13 c QP34- COLUMBIA UNIVERSITY DEPARTMENT OF PHYSIOLOGY THE JOHN G. CURTIS LIBRARY > ^' Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/handbookofphysio1905kirk HALLIBURTON'S HAND-BOOK OF PHYSIOLOGY KIRKES' HAND-BOOK OF PHYSIOLOGY HAND-BOOK PHYSIOLOGY By W. D. HALLIBURTON, M.D., F.R.S. PROFESSOR OF PHYSIOLOGY, KING'S COLLEGE, LONDON. TWENTIETH EDITION WITH NEARLY SEVEN HUNDRED ILLUSTRATIONS INCLUDING SOME COLOURED PLATES. PHILADELPHIA : P. BLAKISTONS SON, & CO. 1012 WALNUT STREET 1905 [Printed in Great Britain ] I\ I AUTHOR'S PREFACE TO THE SIXTH EDITION I have taken advantage of the alteration in the size of the page and of the type which Mr Murray has thought wise to adopt, to make considerable changes in the present edition. I have throughout, however, endeavoured to remember that the main object of the work is to supply students with a complete but elementary text-book. Sections which treat of what may be termed " advanced work " have therefore been made as brief as possible, and have been inserted in small print. The student on reading the book for the first time will find it best to omit these passages. When he has mastered the continuous story told in the large text, he will then be able to study what is given in small type. During the past few years two important advanced text-books have made their appearance ; one published in this country, under the editorship of Professor Schafer, F.K.S., and the other in America, under the editorship of Professor Howell. I am much indebted to both of these for assistance in bringing this book up to date. I have also to thank Professor Schafer for allowing me to copy several of the instructive new diagrams which have appeared in his Essentials of Histology. The parts of this book which have undergone most revision are those relating to the nervous system and to the circulation of the blood. Under the latter head I have devoted some space to those elementary principles of physics which underlie what is often called hemodynamics. Experience in teaching has shown me that although students may have previously received instruction in physics and Vlll PREFACE chemistry, they are not as a rule capable of applying their knowledge to the elucidation of physiological problems. Hence my present attempt to supply them with the necessary aid. My friend Professor T. Gregor Brodie has made a special study of the subject of haemo- dynamics, and I owe him my sincerest thanks for the assistance he has given me in revising the part of the present edition which deals with the circulation. W. D. HALLIBUKTON. King's College, London, 1904. AUTHOR'S PREFACE TO THE PRESENT EDITION In the year that has elapsed since the publication of the last edition, I have again subjected the book to a thorough revision. The only parts, however, which have been materially altered are the chapters relating to the special senses, and to the generative organs and development. I am much indebted to Dr C. S. Myers, Lecturer on Experimental Psychology at this College, for his valued help in revising the account given of the special senses; and to Professor Arthur Eobinson, now of Birmingham University, for great assistance in rewriting the sections relating to generation and development. In former editions the chick has been largely taken as the type of a developing vertebrate animal ; now the main descriptions relate to the mammalian embryo. This has involved the disappearance of numer- ous old illustrations, and the introduction of as many as thirty-six new ones. W. D. HALLIBUKTON. King's College, London, 1905. CONTENTS CHAPTER I Introductory . Definition of the Science of Physiology Physiological Methods The Organs, Tissues, and Cells of the Body Animal and Vegetable Cells . PAGE 1 1 3 4 5 CHAPTER II The Animal Cell ........ 8 Protoplasm ...... 8 Nucleus ...... 10 Attraction Sphere ..... 12 Protoplasmic Movement .... 12 Cell division ...... 16 The Ovum ...... 20 CHAPTER III Epithelium ......... 22 Classification of Epithelium . 22 Pavement Epithelium 22 Cubical, Spheroidal, and Columnar Epithelium 25 Ciliated Epithelium .... 27 Ciliary Motion .... 29 Transitional Epithelium 30 Stratified Epithelium .... 31 Nutrition of Epithelium 33 Chemistry of Epithelium 33 CONTENTS CHAPTER IV The Connective Tissues Areolar Tissue Fibrous Tissue Elastic Tissue . Adipose Tissue Retiform Tissue Adenoid or Lymphoid Tissue Basement Membranes Jelly-like Connective Tissue PAOI 35 36 41 43 43 4G 47 47 48 CHAPTER V The Connective Tissues — continued Cartilage Bone . Ossification Teeth . The Blood 49 49 54 59 64 76 CHAPTER VI Musculab Tissue. ...... 78 Voluntary Muscle ...... 79 Red Muscles ....-•• 87 Cardiac Muscle ...... 87 Plain Muscle ....-•• 87 Development of Muscular Fibres .... 88 CHAPTER VII N uve Structure of . Terminations of Development of 90 90 95 96 CHAPTER VIII IRRITABILITY AM) CoNTHAC 1 II.l'l Y CHAPTER IX Contraction of Mlscxe— Summary 105 CONTENTS XI CHAPTER X Change in Form in a Muscle when i Instruments used Simple Muscle Curve . The Muscle-Wave Effect of two Successive Stimuli Effect of more than two Stimuli Tetanus Voluntary Tetanus . Contracts PAGE 107 107 116 US 119 120 121 121 CHAPTER XI Extensibility, Elasticity, and Work of Muscle 125 CHAPTER XII The Electrical Phenomena of Muscle 133 CHAPTER XIII Thermal and Chemical Changes in Muscle . Fatigue ..... Rigor Mortis ..... Chemical Composition of M.tscle 147 150 153 154 CHAPTER XIV Comparison of Voluntary and Involuntary Muscle 158 CHAPTER XV Physiology of Nerve Classification of Nerves Investigation of Nerve Functions Degeneration of Nerve Roots of the Spinal Nerves . Changes in Nerve during Activity Nerve Impulses Crossing of Nerves . Chemistry of Nerve . 161 161 164 164 16S 171 172 173 175 CHAPTER XVI Electrotonus 179 XII CONTENTS CHAPTER XVII Nerve Centres . Structure of Nerve-Cells The Significance of Nissl's Granules Classification of Nerve-Cells . Law of Axipetal Conduction . The Circulatory System The Heart Course of the Circulation Arteries . Veins Capillaries Lymphatic Vessels CHAPTER XVIII CHAPTER XIX The Circulation of the Blood CHAPTER XX Physiology of the Heart The Cardiac Cycle . Action of the Valves of the Heart Sounds of the Heart . Coronary Arteries Cardiographs . Intracardiac Pressure Frequency of the Heart's Action Work of the Heart Innervation of the Heart The Excised Heart CHAPTER The Circulation in the Blood-vessels Use of the Elasticity of the Vessels Blood-pressure Velocity of the Blood-Flow . The Time of a Complete Circulation The Pulse The Capillary Flow The Venous Flow The Vaso-motor Nervous System Plethysmography Pathological Conditions Local Peculiarities of the Circulation XXI CONTENTS Xlll CHAPTER XXII Lymph and Lymphatic Glands Composition of Lymph Lymphatic Glands Lymph Flow . Relation of Lymph and Blood Formation of Lymph . Osmotic Phenomena . PAGE 314 314 315 317 318 318 321 CHAPTER XXIII The Ductless Glands Spleen Haemolymph Glands Thymus Thyroid Parathyroids . Supra-renal Capsules Pituitary Body Pineal Gland . Coccygeal and Carotid Glands 328 329 333 334 335 337 338 341 341 342 CHAPTER XXIV Respiration Respiratory Apparatus Respiratory Mechanism Nervous Mechanism of Respiration Special Respiratory Acts Effect of Respiration on the Circulation Asphyxia .... Effects of Breathing Gases other than the Atmosph Alterations in the Atmospheric Pressure Chemistry of Respiration 343 343 351 360 364 366 370 373 374 374 CHAPTER XXV The Chemical Composition of the Bodv Carbohydrates Fats . Proteids The Polarimeter Ferments 386 386 393 395 404 405 XIV CONTENTS CHAPTER XXVI The Blood Coagulation of the Blood Plasma and Serum Blood-Corpuscles Blood Platelets Development of the Blood-Corpuscles Chemistry of the Blood-Corpuscles . Haemoglobin .... Immunity .... PAOE 409 412 414 418 423 425 428 429 439 CHAPTER XXVII The Alimextahy Canal 445 CHAPTER XXVIII Food Milk . Eggs . Meat . Flour . Bread . Cooking of Food Accessories to Food 459 461 465 466 467 468 468 469 CHAPTER XXIX Secreting Glands Electrical Variations in Glands 470 473 CHAPTER XXX Saliva ..... The Salivary Glands . Secretory Nerves of Salivary Glands The Saliva .... 474 474 476 479 CHAPTER XXXI The Gastric Juice Composition . Innervation of the Gastric Glands Action of Gastric Juice 481 483 485 486 CONTENTS XV CHAPTER XXXII Digestion in the Intestines .... The Pancreas ..... Composition and Action of Pancreatic Juice Secretory Nerves of the Pancreas The so-called Peripheral Reflex Secretion of the Pancreas The Succus Entericus .... Bacterial Action ..... Leucine and Tyrosine . Extirpation of the Pancreas .... PAGE 490 490 491 493 494 495 498 499 500 CHAPTER XXXIII The Liver Functions Bile .... Glycogenic Function of the Liver Nerves of the Liver . 502 507 508 514 518 CHAPTER XXXIV The Absorption of Food 519 CHAPTER XXXV The Mechanical Processes of Digestion Mastication Deglutition Movements of the Stomach Vomiting Movements of the Intestines 525 525 526 528 530 531 CHAPTER XXXVI The Urinary Apparatus Nerves of the Kidney Activity of the Renal Epithelium Work done by the Kidney Extirpation of the Kidneys . Passage of Urine into the Bladder Micturition 535 543 546 547 548 548 549 XVI CONTENTS CHAPTER XXXVII PAGE The Uhink ......... 551 Urea 552 Ammonia 559 Uric Acid 560 Hippuric Acid 562 Creatinine 563 Inorganic Constituents of Urine 564 Urinary Deposits 567 Pathological Urine 570 The Skin . CHAPTER XXXVIII -.74 CHAPTER XXXIX General Metabolism .... Discharge of Carbon Discharge of Nitrogen Balance of Income and Discharge in Health Inanition or Starvation Exchange of Material in Diseases Luxns Consumption .... 583 586 587 587 5S9 592 594 CHAPTER XL Animal Heat ....... Regulation of the Temperature of Warm-blooded Animals 598 603 CHAPTER XLI The Central Nervous System 606 CHAPTER XLII Structure of the Spinal Cord 608 CHAPTER XLIII The Brain 622 CHAPTER XLIV Structure of the Bulb, Pons, and Mid-Brain The Cranial Nerves .... 626 640 CONTENTS XV11 CHAPTER XLV Structure of the Cerebelli t m . PAGE 648 CHAPTER XLVI Structure of the Cerebrum Histology of the Cortex The Convolutions 652 656 662 CHAPTER XLVII Functions of the Spinal Cord . The Cord as an Organ of Conduction Reflex Action of the Cord Reflex Action in Man Spinal Visceral Reflexes 667 667 669 671 676 CHAPTER XLVIII Functions of the Cerebrum .... . 67S Removal of the Cerebrum .... . 678 Localisation of Cerebral Functions . . 679 Function and Myelination .... . 692 Association Fibres and Centres . 693 Sleep ....... . 697 CHAPTER XLIX Functions of the Cerebellum The Semicircular Canals 702 706 CHAPTER L Comparative Physiology of the Brain 710 Sensation CHAPTER LI 714 CHAPTER LII Cutaneous Sensations Tactile End Organs . Localisation of Tactile Sensations Varieties of Cutaneous Sensations The Kin aesthetic Sense 719 719 723 725 728 XV 111 CONTEXTS CHAPTER LIII Taste and Smell Taste . Smell . PAGE 729 729 734 CHAPTER LIV Hearing Anatomy of the Ear . Physiology of Hearing 738 738 745 CHAPTER LV Voice and Speech Anatomy of the Larynx Movements of the Vocal Cords The Voice Speech Defects of Speech 751 751 757 758 760 761 CHAPTER LVI The Eye and Vision 764 The Eyeball .... 765 The Eye as an Optical Instrument . 776 Accommodation 780 Defects in the Eye . 784 Functions of the Iris . 788 Functions of the Retina 789 The Ophthalmoscope 792 The Perimeter 795 Colour Sensations 7:»6 Changes in the Retina during Activity 801 Various Positions of the Eyeballs . 805 Nervous Paths in the Optic Nerves . SOS Visual Judgments . 809 CHAPTER LVII Trophic Nerves 813 CHAPTER LVII I The Reproductive Organs Male Organs . Female Organs 816 816 821 CONTENTS CHAPTER LIX Development The Ovum Maturation of the Ovum Impregnation Segmentation The Decidua and Foetal Membranes Development of the Foetal Appendages and Membranes Development of the Framework of the Body Development of the Vascular System Development of the Nervous System Development of the Alimentary Canal Development of the Respiratory Apparatus Development of the Genito-urinary Apparatus PAGE 8'27 827 828 830 831 836 839 843 849 858 867 870 871 INDEX 8S1 FAHRENHEIT and CENTIGRADE SCALES. F. 500° 401 392 383 374 350 347 33S 329 320 311 302 284 275 266 248 239 230 212 203 194 176 167 140 122 113 105 104 100 77 68 50 41 32 23 14 + 5 - 4 -13 -22 -40 -76 1 de ( 1-8 „ 3-6 „ 4-5 „ 5-4 „ C. 260" 205 200 195 190 180 175 170 165 160 155 150 140 135 130 120 115 110 100 95 90 80 75 60 50 45 40-54 40 37-8 36-9 35 30 25 20 10 5 - 5 -10 -15 -20 -25 -30 -40 -60 F. = '54°C. = 1°C. = 2°C. = 2-5° C = 3°C. To convert de- grees F. into de- grees C, subtract 32, and multiply by§. To convert de- grees C. into de- grees F., multiply by f , and add 32°. MEASUREMENTS. FRENCH INTO ENGLISH. LENGTH. 10 ^metres 1 = 39;37 English 100 centimetres f , . 1T1< ?nes 1000 millimetres J ( or 1 y a rdand H In.) 1 decimetre "| 10 centimetres V = 3-937 inches lOOmuiimrtresf (or nearly 4 inches). 1 centimetre 10 millimetres 1 millimetre = "3937 or about (nearly £ inch). = nearly ^ inch. Or, One Metre = 39-37079 inches. (It is the ten-millionth part of a quarter of the meridian of the earth.) 1 Decimetre 1 Centimetre 1 Millimetre Decametre Hectometre Kilometre One inch = One foot = One yard = One mile = 4 in. A in. = »A in- = 32-80 feet. = 109-36 yds. = 0-62 mile. 2-539 Centimetres. 3-047 Decimetres. 0-91 of a Metre. 1-60 Kilometre. WEIGHT. (One gramme is the weight of a cubic centimetre of water at A' C. at Paris.) 1 gramme ^ 10 decigrammes | = 15-432349 grs. f (o 1000 milligrammes 10 ceSaTmesj 7 »•* h ? r ™? re 100 milligrammes ) tnan ^ S™"- 1 centigramme 1 = rather more 10 decigrammes f than $, grain. 1 milligramme = rather more than „j| n grain. Or, A grain equals about 1-16 gram., a Troy oz. about 31 grams., a lb. Avoirdupois about k Kilogrm., and 1 cwt. about 50 Kilogrms. CAPACITY. 1,000 cubic decimetres \ = 1 cubic 1,000,000 cubic centimetres ( metre. 1 cubic decimetre ~\ or \ = 1 litre. 1000 cubic centimetres I Or, One Litre = 1 pt. 15 oz. 1 dr. 40. (For simplicity, Litre is used to signify 1 cubic decimetre, a little less than 1 English quart.) Decilitre (100 c.c.) = 3h oz. Centilitre (10 c.c.) = 2| dr. Millilitre (1 c.c.) = 17 m. Decalitre = 2J gals. Hectolitre = 22 gals. Kilolitre (cubic metre) = 27* bushels. A cubic inch = 16-38 c.c. ; a cubic foot = 28-315 cubic dec, and a gallon = 4 54 litres. CONVERSION fcCALE. To convert Grammes to Ounces avoir- dupois, multiply by 20 and divide by 567. To convert Kiloorammes to Pounds, multiply by 1000 and divide by 454. To convert Litres to Gallons, mul- tiply by 22 and divide by 100. To convert Litres to Pints, multiply by 8S and divide by 50. To convert Millimetres to Inches, multiply by 10 and divide by 254. To convert Metres to Yards, multi- ply by 70 and divide by 64. SURFACE MEASUREMENT. . 1 square metre = about 1550 sq. inches (or 10,000 sq. centimetres, or 10-75 sq. ft.) 1 sq. inch = about 6'4 sq. centimetres. 1 sq. foot = „ 930 „ „ ENERGY MEASURE. 1 kilogrammetre = about 7-24 ft. pounds. 1 foot pound = „ -13S1 kgm. 1 foot ton = ,, 310 kgms. 1 Decagramme = 2 dr. 34 gr. 1 Hectogrm. = 3* oz. (Avoir.) 1 Kilogrm. = 21b. 3 oz. 2 dr. (Avoir.) HEAT EQUIVALENT. 1 kilocalorie = 424 kilogrammetres. ENGLISH MEASURES. Apothecaries Weight. Avoirdupois Weight. 7000 grains = Or, 437-5 grains = 1 lb. 16 drams = 1 oz. 16 oz. = 1 lb. 2S lbs. = 1 quarter 4 quarters = 1 cwt. 20 cwt. = 1 ton. Measure of 1 decimetre, 10 centimetres, or 100 millimetres. 10 Cranium. 7 Cervical Vertebrae. Clavicle. Scapula. 12 Dorsal Vertebrae. Humerus. 5 Lumbar Vertebrae. Ilium. Ulna. Radius. Pelvis Bones of the Carpus. Bones of the Meta- carpus. Phalanges of Fingers. Femur. Patella. Tibia. Fibula. Bones of the Tarsus. Bones of the Meta- tarsus. Phalanges of Toes. THE SKELETON (after Holdf.n) Symphysis Pubis. DIAGRAM OF THORACIC AND ABDOMINAL REGIONS. A. Aortic Valve. M. Mitral Valve. P. Pulmonary Valve. T. Tricuspid Valve. HANDBOOK OF PHYSIOLOGY CHAPTEE I INTEODUCTOEY Biology is the science that treats of living things, and it is divided into two main branches, which are called respectively Morphology and Physiology. Morphology is the part of the science that deals with the form or structure of living things, and with the problems of their origin and distribution. Physiology, on the other hand, treats of their functions, that is, the manner in which their individual parts carry out the processes of life. To take an instance : the eye and the liver are two familiar examples of what are called organs ; the anatomist studies the structure of these organs, their shape, their size, the tissues of which they are composed, their position in the body, and the variations in their structure met with in different parts of the animal kingdom. The physiologist studies their uses, and seeks to explain how the eye fulfils the function of vision, and how the liver forms bile, and ministers to the needs of the body in other ways. Each of these two great branches of biological science can be further subdivided according as to whether it deals with the animal or the vegetable kingdom; thus we get vegetable physiology and animal physiology. Human Physiology is a large and important branch of animal physiology, and to the student of medicine is obviously the portion of the science that should interest him most. In order to understand morbid or pathological processes it is neces- sary that the normal or physiological functions should be learnt first. Physiology is not a study which can be put aside and forgotten when a certain examination has been passed; it has a most direct and intimate bearing in its application to the scientific and successful investigation of disease. It will be my endeavour throughout the subsequent pages of this book to point out from time to time the practical relationships between physiology and pathology. 2 INTRODUCTORY [CH. I. Human physiology will bo our chief theme, but it is not a portion of the great science that can be studied independently of its other portions. Thus, many of the experiments upon which our knowledge of human physiology rests have been performed principally on certain of the lower animals. In order to obtain a wide view of vital pro- cesses it will be occasionally necessary to go still further afield, and call the science of vegetable physiology to our assistance. The study of physiology must go hand in hand with the study of anatomy. It is impossible to understand how the body or any part of the body acts unless we know accurately the structure of the organs under consideration. This is especially true for that portion of anatomy which is called Microscopic Anatomy or Histology. Indeed, so close is the relationship between minute structure and function that in this country it is usual for the teacher of physiology to be also the teacher of histology. Another branch of anatomy, namely, Embryology, or the process of growth from the ovum, falls also to some extent within the province of the physiologist. But physiology is not only intimately related in this way to its sister science anatomy, but the sciences of chemistry and physics must also be considered. Indeed, physiology has been sometimes defined as the application of the laws of chemistry and physics to life. That is to say, the same laws that regulate the behaviour of the mineral or inorganic world are also to be found operating in the region of organic beings. If we wish for an example of this we may again go to the eye ; the branch of physics called optics teaches us, among other things, the manner in which images of objects are pro- duced by lenses; these same laws regulate the formation of the images of external objects upon the sensitive layer of the back of the eye by the series of lenses in the front of that organ. An example of the application of chemical laws to living processes is seen in digestion ; the food contains certain chemical substances which are acted on in a chemical way by the various digestive juices in order to render them of service to the organism. The question arises, however, is there anything else ? Are there any other laws than those of physics and chemistry to be reckoned with ? Is there, for instance, such a thing as " vital force " ? It may be frankly admitted that physiologists at present are not able to explain all vital phenomena by the laws of the physical world ; but as knowledge increases it is more and more abundantly shown that the supposition of any special or vital force is unnecessary ; and it should be distinctly recognised that when, in future pages, it is necessary to allude to vital action, it is not because we believe in any specific vital energy, but merely because the phrase is a convenient one for expressing something that we do not fully understand, some- CH. I.] INTRODUCTORY 3 thing that cannot at present be brought into line with the physical and chemical forces that operate in the inorganic world. Physiology proper may be conveniently divided into three main branches : — 1. Chemical physiology ; or the application of chemistry to living processes. 2. Physical physiology; or the application of physics to living processes. 3. The physiology of the nervous system where the application of such laws is at present extremely difficult. But just as there is no hard-and-fast line between physiology and its allies pathology, anatomy, physics, and chemistry, so also there is no absolute separation between its three great divisions ; physical, chemical, and so-called vital processes have to be considered together. Physiology is a comparatively young science. Though Harvey more than three hundred years ago laid the foundation of our science by his discovery of the circulation of the blood, it is only during the last half-century that active growth has occurred. The reasons for this recent progress come under two headings : those relating to observation and those relating to experiment. The method of observation consists in accurately noting things as they occur in nature ; in other words, the knowledge of anatomy must be accurate before correct deductions as to function are possible. The instrument by which such correct observations can be made is, par excellence, from the physiologist's standpoint, the microscope, and it is the extended use of the microscope, and the knowledge of minute anatomy resulting from that use, which has formed one of the greatest- stimuli to the successful progress of physiology during the last sixty years. But important as observation is, it is not the most important method; the method of experiment is still more essential. This consists, not in being content with mere reasonings from structures or occurrences seen in nature, but in producing artificially changed relationships between the structures, and thus causing new combina- tions that if one had waited for Nature herself to produce might have been waited for indefinitely. Anatomy is important, but mere anatomy has often led people astray when they have tried to reason how an organ works from its structure only. Experiment is much more important ; that is, one tests one's theories by seeing whether the occurrences actually take place as one supposes ; and thus the deductions are confirmed or corrected. It is the universal use of this method that has made physiology what it is. Instead of sitting down and trying to reason out how the living machine works, physiologists have actually tried the experiment, and so learnt much more than 4 INTRODUCTORY [CH. I. could possibly have been gained by mere cogitation. Many experi- ments involve the use of living animals, but the discovery of anres- thetics, which renders such experiments painless, has got rid of any objection to experiments on the score of pain. We must next proceed to an examination of the general structure of the body, and an explanation of some of the technical terms which will frequently be used hereafter. The adult body consists of a great number of different parts; and each part has its own special work to do. Such parts of the body are called organs. Each organ does not only its own special work, but acts in harmony with other organs. This relationship between the organs enables us to group them together into what are termed systems. Thus, we have the circulatory system, that is, the group of organs (heart, arteries, veins, etc.) concerned in the circulation of the blood ; the respiratory system, that is, the group of organs (air passages, lungs, etc.) concerned in the act of breathing ; the digestive system, which deals with the digestion of food ; the excretory system, with the getting rid of waste products; the muscular system, with movement; and the skeletal system, with the support of the softer parts of the body. Over and above all these is the nervous system (brain, spinal cord, nerves), the great master system of the body which presides over, controls, and regulates the functions of the other systems. If we proceed still further on our anatomical analysis, and take any orgau, we see that it consists of various textures, or, as they are called, elementary tissues. Just as one's garments are made up of textures (cloth, lining, buttons, etc.), so each organ is composed of corresponding tissues. The elementary tissues come under the following four headings: — 1. Epithelial tissues. 3. Muscular tissues. 2. Connective tissues. 4. Nervous tissues. Each of these is again divisible into sub-groups. Suppose we continue our anatomical analysis still further, we find that the individual tissues are built up of structures which require the microscope for their accurate study. Just as the textures of a garment are made up of threads of various kinds, so also in many of the animal tissues we find threads or fibres, as they are called. But more important than the threads are little masses of living material. Just as the wall of a house is made up of bricks united by cement, so the body walls are built of extremely minute living bricks, united together by different amounts of cementing material. Each one of these living units is called a cell. Some of the tissues already enumerated consist of cells with only very little cement material binding them together ; this, for instance, CH. I.] INTRODUCTORY Protoplasm. Fig. 1.— Vegetable cells. is seen in the epithelial tissues ; but in other tissues, particularly the connective tissues which are not so eminently living as the rest, the amount of cement or intercellular material is much greater, and in this it is that the fibres are developed that confer the necessary strength upon these binding tissues. If, instead of going to the adult animal, we look at the animal in its earliest stage of development, the ovum, we find that it con- sists of a single little mass of living material, a single cell. As development progresses it becomes an adherent mass of cells. In the later stages of development various tissues become differentiated from each other by the cells becoming grouped in different ways, by alterations in the shape of the cells, by de- position of intercellular matter between the cells, and by chemical changes in the living matter of the cells themselves. Thus in some situations the cells are grouped into the various epithelial linings ; in others the cells become elongated and form muscular fibres ; and in others, as in the connective tissues, there is a preponderating amount of inter- cellular material which may become permeated with fibres, or be the seat of the deposition of calcareous salts, as in bone. Instances of chemical changes in the cells themselves are seen on the surface of the body where the superficial layers of the epidermis become horny ; in the mucous glands, where they be- come filled with mucin, and in adipose tissue, where they become charged with fat. The term cell was first used by botanists ; in the popular sense of the word a cell is a space surrounded by a wall, as the cell of a prison, or the cell of a honeycomb. In the vegetable cell there is a wall made of the starch-like material called cellulose, within this is the living matter, and a number of large spaces or vacuoles filled with a watery fluid. The use of the term cell by botanists was therefore completely justified. Bub the animal cell is different ; as a ride, it has no cell-wall, and no vacuoles. It is just a little naked lump of living material. This living material is jelly-like in consistency, possessing the power of movement, and the name protoplasm has been bestowed on it. Fig. 2. — Animal cell consisting of protoplasm containing a nucleus. 6 INTRODUCTORY [CH. I. Somewhere in the protoplasm of all cells, generally near the middle in animal cells, is a roundish structure of more solid consistency than the rest of the protoplasm, called the nucleus. An animal cell may therefore be defined as a mass of protoplasm containing a nucleus. The simplest animals, like the amoebae, consist of one cell only; the simplest plants, like bacteria, torulte, etc., consist of one cell only. J. Fig. 3. — Amoebae ; unicellular animals. Fio. 4.— Cells Of the yeast plant in process of bud- ding ; uniceliular plants. Such organisms are called unicellular. In the progress of their life history the cell divides into two ; and the two new cells separate and become independent organisms, to repeat the process later on. In the case of the higher animals and plants, they are always uni- cellular to start with, but on dividing and subdividing the resulting cells stick together and subsequently become differentiated and altered in the manner already indicated. In spite of these changes, the variety of which produces the great complexity of the adult organism, %9 ^m Fig. 5. — Human colourless blood-corpuscle, showing its successive changes of outline within ten minutes when kept moist on a warm stage. (Schoneld.) there are certain cells which still retain their primitive structure; notable among these are the white corpuscles of the blood. It would appear at first sight an easy problem to distinguish between a living thing, and one which is not living. The principal signs of life are the following : — 1. Irritability ; that is the property of responding by some change under the influence of an external agent or stimulus. The most obvious of these changes is movement (amoeboid movement, ciliary movement, muscular movement, etc.). 2. Power of assimilation, that is, ability to convert into protoplasm the nutrient material or food which is ingested. 3. Power of growth ; this is a natural consequence of the power of assimilation. CH. I.] INTEODUCTOKY 7 4. Power of reproduction ; this is a variety of growth. 5. Power to excrete ; to give out waste materials, the products of other activities. It should, however, be recognised that certain of these five char- acteristics may he absent or latent, and yet the object may be living. For instance, power of movement is absent in many vegetable struc- tures ; certain seeds and spores can be dried and kept for many years in an apparently dead condition, and yet will sprout and grow when placed in appropriate surroundings. Of all the signs of life, those numbered 2 and 5 in the foregoing table are the most essential. Living material is in a continual state of unstable chemical equilibrium, building itself up on the one hand, breaking down on the other ; the term used for the sum total of these intra-molecular rearrangements is metabolism. The chemical sub- stances in the protoplasm which are the most important from this point of view are the complex nitrogenous compounds called Proteids. So far as is at present known, proteid material is never absent from living substance, and is never present in any thing else but that which is alive or has been formed by the agency of living cells. It may therefore be stated that Proteid Metabolism is the most essential characteristic of vitality. CHAPTER II THE ANIMAL CELL An animal cell is usually of microscopic dimensions, in the human body varying from ^ to -oVir of an inch in diameter. It consists of — 1. Protoplasm. This makes up the main substance of the cell. 2. Nucleus: a vesicular body within the protoplasm, generally situated near the centre of the cell. 3. Centrosome and attraction sphere : these are contained within the protoplasm, near the nucleus. These three portions demand separate study. Protoplasm. Until recent years, protoplasm was supposed to be a homogeneous material entirely destitute of structure, though generally containing minute granules of solid consistency, or globules (vacuoles) containing a watery fluid. It has, however, now been shown with high powers of the micro- scope that in many cells the protoplasm consists of two parts, a fine Fjg. G.— (a.) A colourless blood-corpuscle showing the intra-cellular network, and two nuclei with intra- nuclear network. (b.) Coloured blood-corpuscle of newt showing the intra-cellular network of fibrils. Also oval nucleus composed of limiting membrane and fine intra-nuclear network of fibrils, x 800. (Klein and Noble Smith.) network of fibrillse in which the more fluid and apparently structure- less portion of the protoplasm is contained. (See figs. 2 and 6.) CH. II. J PEOTOPLASM 9 The network or spongework is called the reticulum or spongio- plasm, and the more fluid portion in its meshes the enchylema or hyaloplasm. In order to study the microscopic structure of such transparent objects as cells, it is necessary to have recourse to various methods of fixing and stain- ing. When one sees certain appearances after such treatment of the cells, the question arises whether they may not be due to the action of the reagents employed. Appearances which are undoubtedly produced artificially in this way are generally spoken of as artifacts. The network just described is regarded by some observers as an artifact, but it is impossible at present to state this posi- tively. Hardy, in particular, has shown that a film of any colloidal substance like gelatin will, when it sets, present the appearance of a network, and he regards it as probable that the network seen in cells may be due to a similar setting or coagulation of the protoplasm which occurs either when the cell dies, or is fixed by hardening reagents. Butschli regards the spongioplasm as the optical effect of a honeycomb or froth-like structure. There are numerous other views. The granules in protoplasm are partly thickened portions of the spongioplasm, but in addition to this there appear to be free granules, some fatty in nature (staining black with osmic acid), some composed of the substance called glycogen or animal starch (staining reddish-brown with iodine), and sometimes in a few unicellular animals they consist of inorganic (calcareous) matter. But by far the most constant and abundant of the granules are like the main substance of the protoplasm, proteid or albuminous in composition. In all probability the proteid granules are actual constituents of the protoplasm. Substances stored within the proto- plasm, like pigment granules, fat globules, fluid in vacuoles, and glycogen, are spoken of as cell-contents or paraplasm. The chemical structure of protoplasm can only be investigated after the protoplasm has been killed. The substances it yields are (1) Water; protoplasm is semifluid, and at least three-quarters of its weight, often more, are due to water. (2) Proteids, These are the most constant and abundant of the solids. A proteid or albuminous substance consists of carbon, hydrogen, nitrogen, oxygen, with sulphur and phosphorus in small quantities only. In nuclein, a proteid-like substance found in the nuclei of cells, phosphorus is more abundant. The proteid obtained in greatest abundance in the cell protoplasm is called a nucleo-proteid ; that is to say, it is a compound containing varying amounts of this material nuclein with proteid. White of egg is a familiar instance of an albuminous substance or proteid, and the fact (which is also familiar) that this sets into a solid on boiling will serve as a reminder that the greater number of the proteids found in nature have a similar tendency to coagulate under the influence of heat and other agencies. (3) Various other substances occur in smaller proportions, the most con- stant of which are lecithin, a phosphorised fat ; cholesterin, a 10 THE ANIMAL CELL [CH. II. monatomic alcohol ; and inorganic salts, especially phosphates and chlorides of calcium, sodium, and potassium. The large quantity of water present should be particularly noted ; the student when first shown diagrams of the reticulum in proto- plasm is apt to imagine that it consists of a firm solid, like a system of wires pervading a jelly. The reticulum is only slightly more solid than the hyaloplasm. The Nucleus. In form the nucleus is generally round or oval, but it may have in some cases an irregular shape, and in other cases thare may be more than one nucleus in a cell. The nucleus exercises a controlling influence over the nutrition and subdivision of the cell; any portion of a cell cut off from the nucleus undergoes degenerative changes. A nucleus consists of four parts — 1. The nuclear membrane, which encloses it. 2. A network of fibres in appearance like the spongioplasm of the protoplasm but on a larger scale ; that is to say, the threads of which it is composed are much coarser and much more readily seen. The name chromoplasm has been given to this network. 3. The nuclear sap or matrix, a more fluid and homogeneous substance which occupies the interstices of the spongework of chromoplasm. 4. Nucleoli ; these are of two principal varieties ; some are knots or thickened portions of the network (pseudo-nucleoli), and others, the true nucleoli, float freely in the nuclear sap. These four parts of the nucleus are represented in the next diagram. Node of network - "-*■• Nuclear membrane. Nucleolus. Node of network p r ^^-^"WX r: ^rT^-^'- Nuclear matrix. 'Nuclear network. Fig. 7.— The resting nucleus — diagrammatic. (Waldeyer.) The next figure (fig. 8) gives a view of the nucleus, according to the researches of Eabl. He considers that the fibres of the network may be divided into thick fibres which he terms primary, and thinner connecting branches which he terms secondary (shown only on the CH. II.] THE NUCLEUS 11 p.c.f. Fig. 8. — Diagram of nucleus showing the arrangement of chief chromatic filaments. Viewed from the side, the polar end being uppermost, p.c.f. , primary chromatic fila- ments ; n.. nucleolus ; n.o.m., node of mesh- work. (Eabl.) right-hand side of the figure). This observer also supposes that the primary fibres have the looped arrangement depicted in the diagram. In the investigation of microscopic objects, a histologist is nearly always obliged to use staining agents ; the extremely thin objects he examines are so transparent that, without such stains, much of the structure would be invisible. If such dyes as hematoxylin or safranin are employed, it is the nucleus which becomes most deeply stained, and thus stands out on the lighter background of the proto- plasm. But the whole nucleus does not stain equally deeply; it is the chromoplasmic filaments and the nucleoli which have most affinity for the stain, while the nuclear sap is comparatively unaffected. Hence the terms chromatin and achro- matin originally introduced by Fleming. The membrane, the net- work, and the nucleoli are composed of chromatic substance or chromatin ; it is so called not because it has any colour in the natural state, but because it has an affinity for colours artificially added to it. For a corresponding reason, achromatin or achro- matic substance is the name given to the substances which make up the nuclear sap. Balbiani showed that the chromoplasmic filaments are apparently transversely marked into alternate dark and light bands ; this is due to the existence of minute highly refracting particles imbedded in regular series in a clear homogeneous and unstainable matrix (see fig. 9). The term chromatin should properly be restricted to these particles. These particles have special affinity for basic dyes like methyl green, and safranin. Coming next to the chemical composition of the nucleus, it is found to consist principally of proteid and proteid-like substances. The nuclei of cells Fl chromo^ilsmic °fii a a ma y De obtained by subjecting the cells to the fled nt '( S carno y T Sni ' ac ^ on °^ artificial gastric juice; the protoplasm is nearly entirely dissolved, but the nuclei resist the solvent action of the juice. No doubt the nuclei contain several chemical compounds, but the only one of which we have any accu- rate knowledge has been termed nuclein, and this is identical with the substance called chromatin by histologists. It is soluble in alkalis, but precipitated by acids ; it is different from a proteid, as it contains in addition to carbon, nitrogen, oxygen, hydrogen, and sul- phur, an enormous quantity (7 to 8 per cent, or even more) of phos- phorus in its molecule. In many cases nucleins contain iron also. 12 THE ANIMAL CELL [CH. 11. The Attraction Sphere. Eecenfc research has shown that, in addition to the nucleus and protoplasm, most if not all living cells contain another structure ; it consists of a minute particle called a " centrosome," which has an attractive influence on protoplasmic fibrils and granules in its neighbourhood, the whole appearance produced being called an attraction sphere (fig. 10). Fig. 10. — A cell (white blood-cor- puscle) showing it-; attraction sphere. In this, as in most cases, the attraction sphere lies near the nucleus. (Schafer.) Fig. 11. — Ovum of the worm Ascaris, showing a twin attraction sphere. The nucleus with its contorted filament of chromoplasm is repre- sented, but the protoplasm of the cell is not filled in. (v. Beneden.) It is most prominent in cells which are dividing or about to divide. The centrosome, and then the attraction sphere, become double (fig. 11). In all probability the centrosome gives the primary impulse to cell-division. Some cells, like the giant cells of red marrow, contain numerous centrosomes. Protoplasmic Movement. A cell possesses the power of breathing, that is, taking in oxygen ; of nutrition, of building itself up from food materials ; and of excre- tion, or the getting rid of waste material. But the most obvious physiological characteristic of most cells is their power of move- ment. When an amoeba is observed with a high power of the micro- scope, it is found to consist of an irregular mass of protoplasm con- taining one or more nuclei, the protoplasm itself being more or less granular and vacuolated. If watched for a minute or two, an irregular projection is seen to be gradually thrust out from the main body and retracted ; a second mass is then protruded in another direction, and gradually the whole protoplasmic substance is, as it CH. II.] PROTOPLASMIC MOVEMENT 13 were, drawn into it. The Amoeba thus comes to occupy a new position, and when this is repeated several times we have locomotion in a definite direction, together with a continual change of form. These movements, when observed in other cells, such as the colourless blood-cor- Ti puscles of higher animals (fig. 13), in the i0]$i0® branched corneal cells of the frog and ^ ' ./ elsewhere, are hence termed amoeboid. IHlS*^ The projections which are alternately ^ protruded and retracted are called pseudo- podia. Fig. 12.— Amoebae. A streaming movement is not infre- quently seen in certain of the protozoa, in which the mass of protoplasm extends long and fine processes, themselves very little movable, but upon the surface of which freely-moving or stream- ing granules are seen. A gliding movement has also been noticed Fig. 13. — Human colourless blood-corpuscle, showing its successive changes of outline within ten minutes when kept moist on a warm stage. (Schofield.) in certain animal cells ; the motile part of the cell is composed of protoplasm bounding a central and more compact mass ; by means of the free movement of this layer, the cell may be observed to move along. In vegetable cells the protoplasmic movement can be well seen Fig. 14. — (a.) Young vegetable cells, showing cell-cavity entirely filled with granular protoplasm enclosing a large oval nucleus, with one or more nucleoli. (b.) Older cells from same plant, showing distinct cellulose-wall and vacuolation of proto- plasm. in the hairs of the stinging-nettle and Tradescantia and the cells of Yallisneria and Chara ; it is marked by the movement of the granules nearly always imbedded in it. For example, if part of a hair of Tradescantia (fig. 15) be viewed under a high magnifying power, 14 THE ANIMAL CELL [CII. II. 11 of Tradescantia drawn at suc- cessive intervals of two minutes. — The cell- contents consist of a central mass connected by many irregular processes to a peripheral film, the whole forming a vacuolated mass of protoplasm, which is continually changing its shape. (Schorield.) streams of protoplasm containing crowds of granules hurrying along, like the foot-passengers in a busy street, are seen flowing steadily in definite directions, some coursing round the film which lines the interior of the cell-wall, and others flowing towards or away from the irregular mass in the centre of the cell-cavity. Many of these streams of protoplasm run together into larger ones and are lost in the central mass, and thus ceaseless variations of form are produced. The movement of the protoplasmic granules to or from the peri- phery is sometimes called vege- table circulation, whereas the movement of the protoplasm round the interior of the cell is called rotation. The first account of the movement of protoplasm was given by Eosel in 1755, as occurring in a small Proteus, probably a large freshwater amoeba. His description was followed twenty years later by Corti's demonstra- tion of the rotation of the cell sap in Characeae, and in the earlier part of last century by Meyer in Vallisneria, 1827, and by Eobert Brown, 1831, in " Staminal Hairs of Tradescantia." Then came Du- jardin's description of the granular stream- ing in the pseudopodia of Ehizopods ; movements in other animal cells were described somewhat later (Planarian eggs, v. Siebold, 1841 ; colourless blood-cor- puscles, "Wharton Jones, 1846). There is no doubt that the proto- plasmic movement is essentially the same thing in both animal and vegetable cells. But in vegetable cells the cell-wall obliges the movement to occur in the interior, while in the naked animal cells the move- ment results in an external change of form. Although the movements of amoeboid cells may be loosely de- scribed as spontaneous, yet they are produced and increased under the action of external agencies which excite them, and which are Fio. 16. — Cells from the staminal hairs of Tradescantia. .1, fresh in water; 11, the same cell after slight electrical stimulation ; a, b, region of stimulation ; c, d, clumps and knobs of con- tracted protoplasm. (Kiihne.) CH. II.] IERIT ABILITY OF PROTOPLASM 15 therefore called stimuli, and if the movement has ceased for the time, as is the case if the temperature is lowered beyond a certain point, movement may be set up by raising the temperature. Again, contact with foreign bodies, gentle pressure, certain salts, and electricity, produce or increase the movement in the amoeba. The protoplasm is, therefore, sensitive or irritable to stimuli, and shows its irritability by movement or contraction of its mass. The effects of some of these stimuli may be thus further detailed : — - a. Changes of temperature. — Moderate heat acts as a stimulant : the movement stops when the temperature is lowered near the freezing-point or raised above 40° C. (104° F.) ; between these two points the movements increase in activity ; the optimum temperature is about 37° to 38° C. Though cold stops the movement of proto- plasm, exposure to a temperature even below 0° C. does not prevent its reappearance if the temperature is raised; on the other hand, prolonged exposure to a temperature of 42°-45° C. altogether kills the protoplasm and causes it to enter into a condition of coagulation or heat rigor. We have already seen that proteids, the most abundant constituents of protoplasm, are coagulated by heat. o. Chemical stimuli. — Distilled water first stimulates then stops amoeboid movement, for by imbibition it causes great swelling and finally bursting of the cells. In some cases, however (myxomycetes), protoplasm can be almost entirely dried up, but remains capable of renewing its movement when again moistened. Dilute salt solution and very dilute alkalis stimulate the movements temporarily. Acids or strong alkalis permanently stop the movements : ether, chloroform, veratrine and quinine also stop it for a time. Movement is suspended in an atmosphere of hydrogen or carbonic acid, and resumed on the admission of air or oxygen ; complete with- drawal of oxygen will after a time kill protoplasm. c. Electrical. — Weak currents stimulate the movement, while strong currents cause the cells to assume a spherical form and to become motionless. tionless. £7 .y^Ai\^JC^S^A The amoeboid movements of the colourless ?> : jl- 'V^Ay^ corpuscles of the blood may be readily seen ^cJ^ "^^s^ when a drop of blood from the finger is mixed fig. it.— An Ameboid cor- with salt solution, and examined on a warm l^S^nu^™ Spi?- stage with the microscope. If a pseuclopodium 9 ation l of steam > show ; „°- i ■ l lii-i m ° the appearance of oi such a corpuscle is observed under a high the pseudopodia^ (After power, it will be seen to consist of hyaloplasm, tomy?"j Quams Ana * which has flowed out of its spongy home, the reticulum. Later, however, a portion of the reticular part of the protoplasm may enter the pseudopodium. The cells may be fixed 16 tHK ANIMAL CELL [CH. II. by a jet of steam allowed to play for a moment on the surface of the cover glass. The next figure illustrates one fixed in this way. The essential act in the protrusion of a pseudopodium is the liowing of the hyaloplasm out of the spongioplasm ; the retraction of the pseudopodium is a return of the hyaloplasm to the spongio- plasm. The spongioplasm has an irregular arrangement with open- ings in all directions, so that the contractility of undifferentiated cells may exhibit itself towards any point of the compass. The relation of cells to various forms of stimulus has been recently very extensively studied. Various forms of unicellular organisms have been used in these experiments, and the stimuli employed have been chemical, thermal, light, electric currents, and so forth. If the cell moves towards the source of attraction, the term posilivt taxis is employed; if it is repelled, negative taxis. The words, chemo-taxis, ther mo-taxis, photo-taxis, galvano-taxis, etc., indicate the kind of stimulus investigated. Cell Division. A cell multiplies by dividing into two ; each remains awhile in the resting or, more correctly, non-dividing condition, but later it grows and subdivides, and the process may be repeated indefinitely. The supreme importance of the cell, the growth of the body from cells, and the fact that cells are the living units of the organism, were first established in the vegetable world by Schleiden, and extended to the animal kingdom by Theodor Schwann. The ideas of physiologists depending on this idea are grouped together as cellular physiology, which under the guidance of Virchow was ex- tended to pathology also: Virchow expressed the doctrine now so familiar as to be almost a truism in the terse phrase omnis cellula e cellula (every cell from a cell). The division of a cell is preceded by division of its nucleus. Nuclear division may be either (1) simple or direct, which consists in the simple exact division of the nucleus into two equal parts by con- striction in the centre, which may have been preceded by division of the nucleoli ; or (2) indirect, which consists in a series of changes which goes on in the arrangement of the nuclear reticulum, resulting in the exact division of the chromatic fibres into two parts, which form the ohromoplasm of the daughter nuclei. The changes in the nucleus during indirect division constitute karyokinesis (Kapvov, a kernel), or mitosis (///to?, a thread), and direct division is called amitotic or akinetic (/«V>/cnc, movement). It is now believed that the mitotic nuclear division is all but, though not quite, universal. Somewhat different accounts of the stages of the nuclear division have been given by different authorities, accord- ing to the kind of cell in which the nuclear changes have been CH. II.] CELL DIVISION 17 studied. The following figure (fig. 18) shows some of the typical stages of karyokinesis as observed by Klein : — Fig. IS.— Karyokinesis. a, ordinary nucleus of a columnar epithelial cell ; b, c, the same nucleus in the stage of convolution ; d, the wreath or rosette form ; e, the aster, or single star; f, a nuclear spindle from the Descemet's endothelium of the frog's cornea ; g, h, i, diaster ; k, two daughter nuclei. (Klein.) The process may be divided into the following stages : — 1. The non-dividing nucleus (fig. 19.) Node of network Node of network — — *- Nuclear membrane. Nucleolus. Nuclear matrix. Nuclear network. Fig. 19.— The resting nucleus. (Waldeyer.) 2. The spirem or skein stage : the nucleoli dissolve, the secondary fibres disappear, and the primary loops running from polar to anti- polar regions remain (figs. 8, 20). In some cells there is at first one long;, much twisted thread, which subse- quently breaks up into segments. The loops are called chromosomes. 3. Each loop becomes less convo- luted and splits longitudinally into two sister threads, and the achromatic spindle appears (fig. 21, a and b). 4 The equatorial stage; monaster. The nucleus has now two poles, those of the spindle ; and at each pole there is a polar corpuscle or centro- B l.c.f. - i.f. . 20. — Early condition of the skein stage viewed at the polar end. I. c.f., looped chromatic filament, i.f., irre- gular filament. (Eabl.) 18 THE ANIMAL CELL [CH. II. some. The division of the centrosome of the original cell, and then of the attraction sphere into two, usually precedes the commence- A b Achromatic spindle - Outer granular zone. Split fibres. Inner clear zone. Polar corpuscle. Fig. 22. -Monaster stage of karyokinesis. (Waldeyer.) Fiq 21.— Later condition of the skein stase in karyokinesis. a. The thicker primary fibres or chromo- somes become less convoluted and the achromatic spindle appears, b. The chromosomes split into two and the achromatic spindle becomes longitudinal. (Waldeyer.) ment of changes in the nucleus ; the two attraction spheres become prominent in cell division, and the connecting achromatic spindle is probably also formed from them or from the achromatic material of the nucleus. At this stage the nuclear membrane is lost, and thus cell protoplasm and nuclear sap become continuous ; the proto- plasm immediately around the nucleus is clear; outside this is a granular zone, and here the granules are arranged radially from the polar corpuscles. The star-like arrangement of these granules is much better marked in embryonic cells, indeed the lines present very much the appearance of fibrils (see fig. 23). The V- Sria ped chromosomes sink to the equator of the spindle, and arrange them- selves so as to project hori- zontally from it. In cells which are the re- sult of the sexual process, the number of chromosomes is always even, an equal number being contributed by each sex. The number of chromo- somes varies with the species from four to twenty-four ; in man the number is sixteen. -Antipodal zone Fio. 23. — Ovum of the worm Ascaris in process of divi- sion. The attraction spheres are at opposite ends of the ovum ; at the equator of the spindle which unites them, four chromosomes are seen. The proto- plasm of the ovum, except in the equatorial zone of the cell, is arranged in lines radiating from the centre (centrosome) of the attraction sphere. (Waldeyer.) CH. II.] KAKYOKINESIS 19 5. The stage of metahinesis. The sister threads separate, one set going towards one pole, and the other to the other pole of the spindle (fig. 24) : these form the two daughter nuclei. The chromosomes are probably pulled into their new position by the contraction of the spindle fibres attached to them. 6. Each daughter nucleus goes backwards through the same series Fine uniting filaments. Fig. 24. — Metakinesis. a. Early stage, b. Later stage, c. Latest stage — formation of diaster. b. and c. show how the sister threads disentangle themselves from one another. (Waldeyer.) of changes ; the diaster or double star is followed by the dispirem or double skein, until at last two resting nuclei are obtained (fig. 25). A new membrane forms around each daughter nucleus, the spindle atrophies, and the attraction sphere becomes less prominent. The division of the cell protoplasm into two parts around the two nuclei begins in the diaster stage, and is complete in the stage represented in fig. 25. Eemains of spindle. Line of separation of the two cells. Antipole of daughter,.—''/ nucleus. -^ Lighter substance of the ■-*" nucleus. Cell protoplasm. Hilus. Fig. 25. — Final stages of karyokinesis. In the lower daughter nucleus the changes are still more advanced than in the upper. (Waldeyer.) The karyokinetic process has been watched in all its stages by more than one observer. The time occupied varies from half an hour to three hours ; the details, however, must be studied in hardened and appropriately stained specimens. They are most readily seen in cells with large nuclei, such as occur in the epidermis of amphibians. The process varies a good deal in different animal and vegetable 20 THE ANIMAL CELL [CH. II. cells ; such as in the number of chromosomes, and the relative importance of the different stages. All attempted here has been to give an account of a typical case. The phases may be summarised in a tabular way as follows (from " Quain's Anatomy ") : — 1. Resting condition of mother nucleus (fig. 19). (2. Close skein of fine convoluted filaments I (fig. 20). j 3. Open skein of thicker filaments. Spindle [ appears (fig. 21 a). 4. Movement of V-shaped chromosomes to middle of nucleus, and each splits into two sister threads (fig. 21 it). 5. Stellate arrangement of V filaments at equator of spindle (fig. 22). 6. Separation of cleft filaments and move- ment along fibres of spindle (fig. 24 a and h). 7. Conveyance of V filaments towards poles of spindle (fig. 24 c). ( 8. Open skein in daughter nuclei. { 9. Close skein in daughter nuclei (fig. 25). . 10. Restina; condition of daughter nuclei (hg. 25). Network or Reticulum . Skein or Si'irem Cleavage .... Star or Monaster . Divergence or Metakinesis Double Star or Diaster Double Skein or Dispirem Network or Reticulum . The Ovum. The ovary is an organ which produces ova. An ovum is a simple animal cell ; its parts are seen in the next diagram. It is enclosed in a membrane called the zona pellucida or vitelline membrane. The body of the cell is composed of protoplasm loaded - Nucleus or germinal vesicle. "Nucleolus or germinal spot. _ Space left by retraction of protoplasm. .Protoplasm containing yolk spherules. Vitelline membrane. Fig. 26. — Representation of a human ovum. (Cadiat.) with granules of food material, called the yolk or vitellus. The nucleus and nucleolus are sometimes still called by their old names, germinal vesicle and germinal spot respectively. The attraction sphere is not shown in the diagram. The formation of ova will form the subject of a chapter later on, CH. II.] THE OVUM 21 but it is convenient here at the outset to state briefly one or two facts, and introduce to the student a few terms which we shall have to employ frequently in the intervening chapters. The oVum first discharges from its interior a portion of its nucleus, which forms two little globules upon it called the polar globules. Fertilisation then occurs ; that is to say, the head or nucleus of a male cell called a spermatozoon penetrates into the ovum, and becomes fused with the remains of the female nucleus. Cell division or segmentation then begins, and the early stages are represented in the next figure. Fluid discharged from the cells accumulates within the interior of the mulberry mass seen in fig. 27 d, and later, if a section is cut through it, the cells will be found arranged in three layers. The outermost layer is called the epiblast. The middle layer is called the mesoblast. The innermost layer is called the hypoblast. From these three layers the growth of the rest of the body occurs, Fig. 27.— Diagram of an ovum (a) undergoing segmentation. In (b) it has divided into two, in (c) into four; and in (d) the process has resulted in the production of the so-called "mulberry-mass." (Frey.) nutritive material \being derived from the mother in mammals by means of an organ called the placenta.- The epiblast, the outermost layer of the embryo, forms the epi- dermis, the outermost layer of the adult. It also forms the nervous system. The hypoblast, the innermost layer of the embryo, forms the lining epithelium of the alimentary (except that of the mouth and anus which are involutions from the epiblast) and respiratory tracts, that is, the innermost layer of the adult. It also forms the cellular elements in the large digestive glands, such as the liver and pancreas, which are originally, like the lungs, outgrowths from the primitive digestive tube. The mesoblast forms the remainder, that is, the great bulk of the body, including the muscular, osseous, and other connective tissues ; the circulatory and urino-genital systems. CHAPTER III EPITHELIUM The elementary tissues of which the organs of the body are built up may be arranged into four groups : epithelial, connective, muscular, and nervous. The first of these, the epithelial tissues, follows naturally on a study of the animal cell, as an epithelium may be defined as a tissue composed entirely of cells united by a minimal amount of cementing material. As a rule, an epithelium is spread out as a membrane covering a surface or lining the cavity of a hollow organ. These epithelia may be grouped into two great classes, each of which may be again subdivided according to the shape and arrange- ment of the cells of which it is composed. The following table gives the principal varieties : — Class 1. — Simple epithelium ; that is, an epithelium consisting of one layer of cells only. Its subgroups are as follows : — a. Pavement epithelium. b. Cubical and columnar epithelium. c. Ciliated epithelium. Class 2. — Compound epithelium ; that is, an epithelium consist- ing of more than one layer of cells. Its subgroups are as follows : — a. Transitional epithelium. b. Stratified epithelium. This classification does not include the more specialised forms of epithelium found in secreting glands, or in the sense organs, nor structures like hair, and enamel of tooth, which are epithelial in origin. These will be considered in their proper place later on. Pavement Epithelium. This consists of a layer of thin cells, arranged like flat pavement- stones accurately fitting together and united by a small amount of cementing material. The structure of the cells and their outlines may be best demonstrated in the following way : — A portion of the fresh tissue is taken and immersed for a few CH. III.] PAVEMENT EPITHELIUM 23 minutes in a 1 per cent, solution of nitrate of silver ; it is taken out, washed with distilled water, and exposed in water or spirit to sun- light. The silver forms a compound with the cement, which in the \ ^ s Fig. 28. — From a section of the lung of a cat, stained with silver nitrate. N. Alveoli or air-cells, lined with large flat, nucleated cells, with some smaller polyhedral nucleated cells. (Klein and Noble Smith.) light is decomposed or reduced, leading to a fine deposit of silver, showing as black or brown lines between the cells, and accurately denning their outlines. The preparation may then be immersed in some stain like logwood to bring out the nuclei, and finally mounted in the usual way. Fig. 29. — Abdominal surface of. central tendon of the diaphragm of rabbit, showing the general polygonal shape of the endothelial cells ; each cell is nucleated, x 300. (Klein.) Fig. 28 shows the appearance presented in a preparation of lung. In the alveoli or air-sacs of the lung, pavement epithelium of a typical kind is found forming a lining membrane. 24 EPITHELIUM [CH. III. Endothelium. — Epithelium of similar appearance is found lining the interior of the whole of the vascular system, heart, arteries, capil- Fig. 30.— Peritoneal surface of a portion of the septum of the great lympli-sac of a frog. The stomata, some of which are open, some collapsed, are well shown, x 160. (Klein.) laries, veins, and lymphatics, and in the adjuncts of the circulatory system called the serous membranes (pericardium, peritoneum, etc.). This epithelium is formed from the middle layer of the embryo, Fig. 31. — A portion of the great omentum of dog, which shows, amongst the flat endothelium of the surface, small and large groups of germinating endothelium, between which are many stomata. x 300. (Klein.) the mesoblast; most other epithelium is derived either from epiblast or hypoblast. Hence it has received a distinct name, viz.: endothelium. CH. III.] COLUMNAR EPITHELIUM 25 The general appearance presented by endothelium in serous mem- branes is shown in figs. 29, 30, and 31 ; in blood-vessels in fig. 32. The stomata seen in some of the drawings are minute openings sur- rounded by more darkly staining cells, which lead from serous cavities into lymphatic vessels. Cubical, Spheroidal, and Columnar Epithelium. In these forms of epithelium, the cells are not flat, but are thick ; if they approximate cubes or spheres in shape, the epithelium is called cubical or spheroidal respectively. Polyhedral epi- thelium is found in the alveoli of secret- ing glands, such as the salivary glands, liver, and pancreas (see figs. 33 and 34), and will be discussed at length in con- nection with those organs. Cubical epi- thelium is found in the alveoli of the thyroid (see fig. 35), in the tubules of the testis, and in the ducts of some glands. In columnar epithelium the cells are tall, and form a kind of palisade or rows of columns. It is found lining the in- terior of the stomach and intestines, and the ducts of the majority of secreting glands; it forms also the layer on the outer surface of the ovary. In the intestinal epithelium each cell has a distinct brightly refracting and striated border. Fig. 36 shows two isolated cells of this kind. The nucleus with its usual network and the vacuolated condition of the protoplasm are very well seen. The attached border is narrower than the free edge. Amoeboid lymph cells are found in the spaces that must necessarily be left when cells of such a shape cover a surface. Fig. 37 shows a row of columnar cells from the rabbit's intestine. The next figure (fig. 38) shows the arrangement of these cells on the surface of a villus, one of the numerous little projections found in the small intestine. The gaps seen there are due to the formation of what are called goblet cells. In some of the columnar cells, a formation of granules Fig. 32.— Surface view of an artery from the mesentery of a frog, ensheathed in a peri-vascular lymphatic vessel. a, The artery, with its circular muscular coat (media) indicated by broad transverse markings, with an indication of the adventitia out- side. I, Lymphatic vessel ; its wall is a simple endothelial membrane. (Klein and Noble Smith.) 26 EPITHELIUM [CH. III. occurs which consist of a substance called mucigen; these run together, and are discharged from the cell as a brightly refracting globule of mucin, leaving the cell with open mouth like a goblet, the Fio. 33.— Glandular epithelium. Small lobule of a mucous gland of the tongue, showing nucleated glandular cells, x 200. (V. D. Harris.) Fio. 34. — A small piece of the liver of the horse. (Cadiat.) nucleus being surrounded by the remains of the protoplasm in its narrow stem (see fig. 39). This transformation is a normal process continually going on Us a]Q d in the thicker fasciae and aponeuroses of muscle. The tissue is one of great strength; this is conferred upon it by the arrangement of the fibres, the bundles of which run parallel, union here, as elsewhere, giving strength. The fibres of the same bundle now and then intersect each other. The cells in tendons (fig. 61) are forced to take up a similar orderly arrangement, and are ar- ranged in long chains in the ground- substance separating the bundles of fibres, and are more or less regu- larly quadrilateral with large round nuclei containing nucleoli, which are generally placed so as to be nearly contiguous in two cells. Each of these cells consists of a thick body, from which processes pass in various directions into, and partially fill Fig. 60. — Fibrous tissue of tendon, consisting mainly of white fibres. (Strieker.) 42 THE CONNECTIVE TISSUES [CTI. IV. up the spaces between, the bundles of fibres. The cells are generally marked by one or more lines or stripes when viewed longitudinally. Fig. 61. — Caudal tendon of young rat, showing the arrangement, form, and structure of the tendon cells. The bundles of white fibres between which they lie have been rendered transparent and indistinct by the application of acetic acid, x 300. (Klein.) Fig. 62.— Transverse section of tendon from a cross section of the tail of a rabbit, showing sheath, fibrous septa, and branched tendon cells. The spaces left white in the draw- ing represent the tendinous bundles in transverse section, x 250. (Klein.) This appearance], is really produced by the wing-like processes of the cell, which project away from the chief part of the cell in different directions. These processes not being in the same plane as the body of the cell are out of focus, and give rise to these bright stripes when the cells are looked at from above and are in focus. The branched character of the cells is seen in transverse section in fig. 62. The cell spaces in which the cells lie are in arrangement like the Fig. 63.— Cell spaces of tendon, brought into view by treatment with silver nitrate (After Schafer.) cells ; they can be brought into relief by staining with silver nitrate (see fig. 63). CH. IV.] ELASTIC TISSUE 43 . 64. — Elastic fibres from the ligamenta subflava. x 200. (Sharpey.) Elastic Tissue. This is a form of connective tissue in which the yellow or elastic fibres predominate. The yellow fibres are larger than those found in areolar tissue (see fig. 64), and are bound into bundles by areolar tissue. It is found in the ligamentum nuchee of the ox, horse, and many other animals ; in the liga- menta subflava of man ; in the arteries and veins, constituting the fenestrated coat of Henle; in the lungs and trachea; in the stylo-hyoid, thyro-hyoid, and crico- thyroid ligaments; and in the true vocal cords. Elastic tissue occurs in various forms, from a structureless, elastic membrane to a tissue whose chief constituents are bundles of fibres crossing each other at different angles ; when seen in bundles elastic fibres are yellowish in colour, but individual fibres are not so distinctly coloured. The larger elastic fibres are often transversely marked, indicating their mode of origin (see p. 41), and on transverse section are seen to be angular (%. 65). Elastic tissue, being extensible and elastic (i.e., recoiling after it has been stretched), has a most important use in assisting muscular tissue in a mechanical way, and so lessening the wear and tear of such an important tissue as muscle. Thus, in the ligamenta subflava of the human vertebral column it assists in the maintenance of the erect posture; in the ligamentum nuchee in the neck of quadrupeds it assists in the raising of the head and in keeping it in that position. In the arterial walls, and in the air tubes and lungs, it has a similar important action, as we shall see when discussing the subjects of the circulation and respiration. "We now come to those forms of con- nective tissue in which the cells rather than the fibres are most prominent. Adipose Tissue. In almost all regions of the human body a larger or smaller quantity of adipose or fatty tissue is present ; the chief exceptions being the Q, Fig. 65. — Transverse section of a portion of lig. nuchas, " showing the outline of the fibres. (After Stohr.) 44 THE CONNECTIVE TISSUES [ch. rv. subcutaneous tissue of the eyelids, penis and scrotum, the nymphse, and the cavity of the cranium. Adipose tissue is developed in connection with areolar tissue, and forms in its meshes little masses of unequal size and irregular shape, to which the term lobules is applied. Under the microscope adipose tissue is found to consist essentially of little vesicles or cells which present dark, sharply-defined edges when viewed with transmitted light: they are about I i ff or ^-L of an inch in diameter; each consists of a structureless and colourless membrane or bag formed of the remains of the original protoplasm of the cell, filled with fatty matter, which is liquid during life, but is in part solidified (or sometimes crystallised) after death. A nucleus is always present in some part or other of the cell protoplasm, but in the ordinary condition of the cell it is not easily or always visible (fig. 67). This membrane and the nucleus can generally be brought into view by staining the tissue : it can be still more satisfactorily demon- strated by extracting the contents of the fat-cells with ether, when the shrunken, shrivelled membranes remain behind. By mutual pres- Fig. 60. — Fat-cells from the omentum of a rat. (Klein.) Fig. 07. Group of fat-cells (f c) with capillary vessels (c). (Noble Smith.) sure, fat-cells assume a polyhedral figure (fig. 68, b). When stained with osmic acid fat-cells appear black. The oily matter contained in the cells is composed of the com- pounds of fatty acids with glycerin, which are named olein, stearin, and palmitin. Development of Adipose Tissue. — Fat-cells are developed from CH. IY.] ADIPOSE TISSUE 45 connective-tissue corpuscles, especially the " mast "-cells ; these cells may be found exhibiting every intermediate gradation between a N d Fig. 68. — Blood-vessels of'adipose tissue, a, Minute fat-lobule, in which the vessels only are represented, a, artery; v, vein; b, the fat-vesicles of one border of the lobul6 separately represented, x 100. b, Plan of the arrange- ment of the capillaries (c) on the exterior of the vesicles ; more highly magnified. (Todd and Bowman.) Fig. 69. — AJIobuleof developing adipose tissue from an eight months' foetus. a, Spherical or, from pressure, polyhedral cells with large central nucleus, surrounded by protoplasm staining uniformly with haematoxy- lin. 6, Similar cells with spaces from which the fat has been removed by oil of cloves, c, Similar cells show- ing how the nucleus with enclosing protoplasm is being pressed towards periphery, d, Nucleus of endo- thelium of investing capillaries. (M'Carthy.) Drawn by Treves. an ordinary granular corpuscle and a mature fat-cell. The process of development is as follows : a few small drops of oil make their Pig. 70. — Branched connective-tissue corpuscles, developing into fat-cells. (Klein.) appearance in the protoplasm, and by their confluence a larger drop is produced (figs. 69 and 70) : this gradually increases in size at the expense of the original protoplasm of the cell, which becomes cor- 46 THE CONNECTIVE TISSUES [CH. IV. respondingly diminished in quantity till in the mature cell it only forms a thin film, with a flattened nucleus imbedded in its substance (fig. 66). Vessels and Nerves. — A large number of blood-vessels are found in adipose tissue, which subdivide until each lobule of fat contains a fine meshwork of capillaries ensheathing each individual fat-cell (fig. 68). Although nerve fibres pass through the tissue, no nerves have been demonstrated to terminate in it. The Uses of Adipose Tissue. — Among the uses of adipose tissue these are the chief : — a. It serves as a store of combustible matter which may be reabsorbed into the blood when occasion requires, and, being used up in the metabolism of the tissues, helps to preserve the heat of the body. b. The fat which is situated beneath the skin must, by its want of conducting power, assist in preventing undue waste of the heat of the body by escape from the surface. c. As a packing material, fat serves very admirably to fill up spaces, to form a soft and yielding yet elastic material wherewith to wrap tender and delicate structures, or form a bed with like qualities on which such structures may lie, not endangered by pressure. As examples of situations in which fat serves such purposes may be mentioned the palms of the hands, the soles of the feet, and the orbits. d. In the long bones fatty tissue, in the form known as yellow marrow, fills the medullary canal, and supports the small blood- vessels which are distributed from it to the inner part of the substance of the bone. Retiform Tissue. Eetiform or reticular tissue is a kind of connective tissue in which the ground substance is of more fluid consistency than elsewhere. Fig. 71. — Retiform tissue from a lymphatic gland, from a section which has been treated with dilute potash. (Sehafer.) There are few or no elastic fibres in it, but the white fibres run in very_fine bundles forming a close network. The bundles are covered CH.-IV.] LYMPHOID TISSUE 47 and concealed by flattened connective-tissue corpuscles. When these are dissolved by dilute potash, the fibres are plainly seen (fig. 71). The statement has been made that the fibres of retiform tissue are chemically different from those of areolar tissue, in spite of the fact that they are indis- tinguishable microscopically, and in many places continuous with each other. Miss Tebb has conclusively proved that chemical differences do not exist between the two groups of fibres; both are made of collagen, and the substance termed reticulin by Siegfried is an artifact ; it is merely collagen which has been rendered istant and insoluble by the reagents (alcohol, ether) used in its preparation. Adenoid or Lymphoid Tissue. This is retiform tissue in which the meshes of the network are largely occupied by lymph corpuscles. These are in certain foci Fig. 72. — Part of a section of a lymphatic gland, from -which the corpuscles have been for the most part removed, showing the supporting retiform tissue. (Klein and Noble Smith.) actively multiplying ; they get into the lymph stream, which washes them into the blood, where they become the colourless corpuscles. It is found in the lymphatic glands, the thymus, the tonsils, in the follicular glands of the tongue, in Peyer's patches, and in the solitary glands of the intestines, in the Malpighian corpuscles of the spleen, and under the epithelium of many mucous membranes. Basement Membranes. These are homogeneous in appearance, and are found between the epithelium of a mucous membrane and the subjacent connective tissue. They are generally formed of flattened connective-tissue corpuscles 48 THE CONNECTIVE TISSUES [en. IV- joined together by their edges, but sometimes they are made of con- densed ground-substance, not of cells, and in other cases again (as in the cornea) they are of elastic nature. Jelly-like Connective Tissue. We have now considered connective tissues in which fibres of one or the other kind predominate, and some in which the cells are in preponderance. We come lastly to a form of connective tissue in which the ground substance is in excess of the other histological elements. This is called jelly-like connective tissue. The cells and fibres scattered through it are few and far between. It is found FlG. 73.— Tissue of the jelly of Wharton from umbilical cord, a, Connective-tissue corpuscles ; b, fasciculi of connective-tissue fibres ; c, spherical cells. (Frey.) largely in the embryo, notably in the Whartonian jelly, which sur- rounds and protects the blood-vessels of the umbilical cord. In the adult it is found in the vitreous humour of the eye. Various points in the structure of the tissue are illustrated in figs. 58 (p. 40) and 73. The occurrence of large quantities of ground-substance in such tissues has enabled physiologists to examine its chemical nature. Its chief constituents are water, and one or more varieties of mucin, with traces of proteid and mineral salts. CHAPTEE V the connective tissues {continued) Cartilage, Bone, Teeth, Blood Cartilage. Cartilage is popularly termed gristle. It may be divided into two chief kinds : Hyaline cartilage ; here the matrix or ground substance is clear and free from fibres : Fibro -cartilage ; here the matrix is per- Fig. 74. — Section of articular cartilage, a, Group of two cells ; b, group of four cells ; d, protoplasm of cell with e, fatty granules ; c, nucleus. (After Schafer.) vaded with connective-tissue fibres; when these are of the white variety, the tissue is white fibro -cartilage ; when they are of the yellow or elastic variety, the tissue is yellow or elastic fibro-cartilage. i9 D 50 THE CONNECTIVE TISSUES [en. V. Hyaline Cartilage is found in the following places : — 1. Covering the articular ends of bones ; here it is called articular cartilage. 2. Forming the rib-cartilages ; here it is called costal cartilage. 3. The cartilages of the nose, of the windpipe, of the external auditory meatus, and the greater number of the laryngeal cartilages. 4. Temporary cartilage: rods of cartilage which prefigure the majority of the bones in process of development. Articular cartilage : here the cells are rounded and scattered in groups of two and four through the matrix, which is non-fibrillated Fig. 75. — Section of transitional cartilage, a, Ordinary cartilage cells ; b o, those with processes. (After Schiifer.) (fig. 74), and much firmer than the ground-substance of the connective tissues proper ; but it is affected in the same way with silver nitrate. In the neighbourhood of synovial membranes, the connective- tissue fibres of which extend into the matrix, the cells are branched (transitional cartilage), (fig. 75). The next figure (fig. 76) shows the general arrangement of the cell- groups in a vertical section of articular cartilage. Cartilage is free from blood-vessels, and also from nerves. It is nourished by lymph, but canals connecting the cell-spaces are not evident. Costal cartilage : here the matrix is not quite so clear, and the cells CH. V.] CAETILAGE 51 are larger, more angular, and collected into larger groups than in articular cartilage. Under the perichondrium, a fibrous membrane which surrounds the rod of carti- lage, the cells are flattened and lie parallel to the surface ; in the deeper parts they are irregularly arranged ; they frequently contain fat (see fig. 77). The hyaline cartilages of the nose, larynx, and trachea (fig. 78) resemble costal cartilage. Hyaline cartilage in many situations (costal, laryngeal, tra- cheal) shows a tendency to become calcified late in life. On boiling, the ground-substance of cartilage yields a material called chondrin. This resembles gelatin very closely, and the differ- ences in its reactions are due to the fact that chondrin is not a chemical individual, but a mixture of gelatin with varying amounts of mucin-like substances. Fig. 76.— Vertical section of articular cartilage ; a, cell-groups arranged parallel to surface; 6, cell-groups irregularly arranged ; c, cell- groups arranged perpendicularly to surface. 1,^;,;!^,-^',^-^',^ Fig. 77.— Costal cartilage from an adult dog, showing fat-globules in the cartilage-cells. (Cadiat.) <&§T $& <3> <3> H $ Fig. 7S. — Ordinary hyaline cartilage from trachea of a child. The cartilage- cells are enclosed singly or in pairs in a capsule of hyaline substance. x 150 diams. (Klein and Noble Smith.) White Fibro-Cartilage occurs — 1. As inter -articular fibro-cartilage — e.g., the semilunar cartilages of the knee-joint. 2. As circumferential or marginal cartilage, as on the edges of the acetabulum and glenoid cavity. 3. As connecting cartilage — e.g., the inter-vertebral discs. 4. In the sheaths of tendons and sometimes in their substance. In 52 THE CONNECTIVE TISSUES [CH. V. the latter situation the nodule of fibro-cartilage is called a sesamoid fibro-cartilage, of which a specimen may be found in the tendon of the tibialis posticus in the sole of the foot, and usually in the neigh- bouring tendon of the peroneus longus. White fibro-cartilage (fig. 79) is composed of cells and a matrix. The latter is permeated by fibres of the white variety. In this kind of fibro-cartilage it is not unusual to find portions so densely fibrous that no cells can be seen ; but in other parts con- tinuous with these, cartilage-cells are freely distributed. Yellow or Elastic Fibro-Cartilage is found in the pinna of the m Cells of car- tilage. Fibrous matrix. WW .UV' 1 ::^'"'' Flu. 79. — White fibro-carUlage. (Cadiat. ) Fig. 80. — Yellow or elastic fibro-cartilage. (Cadiat.) external ear, in the epiglottis and cornicula laryngis, and in the Eustachian tube. The cells in this variety of cartilage are rounded or oval, with well-marked nuclei and nucleoli (fig. 80). The matrix in which they are seated is pervaded in all directions by fine elastic fibres, which form an intricate interlacement about the cells : a small and variable quantity of non-fibrillated hyaline intercellular substance is present around the cells. Development of Cartilage. — Like other connective tissues, car- tilage originates from mesoblast ; the cells are unbranched, and the disposition of the cells in fully formed cartilage in groups of two, four, etc., is due to the fact that each group has originated from the division of a single cell, first into two, each of these again into two, and so on. This process of cell division is accompanied with the usual karyokinetic changes. CH. V.] CAKTILAGE 53 Each cell deposits on its exterior a sheath or capsule ; on division each of the daughter-cells deposits a new capsule within this, and the process may be repeated (see fig. 81). Thus the cells get more and more separated. The fused capsules form a very large part of the matrix, and indications of their previous existence may sometimes be seen in fully formed cartilage by the presence of faint concentric lines around the cells (see fig. 77). In a variety of cartilage found in the ears of rats and mice called Fig. 81.— Plan of multiplication of cells in cartilage. a, Cell in its capsule ; 6, divided into two, each with a capsule ; c, primary capsule disappeared, secondary capsules coherent with matrix ; d, tertiary division ; e, secondary capsules disappeared, tertiary coherent with matrix. (After Sharpey.) cellular cartilage, the cells never multiply to any great extent, and they are only separated by their thickened capsules. But in most cartilages the cell-capsules will not explain the origin of the whole matrix, but intercellular material accumulates outside the capsules and still further separates the eells. By certain methods of double staining, this twofold manner of formation may be shown very markedly. We have seen that chondrin obtained by boiling cartilage is really a mixture of two substances; one is a mucinoid material, and comes from the capsules ; the other is gelatin, which comes from the rest of the ground-substance which is collagenous. In hyaline cartilage, how- ever, the collagen does not become precipitated to form fibres, but in 54 THE CONNECTIVE TISSUES [CH. V. white fibro-cartilage it does. In yellow fibro-cartilage the matrix is pervaded by a deposit of elastin, which results in the formation of a network of elastic fibres. Bone. Bone contains nearly 50 per cent, of water ; the solid material is composed of earthy and animal matter in the proportion of about 67 per cent, of the former to 33 per cent, of the latter. The earthy matter is composed chiefly of calcium phosphate, but besides this, there is a small quantity (about 11 of the 67 per cent.) of calcium carbonate, calcium fluoride, and magnesium phosphate. The animal matter is chiefly collagen, which is converted into gelatin by boiling. The animal and earthy constituents of bone are so intimately blended and incorporated the one with the other that it is only by severe measures, as for instance by a white heat in one case and by the action of concentrated acids in the other, that they can be separated. Their close union too is further shown by the fact that when by acids the earthy matter is dissolved out, or on the other hand when the animal part is burnt out, the shape of the bone is alike preserved. The proportion between these two constituents of bone varies slightly in different bones in the same individual and in the same bone at different ages. To the naked eye there appear two kinds of structure in different bones, and in different parts of the same bone, namely, the dense or compact, and the spongy or cancellous tissue. Thus, in making a longitudinal section of a long bone, as the humerus or femur, the articular extremities are found capped on their surface by a thin shell of compact bone, while their interior is made up of the spongy or cancellous tissue. The shaft, on the other hand, is formed almost entirely of a thick layer of the compact bone, and this surrounds a central canal, the medullary cavity — so called from its containing the medulla or marrow. In the flat bones, as the parietal bone or the scapula, the can- cellous structure (diploe) lies between two layers of the compact tissue, and in the short and irregular bones, as those of the carpus and tarsus, the cancellous tissue fills the interior, while a thin shell of compact bone forms the outside. Marrow. — There are two distinct varieties of marrow — the red and yellow. Bed marrow is the connective tissue which occupies the spaces in the cancellous tissue ; it is highly vascular, and thus maintains the nutrition of the spongy bone, the interstices of which it fills. It contains a few fat-cells and a large number of marrow-cells. The CH. V.] MARROW 55 marrow-cells are amoeboid, and resemble large leucocytes; the granules of some of these cells stain readily with acid and neutral dyes, but a considerable number have coarse granules which stain readily with basic dyes like methylene blue. Among the cells are some nucleated cells of the same tint as coloured blood-corpuscles. These are termed erythrohlasts. From them the coloured corpuscles of the blood are developed. There are also a few large cells with many nuclei, termed giant cells or myelojplaxes (fig. 82). Yellow marrow fills the medullary cavity of long bones, and con- sists chiefly of fat-cells with numerous blood-vessels; many of its cells also are the colourless marrow-cells first mentioned. Fig. 82. — Cells of the red marrow of the guinea-pig, highly magnified, a, A large cell, the nucleus of which appears to be partly divided into three by constrictions ; 6, a cell, the nucleus of which shows an appearance of being constricted into a number of smaller nuclei ; c, a so-called giant cell or myeloplase, with many nuclei ; d, a smaller myeloplaxe, with three nuclei ; e — i, proper cells of the marrow. (E. A. Schafer.) Periosteum and Nutrient Blood-vessels.— The surfaces of bones, except the part covered with articular cartilage, are clothed by a tough, fibrous membrane, the periosteum ; and it is from the blood-vessels which are distributed in this membrane, that the bones, especially their more compact tissue, are in great part supplied with nourishment ; minute branches from the periosteal vessels enter the little foramina on the surface of the bone, and find their way to the Haversian canals, to be immediately described. The long bones are supplied also by a proper nutrient artery which, entering at some part of the shaft so as to reach the medullary cavity, breaks up into branches for the supply of the marrow, from which again small vessels are distributed to the interior of the bone. Other small blood-vessels pierce the articular extremities for the supply of the cancellous tissue. Microscopic Structure of Bone. — Notwithstanding the differ- ences of arrangement just mentioned, the structure of all bone is found under the microscope to be essentially the same. 56 THE CONNECTIVE TISSUES [CII. V. Examined with a rather high power its substance is found to contain a multitude of small irregular spaces, approximately fusi- form in shape, called lacuna?, with very minute canals or canaliculi leading from them, and anastomosing with similar little prolonga- tions from other lacunae (fig. 83). In very thin layers of bone, no other canals but these may be visible ; but on making a transverse section of the compact tissue as of a long bone, e.g., the humerus or ulna, the arrangement shown in fig. 83 can be seen. The bone seems mapped out into small circular districts, at or about the centre of each of which is a hole, around which is an Fig. 83. — Transverse section of compact bony tissue (of humerus). Three of the Haversian canals are seen, with their concentric rings ; also the lacunae, with the canaliculi extending from them across the direction of the lamellaj. The Haversian apertures were rilled with air and debris in grinding down the section, and therefore appear black in the figure, which represents the object as viewed with transmitted light. The Haversian systems are so closely packed in this section, that scarcely any interstitial lamellae are visible, x 150. (Sharpey.) appearance as of concentric layers ; the lacunce and canaliculi follow the same concentric plan of distribution around the small hole in the centre, with which indeed they communicate. On making a longitudinal section, the central holes are found to be simply the cut extremities of small canals which run lengthwise through the bone, anastomosing with each other by lateral branches (fig. 84); these canals are called Haversian canals, after the name of the physician, Clopton Havers, who first accurately described them. The Haversian canals, the average diameter of which is ^-j^- of an inch, contain blood-vessels, and by means of them blood is conveyed to all, even the densest parts of the bone ; the minute canaliculi and CH. V.] BONE 57 lacunae take up the lymph exuded from the Haversian blood-vessels, and convey it to the substance of the bone which they traverse. The blood-vessels enter the Haversian canals both from without, by traversing the small holes which exist on the surface of all bones beneath the perios- teum, and from within by means of small channels which extend from the medullary cavity, or from the cancellous tissue. The arteries and veins usually occupy separate canals, and the veins, which are the larger, often pre- sent, at irregular intervals, small pouch- like dilatations. Nerve filaments are also found in the Haversian canals, and a little connective tissue with cleft-like lymph spaces. The larger canals may contain a few marrow cells. The lacunae are occupied by branched cells, which are called hone-cells, or hone- corpuscles (fig. 85) ; these closely resemble ordinary branched connective-tissue corpuscles. Bone is thus essentially connective tissue, the ground- substance of which is impregnated with lime salts. The bone-cor- puscles with their processes, occu- pying the lacunae and canaliculi, correspond exactly to the connec- tive-tissue corpuscles lying in branched spaces. The connection of the lacunae by the canaliculi allows the nutrient lymph to pass from place to place. Lamellae of Compact Bone. — In the shaft of a long bone three distinct sets of lamellae can be clearly recognised. 1. Circumferential lamellae ; these are concentrically arranged just beneath the periosteum, and Fig. S5.— Bone-corpuscles with their processes around the medullary Cavity, as seen in a thin section of human bone. r, tt • i n„ ±\ (Roiiett.) 2. Haversian lamellae ; these Fig. 84. — Longitudinal section from the human ulna, showing Haversian canals, lacunae, and canali- culi. (Rollett.) 58 THE CONNECTIVE TISSUES [CH V. are concentrically arranged around the Haversian canals to the number of six to eighteen around each. 3. Interstitial lamellae; these connect the systems of Haversian lamellae, filling the spaces between them, and consequently attaining their greatest development where the Haversian systems are few, and vice versd. The ultimate structure of the lamellae is fibrous. If a thin film be peeled off the surface of a bone, from which the earthy matter has been removed by acid, and examined with a high power of the micro- scope, it will be found composed of very slender fibres decussating 1: V ;/,/>//), >i''7 ,/■ Fig. SO.— Thin layer 'peeled off from a softened bone. This figure, which is in- tended to represent the reticular structure of a lamella, gives a better idea of the object when held rather farther off than usual from the, eye. x 400. (Sharpey.) Fir;. S7. — Lamella; torn off from a decalcified human uarietal bone at some depth from the surface. a, ", Lamella?, showing intercrossing fibres; b, darker part, where several lamellae are super- posed ; c, perforating fibres. Apertures, through which perforating fibres had passed, are seen especially in the lower part, o, a, of the figure. (Allen Thomson.) obliquely, but coalescing at the points of intersection, as if here the fibres were fused rather than woven together (fig. 86). These are called the intercrossing fibres of Sharpey ; they correspond to the white fibres of connective tissue, and form the source of the gelatin obtained by boiling bone. In many cases, as in the parietal bone, the lamellae are perforated by tapering fibres called the perforating fibres of Sharpey, resembling in character the ordinary white or more rarely the elastic fibres, which bolt the neighbouring lamellae together, and may be drawn out when the latter are torn asunder (fig. 87). These perforating fibres originate from ingrowing processes of the periosteum, and in the adult still retain their connection with it. CH. V.] OSSIFICATION 59 Development of Bone. — From the point of view of their develop- ment, all bones may be subdivided into two classes : — (a.) Those which are ossified directly or from the first in a fibrous membrane afterwards called the periosteum — e.g., the bones forming the vault of the skull, parietal, frontal, and a certain portion of the occipital bones. (b.) Those whose form, previous to ossification, is laid down in hyaline cartilage — e.g., humerus, femur. The process of development, pure and simple, may be best studied in bones which are not preceded by cartilage; and without a know- ledge of this process (ossification in membrane), it is impossible to understand the more complex series of changes through which such a structure as the cartilaginous femur of the foetus passes in its transformation into the bony femur of the adult (ossification in cartilage). Ossification in Membrane. — The membrane, afterwards forming the periosteum, from which such a bone as the parietal is developed, consists of two layers — an external fibrous, and an internal cellular or osteo-genetic. The external layer is made up of ordinary fibrous tissue. The internal layer consists of a network of fine fibrils with a large number of nucleated cells (osteoblasts), some of which are oval, others drawn out into long branched processes: it is more richly supplied with capillaries than the outer layer. It is this portion of the periosteum which is immediately concerned in the formation of bone. In such a bone as the parietal, ossification is preceded by an in- crease in the vascularity of this membrane, and then spicules, starting from a centre of ossification near the centre of the future bone, shoot out in all directions towards the periphery. These primary bone spicules consist of fibres which are termed osteo-genetic fibres ; they are composed of a soft, transparent substance called osteogen, around and between which calcareous granules are deposited. The fibres in their precalcified state are likened to bundles of white fibrous tissue, to which they are similar in chemical composition, but from which they differ in being stiffer and less wavy. The deposited granules after a time become so numerous as to imprison the fibres, and bony spiculae result. By the junction of the osteo-genetic fibres and their resulting bony spicules a meshwork of bone is formed. The osteo- genetic fibres, which become indistinct as calcification proceeds, persist in the lamellae of adult bone as the intercrossing fibres of Sharpey. The osteoblasts, being in part retained within the bony layers thus produced, form bone corpuscles. On the bony trabeculse first formed, layers of osteoblastic cells from the osteo-genetic layer of the perios- teum repeat the process just described ; and as this occurs in several thicknesses, and also at the edges of the spicules previously formed, 60 THE CONNECTIVE TISSUES [Cli. V. the bone increases, both in thickness, length and breadth. The pro- cess is not completed by the time the child is born ; hence the fonta- nelles or still soft places on the heads of infants. Fig. 88 represents a small piece of the growing edge of a parietal bone. The bulk of the primitive spongy bone is in time converted into compact bony tissue, with Haversian systems. Those portions in the interior not converted into bone become filled with the red marrow of the cancellous tissue. Ossification in Cartilage. — Under this heading, taking the femur Fig. SS. — Part of the growing edge of the developing parietal bone of a foetal cat. sp, Bony spicules with some of the osteoblasts imbedded in them, producing the lacunae ; of, osteogenic fibres prolonging the spicules with osteoblasts (osf) between them and applied to them. (Bchafer.) or any other long bone as an example, we have to consider the process by which the solid cartilaginous rod which represents the bone in the foetus is converted into the hollow cylinder of compact bone with expanded ends formed of cancellous tissue of which the adult bone is made up. We must bear in mind the fact that this foetal cartila- ginous femur is many times smaller than even the medullary cavity of the shaft of the mature bone, and, therefore, that not a trace of the original cartilage can be present in the femur of the adult. Its pur- pose is indeed purely temporary; and, after its calcification, it is gradually and entirely absorbed. The cartilaginous rod which forme the precursor of a fcetal long CH. V.] OSSIFICATION 61 bone is sheathed in a membrane exactly resembles the periosteum layers, in the deeper one of which spheroidal and branched cells predominate and blood-vessels abound, while the outer layer consists mainly of fibres. Between the cartilaginous pre- figurement of which the foetal long bone consists and the adult bone there are several inter- mediate stages. The process may, however, be most conveniently described as occurring in three principal stages. The first stage consists of two sets of changes, one in the carti- lage, the other under the peri- chondrium. These take place side by side. In the cartilage the cells in the middle * become enlarged and separated from one another. The cartilage-cells on each side get arranged in rows in the direction of the extremities of the cartilaginous rod. If at this stage one cuts the little em- bryonic bone with a knife, the knife encounters resistance, and there is a sensation of grittiness. This is due to the fact that cal- careous particles are deposited in the matrix; and in consequence of this the matrix stains differ- ently with histological reagents from the unaltered matrix. Simultaneously with this, the periosteal tissue is forming layer after layer of true bone ; this is formed exactly in the same way * This is the case in nearly all the long bones, but in the terminal pha- langes the change occurs first, not in the middle but at their distal extremities. termed the perichondrium, which described above ; it consists of two Fig. 89. — Section of two fetal phalanges ; the carti- lage-cells in the centre of B are enlarged and separated from one another by calcified matrix. im, Layer of bone deposited under the perios- teum ; o, layer of osteoblasts by which this layer was formed. The rows of cartilage-cells are seen on each side of the centre of calcifica- tion. In A, the terminal phalanx, the changes begin at the tip. (After Dixey.) C2 THE CONNECTIVE TISSUES [CH. as in such a bone as the parietal ; by the agency of the osteoblasts, osteogenetic fibres, and] then spicules of bone, are formed by deposit of calcareous matter. As the layers are formed, some of the osteo- blasts get walled in between the layers, and become bone cells. In the later part of this stage the calcareous deposit between the cartilage-cells cuts them off from nutrition, and they in consequence waste, leaving spaces that are called the primary areola:. The calcareous deposit creeps up bstween . the rows of cartilage-cells, p 1G- 90. Ossification iu cartilage showing stage of irruption. The shrunken cartilage-cells are seen in the primary areolae. At ir an irruption of the subperiosteal tissue has penetrated the sub- periosteal tony crust. (After Lawrence.) enclosing them in calcified boxes containing one, two, or more cells each. The wasting of the cells leads here also to the formation of primary areolae. We may roughly compare the two sets of cells engaged in the process to two races of settlers in a new country. The cartilage-cells constitute one race, and so successfully build for themselves calcareous homes as to be completely boxed up ; so they waste and disappear, leaving only the walls of their homes enclosing the spaces called primary areolae. The osteoblasts, the other race of cells under the perichondrium, are forming layers of true bone in that situation. CH. V.] OSSIFICATION 63 Some, it is true, get walled in in the process, and become bone- corpuscles, but the system of intercommunicating lacunae and canaliculi maintains their nutrition. These two races are working side by side, and at first do not interfere with each other. But soon comes a declaration of war, and we enter upon the second stage of ossification, which is very appro- priately called the stage of irruption (fig. 90). Breaches occur in the bony wall which the osteoblasts have built like a girdle round the calcifying ^ 1= sT s° ■% & s s cartilage, and through these the peri- Ifs s -i #«T° chondrial tissue pours an invading army § 2 H^^g, S>^=> g into the calcified cartilage. This con- ? ^ =•=> S. S 'S <= sists of osteoblasts, the bone formers; osteoclasts, or the bone destroyers; the latter are large cells, similar to the mye- loplaxes found in marrow (fig. 82). There are also a few fibres, and a store of nutrient supply in the shape of blood- vessels. Having got inside, the osteoclasts set to work to demolish the homes of the cartilage-cells, the walls of the primary areolae, and thus large spaces are formed, which are called the secondary areola?, or the medullary spaces. On the ruins of the calcified cartilage, the osteoblasts pro- ceed to deposit true bone in layers, just as they were wont to do in their own country, under the periosteum. The third stage of ossification is a repetition of these two stages towards the extremities of the cartilage. The carti- lage-cells get flattened and arranged in rows; calcareous deposit occurs around these, and primary areolae result; then follows the advance of the subperiosteal tissue, the demolition of the primary areolae, the formation of secondary areolae, and the deposit of true bone. At the same time, layer upon layer is still being deposited beneath the periosteum, and these, from being at first a mere girdle round the waist of the bone, now extend towards its extremities. The next figure (fig. 91) is a magnified view of the line of advance. The bone which is first formed is less regularly lamellar than that of the adult. The lamellae are not deposited till after birth, and their formation is preceded by a considerable amount of absorption. Fig. 91. — Longitudinal section of ossi- fying cartilage. Calcified trabeculas are seen extending between the columns of cartilage-cells, c, Car- tilage-cells ; a, b, secondary areola?, x 140. (Sharpey.) G4 THE CONNECTIVE TISSUES [cil. V. To carry our similo further, the osteoblasts are not satisfied with the rough constructions that they were first able to make, but having exterminated the cartilage, they destroy (again through the agency of the regiment of giant osteoclasts) their first work, and build regular lamellae, leaving; lacunas for the accommodation of those who desire to retire from active warfare. About this time, too, the marrow cavity is formed by the absorp- tion of the bony tissue that originally occupied the centre of the shaft. Here the osteoclasts have again to do the work, and, with this final act of destruction, all remains of any calcified cartilage of the foetal bone entirely disappear. The formation of a so-called cartilage bone is thus, after all, a formation of bone by subperiosteal tissue, just as it is in the so-called membrane bone. After a time the cartilage at the ends of the shaft begins to ossify independently, and the epiphyses are formed. They are not joined on to the shaft till late in life, so that growth of the bone in length can continue till union takes place. Bone grows in width by the deposition of layers under the perios- teum, like successive rings formed under the bark of a growing tree. This was shown Ions; before the histological details which we have described were made out by Sharpey. Silver rings were placed by Duhamel around the bones of young pigeons. When killed later, the rings were completely covered in by bone ; and in the animals killed last, were even found in the central cavity. Another series of experi- ments with pigs was made by the celebrated John Hunter. The young animals were fed alternately on ordinary food and food dyed by the red pigment madder. The new bony tissue acts like what dyers called a " mordant " : it fixes the dye, and the rings of bone deposited during the madder periods were distinctly red in colour. The importance of the periosteum in bone formation is now recognised by surgeons. When removing a piece of bone they are careful, if possible, to leave the periosteum behind : this leads to regeneration of the lost bone. If it is absolutely necessary to remove the periosteum, successful cases have occurred in which the living periosteum from an animal has effectively been transplanted. The Teeth. During the course of his life, man, in common with most other mammals, is provided with two sets of teeth ; the first set, called the temporary or milk-teeth, makes its appearance in infancy, and is in the course of a few years shed and replaced by the second or per- manent set. CH. V.] THE TEETH 65 The temporary or milk-teeth have only a very limited term of existence. They are ten in number in each jaw, namely, on either side from the middle line two incisors, one canine, and two. deciduous molars, and are replaced by ten permanent teeth. The number of permanent Fig. 92. — Normal well-formed jaws, from which the alveolar plate has been in great part removed so as to expose the developing permanent teeth in their crypts in the jaws. (Tomes.) teeth in each jaw is, however, increased to sixteen by the develop- ment of three molars on each side of the jaw, which are called the permanent or true molars. The following formula shows, at a glance, the comparative arrange- ment and number of the temporary and permanent teeth : — Temporary Teeth. Middle Line of Jaw. LARS. 2 CANINE. INCISORS. 1 2 INCISORS. 2 CANINE. 1 MOLARS 2 = 10 2 = 10 = 20 TRUE MOLARS. BICUSPIDS OR PRE- MOLARS. 2 CANINE. 1 Permanent Teeth. Middle Line of Jaw. INCISORS. 2 CANINE. 1 BICUSPIDS OR PRE- MOLARS. 2 TRUE MOLARS. From this formula it will be seen that the two bicuspid or pre- molar teeth in the adult are the successors of the two deciduous 66 THE CONNECTIVE TISSUES [cn. V. molars in the child. They differ from them, however, in some respects, the temporary molars having a stronger likeness to the per- manent than to their immediate descendants the so-called bicuspids, besides occupying more space in the jaws. The temporary incisors and canines differ from their successors but little except in their smaller size and the abrupt manner in which their enamel terminates at the necks of the teeth, forming a ridge or thick edge. Their colour is more of a bluish-white than of a yellowish shade. The following tables show the average times of eruption of the Temporary and Permanent teeth. In both cases the eruption of any given tooth of the lower precedes, as a rule, that of the corresponding tooth of the upper jaw. Temporary or Milk Teeth. The figures indicate in months the age at which each tooth appears. DECIDUOUS FIRST MOLARS. DECIDUOUS SECOND MOLARS. 12 18 24 Permanent Teeth. The age at which each tooth is cut is indicated in this table in years. FIRST MOLARS. CENTRALS. 1 LATERALS. BICUSPIDS OR PRE- MOLARS. FIRST. SECOND. SECOND MOLARS. THIRD MOLARS OR WISDOMS. 10 11 12 17 to 25 The times of eruption given in the above tables are only approxi- mate: the limits of normal variation are tolerably wide. Certain diseases affecting the bony skeleton, e.g. Eickets, retard the eruptive period considerably. It is important to notice that it is a molar which is the first tooth to be cut in the permanent dentition, not an incisor as in the case of the temporary set, and also that it appears behind the last deciduous molar on each side. The third molars, often called Wisdoms, are sometimes unerupted through life from want of sufficient jaw space and the presence of CH. V.] THE TEETH 67 the other teeth ; cases of whole families in which their absence is a characteristic feature are occasionally met with. When the teeth are fully erupted it will be observed that the upper incisors and canines project obliquely over the lower front teeth, and the external cusps of the upper bicuspids and molars lie outside those of the corresponding teeth in the lower jaw. This arrangement allows to some extent of a scissor-like action in dividing and biting food in the case of incisors ; and a grinding motion in that of the bicuspids and molars when the side to side movements of the lower jaw bring the external cusps of the lower teeth into direct articula- tion with those of the upper, and then cause them to glide down the inclined surfaces of the external and up the internal cusps of these same upper teeth during the act of mastication. The work of the canine teeth in man is similar to that of his incisors. Besides being a firmly implanted tooth and one of stronger substance than the others, the canine tooth is important in preserving the shape of the angle of the mouth, and by its shape, whether pointed or blunt, long or short, it becomes a character tooth of the dentition as a whole in both males and females. Another feature in the fully developed and properly articulated set of teeth is that no two teeth oppose each other only, but each tooth is in opposition with two, except the upper Wisdom, usually a small tooth. This is the result of the greater width of the upper incisors, which so arranges the " bite " of the other teeth that the lower canine closes in front of the upper one. Should a tooth be lost, therefore, it does not follow that its former opponent remaining in the mouth is rendered useless and thereby liable to be removed from the jaw by a gradual process of extrusion commonly seen in teeth that have no work to perform by reason of absence of antagonists. Structure of a Tooth. A tooth is generally described as possessing a crown, neck, and root. The crown is the portion which projects beyond the level of the gum. The neck is that constricted portion just below the crown which is embraced by the free edges of the gum ; and the root includes all below this. On making longitudinal and transverse sections through its centre (figs. 93, 94), a tooth is found to be composed of a hard material, dentine or ivory, which is moulded around a central cavity which resembles in general shape the outline of the tooth ; the cavity is called the pulp cavity from its containing the very vascular and sensitive pulp. The tooth-pulp is composed of loose connective tissue, blood-vessels, 68 THE CONNECTIVE TISSUES [CH. V. nerves, and large numbers of cells of varying shapes ; on the sur- face in close connection with the dentine is a specialised layer of B. a lt-i Fig. 93.— A, Longitudinal section of a human molar tooth ; c, cement ; d, dentine ; e, enamel ; v, pulp- cavity. (Owen.) B, Transverse section. The letters indicate the same as in A. cells called odontoblasts, which are elongated columnar cells with a large nucleus at the tapering ends farthest from the dentine. Lower jaw-bow Dentine. Periosteum of alveolus. Fig. 94. — Frenijlar tooth of cat in, situ. CH. V.] DENTINE 69 The blood-vessels and nerves enter the pulp through a small open- ing at the apical extremity of each root. The exact terminations of the nerves are not definitely known. They have never been observed to enter the dentinal tubes. No lymphatics have been seen in the pulp. A layer of very hard calcareous matter, the enamel, caps that part of the dentine which projects beyond the level of the gum ; while sheathing the portion of dentine which is beneath the level of the gum, is a layer of true bone, called the cement or crusta petrosa. At the neck of the tooth, where the enamel and cement come into contact, each is reduced to an exceedingly thin layer ; here the cement overlaps the enamel, and is prolonged over it. On the surface of the crown of the tooth, when it first comes through the jaw, is a thin membrane called NasmytKs membrane, or the cuticle of the tooth. The covering of enamel becomes thicker towards the crown, and the cement towards the lower end or apex of the root. Dentine or Ivory. Dentine closely resembles bone in chemical composition. It con- tains, however, only 10 per cent, of water. The proportion in a hundred parts of the solids is about twenty-eight animal to seventy- two of earthy matter. The former, like the animal matter of bone, may be converted into gelatin by boiling. It also contains a trace of fat. The earthy matter is made up chiefly of calcium phosphate, with a small portion of the carbonate, and traces of calcium fluoride and magnesium phosphate. Under the microscope dentine is seen to be finely channelled by a multitude of delicate tubes, which by their inner ends com- municate with the pulp-cavity, and by their outer extremities come into contact with the under part of the enamel and cement, and sometimes even penetrate them for a greater or less distance (figs. 95, 97). The matrix in which these tubes lie is composed of " a reticulum of fine fibres of connective tissue modified by calcification, and where that process is complete, entirely hidden by the densely deposited lime salts " (Mummery). In their course from the pulp -cavity to the surface, the minute tubes form gentle and nearly parallel curves, and divide and subdivide dichotomously, but without much lessening of their calibre until they approach their peripheral termination. From their sides proceed other exceedingly minute secondary canals, which extend into the dentine between the tubules and anastomose with each other. The tubules of the dentine, the average diameter of which at their inner and larger extremity is T twit °f an inch, contain fine prolongations from the tooth-pulp, which give the dentine a certain faint sensitiveness under ordinary circumstances, and, 70 THE CONNECTIVE TISSUES [CH. V. without doubt, have to do also with its nutrition. These prolonga- tions from the tooth-pulp are processes of the dentine-cells or odonto- blasts, the columnar cells lining the pulp-cavity ; the relation of these processes to the tubules in which they lie is precisely similar to that of the processes of the bone-corpuscles to the canaliculi of bone. The outer portion of the dentine, underlying the cement, and the enamel to a much lesser degree, forms a more or less distinct layer termed the granular or interglobular layer (fig. 95). It is characterised Fio. 95.— Section of a portion of the dentine and cement from tlie middle of the root of an incisor tooth. a, Dentinal tubules ramifying and terminating, some of them in the interglobular spaces I p and c; d, inner layer of the cement with numerous closely set canaliculi ; e, outer layer of cement ; /, lacuna: ; g, canaliculi. x 350. (Kolliker.) by the presence of a number of irregular minute cavities. The explanation of these will be seen when we study the development of a tooth. Enamel. Enamel is by far the hardest tissue in the body ; it is composed of the same inorganic compounds that enter into the composition of Fig. 00.— Enamel prisms. A, fragments and single prisms of the transversely-striated enamel, isolated by the action of hydrochloric acid. B, surface of a small fragment of enamel, showing the hexa- gonal ends of the fibres with darker centres, x 350. (Kolliker.) CH. V.] ENAMEL 71 dentine and bone. According to Tomes, it contains no animal matter at all and only 2 or 3 per cent, of water. Gelatin is a characteristic product of connective tissue, and enamel is not a connective tissue, but is epithelial in origin. Examined under the microscope, enamel is found composed of six- sided prisms (figs. 96, 97) ttotto °f an i ncn i n diameter, which are set on end on the surface of the dentine, and fit into corresponding depressions in the same. They radiate in such a manner from the dentine that at the top of the tooth they are more or less vertical, while towards the sides they tend to the horizontal direction. Like the dentine tubules, they are not straight, but disposed in wavy and parallel curves. The prisms are marked by transverse lines and are solid. The enamel prisms are connected together by a very minute quantity of hyaline cement substance. In the deeper part of the enamel, between the prisms, are often small lacunas, which have the processes or fibrils lying in the dentinal tubes in connection with them (fig. 97, c). Grusta Petrosa. The crusta petrosa or cement (fig. 95, e, d) is composed of true bone, and in it are lacunce (/) and canaliculi (g), which sometimes communi- cate with the outer finely branched ends of the dentinal tubules, and generally with the interglobular spaces. Its laminae are bolted to- gether by perforating fibres like those of ordi- nary bone (Sharpey's fibres). Cement differs from ordinary bone in possessing no Haversian canals, or, if at all, only in the thickest part. Such canals are more often met with in teeth with the cement hypertrophied than in the normal tooth. Fig. 97.— Thin section of the enamel, and a part of the dentine. a, Cuticular pellicle of the enamel (Nasmyth's membrane) ; 6, enamel columns with fissures between them and cross striae ; c, larger cavities in the enamel, communicating with the extremities of some of the dentinal tubules (d). x 350. (Kolliker.) Development of the Teeth. The first step in the development of the teeth consists in a down- ward growth (fig. 98, A, 1) from the deeper layer of stratified epi- thelium of the mucous membrane of the mouth, which first becomes thickened in the neighbourhood of the maxillae or jaws now in the course of formation. This process passes downward into a recess of 72 THE CONNECTIVE TISSUES [CH. V. i*s i —' A r the imperfectly developed tissue of the embryonic jaw. The down- ward epithelial growth forms the common enamel or dental germ, and its position is indicated by a slight groove in the mucous membrane of the jaw. After this there is an increased development at certain points correspond- ing to the situations of the future milk-teeth. The com- mon enamel germ thus be- comes extended by further growth into a number of special enamel germs (fig. 98, b,) corresponding to each of the milk-teeth, and con- nected to the common germ by a narrow neck (/). Each tooth is thus placed in its own special recess in the embryonic jaw. As these changes proceed, there grows up from the underlying connective tissue into each enamel germ (fig. 98, C, p), a distinct vascular papilla (dental papilla), and upon it the enamel germ be- comes moulded, and presents the appearance of a cap of two layers of epithelium separated by an interval (fig. 98, c,/). Whilst part of the subepithelial tissue is ele- vated to form the dental papilla, the part which bounds the embryonic teeth forms the dental sac (fig. 98, c, s) ; and the rudiment of the jaw sends up processes form- ing partitions between the teeth. In this way small chambers are produced in which the dental sacs are contained, and thus the sockets of the teeth are formed. The papilla is com- posed of nucleated cells arranged in a mesh-work of connective tissue, the outer or peripheral part being covered with a layer of columnar nucleated cells called odontoblasts. 'iY/S)V Fig. 98. — Section of the upper jaw of a fcetal sheep. A.— 1, common enamel germ dipping down into the mucous membrane; 2, palatine process of jaw; 3, Rete Malpighi. B.— Section similar to A, but passing through one of the special enamel germs here becoming flask-shaped ; c, c', epithelium of mouth;/, neck;/, body of special enamel germ. C. — A later stage ; c, outline of epithelium of gum ; /, neck of enamel germ ; /, enamel organ ; p, papilla ; s, dental sac forming ; / p, the enamel germ of per- manent tooth ; 7(i, bone of jaw ; v, vessels cut across. (Waldeyer and Kiilliker.) CH. V.] DEVELOPMENT OF THE TEETH 73 These cells either by secretion, or as some think by direct trans- formation of the outer part of each, form a layer of dentinal matrix on the apex of the papilla, or if the tooth has more than one cusp, then at the apex of each cusp. This layer is first uncalcified {odontogen), but globules of calcareous matter soon appear in it. These, becoming more numerous, blend into the first cap of dentine. In the meanwhile the odontoblasts have formed a second layer of odontogen within this (fig. 99), and this in turn becomes calcified ; thus layer after layer is formed, each extending laterally further than its predecessor ; the layers blend except in some places ; here portions of odontogen remain, which in a tooth macerated for histological purposes get destroyed, and appear as the interglobular spaces (fig. 95), so called because bounded by the deposit of calcareous salts, which occurs, as we have already seen, in the form of globules. As the odontoblasts retire towards the centre, depositing layer after layer of dentine, they leave behind them long filaments of their protoplasm around which the calcareous deposit is moulded ; thus the dentinal tubules occupied by the processes of the odonto- blasts are formed. The other cells of the dental papilla form the cells of the pulp. Formation of the enamel. — The portion of the enamel or dental germ that covers the dental papilla is at this stage called the enamel organ. This consists of four parts (see figs. 100 and 101). 1. A layer of columnar epithelium cells in contact with the dentine. These are called the enamel cells, or adamanto- blasts. 2. Two or three layers of smaller polyhedral nucleated cells, the stratum intermedium of Hannover. 3. A matrix of non-vascular jelly-like tissue containing stellate cells. 4. An outer membrane of several layers of flattened epithelium cells. The first three layers on an enlarged scale are seen in fig. 101. The enamel prisms are formed by the agency of the ends of the Fig. 99. — Part of section of developing tooth of a young rat, showing the mode of deposition of the dentine. Highly magnified, a, Outer layer of fully formed dentine ; 6, uncalcified matrix with one or two nodules of calcareous matter near the calcified parts ; c, odonto- blasts sending processes into the dentine ; d, pulp ; e, fusiform or wedge-shape cells found between odontoblasts ; /, stellate cells of pulp in fibrous connective tissue. The section is stained with carmine, which colours the uncalcified matrix but not the calcified part. (B. A. Schafer.) 74 THE CONNECTIVE TISSUES [CH. V. adamantoblasts which abut on the dental papilla. Each forms a fine deposit of globules staining with osraic acid and resembling keratin in its resistance to mineral acid. At one time it was believed that each adamantoblast was itself calcified and converted into an enamel prism, but this view has been disproved by recent research. The layer of keratin-like material is outside the bodies of the cells, although a process of each adamantoblast extends into it as a tapering fibre (process of Tomes), and it is usually produced simultaneously with the first layer of uncalcified den- tine ; when it undergoes calcifica- tion, the first layer of enamel is complete. The adamantoblasts then repeat the process, first causing a deposition of keratin- like material, and this in turn is calcified, and so on. During the formation of layer after layer of enamel, the adamantoblasts retire. By the time the enamel is ap- proaching completion the other layers of the enamel organ have almost disappeared, and they en- tirely disappear when the tooth emerges through the gum. But for some little time there is a somewhat more persistent mem- brane covering the crown ; this is iSTasmyth's membrane, or the enamel cuticle ; this is the last formed keratinous layer of enamel which has remained uncalcified. As with the dentine, the for- mation of enamel appears first on the apex of each cusp. The cement or crusta petrosa is formed from the internal tissue of the tooth sac, the structure and function of which are identical with those of the osteogenetic layer of the periosteum ; or, in other words, ossification in membrane occurs in it. The outer layer or portion of the membrane of the tooth sac forms the dental periosteum. This periosteum, when the tooth is fully formed, is not only a means of attachment of the tooth to its socket, but also in conjunction with the pulp a source of nourishment to it. Additional laminae of cement are added to the root from time to time during the life of Fig. 100. — Vertical transverse section of the dental sac, pulp, etc., of a kitten, a, Dental papilla or pulp ; b, the cap of dentine formed upon the summit ; o, its covering of enamel ; d, inner layer of epithelium of the enamel organ ; c , gelatinous tissue ; /, outer epithe- lial layer of the enamel organ ; 7, inner layer, and h, outer laver of dental sac. x 14. (Thiersch.) en. v.] DEVELOPMENT OF THE TEETH 75 the tooth (as is especially well seen in the abnormal condition called an exostosis), by the process of ossification taking place in the perios- teum. On the other hand, absorption of the root (such as occurs when the milk-teeth are shed) is due to the action of the osteoclasts of the same membrane. In this manner the first set of teeth, or the milk-teeth, are formed ; and each tooth, as it grows, presses at length on the wall of the sac enclosing it, and, causing its absorption, is cut, to use a familiar phrase. The temporary or milk-teeth are later replaced by the growth of the permanent teeth, which push their way up from beneath them. Wwmmm^mm^ Fig. 101. — Highly magnified view of a piece of the enamel organ in a kitten's canine, d, Superficial layer of dentine, e, Newly formed enamel stained black by osmic acid. T, Tomes' processes from the adamantoblasts, ad. ; str. int., stratum intermedium of the enamel organ, p, Branched cells of the enamel pulp. (After Rose.) Each temporary tooth is replaced by a tooth of the permanent set which is developed from a small sac which was originally an offshoot from the sac of the temporary tooth which precedes it, and called the cavity of reserve (fig. 98, c, fp). Thus the temporary incisors and canines are succeeded by the corresponding permanent ones, the temporary first molar by the first bicuspid ; the temporary second molar develops two offshoots, one for the second bicuspid, the other for the permanent first molar. The permanent second molar is budded off from the first permanent molar, and the wisdom from the perma- nent second molar. The development of the temporary teeth commences about the sixth week of intra-uterine life, after the laying clown of the bony structure of the jaws. Their permanent successors begin to form 76 THE CONNECTIVE TISSUES [CH. V. about the sixteenth week of intra-uterine life. The second permanent molars originate about the third month after birth, and the wisdom teeth about the third year. The Blood. A full consideration of the blood will come later, when we know more about the chemical aspacts of physiology, but it will be impos- sible to discuss all the other phenomena we shall have to study in the meanwhile without some elementary knowledge of the principal properties of this fluid. For that reason, and also to complete our list of the connective tissues, we may here rapidly and briefly enumerate its principal characters. The blood is a fluid which holds in suspension large numbers of solid particles which are called the corpuscles. The fluid itself is called the plasma or liquor sanguinis. It is a richly albuminous fluid ; and one of the proteids in it is called fibrinogen. After blood is shed it rapidly becomes viscous, and then sets into a jelly. The jelly contracts and squeezes out of the clot a straw- coloured fluid called serum, in which the shrunken clot then floats. The formation of threads of a solid proteid called fibrin from the soluble proteid we have called fibrinogen is the essential act of coagulation ; this, with the corpuscles it entangles, is called the clot. Serum is plasma minus fibrin. The following scheme shows the relationships of the constituents of the blood at a glance : — \ Serum -rn j I Plasma I Fibrin } n , , Blood < r. , v - Clot. ( Corpuscles J The corpuscles are of two chief kinds, the red and the white. The white corpuscles are typical animal cells, and we have already made their acquaintance when speaking about amoeboid movements. The red corpuscles are much more numerous than the white, averaging in man 5,000,000 per cubic millimetre, or 400 to 500 red to each white corpuscle. It is these red corpuscles that give the red colour to the blood. They vary in size and structure in different groups of the vertebrates. In mammals they are biconcave (except in the camel tribe, where they are biconvex) non-nucleated discs, in man S2 1 06 inch in diameter ; during foetal life nucleated red corpuscles are, however, found. In birds, reptiles, amphibians and fishes they are biconvex oval discs with a nucleus : they are largest in the amphibia. The most important and abundant of the constituents of the red corpuscles is the pigment which is called haemoglobin. This is a proteid-like substance, but is remarkable as it contains a small amount of iron (about 0'4 per cent.). The blood during life is in constant movement. It leaves the CH. V.] THE BLOOD 77 heart by the vessels called arteries, and returns to the heart by the vessels called veins ; the terminations of the arteries and the com- mencements of the veins are, in the tissues, connected by the thin- walled microscopic vessels called capillaries. In the capillaries, leakage of the blood-plasma occurs ; this exuded fluid (lymph) carries nutriment from the blood to the tissue-elements, and removes from them the waste products of their activity. The lymph is collected by lymphatic vessels, which converge to the main lymphatic, called the thoracic duct. This opens into the large veins near to their entrance into the heart ; and thus the lymph is returned to the blood. But blood is also a carrier of oxygen, and it is the pigment haemoglobin which is the oxygen carrier ; in the lungs the haemoglobin combines with the oxygen of the air, and forms a loose compound of a bright scarlet colour called oxyhemoglobin. This arterial or oxy- genated blood is taken to the heart and thence propelled by the arteries all over the body, where the tissues take the respiratory oxygen from the haemoglobin, and this removal of oxygen changes the colour of blood to the bluish-red tint it has in the veins. The veins take the blood minus a large quantity of oxygen and plus a large quantity of carbonic acid received in exchange from the tissues to the heart, which sends it to the lungs to get rid of its surplus carbonic acid, and replenish its store of oxygen ; then the same round begins over again. CHAPTER VI MUSCULAR TISSUE Muscle is popularly known as flesh. It possesses the power of con- traction, and is, in the higher animals, the tissue by which their movements are executed. The muscles may be divided from a physiological standpoint into two great classes, the voluntary muscles, those which are under the control of the will, and the involuntary muscles, those which are not. The contraction of the involuntary muscles is, however, controlled by the nervous system, only by a different part of the nervous system from that which controls the activity of the voluntary muscles. When muscular tissue is examined with the microscope, it is seen to be made up of small, elongated, thread-bike structures, which are called muscular fibres ; these are bound into bundles by connective tissue, and in the involuntary muscles there is in addition a certain amount of cement substance, stainable by nitrate of silver, between the fibres. The muscular fibres are not all alike; those of the voluntary muscles are seen by the microscope to be marked by alternate dark and light stripings or striations ; these are called transversely striated muscular fibres. The involuntary fibres have not got these markings as a rule. There is one important exception to this rule, namely, in the case of the heart, the muscular fibres of which are involuntary, but transversely striated. There are, however, histological differ- ences between cardiac muscle and the ordinary voluntary striated muscles. The unstriated involuntary muscular fibres found in the walls of the stomach, intestine, bladder, blood-vessels, uterus, and other contractile organs are generally spoken of as plain muscular fibres. From the histological standpoint there are, therefore, three varieties of muscular fibres found in the body of the higher animals: two of them are transversely striated, and one is not. The relationship of this histological classification to the physiological CH. VI.] VOLUNTARY MUSCLE 79 classification into voluntary and involuntary is shown in the follow- ing table : — 1. Transversely striated muscular fibres : a. In skeletal muscle . . . Voluntary. 6. In cardiac muscle \ 2. Plain muscular fibres : I Involuntary In blood-vessels, intestine, uterus, j bladder, etc. ... J All kinds of muscular tissue are therefore composed of fibres, but the fibres are essentially different from those we have hitherto studied in the connective tissues. There, it will be remembered, the fibres are developed between the cells; here, in muscle, the fibres are developed from the cells; that is, the cells themselves become elongated to form the muscular fibres. Voluntary Muscle. The voluntary muscles are those which are sometimes called skeletal, constituting the whole of the muscular apparatus attached to the bones.* Each muscle is enclosed in a sheath of areolar tissue, called the Epimysium ; this sends in partitions, or septa, dividing off the fibres Fig. 102.— A branched muscular fibre from the frog's tongue. (Kolliker.) into fasciculi, or bundles ; the sheath of each bundle may be called the Perimysium. Between the individual fibres is a small amount of loose areolar tissue, called the Endomysium. The blood-vessels and nerves for the muscle are distributed in this areolar tissue. The fibres vary in thickness and length a good deal, but they average -j^jy inch in diameter, and about 1 inch in length. Each fibre is cylindrical in shape, with rounded ends ; many become pro- longed into tendon bundles (fig. Ill), by which the muscle is attached to bone. As a rule they are unbranched, but the muscle fibres of the face and tongue divide into numerous branches before being inserted * The muscular fibres of the pharynx, part of the oesophagus, and of the muscles of the internal ear, though not under the control of the will, have the same structure as the voluntary muscular fibres. 80 MUSCULAR TISSUE [CH. VI. Fig. 103. — Muscular fibre torn across, the sarcolemma still connecting the two parts of the fibre. (Todd and Bow- man.) to the under surface of the skin, or mucous membrane (fig. 102). The fibres in these situations are also finer than in the majority of the voluntary muscles. Each fibre consists of a sheath, called the sarcolemma, enclosing a soft material called the contractile substance. The sarcolemma is homogeneous, elastic in nature, and especially tough in fish and amphibia. It may readily be demonstrated in a microscopic prepara- tion of fresh muscular fibres by applying gentle pressure to the cover slip; the contractile substance is thereby ruptured, leaving the sarcolemma bridging the space (fig. 103). To the sarcolemma are seen adhering some nuclei. The contractile substance within the sheath is made up of alternate discs of dark and light substance. Muscular fibres contain oval nuclei. In mammalian muscle these are situated just beneath the sarcolemma; but in frog's muscle they ^IWlilliiliiiKiiifraiiigJ ^: :: '':;;:i:r':-::::;:::"'N i; ' :: ^:::::-v. '••;::;;:>>:: *::: :;:;••: -:::::::.>,,; -y { 0# ! l :v;j;::::-::::::'::;,if.ri!i- I1 !!!ij' Fig. 104. — Muscular fibre of a mammal highly mag- nified. The surface of the fibre is accurately focussed. (Schiifer.) occur also in the thickness of the muscular fibre. The chromoplasm of the nucleus has generally a spiral arrangement, and often there is a little granular protoplasm (well seen in the muscular fibres of the diaphragm) around each pole of the nucleus. The foregoing facts can be made out with a low power of the microscope ; on examining muscular fibres with a high power other details can be seen. Treatment with different reagents brings out still further points of structure. These are differently described and differently interpreted by different histologists ; and perhaps no subject in the whole of microscopic anatomy has been more keenly debated than the structure of a muscular fibre, and the meaning of the changes that occur when it contracts. A good deal of the difficulty has doubtless arisen from the fact that a muscular fibre is cylindrical, and if one focusses the surface one gets different optical effects from those obtained by focussing deep in the substance of the fibre. I shall, in the following account of the structure of CH. VI.] VOLUNTARY MUSCLE 81 striated muscle, adhere very closely to the writings of Professor Schafer. If the surface is carefully focussecl rows of apparent granules are seen lying at the boundaries of the light streaks, and fine longitudinal lines passing through the dark streaks may be detected uniting the apparent granules (fig. 104). In specimens treated with dilute acids or gold chloride, the granules are seen to be connected side by side, or transversely also. This reticulum (fig. 105), with its longitudinal and transverse meshes, was at one time considered to be the essential contractile portion of the muscular fibre ; it was thought that on contraction the transverse networks, with their enlargements, the granules, became increased by Fig. 105. — Portion of muscle-fibre of water-beetle, showing network very plainly. One of the trans- verse networks is split off, and some of the longitudinal bars are shown broken off. (After Mel- land.) Fig. 106. — Transverse section through muscular fibres of human tongue. The nuclei are deeply stained, situated at the inside of the sar- colemma. Each muscle fibre shows " Cohnheim's areas." x 450. (Klein and Noble Smith.) the longitudinal strands diminishing in length and running into them. Most histologists have rejected this idea, and regard the network as mere interstitial substance lying between the essentially contractile portions of the muscle. A muscular fibre is thus made up of what are variously called fibrils, muscle-columns or sarcostyles ; and the longitudinal interstitial substance with cross networks comprising the reticulum just referred to is called sarcoplasm. By the use of certain reagents, such as osmic acid or alcohol, the muscle-columns or sarcostyles may be completely separated from one another. A transverse section of a muscular fibre (fig. 106) shows the sections of these sarcostyles ; the interstitial sarcoplasm is represented as white in the drawing. The angular fields separated by sarcoplasm may still be called by their old name, areas of Cohnheim. If, instead of focussing the surface of a fibre, it is observed in its F 82 MUSCULAR TISSUE [CH. VI. depth, a fine dotted line is seen bisecting each light stripe ; this has been variously termed Dobie's line, or Krause's membrane (fig. 107). At one time this was believed to be an actual membrane continuous with the sarcolemma. It is probably very largely an optical effect, caused by light being transmitted between discs of different refrangi- bility. If cross membranes do exist they are not very resistant ; this was well shown by an accidental observation first made by Kiihne, and subsequently seen by others. A minute thread-worm, called the Myorectes, was observed crawling up the interior of the contractile 3 *f£\ 5 #S ■> 4V M \<* ■f^r/ SS ! 3SV 5? Fin. 107.— A. Portion of a human muscular fibre, x 800. B. Separated bundles of fibrils equally magnified; a, a, larger, and b, 6, smaller collections; c, still smaller; d, d, the smallest which could be detached, possibly representing a single series of sarcous elements. (Sharpey.) substance of a muscular fibre ; it crawled without any opposition from membranes, and the track it left, closed up slowly behind it without interfering with the normal cross-striations of the contractile substance. This observation strikingly illustrates the fact that the contractile substance in a muscular fibre is fluid, but only semi-fluid, for the closing of the thread-worm's track occurred slowly as a hole always closes in a viscous material. Another appearance which is sometimes seen is a fine clear line running across the fibre in the middle of each dark band. It is called Hensen's line or d'isc. A muscular fibre may not only be broken up into fibrils or muscle- CII. VI.] SARCOUS ELEMENTS 83 columns, but under the influence of some reagents like dilute hydro- chloric acid, it can be broken up into discs, the cleavage occurring in the centre of each light stripe. Bowman, the earliest to study muscular fibres with profitable results, concluded that the subdivision of a fibre into fibrils was a phenomenon of the same kind as the cross cleavage into discs. He considered that both were artificially pro- duced by a separation in one or the other direction of particles of the fibre he called "sarcous elements." The cleavage into discs is how- ever much rarer than the separation into fibrils; indeed, indications of the fibrils are seen in perfectly fresh muscle before any reagent has been added, and this is markedly evident in the wing muscles of many insects. It is now believed that a muscular fibre is built up of contiguous fibrils or sarcostyles, while cleavage into discs is a purely artificial phenomenon. Haycraft, who has also investigated the question of muscular structure, concludes that the cross striation is entirely due to optical phenomena. The sarcostyles are varicose, and where they are en- larged different refractive effects will be produced from those caused by the intermediate narrow portions. This view he has very in- geniously supported by taking negative casts of muscular fibres by pressing them on to the surface of collodion films. The collodion cast shows alternate dark and light bands like the muscular fibres. Schafer is unable to accept this view; he regards the substance of the sarcostyle in its dark stripes as being of different composition, and not merely of different diameter, from the sarcostyle in the region of the light stripes ; it certainly stains very differently with many reagents, especially chloride of gold. His views regarding the inti- mate structure of a sarcostyle have been worked out chiefly in the wing muscles of insects, where the sarcostyles are separated by a considerable quantity of interstitial sarcoplasm, and a brief summary of his conclusions is as follows : — Each sarcostyle is subdivided in the middle of each light stripe by transverse lines (membranes of Krause) into successive portions, which may be termed sarcomeres. Each sarcomere is occupied by a portion of the dark stripe of the whole fibre; this portion of the dark stripe may be called a sarcous element* The sarcous element is really double, and in the stretched fibre (fig. 108, b) separates into two at the line of Hensen. At either end of the sarcous element is a clear interval separating it from Krause' s membrane; this clear interval is more evident in the extended sarcomere (fig. 108, b), but diminishes on contraction (fig. 108, a). The cause of this is to be found in the structure of the sarcous element. It is pervaded with longi- tudinal canals or pores open towards Krause's membrane, but closed * Notice that this expression has a different meaning from what it originally had when used by Bowman. 