76, 608 (auditory centre, music). Munk, Zentralb. 
 f. Phys., 9, 770 {tactile sensibility). 
 
 Fatigue of Nerve Cells (Centres). —Carlson, Am. J. Phys., 1903, 2, 341 
 (retina). Dollev, ib.. 1909, 25, 151 ; J- Med. Res., 1909,21,95; ib., 1911, 
 25, 283 (Purkinje cells); ib., 1913, 29, 65. Eve, J. Phys., 1896, 20, 334. 
 Hodge, J. Phys., 1894-5, 17, 129. Kocher, J. Am. Med. Ass., 1916, 
 67, 278. Legendre and PitRON, J. Phys. Path. Gen., 191 1, 13, 519. 
 Lew, J. Phys., 1900-1, 26, 210; ib., 1903, 28, i. Pugnet, J. Phys. Path. 
 Gen., 1 90 1, 3, 183. 
 
 Sleep. Bri'.sh and Fayerweather, Am. J. Phys., 1901. 5, i9<) (changes in 
 blood- pressure). Brodmann, J. Psych. Neurol., 1, 10; Zentralb. f. 
 Physiol., 16, 310. Goddard, J. Comp. Xcurol., i8g8, 8, 245 (movements 
 of nerve cells). Howell, J. Exp. Med., 1897, 2, 313 (plethysmograms in). 
 Walokn. Am. J. Phys., 1900, 4, 124 (hypnotic sleep). 
 
 Cerebral Circulation. — Brown (E. D.), J. Pharm. Exp. Ther., i9i<>, 8, 185. 
 Cannon (W. B.), Am. J. Phys., 1902, 6, 91 (cerebral pressure after trauma). 
 Grunbaum and Sherrin(;ton, Brain, 25, 270 (apes). Hill (L.), Phil. 
 Trans. Roy. Soc, 1900, B 193, '>9 (ligation of cerebral arteries). Mott 
 
THE CF.XTRAL NERVOUS SYSTEM 1209 
 
 and Hill. J. Phys.. i8ij8-<j. 23, p. xix; H'-. i<)o(». 34, p. iv (histological 
 changes after cerel>ral anceniia). Howkll, Am. J. IMiys., 1808, 1, 57 
 (effect of high arterial pressure). Kkamkk. J. Mxp. Med., nji^. 15, 348 
 (function of circle o/' II illis). Jf.nskn, PHiigcr's Arch., 1905. 107, 81. 
 
 Resuscitation of Central Nervous System. — Pike. Guthkik and Stewart, 
 ;. llxp. yivd.. ii)oS. 10, .)wo; Am, J. Phys., igo8. 21, 339 (reflex excita- 
 bility after cerebral aucBtiiia). Stewart, Guthrie, Burns and Pike, 
 J. lixp. Med., H)Of), 8, ^8(). 
 
 Chemistry 0! Central Nervous System. c;n:s, J. Biol. Ch., 1907, 2, 159 
 (crrel>ron). H.mai, .\m. J. I'livs., 190^,12, lid (effect of partial starvation). 
 Koch (W.). Z. i. Physiol. Ch., 1902. 36, 134 (lecithin, hephalin andcerebrin). 
 Koch (W. and M. L.), J. Biol. Ch.. n)i.<, 15, 4-23 (yat) ; ib.. 1917. 31, 595- 
 Koch and Mann, J. Phys.. 1908. 36, p. xxxvi (human brains). Lkvenk. 
 j. Biol. Ch.. 191J, 13, 463 (sulphatide). Lkvkne and West, J. Biol. 
 Ch., 191 7, 31, 633, (>49; Levene, ib., 1913, 15, 339 (cerebrosides) ; tl>., 191O, 
 24, 41 (kephalin). Rosenheim, Bioch. J., 1913, 7, 604; if^-, I9i4' 8, no 
 igalactosides). Tebb, J. Phys., 1906, 34, loO (cholesterol). 
 
 Cerebrospinal Fluid.— Blumenthal, Ergeb. d. Phys. (Bioch.). 1902, 285. 
 Caktek (W. S.), Arch. Int. Med., 1912, 10, 425 (intraspinal injection of 
 Ringer's solution). Dixon and Halliburton, J. Phys., 1913. 47, ^15 
 (secretion) ; ib., 1914, 48, 12S, 317 (pressure) ; ib., 1916, 50, 198 (circulation). 
 Frazier and Peet, Am. J . Phys.. 1914, 35, 268 (formation and circulation) ; 
 ib., 1915, 36, 4(>4. Kramer (S. P.), New York Med. J., Mar. 16, 1912 
 (circulation). Spina, Pfliiger's Arch., 1899, 76, 204; ib., 1900, 80, 370; 
 ib.. 1901. 83, 120. 415. Thomson. Hall and Halliburton. Proc. Roy. 
 Soc. ii 64, 343 (man). Weed and Gushing. Am. J. Phys.. 1915. 36, 77. 
 
 Chemistry of Cerebrospinal Fluid. — Carlson and Martin, Am. J. Phys.. 1911. 
 29, 64 {pituitary secretion in?). Felton, Hussey and Bayne-Jones. 
 Arch. Int. Med.i 1917, 19, 1085. Fine and Myers, Soc. Exp. Biol. Med.. 
 
 1916. 13, 126 (non-protein N). Halverson and Bergeim. J. Biol. Ch.. 
 
 1917. 29, 337 (calcium). Hurwitz and Tranter. Arch. Int. Med.. 
 1916, 17, 828. Kahn and Neal, Soc. Exp. Biol. Med., 1916, 14, 26. 
 Kramer (S. P.), Brain. 1911, 34, 39. Krause and Corneille. J. Lab. 
 Clin. Med,, 1916, 1, 685; Xawratski, Arch. t. Phys.. 1897. 156 (sugar in). 
 Myers. J. Biol. Ch., 1909, 6, 115: Rosenbloom. Arch. Int. Med., 1914. 
 14, 536 (potassium). Weston, J. Med. Res.. 191 7, 35, 367 (reaction). 
 Woods, Arch. Int. Med., 1915, 16, 577 (nitrogen). 
 
 CHAPTER XVII. 
 
 THE AUTONOMIC NERVOUS SYSTEM. 
 
 Autonomic System.^ANOERSoN (H. K.). J. Phys., 1902, 28, 499 (regeneration 
 of sympathetic). Brown and Sherrington. Q. J. Exp. Phys.. 1911, 4, 
 i9i (pilomotor system). Burton-Opitz (R.). Am. J. Phys.. 1916, 41, 
 103 ; ib., 1917, 42, 498 (depressor function of thoracic sympathetic). Dastre 
 and MoRAT, Arch.de Phys., 1S82, ^t,-j (vasodilatators in cervical sym pathetic) . 
 Edwards (D. J.). Am. J .Phys., 1914. 33, 220 (sympathetic nervous 
 system in the turtle). Gaskell, J. Phys., 1886, 7, i- Herring (P. T.), 
 J. Phys., 1903, 29, 282 (spinal origin of cervical sympathetic). Langley, 
 Ergeb. d. Phys. (Bioph.), 1903, 818 (autonomic system of vertebrates). 
 Langley, J. Phys., 1894-5, 17, 296 (secretory and vasomotor fibres of cat's 
 foot) ; ib.. 1896, 20, 33 (medullated fibres of the sympathetic system). Lang- 
 ley, J. Phys., 1899-1900, 25, 468; ib., 1904, 3i, 244 (commissural fibres in 
 sympathetic system). Langley and Anderson, J. Phys., 1895-6, 19, 71. 
 372 (innervation of pelvic and adjoining viscera); ib., 17, 177 (hypogastric 
 nerves). Langley and Orbeli. J. Phys., 1910, 41, 450; ib., 1911, 42, 
 113 (sympathetic and sacral autonomic system of amphibia). ^Ieltzer 
 (S. J. and C). Am. J. Phys., 1903. 9, 57 {vasomotor nerves of rabbit's ear). 
 
1210 BIBLIOGRAPHY 
 
 CHAPTER XVIII. 
 THE SENSES. 
 
 Helmholtz, Physiologische Optik. Helmholtz. Tonempfindungen (trans- 
 lated by Kills). Mi'LLER. Ergeb. d. Phys. (Bioch.j, 1903, 2O7 {psycho- 
 phvsical methods). 
 
 VISION. 
 
 Eye Liquids. — Henderson (E. E.) and Starling, J. Phys., 1904. 31, 305; 
 Proc. Roy. Soc, IQ06, B 77, 294 [intraocular pressure and secretion). 
 Hill and Flack, ib., \q\z. B 85, 439 [secretion of aqueous). Wessely. 
 I>£;i-h. d Phys., 1903, 365. 
 
 Accommodation. -Barrett, J. Phys., 1885, 6, 46. Beer, Pfliiger's Arch., 
 kS'M, 58, 323; ib., 1897, 67, 541; 69, 507; Science, Nov. 18, 1904. Ein- 
 thovex, Ergeb. d. Phys. (Bioph.), 1902, 680. Hess, Arch. f. Ophthal., 
 42, 288 [velocity of accommodation). Schoen. Pfluger's Arch., 1893. S9, 
 427. Snellen. Ergeb. d. Phys. I Bioph.), 1904, 339 (sAmsco/>v). Stuart 
 (T. P. Anderson), J. Phys., 1904, 31, 38. Tscherning, Arch, de Phys.. 
 1892, 158; ib.. 1894, 40; 1893, 15^' 181; J. Phys. Path. Gen., 1899, 312. 
 
 Iris. — Anderson (H. K ), J. Phys., 1906, 33, 150, 414; ib., 1904, 30, 15. 290; 
 Meltzer and Auer, Am. J. Phys., 1904, 11, 28 [paradoxical dilatation 
 of pupil). Cobb (P.), Am. J. Phys., 1914, 36, 335 [pupil diameter and 
 visual acuity). Guthrie and Ryan, Science, 1910, 31, 395 [effect of 
 asphyxia on pupil). Grunert, Zenlralb. f. Phys., 1899, 12, 406. 
 ScijiFER, O. J. Exp. Phys.. 1908,2, 287 [dilator pupillcs in man). 
 
 Eye Movements and Innervation. — Dodge, Am. J. Phys., 1903, 8, 307- 
 Hofmann, Ergeb. d. Phys. iBioph.), 1903. 799; 1906, 599. Sherrington, 
 J. Phys., 1896, 17, 27; ib., 1916, 50, p. xlvi [apparatus to illustrate 
 Listing-Bonders law). ZoTH, Xagel's Handbuch der Physiologic. 
 
 Retina. — Dittler, Pfliiger's Arch., 1907, 117, 293 [contraction of cones). 
 Ferree nd Rand, Am. J. Phys., 1912, 29, 398; Hansell, Philadelphia 
 Med. J., Oct., 1899; Haycraft'(J. B.), J. Phys., 1910, 40,492 [blindspot). 
 Laurens and Williams, Soc. Exp. Biol. Med., 1916, 13, 183 [movements 
 of retinal elements). Trendelenburg, Ergeb. d. Phys., 191 1, i. 
 TscHERMAK, Ergeb. d. Phys. (Bioph.), 1902, 693 [functions of rods and 
 cones). 
 
 Colour Vision. — Calkins, Arch. f. Phys., 1902, Supp. Bd., 244. Edridge- 
 Green, J. Phvs., 1913, 49, 263. Exner, Zentralb. f. Phys., 1903, 17, 
 24 [Young-Helmholtz system). Franklin (Mrs. C. L.). Z. f. Psych, u. 
 Phys. d. Sinn., 1892, 4; Psychol. Review, 1894, 1896, 1899. Hartridge. 
 J. Phys., 1912. 45, p. xxix [vellow sensation). Hering (E.), Pfluger's 
 Arch., 1888, 42, 3.iO- 
 
 Contrast— After-images.— Edridge-Green, J. Phys., 1912. 43, p xxviii; 
 45, p. XIX {simultaneous colour contrast): ib., 1913. 46, 180; 47, p. vi 
 {after-images). Hartridge, J. Phys.. 1915. 50, .ij {contrast). Tscher- 
 MAK, Ergeb. d. Phys. (Bioph.), 1903. 726 [contrast and irradiation). 
 
 Colour-Blindness.- Collin and Xagel, Z. f. Sinncsphysiol., 1906, 41, 74 
 iviolet blindne^^s). F.dridge-Green, Nature, I'cb. 10, njio, p. 429 [tests); 
 J. Phys., IU12, 43, p. xxxiv; Colour Blindness and Colour Perception, 
 London. Grunert, Graefe's Arch. f. Ophthal., 56, 132. Hess and 
 Hering, Pfluger's Arch., 1898, 71, 103. Hess, Z. f. Psych, u. Physiol, 
 d. Sinn., 29, 99- von Kries, ib.. 32, 113. Peddie. Trans. Roy. Soc. 
 (Edin.), 1896, 301. Pole (\V.), Contemporary Review, May, 1882. 
 S< HENCK, Pfliiger's Arch., 1907. 118, i2y. 
 
 Intermittent Stimulation 0! Retina. -Charpentier, Arch, de Phys., 1896. 
 077 [retinal oscillations). Schenck (F.), Pfluger's .^rch., i90h. 112, 292. 
 Sherrington, J. Phvs., i8i>7, 21, 33 [reciprocal action in retina). 
 Stewart (Ci. N.), Trans. Rov. Soc. (Edin). July lO, 1S88, 443 [colour 
 
THE SENSES '^ii 
 
 phenomena afterwards described/or lienham's top). Bidwul:., I'roc Roy. 
 
 Soc. (Lond ), June 7. i8.,4; Nature. Sept. 6, 1894. 4^6; Percival, Trans. 
 
 Ophthal. Soc. n»oi>, 29, 1 1'>- 
 Talbot's Law. Hvkcm. J. Phys.. 1898-9. 23. p. vii (and flicker). GR#NBAU^I 
 
 (O. V. F.), |. Phvs., 1898. 22, ■\.U- Makuk, Pfliiger s Arch.. iW. 87, 
 
 U=i i'AKKKK .uifl PAirFN. Am. J. Phys.. 1912.31. z^. Stewart (G. N.), 
 
 Trans. Kov. S... . ii:clin.). July lO, 1888, 441 (for very short stimuli). 
 Heliotropism (Phototropism). -Davenport and Cannon. J. P^ys J897 ^ 
 
 22 Holt and Li;i:. Am. ]. Phys,, 1900. 4, 4'>« Loeh and W astkne\s, 
 
 J. Exp. Zool., 1913, 19, 2.^; 20, -:i7; ih.. 1917. 22, 187. 
 
 HEARING, SMELL. TASTE. 
 
 Hearing.— Bkrnouilli, Prii.ger's Arch.. 1910, 134, b^.^EwAi^D (J. R.j. ih 
 i":,s 59 -SS- ib. 190,, 93, 485; Wundt, tb.. 1895. 61, .U9 (labyrinth and 
 hearings EwAi-u. ib'.. 1899. 76, i47 (sound picture theory). ^}^^^^- 
 Frgeb d Phys (Bioph.). 1902, 847. Kol^iak. ib.. 1911. H^ (end apparatus 
 of eighth nerve and its significance) . E. ter Kuile. Pfluger's Arch 1900. 
 79 M(> 484; Meyer (M.), ib.. 1900. 81, 61 (theory of hearing) McKen- 
 DRiCK. Nature. June 15. 1899. i(>3 (perception of musical tone) Parker 
 (G H ) U S. Fish Commission Bull., 1903, 451 Am. Naturalist. 37, 185 
 (hearing in fishes). Wittemaack. Pfliiger's Arch.. 1907, 120, 249 (support 
 of Helmhoitz's resonance theory). Zwaardemaker. Arch. f. Fhys., 190^, 
 bupp Bd 124 (sound-pressure in Corti's organ as the stimulus). 
 
 Smell and Taste.-CusHiNo (H.), Am. J. Phys 1903. 8, p. xxvii; Gowers, 
 T. Phys., 190^ 28, ^,00; Harris (W.), J. Am. Med. Ass 1914. 63, i/2o 
 (course of taste fibres). Parker and Stabler, Am. J. Phys.. 1913. «JA 
 2^0 (distinctions between smell and taste). Zwaardemaker Ergeb. d. 
 Phys. (Bioph.), 1902, 896 (smell); ib.. 1903. 699 (taste); Arch. f. Phys., 
 1907, Suppl. Bd., 59; ib.. 1908. 51. 
 
 COMMON SENSIBILITY. 
 
 Cutaneous Sensations.— Barker (L. F.), J. Exp. Med., 1896, 1, i (localized 
 sfnZypValysi:) . Borino, Q. J . Exp. Phys 1916, 10, i . Head Rivers 
 and Sherren. Brain. 110, 100; Head and Sherren, Bram 110 116. 
 Trotter and Davies. J. Phys., 1909, 38. 134: (Brodmann s) J. f. Psych. 
 Neurol iQi ? 20. 102 (section of cutaneous nerves tn man). Buck (Ai.). 
 Arch f:'Phys . 1901. i. Lombard (W. P.). Am. J. Phys.. 1913. 31. p. xv; 
 Stanley Hall and Albin. Am. J. Phys., 1897, 9. 10 (tickle-sense). 
 Carr Psychol. Review. IQ16, 23. 252 (Head's theory). Elo and Nicolai, 
 Skand Arch. Phys., 1910. 24, 22b (warmth sense). Franz and Ruediger. 
 Am. J. Phys.. 1910, 27, 45 (effect of local anesthetics). Fr.^nz J Comp. 
 Neurol. Psvchol., 190Q, 19, 107 [pressure sense). xo>; FRey. Z. f- BioJ- 
 I9IVI4 63 -07 3^5; J. Am. Med. Ass., 1906, 47, O45 ; Ergeb. d. Ph>-^., 
 iQi'^ 96; May (P.), i6., 1909, 657 (cutaneous sensations). Nac.el, 
 Handbuch d. Physiol., 3. 7^3 (tickling and itching). \eRKES R M. . 
 Pfluger's Arch., 1905, 107, 207 (facilitation and inhibition oj tactile 
 stimuli in the frog). 
 SensibUity of Internal Organs.-HERTZ. The Sensibility of the Alimentary 
 
 Canal igii. Kast and Meltzer, Med. Rec, Dec. 29, 1906. 
 Muscular Sense.-voN Frey, Z. f. Biol., 1914. 63, 129; 64, 203. Lashley, 
 Am. J. Phys., 1917. 43, 169 (accuracy of movement ui absence of e.rcita- 
 tion from moving organ). 
 Localization of Sensations.-BRows (T. G.) and Stewart (R. M.). Bram, 
 1916, 39, 348. Lani.stroth. Arch. Int. Med., 191 5,1%, i^g (referred pain. 
 Head's zones of hyperalgesia) . 
 Hunger and Appetite.— Cannon and Washburn Am. J. Phys., 191 1. 29, 
 441 ; Carlson (A. ].). .\m. J. Phys., 1912-13, 31 131. i7.=5. 212; »fc. 1913. 
 32 ^,69- ib 191 4 33, «)V. 34, 155 {nervous control of hunger contractions). 
 Carlson, Control of Hunger in Health and Disease, Chicago. 191b. 
 
IM2 BIBLICGRAPHY 
 
 Carlson and Lewis. Am. J. I'liys., 1^14, 34, 149 {influence of smoking). 
 Carlson. Orr and McGrath. ib., 33, 119- Ginsburi,, Tlmpowski and 
 Carlson, J. Am. Med. Ass., 1915, 64, 182.2 (hunger tn infants after feeding). 
 Luckhardt, Am. J. Phys., 1915, 39, 335 {dreaming). Lickhardt and 
 Carlson, 16., 1914, 36, 37 {chemical control). Meyer and Carlson, ib., 
 1917, 44, 222 [in fever). Patterson, ib., 1915. 37, 3i<>; I9if>. 42, 56. 
 Rogers and Hardt, ib., 1914, 38, 274. 
 
 CHAPTER XIX. 
 
 REPRODLXTION. 
 
 BiRiAN, Ergeb. d. Phys. (FSioch.). 1904, 84; ib.. 1906, 768 {chemistry of sperma- 
 tozoa). Marshall (F. H. A.), Physiology of Heproduclion, London, 1910. 
 
 Ovary. — Carmichael and ^LJkRSHALL, Proc. Koy. Soc, 1907, B 79, 387 
 [correlation of ovary and uterus). Gi-thrie (C. C), J. Exp. Zool., 1906, 
 3. 5<i} (transplantation of ovaries in chickens) ; Science, Nov., 1909 [guinea- 
 pig graft hybrids): ib.. 191 1, 33, 816 (influence on offspring of engrafted 
 ovarian tissue). Loeb (L.), Soc. Exp. Biol. Med., 19K., 13, 162 [cyclic 
 changes); J. Am. Med. Ass.. 1917, 69, 236 {relation of ovary to uterus and 
 mammary gland). Rosenbloom. J. Biol. Ch., 1912, 13, 511 (I'pms of 
 ovary and corpus luteum). 
 