84 MUSCULAK TISSUE [CII. VI. at Hansen's line. In the contracted muscle the clear part of the muscle substance passes into these pores, disappears from view to a great extent, swells up the sarcous element, widens it and shortens the sarcomere. In the extended muscle, on the other hand, the clear substance passes out from the pores of the sarcous element, and lies between it and the membrane of Krause ; this lengthens and narrows the sarcomere.* This is shown in the diagrams. It may be added that the sarcous element does not lie free in the middle of the sarco- mere, but is attached at the sides to a fine enclosing envelope, and at either end to Krause's membrane by fine lines running through the clear substance (fig. 109, a). This view is interesting, because it brings into harmony amoeboid, ciliary, and muscular movement. In all three instances we have WU'li'i IIIIIIHU I'i>;. 108. — Sarcostyles from the wing-muscles of a wasp. a. a'. Sarcostyles showing degrees of con- traction. b. A sarcostyle extended with the sarcous elements separated into two parts. c. Sarcostyles moderately extended (semidia- grammatic). (E. A. Schiifer.) S.E. Fig. 109.— Diagram of a sarcomere in a moderately extended con- dition, a, and in a contracted condition, b. k, k, Krause's membranes; h, plane of Hensen ; s.e., poriferous sarcous ele- ment. (E. A. Schiifer.) protoplasm composed of two materials, spongioplasm and hyaloplasm. In amoeboid movement the irregular arrangement of the spongioplasm allows the hyaloplasm to flow in and out of it in any direction. In ciliary movement the flow is limited by the arrangement of the spongioplasm to one direction ; hence the limitation of the movement in one direction (see p. 30). In muscle, also, the definite arrangement of the spongioplasm (represented by the sarcous element) in a longi- tudinal direction limits the movement of the hyaloplasm (represented by the clear substance of the light stripe), so that it must flow either in or out in that particular direction. The muscular fibre is made up of sarcostyles and the sarcostyle of sarcomeres. The contraction of * The existence of open pores is not admitted by all observers. These regard the passage of fluid in and out of the sarcous element as due to diffusion through its membrane. CH. VI.] SAECOPLASM the whole muscle is only the sum total of the contraction of all the constituent sarcomeres. In an ordinary muscular fibre it is stated that when it contracts, not only does it become thicker and shorter, but the light stripes become dark and the dark stripes light. This again is only an optical illusion, and is produced by the alterations in the shape of the sarco- styles, affecting the sarcoplasm that lies between them. When the sarcous elements swell during contraction, the sarcoplasm accu- mulates opposite the membranes of Krause, and diminishes in amount opposite the sarcous elements ; the accumulation of sarcoplasm in the previously light stripes makes them appear darker by contrast than the dark stripes proper. This is very well shown in fig. 110. There is no true reversal of the strip- ings in the sarcostyles them- selves. That this is the case can be seen very well when a muscular fibre is examined with polarised light. A polarising microscope contains a Nicol's prism beneath the stage of the micro- scope which polarises the light passing through the object placed on the stage. The eye-piece contains another Nicol's prism, which detects this fact. If the two Nicols are parallel, the light pass- ing through the first passes also through the second ; but if the second is at right angles to the first, the light cannot traverse it and the field appears dark. If an object on the microscope stage is doubly refracting it will appear bright in this dark field ; if it remains dark it is singly refracting. The sarcoplasm is singly refracting or isotropous ; it remains dark in the dark field of the polarising microscope. The muscle columns or sarcostyles are in great measure doubly refracting or anisotropous, and appear bright in the dark field of the polarising microscope. The sarcostyle, however, is not wholly doubly refracting ; the sarcous elements are doubly refracting, and the clear intervals are singly refracting. On contraction there is no reversal of these appearances, though of course the relative thickness of the singly refracting intervals varies inversely with that of the doubly refracting sarcous elements. Ending of Muscle in Tendon. — A tendon-bundle passes to each muscular fibre, and becomes firmly united to the sarcolemma. The Fig. 110. — Wave of contraction passing over a mus- cular fibre of water-beetle, r, r, portions of the fibre at rest ; c, contracted part ; I, I, inter- mediate condition. (Schafer.) 86 MUSCULAR TISSUE [CH. VI. areolar tissue between the tendon-bundles becomes also continuous with that between the muscular fibres (fig. 111). Blood-vessels of Muscle. — The arteries break up into capillaries, which run longitudinally in the endomysium, transverse branches connecting them (fig. 112). No blood-vessels ever penetrate the sarcolemma. The muscular fibres are thus, like other tissues, nourished by the exudation from the blood called lymph. The lymph is removed by lymphatic vessels found in the perimysium. The nerves of voluntary muscle pierce the sarcolemma, and terminate in expansions called end-plates, to be described on p. 9o. Neuro-muscular Spindles. — Bundles of fine Fig. 112.— Three muscular fibres running longitudinally, and two bundles of fibres in trans- verse section, M, from tlie tongue. The capillaries, C, are injected, x 150. (Klein and Noble Smith.) Fig. 111.— Termination of a muscular fibre in a tendon- bundle, ra, sarcolemma; s, the same passing over the end of bundle ; p. extremity of muscular substance c, retracted from the end of sarcolemma tube; t, tendon bundle fixed to sarcolemma. (Ranvier.) muscular fibres enclosed within a thick lamel- lated sheath of connective tissue are found scattered through voluntary muscles ; they are especially numerous near the tendons and in the proximity of intra-muscular septa. It is remarkable that they have not been found in the ocular or tongue muscles. These structures are called neuro- muscular spindles; they vary in length from \ to \ inch, and are about -j4 T inch in diameter. Each receives a nerve fibre which divides into secondary and tertiary branches. The myelin sheath is lost, and the tertiary branches encircle the muscular fibres, breaking up usually into a network. It is believed that these are sensory end organs in the muscle. (See further, chapter on Touch.) CH. VI.J INVOLUNTARY MUSCLE 87 Red Muscles. In many animals, such as the rabbit, and some fishes, most of the muscles are pale, but some few (like the diaphragm, crureus, soleus, semi-membranosus in the rabbit) are red. These muscles contract more slowly than the pale muscles, and their red tint is due to haemo- globin contained within their contractile substance. In addition to these physiological distinctions, there are histo- logical differences between them and ordinary striped muscle. These histological differences are the following : — 1. Their muscular fibres are thinner. 2. They have more sarcoplasm. 3. Longitudinal striation is therefore more distinct. 4. Transverse striation is more irregular than usual. 5. Their nuclei are situated not only under the sarcolemma, but also in the thickness of the fibre. 6. The transverse loops of the capillary network are dilated into little reservoirs, far beyond the size of ordinary capillaries. Cardiac Muscle. The muscular fibres of the heart, unlike those of most of the involuntary muscles, are striated ; but although, in this respect, they resemble the skeletal muscles, they have distinguishing characteristics of their own. The fibres which lie side by side are united at frequent intervals by short branches (fig. 113). The fibres are smaller than those of the ordinary striated muscles, and their transverse striation is less distinct. No sarcolemma can be dis- cerned. Each fibre has only one nucleus which is situated in the middle of its substance. At the junctions of the fibres there is a certain amount of cementing material, stainable by silver nitrate. This is bridged across by fine fibrils from cell to cell. Plain Muscle. Fig. 113. — Muscular fibre-cells from the heart. (E. A. Schafer.) Plain muscle forms the proper muscular coats (1.) of the digestive canal from the middle of the oesophagus to the internal sphincter ani ; (2.) of the ureters and urinary bladder ; (3.) of the trachea and bronchi ; (4) of the ducts of glands ; (5.) of the gall-bladder ; (6.) of 88 MUSCULAR TISSUE [cn. VI. the vesicular seminales ; (7.) of the uterus and Fallopian tubes ; (8) of blood-vessels and lymphatics ; (9.) of the iris, and ciliary muscle of the eye. This form of tissue also enters largely into the composition (10.) of the tunica dartos, the contraction of which is the principal cause of the wrinkling and contraction of the scrotum on exposure to cold. It occurs also in the skin generally, being found surrounding the secret- ing part of the sweat glands and in small bundles attached to the hair follicles ; it also occurs in the areola of the nipple. It is composed of long, fusiform cells (fig. 114), which vary in length, but are not as a rule more than ^} )W inch long. Each cell has an oval or rod-shaped nucleus. The cell substance is longitudinally but not transversely Fio. 114.- -Muscular fibre-cells from the muscular coat of intestine — highly magnified. Xote the longi tudinal striation, and in the broken fibre the sheath is visible. striated. Each cell or fibre, as it may also be termed, has a delicate sheath. The fibres are united by cementing material, which can be stained by silver nitrate. This intercellular substance is bridged across by fine filaments passing from cell to cell. The nerves in involuntary muscle (both cardiac and plain) do not terminate in end-plates, but by plexuses or networks, which ramify between and around the muscular fibres. Development of Muscular Fibres. All muscular fibres (except those of the sweat glands which are epiblastic) originate from the mesoblast. The plain fibres are simply elongated cells in which the nucleus becomes rod-shaped. In cardiac CH. VI.] DEVELOPMENT OF MUSCLE 89 muscle, the likeness to the original cells from which the fibres are formed is not altogether lost, and in certain situations (immediately beneath the lining membrane of the ventricles) there are found peculiar fibres called after their discoverer Purkinje's fibres ; these are large clear quadrangular cells with granular protoplasm contain- ing several nuclei in the centre, and striated at the margin. It appears that the differentiation of these cells is arrested at an early stage, though they con- tinue to grow in size. Voluntary muscular fibres are developed from cells which become elongated, and the nuclei of which mul- tiply. In most striated muscle fibres the nuclei ulti- mately take up a position beneath the cell-wall or sarcolemma which is formed on the surface. Stria- tums appear first along one side, and extend round the fibre (fig. 115), then they extend into the centre. During life new fibres appear to be formed in part by a longitudinal splitting of pre-existing fibres ; this is preceded by a multiplication of nuclei ; and in part by the lengthening and differentiation of embryonic cells (sarcoplasts) found between the fully formed fibres. In plain muscle, growth occurs in a similar way : this is well illustrated in the enlargement of the uterus during pregnancy; this is due in part to the growth of the pre-existing fibres, and in part to the formation of new fibres from small granular cells lying between them. After parturition the fibres shrink to their original size, but many undergo fatty degeneration and are removed by absorption. g. 115. — Develop- ing muscular fibre from fcetus of two months. (Ean- vier). CHAPTER VII NERVE Nervous tissue is the material of which the nervous system is com- posed. The nervous system is composed of two parts, the central nervous system, and the peripheral nervous system. The central nervous system consists of the brain and spinal cord ; the peripheral nervous system consists of the nerves, which conduct the impulses to and from I Fir,. 116. — Two nerve-Iibres of sciatic nerve. a. Node of Ranvier. b. Axis-cylinder, c. Sheath of Schwann, with nuclei. Medul- lary sheath is not stained, x 300. (Klein and Xoble Smith.) Fii.. 117. — Axis cylinder, highly magnified, showing its com- ponent fibrils. (M. Schultze.) the central nervous system, and thus bring the nerve centres into relationship with other parts of the body. Some of the nerves conduct impulses from the nerve-centres and are called efferent ; those which conduct impulses in the opposite direction are called afferent. When one wishes to move the hand, the nervouB impulse starts in the brain and passes down the efferent or motor nerve-tracts to the muscles of the hand, which contract; when CH. VII.] NERVE-FIBRES 91 one feels pain in the hand, afferent or sensory nerve-tracts convey an impulse to the brain which is there interpreted as a sensation. If all the nerves going to the hand are cut through, all com- munication with the nerve-centres is destroyed, and the hand loses the power of moving under the influence of the will, and the brain receives no impulses from the hand, or, as we say, the hand has lost sensibility. This distinction between efferent and afferent nerves is a physiological one, which we shall work out more thoroughly later on. No histological dis- tinction can be made out between motor and sensory nerves, and it is histological structure which we wish to dwell upon in this chapter. Under the microscope nervous tissue is found to consist essen- tially of nerve-cells and their branches. The nerve-cells are contained in the brain and spinal cord, and in smaller collections of cells on the course of the nerves called ganglia. The part of the nerve-centres containing cells is called grey matter. Long branches of the nerve- cells are known , as nerve-fibres. These become sheathed in a manner to be immediately de- scribed, and are contained in the nerves, and in the white matter of brain and spinal cord. The bodies of nerve-cells differ in size, shape, 3 and arrangement, and we shall discuss these fully when we get to the nerve-centres. For the present it will be convenient to confine ourselves to the nerve-fibres as they are found in a nerve. Nerve-fibres are of two histological kinds, medul- lated and non-meclullatecl. Medullated nerve-fibres are found in the white matter of the nerve-centres 11C XT a and in the nerves originating from the brain and riu. lis. — i\erve- p o fibre stained with spinal cord. Non-medullated nerve-fibres occur m osmic acid. A, {■ ,, ,. node ; b, nucleus, the sympathetic nerves. £5 and Ret " The medullated or white fibres are characterised r-i Fig. 119. — A node of Ranvier in a medullated nerve-fibre, viewed from above. The medullary sheath is in- terrupted, and the primi- tive sheath thickened. Copied from Axel Key and Retzius. x V50. ^Klein and Noble Smith. 1 ) 92 NERVE [CH. VII. by a sheath of white colour, fatty in nature, and stained black by osmic acid ; it is called the medullary sheath or white suhstance of Schxoann ; this sheathes the essential part of the fibre which is a process from a nerve-cell, and is called the axis cylinder. Outside the medullary sheath is a thin homogeneous membrane of elastic nature called the primitive sheath or neurilemma. The axis cylinder is a soft transparent thread in the middle of the fibre; it is made up of exceedingly fine fibrils (fig. 117) which stain readily with gold chloride. The medullary sheath gives a character- istic double contour and tubular appearance to the fibre. It is inter- rupted at regular intervals known as the nodes of Eanvier. The stretch of nerve between two nodes is called an inter-node, and in the middle of each inter-node is a nucleus which belongs to the -Small branch of a muscular nerve of the frog, near its termination, showing division of the fibres, a, into two ; b, into three, x 350. (Kiilliker.) primitive sheath. Besides these interruptions, a variable number of oblique clefts are also seen dividing the sheath into medullary seg- ments (fig. 118); but most if not all of these are produced artificially in the preparation of the specimen. The medullary sheath also contains a horny substance called neurokeratin : the arrangement of this substance is in the form of a network or reticulum holding the fatty matter of the sheath in its meshes. The occurrence of horny matter in the epidermis, in the development of the enamel of teeth and in nerve is an interesting chemical reminder that all these tissues originate from the same embryonic layer, the epiblast. The fatty matter consists largely of lecithin, a phosphorised fat, and cholesterin, a monatomic alcohol. Near their terminations the nerve-fibres branch : the branching occurs at a node (fig. 120). Cn. VII.] NERVE-FIBRES 93 Staining with silver nitrate produces a peculiar appearance at the nodes, forming what is known as the crosses of Ranvier. One limb of the cross is produced by the dark staining of cement Fig. 121.— Several fibres of a bundle of medullated nerve-fibres acted upon by silver nitrate to show behaviour of nodes of Ranvier, M, towards this reagent. The silver has penetrated at the nodes, and has stained the axis-cylinder, M, for a short distance. S, the white substance. (Klein and Noble Smith.) substance which occurs between the segments of the neurilemma ; the other limb of the cross is due to the staining of a number of minute Fig. 122.— Transverse section of the sciatic nerve of a cat about x 100.— It consists of bundles {funiculi) of nerve-fibres ensheathed in a fibrous supporting capsule, epineurium, A ; each bundle has a special sheath (not sufficiently marked out from the epineurium in the figure) or perineurium B ; the nerve-fibres N / are separated from one another by endoneurium ; L, lymph spaces ; Ar, artery ; V, vein ; F, fat. Somewhat diagrammatic. (V. D. Harris.) transverse bands in the axis cylinder (Fromann's lines), which is here not closely invested by the medullary sheath (fig. 121). 94 NERVE [CH. VII The arrangement of the nerve-fibres in a nerve is best seen in a transverse section. The nerve is composed of a number of bundles or funiculi of nerve- fibres bound together by connective tissue. The sheath of the whole nerve is called the epineurium ; that of the funiculi the perineurium ; that which passes between the fibres in a funiculus, the cndoneurium (fig. 122). Single nerve-fibres passing to their destination are sur- rounded by a prolongation of the perineurium, known as the Sheath Fiii. 1"23. — Section across the second thoracic anterior root of the dog, stained with osmic acid. (Gaskell.) of Henle. The nerve trunks themselves receive nerve-fibres which ramify and terminate as end-bulbs in the epineurium. The size of the nerve-fibres varies ; the largest fibres are found in the spinal nerves, where they are 14*4 to 19/x in diameter.* Others mixed with these measure 1*8 to 3'6/x. These small nerve-fibres are the visceral nerves ; they pass to collections of nerve-cells called the sympathetic ganglia, whence they emerge as non-medullated fibres, and are distributed to involuntary muscle. They are well seen in * ix — micro-millimetre = r^Vo millimetre. CH. VII.] END-PLATES 95 sections stained by osmic acid, the black rings being the stained medullary sheaths (fig. 123). The non-medullated fibres or fibres of Eemak have no medullary sheath, and are therefore devoid of the double contour of the medul- lated fibres, and are unaffected in appearance by osmic acid. They Fig. 124. — Grey, or non-medullated nerve-fibres. A. From a branch of the olfactory nerve of the sheep ; two dark-bordered or white fibres from the fifth pair are associated with the pale olfactory fibres. B. From the sympathetic nerve, x 450. (Max Sehultze.) consist of an axis cylinder covered by a nucleated fibrillated sheath. They branch frequently. Though principally found in the sympathetic nerves, a few are found in the spinal nerves mixed with the medullated fibres. Termination of Nerves in Muscle. In the voluntary muscles the motor nerve-fibres have special end organs called end-plates. The fibre branches two or three times (figs. 120, 125), and each branch goes to a muscular fibre. Here the neurilemma becomes continuous with the sarcolemma, the medullary sheath stops short, and the axis cylinder branches repeatedly. This ramification is embedded in a layer of granular protoplasm containing numerous nuclei. Considerable variation in shape of the end-plates occurs in different parts of the animal kingdom. Somewhat similar nerve-endings are seen in tendon ; these, however, are doubtless sensory (figs. 126, 127). In the involuntary muscles, the fibres which are for the most part non-medullated form complicated plexuses near their termination. The plexus of Auerbach (fig. 128) between the muscular coats of the intestine is a typical case. Groups of nerve-cells will be noticed at the junctions of the fine nervous cords. From these plexuses fine branches pass off and bifurcate at frequent intervals, until at last ultimate fibrillae are reached. These subdivisions of the axis cylinders do not anastomose with one another, but they come into close relation- 96 NERVE [CIL VII. ship with the involuntary muscular fibres ; though some histologists have stated that they end in the nuclei of the muscular fibres, it is now believed that they do not pass into their interior. Fie. 125.— From a preparation of the nerve-termination in the muscular fibres of a snake, a, End- plate seen in surface view, b, End-plate seen in profile. (Lingard and Klein.) The terminations of sensory nerves are in some cases plexuses, in others special end organs. We shall deal with these in our study of sensation. . 120. — Termination of medullated nerve-fibres in tendon near the mus- cular insertion. (Golgi.) ■ . 127. — One of the reticulated end-plates of fig. 126, more highly magnified, a, medullated. I nerve-fibres; b, reticulated end-plates.^ (Golgi.) Development of Nerve-fibres. A nerve-fibre is primarily an out-growth from a nerve-cell, as is shown in the accompanying diagram. A nerve-cell, though it may have many branches, only gives off one process which becomes the axis cylinder of a nerve-fibre. This acquires a medullary sheath when it passes into the white matter of the brain or spinal cord, and CH. VII.] DEVELOPMENT OF NERVE-FIBRES 97 a primitive sheath when it leaves the nerve-centre and gets into the nerve. But at first the axis cylinder is not sheathed at all. Fig. 128. — Plexus of Auerbach, between the two layers of the muscular coat of the intestine. (Cadiat.) The formation of the sheaths is still a matter of doubt, but the generally accepted opinion is that the primitive sheath is formed by fl'iG. 129. — Multipolar nerve-cell from anterior horn of spinal cord ; a, axis cylinder process. (Max Schultze.) cells which become flattened out and wrapped round the fibre end to end. These are separated at the nodes by intercellular or cement substance stainable by silver nitrate (fig. 121). These cells are G 98 NERVE [CII. VII. probably mesoblastic. The medullary sheath is formed, according to some, by a fatty change occurring in the parts of these same cells which are nearest to the axis cylinder, but it is much more probable that it is formed from the peripheral layer of the axis cylinder ; the presence of neurokeratin in it distinctly points to an epiblastic origin. The fact also that, in the nerve centres, the medullated nerve-fibres have no primitive sheath, and the phenomena of Wallerian degenera- tion, to be described later, all tend to confirm the same view. CHAPTEE VIII IRRITABILITY AND CONTRACTILITY Irritability or Excitability is the power that certain tissues possess of responding by some change to the action of an external agent. This external agent is called a stimulus. Undifferentiated cells like white blood-corpuscles are irritable; when stimuli are applied to them they execute the movements we have learnt to call amoeboid. Ciliated epithelium cells and muscular fibres are irritable ; they also execute movements under the influence of stimuli. Nerves are irritable ; when they are stimulated, a change is pro- duced in them; this change is propagated along the nerve, and is called a nervous impulse ; there is no change of form in the nerve visible to the highest powers of the microscope ; much more delicate and sensitive instruments than a microscope must be employed to obtain evidence of a change in the nerve ; it is of a molecular nature. But the irritability of nerve is readily manifested by the results the nervous impulse produces in the organ to which it goes; thus the stimulation of a motor nerve produces a nervous impulse in that nerve which, when it reaches a muscle, causes the muscle to contract: stimulation of a sensory nerve produces a nervous impulse in that nerve which, when it reaches the brain, causes a sensation. Secreting glands are irritable ; when irritated or stimulated they secrete. The electrical organs found in many fishes like the electric eel, and torpedo ray, are irritable ; when they are stimulated they give rise to an electrical discharge. Contractility is the power that certain tissues possess of respond- ing to a stimulus by change of form. Contractility and irritability do not necessarily go together; thus both muscle and nerve are irritable, but of the two, only muscle is contractile. Some movements visible to the microscope are not due to con- tractility ; thus granules in protoplasm or in a vacuole may often be seen to exhibit irregular, shaking movements due simply to vibrations 100 IRRITABILITY AND CONTRACTILITY [CH. VIII. transmitted to them from the outside. Such movement is known as Brownian movement. Instances of contractility are seen in the following cases : — 1. The movements of protoplasm seen in simple animal and vegetable cells ; in the former we have already considered streaming, gliding, and amoeboid movement (see p. 12) ; in the latter case we have noted the rotatory movements of the protoplasm within the cell wall in certain plants (see p. 13). 2. The movements of pigment cells. These are well seen under the skin of such an animal as the frog ; under the influence of elec- tricity and of other stimuli, especially of light, the pigment granules are massed together in the body of the cell, leaving the processes quite transparent (fig. 130). If the stimulus is removed the granules gradually extend into the processes again. Thus the skin of the frog is sometimes uniformly dusky, and sometimes quite light -#♦ Fig. 130. — Frog's pigment cells. Fig, 131. — Pigment cells frum the retina, a, cells still cohering, seen on their surface ; a, nu- cleus indistinctly seen. In the other cells the nucleus is concealed by the pigment granules. b, two cells seen in profile; a, the outer or posterior part containing scarcely any pig- ment, x 370. (Henle.) coloured. The chamaeleon is an animal which has become almost proverbial, since it possesses the same power to a marked degree. This function is a protective one ; the animal approximates in colour that of its surroundings, and so escapes detection. In the retina we shall find a layer of pigment cells (fig. 131), the granules in which are capable of moving in the protoplasm in a some- what similar way ; the normal stimulus here also is light. 3. Ciliary movement ; here we have a much more orderly move- ment which has already been described (see p. 29). 4. In Vorticellse, a spiral thread of protoplasm in their stalk enables them by contracting it to lower the bell at the end of the stalk. 5. In certain of the higher plants, such as the sensitive and carni- vorous plants, movements of the stalks and sensitive hairs of the leaves occur under the influence of stimuli. 6. Muscular movement. This for the student of human physio- logy is the most important of the series ; it is by their muscles that CH. VIII.] EHYTHMICALITY 101 the higher animals (man included) execute the greater number of their movements. If we contrast together amoeboid, ciliary, and muscular movement, we find that they differ from each other very considerably. Amoeboid movement can occur in any part of an amoeboid cell, and in any direction. Ciliary and muscular movement are limited to one direc- tion ; but they are all essentially similar, consisting of the movement of hyaloplasm in and out of spongioplasm ; it is the arrangement of the spongioplasm that limits and controls the movement of the hyalo- plasm (see also p. 84). Rhythmicality. — In some forms of movement there is not only order in direction, but order in time also. This is seen in ciliary movement, and in many involuntary forms of muscular tissue, such as that of the heart. Here periods of contraction alternate with periods of rest, and this occurs at regular intervals. Under the influ- ence of certain saline solutions,* voluntary muscles may be made artificially to exhibit rhythmic contractions. A familiar instance of rhythmic movement in the inorganic world is seen in a water-tap nearly turned off but dripping ; water accumu- lates at the mouth of the tap till the drop is big enough to fall ; it falls, and the process is repeated. If, instead of water, gum or treacle, or some other viscous substance is watched under similar circumstances, the drops fall much more slowly ; each drop has to get bigger before it possesses enough energy to fall. Thus we may get different degrees or rates of rhythmic movement. So in the body, during the period of rest, the cilium or the heart is accumulating potential energy, till, as it were, it becomes so charged that it dis- charges ; potential energy is converted into kinetic energy or move- ment. When contraction travels as a wave along muscular fibres, or from one muscular fibre to another, the term peristalsis is employed. These waves are well seen in such a muscular tube as the intestine, and are instrumental in moving its contents along. The heart's con- traction is a similar but more complicated peristalsis occurring in a rhythmic manner. Muscle and nerve are admirable tissues for studying irritability and contractility. The question may be first asked, what evidence there is of irrita- bility in muscle ? May not the irritability be a property of the nerve-fibres which are distributed throughout the muscle and ter- minate in its fibres ? The doctrine of independent muscular irrita- * Biedermann's fluid has the following composition : — Sodium chloride 5 grammes, alkaline sodium phosphate 2 gr. , sodium carbonate 0'5 gr. , water 1 litre. If one end of the sartorius of a curarised frog is dipped into this fluid, it contracts rhythmically in a manner analogous to the heart. 102 IRRITABILITY AND CONTRACTILITY [CH. VIII bility was enunciated by Haller more than a century ago, and was afterwards keenly debated. It was finally settled by an experiment of Claude Bernard which can be easily repeated by every student. If a frog is taken and its brain destroyed by pithing, it loses con- sciousness, but the circulation goes on, and the tissues of its body retain their vitality for a considerable time. If now a few drops of a solution of curare, the Indian arrow poison, are injected with a small syringe under the skin of its back, it loses in a few minutes all power of movement. If next the sciatic or any other nerve going to muscle is dissected out and stimulated, no movement occurs in the muscles to which it is distributed. Curare paralyses the motor end-plates, so that for all practical purposes the muscles are nerveless ; or rather nervous impulses cannot get past the end-plates and cause any effect on the muscles. But if the muscles are stimulated themselves they contract. Another proof that muscle possesses inherent irritability was adduced by Kuhne. In part of some of the frog's muscles {e.g. part of the sartorius) there are no nerves at all ; yet they are irritable and contract when stimulated. The evidence of the statement just made that the poisonous effect of curare is on the end-plates is the following: — The experiment described proves it is not the muscles that are paralysed. It must therefore be either the nerves, or the links between the nerve-fibres and the muscular fibres. By a process of exclusion we arrive at the conclusion that it is these links, for the following experiment shows it is not the nerves. The frog is pithed as before, and then one of its legs is tightly ligatured so as to include everything except the sciatic nerve of that leg. Curare is injected and soon spreads by the circu- lating blood all over the body except to the leg protected by the liga- ture. It can get to the sciatic nerve of that leg because that was not tied in with the rest. The sciatic nerve of the other leg is now dissected out; when the muscles supplied by it cease to contract when the nerve is stimulated, the frog may be considered to be fully under the influence of the drug. But on stimulating the sciatic nerve of the protected limb, the muscles respond normally; this shows that the nerve which has been exposed to the action of the poison has not been affected by it. Varieties of Stimuli. The normal stimulus that leads to muscular contraction is a nervous impulse ; this is converted into a muscular impulse (visible as a contraction) at the end-plates. This nervous impulse starts at the nerve-centre, brain or spinal cord, and travels down the nerve to the muscle. In a reflex action the nervous impulse in the nerve- CH. VIII.] VARIETIES OF STIMULI 103 centre is started by a sensory impulse from the periphery ; thus when one puts one's hand on something unpleasantly hot, the hand is removed ; the hot object causes a nervous impulse to travel to the brain, and the brain reflects down to the muscles of the hand another impulse by the motor nerves which causes the muscles to contract in such a manner as to move the hand out of the way. But the details of muscular contraction can be more readily studied in muscles removed from the body of such an animal as the frog, and made to contract by artificial stimuli. When we have con- sidered these, we can return to the lessons they teach us about the normal contractions in our own bodies. The first thing to do is to make from a pithed frog a muscle-nerve preparation ; the muscle usually selected is the gastrocnemius, the large muscle of the calf of the leg, with the sciatic nerve attached. For some experiments the sartorius or gracilis may be used; but nearly all can be demonstrated on the gastrocnemius. The tendon of the gastrocnemius may be tied to a lever with a flag at the end of it, and thus its contractions rendered more evi- dent; the bone at the other end is fixed in a clamp. Stimuli may be applied either to the nerve or to the muscle. If the stimulus is applied to the nerve, it is called indirect stimulation ; the stimulus starts a nervous impulse which travels to the muscle ; the muscle is thus stimulated as it is in voluntary contraction by a nervous impulse. Stimulation of the muscle itself is called direct stimulation. These stimuli may be : 1. Mechanical ; for instance a pinch or blow. 2. Chemical ; for instance salt or acid sprinkled on the nerve or muscle. 3. Thermal ; for instance touching the nerve or muscle with a hot wire. 4. Electrical ; the constant or the induced current may be used. In all cases the result of the stimulation is a muscular contrac- tion. Of all methods of artificial stimulation, the electrical is the one most generally employed, because it is more under control and the strength and duration of the stimuli (shocks) can be regulated easily. We shall therefore have to study some electrical apparatus. Chemical stimuli are peculiar, for some which affect muscle do not affect nerve, and vice versd ; thus glycerine stimulates nerve, but not muscle ; ammonia stimulates muscle, but not motor nerves. We may regard stimuli as liberators of energy ; muscle and nerve Fig. 132.— Muscle-nerve preparation n, nerve ; t, tendo Achillis, femur ; (M'Kendrick.) 104 IRRITABILITY AND CONTRACTILITY [CH. VIII. and other irritable structures undergo disturbances in consequence of a stimulus. The disturbance is some form of movement, visible movement in the case of muscle, molecular movement in the case of nerve. A stimulus may be regarded as added motion. Sir William Gowers compares it to the blow that causes dynamite to explode, or the match applied to a train of gunpowder. A very slight blow will explode a large quantity of dynamite ; a very small spark will fire a long train of gunpowder. So in muscle or nerve the effect is often out of all proportion to the strength of the stimulus ; a light touch on the surface of the body may elicit very forcible nervous and muscular disturbances ; and moreover, the effect of the stimulus is propagated along the nerve or muscle without loss. CHAPTEE IX CONTRACTION OF MUSCLE Muscle undergoes many changes when it contracts ; they may be enumerated under the following five heads : — 1. Changes in form. 2. Changes in extensibility and elasticity. 3. Changes in temperature. 4. Changes in electrical condition. 5. Chemical changes. In brief, each of these changes is as follows : — 1. Changes inform. — The muscle becomes shorter, and at the same time thicker. The amount of shortening varies so that the length of the muscle when contracted is from 65 to 85 per cent, of what it was originally. Up to a certain point, increase of the strength of the stimulus increases the amount of contraction. Fatigue diminishes, and up to about 33° C. the application of heat increases the amount of contraction. Beyond this temperature the muscular substance begins to be permanently contracted, and a condition called heat rigor, due to coagulation of the muscle proteids, sets in a little over 40° C. What the muscle loses in length it gains in width ; there is no appreciable change of volume. Among the changes in form must also be mentioned those changes in the individual muscular fibres which require a microscope for their investigation ; these have been already considered (see p. 84). 2. Changes in elasticity and extensibility. — The contracted muscle is more stretched by a weight in proportion to its length than an uncontracted muscle with the same weight applied to it; the extensibility of contracted muscle is increased ; its elasticity is diminished. 3. Changes in temperature. — When muscle is at work or contract- ing, more energetic chemical changes are occurring than when it is at rest ; more heat is produced and its temperature rises. 4. Changes in electrical condition. — A muscle when it contracts undergoes a diphasic variation in its electrical condition. 105 106 CONTRACTION OF MUSCLE fCH. IX. 5. Chemical changes. — These consist in an increased consumption of oxygen, and an increased output of waste materials such as car- bonic acid, and sarco-lactic acid. After prolonged contraction the muscle consequently acquires an acid reaction. These five sets of changes will form the subjects of the following five chapters. CHAPTER X CHANGE IN FOKM IN A MUSCLE WHEN IT CONTKACTS Though it has been known since the time of Erasistratus (B.C. 304) that a muscle becomes thicker and shorter when it contracts, it was not until the invention of the graphic method by Ludwig and Helm- holtz, about sixty years ago, that we possessed any accurate knowledge of this change. The main fact just stated may be seen by simply looking at a contracting muscle, such as the biceps of one's own arm ; but more elaborate apparatus is necessary for studying the various phases in contraction and the different kinds of contraction that may occur. These may be readily demonstrated on the ordinary muscle-nerve preparation (gastrocnemius and sciatic nerve) from a frog. By the graphic method, one means that the movement is recorded by a writ- ing. We shall find that the same method is applied to the heart's movements, respiratory movements, blood pressure, and many other important problems in physiology. The special branch of the graphic method we have now to study is called myography ; the instrument for writing is called a myograph ; the writing itself is called a myogram. Put briefly, a myograph consists of a writing point at the end of a lever attached to the muscle, and a writing surface which travels at a uniform rate, on which the writing point inscribes its movement. The first thing, however, that is wanted is something to stimulate the muscle and make it contract ; the stimulus is usually applied to the nerve, and the form of stimulus most frequently employed is electrical. The galvanic battery in most common use is the Daniell cell. It consists of a well-amalgamated zinc rod immersed in a cylinder of porous earthenware containing 10 per cent, sulphuric acid; this is contained within a copper vessel (represented as transparent for diagrammatic purposes in fig. 133) filled with saturated solution of copper sulphate. Each metal has a binding screw attached to it, to which wires can be fastened. The zinc rod is called the positive element, the copper the negative element. The distal ends of the wires 108 CHANGE IN* FORM IN A MUSCLE WHEN IT CONTRACTS [CH. X. CuSi Cusn attached to these are called poles or electrodes, and the pair of electrodes may be conveniently held in a special form of holder. The electrode attached to the positive element (zinc) is called the negative pole or kathode ; that attached to the negative ele- ment (copper) is called the positive pole or anode. If now the two electrodes are con- nected together, an electrical, galvanic or constant current flows from the copper to the zinc outside the battery, and from the zinc to the copper through the fluids of the battery ; if the electrodes are not connected the circle is broken, and no current can flow at all If now a nerve or muscle is laid across the two electrodes the circuit is completed, and it will be noticed at the moment of completion of the circuit the muscle enters into contraction ; if the muscle is lifted off the electrodes, another contraction occurs at the moment the circuit is broken. The same thing is done more con- veniently by means of a key : fig. 134 represents two common forms of key. A key is a piece of apparatus by which the current v« CuSO. -Diagram of a Dauiell's Battery. Fig. 134.— A. Du Bois Reymoud's Key. B. Mercury Key. can be allowed to pass or not through the nerve or muscle laid on the electrodes. When the key is open the current is broken, as in the next figure (fig. 135); when it is closed the current is allowed to pass. The opening of the key is called break ; the closing of the key is called make. A contraction occurs only at make and break, not while the current is quietly traversing the nerve or muscle. CH. X.] BATTERIES AND KEYS 109 But it will be seen in the Du Bois Keymond key (fig. 134) that there are four binding screws. This key is used as a bridge or short circuiting key, and for many reasons this is the best way to use it. The next diagram (fig. 136) represents this diagrammatically. The two wires from the battery go one to each side of the key ; the elec- trodes come off one from each side of the key. When the key is open no current can get across it, and therefore all the current has to go to the electrodes with the nerve resting on them ; but when the key is closed, the current is cut off from the nerve, as then practically all of it goes by the metal bridge, or short cut, back to the battery. Theo- retically a small amount of current goes through the nerve ; but the resistance of animal tissues to electrical currents is enormous as com- pared to that of metal, and the amount of electricity that flows through a conductor is inversely proportional to the resistance ; the resistance in the metal bridge is so small that for all practical purposes, all the current passes through it. Another form of electrical stimulus is the induced current, pro- duced in an induction coil. In a battery of which the metals are connected by a wire, we have Fig. 135. Fig. 136. seen that the current in the wire travels from the copper to the zinc ; if we have a key on the course of this wire the current can be made or broken at will. If in the neighbourhood of this wire we have a second wire forming a complete circle, nothing whatever occurs in it while the current is flowing through the first wire, but at the instant of making or breaking the current in the first or primary wire, a momentary electrical current occurs in the secondary wire, which is called an induced current ; and if the secondary wire is not a complete circle, but its- two ends are connected by a nerve, this induction shock traverses the nerve and stimulates it ; this causes a nervous impulse to travel to the muscle, which in consequence contracts. If the first and second wires are coiled many times, the effect is increased, because each turn of the primary coil acts inductively on each turn of the secondary coil. The direction of the current induced in the secondary coil is the same as that of the current in the primary coil at the break ; in the opposite direction at the make. The nearer the secondary coil is to the primary, the stronger are the currents induced in the former. 110 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [cil. X. Fig. 137 represents the Du Bois Eeymond coil, the one generally employed in physiological experiments, c is the primary coil, and d and d' its two ends, which are attached to the battery, a key being interposed for making and breaking ; g is the secondary coil, the two terminals of which are at its far end ; to these the electrodes to the nerve are attached ; the distance between the two coils, and so the strength of the induction currents, can be varied at will. It is only when the primary current is made or broken, or its intensity increased or diminished, that induction shocks occur in the secondary circuit which stimulate the nerve. When one wishes to produce a rapid succession of make and break shocks the automatic interrupter or Fig. 137. — Du Bois Reymond's Induction Coil. Wagner's hammer seen at the right-hand end of the diagram is included in the circuit. The next thing to be noticed is that the break effects are stronger than the make effects ; this is easily felt by placing the electrodes on the tongue. This is due to what is called Faraday's extra current. This is a current produced in the primary coil by the inductive influence of contiguous turns of that wire on each other ; its direction is against that of the battery current at make, and so the make shock is lessened. At the break the extra current is of such short duration (because when the circuit is broken there can be no current at all) that for all practical purposes it may be considered as non-existent. The same difference of strength occurs alternately in the repeated shocks produced by Wagner's hammer. Helmholtz, to obviate this, introduced a modification now known after him. It consists in bridging the current by a side wire, so that the current never CH. X.J THE INDUCTION COIL 111 Fig. 138. entirely ceases in the primary coil, but is alternately strengthened and weakened by the rise and fall of the hammer ; the strengthening corresponds to the ordinary make, and is weakened by the make extra current, which occurs in the opposite direction to the battery current ; the break is also incomplete, and so it is weakened by the break extra current, which being in the same direction as the battery current im- pedes its disappearance. The two next diagrams show the way the interrupter acts. We are supposed to be looking at the end of the primary coil; the battery wires are attached to the binding screws A and E (fig. 138). The current now passes to the primary coil by the pillar on the left and the spring or handle of the hammer as far as the screw (C) ; after going round the primary coil, one turn only of which is seen, it twists round a pillar of soft iron on the right-hand side, and then to the screw E and back to the battery; the result of a current going around a bar of soft iron is to make it a magnet, so it attracts the hammer, and draws the spring away from the top screw C, and thus breaks the current ; the current ceases, the soft iron is no longer a magnet, so it releases the hammer, and contact is restored by the spring; then the same thing starts over again, and so a succession of break and make shocks occurs alter- nately and automatically. In Helmholtz's modifica- tion (fig. 139) the battery wires are connected as before. The interrupter is bridged by a wire from B to C (also shown in fig. 137, e). C is raised out of reach, and the lower screw F is brought within reach of the spring. Owing to the wire BC, the vibration of the hammer never entirely breaks the current. Instead of Wagner's hammer a long vibrating reed constructed on the same principle is often used. This has the advantage that the rate of vibration can be varied at will by means of a sliding Fig. 139. 112 CHANGE IX FORM IN A MUSCLE WHEN IT CONTRACTS [CH. X. clamp which fixes the reed, so that different lengths of it can be made to vibrate. If a long piece of reed vibrates, it does so slowly, and thus successive induction shocks at long intervals can be sent into the nerve. But if one wishes to stimulate a nerve more rapidly, the length of reed allowed to vibrate can be shortened. In Ewald's modification of the coil there is another simple method of modifying the rate of the interrupter. But an hour spent in the laboratorv with an induction coil and cell will teach the student Fig. 140. — Myograph of von Helmkoltz, shown in an incomplete form, a, forceps for holding frog's femur; 6, gastrocnemius; c, sciatic nerve; d, scale pan; c, marker recording on cylinder;/, counterpoise. (M'Kendrick.) much more easily all these facts than any amount of reading and description. We can pass now to the myograph. There are many different forms of this instrument. Fig. 140 shows Helmholtz's instrument. The bony origin of the gastrocnemius is held firmly by forceps, and the tendo Achillis tied to a weighted lever ; the end of the lever is provided with a writing-point such as a piece of pointed parch- ment; when the muscle contracts it pulls the lever up, and this movement is magnified at the end of the lever. The writing-point scratches on a piece of glazed paper covered with a layer of soot ; the paper is wrapped round a cylinder. When the lever goes up the writing-point will mark an up-stroke; when it falls it will mark a CH. X.1 MYOGRAPHS 113 down-stroke, and if the cylinder is travelling, the down-stroke will be written on a different part of the paper than the up-stroke ; thus a muscle curve or myogram is obtained. The paper may then be removed, varnished, and preserved. Fig. 141 shows a somewhat different arrangement. The muscle is fixed horizontally on a piece of cork B, one end being fixed by a pin thrust through the knee-joint into the cork ; the Fig. 141. — Arrangement of the apparatus necessary for recording muscle contractions with a revolving cylinder carrying smoked paper. A, revolving cylinder; B, the muscle arranged upon a cork- covered board which is capable of being raised or lowered on the upright, which also can be moved along a solid triangular bar of metal attached to the base of the recording apparatus — the tendon of the gastrocnemius is attached to the writing lever, properly weighted, by a ligature. The electrodes from the secondary coil pass to the nerve — being, for the sake of convenience, first of all brought to a short-circuiting key, D (Du Bois Reymond's) ; C, the induction coil ; F, the battery (in this fig. a bichromate one) ; E, the key (Morse's) in the primary circuit. tendo Achillis is tied to a lever which is weighted near its fulcrum : the lever is so arranged that it rests on a screw till the muscle begins to contract; the muscle therefore does not feel the weight till it begins to contract, and gives a better contraction than if it had been previously strained by the weight. This arrangement is called after- loading. The writing surface is again a travelling cylinder tightly covered with smoked glazed paper. The rest of the apparatus shows how H 114 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [CH. X. cell, coil, keys, and electrodes are applied with the object of stimulat- ing the nerve. The key E makes and breaks the primary circuit, but the effect is only felt by the muscle-nerve preparation when the short-circuiting key D in the secondary circuit is opened. Instead of the key E it is better to have what is called a " kick- over " key which the cylinder by means of a bar projecting from it knocks over and so breaks the primary circuit during the course of a revolution. The exact position of the writing-point at the moment of break, that is the moment of excitation, can then be marked on the blackened paper. Besides the travelling cylinder there are other forms of writing Fig. 142. — Du Bois Raymond's Spring Myograph. (M'Kendrick.) surface. Thus fig. 142 represents the spring myograph of Du Bois Eeymond. Here a blackened glass plate is shot along by the recoil of a spring ; as it travels it kicks over a key, and the result of this, the muscular contraction, is written on the plate. The pendulum myograph (fig. 143) is another form. The pen- dulum carries a smoked glass plate upon which the writing-point of the muscle lever is made to mark. The break shock is sent into the muscle-nerve preparation by the pendulum in its swing opening a key in the primary circuit. This is shown in an enlarged scale in BC (fig. 143). To keep the preparation fresh during an experiment, it should be covered with a glass shade, the air of which is kept moist by means CH. X.] MYOGRAPHS 115 of wet blotting-paper, is shown in nV 144. A somewhat elaborate form of moist chamber V\ Fig. 143. — Pendulum myograph and accessory parts (Fick's pattern). A, pivot upon which pendulum swings ; B, catch on lower end of myograph opening the key, C, in its swing ; D, a spring-catch which retains myograph, as indicated by dotted lines, and on pressing down the handle of which the pendulum swings along the arc to D on the left of figure, and is caught by its spring. The last piece of apparatus necessary is a time-marker, so that the events recorded in the myogram can be timed. The simplest Fig. 144.— Moist Chamber. M 116 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [CH. X. time-marker is a tuning-fork vibrating 100 times a second. This is struck, and by means of a writing-point fixed on to one of the prongs of the fork, these vibrations may be written beneath the myogram. More elaborate forms of electrical time-markers or chronographs are frequently employed. The Simple Muscle Curve. We can now pass on to results, and study first the result of a single instantaneous stimulus upon a muscle. This causes a single or simple muscular contraction, or as it is often called a twitch. The graphic record of such a contraction is called the simple muscle curve. One of these is shown in the accompanying figure (fig. 145). The upper line (m) is traced by the'end of the lever in connection 145. — Simple muscle curve. (M. Foster.) with a muscle after stimulation of the muscle by a single induction- shock : the middle-line (I) is that described by a lever, which indicates by a sudden drop the exact instant at which the induction-shock is given. The lower wavy line (t) is traced by a tuning-fork vibrating 200 times a second, and serves to measure precisely the time occupied in each part of the contraction. It will be observed that after the stimulus has been applied as indicated by the vertical line s, there is an interval before the con- traction commences, as indicated by the line c. This interval, termed the latent period, when measured by the number of vibrations of the tuning-fork between the lines s and c, is found to be about y-^-sec. During the latent period there is no apparent change in the muscle. The second part is the stage of contraction proper. The lever is raised by the shortening of the muscle. The contraction is at first very rapid, but then progresses more slowly to its maximum, indicated CH. X.] THE SIMPLE MUSCLE CURVE 117 by the line mx, drawn through its highest point. It occupies in the figure -g lb-sec. The next stage is the stage of elongation. After reaching its highest point, the lever begins to descend, in consequence of the elongation of the muscle. At first the fall is rapid, but then be- comes more gradual until the lever reaches the abscissa or base line, and the muscle attains its pre-contraction length, indicated in the figure by the line c'. The stage occupies ^^sec. Very often after the main contraction the lever rises once or twice to a slight extent, producing small curves (as in fig. 147). These contractions are simply due to the elasticity of the muscle and recording apparatus, and are most marked when the contraction is rapid and vigorous. The whole contraction occupies about ^ of a second. With regard to the latent period, it should be pointed out that if the muscle is stimulated indirectly, i.e., through its nerve, some of the apparent lost time is occupied in the propagation of the nervous impulse along the nerve. To obtain the true latent period, this must be deducted. Then there is latency in the apparatus (friction of the lever, etc.) to be taken into account. This can be got rid of by photographing the contracting muscle, on a sensitive photographic plate travelling at an accurately-timed rate. By such means it is found that the true latent period is much shorter than was formerly supposed. It is only -j-i^ of a second. In red muscles it is longer. We now come to the action of various factors in modifying the character of the simple muscle curve. 1. Influence of strength of stimulus. — A minimal stimulus is that which is just strong enough to give a contraction. If the strength of stimulus is increased the amount of contraction as measured by the height of the curve is increased, until a certain point is reached (maximal stimulus), beyond which increase in the stimulus produces no increase in the amount of contraction. The latent period is shorter with a strong than with a weak stimulus. 2. Influence of load. — Up to a certain point increase of load increases the amount of contraction, beyond which it diminishes, until at last a weight is reached which the muscle is unable to lift. The latent period is somewhat longer with a heavy load than with a light one. 3. Influence of fatigue. — This can be very well illustrated by letting the muscle write a curve with every revolution of the cylinder, until it ceases to contract at all. The next diagram shows the early stages of fatigue. At first the con- Fig. 140. — Fatigue. tractions improve, each being a little higher than the preceding ; this is known as the beneficial effect of contraction, and the graphic record is called a staircase. Then the contractions get less and less. But what is most noticeable is that the contrac- 118 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [CII. X. tion is much more prolonged ; the latent period gets longer ; the period of contraction gets longer ; and the period of relaxation gets very much longer ; there is a condition known as contracture, so that the original base line is not reached by the time the next stimulus arrives. In the last stages of fatigue, contracture passes off. I. Effect of temperature. — Cold at first increases the height of contraction, then Fni. 147. — Etl'ect of temperature on a single muscular contraction ; N, normal ; H, warm : C'l, cooling ; C2, very cold ; P, point of stimulation. The above tracing is a considerably reduced facsimile of a tracing taken with the pendulum myograph. diminishes it ; otherwise the effect is very like that of fatigue increasing the duration of all stages of the curve. Moderate warmth increases the height and diminishes the duration of all stages of the curve, latent period included. This may be readily shown by dropping some warm salt solution* on to the muscle before taking its curve. Too great heat (above 42 C.) induces heat rigor due to the coagulation of the muscle proteids. 5. Effect of veratrine. — If this is injected into the frog before the nuiscle-nerve preparation is made, the very remarkable result seen in the next diagram is Fig. 14S. — Veratrine curve, taken on a very slowly-travelling [cylinder ; the time tracing indicates seconds. produced on stimulation ; there is an enormous prolongation of the period of relaxa- tion ; marked by a secondary rise, and sometimes by tremors. After repeated stimulation this effect passes off, but returns after a period of rest. The Muscle-Wave. The first part of a muscle which contracts is the part where the nerve-fibres enter ; but nerve impulses are so rapidly carried to all the fibres that for practical purposes they all contract together. But in a nerveless muscle, that is one rendered physiologically nerve- * Physiological saline solution used for bathing living tissue is a 0'7 to 0"9 per cent, solution of sodium chloride in ordinary tap water. CH. X.] THE MUSCLE-WAVE 119 less by curare, if one end of the muscle is stimulated, the contraction travels as a wave of thickening to the other end of the muscle, and the rate of propagation of this wave can be recorded graphically. The next figure (fig. 149) represents one of the numerous methods that have been devised for this purpose. A muscle with long parallel fibres, like the sartorius, is taken ; it is represented diagrammatically in the figure. It is stimulated at the end, where the two wires, + and — , are placed; it is grasped in two places by pincers, which are opened by the wave of ' thickening ; the opening of the first pair of pincers (1) presses on a drum or tambour connected to a second tambour with a recording lever (!'), and this lever goes up first ; the Fig. 149. — Arrangement for tracing the muscle-wave. (M'Kendrick.) lever (2') of the tambour connected with the second pair of pincers (2) goes up later. If the length of muscle between the pairs of pincers is measured, and by a time-tracing the delay in the raising of the second lever is ascertained, we have the arithmetical data for calculating the rate of propagation of the muscle-wave. It is about 3 metres per second in frog's muscle, but is hastened by warmth and delayed by cold and fatigue. The Effect of Two successive Stimuli. If a second stimulus follows the first stimulus, so that the muscle receives the second stimulus before it has finished contracting under the influence of the first, a second curve will be added to the first, as shown in the accompanying diagram (fig. 150). The third little 120 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [CFI. X. curve is only due to elastic after-vibration. This is called super- position, or summation of effects. If the two stimuli are in such close succession that the second occurs during the latent period of the first, the result will differ according as the stimuli are maximal or submaximal. If they are maximal, the second stimulus is without effect ; hut if submaximal Fig. 160. — Tracing of a double muscle-curve. To be reaa from left to right. While the muscle was engaged in the first contraction (whose complete course, had nothing intervened, is indicated by the dotted line), a second induction-shock was thrown in, at such a time that the second con- traction began just as the first was beginning to decline. The second curve is seen to start from the first, as does the first from the base line. (M. Foster.) the two stimuli are added together, and though producing a simple muscle-curve, produce one which is bigger than either would have produced separately. This is called summation of stimuli. Effect of More than Two Stimuli. Just as a second stimulus adds its curve to that written as the result of the first, so a third stimulus superposes its effect on the Fig. 151. — Curve of incomplete tetanus, obtained from the gastrocnemius of a frog, where the shocks were sent in from an induction coil, about sixteen times a second, by the interruption of the primary current by means of a vibrating spring, which dipped into a cup of mercury, and broke the primary current at each vibration. (Tracing to be read right to left.) second ; a fourth on the third, and so on. Each successive increment is, however, smaller than the preceding, and at last the muscle CH. X.] TETANUS 121 remains at a maximum contraction, till it begins to relax from fatigue. A succession of stimuli may be sent into the nerve of a nerve- muscle preparation by means of the Wagner's hammer of a coil, or the vibrating reed previously mentioned (p. 111). This method of stimulation is called faradisation. Figs. 151 and 152 show the kind of tracings one obtains. The number of contractions corresponds to the number of stimulations ; the condition of prolonged contraction so produced, the muscle never relaxing completely between the individual contractions of which it is made up, is called tetanus: incomplete tetanus, or clonus, when the individual contractions are discernible (fig. 151) ; complete tetanus, as in fig. 152, when the con- tractions are so rapid as to be completely fused to form a continuous line without waves. The rate of faradisation necessary to cause complete tetanus varies a good deal ; for' frog's muscle it averages 15 to 20 per second ; for Fig. 152.— Curve of complete tetanus, from a series of very rapid shocks from a magnetic interrupter. (Tracing to be read right to left.) the pale muscles of the rabbit, 20 per second ; for the more slowly contracting red muscles of the same animal, 10 per second ; and for the extremely slowly contracting muscles of the tortoise 2 per second is enough. "With fatigue, the rate necessary to produce complete tetanus is diminished. Voluntary Tetanus. We have seen that voluntary muscles under the influence of artificial stimuli may be made to contract in two ways : a single excitation causes a single contraction; a rapid series of excitations causes a series of contractions which fuse to form tetanus. We now come to the important question, in which of these two ways does voluntary muscle ordinarily contract in the body ? The answer to this is, that voluntary contraction resembles, though it is not absolutely identical with, tetanus artificially produced. It is certainly never a twitch. The nerve-cells from which the motor fibres originate do not possess the power of sending isolated impulses to the muscles ; they send a series of impulses which result in a 122 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [CH. X. muscular tetanus,* or voluntary tetanus, as it may conveniently be termed. If a stethoscope is placed over any contracting muscle of the human body, such as the biceps, a low sound is heard. The tone of this sound, which was investigated by Wollaston, and later by Helmholtz, corresponds to thirty-six vibrations per second ; this was regarded as the first overtone of a note of eighteen vibrations per second, and for a long time 18 per second was believed to be the rate of voluntary tetanus. The so-called " muscle sound " is, however, no indication of the rate of muscular vibration. Any irregular sound of low intensity will produce the same note ; it is, in fact, the natural resonance-tone of the meuibrana tympani of the ear, and, therefore, selected by the organ of hearing when we listen to any irregular mixture of faint, low-pitched tones and noises. A much more certain indication of the rate of voluntary tetanus is obtained by the graphic method. The myographs hitherto de- scribed are obviously inapplicable to the investigation of such a problem in man. The instrument employed is termed a transmis- sion myograph. The next figure shows the recording part of the apparatus. It is called a Marey's Tambour. It consists of a drum, on the Screw to regulate elevation of lever. Writing lever. Tambour. Tube to receiving tambour. Fig. 153. — Marey's Tambour, to which the movement of the column of air in the first tambour is conducted by a tube, and from which it is communicated by the lever to a revolving cylinder, so that the tracing of the movement is obtained. membrane of which is a metallic disc fastened near one end of a lever, the far extremity of which carries a writing point. The interior of the drum is connected by an india-rubber tube (seen at the right- hand end of the drawing) to a second tambour called the receiving tambour, in which the writing lever is absent. Now if the receiving tambour is held in the hand, and the thumb presses on the metallic * The use of the word tetanus in physiology must not be confounded with the disease known by the same name, in which the most marked symptom is an intense condition of muscular tetanus or cramp. CH. X.] VOLUNTARY TETANUS 123 disc on the surface of its membrane, the air within it is set into vibrations of the same rate as those occurring in the thumb muscles ; and these are propagated to the recording tambour and are written in a magnified form by the end of the lever on a recording travelling surface. The tracing obtained is very like that in fig. 151 ; it is an incom- plete tetanus, which by a time marker can be seen to be made up of 10 to 12 vibrations a second. In some diseases these tremors are much increased, as in the clonic convulsions of epilepsy, or those produced by strychnine poisoning, but the rate is the same. Similar tracings can be obtained in animals by strapping the receiving tambour on the surface of a muscle, and causing it to contract by stimulating the brain or spinal cord. The rate of stimu- lation makes no difference ; however slow or fast the stimuli occur, the nerve-cells of the central nervous system give out impulses at their own normal rate. The same is seen in a reflex action. If a tracing is taken from a frog's gastrocnemius, the muscle being left in connection with the rest of the body, its tendon only being severed and tied to a lever, and if the sciatic nerve of the other leg is cut through, and the end attached to the spinal cord is stimulated, an impulse passes up to the cells of the cord, and is then reflected down to the gastrocnemius, under observation. The impulse has thus to traverse nerve-cells ; the rate of simultation then makes no difference ; the reflex contrac- tion occurs at the same rate, 10 or 12 per second. But now a difficulty arises ; if a twitch only occupies T V of a second, there would be time for ten complete twitches in a second ; they would not fuse to form even an incomplete tetanus. There must be some means by which each individual contraction can be lengthened till it fuses with the next contraction ; or, in other words, our results of electrical stimulation of excised muscles must not be applied without reserve to the contraction of the intact muscles in the living body in response to the will. Eecent experiments made by Sir J. Burclon Sanderson on the electrical variation that accompanies voluntary movements, have shown that this is the case : each com- ponent of the so-called voluntary tetanus is a somewhat prolonged single contraction; a condition which closely resembles the tonic contraction of involuntary muscle. Lever Systems. — The arrangement of the muscles, tendons, and bones presents examples of the three systems of levers winch will be known to anyone who has studied mechanics ; the student of anatomy will have no difficulty in finding examples of all three systems in the body. What is most striking is that the majority of cases are levers of the third kind, in which there is a loss of the mechanical 124 CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [(HI. X. power of a lever, though a gain in the rapidity and extent of the movement. Most muscular acts involve the action of several muscles, often of many muscles. The acts of walking and running are examples of very complicated muscular actions in which it is necessary not only that many muscles should take part, but also must do so in their proper order and in due relation to the action of auxiliary and antagonistic muscles. This harmony in a complicated muscular action is called co-ordination. By the device of taking instantaneous photographs at rapidly repeated intervals during a muscular act, the details of different modes of locomotion in man and other animals have been very thoroughly worked out. With this branch of research the name of Prof. Marey is intimately associated. CHAPTEE XI EXTENSIBILITY, ELASTICITY, AND WORK OF MUSCLE Muscle is both extensible and elastic. It is stretched by a weight, that is, it possesses extensibility ; when the weight is taken off, it returns to its original length, that is, it possesses elasticity. The two properties do not necessarily go together ; thus a piece of putty is very extensible, but it is not elastic ; a piece of steel or a ball of Fig. 154.— (After Waller.) ivory are only slightly extensible, but after the stretching force has been removed they return to their original size and shape very perfectly. A substance is said to be strongly elastic, when it offers a great resistance to external forces ; steel and ivory are strongly elastic. A substance is said to be perfectly elastic, when its return to its original shape is absolute; again steel and ivory. may be quoted as examples. Muscle is very extensible, i.e., it is easily stretched; it is feebly 125 126 EXTENSIBILITY, ELASTICITY, AND WORK OF MUSCLE [CII. XI. elastic, i.e., it opposes no great resistance to external force ; it is, however, perfectly elastic; that is, it returns to its original shape very exactly after stretching. This is true in the case of living muscle within the body, but after very great stretching even in the body, and still more so after removal from the body, when it begins to undergo degenerative changes culminating in death, its elasticity is less perfect. The cohesion of muscular tissue is less than that of tendon. E. Weber stated that a frog's muscle one centimetre square in transverse section will support a weight of a kilogramme (over 2 lbs.) without rupture, but this diminishes as the muscle gradually dies. The extensibility of any material may be studied and recorded by measuring the increase of length which occurs when that material is loaded with different weights. In Helmholtz's myograph (fig. 140), different weights may be placed in the scale-pan beneath the muscle, and the increase of length recorded on a stationary blackened cylinder by the downward movement of the writing point ; the cylinder may then be moved on a short distance, more weight added, and the additional increase of length similarly recorded, and so on for a succession of weights. If this experiment is done with some non-Living substance, like a steel spring or a piece of india-rubber, instead of a living muscle, it is found that the amount of stretching is proportional to the weight ; a weight = 2 produces an extension twice as great as that produced by a weight = 1 ; in this way one obtains a tracing like that seen on the left hand of figure 154, and the dotted line drawn through the lowest points of the extensions is a straight one. With muscle, however, this is different ; each successive addition of the same weight produces smaller and smaller increments of ex- tension, and the dotted line obtained is a curve. A continuous curve of extensibility may be obtained by placing a gradually and steadily increasing force beneath the muscle instead of a succession of weights added at intervals. The most convenient way of doing this is to use a steel spring, which is gradually and steadily extended ; and the writing point connected to the muscle inscribes its excursion on a slowly moving cylinder. If, then, after the muscle has been stretched, the steel spring is gradually and steadily relaxed, the muscle retracts and again writes a curve now in the reverse direction, until it regains its original length.* But in muscles removed from the body, unless they are very slightly loaded, the return to the original length is never complete ; the muscle is * A mathematical examination of these curves shows that they are not rect- angular hyperbolas as they were once considered. They are very variable in form, and cannot be identified with anv known mathematical curve. CH. XI.] CURVES OF EXTENSIBILITY 127 permanently longer to a slight extent, which varies with the amount of the previous loading. If the muscle is slowly loaded and slowly unloaded, the curvature of its tracing is much more marked than if the experiment is done rapidly. The following three tracings are reproduced from some obtained by Dr Brodie. In the method used, the records are not complicated by the curve of a lever, but the movement was simply magnified by a beam of light falling on a mirror attached to the end of the muscle, and reflected on to a travelling photographic plate. Each tracing is to be read from right to left ; the first one (A) shows the result of stretching a steel spring by a steadily increasing force ; the end of the spring gets lower and lower, and describes a straight line ; at the apex of the tracing unloading began and went on steadily till the spring once more regained its initial length. The upstroke, like the downstroke, is a straight line. In B and C muscles were used ; it will be noticed that the muscle does not regain its original length after unloading is completed, and the upward tendency of the tracing beyond this point represents after- retraction. In B, the extension was applied rapidly, the tracing is almost a straight line ; in C, the extension was brought about more slowly, and the tracing is a curve; in both cases the tracing of the period of unloading shows more curvature. This introduces us to what is called after-extension and after- retraction. That is to say, after a muscle is weighted there is an immediate elongation, followed by a gradual elongation which continues for some time ; or if a muscle has been weighted and is then unloaded there is an immediate slackening, followed by a gradual after-retraction. This may be shown by looking at the graphic records shown in the next diagram. It will be noticed that the extension is greatest when the muscle is in a contracted condition, and smallest when it is dead (in rigor). In fatigue the after-extension is very marked, and the return after unloading very imperfect. Fig. 155.— Curves of extensibility. (Brodie.) 128 EXTENSIBILITY, ELASTICITY, AND WORK OF MUSCLE [CH. XI. We may now give the results of an actual experiment ; a muscle was loaded with successive weights of 50, 100, 150, etc., grammes, and its length carefully measured in centimetres. Load .... 50 100 150 200 250 300 Total extension 3-2 6 S 9-5 10 10-3 Increment of extension — 2-8 2 1-5 0-5 0-3 Figure 156 shows that the contracted muscle is more extensible than the uncontracted muscle. This may be still further illustrated by an example given on the opposite page in the form of a diagram. The thick lines represent the con- tracted muscle, the thin ones the un- contracted. It is represented as being stretched by different weights indicated along the top line; and the lengths under the influence of these weights are separated by equal distances. Thus A C represents the length of the uncontracted muscle, A B of the con- tracted muscle when unloaded. A' C and A' B' the same under the influence of a weight of 50 grammes, and so on. The curve connecting the ends of the lengths of the contracted muscle falls faster than that obtained from the uncontracted one, until at the point P under the influence of a weight of 250 grammes, the two curves meet ; that is to say, 250 grammes is the weight which the muscle is just un- able to lift. Suppose a muscle has to lift the weight of 200 grammes, it begins with a length A" C", but when it contracts it has a length A" B", that is, it has contracted a distance of B" C", which is very small; when it has to lift a less weight it shortens more, when a greater weight it shortens less ; till when it shortens least it lifts the greatest weight. This experiment illustrates the general truth that when a muscle is contracted it is more extensible. At the point P the energy tending to shorten the muscle (its contractile power) is exactly equal to the energy tending to lengthen it against its elastic force. Thus we have the apparent paradox at this point that a muscle when in rigor In tetanus Normal Fatigued r Fi<;. 150.- Extensibility of muscle in different states ; tested by 50 grammes applied for short periods. Tracings to be read from left to right. (After Waller.) CH. XI.] weber's paradox 129 contracted has exactly the same length as when uncontracted ; but this is a matter of everyday experience ; if one tries to lift a weight beyond one's strength, one fails to raise it, but nevertheless one's muscles have been contracting in the effort ; they have not contracted in the restricted sense of becoming shorter, but that is not the only change a muscle undergoes when it contracts ; the other changes, electrical, thermal, chemical, etc., have taken place, as evidenced in one's own person by the fact that the individual has got warm in his efforts, or may even feel fatigue afterwards. But the paradox does not end here, for if diagram 157 is again looked at, it will be seen that beyond the point P the two curves cross ; in other words, the muscle may even elongate due to increase of extensibility when it contracts. This is known after its discoverer as Weber's paradox. The increase of extensibility of muscle during Contracted- Uncontracted Fig. 157. contraction is protective and tends to prevent rupture in efforts to raise heavy weights. Influence of Temperature on Extensibility. — If a piece of iced india-rubber is taken and stretched by a weight, its retractility when the weight is removed is very small. If, now, when the weight is on it, it is warmed at one point as by placing the hand on it, its retractility is increased and it contracts, raising the weight. Some physiologists have considered that muscular contraction can be explained in this way ; they have supposed that the heat formed in muscular contraction acts like warmth as applied to india-rubber. This view is, however, incorrect. It is much more probable that there is no causal relationship between the temperature-change and the extensibility-change which occur when muscle contracts; both are simultaneously produced by the stimulus. Moreover, the influence of heat on muscle is by no means the same as that on india-rubber. This influence is not invariable, and 130 EXTENSIBILITY, ELASTICITY, AND WORK OF MUSCLE [CH. XL at certain temperatures near the freezing-point, and under the influence of certain weights, actual elongation may occur when the temperature is raised. Muscular Tonus. In the living animal, muscles are more or less stretched, but never taut between their two attachments. They are in a state of tonicity or tonus, and when divided they contract and the two parts separate. Thus a muscle, even at rest, is in a favourable condition to contract without losing time or energy in taking in slack. Muscular tonus is under the control of the nervous system (on the reflex character of this control, see later, under Tendon Eeflexes) ; the muscles lengthen when their nerves are divided, or when they are rendered physiologically nerveless by curare. Besides the nervous system, the state of muscular nutrition dependent on a due supply of healthy blood must also be reckoned as important in maintaining muscular tonus. "Work of Muscle. The question of muscular work is intimately associated with that of elasticity. In a technical sense, work (W) is the product of the load (/) and the height (h) to which it is raised. W = lxh. Thus in fig. 157, when the muscle is unloaded the work done is nil: W = BCxO = 0. When the load is 250, again the work done is nil, because then h = 0. With the load 50, W = B' C'x 50. If the height is measured in feet and the load in pounds, work is expressed in terms of foot-pounds. If the height is measured in F 1 1 ; . liS.— Diagram to show the mode of measuring muscle work. (M'Kendrick.) millimetres or metres, and the load in grammes, the work is expressed in gramme-millimetres or gramme-metres respectively. This may be shown diagrammatically by marking on a horizontal base line or abscissa, distances proportionate to different weights, and vertical lines (ordinates) drawn through these represent the height to which they are lifted (see fig. 158). In the diagram (fig. 158) the figures along the base line represent grammes, and the figures along the vertical line represent milli- metres. The work done as indicated by the first line is 10x5 = 50 CH. XI.] MUSCULAR WORK 131 gramme-millimetres, the next 20x6 = 120 gramme-millimetres, and so on, while the last on the right, 100 x 3 = 300 gramme-millimetres. It is thus seen that the height of a muscle-curve is no measure of the work done by the muscle unless the weight lifted is taken into account as well. The following figures are taken from an actual experiment done with the frog's gastrocnemius (Weber) : — Weight lifted. Height. "Work done. 5 grammes 27-6 millimetres 15 „ 25*1 25 ,, 11-45 30 „ 7-3 138 gramme-millimetres 376 286 219 Fig. 159. — Dynamometer. The work increases with the weight up to a certain maximum, after which a diminution occurs, more or less rapidly, according as the muscle is fatigued. _ Similar experiments have been made in human beings, weights being lifted by the calf muscles, or elbow muscles, leverage being allowed for. In the higher animals the energy so ob- tained compared with the frog is about twice as great for the same volume of muscular tissue. Fig. 159 represents a com- mon form of dynamometer for clinical use, employed in test- ing the muscles of the arms and hands. It is squeezed by the hand, and an index represents kilogrammes of pressure. The muscle, regarded as a machine, is sometimes compared to artificial machines like a steam-engine. A steam-engine is supplied with fuel, the latent energy of which is transformed into work and heat. The carbon of the coal unites with oxygen to form carbonic acid, and it is in this process of combustion or oxidation that heat and work are liberated. Similar, though more complicated, combus- tions occur in muscle. In a steam-engine a good deal of fuel is con- sumed, but there is great economy in the consumption of the living muscular material. Take the work done by a gramme (about 15 grains) of muscle in raising a weight of 4 grammes to the height of 4 metres (about 13 feet) ; in doing this work probably less than a thousandth part of the muscle has been consumed. Next let us consider the relationship between the work and the 132 EXTENSIBILITY, ELASTICITY, AND WORK OF MUSCLE [OH. XL heat produced. An ordinary locomotive wastes about 96 per cent, of its available energy as heat, only 4 per cent, being represented as work. In the best triple-expansion steam-engine the work done rises to 125 per cent, of the total energy. In muscle, various experimenters give different numbers. Thus, Fick calculated that 33 per cent, of the mechanical energy is avail- able as work ; later he found this estimate too high, and stated the number as 25 ; Chauveau gives 12 to 15 ; M'Kendrick 17. Thus muscle is a little more economical that the best steam-engines ; but the muscle has this great advantage over any engine, for the heat it produces is not wasted, but is used for keeping up the body tempera- ture, the fall of which below a certain point would lead to death not only of the muscles but of the body generally. So far we have been speaking as though the only active phase of muscular con- traction is the period of shortening. It is, however, extremely probable, though not yet proved, that lengthening is also an active process. This was originally mooted by Fick, who pointed out that the fall of a muscle lever during the relaxation period is of variable speed, and is obviously not due to the passive elongation of the muscle by gravity ; the way in which this part of the curve is varied by such agencies as temperature, and drugs like veratrine, also indicates that relaxation is an inde- pendent process. Isotonic and Isometric Curves. — If, in'recording the contraction of a muscle, the load is applied vertically under the muscle, its pull upon the muscle varies during the successive stages of a single contraction, owing to the inertia of the load. In order to avoid this variation in tension, it is usual to apply the weight at a point close to the fulcrum of the recording lever, so that when the lever is raised, the weight remains practically stationary, and thus the error due to its inertia is avoided. In order to apply the necessary tension to the muscle, the weight hanging on the lever must be increased in the ratio of the distances of the muscle and weight from the fulcrum. A twitch recorded under such circumstances is called isotonic, i.e., one in which the tension remains constant throughout. If, on the other hand, the muscle is fixed at both ends, and then excited, the resulting activity expresses itself in a phase of increasing tension followed by one of decreasing tension. If the alterations of tension are recorded, we obtain what is called an isometric curve. This curve is obtained by making the muscle pull against a spring which is so strong that the muscle can only move it to a very slight extent. This slight movement is then highly magnified. The curve thus obtained resembles in its main features an isotonic contraction, but its maximum is reached earlier, and it returns to the zero position sooner. The flat top of the isometric curve described by the earlier observers was due to the imperfection of the instruments employed. The tracings of muscle curves given in previous illustrations (see figs. 145 to 147) were obtained by the isotonic method, but it is probable that the isometric curve is a more faithful record of the variations in the intensity of the contraction process than that yielded by the isotonic method. The momentum or swing of a light lever such as is used for obtaining isotonic curves will no doubt account for the extra upward movement it executes. The whole matter has been keenly discussed, and the foregoing view is that expressed by Kaiser. Schenk, on the other hand, maintains what appears to be an improbable idea that there are really two kinds of change in muscle, which account for the difference obtained bv the two methods. CHAPTER XII THE ELECTRICAL PHENOMENA OF MUSCLE We have seen that the chemical processes occurring in muscular con- traction lead to a transformation of energy into work and heat. These changes are accompanied by electrical disturbances also. The history of animal electricity forms one of the most fascinat- ing of chapters in physiological discovery. It dates from 1786, when G-alvani made his first observations. Galvani was Professor of Anatomy and Physiology at the University of Bologna, and his wife was one day preparing some frog's legs for dinner, when she noticed that the apparently dead legs became convulsed when sparks were emitted from a frictional electrical machine which stood by. Galvani then wished to try the effect of lightning and atmospheric electricity on animal tissues. So he hung up some frogs' legs to the iron trellis- work round the roof of his house by means of copper hooks, and saw that they contracted whenever the wind blew them against the iron. He imagined this to be due to electricity secreted by the animal tissues, and this new principle was called Galvanism. But all his contemporaries did not agree with this idea, and most prominent among his opponents was Volta, Professor of Physics at another Italian university, Pavia. He showed that the muscular contractions were not due to animal electricity, but to artificial electricity pro- duced by contact with different metals. The controversy was a keen and lengthy one, and was terminated by the death of Galvani in 1798. Before he died, however, he gave to the world the experiment known as "contraction without metals," which we shall study presently, and which conclusively proved the existence of animal electricity. Volta, however, never believed in it. In his hand electricity took a physical turn, and the year after Galvani's death he invented the Voltaic pile, the progenitor of our modern batteries. Volta was right in maintaining that galvanism can be produced independently of animals, but wrong in denying that electrical currents could be obtained from animal tissues. Galvani was right in maintaining the existence of animal electricity, but 133 134 THE ELECTRICAL PHENOMENA OF MUSCLE [CH. XII. wrong in supposing that the contact of dissimilar metals with tissues proved his point. This conclusion has been arrived at by certain new methods of investigation. In 1820 Oersted discovered electro-magnetism : that is, when a galvanic current passes along a wire near a magnetic needle, the needle is deflected one way or the other, according to the direction of the current. This led to the invention of the astatic needle and the galvanometer, an instrument by which very weak electrical currents can be detected. For a long time the subject of animal electricity, however, fell largely into disrepute, because of the quackery that grew up around it. It is not entirely free from this evil nowadays ; but the scientific investigation of the subject has led to a considerable increase of knowledge, and among the names of modern physiologists associated with it must be particularly mentioned those of Du Bois Reymond and Hermann. i i Before we can study these it is, however, necessary that we should understand the instruments employed. The Galvanometer. — The essential part of a galvanometer is a magnetic needle suspended by a delicate thread ; a wire coils round it; and if a current flows through the wire, the needle is deflected. Suppose a man to be swimming with the current with his face to the needle, the north-seeking pole is turned to the left hand. But such a simple instrument as that shown in fig. 160 would not detect the feeble currents obtained from animal tissues. It is necessary to increase the delicacy of the apparatus, and this is done in several ways. In the first place, the needle must be rendered astatic, that is, independent of the earth's magnetism. The simplest way of doing this is to fix two needles together (as shown in fig. 161), the north pole of one pointing the same way as the south pole of the other. The current is led over one needle and then over the other ; the effect is to pro- duce a deflection in each in the same direction, and so the sensitive- ness of the instrument is doubled. If now the wire is coiled not only once, but twice or more in the same position, each coil has its effect cm. xil] THE GALVANOMETER 135 on the needles ; the multiplication of the effect of a weak current in this way is accomplished in actual galvanometers by many hundreds of turns of fine wire. Fig. 162 illustrates the best galvanometer: that of Sir William Thomson (now Lord Kelvin). It is called a reflecting galvanometer, because the ob- server does not actually watch the moving needle, but a spot of light reflected on to a scale from a little mirror, which is attached to and moves with the needle. A very small movement of the needle is rendered evident, because the movement of the spot of light being, as it were, at the end of a long lever — namely, the beam of light, magnifies it. Fig. 162.— Reflecting galvanometer. (Thomson.) A. The galva- nometer consists of two systems of small astatic needles suspended by a fine hair from a support, so that each set of needles is within a coil of fine insulated copper wire, that forming the lower coil being wound in an opposite direction to the upper. Attached to the upper set of needles is a small mirror about J inch in diameter ; the light from the lamp at B is thrown upon this little mirror, and is reflected upon the scale on the other side of B, not shown in figure. The coils u I are arranged upon brass uprights, and their ends are carried to the binding screws. The whole appar- atus is placed upon a vulcanite plate capable of being levelled by the screw supports, and is covered by a brass- bound glass shade, the cover of which is also of brass, and supports a brass rod 6, on which moves a weak curved magnet m. C is the shunt by means of which the amount of the current sent into the galvanometer may be regulated. When in use the scale is placed about three feet from the galvanometer, which is arranged east and west, the lamp is lighted, the mirror is made to swing, and the light from the lamp is adjusted to fall upon it, and it is then regulated until the reflected spot of light from it falls upon the zero of the scale. The wires from the non-polarisable electrodes touching the muscle are attached to the outer binding screws of the galvanometer, a key intervening for short circuiting, or if a portion only of the current is to pass into the galvanometer, the shunt should intervene as well with the appropriate plug in. "When a current passes into the galvanometer the needles and. with them, the mirror, are turned to the right or left according to the direction of the current. The amount of the deflec- tion of the needle is marked on the scale by the spot of light travelling along it. Non-polarisable Electrodes. — If a galvanometer is connected 136 THE ELECTRICAL PHENOMENA OF MUSCLE [cil. XII. with a muscle by wires which touch the muscle, electrical currents are obtained in the circuit which are set up by the contact of metal with muscle. The currents so obtained form no evidence of electro- motive force in the muscle itself. It is therefore necessary that the wires from the galvanometer should have interposed be- tween them and the muscle some form of electrodes which are non-polarisable. Fig. 163 shows one of the earliest non-polaris- able electrodes of Du Bois Eeymond. It consists of a zinc trough on a vulcanite base. The inner surface of the trough is amalga- mated and nearly filled with a saturated so- lution of zinc sulphate. In the trough is placed a cushion of blotting-paper, which projects over the edge of the trough ; on it there is a pad of china clay or kaolin, moistened with physiological salt solution (0 8 per cent. NaCl); on this pad one end of the muscle rests. The binding screw (k) connects the instrument to the galvanometer; the other end, or some other part of the same muscle, is connected by another non-polarisable electrode in the same way to the other side of the galvanometer. If there is any electrical difference of potential (that Fig. 163. — Xon-polarisable elec trode of Du Biis Reymond (M'Kendrick.) Fig. 164.— Diagram of Du Bois Reymond's non-polarisable electrodes, a, glass tube tilled with a satu- rated solution of zinc sulphate, in the end, c, of which is china clay drawn out to a point ; the clay is moistened with 0-S NaCl solution ; in the solution a well amalgamated zinc rod is immersed and connected, by means of the wire a, with the galvanometer. The remainder of the apparatus is simply for convenience of application. The muscle and the end of the second electrode are to the right of the figure. is, difference in amount of positive or negative electricity) between the two parts of the muscle thus led off, there will be a swing of the galvanometer needle; the galvanometer detects the existence and direction of any current that occurs. CH. XII.] THE ELECTROMETER 137 Fig. 164 shows a more convenient form of non-polarisable elec- trodes. In order to measure the strength (elec- tromotive force) of such currents, the mere amount of swing of the needle is only a very rough indication, and in accurate work the arrangement shown in fig. 165 must be used. The electromotive force is usually measured in terms of a standard Daniell cell. The two surfaces of the muscle (M) are led off to a galvanometer (B) ; the needle swings, and then a fraction of a Daniell cell is intro- duced in the reverse direction so as to neu- tralise the muscle current, and bring back the needle to rest. From the Daniell cell K, wires pass to the ends a, b of a long platinum wire of high resistance, called the compen- sator ; c is a slider on this wire ; a and c are connected to the galvanometer, the com- mutator C enabling the observer to ensure Fig. 165.— Arrangement for measuring the elec- that the current from the Daniell passes in tromotive force of muscle. (M'Kendrick.) the opposite direction to that produced by the muscle. If the slider c is placed at the end b of the compensator, the whole strength of the Daniell will be sent through the galvanometer and will more than Fig. 166.— Lippmann's Capillary- Electrometer. (After Waller.) 1. Pressure apparatus and microscope on stand of which the capillary tube is fixed. '2. Capillary tube, fixed in outer tube containing 10 per cent, sulphuric acid ; the platinum wires are also shown. 3. Capillary and column of mercury as seen in the field of the microscope. 138 THE ELECTRICAL PHENOMENA OP MUSCLE [CH. XII. neutralise the muscle current ; if c is half way between a and l>, half the Daniell's strength will he sent in ; but this is also too much ; at- will be found to be only quite a small fraction of ah ; and this fraction will correspond to a proportional fraction of the electromotive force of the Daniell cell. Lippmann's Capillary Electrometer. — This instrument is often used instead of the galvanometer. It consists of a glass tube drawn out at one end to a fine capillary and filled with mercury. It is connected to an apparatus by which the Fie. 167.— Frog's heart. Diphasic variation. Simultaneous photograph of a single beat (upper black line), and the accompanying electrical change indicated by the level of the black area, which shows the varying level of mercury in a capillary electrometer. (Waller.) pressure on this mercury can be lowered or increased. The open capillary tube is enclosed within another' tube filled with 10 per cent, sulphuric acid. Two platinum wires fused through the glass, pass respectively into the mercury and the acid, and the other ends of these wires are connected by electrodes to two portions of the surface of a muscle. The capillary tube is observed by a microscope (see fig. 166). The surface of the mercury is in a state of tension which is easily increased or diminished by variations of electrical potential, and the mercury moves in the direction of the negative pole. If the shadow of the mercurial column is thrown upon a travelling sensitive photographic plate, photographs are obtained which show the electrical variations Fig. 108. — Human heart. Diphasic variation, KE, and simultaneous cardiogram, ->->A 1 Couple. 2 Couples. 3 Couples. Fig. ITS.— Scheme of thermo-electric couples. (After Waller.) iron and German silver, or antimony and bismuth. If the number of couples in the circuit is increased, each is affected in the same way, and thus the electrical current is increased through the galvano- meter. The arrangement is shown in the fig. 178, which also indicates the direction of the currents produced, the metals employed being antimony and bismuth. By using 16 couples of this kind Helmholtz was able to detect a change of ^o 1 ^ of a degree Centigrade. Within certain limits, the strength of the current is directly proportional to the rise of temperature at the junction. If two couples are in circuit, as shown in the second diagram, and they are heated equally, no current will pass through the galvano- meter, the current through one couple being opposed by the current through the other. But if the two couples are heated unequally, the direction of swing of the galvanometer needle indicates which is the warmer. To apply this to the frog's gastrocnemius, plunge several needle-shaped couples (diagram 3) into a frog's gastrocnemius of one side and the same number of couples into the gastrocnemius of the other side, and then excite first one then the other sciatic nerve ; a deflection of the galvanometer will be observed first in one, then in CIL XIII.] THE GASES OF MUSCLE 149 the other direction, indicating the production of heat first on one side, then on the other. Chemical Changes in Muscles. The chemical changes which are normally occurring in a resting muscle are much increased when it contracts. Waste products of oxidation are discharged, and the most abundant of these is carbonic acid. Sarco-lactic acid is also produced, and the alkaline reaction of a normal muscle is replaced by an acid one. The muscles of animals hunted to death are acid ; the acid reaction to litmus paper of a frog's gastrocnemius can be readily shown after it has been tetanised for 10 to 15 minutes. The quantity of oxygen consumed is increased, but the con- sumption of oxygen will not account for the much greater increase in the discharge of carbonic acid. This is illustrated by the following table : — Venous Blood. 0, less than C0 2 more than Arterial Blood. Arterial Blood. Of resting muscle 9 per cent. 6 *7l per cent. Of active muscle 12*26 per cent. 10-79 per cent. Indeed, a muscle can be made to contract and give off oxidation products like carbonic acid in an atmosphere containing no oxygen at all. The oxygen used is thus stored up in the muscle previously. The oxygen is not, however, present in the free state, for no oxygen can be detected in the gases obtained from muscles by means of an air-pump. Hermann has supposed that the oxygen enters into the formation of a complex hypothetical compound he calls inogen. On contraction he considers this is broken up into carbonic acid, sarco- lactic acid, and a proteid residue of myosin. There are other chemical changes in the muscle when it contracts — namely, a change of glycogen into sugar, and an increase of nitro- genous waste. The question whether urea is increased during muscular activity is, however, a much debated one, and we shall return to it when we are studying the urine. What is certain is that the increased consumption of carbon (possibly in large measure derived from the carbohydrate stored in the muscle) is a much more marked and immediate feature than an increase in the consumption of nitrogen. 150 THERMAL AND CHEMICAL CHANGES IN MUSCLE [CH. XIII. Fatigue. If the nerve of a nerve-muscle preparation is continually stimu- lated, the muscular contractions become more prolonged (see p. 117), smaller in extent, and finally cease altogether. The muscle is said to be fatigued : this is due to the consump- tion of the substances available for the supply of energy in the muscle, but more particularly to the accumulation of waste products of contraction ; of these, sarco-lactic acid is probably an important one. Fatigue may be artificially induced in a muscle by feeding it on a weak solution of lactic acid, and then removed by washing out the muscle with salt solution containing a minute trace of an alkali. If the muscle is left to itself in the body, the blood-stream washes away the accumulation of acid products, and fatigue passes off. The question next presents itself, where is the seat of fatigue ? Is it in the nerve, the muscle, or the end-plates ? If, after fatigue has ensued and excitation of the nerve of the preparation produces no more contractions, the muscle is itself stimulated, it contracts ; this shows it is still irritable, and, therefore, not to any great extent the seat of fatigue. If an animal is poisoned with curare, and it is kept alive by arti- ficial respiration, excitation of a motor nerve produces no contraction of the muscles it supplies. If one goes on stimulating the nerve for many hours, until the effect of the curare has disappeared, the block at the end-plates* is removed and the muscles contract: the seat of exhaustion is therefore not in the nerves. By a process of exclusion it has thus been localised in the nerve- endings. When the muscle is fatigued in the intact body, there is, however, another factor to be considered beyond the mere local poisoning of the end-plates. This is the effect of the products of contraction passing into the circulation and poisoning the central nervous system. It is a matter of common experience that one's mental state influ- ences markedly the onset of fatigue and the amount of muscular work one can do. This aspect of the question has been specially studied by Waller and by Mosso. Mosso devised an instrument called the ergograph, which is a modification of Waller's dynamograph invented many years previously. The arm, hand, and all the fingers but one are fixed in a suitable holder ; the free finger repeatedly lifts a weight over a pulley, and the height to which it is raised is regis- tered by a marker on a blackened surface. By the use of this and similar instruments it has been shown * Another convenient block which is sometimes used is to throw a constant current into the nerve between the point of excitation and the muscles. This pre- vents the nerve impulses from reaching the muscles. CH. XIII.] FATIGUE 151 that the state of the brain and central nervous system generally is a most important factor in fatigue, and that the fatigue products pro- duced in the muscles during work cause most of their injurious effects by acting on the central nervous system and diminishing its power of sending out impulses. One of the most striking of Mosso's experiments illustrates in a very forcible manner the fact that the central nervous system is more easily fatigued than the nerve-endings in muscle. A person goes on lifting the weight until, under the influence of the will, he is unable to raise it any more. If then without waiting for fatigue to pass off, the nerves going to the finger muscles are stimulated artificially by induction shocks, they once more enter into vigorous contraction. Mosso has also shown that the introduction of the blood of a fatigued animal into the circulation of a normal one will give rise in the latter to all the symptoms of fatigue. The blood of the fatigued animal contains the products of activity of its muscles, but still remains alkaline ; the poisonous substance cannot therefore be free lactic acid; and lactates do not produce the effect. Lactic acid is doubtless one only of the products of muscular activity ; we have at present no accurate knowledge of the chemical nature of the others. The statement that nerves are not fatiguable, does not mean that the nerve fibres undergo no metabolic changes when transmitting a nerve impulse, but that the change is so slight, and the possibilities of repair so great, that fatigue in the usual acceptation of the term cannot be demonstrated. Waller made the interesting but tentative suggestion that the medullary sheath is a great factor in repair, or, in his own words, "the active grey axis both lays down and uses up its own fatty sheath, and it is inexhaustible not because there is little or no expenditure, but because there is an ample re-supply." A year or two after these words were written, Miss Sowton, at Dr Waller's suggestion, undertook a piece of work in order to test the truth of this hypothesis. If the absence of fatigue is due to the presence of the fatty sheath, fatigue ought to be demonstrable in nerve-fibres in which the fatty sheath is absent. She selected the olfactory nerve of the pike as the non-medullated nerve with which to try the experiment, and her results confirmed Dr Waller's expectation ; the galvanometric replies of the nerve become somewhat feebler after repeated stimu- lation. It appeared to me advisable to test the question in another way. The splenic nerves seemed to be the most convenient large bundles of non-medullated fibres for the purpose. Dr T. G. Brodie was associated with me in carrying out the in- vestigation. A dog is anaesthetised, the abdomen opened, the spleen exposed, and the splenic nerves which lie by the side of the main splenic artery are laid bare. It is quite easy to dissect out a length of nerve sufficient for the experiment (1^ to 2 inches). The nerve is then cut as far from the spleen as possible, and the spleen is enclosed in an air oncometer connected to the bellows volume recorder invented by Dr Brodie. On stimulating the nerve with a weak faradic current the organ contracts, and the recording lever fails. The diminution of the size of the spleen is quite visible to the naked eye, however, without the use of any apparatus. The next thing to do is to put a block on the course of the nerve, which will prevent the nerve impulses from reaching the spleen. Here we met with some difficulty. Curare and atropine are both ineffective : the constant current has a great dis- advantage ; non-medullated nerves are so much affected that very feeble constant currents will completely block the transmission of impulses, and not only that, but 152 THERMAL AND CHEMICAL CHANGES IN MUSCLE [CII. XIII. the nerve remains blocked after the current is removed. After the current has been allowed to flow for two minutes the nerve remains impassable to nerve impulses for ;m hour or more, and then slowly recovers. If, therefore, faradic D-o Fio. 179.— Apparatus for obtaining splenic curves, s, spleen in oncometer o, which is made of gutta- percha, and covered with a glass plate (g.p.) luted on with vaseline, m, is the splenic mesentery containing vessels and nerves ; this passes through a slit in the base of the oncometer which is made air-tight with vaseline. The oncometer is connected to the flexible bellows (k) by the india-rubber tube (r), the side tube (t) being closed during an experiment by a piece of glass rod. The recording lever (l)' writes on a revolving drum. excitation of the nerve is kept up all this time and fails to excite the contraction of the spleen after the removal of the constant current, it is impossible to say whether this is due to fatigue of the nerve-fibres on the proximal side of the block, or whether it may not be due to the fact that the block created by the constant current is still effective. Our best results were obtained by using cold instead of a constant current as our blocking agent. Fig. 179 is an outline drawing of the apparatus used, and fig. ISO shows the ' arrangement adopted in connection with the nerve. £"■ § ~^> The nerve (n) rests on a metal tube (t) through which I water can be kept flowing, e is the situation of the w I electrodes. If the nerve is excited, the spleen con- tracts, and the recording lever (in fig. 179) falls. If now brine at to 2° C. is kept flowing through t, the nerve impulses are blocked by the cold, and cannot reach the spleen. Immediately the cold brine is re- placed by warm water at '-W C, the nerve again becomes passable by nerve impulses, and the spleen contracts once more. If while the fluid in t is kept at the low tempera- ture mentioned, the nerve is being excited with strong induction shocks all the time, the spleen remains irre- sponsive ; the nerve impulses are able to reach t but not to pass it. If then warm water is passed through t, and the block produced by the cold is thus removed, and the spleen continues to be irresponsive, we have a proof that the piece of nerve between e and t has been fatigued. But our experiments have shown us that non-medullated nerve is just as difficult to fatigue as medullated nerve. Even after six hours' continuous excitation the nerve is just as excitable as it was at the start, and a full splenic- contraction is obtained when the cold block is removed. We have made similar experiments with vaso-motor nerves, such as the cervical DT _L^ E = . 180. — Arrangement of ap- paratus in connection with the splenic nerve, s is the spleen, and N the main bundle of nerves. The nerve rests on the metal tube (T)through which fluid at the required temperature is kept flowing, and on the electrodes (e) which come from the secondary coil of an inductorium. CH. XIII.] EIGOE MORTIS 153 sympathetic nerve in the rabbit, the splanchnic nerve of the dog, and the sciatic nerve in a curarised dog, and have obtained corresponding results. This confirms the work previously published by Eve. Eve excited the cervical sympathetic for twelve hours, and found no loss of excitability at the end of that time. Eve stimulated the nerve below the upper cervical ganglion, and the main object of his work was to ascertain whether any histological evidence of fatigue could be found in the cells of the ganglion. The only change he could find there was a somewhat diffuse staining of the cells by methylene blue, which he attributes to the formation of acid substances in the cells. A blue stain of similar appearance may be induced in the motor cells of the spinal cord, after exhaustion is produced in them by giving strychnine. In such experiments the spinal cord becomes as a rule distinctly acid to litmus paper. Max Verworn has more recently employed strychnine as a means of producing fatigue. He considers that the only specific effect of this alkaloid is increase of reflex activity, and he attributes the subsequent paralysis to vascular conditions and the accumulation of fatigue products, among which he places carbon dioxide in the first rank. Eve, on the contrary, did not find that carbonic acid alone produces the effects. We must conclude from such experiments that Dr Waller's theory is unproved, and that while fatigue is demonstrable in nerve-cells, it has never yet been shown to occur in nerve-fibres of either the medullated or non-medullated variety. In carrying out these experiments we noticed that though no functional fatigue can be demonstrated, there is noticeable, especially in vaso-motor nerves, a phenomenon which Howell terms stimulation fatigue ; this means that the actual spot of nerve stimulated becomes after a time less excitable, and finally, inexcitable, though it will still transmit impulses, if the excitation is applied above the spot originally stimulated. We think that the use of the term " fatigue " in this con- nection is a mistake ; the prolonged electrical excitation causes injurious polarisa- tion (due to electrolytic changes) of the nerve, which renders it less excitable. This view has been confirmed by Prof. Gotch by means of experiments with the capillary electrometer. This so-called " stimulation fatigue " was not excluded in Miss Sowton's experiments, and will possibly explain her results. The splenic nerves, curiously enough, do not exhibit this phenomenon in any marked degree, and so were peculiarly well adapted to testfthe question of functional fatigue. On a priori grounds we should hardly expect non-medullated nerves to be peculiarly susceptible of real fatigue, when one considers how many of them, like the vaso-constrictors, are in constant action throughout life. Rigor Mortis. After death, the muscles gradually lose their irritability and pass into a contracted condition. This affects all the muscles of the body, and usually fixes it in the natural posture of equilibrium or rest. The general stiffening thus produced constitutes rigor mortis or post- mortem rigidity. The cause of rigor is the coagulation of the muscle-plasma, which is more fully described in the next section. This coagulation results in the formation of myosin, and is gradual in onset. Simultaneously the muscles (a) become shortened and opaque, (b) heat is evolved, (c) they give off carbonic acid, and (d) become acid in reaction ; this is due in part to the formation of sarco-lactic acid, and in part to the forma- tion of acid phosphates. After a varying interval, the rigor passes off, and the muscles are once more relaxed. This sometimes occurs too quickly to be caused by putrefaction, and the suggestion that in such cases at any rate 154 THERMAL AND CHEMICAL CHANGES IN MUSCLE [CH. XIII. such relaxation is due to a ferment-action is very plausible. It is known that a pepsin-like or proteolytic ferment is present in muscle, as in many other animal tissues, kidney, spleen, etc. (Hedin), and that such ferments act best in an acid medium. The conditions for the solution of the coagulated myosin are therefore present, as the reaction of rigored muscle is acid. Order of Occurrence. — The muscles are not affected simultaneously by rigor mortis. It affects the neck and lower jaw first ; next, the upper extremities, extending from above downwards; and lastly, reaches the lower limbs ; in some rare instances it affects the lower extremities before, or simultaneously with, the upper extremities. It usually ceases in the order in which it begins: first at the head, then in the upper extremities, and lastly in the lower extremities. It seldom commences earlier than ten minutes, or later than seven hours after death ; and its duration is greater in proportion to the lateness of its accession. The occurrence of rigor mortis is not prevented by the previous existence of paralysis in a part, provided the paralysis has not been attended with very imperfect nutrition of the muscular tissue. In some cases of sudden death from lightning, violent injuries, or paroxysms of passion, rigor mortis has been said not to occur at all ; but this is not always the case. It may, indeed, be doubted whether there is really a complete absence of the post-mortem rigidity in any such cases ; for the experiments of Brown-Sequard make it probable that the rigidity may supervene immediately after death, and then pass away with such rapidity as to be scarcely observable. Chemical Composition of Muscle. The phenomena of rigor mortis will be more intelligible if we consider the chemical composition of muscle. The connective tissue of muscle resembles connective tissue else- where; the gelatin and fat obtained in analyses of muscle are derived from this tissue. The sarcolemma is composed of a substance which resembles elastin in its solubilities. The contractile substance within the muscular fibres is, during life, of semi-liquid consistency, and contains a large percentage of proteids and smaller quantities of extractives and inorganic salts. By the use of a press this substance can be squeezed out of perfectly fresh muscles, and it is then called the muscle-plasma. After death, muscle-plasma, like blood-plasma, coagulates (thus causing the stiffening known as rigor mortis). The solid clot corre- sponding to the fibrin from blood-plasma is called myosin, and the liquid residue is called the muscle-serum. Pursuing the analogy further, it is found that the coagulation of both muscle-plasma and blood-plasma can be prevented by cold, by strong solutions of neutral salts, and by potassium oxalate, which CH. XIII.] CHEMICAL COMPOSITION OF MUSCLE 155 precipitates, as the insoluble oxalate of calcium, the lime salts essential for the coagulation process. In both cases the clotting is produced by the action of a ferment developed after death. In both cases the precursor of the solid clot is a proteid of the globulin class which previously existed in solution. Fibrin in the blood-clot is formed from the previously soluble fibrinogen of the blood-plasma. Myosin in the muscle-clot is formed from the previously soluble myosinogen * of the muscle-plasma. When the blood-clot contracts it squeezes out blood-serum; when the muscle-clot contracts it squeezes out muscle-serum. The muscle- serum contains small quantities of albuminous material, together with the extractives and salts of the muscle. The origin of the sarco- lactic acid is a controversial question : some believe it originates from the carbohydrate (glycogen and sugar) ; others think it comes from the proteid molecules in the muscle. The general composition of muscular tissue is the following : — Water .... 75 per c Solids .... 25 Proteids .... 18 Gelatin .... Fat ... . •}-2to5 Extractives '. 0-5 Inorganic salts . . 1 to 2 The proteids, as already stated, chiefly pass into the clot : very little is found in the muscle-serum. The extractives comprise a large number of organic substances, all present in small quantities, some of which are nitrogenous, like creatine, creatinine, xanthine, and hypoxanthine : the rest are non- nitrogenous — namely, fats, glycogen, sugar, inosite, and the variety of lactic acid known as sarco-lactic acid. The inorganic salts are chiefly salts of potassium, especially potassium phosphate. The condition of dead muscle reminds one somewhat of contracted muscle. Indeed, the similarity is so striking that Hermann has propounded the idea that contracted muscle is muscle on the road to death, the differences between the two being of degree only. He considers that, on contraction, inogen (see p. 149) is broken up into carbonic acid, sarco-lactic acid, and myosin ; on death the same change occurs, only to a much more marked extent. This idea is a far-fetched one, but it is a useful reminder of the similarities of the two cases. In chemical condition, contracted and dead muscle are alike, so far as the formation of acid products is concerned ; there is, however, no evidence of any formation of a muscle-clot (myosin) during the contraction of living muscle, as there is in dead muscle. Then heat is produced in both cases, * For further details see small text at the end of this chapter. 156 THERMAL AND CHEMICAL CHANGES IN MUSCLE [CH. XIII. and in both cases also the muscle is electro-positive to uncontracted muscle. Here, however, the analogy must end : for living contracted muscle is irritable, dead muscle is not. Living contracted muscle is more extensible than uncontracted muscle ; muscle in rigor mortis is not so (see fig. 156, p. 128). The contraction of living muscle is favoured by feeding it with a solution of dextrose, while the process of rigor is hindered by the same solution. (F. S. Lee.) Our correct knowledge of the proteids of muscle and of the phenomena of rigor mortis date from the year 1864, when Kiihne obtained muscle-plasma by subjecting frozen frog's muscle to strong pressure. A good many years later I was successful in repeating these experiments with mammalian muscle. By fractional heat coagula- tion, and by their varying solubilities in neutral salts, I was able to separate four different proteids in the muscle-plasma. 1. A globulin precipitable by heat at 47° C. This is analogous to the cell- globulin found in most protoplasmic structures. I gave it the name paramyosinogen. 2. A proteid with many of the characters of a globulin, coagulable by heat at 56" C. ; and this I termed myosinogen. 3. A globulin (myo-glohnlin), precipitable by heat at 63° C. 4. An albumin similar in its properties to serum albumin is also present ; but this and the myo-globulin only occur in quite small amounts. In addition to these, there is a small quantity of nuclei-proteid from the nuclei, and in the red muscles haemoglobin is present ; the normal pigment of the so-called pale muscles is termed myo-hwmatin by MacMunn, and this is doubtless a derivative of haemoglobin. The two most abundant and important proteids are the first two in the list, namely, paramyosinogen and myosinogen. They occur in the proportion of about 1 to 4, and both enter into the formation of the muscle-clot (myosin). The myo- globulin is possibly not a separate proteid, but only some myosinogen which has escaped coagulation : the albumin is probably derived from adherent blood and lymph. In 1895 v. Fiirth took up the subject. On the main question we are in substantial agreement, namely, that in the muscle-plasma there are the two proteids just alluded to, and that these both contribute to the formation of the muscle-clot. The main points of difference between us are in the names of the proteids. He uses physio- logical saline solution to extract the muscle-plasma, and this extract coagulates spontaneously on standing ; he is doubtful whether a specific myosin-ferment brings about the change. Paramyosinogen he terms myosin, and this passes directly into the clotted condition {myoxin-fihriti) ; but myosinogen, called myogen by v. Fiirth, first passes into a soluble condition (coagulable by heat at the remarkably low temperature of 40 C.) before it clots : the soluble stage he calls soluble myogen-fibrin, and the clot myogen-fibrin. We may put this in a diagrammatic way as follows : — Muscle Plasma. Paramyosinogen. Myosinogen. (myosin of v. Fiirth.) (myogen of v. Fiirth.) Soluble myogen-fibrin. Myosin-fibrin. Myogen-fibrin. Myosin or Muscle-clot. CH. XIII.] HEAT EIGOU 157 V. Fiirth also calls attention to some characters of myosinogen which separate it from the typical globulins ; e.g., it is not precipitable by dialysing the salts away from its solutions. It may be therefore called an atypical globulin. In mammalian muscle, soluble myogen-fibrin is only found as a stage in the process of rigor mortis, but in the muscles of the frog and other amphibia it is present as such in the living muscle. The muscle-plasma from fishes' muscle contains another proteid termed myo- ■proteid by v. Fiirth. It is precipitable by dialysis, but not coagulable by heat. Brodie, and later, Vernon, did some interesting experiments on heat rigor. When a muscle is heated above a certain temperature it becomes contracted and stiff, losing its irritability completely. This is due to the coagulation of the muscle proteids. If a tracing is taken of the contraction, it is found to occur in a series of steps : the first step in the shortening occurs at the coagulation temperature of the paramyosinogen (47°-50° C), and if the heating is continued, a second shortening occurs at 56° C, the coagulation temperature of myosinogen. If, however, a frog's muscle is used, there are three steps, namely, at 40° (coagulation temperature of soluble myogen-fibrin), 47°, and 56°. This work of Brodie's is especially valuable because it teaches us that the proteids in muscle-plasma, or in saline extracts of muscle, are present also in the actual muscle-substance. He also made clear another important point, namely, that the irritability of the muscle is lost after the first step in the shortening has occurred. In other words, in order to destroy the vitality of muscular tissue, it is not necessary to raise the temperature sufficiently high to coagulate all its proteids, but that when one of the muscular proteids has been coagulated, the living substance as such is destroyed ; the proteids of muscle cannot therefore be regarded as independent units ; the unit is protoplasm, and if one of its essential constituents is destroyed, protoplasm as such ceases to live. Hans Przibram has attempted to classify the animal kingdom on the basis of the muscle-proteids ; his conclusions are based on the examination of only thirty species of animals, and may require revision in the future, but such as they are, they are as follows : — Invertebrates : para-myosinogen present ; myosinogen absent. Vertebrates : para-myosinogen and myosinogen both present. Fishes : in addition to these two principal proteids, soluble myogen-fibrin and myoproteid (in large quantities) occur. Amphibians : like fishes, except that myoproteid is only present in traces. Reptiles, birds, mammals : myoproteid is absent, and soluble myogen-fibrin is only present when rigor mortis commences. Steyrer has recently stated that on prolonged tetanisation (in rabbits' muscle) the amount of paramyosinogen diminishes, but when degeneration occurs after the motor nerves are cut, the amount of this proteid increases. Such results must, however, be accepted with caution until more satisfactory methods than those at present in use are adopted for the estimation of the muscle-proteids. CHAPTER XIV COMPARISON OF VOLUNTARY AND INVOLUNTARY MUSCLE The main difference between voluntary and involuntary muscle is the difference expressed in their names. Voluntary muscle is under the control of that portion of the central nervous system the activity of which is accompanied by volition. Involuntary muscle, on the other hand, is, as a rule, also under the control of the central nervous system, but of a portion of the central nervous system the activity of which is independent of volition. There appear, however, to be exceptions to this rule, and the involuntary muscle executes its con- tractions independently of nervous control ; that is to say, it is sometimes in the truest sense of the term really involuntary. This is very markedly seen in the developing heart of the embryo, which begins to beat before any nerve fibres have grown into it from the central nervous system. Another characteristic of involuntary muscle is a tendency to regular alternate periods of rest and activity, or rhythmicality. This is best exemplified in the heart, but it is also seen in the lymphatic vessels, especially the lymph hearts of the frog, and the mesenteric lymphatic vessels (lacteals) of many animals. It is seen in the veins of the bat's wing, and in the muscular tissue of the spleen, stomach, intestine, bladder, and other parts. A third characteristic of involuntary muscle is peristalsis. If any point of a tube of smooth muscle such as the small intestine is stimulated, a ring-like constriction is produced at this point. After lasting some time at this spot it slowly passes along the tube at the rate of 20 to 30 millimetres per second. This advancing peristaltic wave normally takes place in only one direction, and so serves to drive on the contents of the tube. Involuntary muscle nearly always contains numerous plexuses of non-medullated nerve-fibres with ganglion cells; so that much dis- cussion has taken place on the question whether the phenomena of rhythmicality and peristalsis are properties of the muscular tissue itself or of the nerves mixed with it. The evidence available (namely, 15S CH. XIV.] CONTRACTION OF INVOLUNTARY MUSCLE 159 that portions of muscular tissue entirely free from nerves act in the same way as those that possess nerves) indicates that it is the muscular rather than the nervous tissues that possess these properties ; though it can hardly be doubted that under usual circumstances the contraction of involuntary muscle is influenced and controlled by nervous agency. The artificial stimuli employed for smooth muscle are the same as those used for striated muscle ; single induction shocks are often ineffectual to produce contraction, but the make, and to a less extent the break, of a constant current will act as a stimulus. The faradic current is a good stimulus, but it never throws involuntary muscle into tetanus ; in the heart, strong stimulation will sometimes effect a partial fusion of the beats, but never complete tetanus. The rate of stimulation makes no difference ; in fact, very often a rapid rate of stimulation calls forth less rapidly occurring contractions than a slow rate. A stimulus strong enough to produce a contraction in the heart elicits a maximum contraction (" all or nothing " Waller) ; the pheno- menon known as the staircase (see p. 117) is generally better marked in the case of the heart than in that of voluntary muscle. The contraction of smooth muscle is so sluggish that the various stages of latent period, shortening and relaxation, can be followed with the eye; the latent period often exceeds half a second in duration. It does not obey the " all or nothing " law. The normal contraction of voluntary muscle is a kind of tetanus (see p. 121) ; the normal contraction of cardiac and plain muscle is a much prolonged single contraction. A very valuable piece of evidence in this direction is seen in the experiment on the heart with the physiological rheoscope (see p. 145). Each time the heart contracts the rheoscopic preparation executes a single twitch, not a tetanus. This is an indication that the electrical change is a single one, and not a succession of changes such as occurs in tetanus. When this electrical change is examined with the electrometer, it is seen that it is a diphasic one as in voluntary muscle ; but in a slowly contracting tissue like the heart-muscle the two phases are separated by a prolonged period of equipotentiality, and thus they are rendered more distinct. The illustrations already given (figs. 167 and 168) show this fact graphically. When the heart is beating sluggishly in the rheoscopic experiment above referred to, the separation of the two phases of the electrical change will sometimes cause two twitches in the muscle-nerve preparation. Bayliss and Starling describe the ventricular contraction of the mammalian heart as being accompanied by a triphasic electrical variation ; this is due to the contraction at the base outlasting that at the apex ; if, therefore, base and apex are led off to the electrometer, the first phase is due to increased positivity at the base, the second to that at the apex ; this quickly subsides, but the increased positivity at the base which still continues accounts for the third excursion of the mercury. 160 COMPARISON OF VOLUNTARY AND INVOLUNTARY MUSCLE [CH. XIV. But though involuntary muscle cannot be thrown into tetanus, it has the property of entering into a condition of sustained contrac- tion called tonus. We shall have to consider this question again in connection with the plain muscular tissue of the arterioles. Involuntary muscle when it contracts undergoes thermal and chemical changes similar to those we have dealt with in the case of the voluntary muscles. Involuntary muscle is usually supplied with two sets of nerves, one of which (accelerator) increases and the other of which (inhibitory^ decreases its activity. The nerve-endings in involuntary muscle require a much larger dose of curare to affect them than the end- plates in voluntary muscle. The phenomena of rigor mortis in involuntary muscle have not been so fully studied as in the case of voluntary muscle. It has, however, been shown that the chemical composition of involuntary muscle differs in no noteworthy manner from that of voluntary muscle, and on death the muscle becomes acid ; such products as carbonic acid and sarco-lactic acid are formed. In the heart, stomach, uterus, and rectum, post-mortem rigidity has been noted, and it probably occurs in all varieties of plain muscle. Swale Vincent has shown that the characteristic proteids (paramyosinogen and myosinogen) occur in both striped and unstriped muscle, and the heat rigor curves of involuntary muscle are practically identical with those obtained by Brodie (see p. 157). He is inclined to think that the two proteids are formed by the breaking down of a compound proteid which in living muscle mainly coagulates at 47 J C. This view is taken by Stewart in reference to striped muscle also, but has been very seriously questioned by v. Fiirth. The most striking chemical difference between unstriped and striped muscle is seen in the amount of nucleo-proteid which they contain. Plain muscle contains six to eight times the amount found in voluntary muscle ; cardiac muscle contains an intermediate quantity. CHAPTER XV PHYSIOLOGY OF NEKVE Many points relating to the physiology of nerve have been already studied in connection with muscle. But there still remain further questions upon which we have hardly touched as yet. Classification of Nerves. The nerve-fibres which form the conducting portions of the nervous system may be classified into three main groups, according to the direction in which they normally conduct nerve impulses. These three classes are : — 1. Efferent nerve-fibres. 2. Afferent nerve- fibres. 3. Inter-central nerve-fibres. 1. Efferent or centrifugal nerves are those which conduct im- pulses from the central nervous system (brain and spinal cord) to other parts of the body. When, for instance, there is a wish to move the hand, the impulse starts in the brain, and travels a certain distance down the spinal cord ; it leaves the spinal cord by one or more of the spinal nerves, and so reaches the muscles of the hand which are thrown into contraction. Such nerves are called motor, but all efferent nerves are not motor ; some cause secretion instead of movement, and others may cause a stoppage of movement, etc. A list of the classes of efferent nerves is as follows : — a. Motor. o: Accelerator. c. Inhibitory. d. Secretory. e. Electrical. /. Trophic. a. Motor nerves. Some of these go to voluntary muscles ; others to involuntary muscles, such as the vaso-motor nerves which supply the muscular tissue in the walls of arteries. 161 T 162 PHYSIOLOGY OF NERVE [CH. XY. b. Accelerator nerves are those which produce an increase in the rate of rhythmical action. An instance of these is seen in the sympathetic nerves that supply the heart. c. Inhibitory nerves are those which cause a slowing in the rate of rhythmical action, or it may be its complete cessation. Inhibitory nerves are found supplying many kinds of involuntary muscle ; a very typical instance is found in the inhibitory fibres of the heart which are contained within the trunk of the vagus nerve.* d. Secretory nerves are found supplying many secreting glands, such as the salivary glands, pancreas, gastric glands, and sweat glands. The impulse which travels down a secretory nerve stimulates secretion in the gland it supplies. e. Electrical nerves are found in the few fishes which possess electrical organs. The impulse which travels down these nerves causes the electrical organ to be thrown into activity. /. Trophic nerves are those which control the nutrition of the part they supply. 2. Afferent or centripetal nerves are those which conduct impulses in the reverse direction, namely, from all parts of the body to the central nervous system. When one feels pain in the finger, the nerves of the finger are stimulated, an impulse travels up the nerves to the spinal cord, and then to the brain. The mental process set up in the brain is called a sensation ; the sensation, how- ever, is referred to the end of the nerve where the impulse started, and the sensation of pain does not appear to occur in the brain, but in the finger. This is an instance of a sensory nerve ; and the terms afferent and sensory may often be used synonymously. The nerves of sensation may be grouped as follows : — a. The nerves of special sense ; that is, of sight, hearing, taste, smell, and touch. b. The nerves of general sensibility ; that is, of a vague kind of sensation not referable to any of the special senses just enumerated ; as an instance, we may take the vague feelings of comfort or discomfort in the interior of the body. c. Nerves of pain. It is a moot point whether these are anatomi- cally distinct from the others, for any excessive stimulation of a sensory nerve whether of the special or general kind will cause pain. The words "sensory" and "afferent," however, are not quite synonymous. Just as we may have efferent impulses leaving the * The question has been much debated whether voluntary muscle is provided with inhibitory nerves ; they do, however, appear to be present in certain nerves supplying the muscles of the claws of lobsters and similar crustaceans. CH. XV.] REFLEX ACTION 163 brain for the heart or blood-vessels of which we have no con- scious knowledge, so also afferent impulses may travel to the central nervous system which excite no conscious feelings. The afferent nerve-tracts to the cerebellum form a very good instance of these. Then, too, the excitation of many afferent nerves will excite what are called reflex actions. We are very often conscious of the sensa- tions that form the cause of a reflex action, but we do not necessarily have such sensations. Many reflex actions, for instance, occur during sleep ; many may be executed by the spinal cord even after it has been severed from the brain, and so the brain cannot be aware of what is occurring. A reflex action is an action which is the result of an afferent impulse. Thus a speck of dust falls into the eye, and causes move- ments of the eyelids to get rid of the offending object. The dust excites the sensory nerve-endings in the conjunctiva, an impulse travels to the centre of this nerve in the brain, and from the brain a reflected impulse travels to the muscles of the eyelid. As an instance of a reflex action in which secretion is concerned, take the watering of the mouth which occurs when food is seen or smelt. The nerves of sight or smell convey an afferent impulse to the brain, which reflects, down the secretory nerves, an impulse which excites the salivary glands to activity. These, however, are instances of reflex action which are accom- panied with conscious sensation, but like all pure reflex actions are not under the control of the will. An instance of a reflex action not accompanied with consciousness is seen in a man with his sphial cord cut across or crushed, so that any communication between his brain and his legs is impossible. He cannot move his legs voluntarily, and is unconscious of any feelings in them. Yet when the soles of his feet are tickled he draws his legs up, the centre of reflex action being in the grey matter of the lower region of the spinal cord. For a reflex action, three things are necessary : (1) an afferent nerve, (2) a nerve-centre consisting of nerve-cells to receive the afferent impulse and send out an efferent impulse, and (3) an efferent nerve along which the efferent impulse may travel. If the reflex action is a movement, the afferent nerve is called excito-motor ; if it is a secretion, the afferent nerve is called excito-secretory ; and similarly, afferent nerves may also be excito-accelerator, excito-inhibitory, etc. 3. Intercentral nerves are those which connect nerve-centres together ; they connect different parts of brain, and of the cord to one another, and we shall find in our study of the nerve-centres that they are complex in their arrangement. 