 Corpus Luteum. — Ancel. J. de Phys. Path. Gen., 191 1. 13, 31. Bolin and 
 Ancel, lb.. 1910. 12, 16. Itagaki. Q. J. Exp. Phys., 1^17, 11, i [influence 
 of extracts on plain muscle). Loeb (L.), J. Am. Med. As.s.. 1906, Feb. 10, 
 1906; Anat. Record. 1908, 2, 240. Marshall, Q. J. Exp. Micros. Sc, 
 1905, 49, 189 [development, review). Novak, J. Am. Med. Ass., 1916, 
 67, 1285. Ott and Scott, Soc. Biol. Exp. Med.. 1912, 9, 64 [extracts); ib., 
 1914, 12, 47 (action on mammary glands). Pearl and Surface. J. Biol. 
 Ch., 1914, 19, 263 {effect on ovulation). 
 
 Uterus. — Barry (D. T.), J. Phys., 1915, 50, 259 (uterus contractions and 
 ovarian extract). Cl'shny, J. Phys., 1906, 35, i [movements). Barbour 
 and CoPENHAVER, Soc. Exp. Biol. Med., 1916, 13, 139 (cerebral control 
 of uterus .^). Kurdinowski, Arch. Internat. de Phys., 1904. 1,359; Arch, 
 f. Phys., 1904, Supp. Bd., "^2^ {isolated uterus movements). Loeb (L.), 
 J. Am. -Med. Ass.. 1908. 50,' 1897; Arch. f. Entwick. d. Org., 1909, 27, 
 89 [production of deciduomata). Ott and Scott, J. Exp. Med., 1909. 11, 
 326 [actioti of glandular extracts on uterus contractions). 
 
 Menstruation — (Estrus.— Hammond and Marshall. Proc. Roy. Soc, 1914. 
 B 87, 422 {correlation between ovaries, uterus, and mammary glands). 
 Heape, Brit. Med. J., Dec. 24, 1898 (monkeys). King (J.). Am. J. Phys., 
 1914. 34, 203 (cardio-vascular and temperature variations in women), 
 Loeb (L.). Biol. Bull., 1914, 27, i (correlation between cyclic changes m 
 uterus and ovaries). Marshall and Runciman. J. Phys.. 191 4. 49, 17 
 (ovarv and (gslrus). Marshall and Jolly. Phil. Trans. Roy. Soc, 1903. 
 198, 99 {dog). 
 
 Fertilization.— Fischer and Ostwald. Pfluger's Arch.. 1905. 106, 229 
 iphvsico-chemical theory). Gorham and Tower, .\m. J. Phys., 1903, 
 8, 173. Loeb (J.). Pfluger's Arch., 1904, 103, 257; )7;., 104, 325; I'niv. 
 of Calif. Pub., 1903-7; Harvey Lecture, New York, 1911 ; .\m. Naturalist, 
 1913, 49, 257 (conditions determining entrance of spermatozoon); Arch. f. 
 Entw. d. C)rg., 1914, 11, ^01; Science, Nov. 6, 1914 [ultraviolet light). 
 Lyon (E. P.). Am. J. Phy.s.. 1909, 25, 199 (catalasc). Morgan (T. H.), 
 Science, Feb. 18. 1S98. Nemec, Fertilization Processes, Berlin, 1910. 
 Mathews (\. P.), Am. J. Phys.. 1902. 6, 216; ib., 1907. 18, 89. Robert- 
 son (T. B.), Soc. Exp. Biol. Med.. 1912, 9, 90 (oocylase); J. Biol. Ch.. 
 1912. 11, 339; ib., 12, I, 163. ScHijcKiNG, PflQgers Arch., 1903, 97, 58. 
 
 Artificial Parthenogenesis.— Fischer (M. H.), Am. J. Phys.. 1902, 7, 301: 
 K*'"*^, 9, 100. Greeley, ib., 1902. 6, 296 {produced by lowering of tem- 
 perature). Harvey (E. N.), Biol. Bull.. 1910. 18, 260 (methods). Lillie 
 
UEl'kODLLTlOS 1213 
 
 (K. S.), Am. J. Phys., 1907, 18, p. xvi (by raising leniptralurc). Loeb 
 (J.), Am. J. Fliys.. itioo, 4, 178, |^.^; Die Chemischc Entwickclungserre- 
 j;img dcs Tieiischon ICics, Berlin, i^otj; Arch. f. ICiitwick. d. Org., 1902, 
 13, -tlSi (fiitt/iods) ; I'lliim-r's Arcli., 1907, 118, iSi [osmotic excitation 
 of development in sea-urchin eggs); Proc. Nat. Acad. Sci., i9i(>, 2, 313 
 (sex of parthenogenetic frogs). i\lATnii\vs (A. P.), Am. J. Phys., 1900, 4, 
 343; ib.. 190J, 6, 14.! (by mechanical excitation). McClendon. Am. J. 
 Phys., 191 _•, 29, 29S (in vertebrates). Morgan (T. H.), J. E.xp. Zool., 
 1904. 1, 135 [self-fertilization induced by artificial means). 
 Sex. -DoNCASTER, Determination of Sex, Cambridge, 1914. Kiddle, Science, 
 191 7, 46, 19. Wilson (E. B.), Soc. Exp. Biol. Med., 1905-6, 3, 19. 
 
 Pregnancy. -Hasselbalch, Skand. Arch. Phys., 1912, 27, i (respiratory 
 exchange). Miklin, Am. J. Phys., 1910, 26, 134 (energy metabolism of 
 fregnant dog); ib., 1910. 27, 177 [nitrogen balance). Murlin and Bailey, 
 Arch. Int. Med., 1913, 12, .2i)8 [protein metabolism). 
 
 Abderhalden Reaction. —BoLDYREFF, J. Phys., 1917, 51, p. xxii. Bronfen- 
 HRENNER, J. Lab. Clin. Med., 1915, 1, 79. Wells (H. G.), ib., 1, 175. 
 Williams and Pearce, Soc. Exp. Biol. Med., 1913, 10, 73. Van Slyke 
 ET al., J. Biol. Ch., 1915. 23, 377- 
 
 Development of Egg. — Abderhalden, Pfliiger's Arch., 1915, 147, 99 (com- 
 pounds which influence development) . Babak, Pfliiger's Arch., 1905, 109, 
 70 (central nervous system and metamorphosis of frog). Brown (O. H.), 
 .\m. J. Phys., 1905, 14, 354 (permeability of egg). Eaves, J. Phys., 1910, 
 40, 451 (fat transformations in eggs in development) . Harvey, J. Exp. 
 Zool., 1910, 8, 355 [monbrane formation). Hulton, J. Biol. Ch., 1916, 
 25, 227 [ferment production in response to introduction of placenta). Hyde 
 (1. H.), Am. J. Phys., 1904, 12, 241 [differences of potential in developing 
 eggs). Krogh, Z. f. AUg. Phys., 1914, 16, it>3 (temperature and rate of 
 embryonic development). Loeb (J.), Biol. Bull., 1915. 29, 103 [membrane 
 formation). Loeb and Wasteney's, Bioch. Z., 1911, 37, 401 ; J . Biol. Ch., 
 1913, 14, S^5. 459; ib., 1915, 21, 153 (influence of bases on development 
 and oxidations in sea-urchin eggs). Lillie (R. S.), Am. J. Phys., 1916, 
 40, 249; ib., 1917, 43, 43 (permeability). Lyon, Am. J. Phys., 1904, 11, 
 3J (rhythms in cleavage). Ly'on and Shackell, J. Biol. Ch., 1909, 7, 371- 
 (autolysis of fertilized and unfertilized eggs). Mathews (A. P.), J. Biol. 
 Ch., 1913, 14, 465 [chemical difference between sea-urchin and starfish eggs), 
 McClendon, Am. J. Phys., igiz, 31, 131 (effect of alkaloids); ib., 1915, 
 38, 163 (development and permeability). Meltzer, Am. J. Phys., 1903, 
 9, 246 (effect of agitation). Moore (A. R.), J. Biol. Ch., 1917, 30, 5 
 (cytolysis in echinoderm eggs). Malcolm (J.), J. Phys., 1901, 27, 356 
 [composition of egg-yolk). Mendel and Leavenworth, Am. J. Phys., 
 ii»o8, 21, 77 (changes in purin, cholesterol, etc., content in development). 
 Riddle (O.), Am. J. Phys., 1916, 41, 409 (metabolism of egg-yolk in 
 incubation). Riddle and B.\ssett, ib., 41, 425 (effect of alcohol on size 
 of egg-yolk). Robertson, Soc. Exp. Biol. Med., 19x2, 9, 61 (sea-urchin 
 eggs). Shackell, Science, 191 1, 34, 573 (phosphorus metabolism in 
 nliinodcrm eggs). 
 
 Metabolism of Embryo. — Jones and Aisiriax. J. Biol. Ch., 1907. 3, 227 
 [nuclein ferments). Loghead and Cr.^mer, Proc. Roy. Soc, 1908, B 80, 
 263 (glycogenic changes in placenta and foetus). Mendel and Leaven- 
 worth, Am. J. Phys., 1907, 20, 117 [glycogen in embryo). Mendel and 
 Mitchell, ib.. 20, 81 (inverting enzymes of alimentary tract in embryo); 
 ib.. 20, 97 (enzymes in purin metabolism). Wells and Corper, J. Biol. 
 Ch., 1909, 6, 469 (purin metabolism of foetus and placenta). Zintz and 
 Hasselbalch. Skand. Arch. Phys., 1900, 10, 149 (COo production in 
 embryo) . 
 
 Placenta. — Charrin, Arch, de Phys.. 1898, 703 [transmission of toxins from 
 foetus to mother). Famulener, J. Infect. Dis., 1912, 10, 332 (transmission 
 of inimunity from mother to offspring). Fenger, J. Biol. Ch., 191 7, 29, 
 
I2I.1 UiBLlOGRAPllY 
 
 11) {compoiitwn). Llueker and Pribram, PHuger's Arch., it>io, 134, 
 .531 (relation of placenta and mammary gland). l6b and Higuchi. Bioch. 
 Z.. 1909, 22, 310 {enzymes). Loeb (L.), J. Am. Med. Ass., 1901), 53, 1471 
 (maternal placenta and function of corpus luleum). Rosenheim, J. Phys., 
 1901). 38, 337 (pressor principles from placenta). WERTHEiMERund Meyer, 
 Arch, de Phys., 1890, 193; 1891, 204 (exchanges between mother and 
 feet us). 
 
 Parturition. —Healy and Kastle, Soc. Exp. Biol. Med., 1912, 9, 48 (internal 
 .accretion of mammary gland as a factor). 
 
 Chemistry of Milk. — Milroy, Bioch. J., iyi5, 9, 217 (reaction). Olson, J. 
 
 Biol. Ch.. 1908, 5, 261 (proteins). Osborne and Wakeman, ib., 1915, 21, 
 
 539; i^-. 1916, 28, 1 (phosphatids). Raudnitz, Ergeb. d. Phys. (Bioch.), 
 
 1903, 193. Van Slyke and Bosworth, J. Biol. Ch., 1914, 19, 73 (casein) ; 
 
 ib., 1915, 20, 135; ib., 1916, 24, 173 (goat's milk). 
 Human Milk. — Bosworth, J. Biol. Ch., 1915, 20, 707; Bosworth and Van 
 
 Slvke, ;7)., 1910, 24, 187. Hammett, ib., 1917. 29, 381 (after parturition). 
 
 Holt, Courtney and Fales, Am. J. Dis. Child.. 1915, 10, 229 (salts). 
 
 MEiGsandMARSH, J. Biol. Ch., 1913, 16, 147 (human and cow's). Sikes, 
 
 j. Phys., 1906, 34, 404 (P and Ca). 
 
 Colostrum. — St. Engel, Ergeb. d. Phys., 1911, 41. Kastle and Healy. Soc. 
 Exp. Biol. Med., 1912. 9, 44; Woodward, J. E.xp. Med., 1897, 2, 217 
 (chemistry). 
 
 Secretion of Milk. — Basch, Ergel). d. Phys. (Bioch.), 1903, 320. — Caspaki. 
 .\rch. 1. Phys., 1899, Supp. Bd., 207 (source of milk fat). Bowen, J. Biol. 
 Ch., 1915, 12, II {passage of food and fatty acids into mammary glands). 
 Campbell (J. A.), O. J. Exp. Phys., 191 3, 7, 35 (chemistry of mammary 
 gland). Gaines, Arn. J. Phj's., 1915, 38, 285 (lactation). Ha.mmond (J.), 
 Q. J. Exp. Phys., 1913, 6, 311 ; Hill and Simpson, ib., 1914-15, 8, 103, 377 
 (pituitary extract). Hammett and McNeile, J. Biol. Ch., 1917, 3i0, 145 
 (effect of placenta). Hill and Simpson, Am. J. Phys., 1914. 35, 361 ; ib., 
 1915, 36, 347 (effect of pituitary extract). Marshall and Kirkness, 
 Bioch. J., 1906, 2, i; Paton and Cathcart, J. Phys., 1911, 42, 179; 
 PoRCHER, Arch. Internat. Phys., 1909, 8, 356 (lactose formation). Mac- 
 kenzie (K.), O. J. Exp. Phys., 191 1, 4, 305; Schafer and Mackenzie. 
 Proc. Roy. Soc. 1911, B 84, lO (action of animal extracts). Moore and 
 Parker, Am. J. Phys., 1900, 4, 2.y) (lactose formation). Ott and Scott, 
 Soc. Exp. Biol. Med., 1912, 9, 63; Schafer, Q. J. Exp. Phys., 1913, 6, 17 
 (effect of pituitary and corpus luteum); ib., 1915, 8, 379 (pituitary extract). 
 
 Correlation of Mammary Gland with Other Sexual Organs. — Biedl and 
 
 Ko.sii.sTKiN, Z. Exp. Path. Tlicr., 1910, 8, 338 (honuone which exciies 
 matnmary gland in pregnancy). He.\pe, J. Phys., 1900. 34, p. i. Lane- 
 Claypon and Starling, Proc. Roy. Soc, 1906, B 77, .S05. Loeb (L.) 
 and Hesselberg, J. Exp. Med., i<)i7, 25, 285. 305 (correlation in cycle of 
 uterus, ovaries, and mammary gland). O'Donoghue, J. Phys., 1911, 48, 
 p. xvi (corpus luteum and mammary gland). 
 
 Rrowth. — -Cramer, J. Phys., 1916, 50, 322 (the biochemical mechanism of 
 growth). Hatai, Am. J. Phys., 1907, 18, ^09 (rat). Loeb (J.), Science, 
 191 5, 41, 169 (simplest constituents required for growth in an insect). 
 Robertson (T. B.). Am. J. Phys., 1915, 37, i. 74 (pre- and post-natal 
 grouth of )U(ni). Osborne and Mendel, sec Chapt. X. 
 
 Anastomosis of Bloodvessels. —Carrel (A.) and Guthrie (C. C), J. Am. Med. 
 Ass., 1906, Nov. 17, p. 164S (kidney transplantation); Surg. Gyn. Obst., 
 
 1906, 2, 266 (veins). Carrel, J. Exp. Med., 1910, 12, 139; ib., 19x2, 15, 
 388;i6.,16, i7(aorta). Guthrie, Heart, 1910,2,115 (survival of engrafted 
 organs). Carrel, J. Exp. Med.. 1907, 9, 226: Guthrie, Am. J. Phys.. 
 
 1907, 19, 482 (hetero-transplantation of bloodvessels). Guthrie, Blood- 
 vessel Surgery, London, 1912. Carrel, Johns Hopk. Bull.. 1900. 17, 
 ^^h (surgery of bloodvessels) . Guthrie, J. Am. Med. Ass., 1908, 60, 1035. 
 
REFRODUCTWS 1^15 
 
 Transplantation 0! Organs. — Qakrel. J- Exp. Med.. 1910, 12, i4<» {remote 
 re^ulti. of rtj-'liDitation of kidney and spleen). Giihku;, ib., 12, ^^>^ {sur- 
 vival of engrafted ovaries and testiiies). Githkik ami Li;t, J. Am. Med. 
 Ass., 191.5. 64, i8-'3 {ovarian transplantation). GiiUKit, Arch. Int. 
 Med., 1910, 5, ^3^ {kidney , perfused or not) . Murphy (J. H.), J . I'xp.Med., 
 1913, 17, •I'^.J (transplantability of tissues to the embryo of foreign species); 
 ib., 1914, 19, 513 ; ib.. 19, 181 {ultimate fate of mantmalian tissue implanted 
 in chick embryo). Lokb and Aduison, Arch. f. Entwick. d. Org., 1909, 27, 
 73 {hetero-plastic skin transplantation). I^eb (L.), J. Am. Med. Ass.. 
 1915. 64, 7.25 (changes in chemical environment and growth of tissues) ; 
 J. Med. Res., 1917, 37, 229 (kidney tissue). (Sec also Chapter XI.) 
 
 Tissue Cultures. Baitsell, J. Exp. Med., 1915, 21, 455 (origin of a fibrous 
 tissue in cultures of adult frog tissues). CarREL and Burrows, J. Exp. 
 Med., 1911. 13, 387; Lambert, ib., 1916, 24, 367 (technique); ib.. 13, 416 
 (thyroid). Carrel, J. Exp. Med.. 1913, 18, 287 (connective tissue) ; ib., 17, 
 14 (activation of grotvth of connective tissue); ib., 1912, 15, 51^1; J-Ibeling, 
 ib., 1913, 17, 273 (permanent life of tissues outside of the organism). 
 Inc;ebrigt.sen (R.), J. Exp. Med.. 1913, 18, 412 (regeneration of axis 
 cylinders in vitro); ib., 1916, 23, 251 (life of peripheral nerves in plasma). 
 LoEB (L.), Unte.such. iibcr Umwandlungen u.Thaligkeitenin d.Geweben, 
 Chicago, 1897. LosEE and Ebelin(., J. Exp. Med., 1914, 19, 593 (human 
 tissue). Laubt (R. A.), J. Exp. Med., 1913. 18, 400 (influence of tempera- 
 ture and medium on survival of embryonic tissue in vitro). Lewis (M. R. 
 and W. H.). Am. J. Phys., 1917, 44, 57 (contraction of smooth muscle cells 
 in tissue cultures). Newmann and Burrows, Am. J. Phys., 1917. 42, 
 397 (effect of amino-acids and peptones ongrovuth of cells in vitro) . Walton , 
 J. Exp. Med., 1915, 22, 194 (production of substances inhibiting cell-growth) ; 
 ib., 1914, 20, .5.54 (effect of tissue extracts on growth in vitro). Weil, J . Med. 
 Res., 1912, 26, 159 (tissue cultures in vitro). Uhlenhuth, J. Exp. Med., 
 1915, 22, 76 (skin); ib., 1914, 20, 614. 
 
 Parabiosis. -Rous, Soc. Exp. Biol. Med., 1909. 7, 8 (test for circulating anti- 
 bodies in cancer). 
 
INDEX 
 
 References to the Practical Exercises are in black figures. 
 