164 PHYSIOLOGY OF NERVE [CH. XV. Investigation of the Functions of a Nerve. There are always two main experiments by which the function of a nerve may be ascertained. The first is section, the second is stimulation. Section consists in cutting the nerve and observing the loss of function that ensues. Thus, if a motor nerve is cut, motion of the muscles it supplies can no longer be produced by activity of the nerve-centre ; the muscle is paralysed. If a sensory nerve is cut, the result is loss of sensation in the part it comes from. Stimulation of the cut nerve is the opposite experiment. When a nerve is cut across, one piece of it is still connected with the brain or spinal cord ; this is called the central end ; the other piece, called the peripheral end, is still connected with some peripheral part of the body. Both the central and the peripheral end should be stimu- lated ; this is usually done by means of induction shocks. In the case of a motor nerve, stimulation of the central end produces no result ; stimulation of the peripheral end produces a nervous impulse which excites the muscles to contract. In the case of a sensory nerve, stimulation of the peripheral end has no result, but stimula- tion of the central end causes a sensation, usually a painful one, and reflex actions, which are the result of the sensation. When a nerve is cut across, there are other results than the loss of function just mentioned ; for even though the nerve is still left within the body with a normal supply of blood, it becomes less and less irritable, till at last it ceases to respond to stimuli altogether. This diminution of excitability starts from the point of section and travels to the periphery, but is temporarily preceded by a wave of increased excitability travelling in the same direction (Ritter-Valli law). This loss of excitability of nerve is accompanied with degenera- tive changes which are of so great importance as to demand a separate section. Degeneration of Nerve. Suppose a nerve is cut right across, the piece of the nerve left in connection with the brain or spinal cord remains healthy both in structure and functions ; but the peripheral piece of the nerve loses its functions and undergoes what is generally called, after the dis- coverer of the process, Wallerian degeneration. A nerve is made up of nerve-fibres, and each nerve-fibre is essentially a branch of a nerve- cell ; when the nerve is cut, the axis cylinders in the peripheral portion are separated from the cells of which they are branches and from which they have grown. These separated portions of the axis cylinders die, and the medullary sheath of each undergoes a gradual CH. XV.] DEGENERATION OF NERVE 165 process of disintegration into droplets of myelin, which are ultimately absorbed and removed by the lymphatics. At the same time there is a multiplication of the nuclei of the primitive sheath. This degenera- tive process is evident two or three days after the section has been made. In the case of the non-medullated fibres, there is no medullary sheath to exhibit the disintegrative changes just alluded to ; and the Fig. 181. — Degeneration and regeneration of nerve-fibres, a, nerve-fibre, fifty hours after operation. my, medullary sheath breaking up into myelin drops, p, granular protoplasm replacing myelin. n, nucleus, g, primitive sheath, b, nerve-fibre after four days, cy, axis cylinder partly broken up and enclosed in portions of myelin, c, a more advanced stage in which the medullary sheath has almost disappeared. Numerous nuclei, n", are seen, d, commencing regeneration ; several fibres (i', t") have sprouted from the somewhat bulbous cut end (6) of the nerve-fibre, a, an axis cylinder which has not yet acquired its medullary sheath, s, s', primitive sheath of the original fibre. (Ranvier.) nuclei of the sheath do not multiply ; there is simply death of the axis cylinder. The degeneration occurs simultaneously throughout the whole extent of the nerve ; it does not start from the section and travel to the periphery. Eauvier's original diagram is reproduced in fig. 181. Figs. 182 and 183 are photo-micrographs from actual specimens. A great amount of attention has been directed to this process of degeneration, because it has formed a valuable method of research in 166 PHYSIOLOGY OF NERVE [CH. XV. tracing nervous tracts, and ascertaining the nerve-cells from which they originate. It must not, however, be regarded as an isolated phenomenon in physiology ; it is only an illustration of the universal Fig. 182.— Nerve-fibres from sciatic nerve of cat, four days after the nerve had been cut. This shows an early stage of the degenerative process. COO diameters. (Mott and Halliburton.) truth that any portion of a cell (in this case the axis cylinder process) cut off from the nucleus of the cell degenerates and dies. If a nerve is simply cut, and allowed to heal, regeneration of function in time occurs. This is hastened by the surgeon suturing the cut ends of the nerve together. It must not, however, be supposed that this is due to a restoration of the structure of the fibres in the peripheral portion of the cut nerve. It is due to very fine new nerve-fibres sprouting out from the central end of the cut nerve, and growing distalwards. This is illustrated in D, fig. 181. When Fig. 183.— These are fibres from the sciatic nerve of another cat, ten days after the nerve had been cut. This shows the breaking-up of the medullary sheath in a marked way, and the intense black colour the myelin droplets take with osmic acid. 600 diameters. (Mott and Halliburton.) regeneration does not take place, the central ends of the cut fibres and the cells from which they originate undergo slow atrophic changes (disuse atrophy). The view expressed by the earlier workers on nerve regeneration CH. XV.] REGENERATION OF NERVE 167 that the new fibres grow from the central stump of the cut nerves has been recently ques- tioned. Some believe that regeneration may occur in the peripheral structures. It certainly is the case that the neurilemmal cells ex- hibit a great deal of activity ; they multiply (fig. 184) ; at a later stage they exhibit a phagocytic action in the removal of the degenerated fat (fig. 185) ; and later still they become elongated and spindle-shaped ; they then join together as though they were forming the basis of new nerve-fibres (fig. 186). But the elongating and apparently contiguous cells are probably only forming a new sheath or basis into which the axis cylinder ultimately grows. Howell and Huber, who have recently investi- gated this question, have arrived at the conclusion that the peri- Fig. 184.— Single fibre from a degenerating nerve, eight days after the nerve was cut, stained so as to show the division of a neurilemmal nucleus into two. 870 diameters. (Mott and Halliburton.) Fig. "185. — Degenerated nerve, twenty-sevenf^days after the nerve had been cut. The numerous neurilemmal cells, perhaps aided by phagocytes from the exterior contain within them fatty par- ticles which stain black with osmic acid. They are doubtless active in removing the degenerated myelin. 450 diameters. (Mott and Halliburton.) , ._ . ; Fig. 186. — Degenerated nerve forty-four days after section. The elongation of the neurilemmal cells to form what look like new fibres is well shown. 500 diameters. (Mott and Halliburton.) pheral structures are active in preparing the scaffolding, but that the axis cylinder, the essential portion of a nerve-fibre, has an 168 PHYSIOLOGY OF XEUYE [CH. XV. exclusively central origin. This view I thoroughly endorse. Mott and I have also shown that when the regenerated fibres are again cut, degeneration takes place in the peripheral direction only, and this is a strong piece of evidence that growth had not started from the periphery centralwards, for the direction of nutritive control is always the direction of growth. The manifest activity of the neurilemmal cells is probably largely nutritive rather than formative, but is nevertheless of great impor- tance, for, in situations like the central nervous system, where the neurilemma does not exist, regeneration does not occur. Functions of the Roots of the Spinal Nerves. The general truths enunciated in the two preceding sections are well illustrated by the experiments made to determine the functions of the roots of the spinal nerves. Each spinal nerve originates from the spinal cord by two roots. One of these is called the anterior or ventral root : it consists of nerve-fibres which originate from the large multipolar cells in that portion of the grey matter in the interior of the spinal cord which we shall presently learn to call the anterior horn. These nerve-fibres are all medul- lated ; the large ones join up with the posterior root to form the spinal nerve ; the small nerve-fibres leave the root and pass to the sym- pathetic chain, which then distributes non - medullated fibres to the involuntary muscular fibres of the blood-vessels and viscera. The other root, the posterior or dorsal root, has upon it a collection of nerve-cells forming the spinal ganglion. Each nerve-cell is enclosed within a nucleated sheath of connective tissue origin, and it is from these nerve-cells that the fibres of the posterior roots grow. In the embryo, each nerve-cell has two processes (fig. 187), one of which grows to the spinal cord, where it terminates by branching around the multipolar cells of the grey matter ; the other Fl . 1ST. — a, Bipolar cell from spinal ganglion of a 4i weeks embryo, n, nucleus ; the arrows indicate the direction in which the nerve processes grow, one to the spinal cord, the other to the periphery, b, a cell from the spinal ganglion of the adult; the two processes have coalesced to forma T-shaped junction. (Diagrammatic.) CH. XV.] RECURRENT SENSIBILITY 169 cm process grows outwards to the periphery. In the adult mammal (not in fishes) the two processes coalesce in the first part of their course, forming a T-shaped junction. The first experiments on the functions of the spinal nerve-roots were performed in this country by Sir Charles Bell (1811), and in France by Magendie (1822). These observers found that on section of the anterior roots there resulted paralysis of the muscles supplied by the nerves ; on section of the posterior roots there was loss of sensation. These experiments clearly pointed to the conclusion that the anterior roots contain the efferent (motor) fibres ; and the posterior roots the afferent (sensory) fibres. This conclusion was confirmed by the experiment of stimulation. Stimulation of the peripheral end of the cut anterior root caused muscular movement ; of the central end, no effect. Stimulation of the central end of the cut posterior root caused pain and reflex movements ; of the peripheral end, no effect. Recurrent sensibility. — One of the statements just made requires a slight modification ; namely, excitation of the peripheral end of a divided an- terior root will evoke pain and reflex movements, as well as direct move- ments; that is to say, the anterior root, though composed mainly of motor fibres, contains a few sensory fibres coming probably from the mem- branes of the spinal cord, and then running into the posterior root with the rest of the sensory fibres. They often, however, run down the mixed nerve a considerable distance before returning to the posterior roots. The diagram on this page (fig. 188) illustrates the course of one of these recurrent fibres (r) ; the arrows represent the direction in which it conveys impulses. Degeneration of roots. — The facts in connection with this subject were made out by Waller (1850), and may be best understood by referring to the next diagram (fig. 189). A represents a section of the mixed nerve beyond the union of the roots; the whole nerve beyond the section degenerates, and is shaded black. B represents the result of section of the anterior root ; only the anterior root-fibres degenerate; the sensory fibres of the posterior root remain intact. The small medullated nerve-fibres (not shown in the diagram) also degenerate as far as the ganglion cells of the Spinal Nerve - Fig. 18S. — Diagram to illustrate recurrent sensibility. 170 PHYSIOLOGY OF NERVE [CH. XV. Pin. 189. — Diagram to illustrate Wallerian degene- ration of nerve-roots. sympathetic system with which they communicate. The recurrent sensory fibres in this root do not degenerate with the others, but are found degenerated in the part of the anterior root at- tached to the spinal cord. Section of the posterior root always produces the same phy- siological effect (loss of sensa- tion) * wherever the section is made, but the degeneration effect is different according as the sec- tion is made on the proximal or distal side of the ganglion. If the section is made beyond the ganglion, the degeneration occurs as shown in C beyond the sec- tion in the peripheral portion of the posterior root-fibres ; the anterior root remains intact except for the recurrent sensory fibres which it con- tains. If the section is made as in D, between the ganglion and the cord, the only piece that degenerates is the piece severed from the ganglion and running into the cord ; these fibres may be traced up in the posterior column of the spinal cord until they terminate in grey matter, which they do at different levels. The whole of the sensory fibres including the recurrent ones which are still attached to the ganglion remain histologically healthy. The accompanying figure (fig. 190) is one of the original illustrations made by Dr "Waller, and I am indebted to the present Dr Waller for permission to reproduce it. These facts of degeneration teach us, what we also learn from the study of em- bryology, that the nerve-fibres of the an- terior root are connected to the nerve-cells within the spinal cord, while the posterior root-fibres are connected to the cells of the spinal ganglia ; or, to put it another way, the trophic centres which Fig. 1!»0. — Groups of fibres from the anterior and posterior roots several days after sec- tion of both roots close to the cord; the anterior fibres are degenerated ; the posterior, being still in connection with the nerve-cells from which they grew, are normal. * In order to obtain any appreciable loss of motion or sensation, it is necessary to divide several roots (anterior or posterior as the case may be) as there is a good deal of overlapping in the peripheral distribution of the fibres. CH. XV.] ACTION CURRENT OF NERVE 171 control the nutrition of the nerve-fibres are situated within the cord for the anterior roots, and within the spinal ganglia for the posterior roots. Changes in a Nerve during Activity. When a nerve is stimulated, the change produced in it is called a nervous impulse ; this change travels along the nerve, and the pro- pagation of some change is evident from the effects which follow : sensation, movement, secretion, etc. ; but in the nerve itself very little change can be detected. There is no change in form ; the most deli- cate thermo-piles have failed to detect any production of heat, and we are also ignorant of any chemical changes. The only alteration which can be detected as evidence of this molecular change in a nerve is the electrical one. Healthy nerve is iso-electric, but during the passage of a nervous impulse along it there is a very rapid diphasic variation, which travels at the same rate as the nervous impulse. This is similar to the diphasic change in muscle, which we have already studied, and can be detected in the same way. Waller regards the current of action of any excitable tissue as an index of the magnitude of action, and records the movement of the galvanometer by photograph- ing the excursion of the spot of light on a moving photographic plate. He has in this way obtained records from muscle, nerve, retina, skin, plant tissues, etc. He points out that the only available index of action within the nerve itself is the electrical sign of activity, whereas in muscle the mechanical action can be compared with its accompanying electrical changes. The amount of contraction in a muscle caused by excitation of its nerve is only a very rough, or even a fallacious, indica- tion of the excitability of the nerve, because the nerve is connected to the muscle by motor end-plates, and these, as we have already seen, are fatigued long before the nerve shows any sign of fatigue. Using this method, Waller has obtained a number of interesting results on the variation in nerve action produced by drugs and other agents. He finds that the effect of carbonic acid is to cause a diminution, and finally disappearance of the galvanometric response ; when this gas is replaced by air the nerve recovers, and the action-currents increase. Ether acts similarly ; but with chloroform recovery is difficult to obtain. Small doses of carbonic acid increase the action-currents, and Waller considers that the staircase effect in muscle (p. 117), and the similar progres- sive increase noted in the action-currents of nerve as the result of repeated stimula- tion are due to the evolution of this gas during activity. This hypothesis has been recently confirmed by some experiments of Basyer and Frohlich. They have shown that peripheral nerves participate in respiratory exchanges, using up oxygen and producing carbonic acid in measurable amounts. There can be no doubt that the existence of the electrical variation is as a rule the index of the excitatory alteration in a nerve. In the isolated nerve it is in fact the only change that can be detected. But in the present state of our knowledge we are not justified in assuming that it gives an absolutely faithful record. The electrical variation can be detected in a nerve for many days after its removal from the body. Although the electrical change is a concomitant of the real excitatory process, the former may be therefore perceptible when other evidence of the existence of the latter fails. Moreover, Gotch and Burch have obtained further evidence of the dissociation of the electrical response from the excitatory process. In the frog's sciatic nerve, it is possible with two stimuli in rapid succession to obtain only one electrical response near the seat of excitation which has been cooled, while two such responses occur in a more peripheral warmer region. 172 PHYSIOLOGY OF NERVE [CH. XV. Excitability and conductivity. — It is necessary to distinguish between these two properties of nerve. Changes in excitability, and in the power of conducting nerve impulses, do not necessarily go together, as shown in the following experiment : — The nerve of a frog's leg is led through a glass tube, the ends of which are sealed with clay, care being taken that the nerve is not compressed. The tube is provided with an inlet and outlet, so that gases may be passed through it. Two pairs of electrodes are arranged, so that the nerve can be stimulated either within or outside the little gas chamber. If carbon dioxide or ether vapour is passed through the tube, both excitability and conductivity are in time abolished, but excitability disappears first ; at this stage, if the nerve is stimulated by an induction shock inside the tube, the muscle does not respond, but on stimulating the nerve at the end distant from the muscle and outside the tube, the muscle contracts. The nerve, therefore, is not excitable, though it will conduct impulses. At a later stage shocks administered by either pair of electrodes provoke no contraction. When the poisonous vapour is replaced by air, the nerve recovers, and conductivity returns before excitability. If alcohol vapour is used conductivity is stated to vanish before excitability. Gotch has shown that cold applied to a nerve acts very much like carbonic acid. Intense cold will cause disappearance of both excitability and conductivity ; but cold of such a degree which abolishes the excitability of the nerve to induction shocks, increases its excitability to the constant current, and also to mechanical and thermal stimuli. Velocity of a Nerve Impulse. A nervous impulse is not electricity ; compared to that of electri- city its rate of propagation is extremely slow. It has been measured in motor nerves as follows : a muscle-nerve preparation is made with as long a nerve as possible ; the nerve is stimulated first as near to the muscle, and then as far from the muscle, as possible. The moment of stimulation and the moment of commencing contraction is measured by taking muscle tracings on a rapidly moving surface in the usual way, with a time-tracing beneath. The contraction ensues later, when the nerve is stimulated at a distance from the muscle, than in the other case, and the difference in the two cases gives the time occupied in the passage of the impulse along the piece of nerve, the length of which can be easily measured. A similar experiment can be performed on man by means of the transmission myograph (see p. 122). If a tracing of the contraction of the thumb muscles is taken, the two stimuli may be successively applied through the moistened skin, first at the brachial plexus below the clavicle; and secondly, at the median nerve at the bend of the elbow. Another method, largely employed by Bernstein, is to take the electrical change as the indication of the impulse. The rheotome is the instrument used. If fig. 169 (p. 139) is referred to, and a long nerve substituted for the muscle-nerve preparation, the stimulus is applied at one end, and the change in the electrical condition of the nerve is recorded by the galvanometer, which is connected to the other end of the nerve. The time measurement is effected by the adjustment of the rheotome, which must be such as to tap off the electrical change at the moment it occurs. CH. XV.] NERVE IMPULSES 173 The rate of the transmission of nervous impulses discovered by these methods is, in a frog's motor nerve, 28 to 30 metres a second ; in human motor nerves, 33 metres a second ; in sensory nerves, 30 to 33 metres a second. Direction of a Nerve Impulse. Nerve impulses are conducted normally in only one direction : in efferent nerves from, in afferent nerves to, the nerve-centres. But there are some experiments which point to the conduction occurring under certain circumstances in both directions. Thus, in the rheotome experiment just described, if the nerve is stimulated in the middle instead of at one end, the electrical change (the evidence of an im- pulse) is found to be conducted towards both ends of the nerve. Kiihne's gracilis experiment proves the same point. The gracilis muscle of the frog (fig. 191) is in two portions, with a tendinous in- tersection, and supplied by nerve-fibres that branch into two bundles ; excitation strictly limited to one of these bundles, after division of the tendinous intersection, causes both por- tions of the muscle to contract. Another striking experiment of the same kind can be performed with the nerve that Fl0 ' ^Iner waiier°) rog ' supplies the electrical organ of Malapterurus. This nerve consists of a single axis cylinder and its branches ; stimu- lation of its posterior free end causes the " discharge " of the electrical organ, although the nervous impulse normally travels in the opposite direction. Crossing of Nerves. Some experiments designed to prove the possibility of nervous conduction in both directions were performed many years ago by Paul Bert. He grafted the tip of a rat's tail either to the back of the same rat, or to the nose of another. When union had been effected, the tail was amputated near its base. After a time, irritation of the end of the trunk-like appendage on the back or nose of the rat gave rise to sensation. The impulse thus passed from base to tip, instead of from tip to base, as formerly. This experiment does not, however, prove the point at all ; for all the original nerve-fibres in the tail must have degenerated, and the restoration of sensation was due to new fibres, which had grown into the tail. Exactly the same objection holds to another series of experiments, in winch the 174 PHYSIOLOGY OF NERVE [CII. XV. motor and sensory nerves of the tongue were divided and united crosswise. Eestoration of both movement and sensation does occur, but is owing to new nerve-fibres growing out from the central stumps of the cut nerves. Though these experiments do not prove what they were intended to, they are of considerable interest in themselves. Dr E. Kennedy has recently carried out a very careful piece of work on this question of nerve crossing. He cut in a dog's thigh the nerves supplying the flexor and the extensor muscles, and sutured them together crosswise. Eegeneration of structure and restoration of function occurred equally quickly, as in those cases in which the central ends had been united to the peripheral ends of their own proper nerves. On examining the cortex of the brain in those animals in which nerve-crossing had been accomplished, it was found that stimulation of the region which in a normal animal gave flexion, now gave extension of the limb, and vice versd. A series of equally important experiments have more recently been carried out by Langley, in which he shows that the same facts are true for the nerves that supply involuntary muscle. These nerve-fibres will under certain experimental conditions terminate by arborising around other nerve-cells than those which they normally form connections (synapses) * with. It will be sufficient to give one typical experiment. If the vagus nerve is cut across in the neck, its peripheral end degenerates downwards ; if the cervical sympathetic is cut across below the superior cervical ganglion, its peripheral end degenerates upwards, as far as the ganglion. If subsequently the central end of the cut vagus is united to the peripheral end of the cut sympathetic, in the course of some weeks the vagus fibres grow into the sympathetic and form synapses around the cells of the superior cervical ganglion, and stimulation of the united nerve now produces such effects as are usually obtained when the cervical sympathetic is irritated ; for instance, dilatation of the pupil, raising of the upper eyelid, and constriction of blood-vessels of the head and neck. (See accompanying diagram, fig. 192). Such experiments as these are important because they teach us that though the action of nerves may be so different in different cases (some being motor, some inhibitory, some secretory, some sensory, etc.), after all what occurs in the nerve trunk itself is always the same ; the difference of action is due to difference either in the origin or distribution of the nerve-fibres. If we remember the familiar illustration in which nerve trunks are compared to telegraph wires, we may be helped in realising this. The destina- tion of a certain group of telegraph wires may be altered, and the * The meaning of the term "synapse" is fully explained in Chapter XVII. (p. 198). CH. XV.] CHEMISTRY OF NERVE 175 alteration may produce different consequences at different places ; the electric change, however, in the wires would be the same in all cases. So the nerve impulse going along a nerve is always the same sort of molecular disturbance; if it is made as in the experiment just described, to go by a wrong channel, it produces just the same A B C Super! Ceruica Ganglia on\J l-~Co Fig. 192. — Diagram to illustrate Langley's experiment on vagus and cervical sympathetic nerves. In A, the two nerves are shown intact ; the direction of the impulses they normally carry is shown by arrows, and the names of some of the parts they supply are mentioned. In B, both nerves are cut through. The degenerated portions are represented by discontinuous lines. In C, the union described in the text has been accomplished , and stimulation at the point a' now produces the same results as were in the intact nerves (A) produced by stimulation at a. results as though the impulse had reached its destination by the usual channel. Chemistry of Nervous Tissues. The following table gives some typical analyses of the solids of nervous tissues, but these tissues also contain a large amount of water ; this is present in larger Portion of Nervous System. o Choleste- -g Lecithin, rin and ■§ Fat. 8 I ° Neuro- keratin. Other Organic matters. 03 02 Grey matter of Brain . White matter of Brain . Spinal Cord .... Human Sciatic Nerve . 55 25 23 36 17 19 0-5 10 52 " 9-5 6-7 3-3 1-5 0-6 i 1-1 " 1 75-1 32 | 12 I 11 | 3 I 4 17G NIYSIOLOGY OF NERVE [CH. XV. amount (S3 per cent.) in grey matter than in white matter (70 per cent); in early than in adult life; in the brain than in the spinal cord ; in the spinal cord than in nerves. One should next note the high percentage of proteid. In grey matter, where the cells arc prominent structures, this is most marked, and of the solids, proteid material here comprises more than half of the total. The following are some of my analyses which give the mean of a number of observations on the nervous tissues of human beings, monkeys, dogs, and cats : Percentage of Water. Solids. Proteids in Solids. 51 Cerebral grey matter . 83-5 16-5 ,, white ,, 69-9 30-1 33 Cerebellum .... 79-8 •20-2 42 Spinal cord as a whole 71-6 28-4 31 Cervical cord 72*5 27-5 31 Dorsal cord 69-8 30-2 28 Lumbar cord 7-2-Q 27-4 33 Sciatic nerves 65*1 34-9 29 The most abundant proteid is nucleo-proteid : there is also a certain amount of globulin, which, like the paramyosinogen of muscle, is coagulated by heat at the low temperature of 47° C. A certain small amount of neurokeratin (especially abundant in white matter) is included in the above table with the proteids. The granules in nerve cells (Nissl's bodies), which stain readily with methylene blue, are nucleo- proteid in nature. The next most abundant substances are of a fatty nature ; the most prominent of these is the phosphorised fat called lecithin. In the nervous tissues some of the lecithin is combined with cerebrin to form a complex substance called prota(/on, which crystallises out on cooling a hot alcoholic extract of brain or other nervous structures. Cerebrin is a term which probably includes several sub- stances, which are nitrogenous glucosides ; they yield on hydrolysis the sugar called galactose. They are sometimes called cerebrosides. Kephalin is another phos- phorised fat which is present. The crystalline monatomic alcohol cholesterin is also a fairly abundant constituent of nervous structures, especially of the white substance of Schwann. Finally, there are smaller quantities of other extractives and a small proportion of mineral salts (about 1 per cent, of the solids). In connection with the substances just enumerated, it is necessary to enter a little more fully into the composition of lecithin. An ordinary fat contains the elements carbon, hydrogen, and oxygen, and when it takes up water it is split or hydrolysed into its constituent parts, glycerin and fatty acid. Fat + water. Glvcerin. Fattv acid. Lecithin (C 4 ._,H s4 NP0 9 ) contains not only carbon, hydrogen, and oxygen, but nitrogen and phosphorus as well. When it is hydrolysed, it yields not only glycerin and a fatty acid, but also phosphoric acid, and a nitrogenous base termed choline. Lecithin + water. Glvcerin. Fatty acid. Phosphoric acid. Choline. CH. XV.] CHEMISTEY OF NEEVE DEGENEEATION 177 Fresh nervous tissues are alkaline, but, like most other living structures, they turn acid after death. The change is particularly rapid in grey matter. The acidity is due to lactic acid. Little or nothing is known of the chemical changes nervous tissues undergo during activity. We know that oxygen is very essential, especially for the activity of grey matter ; cerebral anaemia is rapidly followed by loss of consciousness and death. We have already seen that similar respiratory exchanges, though less in amount, are stated to occur in peripheral nerves (see p. 171). Chemistry of nerve degeneration. — Mott and I have shown that in the disease General Paralysis of the Insane, the marked degeneration that occurs in the brain is accompanied by the passing of the products of degeneration into the cerebro-spinal fluid. Of these, nucleo-proteid and choline — a decomposition pro- duct of the lecithin — are those which can be most readily detected. Choline can also be found in the blood. But this is not peculiar to the disease just mentioned, for in various other degenerative nervous diseases (combined sclerosis, disseminated sclerosis, meningitis, alcoholic neuritis, beri-beri, etc.) choline can also be detected in these situations. The tests employed to detect choline are mainly two : (1) a chemical test, namely, the obtaining of the characteristic yellow octahedral crystals of the platinum double salt from the alcoholic extract of the cerebro-spinal fluid or blood ; * (2) a physiological test, namely, the lowering of arterial blood-pressure (partly cardiac in origin, and partly due to dilatation of peripheral vessels) which a saline solution of the residue of the alcoholic extract produces : this fall is abolished, or even replaced by a rise of arterial pressure, if the animal has been poisoned with atropine. It is possible that such tests may be of diagnostic value in the distinction between organic and so-called functional diseases of the nervous system. The chemical test can frequently be obtained with 10 c.c. of blood, or even less. A similar condition can be produced artificially in animals by a division of large nerve trunks ; and is most marked in those animals in which the degenerative process is at its height as tested histologically by the Marchi reaction, f A series of cats was taken, both sciatic nerves divided, and the animals subsequently killed at intervals varying from 1 to 106 days. The nerves remain practically normal as long as they remain irritable, that is up to 3 days after the operation. They then show a progressive increase in the percentage of water, and a progressive decrease in the percentage of phosphorus until degeneration is complete. When regeneration occurs, the nerves return approximately to their previous chemical condition. When the Marchi reaction disappears in the later stages of degeneration, the non- phosphorised fat has been absorbed. This absorption occurs earlier in the peripheral nerves than in the central nervous system. Further, it has been found that in spinal cords in which a unilateral degenera- tion of the pyramidal tract has been produced by a lesion in the opposite hemi- sphere, there is a similar increase of water and diminution of phosphorus on the degenerated side. The following table shows these main results in the experiments on cats just described. * This test is performed as follows : the fluid is diluted with about five times its volume of alcohol and the precipitated proteids are filtered off. The filtrate is evaporated to dryness at 40° C. and the residue dissolved in absolute alcohol and filtered ; the filtrate from this is again evaporated to dryness, and again dissolved in absolute alcohol, and this should be again repeated. To the final alcoholic solution an alcoholic solution of platinum chloride is added, and the precipitate so formed is allowed to settle and washed with absolute alcohol by decantation ; the precipitate is then dissolved in 15-per-cent. alcohol, filtered, and the filtrate is allowed to slowly evaporate in a watch-glass at 40 c C. The crystals can then be seen with the microscope. They are recognised not only by their yellow colour and octahedral form, but by their solubility in water and 15-per-cent. alcohol, but also by the fact that on incineration they yield 31 per cent, of platinum and give off the odour of trimethylaminp. t The Marchi reaction is the black staining tli at the medullary sheath of degenerated nerve-fibres shows when, after being hardened in Miiller's fluid, fjhey are treated with Marchi's reagent, a mixture of Miiller's fluid and osmic acid. Healthy nerve-fibres are not affected by the reagent, but normal adipose tissue is blackened like degenerated myelin. The osmic acid reaction is due to fats like olein. which belong to the acrylic series. M 178 PHYSIOLOGY 01' NERVE [oh. XV. Cat's sciatic nerves. Condil ion of blood. Condition of nerves. CD Percentage of phosphorus in solids. Normal .... 1 to 3 days after section 4 to 6 8 10 13 2.". to 27 29 41 100 to 106 65*] (34-5 69-3 68-2 70-7 71-3 72-1 72-5 72-6 66*2 34-9 35-5 30-7 31-8 29-3 28-7 27-9 27 - 5 27'4 3-8 1-1 0-9 0-9 O'o 0-3 0-2 traces 0-9 | Minimal traces of choline ( present. /Choline more \ abundant. | Choline abun- 1 dant. / Choline much ^ less. / Choline almost ( disappeared. /Choline almost ( disappeared. j Nerves irritable and histologically | healthy. j Irritability lost ; degeneration ! beginning. j Degeneration well shown by Marchi \ reaction. (Marchi reaction still seen, but - absorption of de- generated fat has ! set in. | Absorption of fat practically com- I plete. | Return of function , nerves regener- 1 ated. The above figures relate to the peripheral portions of the nerves. Noll has shown that the phosphorised material protagon also diminishes somewhat in the central ends of cut nerves due to " disuse atrophy." Heat contraction of nerve. — A nerve, when heated, shortens ; this shortening occurs in a series of steps which, as in the case of muscle, take place at the coagula- tion temperatures of the proteids present. The first step in the shortening occurs in the frog at about 40% in the mammal at about 47°, and in the bird at about 52 c C. The nerve is killed at the same temperatures. Cerebro-spinal fluid. — This plays the part of the lymph of the central nervous system, but differs considerably from all other forms of lymph. It is a very watery fluid, containing, besides some inorganic salts similar to those of the blood, a trace of proteid matter (globulin) and a small amount of sugar. It contains the merest trace of choline ; but this is not devoid of significance, for this fact taken in con- junction with another — namely, that physiological saline solution will extract from perfectly fresh nervous matter a small quantity of choline — shows us that lecithin and protagon are not stable substances, but are constantly breaking down and building themselves up afresh ; in fact, undergoing the process called metabolism. This is most marked in the most active region of the brain — viz., the grey matter. CHAPTEE XVI ELECTKOTOXUS When a constant current is thrown into a nerve, there is an excita- tion which leads to a nervous impulse, and this produces a contraction of the muscle at the end of the nerve. Similarly, there is another contraction when the current is taken out. While the current is flowing through the nerve, the muscle is quiescent. But while the current is flowing there are changes in the nerve, both as regards its electrical condition and its excitability. These changes are summed up in the expression electrotonus. In the investigation of this subject the instruments employed are the same as those already described, with the addition of two others that it will be convenient to describe before passing on to the study of electrotonus itself. These are the reverser or commutator, and the rheochord. Pohl's commutator is the form of reverser generally employed. It consists of a block of ebonite provided with six pools of mercury. Fig. 193. — Polil's Commutator, with cross wires. (After Waller.) each of which is provided with a binding screw. The corner pools are connected by diagonal cross wires, and by a cradle consisting of an insulating handle fixed to two arcs of copper wire which can be tilted so that the two middle pools can be brought into communication with either of the two lateral pairs of pools. Fig. 193 shows how, by 180 ELECTROTONUS [CH. XV altering the position of the cradle, the direction of the current from one electrode to the other is reversed. The numbers 1, 2, 3, etc., indicate the path of the current in the two cases. Sometimes the reverser is used without the cross wires for a different purpose. The battery wires are connected as before with the middle mercury pools. Each lateral pair of pools is connected by wires to a pair of electrodes. The two pairs of electrodes may be applied to two portions of a nerve, or to two different nerves, and by tilting the cradle to right or left the current can be sent through one or the other pair of electrodes. The rheochord is an instrument by means of which the strength of a constant current passed through a nerve may be varied. It consists of a long wire (r, r, r) of high resistance stretched on a board. This * Nerue Fig. 194. — Simple Rheochord. is placed as a bridge on the course of the battery current. (See fig. 194.) The current is thus divided into two parts : one part through the bridge, the other through the nerve, which is laid across the two non-polarisable electrodes at the ends of the wires. The resistance through the bridge is varied by the position of the slider (s s). The farther the slider is from the battery end of the instrument the longer is the bridge, and the higher its resistance, so that less current goes that way and more to the nerve. The next figure shows the more complicated form of rheochord invented by Poggendorf. The number of turns of wire is greater, so Fig. 195. — PoggendorFs Rheochord. (M'Kendrick.) that the resistance can be varied to a much greater extent than in the simpler form of the instrument. CH. XVI.] ELECTROTONIC CURRENTS 181 The term " electrotonus " includes two sets of changes in the nerve ; first an electrical change, and secondly changes in excitability and conductivity. We will take the electrical change first. Electrotonic currents. — The constant current is passed through the nerve from a battery, non-polarisable electrodes being used ; it is called the polarising current. If portions of the nerve beyond the electrodes are connected ("led off") as in the diagram (fig. 196) by non-polarisable electrodes to galvanometers, a current will in each case be indicated by the swing of the galvanometer needles. The electrotonic current in the neighbourhood of the negative pole or kathode is called the katelectrotonic current ; and that in the neighbour- hood of the anode is called the anelectrotonic current. In both cases the electrotonic current has the same direction as the polarising current. These currents are dependent on the physical integrity of medullated Anelectrotonic *, X Katelectrotonic Current \ \ > Current Polarising Current Fig. 196. — Electrotonic currents. nerve ; they are not found in muscle, tendon, or n on -medulla ted nerve ; they are absent or diminished in dead or degenerated nerve. They can, however, be very successfully imitated in a model made of zinc wire encased in cotton soaked with salt solution. The electro- tonic currents must be carefully distinguished from the normal current of action, which is a momentary change rapidly propagated with a nervous impulse which may be produced by any method of stimulation. The electrotonic currents are produced only by an electrical (polarising) current; they vary in intensity with the polarising current, and last as long as the polarising current passes through the nerve. After the polarising current is removed, after-electrotonic currents occur in different directions in the three regions tested. (a) In the intrapolar region, the after-current is opposite in direction to the original polarising current ; unless the polarising current is strong and of short duration, when it is in the same direction. (b) In the katelectrotonic region, the after-current has the same direction as the katelectrotonic current. (c) In the anelectrotonic region, the after-current has at first the same, then the opposite direction to the anelectrotonic current. 182 KLRCTIIOTONL'S [CH. XVI. The experiment known as the paradoxical contraction depends upon electrotonic currents. The sciatic nerve of the frog divides in the lower part of the thigh into two parts. If one division is cut across, and its central end stimulated electrically (the spinal cord having been previously destroyed), the muscles supplied by the other branch contract; the nerve-fibres in this branch having been stimu- lated by the electrotonic variation in the divided branch.* Electrotonic alterations of excitability and conductivity. — When a constant current is passed through a nerve, the excitability and conductivity of the nerve are increased in the region of the kathode, and diminished in the region of the anode. When the current is taken out these properties are temporarily increased in the neighbourhood of the anode, and diminished in that of the kathode. This may be shown in the case of a motor nerve by the following experiment. The next diagram represents the apparatus used. Coil EXCITING CIRCUIT Muscle Fig. r. 1 ".— Diagram of apparatus used in testing electrotonic alterations of excitability. An exciting circuit for single induction shocks is arranged in the usual way, the exciting electrodes being placed on the nerve near the muscle. A polarising circuit is also arranged, and includes a battery, key, and reverser ; the current is passed into the nerve by means of non-polarisable electrodes. When the polarising current is thrown into the nerve, or taken out, a contraction of the muscle occurs, but these contractions may be disregarded for the present. The exciting circuit is arranged with the secondary coil so far from the primary that the muscle responds to break only, and the tracing * This experiment must be carefully distinguished from Kiihne's gracilis experiment described on p. 173. In the gracilis experiment the nerve-fibres themselves branch, and any form of stimulation applied to one branch will cause contraction of both halves of the muscle. In the paradoxical contraction, the bundles of nerve-fibres are merely bound side by side, in the sciatic trunk ; there is therefore no possibility of conduction of a nerve impulse in both directions ; the stimidus, moreover, must be an electrical one. CH. XVI. ] CHANGES IN EXCITABILITY 183 may be recorded on a stationary blackened cylinder. The cylinder is moved on a short distance, and this is repeated. The height of the lines drawn may be taken as a measure of the excitability of the nerve. The polarising current is then thrown in, in a descending direction {i.e., towards the muscle) ; the kathode is thus the non-polarisable electrode near to the exciting electrodes. "While the polarising current is flowing, take some more tracings by breaking the exciting current. The increase in the excitability of the nerve is shown by the much larger contractions of the muscle; probably a contraction will be obtained now at both make and break of the exciting current. After removing the polarising current, the contractions obtained by excit- ing the nerve will be for a short time smaller than the normal, but soon return to their original size. Exactly the reverse occurs when the polarising current is ascend- ing, i.e., from the muscle towards the spinal cord. The non-polarisable electrode near the exciting electrodes is now the anode. While the polarising current is passing, the excitability of the nerve is diminished so that induction shocks which previously produced contractions of a certain size, now produce smaller contractions, or none at all. On removing the polarising current, the after-effect is increase of excit- ability. The following figure is a reproduction of a tracing from an actual experiment. The after-effects are not shown. N represents a series of contractions ob- tained when the nerve is normal, K when it is kate- lectrotonic, A when it is anelectrotonic. Exactly similar results are obtained if one" uses mechani- cal stimuli, such as hammer- ing the nerve, instead of induction shocks. The same is true for chemical stimuli. If the exciting electrodes are removed, and salt sprinkled on the nerve near the muscle, the latter soon begins to quiver ; its contractions are increased by throwing in a descending and diminished by an ascend- ing polarising current. The increase in irritability is called katelectrotonus, and the decrease is called anelectrotonus. The accompanying diagram (fig. 199) shows how the effect is most intense at the points {a Jc) where Fig. 19S. — Electrotouus. M, make. 13, break. 184 ELECTROTONUS [CH. XVI. the electrodes are applied, and extends in gradually diminishing intensity on each side of them. Between the electrodes the increase shades off into the decrease, and it is evident that there must he a neutral point where there is neither increase nor decrease of irritability. The position of this neutral point is found to vary with the intensity Fig. 109. —Diagram illustrating the effects of various intensities of the polarising current. », »', nerve ; a, anode ; k, kathode ; the curves above indicate increase, and those below decrease of irritability, and when the current is small the increase and decrease are both small, with the neutral point near a, and as the current is increased in strength, the changes in irritability are greater, and the neutral point approaches k. of the polarising current — when the current is weak the point is nearer the anode, when strong nearer the kathode. Pfluger's law of contraction. — The constant current sometimes causes a contraction both at make and break, sometimes at make only, sometimes at break only. The difference depends on the strength and direction of the current ; and follows from the electrotonic changes of excitability and conductivity we have been studying. Increase of ex- citability acts as a stimulus ; so that at the make the kathode is the stimulating electrode, and at the break the anode is the stimulating electrode. The facts may be demonstrated in the following way (fig. 200) : Fig. 200.— Arrangement of apparatus for demonstrating Pfluger's law. from a battery lead the wires to the middle screws of a reverser (with cross wires), interposing a key ; from one pair of end screws of the reverser lead wires to the binding screws of the rheochord ; from these same screws of the rheochord the non-polarisable electrodes lead to the nerve of a nerve-muscle preparation. The strength of the current is varied by the slider S. The nearer S is to the binding screws the CH. XVI.] PFLtJGER's LAW OP CONTRACTION 185 less is the resistance in the rheochord circuit, and the less the current through the nerve. With a weak current, a contraction occurs at make only, but more readily, i.e. with a weaker current, when its direction is descending, i.e. towards the muscle. With a stronger current (ascending or descending) contraction occurs both at make and break. With a very strong current (six G-roves), the contraction occurs only at make with a descending current ; and only at break with an ascending current. The contractions produced in the muscle of a nerve-muscle preparation by a constant current have been arranged in a table which is known as Pnuger's Law of Contraction. Stkength of Current used. Descending Current. Ascending Current. ' Make. Break. Make. Break. Weak . Moderate Strong . Yes. Yes. Yes. No. Yes. No. Yes. Yes. No. No. Yes. Yes. 1 The increase of irritability at the kathode when the current is made is greater, and so more potent to produce a contraction than the rise of irritability at the anode when the current is broken ; and so with weak currents the only effect is a contraction at the make. But when the strength of the current is increased the rise of excitability is in all eases sufficient to provoke a contraction (moderate effect in above table). The alteration in conductivity is not sufficient to prevent the impulses being propagated to the muscle. With strong currents the case is a little more complicated, because here the diminution of conductivity is so great that certain regions of the nerve become impassable by nerve impulses. When the current has an ascending direction, the impulse at the break is started at the anode, and as this is next to the muscle there is no hindrance to the propagation of the impulse, but at the make the impulse started at the kathode is blocked by the extreme lowering of conductivity at the anode. When the current is descending the kathode is near the muscle, and so the impulse at make reaches the muscle without hindrance ; but at the break, the impulse started at the anode has to traverse a region of nerve, the conductivity of which is so lessened that the excitation is not propagated to the muscle. G. N. Stewart has stated in opposition to the foregoing statements that at the make conductivity is most lowered at the kathode, and at the break at the anode. In other words, conductivity and excitability vary in opposite directions. His results have, however, not been accepted by other physiologists, and are due to a complex set of excitatory and polarisation changes produced by the galvanometric 1S6 BLfiCtROfONtJS [en. XVI. methods he adopted. Gotch's much more trustworthy experiments with the electrometer are directly opposed to those of Stewart. The following simple experiment devised by Gotch appears to be quite conclusive that conductivity like excitability is lessened at the anode when the current is made. Three non-polaris- able electrodes are employed (fig. 201), the current is first closed from A., to K, and the time which intervenes before the muscle contracts is measured ; it is then closed from A, to K, and the time again measured. In both cases, excitation occurs at K, but the time of response in the second case (\ l to K) is longer, because in that case the nerve impulse has to traverse a region of nerve at A, in which the power of conduction is lessened. — — I r- — 1 — Fig. 201.- Diagram to illustrate Gotch's experiment with triple electrodes. Sometimes (when the preparation is specially irritable) instead of a simple contraction a tetanus occurs at the make or break of the constant current. This is due to chemical (electrolytic) changes pro- duced by the current, and is liable to occur at the break of a strong ascending current which has been passing for some time into the preparation, or at the make of a strong descending current; both being conditions which increase the excitability of the piece of nerve nearest to the muscle ; this is called Ritter's tetanus, and may be stopped in the first case by throwing in the current in the same direction, or in the second case by throwing in a current in the opposite direction, i.e., by conditions which lessen the irritability of this piece of nerve. The same general laws hold for muscle as well as for nerve, but are more difficult to demonstrate ; the main fact, however, that the kathode is the stimulating electrode at the make, and the anode at the break, may be shown by the following experiment: if a curarised, that is, a physiologically nerveless muscle, is arranged, as in the experiment, for demonstrating the muscle- wave (see fig. 149, p. 119), and a non-polarisable electrode placed at each end, the muscle-wave at the make of a constant current starts at the kathode and at the break at the anode. An induced current in the secondary circuit of an inductorium may be regarded as a current of such short duration that the opening and closing are fused in their effects. This is true for all induction cur- rents, whether produced by the make or break of the primary circuit. The kathode will always be the more effective in causing contraction. Eesponse of Human Muscles and Nerves to Electrical Stimulation. Perhaps the most important outcome of this study of the response of muscle and nerve to electrical stimulation is its application to the CH. XVI.] REACTION OF DEGENERATION 187 muscles and nerves of the human body, because here it forms a most valuable method of diagnosis in cases of disease. In the normal state, nerves can be stimulated either by induction shocks, or by the make and break of a constant current. In the case of the motor nerves this is shown by the contraction of the muscles they supply ; and in the case of the sensory nerves by the sensations that are produced. In the case of the sensory nerves, the sensation produced by the constant current is most intense at the instant of make and break, or when the strength of the current is changed in the direction either of diminution or increase ; but there is a slight sensation due doubtless to the electrotonic alterations in excitability which we have been studying, during the whole time that the current is passing. When the nutrition of the nerves is impaired, much stronger currents of both the induced and constant kinds are necessary to evoke muscular contractions than in the normal state. When the nerves are completely degenerated (as, for instance, when they are cut off from the spinal cord, or when the cells in the cord from which they originate are themselves degenerated, as in infantile paralysis) no muscular contraction can be obtained on stimulating the nerves even with the strongest currents. The changes in the excitability of the muscles are less simple, because in them there are two excitable structures, the terminations of the nerves, and the muscular fibres themselves. Of these, the nerve-fibres are the more sensitive to induction currents, and the faradic stimulation of a muscle under normal circumstances is by means of these motor nerve-endings. Thus we find that its excita- bility corresponds in degree to that of the motor nerve supplying it. The muscular fibres are, even in the normal state, less sensitive to faradism (that is, a succession of induction shocks) than the nerve, because they are incapable of ready response to stimuli so very short in duration as are the shocks of which a faradic current consists. The proof of this consists in the fact that under the influence of curare, which renders the muscle practically nerveless, the muscle requires a much stronger faradic current to stimulate it than in the normal state. When the nerve is degenerated, the make or break of the constant current stimulates the muscle as readily as in the normal state; but the contraction is propagated more slowly than that which occurs when the nerve-fibres are intact, and is due to the stimulation of the muscular fibres themselves. The fact that, under normal circumstances, the contraction which is caused by the constant current is as quick as that produced by an induction shock, is ground for believing that in health the constant, like the induced current, causes the muscle to contract chiefly by exciting the motor nerves within it. 188 ELECTROTONUS [CH. XVI. AVhen the motor nerve is degenerated, and will not respond to any form of electrical stimulation, the muscle also loses all its power of response to induction shocks. The nerve-degeneration is accom- panied by changes in the nutrition of the muscular fibres, as is evidenced by their rapid wasting, and any power of response to faradism they possessed in the normal state is lost. But the response to the constant current remains, and is indeed more ready than in health, doubtless in consequence of nutritive changes which develop what the older pathologists called, truly enough, " irritable weakness." There is, moreover, a qualitative as well as a quantitative change. In health the first contraction to occur on gradually increasing the strength of the current is at the negative pole, when the circuit is closed (see Pfliiger's law), and a stronger current is required before closure-cou traction occurs at the positive pole. But in the morbid state we are discussing, closure-contraction may occur at the positive pole as readily as at the negative pole. This condition is called the " Reaction of Degeneration." Suppose a patient comes before one with muscular paralysis. This may be due to disease of the nerves, of the cells of the spinal cord, or of the brain. If the paralysis is due to brain disease, the muscles will be slightly wasted owing to disuse, but the electrical irritability of the muscles and nerves will be normal, as they are still in connection with the nerve-cells of the spinal cord that control their nutrition. But if the paralysis is due to disease either of the spinal cord or of the nerves, this nutritive influence can no longer be exercised over the nerves or muscles. The nerves will degenerate ; the muscles waste rapidly ; the irritability of the nerves to both forms of electrical stimulation will be lost; the muscles will not respond to the faradic current, but in relation to the constant current they will exhibit what we have called the " reaction of degeneration." This illustrates the value of the electrical method as a means of diagnosis, that is, of finding out what is the matter with a patient. It is also a valuable means of treatment ; by making the muscles con- tract artificially, their nutrition is kept up until restoration of the nerves or nerve-centres is brought about. Another illustration will indicate that the facts regarding electrotonic variation of excitability are true for sensory as well as for motor nerves ; in a case of neuralgia, relief will often be obtained by passing a constant current through the nerve ; but the pole applied to the nerve must be the anode which produces diminution of excitability, not the kathode which produces the reverse. Waller has pointed out that Pfliiger's law of contraction, as formulated for frogs' muscles and nerves, is true for human muscles and nerves in the main, but there are certain discrepancies. These arise from the method necessarily employed in man being different from those used with a muscle-nerve preparation. In a muscle-nerve preparation the nerve is dissected out, the two electrodes placed on CH. XVI.] THE LAW OF CONTRACTION IN MAN 189 it, and the current has of necessity to traverse the piece of nerve between the two electrodes. In man, the current is applied by means of electrodes or rheophores which consist of metal discs covered with wash leather, and soaked in brine. One of these is placed on the moistened skin over the nerve, and the other on some indifferent point, such as the back. The current finds its way from one electrode to the other, not necessarily through the nerves to any great extent (though it will be concentrated at the nerve as it leaves the anode or reaches the kathode), but diffuses widely through the body, seeking the paths of least resistance. Thus it is impos- sible to get pure anodic or kathodic effects. If the anode is applied over the nerve, the current enters by a series of points (polar zone), and leaves by a second series of points (peripolar zone). The second series of points is very close to the first, as the current leaves the nerve as soon as possible, seeking less resistant paths. The polar zone will be in the condition of anelectrotonus, the peripolar in that of katelectrotonus, so that although the former effect will predominate, the points being more concentrated, the latter effect may prevent a pure anelectrotonic effect being observed (fig. 202). Pfliiger's law of contraction according to which excitation occurs at the kathode on the make of a constant current, and at the anode on the break, holds good for all excitable tissues. The excitation at the break is probably really due to the make of a polarisation current having its kathode at the former anode, and is therefore fundamentally of the same nature as the make contraction ; or, in general Fig. 202. — Electrodes applied to the skin over a nerve-trunk. In a the polar area is anelectrotonic, and the peripolar katelectrotonic. The former condition, therefore, preponderates, since the current is more concentrated. In b the conditions are reversed, the polar zone corresponding here to the kathode. (After Waller.) terms, excitation occurs only at the place where a current leaves the excitable tissue. No doubt the effect is determined by the electrolytic changes occurring at the point of entry and exit of the current ; the development of kat-ions must there- fore be the chemical change that results in excitation. It is difficult to imagine that in a degenerated muscle there should be a reversal of such a fundamental law, and that excitation should be associated with the development of an-ions. Yet this is supposed to occur in the qualitative change known as the " reaction of degenera- tion." Page May has investigated this question afresh, and finds that the reversal of the law is only apparent, not real, and is due to the imperfect method which clinical observers must necessarily employ when testing the electrical reaction of muscles through the skin. By the use of appropriate electrodes on the degenerated muscles of animals, it is possible to detect the source of error. Let us substitute a muscle for a nerve in the diagrams of fig. 202 ; the current enters a few fibres at the anode, then spreads in all directions, and leaves the muscle by a number of diffused kathodic points. If the muscle is degenerated, its excitability is high, and the ready response at the anode when the current is made does not really occur at the actual anode, but in the neighbouring and more widespread peripolar kathodes. In other words, degenerated muscle obeys the general law of excitable tissues, and excitation occurs only at the situation where the current leaves the muscle. At the actual anode there is relaxation or absence of effect ; this is obviously not observable through the human skin because the change is very limited in extent ; it can be actually seen in the exposed muscles of an animal. CHAPTEK XVII NERVE-CENTRES The nerve-centres consist of the brain and spinal cord ; they are characterised by containing nerve-cells, from which the nerve-fibres of the nerves originate. Small collections of nerve-cells are found also in portions of the peripheral nervous system, where they are called ganglia. The spinal ganglia on the posterior roots of the spinal nerves, and the sympathetic ganglia are instances of these. The general arrangement of the cerebro-spinal axis is given in the accompanying diagram. The nerves which take origin from the brain are called cranial nerves; there are twelve pairs of these; some of them, like the olfactory, optic, and auditory nerves, are nerves of special sense ; others supply the region of the head with motor and sensory fibres. One pair (the tenth), called the pneumogastric or vagus nerves, are mainly distributed to the viscera of the thorax and abdomen, and a part of another pair (the eleventh), called the spinal accessory nerves, unites with the vagus prior to such distribu- tion. We shall in our subsequent study of the heart, lungs, stomach and other organs have frequently to allude to these nerves. The first two pairs of cranial nerves (the olfactory and the optic) arise from the cerebrum. The remaining ten pairs are connected with the district of grey matter called the floor of the fourth ventricle or its immediate neighbourhood ; this tract of grey matter is situated at the lower part of the brain where it joins the spinal cord; this portion of the brain is called the Bulb or Medulla oblongata. The spinal nerves are arranged in pairs, 31 in number. Their general structure and functions we have already studied (pp. 168-170). The more intimate structure of the brain and spinal cord we shall consider at length in subsequent chapters. For the present we shall deal with some of the general aspects of the nerve-centres, both as regards structure and function. The brain and spinal cord consist of two kinds of tissue, easily distinguishable by the naked eye. They are called respectively white matter and grey matter. CH. XVII.] WHITE AND GREY MATTER 191 White matter is composed o in structure from the meclul- latecl fibres of nerve by having no primitive sheath (neurilemma). Grey matter is the true central material so far as re- gards function ; that is to say, it is the part which receives and sends out nervous impulses ; it is characterised by containing the bodies of the nerve - cells. In the brain the grey matter is chiefly situated on the surface, forming what is called the cortex; the white matter and cer- tain subsidiary masses of grey matter are in the interior. In the spinal cord, the grey matter is in the in- terior, the white matter outside. In both grey and white matter the nerve-cells and nerve-fibres are supported by a peculiar tissue which is called neuroglia. It is composed of cells and fibres, the latter being prolonged from the cells. Some of the fibres are radially arranged. They start from the outer ends of the ciliated epithe- lium cells that line the central canal of the spinal cord and the ventricles of the brain, and diverge con- stantly branching towards the surface of the organ, where they end by slight enlargements attached to f medullated nerve-fibres, which differ . 203. — View of the cerebrospinal axis of the nervous system. The right half of the cranium and trunk of the body has been removed by a vertical section ; the membranes of the brain and spinal cord have also been removed, and the roots and first part of the fifth and ninth cranial, and of all the spinal nerves of the right side, have been dissected out and laid separately on the wall of the skull and on the several vertebrae opposite to the place of their natural exit from the cranio-spinal cavity. (After Bourgery.) 192 NERVE-CENTRES [CH. XVII. the pia mater. The other fibres of the tissue are cell processes of the neuroglia or glia cells proper, or spicier cells as they are some- times termed (see fig. 204). Neuroglia is thus a connective tissue in function, but it is not one in origin. Like the rest of the nervous system, it originates from the outermost layer of the embryo, the epiblast. All true connective tissues are mesoblastic. Chemically, it is very different from connective tissues. It con- Fio. 204.— Branched neuroglia-cell. (AfterStr.hr.) sists of an insoluble material called neuro-keratin, or nerve-horn, similar to the horny substance, keratin, which is found in the surface layers of the epidermis. Structure of Nerve-Cells. Nerve-cells differ a good deal both in shape and size. In the early embryonic condition, the future nerve-cell is a small nucleated mass of protoplasm without processes. As development progresses branches grow, and by this means it is brought into con- tact with the branches of other nerve-cells. When the nerve-cells degenerate, as they do in some cases of brain and cord disease, there is a reversal of this process ; just as in a dying tree the terminal branches, those most distant from the seat of nutrition, are the first to wither, so it is in the degenerating nerve-cell. If one traces the structure of nerve-cells throughout the zoological series, there is also seen an increase in their complexity, and the number of points of contact produced by an increase in the number and complexity of the branches multiplies (fig. 205). CH. XVII.] NERVE-CELLS 193 The simplest nerve-cells known are termed bipolar. In the lower animals the two processes come off from the opposite ends of the cells ; the cell, in other words, appears as a nucleated enlargement on the course of a nerve-fibre. Fig. 206 (A) shows one of these nerve- cells from the Gasserian ganglion of the pike. The cells of the Gasserian and spinal ganglia in the mammalian embryo are also bipolar, but as development progresses, the two branches become fused for a considerable distance, so that in the fully formed animal each cell appears to be unipolar. This is shown in a more diagram- matic way in fig. 187, p. 168. The bifurcation of the nerve-fibre is Fio. 205. — Diagram after Ramon y Cajal to show the ontogenetic (or embryological) and phylogenetic (i.e. in the animal series) development of a neuron, a, cerebral cell of frog ; b, newt ; c, mouse ; d, man. As the place in the zoological series rises, the neuron increases in complexity and in the number of points of contact ; this is produced partly by an increase of the dendrons, partly by an increase in the side branches or collaterals of the axon, a, b, c, d, e, show the early stages in the development of a similar cell in the human embryo ; the first branch of the cell to appear (in a) is the axon ; the dendrons are later outgrowths. The reversal of this process takes place in primary degeneration. spoken of as a T-shaped junction. As will be seen in fig. 206 (C), the nerve process has a convoluted course on the surface of the cell before it bifurcates. In these ganglia it should be also noted that each cell is enclosed within a connective tissue sheath, and the nuclei seen are those of the connective tissue corpuscles. In the sympathetic ganglia, the cells may have a similar structure, and here also the nucleated sheath is seen. In some cases, however, when there appear to be two fibres connected to a cell, one of them is really derived from another cell, and is passing to end in a ramifi- cation which envelopes the ganglion cell ; it may sometimes be coiled spirally around the issuing nerve-fibre. N 194 NERVE-CENTRES [CH. XVII. The majority of nerve-cells found in the body are multipolar. Here the cell becomes angular or stellate. Fig. 207 shows the usual form of cell present in sympathetic ganglia. From the angles of the cell, branches originate ; the majority of these branches divide and subdivide until each ends in an arborescence of fine twigs or fibrils ; N.S. Fig. 206.— Bipolar nerve-cells. A. From the Gasserian ganglion of the pike (after Bidder). B. From a spinal ganglion of a 4h weeks' human embryo (after His). C. Adult condition of the mammalian spinal ganglion cell : N. S. nucleated sheath ; only the nuclei seen in profile are represented. T. is the T-sbaped junction (after Retzius). but one process, and one process only, of each cell becomes the axis cylinder of a nerve-fibre. Passing next to the central nervous system, we here again find the multipolar cell is the principal kind present. The next figure (fig. 208) shows one of the typical multipolar cells of the spinal cord. Here again, only one process (a) becomes the axis cylinder of a nerve-fibre, and the others break up into arborisa- tions of fibrils. The cells have a finely fibrillar structure, and the fibrils can be traced into the axis cylinder process and the other branches of the cell. Between the fibrils the protoplasm of the cell CH. XV I I.J NERVE-CELLS 195 contains a number of angular or spindle-shaped masses, which have a great affinity of basic aniline dyes like methylene blue. They are Fig. 207. — An isolated sympathetic ganglion cell of man, showing sheath with nucleated cell lining, B. A. Ganglion cell, with nucleus and nucleolus. C. Branched process. D. Axis cylinder process (Key and Retzius.) x 750. known as Nissl's granules. These nerve-cells often contain, especi- ally in the adult, granules of pigment, usually yellow, the nature of which has not been determined. Fig. 20S.— Multipolar nerve- cell _ from anterior horn of spinal cord; a, axis cylinder process. (Max Schultze.) 196 NERVE-CENTRES [OIL XVII. In preparations made by Golgi's chromate of silver method, the cells and their processes are stained an intense black by a deposit of silver. The various structures in the cells (nucleus, granules, fibrils, etc.), are not visible in such preparations, but the great advantage of the method is that it enables one to follow the branches to their finest ramifica- tions. It is thus found that the axis cylinder process is not un- branched, as represented in fig. 208, but invariably gives off side-branches, which are called collaterals ; these pass into the adjacent nerve-tissue. The axis cylinder then acquires the sheaths, and thus is converted Fio. 209.— Pyramidal cell of human cerebral cortex. Golgi's method. into a nerve-fibre. This nerve-fibre sometimes, as in the nerve-centres after a more or less extended course, breaks up into a terminal arborescence enveloping other nerve-cells; the}. collaterals also terminate in a similar way. The longest type I of axis cylinder is that which passes away from the nerve-centre, and gets bound up with other similarly sheathed axis cylinders to form a nerve; but Fio. 210.— Cerebral cortex of mammal, prepared by Golgi's method, a, b, c, d, f, nerve-cells ; k, neuroglia-cell. (Ramon y Cajal.) CH. XVII.] NERVE-CELLS 197 all ultimately terminate in an arborescence of fibrils in various end organs (end-plates, muscle spindles, etc.). In the grey matter of the cerebrum the nerve-cells are various in shape and size, but the most characteristic cells are pyramidal in shape. They are especially large and numerous in what are called the motor areas of the brain. The apex of the cell is directed to the surface ; the apical process is long and tapering, and finally breaks up into fibrils that lie parallel to the surface of the brain {tangential fibres). From the lower angles and other parts branching processes Fig. 211.— Cell of Purkinje from the human cerebellum. Golgi's method. (After Szymonowicz.) originate ; the axis cylinder comes off from the base of the pyramid. (See figs. 209, 210). The grey matter of the cerebellum contains a large number of small nerve-cells, and one layer of large cells. These are flask-shaped, and are called the cells of Purkinje. The neck of the flask breaks up into branches, and the axis cylinder process comes off from the base of the flask (fig. 211). The whole nervous system consists of nerve-cells and their branches, supported by neuroglia in the central nervous system, and by connective tissue in the nerves. Some of the processes of a nerve-cell break up almost immediately into smaller branches ending in arborescences of fine twigs ; these branches, which used to be 198 NERVE-CENTRES [CH. XVII. called protoplasmic processes, are now termed denclrons. One branch becomes the long axis cylinder of a nerve-fibre, but it also ultimately terminates in an arborisation ; it is called the axis cylinder process, or, more briefly, the axon. The term neuron or neurone is applied to the complete nerve-unit, that is, the body of the cell, and all its branches. Some observers have supposed that the axis cylinder pro- cess is the only one that conducts nerve impulses, the denclrons being rootlets which suck up nutriment for the nerve-cell. This view has not, however, been accepted ; the dendrons may be nutri- tive, but there is no doubt that they also, like the rest of the nerve- unit, are concerned in the conduction of nerve impulses. A strong piece of evidence in this direction is the fact that the fibrils of the axis cylinder may be traced through the body of the cell into the dendrons. The next idea which it is necessary to grasp is, that each nerve-unit (cell plus branches of both kinds) is anatomically independent of every other nerve-unit. There is no true anasto- mosis of the branches from one nerve-cell with those of another; the arborisations interlace and intermingle, and nerve impulses are transmitted from one nerve- unit to another, through contiguous, but not through continuous structures. A intermingling of arborisations is Fig. 212.— Reflex action. convenient expression for the synapse (literally, a clasping). Fig. 212 is a diagram of the nervous path in a reflex action. Excitation occurs at S, the skin or other sensory surface, and the impulse is transmitted by the sensory nerve-fibre to the nerve- centre, where it ends not in a cell-body, but by arborising around one or more cell-bodies and their dendrons. The only cell-body in actual continuity with the sensory nerve-fibre is the one in the spinal ganglion (G) from which it grew. The terminal arborisation of the sensory nerve-fibre merely inter- laces with the dendrons of the motor nerve-cell ; yet simply by this synapse, the motor nerve-cell (M C) is affected and sends an impulse by its axis cylinder process to the muscle (M). A very rough illustration which may help one in realising this CH. XVII.] THE NEURON THEOEY 199 s.c. may be taken as follows : Suppose two trees standing side by side ; their stems will represent the axis cylinders; their branches the dendrons. If the trees are close together the branches of one will intermingle with those of the other : there is no actual branch from the one which becomes continuous with any branch of the other; but yet if the stem of one is vigorously shaken, the close intermixture of the branches will affect the other so that it also moves. Another very important general idea which we must next get hold of, is that a nervous impulse does not necessarily travel along the same nerve-fibre all the way, but there is what we may term a system of relays. The nervous system is very often compared to a telegraphic system throughout a country. The telegraph offices represent the nerve-centres, the afferent nerve-fibres correspond to the wires that carry the messages to the central offices, and the efferent nerve-fibres are represented by the wires that convey messages from the central offices to more or less distant parts of the country. This illustration will serve us very well for our present purpose, provided that it is always re- membered that a nervous impulse is not elec- tricity. Suppose, now, one wishes to send a message from the metropolis, which will repre- sent the brain, to a distant house, say in the Highlands of Scotland. There is no wire straight from London to that house, but the message ultimately reaches the house; one wire takes the message to Edinburgh ; another wire carries it on to the telegraph station in the town nearest to the house in question ; and the last part of the journey is accomplished by a mes- senger on foot or horseback. There are at least two relays on the journey. It is just the same with the nervous system. Suppose one wishes to move the arm ; the im- pulse starts in the nerve-cells of the brain, but there are no fibres that go straight from the brain to the muscles of the arm. The impulse travels down the spinal cord, by what are called pyramidal fibres, which form synapses with the nerve-cells of the spinal cord, and r|M Fig. 213. — Diagram of an ele- ment of the motor path. U.S., upper segment ; L.S., lower segment ; C.C., cell of cerebral cor- tex; S.C, cell of spinal cord, in anterior cornu ; M., the muscle ; S., path from sensory nerve-roots. (After Gowers.) 200 NERVE-CENTRES [CH. XVII. from these cells, fresh nerve-fibres pass to the arm-muscles, and continue the impulse. This is shown in the accompanying diagram (fig. 213). The cell of the cerebral grey matter is represented by C. C, the pyramidal nerve-fibre arborises around the cell of the spinal cord (S. C.) from which the motor nerve-fibre arises, and which carries on the impulse. The spinal cord cells are thus surrounded by arborisations (synapses) derived not only from the sensory nerves (S), but by fibres from the upper part of the nervous system. We now see how it is possible that reflex actions in the cord may be controlled by impulses from the brain. The system of relays is still more complicated in the case of sensory impulses, as we shall see later on ; the same is true for the motor path to involuntary muscle, accessory cell-stations being situated in the sympathetic ganglia. We may now return for a moment to the subject of degeneration. If the nerve-fibre is cut off from its connection with the spinal nerve- cell, the peripheral end degenerates as far as the muscle. Suppose, now, the pyramidal fibre were cut across, the piece still attached to the brain-cell would remain in a comparatively normal condition, but the peripheral end would degenerate as far as the synapse round the spinal cell (S. C), but not beyond. We can thus use the degeneration method to trace out tracts of nerve-fibres in the white matter of the central nervous system. The histological change in the fibres is here the same as that already described in the nerves, except that, as there is no primitive sheath, there can be no multiplication of its nuclei ; there is instead an over-growth of neuroglia. Degenerated tracts consequently stain differently from healthy white matter, and can be by this means easily traced. Another method of research which leads to the same results as the degeneration method is called the embryological method. The nerve-fibres which grow from different groups of nerve-cells become fully developed at different dates, and so, by examining brains and cords of embryos of different ages, one is able to make out individual tracts before they have blended in the general mass of white matter. We shall, however, return to this subject when later on we are studying the physiology of the central nervous system in detail. The Significance of Nissl's Granules. If portions of the brain or spinal cord are fixed in absolute alcohol, and sections obtained from the hardened pieces are stained by means of methylene blue, the nerve-cells exhibit a characteristic appearance. The nucleus and nucleolus take up the blue stain, and throughout the cell body a number of angular-shaped masses, which are termed Nissl's granules, are also stained blue. These extend some distance CH. XVII.] nissl's granules 201 into the dendrons, but not into the axon. The substance of which they are composed is termed chromatoplasm, or chromophilic material. The existence of granules in cells which have an affinity for basic dyes like methylene blue is not at all common ; the granules in the majority of the white blood corpuscles, for instance, have an affinity for acid dyes. Micro -chemical methods have shown that the main constituent of the Mssl granules is nucleo-proteid. The name kineto- plasm has been given to it by Marinesco in order to express the idea that it forms a source of energy to the cell. It can hardly be denied that the substance of which the granules are composed, forming as it does so large a proportion of the cell-contents, and made of a material in which nuclein forms an important constituent, is intimately related to the nutritional condition of the neuron. Some have even compared it to the granular material, which is present in secreting cells ; in these cells before secretion occurs, the granules accumulate, and during the act of secretion they are discharged and converted into constituents of the secretion. It is stated by some observers that the Mssl granules are used up during the discharge of energy from nerve-cells, and it certainly is the case that if the cells are examined after an epileptic fit, in which there has been a very massive discharge of impulses, the Mssl granules have disappeared, or at least broken up into fine dust-like particles, so that the cell presents a more uniform blue staining (see fig. 214). It is, however, doubt- ful whether this is due to a transformation associated with intense activity, or whether it may not be caused by venosity of the blood. The cells are very sensitive to altered vascular conditions ; ansemia, for instance, produces a similar change accompanied with swelling of the cell, and swelling and in extreme cases extrusion of the nucleus. High fever (hyperpyrexia) causes a very similar change, which is doubtless associated with the coagulation of the proteids of the cell- protoplasm by the high temperature. Since attention has been directed towards the Mssl granules, a literature which has become alarmingly vast during the last few years has sprung up in relation to them. This is quite easy to understand, for neurologists have by this sensitive test been able to identify changes in the cells which could not be detected by the previous methods of staining. Thus the cells have been examined in various diseases, and after being subjected to the action of various poisons. In a new subject of this kind there is, as would be expected, consider- able divergence of views, and even the fundamental question has not yet been answered satisfactorily whether the Mssl granules are present as such in the living cell, or whether they are artifacts produced by the fixative action of strong alcohol. The fact that they cannot be demonstrated when the cells are stained by the injection of methylene blue into the circulation before the animal is killed is a very strong 202 NERVE-CENTRES [CII. XVII. piece of evidence in favour of the latter view. But, whichever view is correct, the method is a valuable one, and Nissl's views on this question appear to be indisputable : they are briefly as follows : — Healthy cells fixed and stained in a constant manner will appear the same under constant optical conditions, and the appearances then seen form the equivalent of such healthy cells during life. It follows that if the cells prepared by the same method and examined under the same conditions show a difference from the equivalent or symbol of healthy cells, the difference is the measure of some change that has occurred during life. Chromatolysis is the term applied to designate the disappearance FlG. 214. — Nissl's granules. A. Normal pyramidal cell of liuman cerebral cortex. B. Swollen cede- matous pyramidal cell from a case of status epilepticus. Notice diffuse staining, and absence of Nissl's granules ; the nucleus is enlarged and eccentric. The lymph space around the cell is dilated. C. Pyramidal cell of dog after ligature of vessels going to brain and consequent ansemia. Notice great swelling of the nucleus, and advanced chromatolysis, most marked at the periphery of the cell. 700 diameters. (After Mott.) or disintegration of the Nissl granules. The process generally begins at the periphery of the cell and in the dendrons, but in advanced cases the whole cell may be affected. We have already alluded to the fact that chromatolysis occurs in various abnormal states, and the diminu- tion of the chromophilic nucleo-proteid indicates a diminution of the vital interaction of the highly phosphorised nucleus with the sur- rounding cell protoplasm. Chromatolysis alone is not indicative of cell destruction, and a cell may recover its function afterwards. The integrity of the nucleus and of the fibrils is much more important to the actual vitality of the cell. When a nerve-fibre is cut across, the distal segment undergoes Wallerian degeneration ; this is an acute change. But the nerve-cell CH. XVII.] CLASSIFICATION OF NERVE-CELLS 203 and the piece of the nerve-fibre still attached to it do not remain un- affected. If regeneration of the fibre, and restoration of function takes place, no change is observable. But if regeneration does not occur (and it never takes place in the central nervous system), the cell and its processes undergo a slow chronic wasting ; one of the earliest signs of this disuse atrophy is chrornatolysis. Warrington has recently stated a still more interesting fact, namely, that section of the posterior roots causes chrornatolysis in the anterior horn cells of the same side ; this indicates that the loss of sensory stimuli pro- duces a depression of the activity and metabolic functions of the spinal motor cells. We shall see later on that this accords quite well with the physiological effects observed under these conditions. Classification of Nerve-cells according to their Function. In addition to the anatomical classification of the nerve-cells already given, Schafer separates them into four chief classes on a physiological basis : — 1. Afferent or sensory root cells. 2. Efferent root cells. 3. Intermediary cells. 4. Distributing cells. 1. Afferent root cells. — Originally such cells are situated at the periphery, and are connected with a process or afferent fibre which passes to and arborises among the nerve-cells of the central nervous system. This primitive condition is well seen in the earthworm, and persists in the olfactory cells of all vertebrates. As evolution progresses, the peripheral cell sinks below the in- tegument, leaving a process at the surface ; this is seen in the worm Nereis (see fig. 215). Ultimately the body of the cell approaches close to the central nervous system, in the spinal ganglion of the posterior root, and the peripheral sensory nerve-fibre is correspond- ingly longer. The afferent root cells, such as those of the spinal ganglia and the corresponding ganglia of the cranial nerves, are peculiar in possessing no dendrons. 2. Efferent root cells. — The anterior horn cells of the spinal cord are instances of these ; their axons go directly to muscle fibres. 3. Intermediary cells. — These receive impulses from afferent cells, and transmit them either directly, or indirectly through other intermediary cells to efferent cells. The majority of the cells of the brain and cord come under this heading ; they serve the purposes of association and co-ordination, and form the basis of psychical phenomena. 4. Distributing cells. — These are the cells of the sympathetic 204 NERVE-CENTRES [CII. XVII. ganglia ; they are situated outside the central nervous system ; they receive impulses from efferent cells in the central nervous system, and distribute them to involuntary muscles and secreting glands. Earth -worm Nereis Vertebrate Fio. 215. — Diagram to illustrate the primitive conditions of the atferent nerve-cell, and the manner in which it becomes altered in the process of evolution. (After Retzius.) I, integument; C, central nervous system ; the arrows show the direction in which the impulse passes. The Law of Axipetal Conduction. A general law has been laid down by van Gehuchten and Cajal, that all nerve impulses are axipetal, that is, they pass towards the attachment of the axon, by which they leave the body of the cell. In other words, the direction of an impulse is towards the body of the cell in the dendrons, and away from it in the axon. When we further consider that every nervous pathway is formed of a chain of cells, and that the impulse always takes the " forward direction," we see that there is what we may compare to a valved action which permits the passage of impulses in one direction only. The synapses are the situations of these so-called valves. On the onward propagation of a nerve impulse through a chain of neurons, its passage is delayed at each synapse, hence there is additional " lost time " at each of these blocks. The relative number of the blocks furnishes a key to the differences found in reaction time for different reflexes and psychical processes. This we may illustrate by two examples, one taken from the frog, the other from man. 1. If a frog's posterior root is stimulated, the time lost in the spinal cord when the gastrocnemius of the same side contracts is 0"008 sec. ; if the opposite gastrocnemius contracts, the additional CH. XVII.] AXIPETAL CONDUCTION 205 lost time is 0*004 sec. If we assume that in the latter case, two extra synapses have to be jumped, the delay at each is 0'002 sec. 2. In the case of the eye and ear in man the total length of the pathway to the brain is approximately the same, and so the reaction times might be expected to be equal ; but this is not the case ; the reaction time in response to a sudden sound is 0150 sec, in response to a sudden flash of light 0195 sec. The greater delay in response to a visual stimulus directly corresponds to the greater number of synapses through which it has to travel (see later, in the structure of the visual and auditory mechanisms). The valved condition of nervous paths also explains another difficulty. We have seen in p. 173 that under certain circumstances a nervous impulse will travel in both directions along a nerve. Yet when we stimulate the motor fibres in an anterior spinal root, the only effect is a contraction of muscles ; there is no effect propagated backwards in the spinal cord. No doubt a nervous impulse does travel backwards to the anterior horn cells, but it is there extin- guished, it cannot jump the synapses backwards, and there is no negative variation to be detected in a galvanometer connected to the pyramidal tracts in the cord. The law of axipetal conduction is no doubt true for the majority of neurons. But there is at any rate one very striking exception, namely, in the typical afferent root cells ; here the impulse passes to the body of the cell by one axon from the periphery, and away from it to the spinal cord by the other. To say, as some do, that the peripheral process is really a dendron because it conducts impulses centrifugally is simply arguing in a circle. CHAPTER XVIII THE CIRCULATORY SYSTEM The circulatory system consists of the heart, the arteries, or vessels that carry the blood from the heart to other parts of the body, the veins, or vessels that carry the blood back to the heart again, and the capillaries, a network of minute tubes which connect the terminations of the smallest arteries to the commencements of the smallest veins. We shall also have to consider in connection with the circulatory system, (1) the lymphatics, which are vessels that convey back the lymph (the fluid which exudes through the thin walls of the blood- capillaries) to the large veins near to their entrance into the heart, and (2) the large lymph spaces contained in the serous membranes. The Heart. This is the great central pump of the circulatory system. It lies in the chest between the right and left lungs (fig. 216), and is enclosed in a covering called the pericardium. The pericardium is an instance of a serous membrane. Like all serous membranes it consists of two layers ; each consists of fibrous tissue containing elastic fibres ; one layer envelopes the heart and forms its outer covering or epicardium ; this is the visceral layer of the pericardium ; the other layer of the pericardium, called its parietal layer, is situ- ated at some little distance from the heart, being attached below to the diaphragm, the partition between the thorax and the abdomen. The visceral and parietal layers are continuous for a short distance along the great vessels at the base of the heart, and so form a closed sac. This sac is lined by endothelium ; in health it contains just enough lymph (pericardial fluid) to lubricate the two surfaces and enable them to glide over each other smoothly during the move- ments of the heart. The presence of elastic fibres in the epicardium enables it to follow without hindrance the changing shape of the heart itself ; but the parietal layer of the pericardium appears to be inextensible, and so it limits the dilatation of the heart. The pericardium is a comparatively simple serous membrane, because the organ it encloses is a single one of simple external form. All serous membranes 206 CH. XVIII.] THE HEART 207 Larynx are of similar structure ; thus the pleura which encloses the lung, and the peritoneum which encloses the abdominal viscera differ from it only in anatomical arrangement. The great complexity of the peritoneum is due to its enclosing so many organs. Every serous membrane consists of a visceral layer applied to the organ or organs it encloses ; and a parietal layer continuous with this in contiguity with the parietes or body-walls. The Chambers of the Heart. — The interior of the heart is divided by a longitudinal partition into two chief cavities — right and left. Each of these chambers is again subdivided transversely into an upper and a lower portion, called respectively, auricle and ventricle, which freely communicate one with the other ; the aperture of com- munication, however, is guarded by valves, so disposed as to allow blood to pass freely from the auricle into the ven- tricle, but not in the oppo- site direction. There are thus four cavities in the heart — the auricle and ven- tricle of one side being quite separate from those of the other (figs. 217, 218). The right auricle is situ- ated at the right part of the base of the heart in front. It is a thin walled cavity of quadrilateral shape, pro- longed at one corner into a tongue-shaped portion, the right auricular appendix, which slightly overlaps the exit of the aorta, from the heart. The interior is smooth, being lined with the general lining of the heart, the endocardium, and into it open the superior and inferior venae cavse, or great veins, which convey the blood from all parts of the body to the heart. The opening of the inferior cava is protected and partly covered by a membrane called the Eustachian valve. In the posterior wall of the auricle is a slight depression called the fossa ovalis, which corre- sponds to an opening between the right and left auricles which exists in foetal life. The coronary sinus, or the dilated portion of the left coronary vein, also opens into this chamber. The right ventricle occupies the chief part of the anterior surface of the heart, as well as a small part of the posterior surface ; it forms the right margin of the heart. It takes no part in the formation of the apex. On section its cavity, in consequence of the encroachment Diaphragm. Pig. 216.— View of heart and lungs in situ. The front portion of the chest-wall and the outer or parietal layers of the pleurae and pericardium have been re- moved. The lungs are partly collapsed. 208 THE CIKCULATOKY SYSTEM [CII. XV I II. upon it of the septum ventriculorum, is crescentic (fig. 219); into it are two openings, the auriculo-ventricular at the base and the opening of the pulmonary artery also at the base, but more to the left ; both orifices are guarded by valves, the former called tricuspid and the Fio. 217.— The right auricle and ventricle opened, and a part of their right and anterior walls removed, so as to show their interior. J.— 1, superior vena cava; 2, inferior vena cava; 2', hepatic veins cut short ; 3, right auricle ; 3', placed in the fossa ovalis, below which is the Eustachian valve ; 3", is placed close to the aperture Of the coronary vein ; + +, placed in the auriculo-ventricular groove, where a narrow portion of the adjacent walls of the auricle and ventricle has been preserved ; 4, 4, cavity of the right ventricle, the upper figure is immediately below the semilunar valves ; 4', large columna carnea or musculus papillaris; 5, 5', 5", tricuspid valve ; (>, placed in the interior of the pulmonary artery, a pari of the anterior wall of that vessel having been removed, and a narrow portion of it preserved at its commencement, where the semilunar valves are attached ; 7, concavity of the aortic arch close to the cord of the ductus arteriosus ; 8, ascending part or sinus of the arch covered at its commencement by the auricular appendix and pulmonary artery ; 9, placed between the innominate and left carotid arteries ; 10, appendix of the left auricle ; 11, 11, the outside of the left ventricle, the lower figure near the apex. (Allen Thomson.) latter semilunar. In this ventricle are also the projections of the muscular tissue called columnar carnece (described at length, p. 212). The left auricle is situated at the left and posterior part of the base of the heart, and is best seen from behind. It is quadrilateral, and receives on either side two pulmonary veins. The auricular CH. XVIII.] THE HEAET 209 appendix is the only part of the auricle seen from the front, and corresponds with that on the right side, but is thicker, and the Fig. 218. — The left auricle and ventricle opened and a part of their anterior and left walls removed. &. — The pulmonary artery has been divided at its commencement; the opening into the left ventricle is carried a short distance into the aorta between two of the segments of the semilunar valves ; and the left part of the auricle with its appendix has been removed. The right auricle is out of view. 1, the two right pulmonary veins cut short ; their openings are seen within the auricle ; 1', placed within the cavity of the auricle on the left side of the septum and on the part which forms the remains of the valve of the foramen ovale, of which the crescentic fold is seen towards the left hand of 1' ; 2, a narrow portion of the wall of the auricle and ventricle preserved round the auriculo- ventricular orifice ; 3, 3', the cut surface of the walls of the ventricle, seen to become very much thinner towards 3", at the apex ; 4, a small part of the anterior wall of the left ventricle which has been preserved with the principal anterior columna carnea or musculus papillaris attached to it ; 5, 5, musculi papillares ; 5', the left side of the septum, between the two ventricles, within the cavity of the left ventricle ; G, &, the mitral valve ; 7, placed in the interior of the aorta, near its commencement and above the three segments of its semilunar valve which are hanging loosely together; 7', the exterior of the great aortic sinus; 8, the root of the pulmonary artery and its semilunar valves ; 8', the separated portion of the pulmonary artery remaining attached to the aorta by 9, the cord of the ductus arteriosus ; 10, the arteries rising from the summit of the aortic arch. (Allen Thomson.) interior is smoother. The left auricle is only slightly thicker than The left auriculo-ventricular orifice is oval, and a little O the right. 210 THE CIRCULATORY SYSTEM [CH. XVI11. smaller than that on the right side. There is a depression on the septum between the auricles, which is a vestige of the foramen between them, that exists in foetal life. The left ventricle occupies the chief part of the posterior surface. In it are two openings very close together, viz., the auriculo-ventri- cular and the aortic, guarded by the valves corresponding to those of the right side of the heart, viz., the bicuspid or mitral and the semi- lunar. The first opening is at the left and back part of the base of the ventricle, and the aortic in front and towards the right. In this ventricle, as in the right, are the columnae carneoe, which are smaller but more closely reticulated. They are chiefly found near the apex and along the posterior wall. The walls of the left ventricle, which are nearly half an inch in thickness, are, with the exception of the apex, about three times as thick as those of the right. Capacity of the Chambers. — During life each ventricle is capable of containing about three ounces of blood. The capacity of Cavity of right ventricle. Cavity uf left ventricle. Fig. 219. — Transverse section of bullock's heart in a state of cadaveric rigidity. (Dalton.) the auricles is rather less than that of the ventricles : the thick- ness of their walls is considerably less. The latter condition is adapted to the small amount of force which the auricles require in order to empty themselves into their adjoining ventricles ; the former to the circumstance of the ventricles being partly filled with blood before the auricles contract. Size and Weight of the Heart. — The heart is about 5 inches long (about 126 cm.), oh inches (8 cm.) greatest width, and 2| inches (6'3 cm.) in its extreme thickness. The average weight of the heart in the adult is from 9 to 10 ounces (about 300 grms.) ; its weight gradually increases throughout life till middle age ; it diminishes in old age. Structure. — The walls of the heart are constructed almost entirely of layers of muscular fibres (figs. 113 and 220); but a ring of connective tissue, to which some of the muscular fibres are attached, is inserted between each auricle and ventricle, and forms the boundary of the auriculo-ventricular opening. Fibrous tissue also exists at the origins of the pulmonary artery and aorta. CH. XVIII.] THE HEART 211 The muscular fibres of each auricle are in part continuous with those of the other, and partly separate ; and the same remark holds true for the ventricles. Some muscular fibres also pass across Fig. 220. — Network of muscular fibres from the heart of a pig. The nuclei are well shown, x 450. (Klein and Noble Smith.) the tendinous ring which separates each auricle from the correspond- ing ventricle. Endocardium. — As the heart is clothed on the outside by the epicarcliuin, so its cavities are lined by a smooth membrane, the endocardium, which is directly continuous with the internal lining of the arteries and veins. The endocardium is composed of connective tissue with a large admixture of elastic fibres ; its inner surface is covered by endothelium. Here and there muscular fibres are sometimes found in the tissue of the endocardium. Valves. ■ — The arrange- ment of the heart's valves is such that the blood can pass only in one direction (fig. 221). The tricuspid valve (5, fig. 217) presents three principal cusps or subdivisions, and the mitral or bicuspid valve has two such portions (6, fig. 218). But in both valves there is between each two principal portions a smaller one : so that more properly, the tricuspid may be described as consisting of six, and the mitral of four, portions. Each portion is of triangular form. Its base is continuous with the bases of the neighbouring portions, so as to form an annular membrane Fig. 221.— Diagram of the circulation through the heart. (Dalton.) 212 THE CIRCULATORY SYSTEM [CH. XVIII. around the auriculo-ventricular opening, and is fixed to a tendinous ring which encircles the orifice between the auricle and ventricle, and receives the insertions of the muscular fibres of both. In each principal cusp may be distinguished a central part, extending from base to apex, and including about half its width. It is thicker and much tougher than the border pieces or edges. While the bases of the cusps of the valves are fixed to the tendinous rings, their ventricular surface and borders are fastened by slender ten- dinous fibres, the chordce tendinece, to the internal surface of the walls of the ventricles, the muscular fibres of which project into the ventricular cavity in the form of bundles or columns — the columnar carnece. These columns are not all alike, for while some are attached along their whole length on one side, and by their extremities, others are attached only by their extremities ; and a third set, to which the name musculi papillares has been given, are attached to the wall of the ventricle by one extremity only, the other projecting, papilla- like, into the cavity of the ventricle (5, fig. 218), and having attached to it chordae tendinete. Of the tendinous cords, besides those which pass to the margins of the valves, there are some of especial strength, which pass to the edges of the middle and thicker portions of the cusps before referred to. The ends of these cords are spread out in the substance of the valve, giving its middle piece its peculiar strength and toughness ; and from the sides numerous other more slender and branching cords are given off, which are attached all over the ventricular surface of the adjacent border-pieces of the principal portions of the valves, as well as to those smaller portions which have been mentioned as lying one between each two principal ones. Moreover, the musculi papillares are so placed that, from the summit of each, tendinous cords proceed to the adjacent halves of two of the principal divisions, and to one intermediate or smaller division, of the valve. The preceding description applies equally to the mitral and tricuspid valve ; but it should be added that the mitral is considerably thicker and stronger than the tricuspid, in accordance with the greater force which it is called upon to resist. The semilunar valves guard the orifices of the pulmonary artery and of the aorta. They are nearly alike on both sides of the heart ; but the aortic valves are altogether thicker and more strongly con- structed than the pulmonary valves, in accordance with the greater pressure which they have to withstand. Each valve consists of three parts which are of semilunar shape, the convex margin of each being attached to a fibrous ring at the place of junction of the artery to the ventricle, and the concave or nearly straight border being free, so as to form a little pouch like a watch-pocket (7, fig. 218). In the centre of the free edge of the pouch, which contains a fine curd CH. XVIII.] COURSE OF THE CIRCULATION 213 of fibrous tissue, is a small fibrous nodule, the corpus Arantii, and from this and from the attached border fine fibres extend into every part of the mid substance of the valve, except a small lunated space just within the free edge, on each side of the corpus Arantii. Here the valve is thinnest, and composed of little more than the endo- cardium. Thus constructed and attached, the three semilunar pouches are placed side by side around the arterial orifice of each ventricle; they are separated by the blood passing out of the ventricle, but immediately afterwards are pressed together so as to Pulmonary capillaries. Pulmonary artery. Superior cava or vein from head and neck. Bight auricle. Inferior vena cava- Right ventricle. Portal circulation. Second renal circu- lation. Pulmonary veins. Aorta. Arteries to head and neck. Left ventricle. Gastric and intestinal vessels. First renal circulation. Systemic capillaries. Fig. 222. — Diagram of the circulation. prevent any return (6, fig. 217, and 7, fig. 218). Opposite each of the semilunar cusps, both in the aorta and pulmonary artery, there is a bulging outwards of the wall of the vessel : these bulgings are called the sinuses of Valsalva. The valves of the heart are formed of a layer of closely woven connective and elastic tissue, over which, on every part, the endocardium is reflected. Course of the Circulation. The blood is conveyed away from the left ventricle (as in the diagram, fig. 222) by the aorta to the arteries, and returned to the 214 THE CIRCULATORY SYSTEM [on. xviii, ei™ light auricle by the veins, the arteries and veins being continuous with each other at the far end by means of the capillaries. From the right auricle the blood passes to the right ventricle, then by the pulmonary artery, which divides into two, one for each lung, then through the pulmonary capillaries, and through the pulmonary veins (two from each lung) to the left auricle. From here it passes into the left ventricle, which brings us back to where we started from. The complete circulation is thus made up of two circuits, the one, a shorter circuit from the right side of the heart to the lungs and back again to the left side of the heart ; the other and larger circuit, from the left side of the heart to all parts of the body and back again to the right side. The circulations through the lungs and through the system generally are respectively named the Pulmonary and Systemic or lesser and greater circulations. It will be noticed also in the same figure that a portion of the stream of blood having been diverted once into the capillaries of the intestinal canal, and some other abdominal organs, and gathered up again into a single stream, is a second time divided in its passage through the liver, before it finally reaches the heart and completes a revolution. This sub- ordinate stream through the liver is called the Portal circulation. A somewhat similar accessory circulation is that through the kidneys, called the Renal circulation. The difference of colours in fig. 222 indicates roughly the difference between arterial and venous blood. The blood is oxygen- ated in the lungs, and the formation of oxy- hemoglobin gives to the blood a bright red colour. This oxygenated or arterial blood (contained in the pulmonary veins, the left side of the heart, and systemic arteries) is in part reduced in the tissues, and the deoxygenated haemoglobin is darker in tint than the oxyhemoglobin ; this venous blood passes by the systemic veins to the right side of the heart and pulmonary artery to the lungs, where it once more receives a fresh supply of oxygen. N. B. — It should, however, be noted that the lungs, like the rest of the body, are also supplied with arterial blood, which reaches them by the bronchial arteries. Fig. 223. — Minute artery viewed in longitudinal section, e. Nucleated endothelial membrane, with faint nuclei in lumen, looked at from above, i. Elastic mem- brane, m. Muscular coat or tunica media. a. Tunica adventitia. (Klein and Noble Smith.) x 250. The Arteries. The arterial system begins at the left ventricle in a single large trunk, the aorta, which almost immediately after its origin gives off ch. xvii r.] THE ARTERIES 215 xfS^ in the thorax three large branches for the supply of the head, neck, and upper extremities; it then traverses the thorax and abdomen, giving off branches, some large and some small, for the supply of the various organs and tissues it passes on its way. In the abdomen it divides into two chief branches, for the supply of the lower ex- tremities. The arterial branches wherever given off divide and sub- divide, until the calibre of each subdivision becomes very minute, and these minute vessels lead into capillaries. Arteries are, as a rule, placed in situations protected from pressure and other dangers, and are, with few exceptions, straight in their course, and frequently communicate (anastomose or inos- culate) with other arteries. The branches are usually given off at an acute angle, and the sum of the sec- tional areas of the branches of an artery generally exceeds that of the parent trunk ; and as the distance from the origin is increased, the area of the combined branches is increased also. After death, arteries are usually found dilated (not collapsed as the veins are) and empty, and it was to this fact that their name (apr^pla, the windpipe) was given them, as the ancients believed that they conveyed air to the various parts of the body. As regards the arterial system of the lungs, the pulmonary artery is dis- tributed much as the arteries belong- ing to the general systemic circulation. Structure. — The wall of an artery is composed of the following three coats : — (a) The external coat or tunica adventitia (figs. 223 and 224, a), the strongest part of the wall of the artery, is formed of areolar tissue, with which is mingled throughout a network of elastic fibres. At the inner part of this outer coat the elastic network forms, in some arteries, so distinct a layer as to be sometimes called the external elastic coat (fig. 224, e). (b) The middle coat (fig. 224, ra) is composed of both muscular and elastic fibres, with a certain proportion of areolar tissue. In the larger arteries (fig. 226) its thickness is comparatively as well as absolutely much greater than in the small ones ; it constitutes the greater part of the arterial wall. The muscular fibres are unstriped (fig. 225), and are arranged for the most part transversely to the Fig. 224. — Transverse section through a large branch of the inferior mesenteric artery of a pig. e, endothelial mem- brane ; i, tunica elastica interna, no subendothelial layer is seen ; m, mus- cular tunica media, containing only a few wavy elastic fibres ; e, e, tunica elastica externa, dividing the media from the connective-tissue adventitia, a. (Klein and Noble Smith.) x 350. 216 THE CIRCULATORY SYSTEM [CH. XVIII. long axis of the artery ; while the elastic element, taking also a trans- verse direction, is disposed in the form of closely interwoven and branching fibres, which intersect in all parts the layers of muscular fibres. In arteries of various sizes there is a difference in the pro- portion of the muscular and elastic element, elastic tissue prepon- derating in the largest arteries, and unstriped muscle in those of medium and small size. (c) The internal coat is formed by a layer of elastic tissue, called the fenestrated membrane of Henle. Its inner surface is lined with a delicate layer of elongated endothelial cells (fig. 224, e), which make it smooth, so that the blood may flow with the smallest possible amount of resistance from friction. Imme- diately external to the endothelial lining of the artery is fine connective tissue (sub -endothelial layer) with branched cor- puscles. Thus the internal coat consists of three parts, (a) an endothelial lining, (b) the sub-endothelial layer, and (c) elastic layer. Vasa Vasorum. — The walls of the arteries are, like other parts of the body, supplied with little arteries, ending in capillaries and veins, which, branching throughout the external coat, extend for some distance into the middle, but do not reach the internal coat. These nutrient vessels are called vasa vasorum. Nerves. — Most of the arteries are sur- rounded by a plexus of sympathetic nerves, which twine around the vessel very much They terminate in a plexus between the Fig. 225. — Muscular fibre-cells from human arteries, magni- fied 350 diameters. (Kolliker.) o. Nucleus, b. A fibre-cell treated with acetic acid. like ivy round a tree, muscular fibres (fig. 227). The Veins. The venous system begins in small vessels which are slightly larger than the capillaries from which they spring. These vessels are gathered up into larger and larger trunks until they terminate (as regards the systemic circulation) in the two vena? cavse and the coronary veins, which enter the right auricle, and (as regards the pulmonary circulation) in four pulmonary veins, which enter the left auricle. The total capacity of the veins diminishes as they approach the heart ; but, as a rule, their capacity is two or three times that of their corresponding arteries. The pulmonary veins, however, are an exception to this rule, as they do not exceed in capacity the pulmonary arteries. The veins are found after death more or less CH. XVIII.] THE VEINS 217 collapsed, owing to their want of elasticity. They are usually dis- tributed in a superficial and a deep set which communicate fre- quently in their course. Structure. — In structure the coats of veins bear a general resemblance to those of arteries (fig. 228). Thus, they possess outer, middle, and internal coats. (a) The outer coat is constructed of areolar tissue like that of the arteries, but it is thicker. In some veins it contains muscular fibres, which are arranged longitudinally. ' : m$ €7- ^8 Endothelium. Sub-endothelial layer. Elastic intima. Fig. 226. — Transverse section of aorta through internal and about half the middle coat. (b) The middle coat is considerably thinner than that of the arteries ; it contains circular unstriped muscular fibres, mingled with a few elastic fibres and a large proportion of white fibrous tissue. In the large veins, near the heart, namely, the vence cavce and pul- monary veins, the middle coat is replaced, for some distance from the heart, by circularly arranged striped muscular fibres, continuous with those of the auricles. The veins of bones, and of the central nervous system and its membranes have no muscular tissue. (c) The internal coat of veins has a very thin fenestrated membrane, which may be absent in the smaller veins. The 218 tup: circulatory system [cir. xviii. endothelium is made up of cells elongated in the direction of the vessel, but wider than in the arteries. Valves. — The chief influence which the veins have in the circu- lation is effected with the help of the valves, contained in all veins subject to local pressure from the muscles between or near which they run. The general construction of these valves is similar to that of the semilunar valves of the aorta and pulmonary artery, already described ; but their free margins are turned in the opposite direction, i.e., towards the heart, so as to prevent any movement of blood back- ward. They are commonly placed in pairs, at various distances in different veins, but almost uniformly in each (fig. 229). In the smaller veins single valves are often met with; and three or four are sometimes placed to- gether, or near one another, in the largest veins, such as the subclavian, at their junction with the jugular veins. The valves are semilunar; the unattached edge is in some examples con- cave, in others straight. They are composed of an outgrowth of the subendothelial tissue covered with endothelium. Their situa- tion in the superficial veins of the forearm is readily discovered by pressing along their surface, in the direction opposite to the venous current, i.e., from the elbow towards the wrist; when little swellings (fig. 229, c) appear in the position of each pair of valves. These swellings at once disappear when the pressure is removed. Valves are not equally numerous in all veins, and in many they are absent altogether. They are most numerous in the veins of the extremities, and more so in those of the leg than the arm. They are commonly absent in veins of less than a line in diameter, and, as a general rule, there are few or none in those which are not subject to muscular pressure. Among those veins which have no valves may be mentioned the superior and inferior vena cava, the pulmonary veins, the veins in the interior of the cranium and vertebral column, the veins of bone, and the umbilical vein. The valves of the portal tributaries are very inefficient. Lymphatics of Arteries and Veins. — Lymphatic spaces are present Fig. 'J-7.— Ramification of nerves and termination in the muscular coat of a small artery of the frog. (Arnold.) cir. xviii. j THE CAPILLARIES 219 in the coats of both arteries and veins. In the external coat of large vessels they form a plexus of more or less tubular vessels. In smaller vessels they appear as spaces lined by endothelium. Sometimes, as in the arteries of the omentum, mesentery, and membranes of the brain, in the pulmonary, hepatic, and splenic arteries, the spaces are con- tinuous with vessels which distinctly ensheath them — perivascular lym- phatics (fig. 231). The Capillaries. In all vascular textures except some parts of the corpora cavernosa of the penis, of the uterine placenta, and of the spleen, the transmission of the blood from the minute branches of the arteries to the minute veins is affected through a network of capil- laries. Their walls are composed of endo- thelium — a single layer of elongated flattened and nucleated cells, so joined and dovetailed together as to form a continuous transparent membrane (fig. 232). Here and there the endo- thelial cells do not fit quite accu- rately; the space is filled up with cement material ; these spots are called pseudo-stomata. The diameter of the capillary vessels varies somewhat in the different tissues of the body, the most common size being about .j^oo th of an inch (12 /u). Among the smallest may be mentioned those of the brain, and of the fol- licles of the mucous membrane of Fig. 228. — Transverse section through a small artery and vein of the mucous membrane of a child's epiglottis ; the artery is thick-walled and the vein thin- walled, a. Artery, the letter is placed in the lumen of the vessel, e. Endo- thelial cells with nuclei clearly visible ; these cells appear very thick from the contracted state of the vessel. Outside it a double wavy line marks the elastic layer of the tunica intima. m. Tunica media, consisting of unstriped muscular fibres circularly arranged ; their nuclei are well seen. a. Part of the tunica adventitia showing bundles of connec- tive-tissue fibre in section, with the circular nuclei of the .connective-tissue corpuscles. This coat gradually merges into the surrounding connective tissue, v. In the lumen of the vein. The other letters indicate the same as in the artery. The muscular coat of the vein (m) is seen to be much thinner than that of the artery, x 350. (Klein and Noble Smith.) the intestines ; among the largest, those of the skin, lungs, and especially those of the medulla of bones. The size of capillaries varies necessarily in different animals in relation to the size of their blood corpuscles : thus, in the Proteus, the capillary circulation can just be discerned with the naked eye. The form of the capillary network presents considerable variety 220 THE CIRCULATORY SYSTEM [CH. XVIII. in the different tissues of the body: the varieties consist principally of modifications of two chief kinds of mesh, the rounded and the elongated. That kind in which the meshes or interspaces have a V PlO. 229. — Diagram showing valves of veins, a, part of a vein laid open and spread out, with two pairs of valves, b, longitudinal section of a vein, showing the apposition of the edges of the valves in their closed state, c, portion of a distended vein, exhibiting a swelling in the situation of a pair of valves. roundish or polygonal form is the most common, and prevails in those parts in which the capillary network is most dense, such as the lungs (fig. 233), most glands and mucous (membranes, and the Tic. 2S0. — a, vein with valves open. B, with valves closed ; stream of blood passing off by lateral channel. (Dalton.) cutis. The capillary network with elongated meshes is observed in parts in which the vessels are arranged among bundles of fine tubes or fibres, as in muscles and nerves. In such parts, the meshes form parallelograms (fig. 234), the short sides of which may be from three CII. XVIII.] LYMPHATIC VESSELS 221 to eight or ten times less than the long ones ; the long sides are more or less parallel to the long axis of the fibres. The number of the capillaries and the size of the meshes in different parts determine in general the degree of vascularity of those parts. The capillary network is closest in the lungs and in the choroid coat of the eye. It may be held as a general rule, that the more active the functions of an organ are, the more vascular it is. Hence the narrowness of the interspaces in all glandular organs, in mucous Fig. 231. — Surface view of an artery from the mesentery of a frog, ensheathed in a perivascular lym- phatic vessel, a, the artery, with its circular muscular coat (media) indicated by broad transverse markings, with an indication of the adventitia outside. I, lymphatic vessel ; its wall is a simple endothelial membrane. (Klein and Noble Smith.) membranes, and in growing parts, and their much greater width in bones, ligaments, and other comparatively inactive tissues. Lymphatic Vessels. The blood leaves the heart by the arteries ; it returns to the heart by the veins ; but this last statement requires modification, for in the capillaries some of the blood-plasma escapes into the cell spaces of the tissues and nourishes the tissue-elements. This fluid, which is called lymph, is gathered up and carried back again into the blood by a system of vessels called lymphatics. 222 THE CIRCULATORY SYSTEM [ClI. XVIII. The principal vessels of the lymphatic system are, in structure, like small thin-walled veins, provided with numerous valves. The beaded appearance of the lymphatic vessels shown in figs. 23G and Fig. '232. — Capillary blood-vessels from the omentum of rabbit, showing the nucleated endothelial membrane of which they are composed. (Klein and Noble Smith.) 237 is due to the presence of these valves. They commence in fine microscopic lymph-capillaries, in the organs and tissues of the body, and they end in two trunks which open into the large veins near the FlG. 233. — Network of capillary vessels of the air-cells of the horse's lung magnified, a, a, capillaries proceeding from 6, 6, terminal branches of the pulmonary artery. (Fivy.) . 234. — Injected capil- lary vessels of muscle seen with a low mag- nifying power. (Sharpey.) heart (fig. 235). The fluid which they contain, unlike the blood, passes only in one direction, namely, from the fine branches to the trunk, and so to the large veins, on entering which it is mingled with the stream of blood. In fig. 235 the greater part of the contents of CH. XVIII.] THE THORACIC DUCT 223 the lymphatic system of vessels will be seen to pass through a com- paratively large trunk called the thoracic duct, which finally empties its contents into the blood-stream, at the junction of the internal jugular and subclavian veins of the left side. There is a smaller duct on the right side. The lymphatic vessels of the intestinal canal are called lacteals, because during digestion (especially of a meal con- taining fat) the fluid contained in them resembles milk in appear- Lymphatics of head and neck, right. Right internal jugular vein. Right subclavian vein. Lymphatics of right arm . Receptaculum chyli. Lymphatics of lower ex- tremities. Lymphatics of head an 1 neck, left. Thoracic duct. Left subclavian vein. Thoracic duct. Lymphatics of lower ex- tremities. Fig. 235.— -Diagram of the principal groups of lymphatic vessels. (From Quain.) ance ; and the lymph in the lacteals during the period of digestion is called chyle. Chyle is lymph containing finely divided fat-globules. In some parts of its course the lymph-stream passes through lym- phatic glands, to be described later on. Origin of Lymph Capillaries. — The lymphatic capillaries com- mence most commonly either (a) in closely-meshed networks, or (h) in irregular lacunar spaces between the various structures of which the different organs are composed. In serous membranes, such as the 224 THE CIRCULATORY SYSTEM [CII. XVI II. mesentery, they occur as a connected system of very irregular branched spaces partly occupied by connective-tissue corpuscles, and Fin. "230. — Lymphatic vessels of the head and neck and the upper part of the trunk (Mascagni). J. — The chest and pericardium have been opened on the left side, and the left mamma detached and thrown outwards over the left arm, so as to expose a great part of its deep surface. The principal lymphatic vessels and glands are shown on the side of the head and face and in the neck, axilla, and medi- astinum. Between the left internal jugular vein and the common carotid artery, the upper ascending part of the thoracic duct marked 1, and above this, and descending to 2, the arch and last part of the duct. The termination of the upper lymphatics of the diaphragm in the medias- tinal glands, as well as the cardiac and the deep mammary lymphatics, is also shown. Fig. 'J37. — Superficial lymphatics of the forearm and palm of the hand. >.— 5. Two small glands at the bend of the arm. 0. Radial lymphatic vessels. 7. Ulnar lymphatic vessels. 8, 8'. Palmar arch of lymphatics. 9, 9'. Outer and inner sets of vessels. b. Cephalic vein. d. Radial vein. e. Median vein. /. Ulnar vein. The lymphatics are re- presented as lying on the deep fascia. (Mascagni.) in these and other varieties of connective tissue, the cell spaces com- municate freely with regular lymphatic vessels. In many cases, CH. XVIII.] LYMPHATIC CAPILLAEIES 225 though they are formed mostly by the chinks and crannies between the parts which may happen to form the framework of the organ in which they exist, they are lined by a distinct layer of endothelium. The lacteals offer an illustration of another mode of origin, namely, as blind dilated extremities in the villi of the small intestine (see fig. 38, p. 27). Structure of Lymph Capillaries. — The structure of lymphatic capillaries is very similar to that of blood capillaries; their walls consist of a single layer of elongated endothelial cells with sinuous outline, which cohere along their edges to form a delicate membrane. Fig. 23S.— Lymphatics of central tendon of rabbit's diaphragm, stained with silver nitrate. The shaded background is composed of bundles of white fibres, between which the lymphatics lie. I, Lymphatics lined by long narrow endothelial cells, and showing v valves at frequent intervals. (Schofield.) They differ from blood capillaries mainly in their larger and very variable calibre, and in their numerous communications with the spaces of the lymph-canalicular system. In certain parts of the body, stomata exist, by which lymphatic capillaries directly communicate with parts formerly supposed to be closed cavities. They have been found in the pleura, and in other serous membranes ; a serous cavity thus forms a large lymph-sinus or widening out of the lymph-capillary system with which it directly communicates. A very typical plexus of lymphatic capillaries is seen in the central tendon of the diaphragm. Fig. 238 represents the appearance presented after staining with silver nitrate. CHAPTER XIX THE CIRCULATION OF THE BLOOD We have now to approach the physiological side of the subject, and study the means by which the blood is kept in movement, so that it may convey nutriment to all parts, and remove from those parts the waste products of their activity. Previous to the time of Harvey, the vaguest notions prevailed regarding the use and movements of the blood. The arteries were supposed by some to contain air, by others to contain a more subtle essence called animal spirits; the animal spirits were supposed to start from the ventricles of the brain, and they were controlled by the soul which was situated in the pineal gland. How the animal spirits got into the arteries was an anatomical detail which was bridged across by the imagination. There was an idea that the blood moved, but this was considered to be a haphazard, to-and-fro movement, and confined to the veins. The proofs that the movement is in a circle were discovered by William Harvey, and to this eminent discoverer also belongs the credit of pointing out the methods by which every physiological problem must be studied. In the first place there must be correct anatomical knowledge, and in the second there must be experiment, by which deductions from structure can be tested ; moreover, this second method is by far the more important of the two. Harvey's proofs of the circulation came under both these heads. The structural or anatomical facts upon which he relied were the following : — 1. The existence of two distinct sets of tubes in connection with the heart, namely, the arteries and the veins. 2. The existence in the heart and also in the veins, of valves which would only allow the passage of the blood in one direction. His experimental facts were the following: — 3. That the blood spurts with great force and in a jerky manner from an artery opened during life, each jerk corresponding with a beat of the heart. ch. xix.] Harvey's work 227 4. That if the large veins near the heart are tied, the heart becomes pale, flaccid, and bloodless, and on removal of the ligature the blood again flows into the heart. ' 5. If the aorta is tied, the heart becomes distended with blood, and cannot empty itself until the ligature is removed. 6. The preceding experiments were performed on animals, but by the following experiment he showed that the circulation is a fact in man also ; if a ligature is drawn tightly round a limb, no blood can enter it, and it becomes pale and cold. If the ligature is somewhat relaxed so that blood can enter but cannot leave the limb, it becomes swollen. If the ligature is removed, the limb soon regains its normal appearance. 7. Harvey also drew attention to the fact that there is general constitutional disturbance resulting from the introduction of a poison at a single point, and that this can only be explained by a movement of the circulating fluid all over the body. Since Harvey's time many other proofs have accumulated; for instance : — 8. If an artery is wounded, hemorrhage may be stopped by pressure applied between the heart and the wound ; but in the case of a wound in a vein, the pressure must be applied beyond the seat of injury. 9. If a substance which, like ferrocyanide of potassium, can be readily detected, is injected at a certain point into a blood-vessel, it will after the lapse of a short interval have entirely traversed the circulation and be found in the blood collected from the same point. 10. Perhaps the most satisfactory proof of the circulation is one now within the reach of every student, though beyond that of Harvey. It consists in actually seeing the passage of the blood from small arteries through capillaries into veins in the transparent parts of animals, such as the tail of a tadpole or the web of a frog's foot. Harvey could not follow this part of the circulation, for he had no lenses sufficiently powerful to enable him to see it. Harvey's idea of the circulation here was that the arteries carried the blood to the tissues, which he considered to be of the nature of a sponge, and the veins collected the blood again, much in the same way as drainage pipes would collect the water of a swamp. The discovery that the ends of the arteries are connected to the commencements of veins by a definite system of small tubes we now call capillaries, was made by Malpighi, in the year 1661. He first observed them in the tail of the tadpole, and Leeuwenhoek, seven years later, saw the circulation in the lung of the frog. "We can now proceed to study some of the principles on which the circulation depends : — The simplest possible way in which we could represent the 228 THE CIRCULATION OF THE BLOOD [CH. XIX. circulatory system is shown in fig. 239 A. Here there is a closed ring containing fluid, and upon one point of the tube is an enlarge- ment (H) which will correspond to the heart. It is obvious that if such a ring made of an ordinary Higginson's syringe and a tube were placed upon the table, there would be no movement of the fluid in it ; in order to make the fluid move there must be a difference of pressure between different parts of the fluid, and this difference of pressure is caused in the fluid by the pressure on it of the heart walls. If, for instance, one takes the syringe in one's hand and squeezes it, one imitates a contraction of the heart : if the syringe has no valves, the fluid would pass out of each end of it in the direction of the two arrows placed outside the ring. When the pressure on the syringe is relaxed (this would correspond to the interval between the heart beats), the fluid would return into the heart again in the direction of the two arrows placed inside the ring. Fig. 239. — Simple schema of the circulation. This, however, would be merely a to-and-fro movement, not a circula- tion. Fig. 239 B shows how this to-and-fro movement could, by the presence of valves, be converted into a circulation ; when the heart contracts the fluid could pass only in the direction of the outer arrow; when the heart relaxes it could pass only in the direction of the inner arrow; the direction of both arrows is the same, and so if the contraction and relaxation of the heart are repeated often enough the fluid will move round and round within the tubular ring. The main factor in the circulation is difference of pressure. In general terms fluid flows from where the pressure is high to where it is lower. This difference of pressure is produced in the first instance by the contraction of the heart, but we shall find in our study of the vessels that some of this pressure is stored up in the elastic arterial walls, and keeps up the circulation during the periods that the heart is resting. Coming to different groups in the animal kingdom we may take the crayfish or the lobster as instances of animals which possess a CH. XIX.] THE HEART OF WORM, FISH, AND FROG 229 hsemolymph system, that is, there is no distinction between blood and lymph. The heart pumps the circulating fluid along a system of vessels which distribute it over the body ; there are no capillaries, and the hsemolymph is discharged into the tissue spaces ; it is thence drained into channels which convey it to the gills, and after it is aerated there in a set of irregular vessels, it is returned to the peri- cardium. It is sucked from the pericardium into the heart during diastole, through five small orifices in the cardiac wall; during systole these are closed by valves. In these animals the rate of flow of hsemolymph is necessarily slow. In worms, the circulatory system is almost as simple as in the schema just described ; the heart is a long contractile tube provided with valves, which contracts peri- staltically and presses the blood forwards into the aorta at its an- terior end ; this divides into arteries for the supply of the body; the blood passes through these to capil- laries, and is collected by veins which converge to one or two main trunks that enter the heart at its posterior end. In fishes, the into a number of in single file, one other ; the most receives the heart is divided chambers placed in front of the posterior which veins is called the Fig. 240.— The heart of a frog (Rana esculeula) from the front. V, ventricle ; Ad, right auricle; A s, left auricle ; B, bulbus arteri- osus, dividing into right and left aort*. (Bcker.) sinus venosus ; this contracts and forces the blood into the next chamber, called the auricle ; this forces the blood into the next cavity, that of the ventricle, and last of all is the aortic bulb. From the bulb, branches pass to the gills, where they break up into capillaries, and the blood is aerated : it then once more enters larger vessels which unite to form the dorsal aorta, whence the blood is distributed by arteries to all parts of the body; here it enters the systemic capillaries, then the veins which enter the sinus (whence we started) by a few large trunks. Taking the frog as an instance of an amphibian, we find the heart more complex, and the simple peristaltic action of the heart muscle as we have described it in the hearts of worm and fish, becomes correspondingly modified. There is only one ventricle, but there are two auricles, ria;ht and left. 230 THE CIRCULATION OF THE BLOOD [CH. XIX. Aj>. c.s.d A.d. The ventricle contains mixed blood, since it receives arterial Mood from the left auricle (which is the smaller of the two), and venous blood from the right auricle ; the right auricle receives the venous blood from the sinus, which in turn receives it from the systemic veins. The left auricle, as in man, receives the blood from the pulmon- ary veins. When the ventricle con- tracts, it forces the blood onward into the aortic bulb which divides into branches on each side for the supply of the head (fig. 240, 1), lungs and skin (fig. 240, 3), and the third branch (fig. 240, 2), unites with its fellow of the opposite side to form the dorsal aorta for the supply of the rest of the body. Passing from the amphi- bians to the reptiles, we find the division of the ventricle into two beginning, but it is not complete till we reach the birds. The heart reaches its fullest development in mammals, and we have already described the human as an example of the mammalian heart. The sinus venosus is not present as a distinct chamber in the mammalian heart, but is represented by that portion of the riirht auricle at which the lanje veins enter. Fio. 241.— The heart of a frog (Rana esculenta) from the back, s.v., sinus venosus opened ; c.s.s., left vena cava superior; c.s.d., right vena cava superior; c.i., vena cava inferior; v.p., vena pulmonalis ; A.d., right auricle ; A.s., left auricle ; A.p., opening of communi- cation between the right auricle and the sinus venosus. x2J— 3. (Ecker.) CHAPTEE XX PHYSIOLOGY OF THE HEAET The Cardiac Cycle. The series of changes that occur in the heart constitutes the cardiac cycle. This must be distinguished from the course of the circulation. The term cycle indicates that if one observes the heart at any particular moment, the heart from that moment onwards undergoes certain changes until it once more assumes the same condition that it had at the moment when the observation commenced, when the cycle is again repeated, and so on. This series of changes consists of alternate contraction and relaxation. Contraction is known as systole, and relaxation as diastole. The contraction of the two auricles takes place simultaneously, and constitutes the auricular systole ; this is followed by the simul- taneous contraction of the two ventricles, ventricular systole, and that by a period during which the whole of the heart is in a state of relaxation or diastole; then the cycle again commences with the auricular systole. Taking 72 as the average number of heart beats per minute, each cycle will occupy ^ of a minute, or a little more than 0'8 of a second. This may be approximately distributed in the following way :— Auricular systole . about 0"1 + Auricular diastole . 0*7 = 0*8 Ventricular systole . ,, 0*3 + Ventricular diastole . - 5 = - 8 Total systole . . ,, -4 + Joint diastole . . 0-4 = 0'8 If the speed of the heart is quickened, the time occupied by each cycle is diminished, but the diminution affects chiefly the diastole. These different parts of the cycle must next be studied in detail. The Auricular Diastole. — During this time, the blood from the large veins is flowing into the auricles, the pressure iu the veins though very low being greater than that in the empty auricles. The blood expands the auricles, and during the last part of the auricular 231 232 PHYSIOLOGY OF THE HEART [CH. XX. diastole it passes on into the ventricles. The dilatation of the auricles is assisted by the elastic traction of the lungs. The lungs being in a closed cavity, the thorax, and being distended with air, are in virtue of their elasticity always tending to recoil and squeeze the air out of their interior ; in so doing they drag upon any other organ with which their surface is in contact: this elastic traction will be greatest when the lungs are most distended, that is during inspiration, and will be more felt by the thin-walled auricles than by the thick-walled ventricles of the heart. The Auricular Systole is sudden and very rapid ; by contracting, the auricles empty themselves into the ventricles. The contraction commences at the entrance of the great veins, and is thence pro- pagated towards the auriculo-ventricular opening. The reason why the blood does not pass backwards into the veins, but onward into the ventricles, is again a question of pressure ; the pressure in the relaxed ventricles, which is so small as to exert a suction action on the auricular blood, is less than in the veins. Moreover, the auriculo-ventricular orifice is large and widely dilated, whereas the mouths of the veins are constricted by the contraction of their muscular coats. Though there is no regurgitation of the blood backwards into the veins, there is a stagnation of the flow of blood onwards to the auricles. The veins have no valves at their entrance into the auricles, except the coronary vein which does possess a valve ; there are valves, however, at the junction of the subclavian and internal jugular veins. Ventricular Diastole ; during the last part of the auricular diastole and the whole of the auricular systole, the ventricles have been relaxed and then filled with blood. The dilatation of the ventricles is chiefly brought about in virtue of their elasticity ; this is particu- larly evident in the left ventricle with its thick muscular coat. It is equal to 23 mm. of mercury, and is quite independent of the elastic traction of the lungs, which, however, in the case of the thinner-walled right ventricle comes into play. The Ventricular Systole ; this is the contraction of the ventricles, and it occupies more time than the auricular systole; when it occurs the auriculo-ventricular valves are closed and prevent re- gurgitation into the auricles, and when the force of the systole is greatest, and the pressure within the ventricles exceeds that in the large arteries which originate from them, the semilunar valves are opened, and the ventricles empty themselves, the left into the aorta, the right into the pulmonary artery. Each ventricle ejects about 3 ounces of blood with each contraction ; the left in virtue of its thicker walls acts much more forcibly than the right. The greater force of the left ventricle is necessary, as it has to overcome the resistance of the small vessels all over the body ; whereas the right CH. XX.] THE VALVES OF THE HEART 233 ventricle has only to overcome peripheral resistance in the pulmonary district. The shape of both ventricles during systole has been described as under- going an alteration, the diameters in the plane of the base being diminished, and the length of the ventricles slightly lessened. The whole heart, moreover, moves towards the right and forwards, twisting on its long axis and exposing more of the left ventricle anteriorly than when it is at rest. These movements, which were first described by Harvey, have been since Harvey's time believed to be the cause of the cardiac impulse or apex beat which is to be felt in the fifth intercostal space about three inches from the middle line. It has, however, been shown by Haycraft that these changes only occur when the chest walls are open. When the heart contracts in a closed thorax it undergoes no rotation, and the contraction is concentric, that is, equal in all directions. The diminution of the heart's volume which occurs in systole cannot be the cause of the apex beat ; it would rather tend to draw the chest wall inwards than push it outwards. The apex beat is caused by two changes in the physical condition of the heart. In the first place, on systole the heart becomes hard and tense, and secondly, its attachment to the aorta becomes rigid instead of being flexible as it is in diastole. Thus, in systole, the heart becomes rigidly fixed to the aorta, and, as this vessel is curved, it tends to open out into a straight line, but is prevented by the counter- resistance at the two ends of the arch. These are (a) the resistance of the chest wall against the heart, and (J>) that of the vertebrae and ribs against the thoracic aorta. The pressure of the heart against the chest wall is confined to a small area, situated in the fifth intercostal space, because the heart surface is much more curved than the internal thoracic wall. The forward movement this pressure causes is the apex beat. It must be noted that this movement is not over the actual apex of the heart, but is communicated from an area on the anterior cardiac surface. Action of the Valves of the Heart. 1. The Auriculo- Ventricular. — The distension of the ventricles with blood continues throughout the whole period of their diastole. The auriculo-ventricular valves are gradually brought into place by some of the blood getting behind the cusps and floating them up ; by the time that the diastole is complete, the valves are in appo- sition, and they are firmly closed by the reflux current caused by the systole of the ventricles. The diminution in the size of the auriculo-ventricular rings which occur during systole, renders the auriculo-ventricular valves competent to close these openings. The margins of the cusps of the valves are still more secured in apposition with one another, by the simultaneous contraction of the musculi papillares, whose chordae tendinese have a special mode of attachment for this object. The cusps of the auriculo-ventricular valves meet not by their edges only, but by the opposed surfaces of their thin outer borders. The musculi papillares prevent the auriculo-ventricular valves from being everted into the auricle. For the chordae tendineae might allow the valves to be pressed back into the auricle, were it not that when the wall of the ventricle is brought by its contraction nearer the auriculo-ventricular orifice, the musculi papillares more than compensate for this by their own contraction; they hold the cords 234 PHYSIOLOGY OF THE HEART [CII. XX. tight, and, by pulling down the valves, add slightly to the force with which the blood is expelled. These statements apply equally to the auriculo-ventricular valves on both sides of the heart ; the closure of both is generally complete every time the ventricles contract. But in some circumstances the tricuspid valve does not completely close, and a certain quantity of blood is forced back into the auricle. This has been called its safety- valve action. The circumstances in winch it usually happens are those in which the vessels of the lung are already completely full when the right ventricle contracts, as, e.g., in certain pulmonary diseases, and in very active muscular exertion. In these cases, the tricuspid valve does not completely close, and the regurgitation of the blood may be indicated by a pulsation in the jugular veins synchronous with that in the carotid arteries. 2. The Semilunar Valves. — The commencement of the ventricular systole precedes the opening of the aortic valves by a fraction of a second, as is proved by examining records of the intraventricular and aortic pressure curves taken simultaneously. The first result of the contraction of the ventricles is the closure of the auriculo-ventricular valves, and as soon as this has been effected the intraventricular pressure begins to rise. It quickly reaches a point at which it equals the aortic pressure, and then exceeds it, and as soon as this pressure difference has been established the aortic valves are opened and blood flows from the ventricle into the aorta. The valves are kept open as long as the intra-ventricular pressure exceeds the aortic, but as soon as the heart has emptied itself, the ventricle begins to relax, its internal pressure consequently begins to fall, and an instant is quickly reached at which it is exceeded by the aortic. The blood, therefore, tends to flow back from the aorta, and in so doing fills up the pockets of the semilunar valves, which have always remained partly filled, and brings them together with a sharp movement. The movements of the valves are therefore effected by the occurrence of differences of pressure upon their two faces. When they meet they completely close the orifice, because their inner edges, which are thinner than the rest of the valves, are brought into apposition and held so by the high pressure acting on their aortic surfaces only. The Sounds of the Heart. When the ear is placed over the region of the heart, two sounds may be heard at every beat of the heart, which follow in quick succession, and are succeeded by a pause or period of silence. The first or systolic sound is dull and prolonged ; its commencement coincides with the impulse of the heart against the chest wall, and just precedes the pulse at the wrist. The second or diastolic sound CH. XX.] THE HEAET SOUNDS 235 is shorter and sharper, with a somewhat flapping character, and follows close after the arterial pulse. The periods of time occupied respectively by the two sounds taken together and by the pause, are nearly equal. Thus, according to Walshe, if the cardiac cycle be divided into tenths, the first sound occupies -j^-; the second sound, ■j^- ; the first pause (almost imperceptible), -^ ; and the second pause, -j^-. The sounds are often but somewhat inaptly compared to the syllables, liibb — dilp. The events which correspond, in point of time, with the first sound, are (1) the contraction of the ventricles, (2) the first part of the dilatation of the auricles, (3) the tension of the auriculo-ventricular valves, (4) the opening of the semilunar valves, and (5) the propul- sion of blood into the arteries. The sound is succeeded, in about one-thirtieth of a second, by the pulsation of the facial arteries, and in about one-sixth of a second, by the pulsation of the arteries at the wrist. The second sound, in point of time, immediately follows the cessation of the ventricular contraction, and corresponds with (a) the tension of the semilunar valves, (b) the con- tinued dilatation of the auricles, (c) the commencing dilatation of the ventricles, and (d) the opening of the auriculo-ventri- cular valves. The pause imme- diately follows the second sound, and corresponds in its first part with the completed distension of the auricles, and in its second with their contraction, and the com- pleted distension of the ventricles ; the auriculo-ventricular valves are open, and the arterial valves closed during the whole of the pause. Causes. — The exact cause of the first sound of the heart is a matter of discussion. Two factors probably enter into it, viz., first, the vibration of the auriculo-ventricular valves and the chorda? tendineos. This vibration is produced by the increased intraventricular pressure set up when the ventricular systole commences, which puts the valves on the stretch. It is not unlikely, too, that the vibration of the ventricular walls themselves, and of the aorta and pulmonary artery, all of which parts are suddenly put into a state of tension at the moment of ventricular contraction, may have some part in Fig. 242. — Scheme of cardiac cycle. The inner circle shows the events which occur within the heart; the outer the relation of the sounds and pauses to these events. (Sharper and Gairdner.) 236 PHYSIOLOGY OF THE HEART [CH. XX. producing the first sound. Secondly, the muscular sound produced by contraction of the mass of muscular fibres which forms the ventricle. Looking upon the contraction of the heart as a single contraction and not as a series of contractions or tetanus, it is at first sight difficult to see why there should be any muscular sound at all when the heart contracts, as a single muscular contraction does not produce sound. It has been suggested, however, that it arises from the repeated unequal tension produced when the wave of muscular contraction passes along the very intricately arranged fibres of the ventricular walls. Many regard the valvular element is the more important of the two factors, because the sound is loudest at first, when the vibration of the valves commences, and fades away as the vibrations cease. If the sound was mainly muscular, it would be loudest when the muscular contraction was most powerful, which is approximately about the middle of the ventricular systole. The facts of disease lend support to the theory that the first sound is mainly valvular ; for when the valves are incompetent, the first sound is largely replaced by a murmur due to regurgitation of blood into the auricle. After the removal of the heart from the body, the muscular contribution to the first sound is audible, but it is very faint. It is stated to have a somewhat lower pitch than the valvular sound. There is, on the other hand, much to be said against the view that the cause of the first sound is entirely or even largely due to vibration of the auriculo-ventricular valves. Any sound produced by the valves must be very quickly damped by the high pressure acting on their ventricular surfaces only. The sustained character of the sound (throughout practically the whole of the ventricular systole) is on the other hand exactly what is to be expected if it is of muscular origin. The argument that the extent to which the muscle sound contributes to the production of the first sound can be judged from the sound heard in an isolated and empty heart is quite fallacious, since under these conditions the muscle is contract- ing against no resistance. The cause of the second sound is more simple than that of the first. It is entirely due to the vibration consequent on the sudden stretching of the semilunar valves when they are pressed down across the orifices of the aorta and pulmonary artery. The influence of these valves in producing the sound was first demonstrated by Hope, who experimented with the hearts of calves. In these experiments two delicate curved needles were inserted, one into the aorta, and another into the pulmonary artery, below the line of attachment of the semilunar valves, and, after being carried upwards about half an inch, were brought out again through the coats of the respective vessels, so that in each vessel one valve was included between the CH. XX.] THE COEONAEY AETERIES 237 arterial walls and the wire. Upon applying the stethoscope to the vessels, after such an operation, the second sound ceased to be audible. Disease of these valves, when sufficient to interfere with their efficient action, also demonstrates the same fact by modifying the second sound or destroying its distinctness. The contraction of the auricles is inaudible. The first sound is heard most distinctly at the apex beat in the fifth interspace ; the second sound is best heard over the second right costal cartilage — that is, the place where the aorta lies nearest to the surface. The pulmonary and aortic valves generally close simul- taneously. In some cases, however, the aortic may close slightly before the pulmonary valves, giving rise to a " reduplicated second sound." The pulmonary contribution to this sound is best heard over the second left cartilage. The Coronary Arteries. The coronary arteries are the first branches of the aorta; they originate from the sinuses of Valsalva, and are destined for the supply of the heart itself ; the entrance of the coronary vein, into the right auricle, we have already seen (p. 207). Ligature of the coronary arteries causes almost immediate death; the heart, deprived of its normal blood-supply, beats irregu- larly, goes into fibrillary twitchings, and then ceases to contract altogether. In fatty degeneration of the heart in man, sudden death is by no means infrequent. This is in many cases due to a growth in thickness of the walls of the coronary arteries called atheroma, which progresses until the lumen of these arteries is obliterated, and the man dies almost as if they had been ligatured. Self-steering Action of the Heart. — This expression was originated by Briicke. He supposed that the semilunar valves closed the orifices of the coronary arteries during the systole of the heart. Unlike all the other arteries of the body, the coronary arteries would therefore fill only during diastole, and this increased fulness of the vessels in the heart walls during diastole would assist the ventricle to dilate. This, however, is incorrect ; the valves do not cover the mouths of the arteries ; and at the beginning of systole the velocity and pressure in the coronary arteries increase ; but later on during systole the ventricular wall is so strongly contracted that the muscular tension becomes greater than the coronary pressure, and so the coronary arteries and their branches are compressed, and the blood driven back into the aorta ; the coronary arteries are then again filled with the commencing diastole. Self-steering action of the heart therefore exists, but it is brought about in a different way from what Briicke supposed. Cardiographs. A cardiograph is an instrument for obtaining a graphic record of the heart's movements. In animals the heart may be exposed, 238 PHYSIOLOGY OF THE HEART [CII. XX. and levers placed in connection with its various parts may be employed to write on a revolving blackened surface. A simple instrument for the frog's heart is the following : — \F j ^T Fig. 243. — Simple Cardiograph for frog's heart. The sternum of the frog having been removed, the pericardium opened, and the frsenum (a small band from the back of the heart to the pericardium) divided, the heart is pulled through the opening, a minute hook placed in its apex, and this is fixed by a silk thread to a lever pivoted at F as in the figure. The cardiac wave of contrac- tion starts at the sinus, this is followed by the auricular systole, and that by the ventricular systole and pause. This is recorded as in the next figure (fig. 244) 1 > v movements of the writing point at the end of the long arm of the lever. Such apparatus is, however, not applicable to the human heart, and all the various forms of cardiograph devised for this pur- pose are modifications of Marey's tambours. One of those most frequently used is depicted in the next two diagrams. It (fig. 245) consists of a cup-shaped metal box over the open front of which is stretched an elastic india-rubber membrane, upon which is fixed a small knob of hard wood or ivory. This knob, however, may be attached, as in the figure, to the side of the box by means of a spring, and may be made to act upon a metal disc attached to the elastic membrane. The knob is for application to the chest-wall over the apex beat. The box or tambour communicates by means of an air-tight tube with the interior of a second tambour, in connection with which is a long and light lever. The shock of the heart's impulse being communicated to the ivory knob and through it to the first tambour, the effect is at once transmitted by the column of air in the elastic tube to the interior of the second tambour, also closed, and through the elastic and movable lid of the latter to the lever, which is placed in connection with a register- ing apparatus, which consists of a cylinder covered with smoked paper, revolving with a definite velocity. The point of the lever writes upon the paper, and a tracing of the heart's impulse or cardiogram is thus obtained. Fir;. 244.— Cardiogram of frog's heart, c, showing auricular followed by ventricular beat t, time in half seconds. CII. XX.] CARDIOGRAPHS 239 Fig. 247 represents a typical tracing obtained in this way. The Tube to communicate with tambour. Tambour. Ivory Tape to attach the instru- knob. ment to the chest. Fig. 245.— Cardiograph. (Sanderson's.) first small rise of the lever is caused by the auricular, the second Screw to regulate elevation of lever. Writing lever. Tambour. Tube of cardiograph. Fig. 246.— Marey's Tambour, to which the movement of the column of air in the first tambour is con- ducted by a tube, and from which it is communicated by the lever to a revolving cylinder, so that the tracing of the movement of the impulse beat is obtained. larger rise by the ventricular systole ; the downstroke represents the Fig. 247. — Cardiogram from human heart. The variations in the individual beats are due to the influence of the respiratory movements on the heart. To be read from left to right. 240 PHYSIOLOGY OF THE HEART [CH. XX. pause, the tremors at the commencement of which are partly instru- mental and partly caused by the closure of the semilunar valves. Another method of obtaining a tracing from one's own heart consists in dispensing with the first tambour, and placing the tube of the recording tambour in one's mouth, and holding the breath though keeping the glottis open. The chest then acts as the first tambour, and the movements of the lever (cardio-pneumatogram) may be written in the usual way. Intracardiac Pressure. The tracings of the cardiograph are, however, very variable, and their interpretation is a matter of discussion. A much better method of obtaining a graphic record of the events^of the cardiac cycle con- sists in connecting the interior of an animal's heart with recording Fig. 24S.— Apparatus of MM. Chauveau and Marey for estimating the variations of endocardial pressure, and the production of the impulse of the heart. apparatus. There are several methods by which the intracardiac pressure may be recorded. By placing two small indiarubber air-bags or cardiac sounds clown the jugular vein into the interior respectively of the right auricle and the right ventricle, and a third in an intercostal space in front of the heart of a living animal (horse), and placing these bags, by means of long narrow tubes, in communication with three tambours with levers, arranged one over the others in connection with a registering apparatus (fig. 248), Chauveau and Marey were able to record and measure the variations of the intracardiac pressure and the compara- tive duration of the contractions of the auricles and ventricles. By means of the same apparatus, the synchronism of the impulse with the contraction of the ventricles is also shown. In the tracing (fig. 249), the intervals between the vertical lines represent periods of a tenth of a second. The parts on which any CH. XX.] INTRACARDIAC PRESSURE 241 given vertical line falls represent simultaneous events. It will be seen that the contraction of the auricle, indicated by the marked curve at a in the first tracing, causes a slight increase of pressure in the ventricle, which is shown at a' in the second tracing, and produces also a slight impulse, which is indicated by a" in the third tracing. The closure of the semilunar valves causes a momentarily increased pressure in the ventricle at d', affects the pressure in the auricle D, and is also shown in the tracing of the impulse, d".* The large curve of the ventricular and the impulse tracings, between a' and d', and a" and d", are caused by the ventricular con- traction, while the smaller undulations, between B and c, b' and c', b" and g", are caused by the vibrations consequent on the tightening and closure of the auriculo-ventricular valves. Much objection has, however, been taken to this method of investigation. First, because it does not admit of both positive and negative pressure being recorded. Secondly, because the method is only applicable to large animals, such as the horse. Thirdly, because the intraventricular changes of pressure are communicated to the recording tambour by a long elastic column of air; and fourthly, because the tambour arrangement has a ten- dency to record inertia vibrations. Eolleston re-investigated the subject with a more suitable but rather com- plicated apparatus. The principle of the method consisted in placing the cavity of a heart-chamber in communication with a recording apparatus by means of a tube containing saline solution. His recording apparatus consisted of a lever connected to a piston ; the upward and downward movements of the piston-rod were due to the varying pressures exerted on the blood by the contraction and dilatation of the heart; the rise and fall of the lever were controlled by the resistance to torsion of a steel ribbon to which it was attached. The following figure (fig. 250) shows the kind of tracing he obtained. He found: — 1. That there is no distinct and separate auricular contraction marked in the curves obtained from either right or left ventricles, * There can be no doubt that the point d which Marey considered to coincide with the closure of the semilunar valves does not really do so. The closure occurs much earlier (e in fig. 252). Q Fig. 249. — Tracings of (1), Intra-auricular, and (2), Intra-ventricular pressure, and (3), of the impulse of the heart ; to be read from left to right ; ob- tained by Chauveau and Marey's apparatus. 242 PHYSIOLOGY OF THE HEART [CH. XX. the auricular and Yentricular rises of pressure being merged into one continuous rise. 2. That the auriculo-Yentricular valves are closed before any great rise of intraventricular pressure above that which results from the auricular systole occurs {a, fig. 250). The closure of this valve does not produce any notch or wave. 3. That the semilunar valves open at the point in the ventricular Fig. 250. -Curve from left ventricle obtained by Rolleston's apparatus ; the abscissa shows atmospheric pressure. systole, situated (at c) about or a little above the junction of the middle and upper third of the ascending line (a b), and the closure about the shoulder (d). 4. That the minimum pressure in the ventricle may fall below that of the atmosphere, but that the amount varies considerably. Another method of overcoming the imperfections of Marey's tam- bour is by the use of Hiirthle's manometer (fig. 244). In this the tam- bour is very small, the membrane is made of thick rubber, and the V : Fig. 251. — Hiirthle's Manometer. whole, including the tube that connects it to the heart, is filled with a strong saline solution (saturated solution of sodium sulphate). The tracing obtained by this instrument, when connected with the interior of the ventricle, is represented in the next figure. The auricular systole causes a small rise of pressure a b ; it lasts about '05 second. It is immediately followed by the ventricular con- traction, which lasts from B to D. From b to c the ventricle is getting up pressure, so that at c it equals the aortic pressure. This takes '02 to '04 second. Just beyond c the aortic valves open, and blood is driven into the aorta ; the outflow lasts from c to D ('2 CH. XX.] INTRACARDIAC PRESSURE 243 second). At d the ventricle relaxes. The flat part of the curve is spoken of as the systolic plateau, and according to the state of the heart and the peripheral resistance may present a gradual ascent or descent ; it occupies about "18 second. Almost immediately after the D Fig. 252.— Curve of intraventricular pressure. (After Hurthle.) relaxation begins the intraventricular pressure falls below the aortic, so that the aortic valves close near the upper part of the descent at E. The amount of pressure in the heart is measured by a manometer, which is connected to the heart by a tube containing a valve. This was first used by Goltz and Gaule. If the valve permits fluid to go only from the heart, the manometer will indicate the maximum pres- sure ever attained during the cycle. If it is turned the other way, it will indicate the minimum pressure. The following are some of the measurements taken from the dog's heart in terms of millimetres of mercury : — Left ventricle Right ventricle Right auricle . By a negative ( — ) pressure one means that the mercury is sucked up in the limb of the manometer towards the heart. Another valuable instrument introduced by Hiirthle is called the differential manometer. In this instrument, two cannulae are brought into connection with tambours (a and b) which work on points of a lever at equal distances from and on Maximum Minimum pressure. 140 mm. pressure. - 30 to 40 mm 60 mm. - 15 mm. 20 mm. - 7 to 8 mm. ^= B A Pig. 253. — Diagram of Hiirthle's differential Manometer. opposite sides of its fulcrum (f). The lever sets in motion a writing style (s). This instrument enables us to determine the relations of the pressure changes in any two cavities. For instance, suppose a is connected to the left ventricle, and b to the aorta ; when the pressure in the ventricle is greater than that in the aorta, the writing style will be raised ; when the pressure in the aorta is greater than that in the ventricle, the style will fall ; when the two pressures are equal, it will be in the zero position. 244 PHYSIOLOGY OF THE HEART [CH. XX. Frequency of the Heart's Action. The heart of a healthy adult man contracts about 72 times in a minute ; but many circumstances cause this rate, which of course corresponds with that of the arterial pulse, to vary even in health. The chief are age, temperament, sex, food and drink, exercise, time of day, posture, atmospheric pressure, temperature. Some figures in reference to the influence of age are appended. The frequency of the heart's action gradually diminishes from the commencement to near the end of life, but is said to rise again some- what in extreme old age, thus : — Before birth the average number j About the seventh year . from 90 to 85 of pulsations per minute is . 150 | About the fourteenth Just after birth . . from 140 to 130 During the first year . ,, 130 to 115 During the second vear ,, 115 to 100 During the third year . „ 100 to 90 year . . . . ,, 85 to 80 In adult age 80 to 70 In old age . . . ,, 70 to 60 In decrepitude . . ,, 75 to 65 In health there is observed a nearly uniform relation between the frequency of the beats of the heart and of the respirations ; the proportion being, on an average, 1 respiration to 3 or 4 beats. The same relation is generally maintained in the cases in which the action of the heart is naturally accelerated, as after food or exercise ; but in disease this relation may cease. "Work of the Heart. Waller compares the work performed by the heart in the day to that done by an able-bodied labourer working hard for two hours. The heart's work consists in dis- charging blood against pressure, and in imparting velocity to it. Thus, if V repre- sents the output of the heart per beat measured in cubic centimetres, and P the mean pressure in the aorta, m the mass of the blood, and v the velocity imparted to it ; the work IT' is given by the equation : — W = VP + I mv 1 — Vgdh + \ mv 2 where h is the mean pressure in the aorta expressed in centimetres of blood, (/ the density of the blood, and g the acceleration of gravity (981). If now a is the transverse section of the aortic orifice, b that of the aorta, t the duration of the ventricular systole, and ^ the duration of the cardiac cycle, then, if i\ is the mean velocity of the blood in the aorta, V = avt = bvfa. Let us assume that the output of the heart is 110 c.c. per beat. The duration of the cardiac cycle is 0-8 sec, and that of the ventricular systole is 0*3 sec. The diameter of the aorta is about 3 cms. and that of the aortic orifice 2*6 cms. Remem- bering that the radius in each case is half the diameter, we have : — 110 = tt(1-3) 2 x 0-3 x v = 7r(l-5)' J x 0'8 x Vl Therefore » = 86-03, and »j = 19-45 cms. per second. That is, the velocity of the blood as it is discharged from the heart is about 4 -5 times greater than the mean velocity of tin blood in the nor/a. If //represents the mean intraventricular pressure during the time blood is CH. XX.] WORK OF THE HEART 245 being discharged into the aorta, measured in cms. of blood, and h the mean aortic pressure over the same time, then : — v* = 2g(H-h). Or H=h+ 1T 9 ( 86-03)- ~" T 2x981 = h + 3-77 cms. of blood. That is, the mean intraventricular pressure during the time the semilunar valves are open is only 3 "77 cms. of blood or 0'28 cms. of mercury higher than the mean aortic pressure during the same time. We may take the mean aortic pressure during the duration of systole as approximately 12 cms. of mercury or 156 cms. of blood, if we take the density of mercury as being 13 times that of the blood. Now if Ep represents the total potential energy created by the heart per beat, then, Ep = VgdH. A part of this energy, Ek, is converted into kinetic energy since velocity is imparted to the blood. This amount is given by the formula : — E K = ±Vdv 2 . From these two formulas Again = 110 = 110 x 9 x x 1-05 1-05 x (156 x (159-77) + 3- grm. 77) ergs cms. = 18453 '4 grm. cms. Ep VgdH Ek~ ' h Vdv 1 , 2 iE v*. H ' H-h 159-77 - 3-77 = 40 approximately. That is, -jV of the total energy of the heart's beat is used in imparting velocity to the blood. When the blood reaches the aorta its velocity is gradually checked, i.e., some of the kinetic energy imparted to it by the heart is reconverted into energy of pressure. The remaining kinetic energy is given by the equation : — Ek 1 = I mv; 1 _ Vdv* ~ 2, c, e. The mercury which partially tills the tube supports a float in the form of a piston, nearly filling the tube ; a wire is fixed to the float, and the writing style or pen fixed to the wire is guided by passing through the brass cap of the tube ; the pressure is communicated to the mercury by means of a flexible metal tube filled with fluid. mercury, is an ivory float, from which a long steel wire extends upwards, and terminates in a writing-point. The writing-point may be a stiff piece of parchment or a bristle which writes on a moving surface covered with smoked paper, or a small brush kept full of ink which writes on a long strip of white paper made to travel by clock- work in front of it. When the two limbs of the mercury are at rest, the writing-point inscribes a base line or abscissa on the travelling surface ; when the pressure is got up by the syringe it writes a line at a higher level. When the arterial clip is removed it writes waves as shown in the diagram (fig. 270), the large waves corresponding to respiration (the rise of pressure in most animals accompanying CH. XXI.] THE KYMOGRAPH 271 inspiration),* the smaller ones to the individual heart-beats. The blood-pressure is really twice as great as that indicated by the height of the tracing above the abscissa, because if the manometer is of equal bore throughout, the mercury falls in one limb the same distance that it rises in the other ; the true pressure is measured by the difference of level between a and a (fig. 270). Fig. 271 shows a more complete view of the manometer, and Fig. 272.— Diagram of mercurial Kymograph, a, Revolving cylinder, worked by a clockwork arrange- ment contained in the box (b), the speed being regulated by a fan above the box ; the cylinder is supported by an upright (&), and is capable of being raised or lowered by a screw (a), by a handle attached to it; d, c, e, represent the mercurial manometer, which is shown on a larger scale in fig. 271. fig. 272 is a diagram of the arrangement by means of which it is made into a kymograph. Fig. 273 shows a typical normal arterial blood-pressure tracing on a larger scale. In taking a tracing of venous blood-pressure, the pressure is so low and corresponds to so few millimetres of mercury, that a saline solution is usually employed instead of mercury. If the vein which * The explanation of the respiratory curves on the tracing is postpaned till after we have studied Respiration. 272 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXI. is investigated is near the heart, a venous pulse is exhibited on the tracing, with small waves as before corresponding to heart-beats, and Via. 273.— Normal tracing, somewhat magnified, of arterial pressure in the rabbit obtained with the mercurial kymograph. The smaller undulations correspond with the heart-beats, the larger curves with the respiratory movements. The abscissa or base line, which on this scale would be several inches below the tracing, is not shown. (Burdon-Sanderson.) larger waves to respiration, only the respiratory rise in pressure now accompanies expiration. Tho capillary pressure is estimated by the amount of pressure Fio. 274.— A form of Fiek's Spring Kymograph, o, Tube to be connected with artery ; c, hollow spring, the movement of which moves b, the writing lever; e, screw to regulate height of b; d, outside protective spring ; g, screw to fix on the upright of the support. necessary to blanch the skin ; this has been done in animals and men (v. Kries, Eoy and Brown). Other manometers are often employed instead of the mercurial one. Fiek's is one of these. The blood-vessel is connected as before with the manometer, and the pressure got up by the use of a syringe CH. XXI.] FICK S KYMOGKAPH 273 (which is seen in fig. 275, g), before the clip is removed from the artery. The manometer itself is a hollow C-shaped spring filled with liquid ; this opens with increase, and closes with decrease of pressure, and the movements of the spring are communicated to a lever pro- vided with a writing-point. Hiirthle's manometer (see p. 242) is also very much used. The advantage of these forms of manometer is that the character and Fig. 275.— Fick's Kymograph, improved by Hering (after M'Kendrick). a, Hollow spring filled with alcohol, bearing lever arrangement b, d, c, to which is attached the marker e ; the rod c passes downwards into the tube /, containing castor oil, which offers resistance to the oscillations of c ; g, syringe for filling the leaden tube h with saturated sulphate of sodium solution, and to apply sufficient pressure as to prevent the blood from passing into the tube h at i, the cannula inserted into the vessel; I, abscissa-marker, which can be applied to the moving surface by turning the screw m ; k, screw for adjusting the whole apparatus to the moving surface ; o, screw for elevating or depressing the Kymograph by a rack-and-pinion movement ; n, screw for adjusting the position of the tube/. extent of each pressure change is much better seen. In a mercury manometer the inertia is so great that it cannot respond to the very rapid variations in pressure which occur within an artery during each cardiac cycle. If Fick's or Hiirthle's manometer is employed, and the surface travels sufficiently fast, these can be recorded (see fig. 276). These instruments, though useful for recording the complete changes in pressure, require calibration : that is, the extent of move- ment that corresponds to known pressures must be ascertained by S 274 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. actual experiment. They teach us that the highest pressure reached during systole may be twice or thrice the lowest attained during diastole. Fig. 270.— Normal arterial tracing obtained with Fick's Kymograph in the dog. (Burdon-Sauderson.) The following table gives the probable average height of blood- pressure in various parts of the vascular system in man. They have been very largely inferred from experiments on animals : — T , ..,.> ( + 140 mm. (about 6 inches) Large arteries (e.%. carotid) . - v J ° v ° J \ mercury. Medium arteries (e.g. radial) . +110 mm. mercury. Capillaries . + 15 to + 20 3) ) Small veins of arm . + 9 !> > Portal vein + 10 >> > Inferior vena cava + 3 1> > Large veins of neck from to - 8 >> } (Starling.) These pressures are, however, subject to considerable variations ; th3 principal factors that cause variation are the following : — Increase of arterial blood-pressure is produced by — 1. Increase in the rate and power of the heart-beat. 2. Increase in the contraction of the arterioles. 3. Increase in the total quantity of blood (plethora, after a meal, after transfusion). Decrease in the arterial blood-pressure is produced by — 1. Decrease in the rate and force of the heart-beat. 2. Decrease in the contraction of the arterioles. 3. Decrease in the quantity of blood (e.g. after haemorrhage). The above is true for general arterial pressure; but if we are investigating local arterial pressure in any organ, the increase or decrease in the size of the arterioles of other areas may make its effect felt in the special area under investigation. Venous pressure varies directly with the volume of the blood ; in the arteries the effect of increase of fluid is slight and temporary, owing to the rapid adaptability of the peripheral resistance ; the excess of fluid collects in and distends the easily dilatable venous reservoir. With regard to the first and second factors in the foregoing table, venous pressure varies in the opposite way to arterial pressure. CII. XXI.] VENOUS PRESSUKE 275 It is easy to understand how this is ; when the rate of the heart increases, the total volume of blood discharged into the aorta per second is increased ; similarly, an increase in the force of the beat also results in an increase in the cardiac output, and in both cases a more rapid and complete emptying of the auricle is produced. This is felt throughout the whole of the pulmonary circulation, and the accelerated flow therefore causes a fall in the venous pressure. If, however, the rise of pressure is due to a contraction of the arterioles, a stage may be reached in which the heart is no longer able to over- come the high pressure produced. It then fails to empty itself, and Fig. 277. — Effect of weak stimulation of the peripheral end of vagus on arterial blood-pressure (carotid of rabbit), bp, Blood-pressure ; a, abscissa or base line ; t, time in seconds. Note fall of blood- pressure and slow heart-beats. the blood is dammed up on the venous side, i.e. the venous pressure rises. "With regard to the arterioles, contraction means a rise in arterial pressure, because while the amount sent into the arteries remains the same the outflow is cut down. More blood is therefore retained in them ; they become more distended and the pressure rises. The first effect of this upon the venous pressure will be to diminish it, because if more blood is retained in the arteries there is less for the veins and capillaries. Also the rate of flow into the veins is at first decreased, and the venous pressure therefore falls. Moreover, the heart usually responds to a rise in pressure by increasing its force and rate, and consequently more blood is taken from the veins near 276 THE CIKCULATION IN THE BLOOD-VESSELS [CH. XXI. the heart. For both reasons, then, the venous pressure will fall, but that fall is limited, as pointed out above, to such an increase only as the heart is capable of overcoming successfully. Capillary pressure is increased by — 1. Dilatation of the arterioles ; the blood-pressure of the large arteries is then more readily propagated into them. 2. The size of the arterioles remaining the same, increase of arterial pressure from any other cause will produce a rise of capillary pressure. 3. By narrowing the veins leading from the capillary area ; com- plete closure of the veins may quadruple the capillary pressure. This leads secondarily to an increased formation of lymph (dropsy) ; as when a tumour presses on the veins coming from the legs. 4. Any circumstance that leads to increased pressure in the veins will act similarly; this is illustrated by the effects produced by gravity on the circulation, as in alterations of posture. Capillary pressure is decreased by the opposite conditions. Capillary pressure is much more influenced by changes in the venous pressure, than by changes in the arterial pressure, since there is between the arteries and capillaries the variable and usually un- known peripheral resistance of the arterioles. Effect of gravity on the circulation. — The main effect of gravity is that the veins are filled with blood in the part which is placed down. Thus, if an animal is placed suddenly with its legs hanging down, less blood will go to the heart, and the blood-pressure in the arteries will fall temporarily in consequence. This hydrostatic effect of gravity is soon overcome by an increased constriction of the vessels of the splanchnic area, when the vaso-motor mechanism is working normally. The efficient action of the " respiratory pump " is also of importance in counteracting gravity. A very striking illustration of the effect of gravity on the circula- tion can be demonstrated on the eel. The animal is anaesthetised, and a small window is made in the body wall to expose the heart. If the animal is then suspended tail downwards, the beating heart is seen to be empty of blood ; all the blood accumulates in the tail and lower part of the body ; the animal has no " respiratory pump," such as a mammal possesses, to overcome the effects of gravity. If, how- ever, the animal, still with its tail downwards, be suspended in a tall vessel of water, the pressure of the water outside its body enables it to overcome the hydrostatic effect of gravitation, and the heart-cavi- ties once more fill with blood during every diastole. Another experi- ment originally performed by Salathe, can be demonstrated on a " hutch " rabbit. If the animal is held by the ears with its legs hanging down, it soon becomes unconscious, and if left in that position for about half an hour it will die. This is due to anaemia of the CH. XXI.] CAEDIAC NERVES AND BLOOD-PRESSURE 277 brain ; the blood accumulates in the very pendulous abdomen which such domesticated animals acquire, and the vaso-motor mechanism of the splanchnic area is deficient in tone, and cannot be set into such vigorous action as is necessary to overcome the bad effects of gravity. Consciousness is, however, soon restored if the animal is placed in a horizontal position, or if while it is still hanging vertically the abdomen is squeezed or bandaged. A wild rabbit, on the other hand, suffers no inconvenience from a vertical position ; it is a more healthy animal in every respect; its abdomen is not pendulous, and its vaso-motor power is intact. (Leonard Hill.) Fig. 278. — Effect of strong stimulation of the peripheral end of vagus on arterial blood -pressure (carotid of rabbit). Note stoppage of heart and fall of blood-pressure nearly to zero ; after the recommence- ment of the heart, the blood-pressure rises, as in fig." 277, above the normal for a short time. The 'pressure in the Pulmonary Circulation varies from J to -g- (mean ^) of that in the systemic vessels. The influence of the Cardiac Nerves on blood-pressure. The importance of the heart's action in the maintenance of blood-pressure is well shown by the effect that stimulation of the vagus nerve has on the blood-pressure curve. If the vagus of an animal is exposed and cut through, and the peripheral end stimulated, the result is that the heart is slowed or stopped; the arterial blood-pressure conse- quently falls ; the fall is especially sudden and great if the heart is completely stopped. There is a rise in venous pressure. The effect 278 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXI. on arterial pressure is shown in the two accompanying tracings ; fig. 277 representing the effect of partial, and fig. 278 of complete stoppage of the heart; in both cases the animal used was a rabbit, and the artery the carotid. On stimulating the cardiac sympathetic (accelerator and augmentor til ires) the increased action of the heart causes a rise of arterial pres- sure. The effects of stimulating the central end of the vagus and other nerves cannot he understood until we have studied the vaso-motor nervous system. The Velocity of the Blood-flow. We have already seen that the velocity of the current of blood is inversely proportional to the sectional area of the bed through which it flows. The flow is, therefore, swiftest in the aorta and arteries, and slowest in the capillaries. In very round numbers, the rate is about a foot per second in the aorta, and about an inch per minute in the capillaries. The capacity of the veins is about twice or thrice that of the arteries ; so the velocity in the veins is from a half to a third of that in the corresponding arteries. The rate in the veins increases as we approach the heart, as the total sectional area of the venous trunks becomes less and less. The question of velocity is one of great importance, for it is on velocity that the actual amount of blood supplying the tissues mainly depends. In the capillaries the rate can be measured by direct micro- scopic investigation of the transparent portions of animals. E. H. Weber and Valentin were among the earliest to make these measure- ments in the frog, and the mean of their estimates gives the velocity as 25 mnis. per minute in the systemic capillaries. In warm-blooded animals the velocity is somewhat greater ; in the dog it is -^ to -j-j^j- inch (0"5 to 0"75 mm.) per second. It must be remembered that the total length of capillary vessels through which any given portion of blood has to pass probably does not exceed from J^ to ^ inch (0'5 mm.), and therefore the time required for each quantity of blood to traverse its own appointed portion of the general capillary system will scarcely amount to a second. It is during this time that the blood does its duties in reference to nutrition. In the larger vessels direct observations of this kind are not possible, and it is necessary to have recourse to some instrumental method. Volkmann was the first to make more or less accurate measure- ments by introducing a long (J -shaped glass tube into the course of an artery. A diagram of this Jucmodromomcter, as it was termed, is shown in the accompanying diagram (fig. 279); this is filled with silt solution, and provided with a stop-cock a; this tap is so arranged CH. XXI.] THE STROMUHR 279 that the blood can flow straight across from one section of the artery to the other ; then at a given instant it is turned into the position shown in the diagram, and the blood has to traverse the long (J -tube, and the time that it takes to traverse the tube, the length of which is known, is accurately observed. If the sectional area of the tube is the same as that of the artery, the velocity is obtained without further correction; but the difficulty of obtaining glass tubes with the exact calibre of every blood-vessel which one desires to experi- ment with led to the abandonment of this method, and Ludwig's Stromuhr (literally stream-clock) took its place. This consists of a (J -shaped glass tube dilated at a and a, the ends of which, h and i, m Fig. 279.— Volkmann's Hfemodromomtter. Fig. 280.— Ludwig Stromuhr. are of known calibre. The bulbs can be filled by a common opening at k. The instrument is so contrived that at h and V , the glass part is firmly fixed into metal cylinders, attached to a circular horizontal table c c, capable of horizontal movement on a similar table d d, about the vertical axis marked in the figure by a dotted line. The openings in c c', when the instrument is in position, as in fig. 280, corresponds exactly with those in d d' ; but if c c is turned at right angles to its present position, there is no communication between h and a and i and a, but h communicates directly with i ; and if turned through two right angles c' communicates with d, and c with d', and there is no direct communication between h and i. The experiment is performed in the following way : — The artery to be investigated 280 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. is divided and connected with two cannulas and tubes which fit it accurately with h and i; h is the central end, and % the peri- pheral ; the bulb a is filled with olive oil up to a point rather lower than k, and a and the remainder of a is filled with defibrinated blood ; the tube on k is then carefully clamped ; the tubes d and d' are also filled with defibrinated blood. When everything is ready, the blood is allowed to flow into a through h, thus driving the oil over into a' and displacing the defibrinated blood through i into the peripheral end of the artery ; a is then full of oil ; when the blood reaches the former level of the oil in a, the disc c c is turned rapidly through two right angles, and the blood flowing through d into a again displaces the oil, which is driven into a. This is repeated several times, and the duration of the experiment noted. The capacity of a and a is known ; the diameter of the artery is then measured, and as the number of times a has been filled in a given time is known, the velocity of the current can be calculated. We may take an example to illustrate this : — volume per second V Velocity = 77 , = "c". J sectional area b If the capacity of the bulb is 5 c.c, and it required 100 seconds to fill it 10 times, then the amount of blood passing through the instru- ment would be 50 c.c. in 100 seconds, or 0"5 c.c. in 1 second. Next, suppose the diameter of the artery is 4 mm. The sectional area is 7i-r 2 ; r is the radius (2 mm.), and 7r = 31416. From these data we get V 0-5 c.c. 500 cubic millimetres Velocity =-g = 3 . U16 x 22 - 3-1416 x 4 = 39 ' 8 mm - ^ X ^ Many modifications of Ludwig's original instrument have been devised. Fig. 281 shows Tigerstedt's. The tubes A and B are placed in connection with the two ends of the cut artery as before ; there is also a turn-table arrangement at F, by means of which the two upper tubes C and D may be connected as in the figure ; or by twisting it through two right angles, D can be made to communicate with A, and C with B. In place of the two bulbs of Ludwig's instrument there is a glass cylinder H which contains a metal ball E. The whole instrument is washed out with oil to delay clotting, and filled with defibrinated blood. As soon as blood is allowed to flow from the artery, the ball E is driven over by the current till it reaches the other end of the cylinder ; the instru- ment is then rapidly rotated through two right angles, and once more the ball is driven to the opposite end. This is repeated several times, and the number of revolutions during a given period is noted. The capacity of the cylinder minus that of the ball is ascertained, en. xxl] THE VELOCITY PULSE 281 and the velocity is calculated by the same formula as that already given. The Stromuhr has one advantage over the hgemodromometer, in that it enables one to note changes in mean* velocity during the course of an experiment. The mean velocity varies very greatly even during a short experiment. Thus, in the carotid artery of a dog, the velocity of the stream varied from 350 to 730 mm. per second in the course of eighty seconds ; in the same artery of the rabbit the variations were still more extensive (94 to 226 mm. per second — Dogiel). Other instruments have been devised which give the variations in the velocity during the phases of the heart-beat; and some of these lend themselves to the graphic method, and give tracings of what is called the velocity pulse. Before we can understand these, it is necessary first to study the relationship of velocity to blood- pressure. Mere records of blood- pressure give us no indication of the velocity of the blood-stream ; the latter depends, not on the absolute amount of pressure, but on the differences of pressure between successive points of the vascular system. When a fluid is in movement along a tube the forces maintaining the flow are two in number, the one hydro- kinetic, the other hydro - static. Thus, if we consider the flow from one point in the tube to another (say, for example, at 1 cm. dis- tance), the force producing the flow are (1) the kinetic energy pos- 7)1/1/ sessed by the blood when it enters the first spot (i.e. -=- dynes, 9 or -jj— gramme-centimetres) ; and (2) the difference between the two lateral pressures at the two points in question. The important point to remember with respect to the part the pressure plays, is that the actual value of the lateral pressure does not matter, but that the resulting velocity, so far as pressure is concerned, depends only upon the fall of pressure between the two points. Therefore, the measurement to be determined is the rate of fall of pressure, or, as it is usually expressed, the pressure gradient. The steeper this gradient is, the more rapid is the flow. Thus, if an artery is suddenly cut across, the blood will spurt out at a far greater velocity than it possessed when flowing along the intact artery, Pio. 281.— Tigerstedt's Stromuhr. 282 THE CIRCULATION IN THE RLOOD-VESSELS [CII. XXI. because the pressure gradient has been enormously increased in steepness. If, on the other hand, we suddenly cut across a vein along which the blood had been flowing- at the same pace as in the intact artery first investigated, the flow will not be markedly accelerated, because the change in pressure gradient has not been increased to nearly so great an extent. Again, the flow along a vein is just as rapid as along an artery of the same size, for although the actual pressure in the vein is much less, the pressure gradient is just as steep. The influence of the kinetic factor is also of great importance in the consideration of the flow of blood along the arteries and veins. In the first place, it is obviously possible for the blood to flow from one point to another at a higher pressure if the kinetic energy at the first point is more than enough to compensate for the pressure increase. Under such circumstances the velocity at the second point must of course be less than that at the first. This implies, therefore, that the bed of the stream has widened, and under such circumstances the blood could actually flow uphill. In the case of the veins, as we have previously seen, the bed continuously narrows, so that this cannot take place ; still it is possible to conceive such a condition to occur as that in which the blood from a well-filled vein empties into a more collapsed larger vein situated at a higher level. The one instance in which this effect is produced and is of great importance is in the filling of the auricles and ventricles. As these cavities fill, the blood comes to rest and so loses all kinetic energy; consequently the whole of the kinetic energy possessed by the blood flowing in the veins is converted into static energy, that is, into a pressure-head ; in this way the cavities are distended to a much higher pressure than that in the great veins. The acute distension of the right auricle which follows any sudden failure of the right ventricle is brought about chiefly in this way. It is usual to speak of the lateral pressure of the blood on the vessel wall as the pressure-head, and of the kinetic energy measured in terms of a pressure as the velocity -head. We could then say that the velocity between any two points is determined by the difference between the two pressure-heads plus the velocity-head at the first point. One method of recording the velocity -head is by the use of a tube (Pitot's tube) shaped as in the accompanying figure (fig. 282). The blood is made to enter at A, and leave through B ; in the same straight line as A is a tube C, and a second tube D is placed at right angles to the tube B. If the tubes C and D are placed vertically and were sufficiently long, the blood would flow up C until it reached a height which would balance the pressure-head plus the velocity -head ; in D it would only roach a height sufficient to balance CH. XXI.] PITOT S TUBE 283 r~\ B the pressure-head ; the difference in height between the two would therefore give the velocity-head. As the tubes would in this way- be inconveniently long, it is better to use short tubes connected at the top by glass or rubber-tubing. The air contained will be com- pressed, and the two pressure-heads will balance one another, so that the difference in height will again represent the velocity -head ; the velocity will be directly proportional to the square root of this velocity-head. This is the principle of one of the best instruments we possess for determining velocity, namely, Cybulski's photo-hsemato- chometer. The meniscus of the fluid in each tube is photographed on a moving sensitive plate, and in this way a graphic record is obtained of the changes in velocity at times corresponding to different parts of the cardiac cycle. If one wishes to determine the velocity in absolute measures, the instrument must be previously calibrated by passing through it fluids flowing at known rates. It will be sufficient to give the results of one experiment; in the carotid artery during the ventricular systole the flow was at the rate of 238-248 mm. per second; during the diastole it sank to 127-156; in the femoral artery of the same animal, these numbers were 356 and 177 respectively. To determine the pressure gradient in arteries, simultaneous measurements of the lateral pressures in two vessels at different distances from the heart must be recorded. It has been found that the diastolic pressures in the crural and carotid are practically identical, but that the maximum systolic pressure is actually higher in the crural than in the carotid; in the dog the difference may amount to as much as 60 mm. mercury. This difference is partly to be explained in that the carotid arises from the aorta at a right angle, and therefore gives the true pressure-head, while the crural, to a con- siderable extent, faces the stream, ami therefore gives both pressure- head and velocity-head. Unfortunately, at present no really satisfactory measurements are at hand from which the pressure gradient can be determined. Cybulski's instrument is not the only one we possess for obtaining records of the velocity -pulse. Vierordt invented a hsemo-tachometer, employing the principle of the hydrometric pendulum ; his instrument Fig. 2S2.— Diagram to illustrate the principle of Pitot's Tube and Cybulski's Photo-bfemato- chometer. 284 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. was improved by Chauveau. Chauveau's instrument is shown in fig. 283. It consists of a thin brass tube, a, in one side of which is a small perforation closed by thin vulcanised indiarubber. Passing through the rubber is a fine lever, one end of which, slightly flattened, extends into the lumen of the tube, jr while the other moves over the face of a dial. The tube is inserted into the interior of an artery, and liga- tures applied to fix it, so that the "velocity pulse™ »'.<-., the change of velocity with each heart-beat, may be indicated by the movement of the outer extremity of the lever on the face of the dial. In order to obtain the actual value of these move- ments in terms of velocity, the instrument must be calibrated beforehand. The next dia- gram, fig. 284, shows how the instrument may be adapted to give a graphic record. The movements of the pen- dulum are brought to bear upon a tambour B, which communicates by a tube with the recording tambour C. If the mass of the pen- dulum is small, the accuracy of the instrument is considerable. Fig. 285 shows the tracing obtained from the carotid artery of the horse. The pressure curve is placed below it for purpose of comparison. The tracing shows the effects during the time corre- sponding to one cardiac cycle. On both curves the upstroke is the Fig. 2S3. — Diagram of Chauveau's Dromograph. a, Brass tube for introduction into the lumen of the artery, and containing an index needle, which passes through the elastic membrane in its side, and moves by the impulse of the blood current ; c, graduated scale, for measuring the extent of the oscillations of the needle. Fig. 284. — Chauveau's Dromograph connected with tambours to give a graphic record. effect of the ventricular systole ; this terminates at the apex of the first small curve (between the vertical lines 3 and 4) on the down- stroke of the pressure curve, the rest of the downstroke until the commencement of the next systole (line 5) corresponds with the ventricular diastole. Beyond the line 4 is a larger secondary wave, which is known as the dicrotic wave ; the smaller post-dicrotic waves on. xxi.] TIME OF A COMPLETE CIKCULATION 285 are due to elastic vibrations. "We shall be studying all these points more in detail when we come to the pulse. When we compare the two curves together we note that the velocity curve reaches its maxi- mum before the pressure curve ; this is because, as the arteries become overfilled, the heart cannot maintain the initial velocity of output. The blood is thus forced along the arteries ; then comes the diastole, and the recoil of the elastic arteries not only forces the blood onwards, but also produces a back-swing against the closed aortic valves ; this produces the notch before the dicrotic wave; the blood is reflected from the aortic valves, once more producing a positive wave (the dicrotic wave). This affects both speed and pressure. It will be noticed that during the dicrotic notch the pressure falls comparatively little, but in the velocity curve the fall is considerable, and the curve sinks below the base line oo. This negative effect is naturally much Fig. 285.— Velocity curve (V), and pressure curve (P) from the carotid artery of the horse; oo, abscissa of velocity curve; 1, 2, 3, i show simultaneous points on both curves. (Chauveau and Marey.) more marked in the aorta and its first large branches than in situa- tions further from the heart. In actual values Chauveau found that the velocity in the horse's carotid reached 520 mm. per second during systole ; it sank to 220 at the time of the dicrotic wave, and to 150 during diastole. The effect on the blood-flow of functional activity or vaso-motor changes has also been observed. Thus Lortet found that the carotid flow is five or six times greater when the horse is actively masticating than when it is at rest. After section of the cervical sympathetic, the lessening of the peripheral resistance raised the velocity from 540 to 750 mm. per second. The Time of a Complete Circulation. Among the earliest investigators of the question how long an entire circulation takes, was Hering. He injected a solution of potassium ferrocyanide into the central end of a divided jugular vein, and collected the blood either from the other end of the same 286 THE CIRCULATION IN THE BLOOD-VESSELS [(JII. XXI vein, or from the corresponding vein of the other side. The sub- stance injected is one that can be readily detected by a chemical test (the prussian blue reaction). Vierordt improved this method by collecting the blood as it flowed out, in a rotating disc divided into a number of compartments. The blood was tested in each com- partment, and the ferrocyanide discovered in one which in the case of the horse received the blood about half a minute after the injection had been made. The experiment was performed in a large number of animals, and the following were a few of the results obtained : — In the horse . . . .31 seconds. „ dog . . . 16 „ „ cat . . . 6*5 „ fowl . . . 5 At first sight these numbers show no agreement, but in each case it was found that the time occupied was 27 heart-beats. The dog's heart, for instance, beats twice as fast as the horse's, and so the time of the entire circulation only occupies half as much time. The question has recently been re-investigated by Stewart by improved methods, which have shown that the circulation time is considerably less than was found by the researches of Hering and Vierordt. The great objection to the older method is the fact that haemorrhage is occurring throughout the experiment, and this would materially weaken the heart and slow down the circulation. Stewart has employed two methods. In the first, the carotid artery is exposed, and non-polarisable electrodes applied to it. These are placed in circuit with a cell, a galvanometer and one arm of a Wheatstone's bridge. After the resistances in the bridge have been balanced, and the galvanometer needle brought to rest, a small quantity of strong sodium chloride solution is injected into the opposite jugular vein. As soon as the salt reaches the carotid artery, the resistance of the blood is altered, the balance of the Wheatstone's bridge is upset, and the galvanometer needle moves. The period between the injection and the swing of the needle is accurately noted. The second method used is even simpler, and gives practically the same results; a solution of methylene blue is injected into the jugular vein. The carotid artery on the opposite side is exposed, placed upon a sheet of white paper, and strongly illuminated. The time is noted between the injection and the moment when the blue colour is seen to appear in the artery. Stewart has applied these methods also for determining the time occupied by the passage of blood through various districts of the circulation ; the longest circula- tion times were found in the kidney, the portal system, and the lower limbs. He calculates that the total circulation time in man is about 15 seconds. CH. XXI.] THE PULSE 287 None of these methods, however, give the true time of the entire circulation ; they give merely the shortest possible time in which any particle of blood can travel through the shortest pathway. The blood that travels in the axial current, or which takes a broad path- way through wide capillaries, will arrive far more speedily at its destination than that which creeps through tortuous or constricted vessels. The direct observations of Tigerstedt on the output of the left ventricle show that the circulation time of the whole blood is at least five times as long as the period arrived at by the Hering method. It is therefore fallacious to use the circulation times arrived at by Hering's or Stewart's methods as a basis for calculating the total amount of the blood in the body. The Pulse. This is the most characteristic feature of the arterial flow. It is the response of the arterial wall to the changes in lateral pressure caused by each heart-beat. A physician usually feels the pulse in the radial artery, since this is near the surface, and supported by bone. It is a most valuable Fig. 2S6. — Marey's Spliygmograph, modified by Mahomed. indication of the condition of the patient's heart and vessels. It is necessary in feeling a pulse to note the following points : — 1. Its frequency ; that is the number of pulse-beats per minute. This gives the rate of the heart-beats. 2. Its strength ; whether it is a strong, bounding pulse, or a feeble beat ; this indicates the force with which the heart is beating. 288 THE CIRCULATION IN THE BLOOD-VESSELS [GIL XXI. 3. Its regularity or irregularity ; irregularity may occur owing to irregular cardiac action either in force or in rhythm. 4. Its tension ; that is the force necessary to obliterate it. This gives an indication of the state of the arterial walls and the peripheral resistance. In disease there are certain variations in the pulse, of which we shall mention only two ; namely, the intermittent pulse, due to the h ^- Fig. 2S7.- Diagram of the lever of the Sphygmograph. heart missing a beat every now and then; and the water hammer pulse, due either to aortic regurgitation or to a loss of elasticity of the arterial walls; either of these circumstances diminishes the onward flow of blood during the heart's diastole, and thus the sudden- ness of the impact of the blood on the arterial wall during systole is increased. When this condition is due to arterial disease, such as atheroma or calcification, this sudden pulse, combined with the decreased extensibility of the arteries, may lead to rupture of the Fig. 2S8.— The Sphygmograph applied to the arm. walls, and this is especially serious if it occurs in the arteries of the brain (one cause of apoplexy). In order to study the pulse more fully, it is necessary to obtain a graphic record of the pulse-beat, and this is accomplished by the use of an instrument called the sphygmograph. This instrument consists of a series of levers, at one end of which is a button placed over the artery ; the other end is provided with a writing-point to inscribe the magnified record of the arterial movement on a travelling surface. CH. XXI.] SPHYGMOGKAPHS 289 The instruments most frequently used are those of Marey, one of the numerous modifications of which is represented in figures 286, 287, and 288, and of Dudgeon (fig. 289). Fig. 2S9.— Dudgeon's Sphygmograph. The dotted outline represents the piece of blackened paper on which the sphygmogram is written. Each instrument is provided with an arrangement by which the pressure can be adjusted so as to obtain the best record. The measurement of the pressure is, however, rough, and both instruments have the disadvantage of giving oscillations of their own to the sphygmogram ; this is specially notice- able in Dudgeon's sphygmograph. But these defects may be overcome by the use of some form of sphyg- mometer. (See later, p. 292). It is also important to remember that the pad or button placed upon the artery rests partly on the vena comites, so that not only arterial tension but any turgidity arising from venous conges- tion, will affect the height and form of the sphygmographic record. Fig. 290 represents a typical sphyg- mographic tracing obtained from the radial artery an upstroke due to the expansion of the artery, and a downstroke due to its retraction. The descent is more gradual than the up- stroke, because the elastic recoil acts more constantly and steadily T Fig. 290. — Diagram of pulse-tracing, a, up- stroke ; b, downstroke ; c, pre-dierotic wave; d, dicrotic; E,post-dieroticwave. It consists of 290 THE CIRCULATION IX THE BLOOD-VESSELS [CH. XXI. than lli3 hoart-beat. On the descent are several secondary (kata- crotic) elevations. A is the primary, or percussion wave ; C is the pre- dicrotic, or tidal wave; D is the dicrotic wave, and E the post-dicrotic wave, and of these there may be several. In some rare cases there is a secondary wave on the upstroke, which is called an anacrotic wave (fig. 291). These various secondary waves have received different inter- pretations, but the best way of explaining them is derived from information obtained by taking simultaneous tracings of the pulse, aortic pressure, apex beat, and intraventricular pressure, as in the researches of Hiirthle. By this means it is found that the percussion and tidal waves occur during the systole of the heart, and the other waves during the diastole. The closure of the aortic valves occurs just before the dicrotic wave. The secondary waves on the down- stroke other than the dicrotic are due to the elastic tension of the arteries, and are increased in number when the tension of the arteries Fio. 291. — Anacrotic pulse. is greatest. Some of the post-dicrotic waves are also doubtless instrumental in origin. The dicrotic wave has a different origin. It was at one time thought that this wave was due to a wave of pressure reflected from the periphery, but this view is at once excluded by the fact that wherever we take the pulse-tracing, whether from the aorta, carotid, radial, dorsalis pedis, or elsewhere, this secondary elevation always follows the percussion wave after the same interval, shawing that it has its origin in the commencement of the arterial system. Moreover, a single pressure-wave reflected from the periphery would be impossible, as such a wave reflected from one part would be inter- fered with by those from other parts ; moreover, a dicrotic elevation produced by a pressure-wave reflected from the periphery, would be increased by high peripheral resistance, and not diminished as is actually the case. The primary cause of the dicrotic wave is the closure of the semi- lunar valves; as already explained when we were considering the velocity pulse (p. 285), the inflow of blood into the aorta suddenly ceases, and the blood is driven back against the closed aortic doors by the elastic recoil of the aorta ; the wave rebounds from these and is propagated through the arterial system as the dicrotic CH. XXI.] THE PULSE-TRACING 291 elevation. The production of the dicrotic wave is favoured by a low blood-pressure when the heart is beating forcibly, as in fever. Such a pulse is called a dicrotic pulse (fig. 292), and the second beat can be easily felt by the finger on the radial artery. The percussion wave is produced by the ventricular systole expanding the artery. The sharp top at its summit is due to the sudden upward spring of the light lever of the sphygmograph. If it were possible to obtain a true record of what really occurs, we should doubtless have a tracing as shown by the continuous line in the accompanying figure (fig. 293). The apex of the tidal wave, B, marks the fig. 292.— Dicrotic puise. end of the ventricular systole. In our study of intra-cardiac pressure, we saw that the systolic plateau sometimes has an ascending, sometimes a descending, slope (see p. 243) ; we now come to the explanation of this fact. If after the first sudden rise of pressure in the aorta the peripheral resistance is low, and the blood can be driven on from the aorta more rapidly than it is thrown in, the plateau will sink. If, on the other hand, the peripheral resistance is high, the aortic pressure will rise as long as the blood is flowing in, and we get an ascending systolic plateau and an anacrotic pulse. Thus an anacrotic pulse is seen in Blight's disease, where the peripheral resistance is very high. If a long pulse-tracing is taken, the effect of the respiration can be seen causing an increase of pressure, and a slight acceleration of the heart's beats during inspiration. FK puSrac?ngf r .t! n pe?- The main waves of the pulse can be demon- cussion; B tidal; 0, strated without the use of anv instrument at all dicrotic; and d, post- J dicrotic waves. by allowing the blood to spurt from a cut artery on to the surface of a large sheet of white paper travelling past it. We thus obtain what is very appropriately called a hcemautogrwpli (fig. 29-i). A distinction must be drawn between the pulse as felt at any one spot in the course of an artery, and the pulse-wave which is propagated throughout the arterial system. This wave of expansion travels along the arteries, and is started by the propulsion of the contents of the left ventricle into the already full arterial system. The more distant the artery from the heart, the longer the interval that elapses between the ventricular beat and the arrival of the pulse-wave. Thus it is felt in the carotid earlier than in the radial artery, and is still later in the dorsal artery of the foot. The difference of time is, however, very slight ; it is only a minute frac- 292 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. Fig. 294. — Haemauto- graph, to be read from right to left. Lion of a second; the wave travels at the rate of from 5 to 10 metres a second, that is twenty to thirty times the rate of the blood current. The Bali of Propagation of the Pulse-Wave. — The method of ascertaining this may be illustrated by the use of a long elastic tube into which fluid is forced by the sudden stroke of a pump. If a series of levers are placed along the tube at measured distances those nearest the pump will rise first, those farthest from it last. If these are arranged to write on a revolving cylinder under one another, this will be shown graphically, and the time interval between their movements can be measured by a time tracing. The same principle is applied to the arteries of the body ; a series of Marey's tambours are applied to the heart and to various arteries at known distances from the heart ; their levers are arranged to write immediately under one another, as in fig. 248. The difference in time between the commencement of their up- strokes is measured by a time tracing in the usual way. The tracing taken with a sphygmograph is that of the pressure pulse ; we may regard it as a blood- pressure tracing without a base line. The actual measurement of the blood-pressure in the human subject cannot obviously be effected by the appar- atus employed on animals, and numerous instru- ments have been invented for the purpose which may be applied to the vessels without any dissec- tion. One of the simplest of these sphygmometers, as they are termed, has been introduced by Hill and Barnard. The instrument consists of a vertical glass tube about five inches in length, which expands above into a small bulb, and is closed at the top by a glass tap (see fig. 295). A small indiarubber bag is fixed to the tube below ; this is surrounded by a metal cup, attached in such a way that only the base of the bag is exposed. The bag is filled with coloured fluid. On pressing the instrument down over the radial or other artery, the fluid rises in the tube and compresses the air in the bulb ; the air acts as an elastic spring. The more one presses the more the fluid rises ; at a certain height the meniscus of the fluid exhibits more pulsa- tion than it does at any other height {maximal pulsation). The tube is empirically graduated in divisions that correspond to millimetres of mercury pressure. The point of maximal pulsation gives the arterial pressure. Before each observation the tap is opened, and by gentle pressure on the bag the fluid is set at the zero mark on the scale. Thus errors due to changes in barometric pressure or temperature are avoided. We now come to the explanation why the maximal pulsation gives i. 295. -Hill and Barnard's Sphyg- mometer. CH. XXI.] BLOOD-PRESSURE IN MAN 293 us a reading of arterial pressure. If the mean pressure inside and outside an artery be made equal, then the wall of the vessel is able to vibrate at each pulse with the greatest freedom. The mean pressure is less than the systolic, but greater than the diastolic pressure; thus during the heart's systole the artery is opened out to its fullest extent, while during the heart's diastole its lumen is obliterated ; hence the vessel wall swings with the greatest amplitude. If the pressure exerted by the sphygmometer is less than the mean arterial pressure, the artery will not be compressed to its utmost during diastole ; if, on the other hand, the pressure exerted is greater than the mean, the artery will not fully expand during systole. In either case, the pulsation will not be so great as when the pressure exerted on the outside of the artery equals the mean pressure within. By recording the arterial pressure in the dog with a mercury manometer and the sphygmometer simultaneously, the instrument has been found to give fairly accurate results (see note at end of this chapter, p. 313). The normal pressure in the radial artery of healthy young adults is 110 to 120 mm. Hg. It appears to be as constant as the body temperature. In the recumbent posture the pressure is slightly lower than in the erect position. This relation is reversed in condi- tions of exhaustion. During muscular exertion the pressure is raised, while in the subsequent period of rest it is subnormal. Mental work raises the pressure ; during rest and sleep it is lowered. The taking of food produces no noteworthy effect. In disease there are naturally variations in different directions, and the study of these has already yielded valuable results. With this instrument the venous pressure can also be obtained in the manner suggested by Dr George Oliver. On the back of the hand or arm a vein is chosen free from anastomoses, and the sphygmometer is pressed upon the peripheral end of this. The vein is then emptied centrally — i.e., towards the heart — by the pressure of the finger. Next the pressure in the sphygmometer is gradually re- laxed, and the exact height noted at which the vein refills with blood. Since the flow of blood through the capillaries is maintained by the difference in pressure between the artery and vein, we can, by obtaining readings both of the arterial and of the venous pressures, estimate the comparative efficiency of the capillary circulation in man under varying conditions. The Capillary Flow. When the capillary circulation is examined in any transparent part of a living animal by means of the microscope the blood is seen to flow with a constant equable motion ; the red blood-corpuscles 294 THE CIRCULATION IX THE BLOOD-VESSELS [Cll. XXI. move along, mostly in single file, and bend in various ways to accommodate themselves to the tortuous course of the capillary, but instantly recover their normal outline on reaching a wider vessel. At the circumference of the stream in the larger capillaries, and in the small arteries and veins, there is a layer of blood-plasma in contact with the walls of the vessel, and adhering to them, which moves more slowly than the blood in the centre. Anyone who lias rowed on a river will know that the swiftest current is in the middle of the stream. The red corpuscles occupy the middle of the stream and move with comparative rapidity ; the colourless corpuscles run much more slowly by the walls of the vessel ; while next to the wall there is a transparent space in which the fluid is at comparative rest (the so-called " still layer ") ; if any of the corpuscles happen to be forced within it, they move more slowly than before, rolling lazily along the side of the vessel, and often adhering to its wall. Some- times, when the motion of the blood is not strong, many of the white corpuscles collect in a capillary vessel, and for a time entirely prevent the passage of the red corpuscles. When the peripheral resistance is greatly diminished by the dilatation of the small arteries, so much blood passes on from the arteries into the capillaries at each stroke of the heart, that there is not sufficient remaining in the arteries to distend them. Thus, the intermittent current of the ventricular systole is not converted into a continuous stream by the elasticity of the arteries before the capil- laries are reached ; and so intermittency of the flow occurs both in capillaries and veins, and a pulse is produced there. The same pheno- menon may occur when the arteries become rigid from disease, and when the beat of the heart is so slow or so feeble that the blood at each cardiac systole has time to pass on to the capillaries before the next stroke occurs ; the amount of blood sent out at each stroke is then insufficient to properly distend the elastic arteries. It was formerly supposed that the occurrence of any transudation from the interior of the capillaries into the midst of the surrounding tissues was confined, in the absence of injury, strictly to the fluid part of the blood ; in other words, that the corpuscles could not escape from the circulating stream, unless the wall of the containing blood-vessel was ruptured. Augustus Waller affirmed, in 1846, that he had seen blood-corpuscles, both red and white, pass bodily through the wall of the capillary vessel in which they were contained ; and that, as no opening could be seen before their escape, so none could lie observed aftenvards — so rapidly was the part healed. But these observations did not attract much notice until the phenomenon was rediscovered by Cohnheim in 1867. Cohnheim's experiment was performed in the following manner : A frog is curarised; and the abdomen having been opened, a portion CH. XXL] DIAPEDESIS 295 of small intestine is drawn out, and its transparent mesentery spread out under a microscope. After a variable time, occupied by dilatation, following contraction of the minute vessels and accompanying quickening of the blood-stream, there ensues a retardation of the current, and blood-corpuscles begin to make their way through the capillaries and small vessels. Diapedesis, or emigration of the white corpuscles, occurs to a small extent in health. But it is much increased in inflammation, and may go on so as to form a large collection of leucocytes (i.e. white cor- puscles) outside the vessels. The emigration of red corpuscles is only seen in inflammation, and is a passive process ; it occurs when the holes made by the emigrating leucocytes do not close up immediately, and so the red corpuscles escape too. The real meaning of the process of inflam- mation is a subject which is being much dis- cussed now, but it may be interesting to state briefly the views of Metschnikoff, who has in recent years been a prominent investigator of the subject. Even if these views do not repre- sent the whole truth, it can hardly be doubted that the phenomena described play a very important part in the process. Metschnikoff teaches that the vascular phenomena of inflam- mation have for their object an increase in the emigration of leucocytes, which have the power of devouring the irritant substance, and re- moving the tissues killed by the lesion. They are therefore called jyhagocytes (devouring or scavenging corpuscles). It may be that the microbic influence, or the influence of the chemical poisons they produce, is too powerful for the leucocytes ; then they are destroyed, and the dead leucocytes become pus corpuscles ; but if the leuco- cytes are successful in destroying the foreign body, micro-organisms, and disintegrated tissues, they disappear, wandering back to the blood-vessels, and the lost tissue is replaced by a regeneration of the surrounding tissues.* The circulation through the capillaries must, of necessity, be largely influenced by that which occurs in the vessels on either side of them in the arteries or the veins ; their intermediate position causes them to feel at once any alteration in the size, rate, or pres- * This question is closely related to that of immunity, which is discussed in the chapter on the Blood (Chapter XXVI). Fig. 296.— A large capillary from the frog's mesenteiy eight hours after irrita- tion had been set up, showing emigration of leucocytes, a, Cells in the act of traversing the capillary wall ; b, some already escaped. (Frey.) 296 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. sure of the arterial, and more especially of the venous blood -stream. The apparent contraction of the capillaries, on the application of certain irritating substances, and during fear, and their dilatation in blushing, may be referred primarily to the action of the small arteries. The Venous Flow. The blood-current in the veins is maintained primarily by the vis a tergo, that is, the force behind, which is the blood-pressure trans- mitted from the heart and arteries ; but very effectual assistance to the flow is afforded by the action of the muscles capable of pressing on the veins with valves, as well as by the suction action of the heart, and the aspiratory action of the thorax (vis a fronte). The effect of muscular pressure upon the circulation may be thus explained. When pressure is applied to any part of a vein and the current of blood in it is obstructed, the portion behind the seat of pressure becomes swollen and distended as far back as the next pair of valves, which are in consequence closed (fig. 230, B, p. 220). Thus, whatever force is exercised by the pressure of the muscles on the veins, is distributed partly in pressing the blood onwards in the proper course of the circulation, and partly in pressing it backwards and closing the valves behind. The circulation might lose as much as it gains by such an action, if it were not for the numerous communications which the veins make with one another ; through these, the closing up of the venous channel by the backward pressure is prevented from being any serious hindrance to the circulation, since the blood, the onward course of which is arrested by the closed valves, can at once pass through some anastomosing channel, and proceed on its way by another vein. Thus, the effect of muscular pressure upon veins which have valves, is turned almost entirely to the advantage of the circulation. In the web of the bat's wing, the veins are furnished with valves, and possess the remarkable property of rhythmical contraction and dilatation, whereby the current of blood within them is distinctly accelerated (Wharton Jones). The contraction occurs, on an average, about ten times in a minute ; the existence of valves prevents regur- gitation, so the entire effect of the contractions is auxiliary to the onward current of blood. Analogous phenomena have been observed in other animals. A venous pulse is observed under the conditions previously described (p. 294), when the arterioles are dilated so that the arterial pulse passes through the capillaries to the veins. A venous pulse is also seen in the superior and inferior vena cava near to their entrance into the heart ; this corresponds to varia- tions of the pressure in the right auricle. When the ventricle is con- CH. XXI.] THE VASOMOTOR NERVOUS SYSTEM 297 tracting there is a slow rise due to the fact that the blood cannot get into the ventricle, and so distends the auricle; a second short, sharp elevation of pressure is produced by the auricular systole. Altera- tions of venous pressure are also produced in the great veins by the respiratory movements, the pressure sinking during inspiration, and rising during expiration. The Vaso-Motor Nervous System. The vaso-motor nervous system consists of the vaso-motor centre situated in the bulb, of certain subsidiary vaso-motor centres in the spinal cord, and of vaso-motor nerves, which are of two kinds — (a) those the stimulation of which causes constriction of the vessels ; these are called vaso- constrictor nerves; (b) those the stimulation of which causes dilatation of the vessels ; these are called vaso-clilator nerves. The following names are associated with the history of the subject. The muscular structure of arteries was first described by Henle in 1841 ; in 1852 Brown Se'quard made a study of the vaso-constrictor, or, as he termed them, tonic nerves. The vaso-motor centre was dis- covered by Schiff (1855), and more accurately localised by Ludwig (1871). The dilator nerves were also discovered by Schiff; at first they were termed paretic nerves. Other names which must be mentioned in connection with the subject are those of Claude Bernard, Heidenhain, and, in more recent years, G-askelL Langley, and Eamon J Cajal. The nerves supply the muscular tissue in the walls of the blood- vessels and regulate their calibre, but exert their most important action in the vessels which contain relatively the greatest amount of muscular tissue, namely, the small arteries or arterioles. Under ordinary circumstances, the arterioles are maintained in a state of moderate or tonic contraction, and this constitutes the peripheral resistance, the use of which is to keep up the arterial pressure, which must be high enough to force the blood through the capillaries and veins in a continuous stream back to the heart. Another function which is served by this muscular tissue is to regulate the amount of blood which flows through the capillaries of any organ in proportion to its needs. During digestion, for instance, it is necessary that the digestive organs should be supplied with a large quantity of blood : for this purpose the arterioles of the splanchnic area are relaxed, and there is a vast amount of blood in this area, and therefore a correspondingly small amoimt in other areas, such as the skin ; this accounts for the sensation of chilliness experienced after a full meal. The skin vessels form another good example ; one of the most important uses of the skin is to get rid of the heat of 298 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXI. the body in such a way that the body temperature shall remain constant; when excess of heat is produced there is also an increase in the loss of heat; the skin vessels are then dilated, and so more blood is exposed on the surface, and thus an increase in the radiation of heat from the surface is brought about. On the other hand, when it is necessary that the heat produced should be kept in the body, the loss of heat is diminished by a constriction of the skin vessels, as in cold weather. The alteration of the calibre of the vessels is brought about by the action of the vaso-motor nervous system on the muscular tissue of the arterioles. There are certain organs of the body in which the necessity for alterations in their blood-supply does not exist. Such organs are the lungs and the brain. It is in the vessels of these organs that the influence of vaso-motor nerves is at a minimum. The pulmonary vessels are stated by Bradford and Dean to be supplied by nerves which leave the cord in the upper thoracic region ; but on stimulating these the rise of pressure produced is extremely small ; it is very doubtful if the fibres in question are really vaso-constrictors ; the small rise observed may be partly or even wholly due to the accelera- tion of the heart, which is another result of stimulating these nerve- roots. The vaso-motor centre lies in the grey matter of the floor of the fourth ventricle ; it is a few millimetres in length, reaching from the upper part of the floor to within about 4 mm. of the calamus scrip- torius. The position of this centre has been discovered by the following means : when it is destroyed the tone of the small vessels is no longer kept up, and in consequence there is a great and universal fall in arterial blood-pressure; when it is stimulated there is an increase in the constriction of the arterioles all over the body, and therefore a rise of arterial blood-pressure. Its upper and lower limits have been accurately determined in the following way : a series of animals is taken, and the central nervous system divided in a different place in each ; the cerebrum and cerebellum may be cut off without affecting blood-pressure, the vaso-motor centre must therefore be below these; if the section is made just above the medulla, the blood-pressure still remains high, and it is not till the upper limit of the centre is passed that the blood-pressure falls. Similarly, in another series of animals, if the cervical cord is cut through, and the animal kept alive by artificial respiration, there is an enormous fall of pressure due to the influence of the centre being removed from the vessels; in other experiments the section is made higher and higher, and the same result noted, until at last the lower limit of the centre is passed, and the fall of pressure is less and less marked the higher one goes there, until in the animal in which the section is made at the upper boundary of the centre the blood- CH. XXI.] VASOMOTOR NERVES 299 pressure is not affected at all, and the centre can be influenced reflexly by the stimulation of afferent nerves, the pressor and depressor nerves, which we shall be considering immediately. After the destruction of the vaso-motor centre in the bulb, there is a fall of pressure. If the animal is kept alive, the vessels after a time recover their tone, and the arterial pressure rises ; it rises still more on stimulating the central end of a sensory nerve ; this is due to the existence of subsidiary vaso-motor centres in the spinal cord ; for on the subsequent destruction of the spinal cord the vessels again lose their tone and the blood-pressure sinks. The vaso-motor path is down the lateral column of the spinal cord, and the fibres terminate by arborising around the cells in the grey matter of the subsidiary vaso-motor centres, the anatomical position of which is uncertain, though it is probably in the cells of the intermedio-lateral tract. From these cells fresh axis-cylinder processes originate, which pass out as the small medullated nerve- fibres in the anterior roots of the spinal nerves. The vaso-constrictor nerves for the whole body leave the spinal cord by the anterior roots of the spinal nerves from the second thoracic to the second lumbar, both inclusive. They leave the roots by the white rami communicantes, and pass into the ganglia of the sympathetic chain, which lies on each side along the front of the vertebral column. The ganglia on this chain (the lateral ganglia of G-askell) may also be called the chain of vaso-motor ganglia, because here are situated cell stations on the course of the vaso-constrictor nerves for the head, trunk and limbs. That is to say, the small medullated nerve-fibres terminate by arborising around the cells of these ganglia, and a fresh relay of axis-cylinder processes from these cells carry on the impulses. The next figure (fig. 297) represents diagrammatically how this occurs. The sheaths of the fibres are not represented. The cell station of any particular fibre is not necessarily situated in the first ganglion to which it passes ; the fibres of the white ramus communicans of the second thoracic do not, for instance, all have their cell stations in the corresponding thoracic ganglion, but may pass upwards or downwards in the chain to a more or less distant ganglion before they terminate by arborising around a cell or cells. The vaso-constrictor nerves, however, have all cell stations some- where in the sympathetic system, and the new axis-cylinders that arise from the cells of the ganglia differ from those which terminate there in the circumstance that they do not possess a medullary sheath, but they are pale, grey, or non-medullated fibres. Those which are destined for the supply of the vessels of the head and neck pass into the ganglion stellatum or first thoracic ganglion, thence through the annulus of Vieussens to the inferior cervical ganglion, and thence 300 THE CIRCULATION IN THE BLOOD-VESSELS [OH. XXI. along the sympathetic trunk to their destination. Their cell station is in the superior cervical ganglion. Those for the body wall and limbs pass back from the sympathetic ganglia to the spinal nerves by the grey rami communicantes, and are distributed with the other spinal nerve-fibres. The cell stations for the upper limb fibres are in the ganglion stellatum, and for the lower limb fibres in the lower lumbar and upper sacral ganglia. Those for the interior of the body pass into the various plexuses Pig. 297. — Transverse section through half the spinal cord, showing the ganglia. A, anterior coniual cells ; B, axis-cylinder process of one of these going to posterior root ; C, anterior (motor) root ; D, posterior (sensory) root ; B, spinal ganglion on posterior root ; F, sympathetic ganglion; G, ramus communicans; H, posterior branch of spinal nerve; I, anterior branch of spinal nerve; a, long collaterals from posterior root fibres reaching to anterior horn ; &, short collaterals passing to Clarke's column ; c, cell in Clark's column sending an axis-cylinder (d) process to the direct cere- bellar tract ; e, fibre of the anterior root ; /, axis-cylinder from sympathetic ganglion cell, dividing into two branches, one to the periphery, the other towards the cord ; g, fibre of the anterior root terminating by an arborisation in the sympathetic ganglion ; h, sympathetic fibre passing to peri- phery. (Ramon y Cajal.) of sympathetic nerves in the thorax and abdomen, and are distributed to the vessels of the thoracic and abdominal viscera. This set includes the most important vaso-motor nerves of the body, the splanchnics. Their cell stations are situated in the various ganglia of the abdominal plexuses. The vaso-dilator nerves in part accompany those just described, but they are not limited to the outflow from the second thoracic to the second lumbar. Thus, the nervi erigentes originate as white CH. XXI.] VASO-MOTOE NEKVES 301 rami communicantes from the second and third sacral nerves, and the chorda tympani, another good example of a vaso-dilator nerve, is a branch of the seventh cranial nerve. Bayliss has also shown that the posterior root fibres may act as vaso-dilators (see p. 303). All vaso-motor nerves, whether they are constrictor or dilator, differ very markedly from the spinal nerve-fibres which are distri- buted to voluntary muscles in being ganglionated ; that is, in having cell stations or positions of relay on their course from the central nervous system to the muscular fibres they supply. The existence of cell stations between the central nervous system and the muscular fibres is not confined to the nerves of blood-vessels, but is found also in the nerves which supply the heart and other viscera. Moreover, the nerves which supply the voluntary muscles are motor in function ; inhibitory fibres to the voluntary muscles of vertebrates do not exist. But in the case of the involuntary muscles there are usually the two sets of nerve-fibres with opposite functions. In the case of the heart, we have an accelerator set which course through the sympathetic, and an inhibitory set which course through the vagus. In the case of the vessels, we have an accelerator set, which we have hitherto called vaso-constrictors, and an inhibitory set we have been calling vaso-dilators. In the case of the other contractile viscera, we have also viscero- accelerator and viscero-inhibitory, which respectively hasten and lessen their peristaltic movements. Adopting G-askell's nomenclature, we may further term the accelerator groups of nerves katabolic, as they increase the activity of the muscles they supply, bringing about an increase of wear and tear, and an increase in the discharge of waste material. The inhibitory nerves, on the other hand, are anabolic, as they produce a condition of rest in the tissues they supply, and so give an oppor- tunity for repair or constructive metabolism. The distribution of the vaso-motor nerves and the viscero-motor nerves has been within recent years very thoroughly worked out by Langley. The nerves of the various viscera we shall take with the individual organs. In all these cases, there is a cell station somewhere in the sympathetic system, and only one for each nerve- fibre. The preganglionic fibres {i.e., the fibres from the spinal cord to the sympathetic cell station) are usually medullated ; the postgang- lionic fibres {i.e., those that leave the ganglion) are usually non- medullated. But this histological distinction, so much emphasised by Gaskell, is not without exceptions, and the localisation of cell stations is made with far greater certainty by Langley's nicotine 302 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXL method. Nicotine in small doses paralys \s nerve-cells,* but not nerve-fibres; if the drug is injected into an animal, stimulation of the anterior nerve-roots produces no movements of the involuntary muscles, because the paralysed cell stations on the course of the nerve-fibres act as blocks to the propagation of the impulses. If the nicotine is applied locally by painting it over one or more ganglia, there will be a block in those fibres only which have their cell stations in those particular ganglia. Thus, in the lateral chain of ganglia we find the cells on the course of the pilo-motor nerves (i.e., to the muscles of the hairs), of the vaso-constrictors of the head, limbs, and body walls, and possibly of the splenic nerves. In the col- lateral ganglia (i.e., coeliac, mesenteric, etc.) are found, amongst others, the cells on the course of the splanchnic nerves, of the nerves to sweat glands, of the cardiac accelerators, and of the inhibitory fibres of the alimentary canal ; while in the terminal ganglia are placed, among others, the cells on the course of the cardiac inhibi- tory nerves, of the motor fibres to the lower part of the intestine and bladder, and of the inhibitory fibres to the external genital organs. We may now ask what is the object that is served by the existence of ganglia on the course of these nerves. It appears to be a means of distributing nerve- fibres to a vast area of muscular tissue by means of a comparatively small number of nerve-fibres that leave the central nervous system ; for each fibre that leaves the central nervous system arborises around a number of cells, and thus the impulse it carries is transferred to a large number of new axis-cylinder processes. In some cases, it is true, a single nerve-fibre will divide into multitudinous branches to accomplish the same object (as in the supply of the electric organ of Malapterurus, the fibres to the millions of its subdivisions all originating from a single axis-cylinder), but the usual way appears to be a combination of this method with that of subsidiary cell-stations. At one time a ganglion was supposed to be the normal centre for reflex action. The submaxillary ganglion was the battle-field in which this question was fought out in Claud Bernard's time. In the later researches of Langley and Anderson, the only instances where such a thing seemed possible were the following: — When all the nervous connections of the inferior mesenteric ganglion are divided except the hypogastric nerves, stimulation of the central end of one hypogastric causes contraction of the bladder, the efferent path to which is the other hypogastric nerve. In addition, they observed an apparent reflex excitation of the nerve sup- plying the erector muscles of the hairs (pilo-motor nerves) through other sympa- thetic ganglia. In neither case is the action truly reflex, but is caused by the stimulation of the central ends of motor-fibres which issue from the spinal cord, and which after passing through the ganglion send branches down each hypogastric nerve. The experiment is in fact similar to Kiihne's gracilis experiment (p. 173). It certainly is the case that under normal circumstances, the centres for reflex action are in the central nervous system. But there do appear to be some condi- tions in which it is possible for ganglia to assume this function. The recovery * It is still a matter of uncertainty whether this drug acts upon the nerve-cells themselves, or the terminal arborisations (synapses) of the nerve-fibres that surround them. Before the paralytic effect of nicotine comes on, it excites the nerve-cells, and thus in the case of the blood-vessels causes a general constriction of the arterioles and a rise of arterial pressure. CH. XXI.] THE VASO-MOTOR CENTRE 303 of vasomotor tone, and of tone in certain viscera after destruction of extensive tracts of the spinal cord, or the persistence of peristaltic action in the intestine after cutting through all its nerves, are cases in point. (See further, under Intestinal Movements, and Spinal Visceral Reflexes). The observations of W. M. Bayliss on the vaso-diiator nerves of dogs are of considerable interest. He could find no vaso-dilator fibres to the hind limb in the abdominal sympathetic chain ; but the only fibres excitation of which produced vascular dilatation there, are contained in the posterior roots. He also found fibres in the posterior roots of the 12th and 13th thoracic nerves, which act as vaso-dilators of the small intestine. Not only is vaso-dilatation the result of mechanical, electri- cal, or thermal stimulation of these roots, but experiments are adduced which show that in normal reflexes, such as occur when the depressor nerve is stimulated, the dilator impulses travel by the same route. This raises the question whether the posterior roots contain true efferent fibres. ■ The facts of degeneration show that they do not. Bayliss is therefore driven to the conclusion that the same nerve terminations in the periphery serve both to take up sensory impressions, and to convey inhibitory impulses to the muscular structures in which they end. In other words, we have here another example which may be added to those previously mentioned (p. 173), that nerve-fibres may convey impulses in both directions. The term antidromic is used by Bayliss to express the fact that impulses may travel in the reverse direction to that in which they usually pass. The Vasomotor centre can be excited directly, as by induc- tion currents; the result is an increase- of arterial blood -pressure owing to an increase of the contraction of the peripheral arterioles. It can also be excited by the action of poisons in the blood which circulates through it ; thus, strophanthus or digitalis causes a marked rise of general arterial pressure due to the constriction of the peri- pheral vessels brought about by impulses from the centre. It is also excited by venous blood, as in asjjhyxia ; the rise of blood-pressure which occurs during the first part of asphyxia is due to constriction of peripheral vessels ; the fall during the last stage of asphyxia is largely due to heart failure. We shall study asphyxia more at length in connection with respiration. During the period of decreased pressure, waves are often observed on the blood-pressure curve which arise from a slow rhythmic action of the vaso-motor centre. The centre alternately sends out stronger and weaker con- strictor impulses. They are known as the Traubc-Hering waves, and are much slower in their rhythm than the waves on the tracing which are due to respiration. They are not peculiar to asphyxia, but are frequently seen in tracings from normal animals. Fig. 298 represents tracings obtained from a dog under the influence of morphine and curare. The upper curve, taken while artificial respira- tion was being carried on, shows the three sets of waves, first the oscillations due to the heart-beats, next in size those due to the respiratory movements, which in their turn are superposed on the prolonged Traube-Hering waves. The lower tracing was taken immediately after the cessation of the artificial respiration, and shows only the heart-beats and the Traube-Hering waves. The Vaso-motor centre may be excited reflexly. — The afferent 304 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. Fig. 298. — Arterial blood-pressure tracings showing Traube-Hering waves. (Starling.) Fig. -299. —Result on arterial blood-pressure curve of stimulating the central end of cut sciatic nerve in rabbit, up, blood-pressure; a, abscissa or base line; t, time in seconds; e, signal of period of excitation of the nerve. CH. XXI.] PEESSOK AND DEPRESSOR NERVES 305 impulses to the vaso-motor centre may be divided into pressor and depressor. Most sensory nerves are pressor nerves. The sciatic or the vagus nerves may be taken as instances ; when they are divided and their central ends stimulated, the result is a rise of blood-pressure due to the stimulation of the vaso-motor centre, and a consequent constric- tion of the arterioles all over the body, but especially in the splanchnic area. Fig. 299 shows the result of such an experiment. It is necessary in performing such an experiment to administer curare as well as an anaesthetic to the animal, in order to obviate reflex muscular struggles, which would themselves produce a rise in arterial pressure. Many sensory nerves also contain depressor fibres which produce the opposite effect. The most marked bundle of these is known as the depressor nerve. In most animals this is bound up in the trunk of the vagus ; but in some, like the rabbit, cat, and horse, the nerve runs up as a separate branch from the heart (or, according to some recent observations, from the commencement of the aorta), and joins the vagus or its superior laryngeal branch, and ultimately reaches the vaso-motor centre. When this nerve is stimulated (the vagi having been previously divided to prevent reflex inhibition of the heart), a marked fall of arterial blood-pressure is produced (see fig. 300). Stimulation of this nerve affects the vaso-motor centre in such a way that the normal constrictor impulses that pass down the vaso-con- strictor nerves are inhibited. The fall of pressure is very slight after section of the splanchnic nerves, showing that the splanchnic area is the part of the body most affected. The normal function of this nerve is to adapt the peripheral resistance to the heart's action : if the constriction of the arterioles is too high for the heart to overcome, an impulse by this nerve to the vaso-motor centre produces reflexly a lessening of the peripheral resistance. N.B. — The term depressor should be carefully distinguished from inhibitory; stimulation of the peripheral end of the vagus produces a fall of blood-pressure due to inhibition (slowing or stoppage) of the heart (see figs. 277 and 278) ; stimulation of the central end of the depressor nerve produces a lowering of blood-pressure for a different reason, namely, a reflex relaxation of the splanchnic arterioles. Experiments on Vaso-motor nerves. — The experiments on the vaso-motor nerves are similar to those performed on other nerves when one wishes to ascertain their functions. They consist of section and excitation. Section of a vaso-constrictor nerve, such as the splanchnic, causes a loss of normal arterial tone, and consequently the part supplied by the nerve becomes flushed with blood. Stimulation of the peripheral end causes the vessels to contract and the part to become compara- tively pale and bloodless. This can be very readily demonstrated on U 30G THE CIRCULATION EN THE BLOOD- VESSELS [CH. XXI. the ear of the rabbit. This is a classical experiment associated with the name of Claude Bernard. Division of the cervical sympathetic produces an increased redness of the side of the head, and looking at the ear, the transparency of which enables one to follow the phenomena easily, the central artery with its branches is seen to become larger, and many small branches not previously visible come into view. The ear feels hotter, though this effect soon passes off as the exposure of a large quantity of blood to the air causes a rapid loss of heat. On stimulating the peripheral end of the cut nerve, the ear resumes its normal condition, and then becomes paler than usual owing to exces- sive constriction of the vessels. The first part of the experiment, the dilatation following section, can be demonstrated in a very simple way, by pressing the thumb- Fio. 300. — Tracing showing.the effect on blood-pressure of stimulating tlie central end of the Depressor nerve in the rabbit. To be read from right to left. T, indicates the rate at which the recording- surface was travelling, the intervals correspond to seconds ; C, the commencement of faradisation of the nerve ; O, moment at which excitation was discontinued. The effect is some time in develop- ing, and lasts after the current has been taken off. The larger undulations are the respiratory curves ; the pulse oscillations are very small. (Foster.) nail forcibly on the nerve where it lies by the side of the central artery of the ear. Section of a vaso-dilator nerve, such as the chorda tympani, pro- duces no effect on the vessels, but stimulation of its peripheral end causes great enlargement of all the arterioles, so that the submaxillary gland and the neighbouring parts supplied by the nerve become red and gorged with blood, and the pulse is propagated through to the veins ; the circulation through the capillaries is so rapid that the blood loses very little of its oxygen, and is therefore arterial in colour in the veins. Another effect, free secretion of saliva, we shall study in connection with that subject. Other examples of vaso-dilator nerves are the nervi erigentes to the erectile tissue of the penis, etc., and of the lingual nerve to the vessels of the tongue. CH. XXI.] PLETHYSMOGRAPHY 307 It is, however, probable that all the vessels of the body receive both constrictor and dilator nerves. But the presence of the latter is difficult to determine unless they are present in excess ; if they are not, stimulation affects the constrictors most. The effect of section is also inconclusive ; for if a mixed nerve is cut, the only effect observed is a dilatation due to removal of the tonic constrictor influence. To solve this difficult problem, three methods are in use : — 1. The method of degeneration. — If the sciatic nerve is cut, the vessels of the limb dilate. This passes off in a day or two. If the peripheral end of the nerve is then stimulated, the vessels are dilated, as the constrictor fibres degenerate earliest, and so one gets a result due to the stimulation of the still intact dilator fibres. 2. The method of slowly interrupted shocks. — If a mixed nerve is stimulated with the usual rapidly interrupted faradic current, the effect is constriction ; but if the induction shocks are sent in at long intervals (e.g., at intervals of a second), vaso-dilator effects are obtained. This can be readily demonstrated on the kidney vessels by stimulation of the anterior root of the eleventh thoracic nerve in the two ways just indicated. By studying the rate of flow of the blood through the submaxillary gland, in which the vaso-constrictor and dilator fibres run separate courses, it has been shown that if both sets of fibres are simultane- ously excited, constriction is produced during the stimulation, while marked dilatation follows after the stimulation has ceased. Excitation of the constrictors alone is not followed by dilatation. These results explain the mode of action of slowly interrupted shocks, for with each there will only be a very slight constriction, while the dilator effects which run a much slower course will be summed up to produce a marked effect. 3. The influence of temperature. — Exposure to a low temperature depresses the constrictors more than the dilators. If the leg is placed in ice-cold water, stimulation of the sciatic, even if it has only been recently divided, produces a flushing of the skin with blood. Plethysmography. The action of vaso-motor nerves can be studied in another way than by the use of various forms of manometer, which is the only method we have considered so far. The second method, which is often used together with the manometer, consists in the use of an instrument which records variations in the volume of any limb, or organ of an animal. Such an instrument is called a plethysmograph. One of these instruments applied to the human arm is shown in the accompanying figure (fig. 301). Every time the arm expands with every heart's systole, a little 308 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXL of the iluid in the plethysmograph is expelled and raises the lever. Variations in volume due to respiration are also seen in the tracing. An air plethysmograph connected to a sensitive recorder gives equally good results. The same instrument in a modified form applied to such organs as the spleen and kidney is generally called an oncometer, and the recording part of the apparatus, the oncograph. These instruments we owe to Eoy, and the next two figures represent respectively sections of the kidney oncometer and oncograph. An oncometer consists of a metal capsule, of shape suitable to enclose the organ : its two halves are jointed together, and fit accurately except at one opening which is left for the vessels of the organ. A delicate membrane is attached to the rim of each half, the Flo. 301. — Plethysmograph. By means of this apparatus, the alteration in volume of the arm, e, whi( h is enclosed in a glass tube, a, filled with fluid, the opening through which it passes being firmly closed by a thick gutta-percha bmd.F, is communicated to the lever, r>, and registered by arecording apparatus. The fluid in a communicates with that in b, the upper limit of which is above that in a. The chief alterations in volume are due to alteration in the blood contained in the arm. When the volume is increased, fluid passes out of the glass cylinder, and the lever, d, also is raised, and when a decrease takes place the fluid returns again from b to a. It will therefore be evident that the apparatus is capable of recording alterations of the volume of blood in the arm. space between which and the metal is filled with warm oil. The tube from the oncometer is connected to the oil-containing cavity of the oncograph by a tube also containing oil. An increase in the volume of the organ squeezes the oil out of the oncometer into the oncograph, and so produces a rise of the oncograph piston and lever; a contraction of the organ produces a fall of the lever. Very good results are obtained by using saline solution instead of oil; and Schafer has shown in connection with the spleen that a spleen box of simple shape covered with a glass plate, made air-tight with vaseline, and communicating by a tube with a Marey's tambour, gives a far more delicate record of the splenic alterations of volume than the oil oncometer. Tf now we are investicjatimj' the action of the anterior root of CH. XXI.] THE ONCOMETER 309 eleventh thoracic nerve on the vessels of the kidney, a tracing is taken simultaneously of the [arterial blood-pressure in the carotid, and of . 302. — Diagram of Boy's Oncometer, a, represents the kidney enclosed in a metal box, which opens by hinge /; b, the renal vessels and duct. Surrounding the kidney are two chambers formed by membranes, the edges of which are firmly fixed by being clamped between the outside metal capsule, and one (not represented in the figure) inside, the two being firmly screwed together by screws at h, and below. The membranous chamber below is filled with a varying amount of warm oil, according to the size of the kidney experimented with, through the opening, then closed with the plug i. After the kidney has been enclosed in the capsule, the membranous chamber above is filled with warm oil through the tube c, which is then closed by a tap (not represented in the diagram) ; the tube d communicates with a recording apparatus, and any alteration in the volume of the kidney is communicated by the oil in the tube to the chamber d of the Oncograph, fig. 303. Fig. 303.— Roy's Oncograph, or apparatus for recording alterations in the volume of the kidney, etc., as shown by the oncometer— a, upright, supporting recording lever I, which is raised or lowered by needle b, which works through/, and which is attached to the piston e, working in the chamber d, with which the tube from the oncometer communicates. The oil is prevented from being squeezed out as the piston descends by a membrane, which is clamped between the ring-shaped surfaces of cylinder by the screw i working upwards ; the tube h is for filling the instrument. the volume of the kidney by the oncometer. On stimulating the nerve rapidly, there is a slight rise of arterial pressure, but a large 310 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXI. fall of the oncograph lever, showing that the kidney has diminished in volume. It is evident that there must be an active contraction of the arterioles of the kidney, causing it to diminish in size, for the blood-pressure tracing (which is taken as a control to be sure the changes are not otherwise produced) shows that there is no failure of the heart's activity to account for it. We shall return to the subject of the oncometer in connection with the spleen and the kidney. We may, however, say in passing what a very important experimental method plethysmography is becoming. Since the introduction of air oncometers, the method is remarkably easy to apply, and it is now part of the routine practice of physiologists, when they are investigating the action of a drug, or of a nerve, on any organ, to record its volume changes by the plethysmography method. Thus, the salivary glands, lobes of the liver or lung, the limbs, the kidney, spleen, a coil of intestine, etc., can all be easily enclosed in an appropriately shaped gutta-percha box, covered with a glass plate made air-tight with vaseline. There are always two openings to such a box, one to allow the vessels and nerves to enter (leakage of air around these is prevented by packing with cotton-wool soaked in vaseline) ; the other opening is filled up with a piece of glass tubing which is connected by an indiarubber tube to the recording apparatus. The most delicate of the volume recorders is the bellows-recorder of Brodie (see p. 152) and the piston recorder of Hiirthle; a Marey's tambour is not so sensitive, and, moreover, it is a recorder of pressure rather than of volume only. Of all the oncometers, I am inclined to believe that the intestinal oncometer is the most instructive, because the coil of intestine under observation gives a truer record of what is occurring in that important area called the splanchnic area, than any other abdominal organ. Pathological Conditions. The vaso-motor nervous system is influenced to some extent by conditions of the cerebrum, some emotions, such as fear, causing pallor (vaso-constriction), and others causing blushing (vaso- dilatation). It is almost impossible to over-estimate the importance of the study of vaso-motor phenomena, as a means of explaining certain pathological conditions ; our knowledge of the processes concerned in inflammation is a case in point. Disorders of the vessels due to vaso-motor disturbances are generally called angio-neuroses. Of these we may mention the following : — Tache cerebrate is due to abnormal sensitiveness of the vascular nerves ; drawing the finger-nail across the skin causes an immediate wheal, or at least a red mark that lasts a considerable time. At one CH. XXI.] CIRCULATION IN THE BRAIN 311 time this was considered characteristic of affections of the cerebral meninges like tubercular meningitis, and was consequently called the " meningeal streak." It, however, occurs in a variety of pathological conditions of the nervous system, both cerebral and spinal. In certain conditions which lead to angina pectoris the pain in the heart is in part due to its being unable to overcome an immense peripheral resistance, and the condition is relieved by the adminis- tration of drugs like amyl-nitrite or nitro-glycerin, which relax the vessels and cause universal blushing. Raynaud's disease is one in which there is a localised constriction of the vessels which is so effectual as to entirely cut off the blood supply to the capillary areas beyond, and if this lasts any considerable time may lead to gangrene of the parts in question. Local Peculiarities of the Circulation. The most remarkable peculiarities attending the circulation of blood through different organs are observed in the cases of the brain, erectile organs, lungs, liver, spleen, and kidneys. In the Brain. — The brain must always be supplied with blood, for otherwise im- mediate loss of consciousness would follow. Hence, to render accidental oblitera- tion almost impossible, four large arteries are supplied to the brain, and these anas- tomose together in the circle of Willis. The two vertebral arteries are, moreover, protected in bony canals. Two of the brain arteries can be tied in monkeys, and three or even all four in dogs, without the production of serious symptoms. In the last case enough blood reaches the brain by branches from the superior intercostal arteries to the anterior spinal artery. The sudden obliteration of one carotid artery in man may in some cases produce epileptiform spasms ; the sudden occlusion of both occasions loss of consciousness. Uniformity of supply is further ensured by the arrangement of the vessels in the pia mater, in which, previous to their distribu- tion to the substance of the brain, the large arteries break up and divide into innumerable minute branches ending in capillaries, which, after frequent communi- cation with one another, enter the brain and carry into nearly every part of it uni- form and equable streams of blood. The arteries are enveloped in a special lymphatic sheath. The arrangement of the veins within the cranium is also peculiar. The large venous trunks or sinuses are formed so as to be scarcely capable of change of size ; and composed, as they are, of the tough tissue of the dura mater, and, in some instances, bounded on one side by the bony cranium, they are not compres- sible by any force which the fulness of the arteries might exercise through the sub- stance of the brain ; nor do they admit of distension when the flow of venous blood from the brain is obstructed. No valves are placed between the vertebral veins and the vena cava ; the vertebral veins anastomose with the cerebral sinuses. Hence on squeezing the thorax and abdomen, venous blood can be pressed from those parts out of any opening made into the longitudinal sinus. Expiration acts in the same way ; it raises the cerebral venous pressure ; if the skull wall is defective the brain expands owing to the distension of its capillaries during the expiratory act. The exposed brain also expands with each systole of the heart. Owing to the fact that the brain lies enclosed in the cranium, the arterial pulse is transmitted through the brain substance to the cerebral veins, and so the blood issues from these in pulses. Since the brain is enclosed in the rigid cranium the volume of blood in the cerebral vessels cannot alter unless the volume of the other cranial contents alters in the opposite sense. These conditions of the brain and skull led Monro and Kellie many years ago to advance the opinion that the quantity of blood in the brain must be the same at all times. This doctrine has been frequently disputed, and many have advanced the theory that increase or diminution of the blood is accompanied with simultane- 312 THE CIRCULATION IN THE BLOOD-VESSELS [en. XXI. ous diminution or increase of the cerebro-spinal fluid, so that the contents of the cranium are kept uniform in volume. But the recent work of Leonard Hill has shown that the Monro-Kellie doctrine is in the main true. Histological evidence has recently been obtained of the existence of nerve plexuses round the pial arteries. The arteries arc muscular, and the nerves therefore are most probably vaso-motor in function. Experimental evidence so far, however, has not estab- lished that the action of these nerves is a marked one* ; the cerebral circulation passively follows the slightest changes in aortic and, more especially, vena cava pressure, and no active vaso-motor change has been conclusively proved. The velocity of blood -flow through the brain is thus influenced markedly by the con- dition of the vessels of the splanchnic area. If the tone of the skeletal muscles and that of the vessels be suddenly inhibited by fear, or temporarily destroyed by shock the blood will drop owing to its weight into the dilated and supported vessels in the most dependent parts of the body. The flow of blood through the brain will, under these conditions, cease, that is to say, so long as the body is in the erect posture. Thus, to restore a fainting person the head must be lowered between the knees. Muscular exercise, by returning blood to the heart from the veins of the lower parts of the body, conduces to the maintenance of an efficient cerebral circulation. It is not the volume of the blood but the velocity of flow which is altered in the brain by changes in the general circulation. The brain with its circulating blood almost entirely fills the cranial cavity in the living animal ; that is, there is no more cerebro-spinal fluid there than is sufficient to moisten the membranes. Cerebro-spinal fluid escapes into the veins at any pressure above the cerebral venous pressure ; the tension of this fluid and the pressure in the veins are therefore always the same. The fluid probably transudes from the vascular fringes of the choroid plexuses in the ventricles of the brain, and is absorbed by the pial veins. There is not enough of this absorbable fluid present to allow of more than a slight increase of the volume of blood in the brain. If the aortic pressure rises and the vena cava pressure remains constant the conditions in the brain are as follows : — More blood in the arteries, less in the veins, increased velocity of flow. While if the aortic pressure remains constant and the vena cava pressure rises, the conditions are : — Less blood in the arteries, more in the veins, diminished velocity of flow. The brain presses against the cranial wall with a pressure equal to that in the cerebral capillaries. A foreign body introduced within the cranium, such as a blood-clot or depressed bone, produces local anaemia of the brain, by occupying the room of the blood. So soon as the capillaries are thus obliterated the pressure is raised to arterial pressure. This local increase of cerebral tension cannot be trans- mitted by the cerebro-spinal fluid, because this fluid can never be retained in the meningeal spaces at a tension higher than that of the cerebral veins, but is immediately re-absorbed. The anatomical arrangements of the tentorium cerebelli and the falciform ligaments are such as to largely prevent the transmission through the brain-substance of a local increase of pressure. There is complete pressure discontinuity between the cranial and vertebral cavities. The serious results that follow cerebral compression are primarily due to obliteration of the blood-vessels, and consequent anaemia of the brain. A very small foreign body will, if situated in the region of the bulb, produce the gravest symptoms. For the centres which control the vascular and respiratory systems are rendered anaemic thereby. The cerebral hemispheres may, on the other hand, be compressed to a large extent without causing a fatal result. The major symptoms of compression arise as soon as any local increase of pressure is transmitted to the bulb and causes anaemia there. In Erectile Structures. — The instances of greatest variation in the quantity of blood contained, at different times, in the same organs, are found in certain structures which, under ordinary circumstances, are soft and flaccid, but, at certain times, receive an unusually large quantity of blood, become distended and swollen * The only experimental evidence yet adduced as to the functional activity of these nerves is con- tained in the work of Ferrier and Brolie. They jierfused dehbrinated blood through a recently excised brain, and found that the addition of adrenalin to the blood always produced constriction of the vessels and a lessened blood flow. CH. XXI. J ERECTILE STRUCTURES 313 by it, and pass into the state which has been termed erection. Such structures are the corpora cavernosa and corpus spongiosum of the penis in the male, and the clitoris in the female ; and, to a less degree, the nipple of the mammary gland in both sexes. The corpus cavernosum penis, which is the best example of an erectile structure, has an external fibrous membrane or sheath ; and from the inner surface of the latter are prolonged numerous fine lamellee which divide its cavity into small compartments. Within these is situated the plexus of veins upon which the peculiar erectile property of the organ mainly depends. It consists of short veins which very closely interlace and anastomose with each other in all directions, and admit of great variations of size, collapsing in the passive state of the organ, but capable of an amount of dilatation which exceeds beyond comparison that of the arteries and veins which convey the blood to and from them. The strong fibrous tissue lying in the intervals of the venous plexuses, and the external fibrous membrane or sheath with which it is connected, limit the distension of the vessels, and during the state of erection, give to the penis its condition of tension and firm- ness. The same general condition of vessels exists in the corpus spongiosum urethrae, but around the urethra the fibrous tissue is much weaker than around the body of the penis, and around the glans there is none. The venous blood is returned from the plexuses by comparatively small veins. For all these veins one condition is the same ; namely, that they are liable to the pressure of muscles when they leave the penis. The muscles chiefly concerned in this action are the erector penis and accelerator urinse. Erection results from the distension of the venous plexuses with blood. The principal exciting cause in the erection of the penis is nervous irritation, originating in the part itself, and derived reflexly from the brain and spinal cord. The nervous influence is communicated to the penis by the pudic nerves, which ramify in its vascular tissue ; and after their division the penis is no longer capable of erection. Erection is not complete, nor maintained for any time except when, together with the influx of blood, the muscles mentioned contract, and by compressing the veins, stop the efflux of blood, or prevent it from being as great as the influx. The circulation in the Lungs, Liver, Spleen and Ividneys will be described in our study of those organs. Sphygmometers. The disadvantage which the Hill-Barnard sphygmometer (p. 292) possesses, is that in order to press it upon the radial artery, the base of the elastic bag no longer possesses its usual curvature, and thus some of the pressure recorded is employed in an attempt to reduce the deformation of the shape of the bag : the pressure recorded is thus too high. A better instrument is the modification of the Riva Rocci apparatus devised by C. J. Martin. It consists of an elastic bag about three inches wide, which is wrapped around the arm, covered with a sheet of lead and firmly strapped on. Air is forced into the bag by a tube leading from a simple pump ; this tube is also connected by a side branch to a mercury manometer. As one continues to pump and distend the bag, the pressure on the arm is increased until a point is reached when the pulse at the wrist is no longer felt. The pressure necessary to do this is equal to the systolic pressure, and is simultaneously registered by the manometer. CHAPTEK XXII LYMPH AND LYMPHATIC GLANDS As the blood circulates through the capillary blood-vessels, some of its liquid constituents exude through the thin walls of these vessels, carrying nutriment to the tissue elements. This exudation is called lymph; it receives from the tissues the products of their activity, and is collected by the lymph channels, which converge to the thoracic duct — the main lymphatic vessel — and thus the lymph once more re-enters the blood-stream near to the entrance of the large systemic veins into the right auricle. Lymph is a fluid, which comes into much more intimate relation- ship with metabolic processes in the tissues than the blood ; in fact, there is only one situation — the spleen — where the blood comes into actual contact with the elements — that is, cells, fibres, etc. — of a tissue. Composition of Lymph. Lymph is alkaline; its specific gravity is about 1015, and after it leaves the vessels it clots, forming a colourless coagulum of fibrin. It is like blood-plasma in composition, only diluted so far as its proteid constituents are concerned. This is due to the fact that proteids do not pass readily through membranes. The proteids present are called fibrinogen, serum globulin, and serum albumin ; these we shall study with the blood-plasma. The salts are similar to those of blood-plasma, and are present in the same proportions. The waste products, like carbonic acid and urea, are more abundant in lymph than in blood. The total amount of solids dissolved in lymph is about 6 per cent., more than half of which is proteid in nature. When examined with the microscope the transparent lymph is found to contain colourless corpuscles, which are called lymphocytes ; these are cells with large nuclei and comparatively little protoplasm. They pass with the lymph into the blood, where they undergo growth, and are called leucocytes. CH. XXII.] LYMPHATIC GLANDS 315 All the lymphatics pass at some point of their course through lymphatic glands, which are the factories of these corpuscles. Lym- phocytes also pass into the lymph stream wherever lymphoid tissue is found, as in the tonsils, thymus, Malpighian bodies of the spleen, Peyer's patches, and the solitary glands of the intestine. The lymph that leaves these tissues is richer in lymph-cells than that which enters them. When lymph is collected from the thoracic duct after a meal containing fat, it is found to be milky. This is due to the presence in the lymph of minutely subdivided fat particles absorbed from the interior of the alimentary canal. The lymph is then called chyle. The fat particles constitute what used to be called the molecular oasis of chyle. If the abdomen is opened during the process of fat absorp- tion, the lymphatics are seen as white lines, due to their containing this milky fluid. They are consequently called lacteals. The structure and arrangement of the lymphatic vessels are given in Chapter XVIIL, and we have now to study the structure of The Lymphatic Glands. Lymphatic glands are round or oval bodies varying in size from a hemp-seed to a bean, interposed in the course, of the lymphatic vessels, and through which the lymph passes in its course to be dis- charged into the blood-vessels. They are found in great numbers in the mesentery, and along the great vessels of the abdomen, thorax, and neck ; in the axilla and groin ; a few in the popliteal space, but not further clown the leg, and in the arm as far as the elbow. A lymphatic gland is covered externally by a capsule of con- nective-tissue, generally containing some unstriped muscle. At the inner side of the gland, which is somewhat concave (hilus), (fig. 304), the capsule sends inwards processes called trabecules in which the blood- vessels are contained, and these join with other processes prolonged from the inner surface of the part of the capsule covering the convex or outer part of the gland ; they have a structure similar to that of the capsule, and entering the gland from all sides, and freely communicating, form a fibrous scaffolding. The interior of the gland is seen on section, even when examined with the naked eye, to be made up of two parts, an outer or cortical, which is light coloured, Fig. 304. — Section of a mesenteric gland from the ox, slightly magnified, a, Hilus ; 6 (in the central part of the figure), medullary substance; c, cortical substance with indis- tinct alveoli ; d, capsule. (Kolliker.) 316 LYMPH AND LYMPHATIC GLANDS [CH. XXII. and an inner or medullary portion of redder appearance (figs. 304, 305). In the outer part, or cortex, of the gland (fig. 305), the intervals batween the trabecule are large and regular; they are termed alveoli; whilst in the more central or medullary part is a finer meshwork formed by an irregular anastomosis of the trabecular processes. Within the alveoli of the cortex and in the meshwork formed by the trabecule in the medulla, is contained lymphoid tissue ; this occupies the central part of each alveolus ; but at the periphery, surrounding the central portion and immediately next the capsule and trabecular, is a more open meshwork of retiform tissue Fi'.. 305.— Diagrammatic section of lymphatic gland. a.L, afferent; e.L, efferent lymphatics; C, cortical substance; l.h., lymphoid tissue; l.s., lymph-path; c, fibrous capsule sending in trabecular tr. into the substance of the gland. (Sharpey.) constituting the lymph-path, and containing but few lymph-corpuscles. At the inner part of the alveolus, the central mass divides into two or more smaller rounded or cord-like masses which, joining with those from the other alveoli, form a much closer arrangement than in the cortex ; spaces (fig. 306, b) are left within those anastomosing cords, in which are found portions of the trabecular meshwork and the continuation of the lymph-path. The lymph enters the gland by several afferent vessels, which pierce the capsule and open into the lymph-path ; at the same time they lay aside all their coats except the endothelial lining, which is continuous with the lining of the lymph-path. The efferent vessels begin in the medullary part of the gland, and are continuous with CH. XXII.] THE FLOW OF LYMPH 317 ''ihPy,:p- the lymph-path here as the afferent vessels are with the cortical portion. The efferent vessels leave the gland at the hilus, and either at once, or very soon after, join together to form a single vessel. Blood-vessels which enter and leave the gland at the hilus are freely distributed to the trabe- cular and lymphoid tissues. The Lymph Flow. The flow of the lymph towards the point of its discharge into the veins is brought about by several agencies. With the help of the valvular mechanism all occasional pressure on the exterior of the lymphatic and lacteal vessels pro- pels the lymph onward ; thus muscular and other external pressure accelerates the flow of the lymph as it does that of the blood in the veins. The action of the muscular fibres of the small intestine, and the layer of unstriped muscle present in each intestinal villus, assist in propel- ling the chyle ; in the small in- testine of a mouse, the chyle has been seen moving with intermit- tent propulsions that correspond with the peristaltic movements of the intestine. But, for the general propulsion of the lymph and chyle, it is probable that, together with the vis a tergo resulting from external pressure, some of the force is derived from the con- tractility of the vessel's own walls. The respiratory movements, also, favour the current of lymph through the thoracic duct as they do the current of blood in the thoracic veins. Lymph-Hearts. — In amphibia, reptiles and some birds, an important auxiliary to the movement of the lymph and chyle is supplied in certain muscular sacs, named lymph-hear Is, and it has been shown that the caudal heart of the eel is a lymph- heart also. The number and positions of these organs vary. In frogs and toads, there are usually four, two anterior and two posterior. Into each of these cavities several lymphatics open, the orifices of the vessels being guarded by valves, which prevent the retrograde passage of the lymph. From each heart a single vessel proceeds, and conveys the lymph directly into the venous system. Blood is pre- vented from passing into the lymphatic heart by a valve at its orifice. Fig. 306. — A small portion of medullary substance from a mesenteric gland of the ox. d, d, trabe- cule ; a, part of a cord of lymphoid tissue from which all but a few of the lymph-corpuscles have been washed out to show its supporting meshwork of retiform tissue and its capillary blood-vessels (which have been injected, and are dark in the figure) ; 5, 6, lymph-path, of which the retiform tissue is represented only at c, e, x 300. (KSlliker.) 