 Abdominal breathing, 230 
 
 muscles in expiration, 229 
 Abducens, or sixth nerve. 926 
 Aberration, chroniatir, 1027. 1063, II06 
 
 spherical, 1027. 1063, 1106 
 Absorption, 426 
 
 and lipoid solubility, 437 
 
 coefi&cient of gases, 247 
 
 comparative physiology of, 431 
 
 factors concerned in, 435 
 
 from the peritoneal cavity, 439 
 
 from the stomach, 433 
 
 gas exchange in intestine, 436 
 
 in large intestine, 451 
 
 intra- and inter-epithelial, 446 
 
 of bile-constituents in jaundice, 384 
 
 of cane-sugar, 436, 464 
 
 of carbo-hydrates, 445 
 
 of fat, path of, 443.463 
 
 of gases in blood. 250 
 
 of iron, 447 
 
 of light, 1012 
 
 of proteins, 447 
 
 of the food, 431 
 
 physical introduction to, 426 
 theories of, 433-436 
 
 of water and salts. 422, 446 
 
 osmosis and diffusion in, 435 
 
 parenteral, 446 
 Acapnia and blood-pressure, 184 
 
 and mountain sickness, 298 
 
 and shock, 192 
 Acceleration of heart by sipping water, 
 
 171,210 
 Accelerator nerves of heart, 157, 162, 
 
 166, 197, 199 
 Accessory auditory nucleus, 928 
 
 dietetic factors, 617 
 
 vagus nucleus, 929 
 Accommodation, 1020 
 
 mechanism of, 1022 
 
 pupil in, 1023 
 Acerebral tonus, 942, 955 
 Acetaldehyde. 544, 562 
 Acetone, 562 
 
 and katabolism of fatty acids, 567 
 
 ] Acetone in diabetes, 529, 555 
 in urine, 529 
 Aceto-acetic acid, 562, 567 
 
 in diabetes, 555 
 A.C.E. mixture, 63 
 Acetic acid, 556 
 Acid albimiin, 352, 458 
 Acidity of gastric juice, 350, 417 
 Acidosis, 24, 282, 555 
 Acrolein, 12 
 Action currents, 823, 824, 830, 842 
 
 and functional activity, 825 
 
 diphasic. 825 
 
 double conduction of, 792 
 
 electromotive force of. 827 
 
 in polarized nerves. 831 
 
 in voluntary contraction, 762 
 
 monophasic, 825 
 
 of central nervous system, 838 
 
 of eye, 839 
 
 of glands, 83S 
 
 of heart, 88, 833-838, 844 
 
 of muscle, 823, 843 
 
 of phrenic nerves, 827 
 
 of skin, 838 
 
 of spinal cord, 838. 849, 895 
 
 of vagus, 828 
 
 of veratrinized muscles, 829 
 
 propagation of, 824 
 
 rate of propagation of vai-ia- 
 tion,827 
 
 reflex, 913 
 
 theories of, 828 
 Adamkiewicz's reaction of protein, 8 
 Adaptation of digestive juices to food. 
 371, 398, 405. 400. 414 
 of retina, 1047, 1058 
 Addison's disease and adrenals, 655 
 Adenin. 481, 592, 593 
 Adequate stimuli, 901, 1007 
 Adipocere, 564 
 Adii'osophilia, 569 
 Adnnal b*jdics, 655 
 
 ci>inephTin content of. 664 
 
 relation of, to coagulation, 45 
 
 secretory nerves of, 661 
 
 1216 
 
IS DFX 
 
 I 21 7 
 
 A'renal cortex, function of. 665 
 Adrenalin, action of. 01 artiry rin^s. 66, 
 216 
 on coagulation linjc. 45. 656 
 on heart. 655 
 
 on nerve -endings, 182, 635 
 on pupil. 636. 
 on sympathetic, 655. 1005 
 on vaso-motors, 173, 179, 655 
 on veins. 181 
 action of stnall doses of, 660 
 arterio-sclerosis. 660 
 artiticial. 665 
 assay of. 453. 636 
 biological tests for. 46, 656 
 chemistry of. 664 
 formation of. 665 
 function of, 657 
 glycosuria, 550 
 
 secretorv influence of nerves on, 
 661 
 Adsorption, 430 
 Aerotonometer. 258 
 .fiisthesiometer. compasses. 11 15 
 
 Fray's hair. 1080, 1114 
 Afferent impulses, decussation of, 894 
 paths, 892 
 
 scheme of, 880 
 After -brain (rayelencephalon), 850 
 After-images, 1055, llll 
 Agglutination, 30,71 
 
 by foreign serum, 71 
 Agglutininogens, 31 
 Agraphia. 970 
 Alanin, 2, 360, 574. 590 
 
 formation of dextrose from. 538 
 Alanyl-glycyl-tyrosin, 449 
 Albinos, intravascular clotting in. 43 
 Albuminates or derived albumins. 9 
 Albuminoids. 2 
 Albumins, 2.9 
 
 heat -coagulation of, 9 
 in urine. 488. 497. 499,524, 525 
 Albumoses, 3 
 
 action of. on blood -pressure, 173,215 
 
 on coagulation. 37, 45 
 in peptic digestion, 352 
 tests for, in urine. 525 
 Albumosuria. 489. 525 
 Alcohol, 630 
 
 action of, on respiratory centre, 191, 
 631 
 on gastric secretion, 630 
 in diet, 630 
 poisoning, blood -pressure curve in, 
 
 191 
 precipitation of proteins by, 8 
 Alcohols, relation of. to carbohydrates, 3 
 Aldehydase. 272 
 Aldehydes, relation of. to carbo-hydrates, 
 
 .1. 543- 544- 545- S^i 
 Aldohexoses. 543 
 
 Aldol, 362 
 .\lgometer.ioS<) 
 
 .Alimentary canal, anatomy of. 319 
 length of. 320 
 
 time of pa>.sa!;e through. 334 
 glycosuria. 3 jn. 717 
 .Mkali-albuniin. 10, 461 
 Alkalinity of bio jd. etc.. titratabie. 2S 
 .Alkaptonuria. 483. 3.'^I 
 .\llantoin. excretion of. 596 
 Allantois. 1128 
 ' All-or-nothing " law. 154 
 Alloxuric bodies. 48 1 
 .\lveolar air, partial pressure of gases in. 
 
 241. 263 
 Amblyopia after occipital lesion. 966 
 Amboceptors. 28,73 
 Amide-nitrogen in proteolysis, 360 
 Amino-acetic acid, 2 
 Amino-acids, i, 360, 352, 417, 562 
 absorption of. 449, 450 
 changes in liver. 384 
 chemical nomenclature of. 360 
 conversion of. into glycogen and 
 
 dextrose. 536. 538. 590 
 formation of. from tissue-proteins. 
 578 
 of urea from. 582. 584. 586, 588. 
 624 
 in blood. 574 
 in liver diseases. 586 
 in phosphorus poisoning, 563 
 in urine. 481, 488 
 metabolism of. 582 
 synthesis of. by bacteria, 618 
 Amino-bodies. deaminization of, 588 
 Amino-succinic acid. 360 
 Amino-valerianic acid, 360 
 Ammonia, action of. on muscle. 759 
 impermeability of lungs for, 240 
 in proteolysis. 360 
 in the blood, source of, 585. 588 
 
 after Eck's fistula. 585 
 in urine. 480.521 
 
 reflex in hibition of heart by. 170. 
 210 
 Ammonium salts, fomation of urea 
 from. 384. 588 
 sulphate, precipitation of proteins 
 by. 8, 525 
 Amnesia. 970 
 Amnion. 1128 
 Amniotic fluid. 1128, 1134 
 Amoeba, 6. 16. 732 
 Amoeboid movements. 732 
 Ampl^re, 725 
 Amylase. 345. 346 
 
 pancreatic. 358. 362. 461 
 salivary. 346, 417.455 
 Arayl nitrite, action on pulse. 106 
 
 formation of met haemoglobin 
 by, 33 
 
 77 
 
I2l8 
 
 INDEX 
 
 Ainylolytic stage of sastric digestion. 
 
 34S. 356. 417 
 Amylopsin. 358. 362,461 
 
 intlucncc (if bile on. 370 
 Anatiolic liiaiiKcs in living matter. 6 
 Anacrotic [nilse, 106 
 An.i'Sthesia by A.C.J'". mixture, 63 
 
 by chloral. 217 
 
 by chloroform (fir6hant's method). 
 202 
 
 by morphia. 63, 201 
 
 by pressure on brain, 985 
 
 by nrethane. 217 
 
 for animals. 63 
 Anaphylaxis. 32 
 Anastomosis of nerves. o75 
 
 of bloodvessels. 1145 
 Aneleotrotonus. 7S6. 844, 845, 
 Angular gyrus and vision, 066 
 .\nimal board. 201, 214 
 Animal heat. 674 
 
 Animals, localization in different, 980 
 .Anions. 429 
 Ankle-clonus. 915 
 
 Annulus of Vieussens, 157, 162, 179 
 .Anode, 429. 724 
 .Anterior commissure. 922. 893 
 
 horn, cells of. 858. 864. 876 
 connections of, 876 
 
 roots, 797, 876 
 Antero-lateral ascending tract, 866, S73, 
 886 
 connections of, 87^? 
 
 descending tract, 867 
 
 connections of, 884 
 
 ground bundle, 867 
 Antibodies, 31, 648 
 Antidiabetic diet, 554, 356 
 ' .Antidromic ' nerve impulses. 181, 792, 
 
 807 
 .Antiferments. 339. 390. 343 
 
 in intestinal parasites. 390 
 Antigens, 31 
 Antikinase, 44. 391 
 Antilytic secretion, 398 
 Antimony and protein metabolism, 563 
 Antiperistalsis. 330, 332, 421 
 Antipyretics. 704 
 Antithrombin. 38, 39, 42. 44 
 Antitrypsin, 343. 390 
 Antrum pylori. 326. 327 
 Aorta, effect of compression of. 204 
 Aortic insufficiency, efifect of, on pulse, 
 106 
 
 notch, 96 
 
 stenosis, effect of, on pulse, 107 
 
 valves, 87,96.206 
 
 and dicrotic wave. 104 
 Apex-beat, 90,201, 207 
 Apex preparation of heart, 143, 194 
 Aphasia, c)68 
 ,Aphasia. Broca's. 970 
 
 Aphasia, motor. o7o 
 
 sensory, 370, 972 
 
 subcortical, 972 
 
 temporary, 972 
 
 Wcrnickes-, 971 
 Aphemia. 971 
 Apno-a. 2H3, 300 
 
 vagi. 284 
 
 vera, 283 
 .Apocodeine, action of, on vaso-raotors, 
 
 173 
 .Appetite, 1099 
 juice, 1099 
 Aqueduct of Sylvius. 874 
 Aqueous humour. 58 
 
 composition of. 466 
 secretion of. 1016 
 Arachnoid, 861 
 Arachnolvsin, action of, on ervthrocytes, 
 
 28 
 Arcuate fibres, internal, 873 
 Arginase, 587 
 Arginin, 360, 587 
 Argyll-Robertson pupil, 1025 
 Arhythmia. respiratory. 287 
 Aromatic sulphates in urine. 484, 517 
 Arsenic and protein metabolism. 563 
 Arterial blood -pressure, amount of. 112 
 .Arteries, blood -pressure pulse in. 100 
 structure of, 82 
 to insert cannuUe into, 63 
 tone of, 185, 918 
 .Artery rings, action of adrenalin on. 216 
 
 action of serum on, 46 
 Arterioles, resistance in, 129 
 .Arteriosclerosis, velocity of pulse in, 109 
 .Artificial respiration. 202, 230 
 
 with oxygen. 204 
 .Ascending degeneration, 866 
 .Aspartic acid. 360 
 .Asphyxia. 178, 283, 1S7 
 
 condition of ha-moglobin in, 51 
 effect of, on circulation. 172. 187, 
 
 213 
 glycosuria caused by. 548 
 in the fu?tus, 1137 
 
 inlhience of. on bl<x)d-pressure, 213 
 Assimilation limits for carbohydrate, 540, 
 
 551.637 
 Association areas. 973 
 centres, 962, 973 
 fibres, 883. 885 
 .Asthma, spasmodic, and bronchial mus- 
 cles. 287 
 Astigmatism, irregular. 1028 
 
 regular, 1031, 1062, 1105 
 Astrospheres. 1122 
 .Atrio-ventricular bundle. See .Auriculo- 
 
 ventricular bundle 
 .Atropine, action of. on heart. 166. 199 
 on nerve-cells. i,S2 
 on pupil. 1026 
 
iNi)i:.\' 
 
 1219 
 
 Atropine, action of, on salivarv secre- 
 tion. 392, 306. 457 
 Attraction sph«rc, 5. 851, 1079 
 
 in ncrve-cfIN, 851 
 
 Auditory centre. (^28, 066 
 
 nerve, 927. io6») 
 
 cochlear division of, 028 
 vestibul.ir l>r.inch of. gjS 
 ossicles, 1000. io(i<) 
 path, scheme of. 927 
 Auerbach's plexus, 319, 330 
 Augmentation of heart-beat, 157, 172, 
 199 
 nature of. 167 
 primary. 159 
 secondary, 159 
 Aupnientor nerves, effect of, on quiescent 
 
 iieart, 168 
 .\ura. 973 
 Auricular canal, 81 
 fibrillation. 151 
 flutter. 151 
 pressure curve. 98 
 Auriculo-ventricular bundle, 81, 135, 
 138. 147 
 pulse-tracings in disease of. 149 
 junction, stimulation of. 198 
 node, 81, 147 
 valves. 89. 206 
 
 moment of opening of. 96 
 Auscultation of breath-sounds, 231, 304 
 of heart-sounds, 207 
 of lungs, 304 
 Auto-digestion of stomach, 389. 465 
 Autogenetic theory of nerve regenera- 
 tion. 801 
 Autolysis, 578 
 
 Automatic actions of spinal cord, 916 
 Autonomic nervous system. 892, 1003 
 
 functions of, 1005 
 Avalanche theory. 7S5 
 Aviator's sickness. 299 
 Axial strand fibrils. 801 
 .\xis-cylinder or axon, 781. 852. 855 
 bifurcation of. 802 
 fibrils in. 851 
 
 growth of, in cultures. 803 857, 
 Axon-reHexes, 400, 792, 913 
 
 Babinski's sign, 915 
 
 Bacteria and digestion, 422, 423 
 
 in fa?ces. 424 
 
 in intestine. 343, 423. 618 
 
 synthesis of amino-acids by, 618 
 Bactericidal action of gastric juice, 356 
 Balloon ascents, deaths in, 298 
 Baryta, absorption of carbon dioxide by, 
 
 240 
 Basal ganglia. 932 
 
 metabolism. 686 
 Basilar membrane. 1067, 1070 
 Bat's wing, contractile vessels of, 81, i8o 
 
 Batteries, 197, 724 
 
 Heals (hearing). III3 
 
 Beaumont on digestion, 349 
 
 Brchlcrew's nucleus, 928 
 
 lli-ckmann's apparatus. 427. 529 
 
 H( Hows recorder. 302 
 
 Bell's experiments on nerve-roots. Hqi 
 
 Belt rfcordcr for respiration. 233 
 
 Benedict estimation of blood sugar, 717 
 
 Benzoic acid, 481, 580 
 
 Beri-beri caused by polished rice, 632 
 
 thymus in, 633 
 Bert on double conduction in nerves. 792 
 on effects of oxygen at high pres- 
 sure. 2^7 
 Betz cells. 848.875.959 
 Bichromate cell. 197 
 Bidder's ganglia. 141 
 Bile. 363-370 
 
 absorption of. 384, 412 
 acids, 365, 462 
 
 circulation of, 412 
 
 formation of, 384 
 
 Hay's test for, 462 
 
 Pettenkofer's reaction, 366, 462 
 
 adaptation of, to food, 413 
 
 and absorption of fat. 369 
 
 and pancreatic juice, adjuvant 
 
 action of. 367 
 and surface tension, 369, 462 
 as an excretion, 424 
 composition of, 363 
 curve of secretion of. 413 
 digestive functions of. 367 
 formation of. 384, 385 
 freezing-point of, 387 
 gases of, 267, 366 
 in emulsification of fats, 367 
 influence of nerves on secretion of, 
 
 411 
 inhibition of heart by, 172 
 mucin. 364 
 
 pigments. 364. 385, 462 
 circulation of. 412 
 Gmelin's test for. 365. 462 
 production of. in liver. 385 
 relation of. to spleen. 672 
 precipitation of gastric digest by, 
 
 370 
 quantity of. 367 
 rate of secretion of, 413, 419 
 reactions of, 462 
 reinforcing action of, 368 
 salts. 365 
 
 action of, on blood. 28, 70 
 decomposition of. 365 
 in urine. Hay's test. 528 
 influence of. on secretion of 
 bile. 413 
 secretion of. influence of nerves on, 
 411 
 influence of secretin on, 408, 412 
 
INDEX 
 
 Bile, secretory pressure of, 414 
 
 spectrum of, 365 
 Biliary fistula. 369, 412 
 Bilirubin, 364 
 Bilivirdin. 364 
 Bioplasm. See I*rotoplasm, an<4 Living 
 
 matter 
 Bipolar ganglion cells. 856 
 Bird's blood, coagulation of. 36. 43 
 Biuret reaction. 8, 459 
 Bladder. 310 
 
 pressure in. in lulotvirition. 310 
 Blastoderm. 1125 
 Blind spot. 1044. 10(14. 1 107 
 mapping the. 1064 
 Blood, bird's. 36 
 
 carbon dio.xide content of. 26, 255 
 chemical composition of, 47 
 circulation of. 80 
 coagulation of. 33, 62 
 composition of, 49 
 
 -corpuscles, coloured, composition 
 of, 50 
 osmotic resistance of. 73 
 crenation of, 16 
 destruction of, 21 
 dextrose in. 50, 540. 717 
 enumeration of. 18, 67 
 formation of. in embryo. 20 
 gaseous metabolism of, 252 
 life-history of, 20 
 in pernicious anaemia, 21 
 red, 15 
 
 destruction of. 2 1 
 origin of. 20 
 rouleaux formation of, i6 
 shadows or ghosts of. 70 
 size of, 15 
 structure of, 15 
 white. See Leucocytes 
 distribution of. 36. 180 
 » electrical conductivity of. 26. 68 
 flow, calorimetric method of mea- 
 suring. 122 
 in different organs. 127 
 in feet. 127 
 in hands, 126 
 
 measurement of. 219 
 functions of, 59 
 gases of. 245-266 
 
 estimation by ferricyanide. 250 
 quantity of, 250 
 tension of. 258 
 results, 261 
 guaiacum test for. 76 
 kinetic and potential energy of cir- 
 culating, 119 
 lakingof.70 
 
 measurement of velocity of. 120-124 
 morphology of, 14 
 opacity of. 70 
 pigment, microscopic test for. 78 
 
 Blood pigmei\t, preparation of, 73 
 plasma, proteins of, 47, 572 
 
 relative volume of, 27, 68 
 plates, 18 
 platelets and coagulation, 39, 40 
 
 anticoagulants and preserva- 
 tion of, 40 
 
 disintegration of, 40 
 
 functions of, 62 
 precipitin test for, 31 
 quantity of, 53 
 
 in lungs, 224 
 
 which may be lost, 191 
 reaction of, 24. 62 
 regeneration of, 22 
 relative volumes of corpuscles and 
 
 plasma, 27, 68 
 serum, electrical conductivity of, 
 26, 27, 68, 386 
 
 freezing-point of, 386 
 specific gravity of, 26, 62 
 sugar in, 47, 499, 302. 333, 540, 547 
 
 349, 551. 552,636,637,717 
 temperature of, 680, 71 1 
 testing for adrenalin in, 656, 637, 662 
 tests for, 45-47 
 titratable alkalinity, 23 
 vaso-constrictor property of shed, 45 
 velocity of, 117-127 
 
 in arteries, 119, 123 
 
 in capillaries, 120, 130 
 
 in veins, 120, 134 
 
 measurement of, 120, 122, 219 
 vessels, sutiu-ing, 1144 
 viscosity of, 23, 302 
 volume of corpuscles and plasma 
 
 27,68 
 why it does not clot in the vessels, 
 
 45 
 Blood- pressure, arterial, measurement of, 
 107 
 and acapnia, 184 
 
 curves with elastic manometers, 93, 
 III 
 with mercurial manometers, 
 no, 112, 210 
 effect of changes of posture on, 190, 
 213 
 of extracts of bone-marrow on, 
 
 f'71,673 
 of freezing the cord on, 184 
 of ha'niorrhage and transfusion 
 
 on. loi, 214 
 of kidney on, 671 
 of muscular exercise on, 115, 213 
 of nervous tissue on, 673 
 of peptone on, 173, 215 
 of pituitary on, 668 
 of proteoses on, 1 73. 215 
 of suprarenal on, 171,216,635 
 of testicle on, 642 
 of thvmus on. 643 
 
INDllX 
 
 Bloud- pressure, estimation of the arterial, 
 2X0, 213 
 
 factors wliicli niaiiitaiu, 116 
 
 fall of, in sleep, <)«(> 
 
 hydrostatic and hyilrodv naniic ele- 
 ments, I()0 
 
 in capillaries, i.?o, i;,i 
 
 influence of respiration on, 289 
 
 in man, influence of exercise on, 115, 
 measurement of, by stetho- 
 scope, 113, 213 
 
 in pulmonary artery, 1 1(> 
 
 in right and left ventricles, 116, 138 
 
 mean arterial, loq, 1 1 j 
 
 measureme'.it of, loi), 2H 
 
 permanent element iu, 1 1 1 
 
 systolic and diastolic, 113 
 
 tracings, 165, 184, 186, 187, 188, lyi, 
 210, 213, 216, 237, 279, 280 
 Blood-pump, 249 
 
 Blood-serum, freezing-point of, 386 
 Blood-supply, regulation of, 189 
 Bloodvessels, anastomosis of, 1144 
 
 rhythmically contractile, 81, 175, 180 
 
 structure of, 82 
 
 iowe of, 1S4, 996 
 Body, composition of, 6or 
 Bohr, on blood-gases, 254, 261, 264 
 Bolometer, 675, 783 
 