318 LYMPH AND LYMPHATIC GLANDS [CII. XXII. The muscular coat of these hearts is of variable thickness ; in some cases it can only be discovered by means of the microscope ; but in every case it is composed of striped fibres. The contractions of the hearts are rhythmical, occurring about sixty times in a minute. The pulsations of the cervical pair are not always synchronous with those of the pair in the ischiatic region, and even the correspond- ing sacs of opposite sides are not always synchronous in their action. Unlike the contractions of the blood-heart, those of the lymph-heart appear to be directly dependent upon a certain limited portion of the spinal cord. For Volkmann found that so long as the portion of spinal cord corresponding to the third vertebra of the frog was uninjured, the cervical pair of lymphatic hearts continued pulsating after all the rest of the spinal cord and the brain were destroyed ; while destruction of this portion, even though all other parts of the nervous centres were uninjured, instantly arrested the hearts' movements. The posterior, or ischiatic, pair of lymph-hearts were found to be governed, in like manner, by tin- portion of spinal* cord corresponding to the eighth vertebra. Division of the posterior spinal roots did not arrest the movements; but division of the anterior roots caused them to cease at once. Innervation of the Thoracic Duct. — By determining the rate of outflow of a fluid at constant pressure passing through the thoracic duct, Camus and Gley have obtained evidence of the presence of nerves, causing both dilatation and constric- tion of the duct. These are contained in the sympathetic chain below the first thoracic ganglion. The effect of stimulation is principally dilatation. Relation of Lymph and Blood. The volume of blood in the body remains remarkably constant. If the amount is increased by injection of fluids, at first its specific gravity is lessened, but in a short time, often in a few minutes, it returns to the normal. The excess of fluid is got rid of in two ways : (1) by the kidneys, which secrete profusely ; and (2) by the tissues, which become more watery in consequence. After the renal arteries are ligatured, and the kidney is consequently thrown out of action, the excess of water passes only into the tissues. On the other hand, a deficiency of blood (for instance, after haemorrhage) is soon remedied by a transfer of water from the tissues to the blood through the intermediation of the lymph. In severe haemorrhage life has often been saved by injection of saline solution into the vessels, or by transfusion from another person. The transfer of the blood of another animal to the human vascular system is usually dangerous, especially if the blood has been defibrinated, for the serum of one animal is usually poisonous to another, producing various changes, of which a breakdown of the corpuscles (haemolysis) is the most constant sign. Formation of Lymph. Carl Ludwig taught that the lymph flow is conditioned by two factors : first, differences in the pressure of the blood in the capillaries and of the fluid in the tissue spaces, giving rise to & filtration of fluid through the capillary walls; and secondly, chemical differences CH. XXII.] FORMATION OF LYMPH 319 between these two fluids, setting up osmotic interchanges through the wall of the blood-vessel. The accurate meaning of these terras is explained in the section in small print at the end of this chapter. If the lymph is produced by a simple act of filtration, then the amount of lymph must rise and sink with the value of D — d; D representing the capillary blood-pressure, and d the pressure in the tissue spaces. In support of this mechanical theory, various workers in Ludwig's laboratory showed that increased capillary pressure due to obstruction of the venous outflow increases the amount of lymph formed ; and that diminution of the pressure in the lymph spaces, by squeezing out the lymph previously contained in them, leads to an increase in the transudation. On the other hand, there were some facts which could not be well explained by the filtration theory, among which may be mentioned the action of curare in causing an increase of lymph flow. Heidenhain was the first to fully recognise that the laws of filtration and osmosis as applied to dead membranes may be con- siderably modified when the membranes are composed of living cells ; and he considered that the formation of lymph is due to the selective or secretory activity of the endothelial walls of the capillaries. This so-called vital action of the endothelial cells is seen in the fact that after the injection of sugar into the blood, in a short time the per- centage of sugar in the lymph becomes higher than that in the blood. There must, therefore, be some activity of the endothelial cells in picking out the sugar from the blood and passing it on to the lymph. Heidenhain is also the inventor of the term lymphagogues (literally, lymph drivers). These are substances like curare, which have a specific action in causing an increased lymph flow. Heiden- hain considers the majority of these act by stimulating the endothelial cells to activity. This conclusion, however, has been subjected to much criticism. In this country the question has been taken up by Starling, who has. shown that the influence of vital action is not so marked as Heidenhain supposes it to be, but that most of the phenomena in connection with lymph formation can be explained by the simpler mechanical theory. Starling's views may be briefly stated as follows : — The amount of lymph produced in any part depends on two factors : — 1. The pressure at which the blood is flowing through the capil- laries. Heidenhain took the arterial pressure in his experiments as the measure of the capillary pressure ; Starling points out, very 320 LYMPH AND LYMPHATIC GLANDS [CII. XXII. justly, that this is incorrect, as there is between the arteries and the capillaries the peripheral resistance in the arterioles. 2. The permeability of the capillary wall. This varies enormously in different regions; it is greatest in the liver, so that an intra- capillary pressure which would cause lymph to flow here is without effect on the production of lymph in the limits. The flow of lymph may therefore be increased in two ways : — 1. By increasing the intracapillary pressure. This may be clone locally by ligaturing the veins of an organ ; or generally by injecting a large amount of fluid into the circulation, or by the injection of such substances as sugar and salt (Heidenhain's first class of lymphagogues) into the blood. These attract water from the tissues into the blood, and thus increase the volume of the circulating fluid and raise the intracapillary pressure. 2. By increasing the permeability of the capillary wall by injuring its vitality. This may be done locally by scalding a part; or generally, by injecting certain poisonous substances, such as peptone, leech extract, decoction of mussels, etc. (Heidenhain's second class of lymphagogues). These act chiefly on the liver capillaries ; curare acts chiefly on the limb capillaries. In the light of our present knowledge on this question, it is impossible to pronounce any absolutely positive opinion. But facts appear to me to be accumulating which tell in favour of the secretion theory. If the endothelial wall were a non-living membrane, physical processes would obviously explain all the phenomena of lymph forma- tion. But we must recognise that the endothelial cells are alive, and that like other cells they are capable of a selective action which may mask or counteract or assist the purely physical processes. If the action of poisons was simply to injure the vessel wall and increase its permeability, the amount of lymph should be proportional to the intensity of the injury ; but this is not found to be the case, Heidenhain no doubt went too far when he attributed lymph forma- tion almost exclusively to endothelial activity ; and Starling has gone too far in the other direction. My own opinion is that lymph formation is mainly influenced by the physical conditions present, for the action of such thin cells as those of the capillary wall cannot be sufficiently great to entirely counteract these conditions ; at the same time it is impossible to deny that there is some such action as may be described by the terms " selective " or " secretory." The question is closely related to that of absorption from the alimen- tary canal, and we shall find in studying that subject that there is a similar difference of opinion, and that recently published researches confirm the theory of selective activity of the absorptive epithelium. CH. XXII.] THEORY OF SOLUTIONS 321 Osmotic Phenomena. The investigations of physical chemists during recent years have given us new conceptions of the nature of solutions, and these have important bearings on the explanation of osmotic phenomena, and so are interesting to the physiologist. Water is the fluid in which soluble materials are usually dissolved, and at ordinary temperatures it is a fluid the molecules of which are in constant movement ; the hotter the water the more active are the movements of its molecules ; until when at last it is converted into steam, the molecular movements become much more energetic. Perfectly pure water consists of molecules Math the formula H 2 0, and these molecules undergo practically no dissociation into their constituent ions, and it is for this reason that pure water is not a conductor of electricity. If a substance like sugar is dissolved in the water, the solution still remains incapable of conducting an electrical current. The sugar molecules in solution are still sugar molecules ; they do not undergo dissociation. But if a substance like salt is dissolved in the water, the solution is then capable of conducting electrical currents, and the same is true for most acids, bases, and salts. These substances do undergo dissociation, and the simpler materials into which they are broken up in the water are called ions. Thus, if sodium chloride is dissolved in water a certain number of its molecules become dissociated into sodium ions, which are charged positively with electricity, and chlorine ions, which are charged negatively with electricity. Similarly a solution of hydrochloric acid in water con- tains free hydrogen ions and free chlorine ions. Sulphuric acid is decomposed into hydrogen ions and ions of S0 4 . The term ion is thus not equivalent to atom, for an ion may be a group of atoms, like S0 4 , in the example just given. Further, in the case of hydrochloric acid, the negative charge of the chlorine ion is equal to the positive charge of the hydrogen ion ; but in the case of the sulphuric acid, the negative charge of the S0 4 ion is equal to the positive charge of two hydrogen ions. We can thus speak of monovalent, divalent, trivalent, etc., ions. Ions positively charged are called hat-ions because they move towards the kathode or negative pole ; those which are negatively charged are called an-ions because they move towards the anode or positive pole. The following are some examples of each class : — Kat-ions. Monovalent : — H, Na, K, NH 4 , etc. Divalent : — Ca, Ba, Fe (in ferrous salts), etc. Trivalent : — Al, Bi, Sb, Fe (in ferric salts), etc. An-ions. Monovalent :— CI, Br, I, OH, N0 3 , etc. Divalent : — S, Se, S0 4 , etc. Roughly speaking, the greater the dilution the more nearly complete is the dissociation, and in a very dilute solution of such a substance as sodium chloride we may consider that the number of ions is double the number of molecules of the salt present. The ions liberated by the act of dissociation are, as we have seen, charged with electricity, and when an electrical current is led into such a solution, it is conducted through the solution by the movement of the ions. Substances which exhibit the property of dissociation are known as electrolytes. The liquids of the body contain electrolytes in solution, and it is owing to this fact that they are able to conduct electrical currents. This conception of electrolytes which we owe to Arrhenius is extremely impor- tant in view of the question of osmotic pressure, because the act of dissociation increases the number of particles moving in the solution, and so increases the osmotic pressure, for in this relation an ion plays the same part as a molecule. Another physiological aspect of the subject is seen in a study of the actions of mineral salts in solution on living organisms and parts of organisms. Many years ago Ringer showed that contractile tissues (heart, cilia, etc.) continue to manifest their activity in certain saline solutions. We have already seen (p. 256) that Howell considers the cause of rhythmical action in the heart is the presence of these inorganic substances in the blood or lymph which bathes it. X 322 LYMPH AND LYMPHATIC GLANDS [CH. XXII. Loeb and his fellow-workers have confirmed these statements, but interpret them now as ionic action. Contractile tissues will not contract in pure solutions of non-electrolytes (like sugar, urea, albumin). But different contractile tissues differ in the nature of the ions which are most favourable stimuli. Thus cardiac muscle, cilia, amoeboid movement, kuryokinesis, cell division, are all alike in requiring a proper adjustment of ions in their surroundings if they are to continue to act, but the proportions must be different in individual cases. Ions affecting the rhythmical contractions may be divided into three classes : (1) Those which produce such con- tractions ; of these the most efficacious is Xa. (2) Those which retard or inhibit rhythmical contractions ; for instance, Ca and K. (3) Those which act catalytically, that is, they accelerate the action of Na, though they do not themselves produce rhythmical contractions directly : for instance, H and OH. In spite of the antagonistic effect of Ca, a certain minimal amovint of it must be present if contrac- tions are to continue for any length of time. Ions produce rhythmical contraction only because they affect either the physical condition of the colloidal substances (proteid, etc.) in protoplasm, or the rapidity of chemical processes. Loeb has even gone so far as to consider that the process of fertilisation is mainly ionic action. He denies that the nuclein in the head of the spermatozoon is essential, but asserts that all the spermatozoon does is to act as the stimulus in the due adjustment of the proportions of the surrounding ions. He supports this view by numerous experiments on ova, in which, without the presence of spermatozoa, he has produced larvae (generally imperfect ones, it is true) by merely altering the saline constituents of the fluid that bathes them. Whether such a sweeping and almost revolutionary notion will stand the test of further verification must be left to the future. So also must the equally important idea that the basis of a nerve- impulse is electrolytic action. Gramme-molecular Solutions. — From the point of view of osmotic pressure a convenient unit is the gramme-molecule. A gramme-molecule of any substance is the quantity in grammes of that substance equal to its molecular weight. A gramme-molecular solution is one which contains a gramme-molecule of the sub- stance per litre. Thus a gramme-molecular solution of sodium chloride is one which contains 58"5 grammes of sodium chloride (Na = 2o - 0r> : Cl=35"45) in a litre. A gramme-molecular solution of grape sugar (C,;Hj. 2 O i; ) is one which contains 179 "58 grammes of grape sugar in a litre. A gramme-molecule of hydrogen (H. 2 ) is 2 grammes by weight of hydrogen, and if this was compressed to the volume of a litre, it would be comparable to a gramme-molecular solution. It therefore follows that a litre containing 2 grammes of hydrogen contains the same number of molecules of hydrogen in it as a litre of a solution containing 58 '5 grammes of sodium chloride, or one containing 179 "58 grammes of grape sugar, has in it of salt or sugar molecules respectively. To put it another way, the heavier the weight of a molecule of any substance, the more of that substance must be dissolved in the litre to obtain its gramme-molecular solution. Or still another way : if solutions of various substances are made all of the same strength per cent. , the solutions of the materials of small molecular weight will contain more molecules of those materials than the solutions of the materials which have heavy molecules. We shall see that the calculation of osmotic pressure depends upon these facts. Diffusion, Dialysis, Osmosis. — If two gases are brought together within a closed space, a homogeneous mixture of the two is soon obtained. This is due to the movements of the gaseous molecules within the confining space, and the process is called diffusion. In a similar way diffusion will effect in time a homo- geneous mixture of two liquids or solutions. If water is carefully poured on to the surface of a solution of salt, the salt or its ions will soon be equally distributed throughout the whole. If a solution of albumin or any other colloidal substance is used instead of salt in the experiment, diffusion will be found to occur much more slowly. If, instead of pouring the water on to the surface of a solution of salt or sugar, the two are separated by a membrane made of such a material as parchment paper, a similar diffusion will occur, though more slowly than in cases where the membrane is absent. In time, the water on each side of the membrane will contain the same quantity of sugar or salt. Substances which pass through such membranes are called crystalloids. Substances which have such large molecules (starch, pro- CH. XXII.] OSMOSIS 323 teid, etc.) that they will not pass through such membranes are called colloids. Diffusion of substances in solution which have to deal with an intervening membrane is usually called dialysis. The process of filtration (i.e., the passage of materials through the pores of a membrane under the influence of mechanical pressure) may be excluded in such experiments by placing the membrane (m) vertically as shown in the diagram (fig. 307), and the two fluids a and b on each side of it. Diffusion through a membrane is not limited to the molecules of water, but it may occur also in the molecules of certain substances dissolved in the water. But very few or no membranes are equally permeable to water and to molecules of the substances dis- solved in the water. If in the accompanying diagram the compartment a is filled with pure water, and b with a sodium chloride solution, the liquids in the two com- partments will ultimately be found to be equal in bulk as they were at the start, and each will be a solution of salt of half the original strength of that in the compart- ment b. But at first the volume of the liquid in compartment b increases, because more water molecules pass into it from a than salt molecules pass from b to a. The term osmosis is generally limited to the stream of water molecules passing through a membrane, while the term dialysis is applied to the passage of the molecules in solu- tion in the water. The osmotic stream of water is especially important, and in con- nection with this it is necessary to explain the term osmotic pressure. At first, then, osmosis (the diffusion of water) is more rapid than the dialysis (the diffusion of the salt molecules or ions). The older explanation of this was that salt attracted the water, but we now express the fact differently by saying that the salt in solution exerts a certain osmotic pressure : f$ the result of the osmotic pressure is that more water flows from the water side to the side of the solution than in the contrary direction. The osmotic pressure varies with the amount of substance in solution, and is also altered by variations of temperature occurring more rapidly at high than at low temperatures. If we imagine two masses of water separated by a permeable membrane, as many water molecules will pass through from one side as from the other, and so the volumes of the two masses of water will remain un- changed. If now we imagine the membrane m is not per- meable except to water, and the compartment a contains Fig. 307. water, and the compartment b contains a solution of salt or sugar ; under these circumstances water will pass through into b, and the volume of b will increase in proportion to the osmotic pressure of the sugar or salt in solution in b, but no molecules of sugar or salt can get through into a from b, so the volume of fluid in a will continue to decrease, until at last a limit is reached. The determination of this limit, as measured by the height of a column of fluid or mercury which it will support, will give us a measurement of the osmotic pressure. If a bladder containing strong salt solution is placed in a vessel of distilled water, water passes into the bladder by osmosis, so that the bladder is swollen, and a manometer connected with its interior will show a rise of pressure (osmotic pressure). But the total rise of pressure cannot be measured in this way for two reasons : (1) because the salt diffuses out as the water diffuses in ; and (2) because the membrane of the bladder leaks ; that is, permits of filtration when the pressure within it has attained a certain height. It is therefore necessary to use a membrane which will not allow salt to pass out either by dialysis or filtration, though it will let the water pass in. Such membranes are called semipermeable membranes, and one of the best of these is ferrocyanide of copper. This may be made by taking a cell of porous earthenware and washing it out first with copper sulphate and then with potassium ferrocyanide. An insoluble precipitate of copper ferrocyanide is thus deposited in the pores of the earthenware. If such a cell is arranged as in fig. 308, and filled with a 1 per cent, solution of sodium chloride, water diffuses in, till the pressure registered by the manometer reaches the enormous height of 5000 mm. of mercury. If the pressure in the cell 324 LYMPH AND LYMPHATIC GLANDS [CH. XXII M tr\\ is increased beyond this artificially, water will be pressed through the semi-perme- able walls of the cell and the solution will become more concentrated. In other words, in order to make a solution of sodium chloride of greater con- centration than 1 per cent., a pressure greater than 5000 mm. of mercury must be employed. The osmotic pressure exerted by a 2 per cent, solution would be twice as great. Though it is theoretically possible to measure osmotic pressure by a manometer in this direct way, practically it is hardly ever done, and some of the indirect methods of measurement described later are used instead. The reason for this is that it has been found impossible to construct a membrane which is absolutely semi-permeable ; they are all permeable in some degree to the molecules of the dissolved en stalloid. In course of time, therefore, the dissolved crystalloid will be equally distributed on both sides of the membrane, and osmosis of water will cease to be apparent, since it will be equal in both directions. Many explanations of the nature of osmotic pressure have been brought forward, but none is perfectly satisfactory. The following simple ex- planation is perhaps the best, and may be rendered most intelligible by an illustration. Suppose we have a solution of sugar separated by a semi-per- meable membrane from water ; that is, the mem- brane is permeable to water molecules, but not to sugar molecules. The streams of water from the two sides will then be unequal ; on one side we have water molecules striking against the membrane in what we may call normal numbers, while on the other side both water molecules and sugar molecules are striking against it. On this side, therefore, the sugar molecules take up a certain amount of room, and do not allow the water molecules to get to the membrane ; the membrane is, as it were, screened against the water by the sugar, therefore fewer water molecules will get through from the screened to the unscreened side than vice versd. This comes to the same thing as saying that the osmotic stream of water is greater from the unscreened water side to the screened sugar side than it is in the reverse direction. The more sugar molecules that are present, the greater will be their screening action, and thus we see that the osmotic pressure is pro- portional to the number of sugar molecules in the solution, that is, to the concentration of the solution. Osmotic pressure is, in fact, equal to that which the dissolved substance would exert if it occupied the same space in the form of a gas (Van't Hoffs hypo- thesis). The nature of the substance makes no differ- ence ; it is only the number of molecules which causes osmotic pressure to vary. The osmotic pressure, however, of substances like sodium chloride, which are elec- trolytes, is greater than what one would expect from the number of molecules present. This is because the molecules in solution are split into their constituent ions, and an ion plays the same part as a molecule, in questions of osmotic pressure. In dilute solutions of sodium chloride ionisation is more complete, and as the total number of ions is then nearly double the number of original molecules, the osmotic pressure is nearly double what would have been calculated from the number of molecules. The analogy between osmotic pressure and the pressure of gases is very com- plete, as may be seen from the following statements : — 1. At a constant temperature osmotic pressure is proportional to the concentra- tion of the solution (Boyle-Mariotte's law for gases). B -A — 308. — A, outer vessel, con- taining distilled water ; B, inner semi-permeable vessel, containing 1 per cent, salt solution ; M, mercurial manometer. (After Star- ling.) CH. XXII.] OSMOTIC PKESSURE 325 2. With constant concentration, the osmotic pressure rises with and is propor- tional to the temperature (Gay-Lussac's law for gases). 3. The osmotic pressure of a solution of different substances is equal to the sum of the pressures which the individual substances would exert if they were alone in the solution (Henry-Dalton law for partial pressure of gases). 4. The osmotic pressure is independent of the nature of the substance in solution, and depends only on the number of molecules or ions in solution (Avogadro's law for gases). Calculation of Osmotic Pressure. — We may best illustrate this by an example, and to simplify matters we will take an example in the case of a non-electrolyte like sugar. We shall then not have to take into account any electrolytic dissocia- tion of the molecules into ions. We will suppose we want to calculate the osmotic pressure of a 1 per cent, solution of cane sugar. One gramme of hydrogen at atmospheric pressure and 0° C. occupies a volume of 11 - 19 litres ; two grammes of hydrogen will therefore occupy a volume of 22*38 litres. A gramme-molecule of hydrogen — that is, 2 grammes of hydrogen — when brought to the volume of 1 litre, will exert a gas pressure equal to that of 22 "38 litres compressed to 1 litre — that is, a pressure of 22-38 atmospheres. A gramme-mole- cular solution of cane sugar, since it contains the same number of molecules in a litre, must therefore exert an osmotic pressure of 22 -38 atmospheres also. A gramme-molecular solution of cane sugar (C 12 Ho. 2 O n ) contains 342 grammes of cane sugar in a litre. A 1 per cent, solution of cane sugar contains only 10 grammes of cane sugar in a litre ; hence the osmotic pressure of a 1 per cent, solution of cane sugar is ^— x 22*38 atmospheres, or 0*65 of an atmosphere, which in terms of a column of mercury = 760 x 0*65 = 494 mm. It would not be possible to make such a calculation in the case of an electro- lyte, because we should not know how many molecules had been ionised. In the liquids of the body, both electrolytes and non-electrolytes are present, and so a calculation is here also impossible. We have seen that for such liquids the osmotic pressure cannot be directly measured by a manometer, because there are no perfect semi-permeable mem- branes ; we now see that mere arithmetic often fails us ; and so we come to the question to which we have been so long leading up, viz., how osmotic pressure is actually determined. Determination of Osmotic Pressure by means of the Freezing-point. — This is the method which is almost universally employed. A very simple apparatus (Beckmann's differential thermometer) is all that is necessary. The principle on which the method depends is the following : — -The freezing-point of any substance in solution in water is lower than that of water ; the lowering of the freezing-point is proportional to the molecular concentration of the dissolved substance, and that, as we have seen, is proportional to the osmotic pressure. When a gramme-molecule of any substance is dissolved in a litre of water, the freezing-point is lowered by 1*87° C. , and the osmotic pressure is, as we have seen, equal to 22*38 atmospheres, that is, 22*38 x 760 = 17,008 mm. of mercury. We can, therefore, calculate the osmotic pressure of an}^ solution if we know the lowering of its freezing-point in degrees Centigrade ; the lowering of the freezing-point is usually expressed by the Greek letter A. Osmotic pressure = =-== x 17,008. For example, a 1 per cent, solution of sugar would freeze at -0*052° C. ; its .. ., , -052x17,008 _„ , • x , osmotic pressure is therefore 1 -=^ = 4/3 mm., a number approximately equal to that we obtained by calculation. Mammalian blood serum gives A =0*56° C. A - 9 per cent, solution of sodium chloride has the same A ; hence serum and a - 9 per cent, solution of common salt have the same osmotic pressure, or are isotonic. The osmotic pressure of blood . -56x17.008 „„.. , „ ± serum is — — = 498/ mm. of mercury, or a pressure or nearly / atmospheres. 326 LYMPH AND LYMPHATIC GLANDS [CH. XXII. The osmotic pressure of solutions may also be compared by observing their effect on red blood corpuscles, or on vegetable cells such as those in Tradescantia. If the solution is hypertonic, i.e., lias a greater osmotic pressure than the cell contents, the protoplasm shrinks, and loses water, or if red corpuscles are used, they become crenated ; if the solution is hypotonic, i.e„ has a less osmotic pressure than the material within the cell-wall, no shrinking of the protoplasm in the vegetable cell takes place ; and if red corpuscles are used they swell and liberate their pigment. Isotonic solutions, like physiological salt solution, produce neither of these effects, because they have the same molecular concentration and osmotic pressure as the material within the cell-wall. Physiological Applications. — It will at once be seen how important all these considerations are from the physiological standpoint. In the body we have aqueous solutions of various substances separated from one another by membranes. Thus we have the endothelial walls of the capillaries separating the blood from the lymph ; we have the epithelial walls of the kidney tubules separating the blood and lymph from the urine ; we have similar epithelium in all secreting glands ; and we have the wall of the alimentary canal separating the digested food from the blood-vessels and lacteals. In such important problems, then, as lymph-formation, the forma- tion of urine and other excretions and secretions, and absorption of food, we have to take into account the laws which regulate the movements both of water and of substances which are held in solution by the water. In the body osmosis is not the only force at work, but we have also to consider filtration, that is, the forcible passage of materials through membranes, due to differences of mechanical pressure. Further complicating these two processes we have to take into account another force, namely, the secretory or selective activdy of the living cells of which the membranes in question are composed. This is sometimes called by the name vital art Ion, which is an unsatisfactory and unscientific expression. The laws which regulate filtration, inhibition, and osmosis are fairly well known and can be experi- mentally verified. But we have undoubtedly some other force, or some other mani- festation of force, in the case of living membranes. It probably is some physical or chemical property of living matter which has not yet been brought into line with the known chemical and physical forces which operate in the inorganic world. We cannot deny its existence, for it sometimes operates so as to neutralise the known forces of osmosis and filtration. The more one studies the question of lymph-formation, the more convinced one becomes that mere osmosis and filtration will not explain it entirely. The basis of the action is no doubt physical, but the living cells do not behave like the dead membranes of a dialyser ; they have a selective action, picking out some substances and passing them through to the lymph, while they reject others. The question of gaseous interchanges in the lungs is another of a similar kind. Some maintain that all can be explained by the laws of diffusion of gases ; others assert that the action is wholly vital. Probably those are most correct who admit a certain amount of truth in both views ; the main facts are explicable on a physical basis, but there are also some puzzling data that show that the pulmonary epithelium is able to exercise some other force as well which inter- feres to some extent with the known physical process. Take again the case of absorption. The object of digestion is to render the food soluble and diffusible ; it can hardly be supposed that this is useless ; the readily diffusible substances will pass more easily through into the blood and lymph : but still, as Waymouth Reid has shown, if the living epithelium of the intestine is removed, absorption comes very nearly to a standstill, although from the purely physical standpoint removal of the thick columnar epithelium would increase the facilities for osmosis and filtration. The osmotic pressure exerted by crystalloids is very considerable, but their ready diffusibility limits their influence on the flow of water in the body. Thus if a strong solution of salt is injected into the blood, the first effect will be the setting up of an osmotic stream from the tissues to the blood. The salt, however, would soon diffuse out into the tissues, and would now exert osmotic pressure in the opposite direction. Moreover, both effects will be but temporary, because excess of salt is soon got rid of by the excreting organs. Osmotic Pressure of Proteids. — It has been generally assumed that proteids, CH. XXII.] OSMOTIC PRESSURE OF PROTEIDS 327 the most abundant and important constituents of the blood, exert little or no osmotic pressure. Starling, however, has claimed that they have a small osmotic pressure; if this is so, it is of importance, for proteids, unlike salt, do not diffuse readily, and their effect therefore remains as an almost permanent factor in the blood. Starling gives the osmotic pressure of the proteids of the blood-plasma as equal to 30 mm. of mercury.. We should from the theoretical standpoint find it difficult to imagine that a pure proteid can exert more than a minimal osmotic pressure. It is made up of such huge molecules that, even when the proteids are present to the extent of 7 or 8 per cent. , as they are in blood-plasma, there are comparatively few proteid molecules in solution. Still, by means of this weak but constant pressure it is possible to explain the fact that an isotonic or even a hyper- tonic solution of a diffusible crystalloid may be completely absorbed from the peritoneal cavity into the blood. The functional activity of the tissue elements is accompanied by the breaking down of their proteid constituents into such simple materials as urea (and its precursors) sulphates and phosphates. These materials pass into the lymph, and increase its molecular concentration and its osmotic pressure ; thus water is attracted (to use the older way of putting it) from the blood to the lymph, and so the volume of the lymph rises and its flow increases. On the other hand, as these substances accumulate in the lymph they will in time attain there a greater concen- tration than in the blood, and so they will diffuse towards the blood, by which they are carried to the organs of excretion. But, again, we have a difficulty with the proteids ; they are most important for the nutrition of the tissues, but they are practically indiffusible. We must pro- visionally assume that their presence in the lymph is due to filtration from the blood. The plasma in the capillaries is under a somewhat higher pressure than the lymph in the tissues, and this tends to squeeze the constituents of the blood, including the proteids, through the capillary walls. I have, however, already indicated that the question of lymph-formation is one of the many physiological problems which await solution by the physiologists of the future. B. Moore and W. H. Parker confirm Starling's hypotheses that colloids in solution exert a small osmotic pressure, but the direct method is the only one available to determine it, the variations in freezing or boiling points are too small. It was hoped that this pressure could be used for determining the molecular weight of colloids like proteids, but it is found that in the case of substances of known molecular weight such as soaps, the apparent molecular weights are from 20 to 60 times too large. There must thus be a physical union or association of molecules to form a single osmotic unit. It is, therefore, possible that the chemical molecule of a proteid is not so large as has been supposed, but its apparent size is due to a physical aggregation of many molecules. Moore doubts whether the differences in osmotic pressure are sufficiently great to explain absorption, lymph production, or the formation of urine. If this is so, the physiological factor, the so-called vital activity of the cells, must be called in to explain these phenomena. Waymouth Reid finds that absolutely pure proteids exert no osmotic pressure ; the pressure observed is due to saline and other materials from which it is difficult to disentangle the proteid. Dr C. J. Martin has suggested to me a way of illustrating the so-called selective action of living membranes. Suppose a number of fishes are swimming about in a tank, like moving molecules or ions in solution ; across the tank is a wall which divides it into two parts ; the fishes are all in one compartment of the tank. Suppose, next, the wall has in it a number of holes guarded by valves, so arranged that the fish can pass through into the second compartment, but cannot return. After a time, as the fish discover these holes, there will be an equal number of fish in both compartments ; but this is not the end, for on waiting further, more fish will find their way through, and as none are able to return, they will all in time accumu- late in the second compartment. It is not difficult to grasp the idea that the arrange- ment of molecules in a living membrane is possibly such that the orifices through which other molecules pass are valvular, and such a conception is useful if it merely serves to rob the word "vital" of its mystery. CHAPTER XXIII THE DUCTLESS GLANDS The ductless glands form a heterogeneous group of organs, most of which are related in function or development with the circulatory system. They include the lymphatic glands, the spleen, the thymus, the thyroid, the suprarenal capsules, the pineal body, the pituitary body, and the carotid and coccygeal glands. The function of a gland that has a duct is a comparatively simple physiological problem, but the use of ductless glands has long been a puzzle to investigators. Recent research has, however, shown that most of, if not all, the ductless glands do form a secretion, and this internal secretion, as it is termed, leaves the gland by the venous blood or lymph, and thus is distributed and ministers to the needs of parts of the body else- where. Many of the glands which possess ducts and form an external secretion, form an internal secretion as well. Among these, the liver, pancreas, and kidney may be mentioned. In many cases the internal secretion is essential for life, and removal of the gland that forms it, leads to a condition of disease culminating in death. In other cases the internal secretion is not essential, or its place is taken by that formed in similar glands in other parts of the body. The body is a complex machine ; each part of the machine has its own work to do, but must work harmoniously with other parts. Just as a watch will stop if any of its numerous wheels get broken, so the metabolic cycle will become disarranged or cease altogether if any of the links in the chain break down. In unravelling the part which the ductless glands play in this cycle, it is at present impossible in many cases to state precisely what the particular function of each is ; all one can say is, when the gland is removed or its function interfered with, that the meta- bolic round is broken somehow, and that this upsets the whole of the machinery of the body. The difficulty of investigating this subject is increased by the fact that it is impossible to get the internal secretion in a state of purity and examine it ; it is always OH. XXIII.] THE SPLEEN 329 mixed with, and masked by, the lymph or blood into which it is poured. In spite of this, however, our knowledge in this branch of physiology is increasing, particularly in connection with some of these ductless glands. The methods of investigation which have been employed are the following : — 1. Extirpation. — The gland in question is removed, and the effect of the absence of the internal secretion noted. 2. Disease. — In cases where the function of the gland is in abeyance, owing to its being diseased, the symptoms are closely observed. 3. Injection of Extracts. — The gland is taken in a fresh condition ; an extract is made of it, and this is injected into the circulation of healthy animals, and into that of those animals from which the gland has been previously removed, and the effects watched. 4. Transplantation. — After the gland is removed and the usual effect produced, the same gland from another animal is transplanted into the first animal, and restoration of function looked for. The case of the lymphatic glands we have already studied ; they form an internal secretion which consists of lymph-cells, and these furnish the blood with its most important supply of colourless corpuscles. Eemoval of lymphatic glands is not fatal, as the other lymphatic glands and other collections of lymphoid tissue that remain behind carry on the work of those that are removed. The internal secretion theory of the ductless glands is that which is most in vogue at present. It should be mentioned, however, that there is another theory, which may be called the auto-intoxication theory. According to this view the gland is excretory {i.e., gets rid of waste and harmful materials) rather than secretory (i.e., production of something useful to the organism). When the gland is removed, the waste products therefore accumulate and produce harmful results. It is possible that as our knowledge increases, it may be found in certain cases that both these theories may be in part true. The Spleen. The Spleen is the largest of the ductless glands ; it is situated to the left of the stomach, between it and the diaphragm. It is of a deep red colour and of variable shape. Vessels enter and leave the gland at a depression on the inner side called the hilus. The spleen is covered externally almost completely by a serous coat derived from the peritoneum, while within this is the proper fibrous coat or capsule of the organ. The latter is composed of connective- tissue, with a large preponderance of elastic fibres and a certain pro- portion of unstriated muscular tissue. Prolonged from its inner surface are fibrous processes or trabecular, containing much unstriated muscle, which enter the interior of the organ, and, dividing and anastomosing in all parts, form a supporting framework in the 330 THE DUCTLESS GLANDS [CH. XXII!. interstices of which the proper substance of the spleen {spleen-pulp) is contained. At the hilus of the spleen, the blood-vessels, nerves, and lym- phatics enter or leave, and the fibrous coat is prolonged into the spleen substance in the form of investing sheaths for the arteries and veins, which sheaths again are continuous with the trabecular before referred to. The spleen-pulp, which is of a dark red or reddish-brown colour, - I'^i'. < ..'• ; IPfl Fia. 309.— Section of injected dog's spleen, c, capsule; tr, trabecule; m, two Malpighian bodies with numerous small arteries and capillaries ; a, artery ; I, lymphoid tissue, consisting of closely-packed lymphoid cells supported by very delicate retiform tissue ; a light space unoccupied by cells is seen all round the trabecule, which corresponds to the "lymph-path " in lymphatic glands. (Schofield.) is composed chiefly of cells, imbedded in a network formed of fibres, and the branchings of large nucleated cells. The network so formed is thus very like a coarse kind of retiform tissue. The spaces of this network are only partially occupied by cells and form a freely communicating system. Of the cells some are granular corpuscles resembling the lymph-corpuscles, both in general appearance and in being able to perform amoeboid movements; others are red blood- corpuscles of normal appearance or variously changed ; while there CH. XXIII. ] THE SPLEEN 331 are also large cells containing either a pigment allied to the colouring matter of the blood, or rounded corpuscles like red corpuscles. The splenic artery, after entering the spleen by its concave surface, divides and subdivides, with but little anastomosis between its branches; at the same time its branches are sheathed by the pro- longations of the fibrous coat, which they, so to speak, carry into the spleen with them. The arteries soon leave the trabecule, and their outer coat is then replaced by one of lymphoid tissue; they end in an open brush-work of capillaries, the endothelial cells of which become continuous with those of the rete of the spleen-pulp. The veins begin by a similar open set of capillaries from the large blood spaces of the pulp. The veins soon pass into the trabecule, and ultimately unite to form the splenic vein. This arrangement readily allows lymphoid and other corpuscles to be swept into the blood-current. On the face of a section of the spleen can be usually seen readily with the naked eye, minute, scattered, rounded or oval whitish spots, mostly from J^ to -^ inch (J- to -f mm.) in diameter. These are the Malpighian cor- puscles of the spleen, and are situated on the sheaths of the minute splenic arteries. They are in fact outgrowths of the outer coat of .,,-;*. , , . i , . °. P , . , ,-, l1Aft , Fig. 310.— Reticulum of the lymphoid tissue just referred to (see fig. 309). spleen of a cat, shown by Blood capillaries traverse the Malpighian cor- gKffio with selafcine - puscles and form a plexus in their interior. The structure of a Malpighian corpuscle of the spleen is practically identical with that of a lymphoid nodule. The spleen has the following functions : — (1.) The spleen, like the lymphatic glands, is engaged in the formation of colourless blood-corpuscles. For it is quite certain, that the blood of the splenic vein contains an unusually large proportion of white corpuscles ; and in the disease termed leucocythcemia, in which the white corpuscles of the blood are remarkably increased in number, there is found a hypertrophied condition of the spleen, especially of the Malpighian corpuscles. The white corpuscles formed in the spleen also doubtless partly leave that organ by lymphatic vessels. By stimulating the spleen to contract in a case of splenic leucocythsemia by means of an electric current applied over it through the skin, the number of leucocytes in the blood is almost immediately increased. Bemoval of the spleen is not fatal ; but after its removal there is an overgrowth of the lymphatic glands to make up for its absence. (2.) It forms coloured corpuscles, at any rate, in some animals ; in 332 THE DUCTLESS GLANDS [CH. XXIII. these animals, colls are found in the spleen similar to those we have described in red marrow, and called hcematoblasts. In these animals, if the spleen is removed, the red marrow hypertrophies. (3.) There is reason to believe that in the spleen many of the red corpuscles of the blood, those probably which have discharged their office and are worn out, undergo disintegration ; for in the coloured portions of the spleen-pulp an abundance of such corpuscles, in various stages of degeneration, are found, and in those cases of disease in which the destruction of blood-corpuscles is increased (pernicious anaemia) iron accumulates in the spleen as in the liver. It was formerly supposed that the spleen broke down the corpuscles and liberated haemoglobin, which, passing in the blood of the splenic vein to the liver, was discharged by that organ as bile-pigment. But this is not the case; the disintegration does not proceed so far as to actually liberate haemoglobin ; there is no free haemoglobin in the blood-plasma of the splenic vein. (4.) From the almost constant presence of uric acid, in larger quantities than in other organs, as well as of the nitrogenous bodies, xanthine and hypoxanthine, in the spleen, some share in nitrogenous metabolism may be fairly inferred to occur in it. (5.) Besides these direct offices, the spleen fulfils some purpose in regard to the portal circulation with which it is in close connec- tion. From the readiness with which it admits of being distended, and from the fact that it is generally small while gastric digestion is going on, and enlarges when that act is concluded, it is supposed to act as a kind of vascular reservoir, or diverticulum to the portal system, or more particularly to the vessels of the stomach. That it may serve such purpose is also made probable by the enlargement which it undergoes in certain affections of the heart and liver, attended with obstruction to the passage of blood through the latter organ, and by its diminution when the congestion of the portal system is relieved by discharges from the bowels, or by the effusion of blood into the stomach. This mechanical influence on the circulation, however, can hardly be supposed to be more than a very subordinate function. Influence of the Nervous System upon the Spleen. — When the spleen is enlarged after digestion, its enlargement is due to two causes : (1) a relaxation of the muscular tissue which forms so large a part of its framework; (2) a dilatation of the vessels. Both these phenomena are under control of the nervous system. It has been found by experiment that when the splenic nerves are cut the spleen enlarges, and that contraction can be brought about by stimulation of the peripheral ends of the divided nerves. If the splenic nerves are not cut, contraction is produced by (1) stimulation of the spinal cord ; (2) reflexly by stimulation of the central stumps of certain CH. XXIII.] SPLENIC WAVES 333 divided nerves, e.g., vagus and sciatic ; (3) by local stimulation by an electric current ; (4) by the administration of quinine and some other drugs. It has been shown by the oncometer (see p. 308) that the spleen undergoes rhythmical contractions and dilatations, due to the con- traction and relaxation of the muscular tissue in its capsule and trabecular A tracing also shows waves due to the rhythmical alter- ations of the general blood-pressure. Fig. 311 is a typical tracing obtained by Schafer's air oncometer from a dog's spleen. It shows, first, the large waves occurring about once a minute, due to the splenic systole and diastole; secondly, smaller waves on AAA/vvv^/vv^A/v^^^ 0. PRESSURE SECONDS TryvrirvTnrvvrvTvv^'Tvrvrriryr^ Fig. 311. — The upper tracing is the spleen record ; the next is carotid blood-pressure taken with a mercurial kymograph. The straight line beneath this is the abscissa of the arterial pressure ; and the lowest tracing is the time in seconds. this, due to the effect of respiration on the blood-pressure ; and on these, smaller waves still, corresponding with the individual heart- beats. The large waves due to the splenic contractility still go on after the division of all the splenic nerves. These nerve-fibres leave the spinal cord in numerous thoracic anterior roots ; they have cell stations in the sympathetic chain (Schafer) or semi-lunar ganglia (Langley). Hsemolymph Glands. The existence of glands which partake of the nature of the spleen, and of lymphatic glands, has long been known. They have been recently more fully investigated by T. Lewis. He finds them in most mammals, and they can be readily distinguished from ordinary 334 THE DUCTLESS GLANDS [CH. XXIII. lymphatic glands by their red colour. He divides them into (1) hcemal glands, which are characterised by the fact that the sinuses contain blood only. The spleen is in fact a large haemal gland ; and (2) hcemal lymphatic glands, in which the sinuses are filled by a mixture of blood and lymph. The Thymus. This gland is a temporary organ ; it attains its greatest size early after birth, and after the second year gradually diminishes, until in Fi<;. 312.— Thymus of a calf, a, cortex of follicle; 6, medulla; c, interfollicular tissue. Magnified about twelve times. (Watney.) adult life hardly a vestige remains. At its greatest development is a long narrow body, situated in the front of the chest behind the sternum and partly in the lower part of the neck. It is of a reddish or greyish colour, and is distinctly lobulated. The gland is surrounded by a fibrous cap- sule, which sends in processes, forming trabe- cule, that divide the gland into lobes, and carry the blood- and lymph-vessels. The large trabecule branch into small ones, which divide the lobes into lobules. The lobules are further subdivided into follicles by fine connective- tissue. A follicle is polyhedral in shape, and consists of cortical and medullary portions, ceils ; "b, corpuscles Vf \)ot]\ of which are composed of adenoid or lymphoid tissue, but in the medullary portion the matrix is coarser, and is not so filled up with lymphoid cor- puscles as in the cortex. Scattered in the lymphoid tissue of the medulla are the concentric corpuscles of Hassall (fig. 313), which i^yV •' Fig. 313.— The reticulum of the thymus, a, lymph CH. XXIII.] THE THYMUS AND THYEOID 335 consist of a nucleated granular centre, surrounded by flattened nucleated epithelial cells. These are islands of epithelial cells cut off from the epithelium of the pharynx in process of development. They are not occluded blood-vessels, as was at one time supposed. They remind one somewhat of the epithelial nests seen in some varieties of cancer. The arteries radiate from the centre of the gland. Lymph sinuses may be seen occasionally surrounding the periphery of the follicles (Klein). The nerves are very minute. From the thymus various substances may be extracted, many of them similar to those obtained from the spleen, e.g., xanthine, hypo- xanthine, adenine, and leucine. The main constituent of the cells is proteid, and especially nucleo- proteid. Indeed, the thymus is usually employed as the source of nucleo-proteid when one wishes to inject that substance into the blood-vessels of an animal to produce experimentally intravascular clotting. It is, however, not characteristic of the thymus, but is found in all protoplasm. The method of preparation will be given later (see Coagulation of Blood). The thymus takes part in producing the colourless corpuscles like other varieties of lymphoid tissue. In hibernating animals it exists throughout life, and as each successive period of hibernation approaches it greatly enlarges and becomes laden with fat. Hence it appears to serve for the storing-up of materials which, being reabsorbed during the inactivity of the hibernating period, may maintain the respiration and the temperature of the body in the reduced state to which they fall during that time. Some observers state that it is also a source of the red blood -corpuscles, at any rate in early life. Eemoval of the thymus in the frog (in which animal it persists throughout life) produces muscular weakness, paralysis, and finally death. Intravenous injection of extracts of thymus lowers blood- pressure, though the heart may be somewhat accelerated. The Thyroid. The thyroid gland is situated in the neck. It consists of two lobes, one on each side of the trachea, extending upwards to the thyroid cartilage, covering its inferior cornu and part of its body; these lobes are connected across the middle line by a middle lobe or isthmus. It is highly vascular, and varies in size in different individuals. The gland is encased in a capsule of dense areolar tissue. This sends in strong fibrous trabecular, which enclose the thyroid vesicles — which are rounded or oblong irregular sacs, consisting of a wall of thin hyaline membrane lined by a single layer of short cylindrical 336 THE DUCTLESS GLANDS [CII. XXIII. or cubical cells. These vesicles are filled with transparent colloid nucleo-albuminons material. The colloid substance increases with age, and the cavities appear to coalesce. In the interstitial connec- tive-tissue is a round meshed capillary plexus, and a large number of lymphatics. The nerves adhere closely to the vessels. In the vesicles there are, in addition to the yellowish glassy colloid material, epithelium cells, colourless blood-corpuscles, and also coloured corpuscles undergoing disintegration. It is difficult to state definitely the function of the thyroid body ; >«b Fig. 314. — Part of a section of the human thyroid, a, fibrous capsule; b, thyroid vesicles tilled with, e, colloid substance; c, supporting fibrous tissue; d, short columnar cells lining vesicles; J, arteries; g, veins filled with blood; h, lymphatic vessels filled with colloid substance. (S. K. Alcock.) it is one of those organs of great importance in the metabolic round ; and its removal or disease is followed by general disturbances. It no doubt forms an internal secretion ; to this the colloid material men- tioned contributes, as it is found in the lymphatic vessels of the organ. When the gland is diseased in children and its function obliterated, a species of idiocy is produced called cretinism. The same condition in adults is called myxcedema ; the most marked symptoms of this condition are slowness, both of body and mind, usually associated with tremors and twitchings. There is also a peculiar condition of the skin leading to the overgrowth of the CH. XXIII.] THE PARATHYROIDS 337 subcutaneous tissues, which, in time is replaced by fat ; the hair falls off, the hands become spade-like; the whole body is unwieldy and clumsy like the mind. A similar condition occurs after the thyroid is completely removed surgically ; this is called cachexia strumipriva ; this operation, which was performed previous to our knowledge of the importance of the thyroid, is not regarded as justifiable nowadays. Lastly, in many animals removal of the thyroid produces analogous symptoms, in the overgrowth of the connective-tissues especially under the skin, and in the nervous symptoms (twitchings, convul- sions, etc.). The term Myxoedema was originally given under the erroneous idea that the swelling of the body is due to mucin. In the early stages of the disease there is a slight increase of mucin, because all new connective-tissues contain a relatively large amount of ground substance, the most abundant constituent of which, next to water, is mucin. But there is nothing characteristic about that. The discovery of the relationships between the thyroid and these morbid conditions is especially interesting, because important practical results in their treatment have followed close on the heels of experi- mental investigation. The missing internal secretion of the thyroid may be replaced in these animals and patients by grafting the thyroid of another animal into the abdomen; or more simply by injecting thyroid extract subcutaneously ; or even by feeding on the thyroid of other animals. This treatment, which has to be kept up for the rest of the patient's life, is entirely successful. Chemical physiologists have been diligently searching to try and discover what the active material in thyroid extract is which produces such marvellous results ; the view at present held is that the efficacy of thyroid extract is due to a substance which Baumann separated from the gland, and which stands almost unique among physiological compounds by containing a large percentage of iodine in its molecule. Thyro-iodin or Iodo- thyrin, as this substance has been called, is present in combination with proteid matter in the colloid substance. Intravenous injection of thyroid extract in a normal animal lowers blood-pressure ; but in an animal from which the thyroid has been removed it stimulates the heart and raises blood-pressure. Parathyroids. These are small bodies, usually four in number, situated in the neighbourhood of, or embedded in the substance of, the thyroid. They are made up of elongated groups of polyhedral cells, bound together by connective- tissue and well supplied with blood-vessels. Some observers look upon these as being even more essential to healthy life than the thyroid, but this point is by no means decided. Y 338 THE DUCTLESS GLANDS [CH. XXIII. The general idea, however, that prevails is that the thyroid supplies something which is a stimulator of metabolic processes, and that the action on the nervous system is more especially the work of the parathyroids. The Supra-renal Capsules. These are two triangular or cocked-hat-shaped bodies, each resting by its lower border upon the upper border of the kidney. The gland is surrounded by an outer sheath of connective-tissue, Fig. 315.— Vertical section through part of the cortical portion of supra-renal of guinea-pig. a, Cap- sule ; b, zona glomerulosa ; c, zona fasciculata ; d, connective-tissue supporting the columns of the cells of the latter, and also indicating the position of the blood-vessels. (S. K. Alcock.) which sends in fine prolongations forming the framework of the gland. The gland tissue proper consists of an outside firmer cortical portion and an inside soft, dark medullary portion. (1.) The cortical portion is divided into (fig. 315) columnar groups of cells (zona fasciculata). Immediately under the capsule, however, the groups are more rounded (zona glomerulosa), while next to the medulla they have a reticular arrangement (zona reticularis). The cells themselves are polyhedral, each with a clear round nucleus, and often with oil globules in their protoplasm. The blood-vessels run in the fibrous septa between the columns, but do not penetrate between the cells. (2.) The medullary substance consists of a coarse rounded or irregular meshwork of fibrous tissue, in the alveoli of which are CE. XXIII.] THE SUPRA-KENAL BODIES 339 masses of multinucleated protoplasm (fig. 316); numerous blood- vessels ; and an abundance of nerve-fibres and cells. The cells are very irregular in shape and size, poor in fat, and often branched ; the nerves run through the cortical substance, and anastomose over the medullary portion. The cells of the medulla are characterised by the presence of certain reducing substances. One of these takes a brown stain with chromic acid, and gives other colour reactions ; it is, therefore, called a chromogen. Another is similar in many of its characters to jecorin, a lecithin-like substance also found in the liver, spleen, and other organs. The immense importance of the supra-renal bodies was first in- ':%^u'Mi^::y • V\ ; >'e»T?^-r '.' c • * 9 % »° * ' ; ■ ' '-■ ■-Ml i-Siff .-.'.-•■.• -■'.-■ , - :•;■" ■• v "■^fe>--g- r «'' '.' " - -.- ■"ffw T^o'/eli^ Fig. 316. — Section through a portion of the medullary part of the supra-renal of guinea-pig. The vessels are very numerous, and the fibrous stroma more distinct than in the cortex, and is, more- over, reticulated. The cells are irregular and larger, clear, and free from oil globules. (S. K. Alcock.) dicated by Addison, who, in 1855, pointed out that the disease now known by his name is associated with pathological alterations of these glands. This was tested experimentally by Brown-Sequard, who found a few years later that removal of the supra-renals in animals is invariably and rapidly fatal. The symptoms are practically the same (although more acute) as those of Addison's disease, namely, great muscular weakness, loss of vascular tone, and nervous prostra- tion. The pigmentation (bronzing) of the skin, however, which is a marked symptom in Addison's disease, is not seen in animals. The experiments of Brown-Sequard attracted much attention at the time they were performed, but were almost forgotten until quite recently, when they were confirmed by Abelous, Langlois, Schafer, and others. The effects on the muscular system are the most marked results both after removal of the capsules and after injection of an extract of the glands. The effect of injecting such an extract on the voluntary 340 THE DUCTLESS GLANDS [CH. XXIII. muscles is to increase their tone, so that a tracing obtained from them resembles that produced by a small dose of veratrine, namely, a pro- longation of the period of relaxation. The effect on involuntary muscle is equally marked ; there is an enormous rise of arterial blood - pressure due chiefly to a contraction of the arterioles. This is produced by the direct action of the extract on the muscular tissue of the arterioles, not an indirect one through the vaso-motor centre.* The active substance in the extract that produces the effect is known as adrenaline; it is the reducing substance alluded to above which is confined to the medulla of the capsules, and is absent in cases of Addison's disease. The capsules, therefore, form something which is distributed to the muscles and is essential for their normal tone ; when they are removed or diseased the poisonous effects seen are the result of the absence of this internal secretion. Adrenaline has received various names from the different chemists (Abel, v. Fiirth, Takamine, etc.), who have isolated it. It is very powerful ; solutions of one part in a million will produce physiological effects. Its composition is shown by the following formula: — OH V |OH CH.(OH).CH. 2 .NH.CH 3 and it is therefore a methyl-amino derivation of catechol (Pauly, Jowett). Recently compounds closely allied to it have been made synthetically (Stolz, Friedmann, Dakin). Whether this discovery will lead to the same kind of results, as in the case of the thyroid, must be left to the future to decide. There is already some evidence to show that injection of supra-renal extract is beneficial in cases of Addison's disease. The discovery of adrenaline itself is, however, one of immense practical importance. Its action on the small blood-vessels is so powerful that quite weak solutions applied locally will arrest haemorrhage. There are some points of interest in the development and com- parative physiology of the supra-renals. In mammals the medullary portion is developed in connection with the sympathetic, and is at first distinct and outside the cortical portion which is developed in connection with the upper part of the Wolffian body ; it gradually insinuates itself within the cortex (Mitsukiri). In Elasmobranch fishes the supra-renals consist throughout life of separate portions ; one, the inter-renal body, is median in position and single; this corre- sponds to the cortex of the mammalian supra-renal ; extracts of this are inactive, and in the Teleostean fishes, where it is the sole repre- * Although muscular tissue is spoken of in the above description, Brodie's work hows that it is the sympathetic nerve terminals which are really affeclec". CS. XXIII.] PITUITARY AND PINEAL GLANDS 34l sentative of the supra-renal, it may be removed without any harm to the animal. The other portion of the Elasmobranch supra-renal is paired, and derived from the sympathetic ganglia. This corresponds to the medulla ; it contains the same chromogen as the medulla of the mammalian supra-renal, and extracts of it have the same physio- logical action (S. Vincent). The Pituitary Body. This body is a small reddish-grey mass, occupying the sella turcica of the sphenoid bone. It consists of two lobes — a small posterior one, and an anterior larger one, somewhat resembling the thyroid in structure. The anterior lobe is developed as a tubular prolongation from the epiblast of the buccal cavity. The growth of intervening tissue soon cuts off all connection with the mouth. The alveoli are approximately spherical ; they are filled with nucleated cells of various sizes and shapes not unlike ganglion cells, collected together into rounded masses, filling the vesicles, and contained in a colloid substance. The vesicles are enclosed by connective-tissue, rich in capillaries. The posterior lobe is developed from the floor of the third ventricle ; it consists mainly of vascular connective tissue, and includes masses of epithelial cells. In the adult it contains no distinct nerve-cells, but it receives nerve-fibres which originate in the grey matter behind the optic chiasma. Disease of the pituitary body produces the condition called acromegaly, in which the bones of limbs and face hypertrophy. When the gland is removed in animals, tremors and spasms occur like those which take place after removal of the thyroid. Death usually occurs within fourteen days. Some observers have stated that overgrowth of the pituitary occurs after excision of the thyroid. But there is no ground for the assumption that the two glands ha\t a similar function. Acromegaly is a very different disease from myxoedema. The injection of extracts of the organs are also different. Thyroid extract produces a fall of arterial pressure. Extracts of the anterior lobe of the pituitary body are inactive ; but extracts of the posterior lobe or infundibular body contain two active substances, one of which produces a rise, and the other a fall of blood-pressure. A second dose of the former of these injected soon after the first dose is inactive ; and so it is not the same thing as in supra -renal extract. The chemical nature of the two substances is not known. Pituitary extracts when injected into the blood also produce diuresis (Schafer). The Pineal Gland. This gland, which is a small reddish body, is placed beneath the back part of the corpus callosum, and rests upon the corpora 342 THE DUCTLESS GLANDS [CH. XXIII. quadrigemina. It is composed of tubes and saccules lined and some- times filled with epithelial cells, and containing deposits of earthy- salts (brain sand). These are separated by vascular connective tissue. A few small atrophied nerve-cells without axons are also seen. In certain lizards, such as Hatteria, the pineal gland is better developed and is connected by nerve-fibres to a rudimentary third eye situated centrally on the upper surface of the head, but covered by skin. The Coccygeal and Carotid Glands. These so-called glands are situated, the one in front of the tip of the coccyx and the other at the point of bifurcation of the common carotid artery on each side. They are made up of a plexus of small arteries, and are enclosed and supported by a capsule of fibrous tissue. They contain also polyhedral cells collected into spheroidal clumps (carotid gland) or irregular nodules (coccygeal gland). Some of the cells of the carotid gland stain brown with chromic acid like those of the supra-renal medulla. CHAPTEE XXIV RESPIRATION The respiratory apparatus consists of the lungs and of the air-passages which lead to them. In marine animals the gills fulfil the same functions as the lungs of air-breathing animals. The muscles which move the thorax and the nerves that supply them must also be in- cluded under the general heading Eespiratory System ; and, using this expression in the widest sense, it includes practically all the tissues of the body, since they are all concerned in the using up of oxygen and the production of waste materials, like carbonic acid. Essentially a lung or gill is constructed of a thin membrane, one surface of which is exposed to the air or water, as the case may be, while, on the other is a network of blood-vessels — the only separation between the blood and aerating medium being the thin wall of the blood-vessels, and the fine membrane on one side of which vessels are distributed. The difference between the simplest and the most com- plicated respiratory membrane is one of degree only. The lungs or gills are only the medium for the exchange, on the part of the blood, of carbonic acid for oxygen. They are not the seat, in any special manner, of those combustion-processes of which the production of carbonic acid is the final result. These processes occur in all parts of the body in the substance of the tissues. The Respiratory Apparatus. The lungs are contained in the chest or thorax, which is a closed cavity having no communication with the outside except by means of the respiratory passages. The air enters these passages through the nostrils or through the mouth, whence it passes through the larynx into the trachea or windpipe, which about the middle of the chest divides into two tubes, bronchi, one to each (right and left) lung. The Larynx is the upper part of the passage, and will be described in connection with the voice. The Trachea and Bronchi. — The trachea extends from the cricoid cartilage, which is on a level with the fifth cervical vertebra, to a 3in 344 RESPIRATION [CII. XXIV. point opposite the third dorsal vertebra, where it divides into the two bronchi, one for each lung (fig. 317). It measures, on an average, H l Fig. 317. — Outline showing the general form of the larynx, trachea, and bronchi, as seen from the front, h, The great cornu of the hyoid bone : e, epiglottis ; t, superior, and V , inferior cornu of the thyroid carti- lage ; c, middle of the cricoid cartilage ; tr, the trachea, showing sixteen cartila- ginous rings ; b, the right, and b', the left bronchus. (Allen Thomson.) Pig. 318.— Outline showing the general form of the larynx, trachea, and bronchi, as seen from behind, h, Great cornu of the hyoid bone ; t, superior, and t', the inferior cornu of the thyroid cartilage ; e, epiglottis ; a, points to the back of both the arytenoid cartilages, which are surmounted by the cornicula ; c, the middle ridge on the back of the cricoid cartilage ; tr, the posterior membranous part of the trachea ; b, b', right and left bronchi. (Allen Thomson.) four or four and a half inches in length and from three-quarters of an inch to an inch in diameter, and is essentially a tube of fibro-elastic membrane, within the layers of which are imbedded a series of carti- laginous rings, from sixteen to twenty in number. These rings ex- CH. XXIV.] THE TRACHEA AND BRONCHI 345 tend only around the front and sides of the trachea (about two-thirds of its circumference) and are deficient behind; the interval between their posterior extremities is bridged over by a continuation of the fibrous membrane in which they are enclosed (fig. 318). The carti- lages of the trachea and bronchial tubes are of the hyaline variety. Immediately within this tube, at the back, is a layer of un- striped muscular fibres, which extends, transversely, between the ends of the cartilaginous rings to which they are attached, and opposite the intervals between them also ; their function is to diminish, when required, the calibre of the trachea by ap- proximating the ends of the cartilages. Outside these are a few longitudinal bundles of mus- cular tissue, which, like the pre- ceding, are attached both to the fibrous and cartilaginous frame- work. The mucous membrane con- sists to a great extent of loose lymphoid tissue, separated from the ciliated epithelium (fig. 322) which lines it by a homogeneous basement membrane. In the deeper part of the corium of the mucous membrane are many elastic fibres, between which lie connective-tissue corpuscles and capillary blood-vessels. Numerous mucous glands are situated in the substance of the mucous membrane of the trachea ; their ducts perforate the various structures which form the wall of the trachea, and open through the mucous membrane into the interior (fig. 319). The two bronchi into which the trachea divides, of which the right is shorter, broader, and more horizontal than the left (fig. 317), resemble the trachea in structure, with the difference that in them there is a distinct layer of unstriped muscle arranged circularly beneath the mucous membrane, forming the muscularis mucosae. On sSlif'""' 5 -<53> -;-yE'Ml;i;l|l Fig. 319. — Section of the trachea, a, columnar cili- ated epithelium ; 6 and c, corium of the mucous membrane, containing elastic fibres cut across transversely ; d, submucous tissue containing mucous glands, e, separated from the hyaline cartilage, g, by tine fibrous tissue, /; h, external investment of fine fibrous tissue. (S. K. Alcock.) 346 RESPIRATION [CH. XXIV. entering the substance of the lungs the cartilaginous rings, although they still form only larger or smaller segments of a circle, are no longer confined to the front and sides of the tubes, but are distributed impartially to all parts of their circumference. The bronchi divide and subdivide, in the substance of the lungs, into a number of smaller and smaller branches (bronchial tubes), which penetrate into every part of the organ, until at length they end in the smaller subdivisions of the lungs called lobules. All the larger branches have walls formed of fibrous tissue, con- taining portions of cartilaginous rings, by which they are held open, and unstriped muscular fibres, as well as longitudinal bundles of elastic tissue. They are lined by mucous membrane the surface of which, like that of the larynx and trachea, is covered with ciliated Fig. 320.— Transverse section of a bronchial tube, about h inch in diameter, e, Epithelium (ciliated); immediately beneath it is the corium of the mucous membrane, of varying thickness; m, muscular layer; s.m, submucous tissue; /, fibrous tissue; c, cartilage enclosed within the layers of fibrous tissue ; g, mucous gland. (F. E. Schulze.) epithelium, but the several layers become less and less distinct until the lining consists of a single layer of short columnar cells covered with cilia (fig. 320). The mucous membrane is abundantly provided with mucous glands. As the subdivisions become smaller and smaller, and their walls thinner, the cartilaginous rings become scarcer and more irregular, until, in the smaller bronchial tubes, they are represented only by minute and scattered cartilaginous flakes. When the bronchial tubes, by successive branchings, are reduced to about -fo of an inch (-6 mm.) in diameter they lose their cartilaginous element altogether, and their walls are formed only of a fibrous elastic membrane with circular muscular fibres; they are still lined, however, by a thin mucous membrane with ciliated epithelium, the length of the cells bearing the cilia having become so far diminished that the cells are now cubical. In the smaller bronchial tubes the muscular fibres are CH. XXIV.] THE LUNGS 347 relatively more abundant than in the larger ones, and form a distinct circular coat. Tlie Lungs and Pleurae. — The lungs occupy the greater portion of the thorax. They are of a spongy elastic texture, and are composed Fig. 321. — Transverse section of the chest. of numerous minute air-sacs, and on section every here and there the air-tubes may be seen cut across. Any fragment of lung (unless from a child that has never breathed, or in cases of disease in which the lung is consolidated) floats in water ; no other tissue does this. Each lung is enveloped by a serous membrane — the pleura, one layer of which adheres closely to its surface, and provides it with its smooth and slippery covering, while the other adheres to the inner sur- face of the chest-wall. The con- tinuity of the two layers, which form a closed sac, as in the case of other serous membranes, will be best understood by reference to fig. 321. The appearance of a space, however, between the pleura which covers the lung {visceral layer) and that which lines the inner surface of the chest (parietal layer) is in- serted in the drawing only for the sake of distinctness. It does not really exist. The layers are, in health, everywhere in contact one with the other; and between them is only just so much fluid as will ensure the lungs gliding easily, in their expansion and contraction, on the inner surface of the parietal layer, which lines the chest-wall. Fig. 322. — Ciliated epithelium of the human trachea, a, Layer of longitudinally arranged elastic fibres ; 6, basement membrane ; c, deepest cells circular in form ; d, inter- mediate elongated cells ; e, outermost layer of cells fully developed and bearing cilia, x 350. (Kolliker.) 348 RESPIRATION [CH. XXIV. If, however, an opening is made so as to permit air or fluid to enter the pleural sac, the lung, in virtue of its elasticity, recoils, and a considerable space is left between it and the chest- wall. In other words, the natural elasticity of the lungs would cause them at all times to contract away from the ribs were it not that the contraction is resisted by atmospheric pressure which bears only on the inner surface of the air-tubes and air-sacs. On the admission of air into the pleural sac atmospheric pressure bears alike on the inner and outer surfaces of the lung, and their elastic recoil is no longer prevented. Each lung is partially subdivided into separate portions called lobes ; the right lung into three lobes, and the left into two. Each Fig. 323.— Terminal branch of a bronchial tube, with its infundibula and air-sacs, from the margin of the lung of a monkey, injected with quicksilver, a, Terminal bronchial twig; 6 b, infundibula and air- sacs, x 10. (F. E. Schulze.) Fig. 324. — Two small infundibula or groups of air-sacs, a a, with air--.a<\s, b b, and the ultimate bronchial tubes, c c, with which the air-sacs com- municate. From a new-born child. (Kolliker.) of these lobes, again, is composed of a large number of minute parts, called lobules. Each pulmonary lobule may be considered to be a lung in miniature, consisting, as it does, of a branch of the bronchial tube, of air-sacs, blood-vessels, nerves, and lymphatics, with a sparing amount of areolar tissue. On entering a lobule, the small bronchial tube, the structure of which has just been described (a, fig. 323), divides and subdivides; its walls at the same time become thinner and thinner, until at length they are formed only of a thin membrane of areolar, muscular, and elastic tissue, lined by a layer of pavement epithelium not pro- vided with cilia. At the same time they are altered in shape ; each of the minute terminal branches widens out funnel-wise, and its walls are pouched out irregularly into small saccular dilatations, CH. XXIV.] THE AIR VESICLES 349 called air-sacs (fig. 323, I). Such a funnel-shaped terminal branch of the bronchial tube, with its group of pouches or air-sacs, is called an infundibulum (figs. 323, 324), and the irregular oblong space in its centre, with which the air-sacs communicate, an intercellular passage. The air-sacs, or air-vesicles, may be placed singly, like recesses from the intercellular passage, but more often they are arranged in groups, or even in rows, like minute sacculated tubes ; so that a short series of vesicles, all communicating with one another, open by a common orifice into the tube. The vesicles are of various forms, according to the mutual pressure to which they are subject ; their Fig. 325. — Section of lung stained with silver nitrate. A. D., alveolar duct or intercellular passage ; S, alveolar septa; N, alveoli or air-sacs, lined with large flat cells, with some smaller polyhedral cells ; M, plain muscular fibres surrounding the alveolar duct. (Klein and Noble Smith.) walls are nearly in contact, and they vary from -gVth to ^th of an inch ('5 to - 3 mm.) in diameter. Their walls are formed of fine membrane, like those of the intercellular passage; this membrane is folded on itself so as to form a sharp-edged border at each circular orifice of communication between contiguous air-vesicles, or between the vesicles and the bronchial passages. Numerous fibres of elastic tissue are spread out between contiguous air-sacs, and many of these are attached to the outer surface of the fine membrane of which each sac is composed, imparting to it additional strength and the power of recoil after distension. The vesicles are lined by a layer of pavement epithelium (fig. 325) not provided with cilia. Outside the air-vesicles a network of pulmonary capillaries is spread out so densely (fig. 326) that the interspaces or meshes are even narrower than the vessels, 350 RESPIRATION [CII. XXIV. which are, on an average, ^r&Tfth of an inch (8/a) in diameter. Between the air in the sacs and the blood in these vessels nothing intervenes but the thin walls of the air-sacs and of the capillaries ; and the exposure of the blood to the air is the more complete, because the folds of membrane between contiguous air-sacs, and often the spaces between the walls of the same, contain only a single layer of capillaries, both sides of which are thus at once exposed to the air. The arrangement of the capillaries is shown on a larger scale in fig. 233 (p. 222). The vesicles of adjacent lobules do not communicate ; so that, when any bronchial tube is closed or obstructed, the supply of air is lost for all the sacs opening into it or its branches. Fig. 326. -Capillary network of the pulmonary bit x 60. (Kiilliker.) Dd-vessels in the human lung. Blood-supply. — The lungs receive blood from two sources, (a) the pulmonary artery, (b) the bronchial arteries. The former conveys venous blood to the lungs to be arterialised, and this blood takes no share in the nutrition of the pulmonary tissues through which it passes. The branches of the bronchial arteries convey arterial blood from the aorta for the nutrition of the walls of the bronchi, of the larger pulmonary vessels, of the interlobular connective-tissue, etc. ; the blood of the bronchial vessels is returned chiefly through the bronchial and partly through the pulmonary veins. Lymphatics. — The lymphatics are arranged in three sets: — 1. Irregular lacunre in the walls of the alveoli or air-sacs. The lym- phatic vessels which lead from these accompany the pulmonary vessels towards the root of the lung. 2. Irregular anastomosing spaces in the walls of the bronchi. 3. Lymph-spaces in the pul- monary pleura. The lymphatic vessels from all these irregular Ctl. XXIV.] THE KESPIKATORY MECHANISM 351 sinuses pass in towards the root of the lung to reach the bronchial lymphatic glands. Nerves. — The nerves of the lung are to be traced from the anterior and posterior pulmonary plexuses, which are formed by branches of the vagus and sympathetic. The nerves follow the course of the vessels and bronchi, and in the walls of the latter many small ganglia are situated. The Respiratory Mechanism. Eespiration consists of the alternate expansion and contraction of the thorax, by means of which air is drawn into or expelled from the lungs. These acts are called Inspiration and Expiration respectively. For the inspiration of air into the lungs it is evident that all that is necessary is such a movement of the side-walls or floor of the chest, or of both, that the capacity of the interior shall be enlarged. By such increase of capacity there will be a diminution of the pressure of the air in the lungs, and a fresh quantity will enter through the larynx and trachea to equalise the pressure on the inside and outside of the chest. For the expiration of air, on the other hand, it is also evident that, by an opposite movement which shall diminish the capacity of the chest, the pressure in the interior will be increased, and air will be expelled, until the pressure within and without the chest are again equal. In both cases the air passes through the trachea and larynx, whether in entering or leaving the lungs, there being no other com- munication with the exterior of the body ; and the lung, for the same reason, remains, under all the circumstances described, closely in contact with the walls and floor of the chest. To speak of expansion of the chest, is to speak also of expansion of the lung. The move- ments of the lung are therefore passive, not active, and depend on the changes of shape of the closed cavity in which they are contained. A perforation of the chest-wall would mean that the lung on that side would no longer be of use ; a similar injury on the other side (double pneumothorax) would cause death. If the two layers of the pleura were adherent, those portions of the lung would be expanded most where the movements of the chest are greatest. The existence of the two layers prevents this, and thus the lung is equally expanded throughout. Inspiration. — The enlargement of the chest in inspiration is a muscular act ; the effect of the action of the inspiratory muscles is an increase in the size of the chest-cavity in the vertical, and in the lateral and antero-posterior diameters. The muscles engaged in ordinary inspiration are the diaphragm ; the external intercostals ; parts of the internal intercostals ; the levatores costarum ; and ser- ratus posticus superior. 352 RESPIRATION [CH. XXIV. The vertical diameter of the chest is increased by the contraction and consequent descent of the diaphragm ; at rest, the diaphragm is dome-shaped with the convexity upwards ; the central tendon forms a slight depression in the middle of this dome. On contraction the muscular fibres shorten, and so the convexity of the double dome is lessened. The central tendon, which was formerly regarded as remaining fixed, is drawn down a certain distance, but the chief movement is at the sides. For the effective action of this muscle, its attachment to the lower ribs is kept fixed by the contraction of the quaclratus lumborum. The diaphragm is supplied by the phrenic nerves. The increase in the lateral and anteroposterior diameters of the Vir.. 3'27. — Diagram of axes of movement of ribs. chest is effected by the raising of the ribs, the upper ones being fixed by the scaleni. The greater number of the ribs are attached very, obliquely to the spine and sternum. The elevation of the ribs takes place both in front and at the sides — the hinder ends being prevented from performing any upward movement by their attachment to the spine. The movement of the front extremities of the ribs is of necessity accompanied by an upward and forward movement of the sternum to which they are attached, the movement being greater at the lower end than at the upper end of the latter bone. The axes of rotation in these movements are two : one correspond- ing with a line drawn through the two articulations which the rib forms with the spine {a, b, fig. 327) ; and the other with a line drawn CH. XXIV.] EESPIEATOET MUSCLES 353 from one of these (head of rib) to the sternum (A B, fig. 327) ; the motion of the rib around the latter axis being somewhat after the fashion of raising the handle of a bucket. The elevation of the ribs is accompanied by a slight opening out of the angle which the bony part forms with its cartilage ; and thus an additional means is provided for increasing the antero-posterior diameter of the chest. The muscles by which the ribs are raised, in ordinary quiet inspiration, are the external intercostals, and that portion of the internal intercostals which is situated between the costal cartilages ; and these are assisted by the levatores costarum, and the serratus posticus superior. In tranquil breathing, the expansive movements of the lower part of the chest are greater than those of the upper. In forced inspira- tion, on the other hand, the greatest extent of movement appears to be in the upper antero-posterior diameter. In extraordinary or forced inspiration, as in violent exercise, or in cases in which there is some interference with the due entrance of air into the chest, and in which, therefore, strong efforts are necessary, other muscles than those just enumerated are pressed into service. It is impossible to separate by a hard-and-fast line the muscles of ordinary from those of extraordinary inspiration; but there is no doubt that the following are but little used as respiratory agents, except in cases in which unusual efforts are required — the sterno- mastoid, the serratus magnus, the pectorales, and the trapezius. Laryn- geal and face muscles also come into play. The expansion of the chest in inspiration presents some peculi- arities in different persons. In young children, it is effected chiefly by the diaphragm, which being highly arched in expiration, becomes flatter as it contracts, and, descending, presses on the abdominal viscera, and pushes forward the front walls of the abdomen. The movement of the abdominal walls being here more manifest than that of any other part, it is usual to call this the abdominal type of respira- tion. In men, together with the descent of the diaphragm, and the pushing forward of the front wall of the abdomen, the chest and the sternum are subject to a wide movement in inspiration (inferior costal type). In women, the movement appears less extensive in the lower, and more so in the upper, part of the chest (superior costal type). There are also differences in different animals. In the frog, for example, the air is forced into the lungs by the raising of the floor of the mouth, the mouth and nostrils being closed. Expiration. — From the enlargement produced in inspiration, the chest and lungs return, in ordinary tranquil expiration, by their elasticity ; the force employed by the inspiratory muscles in distend- ing the chest and overcoming the elastic resistance of the lungs and z 354 RESPIRATION [CII. XXIV. chest-walls, is returned as an expiratory effort when the muscles are relaxed. This elastic recoil of the chest and lungs is sufficient, in ordinary quiet breathing, to expel air from the lungs in the intervals of inspiration, and no muscular power is required. In all voluntary expiratory efforts, however, as in speaking, singing, blowing, and the like, and in many involuntary actions also, as sneezing, coughing, etc., something more than merely passive elastic power is necessary, and the proper expiratory muscles are brought into action. By far the chief of these are the abdominal muscles, which, by pressing on the viscera of the abdomen, push up the floor of the chest formed by the diaphragm, and by thus making pressure on the lungs, expel air from them through the trachea and larynx. All muscles, however, which depress the ribs, must act also as muscles of expiration, and therefore we must conclude that the abdominal muscles are assisted in their action by the interosseous part of the internal inter costals, the triangularis sterni, the serratus posticus inferior, and quadratics lumborum. When by the efforts of the expiratory muscles, the chest has been squeezed to less than its average diameter, it again, on relaxation of the muscles, returns to the normal dimensions by virtue of its elasticity. The construction of the chest-walls, therefore, admirably adapts them for recoiling against and resisting as well undue contraction as undue dilatation. In the natural condition of the parts, the lungs can never contract to the utmost, but are always more or less " on the stretch," being kept closely in contact with the inner surface of the chest walls. Methods of recording Respiratory Movements. The movements of respiration may be recorded graphically in several ways. One method is to introduce a tube into the trachea of an animal, and to connect this tube by some gutta-percha tubing with a "["-piece introduced into the cork of a large bottle, the other end of the T having attached to it a second piece of tubing, which can remain open or can be partially or completely closed by means of a screw clamp. Into the cork is inserted a second piece of glass tubing connected with a Marey's tambour by suitable tubing. This second tube communicates any altera- tion of the pressure in the bottle to the tambour, and this may be made to write on a recording surface. There are various instruments for recording the movements of the chest by application of apparatus to the exterior. Such is the stethograph of Burdon- Sanderson (fig. 329). This consists of a frame formed of two parallel steel bars joined by a third at one end. At the free end of the bars is attached a leather strap, by means of which the apparatus may be suspended from the neck. Attached to the inner end of one bar is a tambour and ivory button, to the end of the other an ivory button. When in use, the apparatus is suspended with the transverse bar posteriorly, the button of the tambour is placed on the part of the chest the move- ment of which it is desired to record, and the other button is made to press upon the corresponding point on the other side of the chest, so that the chest is, as it were, held between a pair of callipers. The tambour is connected by tubing and a T-piece with a recording tambour and with a ball, by means of which air can be squeezed into the cavity of the tambour. When in work the tube connected with the air ball is shut off by means of a screw clamp. The movement of the chest is thus communicated to the recording tambour. en. xxiv.] STETHOGEAPHS 355 A simpler form of this apparatus consists of a thick india-rubber bag of ellipti- cal shape about three inches long, to one end of which a rigid gutta-percha tube is Fig. 32S. — Stethograph. h, tambour fixed at right angles to plate of steel/,- c and d, arms by which instrument is attached to chest by belt e. When the chest expands, the arms are pulled asunder, which bends the steel plate, and the tambour is affected by the pressure of b, which is attached to it on the one hand, and to the upright in connection with horizontal screw g. (Modified from Marey's instrument.) attached. This bag may be fixed at any required place on the chest by means of a strap and buckle. By means of the gutta-percha tube the variations of the pres- Fig. 329. — Stethograph. (Burdon-Sanderson.) 356 RESPIRATION [CII. XXIV. sure of air in the bag produced by the movements of the chest are communicated to a recording tambour. This apparatus is a simplified form of Marey's stetho- graph (fig. 328). The variations of intrapleural pressure may be recorded by the introduction of a cannula into the pleural cavity, which is connected with a mercurial manometer. Finally, it has been found possible in various ways to record the diaphragmatic movements by the insertion of an elastic bag connected with a tambour into the abdomen below it (phrenograph), by the insertion of needles into different parts of its structure, or by recording the contraction of isolated strips of the diaphragm. Such a strip attached in the rabbit to the xiphisternal cartilage may be detached, and attached by a thread to a recording lever. This method was largely used by Head ; this strip serves as a sample of the diaphragm. Fig. 330 shows a tracing obtained in this way ; but in tracings taken with a Fig. 330. — Tracing of the normal diaphragm respirations of rabbit, a, with quick movement of drum. b, with slow movement. The upstrokes represent inspiration ; the downstrokes, expiration. To be read from left to right. The time tracing in each case represents seconds. (Marckwald.) stethograph, or any of the numerous arrangements of tambours which are applied to the chest-walls of men and animals, the large up-and-down strokes due to the respiratory movements have upon them smaller waves due to heart-beats. The acts of expansion and contraction of the chest take up under ordinary circumstances a nearly equal time. The act of inspiring air, however, especially in women and children, is a little shorter than that of expelling it, and there is commonly a very slight pause between the end of expiration and the beginning of the next inspira- tion. If the ear be placed in contact with the wall of the chest, or be separated from it only by a good conductor of sound or stethoscope, a faint respiratory or vesicular murmur is heard during inspiration. This sound varies somewhat in different parts — being loudest or CH. XXIV.] TIDAL AIR 357 coarsest in the neighbourhood of the trachea and large bronchi (tracheal and bronchial breathing), and fading off into a faint sighing as the ear is placed at a distance from these (vesicular breathing). It is best heard in children, and in them a faint murmur is heard in ex- piration also. The cause of the vesicular murmur has received various explanations ; but most observers hold that the sound is produced by the air passing through the glottis and larger tubes, and that this sound is modified in its conduction through the substance of the lung. The alterations in the normal breath sounds, and the various additions to them that occur in different diseased conditions, can only be properly studied at the bedside. Respiratory movements of the Nostrils and of the Glottis. — During the action of the muscles which directly draw air into the chest, those which guard the opening through which it enters are not pas- sive. In hurried breathing the instinctive dilatation of the nostrils is well seen, although under ordinary conditions it may not be notice- able. The opening at the upper part of the larynx or rima glottidis is slightly dilated at each inspiration for the more ready passage of air, and becomes smaller at each expiration ; its condition, therefore, corresponds during respiration with that of the walls of the chest. There is a further likeness between the two acts in that, under ordi- nary circumstances, the dilatation of the rima glottidis is a muscular act and its narrowing chiefly an elastic recoil. Terms used to express Quantity of Air breathed. — a. Tidal air is the quantity of air which is habitually and almost uniformly changed in each act of breathing. In a healthy adult man it is about 20 cubic inches, or about 300 c.c. It will be seen that this amount of air is not nearly sufficient to fill the lungs; it fills the upper respiratory passages ; Zuntz gives the capacity of the upper air passages and bronchial tubes as 140 c.c, and if this low estimate is correct, about half the tidal air is required to fill this space. At the end of an expiration, however, the tubes and alveoli are not empty of air, and the sudden inrush of atmospheric air during inspiration effects a complete mixture of this air with that left in the air passages ; it is possible that the air in the axial stream of the current may penetrate as far even as the alveoli, but what is sucked into the alveoli is mainly some of the mixture from the bronchial passages, and that in turn is derived from the mixture (containing more atmos- pheric air in proportion) in the upper air cavities. During expiration the air which leaves the lungs may come in part from the alveoli, but the effect of the stream of outgoing air is mainly as before to effect a thorough admixture of the air in the intermediate air passages ; thus the alveolar air will become mixed with that in the bronchial tubes, and that in turn will be mixed with that in the upper air chambers. In a succession of alternate inspirations and expirations adequate 358 RESPIRATION [CH. XXIV. ventilation is secured, but obviously the composition of the expired air is not the same as that of alveolar air, for the latter, though it is ultimately breathed out, is diluted on its upward journey by mixture with the bronchial air, and that in its turn with the air of the upper air chambers ; in other words, the expired air is alveolar air (rich in carbon dioxide) diluted with bronchial air (richer in oxygen) and with atmospheric air (still richer in oxygen). No doubt diffusion of gases occurs as well, oxygen diffusing inwards and carbon dioxide outwards, but this molecular movement is too slow to be of any real use in aerating the blood, for almost immediately the respiratory movements cease, death occurs. b. Complemented air is the quantity over and above this which can be drawn into the lungs in the deepest inspiration ; its amount varies, but it may be reckoned as 100 cubic inches, or about 1600 c.c. c. Reserve or supplemental air. — After ordinary expiration, such as that which expels the breathing or tidal air, a certain quantity of air, about 100 cubic inches (1600 c.c.) remains in the lungs, which may be expelled by a forcible and deeper expiration. This is termed reserve or supplemental air. d. Residual air is the quantity which still remains in the lungs after the most violent expiratory effort. Its amount depends in great measure on the absolute size of the chest, but may be estimated at about 100 cubic inches, or about 1600 c.c. The total quantity of air which passes into and out of the lungs of an adult, at rest, in 24 hours, varies from 400,000 (Marcet) to 680,000 (Hutchinson) cubic inches. This quantity, however, is increased, and may be more than doubled by exertion. e. Respiratory or Vital Capacity. — The vital capacity of the chest is indicated by the quantity of air which a person can expel from his lungs by a forcible expiration after the deepest inspiration possible. The average capacity of an adult, at 15"4° C. (60° F.), is about 225 to 250 cubic inches, or 3500 to 4000 c.c. It is the sum of the com- plemental, tidal, and supplemental air. The respiratory capacity, or as John Hutchinson called it, vital capacity, is usually measured by a modified gasometer or spirometer, into which the experi- menter breathes, — making the most prolonged expiration possible after the deepest possible inspiration. The quantity of air which is thus expelled from the lungs is indicated by the height to which the air-chamber of the spirometer rises ; and by means of a scale placed in connection with this, the number of cubic inches is read off. In healthy men, the respiratory capacity varies chiefly with the stature, weight, and age. It was found by Hutchinson, from whom most of our information on this subject is derived, that at a temperature of 15'4 C C. (60° R), CH. XXIV.] VITAL CAPACITY 359 225 cubic inches is the average vital or respiratory capacity of a healthy person, five feet seven inches in height. Circumstances affecting the amount of respiratory capacity. — For every inch of height above this standard the capacity is increased, on an average, by eight cubic inches ; and for every inch below, it is diminished by the same amount. The influence of weight on the capacity of respiration is less manifest and con- siderable than that of height ; and it is difficult to arrive at any definite conclusions on this point, because the natural average weight of a healthy man in relation to stature has not yet been determined. As a general statement, however, it may be said that the capacity of respiration is not affected by weights under 161 pounds, or 11| stones ; but that, above this point, it is diminished at the rate of one cubic inch for every additional pound up to 196 pounds, or 14 stones. By age, the capacity is increased from about the fifteenth to the thirty-fifth year, at the rate of five cubic inches per year ; from thirty-five to sixty-five it diminishes at the rate of about one and a half cubic inch per year ; so that the capacity of respiration of a man of sixty years old would be about 30 cubic inches less than that of a man forty years old, of the same height and weight. Sex.— The vital capacity of an adult man to that of a woman of the same height is 10 to 7. The number of respirations in a healthy adult person usually ranges from 14 to 18 per minute. It is greater in infancy and childhood. It varies also much according to different circumstances, such as exercise or rest, health or disease, etc. Variations in the number of respirations correspond ordinarily with similar variations in the pulsations of the heart. In health the proportion is about 1 to 4, or 1 to 5, and when the rapidity of the heart's action is increased, that of the chest movement is commonly increased also ; but not in every case in equal proportion. It happens occasionally in disease, especially of the lungs or air-passages, that the number of respiratory acts increases in quicker proportion than the beats of the pulse ; and, in other affections, much more commonly, that the number of the pulse-beats is greater in proportion than that of the respirations. The Force of Inspiratory and Expiratory Muscles. — The force with which the inspiratory muscles are capable of acting is greatest in individuals of the height of from five feet seven inches to five feet eight inches, and will elevate a column of nearly three inches (about 60 mm.) of mercury. Above this height the force decreases as the stature increases ; so that the average of men of six feet can elevate only about two and a half inches of mercury. The force manifested in the strongest expiratory acts is, on the average, one-third greater than that exercised in inspiration. But this difference is in great measure due to the power exerted by the elastic reaction of the walls of the chest ; and it is also much influenced by the disproportionate strength which the expiratory muscles attain, from their being called into use for other purposes than that of simple expiration. The force of the inspiratory act is, therefore, better adapted than that of the expiratory for testing the muscular strength of the body. (John Hutchinson.) 360 RESPIEATION [CH. XXIV. In ordinary quiet breathing, there is a negative pressure of only 1 mm. during inspiration, and a positive pressure of from 2 to 3 mm. mercury during expiration. The instrument used by Hutchinson to gauge the inspiratory and expiratory power was a mercurial manometer, to which was attached a tube fitting the nostrils, and through which the inspiratory or expiratory effort was made. The greater part of the force exerted in deep inspiration is employed in overcoming the resistance offered by the elasticity of the lungs. In man the pressure exerted by the elasticity of the lungs alone is about 6 mm. of mercury. This is estimated by tying a manometer into the trachea of a dead subject, and observing the rise of mercury that occurs on puncture of the chest-walls. If the chest is distended beforehand so as to imitate a forcible inspiration, a much larger rise (30 mm.) of the mercury is obtained. In the body this elastic force is assisted by the contraction of the plain muscular fibres of the alveoli and bronchial tubes, the pressure of which probably does not exceed 1 or 2 mm. Hutchinson calculated that the total force to be overcome by the muscles in the act of inspiring 200 cubic inches of air is more than 450 lbs. It is possible that the contractile power which the bronchial tubes and air-vesicles possess, by means of their muscular fibres, may assist in expiration ; but it is more likely that the chief purpose of this muscular tissue is to regulate and adapt, in some measure, the quantity of air admitted to the lungs, and to each part of them, according to the supply of blood : the muscular tissue also contracts upon and gradually expels collections of mucus, which may have accumulated within the tubes, and which cannot be ejected by forced expiratory efforts, owing to collapse or other morbid conditions of the portion of lung connected with the obstructed tubes (Gairdner). The Nervous Mechanism of Respiration. In the central nervous system there is a specialised small district called the respiratory centre. This gives out impulses which travel down the spinal cord to the centres of the spinal nerves that innervate the muscles of respiration. It also receives various afferent fibres, the most important of which are contained in the trunk of the vagus. The vagus is chiefly an afferent nerve in relation to respira- tion. It, however, also is in a minor degree efferent, for it supplies the muscular tissue of the lungs and bronchial tubes, and exercises a trophic influence on the lung. The respiratory centre was discovered by Flourens ; it is situated at the tip of the calamus scriptorius, and almost exactly coincides in position with the centre of the vagus. The existence of subsidiary CH. XXTV.] NEKVOUS MECHANISM OF EESPIEATION 361 respiratory centres in the spinal cord has been mooted, but the balance of experimental evidence is against their existence. Flourens found that when the respiratory centre is destroyed, respiration at once ceases, and the animal dies. He therefore called it the " vital knot " (noeud vitale). The centre is affected not only by the afferent impulses which reach it from the vagus, but also by those from the cerebrum ; so that we have a limited amount of voluntary control over the respiratory movements. The sensory nerves of the skin have also an effect. The action of the air on the body of a new-born child is no doubt the principal afferent cause of the first respirations. During foetal life, the need of the embryo for oxygen is very small, and is amply met by the trans- ference of oxygen from the maternal blood through the thin walls of the foetal capillaries in the placenta. The application of cold water to the skin always causes a deep inspiration ; this is another instance of the reflex effect which follows stimulation of the cutaneous nerves. Stimulation of the central end of the splanchnics causes expiration. Stimulation of the central end of the glosso-pharyngeal causes an inhibition of the respiratory movements for a short period ; this accounts for the very necessary cessation of breathing during swallow- ing. Stimulation of the central end of the cut superior laryngeal nerve, or of its terminations in the mucous membrane of the larynx, as when a crumb is " swallowed the wrong way," produces inhibition of inspiratory and increase of expiratory efforts, culminating in coughing. These nerves, however, are none of them in constant action as the vagi are, and the influence of the vagus is somewhat complicated. Still, respiration continues after the vagi are cut. The character of the respiration becomes altered, especially if both nerves are severed ; it is slower and deeper. This is due to the cessation of the impulses that normally run up the vagi to the respiratory centre. The animal, however, lives a considerable time ; a warm-blooded animal usually dies after about a week or ten days from vagus pneumonia, due to the removal of trophic influences from the lungs. Cold-blooded animals live longer; they exhibit fatty degeneration of the heart-muscle also. The question has been much debated whether the activity of the respiratory centre is automatic or reflex ; that is to say, whether the rhythmic discharges proceeding from it depend on local changes induced by the condition of its blood supply, or on the repeated stimulations it receives by afferent nerves. There appears every reason to believe that the centre has the power of automatism, but this is never excited under normal circumstances. Normally, the respiratory process is a series of reflex actions. 362 RESPIRATION [CH. XXIV. The evidence in favour of the automatic activity of the centre is the following :— (1.) If the spinal cord is cut just below the bulb, respiration ceases, except in the case of the facial and laryngeal muscles, which are supplied by nerves that originate above the point of injury. The alfe nasi work vigorously. Such respiration is not effective in drawing any air into the chest, and so the animal soon dies ; but the forcible efforts of these muscles show that the respiratory centre is in a state of activity, sending out impulses to them. If the two vagus nerves are cut, these movements continue ; this shows that afferent impulses from the vagus are not essential. As the blood gets more and more venous, the movements become more pronounced. The question has arisen whether this increased activity of the respiratory centre is due to increase of carbonic acid, or decrease of oxygen in the blood which it receives. The balance of evidence shows that the increase in the carbonic acid is the more important of the two. (2.) In asphyxia, one always gets great increase of respiratory activity, called dyspnoea ; this is produced by the stimulation of the centre by venous blood. It is not due (or not wholly due) to the action of the venous blood on the terminations of the vagi in the lungs, as the same phenomenon occurs when these nerves are cut ; and, moreover, dyspnoea takes place if the venous blood is allowed to circulate through the brain alone, and not through the lungs at all. For instance, it ensues when localised venosity of the blood is produced in the brain by ligature of the carotid and vertebral arteries. But, as before stated, the normal activity of the respiratory centre is not automatic, it is reflex, and the principal afferent channel is the vagus. The way in which it works has been made out of recent years by Marckwald, Hering, and Head. The following is a brief re'sume' of Head's results : — His method of recording the movements was by means of that con- venient slip of the diaphragm which is found in rabbits (see p. 356). His method of dividing the vagus was by freezing it ; he laid it across a copper wire, the end of which was placed in a freezing mixture. This method is free from the disadvantage which a cut with a knife or scissors possesses, namely, a stimulation at the moment of section. On dividing one vagus, respiration became slightly slower and deeper ; on dividing the second nerve, this effect was much more marked. On exciting the central end of the divided nerve, inspiratory efforts increased until at last the diaphragm came to a standstill in the inspiratory position. But if a weak stimulus was employed, the reverse was the case ; the expiratory efforts increased, inspiration becoming weaker and weaker, until at last the diaphragm stopped in CH. XXIV.] POSITIVE AND NEGATIVE VENTILATION 363 the position of expiration. This result always follows stimulation of the superior laryngeal nerve. Most of these facts were known previously, but the interpretation of them, in the light of further experiments immediately to be described, is the following : — That there are in the vagus two sets of fibres, one of which pro- duces an increased activity of the inspiratory part of the respiratory centre, and the other an increased activity of the expiratory part of that centre. Stimulation of the first stops expiration and produces inspiration ; stimulation of the second does the reverse. The question now is, What is it that normally produces this alternate stimulation of the two sets of fibres ? If we discover this we shall discover the prime moving cause in the alternation of the inspiratory and expiratory acts. It was sought and found in the alternate distension and con- traction of the air-vesicles of the lungs where the vagus terminations are situated. In one series of experiments positive ventilation was per- formed ; that is, air was pumped repeatedly into the lungs, and so increased their normal disten- sion ; this was found to decrease the inspiratory contractions of the diaphragm, until at last they ceased altogether, and the diaphragm stood still in the expiratory position (fig. 331, A). In a second series of ex- periments, negative ventilation was performed ; that is, the air was pumped repeatedly out of the lungs, and a condition of collapse of the air-vesicles produced. This was found to increase the inspiratory con- tractions of the diaphragm, expiration became less and less, and at last the diaphragm assumed the position of inspiratory standstill (fig. 331, B). Distension of the air- vesicles, therefore, stimulates the fibres of the vagus which excite the expiratory phase of respiration; collapse stimulates those which excite the inspiratory phase. Ordinary respiration is an alternate positive and negative ventilation, though not so excessive as in the experiments just described. Inspiration is positive ventilation, and so provides the nervous mechanism of respiration with a stimulus that leads to expiration. Expiration is a negative ventilation, and so provides the stimulus that leads to inspiration. Fig. 331. — Tracings of diaphragm. The upward move- ments of the tracings represent inspiration ; the downward movements, expiration. A, result of positive, B, of negative ventilation. (After Head.) 364 RESPIRATION [CH. XXIV. It is probable that of the two sets of impulses, those which are started by the inspiratory movement play a more active part in the regulation of respiration than those started by the expiratory move- ment. Gad explains the latter by supposing they are simply due to a cessation of the former, or, in other words, that there only exists one class of afferent fibres in the vagus concerned in respiration. This view has not, however, met with general acceptance, and is against the mass of experimental evidence. Apncea — If positive and negative ventilation are used together rapidly and alternately at a rate quicker than the respiratory rhythm, both inspiratory and expiratory processes are inhibited, and the respira- tion ceases for a short time. This follows naturally from the experi- ments previously described. This can be done on an animal with a pair of bellows fixed to a tube in the trachea ; or voluntarily by one- self taking a number of deep breaths rapidly. This condition, called apnaa, is not due, as at one time supposed, to over-oxygenation of the blood, but is produced reflexly. Under normal circumstances arterial blood is always fully oxygenated. It is observed if inert gases, like nitrogen or hydrogen, are used instead of air. The pause, however, is then shorter, as the blood becomes venous, and in a short time stimulates the respiratory centre to activity. Under abnormal circumstances, namely, after division of the vagi, apncea cannot obviously be due to such reflex action. In such de- pressed conditions of the respiratory centre, the blood becomes more venous than normal, and then the rapid inflation of the lungs with air will produce an apnceic condition. Fredericq still holds that ordinary apncea has a chemical rather than a nervous origin. He attributes it, however, not to over-oxygenation, but to a lessening of the carbonic acid in the blood. Special Respiratory Acts. Coughing. — In the act of coughing there is first of all a deep in- spiration, followed by an expiration ; but the latter, instead of being easy and uninterrupted, as in normal breathing, is obstructed, the glottis being momentarily closed by the approximation of the vocal cords. The abdominal muscles, then strongly acting, push up the viscera against the diaphragm, and thus make pressure on the air in the lungs until its tension is sufficient to noisily open the vocal cords which oppose its outward passage. In this way considerable force is exercised, and mucus or any other matter that may need expulsion from the air-passages is quickly and sharply expelled by the out- streaming current of air. The act is a reflex one, the sensory surface which is excited being the mucous membrane of the larynx, and the superior laryngeal nerve is the afferent nerve; stimulation of other parts of the respiratory mucous membrane will also produce cough, CH. XXIV.] CHBYNE-STOKES BKEATHING 365 and the point of bifurcation of the trachea is specially sensitive. Other sensory surfaces may also act as the "signal surface" for a cough. Thus, a cold draught on the skin, or tickling the external auditory meatus, in some people will set up a cough. The question has been discussed whether such a thing as a stomach cough exists ; it has not been produced experimentally, but there is no reason why irritation of the gastric mucous membrane, supplied as it is by the vagus, should not cause the reflex act of coughing. Sneezing. — The same remarks that apply to coughing are almost exactly applicable to the act of sneezing; but, in this instance, the blast of air, on escaping from the lungs, is directed, by an instinctive contraction of the pillars of the fauces and descent of the soft palate, chiefly through the nose, and any offending matter is thence expelled. The " signal surface " is usually the nasal mucous membrane, but here, as in coughing, other causes (such as a bright light) will some- times set the reflex going. Hiccough is an involuntary sudden contraction of the diaphragm, causing an inspiration which is suddenly arrested by the closure of Fig. 332.— Cheyne-Stokes respiration. (After Waller.) the glottis, causing a characteristic sound. It arises from gastric irritation. Snoring is due to vibration of the soft palate. Sobbing consists of a series of convulsive inspirations at the moment of which the glottis is partially closed. Sighing and Yawning are emotional forms of inspiration, the latter associated with stretching movements of jaws and limbs. They appear to be efforts of nature to correct, by an extra deep inspiration, the venosity of the blood due to inactivity produced by ennui or grief. Their contagious character is due to sympathy. Among abnormal disturbances of the nervous mechanism of respiration, the following diseases must be mentioned: laryngismus stridulus, asthma, and whooping-cough. Cheyne-Stokes respiration is due to rhythmical activity of the respiratory centre. It reminds one somewhat of the Traube-Hering waves due to a similar rhythmical activity of the vaso-motor centre. It is seen in many nervous diseases and in fatty degeneration of the heart. A typical tracing of the condition is given above (fig. 332). It is seen to a slight extent during ordinary sleep, and is very marked in hibernating animals. 36G RESPIRATION [CH. XXIV: Pembrey and Pitts have recently taken graphic records of this condition in the hibernating dormouse, hedgehog, marmot and bat. In some cases the respiration has the typical Cheyne-Stokes character Flo. 333. — Cheyne-Stokes respiration in hibernating dormouse. The line marked y gives time in seconds Line 1 gives the tracing of a respiratory group which occurred once every SO seconds, the tempera- ture of the animal being 11° C. On warming the animal to 13° C. the respiratory groups became more frequent (line 2). On warming the animal still further it awakened, and breathing, at lirst accompanied by shivering, became continuous. (Pembrey and Pitts.) with a gradual waxing and waning (fig. 333). In other cases periods of respiratory activity alternate with periods of apnoea, but all the respiratory efforts are about equal in force. (Biot's respiration.) The Effect of Respiration on the Circulation. The main effect of respiration on the circulation is shown in the accompanying figure. It will be noticed that the arterial pressure Fig. 334. — Comparison of blood-pressure curve with curve of intra-thoracic pressure. (To be read from left to right.) a is the curve of blood-pressure with its respiratory undulations, the slower beats on the descent being very marked ; b is the curve of intra-thoracic pressure obtained by connecting one limb of a manometer with the pleural cavity. Inspiration begins at i and expiration at e. The intra-thoracic pressure rises very rapidly after the cessation of the inspiratory etlbrt, and then slowly falls as the air issues from the chest; at the beginning of the inspiratory effort the fall becomes more rapid. (M. Foster.) rises with inspiration and falls with expiration, but that the two events are not quite synchronous, the rise of pressure beginning a CH. XXIV.] EFFECT OF RESPIRATION ON CIRCULATION 367 little later than the inspiratory act, and the fall a little later than the expiratory act. It will also be seen that the heart beats more rapidly during the rise of blood-pressure than during the fall. This difference disappears when the vagi are cut. Eespiratory undulations, however, are still present, though not so marked as before ; hence the cardiac variations are not their sole cause. They are chiefly the result of the mechanical conditions dependent on the lungs and heart with its large vessels being contained within the air-tight thorax. When the capacity of the chest is increased in inspiration, the tension of the lung tissue due to its greater expansion is increased ; hence the difference between the intra-pleural pressure, and that in the lungs (which is atmos- pheric) becomes more marked, for the difference of pressure is to be measured by the elastic force of the lung tending to produce its collapse. If the intra-thoracic pressure is measured, it is found that it varies from — 5 to — 7 mm. of mercury at the end of expiration to — 30 at the end of a deep inspiration ; that is to say, from 5 to 7 to 30 mm. less than the atmospheric pressure (760 mm. of mercury). The pressure outside the heart and large vessels is correspondingly diminished to the same extent, and produces its main effect (distension) upon the veins because they are never fully distended, and because the pressure within them is low. This increase in the "pressure gradient" (i.e., the rate of fall of pressure) between the intra and extra thoracic great veins results in a proportionately more rapid flow of blood into the thorax, and therefore into the right side of the heart ; for within certain limits the right heart can be easily expanded more fully if a greater supply of blood is provided. Consequently, the output from the right side increases, and thus vid the pulmonary circuit the inflow into the left heart is increased ; in its turn, therefore, the output from the left ventricle rises, and so the aortic pressure is raised. If the aorta and its branches within the thorax were as undistended as the veins and right auricle, this effect would be counteracted, but inasmuch as the aorta and arteries are thick -walled and already over-distended, an increased inflow into them must lead to a further distension, i.e., a further rise of pressure. For we may altogether neglect the change in rate of flow along these vessels due to the change in pressure gradient, not because it is insufficient in itself to produce a distinct change in the flow, if the blood were free to move easily, but because the outflow from the arteries has to take place through a high peripheral resistance, and this small pressure change is not able to exert any appreciable effect in accelerating the flow through such a high peripheral resistance. We must note, too, that the change in pressure gradient would tend to decrease the out- flow, not to increase it. The pressure gradient in arteries and in veins are about equal in magnitude, that in the veins being probably 368 KESPIKATION [CH. XXIV. steeper than that in the large arteries. All these conditions are reversed when, with the expiratory act, the thorax returns to its former size, and the arterial blood-pressure falls in consequence. The effect of inspiration on arterial blood-pressure is at first assisted by the pressure of the diaphragm as it descends on the abdominal veins, and blood is thus sent upwards into the chest by the vena cava inferior. On the other hand, this is to some extent counterbalanced by the obstruction in the passage of the blood downwards in the abdominal aorta, and upwards from the veins of the lower extremities, but again the veins are the vessels more easily influenced by moderate changes in external pressure. We now come to the cause of the delay we have noted in the blood-pressure tracing in following the respiratory movements. One effect of the diminished intra-thoracic pressure which occurs during inspiration is an increase in the capacity of the pulmonary capillaries, and thus, though more blood is sent into the pulmonary circulation, the resulting increase in outflow is for a time delayed because the capacity of the pulmonary vessels has simultaneously become greater. As soon as this increase in capacity is satisfied, the accelerated flow from the right heart makes itself felt on the left side with the results already explained. In some animals, such as the rabbit, the rise of blood-pressure occurs during expiration, and the fall accompanies inspiration. This is simply because the rabbit is an animal which breathes very quickly ; we have seen there is a delay in the inspiratory rise of pressure; if the animal breathes quickly enough, inspiration is over and expiration has begun before the rise of pressure occurs. By making the rabbit breathe slowly (Fredericq accomplished this by cooling the medulla oblongata), the tracing obtained is similar to that which is got from an animal like a dog, which normally breathes slowly. When the chest of an animal is freely opened, and artificial respiration performed in order to keep it alive, respiratory undulations on the arterial pressure curve are still seen, but they are in the reverse direction. These obviously cannot be produced in the mechanical way just described. The forcible inflation with air at first squeezes more blood out of the alveolar capillaries, that is, the capacity of these vessels is diminished, and this temporarily increases the quantity of blood thrown into the left ventricle, and so causes a rise of arterial pressure. But the increased intra-alveolar pressure has also been shown to lead to an increased resistance to the pulmonary circulation, and the rate of flow into the left side consequently falls ; the aortic pressure therefore falls ; while the pressure in the pulmonary artery rises. If the high positive intra-pulmonary air-pressure persisted, a condition would soon be reached, in which the increased blood-pressure in the pulmonary artery would lead to a greater flow, CH. XXIV.] EFFECT OF RESPIRATION ON CIRCULATION 369 and the aortic blood-pressure would remain constant ; this, however, has been shown to take a much longer time than an ordinary respira- tion period. Hence the main effect of inflations of the lungs at the ordinary respiration rate is to diminish the aortic blood-pressure ; this rises again for the opposite reasons, in the intervals of deflation, which correspond to expiration. If artificial respiration is performed while the thorax is not opened, a further complication arises from the fact that the increased intra- pleural pressure decreases the rate of flow of blood into the thorax, and under these conditions the blood-pressure in the pulmonary artery falls, and in consequence the fall in the aortic blood-pressure becomes more marked with each inflation than it does when the thorax is open. The last point of detail we have to consider is the cause of the greater frequency of the heart during the inspiratory phase, a phenomenon which is evidently due to lessening of vagus action, since the inequality of the heart rate disappears when the vagi are cut. The question before us is, What is the cause of the rhythm in the activity of the vagus centre ? There appear to be two factors concerned in its causation : one is a reflex action, the other is what may be termed a central overflow. We will consider these separately. 1. The reflex. Stimulation of the pulmonary branches of the vagus by electrical stimuli, or of their terminations in the alveoli by certain irritating vapours like bromine, causes a reflex inhibition of the heart ; great distension of the alveoli has a similar effect, but moderate distension, such as occurs in an ordinary inspiration, has the opposite reflex effect, causing the heart to beat more rapidly. The afferent fibres from the pulmonary alveoli enter the bulb by the upper set of the rootlets of the combined glossopharyngeal- vagus-spinal accessory nucleus (the a group, p. 247). Sometimes the rootlets of this group are three in- number, sometimes two. When there are two, the lower rootlet, when there are three the lower two rootlets, contain the fibres in question (Cadman). 2. The overflow. The respiratory centre exhibits alternate phases of activity, or what is termed a rhythmical action. It is in close anatomical connection with two other important centres in the bulb, namely, the cardio-inhibitory and the vaso-motor centres. Consider- ing how closely these three centres are connected by association fibres, it is not surprising that the cells of the two latter centres should be affected by the rhythm of the cells of the respiratory centre, and the term overflow is an expression that roughly indicates what occurs. This overflow from the respiratory centre affects its two neighbours in the same way. During inspiration the activity of both the cardio-inhibitory centre and of the vaso-motor centre is diminished, hence the heart beats faster. The factor which we have 2 A 370 KESPIRATION [CH. XXIV. termed the overflow is more important than that which we have described as the reflex. These facts show us that the parallelism of the respiratory and arterial pressure curves is not merely the result of the mechanical conditions already described, though these are the most important. But in the normal condition with the thorax closed, and the vagi uncut, certain nervous factors come also into play. During inspira- tion these are : — 1. A reflex from the terminations of the vagi in the pulmonary alveoli, which produces a lessening of vagus action, and so quickening of the heart. 2. An overflow from the respiratory to the cardio-inhibitory centre, which is still more powerful in producing the same effect. 3. An overflow from the respiratory to the vaso-motor centre, which produces decreased constriction of the systemic arterioles. By itself the third nervous factor would lessen arterial pressure, but in conjunction with the other two, and in conjunction also with the mechanical conditions described, the main result is a rise of arterial pressure during inspiration. Valsalva's Experiment. — In speaking of the effects of expiration, we have considered only ordinary quiet expiration. With forced expiration, there is considerable impediment to the circulation ; this is markedly seen in what is called Valsalva's experiment. This con- sists in making a forced expiratory effort with the mouth and nose shut ; the effects are most marked in people with an easily compres- sible thorax. By such an act the intrathoracic and abdominal pressures rise so greatly that the outlets of the veins of the limbs, head, and neck into the thorax are blocked. At first, the blood in the abdominal veins is drawn on into the right heart ; this produces a slight rise of arterial pressure ; but soon, if the effort is continued, the lungs are emptied of blood, the filling of the right heart is opposed, and the blood is dammed back in the peripheral veins, where the pressure rises to mean arterial pressure. The arterial pressure begins then to fall; but before any considerable fall occurs, the expiratory effort ceases from exhaustion of the subject of the experi- ment, and a deep inspiration is taken. During this inspiration, the blood delivered by the right heart is all used in the filling of the dilated and comparatively empty pulmonary vessels ; thus several beats of the left ventricle become abortive, and produce no effect on the radial artery ; the face blanches, and the subject becomes faint from cerebral anaemia. Asphyxia. Asphyxia may be produced in various ways : for example, by the prevention of the due entry of oxygen into the blood, either by CH. XXIV.] ASPHYXIA 371 direct obstruction of the trachea or other part of the respiratory passages, or by introducing instead of ordinary air a gas devoid of oxygen, or by interference with the due interchange of gases between the air and the blood. The symptoms of asphyxia may be roughly divided into three stages : (1) the stage of exaggerated breathing ; (2) the stage of con- vulsions ; (3) the stage of exhaustion. In the first stage the breathing becomes more rapid, and at the same time deeper than usual, inspiration at first being especially exaggerated and prolonged. The muscles of extraordinary inspiration are called into action, and the effort to respire is laboured and painful. This is soon followed by a similar increase in the expiratory efforts, which become excessively prolonged, being aided by all the muscles of extraordinary expiration. During this stage, which lasts a vary- ing time from a minute upwards, according as the deprivation of oxygen is sudden or gradual, the lips become blue, the eyes are prominent, and the expression intensely anxious. The prolonged respirations are accompanied by a distinctly audible sound; the muscles attached to the chest stand out as distinct cords. This stage includes the two conditions hyperpncea (excessive breathing) and dyspnoea (difficult breathing), which follows later. It is due to the increasingly powerful stimulation of the respiratory centre by the increasingly venous blood. In the second stage, which is not marked by any distinct line of demarcation from the first, the violent expiratory efforts become convulsive, and then give way, in men and other warm-blooded animals, to general convulsions, which arise from the further stimula- tion of the centres in brain and cord by venous blood. Spasms of the muscles of the body in general occur, and not of the respiratory muscles only. The convulsive stage is a short one, and lasts less than a minute. The third stage, or stage of exhaustion. In it the respirations all but cease, the spasms give way to flaccidity of the muscles, there is insensibility, the conjunctivas are insensitive and the pupils are widely dilated. Every now and then a prolonged sighing inspiration takes place, at longer and longer intervals, until breathing ceases altogether, and death ensues. During this stage the pulse is scarcely to be felt, but the heart may beat for some seconds after the respira- tion has stopped. The condition is due to the gradual paralysis of the centres by the prolonged action of the venous blood. This stage may last three minutes and upwards. After death from asphyxia it is found in the great majority of cases that the right side of the heart, the pulmonary arteries, and the systemic veins are gorged with dark, almost black, blood, and the left side of the heart, the pulmonary veins, and the arteries are 372 RESPIRATION [CH. XXIV. empty. The explanation of these appearances may be thus summar- ised : when oxygenation ceases, venous blood at first passes freely through the lungs to the left heart, and so to the great arteries. si" Owing to the stimulation of the vaso-motor centres, by the venous blood, the arterioles, particularly those of the splanchnic area, are constricted ; the arterial blood-pressure therefore rises, and the left side of the heart becomes distended. The highly venous blood CH. XXIY.] ASPHYXIA 373 passes through the arterioles, and, favoured by the laboured respira- tory movements, arrives at the right side of the heart, which it fills and distends ; the right side of the heart is becoming feebler at the same time, and therefore unable to effectively discharge its blood through the pulmonary circuit. Simultaneously the left ventricle is also becoming weakened, and therefore its suction action diminishes. In this way the blood is dammed back in the right heart and veins. In the third stage of asphyxia, the left side of the heart therefore gets into the empty condition in which it is found after death. Some consider that the early onset of rigor mortis in the left ventricle may be in part a cause of its contracted and empty condition. In the first and second stages of asphyxia, the arterial pressure rises until it reaches a point far above the normal ; this is due to the constriction of the arterioles. The fall of pressure in the last stage is mainly due to heart failure. If the vagi are not divided previously, the rise of pressure is much less, and the heart beats very slowly : this enables the heart to last longer, and is due to excitation of the cardio-inhibitory centre by venous blood. The accompanying photo- graph of a tracing, which I owe to Prof. C. J. Martin, shows these effects ; it has been somewhat reduced in size for purposes of repro- duction. The lower tracing is that of venous pressure taken with a salt solution manometer from the jugular vein. It will be noticed that the fall of arterial pressure in the last stage is accompanied with a great rise of venous pressure due to the venous congestion just described. Effects of Breathing Gases other than the Atmosphere. The diminution of oxygen has a less direct influence in the production of asphyxia than the increased amount of carbonic acid. Nevertheless, the fatal effect of carbonic acid in the blood when a due supply of oxygen is maintained, resembles rather the action of a narcotic poison than it does asphyxia. Then, again, we must carefully distinguish the asphyxiating effect of an insufficient supply of oxygen from the directly poisonous action of such a gas as carbonic oxide, which is contained to a considerable amount in common coal-gas. The fatal effects often produced by this gas (as in accidents from burning charcoal stoves in small, close rooms) are due to its entering into combination with the haemoglobin of the blood-corpuscles, and thus expelling the oxygen. Hydrogen may take the place of nitrogen if the oxygen is in the usual proportion, with no marked ill effect. Sulphuretted hydrogen interferes with the oxygenation of blood. Nitrous oxide acts directly on the nervous system as a narcotic. Certain gases, such as carbon dioxide in more than a certain proportion ; sulphurous and other acid gases, ammonia, and chlorine produce spasmodic closure of the glottis, and are irrespirable. Alterations in the Atmospheric Pressure. The normal condition of breathing is that the oxygen of the air breathed should be at the pressure of a of the atmosphere, viz., i of 760 mm. of mercury, or 152 mm., 374 RESPIRATION [CH. XXIV. but considerable variations may occur without producing ill effects. This is due to the fact that the blood gases are mostly in a state of chemical combination, not of simple solution. Variations beyond certain limits are, however, fatal. When the tension of oxygen exceeds 31 atmospheres {i.e., in air at a pressure of 17 atmos- pheres), slow but powerful poisonous (narcotic) effects are produced on all living matter. (Bert.) The excised sartorius is paralysed by about half an hour's exposure to 80 atmospheres of oxygen ; and the excised frog's heart ceases to beat in about two hours under the same conditions. It is dangerous for men to work in caissons where the atmospheric pressure is greater than 4 atmospheres. Even lower pressures may be followed on " decompression " (i.e., on coming out of the increased pressure), by what are called ''bends," that is, pains in the joints and muscles by paralysis, and auditory symptoms such as deafness and vertigo. The cause of such symptoms is probably the setting free of bubbles of nitrogen in the lymph spaces and capillaries ; any oxygen set free is rapidly re-absorbed by the blood. Capillary embolism from gas bubbles in the central nervous system is the most probable cause of the paralysis. (Bert.) Oxygen poisoning may be a secondary cause of the symptoms. Short shifts are essential for caisson workers, for then the body has not time to become saturated with gas at the caisson pressure. Decompres- sion must also be gradual and slow. A toad was but slightly effected by 5 minutes' exposure to 20 atmospheres of oxygen, but after 40 minutes on "decompression" it went into tetanic convulsions and died ; the heart was distended with frothed blood ; bubbles of gas were in all the lymph spaces, in the anterior chamber of the eye, and other parts. A mouse in a similar high pressure is narcotised, and on " decompression " convulsions and death ensue. (L. Hill.) Prolonged exposure to 2 atmospheres of oxygen is followed by pneumonia. (Lorrain Smith.) Mechanical pressure by itself has little or no influence ; thus frog's muscle is not injured by exposure to fluid pressure in salt solution equal to 400 atmospheres. Crustacea are found alive on marine telegraph cables at a depth where the pressure is as great. Turning now to diminution of pressure, we findthat " mountain sickness " occurs at the height of 4800 metres, the summit of Mt. Blanc. Here the pressure of oxygen is only 1 1 '53 per cent, of an atmosphere. The malady is increased by muscular effort, and is due to want of oxygen. In those who habitually live in high altitudes, the number of red blood-corpuscles is increased. Croce-Spinelli, the balloonist, perished at an altitude of 8600 metres, where the tension of oxygen would be 7 per cent, of an atmosphere. His companion Tissandier recovered. In such cases muscular paralysis occurs before loss of consciousness. Higher ascents could be made by aeronauts if they breathed oxygen from a gas cylinder. (Bert.) That death is due to want of oxygen and not to the setting free of gas bubbles in the blood is shown by the following fact : a sparrow lived in pure oxygen at 95 mm. of mercury pressure. Haldane has shown that animals can live in two atmospheres of oxygen after all the haemoglobin is taken up by carbonic oxide, for then sufficient oxygen is dissolved in the blood-plasma. Chemistry of Eespiration. The air in the air vesicles and the blood in the capillaries are separated only by the thin capillary and alveolar walls. The blood parts with its excess of carbonic acid and watery vapour to the alveolar air ; the blood at the same time receives from the alveolar air a supply of oxygen which renders it arterial. The intake of oxygen is the commencement, and the output of carbonic acid is the end of the series of changes known as respiration. The gaseous interchange in the lungs is often called external respira- tion. The actual combustion processes take place all over the body and constitute what is known as internal or tissue-respiration. The CH. XXIV.] COMPOSITION OF THE AIR 375 oxygen which goes into the blood is held there in loose combination as oxyhemoglobin. In the tissues this substance parts with its respiratory oxygen. The oxygen does not necessarily undergo immediate union with carbon to form carbonic acid, and with hydrogen to form water, but in most cases as in muscle, is held in reserve by the tissue itself. Owing to this reserve oxygen, a muscle will contract in an atmosphere of pure nitrogen and yet give off carbonic acid; and a frog will live under the same conditions and give off carbonic acid for several hours. Besides carbonic acid and water, certain other products of combustion are generated ; those like urea and uric acid, which are the result of nitrogenous metabolism, ultimately leave the body in the urine. The carbonic acid and a portion of the water find an outlet by the lungs. Inspired and Expired Air. — The composition of the inspired or atmospheric air and the expired air may be compared in the following table : — Inspired air. Expired air. Oxygen . Nitrogen Carbonic acid Watery vapour Temperature . 