 Bone-marrow and blood-formation, 20, 
 22 
 
 action of extracts of, 671, 673 
 Bones, competition of, boi, 621 
 
 influence of pituitary on, 670 
 of testicles on, 642 
 ■ Boot ' electrodes, 842 
 Brain, anaemia of, 986 
 
 chemistry of, 991 
 
 circulation in, 9S9 
 
 condition of, isolated, 975 
 in sleep, 913 
 
 development of, 849 
 
 functions of, 931 
 
 heat-production in, 689 
 
 influence of, on spinal reflexes, 910, 
 lOOI 
 
 respiratory changes in volume of, 
 
 295 
 resuscitation of, 990 
 size of, at different ages, 988 
 
 and intelligence, 988 
 temperature of, 712 
 volume, respiratory variations in, 
 
 295 
 Bread, 720 
 
 Breast-feeding, superiority of, 1140 
 Breath, holding, 234 
 Broca's area, 971, 974 
 
 aphasia, 970 
 Bronchi, 223 
 
 movements of, in respiration, 231 
 
 nerves of, 287 
 
 Bronchial breathing, 231 
 
 nuiscles, innervation ai, 287 
 Bronchoscope, 231 
 Brownian motion, 454 
 Bro\vn-Se(|uard's syndrome, 894 
 Brunner's glands, 380, 383 
 ' BufTy ' coat, 39 
 Burdach's tract, 866 
 
 connections of, 870 
 Burdon-Sanderson on negative variation, 
 
 825, 82(. 
 Burns, superficial, death from, 299 
 Buttermilk diet, 422 
 Butyric acid, 562 
 
 fermentation, 423 
 
 Cachexia strumipriva, 648 
 Ca>cum, nerves of, t,},2 
 Caffeine, 481, 583, 594, 632 
 
 as diuretic, 3o<) 
 Caisson disease, 297 
 Calcium and bone formation, 621 
 
 delicieficy of, 621 
 
 relation of, to heart-beat, 152, 200 
 Calorimeter, air, 67<; 
 
 differential micro-, 680 
 
 respiration, 240, h-f), 678, 721 
 At\vater"s, ()76 
 
 water equivalent of, 721 
 Calorimetric method for blood-flow in 
 hands, 219 
 for vaso-motor reflexes, 188, 221 
 Calorimetry, 675,721 
 Campbell, visuo-psychic area of, 966 
 Cancer, gastric juice in, 350 
 Cane-sugar, absorption of, 435, 445, 464 
 
 inversion of, 10, 339 
 
 by gastric juice, 356 
 
 tests for, II 
 Cannula, three-way, 212 
 
 gastric, 459 
 
 to put into an artery, 63 
 trachea, 202 
 vein, 215 
 Capillaries, blood-pressure in, 131 
 
 changes of calibre of, 173 
 
 circulation in, 120, 129, 193 
 
 pulse in, 131 
 
 resistance in, 120, 130 
 
 total cross-section of, 130 
 
 velocity of blood in, 130 
 Capillary electrometer, 728, 729, 842 
 Caproic acid, 566 
 
 Capsule, internal. See Internal capsule 
 Carbo-hydrates, absorption of. 445 
 
 amount of, in standard diet, 623, 625 
 
 assimilation limits, 540, 551, 637 
 
 composition of , i , 3 
 
 constitution of, 3 
 
 intermediary, metabolism of, 542 
 in diabetes, 553 
 
 metabolism of, 533 
 
INDEX 
 
 Carbo-liydratcs.Mnlisch's test for, II 
 necessity of, in luitritiim, 607 
 passage uf, tiiioiigli placenta, 1131 
 protein-sparing action of, 606 
 reactions of, 10 
 tests for, 10 
 
 tolerance after pancreatectomy, 637 
 Carbon balance-sheet, 618 
 equilibrium, 618 
 dioxide, action of, on respiratory 
 centre, 2^ii 
 and blood- flow in heart, 178 
 distribution in blood, 255 
 estimation of, ::4o, 305 
 excretion, influence of forced 
 respiration on, 245 
 mechanism of, 264 
 in alveolar air, 241 
 in blood, condition of, 257 
 in fu'tal blood, 1129 
 influence on ha;moglobin, 255 
 in serum, 255, 256 
 in \enous blood, tension of, 261 
 partial pressure of, in alveoli, 
 261, 264 
 in blood, 259, 261 
 in tissues and liquids, 
 
 272,273 
 production, Haldanc's appara- 
 tus for measuring, 304, 305 
 production of, in different 
 animals, 244 
 in muscular work, 242 
 in relation to body-weight, 
 
 244 
 in rigor, 270, 777 
 tension of, in tissues, 272 
 washing out of, 245, 283 
 monoxide method for quantity of 
 
 blood, 56 
 necessary quantity in diet, 625 
 Carbonic acid and urea formation, 589 
 
 oxide hamoglobin, 53, 74 
 Cardiac cycle, 85 
 death, 171 
 impulse, 90, 208 
 nerves, 157, it).', 196, 198, 203 
 sound, 96 
 sphincter, 320 
 Cardio-augmentor centre, 169 
 Cardiogram, 91 , 207 
 inversion of, 01 
 Cardiograph, 90, 208 
 Cardio-inhibitory and augmcntor centres, 
 169 
 tone of, 169 
 Cardiometer, 139 
 Cardiophonograin, 88 
 Cardiopneumatic movements, 128, 303 
 Carnosii\ in muscle, 767 
 Casein. 354 
 
 as adequate protein, 613 
 
 Caseinogen, 354,719 
 Castration, effects of, 640, 643 
 
 on thynms, 644 
 Catalase, 76, 271 
 Catalysers, 339 
 Catheterism,7l6 
 Catheter, pulmonary, 259 
 Cells, structure of, 4 
 Cellulose, digestion of, 423 
 Central canal of cord, 849, 861 
 gi-ey axis, 861 
 
 nervous system, action currents of, 
 838 
 arrangement of white and 
 
 grey matter in, 861 
 development of, 849 
 functions of, 887 
 general arrangement of, 
 
 «6i 
 histological elements of, 
 
 850-861 
 localization of function in, 
 
 975 
 methods of study of, 848 
 structure of, 847 
 Centre for smell, 967 
 for taste, 968 
 of gravity of body, 946 
 thumb, 973 
 Centres, cardio-inhibitory and augmen- 
 tor, 169 
 heat, 701 
 
 ' motor,' of cortex, looi 
 nmsical, 967 
 of cord and bulb, 919 
 sensory, of cortex, 965-968 
 vasomotor, 182-185 
 Centrifuge, 64 
 Centrosome, 5, 851 
 
 in the ovum, 1122 
 Cerebellar ataxia, 935 
 Cerebellum, anat<imical division of, 942 
 connections of, 885, 935 
 functions of, 933 
 inferior pedimcle of, 885 
 Incalization of function in, 942-944 
 middle peduncle of, 886 
 peduncles of, 885 
 structure of, 934 
 superior peduncle of, 886 
 worm of, 874, 885, 942 
 Cerebral anaemia, 190, 986, 989, 990 
 
 stimulation of vagus after, 187 
 circulation, f)89 
 ct)rtex, and respiration, 276 
 
 clinical and pathological obser- 
 vations on, 962 
 development of, 862 
 functions of, 947 
 histological differentiation uf, 
 
 ..5« 
 inhibition from, 954 
 
IMDEX 
 
 1223 
 
 Cerebral cortex, Uyers of, <)3S 
 
 lucali/atioii <>f l'uuctii)ii in, ()5i 
 ' inotiir ' areas of, 1J51 
 sensory areas of, <>b5 
 stability of reactions of, i)^t, 
 
 hemispheres, excision of, i)4 7-().ji) 
 frog, 047, 1000 
 piReon, <)4H, lOOI 
 
 localization, I'lechsig's areas, 961 
 
 peduncle, H8^ 
 
 vesicles, 841) 
 Ccrebrins, 794, <^<>i 
 Ccrebro-spinal fluid, 58, 466, 992 
 
 displacement of, 295 
 
 secretion of, 99^ 
 ferebrum, effects of removal of, 947-()49 
 Cervical sympathetic. Sec Sympathetic 
 Chalk-stones, 487, 590 
 C heese, 626,719 
 
 Chemical regulation of respiration, 281 
 ' Chemical tone,' 695 
 Chemiotaxis, 61 
 
 in nerve regeneration, 800 
 Cheyne-Stokes respiration, 287, 300 
 Chiasma, optic, 923 
 Child, food requirement of, 628 
 
 basal metabolism of, 628, 686 
 
 gaseous exchange in, 243 
 Chloral, anaesthesia by, 190, 213 
 Chlorides, estimation of, 515 
 Chloroform an;esthcsia, inhibition in, 170 
 
 passage of, through placenta, 1130 
 Cholesterol or cholesterin, 4, 47, 570, 794, 
 991 
 
 circulation of. 571 
 
 in bile, 36(1, 41^ 
 
 reactions of, 463 
 Cholic acid, 365, 3^6 
 Cholin, 4, 421, 571 
 Cholohsematin, 365 
 Chorda tympani, 179, 391-393,456 
 
 stimulation, of, 456 
 Chordo-lingual triangle, 391 
 Chorion, 11 28 
 
 Choroidal epithelium, 1016, 1048 
 Choroid plexus, 992 
 Chromaffin cells, 665 
 Chromatin, 5 
 
 changes in, in nerve-cells, 983, 984 
 
 extranuclear, 984 
 Chromogen, 482 
 Chromophanes, 1049 
 Chromosomes, 6, 1122 
 Chrysotoxin, action of, on blood-pres- 
 sure, 173 
 Chyle, 14,58,443 
 
 composition of fistula, 58 
 Chyme, 326 
 
 passage of, through p>Iorus, 327, 
 408 
 
 to obtain normal, 459 
 Cbymosin (vide Reunin), 353 
 
 Cilia, 733 
 
 movem'-nts <jf, 811 
 work done by, 734 
 Ciliary ganglion, 924 
 muscle, 924, 1022 
 nerves, 1033 
 processes, 1014 
 
 and secretion of aijueous hu- 
 lunnr, 1016 
 Cinematograph, 945, 1042 
 Circulating blood, microscopic examina- 
 tion of, 193 
 liquids, 14 
 Circulation, changes in, at birth, 1138 
 Comparative, 80 
 cross, through brain, 284 
 general view of, 81 
 in brain, 989 
 in capillaries, 129, 131 
 in the embryo, 1138 
 in the frog's web, 15, 193 
 in the lungs, 137, 223 
 in the tadpole, 193 
 influence of posture on, 190, 213 
 of lymph, 192 
 time, 135-138 
 
 electrical method, 135-137 
 Hering's method, 135 
 methylene blue method, 137, 
 
 217 
 pulmonary, 137, 698 
 Circus movements, 943 
 Citrates and coagulation, 37 
 Clarke's column, 864 
 
 connections of, 872 
 Coagulated proteins, reactions of, 9 
 Coagulation of blood, 42, 62 
 
 action of fluorides on, 37 
 
 of citrates on, 37 
 birds, 36 
 calcium in, 36 
 factors in, 42 
 hirudin and, 37 
 influence of platelets in, 37 
 of proteoses on, 37 
 of tissue extracts on, 36 
 influences restraining, 42 
 intravascular, 42 
 leech extract and, 38 
 manganese and, 37 
 of crayfish, 40 
 of Linuilus, 40 
 peptones and, 37 
 relation of adrenals to, 45 
 
 liver to, 44 
 studied with ultramicroscope, 
 39 
 of lymph, 57 
 
 temperature, to determine, 9 
 Coaguliiis, 41 
 Coal-gas poisoning, 53, 74 
 Cobra-veuom and coagulation, 43 
 
1224 
 
 INDEX 
 
 Cocaine, action of, on ncrvts, 791 
 on pupil, 1026 
 fever, 704 
 Coclilea, 927, 1067, 1068, 1069 
 Cochlear root of eighth nerve, 874, 928 
 Cocoa, 594, 630, 631 
 
 Co-enzymes or co-ferments, 343, 368, 548 
 toffee, 5<)4, 631, 632 
 Cola-nut, 632 
 
 Cold sensations, 1041, 1082, 1084, 1115 
 after section of cutaneous 
 
 nerves, 1088, 1091 
 paths for, 896 
 Collaterals, 781, 852 
 
 of posterior root fibres, 871 
 Colon, movements of, 330, 333 
 
 innervation of, 332 
 Colostrum, 11 39 
 Colour, body and surface, 1012 
 blindness, 1059, 1 1 12 
 temporary, 1061 
 mixing, 1052, IIII 
 triangle, 1054 
 vision, 1 05 1 
 
 Hering's theory of, 1057 
 V'oung-Helinholtz theory of, 
 1053 
 Ctiloured shadows, 1056 
 Colours, complementary, 1052,1068, IIII 
 
 primary, 1033 
 Coma, congestion of brain in, 985 
 
 diabetic, 555 
 Comma tract, 867, 871 
 Commissural fibres, 863, 893 
 Common path, principle of the, 899 
 Conunutator, Pohl's, 732 
 Compensator, 727 
 
 Compensatory pulse of heart, 155, 156 
 Complement, 28, 72 
 Complemental air, 233, 303 
 Complementary colours, 1032, IIII 
 Condensed air, effects of breathing, 295 
 Conditioned reflexes, 973 
 Conduction, double, in nerve, 791 
 irreciprocal, 792 
 isolated, law of, 793 
 loss of heat by, 681 
 Conductivity, molecular, 429 
 of nerve, 786, 790 
 
 anaesthetics and, 7(»o, 814 
 effect of temperature on, 791 
 electrical currents on, 786, 
 787,844 
 specific, of electrolytes, 429 
 Congo-red as test for acids, 351 
 Conjugate deviation, <)(>3 
 Conjugated proteins, 2 
 Conservation of energv, law of, in body, 
 
 679, 683 
 Consonants, 313 
 
 Contraction, formula of, 788, 845 
 for nerves in situ, 789 
 
 C.oiitrac tioii, law of, for human uerscs, 846 
 paradoxical, ^^2, 844 
 seccjndary, 832, 842 
 Contractions, superpositimi of, 756, 816 
 Contrast (vision), 1056 
 Co-ordination of movements, 945, 981 
 
 of reflexes, 908 
 Cure models, and electrotonic currents, 
 
 831 
 Cornea, radius of curvature of, 1017 
 Corneal reflex, 914 
 Corona radiata, 862, 875, 883 
 
 path from cortex in, 877 
 Corpora Araiitii, 87 
 
 quadrigemina, 874, 881, 932 
 and respiration, 276 
 anterior, i)2i, 932 
 posterior, 928,932 
 striata, 850, 862, 870 
 
 and temperature regulation, 701 
 Corpuscles and plasma, relative volume, 
 
 27, 68. See Blood 
 Corpus callosum, 863, 883 
 dentatum, 863 
 luteum, 643, 1120, 1121 
 
 and menstruation, 1121 
 
 hsematoidin in, 383 
 
 internal secretion of, 643, 1078, 
 
 1121 
 origin of, 1121 
 striatum, 850, 862, 870 
 Cortex of brain, functions of, 947 
 ' motor ' areas of, 951 
 sensory areas of, 965 
 Corti, ganglion of, 927 
 
 organ of, 927, 1067, 1069, 1074 
 Cortical epilepsy, 972 
 grey matter, 861 
 Costal breathing, 229 
 Cotton seed, 361 
 Coughing, 288 
 
 Cranial conduction of sound, 1071, III3 
 nerves, 920 
 
 bifurcation of afferent fibres, 
 
 924, 925, 926, 928 
 homologies of, 921 
 nuclei of, 920 
 Crayfish blood, clotting of, 40 
 Cream. 718 
 Creatiii, 481, 703 
 
 Creatin and creatinin in protein meta- 
 bolism, 597 
 in muscle, 768 
 Creatinin, 481, 523 
 
 excretion and muscular work, 611 
 in fever, 703 
 source of urinary, 598 
 Crenation, 16 
 Crista acustica, 936 
 Cross circulation through brain, 284 
 Crossed pyramidal tract, 866, 875, 879 
 connections of, 875 
 
INDEX 
 
 122i 
 
 Crowbar case, American, 974 
 
 Crura cerebri, 870, 874 
 
 Cnista, 870 
 
 Cultivation of tissues outside the body, 
 
 ii4i 
 Cuneate funiculus, 86() 
 nucleus, 86(» 
 
 relation of, to fillet, 874 
 Cuneus and vision, 966 
 Cuorin, 371 
 Curara, 18:: 
 
 action of, on gaseous exchange, 244, 
 
 541 
 on heat production, 694, 702 
 on nerve-endings, 182 
 on skeletal nuiscle, 738, 811 
 on \oiiiitinj,', v^O 
 Curdling of milk by rennin, 353, 354, 459, 
 
 7t9 
 Current intensity and stimulation, 741, 
 784 
 of action. See Action current 
 of rest. See Demarcation current 
 Cushny's views on urine secreticjn, 502 
 Cutaneous burns, death from, 299 
 excretion, 511 
 nerves, section of, 1085 
 respiration, 299 
 sensations, 1078 
 
 Boring's experiments, 1091 
 cortical centres for, 969 
 localization of, io()3 
 Trotter and Davies' experi- 
 ments, 1085 
 Cybulski's arrangement (velocity of 
 
 bkx^d), 123 
 Cyclic compounds, 615, 616, 618 
 Cyclopoiesis, 615, 616, 618 
 Cystein, 360, 365, 381, 582 
 Cysteinic acid, 366 
 Cystinuria, 366, 488, 579 
 Cytolysins, 31 
 Cytoplasm, 5 
 Cytosin, 593 
 
 Dancing mice, labyrinth in, 945 
 Daniell cell, 197, 7-24 
 
 Daphnia, Metchnikoff's researches on, 60 
 Dark-adapted eye, 1047, 1049, 1058 
 Daturine, action of, on pupil. 1026 
 ' Dead space,' respiratory, 236 
 Deaf-mutes, atrophy of temporal con- 
 volutions in, 967 
 
 equilibration in, 940 
 Decerebrate rigidity, 917, 942, 955, 
 1000 
 
 preparation, 998 
 Dcccrebrator, 999 
 Decidua, 1076, 1083 
 
 absorption of, by leucocytes, 60 
 
 artificial production of. 1078 
 Decinormal solutions, 479, 522 
 
 Decussation of afferent impulses, 894 
 
 of efferent impulses, 893 
 
 ..f fillet, 870 
 
 of optic nerve, 923, 966 
 
 i>f pyramids, 869, 875, 878 
 
 of sensory paths, 894 
 Defacation, 332 
 Deficiency diseases, 617, 632 
 
 phenomena after nervous lesions, 88 i 
 Degeneration of nmscle, 804 
 
 of nerves, 795, 797 
 
 chemistry of, 798 
 
 of spinal roots, 797 
 
 reaction of, 804 
 Deglutition, 322 
 
 centre, 325 
 
 nerves of, 325 
 
 reflex, looo 
 
 sounds, 324 
 Deiters' nucleus, 884, 886, 893, 928 
 Delirium cordis, 151, 205 
 Demarcation current, 823, 842 
 
 electromoti\T force of, 826 
 theories of, 828 
 Dendrites, 852 
 
 amoeboid movements of, 852 
 
 and sleep, 986 
 Dentate nucleus, 863, 869, 886 
 
 of olive, 869 
 Depressor nerves, 170, 173, 185, 186 
 pressor action of, 188 
 
 reflex, reversal of, 904 
 
 in cerebral ana?mia, 188 
 Descending degeneration, 866, 875 
 Deutero-proteose, 3, 10 
 Development of embryo, 1124 
 
 of ovum, 1 122 
 Dextrins, 3, il, 347, 455, 715 
 
 formed in salivary digestion, 347,455 
 
 tests for, 11,715 
 Dextrose, 3, 47, 338, 347, 455, 525, 5:.4 
 537 
 
 estimation of, in urine, 525 
 
 in blood, 47, 50, 446, 499, 500, 540, 
 552 
 estimation of, 717 
 
 in lymph, 446 
 
 ratio to nitrogen in urine iu diabetes, 
 551 
 
 tests for, 10, 488 
 
 Trommer's test for, 10 
 Diabetes, 546, 552 
 
 dextrose-nitrogen ratio in, 551 
 
 diet in, 534, 556 
 
 mellitus, 532 
 
 oxygen consumption in, 242 
 
 pancreatic, 346, 354, 636 
 
 phlorhizin, 331, 717 
 
 reaction of blood in, 24 
 
 respiratory quotient in, 242 
 
 sugar-destroying power of blood iu, 
 554 
 
1226 
 
 INDEX 
 
 Diabetic coma, 555 
 Diapcdcsis, 61, 194 
 Diaphragm in iispiratioii, 226, 228, 275 
 
 recording movements of, 2,^3 
 Diastases, 87, 344, 370, 384, 534 
 Diastase, salivary, 344 
 Diastole of heart, 87 
 Dichromatic vision, 1060, III2 
 Dicrotic wave of pulse, 104, 1 1 1 
 Dietaries, standard, 623, 625, 627 
 Dietetics, 622 
 Diet in diabetes, 554, 556 
 Diffusion, 426 
 
 circles, 1021, 1062 
 
 of gases, 246 
 
 through lungs, 264 
 Digestion as a whole, 416 
 
 and absorption, time recjuired fur, 
 464 
 
 bacteria and, 422, 423 
 
 changes in acidity of gastric contents 
 in, 418 ^ 
 
 chemical phenomena of, 336-374 
 
 comparative, 318 
 
 gaseous exchange during, 243 
 
 heat-production in, 713 
 
 in intestines, 418 
 
 in stomach, 416 
 
 mechanical phenomena of, 321 
 
 of carbo-hydrates, 356, 362. 416 
 
 of fats, 355, 363. 367, 461, 463, 464 
 
 of proteins, 351, 358, 417, 458, 460 
 
 significance of, 321 
 
 time required for, 418, 464 
 Digestive glands, microscopical changes, 
 
 374 
 juices, adaptation of, to food, 369, 
 398, 404, 410, 415 
 process of formation of, 383 
 protection of mucous mem- 
 brane from, 389 
 summary, 415, 416 
 organs in different animals, 318 
 Digitalis, diuretic action of, 509 
 Dilator of pupil, 1025 
 Diopter, 1021 
 Diphasic variations, 825 
 Diphtheria toxin, action of enzymes on, 
 