20 # 96 vols, per cent. 79 0-04 „ variable >» 16*03 vols, per cent. 79 4-4 „ saturated that of body (37° C.) The nitrogen remains unchanged. The recently discovered gases argon, crypton, etc., are in the above table reckoned in with the nitrogen. They are, however, only present in minute quantities. The chief change is in the proportion of oxygen and carbonic acid. The loss of oxygen is about 5, the gain in carbonic acid about 4 - 5. If the inspired and expired airs are carefully measured at the same tempera- ture and barometric pressure, the volume of expired air is thus found to be rather less than that of the inspired.* The conversion of oxygen into carbonic acid would not cause any change in the volume of the gas ; for a molecule of oxygen (0 2 ) would give rise to a molecule of carbonic acid (C0 2 ) which would occupy the same volume (Avo- gadro's law). It must, however, be remembered that carbon is not the only element which is oxidised. Fat and proteid contain a number of atoms of hydrogen, which, during metabolism, are oxidised to form water ; a small amount of oxygen is also used in the formation of urea. Carbohydrates contain sufficient oxygen in their own mole- cules to oxidise their hydrogen ; hence the apparent loss of oxygen is least when a vegetable diet (that is, one consisting largely of starch * This diminution of volume will cause a slight rise in the proportionate volume of nitrogen per cent. 376 KESPIRATION [CH. XXIV. and other carbohydrates) is taken, and greatest when much fat and proteid are eaten. The quotient n " t -11 * s ca ^ e ^ ^ e res P^ ra i° r y 4*5 quotient. Normally it is —z- = 0'9, but it varies considerably with diet o as just stated. It varies also with muscular exercise as the output of carbonic acid is then increased both absolutely and relatively to the amount of oxygen used up. The amount of respiratory interchange of gases is estimated by enclosing an animal in an air-tight chamber, except that there is a tube entering and another leaving it ; by one tube oxygen or air can enter, and is measured by a gas-meter as it passes in. The air is drawn through the chamber, and leaves it by the other tube ; this air has been altered by the respiration of the animal, and in it the car- bonic acid and water are estimated ; the carbonic acid is estimated by drawing the air through tubes containing a known amount of an Fig. 336. — Haldane's apparatus for estimating the carbonic acid and aqueous vapour given oil by an annual. alkali; this combines with the carbonic acid and is increased in weight : the increase in weight gives the amount of carbonic acid ; the alkali used in Eegnault and Eeiset's apparatus was potash ; Pettenkofer used baryta water ; Haldane recommends soda-lime. The water is estimated in tubes containing pumice moistened with sul- phuric acid. The accompanying drawing (fig. 336) shows the essential part of the simple but effective apparatus used by Haldane. The animal is placed in the vessel A ; air is sucked through the apparatus (which must be perfectly air-tight) by a water pump at a suitable rate. The arrows indicate the direction in which the air passes. It goes first through two Woulffs bottles, 1 and 2. No. 1 contains soda-lime, which frees the air from carbonic acid ; No. 2 contains pumice-stone moistened with sulphuric acid, which frees the air from aqueous vapour. The air next reaches the animal chamber, and the animal gives off to it carbonic acid and aqueous vapour. It passes then through the three bottles, 3, 4, and 5. No. 3 contains pumice and sulphuric acid, which removes the water ; No. 4 contains soda-lime, CH. XXIV.] ANALYSIS OF EXPIKED AIE 377 which absorbs the carbonic acid ; and No. 5 contains pumice and sul- phuric acid, which absorbs any water carried over from bottle 4. The increase of weight in bottle 3 at the end of a given time {e.g., an hour) is the weight of water given off by the animal in that time ; the in- crease of weight in bottles 4 and 5 weighed together gives the amount of carbonic acid produced by the animal in the same time. Eanke gives the following numbers from experiments made on a man, who was taking a mixed diet consisting of 100 grammes of proteid, 100 of fat, and 250 of carbohydrate in the twenty-four hours. The amount of oxygen absorbed in the same time was 666 grammes; of which 560 passed off as carbonic acid, 9 in urea, 19 as water formed from the hydrogen of the proteid, and 78 from that of the fat. Vierordt from a number of experiments on human beings gives the following numbers : the amount of oxygen absorbed in the twenty-four hours, 744 grammes ; this leads to the formation of 900 grammes of carbonic acid (this contains about half a pound of carbon) and 360 grammes of water. The respiratory interchange is lessened during sleep. It is especi- ally small in the winter sleep of hibernating animals. Circumstances affecting the amount of carbonic acid excreted, (a) Age and sex. In males the quantity increases with growth till the age of 30 ; at 50 it begins to diminish again. In females the decrease begins when menstruation ceases. In females the quantity exhaled is always less than in males of the same age. (b) Respiratory movements. — The quicker the respiration the smaller is the pro- portionate quantity of carbonic acid in each volume of expired air. The total quantity is, however, increased, not because more is formed in the tissues, but more is got rid of. The last portion of the expired air which comes from the more remote parts of the lungs is the richest in carbonic acid. (c) External temperature. — In cold-blooded animals, a rise in the external temperature causes a rise in their body temperature, accompanied with increased chemical changes, including the formation of a larger amount of carbonic acid. In warm-blooded animals, it is just the reverse ; in cold weather the body temperature has to be kept at the normal level, and so increased combustion is necessary. (d) Food. — This produces an increase which usually comes on about an hour after a meal. (e) Exercise. — Moderate exercise causes an increase of about 30 to 40 per cent, in the amount excreted. With excessive work, the increase is still greater. Diffusion of Gases within the Lungs. — If two chambers con- taining a mixture of gases in unequal amount are connected together, a slow movement called diffusion takes place until the percentage amount of each gas in each chamber is the same. Let us suppose that one chamber contains a large quantity of oxygen and a small quantity of carbonic acid ; and the other a small quantity of oxygen and a large quantity of carbonic acid ; the oxygen moves from the first to the second, and the carbonic acid from the second to the first chamber. The pressure of a gas is proportional to the percentage 378 RESPIRATION [CH. XXIV. amount in which it is present in a mixture. This is true for each gas in a mixture, the presence of the others making no difference. In the atmosphere, for instance, the total barometric pressure is 760 mm. of mercury ; the amount of oxygen in the air is roughly one- fifth, and the pressure it exercises is also one-fifth of 760 ; the nitro- gen accounts for the other four-fifths. The carbonic acid is present in such small quantities that the pressure it exercises is only a frac- tion of a millimetre. In the alveolar air (which can be obtained by catheterisation) the carbonic acid is present in larger and the oxygen in smaller amount ; and in the intermediate air passages there is an intermediate condi- tion : hence, as in the two chambers we first considered, oxygen diffuses down to the air vesicles, and carbonic acid from them. These movements are, however, by themselves too slow to be efficient, and are assisted by the large draughts which are created in the respiratory tract by the respiratory movements of the chest. Catheterization of the lungs. — In animals determinations of the composition of the alveolar air have been made in an occluded portion of the lung by Pfhiger's lung catheter. This consists of a fine elastic catheter surrounded by a tube with an enlargement towards the free end. It is introduced through the dog's trachea into a bronchus, and it must be small enough to allow air to pass freely to other parts of the lung. The rubber enlargement is then inflated ; this shuts off a portion of the lung, from which the alveolar air is then withdrawn by the inner tube. In such experiments, the alveolar air was found to contain 3 "5 per cent, of carbon dioxide, whereas the expired air contained 2 "8 per cent. The number 3*5 is higher than normal, for under the conditions of the experiment it was undiluted with any tidal air. Analysis of the air so obtained gives its composition after an equilibrium has been set up with the gases of the blood, which is passing through the occluded por- tion of the lung. Gases of the Blood. — From 100 volumes of blood, about 60 volumes of gas can be removed by the mercurial air-pump. The average composition of this gas in dog's blood is : — Venous blood. 8 to 12 1 to 2 46 The nitrogen in the blood is simply dissolved from the air just as water would dissolve it; it has no physiological importance. The other two gases are present in much greater amount than can be explained by simple solution ; they are, in fact, chiefly present in loose chemical combinations. Less than one volume of the oxygen and about two of carbonic acid are present in simple solution in the plasma. Oxygen in the Blood. — The amount of gas dissolved in a liquid varies with the pressure of the gas ; double the pressure and the amount of gas dissolved is doubled. The oxygen of the blood does not vary directly with oxygen pressure, for the amount of Arterial blood. Oxygen . 20 Nitrogen 1 to 2 Carbonic acid 40 CH. XXIV.] OXYGEN IN THE BLOOD 379 that gas in simple solution forms only a small fraction of the total present. This small amount is of course doubled by doubling the pressure, but such an increase is insignificant, the bulk of the oxygen being in chemical union with haemoglobin. The oxygen of oxyhemoglobin can be replaced by equivalent quantities of other gases like carbonic oxide. The tension or partial pressure of oxygen in the air of the alveoli is less than that in the atmosphere, but greater than that in venous blood ; hence oxygen passes from the alveolar air into the blood-plasma ; the oxygen immediately combines with the haemoglobin, and thus leaves the plasma free to absorb more oxygen ; and this goes on until the haemoglobin is entirely, or almost entirely, saturated with oxygen. The reverse change occurs in the tissues when the partial pressure of oxygen is lower than in the plasma, or in the lymph that bathes the tissue elements ; the plasma parts with its oxygen to the lymph, the lymph to the tissues ; the oxyhaemoglobin then undergoes dissociation to supply more oxygen to the plasma and lymph, and thus in turn to the tissues once more. This goes on until the oxyhaemoglobin loses a great portion of its store of oxygen, but even in asphyxia it does not lose all. The following values are given by Fredericq for the tension of oxygen in percentages of an atmosphere. His experiments were made on dogs. External air 20*96 Alveolar air 18 Arterial blood . 14 Tissues The arrow shows the direction in which the gas passes. When the gases are being pumped off from the blood, very little oxygen comes off till the pressure has been greatly reduced, and then, at a certain point, it is disengaged at a burst. This shows that it is not in simple solution but is united chemically to some constituent of the blood, which is suddenly dissociated at the reduced pressure. This constituent of the blood is haemoglobin. The avidity of the tissues for oxygen is shown by Ehrlich's experi- ments with methylene blue and similar pigments. Methylene blue is more stable than oxyhaemoglobin; but if it is injected into the circulation of a living animal, and the animal killed a few minutes later, the blood is found dark blue, but the organs (especially those which like glandular organs are in a state of activity) colourless. On exposure to oxygen the organs become blue. In other words, the tissues have removed the oxygen from methylene blue to form a colourless reduction product ; on exposure to the air this once more unites with oxygen to form methylene blue. Carbonic Acid in the Blood — What has been said for oxygen holds good in the reverse direction for carbonic acid. Compounds are 380 RESPIRATION [CH. XXIV. formed in the tissues where the tension of the gas is high : these pass into the lymph, then into the blood, and in the lungs they undergo dissociation, carbonic acid passing into the alveolar air, where the tension of the gas is comparatively low, though it is greater here than in the expired air. The relations of this gas and the compounds it forms are more complex than in the case of oxygen. If blood is divided into plasma and corpuscles, it will be found that both yield carbonic acid, but the yield from the plasma is the greater. If we place blood in a vacuum it bubbles, and gives out all its gases ; addition of a weak acid causes no further liberation of carbonic acid. When plasma or serum is similarly treated the gas also comes off, but about 5 per cent, of the carbonic acid is fixed — that is, it requires the addition of some stronger acid, like phosphoric acid, to displace it. Fresh red corpuscles will, however, take the place of the phosphoric acid, and thus it has been surmised that oxyhemoglobin h as the properties of an acid. One hundred volumes of venous blood contain forty-six volumes of carbonic acid. Whether this is in solution or in chemical combina- tion is determined by ascertaining the tension of the gas in the blood. One hundred volumes of blood-plasma would dissolve more than an equal volume of the gas at atmospheric pressure, if its solubility in plasma were equal to that in water. If, then, the carbonic acid were in a state of solution, its tension would be very high, but it proves to be only equal to 5 per cent, of an atmosphere. This means that when venous blood is brought into an atmosphere containing 5 per cent, of carbonic acid, the blood neither gives off any carbonic acid nor takes up any from that atmosphere. The instrument used in such deter- minations is called an aerotonometer (see p. 381). Hence the remainder of the gas, 95 per cent., is in a condition of chemical combination. The chief compound appears to be sodium bicarbonate. The carbonic acid and phosphoric acid of the blood are in a state of constant struggle for the possession of the sodium. The salts formed by these two acids depend on their relative masses. If carbonic acid is in excess, we get sodium carbonate (N"a 2 C0 3 ), and mono-sodium phosphate (NaH 2 P0 4 ); but if the carbonic acid is diminished, the phosphoric acid~ obtains the greater share of sodium to form disodium phosphate (Na 2 HP0 4 ). In this way, as soon as the amount of free carbonic acid diminishes, as in the lungs, the amount of carbonic acid in combination also decreases ; whereas in the tissues, where the tension of the gas is highest, a large amount is taken up into the blood, where it forms sodium bicarbonate. The tension of the carbonic acid in the tissues is high, but one cannot give exact figures ; we can measure the tension of the gas in certain secretions : in the urine it is 9, in the bile 7 per cent. The tension in the cells themselves must be higher still. CH. XXIV.] CARBONIC ACID IN THE BLOOD 381 The following figures (from Fredericq) give the tension of carbonic dioxide in percentages of an atmosphere : — Tissues 5 to 9 'j Venous blood . 3 S to 5 -4 -in dog. Alveolar air . . . . . . . 2 - 8 J External air - 03 The arrow indicates the direction in which the gas passes, namely, in the direction of pressure from the tissues to the atmosphere. In some other experiments, also on dogs, the following are the figures given : — - Arterial blood 2*8 ^ Venous blood . . . . . . . . . . 5'4 y Alveolar air . ■. 3*56 i Expired air . . . . . . . . . . 2'8 » It will be seen from these figures that the tension of carbonic acid in the venous blood (5 "4) is higher than in the alveolar air (3 '5 6) ; its passage into the alveolar air is therefore intelligible by the laws of diffusion. Diffusion, however, should cease when the tension of the gas in the blood and alveolar air are equal. But the transference goes beyond the establishment of such an equilibrium, for the tension of the gas in the blood continues to sink until it is ultimately less (2 '8) than in the alveolar air. The whole question is beset with great difficulties and contradic- tions. Analyses by different observers have given very different results, but if such figures as those just quoted are ultimately found to be correct, we can only explain this apparent reversal of a law of nature by supposing with Bohr that the alveolar epithelium possesses the power of excreting carbonic acid, just as the cells of secreting glands are able to select certain materials from the blood and reject others. Eecent work by Bohr and Haldane has also shown that in all probability the same explanation — epithelial activity — must be called in to account for the absorption of oxygen. In the swirn- bladder of fishes (which is analogous to the lungs of mammals) the oxygen is certainly far in excess of anything that can be explained by mere diffusion. The storage of oxygen, moreover, ceases when the vagus nerves which supply the swim-bladder are divided. The Aerotonometer. — This instrument was invented by Pfl. ger, and of the modifications that have been introduced since then, that of Fredericq is the simplest. It merely consists of a long glass tube surrounded by a water-jacket at body temperature. The tube is filled with a known mixture of gases, and the blood from the carotid artery is allowed to slowly trickle down the tube ; the blood then returns to the jugular vein. In order that the experiment may be continued for an hour or more, the animal's blood must be rendered incoagulable ; this may be done by a previous injection of "peptone." This has the disadvantage of lowering the car- bonic acid tension of the blood. Another way of rendering the blood incoagulable is to collect it, defibrinate it, and then return it to the circulation. The last step in 382 RESPIRATION [CH. XXIV. the experiment consists in examining the composition of the gases left in the tube. The principle upon which the instrument rests is this : — If blood is brought into contact with a mixture of oxygen, nitrogen, and carbonic acid gas, it gives off some of its gases if their partial pressure is greater in the blood than the respective tensions of the gases in the mixture ; if, on the other hand, the tension is lower in the blood than in the mixture for any gas or gases, they pass from the mixture to the blood. These interchanges go on until equilibrium is established. For example, suppose the aerotonometer contains at the start 10 per cent, of oxygen, 5 of carbonic- acid, and 85 of nitrogen. Blood is then passed through it for an hour, and the gases are again analysed, and the mixture then contains 14 per cent, of oxygen, 2*8 of carbon dioxide, and the rest nitrogen ; the tension of oxygen and carbon dioxide in the blood will then respectively be 14 and 2 "8 per cent, of an atmosphere. The Carbonic Oxide Method of Estimating the Oxygen Tension of Arterial Blood. — This method was devised by Haldane, and is considered by him and Lorrain Smith to give more trustworthy results than those obtained by the aerotonometer. If blood is exposed to a mixture of carbonic oxide and oxygen, the haemoglobin will become saturated by these gases according to their relative tensions. If a number of experiments are performed using different percentages of carbonic oxide, the results may be expressed graphically as the curve of dissociation of carboxyhaemoglobin in air. When in place of such experiments in vitro, an animal is made to breathe air containing a known percentage of carbonic oxide, the comparison of the saturation of its blood with the saturation of its blood in vitro exposed to the same percentage of carbonic oxide in air (which has an oxygen tension of 20*9 per cent.) gives us the means of discovering the oxygen tension in the arterial blood of the lung capillaries ; this will be higher or lower than that of the air according as the saturation by carbonic oxide is correspondingly lower or higher. A small animal like a mouse is made to breathe air containing a known percentage of carbonic oxide. After a sufficient time the animal is killed and the amount of carboxyhaemoglobin is determined colorimetrically in a drop of its blood. The data thus obtained are compared with the data previously expressed in the curve of dissociation of carboxyhaemoglobin in air; it is then easy to calculate whether the oxygen tension in the blood is higher or lower than that of air. The results of the method show generally that the tension of oxygen in the arterial blood as it leaves the lungs is higher than could result from simple diffusion of the oxygen through the alveolar epithelium ; in other words the epithelial cells are capable of secreting oxygen into the blood until an oxygen-pressure is reached considerably above that in the alveolar air. The results expressed in percentages of an atmosphere are as follows : — Oxygen tension of arterial blood in man, 38 - 5 ; in mouse, 22 - 6 ; in dog, 21 ; in cat, 35"3 ; in rabbit, 27 - 6, and in birds, 30 to 50 per cent. The results in the case of man and larger animals probably require revision, as it is not certain that the time allowed for the establishment of the balance of carbonic oxide and oxygen has been sufficient in any of the experiments. Tissue Respiration. — Before the processes of respiration were fully understood the lungs were looked upon as the seat of combus- tion ; they were regarded as the stove for the rest of the body to which effete material was brought by the venous blood to be burnt up. When it was shown that the venous blood going to the lungs already contained carbonic acid, and that the temperature of the lungs is not higher than that of the rest of the body, this explanation had of necessity to be dropped. Physiologists next transferred the seat of combustion to the blood ; but since then numerous facts and experiments have demon- strated that it is in the tissues themselves, and not in the blood, that combustion occurs. The methylene-blue experiments already described en. xxiv.] VENTILATION 383 (p. 379) show this; and the following experiment is also quite conclusive. A frog can be kept alive for some time after salt solution is substituted for its blood. The metabolism goes on actively if the animal is kept in pure oxygen. The taking up of oxygen and giving out of carbonic acid must therefore occur in the tissues, as the animal has no blood. Ventilation. — It is necessary to allude in conclusion to this very important practical outcome of our con- sideration of respiration. Some Continental observers have stated that certain noxious substances are ordinarily contained in expired air which are much more poisonous than carbonic acid, but researches in this country have failed to substantiate this. If precautions be taken by absolute clean- liness to prevent admixture of the air with exhalations from skin, teeth, and clothes, the expired air only contains one noxious substance, and that is carbonic acid. Absolute cleanliness is, however, not the rule; and the air of rooms becomes stuffy when the amount of expired air in them is just so much as to raise the per- centage of carbonic acid to 0"1 per cent. An adult gives off about 0'6 cubic feet of carbonic acid per hour, and if he is supplied with 1000 cubic feet of fresh air per hour he will add 0'6 to the 0*4 cubic feet of carbonic acid it already con- tains ; in other words, the percentage of that gas will be raised to O'l. An hourly supply of 2000 cubic feet of fresh air will lower the percentage of carbonic acid to - 07, and of 3000 cubic feet to 0'06, and this is the supply which is usually recommended. In order that the air may be renewed with- out giving rise to draughts, each adult should be allotted sufficient space in a room, at least 1000 cubic feet. Fig. 337. — Lud wig's Mercurial Pump. The Mercurial Air-Pump. The extraction of the gases from the blood is accomplished by means of a mercurial air-pump, of which there are many varieties, those of Ludwig, Alvergniat, Geissler and Sprengel being the chief. The principle of action in all is the same. Ludwig's pump, which may be taken as a type, is represented in fig. 337. It con- 384 EESPIKATION [CH. XXIV. sists of two fixed glass globes, C and F, the upper one communicating by means of the stopcock, X>, and a stout indiarubber tube with another glass globe, L, which can be raised or lowered by means of a pulley ; it also communicates by means of a stopcock, B, and a bent glass tube. A, with a gas receiver (not represented in the figure) ; A dips into a bowl of mercury, so that the gas may be received over mercury. The lower globe, F, communicates with O by means of the stopcock, E, with /, in which the blood is contained by the stopcock, G, and with a movable glass globe, M, similar to L, by means of the stopcock, H, and the stout indiarubber tube, K. In order to work the pump, L and M are filled with mercury, the blood from which the gases are to be extracted is placed in the bulb 7, the stopcocks, H, E, I), and B, being open, and G closed. M is raised by means of the pulley until .Pis full of "mercury, and the air is driven out ; E is then closed, and L is raised so that C becomes fidl of mercury, and the air is driven off. B is then closed. On lowering L the mercury runs into it from Cand a vacuum is established in C. On opening E and lowering M, a vacuum is similarly established in Ft if G is now B.B Fig. 388.— L. Hill's Air-pump. Fig. 330.— Waller's apparatus for gas analysis. opened, the blood in / will enter into ebullition, and the gases will pass off into F and C, and on raising il/and then L, the stopcock B being opened and G closed, the gas is driven through A, and is received into the receiver over mercury. By repeating this operation several times the whole of the gases of the specimen of blood is obtained, and may be estimated. The very simple air-pump (fig. 338) devised by Leonard Hill will be, however, amply sufficient for most purposes. It consists of three glass bulbs ; (B.B.), which we will call the blood bulb : this is closed above by a piece of tubing and a clip, a ; this is connected by good indiarubber tubing to another bulb, d. Above d, how- ever, there is a stopcock with two ways cut through it ; one by means of which B. B. and d may be connected, as in the figure ; and another seen in section, which unites d to the tube e, when the stopcock is turned through a right angle. In intermediate CH. XXIV.] GAS ANALYSIS 385 positions, the stopcock cuts off all communication from d to all parts of the apparatus above it ; d is connected by tubing to a receiver, R, which can be raised or lowered at will. At first the whole apparatus is filled with mercury, R being raised. Then, a being closed, R is lowered, and when it is more than the height of the barometer (30 inches) below the top of B. B. the mercury falls and leaves the blood bulb empty ; by lowering R still further, d can also be rendered a vacuum. A few drops of mercury should be left behind in B.B. B.B. is then detached from the rest of the apparatus and weighed, the clips, a and b, being tightly closed. Blood is then introduced into it by connecting the tube with the clip a on it to a cannula filled with blood inserted in an artery or vein of a living animal. Enough blood is with- drawn to fill about half of one of the bulbs. This is defibrinated by shaking it with the few drops of mercury left in the bulbs. It is then weighed again ; the increase of weight gives the amount of blood which is being investigated. B.B. is then once more attached to the rest of the apparatus, hanging downwards, as in the side drawing in fig. 338, and the blood gases boiled off; these pass into d, which has been made a vacuum ; and then by raising R again, the mercury rises in d, pushing the gases in front of it, through the tube, e (the stopcock being turned in the proper direction), into the eudiometer, E, which has been filled with and placed over mercury. The gas can then be measured and analysed. Gas analysis. — There are many pieces of apparatus devised for this purpose. In physiology, however, we have generally to deal with only three gases, oxygen, nitrogen, and carbonic acid. Waller's modification of Zuntz's more complete apparatus will be found very useful in performing gas analysis, say, of the expired air, or of the blood gases. A 1 00 c.c. measuring-tube graduated in tenths of a cubic centimetre between 75 and 100 ; a filling bulb (A) and two gas pipettes are connected up as in the diagram (fig. 339). It is first charged with acidulated water up to the zero mark by raising the filling bulb, tap 1 being open. It is then filled with 100 c.c. of expired air, the filling bulb being lowered till the fluid in the tube has fallen to the 100 mark. Tap 1 is now closed. The amount of carbonic acid in the expired air is next ascertained ; tap 2 is opened, and the air is expelled into the gas pipette containing strong caustic potash solution by raising the filling bulb until the fluid has risen to the zero mark of the measuring tube. Tap 2 is closed, and the air left in the gas pipette for a few minutes, during which the carbonic acid is absorbed by the potash. Tap 2 is then opened and the air drawn back into the measuring tube by lowering the filling bulb. The volume of air {minus the carbonic acid) is read, the filling bulb being adjusted so that its contents are at the same level as the fluid in the measuring tube. The amount of oxygen is next ascertained in a precisely similar manner by sending the air into the other gas pipette, which contains sticks of phosphorus in water, and measuring the loss of volume (due to absorption of oxygen) in the air when drawn back into the tube. 2 B CHAPTER XXV THE CHEMICAL COMPOSITION OF THE BODY The body is built up of a large number of chemical elements, which are in most instances united together into compounds. The elements found in the body are carbon, nitrogen, hydrogen, oxygen, sulphur, phosphorus, fluorine, chlorine, iodine, silicon, sodium, potassium, calcium, magnesium, lithium, iron, and occasionally traces of manganese, copper, and lead. Of these very few occur in the free state. Oxygen (to a small extent) and nitrogen are found dissolved in the blood ; hydrogen is formed by putrefaction in the alimentary canal. With some few exceptions such as these, the elements enumerated above are found combined with one another to form what are called compounds. The compounds, or, as they are generally termed in physiology, the proximate principles, found in the body are divided into — (1) Mineral or inorganic compounds. (2) Organic compounds, or compounds of carbon. The inorganic compounds present are water, various acids (such us hydrochloric acid in the gastric juice), ammonia (as in the urine), unci numerous salts, such as calcium phosphate in bone, sodium chloride in blood and urine, and many others. The organic compounds are more numerous ; they may be sub- divided into — (Proteids — e.g. albumin, myosin, casein. Albuminoids — <'.I /, muill ; r hn % ilta ° a * t . hnh ^ acids The subdivision of organic proximate principles into proteids, fats, and carbohydrates forms the starting-point of chemical physiology. Carbohydrates. The Carbohydrates are found chiefly in vegetable tissues, and many of them form important foods. Some carbohydrates are, how- CH. XXV.] CARBOHYDRATES 387 ever, found in or formed by the animal organism. The most important of these are glycogen, or animal starch ; dextrose ; and lactose, or milk sugar. The carbohydrates may be conveniently defined as compounds of carbon, hydrogen, and oxygen, the two last named elements being in the proportion in which they occur in water. But this definition is only a rough one, and if pushed too far would include many substances like acetic acid, lactic acid, and inosite, which are not carbohydrates. Eesearch has shown that the chemical constitution of the simplest carbohydrates is that of an aldehyde, or a ketone, and that the more complex carbohydrates are condensation products of the simple ones. In order, therefore, that we may understand the constitution of these substances, it is first necessary that we should understand what is meant by the terms aldehyde and ketone. A primary alcohol is one in which the hydroxy 1 (OH) is attached to the last carbon atom of the chain ; its end group is CH 2 OH. Thus the formula for common alcohol (primary ethyl alcohol) is CH 3 .CH 2 OH. The formula for the next alcohol of the same series (primary propyl alcohol) is CH 3 .CH 2 .CH 2 OH. If a primary alcohol is oxidised, the first oxidation product is called an aldehyde ; thus ethyl alcohol yields acetic aldehyde : — CH 3 .CH,OH + O = CH 3 .CHO + H 2 0. [Ethyl alcohol.] [Acetic aldehyde.] The typical end-group CHO of the aldehyde is not stable, but is easily oxidisable to form the group COOH, and the compound so formed is called an acid ; in this way acetic aldehyde forms acetic acid : — CH 3 .CHO + O = CH 3 .COOH. [Acetic aldehyde.] [Acetic acid.] The majority of the simple sugars are aldehydes of more complex alcohols than this ; they are spoken of as aldoses. The readiness with which aldehydes are oxidisable renders them powerful reducing agents, and this furnishes us with some of the tests for the sugars. Let us now turn to the case of the ketones. A secondary alcohol is one in which the OH group is attached to a central carbon atom ; thus secondary propyl alcohol has the formula CH 3 .CHOH.CH 3 . Its typical group is therefore CHOH. When this is oxidised, the first oxidation product is called a ketone, thus : — CH 3 .CHOH.CH 3 + O = CH 3 .CO.CH 3 + H 2 0. [Secondary propyl alcohol.] [Propyl ketone.] 388 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. It therefore contains the group CO in the middle of the chain. Some of the sugars are ketones of more complex alcohols ; these are called ketoses. The only one of these which is of physiological interest is levulose. The alcohols of which we have already spoken are called monatomic, because they contain only one OH group. Those which contain two OH groups (like glycol) are called diatomic; those which contain three OH groups (like glycerin) are called triatomic ; and so on. The hexatomic alcohols are those which contain six OH groups. Three of these hexatomic alcohols with the formula C G H 8 (OH) 6 are of physiological interest ; they are isomerides, and their names are sorbite, mannite, and dulcite. By careful oxidation their aldehydes and ketones can be obtained ; these are the simple sugars ; thus, dextrose is the aldehyde of sorbite; mannose is the aldehyde of mannite; levulose is the ketone of mannite ; and galactose is the aldehyde of dulcite. These sugars all have the empirical formula C^H^O^ The constitutional formula for dextrose is : — H H H H H H I I I I I I H C -C C C C C I I I I I I OH OH OH OH OH O By further oxidation, the sugars yield acids with various names. If we take such a sugar as a typical specimen, we see that their general formula is and as a general rule n = m; that is, the number of oxygen and carbon atoms are equal. This number in the case of the sugars already mentioned is six. Hence they are called hexoses. Sugars are known to chemists, in which this number is 3, 4, 5, 7, etc., and these are called trioses, tetroses, peutoses, heptoses, etc. The majority of these have no physiological interest. It should, however, be mentioned that a pentose has been obtained from the nucleoproteid of the pancreas, of the liver, and of yeast. If the peutoses that are found in various plants are given to an animal, they are excreted in great measure unchanged in the urine. The hexoses are of great physiological importance. The principal ones are dextrose, levulose, and galactose. These are called mono- saccharides. Another important group of sugars are called disac- charides ; these are formed by what is called condensation ; that is, two molecules of monosaccharide combine together with the loss of a molecule of water, thus : — C H 12 O (3 + C H 12 O 6 - C 12 H 22 O n + H 2 0. The principal members of the disaccharide group are cane-sugar, lactose, and maltose. If more than two molecules of the mono- CH. XXV.] SUGAES 389 saccharide group undergo a corresponding condensation, we get what are called polysaccharides. rcC 6 H 12 6 = (C,H 10 O 5 ) n + nU.p. The polysaccharides are starch, glycogen, various dextrins, cellu- lose, and gums. We may, therefore, arrange the important carbo- hydrates of the hexose family in a tabular form as follows : — 1. Monosaccharides or Glucoses, C 6 H I2 O e . 2. Disaccharides, Sucroses, or Saccharoses, C m H m O h . 3. Polysaccharides or Amy- loses (C 6 H 10 O 5 ),i. + Dextrose. - Levulose. + Galactose. + Cane sugar. + Lactose. + Maltose. + Starch. + Glycogen. + Dextrin. Cellulose. Gums. The + and — signs in the above list indicate that the substances to which they are prefixed are dextro- and levo-rotatory respectively as regards polarised light. (See Polarimeter, p. 404.) The formulae given above are merely empirical ; the quantity n in the starch group is variable and often large. The following are the chief facts in relation to each of the principal carbohydrates. Dextrose or Grape Sugar. — This carbohydrate is found in fruits, honey, and in minute quantities in the blood and numerous tissues, organs, and fluids of the body. It is the form of sugar found in large quantities in the blood and urine in the disease known as diabetes. Dextrose is soluble in hot and cold water and in alcohol. It is crystalline, but not so sweet as cane sugar. When heated with strong potash certain complex acids are formed which have a yellow or brown colour. This constitutes Moore's test for sugar. In alkaline solu- tions dextrose reduces salts of silver, bismuth, mercury, and copper. The reduction of cupric to cuprous salts constitutes Trommer's test, which is performed as follows : put a few drops of copper sulphate into a test-tube, then solution of dextrose, and then strong caustic potash. On adding the potash a precipitate is first formed which dissolves, forming a blue solution. On boiling this a yellow or red precipitate (cuprous hydrate or oxide) forms. On boiling a solution of dextrose with an alkaline solution of picric acid, a dark red opaque solution due to reduction to picramic acid is produced. Another important property of grape sugar is that under the influence of yeast it is converted into alcohol and carbonic acid (C 6 H 12 6 = 2C,H 6 + 2C0 2 ). Dextrose may be estimated by the fermentation test, by the polari- 390 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. meter, and by the use of Fehling's solution. The last method is the most important : it rests on the same principles as Trommer's test, and wo shall study it in connection with diabetic urine. Levulose. — When cane sugar is treated with dilute mineral acids it undergoes a process known as inversion — i.e., it takes up water and is converted into equal parts of dextrose and levulose. The previously dextro-rotatory solution of cane sugar then becomes levo-rotatory, the levo-rotatory power of the levulose being greater than the dextro- rotatory power of the dextrose formed. Hence the term inversion. The same hydrolytic change is produced by certain ferments, such as the invert ferment of the intestinal juice. Pure levulose can be crystallised, but so great is the difficulty of obtaining crystals of it that one of its names was uncrystallisable sugar. Small quantities of levulose have been found in blood, urine, and muscle. It has been recommended as an article of diet in diabetes in place of ordinary sugar ; in this disease it does not appear to have the harmful effect that other sugars produce. Levulose gives the same general reactions as dextrose. Galactose is formed by the action of dilute mineral acids or in- verting ferments on lactose. It resembles dextrose in its action on polarised light, in reducing cupric salts in Trommer's test, and in being directly fermentable with yeast. When oxidised by means of nitric acid it yields an acid called mucic acid (C 6 H 10 O 8 ), which is only slightly soluble in water. Dextrose when treated in this way yields an iso- meric acid — i.e., an acid with the same empirical formula, called sac- charic acid, which is very soluble in water. Cane Sugar is generally distributed in the vegetable kingdom, but especially in the juices of the sugar cane, beetroot, mallow, and sugar maple. It is a substance of great importance as a food. It undergoes inversion in the alimentary canal. It is crystalline, and dextro-rotatory. With Trommer's test it gives a blue solution, but no reduction occurs in boiling. After inversion it is, of course, strongly reducing. Inversion may be accomplished by boiling with dilute mineral acids, or by means of inverting ferments such as that occurring in the intestinal juice. It then takes up water, and is split into equal parts of dextrose and levulose. C 12 H O) n + H 2 = C,H,A + C H 12 6 . [Cane sugar.] [Dextrose.] [Levulose.] With yeast, cane sugar is first inverted by means of a special soluble ferment secreted by the yeast cells, and then there is an alcoholic fermentation of the glucoses so formed. Lactose, or Milk Sugar, occurs in milk. It is occasionally found in the urine of women in the early days of lactation, or after C1I. XXY.] SUGARS 391 weaning. It is crystallisable, dextro-rotatory, much less soluble in water than other sugars, and has only a slightly sweet taste. It gives Trommer's test, but when the reducing power is tested quanti- tatively by Fehling's solution it is found to be a less powerful reduc- ing agent than dextrose, in the proportion of 7 to 10. When hydrolysed by similar agencies as those mentioned in con- nection with cane sugar, it takes up water and splits into dextrose and galactose. C 12 H 22 O u + H 2 = C 6 H 12 O fi + C 6 H ]2 6 . [Lactose.] [Dextrose.] [Galactose.] With yeast it is first inverted, and then alcohol is formed. This, how- . ever, occurs slowly. The lactic acid fermentation which occurs when milk turns sour is brought about by lactic acid micro-organisms which are somewhat similar to yeast cells. Putrefactive bacteria in the intestine bring about the same result. The two stages of the lactic acid fermentation are represented in the following equations : — (1.) C 12 H 22 O n + H 2 = 4C 3 H 6 O r [Lactose.] [Lactic acid.] (2.) 4C 3 H O 3 = 2C 4 H 8 2 + 4CO, + 4H 2 . [Lactic acid.] [Butyric acid.] Maltose is the chief end product of the action of malt diastase on starch, and is also formed as an intermediate product in the action of dilute sulphuric acid on the same substance. It is the chief sugar formed from starch by the diastatic ferments contained in the saliva and pancreatic juice. It can be obtained in the form of acicular crystals, and is strongly dextro-rotatory. It gives Trommer's test ; but its reducing power, as measured by Fehling's solution, is one-third less than that of dextrose. With yeast it yields alcohol. By prolonged boiling with water, or, more readily, by boiling with a dilute mineral acid, or by means of an inverting ferment, such as occurs in the intestinal juice, it is converted into dextrose. Ci^ !! + H 2° = 2C 6 H 12 6 . [Maltose.] [Dextrose.] Phenyl Hydrazine Test. — The three important reducing sugars with which we have to deal in physiology are dextrose, lactose, and maltose. They may be distinguished by their relative reducing powers on Fehling's solution, or by the characters of their osazones. The osazone is formed in each case by adding phenyl hydrazine hydro- chloride, and sodium acetate, and boiling the mixture for half an hour. In each case the osazone is deposited in the form of bright canary- coloured, needle-like crystals, usually in bunches, which differ in their crystalline form, melting-point, and solubilities. Cane sugar does pot yield an osazone, 302 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. Starch is widely diffused through the vegetable kingdom. It occurs in nature in the form of microscopic grains, varying in size and appearance, according to their source. Each consists of a central spot, round which more or less concentric envelopes of starch proper 01 granulose alternate with layers of cellulose. Cellulose has very little digestive value, but starch is a most important food. Starch is insoluble in cold water : it forms an opalescent solution in boiling water, which if concentrated gelatinises on cooling. Its most characteristic reaction is the blue colour it gives with iodine. On heating starch with mineral acids, dextrose is formed. By the action of diastatic ferments, maltose is the chief end product. In both cases dextrin is an intermediate stage in the process. Before the formation of dextrin the starch solution loses its opal- escence, a substance called soluble starch being formed. This, like native starch, gives a blue colour with iodine. Although the mole- cular weight of starch is unknown, the formula for soluble starch is probably 5(C 1 oH., O 10 )., . Equations that represent the formation of sugars and dextrins from this are very complex, and are at present only hypothetical. Dextrin is the name given to the inter- mediate products in the hydration of starch or glycogen, and two chief varieties are distin- guished : — erythro-dextrin, which gives a reddish- brown colour with iodine; and achroo -dextrin, Fig. 340. -Grains of potato which does not. It is readily soluble in water, but insoluble in alcohol and ether. It is gummy and amorphous, ft does not give Trommer's test, nor does it ferment with yeast. It is dextro- rotatory. By hyd rating agencies it is converted into glucose. Glycogen, or animal starch, is found in liver, muscle, and white blood corpuscles. It is also abundant in all embryonic tissues. Glycogen is a white tasteless powder, soluble in water, but it forms, like starch, an opalescent solution. It is insoluble in alcohol and ether. It is dextro-rotatory. With Trommer's test it gives a blue solution, but no reduction occurs on boiling. With iodine it gives a reddish or port-wine colour, very similar to that given by erythro-dextrin. Dextrin may be distinguished from glycogen by (1) the fact that it gives a clear, not an opalescent, solu- tion with water ; and (2) it is not precipitated by basic lead acetate as glycogen is. It is, however, precipitated by basic lead acetate and ammonia. (3) Glycogen is precipitated by 55 per cent, of alcohol ; the dextrins require 85 per cent, or more. Cellulose. — This is the colourless material of which the cell-walls and woody fibres of plants are composed. By treatment with strong mineral acids it is, like starch, converted into glucose, but with much en. xxv.] THE FATS 393 greater difficulty. The various digestive ferments have little or no action on cellulose ; hence the necessity of boiling starch before it is taken as food. Boiling bursts the cellulose envelopes of the starch grains, and so allows the digestive juices to get at the starch proper. Cellulose is found in a few animals, as in the test or outer invest- ment of the Tunicates. [Inosite, or muscle sugar (C 6 H 12 6 ), is found in muscle, kidney, liver, and other parts of the body in small quantities. It is also largely found in the vegetable kingdom. It is crystallisable, and has the same formula as the glucoses. It is, however, not a sugar, and careful analysis has shown that it really belongs to the aromatic series.] The Fats. Fat is found in small quantities in many animal tissues. It is, however, found in large quantities in three situations, viz., marrow, adipose tissue, and milk. The contents of the fat cells of adipose tissue are fluid during life, the normal temperature of the body (37° C, or 99° F.) being con- siderably above the melting-point (25° C.) of the mixture of the fats found there. These fats are three in number, and are called palmitin, stearin, and olein. They differ from one another in chemical com- position and in certain physical characters, such as melting-point and solubilities. Olein melts at —5° C, palmitin at 45° C, and stearin at 53-66° C. It is thus olein which holds the other two dissolved at the body temperature. Fats are all soluble in hot alcohol, ether, and chloroform, but insoluble in water. Chemical Constitution of the Fats. — The fats are compounds of fatty acids with glycerin, and may be termed glycerides or glyceric ethers. The term hydrocarbon, applied to them by some authors, is wholly incorrect. The fatty acids form a series of acids derived from the monatomic alcohols by oxidation. Thus, to take ordinary ethyl alcohol, C 2 H 6 0, the first stage in oxidation is the removal of two atoms of hydrogen to form aldehyde, C 2 H 4 ; on further oxidation an atom of oxygen is added to form acetic acid, C 2 H 4 2 . A similar acid can be obtained from all the other alcohols, thus : — From methyl alcohol CH.,.HO, formic acid H.COOH is obtained „ ethyl Coh;.ho, acetic „ CH.,COOH ,, propyl c 3 h;.ho, propionic „ G>H,.COOH „ butyl C 4 H 9 .HO, butyric ,, C^.COOH ,, amyl ,, C 5 H n .HO, valeric „ C 4 H 9 .COOH ,, hexyl ,, C 6 H 13 .HO, caproic ,, C a H n .COOH and so on. 394 THE CHEMICAL COMPOSITION OF THE BODY [CIl. XXY. Or in general terms : — From the alcohol with formula C n H-2 nfl .HO, tho acid with formula Gn-iH 2 n-i-COOH is obtained. The sixteenth term of this series has the formula C10H31.COOH, and is called palmitic acid ; the eighteenth has the formula C17H35.COOH, and is called stearic acid. Each acid, as will be seen, consists of a radicle, Cn-iH 2 n-iCO, united to hydroxyl (OH). Oleic acid, however, is not a member of this series, but belongs to a somewhat similar series known as the acrylic series, of which the general formula is C n _iHon-3-COOH. It is the eighteenth term of the series, and its formula is C17H33.COOH. The first member of the group of alcohols from which this acrylic series of acids is obtained is called alh/l alcohol (CH 2 : CH.CH 2 OH); the aldehyde of this is acrolein (CH., : CH.CHO), and the formula for the acid (acrylic acid) is CH. 2 :CH.COOH. It will be noticed that two of the carbon atoms are united by two valencies, and these bodies are therefore unsaturated ; they are unstable and are prone to undergo by uniting with another element a conversion into bodies in which the carbon atoms are united by only one bond. This accounts for their reducing action, and it is owing to this that the colour reactions with osmic acid and Sudan III. are due. Fat which contains any member of the acrylic series like oleic acid blackens osmic acid, by reducing it to a lower (black) oxide. Fats like palmitin and stearin do not give this reaction. Glycerin or Glycerol is a triatomic alcohol, C 3 H 5 (HO) 3 — i.e., three atoms of hydroxyl united to a radicle glyceryl (C 3 H 5 ). The hydrogen in the hydroxyl atoms is replaceable by other organic radicles. As an example, take the radicle of acetic acid called acetyl (CH 3 .CO). The following formula! represent the derivatives that can be obtained by replacing one, two, or all three hydroxyl hydrogen atoms in this way : — (OH (OH (OH (O.CH-.CO CH,- oh c,h J oh c,hJ o.ch,co c 3 h 5 o.ch:,co I oh to.cH :; .co Io.ch;.co (o.ch,.co [Glycerin.] [Monoacetin.] [Piacetin.] [Triacetin.] Triacetin is a type of a neutral fat; stearin, palmitiu, and olein ought more properly to be called tristearin, tripalmitin, and triolein respectively. Each consists of glycerin in which the three atoms of hydrogen in the hydroxyls are replaced by radicles of the fatty acid. This is represented in the following formula} : — Add. Radicle. Fat. Palmitic acid C^H^.COOH Palmityl C^H^CO Palmitin C,H-,(OC],H 31 .CO), Stearic acid Cj-H^.COOH Stearyl C 17 H,,.CO Stearin C',H,(OC 17 H^.CO) 3 Oleic acid C 17 H 3 'l.COOH Oleyl C l7 H«.CO Olein C s H 8 (OC l7 H 38 .CO^ Decomposition Products of the Fats. — The fats split up into the substances out of winch they are built up. Under the influence of superheated steam, mineral acids, and in the body by means of certain ferments (for instance, the fat-splitting ferment, steapsin, of the pancreatic juice), a fat combines with water CH. XXV.] THE PEOTEIDS 395 and splits into glycerin and the fatty acid. The following equation represents what occurs in a fat, taking tripalmitin as an example : — C 3 H 5 (O.C 15 H 31 CO)3 + 3H 2 = C 3 H 5 (OH) 3 3C 15 H 31 CO.OH. [Tripalmitin — a fat.] [Glycerin.] [Palmitic acid— a fatty acid. In the process of saponification much the same sort of reaction occurs, the final products being glycerin and a compound of the base with the fatty acid which is called a soap. Suppose, for instance, that potassium hydrate is used ; we get — C 3 H 5 (O.C ;5 H 31 CO) 3 + 3KHO = C 3 H 5 (OH) 3 + 3C 15 H 31 CO.OK. [Tripalmitin — a fat.] [Glycerin.] [Potassium palmitate — a soap.] Emulsification. — Another change that fats undergo in the body is very different from saponification. It is a physical rather than a chemical change ; the fat is broken up into very small globules, such as are seen in the natural emulsion — milk. Lecithin (C^H^NPOg). — This is a very complex fat, which yields on decomposition not only glycerin and fatty acids {stearic and oleic), but phosphoric acid, and an alkaloid [lSr.(CH 3 ) 3 C H e 2 ] called choline in addition. This substance is found to a great extent in the nervous system (see p. 175), and to a small extent in bile. Together with cholesterin, a crystallisable, monatomic alcohol (C, 7 H 45 .HO), which we shall consider more at length in connection with the bile, it is found in small quantities in the protoplasm of all cells. The Proteids. The proteids are the most important substances that occur in animal and vegetable organisms ; none of the phenomena of life occur without their presence ; and though it is impossible to state positively that they occur as such in living protoplasm, they are invariably obtained by subjecting living structures to analysis. Proteids are highly complex compounds of carbon, hydrogen, oxygen, nitrogen, and sulphur occurring in a solid viscous condition or in solution in nearly all the liquids and solids of the body. The different members of the group present differences in chemical and physical properties. They all possess, however, certain common chemical reactions, and are united by a close genetic relationship. The various proteids differ a good deal in elementary composition. Hoppe-Seyler gives the following percentages : — From .... To c H N S 51-5 6-9 15-2 0-3 20-9 54-5 7-3 17-0 2-0 23-5 We are, however, not acquainted with the constitutional formula of proteid substances. There have been many theories on the subject, 396 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. but practically all that is known with certainty is that many different substances may be obtained by the decomposition of proteids. How they are built up into the proteid molecule is unknown. The decom- positions that occur in the body are, moreover, different from those which can be made to occur in the laboratory ; hence the conclusion that living protoplasm differs from the non-living proteid material obtainable from it. (1) In the body. Carbonic acid, water, and urea are the chief final products. Glycocine, leucine, creatine, uric acid, ammonia, etc., are probably intermediate products. Carbohydrates (glycogen) and fats may also originate from proteids. (2) Outside the body. Various strong reagents break up proteids into ammonia, carbonic acid, amines, hexone bases, fatty acids, amido- acids like leucine and arginine, and aromatic compounds like tyrosine. Solubilities. — All proteids are insoluble in alcohol and ether. Some are soluble in water, others insoluble. Many of the latter are soluble in weak saline solutions. Some are insoluble, others soluble in concentrated saline solutions. It is on these varying solubilities that proteids are classified. All proteids are soluble with the aid of hsat in concentrated mineral acids and alkalies. Such treatment, however, decomposes as well as dissolves the proteid. Proteids are also soluble in gastric and pancreatic juices ; but here, again, they undergo a change, being con- verted into a hydrated variety of proteid, of smaller molecular weight, called peptone. The intermediate substances formed in this process are called proteoses or albumoscs. Commercial peptone contains a mixture of proteoses and true peptone. Heat Coagulation. — Most native proteids, like white of egg, are rendered insoluble when their solutions are heated. The temperature of heat coagulation differs in different proteids ; thus myosinogen and fibrinogen coagulate at 56° C, serum albumin and serum globulin at about 75° C. The proteids which are coagulated by heat come under two classes : the albumins and the globulins. These differ in solubility ; the albumins are soluble in distilled water, the globulins require salts to hold them in solution. Indiffusibility. — The proteids (peptones excepted) belong to the class of substances called colloids by Thomas Graham ; that is, they pass with difficulty, or not at all, through animal membranes. In the construction of dialysers, vegetable parchment is largely used. Proteids may thus be separated from diffusible {crystalloid) sub- stances like salts, but the process is a tedious one. If some serum or white of egg is placed in a dialyser (fig. 341) and distilled water outside, the greater amount of the salts passes into the water through the membrane and is replaced by water ; the two proteids albumin CH. XXV.] PROPERTIES OF PROTEIDS 397 and globulin remain inside ; the globulin is, however, precipitated, as the salts which previously kept it in solution are removed. Crystallisation. — Haemoglobin, the red pigment of the blood, is a proteid substance and is crystallisable (for further details, see The Blood, Chapter XXVI.). Like other proteids it has an enormously large molecule ; though crystalline, it is not, however, crystalloid in Graham's sense of that term. Blood pigment is not the only crystallisable proteid. Long ago crystals of proteid (globulin or vitellin) were observed in the aleurone grains of many seeds, and in the somewhat similar granules occurring in the egg-yolk of some fishes and amphibians. By appropriate methods these have been separated and re-crystallised. Further, egg-albumin itself has been crystallised. If a solution of white of egg is diluted with an equal volume of saturated solu- tion of ammonium sulphate, the globulin present is precipitated and is removed by filtration. The filtrate is now allowed to remain some days at the temperature of the air, and as it becomes more concen- trated from evaporation, minute spheroidal globules and finally minute needles, either aggregated or separate, make their appear- ance (Hofmeister). Crystallisation is more rapid if a little acetic or sulphuric acid is added (Hopkins). Serum albumin (from horse and rabbit) has also been similarly crystallised (Giirber). Action on Polarised Light. — All pro- teids are levo-rotatory, the amount of rotation varying with individual proteids. Several of the compound proteids, e.g., haemoglobin, and nucleo - proteids are dextro-rotatory, though their proteid components are levo-rotatory (Gamgee). Colour Reactions. — The principal colour reactions by which proteids are recognised are the following: — (1) The xanthoproteic reaction ; if a few drops of nitric acid are added to a solution of a proteid like white of egg, the result is a white precipitate ; this and the surrounding liquid become yellow on boiling and are turned orange by ammonia. The preliminary white pre- cipitate is not given by some proteids like peptones ; but the colours are the same. (2) Milton's reaction. Millon's reagent is a mixture of mercuric and mercurous nitrate with excess of nitric acid. This drives a white Fig. 341. — Dialyser made of a tube of parchment paper, suspended in a vessel through which water is kept flowing. 398 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. precipitate with proteids which is turned brick-red on boiling. This reaction and the preceding (xanthroproteic) depend on the presence in proteids of aromatic radicles. (3) Copper sulphate (Rose's or Piotrowski's) test. A trace of copper sulphate and excess of strong caustic potash give with most proteids a violet solution. Proteoses and peptones, however, give a rose-red colour instead; this same colour is given by the substance called biuret ; hence the test is generally called the biuret reaction. This name does not imply that biuret is present in proteid; but both proteid and biuret give the reaction because they possess a common radicle, probably CONH. Biuret is formed by heating solid urea ; ammonia passes off and leaves biuret thus : — 2CON. 2 H 4 - NH 3 = qO,N 3 H 5 . [Urea.] [Ammonia.] [Biuret.] (4) Adamkiewicz reaction (Hopkins' modification). When a solu- tion of proteid is added to a dilute solution of glyoxylic acid, and then excess of sulphuric acid is added, an intense violet colour is obtained. Precipitants of Proteids. — Solutions of most proteids are pre- cipitated by: — 1. Strong acids like nitric acid. 2. Picric acid. 3. Acetic acid and potassium ferrocyanide. 4. Acetic acid and excess of a neutral salt like sodium sulphate; when these are boiled with the proteid solution. 5. Salts of the heavy metals like copper sulphate, mercuric chloride, lead acetate, silver nitrate, etc. 6. Tannin. 7. Alcohol. 8. Saturation with certain neutral salts such as ammonium sulphate. It is necessary that the words coagulation and precipitation should in connection with proteids be carefully distinguished. The term coagulation is used when an insoluble proteid (coagulated proteid) is formed from a soluble one. This may occur : 1. When a proteid is heated — heat coagulation ; 2. Under the influence of a ferment; for instance, when a curd is formed in milk by rennet or a clot in shed blood by the fibrin ferment — -ferment coagulation ; 3. When an insoluble precipitate is produced by the addition of certain reagents (nitric acid, picric acid, tannin, etc.). There are, however, other precipitants of proteids in which the precipitate formed is readily soluble in suitable reagents like saline solutions, and the proteid continues to show its typical reactions. ClI. XXV.] CLASSIFICATION OF PROTEIDS 399 Such precipitation is not coagulation. Such a precipitate is produced by saturation with ammonium sulphate. Certain proteids, called globulins, are more readily precipitated by such means than others. Thus, serum globulin is precipitated by half-saturation with ammonium sulphate. Full saturation with ammonium sulphate precipitates all proteids but peptone. The globulins are precipitated by certain salts, like sodium chloride and magnesium sulphate, which do not precipitate the albumins. The precipitation produced by alcohol is peculiar in that after a time it becomes a coagulation. Proteid freshly precipitated by alcohol is readily soluble in water or saline media ; but after it has been allowed to stand some weeks under alcohol it becomes more and more insoluble. Albumins and globulins are most readily rendered insoluble by this method ; proteoses and peptones are never rendered insoluble by the action of alcohol. This fact is of value in the separation of these proteids from others. Classification of Proteids. Both animal and vegetable proteids can be divided into the follow- ing classes. We shall, however, be chiefly concerned with the animal proteids : — If we use the term proteid in the widest sense, the first main subdivision of these substances is into — A. The Simple Proteids. B. The Conjugated or Compound Proteids. C. The Albuminoids. D. The Protamines. We will take these classes one by one. A. The Simple Proteids. Class I. Albumins. — These are soluble in water, in dilute saline solutions, and in saturated solutions of sodium chloride and magnesium sulphate. They are, however, precipitated by saturating their solu- tions with ammonium sulphate. Their solutions are coagulated by heat, usually at 70-73° C. Serum albumin, egg albumin, and lact- albumin are instances. Class II. Globulins. — These are insoluble in water, soluble in dilute saline solutions, and insoluble in concentrated solutions of neutral salts like sodium chloride, magnesium sulphate, and ammonium sulphate. A globulin dissolved in a dilute saline solution may there- fore be precipitated — 1. By removing the salt — by dialysis (see p. 396). 2. By increasing the amount of salt. The best salts to employ are 400 THE CHEMICAL COMPOSITION OF THE BODY [CII. XXV. ammonium sulphate (half-saturation) or magnesium sulphate (com- plete saturation). This method is often called " salting out." The globulins are coagulated by heat ; the temperature of heat coagulation varies considerably. The following are instances : — (a) Fibrinogen I • 1 1 j i ~, ), / c °, , i • / t i i • x r m blood-plasma. (b) Serum globulin (paraglobulm) J r (c) Paramyosinogen in muscle. (d) Crystallin in the crystalline lens. If we compare together these two classes of proteids, the most important of the native proteids, we find that they all give the same general tests, that all are coagulated by heat, but that they differ in their solubilities. This difference in solubility may be stated in tabular form as follows : — Reagent. Albumin. Globulin. Dilute saline solution .... Saturated solution of magnesium sul- phate or sodium chloride . Half-saturated solution of ammonium Saturated solution of ammonium sul- soluble soluble soluble soluble insoluble insoluble soluble insoluble insoluble insoluble Class III. Class IV. Proteoses Peptones C These products of digestion will be < in connection with that studied ( subject. Class V. Coagulated Proteids. — There are two main subdivisions of these : — (a) Proteids in which coagulation has been produced by heat; they are insoluble in water, saline solutions, weak acids, and weak alkalis; they are soluble after prolonged boiling in concentrated mineral acids ; dissolved by gastric and pancreatic juices, they give rise to peptones. (5) Proteids in which coagulation has been produced by fer- ments : — i. Fibrin (see Blood), ii. Myosin (see Muscle), iii. Casein (see Milk). Appendix to the class of simple proteids. Albuminates are compounds of proteid with mineral substances. Thus, if a solution of copper sulphate is added to a solution of albumin a precipitate of copper albuminate is obtained. Similarly, by the addition of other salts of the heavy metals other metallic albuminates are obtainable. The albuminates which are obtained by the action of dilute acids and alkalis on either albumins or globulins are, however, of greater physiological interest, and it is to these we shall confine our attention. CII. XXV.] THE CONJUGATED PROTEIDS 401 The general properties of the acid-albumin or syntonin, and the alkali- albumin, which are thereby respectively formed, are as follows : they are insoluble in pure water, but are soluble in either acid or alkali, and are precipitated by neutralisation unless certain salts, like sodium phosphate, are present. Like globulins, they are precipitated by saturation with such neutral salts as sodium chloride and magnesium sulphate. They are not coagulated by heat. A variety of alkali-albumin (probably a compound containing a large quantity of alkali) may be formed by adding strong potash to undiluted white of egg. The resulting jelly is called ZieberJciihn's jelly. A similar jelly is formed by adding strong acetic acid to undiluted egg-white. The halogens (chlorine, bromine, and iodine) also form albumin- ates, and may be used for the precipitation of proteids. B. The Conjugated Proteids. These complex substances are compounds of albuminous substances with other organic materials, which are, as a rule, also of complex nature. They may be divided into the following groups : — 1. Haemoglobin and its allies. These are compounds of proteid with an iron-containing pigment. All will be fully discussed under Blood. 2. Gluco-proteids. These are compounds of proteids with members of the carbohydrate group. This class includes the mucins and substances allied to mucins called mucoids. Mucin. — This is a widely distributed substance, occurring in epithelial cells or shed out by them (mucus, mucous glands, goblet cells). There are several varieties of mucin, but all agree in the following points : — (a) Physical character. Viscid and tenacious. (b) Precipitability from solutions by acetic acid. They are soluble in dilute alkalis, like lime water. (c) They are all compounds of a proteid with a carbohydrate radicle, which by treatment with dilute mineral acid can be hydrated into a reducing but non-fermentable sugar. It is probable that the carbohydrate radicle may differ in different mucins ; in some cases it is certainly the case that the so-called sugar derived from it is not sugar, but a nitrogenous derivative of sugar called glucosamine (C 6 H n 5 NH 2 ) — i.e., glucose in which HO is replaced by NH 2 . The mucoids generally resemble the mucins but differ from them in minor details. The term is applied to the mucin-like substances found in the ground substance of connective tissues (tendo-mucoid, chondro-mucoid, etc.). Another (ovo-mucoid) is found in white 2 C 402 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. of egg, and others (pseudo-mucin and paramucin) are occasionally found in dropsical effusions. Dr Pavy has shown that a small quantity of a similar carbohydrate can he split off from various other proteids, which we have already classified as simple proteids. 3. Nucleins and Nucleo-pkoteids. These are compounds of proteid with a complex organic acid called nucleic acid, which con- tains phosphorus. Nucleo-proteids. — Compounds of proteids with nuclein. They are found in the nuclei and protoplasm of cells. Oaseinogen of milk and vitellin of egg-yolk are similar substances. In physical characters they often closely simulate mucin ; in fact, the substance called mucin in the bile is in some animals a nucleo-proteid. They may be distinguished from mucin by the fact that they yield on gastric digestion not only peptone but also an insoluble residue of nuclein which is soluble in alkalis, is precipitable by acetic acid from such a solution, and contains a high percentage (10-11) of phosphorus. Some of the nucleo-proteids also contain iron, and it is probable that the normal supply of iron to the body is contained in the nucleo- proteids, or haematogens (Bunge), of plant and animal cells. The relationship of nucleo-proteids to the coagulation of the blood is described in the next chapter. Nucleo-proteids may be prepared from cellular structures like testis, thymus, kidney, etc., by two methods : — 1. Wooldridge's method. — The organ is miuced and soaked in water for twenty-four hours. Acetic acid added to the aqueous extract precipitates the nucleo-proteid, or, as Wooldridge called it, tissue fibrinogen. 2. Sodium chloride method. — The minced organ is ground up in a mortar with solid sodiuni chloride ; the resulting viscous mass is poured into excess of distilled water, and the nucleo-proteid rises in strings to the top of the water. The solvent usually employed for a nucleo-proteid, whichever method it is prepared by, is a 1 per cent, solution of sodium carbonate. Nuclein is the chief constituent of cell-nuclei. Its physical characters are somewhat like those of mucin, but it differs chemically in its high percentage of phosphorus. It is identical with the chromatin of histologists (see p. 11). On decomposition, it yields an organic acid called nucleic acid, together with a variable amount of proteid. Nucleic acid on decomposition yields phosphoric acid and various bases of the xanthine group. Some forms of nuclein, called pscudo -nuclein, such as are obtained from casein and vitellin, differ from the true nucleins in not yielding these xanthine compounds, or, Cn. XXV.] NUCLEO-PKOTEIDS AND ALBUMINOIDS 403 as they are sometimes termed, cdloxuric or purine bases. The purine bases are closely allied chemically to uric acid, and we shall have to consider them again in relation to that substance. The following diagrammatic way of representing the decomposi- tion of nucleo-proteid will assist the student in remembering the relationships of these substances : — Ntjcleo-Proteid subjected to gastric digestion yields Proteid converted into peptone, Nuclein, which remains as an insoluble which goes into solution. residue. If this is dissolved in alkali and hydrochloric acid added, it yields Proteid — converted into acid A precipitate consisting of nucleic albumin in solution. acid. If this is heated in a sealed tube with hydrochloric acid, it yields a number of imperfectly known sub- stances like thymic acid and in some cases a reducing sugar. But the best known and constant products of its decomposition are Phosphoric acid. Purine bases, viz. : Adenine. Hypoxanthine. Guanine. Xanthine. The nuclein obtained from the nuclei or heads of the spermatozoa consists of nucleic acid without any proteid admixture. In fishes' spermatozoa, however, the nucleic acid is united to protamine, the chemical properties of which we shall be considering immediately. C. ALBUMINOIDS. The albuminoids are a group of substances which, though similar to the proteids in many particulars, differ from them in certain other points. The principal members of the group are the following : — Collagen, the substance of which the white fibres of connective- tissue are composed. Some observers regard it as the anhydride of gelatin. In bone it is often called ossein. Gelatin — This substance is produced by boiling collagen with water. It possesses the peculiar property of setting into a jelly when a solution made with hot water cools. It gives most of the proteid colour tests. Most observers state, however, that it contains very little 404 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. sulphur. On digestion it is like proteid converted into peptone-like substances, and is readily absorbed. Though it will replace in diet a certain quantity of proteid, acting as what is called a ' proteid-sparing ' food, it cannot altogether take the place of proteid as a food. Animals fed on gelatin instead of proteid waste rapidly. Ghondrin, the very similar substance obtained from hyaline cartilage, is a mixture of gelatin with mucinoid materials. Elastin. — This is the substance of which the yellow or elastic fibres of connective-tissue are composed. It is a very insoluble material. The sarcolemma of muscular fibres and certain basement membranes are very similar. Keratin, or horny material, is the substance found in the surface layers of the epidermis, in hairs, nails, hoofs, and horns. It is very insoluble, and chiefly differs from proteids in its high percentage of sulphur. A similar substance, called neurokeratin, is found in neuroglia and nerve-fibres. In this connection it is interesting to note that the epidermis and the nervous system are both formed from the same layer of the embryo — the epiblast. Chitin and similar substances found in the exoskeleton of many invertebrates. D. The Protamines. Protamines. — These are basic substances which are combined with nuclein in the heads of the spermatozoa of certain fishes (salmon, sturgeon, etc.). They resemble proteids in many of their characters ; e.g., they give Piotrowski's reaction and some of the other tests for proteids. They are regarded by Kossel as the simplest proteids. By decomposition in various ways they yield bases containing six atoms of carbon, and called in consequence the hexone bases ; the bases are named lysine (C e H u N".,0.,), arginine (CcHj^O.,), and histidine (C G H 9 NA). The more complex proteids and albuminoids yield these bases also ; therefore Kossel considers that all these substances contain a protamine nucleus. The more complex proteids, however, yield many other products of decomposition in addition to these bases, such as leucine and tyrosine. The Polarimeter. This instrument is one by means of which the action of various subst inces on the plane of polarised light can be observed and measured. Most of the carbohydrates are dextro-rotatory. All the proteids are levo-rotatorv. There are many varieties of the instrument ; these can only be properly studied in a practical class, and all one can do here is to state briefly the principles on which they are constructed. Suppose one is shooting arrows at a fence made up of narrow vertical palings ; suppose also that the arrows are flat like the laths of a Venetian blind. If the CH. XXV.] FERMENTATION 405 arrows are shot vertically they will pass easily through the gaps between the palings, but if they are shot horizontally they will be unable to pass through at all. This rough illustration will help us in understanding what is meant by polarised light. Ordinary light is produced by the undulations of aether occurring in all directions at right angles to the path of propagation of the wave. Polarised light is produced by undulations in one plane only; we may compare it to our flat arrows. In a polarimeter, there is at one end of the instrument a Nicol's prism, which is made of Iceland spar. This polarises the light which passes through it ; it is called the polariser. At the other end of the instrument is another called the analyser. Between the two is a tube which can be filled with fluid. If the analyser is parallel to the polariser the light will pass through to the eye of the observer. But if the analyser is at right angles to the polariser it is like the flat arrows hitting horizontally the vertical palings of the fence, and there is darkness. At inter- mediate angles there will be intermediate degrees of illumination. If the analyser and polariser are parallel and the intermediate tube filled with water, the light will pass as usual, because water has no action on the plane of polarised light. But if the water contains sugar or some " optically active " substance in solution the plane is twisted in one direction or the other according as the sub- stance is dextro- or levo-rotatory. The amount of rotation is measured by the number of angles through which the analyser has to be turned in order to obtain the fidl illumination. This will vary with the length of the tube and the strength of the solution. Ferments. The word fermentation was first applied to the change of sugar into alcohol and carbonic acid by means of yeast. The evolution of carbonic acid causes frothing and bubbling ; hence the term " fermentation." The agent, yeast, which produces this, is called the ferment. Microscopic investigation shows that yeast is composed of minute rapidly-growing unicellular organisms (torulse) belonging to the fungus group of plants. The souring of milk, the transformation of urea into ammonium carbonate in decomposing urine, and the formation of vinegar (acetic acid) from alcohol are brought about by very similar FlG - 342.— ceiis of the P J J yeast plant m process organisms, lhe complex series or changes known of budding, as putrefaction, which are accompanied by the formation of malodorous gases, and which are produced by the various forms of bacteria, also come into the same category. That the change or fermentation is produced by these organisms is shown by the fact that it occurs only when the organisms are present, and stops when they are removed or killed by a high tem- perature or by certain substances (carbolic acid, mercuric chloride, etc.) called antiseptics. The " germ theory " of disease explains the infectious diseases by considering that the change in the system is of the nature of fermen- tation, and, like the others we have mentioned, produced by microbes ; the transference of the bacteria or their spores from one person to another constitutes infection. The poisons produced by the growing 406 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. bacteria appear to be either alkaloidal (ptomaines) or proteid in nature. The existence of poisonous proteids is a very remarkable thing, as no chemical differences can be shown to exist between them and those which are not poisonous, but which are useful as foods. The most virulent poison in existence, namely snake poison, is a proteid of the proteose class. There is another class of chemical transformations which at first sight differ very considerably from all of these. They, however, resemble these fermentations in the fact that they occur inde- pendently of any apparent change in the agents that produce them. The agents that produce them are not living organisms, but chemical substances, the result of the activity of living cells. 000° Is ^ J? d ■*' 7 d? J Fig. 343. — Types of micro-organisms : a, micrococci arranged singly ; in twos, diplococci — if all the micrococci at a were grouped together they would be called staphylococci — and in fours, sarcinae ; b, micrococci in chains, streptococci ; c and d, bacilli of various kinds (one is represented with a flagellum); c, various forms of spirilla ; /, spores, either free or in bacilli. The change of starch into sugar by the ptyalin of the saliva is an instance. Ferments may therefore be divided into two classes : — 1. The organised ferments — torulse, bacteria, etc. 2. The unorganised ferments, or enzymes — like ptyalin. The distinction between organised ferments and enzymes is, how- ever, more apparent than real; for the micro-organisms exert their action by enzymes which they secrete. This has long been known in connection with the invertin of yeast, and for the enzyme secreted by the micrococcus ureee, which converts urea into ammonium carbonate. In recent years Buchner, by crushing yeast cells, succeeded in obtaining from them an enzyme which produces the alcoholic fer- mentation, and there is no doubt that what is true for yeast is equally true for all the organised ferments, and in several cases this has been already proved experimentally. The unorganised ferments may be classified as follows : — (a) Amylolytic — those which change amyloses (starch, glycogen) into sugars. Examples : ptyalin, diastase, amylopsin. CH. XXV.] VAEIETTES OF FERMENTS 407 (b) Proteolytic — those which change proteicls into proteoses and peptones. Examples : pepsin, trypsin. (c) Steatolytic — those which split fats into fatty acids and glycerin. An example, steapsin, is found in pancreatic juice. (d) Inversive — those which convert saccharoses (cane sugar, maltose, lactose) into glucose. Examples : invertin of intestinal juice and of yeast cells. (e) Coagulative — those which convert soluble into insoluble proteids. Examples : rennet, fibrin ferment. Most ferment actions are hydrolytic — i.e., water is added to the material acted on, which then splits into new materials. This is seen by the following examples : — 1. Conversion of cellulose into carbonic acid and marsh gas (methane) by putrefactive organisms — ■ (C 6 H 10 O 5 > + »H 2 = 3«C0 o + 3«CH 4 . [Cellulose.] [Water.] [Carbonic [Methane.] acid.] 2. Inversion of cane sugar by the unorganised ferment invertin — C 12 H 22 O n + H 2 = C 6 H 12 6 + C 6 H 12 0„ [Cane sugar.] [Water.] [Dextrose.] [Levulose.] Some enzymes, called oxidases, are oxygen carriers, and produce oxidation. They occur in living tissues. A remarkable fact concerning the ferments is that the substances they produce in time put a stop to their activity ; thus, in the case of the organised ferments, the alcohol produced by yeast, the phenol, cresol, etc., produced by putrefactive organisms from proteids, first stop the growth of and ultimately kill the organisms which produce them. In the case of the enzymes also the products of their activity hinder and finally stop their action, but on the removal of these pro- ducts the ferments resume work. This fact suggested to Croft Hill the question whether ferments will act in the reverse manner to their usual action ; and in the case of one ferment, at any rate, he found this to be the case. Inverting ferments, as we have just seen, usually convert a disaccharide into monosaccharides. One of these inverting ferments, called maltose, converts maltose into dextrose. If the ferment is allowed to act on strong solutions of dextrose, it converts a small proportion of that sugar back into maltose again. This discovery of Croft Hill's has since been confirmed by others in relation to other enzymes. Ferments act best at a temperature of about 40" C. Their activity is stopped, but the ferments are not destroyed, by cold ; it is stopped and the ferments killed by too great heat. A certain amount of moisture and oxygen is also necessary ; there are, however, certain micro-organisms that act without free oxygen, and are called anae- 408 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV. robic in contradistinction to those which require oxygen, and are called aerobic. The chemical nature of the enzymes, or unorganised ferments, is very difficult to investigate ; they are substances that elude the grasp of the chemist to a great extent. So far, however, research has taught us that they are either proteid in nature or are substances closely allied to the proteids. CHAPTER XXVI THE BLOOD The blood is the fluid medium by means of which all the tissues of the body are directly or indirectly nourished ; by means of it also such of the materials resulting from the metabolism of the tissues which are of no further use in the economy are carried to the excre- tory organs. It is a somewhat viscid fluid, and in man and in all other vertebrate animals, with the exception of two,* is red in colour. It consists of a yellowish fluid, called plasma or liquor sanguinis, in which are suspended numerous blood corpuscles, which are, for the most part, coloured, and it is to their presence that the red colour of the blood is due. Even when examined in very thin layers, blood is opaque, on account of the different refractive powers possessed by its two con- stituents, viz., the plasma and the corpuscles. On treatment with ether, water, and other reagents, however, it becomes transparent and assumes a lake colour, in consequence of the colouring matter of the corpuscles having been discharged into the plasma. The average specific gravity of blood at 15° C. (60° F.) varies from 1055 to 1062. A rapid and useful method of estimating the specific gravity of blood was invented by Eoy. Drops of blood are taken and allowed to fall into fluids of known specific gravity. When the drop neither rises nor sinks in the fluid it is taken to be of the same specific gravity as that of the standard fluid. The reaction of blood is faintly alkaline and the taste saltish. Its temperature varies slightly, the average being 37'8° 0. (100° F.). The blood-stream is warmed by passing through the muscles, nerve centres, and glands, but is somewhat cooled on traversing the capillaries of the skin. Eecently drawn blood has a distinct odour, which in many cases is characteristic of the animal from which it has been taken ; it may be further developed by adding to blood a mixture of equal parts of sulphuric acid and water. Quantity of the Blood. — The quantity of blood in any animal * The am/phioxus and the Jeptocephahts. 11 THE BLOOD [CH. XXVI. under normal conditions bears a fairly constant relation to the body- weight. The methods employed for estimating it are not so simple as might at first sight have been thought. For example, it would not be possible to get any accurate information on the point from the amount obtained by rapidly bleeding an animal to death, for then an indefinite quantity would remain in the vessels ; nor, on the other hand, would it be possible to obtain a correct estimate by less rapid bleeding, as, since life would be more prolonged, time would be allowed for the passage into the blood of lymph from the lymphatic vessels and from the tissues. In the former case, therefore, we should nnder-estimate, and in the latter over-estimate, the total amount of the blood. The method usually employed is the following : — A small quantity of blood is taken from an animal by venesection ; it is defibrinated and measured, and used to make standard solutions of blood. The animal is then rapidly bled to death, and the blood which escapes is collected. The blood-vessels are next washed out with saline solu- tion until the washings are no longer coloured, and these are added to the previously withdrawn blood ; lastly, the whole animal is finely minced with saline solution. The fluid obtained from the mincings is carefully filtered and added to the diluted blood previously obtained, and the whole is measured. The next step in the process is the com- parison of the colour of the diluted blood with that of standard solu- tions of blood and water of a known strength, until it is discovered to what standard solution the diluted blood corresponds. As the amount of blood in the corresponding standard solution is known, as well as the total quantity of diluted blood obtained from the animal, it is easy to calculate the absolute amount of blood which the latter contained, and to this is added the small amount which was with- drawn to make the standard solutions. This gives the total amount of blood which the animal contained. It is contrasted with the weight of the animal, previously known. The result of experiments performed in this way showed that the quantity of blood in various animals differs a good deal, but in the dog averages T V to -^ of the total body-weight. An estimate of the quantity in man which corresponded nearly with this proportion has been more than once made from the follow- ing data. A criminal was weighed before and after decapitation ; the difference in the weight represented the quantity of blood which escaped. The blood-vessels of the head and trunk were then washed out by the injection of water until the fluid which escaped had only a pale red or straw colour. This fluid was also weighed; and the amount of blood which it represented was calculated by comparing the proportion of solid matter contained in it with that of the first blood which escaped on decapitation. (Weber and Lehmann.) CH. XXVI.] THE QUANTITY OF BLOOD 4li Haldane and Lorrain Smith have recently investigated the ques- tion by another method. The data required are (1) the percentage of haemoglobin in the blood, and (2) the extent to which the haemo- globin is saturated by a measured amount of carbonic oxide absorbed into the blood. The percentage of haemoglobin is determined colorimetrically by the Gowers' or Gowers'-Haldane haemoglobinometer (see p. 438). In the latter instrument the standard 100 per cent, of colour corresponds to a capacity of 18'5 c.c. of oxygen or carbonic oxide per 100 c.c. of blood. The subject whose blood is to be measured breathes a known volume of carbonic oxide, and a few drops of the blood are taken and the saturation of his haemoglobin is determined colorimetrically. From this result the total capacity of the blood for carbonic oxide is calculated. The "carbonic oxide capacity" is the same as the " oxygen capacity." The volume of the blood is then calculated from the total " oxygen capacity," and the percentage capacity as deter- mined by the haemoglobinometer. The following is an example : — The subject's blood in a given case has, let us say, the colour of the 100 per cent, standard, and therefore has a capacity of 18"5 c.c. per 100 c.c. blood. He is then allowed to breathe 75 c.c. of carbonic oxide, and it is then found that his blood is 15 per cent, saturated. The amount required to completely saturate his blood, or in other words his total capacity, must be 75 x ^ = 500 c.c. Since 18'5 c.c. of this total is carried by 100 c.c. of his blood, the total volume required to contain 500 c.c. is 500 x T77 ^= 2700 c.c. The subject has therefore 18'o 2 '7 litres of blood. The total weight is obtained by multiplying the volume by the specific gravity (about T055). Some of the results of this method are as follows : — The mass of the blood in man is about 4 - 9 per cent. (onTr) of the body- weight. The corresponding ratio of the blood volume is 4 - 62 c.c. per 100 grammes or t^t, The commonly accepted estimate of the mass of the blood is thus too high. In pathological conditions the numbers are different ; thus in anaemia from haemorrhage, the volume ratio is 6'5, in pernicious anaemia 8"6, in chlorosis 10"8. In other words, in various forms of anaemia the actual volume of the blood is increased. Prof. Lorrain Smith has pointed out to me that the decapitated criminal investigated by Weber and Lehmann mentioned above, suffered from scurvy, a disease which is accompanied by anaemia ; hence the total volume of his blood was pathologically high. 4 12 THE BLOOD [Oil. XXVI. Coagulation of the Blood. One of the most characteristic properties which the blood pos- sesses is that of clotting or coagulating. This phenomenon may be observed under the most favourable conditions in blood which has been drawn into an open vessel. In about two or three minutes, at the ordinary temperature of the air, the surface of the fluid is seen to become semi-solid or jelly-like, and this change takes place in a minute or two afterwards at the sides of the vessel in which it is contained, and then extends throughout the entire mass. The time which is occupied in these changes is about eight or nine minutes. The solid mass is of exactly the same volume as the previously liquid blood, and adheres so closely to the sides of the containing vessel that if the Pig. 344.— Reticulum of fibrin, from a drop of human blood, after treatment with rosanilin. The entangled corpuscles are not seen. (Ranvier.) latter is inverted none of its contents escape. The solid mass is the crassamentum, or clot. If the clot is watched for a few minutes, drops of a light straw-coloured fluid, the serum, may be seen to make their appearance on the surface, and, as they become more and more numerous, to run together, forming a complete superficial stratum above the solid clot. At the same time the fluid begins to transude at the sides and at the under-surface of the clot, which in the course of an hour or two floats in the liquid. The first drops of serum appear on the surface about eleven or twelve minutes after the blood has been drawn ; and the fluid continues to transude for from thirty- six to forty-eight hours. The clotting of blood is due to the development in it of a sub- stance called fibrin, which appears as a meshwork (fig. 344) of fine fibrils. This meshwork entangles and encloses within itself the blood corpuscles. The first clot formed, therefore, includes the whole of CH. XXVI.] COAGULATION OF THE BLOOD 413 the constituents of the blood in an apparently solid mass, but soon the fibrinous meshwork begins to contract, and the serum which does not belong to the clot is squeezed out. When the whole of the serum has transuded the clot is found to be smaller, but firmer, as it is now made up chiefly of fibrin and blood corpuscles. Thus coagulation re-arranges the constituents of the blood ; liquid blood is made up of plasma and blood corpuscles, and clotted blood of serum and clot. Fibrin is formed from the plasma, and may be obtained free from corpuscles when blood-plasma is allowed to clot, the corpuscles having previously been removed. It may be also obtained from blood by whipping it with a bunch of twigs ; the fibrin adheres to the twigs and entangles but few corpuscles. These may be removed by washing with water. Serum is plasma minus fibrin. The relation of plasma, serum, and clot can be seen at a glance in the following scheme of the constituents of the blood : — t,, fSerum rJasma ^., . N ^ribrirn Blood-, Idot I Corpuscles J It may be roughly stated that in 100 parts by weight of blood 60-65 parts consist of plasma and 35-40 of corpuscles. The huffy coat is seen when blood coagulates slowly, as in horse's blood. The red corpuscles sink more rapidly than the white, and the upper stratum of the clot (buffy coat) consists mainly of fibrin and white corpuscles. Coagulation is hastened by — 1. A temperature a little over that of the body. 2. Contact with foreign matter. 3. Injury to the vessel walls. 4. Agitation. 5. Addition of calcium salts. Coagulation is hindered or prevented by — 1. A low temperature. In a vessel cooled by ice, coagulation may be prevented for an hour or more. 2. The addition of a large quantity of neutral salts like sodium sulphate or magnesium sulphate. 3. Contact with the living vascular walls. 4. Contact with oil. 5. Addition of soluble oxalates. These precipitate the calcium necessary for coagulation as insoluble calcium oxalate. Sodium fluoride or citrate may be used instead of the oxalate. 6. Injection of commercial peptone (which consists chiefly of proteoses) into the circulation of the living animal. 414 THE BLOOD ['II XXVI. 7. Addition of leech extract. This acts in virtue of a proteose it contains. The theory generally received which accounts best for the coagula- tion of the blood is that of Hammarsten, and it may be briefly stated as follows : When blood is in the vessels one of the constituents of the plasma, a proteid of the globulin class called fibrinogen, exists in a soluble form. When the blood is shed the fibrinogen molecule is split into two parts : one part is a globulin, which remains in solution ; the other is the insoluble material fibrin. This change is brought about by the activity of a special unorganised ferment called the fibrin-ferment or thrombin. This ferment does not exist in healthy blood contained in healthy blood-vessels, but is one of the products of the disintegration of the white corpuscles and blood platelets that occurs when the blood leaves the vessels or comes into contact with foreign matter. To this it may be added, as the result of recent research, that a soluble calcium salt is essential for the formation of the ferment ; that the fibrin-ferment belongs to the class of nucleo-proteids ; that other nucleo-proteids (Wooldridge's tissue-fibrinogens) obtained from most of the cellular organs of the body produce intravascular clotting when injected into the circulation of a living animal. The substance which is converted into fibrin-ferment or thrombin by the action of a calcium salt may be conveniently termed prothrombin. The process of fibrin formation may therefore be represented in the following tabular way : — In the plasma a proteid substance From the colourless corpuscles a exists, called — nucleo-proteid is shed out, called — Fibrinogen. Prothrombin. By the action of calcium salts prothrombin is converted into fibrin- ferment, or Thrombin. Thrombin acts on fibrinogen in such a way that two new substances are formed. One of these is unimportant, viz., The other is important, viz., a globulin (Jibrino-globulin) which Fibrin, which entangles the cor- remains in solution. Its amount is puscles and so forms the Clot. very small. The Plasma and Serum. The liquid in which the corpuscles float may be obtained by employing one or other of the methods already described for pre- CH. XXVI.] THE PLASMA AND SERUM 415 venting the blood from coagulating. The corpuscles, being heavy, sink, and the supernatant plasma can then be removed by a pipette or siphon, or more thoroughly by the use of a centrifugal machine (see fig. 345). On counteracting the influence which has prevented the blood from coagulating, the plasma then itself coagulates. Thus plasma Pig. 345.— Plan and section of centrifugal machine, a, an iron socket secured to top of table b ; c, a steel spindle carrying the turntable d, and turning freely in a ; e, a flange round turntable d ; f f, shallow grooves on face of d in which the test tubes are fixed by clamps g g ; h, a pulley fixed to end of spindle c, and turned by the cord k ; 1 1 are two guide pulleys for cord k. The upper part of the figure is a surface view of the rotating turntable. (Gamgee.) obtained by the use of cold clots on warming gently ; plasma which has been decalcified by the action of a soluble oxalate clots on the addition of a calcium salt ; plasma obtained by the use of a strong solution of salt coagulates when this is diluted by the addition of water, the addition of fibrin-ferment being necessary in most cases ; where coagulation occurs without the addition of fibrin-ferment no doubt some is present from the partial disintegration of the corpuscles 416 THE BLOOD [CIL XXVI. which has already occurred. Pericardial and hydrocele fluids resemble pure plasma very closely in composition. As a rule, however, they contain few or no white corpuscles, and do not clot spontaneously, but after the addition of fibrin-ferment, or liquids like serum that contain fibrin-ferment, they always yield fibrin. Pure plasma may be obtained from horse's veins by what is known as the " living test-tube " experiment. If the jugular vein is ligatured in two places so as to include a quantity of blood within it, then removed from the animal and hung in a cool place, the blood will not clot for many hours. The corpuscles settle, and the supernatant plasma can be removed with a pipette. The plasma is alkaline, yellowish in tint, and its specific gravity is about 1026 to 1029. 1000 parts of plasma contain : — Water 902-90 Solids 97-10 Proteids : 1. yield of fibrin 4 '05 2. other proteids 78 '84 Extractives (including fat) 5*66 Inorganic salts 8*55 In round numbers, plasma contains 10 per cent, of solids, of which 8 are proteid in nature. Note, however, the comparatively small yield of fibrin. Serum contains the same three classes of constituents — proteids, extractives, and salts. The extractives and salts are the same in \>oth liquids. The proteids are different, as is shown in the following §) \§ and finally to disappear. O* *^ V7 \^ Chloroform, ether, and other reagents that dissolve fats f^\ dissolve the fatty substance (lecithin, etc.) of the membrane &~-J that surrounds the corpuscles, and so produce laking of the j, 1( . 3.-,i _Efiect of blood. tannin. Tannic acid. — When a 2 per cent, fresh solution of tannic acid is applied to frog's blood it causes the appearance of a sharply-defined little knob, projecting from the free surface {Roberts' macula) : the colouring matter becomes at the same time concentrated in the nucleus, which grows more dis- tinct (fig. 351). A somewhat similar effect is produced on the human red blood- corpuscle, the colouring matter being discharged and coagulated as a little knob of haematin on the surface of the corpuscle. Ilnric acid. A 2 per cent, solution applied to nucleated red blood-cells (frog) will cause the concentration of all the colouring matter in the nucleus ; the coloured body thus formed gradually quits its central position, and comes to be partly, sometimes entirely, pro- Fig. 352.— Effect ,,, "-,-; —Effect truded ^ rom tne surface of the now colourless of boric acid. of heat. "' ce ^ ( n g- 352). The result of this experiment led Briicke to distinguish the coloured contents of the cell (zooid) from its colourless stroma or envelope (aicoid). When applied to the non-nucleated mammalian corpuscle its effect merely resembles that of other dilute acids. Heed.— The effect of heat up to 50—60 C. (120—140 F.) is to cause the forma- tion of a number of bud-like processes. n CH. XXVI.] THE WHITE CORPUSCLES 421 Electricity causes the red blood-corpuscles to become crenated, and at length mulberry-like. Finally they recover their round form and become quite pale. The Colourless Corpuscles. — In human blood the white or colourless corpuscles or leucocytes (when at rest) are nearly spherical masses of granular protoplasm. In all cases one or more nuclei exist in each corpuscle. The size of the corpuscles varies considerably, but averages ^-Vo °f an i ncn (10/") i n diameter. In health, the proportion of white to red corpuscles, which, taking an average, is about 1 to 500 or 600, varies considerably even in the course of the same day. The variations appear to depend chiefly on the amount and probably also on the kind of food taken ; the number of leucocytes is generally increased by a meal, and diminished by fasting. Also in young persons, during pregnancy, and after great loss of blood, there is a larger proportion of colourless blood-cor- puscles. In old age, on the other hand, their proportion is diminished. There are four principal varieties of colourless corpuscles found in human blood : — 1. Poly -morpho -nuclear cells. — These contain several nuclei united by fine threads of chromatin. Their protoplasm is filled with fine granules, which are termed oxyphile on account of their affinity for acid dyes like eosin. These are the most important leucocytes, con- stituting from 60 to 70 per cent, of the total. 2 Eosinopliile cells. — These are not so actively amoeboid as the first variety. Their nucleus is simple or lobed. Their protoplasmic granules are large, and are much more deeply stained by eosin than the fine granules of the first variety. They comprise about 5 per cent, of the total leucocytes. 3. Lymphocytes. — These have a large spherical nucleus and a limited amount of clear protoplasm around it. Transitional forms between them and the next variety are also found. They constitute from 15 to 30 per cent, of the total. 4. Hyaline cells. — These differ from the last by having more proto- plasm around the nucleus. The protoplasm is amoeboid, and is clear. It, however, stains slightly with methylene blue, and this is perhaps due to the presence of fine basophile granules. The nuclei of all these varieties are basophile, i.e., they have a strong affinity for basic aniline dyes like methylene blue. Cells, with large basophile granules, are very rare in healthy human blood. Amoelboid. Movement. — The remarkable property of the colour- less corpuscles of spontaneously changing their shape was first demon- strated by Wharton Jones in the blood of the skate. If a drop of blood is examined with a high power of the microscope, under condi- tions by which loss of moisture is prevented, and at the same time the temperature is maintained by a warm stage at about that of the 422 THE BLOOD [CH. XXVI. body, 37 c C. (985~ F.), the colourless corpuscles will be observed slowly to alter their shapes, and to send out processes at various parts of their circumference. The amoeboid movement, which can be demonstrated in human colourless blood -corpuscles, can be more readily seen in newt's blood. The full consideration of amoeboid movement is given on p. 12. An interesting variety of amoeboid movement is that which leads to the ingestion of foreign particles. This gives to the leucocytes their power of taking in and digesting bacilli (phagocytosis). The multi- nucleated, finely granular corpuscles are the most vigorous phagocytes. Heulthy bacillus... Healthy bacillus ... .Healthy bacillus. i\ Partially digested bacillus mm Partially digested leucocyte... Nuclei vacuolated — ^< : # r A s -_ Nucleus. ..Bacillus in leucocyte. ....' Partially digested leucocyte. % — Foreign matter. ' lig, ., Particles of foreign matter. Particles of foreign matter. i*~^|p'- Particles of foreign matter. Leucocytes \ \ Fig. 354.— Macrophages containing bacilli and other structures undergoing digestion. (Rufl'er.) The accompanying figure illustrates this ; the cells represented, how- ever, are not leucocytes, but the large amoeboid cells found in connec- tive tissues, especially in inflamed parts. The process of emigration of the leucocytes is described on p. 295. Action of Reagents on the colourless corpuscles. — Water causes the corpuscles to swell and their nuclei to become apparent. Acetic acid (1 per cent.) has a similar action ; it also causes the granules to aggre- gate round the nucleus. Dilute alkalis produce swelling and bursting of the corpuscles. CH. XXVI.] H^IMACYTOMETEKS 423 The Blood-Platelets. Besides the two principal varieties of blood-corpuscles, a third kind has been described under the name blood-platelets {Blut-platchen). These are colourless disc-shaped or irregular bodies, much smaller than red corpuscles. Different views are held as to their origin. At first they were regarded as immature red corpuscles ; but this view has been discarded. Some state that they are merely a precipitate of nucleo- proteid which occurs when the plasma dies or is cooled. There is, however, no doubt that they do occur in living blood, and have been seen to undergo amoeboid movement ; some observers state that they are nucleated. Enumeration of the Blood-Corpuscles. Several methods are employed for counting the blood-corpuscles ; most of them depend upon the same principle, i.e., the dilution of a minute volume of blood with a given volume of a colourless saline solution similar in specific gravity to blood Fig. 355. — Hemacytometer. (Gowers.) plasma, so that the size and shape of the corpuscles is altered as little as possible. A minute quantity of the well-mixed solution is then taken, examined under the microscope, either in a flattened capillary tube (Malassez) or in a cell (Hayem & Nachet, Gowers) of known capacity, and the number of corpuscles in a measured length of the tube, or in a given area of the cell, is counted. The length of the tube and the area of the cell are ascertained by means of a micrometer scale in the micro- scope ocular ; or in the case of Gowers' modification, by the division of the cell area into squares of known size. Having ascertained the number of corpuscles in the diluted blood, it is easy to find out the number in a given volume of normal blood. 424 THE BLOOD [CH. XXVI. Gowers' Hemacytometer consists of a small pipette (a), which, when filled up to a mark on its stem holds 995 cubic millimetres. It is furnished with an india- rubber tube and glass mouth-piece to facilitate filling and emptying ; a capillary tube (b) marked to hold 5 cubic millimetres, and also furnished with an indiarubber tube and mouth-piece ; a small glass jar (n) in which the dilution of the blood is Fig. 356. | c | | m 1 ; | performed ; a glass stirrer (e) for mixing the blood and salt solution thoroughly ; (f) a needle, the length of which can be regulated by a screw ; a brass stage plate (c) carrying a glass slide, on which is a cell one-fifth of a millimetre deep, and the bottom of which is divided into one-tenth millimetre squares. On the top of the cell a cover-slip rests. A standard saline solution of sodium sulphate, or similar salt, of specific gravity 1025, is made, and 995 cubic millimetres are measured by means of the pipette into the glass jar, and with this 5 cubic millimetres of blood, obtained by pricking the finger with the needle, and measured Fir ; . as7. in the capillary pipette (b) are thoroughly mixed by the glass stirring-rod. A drop of this diluted blood is then placed in the cell and covered with a cover-slip, which is fixed in position by means of the two lateral springs. The layer of diluted blood between the slide and cover-glass is one-fifth of a milli- metre thick. The preparation is then examined under a microscope with a power of about 400 diameters, and focussed until the lines dividing the cell into squares are visible. After a short delay, the red corpuscles which have sunk to the bottom of the cell, and are resting on the squares, are counted in ten squares, and the number of white corpuscles noted. By adding together the numbers counted in ten (one- tenth millimetre) squares, and, as the blood has been diluted, multiplying by ten thousand, the number of corpuscles in one cubic millimetre of blood is obtained. The average number of corpuscles per cubic millimetre of healthy blood, according to Vierordt and Welcker, is 5,000,000 in adult men, and 4,500,000 in women ; this corresponds to an average of 50 and 45 corpuscles respectively per square of Gowers' instrument. A haemacytometer of another form, and one that is much used at the present time, is known as the Thoma-Zeiss haema- cytometer. It consists of a carefully graduated pipette, in which the dilution of the blood is done ; this is so formed that the capillary stem has a capacity equalling one-hundredth of the bulb above it. If the blood is drawn up in the capillary tube to the line marked 1 (fig. 357) the saline solution may afterwards be drawn up the stem to the line 101 ; in this way we have 101 parts, of which the blood forms 1. As the con- tents of the stem can be displaced unmixed we shall have in the mixture the proper dilution. The blood and the saline so- lution are well mixed by shaking the pipette, in the bulb of which is contained a small glass bead for the purpose of aid- ing the mixing. The other part of the instrument consists of a glass slide (fig. 356) upon which is mounted a covered disc, m, accurately ruled so as to present one square millimetre divided into 400 squares of one-twentieth of a millimetre each. The micrometer thus made is surrounded by another annular cell, c, which has such a height as to make the cell project exactly one-tenth millimetre beyond m. If a drop of the diluted blood is placed upon m, and e is covered with a perfectly flat cover-glass, the volume of the diluted blood above each of the squares of the micrometer, i.e., above each -jl T ,, will be j^V?, of a cubic millimetre. An average of ten or more Figs. 356 and 357.— Thoma-Zeiss Hiimacytometer. CH. XXYI.] DEVELOPMENT OF BLOOD-CORPUSCLES 425 squares is then taken, and this number multiplied by 4000 x 100 gives the number of corpuscles in a cubic millimetre of undiluted blood. Dr George Oliver's Haemacytometer is a much easier instrument to use, and the results obtained are accurate ; it does not enable one, however, to ascertain the proportion of red and white corpuscles. A small measured quantity of blood is taken up into a pipette and washed out into a graduated flattened test-tube with Hayem's fluid (sodium chloride 0"5 gramme, sodium sulphate - 25 gr. , corrosive sublimate 0*25 gr., distilled water 100 c.c). The graduations of the tube are so adjusted that with normal blood (i.e., blood containing 5,000,000 red corpuscles per cubic millimetre) the light of a small wax candle placed three yards from the eye in a dark room, is just visible as a thin bright line when looked at through the tube held edgeways between the fingers, and filled up to the 100 mark with Hayem's fluid. If the number of corpuscles is less than normal, less of the diluting solution is required before the light is transmitted ; if more than normal, more of the solu- tion is necessary. The graduations of the tube correspond to percentages of the normal standard which is taken as 100. Development of the Blood-Corpuscles. The first formed blood-corpuscles of the human embryo differ much in their general characters from those which belong to the later periods of intra-uterine, and to all periods of extra-uterine, life. Their manner of origin is at first very simple. Surrounding the early embryo is a circular area, called the vascular area, in which the first rudiments of the blood-vessels and blood-corpuscles are developed. Here the nucleated embryonic cells of the mesoblast, from which the blood-vessels and corpuscles are to be formed, send out processes in various directions, and these, joining together, form an irregular mesh work. The nuclei increase in number, and collect chiefly in the larger masses of protoplasm, but partly also in the processes. These nuclei gather around them a certain amount of the protoplasm, and, becoming coloured, form the red blood - corpuscles. The protoplasm of the cells and their branched network in which these corpuscles lie then become hollowed out into a system of canals enclosing fluid, in which the red nucleated corpuscles float. The corpuscles at first are from about 25 \ to T -roo- of an inch (IOju. to 16^) in diameter, mostly spherical, and with granular contents, and a well-marked nucleus. Their nuclei, which are about 50 \ of an inch (5^) in diameter, are central and circular. The corpuscles then strongly resemble the colourless corpuscles of the fully developed blood, but are coloured. They are capable of amoeboid movement and multiply by division. When, in the progress of embryonic development, the liver begins to be formed, the multiplication of blood-cells in the whole mass of blood ceases, and new blood-cells are produced by this organ, and also by the lymphatic glands, thymus and spleen. These are at first colourless and nucleated, but afterwards acquire the ordinary blood- tinge, and resemble very much those of the first set. They also multiply by division. In whichever way produced, however, whether 426 THE BLOOP [CH. XXVI. from the original formative cells of the embryo, or by the liver and the other organs mentioned above, these coloured nucleated cells begin very early in foetal life to be mingled with coloured non- Fig. 35S.— Part of the network of developing blood-vessels in the vascular area of a guinea-pig. hi, blood-corpuscles becoming free in an enlarged and hollowed-OUt part of the network; a, process of protoplasm. (E. A. Schlifer.) nucleated corpuscles resembling those of the adult, and at about the fourth or fifth month of embryonic existence are completely replaced by them. Origin of the Matured Coloured Corpuscles. — The non-nucleated red corpuscles may possibly be derived from the nucleated, but in l'i'i. 359. — Development of red corpuscles in connective tissue cells. From the subcutaneous tissue of a new-bom rat. h, a cell containing hamoglobin in a diffused form in the protoplasm ; h', one containing coloured globules of varying size and vacuoles ; h", a cell filled with coloured globules of nearly uniform size ; /,/, developing fat cells. (E. A. Schafer.) all probability are an entirely new formation. Their chief origin is : — From the medulla of bone. — It has been shown that coloured cor- puscles are to a very large extent derived during adult life from the large pale cells in the red marrow of bones, especially of the ribs. These cells become coloured from the formation of haemoglobin chiefly in one part of their protoplasm. This coloured part becomes separated CH. XXVI.] DEVELOPMENT OF BLOOD-CORPUSCLES 427 from the rest of the cell and forms a red corpuscle, being at first cup- shaped, but soon taking on the normal appearance of the mature cor- puscle. Mingled with the amoeboid colourless marrow cells (p. 55) are a number of other smaller amoeboid cells called erythroblasts (fig. 361); these are tinted with haemoglobin ; they divide and multiply, lose their nucleus, and are thus transformed into discoid blood-corpuscles. From the tissue of the spleen. — It is probable that coloured as well as colourless corpuscles may be produced in the spleen from cells similar to the erythroblasts of red marrow. The belief which formerly pre- vailed that the red corpuscles are derived from the white or from the platelets has now been discarded. During foetal life, and possibly in some animals, e.g. the rat, which are born in an immature condition, for some little time after birth, the blood discs have been stated by Schafer to arise in the connective tissue cells in the following way. Small globules, of varying size, of colouring matter arise in the pro- toplasm of the cells (fig. 359), and the cells themselves become branched, their branches joining the branches of similar cells. The cells next become vacuolated, and the red globules are free in a cavity filled with fluid (fig. 360) ; by the extension of the cavity of the cells into their processes anastomosing vessels are produced, which ultimately join with the previously Fig. 360.— Further development of blood-cor- puscles in connective tissue cells and trans- formation of the latter into capillary blood-vessels, a, an elongated cell with a cavity in the protoplasm occupied by fluid and by blood-corpuscles which are still globular; b, a hollow cell, the nucleus of which has multiplied. The new nuclei are arranged around the wall of the cavity, the corpuscles in which have now become dis- coid ; e, shows the mode of union of a " hsemapoietic " cell, which, in this instance, contains only one corpuscle, with the pro- longation (fit) of a previously existing vessel ; a and c, from the new-born rat : b, from the fatal sheep. (E. A. Schafer.) _j Fig. 361. -Coloured nucleated corpuscles, from the red marrow of the guinea-pig (E. A. Schafer.) existing vessels, and the globules, now having the size and appearance of the ordinary red corpuscles, are passed into the general circulation. This method of formation is called intracellular. Without doubt, the red corpuscles have, like all other parts of the organism, a tolerably 428 THE BLOOD [CH. XXVI. definite term of existence, and in a like manner die and waste away when the portion of work allotted to them has been performed. Neither the length of their life, however, nor the fashion of their decay, has been yet wholly made out. A certain number of the coloured corpuscles undergo disintegration in the liver and spleen ; corpuscles in various degrees of degeneration have been observed in the latter organ. Origin of the White Corpuscles. — The hyaline corpuscles are derived from the lymphocytes which are formed in the lymphatic glands, and enter the blood-stream by the thoracic duct. The finely granular leucocytes which are the most numerous white corpuscles in the blood originate either in the same way, or by cell division in the blood-stream itself. Most observers consider tln\ arise in the red marrow. The coarsely granular eosinophile corpuscles, which form about 5 per cent, of the total leucocytes in normal blood, are found in larger numbers in the connective tissue in various parts of the body ; they are found in special abundance in red marrow, in which at one time they were supposed to originate. Most look upon each eosinophile corpuscle as a little unicellular gland, and the mass of corpuscles as a migratory glandular tissue. Chemistry of the Blood-Corpuscles. The white blood-corpuscles. — Our chemical knowledge of the white corpuscles is small. Their nucleus consists of nuclein, their cell protoplasm yields proteids belonging to the globulin and nucleo- proteid groups. The nucleo-proteid obtained from, them is not quite the same thing as fibrin-ferment {thrombin) ; it is probably the zymogen or precursor of the ferment (prothrombin) ; the action of the calcium salts of the plasma in shed blood is to convert prothrombin into thrombin (see p. 414). The protoplasm of these cells often contains small quantities of fat and glycogen. The red hlood-corpuscles. — 1000 parts of red corpuscles con- tain : — Water Solids [° r e anic . (Inorganic ....... One hundred parts of the dry organic matter contain Proteid ........ Haemoglobin ....... Lecithin ........ Cholesterin ........ The proteid present is identical with the nucleo-proteid of white corpuscles. The mineral matter consists chiefly of chlorides of 688 .".0:5-88 parts. 8-12 » itain — 5 to 12 86 to 94 parts. 1-8 ,, o-i ,, CH. XXVI.] HAEMOGLOBIN 429 potassium and sodium, and phosphates of calcium and magnesium. In man potassium chloride is more abundant than sodium chloride ; this, however, does not hold good for all animals. Oxygen is contained in combination with the haemoglobin to form oxyhemoglobin. The corpuscles also contain a certain amount of carbonic acid. Haemoglobin and Oxyhemoglobin. — The pigment is by far the most abundant and important of the constituents of the red corpuscles. It is a substance which gives the reactions of a proteid, but differs from most other proteids in containing the element iron, and in being readily crystallisable. It exists in the blood in two conditions : in arterial blood it is combined loosely with oxygen, is of a bright red colour, and is called oxyhemoglobin ; the other con- dition is the deoxygenated or re- duced hemoglobin (better called simply haemoglobin). This is found in the blood after asphyxia. It also occurs in all venous blood — that is, blood which is return- ing to 'the heart after it has sup- plied the tissues with oxygen. Venous blood, however, always contains a considerable quantity of oxyhemoglobin also. Hemo- globin is the oxygen-carrier of the body, and it may be called a respiratory pigment.* Crystals of oxyhemoglobin -f- may be obtained with readiness from the blood of such animals as the rat, guinea-pig, or clog; with difficulty from other animals, such as man, ape, and most of the common mammals. The follow- ing methods are the best : — 1. Mix a drop of defibrinated blood of the rat on a slide with a drop of water ; put on a cover-glass ; in a few minutes the corpuscles are rendered colourless, and then the oxyhemoglobin crystallises out from the solution so formed. 2. Microscopical specimens may also be made by Stein's method, * In the blood of invertebrate animals haemoglobin is sometimes found, but usually in the plasma, not in special corpuscles. Sometimes it is replaced by other respiratory pigments, such as the green one, chlorocruorin, found in certain worms, and the blue one, hsemccyanin, found in many molluscs and Crustacea. Chloro- cruorin contains iron ; haemocyanin contains copper. t Crystals of haemoglobin can also be obtained by carrying out the crystal- lisation in an atmosphere free from oxygen. Fig. 362.— Crystals of oxyhemoglobin— prismatic, from human blood. 430 THE BLOOD [CH. XXVI. which consists in using Canada balsam instead of water in the fore- going experiment. 3. On a larger scale, crystals may be obtained by mixing the blood with one-sixteenth of its volume of ether ; the corpuscles dis- solve, and the blood assumes a laky appearance. After a period vary- ing from a few minutes to days, abundant crystals are deposited. In nearly all animals the crystals are rhombic prisms (fig. 362) ; but in the guinea-pig they are rhombic tetrahedra, or four-sided pyramids (fig. 3G3); in the squirrel and hamster, hexagonal plates (%. 364). The crystals contain a varying amount of water of crystallisation ; this probably explains their different crystalline form and solubilities. Several observers have analysed haemoglobin. They find carbon, Fig. 363. -Oxyhemoglobin crystals— tetrahedral, from blood of the guinea-pig. Fig. 364.— Hexagonal oxyhemoglobin crystals, from blood of squirrel. (After Funke.) hydrogen, nitrogen, oxygen, sulphur and iron. The percentage of iron is - 4 The amounts of the other elements are variously given, but roughly they are the same as in the proteids. On adding an acid or alkali to haemoglobin, it is broken up into two parts — a brown pigment called hcematin, which contains all the iron of the original substance, and a proteid called globin. Haematin is not crystallisable ; it has the formula C 34 H 35 N 4 Fe0 5 (Hoppe-Seyler), or C 32 H 30 N 4 FeO 3 (Nencki and Sieber) ; its consti- tutional formula is, however, not known. Haematin presents different spectroscopic appearances in acid and alkaline solutions (see accom- panying plate). On decomposition it yields pyrrol derivatives. Globin is a somewhat curious proteid ; it is coagulable by heat, soluble in dilute acids, and precipitable from such solutions by ammonia. It closely resembles a substance previously separated from red corpuscles by Kossel, and termed by him histone. (Schulz.) CH. XXVI.] DEEIVATIYES OF HAEMOGLOBIN 431 Haemochromogen is sometimes called reduced haematin ; it may be formed by adding a reducing agent like ammonium sulphide to an alkaline solution of haeniatin. Its absorption spectrum shown on the accompanying plate (No. 8), forms the best spectroscopic test for blood pigment; the suspected pigment is dissolved in potash, and ammonium sulphide added. Very dilute specimens show the absorp- tion bands, especially the one midway between D and E. Haemin is of great importance, as the obtaining of this substance forms the best chemical test for blood. Haemin crystals may be pre- pared for microscopical examination by boiling a fragment of dried blood with a drop of glacial acetic acid on a slide ; on cooling, triclinic plates and prisms of a dark brown colour, often in star-shaped clusters and with rounded angles (fig. 365), separate out. In the case of an old blood stain it is necessary to add a crystal of sodium chloride. Fresh blood contains sufficient sodium chloride in itself. Fig. 365. — Haamin crystals. (Frey.) Fig. 366. — Haematoidin crystals. (Frey.) The action of the acetic acid is (1) to split the haemoglobin into haematin and globin ; and (2) to evolve hydrochloric acid from the sodium chloride. Hsernin is usually stated to be a combination of haematin with hydrochloric acid. Haemin may be prepared in other ways, but if prepared with the use of acetic acid, Nencki and Zaleski have shown that it also contains an acetyl group, and ascribe to it the empirical formula, Cg^HgoC^N^ClFe. The chlorine and acetyl are both attached to the iron atom. Haematoporphyrin is iron-free haematin ; it may be prepared by mixing blood with strong sulphuric acid ; the iron is taken out as ferrous sulphate. It is also found sometimes in nature ; it occurs in certain invertebrate pigments, and may also be found in certain forms of pathological urine. Even normal urine contains traces of it. It presents different spectroscopic appearances according as it is dis- solved in acid or alkaline media. The absorption spectrum figured (No. 9) is that of acid haematoporphyrin. (See note, p. 444.) Haematoidin. — This substance is found in the form of yellowish- red crystals (fig. 366) in old blood extravasations, and is derived from the haemoglobin. Its crystalline form and the reaction it gives with 432 THE BLOOD [CH. XXVI. fuming nitric acid shows it to be closely allied to Bilirubin, the chief colouring matter of the Bile, and on analysis it is found to be identical with it. Like hsematoporphyrin, haeniatoidin is free from iron. These two substances are not identical {e.g., haematoidin shows no spectroscopic bands) ; they are probably isomeric. Compounds of Haemoglobin. Haemoglobin forms at least four compounds with gases : — With oxviren ' L Oxyhaemoglobin. witn oxygen ^ Methaemoglobin. With carbonic oxide . . . .3. Carbonic oxide haemoglobin. With nitric oxide . . . .4. Nitric oxide haemoglobin. These compounds have similar crystalline forms ; they each probably consist of a molecule of haemoglobin combined with one of the gas in question. They part with the combined gas somewhat readily ; they are arranged in order of stability in the above list, the least stable first. Oxyhemoglobin is the compound that exists in arterial blood. Many of its properties have been already mentioned. The oxygen linked to the haemoglobin, which is removed by the tissues through which the blood circulates, may be called the respiratory oxygen of haemoglobin. The processes that occur in the lungs and tissues, resulting in the oxygenation and de-oxygenation respectively of the haemoglobin, may be imitated outside the body, using either blood or pure solutions of haemoglobin. The respiratory oxygen can be removed, for example, in the Torricellian vacuum of a mercurial air- pump, or by passing a neutral gas like hydrogen through the blood, or by the use of reducing agents like ammonium sulphide or Stokes' reagent.* One gramme of haemoglobin will combine with 1'34 c.c. of oxygen. If any of these methods for reducing oxyheemoglobin is used, the bright red (arterial) colour of oxyhemoglobin changes to the purplish (venous) tint of haemoglobin. On once more allowing oxygen to come into contact with the haemoglobin, as by shaking the solution with the air, the bright arterial colour returns. These colour-changes may be more accurately studied with the spectroscope, and the constant position of the absorption bands seen constitutes an important test for blood pigment. It will be first necessary to describe briefly the instrument used. The Spectroscope. — When a ray of white light is passed through * Stokes' reagent must always be freshly prepared ; it is a solution of ferrous sulphate to which a little tartaric acid has been added, and then ammonia till the reaction is alkaline. CH. XXVI.] THE SPECTKOSCOPE 433 a prism, it is refracted or bent at each surface of the prism ; the whole ray is, however, not equally bent, but it is split into its constituent colours, which may be allowed to fall on a screen. The band of colours beginning with the red, passing through orange, yellow, green, blue, and ending with violet, is called a spectrum : this is seen in nature in the rainbow. It may be obtained artificially by the glass prism or prisms of a spectroscope. The spectrum of sunlight is interrupted by numerous dark lines crossing it vertically, called Frauenhofer's lines. These are perfectly constant in position and serve as landmarks in the spectrum. The more prominent are A, B, and C, in the red ; D, in the yellow ; E, b, and F, in the green ; G and H, in the violet. These lines are due to certain volatile substances in the solar atmosphere. If the light from burning sodium or its compounds is examined spectroscopically, it will be found to give a bright yellow line, or, rather, two bright yellow lines very close together. Potassium gives two bright red lines and one violet line ; and the other elements, when incandescent, give characteristic lines, but none so simple as sodium. If now the flame of a lamp is examined, it will be found to give a continuous spectrum like that of sunlight in the arrangement of its colours, but unlike it in the absence of dark lines ; but if the light from the lamp is made to pass through sodium vapour before it reaches the spectro- scope, the bright yellow light will be found absent, and in its place a dark line, or, rather, two dark lines very close together, occupying the same position as the two bright lines of the sodium spectrum. The sodium vapour thus absorbs the same rays as those which it itself produces at a higher temperature. Thus the D line, as we term it in the solar spectrum, is due to the presence of sodium vapour in the solar atmosphere. The other dark lines are similarly accounted for by other elements. The large form of spectroscope (fig. 367) consists of a tube A, called the collimator, with a slit at the end S, and a convex lens at the end L. The latter makes the rays of light passing through the slit from the source of light, parallel : they fall on the prism P, and then the spectrum so formed is focussed by the telescope T. A third tube, not shown in the figure, carries a small transparent scale of wave-lengths, as in accurate observations the position of any point in the spectrum is given in the terms of the corresponding wave-lengths. If we now interpose between the source of light and the slit S a piece of coloured glass (H in fig. 367), or a solution of a coloured substance contained in a vessel with parallel sides (the haematoscope of Herrmann), the spectrum is found to be no longer continuous, but is interrupted by a number of dark shadows, or absorption bands corresponding to the light absorbed by the coloured medium. Thus a 2 E 434 THE BLOOD [CH. XXVI. solution of oxyhemoglobin of a certain strength gives two bands between the D and E lines ; haemoglobin gives only one ; and other red solutions, though to the naked eye similar to oxyhemoglobin, will give characteristic bands in other positions. A convenient form of small spectroscope is the direct vision spectroscope, in which, by an arrangement of alternating prisms of crown and flint glass, the spectrum is observed by the eye in the same line as the tube furnished with the slit — indeed, slit and prisms are both contained in the same tube. In the examination of the spectrum of small coloured objects a combination of the microscope and direct vision spectroscope, called the micro-spectroscope, is used. Fig. 3G7. — Diagram of Spectroscope. The next figure illustrates a method of representing absorption spectra diagrammatically. The solution was examined in a layer 1 centimetre thick. The base line has on it at the proper distances the chief Frauenhofer lines, and along the right-hand edges are percentages of the amount of oxyhemoglobin present in I, of hemoglobin in II. The width of the shadings at each level repre- sents the position and amount of absorption corresponding to the percentages. The characteristic spectrum of oxyhemoglobin, as it actually appears through the spectroscope, is seen in the accompanying coloured plate (spectrum 2). There are two distinct absorption bands between the D and E lines; the one nearest to D (the a band) is narrower, darker, and has better-defined edges than the other (the /3 band). As will be seen on looking at fig. 368, a solution of oxyhemoglobin of concentration greater than 0"65 per cent, and less than 0'85 per cent, (examined in a cell of the usual thickness of 1 centimetre) gives one thick band overlapping both D and E, and a stronger solution only lets the red light through between C and D. A solution which gives the two characteristic bands must therefore be BLOOD-SPECTRA COMPARED WITH SOLAR SPECTRUM. 1. Solar spectrum. 2. Spectrum of dilute solution of oxyhemoglobin. 3. „ „ haemoglobin. 4. ,, „ carbonic oxide haemoglobin. 5. ,, „ acid haematin in ethereal solution. 6. ., ,, alkaline haematin. 7. „ ,, methaemoglobin. 8. „ ,, haemochromogen. 9. „ ,, acid haematoporphyrin. [To face page 434. CH. XXVI.] ABSORPTION SPECTRA 435 a dilute one. The one band (y band) of haemoglobin (spectrum 3) is not so well denned as the aor/3 bands. On dilution it fades rapidly ; so that in a solution of such strength that both bands of oxyhemoglobin would be quite distinct, the single band of. hemoglobin has disappeared from view. The oxyhemoglobin bands can be distinguished in a solution which contains only one part of the pigment to 10,000 of water, and even in more dilute solutions which seem to be colourless the a band is still visible. Haemoglobin and its compounds also show absorption bands in the ultra-violet portion of the spectrum. This portion of the spectrum is not visible to the eye, but can be rendered visible by allowing the spectrum to fall on a fluorescent screen, or on a sensitive photographic J Fig. 338. — Graphic lepresentaliuns of Che amount of absorption of light by solution of (I) oxyhemo- globin, (II) of haemoglobin, of different strengths. The shading indicates the amount of absorption of the spectrum ; the figures on the right border express percentages. (Rollett.) plate. In order to show absorption bands in this part of the spectrum very dilute solutions of the pigment must be used. Oxyhemoglobin shows a band (Soret's band) between the lines G and H. In hemoglobin, carbonic oxide hemoglobin, and nitric oxide hemoglobin, this band is rather nearer G-. Methemoglobin and hematoporphyrin show similar bands. We owe most of our knowledge of the " photographic spectrum " to Prof. G-amgee, through whose kindness I am enabled to present reproductions of two of his numerous photographs (figs. 369 and 370). Methsemoglobin. — This may be produced artificially in various ways, as by adding potassium ferricyanide or amyl nitrite to blood, and as it also may occur in certain diseased conditions in the urine, it is of considerable practical importance. It can be crystallised, and is found to contain the same amount of oxygen as oxyhemoglobin, only combined in a different way. The oxygen is not removable by the air-pump, nor by a stream of neutral gas like hydrogen. It can 436 THE BLOOD [CII. XXVI. however, by reducing agents like ammonium sulphide, be made to yield haemoglobin. Methsenioglobm is of a brownish-red colour, and gives a characteristic absorption band in the red between tin 1 C and Fig. 369.— The photographic spectrum of haemoglobin and oxyhemoglobin. (Gamgee.) D lines (spectrum 7 in coloured plate). In dilute solutions other bands can be seen. Potassium ferricyanide is the most convenient reagent for making- methapmo- globin. It is, however, necessary to mention that it produces another effect as Fio. 370.