 372 
 Diplopia, 924, 1037 
 Direct cerebellar tract, 866, 872, 892 
 connections of, 872 
 pyramidal tract, 866, 875, 878 
 Disaccharides, 3, 371 
 
 absorption of, 445 
 J^ischarge of ventricle, period of, 87, 1)7 
 Dispersion in eye, 1028 
 Dissociation of oxyhaemoglobiu, 253, 273 
 Diuresis by salts, 509 
 Diuretics, 509 
 
 Double conduction in nerve, 792 
 Dromograph, 122 
 
 Dulcitc, 3 
 
 Duodciunn, digestion in, 417 
 
 glycosuria after removal of, 640 
 
 reaction of contents of, 419 
 Dura mater, X(>i 
 Dyspnoea, 283 
 
 heat, 283, 302 
 
 respiratory quotient in, 241 
 
 ICar, anatomy of, 1065 
 
 ossicles of, 10O5, 1066 
 functions of, 1069 
 
 resonance tone of, 89, 760 
 Hchidnase, 53 
 Kck's fistula, 385, 585 
 Ectoderm, 6, 11 24 
 Ectoplasm, 4 
 Edestin, 607 
 
 tryptic digestion of, 361 
 Ivffector organs, 898 
 
 Efferent impulses, decussation of, 869, 
 875, 878, 893 
 paths of, 893 
 scheme of, 890 
 Egg-albmnin, absorption of, 447 
 
 amino-acids in, i 
 
 excretion of, 448, 500, 716 
 
 reactions of, 9 
 Eggs, iron in, 622 
 lilu-lich's triacid stain, i 7 
 Eighth nerve. Sec Auditory nerve 
 Elasticity of muscle, 735 
 Electric fishes, 840 
 
 signal, 7:^2 
 Electrical conductivity c)f blood, 26, 68 
 of gastric juice, 387 
 of milk, 1 139 
 of serum, 69, 386 
 
 organ, 841 
 
 response. See .\ction current 
 l-"Iectro-cardiogram. human, 835-838 
 Electrodes, to make, 808 
 
 unpolarizable, 731, 842 
 Electrolytes, 428 
 Electrometer, 727 
 
 capillary, 728, 729, 826, 842 
 Electroinotive force, 725, 827 
 Electrons, 429 
 
 Electrotonic alterations of excitability 
 and conductivity, 786, 844 
 
 currents, 830, 844 
 Electrotonus, 785, 844 
 Eleventh nerve, 931 
 Emboli, artificial, 848 
 Embryo and uterus, coimections be- 
 tween, 1 126 
 
 asphyxia in, 1137 
 
 circulation in, 11 26, 1138 
 
 development of, 11 22, 11 26 
 
 formation of the, 1124 
 
 gases of blood in, 11 29 
 
 glycogen in, 538, 1131. ii33 
 
INDEX 
 
 1227 
 
 Embryo, heat-production in, 1135 
 
 inverting enzymes in, 371 
 
 liver in, 11 32 
 
 metabolism of, 11 33 
 
 physiology of, ii^K, 1129 
 Emetics, ;,v>, 459, 464 
 limmetropic evf, loji) 
 Emotions, genesis of, 1)74 
 ICnuiIsitication, iz, 367 
 Emulsin, 338, 340 
 Endocardiac pressure, o-, 'M 
 
 amount of, in ventricle, 92, 94 
 curves of, ()3, ()6, «)7 
 measurement of, 93 
 negative, lot 
 l-2ndocrine glands, 635 
 luidoderm, 6, 1125 
 Endo-enzymes, 337 
 Endogenous fibres of cord, .S()3, 867, 897 
 
 metabolism of proteins, 573 
 Endoplasjn, 4 
 
 Endothermic reactions, 689 
 Enemata, 331, 451 
 
 Energy of food, influence of hydrolysis 
 on, 683 
 
 law of conservation of, in body, 679, 
 683 
 Engrafting, 641, 1142 
 Enterokinase, 372, 415 
 
 nature of, 373 
 Enzjnnes. See Ferments 
 Ependyma, 861 
 lipiblast. See Ectoderm 
 Epicritic sensibility, 1091 
 Epiglottis, 323 
 Epilepsy, cortical, 972 
 
 Jacksonian, 972 
 
 produced by absinthe, 964 
 Epinephrin, 66, 173, 655. See Adrenalin 
 
 function of, 657 
 
 indispensability of, 657 
 
 partition of, in blood, 659, II49 
 
 secretion of, 661 
 
 testing for, 656 
 Equilibration and afferent impressions 
 from muscles, 941 
 from skin, <)4i 
 
 and orientation, afferent impulses 
 concerned in, 935, 936 
 
 cerebellum and, 934 
 
 Deiters" nucleus and, 929 
 
 in dog, 937 
 
 in dogfish, 938 
 
 in pigeon, 937 
 
 muscular nerves and, 941 
 
 postural reflexes and, 938 
 
 semicircular canals and, 928, 929, 
 936-941 
 
 skin and, 941 
 Erection centre, 183 
 Erepsin, 371 
 Ergograph, 642, 750, 752, 813 
 
 Ergot and blood-pressure, 173 
 lilrucic acid, 556, 558 
 Erythroblasts, 21 
 
 Ervthrocytes, 15. S^c Blood-corpuscles, 
 red 
 
 enuineration of, 19, 67 
 
 gases of, 250-^57 
 
 life-history of, 20 
 lirythrodextrin, 11, 347, 455, 715 
 Esbach's method of estimating albumin, 
 
 525 
 
 Eserine, action f)f, on accommodation, 
 lozz 
 on pupil, 1020 
 Ether, action of, on blood-corpuscles, 28, 
 
 29,70 
 Ethyl butyrate, synthesis of, by lipase, 
 
 338, 444 
 Eudiometer, 249 
 Euglobulin, 48 
 Eustachian tube, 297, 1065 
 
 \alve, 1 132 
 Evaporation, loss of heat by, 682 
 Excitability, aproperty of living matter, 7 
 
 and conductivity, voltaic current 
 and, 787, 844 
 
 direct, of muscle, 738, 81 1 
 
 of nerve, effect of temperature on, 
 784, 790 
 electrical currents on, 758, 
 785,844 
 Excitable tissues, the, 724 
 Excretion, 475 
 
 Exogenous metabolism of proteins, 573 
 Exothermic reactions, 689 
 Expectoration, 475 
 Expiration, 226, 229 
 
 duration of, 234 
 
 forced, 230 
 Expired air, composition of, 239-241, 305 
 Extensibility of muscle, 736 
 Extension reflex, crossed, 902, 997, 998 
 Extensor thrust reflex, the, 901 
 Extero-ceptive reflexes, 014 
 Extra contraction of heart, 155 
 
 systoles, in man, 155, 156 
 Exudation, inflammatory, 6r 
 Eye, action currents of, 830 
 
 artificial, Kiihne's, 1 104 
 
 chemistry of refractive media, 1016 
 
 compound of insects, 1013 
 
 defects of, 1027 
 
 development of, 850 
 
 dissection of, IIOI 
 
 extriiisic muscles of, 1063 
 
 liquids, 1016 
 
 secretion of, 1016 
 
 movements of, 1062 
 
 nerves of, 1023, 1024 
 
 optical constants, 1017 
 
 pupillo-constrictor fibres, 1023, liio 
 dilator fibres, 1023, mo 
 
12 28 
 
 INDEX 
 
 live, reduced, 1019 
 refraction in, 1017 
 retinal fatigue, 1055, III2 
 structure of, 1014. IIOI 
 visual acuity, liil 
 
 Facial uerve, 926 
 
 union of, with accessory, 976 
 palsy, 926 
 I-acilitation of reflexes, <)09 
 
 in motor cortex. 934 
 Faxes, action of extracts of, 424 
 bacteria in, 4J4 
 composition of, 423 
 microscopical examination of, 463 
 odour of, 424 
 I'asling men, metabolism in, 604 
 
 hunger sensations in, 1096 
 Fat, absorption of, 441, 463 
 
 influenced by bile, ',69 
 amount of, in standard diet, 623, 625, 
 
 627 
 chemistn,- of, 556 
 composition of, i 
 excretion of, into intestine. 443 
 formation of, from carbo-hydrates, 
 560 
 protein, 561 
 intermediary metabolism of, 565 
 melting-point of, 12 
 metabolism of, 556 
 liver and, 567 
 migration of, 557, 563, 568 
 
 in phosphorus poisoning, 563 
 mobilization of, 565 
 non-nutritive function of, 568 
 passage out of, intestinal epithelium, 
 
 44- 
 storing of, 558 
 synthesis of, in intestinal nmcosae, 
 
 443. 444 
 Fatigue, changes in nerve cells, 859, 
 
 983 
 influence of, on muscular contrac- 
 tions, 749, 813 
 on nmscle-curve, 813 
 muscular, cause of, 751 
 of muscle-nerve preparation, seat of 
 
 exhaustion in, 752, 813 
 seats of, in voluntary contraction, 
 
 753 
 Fats, constitution of, 3, 556 
 
 tests for, II 
 Fatty acids, absorption of, 443 
 
 and glycogen formation, 538 
 decomposition of, in body, 566 
 formation of, from carbo-hy- 
 drate, 561 
 synthesis of, to fat, 444 
 tests for, 12 
 Fechncr"s law, 1100 
 Fehliug's solution, 526 
 
 Fehling's solution, Benedict's m<xlifica' 
 tion of, 527 
 
 test for sugar, 525 
 Ferment action, quantitative estiiuatiou 
 of, 34^. 453 
 
 cellulose-dissolving, 423 
 
 mode of action of, 339, 341 
 
 re\ersible action of, 339 
 Fermentation, butyric acid, 423 
 
 lactic acid, 423 
 Ferments, 336 
 
 autolytic, 599 
 
 in the liver, 600 
 
 intracellular, 337 
 
 list of, 345 
 
 specificity of, 340 
 Fever, aseptic, 707 
 
 caused by cocain, 704 
 by xanthin, 707 
 
 changes in urine in, 703 
 
 derangement of heat regulation in, 
 705 
 
 metabolism in, 706 
 
 nervous, 708 
 
 production of heat in, 704 
 
 ' puncture,' 701 
 
 ' retention theory,' 706 
 
 significance of, 708 
 
 vaso-motors in, 706 
 Fibrillary contraction, 151. 205 
 Fibrin-ferment, 34. Sec Thrombin 
 
 formation of, 35 
 
 preparation of, 65 
 Fibrinogen, 34 
 
 production of, in liver, 35 
 Fibrino-globulin, 47 
 Picks theory of fusion of visual stimuli, 
 
 1050 
 Fillet, 874, 88 1 
 Flavour, 1078 
 Flechsig's developmental cortical zones, 
 
 961 
 Flexion reflex, U03. 997 
 Flour, 719 
 
 Flow of liquids, with intermittent pres- 
 sure, 85 
 Fluoride plasma, clotting of, 38 
 Fluorides, action of, on coagulation, 
 
 37.64 
 laHal heart, 11 35 
 I'olin's method of estimating anunonia. 
 
 crcatiiiiii. 524 
 
 indican, 518 
 
 uric acid, 523 
 Food substances, 320 
 Foods, isiidynainic relations of, 773 
 specilic dynamic action of, 680 
 Foramen of Monro, 850 
 Forced movements, 944 
 Fore brain, 850 
 Formaldehyde reaction for proteins, 8 
 
INDEX 
 
 1:29 
 
 Formatio reticularis, 870 
 
 I-'orinic acid, 55() 
 
 I'ornmla of contraction. See Law of 
 
 contraction, 845 
 Freezing-point, determination of, 529 
 !•" rev's a>sthesioineter, loHu 
 Frog, heart of, anatomy, 194 
 
 to pith a, 193 
 
 vagus, dissection of, 196 
 stimulation of, 198 
 
 web of, circulation in, 193 
 Function, localization of, in cortex, 975 
 l'"undus of stomach, 326 
 Funiculus cuneatus, 869 
 
 gracilis, 861 » 
 
 Gall-bladder, 411, 419 
 
 reflex contraction of, 412 
 Gall-stone, pain caused by, 901 
 Galvani's experiment, ^zz, 842 
 Galvanometers, 726 
 string, 727, 836 
 Ganglia habenula-, 933 
 
 of posterior roots, development of, 
 850 
 Ganglion cells, sympathetic, 856 
 spirale, 927 
 vestibulare, 927 
 Gaskell's method (heart), 195 
 Gas-pump, 249 
 Gaseous exchange in lungs, mechanism 
 
 of, 263 
 Gases, absorption coefficient of, 247 
 diffusion of, 246 
 of blood, 243 
 
 extraction of, 249 
 quantity of, 250 
 tension of, 258 
 of muscle, 268, 269 
 partial pressure of, 247 
 tension of, 248 
 
 in tissues, 267 
 Gasserian ganglion, development of, 854 
 Gastric digestion, role of HCl in, 353 
 testing for products of, 458 
 glands, influence of nerves on, 401 
 secretory changes in, 378-381 
 juice, 349 
 
 acidity of, 350 
 
 antiseptic function of, 356 
 
 artificial, 458 
 
 Beaumont's work on, 349 
 
 chemistry of, 350 
 
 digestion of proteins bv, 351, 
 
 458 
 
 electrical conductivity of, 387 
 freezing-point of, 387 
 hydrochloric acid of, 350 
 in cancer, 350 
 
 influence of substances on se- 
 cretion of, 403, 405 
 lactic acid in, 351 
 
 Gastric juice, milk-curdling action of, 
 
 353 
 psychical secretion of, 404 
 to obtain pure, 459 
 secretion, 401 
 Gelatin as a forjd, 614 
 from nerves, 795 
 tests for, 9 
 Geminal fibres, 879 
 Gemmules, 852 
 Geniculate bodies, 923 
 Giant pyramids of Betz, 959 
 Gianuzzi, crescents of, 375 
 Gibbs, thermodynamic law, 431 
 Glands, action currents of, 838 
 
 iieat-production in, 689 
 Gliadin, feeding with, 617 
 Globin, 54 
 
 Globulins, tests for, 9 
 Glomerulus, function of, 492, 493, 495, 
 
 497- 305 
 Glosso-pharyngeal nerve, 929 
 
 and taste, 925 
 Glottis, in voice production, 308, 312 
 Gluco-proteins, 2 
 Glucose, 10. See Dextrose 
 Glutamic or glutaminic acid, 360, 575 
 Glycerine, i, 363, 366, 536, 556 
 
 formation of, from carbo-hydrates, 
 561 
 of glycogen from, 536 
 tests for, 12 
 Glycerose, 537 
 
 Glyceryl-phosphoric acid, 366, 421, 571 
 Glycin or glycocoll, i, 360, 576, 580, 581 
 Glycocholic acid, 365 
 Glycogen, 3, 523 
 
 and lactic acid, production in mus- 
 cle, 771 
 as reserve material, 539 
 extra hepatic, 538 
 
 formation of, from protein, 535, 538 
 formers, 536 
 
 function and fate of, 539 
 in liver, 534 
 in liver capillaries, 535 
 in muscle, 767, 768 
 preparation of, 715 
 Glycogenase, 600 
 i Glycogenolytic nerve fibres, 549 
 ! Glycolysis, 540 
 i pancreas and, 545 
 
 Glyconic acid, 543 
 
 Glycosuria, after injection of sugar iato 
 the blood, 716 
 adrenalin, 550 
 alimentary, 540, 717 
 caused by drugs, 552 
 phlorhizin, 551, 717 
 produced by asphyxia, 548 
 puncture, 547 
 relation of adrenals to, 548 
 
IXDEX 
 
 Glycurcmic acid, 47, .jHj, 526, 543 
 Glvoxal (inethxl-). coiuersioii into lactic 
 
 acid, 545 
 Goitre, cxophtliahiiic, 650 
 
 i)f brook trout, 649 
 Golgi's method, 851 
 Goll, column of, 863, 866 
 connections of, 870 
 Gout, 487, 590 
 Gowers, tract of, 866 
 Graafian follicles in ovarian grafts, 641 
 Gracile funiculus, 86c) 
 Gracilis experiment of Klihiie, 913 
 (irafting tissues, 641, 1142 
 Gramme-molecular weight, 426 
 ' Granule-cell," 856 
 Ground bundles of cord, 867 
 Growth, foods adequate for, 614-618 
 Guaiconic acid and oxydases, 272 
 Guaiacuni test for blood, 76, 272 
 Guanidin and parathyroid, 647 
 Guanin, 592, 593 
 Gudernatsch on influence of thyroid on 
 
 tadpoles, 653 
 Giinzburg's reagent for hydrochloric acid, 
 
 460 
 Gyinnotus, 841 
 
 Gyrus postcentralis, stimulation of, 963 
 precentralis, 963 
 
 Ha^matachomcter, 121 
 
 Hiematin, 54 
 acid, 34, 75 
 alkaline, 34, 75 
 
 Haematocrite, 27, 68 
 
 Haematoidin, 383 
 
 Ha?matopoiesis, 20 
 
 Haematoporphyrin, 35, 76 
 in urine, 483 
 
 Haemin, 35, 79 
 
 Haemochromogen, 54, 76 
 
 HaMiioglobin, composition of, 50 
 crystallization of, 32 
 crystals, preparation of, 73 
 curves of dissociation, 233-233 
 influence of carbon dioxide on, 233 
 intracorpuscular crystallization of, 
 
 52 
 quantitative estimation of, 76 
 spectroscope examination of, 74 
 spectrum of, 51, 53 
 
 Hsemoglobinometer, 76 
 
 Hainoglobinuria, part)xysmal, 483 
 
 Hii'molysis, 28, 71 
 
 by foreign seruni, -/l 
 mechanism of, 29 
 
 H;rmometer, 77 
 
 Ha'mophilia, coagulation in, 45 
 
 Hitmorrhage and transfusion, influence 
 of, on blood-pressure, 191,214 
 quantity of blood which may be 
 lost in, 191 
 
 Hair-cells of internal ear, 937 
 Haldane's apparatus for CO,. 304 
 
 for H2O and CO^, 305 
 Harmonics, 310 
 Hay's test for bile-salts, 528 
 Head, transplanting of, 973 
 Hearing, 1064 
 
 analysis of complex sounds, 1072 
 
 l)eats, 1113 
 
 cranial conduction of sound, 1071, 
 
 III3 
 monochord, III3 
 perception of pitch, 1073 
 range of, 1075 
 
 sympathetic vibration, 313, 1113 
 theories of, 1074 
 Heart, action current of, 833, 844 
 ' all or nothing ' law of, 134 
 apex, preparation of, 194 
 arrangement of libres in, 78 
 augmentor nerves of, 157, 162, 165, 
 
 168, 198 
 auricular flutter, 151 
 automatism of, 142 
 beat, 83, 194, 201 
 cause of, 141 
 
 chemical conditions of, 152 
 neurogenic and myogenic hypo- 
 thesis of, 142 
 standstill, action of augmentor 
 nerves in, 168 
 conduction and co-ordination in, 
 
 146 
 conductivity of, 142 
 excitability of, 142 
 extra systoles of, 133 
 extrinsic nerves of, 156 
 ' fractionate ' contraction of, 163 
 ganglion cells of, 141, 163 
 impulse of, 90 
 inhibitory ner\-es of, 137, 162, 164, 
 
 198, 203, 212 
 inhibition of, 136, 167 
 intrinsic nerves of, 141, 157 
 nniscle, action of inorganic salts on, 
 
 198 
 of l.inuilus, 143 
 output of, 139 
 pacemaker of, 143 
 pause of, 97 
 perfusion of, 153, 205 
 pressure in, variations of, 97 
 refractory period and extra contrac- 
 tion of, 133 
 resuscitation of, 153 
 rhythmicity of, 142 
 sounds of, 88, 207, 837 
 source of energy of contraction of, 
 
 77- 
 suction action of, loi 
 temperature in, 710 
 tonicity of, 142 
 
/.v/)/;a 
 
 I-J3I 
 
 Heart tracings, i(>.», iri. 194, 203, H37 
 
 siiuuUanr<)\is, (loiu auiiclf and 
 Nfiitriclo, 1611, 161, 196 
 valves t)(, 80, 204, 206 
 wDik done by, 138 
 Heat centres, 701 
 
 coagulation, 9, 819 
 distribution of, 7o<) 
 equivalents of food substances, 
 
 684 
 given off in respiration, measure- 
 ment of, 08:1,721 
 liberated in cleavage of food sub- 
 stances, 683 
 loss, 681 
 
 regulation of, involuntary, 690 
 voluntary, 692 
 production, amount of, 683 
 and work, 684 
 effect of curara on, 694 
 in brain, 689 
 in digestion, 686, 713 
 in fever, 704 
 in glands, 689 
 in heart, 688 
 in muscles, 687 
 in rigor, 778 
 of different classes of workers, 
 
 685, 687 
 relation of, to muscular work, 
 
 764, 765 
 regulation of, involuntary, 693 
 
 voluntary, 692 
 seats of, 686 
 
 surface and blood-flow relations, 
 696 
 rigor. See Rigor, heat, 777, 820 
 sources of, in body, 683 
 standstill of heart, 159, 194 
 Heller's test for albumin, 524 
 Helmholtz's theory (vision), 1053 
 (vowel sounds), 314 
 (pitch perception), 1073 
 Hemeralopia, 1060 
 Hemianesthesia, capsular, 881 
 Hemianopia, 923, 965 
 Heniibilirubin, 365 
 Hemiplegia, reflexes in, 911 
 Hering's theory of colour vision, 1657 
 Herpes zoster and trophic nerves, 806 
 Hexoses, 3, 537 
 
 Hibernating animals, temperature regu- 
 lation in, 703 
 respiratory quotient in, 241 
 Hiccup, 288 
 Hippuric acid, 524, 380, 614 
 
 formation, 580 
 Hirudin and coagulation, 37 
 Histidin, 54, 360 
 Histones, 2 
 
 Holmgren's wools, 1 112 
 Homogentisinic acid, 483, 525 
 
 Hoinoiotliernial atiimals, production of 
 carbon dioxide in, 244 
 tliermotaxis in, 690 
 Homo-lateral fibres, 879 
 Homologous stimuli, 1007 
 Hormones, 404 
 
 Humidity of air and heat regulation, 691 
 Himger sensation, 930, 1096 
 Hydr;L>mic plethora, 462, 500 
 Hydrocele fluid, 39 
 
 coagulation of, 35 
 Hydrochloric acid in gastric juice, 350 
 
 formation of, 379, 380 
 Hvdrogen, income and expenditure of, 
 
 619 
 Hydrogen ion concentration of blood, 
 
 24 
 
 and respiratory centre, 282 
 
 of duodenal contents, 419 
 
 of gastric contents, 420 
 
 of milk, 1 1 39 
 Hydrolysis, 2 
 Hydrostomia, 401 
 
 Hyoscyamine, action of, on pupil, 1026 
 Hyperglycajmia, 300, 540 
 
 adrenalin, 550 
 
 alimentary, 540 
 
 asphyxia, 548 
 
 in diabetes, 552 
 
 pancreatic, 546, 636 
 
 puncture, 547 
 
 relation of adrenal to 548 
 Hyperis'otonic solutions, 428 
 Hypermetropia, 1030 
 Hyperpna>a, 283 
 Hypoglossal nerve, 931 
 Hypoisotonic solutions, 428 
 Hypophysin, 668 
 
 Hypophysis. See Pituitary body 
 Hypoxanthin, 589, 592, 593 
 
 Identical points, theory of, 1037 
 Idio-muscular contraction, 759 
 Ileo-ca'cal valve, 331 
 
 colic sphincter, 331 
 Illusions, optical, 1041 
 Imbibition, 426 
 Indicau, 484, 517 
 
 estimation of, 518 
 Indol, formation of, in intestine, 422 
 Indophenyloxydase, 272 
 Induction machine, arranged for tetanus, 
 200 
 
 arranged for single shocks, 808 
 Inductorium, 730 
 Infundibulum, infundibular body, 666, 
 
 933 
 Inhibition from the cortex, 954 
 
 in reflex action, 903 
 
 nature of, 167 
 
 of heart, 156 
 Inorganic salts. See Salts 
 
12^2 
 
 INDF.X 
 
 Inosinic acid, 767 
 Inosit, 767 
 Inspiration, 226 
 forced, 230 
 muscles of, 226, ^27 
 Intellectual processes, seat of, 973 
 Intelligence, size of brain and, 088 
 Intermedio-lateral tract, 864, 865 
 Internal capsule, 881 
 
 frontal fibres in, 882 
 occipito-temporal fibres in, 882 
 respiration, 265 
 secretion of adrenal, 655 
 of kidney, 671 
 of ovaries, 641 
 of pancreas, 6;,6 
 of parathyroid, 646 
 of pituitary body, 666 
 of pineal gland, 671 
 of spleen, 672 
 of testicles, 640 
 of thymus, 643 
 of thyroid, 645, 6^7 
 Intestinal epithelium, permeability of, 
 437 
 juice, adaptation of, to food, 415 
 collection of, 370 
 composition of, 371 
 influence of nerves on, 414 
 segments, effect of blood-serum on 
 contractions of, 453 
 action of epinephrin on, 453, 657 
 658 
 Intestine, large, absorption in, 422, 451 
 
 movements of, 330 
 Intestines, absorption of water in, 421 
 contraction of isolated, 452, 330 
 digestion in, 418 
 movements of, 328 
 nerves of, 331, 332 
 reaction of contents of, 419, 420 
 resection of, 451 
 Intraocular tension, 1017 
 Intrathoracic pressure, 236, 237 
 Invertase, 338, 339 
 
 in intestinal juice, 371 
 Inversion of carbo-hydrates, 356 
 Iodine, influence of, on thyroid, 650-654 
 loHS, 420 
 
 Iris, effect of stimulation of sympathetic 
 on, 1023, llio 
 functions of, 1026 
 in accommodation, 1023 
 local mechanism of, 1025 
 nerves of, 1023 
 Iron, absorption of, 447 
 in eggs, 622 
 in liver cells, 463 
 in milk, 622 
 Irradiation, 1061 
 Island of Reil, 973 
 Islets of Langerhans, 638 
 
 Isodynamic relation of food substances 
 
 773 
 Is<jmaltose, 338 
 Isotonic and isometric contraction, 747 
 
 solutions, 428 
 Itching, sensation of, 1085 
 
 Jacksonian epilepsy, 972 
 
 Japanese dancing mice, labyrinth of, 945 
 
 Jaundice, 384, 414 
 
 colour of stools in, 369 
 
 haematogenic, 385 
 Jaw- jerk, 915 
 
 Karyokinesis, 5 
 Karyosome. See Nucleolus 
 Katabolism. See Metabolism 
 Kephalin, 42, 571, 794, 991 
 Ketohexoses, 537 
 Ketones, 537 
 
 Kidnev, bloodvessels and tubules of, 
 ■489 
 
 excretion of pigments by, 495 
 
 formation of hippuric acid in, 580 
 
 gas exchange of, 266, 504 
 
 internal secretion of, 671 
 
 nerves of, 504 
 
 tubules of, 490, 492 
 Kinasthetic area, 963 
 Knee-jerk, 904, 915 
 
 reinforcement of, 911 
 Kreatin and kreatinin. 5^^ Creatin and 
 
 Creatinin 
 Kiihne's artificial eye, II04 
 
 Labyrinth, 927, 1067 
 
 and equilibration, 936, 938 
 and postural reflexes, 918 
 Laccase, 272, 337 
 Lachrymal glands. 475 
 Lactalbumin, 719 
 Lactase, 338, 340, 371, 410 
 Lacteals, 463 
 
 absorption of fat by, 443 
 Lactic acid and heat-production in 
 muscle, 767 
 as stage in decomposition of, 
 
 dextrose, 543 
 fermentation, 423 
 formation of, in muscle, 769 
 Hopkins's reaction for, 821 
 in metabolism, 544, 345 
 in nervous tissue, 705 
 in stomach, 350 
 precursor of, in muscle, 770 
 Iffelmann's test for, 460 
 Lakin;, of blood, 28. See Ha?moIysis 
 Landergrens hypothesis, 551 
 Langerhans, islets of, 638 
 Lanolin, and fat absorption, 442 
 Larynx, action of muscles of, 308 
 and voice i)r(>ducti<>n, 307 
 
tSDE V 
 
 I2J3 
 
 Latent period of muscular contraction, 
 
 rts.815 
 L.iler.il uriinnd-bundlo, Sh~ 
 
 nucleus of bulb, K; 5 
 Law of contraction, 788, 845 
 Lecithin, i, 47, .^66, 571, 7<>4, «ic>i 
 
 digestion of, 421 
 l.eclanciie battery, 198 
 Leech extract and coaijulation, 38 
 Left-handed people, aphasia in, 971 
 Legal's test for acetone, 529 
 Leucin, .^60,461, 4>SS 
 Lcuc<.)cytes, chemistry <A, 55 
 
 cosinophile, 17 
 
 number of, K) 
 
 origin of, 22 
 
 polymorphonuclear, 17 
 
 transitional, 17 
 
 \ arieties of, 17 
 Leucocytosis, ly 
 Leuka-mia, 19 
 
 Lcvatores costarum, action of, in respira- 
 tion, 227 
 Levulose, 336, 538 
 
 formation of glycogen from, 537 
 Liebcn's test for acetone, 529 
 Lieberkiihn'ii crypts, 370, 374, 375 
 
 functions of, 431 
 Lime salts, deficiency of, changes caused 
 
 by, 621 
 Linmlus heart, 143 
 Linolic acid, 336 
 Lipase, 48, 338 
 
 gastric, 335 
 
 pancreatic, 363 
 
 reversible action of, 338, 444 
 Lipoids, I, 3 
 Lipoid-solubility of absorbed substances, 
 
 437 
 Liquids, fiow of, 83 
 Lissauer, tract of, 866 
 Listing's law, 1063 
 Liver and aniino-acids, 584 
 
 and coagulation, 44 
 
 and deamidization, 388 
 
 and ghcogen formation, 533, 535 
 
 and metabolism of fat, 567 
 
 and urea formation, 384 
 
 cells, iron in, 383, 463 
 
 temperature, 689, 71.: 
 Li\ing matter, chemical composition 
 of, I 
 functions of, 6 
 structure of, 4 
 Living test-tube experiment, 34 
 Localization in different animals, 980 
 
 of functiori in cortex, 973 
 Locomotion, 946 
 Locomotor ataxia, disappearance of 
 
 knee-jerk in, 915 
 Lungs, area of, 224 
 
 auscultation of, 231, 304 
 
 Lung., blood-supply of, 223 
 
 circulation time of, 224 
 
 mechanism of gas exchange in, 263 
 
 i|uaiitit-\- of blood in, 224 
 Lynipli, Composition of, 57 
 
 different kinds o{, 466 
 
 flow, factors in, 192 
 
 formation, and activity of organs, 
 47^ 
 factors concerned in, 467 
 influence of nerves on, 473 
 
 freezing-point of, 473 
 
 hearts, 192, 193 
 
 post-mortem flow of, 474 
 
 pressure of, 192 
 
 r.ite of flow of, 192 
 Lyniphagogues, 468 
 Lymphatic circulation, 192 
 
 glands, 192 
 Lymphatics, valves of, 192 
 Lymphoblasts, 22 
 Lymphocytes, 17 
 Lysin, 360 
 
 synthesis of, in body, 614 
 
 Macula lutea, 973, I107 
 Magendie-Bell law, 891 
 Make and break sliocks, 807 
 Malapterurus electricus, 840 
 
 nerve of electrical organ, 850 
 Maltase, 340, 345 
 
 in intestinal juice, 371 
 Maltose, absorption of, 443 
 Mammary glands, fat formation in, 565, 
 I 1141 
 
 j line, 90 
 
 j Manganese salts and coagulation, 37 
 Mannite, 3 
 Manometer, 92 
 
 differential, 96 
 
 Hiirthle's elastic, n.) 
 
 maximum and mininmm, 92 
 
 optical, 93 
 
 with side-tube, 212 
 Marchi staining reaction, 797 
 Marginal veil, 830, 858 
 Marie, tract of, 867 
 Mariotte's experiment, 1044, I107 
 Mast cells, 18 
 Mastication, 321 
 Mate, 632 
 
 Maxwell's spot fxisioii), 1107 
 Meconium, 424 
 Mediastinum, 223 
 
 Medulla oblongata, structure of, 869 
 ' Medullary' groove, 849 
 
 sheath, development of, 959 
 Megakaryocytes, 18 
 Megaloblasts, 21 
 Meissner's plexus, 320 
 Meniere's disease, 940 
 Menstruation, 1120 
 
 78 
 
1234 
 
 INDEX 
 
 Mcrcapturic acid, 581 
 Mrscncrphal'iii, 850 
 Motatxjiisin, 6 
 basal, Mit 
 
 in fcvrr, 706 
 
 in starvation, 60; 
 
 intermediary, of carbo-hydrates, 542 
 of fat, 565 
 
 of aniinoacids, 58J 
 
 of nucleic acids and purin basts, 592 
 
 of phosphatides, 571 
 
 of proteins, 57- 
 
 and muscular work. 610 
 in star\ation, 603 
 
 of sterins, 570 
 
 relation of, to surface, 695, 696 
 Meta-proteins, 3 
 Metcnccphalon, 850 
 Metharnioglobin, 53, 75 
 Methylene blue, behaviour of, in tissues, 
 
 137,218,956 
 Mcthylglyoxal, 545 
 Methyl orange as indicator, 523 
 Metronome, 195 
 Metts tubes, 34^, 454 
 Microblasts, 21 
 Microtonometer, 259 
 Micturition, 510 
 
 centre, 511, 915, 920 
 Milk, 1 1 39 
 
 as a food, 62 1 
 
 chemistr>- of, 629. 718, 1139 
 
 clotting of, 353.719 
 
 digestion of, 353, 417 
 
 hydrogen ion concentration of, 11 39 
 
 secretion of, 11 40 
 Millon's reagent, 8 
 Mitosis, 5 
 
 Mitral valve, 86, 96 
 Moist chamber, 809, 843 
 Molecular concentration, 420 
 Molisch's test for carbo-hydrates, 11 
 Monakow's tract, S67 
 Monochord, III3 
 Monosaccharides, absorption of, 445 
 
 fonnation of glycogen from, 537 
 Monro, foramen of, 850 
 Morphine, quantity of, for dogs, 63 
 Morphology of the blood, 14 
 Motor aphasia, 970 
 ■ Motor ' areas, 951 
 Mountain sickness, 298 
 Movements, forced, 044 
 Mucin in bile, 3O4.462 
 
 in >aliva, 344, 454 
 Mucous glands, secretory changes in, 381 
 Miillers experiment, 296 
 Muscarine, action of, on heart, 164, 199 
 Muscle, action of curara on, 738, 811 
 
 action of nicotine on. 730 
 
 anaerobic contraction of, 269, 306, 
 770 
 
 Muscle, arrangement for tracings, 8l3 
 chemistry of, 767, 819 
 composition of, 767 
 contraction of, 743 
 theories of, 744 
 influence of load on, 747. 813 
 of temperature on, 749, 813 
 degeneration of, 804 
 diffraction spectrum, 745 
 direct excitability of, 738, 81I 
 direct stimulation of, 740 
 efficiency of, 765 
 elasticity of, 736 
 extensibility of, 736 
 fatigue of, 749. 813 
 cause of, 751 
 seats of, 75^. 753- 813 
 formation of lactic acid in, 751, 769 
 
 820 
 gases of, 270 
 
 general physiology of, 723 
 heat- production in, 686, 762, 764 
 ' idio-muscular ' contraction of, 
 
 759 
 nerve preparation, 808 
 
 fatigue of, 752, 813 
 of eyes, extrinsic, 1063 
 oxygen consumption of, 269 
 permeability of, 773 
 physical properties of, 735 
 reaction of, 769, 820 / 
 receptive substances of, 739 
 respiration of, 269 
 smooth, contraction of, 745, 747, 817 
 
 wave of contraction in, 759 
 spindles, 804 
 stimulation, 737 
 structure of, 742 
 trough, 809 
 Muscular contraction and lactic acid, 767, 
 770 
 changes during, 744 
 chemical phenomena of, 767 
 CCj production in, 270, 768 
 duration of, 745 
 graphic record of, 811 
 heat-production in, 762, 763 
 in absence of oxygen, 269. 306, 
 
 770 
 influence of fatigue, 749. 812 
 of load on, 747, 813 
 of mental fatigue on, 754 
 of previous stimulation > n, 
 
 749,813 
 of temperature on, 749, 
 
 813 
 of veratrine, on 754, 814 
 isotonic and isometric, 747 
 latent period of, 745, 815 
 mechanical phenomena of, 745 
 optical phenomena of, 742 
 oxygen cunsuniption in, 768 
 
INDEX 
 
 1335 
 
 Muscular ctmtraction, physico-chemical 
 cuiiditioiis of, 773 
 rate of wave of, 751) 
 relation between nieclianical 
 energy and beat-production, 
 765 
 relation of glycogen to, 771 
 substances metabolized in, 771 
 superposition of, 736, 816 
 theories of, 744 
 time relations of, 747 
 voluntary, 760 
 work done in, 747 
 sensations, 101)4 
 tissue, action of extracts of, 673 
 tone, 917, 938, 1000 
 work and nitrogenous metabolism, 
 610 
 source of energy of, 611, 767, 
 771 
 Musical centres, 967 
 Myelencephalon, 830 
 Myelin sheath, fragmentation of, 796 
 Myelination of tracts at different times, 
 
 <)0I 
 
 Myeloblasts, 22 
 Myocardiograph, 162. 203 
 Myograph, 195, 743, 812 
 
 spring, 74t), 815 
 Myohamatin, 767 
 Myosin, 820 
 Myosinogen, 820 
 Myxcedema, 648 
 
 Negative variation. See Action current 
 Nerve, carbon dioxide production in, 
 782 
 chemical changes in, 782 
 chemistry of, 794 
 conductivity of, 790 
 
 anaesthetics and, 814 
 degeneration of, 795 
 
 phosphorus in, 797 
 endings, action of drugs on, 182 
 excitability of, 784 
 
 and conductivity of, 786 
 fibres, inedullated, 781, 860 
 
 structure of, 781, 851 
 heat-production in, 782 
 impulse, nature of, 781 
 
 velocity of, 793, 818 
 
 temperature coefi&cieat of, 
 782 
 muscle preparation, 808 
 pattern of, 799 
 polarization of, 829 
 propagated disturbance of, 781 
 regeneration of, 798 
 
 autogenetic, 802 
 
 chemiotaxis in, 800 
 stimulation of, 783 
 trunks, cooling of, 979 
 
 Nerves, anastomosis of, 798, 976 
 classification of, 807 
 posterior roots, section of, 797, 964 
 preganglionic, 185, 865 
 specilic energy of, 979 
 trophic, 805 
 Nerve-cells, growth in vitro, 802, 803, 856, 
 857 
 effect of anaemia on, 859 
 anaesthetics on, 859 
 division of axons on, 795, 859 
 fatigue on, 859, 983, 984 
 of Golgi's second type, 856 
 Nervi erigentes, r8o, 332, 334 
 Nervous activity, chemistry of, 782, 795, 
 
 991 
 Nervous system, autonomic, 1003 
 
 development of, in different 
 animals, 898 
 tissue, action of extracts of, 673 
 Neural canal, 849 
 
 groove, 849 
 Neuroblasts, 849, 858 
 Neuroglia, 861 
 Neurokeratin, 795 
 Neurons, 851 
 
 growth of, 857 
 nutrition of, 858 
 scheme of lower motor, 855 
 varieties of, 835, 856 
 Nicotine, action of, on ganglion cells of 
 heart, 166 
 on skeletal muscle, 740 
 on sympathetic, 182, 1005 
 effect of, on nerve-cells, 182, 913 
 Night-blindness, 1060 
 Nissl substance, 851, 984 
 Nitrogen balance-sheet, 602 
 
 necessary quantit}- of, in diet, 623, 
 
 624, 625 
 total, estimation of, 521 
 
 variation of, with protein in 
 food, 720 
 Nitrogenous equilibrium, O02 
 
 protein necessary for, 605 
 metabolism and muscular work, 
 610 
 Norleucin, 360 
 Normal solution, 479 
 Normoblasts, 21 
 Nuclease, 594 
 Nucleic acids, chemistry of, 593 
 
 metabolism of, 592 
 Nuclco-proteins, i, 2, 47 
 digestion of, 417, 592 
 Nucleosides, synthesis of, 597 
 Nucleotidase, 594 
 Nucleotids, 593 
 Nucleus, 5 
 
 globosus, 885 
 importance of, for cell, 795 
 tecti, 885, 928 
 
1236 
 
 INDEX 
 
 Oatmeal as a food, 626 
 
 in dialx'tos, 555 
 Obesity, 568 
 
 Banting cure for, 606 
 
 trcatiiH'iit of, 570 
 Occipital lesions, 0^)6 
 Oculo-niotor nerve, t)Z\, ijSj, 1023 
 Odours, classification of, 107b 
 Uisophagus, contractions of, 323, 817 
 
 pulse, 90 
 Ohm's law, 725 
 Oleic acid, 556 
 Olein, 4 
 
 Olfactometer, 1076 
 Olfactory bulb, 922 
 
 nerve, 921 
 Olivospinal tract, 867, 885 
 Oncometer, 507 
 Oophorin, 642 
 
 Oplitliahnometer, 1021, I105 
 Ophthalmoscope, 1031, II08 
 
 (ieneva, 1 1 10 
 Opsonins, 61 
 Optical illusions, 1041 
 Optic lobes, 932 
 
 and inhibition of reflexes, 910, 
 996 
 
 nerve, 922 
 
 radiation, 883, 923 
 thalaums, 883, 932 
 Orcin reaction for pentoses, 528 
 Orientation, mechanism of, 936 
 Ornithin, 587, 613 
 Osmosis, 426 
 
 and diffusion, in lymph formation, 
 
 471 
 Osmotic pressure, 426 
 
 resistance of coloured corpuscles, 73 
 Ossicles, auditory, 1066, 1069 
 Otoliths, 937 
 Output of heart, 139 
 Ovaries, internal secretion of, 641 
 Ovary, influence on metabolism, 642 
 Overtones, 310, 313 
 Ovum, development of the, 1 122 
 Oxalates, action of, on coagulation, 37, 64 
 
 in urinary sediments, 478, 532 
 Oxalic acid, 481 
 Oxidation, seats of, 265 
 Oxidative process, nature of, 271 
 Oxidizing ferments or oxydases, 271, 272, 
 