— The photographic spectrum of oxyhEemoglobin and methsemoglobin. (Gamgee.) well, namely, it causes an evolution of gas, if the blood has been previously laked by the addition of an equal quantity of water. This gas is oxygen ; in fact, all the CH. XXVI.] CAKBONIC OXIDE HEMOGLOBIN 437 oxygen combined as oxyhaemoglobin is discharged, and this may be collected and measured ; the addition of a small amount of sodium carbonate or ammonia to the blood is necessary to prevent the evolution of any carbonic acid. This discharge of oxygen from oxyhaemoglobin is at first sight puzzling, because, as just stated, methaemoglobin contains the same amount of oxygen that is present in oxyhaemo- globin. What occurs is that after the oxygen is discharged from oxyhaemoglobin, an equal quantity of oxygen, due to the oxidising action of the reagents added, takes its place ; this new oxygen, however, is combined in some way different from that which was previously united to the haemoglobin. (Haldane.) Carbonic oxide haemoglobin may be readily prepared by passing a stream of carbonic oxide or coal gas through blood or through a solution of oxyhemoglobin. It has a peculiar cherry-red colour. Its absorption spectrum is very like that of oxyhaemoglobin, but the two bands are slightly nearer the violet end of the spectrum (spectrum 4 in coloured plate). Eeducing agents, like ammonium sulphide, do not change it ; the gas is more firmly combined than the oxygen in haemoglobin. CO -haemoglobin forms crystals like those of oxyhaemo- globin. It resists putrefaction for a very long time. Carbonic oxide is given off during the imperfect combustion of carbon such as occurs in charcoal stoves or during the explosions that occur in coal-mines ; it acts as a powerful poison, by combining with the haemoglobin of the blood, and thus interferes with normal respira- tory processes. The bright colour of the blood in both arteries and veins, and its resistance to reducing-agents, are in such cases characteristic. Nitric Oxide Haemoglobin. — When ammonia is added to blood, and then a stream of nitric oxide passed through it, this compound is formed. It may be obtained in crystals isomorphous with oxy- and CO-haemoglobin. It also has a similar spectrum. It is even more stable than CO-haemoglobin ; it has no practical interest, but is of theoretical importance as completing the series. Bohr has advanced a theory that haemoglobin forms a compound with carbonic acid, and that there are numerous oxyhemoglobins containing different amounts of oxygen, but his views have not been accepted. Estimation of Haemoglobin. — The most exact method is by the estimation of the amount of iron (dry haemoglobin containing *42 per cent, of iron) in the ash of a given specimen of blood, but as this is a somewhat complicated process, various coloriraetric methods have been proposed which, though not so exact, have the advantage of simplicity. Growers' Haemoglobinometer. — The apparatus (fig. 371) consists of two glass tubes of the same size. One contains glycerin jelly tinted with carmine to a standard colour — viz., that of normal blood diluted 100 times with distilled water. The finger is pricked and 20 cubic millimetres of blood are measured out by the capillary pipette, B. This is blown out into the other tube and diluted with distilled water, added drop by drop from the pipette stopper of the bottle, A, until the tint of the diluted blood reaches the standard colour. This tube is graduated into 100 parts. If the tint of the diluted blood is the same as the standard when the tube is filled up to the graduation 100, the quantity of oxyhaemoglobin in the blood is normal. If it has to be diluted more largely, the oxyhaemoglobin is in excess ; if to a smaller extent, it is less than normal. If the blood has, for instance, to be diluted 438 THE BLOOD [('II. XXVI 1 1 1 > to the graduation SO, the amount of haemoglobin is only halt' what it ought to be — 50 per cent, of the normal — and so for other percentages. Haldane's Modification of Gowers' Instrument is the one most frequently used now, and gives very accurate results. Instead of tinted gelatin, the standard of comparison is a sealed tube filled with a solution of carbonic oxide haemoglobin. This keeps unchanged for years. A stream of coal gas is passed through the blood Von Fleischl's UiL-inugloUuoiiii to be examined. This converts all the haemoglobin present into carbonic oxide haemoglobin ; this is then diluted with water to match the standard. Von Fleischl's Haemometer. The apparatus (fig. 372) consists of a stand CH. XXVI.] TESTS FOE BLOOD 439 bearing a white reflecting surface (S) and a platform. Under the platform is a slot carrying a glass wedge stained red (K) and moved by a wheel (R). On the platform is a small cylindrical vessel divided vertically into two compartments, a and a'. Fill with a pipette the compartment a' over the wedge with distilled water. Fill about a quarter of the other compartment (a) with distilled water. Prick the finger and fill the short capillary pipette provided with the instru- ment with blood. Dissolve this in the water in compartment a, and fill it up with distilled water. Having arranged the reflector (S) to throw artificial light vertically through both compartments, look down through them, and move the wedge of glass by the milled head (T) until the colour of the two is identical. Read off the scale, which is so constructed as to give the percentage of haemoglobin. Dr George Oliver's Method consists in comparing a specimen of blood suitably diluted in a shallow white palette with a number of standard tests very carefully prepared by the use of Lovibond's coloured glasses. These standards are much better matches for blood in various- degrees of dilution than in most colori- metric methods. The yellow tint of diluted haemoglobin is very successfully imitated. Tests for Blood. — These may be gathered from preceding descrip- tions. Briefly, they are microscopic, spectroscopic, and chemical. The best chemical test is the formation of hsemin crystals. The old test with tincture of guaiacum and hydrogen peroxide, the blood causing the red tincture to become green, is very untrustworthy, as it is also given by many other organic substances. In medico-legal cases it is often necessary to ascertain whether or not a red fluid or stain upon clothing is or is not blood. In any such case it is advisable not to rely upon one test only, but to try every means of detection at one's disposal. To discover whether it is blood or not is by no means a difficult problem, but to distinguish human blood from that of the common mammals is possible only by the " biological " test described at the end of the next section. Immunity. The chemical defences of the body against injury and disease are numerous. The property that the blood possesses of coagu- lating is a defence against haemorrhage; the acid of the gastric juice is a great protection against harmful bacteria introduced with food. Bacterial activity in urine is inhibited by the acidity of that secretion. Far more important and widespread in its effects than any of the foregoing is the bactericidal {i.e. bacteria killing) action of the blood and lymph ; a study of this question has led to many interesting results especially in connection with the problem of immunity. This subject is one of great importance. It is a familiar fact that one attack of many infective maladies protects us against another attack of the same disease. The person is said to be immune either partially or completely against that disease. Vaccination produces in a patient an attack of cowpox or 440 THE BLOOD [CH. XXVL vaccinia. This disease is either closely related to smallpox, or maybe it is smallpox modified and rendered less malignant by passing through the body of a calf. At any rate, an attack of vaccinia renders a person immune to smallpox, or variola, for a certain number of years. Vaccination is an instance of what is called protective inocula- tion, which is now practised with more or less success in reference to other diseases like plague and typhoid fever. The study of immunity has also rendered possible what may be called curative inoculation, or the injection of antitoxic material as a cure for diphtheria, tetanus, snake poisoning, etc. The power the blood possesses of slaying bacteria was first dis- covered when the effort was made, to grow various kinds of bacteria in it ; it was looked upon as probable that blood would prove a suit- able soil or medium for this purpose. It was found in some instances to have exactly the opposite effect. The chemical characters of the substances which kill the bacteria are not fully known ; indeed, the same is true for most of the substances we have to speak of in this connection. Absence of knowledge on this particular point has not, however, prevented important discoveries from being made. So far as is known at present, the substances in question are proteid in nature. The bactericidal powers of blood are destroyed by heating it for an hour to 55° C. Whether the substances are enzymes is a disputed point. So also is the question whether they are derived from the leucocytes ; the balance of evidence appears to me to be in favour of this view in many cases at any rate, and phagocytosis becomes more intelligible if this view is accepted. The substances, whatever be their source or their chemical nature, are sometimes called alexins, but the more usual name now applied to them is that of bacterio-lysins. Closely allied to the bactericidal power of blood, or blood- serum, is its globulicidal power. By this one means that the blood-serum of one animal has the power of dissolving the red blood-corpuscles of another species. If the serum of one animal is injected into the blood-stream of an animal of another species, the result is a destruction of its red corpuscles, which may be so excessive as to lead to the passing of the liberated haemoglobin into the urine (hemoglobinuria). The substance or substances in the serum that possess this property are called hemolysins, and though there is some doubt whether bacterio-lysins and haeniolysins are absolutely identical, there is no doubt that they are closely related substances. Another interesting chemical point in this connection is the fact that the bactericidal power of the blood is closely related to its alkalinity. Increase of alkalinity means increase of bactericidal power. Venous blood contains more diffusible alkali than arterial blood, and is more bactericidal ; dropsical effusions are more alkaline CH. XXVI.] IMMUNITY 441 than normal lymph, and kill bacteria more easily. In a condition like diabetes, when the blood is less alkaline than it should be, the susceptibility to infectious diseases is increased. Alkalinity is probably beneficial because it favours those oxidative processes in the cells of the body which are so essential for the maintenance of healthy life. Normal blood possesses a certain amount of substances which are inimical to the life of our bacterial foes. But suppose a person gets run down ; every one knows he is then liable to " catch anything." This coincides with a diminution in the bactericidal power of bis blood. But even a perfectly healthy person has not an unlimited supply of bacterio-lysin, and if the bacteria are sufficiently numerous he will fall a victim to the disease they produce. Here, however, comes in the remarkable part of the defence. In the struggle he will produce more and more bacterio-lysin, and if he gets well it means that the bacteria are finally vanquished, and his blood remains rich in the particular bacterio-lysin he has produced, and so will render him immune for a time to further attacks from that particular species of bacterium. Every bacterium seems to cause the develop- ment of a specific bacterio-lysin. Immunity can more conveniently be produced gradually in animals, and this applies, not only to the bacteria, but also to the toxins they form. If, for instance, the bacilli which produce diphtheria are grown in a suitable medium, they produce the diphtheria poison, or toxin, much in the same way that yeast-cells will produce alcohol when grown in a solution of sugar. Diphtheria toxin is associated with a proteose, as is also the case with the poison of snake venom. If a certain small dose called a " lethal dose " is injected into a guinea- pig the result is death. But if the guinea-pig receives a smaller dose it will recover ; a few days after it will stand a rather larger dose ; and this may be continued until, after many successive gradually increasing doses, it will finally stand an amount equal to many lethal closes without any ill effects. The gradual introduction of the toxin has called forth the production of an antitoxin. If this is done in the horse instead of the guinea-pig the production of antitoxin is still more marked, and the serum obtained from the blood of an immunised horse may be used for injecting into human beings suffering from diphtheria, and rapidly cures the disease. The two actions of the blood, antitoxic and antibacterial, are frequently associated, but may be entirely distinct. The antitoxin is also a proteid probably of the nature of a globulin ; at any rate it is a proteid of larger molecular weight than a proteose. This suggests a practical point. In the case of snake-poisoning the poison gets into the blood rapidly owing to the comparative ease with which it diffuses, and so it is quickly carried all over the body. In 442 THE BLOOD [CH. XXVI. treatment with the antitoxin or antivenin, speed is everything if life is to be saved ; injection of this material under the skin is not much good, for the diffusion into the blood is too slow. It should be injected straight away into a blood-vessel. There is no doubt that in these cases the antitoxin neutralises the toxin much in the same way that an acid neutralises an alkali. If the toxin and antitoxin are mixed in a test-tube, and time allowed for the interaction to occur, the result is an innocuous mixture. The toxin, however, is merely neutralised, not destroyed; for if the mixture in the test-tube is heated to 68° C. the antitoxin is coagulated and destroyed and the toxin remains as poisonous as ever. Immunity is distinguished into active and passive. Active im- munity is produced by the development of protective substances in the body ; passive immunity by the injection of a protective serum. Of the two the former is the more permanent. Ricin, the poisonous proteid of castor-oil seeds, and abrin, that of the Jequirity bean, also produce, when gradually given to animals, an immunity, due to the production of antiricin and antiabrin respectively. Ehrlich's hypothesis to explain such facts is usually spoken of as the side-chain theory of immunity. He considers that the toxins are capable of uniting with the protoplasm of living cells by possessing groups of atons like those by which nutritive proteids are united to cells during normal assimilation. He terms these haptophor groups, and the groups to which these are attached in the cells he terms receptor groups. The introduction of a toxin stimulates an excessive production of receptors, which are finally thrown out into the circula- tion, and the free circulating receptors constitute the antitoxin. The comparison of the process to assimilation is justified by the fact that non-toxic substances like milk or egg-white introduced gradually by successive doses into the blood-stream cause the formation of anti- substances capable of coagulating them. Up to this point I have spoken only of the blood, but month by month workers are bringing forward evidence to show that other cells of the body may by similar measures be rendered capable of producing a corresponding protective mechanism. One further development of the theory I must mention. At least two different substances are necessary to render a serum bactericidal or globulicidal. The bacterio-lysin or hsemolysin consists of these two substances. One of these is called the immune body, the other the complement. We may illustrate the use of these terms by an example. The repeated injection of the blood of one animal {e.g. the goat) into the blood of another animal {e.g. a sheep) after a time renders the latter animal immune to further injections, and at the same time causes the production of a serum which dissolves readily CH. XXVI.] ehklich's side-chain theory 443 the red blood-corpuscles of the first animal. The sheep's serum is thus hseniolytic towards goat's blood-corpuscles. This power is destroyed by heating to 56° C. for half an hour, but returns when the fresh serum of any animal is added. The specific immunising substance formed in the sheep is called the immune body; the ferment-like substance destroyed by heat is the complement. The latter is not specific, since it is furnished by the blood of non-immunised animals, but it is nevertheless essential for haemolysis. Ehrlich believes that the immune body has two side groups — one which connects with the receptor of the red corpuscles, and one which unites with the hapto- phor group of the complement, and thus renders possible the ferment- like action of the complement on the red corpuscles. Various antibacterial serums which have not been the success in treating disease they were expected to be, are probably too poor in comple- ment, though they may contain plenty of the immune body. To put it another way : the cell-dissolving substances cannot act on their objects of attack without an intermediate substance to anchor them on to the substance in question. This intermediary substance, known as the immune body or amboceptor, is specific, and varies with the substance to be attacked (red corpuscles, bacterium, toxin, etc.). The complement may be compared to a person who wants to unlock a door ; to do this effectively he must be provided with the proper key (amboceptor or immune body). Quite distinct from the bactericidal, globulicidal, and antitoxic properties of blood is its agglutinating action. This is another result of infection with many kinds of bacteria or their toxins. The blood acquires the property of rendering immobile and clumping together the specific bacteria used in the infection. The test applied to the blood in cases of typhoid fever, and generally called Widal's reaction, depends on this fact. The substances that produce this effect are called agglutinins. They also are probably proteid-like in nature, but are more resistant to heat than the lysins. Prolonged heating to over 60° C. is necessary to destroy their activity. Lastly, we come to a question which more directly appeals to the physiologist than the preceding, because experiments in relation to immunity have furnished us with what has hitherto been lacking, a means of distinguishing human blood from the blood of other animals. The discovery was made by Tchistovitch (1899), and his original experiment was as follows:— Eabbits, dogs, goats, and guinea-pigs were inoculated with eel-serum, which is toxic : he thereby obtained from these animals an antitoxic serum. But the serum was not only antitoxic, but produced a precipitate when added to eel-serum, but not when added to the serum of any other animal. In other words, 444 THE BLOOD [CH. XXVI. not only has a specific antitoxin been produced, but also a specific precipitin. Numerous observers have since found that this is a general rule throughout the animal kingdom, including man. If, for instance, a rabbit is treated with human blood, the serum ultimately obtained from the rabbit contains a specific precipitin for human blood ; that is to say, a precipitate is formed on adding such a rabbit's serum to human blood, but not when added to the blood of any other animal. There may be a slight reaction with the blood of allied animals ; for instance, with monkey's blood in the case of man. The great value of the test is its delicacy ; it will detect the specific blood when it is greatly diluted, after it has been dried for weeks, or even when it is mixed with the blood of other animals. We thus see that the means of defence in the body are numerous. In some eases bacteria are killed by the bacteriolysins of the blood ; in other cases the toxins the bacteria produce are neutralized by antitoxins. In other cases still the bacteria are directly attacked and devoured by the white corpuscles or phagocytes. In connec- tion with phagocytosis great differences are noticeable ; this is partly explained by what is called chemotaxis ; some bacteria produce chemical substances that attract the leucocytes to their neighbourhood (position chemotaxis) : in other cases, such chemical magnets are not produced, or even negative chemotaxis may occur and the phagocytes be repelled. The recent discovery of opsonins by A. E. Wright is in this connection one of great importance ; it illustrates how the body fluids and the leuco- cytes co-operate, and further shows how elaborate are the means the body possesses for combating bacterial invasion. The word opsonin is derived from a Greek word which means " to prepare the feast." Washed bacteria from a culture are distasteful to phagocytes ; but if the bacteria have been previously soaked in serum, especially if that serum has been obtained from the blood of an animal previously immunised against that special bacterium, then the leucocytes devour them eagerly ; in other words, something has been added to the bacterium to make it tasty, and each kind of bacterium apparently requires its own special sauce or opsonin. Haematoporphyrin (see p. 431). If oxyhemoglobin is treated with dilute acids the result is a formation of haematin and globin, but if strong sulphuric acid is employed the iron is removed from the haematin and so haematoporphyrin is obtained. The stability of the iron in the molecule is due to the presence of oxygen, for with the reduced pigment, haematoporphyrin is obtained even when dilute acids are employed. Pure haematoporphyrin can once more be converted into haematin (that is, the iron can be replaced) by warming a solution in dilute ammonia and adding a little Stokes' fluid, and a few drops of a reducing agent like hydrazine hydrate. If cuprammonium solution is used instead of Stokes' fluid in this experiment, a copper compound of haematoporphyrin is obtained, which is identical with turacin, the bright red copper containing pigment found in the plumage of the plantain- eating birds. (Laidlaw.) CKAPTEK XXVII THE ALIMENTAEY CANAL The alimentary canal consists of a long muscular tube lined by mucous membrane beginning at the mouth, and terminating at the anus. It comprises the mouth, pharynx, oesophagus, stomach, small intestine and large intestine. Opening into it are numerous glands which pour juices into it ; these bring about the digestion of the food as it passes along. Some of the glands, like the gastric and intestinal glands, are situated in the lining mucous membrane of the canal; others, like the salivary glands, liver, and pancreas, are situated at a distance from the main canal, and pour their secretion into it by means of side tubes or ducts. The Mouth This cavity is lined by a mucous membrane consisting of a corium of fibrous tissue with numerous patches of lymphoid tissue in it, especially in the posterior regions ; and an epithelium of the stratified variety closely resembling the epidermis. The surface layers, like those of the epidermis, are made of horny scales. Opening into the mouth are a large number of little mucous glands, and the salivary glands pour their secretion into the mouth also. The teeth (p. 64) have been previously studied. The tongue will be considered later in connection with taste. The Phaeynx That portion of the alimentary canal which intervenes between the mouth and the oesophagus is termed the Pharynx. It is con- structed of a series of three muscles with striated fibres (constrictors), which are covered by a thin fascia externally, and are lined internally by a strong fascia (pharyngeal aponeurosis), on the inner aspect of which is areolar (submucous) tissue and mucous membrane, con- tinuous with that of the mouth, and, as regards the part concerned in swallowing, identical with it in general structure. The epithelium of this part of the pharynx, like that of the mouth, is stratified. 446 THE ALIMENTARY CANAL [CH. XXVII. The upper portion of the pharynx into which the nares open is lined with ciliated epithelium. The pharynx is well supplied with mucous glands. Between the anterior and posterior arches of the soft palate are situated the Tonsils, one on each side. A tonsil consists of an eleva- tion of the mucous membrane presenting 12 to 15 orifices, which Lead into crypts or recesses, in the walls of which are placed nodules of lymphoid tissue (fig. 373). These nodules are enveloped in a less dense adenoid tissue which reaches the mucous surface. The surface is covered with stratified epithelium, and the corium may present rudimentary papillae formed of adenoid tissue. The tonsil is bounded AmW Fig. 373.— Vertical section through a crypt of the human tonsil. 1, entrance to the crypt ; 3 and 3, the framework of adenoid tissue; 4, the enclosing fibrous tissue; o and b, lymphoid nodules; 5 and c, blood-vessels. (Stohr.) beneath by a fibrous capsule (fig. 373, 4). Into the crypts open the ducts of numerous mucous glands. The (Esophagus or Gullet The CEsophagus or Gullet, the narrowest portion of the alimentary canal, is a muscular tube, nine or ten inches in length, which extends from the lower end of the pharynx to the cardiac orifice of the stomach. It is made up of three coats — viz., the outer, muscular ; the middle, submucous ; and the inner, mucous. The muscular coat is covered externally by a varying amount of loose fibrous tissue. It is composed of two layers of fibres, the outer being arranged longi- tudinally, and the inner circularly. At the upper part of the ceso- CH. XXVII.] THE (ESOPHAGUS 447 phagus this coat is made up principally of striated muscle fibres ; they are continuous with the constrictor muscles of the pharynx ; but lower down the unstriated fibres become more and more numerous, and towards the end of the tube form the entire coat. The muscular coat is connected with the mucous coat by a more or less developed layer of areolar tissue, which forms the submucous coat, in which are contained in the lower half or third of the tube many mucous glands, the ducts of which, passing through the mucous membrane, open on Fig. 374. — Section of the mucous membrane and submucous coat of the cesophagus. its surface (fig. 374). In the deepest part of the mucous membrane is a well-developed layer of longitudinally arranged unstriated muscle, called the muscularis mucosce. The corium of the mucous membrane is composed of fine connective tissue, which, towards the surface, is elevated into papillse. It is covered with a stratified epithelium, of which the most superficial layers are composed of squamous cells. The epithelium is arranged upon a basement membrane. In newly-born children the corium exhibits, in many parts, the structure of lymphoid tissue (Klein). 448 the alimentary canal [ch. xxvii. The Stomach The stomach is a dilatation of the alimentary canal placed between and continuous with the oesophagus, which enters its larger or cardiac end on the one hand, and the small intestine, which commences at its narrowed end or pylorus, on the other. Its wall is composed of four coats, (1) an external or peritoneal, (2) muscular, (3) submucous, and (4) mucous coat ; with blood-vessels, lymphatics, and nerves distributed in and between them. (1) The peritoneal coat has the structure of serous membranes in general. (2) The muscular coat consists of three separate layers or sets of fibres, which, according to their several directions, are named the longitudinal, circular, and oblique. The longitudinal set are the most superficial : they are continuous with the longitudinal fibres of the oesophagus, and spread out in a diverging manner over the cardiac end and sides of the stomach. They extend as far as the pylorus, being especially distinct at the lesser or upper curvature of the stomach, along which they pass in several strong bands. The next set, the circular or transverse fibres, are most abundant at the middle and in the pyloric portion of the organ, and form the chief part of the thick projecting ring of the pylorus. They are continuous with the circu- lar layer of the intestine. The deepest set of fibres are the oblique, continuous with the circular muscular fibres of the oesophagus : they are comparatively few in number, and are found only at the cardiac portion of the stomach; they form a sphincter around the cardiac orifice. The muscular fibres of the stomach and of the intestinal canal are unstriated, being composed of elongated, spindle-shaped fibre-cells. (3) The submucous coat consists of loose areolar tissue, which connects the muscular coat to the mucous membrane. It contains blood-vessels and nerves ; in the contracted state of the stomach it is thrown into numerous, chiefly longitudinal, folds or rugse, which dis- appear when the organ is distended. (4) The mucous membrane is composed of a corium of fine con- nective tissue, which approaches closely in structure to adenoid tissue ; this tissue supports the tubular glands of which the super- ficial and chief part of the mucous membrane is composed, and pass- ing up between them assists in binding them together. The glands are separated from the rest of the mucous membrane by a very fine homogeneous basement membrane. The corium is covered with a layer of columnar epithelium, which passes down into the mouths of the glands. At the deepest part of the mucous membrane are two thin layers (circular and longitudinal) of unstriped muscular fibres, called the muscularis mucosa?. CH. XXVII.] THE STOMACH 449 When examined with a lens, the internal or free surface of the stomach presents a peculiar honeycomb appearance, produced by shallow polygonal depressions, the diameter of which varies generally from 77-g-oth to ^j-th of an inch (about 125/x) ; but near the pylorus is as much as T ^o-th of an inch (250/x). In the bottom of these little pits, and to some extent between them, minute openings are visible, which are the orifices of the ducts of perpendicularly arranged tubular glands (fig. 375), imbedded side by side in sets or bundles, on the surface of the Fig. 376. — Transverse section through lower part of cardiac glands of a cat. a, parietal cells ; 6, central cells ; c, transverse section of capillaries. (Frey.) mucous membrane, and composing nearly the whole structure. The glands of the mucous membrane are of two varieties, (a) Cardiac, (b) Pyloric. (a) Cardiac glands are found throughout the whole of the cardiac half and fundus of the stomach. They are arranged in groups of four or five, which are separated by a fine connective tissue. Two or three tubes open into one duct, which forms about a third of the whole length of the tube and opens on the surface. The ducts are lined with columnar epithelium. Of the gland-tube proper, i.e. the part of the gland below the duct, the upper third is the neck and the rest the body. The neck is narrower than the body, and is lined with 2 F Fio. 375. — From a vertical section through the mucous membrane of the cardiac end of stomach. Two glands are shown with a duct common to both, a, duct with columnar epithelium becoming shorter as the cells are traced downward ; n, neck of gland tubes, with central and parietal cells ; 6, fundus with curved caecal extremity — the parietal cells are not so numerous here. (Klein and Noble Smith.) 450 THE ALIMENTARY CANAL [CII. XXVII. coarsely granular polyhedral cells which are continuous with the columnar cells of the duct. Between these cells and the basement membrane of the tubes, are large oval or spherical cells, opaque or granular in appearance, with clear oval nuclei, bulging out the base- ment membrane ; these cells are called parietal cells. They do not form a continuous layer. The body which is broader than the neck, and terminates in a blind extremity or fundus near the muscularis mucosae, is lined by cells continuous with the central cells of the 1 ■am.s2y- -%^'j>. the Fig. 377.— Section showing pyloric glands, s, free sur- face ; d, ducts of pyloric glands ; n, neck of same ; m, the gland tubules ; mm, muscularis mu- cosae. (Klein and Noble Smith.) Fig. 37S. —Plan of the blood-vessels of the stomach, as they would be seen in a vertical section, a, arteries, passing up from the vessels of submucous coat ; b, capillaries branching between and around the tubes ; c, superficial plexus of capillaries occupying the ridges of the mucous membrane ; d, vein formed by the union of veins which, having collected the blood of the superficial capillary plexus, are seen passing down between the tubes. (Brinton.) neck, but longer, more columnar and more transparent. In this part are a few parietal cells of the same kind as in the neck (fig. 375). (6) Pyloric Glands. — These glands (fig. 377) have much longer ducts than the cardiac glands. Into each duct two or three tubes open by very short and narrow necks, and the body of each tube is branched, wavy, and convoluted. The lumen is large. The ducts are lined with columnar epithelium, and the neck and body with shorter and finely granular cubical cells, which correspond with the central cells of the cardiac glands. As they approach the duodenum the pyloric glands become larger, more convoluted and more deeply CH. XXVI 1.] THE INTESTINES 451 situated. They are directly continuous with Brunner's glands in the duodenum. Lymphatics. — Lymphatic vessels surround the gland tubes to a greater or less extent. Towards the fundus of the cardiac glands are found masses of lymphoid tissue, which may appear as distinct follicles, somewhat like the solitary glands of the small intestine. Blood-vessels. — The blood-vessels of the stomach, which first break up in the sub-mucous tissue, send branches upward between the closely packed glandular tubes, anastomosing around them by means of a fine capillary network, with oblong meshes. Continuous with this deeper plexus, or prolonged upwards from it, is a more superficial network of larger capillaries, which branch densely around the orifices of the tubes, and form the framework on which are moulded the small elevated ridges of mucous membrane bounding the minute, polygonal pits before referred to. From this superficial network the veins chiefly take their origin. Thence passing down between the tubes, with no very free connection with the deeper inter-tubular capillary plexus, they open finally into the venous network in the submucous tissue (fig. 378). Nerves. — The nerves of the stomach are derived from the pneumo- gastric and sympathetic, and form two plexuses, one in the sub- mucous and the other between the muscular layers. These plexuses are continuous with those which occur in the same situations in the intestine, and which we shall again refer to there. The Intestines. The Intestinal Canal is divided into two chief portions, named, from their differences in diameter, the small and large intestine. These are continuous with each other, and communicate by means of an opening guarded by a valve, the ileo-cmcal valve, which allows the passage of the products of digestion from the small into the large bowel, but not, under ordinary circumstances, in the opposite direction. The Small Intestine, the average length of which in an adult is about twenty feet, has been divided, for convenience of descrip- tion, into three portions, viz., the duodenum, which extends for eight or ten inches beyond the pylorus ; the jejunum, which forms two-fifths, and the ileum, which forms three-fifths of the rest of the canal. Like the stomach, it is constructed of four coats, viz., the serous, muscular, submucous, and mucous. (1.) The serous coat is formed by the visceral layer of the peritoneum, and has the structure of serous membranes in general. (2.) The muscular coat consists of an internal circular and an external longitudinal layer: the former is usually considerably the 452 THE ALIMENTARY CANAL [Cll. XXVII. thicker. Both alike consist of bundles of imstriped muscle supported by connective tissue. They are well provided with lymphatic vessels, which form a set distinct from those of the mucous mem- brane. Between the two muscular coats is a nerve-plexus (Auerbach's plexus) (fig. 380), similar in structure to Meissner's (in the submucous coat), but coarser and with more numerous ganglia. (3) Between the mucous and muscular coats is the submucous coat, which consists of connective tissue in which numerous blood-vessels and lymphatics ramify. A fine plexus, consisting mainly of non-medullated nerve-fibres, Meissner's plexus, with ganglion cells at its nodes, occurs in the submucous tissue from the stomach to the anus. (4) The mucous membrane is the most important coat in relation to the function of digestion. Its general structure resembles that Fio. 379. — Horizontal section of a small frag- ment of the mucous membrane, includ- ing one entire crypt of Lieberkiihn and parts of several others. The glands are separated by loose adenoid tissue. Fig. 3S0. —Auerbach's nerve-plexus in small intestine. Ganglion-cells are imbedded in the plexus, the whole of which is enclosed in a nucleated sheath. (Klein.) of the stomach, and, like it, is lined on its inner surface by columnar epithelium. Adenoid tissue (fig. 379) enters largely into its construc- tion ; and on its deep surface is the muscularis mucosa: (m, fig. 382), CH. XXVII.] THE INTESTINES 453 the fibres of which are arranged in two layers : the outer longitudinal and the inner circular. Valvules Conniventes. — The valvulse conniventes (fig. 381) com- mence in the duodenum, about one or two inches beyond the pylorus, and, becoming larger and more numerous immediately beyond the entrance of the bile duct, continue thickly arranged and well developed throughout the jejunum; then, gradually diminishing in size and number, they cease near the middle of the ileum. They are formed by a doubling inwards of the mucous membrane; the crescentic, nearly circular, folds thus formed are arranged transversely to the axis of the intestine, but each individual fold seldom extends around more than \ or 4 of the bowel's circumference. Unlike the rugse in the oesophagus and stomach, they do not disappear on distension of the canal. Their function is to afford a largely increased surface for secretion and absorption. They are covered with villi. Villi— The Villi (figs. 382, 383, and 384) are confined exclusively to the mucous membrane of the small intestine. They are minute vascular processes, from -^ to J of an inch ("5 to 3 mm.) in length, covering the surface of the mucous membrane, and giving it a peculiar velvety, fleecy appearance. Krause estimates them at fifty to ninety in number in a square line at the upper part of the small intestine, and at forty to seventy in the same area at the lower part. They vary in form even in the same animal, and differ according as the lymphatic vessels or lacteals which they contain are empty or full ; being usually, in the former case, fiat and pointed at their summits, in the latter cylindrical. Each villus consists of a small projection of mucous membrane ; its interior consists of fine adenoid tissue, which forms the frame- work in which the other constituents are contained. The surface of the villus is clothed by columnar epithelium, which rests on a fine basement membrane; while within this are found, reckoning from without inwards, blood-vessels, fibres of the muscularis mucosae, and a lymphatic or lacteal vessel sometimes looped or branched (fig. 384). The epithelium is continuous with that lining the other parts of the mucous membrane. The cells are arranged with their long axis radiating from the surface of the villus (fig. 383), and their smaller ends resting on the basement membrane. The free surface of the epithelial cells of the villi, like that of the cells which cover the Fig. 3S1. — Piece of small in- testine (previously dis- tended and hardened by alcohol), laid open to show the normal posi- tion of the valvulse conniventes. Natural size. 454 THE ALIMENTARY CANAL [CH. XXVI I. general surface of the mucous membrane, is surmounted by a bright striated border (see pp. 25-27). Immediately beneath the basement membrane there is a rich supply of Hood-vessels. Two or more minute arteries are distributed within each villus ; and from their capillaries, which form a dense network, proceed one or two small veins, which pass out at the base of the villus. The layer of the muscularis mucosae in the villus forms a kind of thin hollow cone immediately around the central lacteal, and is, therefore, situated be- neath the blood-vessels. It is instru- mental in the propulsion of chyle along the lacteal. The lacteal vessels form the com- 'd I v ~j~J%33i Fig. 382.— Vertical section of duode- num, showing a, villi ; b, crypts of .Lieberkuhn, and c, Brunner's glands in the subrnucosa s, with ducts, d ; muscularis mucosa?, m ; and circular muscular coat, /. (Schotield.) Fig. 3S3.— Vertical section of a villus of the small intestine of a cat. a, striated border ol the epithelium ; b, columnar epithelium ; c, goblet cells ; d, central lymph-vessel ; e, smooth muscular libres ; /, adenoid stroma of the villus in which lymph corpuscles lie. (Klein.) mencement of the intestinal lymphatic system. Each begins almost at the tip of the villus commonly by a dilated extremity. In the larger villi there may be two small lacteal vessels which join, or the lacteals may form a network in the villus (fig. 384). Glands.— The glands are of two kinds :— viz., those of Lieberktihn and of Brunner. Peyer's patches and the solitary follicles are com- posed of lymphoid nodules. Though sometimes called glands, they form no external secretion. The glands or crypts of Lieberkuhn are tubular depressions of the CH. XXVII.] THE INTESTINES 455 intestinal mucous membrane, thickly distributed over the whole surface both of the large and small intestines. In the small intestine they are visible only with the aid of a lens ; and their orifices appear as minute dots scattered between the villi. They are larger in the large intestine, and increase in size the nearer they approach the anal end of the intestinal tube; and in the rectum their orifices may be visible to the naked eye. In length they vary from y^- to -^ of an inch. Each tubule (fig. 386) is constructed of a fine basement Fig. 384.— A. Villus of sheep. B. Villi of man. (Slightly altered from Teichmarm.) membrane, lined by a layer of columnar epithelium, many of the cells of which are goblet cells. Brunners glands (fig. 382) are confined to the duodenum ; they are most abundant and thickly set at its commencement, and diminish gradually as the duodenum advances. They are situated beneath the muscularis mucosae, imbedded in the submucous tissue ; each gland is a branched and convoluted tube, lined with columnar epithelium. In structure they are very similar to the pyloric glands of the stomach, but they are more branched and convoluted, and their ducts are longer. The duct of each gland passes through the muscularis mucosae, and opens on the surface of the mucous membrane. 456 THE ALIMENTARY CANAL [CH. XXVII. Peyrr's patches are found in greatest abundance in the lower part of the ileum near to the ileo-csecal valve. They consist of aggregated groups of lymphoid nodules ; they vary from one to three inches in Fig. 385. —Transverse section through four cry jits of Lieberkuhn from the large intestine of the pig. They are lined by columnar epithelial cells, the nuclei being placed in the outer part of the cells. The divisions between the cells are seen as lines radiating from l, the lumen of the crypt; Q, epithelial cells, which have become transformed into goblet cells, x 350. (Klein and Noble Smith.) Fig. 386.— A gland of Lieberkuhn in longitudinal sec- tion. (Briuton.) length, and are about half-an-inch in width, chiefly of an oval form, their long axes being parallel with that of the intestine. They are almost always placed opposite the attachment of the mesentery. When the lymphoid nodules occur singly, as they often do both in small and large intestines, they are called solitary glands, or follicles. Fio. 3S7. — Agminate follicles, or Peyer's patch, in a state of distension, x 5. (Boehm.) The Large Intestine in an adult is from about 4 to 6 feet long ; it is subdivided for descriptive purposes into three portions, viz. : — the crccum, a short wide pouch, communicating with the lower end of the small intestine through an opening, guarded by the ileo-cxcal valve ; CH. XXVII.] THE INTESTINES 457 the colon, continuous with the caecum, which forms the principal part of the large intestine, and is divided into ascending, transverse, and descending portions ; and the rectum, which, after dilating at its lower part, again contracts, and immediately afterwards opens externally through the anus. Attached to the caecum is the small appendix vermiformis. Like the small intestine, the large intestine is constructed of four coats, viz., the serous, muscular, submucous, and mucous. The serous coat has connected with it the small processes of peritoneum containing fat, called appendices epiploicce. The fibres of the muscular coat, like those of the small intestine, are arranged in two layers — the outer longitudinal, the inner circular. In the caecum and colon, the longi- tudinal fibres, instead of being, as in the small intestine, thinly dis- posed in all parts of the wall of the bowel, are collected, for the most part, into three strong bands, which, being shorter, from end to end, than the other coats of the intestine, hold the canal in folds, bounding in- termediate sacculi. On the division of these bands, the intestine can be drawn out to its full length, and it then assumes a uniformly cylindrical form. In the rectum, the fasciculi of these longitudinal bands spread out and mingle with the other longitudinal fibres, form- ing with them a thicker layer of fibres than exists in any other part of the intestinal canal. The circular muscular fibres are spread over the whole bowel, but are somewhat more marked in the intervals between the sacculi. Towards the lower end of the rectum they become more numerous, and at the anus they form a strong ring called the internal sphincter muscle. The mucous membrane of the large, like that of the small intestine, is lined throughout by columnar epithelium, but, unlike it, is quite destitute of villi, and is not projected in the form of valvules con- niventes. It is bounded below by the muscularis mucosa. The arrangement of ganglia and nerve-fibres in the large resembles that in the small intestine. Glands. — The glands with which the large intestine is provided are simple tubular glands, or glands of Lieberkiihn ; they resemble those of the small intestine, but are somewhat larger and more numerous, and contain a very great number of goblet cells ; nodules of adenoid or lymphoid tissue are most numerous in the caecum and vermiform appendix. They resemble in shape and structure the solitary glands of the small intestine. Peyer's patches are not found in the large intestine. Ileo-cazcal Valve. — The ileo-caecal valve is situated at the place of junction of the small with the large intestine, and guards against any reflux of the contents of the latter into the ileum. It is composed of two semilunar folds of mucous membrane. Each fold is formed by a doubling inwards of the mucous membrane, and is strengthened on 458 THE ALIMENTARY CANAL [CIT. XXVII. the outside by some of the circular muscular fibres of the intestine, which are contained between the outer surfaces of the two layers of which each fold is composed. "While the circular muscular fibres, however, at the junction of the ileum with the caecum are contained between the outer opposed surfaces of tho folds of mucous membrane which form the valve, the longitudinal muscular fibres and the peri- toneum of the small and large intestine respectively are continuous with each other, without dipping in to follow the circular fibres and the mucous membrane. In this manner, therefore, the folding in- wards of these two last-named structures is preserved, while on the other hand, by dividing the longitudinal muscular fibres and the peri- toneum, the valve can be made to disappear, just as the constrictions between the sacculi of the large intestine can be made to disappear by performing a similar operation. The mucous membrane of the ileum is continuous with that of the caecum. That surface of each fold of the ileo-caecal valve which looks towards the small intestine is covered with villi, while that which looks to the caecum has none. When the caecum is distended, the margins of the folds are stretched, and thus are brought into firm apposition one with the other. CHAPTEE XXVIII FOOD The chief chemical compounds or proximate principles in food are: — 1. Proteids . . . "I 2. Carbohydrates f organic. 3. Fats J t:Sf :::::::: : :W^- In milk and in eggs, which form the exclusive foods of young animals, all varieties of these proximate principles are present in suitable proportions. Hence they are spoken of as perfect foods. Eggs, though a perfect food for the developing bird, contain too little carbohydrate for a mammal. In most vegetable foods carbohydrates are in excess, while in animal food, like meat, the proteids are pre- dominant. In a suitable diet these should be mixed in proper proportions, which must vary for herbivorous and carnivorous animals. A healthy and suitable diet must possess the following cha- racters : — 1. It must contain the proper amount and proportion of the various proximate principles. 2. It must be adapted to the climate ; to the age of the individual, and to the amount of work done by him. 3. The food must contain not only the necessary amount of proximate principles, but these must be present in a digestible form. As an instance of this, many vegetables (peas, beans, lentils) contain even more proteid than beef or mutton, but are not so nutritious, as they are less digestible, much passing off in the f ceces imused. The nutritive value of a diet depends chiefly on the amount of carbon and nitrogen it contains. A man doing a moderate amount of work will eliminate, chiefly from the lungs, in the form of carbonic acid, from 250 to 280 grammes of carbon per diem. During the same time he will eliminate, chiefly in the form of urea in the urine, about 459 460 food [cir. xxvin. 15 to 18 grammes of nitrogen. These substances are derived from the metabolism of the tissues, and various forms of energy, mechanical motion and heat being the chief, are simultaneously liberated. During muscular exercise the output of carbon greatly increases ; the increased excretion of nitrogen is not nearly so marked. Taking, then, the state of moderate exercise, it is necessary that the waste of the tissues should be replaced by fresh material in the form of food ; and the proportion of carbon to nitrogen should be the same as in the excre- tions : 250 to 15, or 166 to 1. The proportion of carbon to nitrogen in proteid is, however, 53 to 15, or 3'5 to 1. The extra supply of carbon must come from non-nitrogenous food — viz., fat and carbohydrate. Moleschott gives the following daily diet : — Proteid 1 20 grras. Fat 90 „ Carbohydrate 333 „ Kanke's diet closely resembles Moleschott's ; it is — Proteid 100 grms. Fat 100 „ Carbohydrate ......... 250 ,, Such typical diets as these must not be considered as more than rough averages of what is necessary for a man in the course of the day. Actual experience shows that in the diets of different nations there are considerable variations from this standard without the production of ill effects. Age, and the amount of work done, also influence the amount of food necessary ; growing children, for instance, require a relatively rich diet ; thus, milk, the diet of the infant, is proportionally twice as rich in proteids, and half as rich again in fats, as the normal diet given above. During work more food is necessary than during inactivity. Some attention has recently been devoted to the question whether as much daily food is necessary as given in the foregoing paragraphs. Hirschfeld showed that for a short time nitrogenous equilibrium can be maintained on a smaller daily supply of nitrogen than 15 grammes. But experiments of others extended over a longer period have shown that sooner or later the body begins to waste if the 15 grammes daily are not supplied. This objection, however, cannot be urged against the experiments of E. O. Neumann, which lasted for three years. The weak point of this research is that it was made only upon one person, namely himself. His diet on the average consisted of 74 grammes of proteid, 117 of fat, and 213 of carbohydrate (equivalent to a total heat value of 2367 large calories, see Chapter XL.). He lost no weight, and part of the time even gained weight ; he enjoyed good health, and did his daily duties without inconvenience. A practical point is that his food cost him only 7id. a day. CH. XXVIII.] MILK 461 There have been other experiments which show that even Euro- peans can thrive on diets even scantier than this. But to most English people Eanke's and Moleschott's diets would not appear to err on the side of generosity. From the composition of the more commonly used foods taken in fairly average amounts, G. 1ST. Stewart calculates that 500 grammes of bread and 250 grammes of lean meat constitute a fair quantity for a man fit for hard work. Adding 500 grammes of milk, 75 grammes of oatmeal porridge, 30 grammes of butter, and 450 grammes of potatoes, we get, approximately, 20 grammes of nitrogen and 300 grammes of carbon contained in 135 grammes of proteid, 97 grammes of fat, and about 400 grammes of carbohydrate. Milk. Milk, which we have already spoken of as a perfect food, is only so for young children. For those who are older, it is so voluminous that unpleasantly large quantities of it would have to be taken in the course of the day to ensure the proper supply of nitrogen and carbon. More- over, it is relatively too rich in proteid and fat. It also contains too little iron (Bunge): hence children weaned late become anaemic. The microscope reveals that it con- sists of two parts : a clear fluid and a number of minute particles that float in it. These consist of minute oil globules, varying in diameter from 0-0015 to 0-005 millimetre (fig. 388). FlG . 3 ss.-Giobuies of cows m uk. x 400. The milk secreted during the first few days of lactation is called colostrum. It contains very little caseinogen, but large quantities of albumin and globulin instead. It coagulates like white of egg when boiled. Microscopically, cells from the acini of the mammary gland are seen, which contain fat globules in their interior ; they are called colostrum corpuscles. Reaction and Specific Gravity. — The reaction of fresh cow's milk and of human milk is amphoteric ; that is, it turns blue litmus rod, and red litmus blue. This is due to the presence of both acid and alkaline salts. All milk readily turns acid or sour as the result of fermentative change, part of its lactose being transformed into lactic acid. The specific gravity of milk is usually ascertained with the hydrometer. That of normal cow's milk varies from 1028 to 1034. When the milk is skimmed the specific gravity rises, owing to the removal of the light constituent, the fat, to 1033 to 1037. In all 462 FOOD [CH. XXVIII. cases the specific gravity of water, with which other substances are compared, is taken as 1000. Composition — Bunge gives the following table, contrasting the milk of woman, and the cow : — Woman. Cow. Proteids (chiefly caseinogen) Butter (fat) Per cent. 1-7 3-4 6-2 0-2 Per cent. 3-5 3-7 4-9 0-7 Hence, in feeding infants on cow's milk, it is necessary to dilute it, and add sugar to make it approximately equal to natural human milk. The Proteids of Milk. — The principal proteid in milk is called caseinogen ; it is precipitable by acids such as acetic acid, and also by saturation with magnesium sulphate, or half saturation with ammonium sulphate, so resembling globulins ; it is coagulated by rennet to form casein. Cheese consists of casein with the entangled fat. The other proteid in milk is an albumin. It is present in small quantities only ; it differs in some of its properties (specific rotation, coagulation temperature, and solubilities) from serum-albumin ; it is called lact- albumin. The Coagulation of Milk. — Rennet is the agent usually employed for this purpose : it is a ferment secreted by the stomach, especially in sucking animals, and is generally obtained from the calf. The curd consists of the casein and entangled fat: the liquid residue called whey contains the sugar, salts, and albumin of the milk. There is also a small quantity of a new proteid called whey-proteid which differs from caseinogen by not being convertible into casein ; this is produced by the decomposition of the caseinogen molecule during the process of curdling. The curd formed in human milk is more finely divided than that in cow's milk; and it is more digestible. In feeding children and invalids on cow's milk, the lumpy condition of the curd may be ob- viated by the addition of lime water or barley water to the milk. There appears to be no chemical difference between the caseinogen of human and that of cow's milk ; variations in the amount of calcium salts, and of citric acid account for the differences described. The addition of rennet produces coagulation in milk, provided that a sufficient amount of calcium salts is present. If the calcium salts are precipitated by the addition of potassium oxalate, rennet causes no formation of casein. The process of curdling in milk is a CH. XXVIII.] MILK 463 double one ; the first action due to rennet is to produce a change in caseinogen ; the second action is that of the calcium salt which precipitates the altered caseinogen as casein. In blood, also, calcium salts are necessary for coagulation, but there they act in a different way, namely, in the production of fibrin ferment (see p. 414). Caseinogen is not a globulin, though it is, like globulins, readily precipitated by neutral salts. It differs from a globulin in not being coagulated by heat. It is a nucleo-proteid ; that is, a com- pound of a proteid with the proteid-like but phosphorus-rich material called pseudo-nuclcin (see p. 402). In milk it is combined with calcium to form calcium casein ogenate ; when acetic acid is added we therefore get calcium acetate and free caseinogen. The Fats of Milk. — The chemical composition of the fat of milk (butter) is very like that of adipose tissue. It consists chiefly of palmitin, stearin, and olein. There are, however, smaller quantities of fats derived from fatty acids lower in the series, especially butyrin and caproin. The relation between these varies somewhat, but the proportion is roughly as follows : — Olein, f ; palmitin, J ; stearin, ^ ; butyrin, caproin, and caprylin, ^. The old statement that each fat globule is surrounded by a film of caseinogen is, according to Eamsden's recent observations, correct. Milk also contains small quantities of lecithin, a phosphorised fat; of cholesterin, an alcohol which resembles fat in its solubilities, and a yellow fatty pigment or lipochrome. Milk Sugar, or Lactose. — This is a saccharose (C 12 H 22 O n ). Its properties have already been described in Chap. XXV., p. 390. Souring of Milk. — When milk is allowed to stand the chief change which it is apt to undergo is a conversion of a part of its lactose into lactic acid. This is due to the action of micro-organisms, and would not occur if the milk were contained in closed sterilised vessels. Equations showing the change produced are given on p. 391. When souring occurs, the acid formed precipitates a portion of the caseinogen. This must not be confounded with the formation of casein from caseinogen which is produced by rennet. There are, however, some bacteria which, like rennet, produce true coagula- tion. Alcoholic Fermentation in Milk. — When yeast is added to milk, the sugar does not readily undergo the alcoholic fermentation. Other somewhat similar fungoid growths are, however, able to produce the change, as in the preparation of koumiss ; the milk sugar is first inverted, that is dextrose and galactose are formed from it (see p. 391), and it is these sugars from which alcohol and carbonic acid originate. The Salts of Milk. — The chief salt present is calcium phosphate ; a small quantity of magnesium phosphate is also present. The other salts are chiefly chlorides of sodium and potassium. 464 FOOD [ell. XXVIII. The Mammary Glands. The mammary glands are composed of large divisions or lobes, and these are again divisible into lobules ; the lobules are composed of the convoluted and dilated subdivisions of the main ducts held together by connective-tissue. Covering the general surface of the gland, with the exception of the nipple, is a considerable quantity of fat, itself tabulated by sheaths and processes of areolar tissue (fig. :'.S9) connected both with the skin in front and the gland behind ; the same bond of connection extends also from the under surface of the gland to the sheathing connective-tissue of the great pectoral muscle on which it lies. The main ducts of the gland, fifteen to twenty in number, called the lactiferous ducts, are formed by the union of the smaller (lobular) ducts, and open by small separate orifices through the nipple. At the points of junction of lobular ducts to form lactiferous ducts, and Fig. 389. — Dissection of the lower half of the female mamma, during the period of lactation. 5. — In the left-hand side of the dissected part the glandular lobes are exposed and partially unravelled ; and on the right-hand side, the glandular substance has been removed to show the reticular loculi of the connective-tissue in which the glandular lobules are placed : 1, upper part of the mamilla or nipple ; 2, areola ; 3, subcutaneous masses of fat ; 4, reticular loculi of the connective-tissue which support the glandular substance and contain the fatty masses ; 5, one of three lactiferous ducts shown passing towards the mamilla where they open ; 6, one of the sinus lactei or reservoirs ; 7, some of the glandular lobules which have been unravelled ; I 1 , others massed together. (Luschka.) just before these enter the base of the nipple, the ducts are dilated ; and during the period of active secretion by the gland, the dilatations form reservoirs for the milk, which collects in and distends them. The walls of the gland-ducts are formed of areolar with some unstriped muscular tissue, and are lined internally by short columnar and near the nipple by flattened epithelium. The alveoli consist of a basement membrane of flattened cells lined by low columnar epithelium (fig. 390). The nipple is composed of areolar tissue, and contains unstriped muscular fibres. Blood-vessels are also freely supplied to it, so as to give it an erectile structure. On its surface are very sensitive papillae ; and around it is a small area or areola of pink or dark-tinted skin, on which are to be seen small projections formed by minute secreting glands. Blood-vessels, nerves, and lymphatics are plentifully supplied to the mammary CH. XXVIII.] EGGS 465 glands ; the calibre of the blood-vessels, as well as the size of the glands, varies very greatly under certain conditions, especially those of pregnancy and lactation. The secretory nerves of the mammary glands have not yet been discovered. The alveoli of the glands during the secreting periods are found to be lined with very short columnar cells, with nuclei situated towards the centre. The edges of the cells towards the lumen may be irregular and jagged, and the remainder of the alveolus is filled up with the materials of the milk. During the intervals between the acts of discharge, the cells of the alveoli elongate towards the lumen, their nuclei divide, and in the part of the cells towards the lumen a collection of oil globules and of other materials takes place. The next stage is that the cells divide and the part of each towards the lumen containing a nucleus and the materials of the secretion, disintegrates and goes to form the solid part of the milk. The cells also secrete water, salts, and milk sugar. The fat, etc. , of milk are not simply picked out from the blood by the secreting cells, but these materials are formed by metabolic processes within the protoplasm of the cells. In the earlier days of lactation, epithelial cells only partially transformed are discharged in the secretion ; these are termed colostrum cor- puscles. It is stated that colostrum possesses a purgative action. During pregnancy the mammary glands undergo changes {evolution) which are readily observable. They enlarge, become harder, and more distinctly lobulated ; the veins on the sur- face become more prominent. The areola becomes enlarged and dusky, with projecting papillae ; the nipple, too, becomes more prominent, and milk can be squeezed from the orifices of the ducts. This is a very gradual process, which commences about the time of conception, and progresses steadily during the whole period of gestation. In the gland itself solid columns of cells bud off from the old alveoli to form new alveoli. But these solid columns after a while are converted into tubes by the central cells becoming fatty and being discharged as the colostrum corpuscles above mentioned. After the end of lactation, the mamma gradually returns to its original size {involution). The acini, in the early stages of involution, are lined with cells in all degrees of vacuolation. As involution proceeds, the acini diminish considerably in size, and at length, instead of a mosaic of lining epithelial cells (twenty to thirty in each acinus), we have five or six nuclei (some with no surrounding protoplasm) lying in an irregular heap within the acinus. During the later stages of involution, large yellow granular cells are to be seen. As the acini diminish in size, the connective-tissue and fatty matter between them increase, and in some animals, when the gland is completely inactive it is found to consist of a thin film of glandular tissue overlying a thick cushion of fat. Many of the products of waste are carried off by the lymphatics. Eggs. In this country the eggs of hens and ducks are those particularly selected as foods. The chief constituent of the shell is calcium car- bonate. The white is composed of a richly albuminous fluid enclosed in a network of firmer and more fibrous material. The amount of solids is 13 - 3 per cent. ; of this 12'2 is proteid in nature (egg-albumin, with smaller quantities of egg-globulin, and of a mucinoid substance called ovo-mucoid), and the remainder is made up of sugar (0'5 per 2 G Fig. 390.— Section of mammary gland of bitch, showing acini, lined with epithelial cells of a short columnar form, x 200. (V. D. Harris.) 466 FOOD [CH. XXVIII. cent.), traces of fats, lecithin and cholesterin, and 0'6 per cent, of inorganic salts. The yolk is rich in food materials for the develop- ment of the future embryo. In it there are two varieties of yolk- spherules, one kind yellow and opaque (due to admixture with fat and a yellow lipochrome), and the other smaller, transparent and almost colourless ; these are proteid in nature, consisting of the nucleo-proteid called vitcllin. Small quantities of sugar, lecithin, cholesterin and inorganic salts are also present. The nutritive value of eggs is high, as they are so readily digest- ible ; but the more an egg is cooked the more insoluble do its proteid constituents become. Meat. This is composed of the muscular and connective (including adipose) tissues of certain animals. The flesh of some animals is not eaten ; in some cases this is a matter of fashion, in others, owing to an unpleasant taste, such as the flesh of carnivora is said to have ; and in other cases {e.g. the horse) because it is more lucrative to use the animal as a beast of burden. Meat is the most concentrated and most easily assimilable of nitrogenous foods. It is our chief source of nitrogen. Its chief solid constituent is proteid, and the principal proteid is myosin. In addition to the extractives and salts contained in muscle, there is always a certain percentage of fat, even though all visible adipose tissue is dissected off. The fat-cells are placed between the muscular fibres, and the amount of fat so situated varies in different animals ; it is particularly abundant in pork ; hence the indigestibility of this form of flesh : the fat prevents the gastric juice from obtaining ready access to the muscular fibres. The following table gives the chief substances in some of the principal meats used as food : — Constituents. Water Solids Proteids and gelatin : Fat . Carbohydrate . Salts Ox. 76-i 23-3 20-0 1-5 0-6 1-2 Calf. 75 '6 24-4 19-4 2-9 0-8 1-3 72-6 27-4 19-9 6-2 0-6 1-1 Horse. Fowl. Pike. 7 1 ••■; 70-8 79-3 25*7 29-2 20-7 21-6 22-7 18-3 2-5 4-1 0-7 0-6 1-3 0-9 1-0 1-1 0-8 The large percentage of water in meat should be particularly noted; if a man wished to take his daily supply of 100 grammes of * The flesh of young animals is richer in gelatin than that of old; thus 1000 parts of beef yield 6, of veal 50, parts of gelatin. CH. XXVIII.] FLOUK 467 proteicl entirely in the form of meat, it would be necessary for him to consume about 500 grammes (i.e., a little more than 1 lb.) of meat. Flour. The best wheat flour is made from the interior of wheat grains, and contains the greater proportion of the starch of the grain and most of the proteid. Whole flour is made from the whole grain minus the husk, and thus contains not only the white interior but also ths harder and browner outer portion of the grain. This outer region contains a somewhat larger proportion of the proteids of the grain. Whole flour contains 1 to 2 per cent, more proteid than the best white flour, but it has the disadvantage of being less readily digested. Brown flour contains a certain amount of bran in addition ; it is still less digestible, but is useful as a mild laxative, the insoluble cellulose mechanically irritating the intestinal canal as it passes along. The best flour contains very little sugar. The presence of sugar indicates that germination' has commenced in the grains. In the manufacture of malt from barley this is purposely allowed to go on. When mixed with water, wheat flour forms a sticky, adhesive mass called dough. This is due to the formation of gluten, and the forms of grain poor in gluten cannot be made into dough (oats, rice, etc.). Gluten does not exist in the flour as such, but is formed on the addition of water from the pre-existing globulins in the flour. The following table contrasts the composition of some of the more important vegetable foods : — Constituents. Wheat. Barley. Oats. Rice. Lentils. Peas. Potatoes. Water . 13-6 ! 13-8 12-4 13-1 12-5 14-8 76-0 Proteid 12-4 11-1 10-4 7-9 24-8 23-7 2-0 Fat . 1-4 2*2 5*2 0'9 1-9 1-6 0-2 Starch 67-9 64-9 57-8 76*5 54-8 49-3 20-6 Cellulose 2-5 5-3 11-2 0-6 3-6 7*5 0-7 Mineral salts 1-8 2-7 3-0 1-0 2-4 3-1 1-0 We see from this table — 1. The great quantity of starch always present. 2. The small quantity of fat ; that bread is generally eaten with butter is a popular recognition of this fact. 3. Proteid, except in potatoes, is pretty abundant, and especially so in the pulses (lentils, peas, etc.). The proteid in the pulses is not gluten, but consists of vitellin and globulin-like substances. In the mineral matters in vegetables, salts of potassium and magnesium are, as a rule, more abundant than those of sodium and calcium. 4G8 FOOD [CH. XXVIII. Bread. Bread is made by cooking the dough of wheat flour mixed with yeast, salt, and flavouring materials. A ferment in the flour acts at the commencement of the process, when the temperature is kept a little over that of the body, and forms dextrin and sugar from the starch, and then the alcoholic fermentation, due to the action of the yeast, begins. The bubbles of carbonic acid, burrowing passages through the bread, make it light and spongy. This enables the digestive juices subsequently to soak into it readily and affect all parts of it. In the later stages, viz., baking, the temperature is raised, the gas and alcohol are expelled from the bread, the yeast is killed, and a crust forms from the drying of the outer portions of the dough. White bread contains, in 100 parts, 7 to 10 of proteid, 55 of carbohydrates, 1 of fat, 2 of salts, and the rest water. Cooking of Pood. The cooking of foods is a development of civilisation and serves many useful ends : — 1. It destroys all parasites and danger of infection. This relates not only to bacterial growths, but also to larger parasites, such as tapeworms and trichinae. 2. In the case of vegetable foods it breaks up the starch grains, bursting the cellulose and allowing the digestive juices to come into contact with the granulose. 3. In the case of animal foods it converts the insoluble collagen of the universally distributed connective tissues into the soluble gelatin. The loosening of the fibres is assisted by the formation of steam between them. By thus loosening the binding material, the more important elements of the food, such as muscular fibres, are rendered accessible to the gastric and other juices. Meat before it is cooked is generally kept a certain length of time to allow rigor mortis to pass off. Of the two chief methods of cooking, roasting and boiling, the former is the more economical, as by its means the meat is first sur- rounded with a coat of coagulated proteid on its exterior, which keeps in the juices to a great extent, letting little else escape but the drip- ping (fat). Whereas in boiling, unless both bouillon and bouilli are used, there is considerable waste. Cooking, especially boiling, renders the proteids more insoluble than they are in the raw state ; but this is counterbalanced by the other advantages that cooking possesses. In making beef tea and similar extracts of meat it is necessary that the meat should be placed in cold water, and this is gradually and carefully warmed. In boiling a joint it is usual to put the meat CH. XXVIII.] ACCESSOEIES TO FOOD 469 into boiling water at once, so that the outer part is coagulated, and the loss of material minimised. An extremely important point in this connection is that beef tea and similar meat extracts should not be regarded as foods. They are valuable as pleasant stimulating drinks for invalids, but they contain very little of the nutritive material of the meat, their chief con- stituents, next to water, being the salts and extractives of flesh. Soup contains the extractives of meat, a small proportion of the proteids, and the principal part of the gelatin. The gelatin is usually increased by adding bones and fibrous tissue to the stock. It is the presence of this substance which causes soup when cold to gelatinise. Accessories to Food. Among these must be placed alcohol, the value of which within moderate limits is not as a food but as a stimulant; condiments (mustard, pepper, ginger, curry powder, etc.), which are stomachic stimulants, the abuse of which is followed by dyspeptic troubles; and tea, coffee, cocoa, and similar drinks. These are stimulants chiefly to the nervous system ; tea, coffee, mate (Paraguay), guarana (Brazil), cola nut (Central Africa), bush tea (South Africa), and a few other plants used in various countries all owe their chief property to an alkaloid called theine or caffeine (C s H 10 N 4 O 2 ) ; cocoa to the closely related alkaloid, theobromine (C 7 H 8 N" 4 2 ) ; coca to cocaine. These alkaloids are all poisonous, and used in excess, even in the form of infusions of tea and coffee, produce over-excitement, loss of diges- tive power, and other disorders well known to physicians. Coffee differs from tea in being rich in aromatic matters ; tea contains a bitter principle, tannin ; to avoid the injurious solution of too much tannin, tea should only be allowed to infuse (draw) for a few minutes. Cocoa is not only a stimulant, but a food in addition ; it contains about 50 per cent, of fat, and 12 per cent, of proteid. In manufac- tured cocoa, the amount of fat is reduced to 30 per cent., and the amount of proteid rises proportionately to about 20 per cent. The quantity of cocoa usually consumed is too small for these food materials to count very much in the daily supply. The amount of proteid in solution (mainly albumose) in a breakfast cup of cocoa is under half a gramme ; most of the food stuffs are in suspension, for cocoa is drunk " thick," not as a clear infusion. Green vegetables are taken as a palatable adjunct to other foods, rather than for their nutritive properties. Their potassium salts are, however, abundant. Cabbage, turnips, and asparagus contain 80 to 92 water, 1 to 2 proteid, 2 to 4 carbohydrates, and 1 to 1*5 cellulose per cent. The small amount of nutriment in most green foods accounts for the large meals made by, and the vast capacity of the alimentary canal of, herbivorous animals. CHAPTEE XXIX SECRETING GLANDS Before passing on to the action of the digestive secretions on foods, it will be well to discuss the varieties of glands by means of which these substances are formed. It is the function of gland-cells to produce by the metabolism of their protoplasm certain substances called secretions. These materials are of two kinds; viz., those which are employed for the purpose of serving some ulterior office in the economy, and those which are dis- charged from the body as useless or injurious. In the former case the separated materials are termed secretions ; in the latter they are termed excretions. The secretions, as a rule, consist of substances which do not pre- exist in the same form in the blood, but require special cells and a process of elaboration for their formation, e.g., the liver cells for the formation of bile, the mammary gland-cells for the formation of milk. The excretions, on the other hand, commonly consist of substances which exist ready-formed in the blood, and are merely abstracted therefrom. If from any cause, such as extensive disease or extirpa- tion of an excretory organ, the separation of an excretion is prevented, and an accumulation of it in the blood ensues, it frequently escapes through other organs, and may be detected in various fluids of the body. An instance of this is seen after the kidneys have been removed. Urea then accumulates in the blood. But this is never the case with secretions ; for, after the removal of the special organ by which each of them is manufactured, the secretion is no longer formed. The circumstances of their formation, and their final destination, are, however, the only particulars in which secretions and excretions can be distinguished ; for, in general, the structure of the parts engaged in eliminating excretions is as complex as that of the parts concerned in the formation of secretions. It will, therefore, be sufficient to speak in general terms of the process. Every secreting apparatus consists essentially of a layer of secret- ing cells arranged round a central cavity ; they take from the lymph 470 CH. XXIX.] SECRETING MEMBRANES 471 which bathes them the necessary material, and transform it into the secretion which they pour at high pressure into the cavity. The principal secreting organs are the following : — (1) the serous and synovial membranes; (2) the mucous membranes with their special glands, e.g., the buccal, gastric and intestinal glands ; (3) the salivary glands and pancreas; (4) the mammary glands; (5) the liver ; (6) the lacrimal gland ; (7) the kidney and skin ; and (8) the testes. Serous membranes. — We have already discussed the structure of serous membranes (p. 206), and also the question whether the lymph is a true secretion (pp. 318-320). The synovial membranes line the joints and the sheaths of tendons and ligaments with which we may include the synovial bursas. The contents of these sacs is called synovia ; it lubricates the surfaces of the joint, and so ensures an easy movement. Synovia is a rich lymph plus a mucinoid mate- rial ; and it is this latter constituent which gives the secretion its viscidity. It is thus a true secretion; and is formed by the epithelial cells which form an imperfect lining to the sac, and which are especially accumulated on the processes of the synovial fringes (fig. 391). A mucous membrane consists of two parts : the epithelium on its surface, and the corium of connective tissue beneath. The epithelium generally rests on a basement membrane which is usually composed of clear flattened cells placed edge to edge. The name mucous is derived from the fact that these membranes all secrete mucin, the chief constituent of mucus ; this may be formed from the surface epithelium cells breaking down into goblet cells (see p. 26), or an analogous process may occur in the cells of little glands called mucous glands, situated more or less deeply under the epi- thelium, and opening on the surface by ducts. Many mucous membranes {e.g., that of the stomach) form other secretions as well. Mucous membranes line all those passages by which internal parts Fig. 391. — Section of synovial membrane, a, epithelial covering of the elevations of the membrane ; b, underlying tissue containing fat and blood- vessels ; c, ligament covered by the synovial mem- brane. (Cadiat.) 472 SECRETING GLANDS [CH. XXIX. communicate with the exterior. The principal tracts are the Digestive, Respiratory, and Genito -urinary. Secreting glands may be classified according to certain types, which are the following: — 1. The simple tubular gland (a, fig. 392), examples of which are furnished by the crypts of Lieberkiihn in the Fig. 392.— Diagram of types of secreting glands, a, simple glands, viz., g, straight tube; h, sac; {, coiled tube, b, maltilocular crypts ; k, of tubular form ; I, saccular! c, racemose, or saccular compound gland ; to, entire gland, showing branched duct and lobular structure ; n, a lobule, detached with o, branch of duct proceeding from it. n, compound tubular gland. (Sharpey.) intestinal wall. To the same class may be referred the elongated and tortuous sudoriferous glands. 2. The compound tubular glands (d, fig. 392) form another division. These consist of main gland-tubes, which divide and sub-divide. 3. The racemose glands are those in which a number of vesicles or acini are arranged in groups or lobules (c, fig. 392). The Meibo- CH. XXIX.] ELECTEICAL CHANGES IN GLANDS 473 mian follicles are examples of this kind of gland. Some glands, like the pancreas, are of a mixed character, combining some of the char- acters of the tubular with others of the racemose type; these are called tubulo-racemose or tubulo-acinous glands. These glands differ from each other only in secondary points of structure, but all have the same essential character in consisting of rounded groups of vesicles containing gland-cells, and opening by a common central cavity into minute ducts, which ducts in the large glands converge and unite to form larger and larger tubes, and at length open by one common trunk on a free surface. The larger racemose glands, like the salivary glands, are called compound racemose glands. On internal secretions, see p. 328. Electrical Variations in G-lands. These have been studied in many glandular organs, but especially in the salivary glands and skin. In the submaxillary gland the hilus is electro-negative to the external surface of the organ ; a current therefore passes from hilus to surface through the galvano- meter. If the chorda tympani is stimulated by rapidly interrupted shocks, the surface becomes still more positive. This is the opposite to what occurs in a muscle ; there the current of action is in the reverse direction to the demarcation current ; the change in the gland is a positive variation in the arithmetical sense. This is abolished by a small dose of atropine ; stimulation then causes a small negative variation which is abolished by a larger dose of atropine. If, before atropine is given, slowly interrupted shocks are used, or rapidly interrupted shocks too weak to excite secretion are employed, the electrical response of the organ is a negative variation. The same is true for stimulation of the sympathetic. Single induction shocks applied to the chorda tympani cause a diphasic variation, first the surface of the gland becoming more positive and then the hilus. The two changes are believed to be due to the fact that secretory nerves are of two kinds : anabolic, which increase the building up of the glandular protoplasm ; and katabolic, which increase the disintegrative side of metabolism, and so lead to secretion. It is important to remember the existence of the skin currents, for they interfere with any attempt to determine the electrical change in muscles through the intact skin. This interference will naturally be greater, the richer the portion of skin is, in secreting glands. The most satisfactory work on skin currents is that recently carried out by Waller. He speaks of them as glandular and epithelial, and regards them as important signs of life here as in other tissues (eye, muscle, nerve, plant tissues, etc. ) which he has studied. He has worked with the skin of the frog, cat, and other animals, including fresh human skin obtained from surgical operations. The skin may be excited either directly or indirectly through the nerves that supply it. The main results obtained are very simple, and* are also true for mucous membranes, and such epithelial structures as the crystalline lens. The normal current of unexcited living skin is ingoing. The normal response of excited skin is outgoing. This is explained in the following way :— In a passive mass of living animal material acted upon by its environment, there must be most change occurring on its surface, a point on the surface will therefore be electropositive to any point in the interior. If the same mass is excited, chemical changes will be greater in its interior than at the surface ; hence internal points become less electronegative than they were before, or even electropositive in relation to the external surface, hence the current of action through the mass of skin is outgoing, and will therefore pass through the galvanometer from the external to the internal surface. CHAPTER XXX SALIVA The saliva is formed by three pairs of salivary glands, called the parotid, submaxillary, and sublingual glands. The Salivary Glands. These are typical secreting glands. They are made up of lobules united by connective tissue. Each lobule is made of a group of tubulo- saccular alveoli or acini, from which a duct passes ; this unites with other ducts to form larger and larger tubes, the main duct opening into the mouth. Each alveolus is surrounded by a ~r\ plexus of capillaries ; the lymph which W exudes from these is in direct contact m with the basement membrane that en- g closes the alveolus. The basement mem- brane is lined by secreting cells which surround the central cavity or lumen. The basement membrane is thin in ^ many places, to allow the lymph more fig. 393.— From a section through a readv access to the secretins cells ; it salivary gland, a, serous or albumi- • .• i i ,i i nous alveoli; 6, intralobular duct IS COlltmued along the dllCtS. cutteansversely. (Klein and Xob.e ThQ secreting epithelium is C01I1- posed of a layer of polyhedral cells. The epithelium of the ducts is columnar, except where it passes into an alveolus ; at this point it is flattened. The columnar epithelium cells of the ducts exhibit striatums in their outer part (see fig. 393) ; the inner zone of each cell is made of granular protoplasm. The largest ducts have a wall of connective tissue outside the basement- membrane, and a few unstriated muscular fibres. The secreting cells differ according to the substance they secrete. In alveoli that secrete mucin (such as those in the dog's submaxillary, CH. XXX.] THE SALIVAEY GLANDS 475 and some of the alveoli in the human submaxillary) the cells after treatment with water or alcohol are clear and swollen (fig. 395); this is the appearance they usually present in sections of the organ. But if examined in their natural state by teasing a portion of the fresh Fir. 394.— Section of submaxillary gland of dog. Showing gland-cells, 6, and a duct, a, b, in section. (Kolliker.) gland in serum, they are seen to be occupied by large granules com- posed of a substance known as mucigen or mueinogen. When the gland is active, mucigen is transformed into mucin and discharged as a clear droplet of that substance into the lumen of the alveolus. Out- side these are smaller, highly granular cells containing no mucigen ; these marginal cells stain darkly, and generally form crescentic groups {crescents or demilunes of GTianuzzi) next to the basement membrane. They do not secrete mucin, but are albuminous cells. After secretion their granules are lessened. In those alveoli which do not secrete mucin, but a watery non- viscid saliva (parotid, and some of the alveoli of the human sub- maxillary), the cells are filled with small granules of albu- minous nature. Such alveoli are called serous or albuminous, to dis- tinguish them from the mucous alveoli we have just described. These yield to the secretion its ferment, ptyalin. The granular substance within the cell is the mother substance of the ferment {zymogen), not the ferment itself. It is converted into the ferment in the act of secretion. We shall study the question of zymogens Fig. 395.— Section through a mucous gland hardened in alcohol. The alveoli are lined with transparent mucous cells, and outside these are the demilunes. (Heidenhain.) 476 SALIVA [CII. XXX. more fully in connection with the gastric glands and the pancreas where they have been separated from the ferments by chemical methods. In the case of saliva we may term the zymogen, ptyalinogen provision- ally, but it has never been satisfactorily separated chemically from ptyalin. After secretion, due to the administration of food or of such a drug as pilocarpine, the cells shrink,, they stain more readily, their Fio. 396. — Alveoli of parotid gland. A, before secretion ; B, in the first stage of secretion ; C, after prolonged secretion. (Langley.) nuclei become more conspicuous, and the outer part of each cell becomes clear and free from granules (fig. 396). The Secretory Nerves of Salivary Glands. The nerve-fibres which are derived from cranial and sympathetic nerves ramify between the gland-cells, but have never actually been traced into them. These nerves control and regulate the secretion of saliva. The general truth concerning the existence of secretory nerves, we have already become acquainted with (p. 162). The subject has been worked out most thoroughly in connection with the salivary glands, particularly the submaxillary gland of the dog, which we will take first. The Submaxillary and Sublingual Glands. — These glands receive two sets of nerve-fibres ; namely, from the chordi tympani and the sympathetic. The chorda tympani is given off from the seventh cranial nerve in the region of the tympanum.* After quitting the temporal bone it passes downwards and forwards, and joins the lingual nerve, with which it is bound up for a short distance. On leaving the lingual nerve it traverses the submaxillary ganglion ; it then runs parallel to the duct of the gland, gives off a branch to the sublingual gland, and * Though the chorda tympani is usually spoken of as a branch of the seventh nerve, it is probable that some of its sensory fibres are derived from the glosso- pharyngeal ; the origin of its secretory fibres is not known. CH. XXX.] SECRETORY NERVES 477 others to the tongue. The main nerve enters the hilus of the sub- maxillary gland, where it traverses a second ganglion concealed within the substance of the gland, and which may be called after its dis- coverer, Langley's ganglion. The sympathetic branches to these two glands are derived from the plexus around the facial artery, and accompany the arteries which supply the glands. Section of the nerves produces no immediate result ; but after a few days an abundant secretion of thin watery saliva takes place; this is called paralytic secretion, and is produced either by the activity of the local nervous mechanism, which is then uncontrolled by impulses from the central nervous system ; or else, it is a degenerative effect analogous to the fibrillar contractions which occur in degenerating muscles after severance of their nerves. If the operation is per- formed on one side, the glands of the opposite side also show a similar condition, and the thin saliva secreted there is called the antilytic secretion. Stimulation of the peripheral end of the divided chorda tympani produces an abundant secretion of saliva, which is accompanied by vaso-dilatation (see p. 306). Stimulation of the peripheral end of the divided sympathetic causes a scanty secretion of thick viscid saliva, accompanied by vaso-constriction. The abundant secretion of saliva, which follows stimulation of the chorda tympani, is not merely the result of a filtration of fluid from the blood-vessels, in consequence of the largely increased circulation through them. This is proved by the fact that, when the main duct is obstructed, the pressure within it may considerably exceed the blood-pressure in the arteries,* and also that when into the veins of the animal experimented upon, some atropine has been previously injected, stimulation of the peripheral end of the divided chorda produces all the vascular effects as before, without any secretion of saliva accompanying them. Again, if an animal's head is cut off, and the chorda be rapidly exposed and stimulated with an interrupted current, a secretion of saliva ensues for a short time, although the blood-flow is necessarily absent. These experiments serve to prove that the chorda contains two sets of nerve-fibres, one set (vaso- dilator) which, when stimulated, cause the vessels to dilate; while another set, which are paralysed by atropine, directly stimulate the cells themselves to activity, whereby they secrete and discharge the constituents of the saliva which they produce. On the other hand, the sympathetic fibres are also of two kinds, vaso-constrictor and * The student should not suppose that the saliva is normally secreted at such high pressure. If it were so the saliva would spurt from the salivary duct with greater force than the blood would spurt from the arteries when they are cut. The high pressure alluded to in the text only occurs when the duct is obstructed, and indicates what enormous force the secreting cells can exercise. 478 SALIVA [en. XXX. secretory, the latter being paralysed by atropine. The chorda tympani nerve is, however, the principal nerve through which efferent impulses proceed from the central nervous system to excite the secretion of these glands. The function of the ganglia has been made out by Langley by the nicotine method (see p. 302). At one time the submaxillary ganglion was supposed to be the seat of reflex action for the secretion. This, however, is not the case. The ganglia are cell-stations on the course of the fibres to the submaxillary and sublingual glands. Nicotine applied locally has the power of paralysing nerve-cells, but not nerve- fibres. If the submaxillary ganglion is painted with nicotine, and the nerve stimulated on the central side of the ganglion, secretion from the submaxillary gland continues, but that from the sublingual gland ceases. The paralysed nerve-cells in the ganglion act as blocks to the propagation of the impulse, not to the submaxillary, but to the sublingual gland. The cell station for the submaxillary fibres is in Langley's ganglion. Parotid Gland. — This gland also receives two sets of nerve-fibres analogous to those we have studied in connection with the submaxil- lary gland. The principal secretory nerve-fibres are glosso -pharyngeal in origin ; the sympathetic is mainly vaso-constrictor, but in some animals does contain a few secretory fibres also. When secretory nerves are stimulated, the main result is secretion leading to a diminution of the granules in the cells. The accompany- ing vascular condition determines the quantity of saliva secreted. Electrical changes also accompany secretory activity (see p. 473). A rise of temperature is stated to occur, but if this is the case it is very slight, and many observers have not been able to detect it. Reflex Secretion. — Under ordinary circumstances the secretion of saliva is a reflex action. The principal afferent nerves are those of taste ; but the smell or sight of food will also cause " the mouth to water " ; and under certain circumstances, as before vomiting, irrita- tion of the stomach has a similar effect. These sensory nerves stimu- late a centre in the medulla from which efferent secretory impulses are reflected along the secretory nerves (chorda tympani, etc.) to the glands. Pawlow has made some interesting observations on the salivary glauds. He made an external fistula of the submaxillary duct in the dog, and found that the sight of food, the smell of food, or the administration of any kind of food, caused secretion ; acid or even sand introduced into the mouth produced a similar effect. By means of similar experiments on the parotid secretion, very different results were obtained. If the dog was shown meat, or the meat was given to it to eat, there was practically no secretion. If, however, the meat was given as a dry powder, a copious secretion followed ; dry bread CH. XXX.] COMPOSITION OF SALIVA 479 produced a similar effect ; in fact, the parotid secretion flows freely if dry food is simply shown to the animal ; of course, in all such experiments, the dog must be hungry. Such observations bring the salivary secretion into line with the other digestive juices ; they show the psychical element involved, and point out also the wonderful adaptation of the secretory process to the needs of the animal ; thus the submaxillary saliva, winch is mainly a lubricant in virtue of its mucin, flows whatever the food may be, whereas moist food requiring no watery saliva from the parotid excites the flow of none. Extirpation of the Salivary Glands. — These may be removed without any harmful effects in the lower animals. The Saliva. The saliva is the first digestive juice to come in contact with the food. The secretions from the different salivary glands differ some- what in composition, but they are mixed in the mouth ; the secretion of the minute mucous glands of the mouth and a certain number of epithelial cells and ddbris are added to it. The so-called "salivary corpuscles " are derived from the glands themselves or from the tonsils. On microscopic examination of mixed saliva a few epithelial scales from the mouth and salivary corpuscles from the salivary glands are seen. The liquid is transparent, slightly opalescent, of slimy consistency, and may contain lumps of nearly pure mucin. On standing it becomes cloudy owing to the precipitation of calcium carbonate, the carbonic acid, which held it in solution as bicarbonate, escaping. Of the three forms of saliva which contribute to the mixture found in the mouth the sublingual is richest in solids (2'75 per cent.). The submaxillary saliva comes next (21 to 2 - 5 per cent.). When artificially obtained by stimulation of nerves in the dog the saliva obtained by stimulation of the sympathetic is richer in solids than that obtained by stimulation of the chorda tympani. The parotid saliva is poorest in total solids (0 - 3 to 0"5 per cent.), and contains no mucin. Mixed saliva contains in man an average of about 0'5 per cent, of solids : it is alkaline in reaction, due to the salts in it ; and has a specific gravity of 1002 to 1006. The solid constituents dissolved in saliva may be classified thus : Organic It. | c. Proteid : of the nature of a globulin. V. d. Potassium sulphocyanide. Mucin : this may be precipitated by acetic acid. Ptyalin : an amylolytic ferment. Sodium chloride : the most abundant salt. Inorganic . - /. Other salts : sodium carbonate, calcium phosphate and { carbonate : magnesium phosphate ; potassium chloride. 480 SALIVA [cu. XXX. The action of saliva is twofold, physical and chemical. The physical use of saliva consists in moistening the mucous membrane of the mouth, assisting the solution of soluble substances in the food, and in virtue of its mucin, lubricating the bolus of food to facilitate swallowing. The chemical action of saliva is duo to its active principle, ptyalin. This substance belongs to the class of unorganised ferments, and to that special class of unorganised ferments which are called amylolytic (starch splitting) or cliastatic (resembling diastase, the similar ferment in germinating barley and other grains). The starch is first split into dextrin and maltose ; the dextrin is subsequently converted into maltose also : this occurs more quickly with erythro-dextrin, which gives a red colour with iodine, than with the other variety of dextrin called achroo-dextrin, which gives no colour with iodine. Brown and Morris give the following equa- tion : — 10(C 6 H 10 O 5 )n + 4nH 2 [Starch.] '' [Water.] = 4nC 1 ,H 2 p n + (C 6 H, O 5 )„ + (C 6 H 10 O 5 ) n . [Maltose.] [Achroo-dextrin.] [Erythro-dextrin.] Ptyalin acts in a similar way, but more slowly on glycogen : it has no action on cellulose; hence it is inoperative on uncooked starch grains, for in them the cellulose layers are intact. Ptyalin acts best at about the temperature of the body (35-40° C). It acts best in a neutral medium ; a small amount of alkali makes but little difference ; a very small amount of acid stops its activity. The conversion of starch into sugar by swallowed saliva in the stomach continues for a certain time. It then ceases owing to the hydrochloric acid secreted by the glands of the stomach. The acid which is first poured out neutralises the saliva, and combines with the proteids of the food, but when free acid appears ptyalin is de- stroyed, and so it cannot resume work when the acid is neutralised in the duodenum. Another amylolytic ferment contained in pan- creatic juice (to be considered later) continues the digestion of starch in the intestine. Cannon has recently shown that salivary digestion continues in the stomach for longer than one supposed. The food lying in the fundus of the stomach undergoes amylolysis for at least two hours, because the absence of peristalsis in this region until quite late stages in digestion prevents admixture with gastric juice, especially in the interior of the swallowed masses. CHAPTEE XXXI THE GASTEIC JUICE The juice secreted by the glands in the mucous membrane of the stomach varies in composition in the different regions, but the mixed gastric juice, as it may be termed, is a solution of a proteolytic ferment called pepsin in a saline solution, which also contains a little free hydrochloric acid. The gastric juice can be obtained during the life of an animal by means of a gastric fistula.* G-astric fistulse have also been made in human beings, either by accidental injury or by surgical operations. The most celebrated case is that of Alexis St Martin, a young Canadian, who received a musket wound in the abdomen in 1822. Observations made on him by Dr Beaumont formed the starting- point for our correct knowledge of the physiology of the stomach and its secretion. We now make artificial gastric juice by mixing weak hydrochloric acid (0'2 per cent.) with the glycerin extract of the stomach of a recently-killed animal. This artificial juice acts like the normal juice. Two kinds of glands are distinguished in the stomach, which differ from each other in their position, in the character of their epithelium, and in their secretion. Their structure will be found described on pp. 449, 451. We may, however, repeat that the cardiac glands are those situated in the cardiac part of the stomach: their ducts are short, their tubules long in proportion. The latter are filled with polyhedral cells, only a small lumen being left; they are more coarsely granular than the corresponding cells in the pyloric glands. They are called principal or central cells. Between them and the basement membrane of the tubule are other cells which stain readily with aniline dyes. They are called parietal or oxyntic cells. The * A gastric fistula is made by cutting through the abdominal wall so as to expose the stomach. The stomach is then attached to the edges of the abdominal wound, and a small orifice is finally made through the wall of the stomach. When the wound heals there is then a free communication between the stomach and the exterior. 2 H 482 THE GASTRIC JUICE [CII. XXXL pyloric glands, in the pyloric part of the stomach, have long ducts and short tubules lined with cubical granular cells. There are no parietal cells. The central cells of the cardiac glands and the cells of the pyloric glands are loaded with granules. During secretion they discharge their granules, those that remain being chiefly situated near the lumen, leavino- in each cell a clear outer zone. These are the cells that secrete the pepsin. Like secreting cells generally, they select certain materials from the lymph that bathes them; these materials are worked up by the protoplasmic activity of the cells into the secretion, which is then discharged into the lumen of the gland. The most important substance in a digestive secretion is the ferment. In the case of the gastric juice this is pepsin. We can trace an intermediate step in this process by the presence of the granules. The granules are not, however, composed of pepsin, but of a mother-substance which is readily converted into pepsin. "We shall find a similar ferment precursor in the cells of the pancreas, and the term zymogen is applied to these ferment precursors. The zymogen in the gastric cells is called pepsinogen. The rennet-ferment or rennin that causes the curdling of milk is distinct from pepsin, but is formed by the same cells. The parietal cells undergo merely a change of size during secre- tion, being at first somewhat enlarged, and after secretion they are somewhat shrunken. They are also called oxyntic (acid-forming) cells, because they secrete the hydrochloric acid of the juice. Heidenhain succeeded in making in one dog a cul-de-sac of the fundus, in another of the pyloric region of the stomach ; the former secreted a juice containing both acid and pepsin ; the latter, parietal cells being absent, secreted a viscid alkaline juice containing pepsin. The forma- tion of a free acid from the alkaline blood and lymph is an important problem. There is no doubt that it is formed from the chlorides of the blood and lymph, and of the many theories advanced as to how this is done, Maly's is, on the whole, the most satisfactory. He con- siders that it originates by the interaction of the calcium chloride with the di-sodium hydrogen phosphate of the blood, thus : — 2N T a 2 HP0 4 + [Di-sodium hydrogen phosphate.] or more simply by the interaction of sodium chloride and sodium di- hydrogen phosphate, as is shown in the following equation : — NaH o P0 4 + NaCl = Na 2 HP0 4 + HC1. [Sodium di'hydrogen [Sodium [Di-sodium hydrogen [Hydro- phosphate.] chloride.] phosphate.] chloric acid.] The sodium di-hydrogen phosphate in the above equation is 3CaCl 9 = = Ca 3 (P0 4 ) : , + 4NaCl + 2HC1, [Calcium [Calcium ~ [Sodium [Hydrochloric chloride.] phosphate.] chloride.] acid.] CH. XXXI.] COMPOSITION OF GASTRIC JUICE 483 derived from the interaction of the di-sodium hydrogen phosphate and the carbonic acid of the blood, thus : — N T a 2 Hr0 4 + C0 2 + H 2 = NaHC0 3 + NaH 2 P0 4 . But, as Gamgee has pointed out, these reactions can hardly be considered to occur in the blood generally, but rather in the oxyntic cells, which possess the necessary selective powers in reference to the saline constituents of the blood, and the hydrochloric acid, as soon as it is formed, passes into the secretion of the gland in consequence of its high power of diffusion. Composition of Gastric Juice. The following table gives the percentage composition of the gastric juice of man and the dog : — Constituents. Human. Dog. 1 Water ....... 99-44 97-30 Organic substances (chiefly pepsin) HC1 0-32 0-20 1-71 0-40 to 0-60 CaCl., . NaCf . 0-006 0-14 0-06 0-25 KC1 . 0-05 0-11 NH 4 C1. Ca 3 (P0 4 ). 2 Mg 3 (P0 4 ), FeP0 4 . I .o-oi 0-05 0-17 0-02 0-008 One sees from this how much richer in all constituents the gastric juice of the dog is than that of man. Carnivorous animals have always a more powerful gastric juice than other animals ; they have more work for it to do ; but the great contrast seen in the table is, no doubt, partly clue to the fact that the persons from whom it has been possible to collect gastric juice have been invalids. In the foregoing table one also sees the great preponderance of chlorides over other salts ; apportioning the total chlorine to the various metals present, that which remains over must be combined with hydrogen to form the free hydrochloric acid of the juice. In recent years, the composition and action of the gastric juice has been studied by Pawlow. By an ingenious surgical operation, he succeeded in separating from the stomach of dogs a diverticulum which pours its secretion through an opening in the abdominal wall ; the nerves of this small stomach are intact, and the amount of juice that can be collected from it when it is active amounts to several hundred cubic centimetres in a few hours. Pawlow thus obtained a pure gastric juice, which enabled him to study its action and com- 484 THE GASTRIC JUICE [CH. XXXI. position. It is clear, colourless, has a specific gravity of 1003 — 100G, and is feebly dextro-rotatory. It contains 0*4 to 06 per cent, of hydrochloric acid. It is strongly proteolytic, and inverts cane sugar. When cooled to r C. it deposits a precipitate of pepsin, and this carries down with it the acid in loose combination, especially in the layers first deposited. Its percentage composition is very similar to that of a proteid, only it contains chlorine in addition to the usual elements. The numbers agree closely with those obtained by Kiihne, who used ammonium sulphate as the precipitant. The following are the analytical figures : — Pepsin precipitated Precipitated by by cold. Am„S0 4 . Per cent. Per cent. Carbon .... 50-73 . . 50*37 Hydrogen .... 7*23 . . 6*88 Chlorine . . . . 1*01 to 1*17 . . 0*89 Sulphur .... 0-98 . 1-34 Nitrogen .... Not estimated . . 14*55 to 15-0 Oxygen .... The remainder . . The remainder. Pepsin stands apart from nearly all other ferments by requiring an acid medium in order that it may act. Probably a compound of the two substances, called pepsin-hydrochloric acid, is the really active agent. Other acids may take the place of hydrochloric acid, but none act so well. Lactic acid is often found in gastric juice: this is derived by fermentative processes from the food. The digestive powers of the acids are proportional to their dissociation and the number of H ions liberated. The anions, however, modify this by having different powers of retarding the action. The greater suitability of hydrochloric over lactic acid, for instance, in gastric digestion is due to the fact that the former acid more readily undergoes dissociation. Hydrochloric acid is absent in some diseases of the stomach ; the best colour tests for it are the following : — (a) Gunsberg's reagent consists of 2 parts of phloroglucinol, 1 part of vanillin, and M0 parts of rectified spirit A drop of filtered gastric juice is evaporated with an equal quantity of the reagent Red crystals form, or if much peptone is present, there will be a red paste. The reaction takes place with one part of hydrochloric acid in 10,000. The organic acids do not give the reaction. (/<) Trop;i'olin test. Drops of a saturated solution of tropaeolin -00 in 94 per cent, methylated spirit are allowed to dry on a porcelain slab at 40 C. A drop of the fluid to be tested is placed on the tropaeolin drop, still at 40 C. ; and if hydro- chloric acid is present, a violet spot is left when the fluid has evaporated. A drop of 0*006 per cent hydrochloric acid leaves a distinct mark. (c) Topfer's test A drop of dimethyl-amido-azo-benzol is spread in a thin film on a white plate. A drop of dilute hydrochloric acid (up to 1 in 10,000) strikes with this in the cold a bright red colour. Lactic acid is soluble in ether, and is generally detected by making an ethereal extract of the stomach contents, and evaporating the ether. If lactic acid is present in the residue it may be identified by the following way : — A solution of dilute ferric chloride and carbolic acid is made as follows : — 10 c.c. of a 4-per-cent solution of carbolic acid. 20 c.c. of distilled water. 1 drop of the liquor ferri perchloridi of the British Pharmacopoeia. On mixing a solution containing a mere trace (up to 1 part in 1 0.000) of lactic CH. xxxl] innervation of the gastric glands 485 acid with this violet solution, it is instantly turned yellow. Larger percentages of other acids (for instance, more than *2 per cent of hydrochloric acid) are necessary to decolorise the test solution. The Innervation of the Gastric Glands. As long ago as 1852 Bidder and Schmidt showed in a dog with a gastric fistula that the sight of food caused a secretion of gastric juice ; and in 1878 Eichet observed that in a man with complete occlusion of the gullet the act of mastication caused a copious flow of gastric juice. There could therefore have been no doubt that the glands are under the control of the nervous system, but the early attempts to discover the secretory nerves of the stomach were un- successful. The Eussian physiologist Pawlow has solved the problem by the employment of new methods. He experimented on dogs. In the first place he separated off the diverticulum, which we have described on p. 483, and by careful experiments he showed that the secretion of this small stomach is an exact sample, both as regards composition and rate of formation, of that which occurs in the main stomach, which is still left in continuity with the oesophagus above and the duodenum below. Another procedure adopted was to divide the oesophagus, and to attach the two cut ends to the opening in the neck. The animal was fed by the lower segment, but any food taken into the mouth, or any saliva secreted there, never reached the stomach, but fell out through the opening of the upper segment. These animals were kept alive for months, and soon accommodated themselves to their new con- ditions of life. The animals could thus be subjected to, (1) real feeding, (2) sham feeding, by allowing them to eat food which subse- quently tumbled out through the neck opening, and (3) psychical feeding, in which the animal was shown the food but was not allowed to eat it. The psychical element is important. Mechanical excitation of the stomach wall produces no secretion. If water is introduced there is a slight flow, and even if meat is introduced into the main stomach without the knowledge of the clog, the juice formed is scanty and of feeble digestive power. There is, moreover, no connection between the acts of mastication and swallowing with that of gastric secretion. Sham feeding with stones, butter, salt, pepper, mustard, extract of meat, and acid, though it excited a flow of saliva, produced no effect on the stomach. If, however, meat was used for the sham feeding, an abundant and active secretion occurred in the stomach (that of the small stomach was actually examined) after a latency of about five minutes. The secretion is thus adapted to the kind of food the dog has to digest ; the larger the proportion of proteid in the diet, the more abundant is the juice, and the richer both in pepsin and acid. 486 THE GASTRIC JUICE [CH. XXXI. Indeed, if the animal is hungry and shown the meat and not allowed to swallow it, the effect is as great. The following striking experiment also shows the importance of the psychical element. Two dogs were taken, and a weighed amount of proteid introduced into the main stomach in each without their knowledge ; one was then sham fed on meat, and one and a half hours later the amount of proteid digested by this dog was five times greater than that which was digested by the other. In the meat, however, it is not the proteid which acts most strongly as the stimulus ; egg-white, for instance, is not a stronger stimulus than water, but extract of meat is a powerful stimulus ; what the exact extractives are that act in this way is not yet known, and Herzen has since shown that dextrin acts even more powerfully. Herzen distinguishes between succagogues (juice-drivers) like Liebig's extract, and peptogens like dextrin, which produce not only an increased flow, but a juice rich in pepsin-hydrochloric acid. The products of proteolysis are also peptogenic, so that when once digestion has started, a stimulus for more secretion is provided. If the vagi are cut (below the origin of the recurrent laryngeal to avoid paralysis of the larynx), and then sham feeding is performed with meat, no secretion is obtained ; the vagi therefore contain the secretory fibres. The experiment of stimulating the peripheral end of the cut nerve confirmed this hypothesis. The nerve was cut in the neck four or five days before it was stimulated ; in this time degeneration of the cardio-inhibitory fibres took place, so that stoppage of the heart did not occur when the nerve was stimulated ; under these circumstances a secretion was obtained with a long latency ; the latency is explained by the presence of secreto-inhibitory fibres. Atropine abolishes the action of the vagus. In other animals the spinal cord was cut at the level of the first cervical nerve, and the animal kept alive by artificial respiration ; the vagus nerve was then cut, and its peripheral end stimulated ; an abundant secretion usually followed. Division of the cord renders an anaesthetic unnecessary, and also prevents the afferent impulses set up by the operation passing to the vagal centres, and thus exciting the inhibitory impulses which pass down the vagus, and tend to prevent secretion under ordinary circumstances. Pawlow thinks that the sympathetic also contains some secretory fibres, but this has not yet been proved. Action of Gastric Juice. The principal action of the gastric juice consists in converting the proteids of the food into the diffusible peptones. In the case of milk this is preceded by the curdling clue to rennet (see p. 462). CH. XXXI.] PEOTEOSES AND PEPTONES 487 There is a still further action — that is, the gastric juice is anti- septic ; putrefactive processes do not normally occur in the stomach, and the organisms that produce such processes, many of which are swallowed with the food, are in great measure destroyed, and thus the body is protected from them. The formation of peptones is a process of hydrolysis; peptones may be formed by other hydrating agencies like superheated steam and heating with dilute mineral acids. There are certain intermediate steps in this process: the intermediate substances are called pro- peptones or proteoses. The word " proteose " includes the albumoses (from albumin), globuloses (from globulin), vitelloses (from vitellin), etc. Similar substances are also formed from gelatin (gelatinoses) and elastin (elastoses). Another intermediate step in gastric digestion is called para- peptone : this is acid albumin or syntonin. The products of digestion of albumin may be classified, according to the order in which they are formed, as follows : — 1. Parapeptone, or acid albumin. (, . t-. . ,, , The primary albumoses, i.e., (a) Proto-albumose \ £ J hih are formed (6) Hetero-albumose J £ rgt (c) Deutero-albumose 3. Peptone. It is doubtful whether all the proteid present passes through the acid-albumin stage. The primary albumoses are precipitated by saturation with magnesium sulphate or sodium chloride. Deutero-albumose is not; it is, however, precipitated by saturation with ammonium sulphate. Proto- and deutero-albumose are soluble in water ; hetero-albumose is not ; it requires salt to hold it in solution. Peptones. — They are soluble in water, are not coagulated by heat, and are not precipitated by nitric acid, copper sulphate, ammonium sulphate, and a number of other precipitants of proteids. They are precipitated but not coagulated by alcohol. They are also precipi- tated by tannin, picric acid, potassio-mercuric iodide, phospho- molybdic acid, and phospho-tungstic acid. They give the biuret reaction (rose-red solution with a trace of copper sulphate and caustic potash or soda). Peptone is readily diffusible through animal membranes. The utility of the formation of diffusible substances during digestion is obvious. Proteoses. — They are not coagulated by heat; they are precipi- tated but not coagulated by alcohol: like peptone they give the biuret reaction. They are precipitated by nitric acid, the precipitate being soluble on heating, and reappearing when the liquid cools. 488 THE GASTRIC JUICE [CII. XXXI. This last is a distinctive property of proteoses. They are slightly diffusible. Variety of proteid. Action of beat. Action of alcohol. Action of nitric acid. Action of ammonium sulphate. Action of copper sulphate and caustic potash. Diffusi- bility. Albumin Globulin Proteoses (albumoses) Peptones Coagulated Ditto. Not coagulated Not coagulated Precipitated, then coagu- lated Ditto. Precipitated, but not co- agulated Precipitated, but not co- agulated Precipitated in the cold ; not readily soluble on heating Ditto. Precipitated in the cold ; readily sol- u bl e o n heating; the precipitate reappears on cooling* Not precipi- tated Precipitated by complete saturation Precipitated by half satu- ration ; also precipitated by MgSO t . Precipitated by satura- tion Not precipi- tateu Violet colour Ditto. Rose-red colour (biuret reaction) Rose-red colour (biuret reaction) Nil Ditlo. Slight Great The above table will give us at a glance the chief characters of paptones and proteoses in contrast with those of the native proteids, albumins, and globulins. We see that the main action of the gastric juice is upon the proteids of the food, converting them, into more soluble and diffusible products. The fats are not chemically altered in the stomach,f their proteid envelopes are, however, dissolved, and the solid fats are melted. Starch is unaffected ; but cane sugar is inverted. The inversion of cane sugar is largely due to the hydrochloric acid of the juice, and is frequently assisted by inverting ferments contained in the vegetable food swallowed. The question has been often raised why the stomach does not digest itself during life. The mere fact that the tissues are alkaline and pepsin requires an acid medium in which to act is not an explanation, but only opens up a fresh difficulty as to why the pancreatic juice which is alkaline does not digest the intestinal wall. To say that it is the vital properties of the tissues that enable them to resist digestion only shelves the difficulty and gives no real explanation of the mechanism of defence. Recent studies on the important question of immunity (see p. 439) * In the case of deutero-albumose this reaction only occurs in the presence of excess of salt. t According to some recent observations, a small amount of fat-splitting does occur in the stomach. en. xxxi.] mett's tubes 489 have furnished us with the key to the problem ; just as poisons introduced from without stimulate the cells to produce antitoxins, so harmful substances produced within the body are provided with anti-substances capable of neutralising their effects ; for this reason the blood does not normally clot within the blood-vessels, and Weinland has shown that the gastric epithelium forms an antipepsin, the intestinal epithelium an antitrypsin, and so on. Mett's Tubas. A method which is now generally employed for estimating the proteolytic activity of a digestive juice is one originally introduced by Mett Pieces of capillary glass tubing of known length are filled' with white of egg. This is set into a solid by heating to 95° C. They are then placed in the digestive fluid at 36° C, and the coagulated egg-white is digested. After a given time the tubes are removed ; and if the digestive process has not gone too far, only a part of the little column of coagulated proteid will have disappeared ; the length of the remaining column is easily measured, and the length that has been digested is a measure of the digestive strength of the fluid. Hamburger has used the same method in investigating the digestive action of juices on gelatin. The tubes are filled with warm gelatin solution, and this jellies on cooling. They are placed as before in the digestive mixture, and the length of the column that disappears can be easily measured. These experiments must, how- ever, be performed at room temperature, for the usual temperature (36 = — 40" C.) at which artificial digestion is usually carried out would melt the gelatin. He has also used the same method for estimating amylolytic activity, by filling the tubes with thick starch paste. Schutz' Law. E. Schutz stated in 1885 that the amount of peptic activity is proportional to the square root of the amount of pepsin. This was confirmed by Borissow, who used Mett's capillary tube method. An example (taken from the work of E. Schiitz, who estimated the amount of the digestive products in solution by means of nitrogen determinations) will suffice. Amount of Solution of Pepsin in Cubic Centimetres. Digested Nitrogen in Found. Grammes. Calculated. 1 4 9 16 0-0230 0-0427 0-0686 0-0889 0-0223 0-0446 0-0669 0-0S92 This work was an early attempt to deal with enzyme action on exact mathemati- cal lines, a branch of the subject now being extensively studied. Some have stated that the law holds more or less exactly for other enzymes ; in other cases the rela- tionship is different. The usual method now adopted is to estimate the velocity of reaction, that is, the time occupied by the ferment in accomplishing a given end on a fixed amount of material. If, for instance, one takes a series of tubes, each con- taining the same amount of milk, and adds to each different known amounts of rennet, the time occupied in producing curdling is accurately noted. In this case, and in similar experiments with blood or blood-plasma and fibrin ferment, the amount of ferment multiplied by the coagulation time is constant ; thus, if two drops of rennet produce coagulation in 30 seconds, four drops will curdle the same amount of milk in 15 seconds. The same simple relationship also probably holds for the action of invertin, erepsin, and trypsin. CHAPTER XXXII DIGESTION IN THE INTESTINES Here we have to consider the action of pancreatic juice, of bile, and of the succus entericus. The Pancreas. This is a tubulo-racemose gland closely resembling the salivary glands in structure. The principal differences are that the alveoli or acini are more tubular in character ; the connective tissue between them is looser, and in it are small groups of epithelium-like cells, which are supplied by a close network of capil- laries (fig. '398). The secreting cells of the pancreas are polyhedral. When examined in the fresh condition, or in preparations preserved by osmic acid, their protoplasm is seen to be tilled in the inner two-thirds with small granules ; but the outer third is left clear, and stains readily with protoplasmic dyes (fig. 397). During secretion the granules are discharged ; the clear zone conse- quently becomes wider, and the granular zone narrower. These granules indicate the presence of a zymogen which is called tripsinogen; that is, the precursor of trypsin, the most important ferment of the pancreatic juice. In the centre of the acini, spindle-shaped cells {centro- acinar cells) are often seen ; their function and origin are unknown. 490 Fio. 397. — Section of the pancreas of a dog during digestion, a, alveoli lined with cells, the clear outer zone of which is well stained with hematoxylin ; 4 H 40 O,- [Glycocholic acid.] [Glycine.] [Cholalic acid.] The glycocholate of soda has the formula (^H^NaNO,;. Taurocholic acid (C. 26 H 4;i lSr0 7 S) similarly splits into taurine or amino-isethionic acid and cholalic acid. C,,H 4 .NO r S + H,0 = CH-XO3S + C, 4 H 40 O f) [Taurocholic acid.] [Taurine.] [Cholalic acid.] The taurocholate of soda has the formula C 2G H 44 NaiN"0 7 S. The colour reaction called Pettenkofer's reaction, is due to the presence of cholalic acid. Small quantities of cane sugar and strong sulphuric acid are added to the bile. The sulphuric acid acting on sugar forms a small quantity of a substance called furfur aldehyde, in addition to other products. The furfuraldehyde gives a brilliant purple colour with cholalic acid. The Bile Pigments. — The two chief bile pigments are bilirubin and biliverdin. Bile which contains chiefly the former (such as dog's bile) is of a golden or orange-yellow colour, while the bile of many herbivora, which contains chiefly biliverdin, is either green or bluish- green. Human bile is generally described as containing chiefly bilirubin, but there have been some cases described in which biliverdin was in excess. The bile pigments show no absorption bands with the spectroscope; their origin from the blood pigment has already been stated. Bilirubin has the formula C 16 H 1S N 2 3 : it is thus an iron-free derivative of hamioglobin. The iron is apparently stored up in the liver cells, perhaps for future use in the manufacture of new haemo- globin. The bile contains only a trace of iron. CH. XXXIII.] THE BILE 511 Biliverdin has the formula C 16 H 18 1S[ 2 4 (i.e., one atom of oxygen more than in bilirubin) : it may occur as such in bile ; it may be forinad by simply exposing red bile to the oxidising action of the atmosphere ; or it may be formed as in G-melin's test by the more vigorous oxidation produced by fuming nitric acid. Gmelin's test consists in a play of colours — green, blue, red, and finally yellow, produced by the oxidising action of fuming nitric acid (that is, nitric acid containing nitrous acid in solution). The end or yellow product is called choletelin, C 16 H 1S N" 2 6 . HydrobiliruTbin. — If a solution of bilirubin or biliverdin in dilute alkali is treated with sodium amalgam or allowed to putrefy, a brownish pigment, which is a reduction product, is formed called hydrobilirubin, C^H^IS^O;-. With the spectroscope it shows a dark absorption band between b and F, and a fainter band in the region of the D line. This substance is interesting because a similar substance is formed from the bile pigment by reduction pro- cesses in the intestine, and constitutes stercobilin, the pigment of the faeces. Some of this is absorbed and ultimately leaves the body in the urine as one of its pigments called urobilin. A small quantity of urobilin is sometimes found preformed in the bile. The identity of urobilin and stercobilin has been fre- quently disputed, but the recent work of Garrod and Hopkins has confirmed the old statement that they are the same substance with different names, fig. 409.— crystaiiinescaies of cholesterin. Hydrobilirubin differs from urobilin in containing more nitrogen in its molecule (9 - 2 instead of 4*1 per cent.). Cholesterin. — This substance is contained not only in bile, but very largely in nervous tissues. Like lecithin, it is an abundant constituent of the white substance of Schwann. It is found also in blood-corpuscles. In bile it is normally present in small quantities only, but it may occur in excess, and form the concretions known as gall-stones, which are usually more or less tinged with bilirubin. Though its solubilities remind one of a fat, cholesterin is not a fat. It is, in fact, chemically speaking, a monatomic alcohol. Its formula is C 27 H 45 .HO. From alcohol or ether containing water it crystallises in the form of rhombic tables, which contain one molecule of water of crystal- lisation : these are easily recognised under the microscope (see fig. 409). 512 THE LIVEK [CJI. XXXIII. It gives the following colour tests : — 1. Heated with sulphuric acid and water (5 : 1), the edges of the crystals turn red. 2. A solution of cholesterin in chloroform, shaken with an equal amount of concentrated sulphuric acid, turns red, and ultimately purple, the subjacent acid accpuiring a green fluorescence. (Salkowski's reaction.) " The mode of origin of cholesterin in the body has not been clearly made out. Whether it is formed in the tissues generally, in the blood, or in the liver, is not known ; nor has it been determined conclusively that it is derived from albuminous or nervous matter. It is also doubtful if we are to regard it as a waste substance of no use to the body, as its presence in the blood-corpuscles, in nervous matter, in the egg, and in vegetable grains, points to a possible function of a histogenetic or tissue-forming character." (McKendrick.) A substance called iso-cholesterin, isomeric with ordinary chole- sterin, is found in the fatty secretion of the skin (sebum) ; it is largely contained in the preparation called lanoline made from sheep's- wool fat. It does not give Salkowski's reaction with chloroform and sulphuric acid just described. The Uses of Bile. — Bile is doubtless, to a large extent, excretory. Some state that it has a slight action on fats and carbohydrates, but its principal action is as a coadjutor to the pancreatic juice (especially in the digestion of fat). In some animals it has a feeble diastatic power. Bile is said to be a natural antiseptic, lessening the putrefactive processes in the intestine. This is very doubtful. Though the bile salts are weak antiseptics, the bile itself is readily putrescible, and the power it has of diminishing putrescence in the intestine is due chiefly to the fact that by increasing absorption it lessens the amount of putrescible matter in the bowel. When the bile meets the chyme the turbidity of the latter is increased owing to the precipitation of unpeptonised proteid. This is an action due to the bile salts, and it has been surmised that this conversion of the chyme into a more viscid mass is to hinder some- what its progress through the intestines ; it clings to the intestinal wall, thus allowing absorption to take place. Bile is alkaline ; it therefore assists the pancreatic juice in neutral- ising the acid mixture that leaves the stomach. Bile assists the absorption of fats, as we shall see in studying that subject. It is also a solvent of fatty acids. We have seen that fistula bile is poor in solids as compared with normal bile, and that this is explained on the supposition that the normal bile circulation is not occurring — the liver cannot excrete CH. XXXIII.] THE BILE 513 what it does not receive back from the intestine. Schiff was the first to show that if the bile is led back into the duodenum, or even if the animal is fed on bile, the percentage of solids in the bile excreted is at once raised. It is on these experiments that the theory of a bile circulation is mainly founded. The bile circulation relates, however, chiefly, if not entirely, to the bile salts : they are found but sparingly in the fasces ; they are only represented to a slight extent in the urine : hence it is calculated that seven-eighths of them are re-absorbed from the intestine. Small quantities of cholalic acid, taurine, and glycine are found in the faeces ; the greater part of these products of the decom- position of the bile salts is taken by the portal vein to the liver, where they are once more synthesised into the bile salts. Some of the taurine is absorbed and excreted as tauro-carbamic acid in the urine. Some of the absorbed glycine may be excreted as urea or uric acid. The cholesterin and mucus are found in the fasces ; the pigment is changed into stercobilin (see p. 511). The bile-expelling mechanism must be carefully distinguished from the bile-secreting action of the liver-cells. The bile is forced into the ducts, and ultimately into the duodenum, by the pressure of newly-formed bile pressing on that previously in the ducts, and this is assisted by the contraction of the plain muscular fibres of the larger ducts and gall-bladder, which occurs reflexly when the food enters the duodenum. In cases of obstruction, as by a gall-stone, in the ducts, this action becomes excessive, and gives rise to the intense pain known as hepatic colic. Many so-called cholagogues (bile-drivers), like calomel, act on the bile-expelling mechanism and increase the peristalsis of the muscular tissue ; they do not really cause an increased formation of bile. Jaundice. — The commonest form of jaundice is produced by obstruction in the bile ducts preventing the bile entering the intestine. A very small amount of obstruction, for instance, a plug of mucus produced in excess owing to inflammatory pro- cesses, will often be sufficient, as the bile is secreted at such low pressure. Under these circumstances, the fasces are whitish or clay coloured, and the bile passing backwards into the lymph,* enters the blood and is thus distributed over the body, causing a yellow tint in the skin and mucous membranes, and colouring the urine deeply. In some cases of jaundice, however {e.g., produced by various poisons), there is no obvious obstruction ; the causes of non- obstructive, or blood-jaundice, form a pathological problem of some interest. A few years ago it was believed that the bile pigment was * The absorption is by the lymph, because if jaundice is produced in an animal by ligature of the bile duct, it will cease when the thoracic duct is tied. 2 K 514 THE LIVElt [CH. XXXIll. actually produced in the blood. But all recent work shows that the liver is the only place where production of bile occurs, and that in all cases of so-called non-obstructive jaundice, the bile is absorbed from the liver. There may be obstruction present in the smaller ducts, or the functions of the liver may be so upset that the bile passes into the lymph even when there is no obstruction. The Glycogenic Function of the Liver. The important fact that the liver normally forms sugar, or a substance readily convertible into it, was discovered by Claude Bernard in the following way: he fed a dog for seven days with food containing a large quantity of sugar and starch ; and, as might be expected, found sugar in both the portal and hepatic blood. But when this dog was fed with meat only, to his surprise, sugar was still found in the blood of the hepatic veins. Eepeated experiments gave invariably the same result ; no sugar was found, under a meat diet, in the portal vein, if care were taken, by applying a ligature on it at the transverse fissure, to prevent reflux of blood from the hepatic venous system. Bernard found sugar also in the substance of the liver. It thus seemed certain that the liver formed sugar, even when, from the absence of saccharine and amyloid matters in the food, none could have been brought directly to it from the stomach or intestines. Bernard found, subsequently, that a liver, removed from the body, and from which all sugar had been completely washed away by injecting a stream of water through its blood-vessels, contained sugar in abundance after the lapse of a few hours. This post-mortem pro- duction of sugar was a fact which could only be explained on the supposition that the liver contained a substance readily convertible into sugar; and this theory was proved to be correct by the dis- covery of a substance in the liver allied to starch, and now termed glycogen or animal starch. We are thus led to the conclusion that glycogen is formed first and stored in the liver cells, and that the sugar, when present, is the result of its transformation. Source of Glycogen. — Although the greatest amount of glycogen is produced by the liver upon a diet of starch or sugar, a certain quantity is produced upon a proteid diet. It must, then, be produced by protoplasmic activity within the cells. The glycogen when stored in the liver cells may readily be demonstrated in sections of liver containing it by its reaction (red or port-wine colour) with iodine, and moreover, when the hardened sections are soaked in water in order to dissolve out the glycogen, the protoplasm of the cell is so vacuolated as to appear little more than a framework. In the liver of a hiber- CH. XXXIII.] GLYCOGENIC FUNCTION 515 nating frog the amount of glycogen stored up in the outer parts of the liver cells is very considerable. Average Amount of Glycogen in the Liver of Dogs under various Diets (Pavy). Amount of Diet. Glycogen in Liver. Animal food 7*19 per cent. Animal food with sugar (about J-lb of sugar daily) . 14 "5 ,, Vegetable diet (potatoes, with bread or barley-meal) . 17*23 ,, The dependence of the formation of glycogen on the kind of food taken is also well shown by the following results, obtained by the same experimenter : — Average Quantity of Glycogen found in the Liver of Rabbits after Fasting, and after a Diet of Starch and Sugar respectively. Average amount of Glycogen in Liver. After fasting for three days Practically absent. „ diet of starch and grape-sugar . . . 15 "4 per cent. ,, ,, cane-sugar 16*9 ,, The diet most favourable to the production of a large amount of glycogen is a mixed diet containing a large amount of carbohydrate, but with some proteid. Fats taken in as food do not increase the amount of glycogen in the cells. Glycerin injected into the ali- mentary canal may increase the glycogen of the liver, probably because it hinders the conversion of glycogen into sugar ; the glycogen therefore is allowed to accumulate in the liver. Destination of Glycogen. — There are two chief theories as to the destination of hepatic glycogen. (1.) That the glycogen is converted into sugar during life by the agency of a ferment (liver diastase) also formed in the liver ; and that the sugar is conveyed away by the blood of the hepatic veins, to undergo combustion in the tissues. (2.) That the conversion into sugar only occurs after death, and that during life no sugar exists in healthy livers, glycogen not undergoing this transformation. The first view is that of Claude Bernard, and has been adopted by the majority of physiologists. The second view is that of Pavy: he denies that the liver is a sugar-forming organ, he regards it as a sugar-destroying organ; the sugar is stored as animal starch, but never again leaves the liver as sugar during life. He has been unable to find more sugar in the hepatic blood than in the portal blood. Other observers have found an increase in the sugar of the blood leaving the liver, but the estimation of sugar in a fluid rich in proteids is a matter of great difficulty. Even if the increase is so small as hardly to be detected, it must be remembered that the whole blood of the body passes through the liver about twice a minute, so that a very small increase each time would mount up to a large total. 516 THE LIVER [CH. XXXIIL Pavy further denies that the post-mortem formation of sugar from glycogen that occurs in an excised liver is a true picture of what occurs during life, but is due to a ferment which is only formed after death. During life, he regards the glycogen as a source of other substances, Like fat and proteid. It is certainly a fact that increase of carbohydrate food leads to the formation of fat in the body and in the liver-cells. In support of the theory that glycogen may also con- tribute to the formation of proteids, he has shown that many proteids contain a carbohydrate radicle. The whole question is under keen discussion at present. We may state, however, that the prevalent opinion is that the liver- cells may be able to convert part of the store of glycogen into fat, but that most of the glycogen leaves the liver as sugar (dextrose), so justifying the name (literally, mother substance of sugar) given to it by Bernard. Diabetes. — In certain disorders of hepatic metabolism, the glycogenic function is upset, and excess of sugar passes into the blood, leaving the body in the urine {glycosuria). This may be due to an increased formation of sugar from glycogen, or to a diminished formation of glycogen from the sugar of the portal blood, according as either Bernard's or Pavy's view of the liver function is adopted. In many cases the diabetic condition may be removed by a close attention to diet; starchy and saccharine food must be rigidly abstained from. In other cases, which are much more serious, diet makes little or no difference. Under these circumstances the sugar must come from the metabolism of the proteid constituents of protoplasm. The disease diabetes is not a single one ; the term includes many pathological conditions, which all possess in common the symptom of excess of sugar in the blood and urine. A diabetic condition may be produced in animals artificially in several ways : — (1) By diabetic puncture. — Claude Bernard was the first to show that injury to the floor of the fourth ventricle in the region of the vaso-motor centre leads to glycosuria. The injury produces a dis- turbance of the vaso-motor mechanism, but diabetes cannot be regarded as purely vaso-motor in origin. This condition is of interest, because brain disease in man, especially in the region of the bulb, is frequently associated with glycosuria. (2) By extirpation of the pancreas. — (See also p. 500). It is probable that in diabetes, the oxidative powers of the body-cells are lessened. Nevertheless, other diseases in which diminished oxidation occurs are not necessarily accompanied with glycosuria. The diffi- culty in diabetes probably lies in an impairment of the capacity of the cells of the body to prepare the sugar for oxidation. In thia Cn. XXXIII.] DIABETES 517 process the sugar or its derivative glycuronic acid is split into smaller molecules and ultimately into water and carbon dioxide. The close relationship of sugar and glycuronic acid is shown by the following formulae : — COH COH (CHOH) 4 (CHOH) 4 CH 2 OH COOH [Dextrose.] [Glycuronic acid.] That is two hydrogen atoms in the CH 2 OH group are replaced by one of oxygen. This oxidation is readily brought about in the body, and glycuronic acid is usually found in diabetic urine ; but the further oxidation into water and carbon dioxide is a more difficult task, because it involves the disruption of the linkage of the carbon atoms. Perhaps it is here that the internal secretion of the pancreas is effective. This, however, is at present a mere theory, and certainly Lepine's idea that the ferment of the pancreatic internal secretion is one which initiates glycolysis or sugar-splitting in the Mood, has been abundantly disproved. It may be that the active principle of the pancreatic internal secretion stimulates the glycolytic action of the tissue-cells. It is conceivable that in the other great cause of glycosuria, namely, injury to nervous structures, as in Bernard's puncture experiment, the derangement of the nervous system exerts some unknown influence on the pancreas as well as on the liver. (3) By administration of phloridzin. — Many poisons produce temporary glycosuria, but the most interesting and powerful of these is phloridzin. The diabetes produced is very intense. Phloridzin is a glucoside, but the sugar passed in the urine is too great to be accounted for by the small amount of sugar derivable from the drug. Besides that, phloretin, a derivative of phloridzin, free from sugar, produces the same results. Phloridzin produces diabetes in starved animals, or in those in which any carbohydrate store must have been got rid of by the previous administration of the same drug. Phloridzin-diabetes is therefore analogous to those intense forms of diabetes in man in which the sugar must be derived from protoplasmic metabolism. A puzzling feature is the absence of an increase of sugar in the blood ; if the phloridzin is directly injected into one renal artery, sugar rapidly appears in the secretion of that kidney ; the sugar is formed within the kidney cells from some substance in the blood, but whether that substance is proteid or not is uncertain. The action of the kidney cells in forming sugar has been compared to that of the mammary cells in forming lactose. Acetonemia. — Death in diabetic patients is usually preceded by deep coma, or unconsciousness. Some poison must be produced that acts soporifically upon the brain. The breath and urine of these 518 THE LIVER [CH. XXXIII. patients smell strongly of acetone ; hence the term acetonemia. This apple-like smell should always suggest the possible onset of coma and death, but it is exceedingly doubtful whether acetone (which can certainly be detected in the urine) is the true poison ; ethyl-diacetic acid, which accompanies, and is the source of the acetone, was regarded by some as the actual poison, but these substances, when introduced into the circulation artificially, do not cause serious symptoms. The principal poison is amido-hydroxy butyric acid. The alkalinity and carbonic acid of the blood are decreased, and the ammonia of the urine is increased ; this indicates an attempt of the body to neutralise the poisonous acids. The Nerves of the Liver. Claude Bernard observed that an increase of sugar in the blood is brought about by stimulation of the central and peripheral ends of the divided vagus, and that on the section of both vagi sugar dis- appears from the blood, and glycogen from the liver and tissues generally. These results have been confirmed in recent experiments, and it has been in addition found that stimulation of the cceliac plexus also leads to a loss of glycogen in the liver, with a correspond- ing production of glucose that passes into the blood. The disappear- ance of glycogen from the liver cells after the stimulation of these nerves can also be seen histologically (Cavazzani). These results are due to a direct influence of the nerves on the liver cells, for they are obtained after the circulation is stopped by ligature of the aorta and portal vein (Morat and Dufourt). Vaso-motor nerves. — The vaso-constrictor fibres for the portal vein leave the spinal cord in the third to the eleventh thoracic nerves inclusive (Bayliss and Starling). The nerves of the hepatic artery are constrictors contained in the splanchnic, and dilators in both splanchnic and vagus. CHAPTEE XXXIV THE ABSORPTION OF FOOD Food is digested in order that it may be absorbed. It is absorbed in order that it may be assimilated, that is, become an integral part of the living material of the body. The digested food thus diminishes in quantity as it passes along the alimentary canal, and the faeces contain the undigested or indi- gestible residue. In the mouth and oesophagus the thickness of the epithelium and the quick passage of the food through these parts reduce absorption to a minimum. Absorption takes place more rapidly in the stomach : the small intestine with its folds and villi to increase its surface is, however, the great place for absorption ; and although the villi are absent from the large intestine, absorption occurs there also, but to a less extent. Foods such as water and soluble salts like sodium chloride are absorbed unchanged. The organic foods are, however, considerably changed, colloid materials like starch and proteid being converted respectively into the diffusible materials sugar and peptone. There are two channels of absorption, the blood-vessels (portal capillaries) and the lymphatic vessels or lacteals. Absorption, however, is no mere physical process of osmosis and nitration. We must also take into account the fact that the cells through which the absorbed substances pass are living, and in virtue of their inherent activity not only select materials for absorption, but also change those substances while in contact with them. These cells are of two kinds — (1) the columnar epithelium that covers the surface ; and (2) the lymph cells in the lymphoid tissue beneath. It is now generally accepted that of the two the former, the columnar epithelium, is the more important. Absorption of Carbohydrates. — Though the sugar formed from starch by ptyalin and amylopsin is maltose, that found in the blood is glucose. Under normal circumstances little, if any, is absorbed by the lacteals. The glucose is formed from the maltose by the succus entericus, aided by the action of the epithelial cells through which it m 520 THE ABSORPTION OF FOOD [cil. XXXIV. passes. Cane sugar and milk sugar are also converted into glucoses before absorption. The carbohydrate food which enters the blood as glucose is taken to the liver, and there stored up in the form of glycogen — a reserve store of carbohydrate material for the future needs of the body. Glycogen, however, is found in animals who take no carbohydrate foad. It must, then, be formed by the protoplasmic activity of the liver cells from their proteid constituents. The glycogenic function of the liver is discussed in the chapter preceding this. Glucose is the only sugar from which the liver is capable of forming glycogen. If other carbohydrates like cane sugar or lactose are injected into the blood-stream direct, they are unaltered by the liver, and finally leave the body by the urine. Absorption of Proteids. — A certain amount of soluble proteid is absorbed unchanged. Thus, after taking a large number of eggs, egg albumin is found in the urine. Patients fed per rectum derive nourishment from proteid food, though proteolytic ferments are not present in this part of the intestine. Most proteid, however, is normally absorbed as peptone and proteose or their decomposition products. Peptones and proteoses are absent from the blood under all circumstances, even from the portal blood during the most active digestion. In other words, during absorption the epithelial cells change the products of proteolysis back once more into native proteids (albumin and globulin). The greater part of the proteid absorbed passes into the blood ; a little into the lymph also; but this undergoes the same change. When peptone (using the word to include the proteoses also) is injected into the blood-stream, poisonous effects are produced, the coagulability of the blood is lessened, the blood-pressure falls, secre- tion ceases, and in the dog 0'3 gramme of "peptone" per kilogramme of body-weight is sufficient to kill the animal. The epithelial cells of the alimentary canal thus protect us from those poisonous effects by converting the harmful peptone into the useful albumin. The whole question of proteid absorption is in a very unsettled state just now. Cohnheim*s discovery of erepsin (p. 497) appears to lend support to the view that the peptones are very largely broken up into simpler substances, but the absence of these in the blood-stream shows that the absorptive epithelium is capable of resynthesising them into proteids. Several observers have noted the small amount of peptones obtainable from the intestinal contents ; this may be due to the fact that they are so rapidly absorbed, or it may be due to their having been broken up into simpler substances by trypsin and erepsin. On the other hand, there are some observers who hold that the importance of erepsin has been exag- gerated, and that the absorptive epithelium can also resynthesise proteids from proteoses and peptone. It is, however, undeniable that the body can be maintained in health and nitrogenous equilibrium by feeding it on the final cr3 r stalline products of pancreatic action (Loewi), and it is probable that the synthesis of the body proteids from these is accomplished mainly by the intestinal epithelium. CH. XXXIV.] ABSORPTION OF FATS 521 Absorption of Pats. — The fats undergo in the intestine two changes : one a physical change (emulsification), the other a chemical change (saponification). The lymphatic vessels are the great channels for fat absorption, and their name lacteals is derived from the milk- like appearance of their contents (chyle) during the absorption of fat. The course which the minute fat-globules take may be studied by killing animals at varying periods after a meal of fat, and making osmic acid microscopic preparations of the villi. Figs. 410 and 411 illustrate the appearances observed by Schafer. The columnar epithelium cells become first filled with fatty globules of varying size, which are generally larger near the free border. The globules pass down the cells, the larger ones break- ing up into smaller ones during the journey; they are then transferred to the amoeboid cells of the lym- phoid tissue beneath : these ultimately penetrate into the central lacteal, where they either disintegrate or discharge their cargo into the lymph - stream. The globules are by this time divided into immeasurably small ones, the molecular^ basis of chyle. The chyle ' enters the blood-stream by the thoracic duct, and after an abundant fatty meal the blood-plasma is quite milky ; the fat droplets are so small that they circulate without hindrance through the capillaries. The fat in the blood after a meal is eventually stored up especially in the cells of adipose tissue. It must, however, be borne in mind that the fat of the body is not exclusively derived from the fat of the food, but it may originate also both from proteid and from carbohydrate. The great difficulty in fat absorption was to explain how the fat first gets into the columnar epithelium : these cells will not take up other particles, and it appears certain that the epithelial cells do not in the higher animals protrude pseudopodia from their borders (this, however, does occur in the endoderm of some of the lower inverte- Fig. 410.