 306 
 Oxybutyric acid, 555. 5('-. 567 
 Oxydases, 48, 76, 271, 3°^ 
 Oxygen absorption, mechanism of, 263 
 
 capacity of bhjod, 251 
 
 coefficient of utilization of, 697 
 
 consumption of, 242, 243 
 
 in different animals, 245 
 of different tissues, 268, 271 
 
 deficit, 620 
 
 diitiibutiou of, in blood, 252 
 
 Oxygen, income and expenditure of, 619 
 partial pressure of, in aheoli, 241 
 
 261, 263 
 passage from blood into tissues, 266 
 tension in blood, 258, 261, 262 
 
 Oxyntic cells, 375, 378, 380 
 
 Oxyprolin, 360 
 
 Pain, in internal organs, 901, 1093 
 referred, 891 
 
 sensations, 1085, 1089, II16 
 paths for, 896 
 Pancreas and glycolysis, 546 
 
 and spleen, nnitua! relations of, 41 1 
 influence of nerves on, 405, 407 
 internal secretion, 636 
 islet tissue of, 638 
 removal of, in pregnancy, 638 
 secretory changes in, 376 
 Pancreatic diabetes, 546, 636 
 
 juice, adaptation of, to lactose, 410 
 and bile, adjuvant action of, 
 
 367, 368 
 artificial, 460 
 composition of, 358 
 ferments of, 35S-363, 460 
 freezing-point of, 386 
 rate of secretion of, 410 
 secretion, influence of food on, 
 409 
 Panniculus adiposus, 568 
 Parabiosis, 638, 1146 
 Paradoxical contraction, 832, 844 
 Paraglobulin, 48 
 
 ' I^aralytic ' secretion of intestinal juice, 
 414 
 of saliva, 397 
 Paraphasia, 972 
 Parasternal line, 90 
 Parathyroid, effects of removal of, 646 
 
 location of, 645 
 Parenteral absorption of proteins, 33 
 Parotid, secretory ciiaiiges in, 375, 376 
 Paroxysmal tachycardia, electro-cardio- 
 gram, 836 
 Parthenogenesis, 1123 
 Partial pressure of gases, 248 
 Parturition, 1137 
 
 I'edunck\ inferior, of cerebellum, 885 
 i'ellagra and vitamines, 632 
 Pelvic nerves, 179, },},i 
 Pendulum movements of intestines, 328 
 Pengavar Djambi as styptic, looi 
 Pentoses, 528, 593 
 Pentosuria, 487 
 Peptases, 361 
 Peptides, 2 
 Peptones and coagulation, 37 
 
 tests for, 10 
 Percussion, 232 
 Perfusion of heart, 205 
 Perikaryon, 850 
 
TNDEX 
 
 1237 
 
 Perimetry, 1048 
 
 Periodic brfathinp, production of, 287, 
 
 300 
 Peripheral reflex centres, 912 
 Peristalsis, 324, ,326, .121), 3;,o 
 Peritoneal cavity, absorption from, 439 
 Peroxydase, 76 
 
 Persistence theory (vision) 1050 
 Perspiration, visible and invisible, 512 
 Pettenkofer's test for bile acids, 366,462 
 Phagocytosis, 59 
 
 Phakoscope, Helmholtz's, 102 1, 1 103 
 Phenol, excretion in starvation, 604 
 Phenyl-alanin, 2, 352, 360 
 Phenyl-hydrazine test for sugar, 525 
 I'hlebogram, loi 
 Phlorhizin glycosuria, 551,717 
 Phloroglucin reaction for pentoses, 528 
 Phosphocaniic acid, 767 
 Phosphates, estimation of, 516 
 Phosphate triple, sediments, 479, 531 
 Phosphatides, 571, 794 
 digestion of, 421 
 metabolism of, 571 
 synthesis of, 597, 607 
 Phospho-proteins, 2 
 
 Phosphorus in degenerated nerve, 797, 
 798 
 in milk, 621 
 
 poisoning and fat migration, 563 
 Photo-electric reaction of eye, 839 
 Phrenic nerves and respiration, 275 
 afferent fibres in, 284 
 anastomosis of, with sympa- 
 thetic, 801 
 Phytosterins, 366, 570 
 Pia mater, 861 
 
 Pilocarpine, action of, on nerve-endings, 
 182 
 effect of, on heart, 166, 199 
 on salivary secretion, 457 
 on pupil, 1026 
 PUo-motor nerves, 180, 913, 1004 
 Pineal gland, 671, 933 
 Piotrowski's test, 8 
 Piston recorder, 233 
 Pitch, 310 
 Pithing a frog, 193 
 Pilot's tubes, 121 
 Pituitary body, 666, 933 
 
 action of extracts of, 668 
 functions of, 670 
 removal of, 667 
 Pituitrin, testing for, 670 
 Placenta, exchange of materials in, 1129 
 IMantar reflex, 915 
 Plasma, proteins of, 49 
 Plasmine of Denis, 34 
 I'lasmolysis, 428 
 }'latelets and coagulation, 37 
 I'lethysmograph, 128 
 Plethysmographic tracings, 129, 210 
 
 Pleural cannula, 234 
 
 Poikiloi hernial animals, production of 
 carbon dioxide in, 244 
 heat in, 693 
 Poiseuille's lasvs of flow, 85 
 
 space, 15, 193 
 Polar stimulation, law of, 741 
 I'olariincter, 528 
 
 Polarization of muscle and nerve, 829 
 Polygraph, 103 
 
 tracings, 209 
 Polymorphonuclear leucocytes, 17 
 Polypeptides, 2, 352, 361, 578 
 Polysaccharides, 3, 347, 348, 535, 537 
 Pons, 932 
 
 connections of, 883 
 grey matter of, 883 
 Post-central gyrus, 963 
 Posterior longitudinal bundle, 885 
 Posterior root ganglia, development of, 
 
 850 
 Post-sphygmic interval of heart, 97 
 Postural reflexes, 917, looo 
 Potassium in muscle, 767 
 
 salts, influence of, on heart-beat, 153, 
 200 
 Potential, electrical, 725 
 Precentral gyrus, 963 
 Precipitins, 31 
 Prepyramidal tract, 867 
 Presphygmic interval of heart, 97 
 Pressor nerves, 173 
 
 bases, 672 
 Pressure sensations, 1041, 1081, 1114 
 blood-, measurement of arterial, 109- 
 112, 210 
 in man, 1 13-1 16, 213 
 influence of exercise, 115 
 Primary colours, 1053 
 Prisms, loio 
 
 Proferment, 343, 351, 358, 376, 382 
 Prolamins, 615 
 Pi-olin, 352, 360 
 Propionic acid, 556 
 
 transformation into dextrose 
 538 
 Proprio-ceptive fields, 914 
 
 spinal fibres, 868 
 Prosecretin, 408 
 Protamins, 2 
 
 and coagulation, 44 
 Proteins, i 
 
 absorption of, 447 
 
 ' building stones ' of, 576 
 
 cleavage of, and absorption, 448 
 
 products of, 360 
 colour reactions of, 8 
 complete and incomplete, 613 
 consumption determined by supply, 
 
 607 
 digestion of, 351, 359, 361, 370, 417 
 formaldehyde reaction, 8 
 
123* 
 
 INDEX 
 
 Proteins, formation of glycogen from, 536 
 of sugar from, 538 
 
 general reactions of, 7 
 
 Heller's test fur, 524 
 
 in nutrition, relative value of dif- 
 ferent, 612 
 
 living and dead, 576 
 
 metabolism of, 572 
 
 necessary amount of, 623, 624 
 
 of tissues, specificity of, 321, 575 
 
 parenteral absorption of, 33 
 
 precipitation reactions of, 8 
 
 specific dynamic action of, 686 
 
 synthesis of, 573, 612 
 
 temperature of coagulation, 9 
 Protein-sparing action of fat, 606 
 
 of carbo-hydrates, 606 
 Proteoses, 3 
 
 action of, on coagulation, 37, 63 
 on clotting, 44 
 
 (and peptones), influence on blood- 
 pressure, 173, 215 
 
 formed in gastric digestion, 352, 458 
 action of erepsiii on, 371 
 of trypsin on, 362 
 
 in blood and tissues, 574 
 
 in urine, 489, 525 
 
 secondary, 13 
 
 tests for, 10 
 Prothrombin, 36 
 Protoplasm, structure of, 4 
 Prozymogen, 343, 351, 358, 382 
 
 granules, 376 
 Pseudo-globulin, 49 
 
 -podia, 17 
 
 reflexes, 904 
 Psychical secretion, 309, 404, 1099 
 Ptyalin, 346, 416, 455 
 ' Puberty gland,' 642 
 P\ilm()nary catheter, 259 
 
 circulation, 223 
 
 ventilation, 235 
 
 regulation of, 281 
 Pulse, anacrotic, 106 
 
 arterial, loi 
 
 curve, variation in form of, 106 
 
 effect of amyl-nitrite, 208 
 exercise on, 208 
 
 frequency of, 107, 210 
 
 tracings, 103, 209 
 
 venous, 09, 100, loi, 131, 209 
 
 wave, rate of propagation of, 108 
 Pulsus alternans, 155 
 
 bigeminus, 155 
 Pulvhiar, i)2i, 933 
 ' Puncture ' fever, 70X 
 
 glycosuria, 547 
 Pupilln-dilatitr fibres, 1023, 1025, 1 1 10 
 Purin bases in urine, 481 
 
 metabolism of, 592 
 
 bodies, chemistry of, 593 
 
 excretioQ of, 594 
 
 Purkinje fibres of heart, 147 
 Purkinje's figures, 1042, III3 
 Putrefaction in intestine, 422, 588 
 
 of proteins, action i>f products of, 
 072 
 Pyloric sphincter, relaxation of, 327, 418 
 Pyramidal cells, 853, 875, 958, 959 
 
 development of, 854 
 
 path in internal capsule, 878, 882 
 
 tracts, 866 
 
 connections of, 875 
 in different animals, 877 
 Pyramids, decussation of, 869, 875, R78 
 Pyrimidin bases, 593, 595, 597 
 Pyruvic acid, 544. 545, 546 
 
 Quadratus lumborum, action of, in 
 respiration, 227 
 
 Radiation from the skin, 681, 683 
 Radiometer, 681 
 Raftinose, 340 
 
 Rarefied air, effects of breathing, 295, 298 
 Rations, soldiers', 623, 627 
 Reaction of blood, 24 
 of degeneration, 804 
 of gastric juice, 420 
 of intestinal contents, 419 
 of milk, 1 139 
 of urine, 479 
 ■ Receptive ' substances, 182, 739 
 Receptor in reflex action, role of, 900 
 Receptors, 898 
 
 Reciprocal relation of vasomotors, 186 
 Recurrent sensibility, 892 
 Refened pain, 891 
 
 Reflex action, anatomical basis of, 8y8 
 extensor thrust, 904 
 flexion, i(03, 904, 997 
 inhibition in, 903 
 irradiation of, 905 
 of spinal cord, 897 
 scratch, 901, 902, 997 
 arc, fatigue of, 902 
 
 isolated conduction of impulses 
 
 in, 890 
 peculiarities of conduction in, 
 
 902 
 properties of, 902 
 refractory state in, 903 
 cardiac death, 171 
 centres in cord, 915 
 peripheral, 912 
 inhibition of heart, 170, 210 
 time, 014 
 Reflexes, axon, 803, 913 
 common path of, 899 
 co-ordination of, 908 
 effect of strychnine on, 899 
 tetanus toxin on, 899 
 facilitation of, 909 
 in disease, 914 
 
INDEX. 
 
 1239 
 
 Reflexes, influence of brain on spinal, 910, 
 996 
 in heniiplcRia, ')i i 
 inhibition nf antagonistic, 910 
 lurp spinal, 007 
 p<istnral, «)i/, lOOO 
 reiiiforcemeiii of, .ni, 998 
 reversal of, iHH, 00^, <)04 
 role of the receptor in, 900 
 short spinal, ')o6 
 
 simultaneous, combination of, 908 
 successive combinations of, 008, 909 
 superficial, 914 
 vasomotor, 185, 212 
 Refractory period of heart, 155 
 Rffjeneralion, of nerves, 798 
 
 autogenetic theory, 801 
 bifurcation of axons in, 802 
 of tissues, 1117 
 Reil, islaticl of, 973 
 Renal calculus, pain caused by, 901 
 Rennin, 33.^, 459, 719 
 
 functi<-)n of, 354 
 Reproduction, 11 17 
 
 in higher animals, 1118 
 Reserve air, 236, 303 
 Resistance, electrical, 724 
 measurement of, 725 
 of blood, 26,68 
 Resonance, 232, 310, 314 
 Respiration, accessoi^- phenomena of, 231 
 afferent nerves of, 276, 300 
 and blood-pressure, iii, 289 
 and nervous system, 274 
 artificial, 202, 230 
 
 by insufflation of oxygen, 204, 
 
 236 
 influence of, on blood-pressure, 
 292 
 breaking-point in, 234 
 calorimeter, 240, 676 
 chemical regulation of, 281 
 chemistry of, 239 
 comparative, 222 
 cutaneous, 299 
 efferent nerves of, 274 
 external, 225 
 
 forced, influence on carbon dioxide 
 excretion, 234, 245, 282, 283, 300 
 frequency of, 234 
 
 heat given off in, 681, 682, 683, 721 
 in condensed and rarefied air, 295 
 influence of cutaneous nerves on, 280 
 of muscular exercise on, 280 
 of superior laryngeal nerve on, 
 
 278,301 
 of vagi on, 276, 300 
 internal, 222, 265 
 mechanical phenomena of, 225 
 methods in chemistry of, 239, 305, 
 
 306 
 of muscle, 269 
 
 Respiration, regulation of, 276, 281 
 
 types of, 229 
 Respiratory apparatus, physiological 
 anatomy fif, 22 '» 
 capacity, 2i<t, 303 
 centre, 274 
 
 action of carix m dioxide on, 281, 
 282 
 of deficiency of oxygen 
 on, 281 
 automaticity of, 284 
 spinal, 285 
 ' dead space,' 236 
 exchange, 239, 242, 243, 305 
 
 gravimetric method, 240, 306 
 Zuntz's method, 239 
 movements, tracings of, 233, 278, 
 279, 280, 289, 301, 302 
 in man, 233, 289. 301 
 recording of, 233, 301 
 pressure, 238, 304 
 quotient, 241 
 sounds, 231 
 
 tracings, 233, 278, 279, 280, 289, 301, 
 302 
 Restiforni body, 885, 892 
 Resuscitation of heart, 153 
 
 of central nervous system, 990 
 scratch reflex in, 908 
 Reticular formation, 865, 870 
 Retina, development of, 850 
 
 epithelium, pigmented, 1048 
 fatigue of, 1049, 1055, 1056, Ilii 
 formation of image on, 1017, 1102 
 intermittent stimulation of, 1050, 
 
 II13 
 sensibility of different parts, 1058 
 time needed for excitation, 1049 
 Retinoscope, Geneva, ilio 
 Retinoscopy, 1034, 1 109 
 Rexerser, current, 732 
 Rheocord, 727, 810 
 Rhinencephalon, 922, 968 
 Rhcxlopsin, 1046 
 Ribose, 593 
 
 Right-handed people, aphasia in, 971 
 Rigor, heat-, production of carbon 
 dioxide in, 270, 777 
 mortis, 774 
 
 and muscular contraction, 776 
 production of carbon dioxide 
 in, 270, 777 
 of lactic acid in, 776, 
 208 
 removability of, 779 
 time of onset of, 776, 778 
 production of heat in, 778 
 Ringer's solution, 66 
 Ritters tetanus, S31, 846 
 Ritter-\'alli law, 785 
 
 Riva-Rocci apparatus for blood-pressure, 
 "3.213 
 
I -MO 
 
 IXDEX 
 
 Rulandic aroa of cortpx, 051 
 
 spiisoiy fiinctiun of, 963 
 fissure, 875 
 
 Thane's rule, for position of, 
 956, 963 
 Rontgen rays for study of gastro-intes- 
 
 tiiial movements, 327, 328 
 Rouleaux formation, ib 
 Rubro-spinal tract, 867 
 
 connections of, 884 
 
 Saliva, action of, in stomach, 348, 417 
 amylolytic action of, 346, 454 
 antilytic secretion of, 398 
 chemistry of, 344, 454 
 effect of drugs on secretion of, 392, 
 
 394,457 
 freezing-point of, 387 
 functions of, 346 
 paralytic secretion of, 397 
 psychical secretion of, 399 
 reflex secretion of, 398 
 Salivary centre, 400 
 
 glands, cranial nerves of, 391, 394, 
 
 396,456 
 extirpation of, 673 
 oxvgen consumption in, 266, 
 
 268 
 secretory changes in, 375, 3S2 
 secretory pressure in, 393 
 sympathetic nerves of, 391, 394, 
 
 397, 457 
 trophic-secretory fibres of, 395 
 Salt hunger. 381, 621 
 
 solution, physiological, 194 
 Salts, absorption of, 446 
 
 in diet, 620, 625, 629 
 
 in fixxl, r61e of, in nutrition, 625 
 Saponification, II, 367, 421 
 Saponin, laking of blood by, 70 
 Sarkin, 589 
 
 Scalene muscles in respiration, 227 
 Scheiner's experiment (vision), 1031, II03 
 Schiitz's law of ferment action, 342 
 Sclero-proteins, 2 
 Scratch reflex, 901 
 
 in resuscitation, 908 
 Scurvy and deficiency in diet, 632 
 Sealing of wounded vessels, 46 
 Sebaceous glands, fat formation in, 365 
 Sebum, 312 
 
 Secondary contraction, 203, 833, 842 
 Secretin, 407 
 Secretion, internal, 633 
 Segmentation of f(X)d in intestine, 329 
 Semicircular canals and equilibration, 
 
 936 
 Semilunar valves, 8g 
 
 and dicrotic wave, 105 
 moment of closure of, 96 
 Semisection of cord, effects of, 894 
 Sensation, relation of stimulus to, iioo 
 
 Sensations, cold, 1082 
 
 cutaneous, 1078 
 
 heat, 1 08 1 
 
 hunger, 1096 
 
 muscular, 1094 
 
 ordinary, cerebral localization of, 968 
 
 pain, 1083 
 
 tactile, cerebral localization of, 968, 
 969 
 
 thirst, 1096 
 
 touch, 1078, 1080 
 Sensibility, recurrent, 797, 892 
 Sensori-motor area, 963 
 Sensory aphasia, 972 
 
 areas, visual centres, 923, 965 
 
 functions of Rolandic area, 963 
 
 paths, decussation of, 894 
 in internal capsule, 881 
 scheme of, 880 
 Septo-marginal bundle, 868 
 Serin, 360 
 
 Serratus posticus, action of, in respira- 
 tion, 227 
 Serum, action of, on artery rings, 46, 66 
 
 albumin, 47, 65, 3"3, 819 
 
 coagulation of, 47 
 
 composition of, 47, 65 
 
 globulin, 34, 47, 65, 575 
 
 immvme, 31 
 
 inorganic salts of, 49 
 
 proteins, 49, 65, 37-2 
 Sexual organs, internal secretion of, 640 
 Sham feeding, 402 
 Shock, anaphylactic or protein 32 
 
 spinal, 888, 912 
 
 surgical or vascular, i<)2 
 Sighing, 2S8 
 Sino-auricular node, 81 
 Sinus venosus, 80, 81, 141, 194 
 
 stimulation of, 198 
 Skate, electrical organ, 841 
 Skatol, 424 
 
 formation of, in intestine, 422 
 Skatoxyl in urine, 484, 518 
 Skiascopy, 1034, II09 
 Skin, action currents of, 838 
 
 effects of varnishing, 21)9, 699 
 
 excretion by, 311 
 
 respiration by, 299 
 
 sensations, 1078 
 Smell, 1073, III4 
 
 centre for, 022, 967 
 Smi.Dth nniscle, composition of, 768 
 Snake-venotn, effect of, on coagulation 
 
 43 
 Sneezing, 288 
 
 Solutions, scheme for testing, 13 
 Sorbite, 3 
 Sp<'citic energy of nerves, 979 
 
 dynamic action of f(X)ds, 686 
 Speech, 312 
 
 nervous mechanisra of, 315 
 
INDEX 
 
 1241 
 
 Sprnnin, 642 
 SphiiictiT aui, 320, 33:1 
 
 caidiar, 320, 324, 331. 335, 336 
 
 ileocolic, 331, 335, 421 
 
 pylori, 320, 326, 327. 331. 335. 
 
 418 
 vesicae, 510 
 Sphygmograph, Marey's, 103 
 
 Dudgeon's, 208 
 Sphygmographic tracings, 103, 104, 209 
 Sphyginoniauomcter of Erhmger, 114 
 
 of Hill and Barnard, 113 
 Spinal accessory nerve, ()3i 
 
 united with fa:ial, 976 
 cord and bulb, centres of, 919 
 automatism of, 916 
 conduction of nervous im- 
 pulses by, 890 
 consciousness in, 889 
 effects of transection of, 888 
 grey matter of, 863 
 reflex action of, 897 
 scheme of cross-section of, 867 
 section of, to show tracts, 865 
 semisection of, effects of, 894 
 ganglia and reflexes, 912 
 cells of, 854 
 development of, 850 
 fatigue of, 913 
 roots, degeneration of, 797 
 
 function of, 891 
 shock, 888, 912 
 Spinotectal fibres, 874 
 Spino-thalaniic fibres, 874 
 Spirograph of Fitz, 233, 300 
 Spirometer, 233, 303 
 Splanchnic nerves and adrenals, 661 
 and hyperglycemia, 547, 55° 
 and intestines, 332 
 and kidneys, 506 
 vasomotors in, 177 
 Spleen and hannatopoiesis, 21 
 
 and pancreas, mutual relations of, 
 
 411 
 functions of, 672 
 grafting of, 672 
 proteolytic enzyme of, 411 
 Spongioblasts, 849 
 Staircase phenomenon, 156, 749 
 Standing, 943 
 
 Stannius' experiment, 144. 194. ^99 
 Starch, tests for, II 
 Starvation, excretion of urea in, 604 
 loss of weight of organs in, 603 
 metabolism in, 604 
 protein metabolism in, 602 
 Stasis, 61, 103 
 Steapsin, 358, 363. 4^1 
 Stearic acid, 536, 55^ 
 Stercobiliii, 424 
 Stereognosis, 963 
 Stereoscopic vision, 1039 
 
 Sterins, or sterols, 366 
 (ligesiion of, 421 
 metabolism of, 570 
 Stilling, cervical and sacral nuclei of, 864 
 Stiinulaiils in diet, 630 
 Stimulation hv voltaic current, 741, 784. 
 810, 845 
 chemical, 737, 783 
 law of polar, 741, 810, 845 
 recording beginning and end of, 201 
 Stimuli, adequate, 901, 979, 1007 
 different kinds of, 7^7 
 summation of, 736, 816 
 Stimulus, relation of, to sensation, iioo 
 
 Weber's law, iioo 
 Stokes- Adams disease, 150 
 Stomach, absorption of proteins by, 418 
 auto-digestion of, 388, 465 
 digestion of fat in, 355, 421 
 excision of, 357 
 movements of, 326 
 nerves of, 331, 401 
 pouch, 403 
 
 protection from gastric juice, 388 
 Stria; acustica-, 928 
 Striped muscle, structure of, 742 
 Stromuhr, 120 
 
 Strychnine and reversal of reflexes, 904 
 effect of, on reflexes, 899 
 in localization of sensory cortical 
 zones, 968 
 Substantia nigra, 870 
 Substrate, 338 
 Succus entericus, 370. See Intestinal 
 
 juice 
 Suckling, food requirement of, 628 
 Sugar and muscular work, 541, 772 
 constitution of, 337 
 consumption of, in diabetes, 554 
 destruction of, 541 
 formation of, from amino-acids, 538, 
 545, 590 
 from fatty acids, 538, 545, 566 
 in blood, 47, 50, 446, 499, 500, 540, 
 
 552, 717 
 intermediary metabolism of, 542 
 ill urine, tests for, 488, 525 
 regulating centre, 548 
 
 mechanism, 547 
 tolerance, 340, 351, 637 
 Sulphates in urine, 484 
 
 estimation of, 517 
 Sulphocyanide in saliva, 346, 454 
 Summation of stimuli, 736, 816 
 Superposition of contractions, 756, 816 
 Supplemental air, 236, 303 
 Suprarenal capsules and coagulation, 45 
 extract, effect of, on blood-pressure, 
 173, 177, 216, 655 
 Suprarenals, 655. See Adrenals 
 Suprarenin. See Adrenalin and Epi- 
 nephrin 
 
124: 
 
 INDEX 
 
 Surface and mass of body, relation be- 
 tween, 693 
 lieat-pioduction and blrx^id-flow, re- 
 lations of, 696 
 phenomena and absorption, 431 
 tension, 429 
 
 and muscular contraction, 744 
 Surgical shock, 192 
 Suturing bloodvessels, 1145 
 Sweat-centre, 513 
 
 composition of, 511 
 function of, 514 
 quantity of, 512 
 
 secretion of, influence of nerves on, 
 513 
 Swim-bladder, secretion of gases in, 265 
 Sympathetic cardiac tibres of, in frog, 
 
 137, 196, 199 
 cervical, vaso-motor fibres in, 175 
 ganglion cells, action of nicotine on, 
 
 182 
 nervous system, 1003 
 vibration, 314, 760, 1073, II13 
 Synapse, 852 
 
 resistance of, 899 
 Syntheses in the body, 542, 570, 571, 573, 
 
 578, 579. 580, 591, 597 
 Systoles, extra, 155 
 
 Tachycardia, 930 
 Tactile sensations, 1079 
 
 cortical centres for, 968 
 
 paths for, 896 
 Tadpole test for thyroid active substance, 
 
 633 
 Talbofs law, 1040, 1113 
 Tambour, 91 
 
 for respiratory movements, 233 
 
 Marey's, 208 
 Taste, 1077, I113 
 
 centre for, 968 
 
 ners'es of, 925 
 Taurin, 365, 579 
 Taurocholic acid, 365, 462 
 Tea, 594, 630 
 Tears, 475 
 Teeth, 320 
 
 Tegmentum, 870, 874 
 Telencephalon, 850 
 Telodendrion, 852 
 Temperature, 674 
 
 daily curve of, 712 
 
 discrimination, 1116 
 
 in cavities of heart, 710 
 
 in mouth, 712 
 
 in rectum, 712 
 
 normal variations in, 71a 
 
 of blood, 711 
 
 of body, 680 
 
 measurement of, 675 
 
 of brain, 689, 712 
 
 of coagulation, 9 
 
 Temperature of different parts, 711, 712 
 of skin, 676, 712 
 post-mortem rise of , 714 
 regulation, 690 
 
 influence of curara on, 693 
 in iiibernating animals, 703 
 sensations, 1082, 1088, 1092, HIS 
 
 paths for, 896 
 topography, 709 
 Tension of carbon dioxide in blood, 261, 
 264 
 of gases, 247 
 
 in alveoli, 241, 263 
 of oxygen in blood, 253, 261 
 
 measurement of, 238 
 surface. See Surface tension 
 Testes, interstitial cells of, 641 
 Testicle, action of extracts of, 642 
 Testicles, internal secretion of, 640 
 Tetanizing current, arrangement for, 
 
 200 
 Tetanus (electrical), composition of, 756, 
 816 
 Ritter's, 831,846 
 secondary, 203, 833, 842 
 toxin effect of, on reflexes, 899 
 Tetany, after parathyroidectomy, 646 
 Tethelin, 670 
 
 Thalamico-spinal tract, 867, 883 
 Thane's method for position of fissure of 
 
 Rolando, 956, 963 
 Theine. 481, 383, 394, 632 
 Theobromine, 481, 583, 594, 631 
 Theophyllin, 481, 594 
 Theory, Hering's, of colour vision, 1057 
 of identical points, 1037 
 Young-Helmholtz, 1053 
 Thermo-electric junction, 675, 680, 763 
 Thermogenic nerves, 780 
 Thermometer, electrical resistance, 676, 
 677, 783 
 maximum, 675 
 Thermometry, 674 
 Thermopile, 763 
 Thennotaxis, 690 
 Thirst, sensation of, 930, 1099- 
 Thiry s fistula, 370 
 Thrombin, 35 
 
 formation of, 36 
 
 nature of action on fibrinogen, 41 
 preparation of, 41 
 specificity of, 40 
 Thrombocytes. See Bl(x»d plates 
 Thrombogen, 36 
 sources of, 38 
 specificity of, 40 
 Thronibokinase, 36 
 preparation of, 65 
 sources of, 38, 40 
 specificity of, 40 
 Thromboplastic substances, 41 
 Thrombo-regulative mechanism, 43 
 
ISDEX 
 
 1243 
 
 Thrombrisis, 45 
 Thro'ubotaxis, 42 
 Tluinib ceiitrt', 073 
 Tliyinin, s>},\ 
 
 Thymus, iiivolutidn of, 644 
 grafting oi, 645 
 lymphocytes of, 643 
 Illation of, to sexual glands, 644 
 removal ot, 645 
 Thyroid and heat-production, 650, 699 
 changes with meat diet, 650 
 grafting of, 648 
 hyperplasia of, 640 
 influence of iodine on, 650 
 
 of nutritive conditions on, C40 
 iodine in, 632 
 
 influence on tadpoles, 653 
 nerves of, 653 
 Thyroidin, 649 
 Thyroids, effects of excision of, 647, 
 
 648 
 Tickling, sensation of, 1078, 1080 
 Tidal air, 235 
 
 measurement of, 303 
 Timbre of sounds, 310 
 
 of vowels, 313 
 Time-markers, 195, 732 
 Tissue extracts and coagulation, 36 
 
 respiration, 265, 269 
 Tissues, cultivation of, outside the body, 
 1142 
 gas tensions in, 267 
 transplantation of, 641, 1142 * 
 Tone of muscles, 917 
 vaso-motor, 184 
 Tonsils, 320 
 Topognosis, 963 
 Torpedo, 840 
 Torricelli's theorem, 83 
 Touch, 1079, 1080, 1114 
 
 spots, 1080 
 Trachea, to put a cannula in, 202 
 Tracheal cannula, 201 
 Tracts in spinal cord, 865 
 
 myelination of, 961 
 Transfusion, influence on blood-pressure, 
 
 191,214 
 Transplantation of tissues, 641, 1142 
 Traube-Hering curves, 294 
 Tricuspid valve, 86, 96 
 Trigeminus nerve, 924 
 Tripalmitin, 556 
 Tristearin, i, 556 
 Trochlear nerve, 924 
 Trommer's test, for sugar, 10, 525 
 Trophic nerves, 805 
 
 tone, 919 
 Trypsin, 345. 358, 359, 411, 418, 420, 
 
 460 
 Trypsinogen, 358, 372, 377, 389, 39i 
 Tryptophane, 2, 360, 487, 615 
 'Twitch,' 745,811 
 
 Tympammi, 1065 
 
 Tyrosin, 2, 360,462, 4«S. 575. 576 
 
 Morner's test for, 462 
 Tyrosinase, 272 
 
 Uffelmann's test for lactic acid, 460 
 Ultra- microscope, coagulation studied 
 
 I'V. 39 
 Uncinate gyrus, 968 
 Uracil, 593 
 Urea, in blood, 47, 400 
 
 estimation of, 518, 520 
 
 excretion of, by kidney, 402, 496, 497, 
 498, 502 
 in fever, 706, 707 
 in starvation, 604 
 premortal rise in starvation, 
 603 
 
 formation of, 583 
 
 processes of formation of, 588 
 Urease, 478 
 
 method of estimating urea, 518 
 Uric acid, 481, 523 
 
 destruction of, 595 
 
 exogenous and endogenous, 595 
 
 formation of, 585, 590 
 
 in gout, 487, 590 
 
 sources of, 591 
 Uricolysis, 595, 596 
 Uricoxydase, 596 
 Urine, acidity of, 478, 479, 515 
 
 albumose in, 509, 525, 572 
 
 alkapton in, 483, 581 
 
 amino- acids in, 481, 488, 579 
 
 ammonia in, 480, 519, 521 
 
 bile-pigments in, 483, 531 
 
 bile-salts in, 489, 528, 531 
 
 carbo-hydrates in, 482 
 
 chlorides in, 477, 483, 515 
 
 composition of, 476 
 
 creatinin in, 481, 523 
 
 cystin in, 488, 532, 579 
 
 ethereal sulphates in, 484, 517 
 
 expulsion of 510 
 
 ferments in, 483 
 
 freezing-point of, 485, 529 
 
 ha-matoporphyrin in, 483 
 
 hippuric acid in, 481, 524 
 
 in disease, 485, 524 
 
 in fever, 703 
 
 incontinence of, 511 
 
 indican, indoxyl in, 484, 487, 517 
 
 oxalic acid in, 478, 481, 532 
 
 phenol in, 484, 604 
 
 phosphates in, 483, 516 
 
 phvsico-chemical analysis of, 4S5, 
 
 529 
 
 pigments of, 482 
 proteins in, 482, 488, 524 
 purin bases in, 481 
 reabsorption of, from the tubules, 
 494. 502 
 
1244 
 
 INDEX 
 
 Urine, secretion of, 489 
 
 Heidenhain's experiments on, 
 
 495 
 influence of circulation on, 506 
 
 of nerves on, 308 
 Nussbaum's experiments on, 
 
 498 
 pigments, by the kidney, 495 
 theories of, 491, 502 
 work done by kidney in, 504 
 secretory pressure of, y>(^ 
 sediments of, 478, 479, 488, 531 
 skatoxyl in, 484, 518 
 specific gravity of, 4 7(>, 515 
 sugar in, 487, 488, 526 
 sulphates in, 484, 517 
 systematic examination of, 531 
 temperature of, 712 
 total nitrogen in, 477, 521 
 urea in, 480, 487, 518 
 uric acid in, 480, 4S7, 523, 531 
 Urobilin, 365, 424, 482 
 Urobilinogen, 365 
 Urochrome, 482 
 Uroerythrin, 482 
 ' Urohypertensine,' 672 
 Urorosein, 482 
 
 Uterus rings and segments, isolated, II47 
 Utricle, 936, 1067 
 
 Vago-sympathetic nerve, in frog, 141, 
 
 196, 198, 199 
 Vagotomy, death after double, 286 
 Vagus, stimulation during resuscitation 
 after cerebral ana-mia, 187 
 in mammals, 162, 164, 203, 212 
 inspiratory and expiratory fibres in, 
 
 276-279 
 negative variation of, 277, 828 
 nerve, functions of, 929 
 of frog, dissection of, 196 
 relation of, to respiration, 276 
 stimulation of, in dog, 203, 212 
 in frog, 198 
 Valin, 360 
 
 Valsalva's experiment, 296 
 Valves of veins, 82 
 
 semilunar, moment of closure, 96 
 Varnishing the skin, 299, SM. 690 
 Vaso-constrictor and vaso-dil ator nerves, 
 173 
 differences in excitability of, 175 
 property of shed blood, 45 
 Vaso-dilator fibres, 179 
 
 in cervical sympathetic, 176 
 Vaso-dilators of chorda tympani, 179, 
 392 
 of nervi erigentes, 179, 180 
 Vaso-motor centres, 182 
 
 anatomical relations of, 185 
 nature of tone of, 184 
 spinal, 183 
 
 Vaso-motor nerves, 173, 175, 176 
 
 course of, 181 
 
 in cervical sympathetic, 175 
 
 in splanclinir, 1 77 
 
 ill trigeminus, 176 
 
 of brain, i 7() 
 
 of extremities, 177 
 
 of heart, 178 
 
 of lungs, 179 
 
 of muscle, 178 
 
 of veins, 180 
 
 reciprocal relations of, 186 
 reflexes, 183, 212 
 
 studied by calorimetric method, 
 188, 221 
 tone, 184 
 Vaso-niotors, methods of investigating, 
 
 174 
 Veins, action of adrenalin on, 181 
 circulation in, 132 
 factors concerned in flow in, 133 
 pressure in, 132 
 measurement of, in man, 133 
 pulse in, 100, 131 
 vaso-motor nerves of, 180 
 velocity of blood in, 134 
 Vella's fistula, 370 
 Velcjcity of blood, 117, 127 
 in capillaries, 130 
 in veins, 134 
 measurement of, 120 
 Vena porta?, vaso-motor nerves of, 180 
 Veuous blood, tension of carbon idoxide 
 in, 261 
 pressure-curve, 98, 100 
 pulse, 99, 100, 131, 134 
 tracing, 100, 209 
 Ventilation, 242 
 
 pulmonary, 235, 281 
 Ventricle, suction action of, loi 
 Ventricular pressure-curve, 94 
 Wratrine, action of, on muscle, 754, 814 
 Vesicular murmur, 231 
 Vestibule, paths from, 928 
 Vestibulo-spinal tract, 867 
 
 connections of, 884 
 Visceral pain, 891, 901 
 Visuo-psychic area of Campbell, 966 
 Vision, ;ifter-images, 1053 
 
 apparent size of objects, 1042 
 astigmatism, 1031, 1105 
 blind spot, 1044, 1 107 
 colour, 1 05 1 
 
 Hering's theory, 1057 
 mixing, 1033, IIII 
 triangle, 1034 
 
 \'oiing-Helnili(jlt7. theory, 1053 
 Cf)lour-blindness, io5(), 11 12 
 ct)mparative anatomy, 1013 
 contrast, 1036 
 duration of stimuli, 1049 
 I'icks persistence theory, 1050 
 
IXDHX 
 
 1245 
 
 Vision, Holnigron's wools, 11 12 
 
 irradiation, 1061 
 
 Listing's law, 1063 
 
 Maxwell's spot, 1107 
 
 nu-asurcment of field of, 1038, II06 
 
 oplithalnionictcr, loji, II05 
 
 ophthalmoscope, m;!, II08 
 
 pfriinetr\', los^s, 1106 
 
 Purkinje's linuri's, 104J. III3 
 
 relation of rods and cones to, 1045 
 
 skiascopy, 1034, 1109 
 
 stereoscopic, 1039 
 
 Talbot's law, 1050, III3 
 
 thet)ry of identical points, 1037 
 Visual acuity, IIII 
 
 centres, 965 
 
 path, 883, 923, 966 
 
 purple, 840, 1047 
 Vital capacity, 236, 303 
 Vitaniines, 617, 632 
 Vitreous humour, 466. 1016 
 Vivi-diffusion apparatus, 48 
 V^ocal cords, 307 
 
 in voice production, 308 
 movements of, in respiration, 
 
 311 
 paralysis of, 316 
 Voice, 307 
 
 air-pressure necessary for, 309 
 falsetto, 312 
 in children, 310 
 nervous mechanism of, 315 
 \oltaic current, alterations in excita- 
 bilitv and conductivity by, 
 785-788, 844-846 
 stimulation by, 741, 784, 810 
 Volume pulse, 127 
 Voluntary contraction, 760 
 
 electrical changes in, 762 
 fatigue in, 753 
 movements, acquisition of, 981 
 Vomiting, 335 
 centre, 336 
 
 VoniitJMf;, induced by apomorphine, 336, 
 
 459. 464 
 Vowel cavities, 314 
 
 formation, theories of, 314 
 V(jwels, timbre of, 313 
 
 Warmth, sensations of, 1081 
 Water, absorption of, 446 
 
 in diet, 029 
 
 production of, in the body, 620 
 Weber's law (stinmli), iioo 
 Wernicke, aphasia ot, 971 
 
 zone of, 971 
 Wharton's duct, 391 
 
 insertion of cammla in, 456 
 Wheatstone's bridge, 726 
 Whey protein, 354, 719 
 Word- blindness, 972 
 
 -deafness, 967, 972 
 Wounded vessels, sealing of, 46 
 
 Xanthin, 481, 589, 592, 593 
 
 fever, 707 
 Xanthoproteic reaction, 8 
 Xerostomia, 400 
 
 Yawning, 288 
 
 Yeast and vitamines, 633 
 
 test for sugar, 4S8, 526 
 Yellow atrophy, acute, and excretion of 
 amino-acids, 586 
 spot, 975, 1 107 
 Yohimbine, action on refractor>- period 
 in nerve, 783 
 vaso-dilator action on submaxillary, 
 
 Youug-Helmholtz theory of colour vision, 
 1053 
 
 Zein, as a food, 615 
 Zoosterins, 366, 570 
 Zymase, 337 
 
 Zymogen, 351, 356, 382, 383, 389 
 granules, 376 
 
 BAILLlfeRE, TINDALL AND COX, 8 HENRIETTA STREET, COVENT GARDEN, LONDOH 
 
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