— Section of the villus of a rat killed during fat g;a- absorption, ep, epithelium ; str, striated border ; j°l>:C, lymph-cells; c', lymph-cells in the epithelium; "i/itnZ, central lacteal containing disintegrating lymph- ."■ — corpuscles. (E. A. Schafer.) 522 THE ABSORPTION OF FOOD [OH. XXXIV brates) ; moreover, fat particles have never been seen in the striated border of the cells. Eecent research has shown that particles may be present in the epithelium and lymphoid cells while no fat is being absorbed. These particles are apparently protoplasmic in nature, as they stain with reagents that stain protoplasmic granules ; they, however, also stain darkly with osmic acid, and so are apt to be mistaken for fat. There is, however, no doubt that the particles found during fat absorption are composed of fat. There is also no doubt that the epithelial cells have the power of forming fat out of the fatty acids and glycerin into which fats have been broken up in the intestine. Munk, who has performed a large number of experiments on the subject, showed that the splitting of fats into glycerin and fatty acids occurs to a much greater extent than was formerly supposed ; these substances, being soluble, pass readily into the epithelium cells ; and these cells per- form the synthetic act of building them into fat once more, the fat so formed appearing in the form of small globules, surrounding or becoming mixed with the protoplasmic granules that are ordinarily present. Another remarkable fact which he made out is that after feeding an animal on fatty acids the chyle contains fat. The necessary glycerin must have been formed by protoplasmic activity during absorption. The more recent work of Moore and Rockwood has shown that fat is absorbed entirely as fatty acid or soap ; and that preliminary emulsification, though advantageous for the formation of these substances, is not essential. We thus see how with increase of knowledge due to improved methods of research, a complete change has come in the ideas physio- logists hold regarding this r.xbject. It is not so many years ago, that the physical change — emulsification — which fats undergo in the intestine was considered to be more important than the chemical changes — fat-splitting and saponification. In fact, the small amount of chemical change which was supposed to occur was regarded as quite subordinate, and of value merely in assisting the process of emulsification. We now know that the exact converse is the truth ; the chemical change is the important process, and emulsification the subordinate one. Bile aids the digestion of fat, in virtue of its being a solvent of fatty acids, and it probably assists fat absorption by reducing the surface tension of the intestinal contents; membranes moistened Fig. 411. — Mucous membrane of frog's intes- tine during fat absorption, ep, epithe- lium; sir, striated border; C, lymph corpuscles ; I, lacteal. (E. A. Schafer.) CH. XXXIV.] PHYSIOLOGICAL FACTOE IN ABSOEPTION 523 with bile allow fatty materials to pass through them more readily than would otherwise be the case. In cases of disease in which bile is absent from the intestines, a large proportion of the fat in the food passes into the faeces. Since the days of Lieberkuhn it has been the desire of physiologists to prove that the absorption of solutions from the intestines can be explained upon some simple physical basis. Thus the processes of nitration, osmosis, and imbibition, either alone or in combination, have been in turn called upon as affording the requisite explanation. Such theories have alternated with others in which the physical cause has been either wholly or in part rejected as inadequate, and the deficiencies of the physical cause supplemented by the physiological, vital, or selective action of the epithelial lining of the alimentary tract. The difficulty of the problem does not, however, entirely depend on the impos- sibility of defining the word vital, but also on the complicated nature of the physical processes to which we have alluded. Since the days when Fischer and Dutrochet inaugurated our elementary knowledge of osmotic phenomena, a great amount of research has been expended in making that knowledge more accurate, but even at the present day it is doubtfid whether all the aspects of the question are fully understood (see also p. 321). The subject has, in recent years, been taken up by Waymouth Reid, who has made a life-study of such phenomena, and whose work must be regarded as authoritative. The animals he experimented on were dogs, and the material selected for absorption was the serum or plasma of the blood from the same animals. The sub- stances to be absorbed were thus of the same kind as those in the blood and lymph on the other side of the absorptive epithelium. The serum or plasma was analysed, introduced into an isolated loop of the gut, and at the end of a given time the con- tents of the loop were again analysed. The pressure in the loop and in the mesen- teric veins was estimated manometrically during the progress of the experiment ; allowance was made for the secretion of intestinal juice, and other precautions taken to make each experiment as complete as possible. It was found that the absorption by an animal of its own serum or plasma takes place under conditions in which nitration or osmosis into blood capillaries or lacteals and also adsorption (or imbibition) are excluded. The active force must therefore by a process of exclusion reside in the physiological activity of the lining epithelium. The same conclusion was reached by another method, namely, that when the epithelium is removed, injured or poisoned, the absorption either ceases or is markedly lessened, and this in spite of the fact that removal of the epithelium must increase the facilities for osmosis and nitration. The activity of the cells is characterised by a slower uptake of the organic solids of the serum than of water, and a quicker uptake of the salts than of the water ; but the absolute numerical relations vary in different regions of the intestine. The state of nutrition of the cells is the main factor in their activity ; specific absorptive nerve-fibres were sought for, but not found. The absorption of water from the gut depends partly on the physical relation of the osmotic pressure of the solution in the intestine to that of the blood plasma ; but even the absorption of water is influenced by the physiological regulation of this difference by the directing or, as it may be termed, orienting mechanism of the cells. Such orienting action was first noted in connection with salts by Otto Cohnheim ; he showed that, in an intestinal loop with injured cells, sodium chloride enters its lumen from the blood though the same salt is being actively absorbed from a normal loop in the same animal at the same time. In all probability the cell activity which causes the organic constituents of serum to pass into the blood is of the same nature as that involved in the orienting action of the cells upon salts in solution. Reid's conclusions with regard to the absorption of peptone and sugar are as follows : — The chief factor in the absorption of peptone is an assimilation (or absorption) by the cells, while in the absorption of glucose diffusion variable by the permeability of the cells (and so probably related to their physiological condition) is 524 THE ABSORPTION OF FOOD [CH. XXXIV. the main factor. By removal of the epithelium the normal ratio of peptone to glucose absorption is upset, and the value tends to approach that of diffusion of these substances through parchment papor into serum. The faeces are alkaline, and contain the following substances : — 1. Water : in health from 68 to 82 per cent. ; in diarrhoea it is more abundant still. 2. Undigested food; that is, if food is taken in excess, some escapes the action of the digestive juices. On a moderate diet unaltered proteid is never found. 3. Indigestible constituents of the food : cellulose, keratin, mucin, chlorophyll, gums, resins, cholesterin. 4. Constituents digestible with difficulty : uncooked starch, tendons, elastin, various phosphates, and other salts of the alkaline earths. 5. Products of decomposition of the food : indole, skatole, phenol, acids such as fatty acids, lactic acid, etc. ; hsematin from haemoglobin ; insoluble soaps like those of calcium and magnesium. 6. Bacteria of all sorts, and debris from the intestinal wall ; cells, nuclei, mucus, etc. 7. Bile residues : mucus, cholesterin, traces of bile acids and their products of decomposition, stercobilin from the bile pigment. The average quantity of solid faecal matter passed by the human adult per diem is 6 to 8 ounces. Meconium is the name given to the greenish-black contents of the intestine of new-born children. It is chiefly concentrated bile, with de'bris from the intestinal wall. The pigment is a mixture of bilirubin and biliverdin, not stercobilin. CHAPTER XXXV THE MECHANICAL PEOCESSES OF DIGESTION UndEr this head we shall study the neuro-inuscular mechanism of the alimentary canal, which has for its object the onward movement of the food, and its thorough admixture with the digestive juices. We shall therefore have to consider mastication, deglutition, the move- ments of the stomach and intestines, defalcation, and vomiting. Mastication. The act of mastication is performed by the biting and grinding movement of the lower range of teeth against the upper. The simultaneous movements of the tongue and cheeks assist partly by crushing the softer portions of the food against the hard palate and gums, and thus supplement the action of the teeth, and partly by returning the morsels of food to the teeth again and again, as they are squeezed out from between them, until they have been sufficiently chewed. The act of mastication is much assisted by the saliva, and the intimate incorporation of this secretion with the food is called insalivation. Mastication is much more thoroughly performed by some animals than by others. Thus, dogs hardly chew their food at all, but the oesophagus is protected from abrasion by a thick coating of very viscid saliva which lubricates the pieces of rough food. In vegetable feeders, on the other hand, insalivation is a much more important process. This is especially so in the ruminants ; in these animals, the grass, etc., taken, is hurriedly swallowed, and passes into the first compartment of their four-chambered stomach. Later on, it is returned to the mouth in small instalments for thorough mastication and insalivation ; this is the act of rumination, or u chewing the cud " ; it is then once more swallowed and passes on to the digestive regions of the stomach. In man, mastication is also an important process, and in people 525 526 THE MECHANICAL PROCESSES OF DIGESTION [CH. XXXV. who have lost their teeth severe dyspepsia is often produced, which can be cured by a new set of teeth. Deglutition. When properly masticated, the food is transmitted in successive portions to the stomach by the act of deglutition or swallowing. This, for the purpose of description, may be divided into three acts. In the first, particles of food collected as a bolus are made to glide between the surface of the tongue and the palatine arch, till they have passed the anterior arch of the fauces ; in the second, the morsel is carried through the pharynx; and in the third, it reaches the stomach through the oesophagus. These three acts follow each other rapidly. (1.) The first act is voluntary, although it is usually per- formed unconsciously; the morsel of food when sufficiently masti- cated, is pressed between the tongue and palate, by the agency of the muscles of the former, in such a manner as to force it back to the entrance of the pharynx. (2.) The second act is the most complicated, because the food must go past the posterior orifice of the nose and the upper opsning of the larynx without entering them. When it has bssn brought, by the first act, between the anterior arches of the palate, it is moved onwards by the movement of the tongue backwards, and by the muscles of the anterior arches contracting on it and then behind it. The root of the tongue being retracted, and the larynx being raised with the pharynx and carried forwards under the base of the tongue, the epiglottis is pressed over the upper opening of the larynx, and the morsel glides past it; the closure of the glottis is additionally secured by the simultaneous contraction of its own muscles : so that, even when the epiglottis is destroyed, there is little danger of food passing into the larynx so long as its muscles can act freely. In man, and some other animals, the epiglottis is not drawn as a lid over the larynx during swallowing. At the same time, the raising of the soft palate, so that its posterior edge touches the back part of the pharynx, and the approximation of the sides of the posterior palatine arch, which move quickly inwards like side curtains, close the passage into the upper part of the pharynx and the posterior nares, and form an inclined plane, along the under surface of which the morsel descends ; then the pharynx, raised up to receive it, in its turn contracts, and forces it onwards into the oesophagus. The passage of the bolus of food through the three constrictors of the pharynx is the last step in this stage. (3.) In the third act, in which the food passes through the oesophagus, every part of that tube, as it receives the morsel and is dilated by it, is stimulated to contract : hence an undulatory or peristaltic contraction of the oesophagus occurs, which is easily observable through the skin in long-necked animals like the CH. XXXV.] DEGLUTITION 527 swan. If we suppose the bolus to be at one particular place in the tube, it acts stimulatingly on the circular muscular fibres behind it, and inhibitingly on those in front ; the contraction therefore squeezes it into the dilated portion of the tube in front, where the same pro- cess is repeated, and this travels along the whole length of the tube. The second and third parts of the act of deglutition are involuntary. The action of these parts is more rapid than peristalsis usually is. This is due to the large amount of striated muscular tissue present. It serves the useful purpose of getting the bolus as quickly as possible past the opening of the respiratory tract. Nervous Mechanism. — The nerves engaged in the reflex act of deglutition are : — sensory, branches of the fifth cranial nerve supplying the soft palate and tongue; glossopharyngeal, supplying the tongue and pharynx ; the superior laryngeal branch of the vagus, supplying the epiglottis and the glottis ; while the motor fibres concerned are : — branches of the fifth, supplying part of the digastric and mylo-hyoid muscles, and the muscles of mastication; the bulbar part of the spinal accessory through the pharyngeal plexus, supplying the levator palati, probably by rootlets which are glosso-pharyngeal in origin ; the glosso-pharyngeal and vagus, and possibly the bulbar part of the spinal accessory, supplying the muscles of the pharynx through the phar- yngeal plexus; the vagus, in virtue of its spinal accessory roots, supplying the muscles of the larynx through the inferior laryngeal branch ; and the hypo-glossal, the muscles of the tongue. The nerve- centre by which the muscles are harmonised in their action, is situated in the medulla oblongata. Stimulation of the vagi gives rise to peri- stalsis of the oesophagus. The cell stations of these fibres are in the ganglion trunci vagi. Division of both pneumogastric nerves gives rise to paralysis of the oesophagus and stomach, and firm contraction of the cardiac orifice. These nerves therefore normally supply the oesophagus with motor, and the cardiac sphincter with inhibitory fibres. If food is swallowed after these nerves are divided, it accumu- lates in the gullet and never reaches the stomach. In discussing peristalsis on a previous occasion (p. 158), we arrived at the conclusion that it is an inherent property of muscle rather than of nerve ; though normally it is controlled and influenced by nervous agency. This nervous control is especially marked in the oesophagus; for if that tube is divided across, leaving the nerve branches intact, a wave of contraction will travel from one end to the other across the cut. Swallowing of Fluids. — The swallowing both of solids and liquids is a muscular act, and can, therefore, take place in opposition to the force of gravity. Thus, horses and many other animals habitually drink up-hill, and the same feat can be performed by jugglers. 528 THE MECHANICAL PROCESSES OF DIGESTION [CII. XXXV. In swallowing liquids the two mylo-hyoid muscles form a diaphragm below the anterior part of the mouth. The stylo-glossi draw the tongue backwards and elevate its base ; the two hyo-glossi act with these, pulling the tongue backwards and downwards. The action of these muscles resembles that of a force-pump projecting the mass of fluid down into the oesophagus; it reaches the cardiac orifice with great speed, and the pharyngeal and oesophageal muscles do not contract on it at all, but are inhibited during the passage of the fluid through them (Kronecker). This is proved in a striking way in cases of poisoning by corrosive substances like oil of vitriol ; the mouth and tongue are scarred and burnt, but the pharynx and oesophagus escape serious injury, so rapidly does the fluid pass along them; the cardiac orifice of the stomach is the next place to show the effects of the corrosive. There is, however, no hard-and-fast line between the swallowing of solids and fluids : the more liquid the food is, the more does the force-pump action just described manifest itself. Movements of the Stomach. The gastric fluid is assisted in accomplishing its share in digestion by the movements of the stomach. In graminivorous birds, for example, the contraction of the strong muscular gizzard affords a necessary aid to digestion, by grinding and triturating the hard seeds which constitute their food. But in the stomachs of man and other Mammalia the movements of the muscular coat are too feeble to exercise any such mechanical force on the food ; neither are they needed, for mastication has already done the mechanical work of a gizzard ; and it has been demonstrated that substances are digested even when enclosed in perforated tubes, and consequently protected from mechanical influence. When digestion is not going on, the stomach is uniformly con- tracted, its orifices not more firmly than the rest of its walls ; but, if examined shortly after the introduction of food, it is found closely encircling its contents, and its orifices are firmly closed like sphincters. The cardiac orifice, every time food is swallowed, opens to admit its passage into the stomach, and immediately again closes. The pyloric orifice, during the first part of gastric digestion, is usually so com- pletely closed, that even when the stomach is separated from the intestines, none of its contents escape. But towards the termination of the digestive process, the pylorus offers less resistance to the passage of substances from the stomach ; first it yields to allow the successively digested portions to go through it ; and then it allows the transit even of undigested substances. The peristaltic action of the muscular coat, whereby the digested portions are gradually CH. XXXV.] MOVEMENTS OF THE STOMACH 529 moved towards the pylorus, also ensures thorough admixture with the gastric juice. The movements are observed to increase as the process of chymification advances, and are continued until it is completed. The contraction of the fibres situated towards the pyloric end of the stomach is more energetic and more decidedly peristaltic than those of the cardiac portion. Thus, it was found in the case of St Martin, that when the bulb of a thermometer was placed about three inches from the pylorus, through the gastric fistula, it was tightly embraced from time to time, and drawn towards the pyloric orifice for a distance of three or four inches. The object of this movement appears to be, as just said, to carry the food towards the pylorus as fast as it is formed into chyme, and to propel the chyme into the duodenum ; the undigested portions of food are kept back until they are also reduced into chyme, or until all that is digestible has passed out. The action of these fibres is often seen in the con- tracted state of the pyloric portion of the stomach after death, when it alone is contracted and firm, while the cardiac portion forms a dilated sac. Sometimes, by a predominant action of strong circular fibres placed between the cardia and pylorus, the two portions, or ends, as they are called, of the stomach, are partially separated from each other by a kind of hour-glass contraction. The subject has recently been taken up by Cannon. He gave an animal food mixed with bismuth subnitrate, and obtained by the Eontgen rays shadow photographs of the stomach, because the bismuth salt renders its contents opaque. His results mainly confirm those of the earlier investigators; the principal peristalsis occurs in the pyloric portion of the stomach. The cardiac portion presses steadily on its contents, and as they become chymified, urges them onwards towards the pyloric portion; the latter empties itself gradually through the pylorus into the duodenum, and in the later stages of digestion the cardiac part also is constricted into a tube. Under ordinary circumstances, three or four hours may be taken as the average time occupied by the digestion of a meal in the stomach. But the digestibility and quantity of the meal, and the state of body and mind of the individual, are important causes of variation. The pylorus usually opens for the first time about twenty minutes after digestion begins; it, however, quickly closes again. The acid chyme provides a chemical stimulus for pancreatic secretion, and the strongly alkaline pancreatic juice neutralises it; as soon as the intestinal contents are neutral, the pylorus again opens, more acid chyme is thrust into the duodenum; more pancreatic juice provided ; and so on until the stomach is finally emptied. Influence of the Nervous System. — The normal movements of the stomach during gastric digestion are in part controlled by the 2 L 530 THE MECHANICAL PROCESSES OF DIGESTION [CII. XXXV. plexuses of nerves and ganglia contained in its walls. The stomach is also connected with the higher nerve-centres by means of branches of the vagi and of the splanchnic nerves through the solar plexus. The vagi (especially the left) contain the acclerator nerves of the stomach ; when they are stimulated the result is peristaltic move- ment. The sympathetic fibres are inhibitory ; when they are stimu- lated peristalsis ceases. The cell stations on the course of the vagus fibres are in the ganglion trunci vagi ; the post-ganglionic fibres that issue from this ganglion are non-medullated. The sympathetic fibres leave the spinal cord by the anterior roots of the spinal nerves from the fifth to the eighth thoracic. They pass into the sympathetic system, have cell stations in the cceliac ganglion, and ultimately pass to the stomach by the splanchnic nerves. It seems probable that automatic rhythmical contraction is inherent in the muscular coat of the stomach, and that the central nervous system is only employed to regulate it by impulses passing down by the vagi or splanchnic nerves. The secretory nerves of the gastric glands are treated on p. 485. Vomiting. The expulsion of the contents of the stomach in vomiting, like that of mucus or other matter from the lungs in coughing, is preceded by an inspiration ; the glottis is then closed, and immediately after- wards the abdominal muscles strongly act ; but here occurs the difference in the two actions. Instead of the vocal cords yielding to the action of the abdominal muscles, they remain tightly closed. Thus the diaphragm, being unable to go up, forms an unyielding surface against which the stomach can be pressed. At the same time the cardiac sphincter being relaxed, and the orifice which it naturally guards being dilated, while the pylorus is closed, and the stomach itself also contracting, the action of the abdominal muscles expels the contents of the organ through the oesophagus, pharynx, and mouth. The reversed peristaltic action of the oesophagus possibly increases the effect. It has been frequently stated that the stomach itself is quite passive during vomiting, and that the expulsion of its contents is effected solely by the pressure exerted upon it when the capacity of the abdomen is diminished by the contraction of the diaphragm, and subsequently of the abdominal muscles. The experiments and observations, however, which are supposed to confirm this statement, only show that the contraction of the abdominal muscles alone is sufficient to expel matters from an unresisting bag through the oesophagus ; and that, under very abnormal circumstances, the stomach, Cn. XXXV.] MOVEMENTS OF THE INTESTINES 531 by itself, cannot expel its contents. They by no means show that in ordinary vomiting the stomach is passive, for there are good reasons for believing the contrary. In some cases of violent vomiting the contents of the duodenum are passed by anti-peristalsis into the stomach, and are then vomited. Where there is obstruction to the intestine, as in strangulated hernia, the total contents of the small intestine may be vomited. Nervous mechanism. — Some few persons possess the power of vomiting at will, or the power may be acquired by effort and practice. But normally the action is a reflex one. The afferent nerves are principally the fifth, and glosso-pharyngeal (as in vomiting produced by tickling the fauces), and the vagus (as in vomiting produced by gastric irritants) ; but vomiting may occur from stimulation of other sensory nerves, e.g., those from the kidney, uterus, testicle, etc. The centre may also be stimulated by im- pressions from the cerebrum and cerebellum, producing so-called central vomiting occurring in diseases of those parts. The centre for vomiting is in the medulla oblongata, and coincides with the centres of the nerves concerned. The efferent (motor) impulses are carried by the vagi to the stomach, by the phrenics to the diaphragm, and by various other spinal nerves to the abdominal muscles. Emetics. — Some emetics produce vomiting by irritating the stomach ; others, like tartar emetic, apomorphine, etc., by stimulating the vomiting; centre. Movements of the Intestines. The movement of the intestines is peristaltic or vermicular, and is effected by the alternate contractions and dilatations of successive portions of the muscular coats. The contractions, which may commence at any point of the intestine, extend in a wave-like manner along the tube. They are similar to what we have described in the oesophagus. In any given portion, the longitudinal muscular fibres contract first, or more than the circular ; they draw a portion of the intestine upwards, over the substance to be propelled, and then the circular fibres of the same portion contracting in succession from above downwards, press the substance into the portion next below, in which at once the same succession of actions next ensues. These movements take place slowly, and, in health, commonly give rise to no sensation; but they are perceptible when they are accelerated under the influence of any irritant. The movements of the intestines are sometimes retrograde ; and there is no hindrance to the backward movement of the contents of the small intestine, as in cases of violent vomiting just referred to. 532 THE MECHANICAL PROCESSES OF DIGESTION [CH. XXXV. But almost complete security is afforded against the passage of the contents of the large into the small intestine by the ileocsecal valve. Proceeding from above downwards, the muscular fibres of the large intestine become, on the whole, stronger in direct proportion to the greater strength required for the onward moving of the feces, which are gradually, owing to the absorption of water, becoming firmer. The greatest strength is in the rectum, at the termination of which the circular unstriped muscular fibres form a strong band called the internal sphincter ; while an external sphincter muscle with striped fibres is placed rather lower down, and more externally, and holds the orifice closed by a constant slight tonic contraction. Nervous mechanism. — Experimental irritation of the brain or cord produces no evident or constant effect on the movements of the intestines during life ; yet in consequence of certain mental conditions the movements are accelerated or retarded ; and in paraplegia the intestines appear after a time much weakened in their power, and costiveness, with a tympanitic condition, ensues. As in the case of the oesophagus and stomach, the peristaltic movements of the intestines may be directly set up in the muscular fibres by the presence of food or chyme acting as the stimulus. Few or no movements occur when the intestines are empty. The small intestines are connected with the central nervous system by the vagi and by the splanchnic nerves. The fibres which leave the medulla in the vagal rootlets are fine medullated ones : they arborise around cells in the ganglion trunci, whence non-medullated fibres continue the impulse to the intestinal walls ; they pass through the solar plexus, but are not connected with nerve-cells in that plexus. In animals stimulation of the pneumogastric nerves induces peri- staltic movements of the intestines. If the intestines are contracting peristaltically before the stimulus is applied, the movements are inhibited for a brief period, after which they are greatly augmented. The sympathetic fibres leave the cord as fine medullated fibres by the anterior roots from the sixth thoracic to the first lumbar, pass through the lateral chain, but do not reach their cell-stations until they arrive at the superior mesenteric ganglia : thence they pass as non-medullated fibres to the muscular coats. Stimulation of these fibres causes inhibition of any peristaltic movements that may be present. These nerves also contain vaso-motor fibres, and section of these leads to vaso-dilatation and a great increase of very watery succus entericus. Peristalsis in the small intestine can be excited artificially even when all nerves running to it from the central nervous system have been cut through. After pinching any particular spot a wave of inhibition travels downwards, and a wave of contraction upwards. (Starling.) CH. XXXV.] MOVEMENTS OF THE INTESTINES 533 In the case of the large intestine there is no supply from the vagus. The inferior mesenteric nerves are inhibitory in function, and the pelvic nerves take the place of the vagal fibres as excitatory : this refers to both coats of the muscular wall. If one pinches any parti- cular spot, the upward wave of contraction is not so marked as in the small intestine, but the downward travelling wave of inhibition is well seen. Duration of Intestinal Digestion. — The time occupied by the journey of a given portion of food from the stomach to the anus, varies considerably even in health, and on this account probably it is that such different opinions have been expressed in regard to the subject. About twelve hours are occupied by the journey of an ordinary meal through the small intestine, and twenty-four to thirty- six hours by the passage through the large bowel. Drugs given for relief of diarrhoea or constipation act in various ways : some influence the amount of secretion and thus increase or diminish the fluidity of the intestinal contents ; others acting on the muscular tissue or its nerves increase or diminish peristalsis. The description just given of the intestinal movements relates to the principal movement observable, and which is of a peristaltic character. The rate of propa- gation of the peristaltic wave is slow but variable ; it may be as small as 1 centi- metre per minute. Starling in his recent work on the subject has called attention to another kind of movement which he terms swaying or pendulum movement. These movements, and also the true peristaltic waves, may be seen in the small intestine in a warm saiine bath even after all the nerves connecting them to the central nervous system have been cut through ; the pendulum movements consist of slight waves of contraction affect- ing both muscular coats, and these are rapidly propagated at the rate of 2 to 5 centi- metres per second. They cause a movement of the intestines from side to side, and occur at regular intervals of 5 or 6 seconds Their use appears to bring about a mixing of the intestinal contents ; they are not able to move the contents onwards. Thsy differ from the true peristaltic waves in being myogenic : that is, they are due to the rhythmicality of the muscular fibres themselves, and are propagated from one muscular fibre to another. They are not abolished by painting the intestine with cocaine, or by an injection of nicotine. The true peristaltic waves cease under these circumstances, and they are, therefore, co-ordinated reflex actions, but as they continue after all nerves connecting the intestines to the central nervous system are severed, they must be carried out by the local nervous mechanism. This is the only example known of a true reflex action dependent on peripheral nervous structures. Intestinal Oncometer. — To study the volume changes of vascular origin, a loop of intestine is enclosed in an oncometer like that described on p. 152 (fig. 179). This is a most valuable application of plethysmography, for the loop gives an accurate record of what is occurring in the splanchnic area. Defsecation. — The act of the expulsion of fasces is in part due to an increased reflex peristaltic action of the lower part of the large intestine, namely, of the sigmoid flexure and rectum, and in part to the action of the abdominal muscles. In the case of active voluntary efforts, there is usually, first, an inspiration, as in the case of coughing, sneezing, and vomiting ; the glottis is then closed, and the diaphragm fixed. The abdominal muscles arc contracted, as in expiration ; but 534 THE MECHANICAL PROCESSES OF DIGESTION [CH. XXXV. as the glottis is closed, the whole of their pressure is exercised on the abdominal contents. The sphincter of the rectum being relaxed, the evacuation of its contents takes place accordingly, the effect being increased by the peristaltic action of the intestine. Nervous Mechanism. — The anal sphincter muscle is normally in a state of tonic contraction. The nervous centre which governs this contraction is situated in the lumbar region of the spinal cord, inas- much as in cases of division of the cord above this region the sphinc- ter regains, after a time, to some extent the tonicity which is lost immediately after the operation. By an effort of the will, acting on the centre, the contraction may be relaxed or increased. Such volun- tary control over the act is obviously impossible when the cord is divided. In ordinary cases the apparatus is set in action by the gradual accumulation of foeces in the sigmoid flexure and rectum, pressing by the peristaltic action of these parts of the large intestine against the sphincter, and causing by reflex action its relaxation ; this sensory impulse acts upon the brain and reflexly through the spinal centre. At the same time that the sphincter is inhibited or relaxed, impulses pass to the muscles of the lower intestine increas- ing their peristalsis, and to the abdominal muscles as well. Both inhibitory and motor fibres for the lower part of the intes- tine leave the cord by anterior roots lower than those which contain the fibres for the small intestine. The cell-stations are situated in the inferior mesenteric ganglia, or along the course of the colonic or hypogastric nerves. The lower portion of the large intestine resembles the oesophagus in being more under external nervous control than the small intestine. CHAPTEE XXXVI THE URINARY APPARATUS This consists of the kidneys ; from each a tube called the ureter leads to the bladder in which the urine is temporarily stored ; from the bladder a duct called the urethra leads to the exterior. The Kidneys are two in number, and are situated deeply in the lumbar region of the abdomen on either side of the spinal column behind the peri- toneum. They correspond in position to the last dorsal and three upper lumbar vertebrae ; the right is slightly below the left in consequence of the position of the liver on the right side of the abdomen. They are about 4 inches long, 2\ inches broad, and 1^ inch thick. The weight of each kidney is about 4J oz. Structure. — The kidney is covered by a fibrous capsule, which is slightly attached at its inner surface to the proper substance of the organ by means of very fine bundles of areolar tissue and minute blood - vessels. From the healthy kidney, therefore, it may be easily torn off without much injury to the subjacent cor- tical portion of the organ. At the hilus of the kidney, it becomes con- tinuous with the external coat of the upper and dilated part of the ureter (fig. 412). On dividing the kidney into two equal parts by a section carried through its long convex border it is seen to be composed of two Fig. 412. — Plan of a longitudinal section through the pelvis and substance of the right kidney, i : a, the cortical sub- stance ; h, b, broad part of the pyramids of Malpighi ; c, e, the divisions of the pelvis named calyces, laid open ; d , one of those unopened ; d, summit of the pyramid projecting into calyces ; e, e, section of the narrow part of two pyramids near the calyces ; p, pelvis or enlarged portion of the ureter within the kidney ; v, the ureter ; s, the sinus ; h, the hilus. 536 THE URINARY APPARATUS [CH. XXXVI. portions called respectively cortical and medullary ; the latter is composed of about a dozen conical bundles of urinary tubules, each bundle forming what is called a pyramid. The upper part of the ureter or duct of the organ is dilated into the pelvis ; and this, again, after separating into two or three principal divisions, is finally sub- divided into still smaller portions, varying in number from about 8 to 12, called calyces. Each of these little calyces or cups receives the pointed extremity ox papilla of a pyramid. The number of pyramids varies in different animals; in some there is only one. The kidney is a compound tubular gland, and both its cortical and medullary portions are composed of tubes, the tubuli uriniferi, which, by one extremity, in the cortical portion, commence around tufts of capillary blood-vessels, called Mal- pighian bodies, and, by the other, open through the papillae into the pelvis of the kidney, and thus discharge the urine which flows through them. They are bound together by connective tissue. In the pyramids the tubes are straight — uniting to form larger tubes as they de- scend through these from the cortical por- tion ; while in the latter region they spread out more irregularly, and become much con- voluted. But in the boundary zone between cortex and medulla, small collections of straight tubes called medullary rays project into the cortical region. Tubuli Uriniferi. — The tubuli uriniferi (fig. 417) are composed of a basement mem- brane, lined internally by epithelium. They vary considerably in size in different parts of their course, but are, on an average, about -g-^o of an inch (^ T mm.) in diameter, and are found to be made up of several distinct portions which differ from one another very markedly, both in situation and structure. Each begins in the cortex as a dilatation called the Capsule of Bowman ; this encloses a tuft or glomerulus of capillaries called a Malpighian corpuscle. The tubule leaves the capsule by a neck, and then becomes convoluted {first convoluted tubule), but soon after becomes nearly straight or slightly spiral {spiral tubule) ; then rapidly narrowing it passes down into the medulla as the descending tubule of Henle ; this turns round, forming a loop {loop of Henle), and passes up to the cortex again as the assending tubule of Henle. It then becomes larger and irregularly zigzag {zigzag tubule) and again con- voluted {second convoluted tubule). Eventually it narrows into a i& ti ■ 5*3 ! !.-£» = Fig. 413. Portion of a secreting tubule from the cortical sub- stance of the kidney, b. The epithelial or gland-cells, x 700 times. CH. XXXVI.] THE KIDNEY TUBULES 537 junctional tubule, which joins a straight or collecting tubule. This passes straight through the medulla, where it joins with others to Fig. 414. — A diagram of the uriniferous tubes. A, cortex limited externally by tlie capsule ; a, subcapsular layer not containing Malpighian corpuscles ; a', inner stratum of cortex, also without Malpighian capsules ; B, boundary layer; C, medullary part next the boundary layer; 1, Bowman's capsule of Malpighian corpuscle ; 2, neck of capsule ; 3, first convoluted tubule ; 4, spiral tubule ; 5, descending limb of Henle's loop ; 6, the loop proper ; 7, thick part of the ascending limb ; S, spiral part of ascending limb ; 9, narrow ascending limb in the medullary ray ; 10, the zigzag tubule ; 11, the second convoluted tubule ; 12, the junctional tubule ; 13, the collecting tubule of the medullary ray ; 14, the collecting tube of the boundary layer ; 15, duct of Bellini. (Klein.) form one of the ducts of Bellini that open at the apex of the pyramid. These parts are all shown in fig. 414. 538 THE URINARY APPARATUS [CH. XXXVI. The character of the epithelium that lines these several parts of the tubules is as follows: — In the capsule, the epithelium is flattened and reflected over the glomerulus. The way in which this takes place in process of development is shown in figs. 415 and 416. In the neck the epithelium is still flattened, but in some animals, like frogs, where the neck is longer, the epithelium is ciliated. In the first convoluted and spiral tubules, it is thick, and the cells Fig. 415. — Transverse section of a deve- loping Malpighian capsule and tuft (human), x 300. From a foetus at about the fourth month ; a, flattened cells growing to form the capsule ; 6, more rounded cells ; continuous with the above, reflected round c, and finally enveloping it ; c, mass of em- bryonic cells which will later become developed into blood-vessels. (W. Pye). Fig. 416.— Epithelial elements of a Malpi- ghian capsule and tuft, with the com- mencement of a urinary tubule show- ing the afferent and efferent vessel ; a, layer of flat epithelium forming the capsule ; ft, similar, but rather larger epithelial cells, placed in the walls of the tube ; c, cells, covering the vessels of the capillary tuft ; d, commence- ment of the tubule, somewhat nar- rower than the rest of it. (W. Pye). show a librillated structure, except around the nucleus, where the protoplasm is granular. The cells interlock laterally and are difficult to isolate. In some animals they are described as ciliated. In the narrow descending tubule of Henle and in the loop itself, the cells are clear and flattened and leave a considerable lumen ; in the ascending limb they again become striated and nearly fill the tubule. In the zigzag and second convoluted tubules the fibrillations become even more marked. The junctional tubule has a large lumen, and is lined by clear flattened cells; the collecting tubules and ducts of Bellini are lined by clear cubical or columnar cells. Blood-Vessels of Kidney — The renal artery enters the kidney CH. XXXVI.] THE KIDNEY TUBULES 539 lllllllW:' Fig. 417. — From a vertical section through the kidney of a dog — the capsule of which is supposed to be on the right, a, the capillaries of the Malpighian corpuscle, "which are arranged in lobules ; n, neck of capsule ; c, convoluted tubes cut in various directions ; li, zigzag tubule ; d, e, and /, are straight tubes in a medullary ray ; d, collecting tube ; e, spiral tube ; /, narrow section of ascending limb. x 3S0. (Klein and Noble Smith.) Fig. 418. — Transverse section of a renal papilla : a, large tubes or ducts of Bellini ; b, c, and d, smaller tubes of Henle ; e, f, blood capillaries, distinguished by their flatter epithelium. (Cadiat.) 540 THE URINARY APPARATUS [CH. XXXVI. at the hilus, and divides into branches that pass towards the cortex, then turn over and form incomplete arches in the region between cortex and medulla. From these arches vessels pass to the surface which are called the interlobular arteries ; they give off vessels at right angles, which are the afferent vessels of the glomeruli; a glomerulus is made up of capillaries as previously stated. From each, a smaller vessel {the efferent vessel of the glomerulus) passes out, and like a portal vessel on a small scale, breaks up once more into capillaries which ramify between the con- voluted tubules. These unite to form veins {interlobular veins) which accompany the inter- lobular arteries; they pass to venous arches, parallel to, but more complete than the corre- sponding arterial arches; they ultimately unite to form the renal vein that leaves the hilus. These veins receive also others which have a stellate arrange- ment near the capsule {vence stellulos). The medulla is supplied by pencils of fine straight arterioles which arise from the arterial arches. They are called arterial rectaz. The efferent vessels of the glomeruli nearest the me- dulla may also break up into similar vessels which are called false arteries rectos. The veins {venos rectos) take a similar course and empty themselves into the venous arches. In the boundary zone groups of vasa recta alter- nate with groups of tubules, and give a striated appearance to this portion of the medulla. The Ureters — The duct of each kidney, or ureter, is a tube about the size of a goose-quill, and from twelve to sixteen inches in Fir,. 419. — Vascular supply of kidney, a, part of arterial arch; '/, interlobular artery ; c, glo- merulus ; d, efferent vessel passing to the medulla as false arteria recta ; e, capillaries of cortex ; /, capillaries of medulla ; g, venous arch ; h, straight veins of medulla ; i, inter- lobular vein ; j, vena stellula. (Cadiat.) CII. XXXVI.] THE BLADDER AND URETHRA 541 is coin- length, which, continuous above with the pelvis, ends below by per- forating obliquely the. walls of the bladder, and opening on its internal surface. It is constructed of three coats : (a) an outer fibrous coat ; (5) a middle muscular coat, of which the fibres are unstriped, and arranged in three layers — the fibres of the central layer being circular, and those of the other two longitudinal in direction; the outermost longitudinal layer is, however, present only in the lower part of the ureter; and (c) a mucous membrane continuous with that of the pelvis above, and of the urinary bladder below. It posed of areolar tissue lined by transitional epithelium. The Urinary Bladder, which forms a receptacle for the temporary lodgment of the urine, is pyriform; its widest part, which is situate above and behind, is termed the fundus; and the narrow constricted portion in front and below, by which it becomes con- tinuous with the urethra, is called its cervix or neck. It is constructed of four coats, — serous, muscular, areolar or submucous, and mucous, (a) The serous coat, which covers only the posterior and upper part of the bladder, has the same structure as the peritoneum, with which it is continuous, (b) The fibres of the muscular coat, which are unstriped, are arranged in three layers, of which the exter- nal and internal have a general longitudinal, and the middle layer a circular direction. The latter are especially developed around the cervix of the organ and form the sphincter vesica, (c) The areolar or submucous coat is constructed of con- nective-tissue with a large portion of elastic fibres, (cl) The mucous membrane is like that of the ureters. It is provided with mucous glands, which are most numerous near the neck of the bladder. The bladder is well provided with blood- and lymph-vessels, and with nerves. The latter consist of branches from the sacral and hypo- gastric plexuses. Ganglion cells are found, here and there, on the course of the nerve-fibres. The Urethra. — This occupies the centre of the corpus spongiosum in the male. As it passes through the prostate it is lined by transi- tional, but elsewhere by columnar epithelium, except near the orifice, where it is stratified like the epidermis with which it becomes con- tinuous. The female urethra has stratified epithelium throughout. Fig. 420. — Diagram showing the relation of the Malpighian body to the uriniferous ducts and blood-vessels, a, one of the interlobular arteries ; a', afferent artery passing into the glomerulus ; c, capsule of the Malpighian body, form- ingthe commencement of and continuous with t, the urini- ferous tube ; e', e', efferent vessels which subdivide and form a plexus, p, surround- ing the tube, and finally terminate in the branch of the renal vein e. (After Bow- man.) 542 THE URINARY APPARATUS [cn. XXXVI. The epithelium rests on a vascular corium, and this is covered by submucous tissue containing an inner longitudinal and an outer Fig. 421. — Malpighian corpuscle, injected through the renal artery with coloured gelatin ; a, glomerular vessels ; b, capsule ; c, anterior capsule ; d , afferent vessel of glomerulus ; c, eflcrent vessels ; /, epithelium of tubes. (Cadiat.) circular muscular layer. Outside this a plexus of veins passes in- sensibly 'into the surrounding erectile tissue. Fig. 422.— Section of a small portion of the prostate, a, gland duct cut across obliquely; 6, gland structure ; c, prostatic calculus. (Cadiat.) CH. XXXVI.] FUNCTIONS OF THE KIDNEYS 543 Into the urethra open a number of oblique recesses or lacunce, a number of small mucous glands (glands of Littre), two compound racemose glands (Cowper's glands), the glands of the prostate, and the vas deferens. The prostate, which surrounds the commencement of the male urethra, is a muscular and glandular mass. Its glands are tubular and lined by columnar epithelium. The Functions of the Kidneys. The main function of the kidneys is to separate the urine from the blood. The true secreting part of the kidney is the glandular epithelium that lines the convoluted portions of the tubules ; there is in addition to this what is usually termed the filtering apparatus : we have already seen that the tufts of capillary blood-vessels called the Malpighian glomeruli are supplied with afferent vessels from the renal artery; the efferent vessels that leave these have a smaller calibre, and thus there is high pressure in the Malpighian capillaries. Certain constituents of the blood, especially water and salts, pass through the thin walls of these vessels into the surrounding Bowman's capsule which forms the commencement of each renal tubule. Though the process which occurs here is generally spoken of as a filtration, yet it is no purely mechanical process, but the cells exercise a selective influence, and prevent the albuminous constituents of the blood from escaping. During the passage of the water which leaves the blood at the glomerulus through the rest of the renal tubule, it gains the constituents urea, urates, etc., which are poured into it by the secreting cells of the convoluted tubules. The term excretion is better than secretion as applied to the kidney, for the constituents of the urine are not actually formed in the kidney itself (as, for instance, the bile is formed in the liver), but they are formed elsewhere; the kidney is simply the place where they are picked out from the blood and eliminated from the body. The Nerves of the Kidney. Nerves. — The nerves of the kidney are derived from the renal plexus of each side. This consists of both medullated and non- medullated nerve-fibres, the former of varying size, and of nerve-cells. Fibres from the anterior roots of the eleYenth, twelfth, and thirteenth dorsal nerves (in the dog) pass into this plexus. They are both vaso-eonstrictor and vaso-dilator in function. The nerve-cells on the course of the constrictor fibres are situated in the cceliac, mesen- teric, and renal ganglia ; the cells on the course of the dilator fibres are placed in the solar plexus and renal ganglia. These nerves are thus vaso-motor in function ; we have at present 544 THE URINARY APPARATUS [CH. XXXVI. no knowledge of true secretory nerves to the kidney ; the amount of urine varies directly with the blood-pressure in its capillaries. Increase in the quantity of urine accompanies a rise of intra- capillary pressure. This may be produced by increasing the general blood-pressure ; and this in turn may be produced in the following ways : — (1.) By increase in the force or frequency of the heart-beat. (2.) By constriction of the arterioles of areas other than that of the kidney, as in cold weather, when the cutaneous capillaries are constricted.* (3.) By increase in the total contents of the vascular system, as after drinking large quantities of fluid. The blood-pressure in the renal capillaries may also be increased locally by anything which leads to relaxation of the renal arterioles. Decrease in the quantity of urine is produced by the opposites in each case. If the renal nerves are divided, the renal arterioles are relaxed, and pressure in the renal capillaries is raised, so there is an increased flow of urine. This is accompanied by an increase in the volume of the kidney, as can be seen by the oncometer. Stimulation of the divided nerves produces a diminution in the amount of urine, and a shrinkage of the kidney due to a constriction of its blood-vessels.1* If the splanchnic nerves are experimented with instead of the renal, the effects are not so marked, as these nerves have a wide distribution, and section leads to vascular dilatation in the whole splanchnic area; hence the increase in pressure in the renal capillaries is not so noticeable. Puncture of the floor of the fourth ventricle in the neighbourhood of the vaso-motor centre (close to the spot, puncture of which pro- duces glycosuria) leads to a relaxation of the renal arterioles and a consequent large increase of urine (polyuria). Section of the spinal cord just below the medulla causes a cessation of secretion of urine, because of the great fall of general blood-pressure which occurs. If the animal is kept alive, however, blood-pressure goes up after a time, owing to the action of subsidiary vaso-motor centres in the cord. When this has occurred stimulation of the peripheral end of the cut spinal cord again causes urinary secretion to stop, because the renal artery (like the other arteries of the body) is so constricted that the pressure in the renal capillaries becomes too low for secretion to occur. * The reciprocal action between skin and kidneys will be discussed more fully in the chapter on the skin. t The nerves also contain vaso-dilator fibres, which are excited when a slow rate of stimulation is used (see p. 307). CH. XXXVI.] THE KIDNEY ONCOMETER 545 We thus see that the amount of urine varies with blood-pressure. But such a statement does not give the whole truth. Increase of blood-pressure and an increased amount of blood flowing through the kidney go together when the blood is circulating normally, and it is really the increase in the amount of blood which causes the rise in Fig. 423. — Oncometers for kidneys of different sizes. the amount of urine secreted. If the blood-pressure is increased without allowing the blood to flow, the amount of urine formed is not raised. This can be done by ligaturing the renal vein ; the blood- pressure within the kidney then rises enormously, but the flow of urine stops. The Oncometer is an instrument constructed on plethysmo- graphic principles, by means of which the volume of the kidney is Fig. 424.— Curve taken by renal oncometer compared with that of ordinary blood-pressure, curve ; b, blood-pressure curve. (Roy.) a, Kidney registered. The general characters of this instrument are described in the diagrams on p. 309. The special form adapted for the kidney is shown in fig. 423. An air oncometer connected with a Marey's tambour or a bellows recorder gives equally good or even better results. It is found that the effect on the volume of the organ of dividing 2 M 546 THE URINARY APPARATUS [OH. XXXVI. or stimulating nerves corresponds to blood-pressure. A rise of blood- pressure in the renal artery is produced by constriction of the renal arterioles ; this is accompanied by a fall of pressure in the renal capillaries, and a shrinkage of the kidney. Increase in the volume of the kidney is produced by the opposite circumstances. The accompanying tracing (fig. 424) shows that in a kidney curve one gets a rise of volume due to each heart-beat, and larger waves which accompany respiration. In many cases larger sweeping waves (Traube-Hering curves) are often shown as well. If a kidney curve is compared with a tracing of arterial pressure, it will be seen that the rise of arterial pressure coincides with a fall of the oncograph lever due to constriction of the renal vessels. Diuretics are drugs which produce an increased flow of urine ; they act in various ways, some by increasing the general blood- pressure, others by acting locally upon the kidney (increasing its volume as measured by the oncometer) ; under this latter head are doubtless to be included some also which act on the renal epithelium rather than on the blood-vessels. Activity of the Renal Epithelium. The epithelium of the convoluted tubules has a structure which suggests from its resemblance to other forms of secreting epitheliums, that its function here also is secreting. This is confirmed by the manner in which the blood-vessels break up into capillaries around these tubules ; and is further confirmed by experiments. Heidenhain showed that if a substance called sodium sulphindigo- tate, which ordinarily produces blue urine, is injected into the blood (after section of the medulla oblongata, which causes lowering of the blood-pressure in the renal glomeruli), when the kidney is examined, the cells of the convoluted tubules — and of these alone — are stained with the substance, which is also found in the lumen of the tubules. This shows that the pigment is eliminated by the cells of the con- voluted tubules, and that when by diminishing the blood-pressure, the filtration of urine is stopped, the pigment remains in the convoluted tubes, and is not, as it would be under ordinary circum- stances, swept away from them by the flushing of them by the watery part of the urine derived from the glomeruli. It therefore is probable that the cells, if they excrete the pigment, excrete urea and other substances also. But the proof is not absolute, for the pigment is a foreign substance. Urea is a very difficult substance to trace in this way because it does not leave any coloured trail behind it. In birds the place of urea is taken by uric acid, and the urates can be actually traced, because they are deposited as crystals, and can be seen in the CH. XXXVI.] ACTIVITY OF THE RENAL EPITHELIUM 547 cells and convoluted tubes much in the same way as Heidenhain's blue pigment. Other experiments, however, have been undertaken to prove the point for the case of urea. If the part of the cortex of the kidney which contains the glomeruli is removed, urea still continues to be formed. This is a proof that the excretion is performed by the portions of the con- voluted tubules that remain. By using the kidney of the frog or newt, which has two distinct vascular supplies, one from the renal artery to the glomeruli, and the other from the renal-portal vein to the convoluted tubes, Nussbaum stated that certain foreign substances, e.g. peptones and sugar, when injected into the blood, are eliminated by the glomeruli, and so are not got rid of when the renal arteries are tied ; whereas certain other substances, e.g. urea, when injected into the blood, are eliminated by the convoluted tubes, even when the renal arteries have been tied. These experiments have, however, been subjected to considerable criticism, and some observers have failed to obtain the same result. A re-investigation of the subject has been recently undertaken by Dr A. P. Beddard. He finds that ligature of all the arteries to the kidneys in the frog cuts the glomeruli completely out of the circula- tion. Adami's failure to confirm Nussbaum was due, not as he supposed to anastomoses between the terminations of the renal artery and the renal-portal system, but to incomplete ligature of the arteries. When the glomeruli are shut off in this way, no secretion takes place either spontaneously or after injection of urea, which is a diuretic ; the contrary results obtained by Nussbaum were due to imperfect ligature, so that a number of glomeruli were left intact. ISTussbaum's anatomical facts were therefore right, but his physio- logical experiments were faulty. A certain supply of arterial blood is necessary to the normal life of the renal epithelium, for this undergoes fatty degeneration and comes away (desquamates) in con- sequence of the occlusion of the glomeruli. Beddard's experiments, though important, do not really settle the question concerning the normal function of the epithelium of the tubules ; they suggest that another series of experiments must be undertaken, in which an adequate supply of oxygen to the epithelium is ensured after com- plete ligature of all the arteries. The Work done by the Kidney. We have already seen (p. 321) the great importance a study of osmosis in the body has in the understanding of many physiological facts. The urine is separated from the blood by a process which is not simply nitration, and if we measure the work of the kidney it is found to be vastly greater than could be produced by the intra-capillary blood-pressure. Ludwig held that re-absorption of some of the water and salts which escape at the glomeruli takes 548 THE URINARY APPARATUS [CH. XXXVI. place in the tubules. Cushny finds this may occur to some extent, but the main function of the tubules is undoubtedly secretion, not absorption. The work done by the kidney cells in order to separate from the blood-plasma a fluid with the much higher osmotic pressure of urine can be estimated. We may take some examples from Dreser's work. He took the case in which 200 c.c. of urine were excreted during a night ; the blood plasma in this case had an osmotic pressure = 0*92 per cent solution ; while that of the urine was =4 - per cent, solution of sodium chloride. To measure the work of the kidney we may take the mean of 0"92 and 4 as the average concentration of the salt during the process of excretion, and thus it is found that the kidney did about IS kilogramme- metres of work. In another case of more concentrated urine obtained from a cat previously deprived of water for three days, the numbers were respectively l'l and 8 - 0. The difference was equal to a pressure of 498 metres of water ; so that at the end the kidney had separated urine from the blood against a pressure of 49,S00 grammes per square centimetre, a force about six times greater than the maximum force of muscle. Extirpation of the Kidneys. Extirpation of one kidney for stone, etc., is a common operation. It is not followed by any untoward result. The remaining kidney enlarges and does the work previously shared between the two. Extirpation of both kidneys is fatal ; the urea, etc., accumulate in the blood, and the animal dies in a few days; ursemic convulsions (see p. 556) do not occur in such experiments. Ligature of both renal arteries amounts to the same tbing as extirpation of the kidneys, and leads to the same result. If the ligature is released the kidney once more sets to work, but the urine secreted at first is albuminous, owing to the epithelium having been impaired by being deprived for a time of its blood supply. Removal of one kidney, followed at a later period by removal of a half or two-thirds of the other, leads in dogs, in which the operation has been performed by Bradford, to a surprising result. After the second operation the urine is increased in amount, and the quantity of urea is much greater than normal. This comes from a disintegra- tion of the nitrogenous tissues ; the animal wastes rapidly and dies in a few weeks. It is thus evident that the kidneys play an important role in nitrogenous metabolism apart from merely excreting waste substances. The exact explanation has still to be found, but it is possible that the kidney, like the pancreas and liver, and many duct- less glands, forms an internal secretion (see p. 328). The Passage of Urine into the Bladder. As each portion of urine is secreted it propels that which in already in the uriniferous tubes onwards into the pelvis of the kidney. Thence through the ureter the urine passes into the bladder, into which its rate and mode of entrance has been watched in cases of ectopia vesicae, i.e. of such fissures in the anterior and lower part of CH. XXXYI.] MICTURITION 549 the walls of the abdomen, and of the front wall of the bladder, as expose to view its hinder wall together with the orifices of the ureters. The urine does not enter the bladder at any regular rate, nor is there a synchronism in its movement through the two ureters. During fast- ing, two or three drops enter the bladder every minute ; each drop as it enters first raises up the little papilla through which the ureter opens, and then passes slowly through its orifice, which at once again closes like a sphincter. In the recumbent posture, the urine collects for a little time in the ureters, then flows gently, and, if the body is raised, runs from them in a stream till they are empty. Its flow is aided by the peristaltic contractions of the ureters, and is increased in deep inspiration, or by straining, and in active exercise, and in fifteen or twenty minutes after a meal. The urine is prevented from regurgitation into the ureters by the mode in which these pass through the walls of the bladder, namely, by their lying for between half and three-quarters of an inch between the muscular and mucous coats before they turn rather abruptly forwards, and open through the latter into the interior of the bladder. Micturition. The contraction of the muscular walls of the bladder may by itself expel the urine with little or no help from other muscles. In so far, however, as it is a voluntary act, it is performed by means of the abdominal and other expiratory muscles, which in their contrac- tion press on the abdominal viscera, the diaphragm being fixed, and cause the expulsion of the contents of those whose sphincter muscles are at the same time relaxed. The muscular coat of the bladder co-operates, in micturition, by reflex involuntary action, with the abdominal muscles ; and the act is completed by the accelerator urinm, which, as its name implies, quickens the stream, and expels the last drop of urine from the urethra. The act, so far as it is not directed by volition, is under the control of a nervous centre in the lumbar spinal cord, through which, as in the case of the similar centre for defsecation, the various muscles concerned are harmonised in their action. It is well known that the act may be reflexly induced, e.g. in children who suffer from intestinal worms, or other such irritation. Generally the afferent impulse which calls into action the desire to micturate is excited by over-distension of the bladder, or even by a few drops of urine passing into the urethra. The impulse passes up to the lumbar centre, and produces, on the one hand, inhibition of the sphincter, and on the other hand contraction of the necessary muscles for the expulsion of the contents of the bladder. The tonic action of the lumbar centre can also be inhibited by the will. The bladder receives nerves from two sources : — (1) from the 550 THE URINARY APPARATUS [CH. XXXVI. lower dorsal and upper lumbar nerves ; these fibres pass to the sympathetic chain, from here to the inferior mesenteric ganglion, and ultimately reach the bladder by the hypogastric nerves. Stimu- lation of these nerves causes contraction of the circular fibres of the bladder, including the sphincter; (2) from the second and third sacral nerves; these run to the bladder by the nervi erigentes. Stimulation of these nerves causes relaxation of the sphincter and contraction of the detrusor urinee. (Zeissl.) Langley and Anderson find, however, that stimulation of both sets of nerves causes contrac- tion of both longitudinally and circularly arranged muscle bundles. CHAPTEE XXXVII THE UEI-NE Quantity. — A man of average weight and height passes from 1400 to 1600 c.c, or about 50 oz. daily. This contains about 50 grammes (1| oz.) of solids. For analytical purposes it should be collected in a tall glass vessel capable of holding 3000 c.c, which should have a smooth-edged neck accurately covered by a ground-glass plate to exclude dust and prevent evaporation. The vessel, moreover, should be graduated so that the amount may be easily read off. From the total quantity thus collected in the twenty-four hours, samples should be drawn off for examination. Colour. — This is some shade of yellow which varies considerably in health with the concentration of the urine. It is due to a mixture of pigments ; of these urobilin is the one of which we have the most accurate knowledge. Urobilin has a reddish tint, and is undoubtedly derived from the blood pigment, and, like bile pigment, is an iron- free derivative of haemoglobin. The theory usually accepted con- cerning its mode of origin is that bile pigment is in the intestines converted into stercobilin; that most of the stercobilin leaves the body with the fasces ; that some is reabsorbed and is excreted with the urine as urobilin. Both stercobilin and urobilin are very like the artificial reduction product of bilirubin called hydrobilirubin (see p. 511). Normal urine, however, contains very little urobilin. The actual body present is a chromogen or mother substance called urobilinogen, which by oxidation — for instance, standing exposed to the air — is converted into the pigment proper. In certain diseased conditions the amount of urobilin is considerably increased. The most abundant urinary pigment is a yellow one, named urochrome. It shows no absorption bands. It is probably an oxida- tion product of urobilin. (Eiva, A. E. G-arrod.) Reaction. — The reaction of normal urine is acid. This is not due to free acid, as the uric and hippuric acids in the urine are combined as urates and hippurates respectively. The acidity is due to acid salts, of which acid sodium phosphate is the most important. Under 552 THE URINE [CH. XXXVII. certain circumstances the urine becomes less acid and even alkaline ; the most important of these are as follows : — 1. During digestion. Here there is a formation of free acid in the stomach, and a corresponding liberation of bases in the blood, which, passing into the urine, diminish its acidity, or even render it alkaline. This is called the alkaline tide ; the opposite condition, the acid tide, occurs after a fast — for instance, before breakfast. 2. In herbivorous animals and vegetarians. The food here con- tains excess of alkaline salts of acids like tartaric, citric, malic, etc. These acids are oxidised into carbonates, which, passing into the urine, give it an alkaline reaction. Specific Gravity. — This should be taken in a sample of the twenty-four hours' urine with a urinometer. The specific gravity varies inversely as the quantity of urine passed under normal conditions from 1015 to 1025. A specific gravity below 1010 should excite suspicion of hydruria; one over 1030, of a febrile condition, or of diabetes, a disease in which it may rise to 1050. The specific gravity has, however, been known to sink as low as 1002 (after large potations, urina potus), or to rise as high as 1035 (after great sweating) in perfectly healthy persons. Composition. — The following table gives the average amounts of the urinary constituents passed by a man in the twenty-four hours : — Total quantity of urine 1500*00 grammes Water 1440-00 Solids 60-00 Urea 35-00 Uric acid 0-75 Sodium chloride 16-5 Phosphoric acid :'.-5 Sulphuric acid 2-0 Ammonia 0-65 Creatinine 0-9 Chlorine . 11-0 Potassium 2-5 Sodium . 5-5 Calcium . 0-26 Magnesium 0-21 The most abundant constituents of the urine are water, urea, and sodium chloride. In the foregoing table one must not be misled by seeing the names of the acids and metals separated. The acids and the bases arc combined to form salts, such as urates, chlorides, sulphates, phosphates, etc. Urea. Urea, or Carbamide, CO(NH 2 ).>, is isomeric (that is, has the same empirical, but not the same structural formula) with ammonium cyanate (NH 4 ) CNO, from which it was first prepared synthetically CH. XXXVII.] UREA by Wohler in 1828. Since then it has been prepared synthetically in other ways. Wohler's observation derives interest from the fact that this was the first organic substance which was prepared syntheti- cally by chemists.* When crystallised out from the urine it is found to be readily soluble both in water and alcohol : it has a saltish taste, and is neutral to litmus paper. The form of its crystals is shown in fig. 425. When treated with nitric acid, nitrate of urea (CON 2 H 4 .HN0 3 ) is formed ; this crystallises in octahedra, lozenge-shaped tablets or hexagons (fig. 426). When treated with oxalic acid, flat or prismatic crystals of urea oxa- late (CON,H 4 .H,C,0 4 + H,0) are formed (fig. 427)." These crystals may be readily ob- tained by adding excess of the respective acids to urine which has been concen- trated to a third or a quarter of its bulk. Under the influence of an organised ferment, the torula or micro- coccus ureas, which grows readily in stale urine, urea takes up water, and is converted into ammonium carbonate [CON. 2 H 4 + 2H 2 = (NH 4 ).,C0 3 ]. Hence the ammoniacal odour of putrid urine. By means of nitrous acid, urea is broken up into carbonic acid, water and nitrogen, CON 2 H 4 + 2HN0 2 = C0 2 + 3H 2 + 2N 2 . The Fig. 425. — Crystals of Urea. Fig. 426.— Crystals of Urea nitrate. Fig. 427. — Crystals of Urea oxalate. evolution of gas bubbles which takes place on the addition of fuming nitric acid may be used as a test for urea. Hypobromite of soda decomposes urea in the following way : — - CON 9 H 4 [Urea.] 3NaBrO [Sodium hypobromite.] = CO., + N 2 + [Carbonic [Nitrogen.] acid.] 2H,0 [Water.] + 3NaBr. [Sodium bromide.] * Meldola has pointed out that the English chemist Henry Hennell prepared alcohol from defiant gas simultaneously with Wohler's synthesis of urea. The honour of founding the science of organic chemistry must, therefore, be shared between the two men. 554 THE URINE [('II. XXXVII. This reaction is important, for on it one of the readiest methods for estimating urea depends. There have been various pieces of apparatus invented for rendering the analysis easy; but the one described below is the best. If the experiment is performed as directed, nitrogen is the only gas that comes off, the carbonic acid being absorbed by excess of soda. The amount of nitrogen is a measure of the amount of urea. Dupre's apparatus (fig. 428) consists of a bottle (A) united to a measuring tube by indiarubber tubing. The measuring tube (C) is placed within a cylinder of water (D), and can be raised and lowered at will. Measure 25 c.c. of alkaline solution of sodium hypobromite (made by mixing :.' c.c. of bromine with 23 c.c. of a 40 per cent solution of caustic soda) into the bottle A. Measure 5 c.c. of urine into a small tube (B), and lower it carefully, so that no urine spills, into the bottle. Close the bottle securely with a stopper perforated by a glass tube ; this glass tube (the bulb blown on this tube prevents froth from passing into the rest of the apparatus) is connected to the measuring tube by india- rubber tubing and a T-P'ece. The third limb of the T-piece is closed by a piece of indiarubber tubing and a pinch-cock, seen at the top of the figure. Open the pinch-cock and lower the measuring tube until the sur- face of the water with which the outer cylinder is filled is at the zero point of the graduation. Close the pinch- cock, and raise the measuring tube to ascertain if the apparatus is air-tight. Then lower it again. Tilt the bottle A so as to upset the urine, and shake well for a minute or so. During this time there is an evolution of gas. Then immerse the bottle in a large beaker con- taining water of the same temperature as that in the cylinder. After two or three minutes raise the measur- ing tube until the surfaces of the water inside and out- side it are at the same level. Read off the amount of gas (nitrogen) evolved. 3-v4 c.c. of nitrogen are yielded by O'l gramme of urea. From this the quantitj- of urea in the ."> c.c. of urine and the percentage of urea can be calculated. If the total urea passed in the twenty-four hours is to be ascertained, the twenty- four hours' urine must be carefully measured and thoroughly mixed. A sample is then taken from the total for analysis ; and then, by a simple sum in proportion, the total amount of urea is ascertained. Another method (Liebig's) of estimating urea in urine is the following : — Take 40 c.c. of urine; add to this 20 c.c. of baryta mixture (two volumes of barium hydrate and one of barium nitrate, both saturated in the cold). Filter off the pre- cipitate of barium phosphate and sulphate which is formed. Take 15 c.c. of the filtrate (this corresponds to 10 c.c. of urine) in a beaker. Run into it from a burette standard mercuric nitrate solution of such a strength that 1 c.c. exactly precipitates 0-01 gramme of urea as a compound with the formula (CON 2 H 4 )oHg(XO :i ). J (HgO) :j . The solution is run in until the precipitate ceases to form, and free mercuric nitrate is present in the mixture ; this can be detected by the yellow colour a drop of the mixture gives with a drop of saturated solution of sodium carbonate on a white slab. The amount used from the burette can be read off, and the percentage of urea calculated. In another specimen of the same urine, the chlorides are then esti- Fig. 42S.— Dupr ■■- Urea Apparatus. CH. XXXVII.] FORMATION OF UEEA 555 mated, and 1 gramme of urea subtracted for every 1*3 gramme of sodium chloride formed. These two methods give nearly identical results ; the former is the easier to perform, and the results are sufficiently accurate for ordinary purposes. A more accurate determination can be best made by the method introduced by Morner and Sjoquist. The following reagents, etc., are wanted : — (i.) A saturated solution of barium chloride containing 5 per cent, of barium hydrate ; (ii.) A mixture of alcohol and ether in the proportion 2:1; (iii.) The apparatus, etc., necessary for carrying out Kjeldahl's method of estimating nitrogen. 5 c.c. of urine are mixed with 5 c.c. of the barium mixture, and 100 c.c. of the ether-alcohol mixture. By this means all nitrogenous substances except urea are precipitated. Twenty-four hours later this is filtered off, and the precipitate is washed with 50 c.c. of the ether- alcohol mixture. The washings are added to the filtrate, and a little magnesia is added to drive off ammonia. The fluid is then evaporated down at 55° C. until its volume is about 10 c.c, and the nitrogen in this estimated by Kjeldahl's method. The nitrogen found is multiplied by 2 , 143, and the result is the amount of the urea. Kjeldahl's method of estimating nitrogen consists in boning the material under investigation with strong sulphuric acid. The nitrogen present is by this means converted into ammonia. Excess of soda is then added, and the ammonia distilled over into a known volume of standard acid. The amount of diminution of acidity in the standard enables one to calculate the amount of ammonia, and thence the amount of nitrogen. The quantity of urea is variable, the chief cause of variation being the amount of proteid food ingested. In a man in a state of nitrogenous equilibrium, taking daily 100 grammes of proteid in his food, the quantity of urea secreted daily is about 33 to 35 grammes (500 grains). The normal percentage in human urine is 2 per cent. ; but this also varies, because the concentration of the urine varies considerably in health. In dogs it may be 10 per cent. The excretion of urea is usually at a maximum three hours after a meal, especially after a meal rich in proteids. The urea does not come, however, direct from the food ; the food must be first assimi- lated, and become part of the body, before it can break down to form urea. Food increases the elimination of urea because it stimulates the tissues to increased activity; their waste nitrogenous products are converted into urea, which, passing into the blood, is directly excreted by the kidneys. The greater the amount of proteid food given, the more waste products do the tissues discharge from their protoplasm, in order to make room for the new proteid which is built into its substance. Eecent experiments by Chittenden and others have shown that nitrogenous equilibrium can be maintained on a diet containing only half the usual amount of proteid. In such people the excretion of urea falls correspondingly, the other nitrogenous constitutents of the urine remaining fairly constant. Muscular exercise has little immediate effect on the amount of urea discharged. In very intense muscular work there is a slight immediate increase of urea, but this is quite insignificant when com- pared to the increase of work. This is strikingly different from what occurs in the case of carbonic acid ; the more the muscles work, the more carbonic acid do they send into the venous blood, which is 556 THE UKINE [CH. XXXVII. rapidly discharged by the expired air. Eecent careful research has, however, shown that an increase of nitrogenous waste does occur on muscular exertion, but appears as urea in the urine to only a slight extent on the day of the work ; the major part is excreted during the next day. Where is Urea formed ? — The older authors considered that it was formed in the kidneys, just as they also erroneously thought that carbonic acid was formed in the lungs. PreVost and Dumas were the first to show that after complete extirpation of the kidneys the formation of urea goes on, and that it accumulates in the blood and tissues. Similarly, in those cases of disease in which the kidneys cease work, urea is still formed and accumulates. This condition is called urcemia, and unless the urea be discharged from the body the patient dies in a condition of coma preceded by convulsions. Vra mia. — This term was originally applied on the erroneous supposition that it is urea or some antecedent of urea which acts as the poison. There is no doubt that the poison is not any constituent of normal urine ; if the kidneys of an animal are extirpated, the animal dies in a few days, but there are no symptoms of uraemia. In man, also, if the kidneys are healthy or approximately so, and suppression of urine occurs from the simultaneous blocking of both renal arteries by clot, or of both ureters by stones, again uraemia does not follow. On the other hand, uraemia may occur even while a patient with diseased kidneys is passing a considerable amount of urine. What the poison is that is responsible for the convulsions and coma, is unknown. It is doubtless some abnormal katabolic product, but whether this is produced by the diseased kidney cells, or in some other part of the body, is also unknown. Where, then, is the seat of urea formation ? Nitrogenous waste occurs in all the living tissues, and the principal final result of this proteid metabolism is urea. It may not be that the formation of urea is perfected in each tissue, for if we look to the most abundant tissue, the muscular tissue, urea is absent, or nearly so. Yet there can be no doubt that the chief place from which urea ultimately comes is the muscular tissue. Some intermediate step occurs in the muscles ; the final steps occur elsewhere. In muscles we find a substance called creatine in fairly large cpaantities. If creatine is injected into the blood it is discharged as creatinine. But there is very little creatinine in normal urine ; what little there is can be nearly all accounted for by the creatine in the food ; the muscular creatine is discharged as urea ; moreover, urea can be artificially obtained from creatine in the laboratory. Similarly, other cellular organs, spleen, lymphatic glands, secreting glands, participate in the formation of urea ; but the most important appears to be the liver : this is the organ where the final changes take place. The urea is then carried by the blood to the kidney, and is there excreted. The facts of experiment and of pathology point very strongly CH. XXXVII.] FOEMATION OF UREA 557 in support of the theory that urea is formed in the liver. The principal are the following : — 1. After removal of the liver in such animals as frogs, urea formation almost ceases, and ammonia is found in the urine instead. 2. In mammals, the extirpation of the liver is such a severe operation that the animals do not live. But the liver of mammals can be very largely thrown out of gear by connecting the portal vein directly to the inferior vena cava (Eck's fistula). This experiment has been done successfully in dogs ; the amount of urea in the urine is lessened, and its place is taken by ammonia. 3. When degenerative changes occur in the liver, as in cirrhosis of that organ, the urea formed is much lessened, and its place is taken by ammonia. In acute yellow atrophy urea is almost absent in the urine, and, again, there is considerable increase in the ammonia. In this disease leucine and tyrosine are also found in the urine ; undue stress should not be laid upon this latter fact, for the leucine and tyrosine doubtless originate in the intestine, and, escaping further decomposition in the degenerated liver, pass as such into the urine. We have to consider next the intermediate stages between proteid and urea. A few years ago Drechsel succeeded in artificially pro- ducing urea from casein. More recent work has shown that this is true for other proteids also. If a proteid is decomposed by hydro- chloric acid, a little stannous chloride being added to prevent oxidation, a number of products are obtained, such as ammonium salts, leucine, tyrosine, aspartic, and glutaminic acids. This was known before, so the chief interest centres round two new sub- stances, precipitable by phosphotungstic acid. One of these is called lysine (C 6 H 14 N 2 0. 2 , di-amino-caproic acid) ; the other was first called lysatinine. Hedin then showed that lysatinine is a mixture of lysine with another base called arginine (C 6 H 14 ]Sr 4 0. 2 ) ; it is from the arginine that the urea comes in the experiment to be next described. Arguing from some resemblances between this substance and creatine, Drechsel expected to be able to obtain urea from it, and his expectation was confirmed by experiment. He took a silver compound of the base, boiled it with barium carbonate, and after twenty -five minutes' boiling obtained urea. (See note on p. 573.) It is, however, extremely doubtful whether the chemical decom- positions produced in laboratory experiments on proteids are com- parable to those occurring in the body. Many physiologists consider that the amino-acids are intermediate stages in the metabolic processes that lead to the formation of urea from proteids. We have already alluded to this question in relation to the creatine of muscle, and we are confronted with the difficulty that injection of creatine into the blood leads to an increase not of urea, but of creatinine 558 THE URINE [CH. XXXVII. in the urine. If creatine is an intermediate step, it must undergo some further change before it leaves the muscle. Other amino-acids, such as glycine (amino-acetic acid), leucine (amino-caproic acid), and arginine are probably to be included in the same category ; there is, however, no evidence that tyrosine acts in this way. The facts upon which such a theory depends are (1) that the introduction of glycine or leucine into the bowel, or into the circulation, leads to an increase of urea in the urine ; and (2) that amino-acids appear in the urine of patients suffering from acute yellow atrophy of the liver. Then, again, it is perfectly true that, in the laboratory, urea can be obtained from creatine, and also from uric acid, but such experiments do not prove that creatine or uric acid are normally intermediate pro- ducts of urea formation in the body. Still, if we admit, for the sake of argument, that amino-acids are normally intermediate stages in proteid metabolism, and glance at their formulae — Glycine C. 2 H 5 NO„ Leucine C 6 H 13 N0 2 i Creatine C 4 HgN 3 2 , — we see that the carbon atoms are more numerous than the nitrogen atoms. In urea, CON 2 H 4 , the reverse is the case. The amino-acids must therefore be split into simpler compounds, which unite with one another to form urea. Urea formation is thus, in part, synthetic. There have been various theories advanced as to what these simpler compounds are. Some have considered that cyanate, others that carbamate, and others still that carbonate of ammonium is formed. Schroder's work, which has been confirmed by subsequent investigators, proves that ammonium carbonate is one of the urea precursors, if not the principal one. The equation which represents the reaction is as follows : — (XH 4 ),C0 3 - 2H 2 = CON 2 H 4 . [Ammonium [Water.] [Urea.] carbonate.] Schroder's principal experiment was this : a mixture of blood and ammonium carbonate was injected into the liver by the portal vein ; the blood leaving the liver by the hepatic vein was found to contain urea in great abundance. This does not occur when the same experi- ment is performed with any other organ of the body, so that Schroder's experiments also prove the great importance of the liver in urea formation. There is, however, no necessity to suppose that the formation of amino-acids is a necessary preliminary to urea formation. The con- version of the leucine and arginine formed in the intestine into ammonium salts and then into urea does certainly occur, but this only accounts for quite an insignificant fraction of the urea in the CH. XXXVII.] AMMONIA 559 urine. If the same occurs in tissue metabolism, we ought to find considerable quantities of leucine, glycine, creatine, arginine, and such substances in the blood, leaving the various tissues and entering the liver ; but we do not. We do, however, constantly find ammonia, which, after passing into the blood or lymph, has united with carbonic acid to form either carbonate or carbamate of ammonium. It is quite probable that the nitrogenous waste that leaves the muscles and other tissues is split off from them as ammonia, and not in the shape of large molecules of amino-acid, which are subsequently converted into ammonia. The experiments outside the body which most closely imitate those occurring within the body are those of Drechsel, in which he passed strong alternating currents through solutions of proteid-like materials. Such alternating currents are certainly absent in the body, but their effect, which is a rapidly changing series of small oxidations and reductions, are analogous to metabolic processes ; under such circumstances the carbon atoms are burnt off as carbon dioxide, and the nitrogen is split off in the form of ammonia; by the union of these two substances ammonium carbonate is formed. The following structural forrnulse exhibit the relationship between ammonium carbonate, ammonium carbamate, and urea. The loss of one molecule of water from ammonium carbonate produces ammonium carbamate; the loss of a second molecule of water produces urea — ■ /O.NH 4 /NH, /NH 2 ° = C \O.NH 4 ° = c \O.NH 4 u = C \NH 2 [Ammonium carbonate.] [Ammonium carbamate.] [Urea or carbamide.] Ammonia. The urine of man and carnivora contains small quantities of ammonium salts. In man the daily amount of ammonia excreted varies between 0'3 and 1*2 grammes; the average is 0"7 gramme. The ingestion of ammonium carbonate does not increase the amount of ammonia in the urine, but increases the amount of urea, into which substance the ammonium carbonate is easily converted. But if a more stable salt, like ammonium chloride, is given, it appears as such in the urine. Under normal circumstances the amount of ammonia depends on the adjustment between the production of acid substances in meta- bolism and the supply of bases in the food. Ammonia formation is the physiological remedy for deficiency of bases. When the production of acids is excessive (as in diabetes), or when mineral acids are given by the mouth or injected into the blood-stream, the result is an increase of the physiological remedy, 560 THE URINE [CH. XXXVII. and excess of ammonia passes over into the urine. Under normal circumstances ammonia is kept at a minimum, being finally converted into the less toxic substance urea, which the kidneys easily excrete. The defence of the organism against acids which are very toxic, is an increase of ammonia formation, or, to put it more correctly, less of the ammonia formed is converted into urea. Under the opposite conditions, namely, excess of alkali, either in food or given as such, the ammonia disappears from the urine, all being converted into urea. Hence the diminution of ammonia in the urine of man on a vegetable diet, and its absence in the urine of herbivorous animals. Not only is this the case, but if ammonium chloride is given to a herbivorous animal like a rabbit, the urinary ammonia is but little increased. It reacts with sodium carbonate in the tissues, forming ammonium carbonate (which is excreted as urea) and sodium chloride. Herbivora also suffer much more from, and are more easily killed by, acids than carnivora, their organisation not permitting a ready supply of ammonia to neutralise excess of acids. Uric Acid. Uric Acid (C 5 N 4 H 4 3 ) is, in mammals, the medium by which a very small quantity of nitrogen is excreted from the body. It is, however, in birds and reptiles the principal nitrogenous constituent of their urine. It is not present in the free state, but is combined with bases to form urates. It may be obtained from human urine by adding 5 c.c. of hydro- chloric acid to 100 c.c. of the urine, and allowing the mixture to stand for twelve to twenty-four hours. The crystals which form are deeply tinged with urinary pigment, and though by repeated solution in caustic soda or potash, and precipitation by hydrochloric acid, they may be obtained fairly free from pigment, pure uric acid is more readily obtained from the solid urine of a serpent or bird, which consists principally of the acid ammonium urate. This is dissolved in soda, and then the addition of hydrochloric acid produces as before the crystallisation of uric acid from the solution. The pure acid crystallises in colourless rectangular plates or prisms. In striking contrast to urea it is a most insoluble substance, requiring for its solution 1900 parts of hot and 15,000 parts of cold water. The forms which uric acid assumes when precipitated from human urine, either by the addition of hydrochloric acid or in certain pathological processes, are very various, the most frequent being the whetstone shape; there are also bundles of crystals resembling sheaves, barrels, and dumb-bells (see fig. 429). The murexide test is the principal test for uric acid. The test CH. XXXVII.] URIC ACID 561 has received the name on account of the resemblance of the colour to the purple of the ancients, which was obtained from certain snails of the genus Murex. It is performed as follows : place a little uric acid or a urate in a capsule ; add a little dilute nitric acid and evaporate to dryness. A yellowish-red residue is left. Add a little ammonia carefully, and the residue turns violet; this is clue to the forma- tion of purpurate of ammonia. On the addition of potash the colour becomes bluer. Another reaction that uric acid un- dergoes (though it is not applicable as a test) is, that on treatment with certain oxidising reagents urea and oxalic acid can be obtained from it. Alloxan (C 4 H.,lSr 2 4 ) or allantoin (C 4 H 6 lSr 4 3 ) are intermediate products. It is, however, doubtful whether a . ' . . , , Fig. 429.— Various forms of uric acid similar oxidation occurs in the normal crystals. metabolic processes of the body. Uric acid is dibasic, and thus there are two classes of urates — the normal urates and the acid urates. A normal urate is one in which two atoms of the hydrogen are replaced by two of a monad metal like sodium ; an acid urate is one in which only one atom of hydrogen is thus replaced. The formulae would be — C 5 H 4 N 4 3 = uric acid. C 5 H 3 NaN" 4 3 = acid sodium urate. C 5 H 2 Na 2 ]Sr 4 3 = normal sodium urate. The acid sodium urate is the chief constituent of the pinkish deposit of urates, which often occurs in urine, and is called the lateritious deposit. If uric acid is represented by H. 2 U, the normal urates may be represented by M 2 U, and the acid urates by MHU. Bence Jones, and later Sir W. Roberts, considered that the urates actually occurring in urine are what are termed quadri- urates MHU.H,U. There is much doubt whether such compounds really exist ; if they do, they are readily decomposed into acid urate, MHU, and free uric acid, H 2 U. The quantity of uric acid excreted by an adult varies from 7 to 10 grains (0"5 to 0*75 gramme) daily. The best method for determining the quantity of uric acid in the urine is that of Hopkins. Ammonium chloride in crystals is .added to the urine until no more will dissolve. This saturation completely precipitates all the uric acid in the form of ammonium urate. After standing for two hours the precipitate is collected on 2 N 562 THE URINE [CH. XXXVII. a filter, washed with saturated solution of ammonium chloride, and then dissolved in weak alkali. From this solution the uric acid is precipitated by neutralising with hydrochloric acid. The precipitate of uric acid is collected on a weighed filter, dried, and weighed; or the crystals may be dissolved in sodium carbonate solution, and titrated with standard solution of potassium permanganate, until a diffused pink flush appears throughout the solution. Origin of Uric Acid. — Uric acid is not made by the kidneys. When the kidneys are removed uric acid continues to be formed and accumulates in the organs, especially in the liver and spleen. The liver has been removed from birds, and uric acid is then hardly formed at all, its place being taken by ammonia and lactic acid. It is there- fore probable in these animals that ammonia and lactic acid are normally synthesised in the liver to form uric acid. The chief conditions which lead to an increase of uric acid are : — 1. Increase of meat diet and diminution of oxidation processes, such as occur in people with sedentary habits. 2. Pathological conditions allied to gout. 3. Increase of white corpuscles in the blood, especially in the disease known as leucocythcemia. This latter fact is of great interest, as leucocytes contain large quantities of nuclein. Nuclein yields nitrogenous (purine) bases (adenine, hypoxanthine, etc.), which are closely related to uric acid. The close relationship of the purine bases to uric acid has been clearly demon- strated by the work of Emil Fischer, for they are all derivatives of the substance called purine. The names and formulae of these substances are as follows : — Purine C S H 4 N 4 Hypoxanthine (monoxy-purine) r, . , Xanthine (dioxy-purine) Purine bases. Aden i ne (kminS-purine) ^Guanine (amino-oxy-purine) Uric acid (trioxy-purine) C 5 H 4 N 4 C 5 H 4 N 4 0., C,H..N 4 .NH„ C 5 H.;N 4 O.NH n C,H 4 N 4 :; We have here a way in which uric acid may arise by oxidation from the nuclein bases, and thus ultimately from the nuclei of cells. Certain forms of diet increase uric acid formation by leading to an increase of leucocytes and consequently increase in the metabolism of their nuclei ; in some cases, however, the increase is chiefly due to nuclein in the food. Uric acid, which comes from nuclein or purine substances in the food, is termed exogenous ; that which arises from metabolism is termed endo- genous. Although special attention has been directed to the nuclei of leucocytes because these can be readily examined during life, it must be remembered that the nuclein metabolism of all cells may contribute to uric acid formation. The synthetic formation of uric acid from ammonia and lactic acid, which is so important in birds, occurs in mammals to a slight extent only. Hippuric Acid. Hippuric Acid (C 9 H 9 N0 3 ), combined with bases to form hip- purates, is present in small quantities in human urine, but in large quantities in the urine of herbivora. This is due to the food of CH.1 XXXVII.] CREATININE 563 herbivora containing substances belonging to the aromatic group — the benzoic acid series. If benzoic acid is given to a man, it unites with glycine with the elimination of a molecule of water, and is excreted as hippuric acid — C 6 H 5 .COOH + CH,.NH., CH 9 NH.CO.C 6 H £ [Benzoic acid.] COOH [Glycine.] COOH [Hippuric acid.] + H 9 [Water.] This is a well-marked instance of synthesis carried out^ in the animal body, and experimental investigation shows that it is accom- plished by the living cells of the kid- ney itself ; for if a mixture of glycine, benzoic acid, and blood is injected through the kidney (or mixed with a minced kidney just removed from the body of an animal), their place is found to have been taken by hippuric acid. FiG-5430. — Crystals of hippuric acid. Creatinine. The creatinine of the urine is next to urea its most abundant nitro- genous constituent. Some is derived directly from the creatine of the meat in the food. The remainder is a product of proteid katabolism, and the creatine of the muscles is possibly an intermediate stage in its formation. This amount remains very constant even when the proteid of the food is greatly reduced in quantity. (Folin.) The formation of creatinine from creatine is represented in the following equation : — C 4 H 9 N 3 2 - H 2 = C 4 H r N 3 0. [Creatine.] [Water.] [Creatinine.] Creatine and creatinine are of considerable chemical interest, because urea can be obtained from them as one of their decomposition products in the laboratory; the equation which represents the formation of urea from creatine is as follows : — C 4 H 9 N 3 2 + H.p [Creatine.] " [Water.] CON 9 H 4 [Urea.] + C 3 H r N0. 2 . [Sarcosine.] The second substance formed is sarcosine. Sarcosine is methyl- glycine — that is, amino-acetic acid in which one H is replaced by methyl (OIL) /NH.CH 3 ^ 2 \COOH. 564 THE URINE [CH. XXXVII. Creatinine with zinc chloride gives a characteristic crystalline precipitate (groups of fine needles) with composition C 4 H 7 N 3 O.ZnCl,. According to the recent researches of G. S. Johnson, urinary creatinine, though isomeric with the creatinine obtained artificially from the creatine of flesh, differs from it in some of its properties, such as reducing power, solubility, and character of its gold salts. The reducing action of urinary creatinine has led to some confusion, for some physiologists have supposed that the reducing action on Fehling's solution and picric acid of normal urine is due to sugar, whereas it is really chiefly due to creatinine. The readiest way of separating creatinine from urine is the following: — To the urine a twentieth of its volume of a saturated solution of sodium acetate is added, and then one-fourth of its volume of a saturated solution of mercuric chloride : this produces an immediate abundant precipitate of urates, sulphates, and phosphates, which is removed by nitration ; the filtrate is then allowed to stand for twenty-four hours, when the precipitation of a mercury salt of creatinine (C 4 H 5 HgN 3 OHCl) 4 (HgCl 2 ) 3 + 2H o occurs in the form of minute spheres, quite typical on micro- scopic examination. This compound lends itself very well to quan- titative analysis. It may be collected, dried, and weighed, and one-fifth of the weight found is creatinine. Creatinine may be obtained from it by suspending it in water, decomposing it with sulphuretted hydrogen, and filtering. The filtrate deposits creatinine hydrochloride, from which lead hydrate liberates creatinine. An important point in Johnson's process is that all the operations are carried out in the cold ; if heat is applied one obtains the creatinine of former writers, which has no reducing power. The Inorganic Constituents of Urine. The inorganic or mineral constituents of urine are chiefly chlorides, phosphates, sulphates, and carbonates ; the metals with which these are in combination are sodium, potassium, ammonium, calcium, and magnesium. The total amount of these salts varies from 19 to 25 grammes daily. The most abundant is sodium chloride, which averages in amount 10 to 16 grammes per diem. These sub- stances are derived from two sources — first from the food, and secondly as the result of metabolic processes. The chlorides and most of the phosphates come from the food ; the sulphates and some of the phos- phates, as a result of metabolism. The salts of the blood and of the urine are much the same, with the important exception that, whereas the blood contains only traces of sulphates, the urine contains abundance of these salts. The sulphates are derived from the changes that occur in the proteids of the body; the nitrogen of CH. XXXVII.] INOEGANIC SALTS 565 proteids leaves the body as urea and uric acid ; the sulphur of the proteids is oxidised to form sulphuric acid, which passes into the urine in the form of sulphates. The excretion of sulphates, more- over, though it occurs earlier than that of urea, runs parallel with it. Chlorides. — The chief chloride is that of sodium. The ingestion of sodium chloride is followed by its appearance in the urine, some on the same day, some on the next day. Some is decomposed to form the hydrochloric acid of the gastric juice. The salt, in passing through the body, fulfils the useful office of stimulating metabolism and secretion. Sulphates. — The sulphates in the urine are principally those of potassium and sodium. They are derived from the metabolism of proteids in the body. Only the smallest trace enters the body with the food. Sulphates have an unpleasant bitter taste (for instance, Epsom salts) : hence we do not take food that contains them. The sulphates vary in amount from 1*5 to 3 grammes daily. In addition to these sulphates there is a small quantity, about one-tenth of the total sulphates, that are combined with organic radicles : these are known as ethereal sulphates, and they originate from putrefactive processes occurring in the intestine. The chief of these ethereal sulphates are phenyl sulphate of potassium and indoxyl sulphate of potassium. The latter originates from the indole formed in the intestine, and as it yields indigo when treated with certain reagents it is sometimes called indican. It is very important to remember that the indican of urine is not the same thing as the indican of plants, which is a glucoside. Both yield indigo, but there the resemblance ceases. The formation of these sulphates is somewhat important; the aromatic substances liberated by putrefactive processes in the intestine are poisonous, but their conversion into ethereal sulphates renders them harmless. The equation representing the formation of potassium phenyl-sulphate is as follows : — C 6 H 5 OH + SO./gJJ = SO/^^ U > + H,0. [Phenol.] [Potassium [Potassium [Water.] hydrogen phenyl-sulphate.] sulphate.] Indole (C 8 H 7 N) on absorption is converted into indoxyl : — P tt /C.OH:CH The equation representing the formation of potassium indoxyl-sulphate is as follows : — C 8 H v NO + S0. 2 <^§^ = SO./q^ sH6N + H 2 0. [Indoxyl.] [Potassium [Potassium [Water.] hydrogen indoxyl-sulphate.] sulphate.] 5oG THE UHINR [CH. XXXVII. Carbonates. — Carbonates and bicarbonates of sodium, calcium, magnesium, and ammonium are only present in alkaline urine. They arise from the carbonates of the food, or from vegetable acids (malic, tartaric, etc.) in the food. They are, therefore, found in the urine of herbivora and vegetarians, whose urine is thus rendered alkaline. Urine containing carbonates becomes, like saliva, cloudy on standing, the precipitate consisting of calcium carbonate, and also phosphates. Phosphates. — Two classes of phosphates occur in normal urine : — (1) Alkaline phosphates — that is, phosphates of sodium (abundant) and potassium (scanty). (2) Earthy phosphates — that is, phosphates of calcium (abundant) and magnesium (scanty). The composition of the phosphates in urine is liable to variation. Via. 431. — Urinary sediment of triple phos- phates (large prismatic crystals) ami urate of ammonium, from urine which had undergone alkaline fermentation. Fin. 432. — Mucus deposited from urine. In acid urine the acidity is due to the acid salts. These are chiefly : — Sodium dihydrogen phosphate, NaH.,P0 4 , and calcium dihydrogen phosphate, Ca(rIoP0 4 ) 2 . In neutral urine, in addition, disodium hydrogen phosphate (Na.,HP0 4 ), calcium hydrogen phosphate, CaHP0 4 , and magnesium hydrogen phosphate, MgHP0 4 , are found. In alkaline urine there may be instead of, or in addition to, the above, the normal phosphates of sodium, calcium, and magnesium [Na 3 P0 4 , Ca 3 (P0 4 ) 2 , Mg 3 (PO d ).,]. The earthy phosphates are precipitated by rendering the urine alkaline by ammonia. In decomposing urine, ammonia is formed from the urea: this also precipitates the earthy phosphates. The phosphates most frequently found in the white creamy precipitate which occurs in decomposing urine are: — (1) Triple phosphate or ammonio - magnesium phosphate CH. XXXVII.] UEINAEY DEPOSITS 567 (NH 4 MgP0 4 + 6H 2 0). This crystallises in "coffin-lid " crystals (see fig. 431) or feathery stars. (2) Stellar phosphate, or calcium phosphate; this crystallises in star-like clusters of prisms. As a rule normal urine gives no precipitate when it is boiled ; but sometimes neutral, alkaline, and occasionally faintly acid urines give a precipitate of calcium phosphate when boiled : this precipitate is amorphous, and is liable to be mistaken for albumin. It may be distinguished readily from albumin, as it is soluble in a few drops of acetic acid, whereas coagulated proteid does not dissolve. The phosphoric acid in the urine chiefly originates from the phos- phates of the food, but is partly a decomposition product of the phos- phorised organic materials in the body, such as lecithin and nuclein. The amount of P 2 5 in the twenty-four hours' urine varies from 2 - 5 to 3 '5 grammes, of which the earthy phosphates contain about half (1 to 1-5 gr.). Tests for the Inorganic Salts of Urine. Chlorides. — Acidulate with nitric acid and add silver nitrate ; a white precipitate of silver chloride, soluble in ammonia, is produced. The object of acidulating with nitric acid is to prevent phosphates being precipitated by the silver nitrate. Sulphates. — Acidulate with hydrochloric acid, and add barium chloride. A white precipitate of barium sulphate is produced. Hydrochloric acid is again added first, to prevent precipitation of phosphates. Phosphates. — i. Add ammonia; a white crystalline precipitate of earthy (that is, calcium and magnesium) phosphates is produced. This becomes more apparent on standing. The alkaline (that is, sodium and potassium) phosphates remain in solution, ii. Mix another portion of urine with half its volume of nitric acid ; add ammonium molybdate, and boil. A yellow crystalline precipitate falls. This test is given by both classes of phosphates. Quantitative estimation of the salts is accomplished by the use of solutions of standard strength, which are run into the urine till the formation of a precipitate ceases. The standards are made of silver nitrate, barium chloride, and uranium nitrate or acetate for chlorides, sulphates and phosphates respectively. Urinary Deposits. The different substances that may occur in urinary deposits are formed elements and chemical substances. The formed or anatomical elements may consist of blood corpuscles, pus, mucus, epithelium cells, spermatozoa, casts of the urinary tubules, fungi, and entozoa. All of these, with the exception of a small quantity of mucus, which forms a flocculent cloud in the urine, are pathological, and the microscope is chiefly employed in their detection. The chemical substances are uric acid, urates, calcium oxalate, calcium carbonate, and phosphates. Earer forms are leucine, tyrosine, xanthine, and cystin. We shall, however, here only consider the commoner deposits, and for their identification the microscope and chemical tests must both be employed. 568 THE URINE [CII. XXXVII. Deposit of Uric Acid. — This is a sandy reddish deposit resembling cayenne pepper. It may be recognised by its crystalline form (fig. 429, p. 561) and the murexide reaction. The presence of these crystals generally indicates an increased formation of uric acid, and, if excessive, may lead to the formation of stones or calculi in the bladder. Deposit of Urates. — This is much commoner, and may, if the urine is concentrated, occur in normal urine when it cools. It is generally found in the concentrated urine of fevers ; and there appears to be a kind of fermentation, called the acid fermentation, which occurs in the urine after it has been passed, and which leads to the same result. The chief constituent of the deposit is the acid Fio. 433. — Crystals of calcium oxalate. Fig. 434. — Crystals of cystin. sodium urate, the formation of which from the normal sodium urate of the urine may be represented by the equation : — 2C 5 H.,N T a,N 4 3 + H 2 + CO, = 2C 6 HLNaN 4 3 + Na 2 C0 3 . [Normal sodium [Water.] [Carbonic [Acid sodium urate.] [Sodium urate.] acid.] carbonate.] This deposit may be recognised as follows : — (1) It has a pinkish colour ; the pigment called uro-erythrin is one of the pigments of the urine, but its relationship to the other urinary pigments is not known. (2) It dissolves upon warming the urine. (3) Microscopically it is usually amorphous, but crystalline forms similar to those depicted in fig. 431 may occur. Crystals of calcium oxalate may be mixed with this deposit (see fig. 433). Deposit of Calcium Oxalate. — This occurs in envelope crystals (octahedra) or dumb-bells. It is insoluble in ammonia, and in acetic acid. It is soluble with difficulty in hydrochloric acid. Deposit of Cystin. — Cystin (C G H 12 N 2 S.,0 4 ) is recognised by its colourless six-sided crystals (fig. 434). These are rare: they occur CH. XXXVII.] UKINAEY DEPOSITS 5G9 only in acid urine, and they may form concretions or calculi. Cystinuria (cystin in the urine) is hereditary. Deposit of Phosphates. — These occur in alkaline urine. The urine may be alkaline when passed, due to fermentative changes occurring in the bladder. All urine, however, if exposed to the air (unless the air is perfectly pure, as on the top of a snow mountain), will in time become alkaline, owing to the growth of the micrococcus urece. This forms ammonium carbonate from the urea. CON 2 H 4 + 2H 2 = (NH 4 ) 2 C0 3 . [Urea.] [Water.] [Ammonium carbonate.] The ammonia renders the urine alkaline and precipitates the earthy phosphates. The chief forms of phosphates that occur in urinary deposits are— (1) Calcium phosphate, Ca 3 (P0 4 ) 2 ; amorphous. (2) Triple or ammonio-magnesium phosphate, MgN"H 4 P0 4 ; coffin- lids and feathery stars (fig. 431). _ (3) Crystalline phosphate of calcium, CaHP0 4 , in rosettes of prisms, in spherules, or in dumb-bells. (4) Magnesium phosphate, Mg 3 (P0 4 ) 2 + 22H 2 0, occurs occasion- ally, and crystallises in long plates. All these phosphates are dissolved by acids, such as acetic acid, without effervescence. A solution of ammonium carbonate (1 in 5) eats magnesium phosphate away at the edges ; it has no effect on the triple phosphate. A phosphate of calcium (CaHP0 4 + 2H 2 0) may occasionally be deposited in acid urine. Pus in urine is apt to be mistaken for phosphates, but can be distinguished by the microscope. Deposit of calcium carbonate, CaC0 3 , appears but rarely as whitish balls or biscuit-shaped bodies. It is commoner in the urine of herbivora. It dissolves in acetic or hydrochloric acid, with effervescence. The following is a summary of the chemical sediments that may occur in urine : — CHEMICAL SEDIMENTS IN URINE. In Acid Urixe. i Ix Alkaline Urine. Uric Acid,— Whetstone, dumb-bell, I Phosphates. — Calcium phosphate, or sheaf-like aggregations of crystals ; Ca f (P0 4 ),. Amorphous, deeply tinged by pigment. triple phosphate, Urates.— Generally amorphous. The ; MgNH 4 P0 4 + 6H. 2 0. Coffin-lids or acid urate of sodium and of ammonium feathery stars, may sometimes occur in star-shaped i Calcium hydrogen phosphate, clusters of needles or spheroidal clumps \ CaHP0 4 . Rosettes, spherules, ordumb- with projecting spines. Tinged brick- bells. red. Soluble on warming. Magnesium phosphate, Calcium Oxalate, — Octahedra, so- ' Mg 3 (P0 4 ) 2 + 22H„0. Long plates. 570 THE URINE [CII. XXXVII. CHEMICAL SEDIMENTS IN URINE— Continued. Is Acid Urine. called envelope crystals. Insoluble in acetic acid. Cystin. — Hexagonal plates. Rare. Leucine and Tyrosine. — Rare. Calcium Phosphate, CaHPO, + 2H,0.— Rare. In Alkaline Uhihe. All the preceding are soluble in acetic acid without effervescence. Calcium Carbonate, CaC0 3 .— Biscuit- shaped crystals. Soluble in acetic acid with effervescence. Ammonium I' rati , C,H 2 (NHJ. 2 .N 4 0,. — "Thorn-apple" spherules. L, acint ami Tyrosine. — Very rare. Pathological Urine. Under this head we shall briefly consider only those abnormal constituents which are most frequently met with. Proteids. — There is no proteid matter in normal urine * and the most common cause of the appearance of albumin in the urine is disease of the kidney (Bright's disease). The term "albumin" is the one used by clinical observers. Properly speaking, it is a mixture of serum albumin and serum globulin. Of these, serum albumin is usually the more abundant. Globulins, and especi- ally englobulins, have probably larger molecules, so escape of globulin indicates more serious damage to the renal cells. The best methods of testing for and estimating the proteid are the following: — (a) Boil the top of a long column of urine in a test-tube. If the urine is acid, the albumin is coagulated. If the quantity of albumin is small, the cloudiness produced is readily seen, as the unboiled urine below it is clear. This is insoluble in a few drops of acetic acid, and so may be distinguished from phosphates. If the urine is alkaline, it should be first rendered acid with a little dilute acetic acid. (I>) Heller's Nitric-acid Test.— Pour some of the urine gently on to the surface of some nitric acid in a test-tube. A ring of white precipitate occurs at the junction of the two liquids. This test is used for small quantities of albumin. {<■) Estimation of Albumin by Esbach's Albuminometer. — Esbach's reagent for precipitating the albumin is made by dissolving 10 grammes of picric acid and 20 grammes of citric acid in 800 or 900 c.c. of boiling water, and then adding sufficient water to make up to a litre (1000 c. a). The albuminometer is a test-tube graduated as shown in fig. 43o. Pour the urine into the tube up to the mark U ; then the reagent up to the mark R. Close the tube with a cork, and to ensure complete mixture, tilt it to and Fig. 435.— Esbach's Albuminometer. * This absolute statement is true for all practical purposes. Morner, however, has stated that a trace of proteid matter (serum albumin plus the proteid constituent of mucin) does occur in normal urine ; but the trace is negligible, many hundreds of litres of urine having to be used to obtain an appreciable quantity. CH. XXXVII.] PATHOLOGICAL URINE 571 fro a dozen times without shaking. Allow the corked tube to stand upright twenty- four hours ; then read off on the scale the height of the coagulum. The figures indi- cate grammes of dried albumin in a litre of urine. The percentage is obtained by dividing by 10. Thus, if the coagulum stands at 3, the amount of albumin is 3 grammes per litre, or 0'3 gr. in 100 c.c. If the sediment falls between any two figures, the distance J, \, or f from the upper or lower figure can be read off with sufficient accuracy. Thus, the surface of the sediment being midway between 3 and 4 would be read as 3 '5. When the albumin is so abundant that the sediment is above 4, a more accurate result is obtained by first diluting the urine with one or two volumes of water, and then multiplying the resulting figure by 2 or 3, as the case may be. If the amount of albumin is less than *05 per cent, it cannot be accurately estimated by this method. A condition called " peptonuria," or peptone in the urine, is observed in certain pathological states, especially in diseases where there is a formation of pus, and particularly if the pus is decomposed owing to the action of a bacterial growth called staphylococcus ; one of the products of disintegration of pus cells appears to be peptone ; and this leaves the body by the urine. The term " peptone," how- ever, is in the strict sense of the word incorrect ; the proteid present is deutero-proteose. In the disease of bone called " osteomalacia " a ■ proteose is also usually found in the urine. This more nearly resembles hetero-proteose in its properties. Sugar. — Normal urine contains no sugar, or so little that for clinical purposes it may be considered absent. It occurs in the disease called diabetes mellitus, which can be artificially produced by puncture of the medulla oblongata, or by extirpation of the pancreas. The disease as it occurs in man may be due to disordered metabolism of the liver, to disease of the pancreas, and to other not fully under- stood causes (see p. 516). The sugar present is dextrose. Lactose may occur in the urine of nursing mothers. Diabetic urine also contains hydroxybutyric acid, and may contain or yield on distillation acetone, and ethyl- diacetic acid. The methods usually adopted for detecting and estimating the sugar are as follows : — (a) The urine has generally a high specific gravity. (6) The presence of sugar is shown by the reduction (yellow precipitate of cuprous oxide) that occurs on boiling with Fehling's solution. Fehling's solution is an alkaline solution of copper sulphate to which Rochelle salt has been added. The Rochelle salt (double tartrate of potash and soda) holds the cupric hydrate in solution. Fehling's solution should always be freshly prepared, as, on standing, an isomeride is formed from the tartaric acid, which reduces the cupric to cuprous oxide. Fehling's solution should, therefore, always be tested by boiling before it is used. If it remains clear on boiling, it is in good condition. (c) Picric Acid Test. — Take a drachm (about 4 c.c.) of diabetic urine ; add to it an equal volume of saturated aqueous solution of picric acid, and half the volume (i.e., 2 c.c.) of the liquor potassag of the British Pharmacopoeia. Boil the mixture for about a minute, and it becomes so intensely dark red as to be opaque. Now do the same experiment with normal urine. An orange-red colour appears even in the cold, and is deepened by boiling, but it never becomes opaque, and so the urine for clinical purposes may be considered free from sugar. This reduction of picric acid by normal urine is due to creatinine (see p. 564). 572 THE URINE [CII. XXXVII. (d) Quantitativi Determination of Sugar in Urine. — Fehling's solution is pre- pared as follows:- 31 "639 grammes of copper sulphate are dissolved in about 200 c.c. of distilled water; 173 grammes of Roehelle salt are dissolved in 600 C.C. of a 14 per cent, solution of caustic soda. The two solutions are mixed and diluted to a litre. Ten c.c. of this solution are equivalent to - 0."> gramme of dextrose. Dilute 10 c.c. of this solution with about 40 c.c. of water, and boil it in a porcelain basin. Run into this from a burette the urine (which should be previously diluted with nine times its volume of distilled water) until the blue colour of the copper solution disappears — that is, till all the cupric hydrate is reduced. The mixture in the basin should be boiled after every addition. The quantity of diluted urine used from the burette contains 0"05 gramme of sugar. Calculate the percentage from this, remembering that the urine has been diluted to ten times its original volume. Pavy's modification of Fehling's solution is often used. Here ammonia holds the copper in solution, and no precipitate forms on boiling with sugar, as ammonia holds the cuprous oxide in solution. The reduction is complete when the blue colour disappears; 10 c.c. of Pavy's solution = 1 c.c. of Fehling's solution = 0*005 gramme of dextrose. In some cases of diabetic urine where there is excess of ainmonio-magnesic phosphate, the full reduction is not obtained with Fehling's solution, and when the quantity of sugar is small it may be missed. In such a case excess of soda or potash should be first added, the precipitated phosphates filtered off, and the filtrate after it has been well boiled may then be titrated with Fehling's solution. Fehling's test is not absolutely trustworthy. Often a normal urine will decolorise Fehling's solution, though seldom a red precipitate is formed. This is due to excess of urates and creatinine. Another substance called glycuronic acid (C, ; H ln 7 ) is, however, very likely to be confused with sugar by Fehling's test; the cause of its appearance is sometimes the administration of drugs (chloral, camphor, etc.); but sometimes it appears independently of drug treatment. (See p. 517.) In the rare and hereditary condition called alcaptonuria, confusion may also arise. Alcapton is a substance which originates from tyrosine by an unusual form of metabolism. It gives the urine a brown tint, which darkens on exposure to the air. It is an aromatic substance, which Baumann and Wolkow and later Garrod identified with homogentisinic acid (C i; H ; .(OH).,CH.,.COOH) (e) A good confirmatory test for sugar is the fermentation test, which is per- formed as follows : — Half fill a test-tube with the urine and add a little German yeast. Fill up the tube with mercury ; invert it in a basin of mercury, and leave it in a warm place for twenty-four hours. The sugar will undergo fermentation : carbonic acid gas accumulates in the tube, and the liquid no longer gives the tests for sugar, or only faintly, but gives those for alcohol instead. The specific gravity falls. A control experiment should be made with yeast and water in another test-tube, as a small yield of carbonic acid is sometimes obtained from impurities in the yeast. (/) The phenylhydrazine test (p. 391) may also be applied. Bile. — This occurs in jaundice. The urine is dark-brown, greenish, or in extreme cases almost black in colour. The most readily applied test is Gmelin's test for the bile pigments. Petten- kofer's test for the bile acids seldom succeeds in urine if the test is done in the ordinary way. The best method is to warm a thin film of urine and cane sugar solution in a flat porcelain dish. Then dip a glass rod in strong sulphuric acid, and draw it across the film. Its track is marked by a purplish line. Excess of urobilin should not be mistaken for bile pigment. Blood. — When haemorrhage occurs in any part of the urinary tract, blood appears in the urine. It is found in the acute stage of Bright's disease. If a large quantity is present, the urine is deep CH. XXXVII.] PATHOLOGICAL URINE 573 red. Microscopic examination then reveals the presence of blood corpuscles, and on spectroscopic examination the bands of oxyhemo- globin are seen. If only a small quantity of blood is present, the secretion — especially if acid — has a characteristic reddish-brown colour, which physicians term " smoky." The blood pigment may, under certain circumstances, appear in the urine without the presence of any blood corpuscles at all. This is produced by a disintegration of the corpuscles occurring in the circulation, and the most frequent cause of this is a tropical disease allied to ague, which is called paroxysmal hwmogldbinuria (Black- water fever). The pigment is in the condition of methsemoglobin mixed with more or less oxyhemoglobin, and the spectroscope is the means used for identifying these substances. Pus occurs in the urine as the result of suppuration in any part of the urinary tract. It forms a white sediment resembling that of phosphates, and, indeed, is always mixed with phosphates. The pus corpuscles may, however, be seen with the microscope ; their nuclei are rendered evident by treatment with 1 per cent, acetic acid, and the pus corpuscles are seen to resemble white blood-corpuscles, which, in fact, they are in origin. They dissolve in glacial acetic acid. Some of the proteid constituents of the pus cells — and the same is true for blood — pass into solution in the urine, so that the urine pipetted off from the surface of the deposit gives the tests for albumin. On the addition of liquor potassae to the deposit of pus cells, a ropy gelatinous mass is obtained. This is distinctive. Mucus treated in the same way is dissolved. Arginine and Arginase. We have seen (p. 557) that arginine belongs to the same class of substances as creatine. Creatine (rnethyl-guanidine-acetic acid) has NH\ ! the formula /C : - N(CH>)CH.,COOH. On decomposition this takes up a NH 2 / : molecule of water, and splits in the situation of the dotted line in the above formula into urea ^h' 2 ^ 00 ' and sarcosine NH(CH 3 )CH,COOH (see also p. 563). The formula for arginine differs from that of creatine on the right-hand side of the formula, where the sarcosine group is replaced by that of diamino-valeric acid or ornithine. The decomposition of arginine into urea and ornithine can be brought about by a ferment called arc/incise (Kossel and Dakin) which occurs in the tissues, especially in the liver. This is the first discovery of a urea-forming ferment. CHAPTER XXXVIII THE SKIN AND ITS APPENDAGES The skin is composed of two parts, epidermis or cuticle, and dermis or cutis vera. The Epidermis is composed of a large number of layers of cells ; it is a very thick stratified epithelium. The deeper layers are proto- Fio. 436. — Verticarsection of the epidermis of the prepuce, a, stratum comeum, of very few layers the stratum lucidum and stratum granulosum not being distinctly represented ; b, e, d, and e, the layers of the stratum Malpighii, a certain number of the cells in layers d and e showing signs of division ; it consists chiefly of prickle cells ; g, connective-tissue cells in cutis vera. (Cadiat.) plasmic, and form the rete mucosum, or Malpighian layer ; the surface layers are hard and horny ; this horny layer is the thickest part of the epidermis, and is specially thick on the palms and soles, where CH. XXXVIII.] THE EPIDEKMIS 575 it is subjected to most friction. The cells of the deepest layers of the Malpighian layer are columnar in shape ; the layers next to these are composed of polyhedral cells, which become flatter as they approach the horny layers. Between these cells are fine intercellular passages, bridged across by fine protoplasmic processes, which pass from cell to cell ; the spaces between the cells serve for the passage of lymph. It is in the cells of the Malpighian layer that pig- ment granules are deposited in the coloured races. Between the horny layer and the Malpighian layer are two intermediate strata, in which the transformation of protoplasm into horny material {kera- tin) is taking place. In the first of these — that is, the one next to the Malpighian layer, the cells are flat- tened, and filled with large granules of eleiclin, an intermediate sub- stance in the formation of horn. This layer is called the stratum granulosum. Above this are several layers of clear, more rounded cells, which constitute the stratum lucidum ; and above this the horny layer Fig. 437. — Vertical section of skin. A. Sebaceous gland opening into hair follicle. B. Muscu- lar fibres. C. Sudoriferous or sweat-gland. D. Subcutaneous fat. E. Fundus of hair follicle, with hair papilla. (Klein.) 576 THE SKIN AND ITS APPENDAGES [CH. XXXVIII. proper, many strata deep, begins. The cells become more and more scaly as they approach the surface, where they lose their nuclei and eventually become detached. The epidermis grows by a multiplication of the deepest layer of Fig. 438.— Surface of a white hair, magnified 100 diameters. The wavy lines mark the upper or free edges of the cortical scales. B, separated scales, magnified 350 diameters. (Kolliker.) cells (fie. 436 e) ; the newly-formed cells push towards the surface those previously formed, in their progress undergoing the transfor- mation into keratin. The epidermis has no blood-vessels; nerve-fibrils pass into its deepest layers, and ramify between the cells. The Dermis is composed of dense fibrous tissue, which becomes looser and more reticular in its deeper part, where it passes by insensible degrees into the areolar and adipose tissue of the sub- cutaneous region. The denser superficial layer is very vascular, and is covered with minute papillce ; the epidermis is moulded over these, and in the palms and soles, where the papillae are largest and are disposed in rows, their presence is indicated by the well-known ridges on the surface. The papillce contain loops of capil- laries, and in some cases, especially in the palm of the hand and fingers, they contain tactile corpuscles (which will be more fully described in connection with the sense of touch). Special capillary networks are distributed to the sweat-glands, sebaceous glands, and hair follicles. The deeper portions of the dermis in the scrotum, penis, and nipple, contain involuntary muscular tissue; there is also a bundle of muscular tissue attached to each hair follicle. Fig. 430. — Longitudinal section of a hair follicle, a and 6, external root- sheath ; c, internal root-sheath ; d, fibrous layer of the hair ; e, me- dulla; /, hair papilla ; g, blood- vessels of the hair papilla; h, dermic coat. (Cadiat.) CH. XXXVIII.] THE NAILS AND HALES 577 The Nails are thickenings of the stratum lucidum. Each lies in a depression called the bed of the nail, the posterior part of which is overlapped by epidermis, and called the nail-groove. The dermis beneath is beset with longitudinal ridges instead of papillae; these are very vascular ; but in the lunula, the crescent at the base of the nail, there are papillae, and this part is not so vascular. The Hairs are epidermal growths, contained in pits called hair follicles. The part within the follicle is called the root of the hair. The main substance of the hair is composed of pigmented horny fibrous material, in reality long fibrillated cells. It is covered by a Fig. 440. — Transverse section of a hair and hair follicle made below the opening of the sebaceous gland. a, medulla, or pith of the hair ; 6, fibrous layer ; c, cuticle ; d, Huxley's layer ; e, Henle's layer of internal root-sheath ; /and g, layers of external root-sheath, outside of g is the basement membrane or hyaline layer ; h, dermic (fibrous) coat of hair follicle ; i, vessels. (Cadiat.) layer of scales imbricated upwards (hair cuticle). In many hairs the centre is occupied by a medulla, formed of rounded cells containing eleidin granules. Minute air-bubbles may be present in both medulla and fibrous layer, and cause the hair to look white by reflected light. The grey hair of old age, however, is produced by a loss of pigment. The root is enlarged at its extremity into a Jcnoh, into which pro- jects a vascular papilla from the true skin. The hair follicle consists of two parts, one continuous with the epidermis, called the root-sheath, the other continuous with the dermis, called the dermic coat. The two are separated by a basement mem- brane called the hyaline layer of the follicle. The root-sheath con- 2 578 THE SKIN AND ITS APPENDAGES [CH. XXXVIII. sists of an outer layer of cells like the Malpighian layer of tho epidermis, with which it is directly continuous (outer root-sheath), and of an inner horny layer (inner root-sheath), continuous with the horny layer of the epidermis. The inner root-sheath consists of three layers, the outermost being composed of long, non-nucleated cells (Henle's layer), the next of squarish nucleated cells (Huxley's layer), and the third is a cuticle of scales, imbri- cated downwards, which tit over the scales of the cuticle of the hair itself. A small bundle of plain mus- cular fibres is attached to each follicle (fig. 437). When it con- tracts, as under the influence of cold, or of certain emotions such as fear, the hair is erected and the whole skin is roughened ("goose skin "). The nerves supplying these muscles are called pilo-motor nerves. The distribution of these nerves closely follows those of the vaso-constric tor nerves of the skin; Flu. 441. — Sebaceous gland from human skin. (Klein and Noble Smith.) their cell stations are in the lateral sympathetic chain. The sebaceous glands (figs. 437 and 441) are small saccular glands, with ducts opening into the upper portion of the hair fol- licles. The secreting cells become charged with fatty matter, which is discharged into the lumen of the saccules owing to the disintegration of the cells. The secretion, sebum, contains isocholesterin (see p. 512) in addition to fatty matter. It acts as a lubricant to the hairs. The sweat-glands are abundant over the whole human skin, but are most numerous where hairs are absent, on the palms and soles. Each consists of a coiled tube in the deepest part of the dermis, the 442. —Terminal tubules of sudoriferous or sweat-glands, cut in various directions from the skin of the pig's ear. (V. D. Harris.) CH. XXXVIII.] FUNCTIONS OF THE SKIN 579 duct from which passes up through the dermis, and by a corkscrew- like canal through the epidermis to the surface. The secreting tube is lined by one or two layers of cubical or columnar cells; outside this is a layer of longitudinally arranged muscular fibres, and then a basement-membrane. The duct is of similar structure, except that there is usually but one layer of cubical cells, and muscular fibres are absent ; the passage through the epidermis has no proper wall ; it is merely a channel excavated between the epidermal cells. The ceruminous glands of the ear are modified sweat-glands. The Functions of the Skin Protection. — The skin acts as a protective organ, not only by mechanically covering and so defending internal structures from external violence, but more particularly in virtue of its being an organ of sensation (see later in the chapter on Touch). Heat Regulation. — See Chapter XL. Respiration. — A small amount of respiratory interchange of gases occurs through the skin, but in thick-skinned animals this is very small. In man, the carbonic acid exhaled by the skin is about yA^- to 2I5-0 °f that which passes from the lungs. But in thin-skinned animals, like frogs, cutaneous respiration is very important ; after the removal of the lungs of a frog, the respiratory interchange through the skin is sufficient to keep the animal alive, the amount of carbonic acid formed being about half as much as when the lungs are present (Bischoff). Absorption. — This also is an unimportant function ; but the skin will in a small measure absorb oily materials placed in contact with it ; thus in some cases infants who will not take cod-liver oil by the mouth, can yet be dosed with it by rubbing it into the skin. Many ointments also are absorbed, and thus general effects produced by local inunction. Secretion. — The secretions of the skin are two in number. The sebum is the natural lubricant of the hairs. The secretion of sweat is an important function of the skin, and we will therefore discuss it at greater length. The Sweat Physiology of the Secretion of Sweat. — We have seen that the sweat-glands are most abundant in man on the palms and soles, and here the greatest amount of perspiration occurs. Different animals vary a good deal in the amount of sweat they secrete, and in the place where the secretion is most abundant. Thus the ox perspires less than the horse and sheep; perspiration is absent from rats^ 580 THE SKIN AND ITS APPENDAGES [CH. XXXVIII. rabbits, and goats ; pigs perspire mostly on the snout ; dogs and cats on the pads of the feet. As long as the secretion is small in amount, it is evaporated from the surface at once ; this is called insensible perspiration. As soon as the secretion is increased or evaporation prevented, drops appear on the surface of the skin. This is known as sensible perspiration. The relation of these two varies with the temperature of the air; the drier and hotter the air, the greater being the proportion of insensible to sensible perspiration. In round numbers the total amount of sweat secreted by a man is two pounds in the twenty-four hours. The amount of secretion is influenced by the vaso-motor nerves ; an increase in the size of the skin-vessels leads to increased, a con- striction of the vessels to diminished, perspiration. There are also special secretory fibres, stimulation of which causes a secretion even when the circulation is suspended, as in a recently amputated limb. These fibres are paralysed by atropine. They are contained in the same nerve-trunks as the vaso-motor nerves, as are also the nerve- fibres which supply the plain muscular fibres of the sweat-glands which act during the expulsion of the secretion. The secretory nerves for the lower limbs issue from the spinal cord by the last two or three dorsal and first two or four lumbar nerves (in the cat) ; they have cell stations in the lower ganglia of the lateral chain, and pass to the abdominal sympathetic and thence to the sciatic nerve. They are controlled by a centre in the upper lumbar region of the cord ; those for the upper limbs leave the cord by the sixth, seventh, and eighth anterior thoracic roots, have cell stations in the ganglion stellatum, and ultimately pass to the ulnar and median nerves ; they are controlled by a centre in the cervical enlargement of the cord. The secretory fibres for the head pass in the cervical sympathetic, and in some branches of the fifth cranial nerves. These subsidiary centres are dominated by one in the medulla oblongata (Adam- kiewicz). These facts have been obtained by experiments on animals (cat, horse). The sweat-centres may be excited directly by venous blood, as in asphyxia ; or by over -heated blood (over 45° C.) ; or by certain drugs (see further) ; or reflexly by stimulation of afferent nerves such as the crural and peroneal. Nervous diseases are often accompanied with disordered sweat- ing; thus unilateral perspiration is seen in some cases of hemi- plegia; degeneration of the anterior nerve-cells of the cord may cause stoppage of the secretion. It is sometimes increased in paralysed limbs. The changes that occur in the secreting cells have been investi- gated by Eenaut in the horse. When charged they are clear and swollen, the nucleus being situated near their attached ends; CH. XXXVIII.] THE SWEAT 581 when discharged they are smaller, granular, and their nucleus is more central. The sweat, like the urine, must be regarded as an excretion, the secreting cells eliminating substances formed elsewhere. Composition of the Sweat. — Sweat may be obtained in abundant quantities by placing the animal or man in a closed hot-air bath, or from a limb by enclosing it in a vessel made air-tight with an elastic bandage. Thus obtained, it is mixed with epidermal scales and a small quantity of fatty matter from the sebaceous glands. The con- tinual shedding of epidermal scales is in reality an excretion. Keratin, of which they are chiefly composed, is rich in sulphur, and, consequently, this is one means by which sulphur is removed from the body. The reaction of sweat is acid, and the acidity, as in the urine, is due to acid sodium phosphate. In profuse sweating, however, the secretion usually becomes alkaline or neutral. It has a peculiar and characteristic odour, which varies in different parts of the body, and is due to volatile fatty acids ; its taste is saltish, its specific gravity about 1005. In round numbers the percentage of solids is 1*2, of which 0'8 is inorganic matter. The following table is a compilation from several analyses : — Water . 9S-88 per cent. Solids . 1-12 ,, Salts . 0-57 NaCl . 0-22 to 0-33 J5 Other salts . 0-18 " (alkaline sulphates, phosphates, lactates, and potassium Fats Epithelium Urea 0-41 0-17 . 0-08 M chloride) (including fatty acids and isocholesterin) The salts are in kind and relative quantity very like those of the urine. Funke was unable to find any urea, but most other observers agree on the presence of a minute quantity. It appears to become quickly transformed into ammonium carbonate. The proteid which is present is probably derived from the epithelial cells of the epidermis, sweat-glands, and sebaceous glands, which are suspended in the excretion; but in the horse there is albumin actually in solution in the sweat. Abnormal, Unusual, or Pathological Conditions of the Sweat. — Drugs. — Certain drugs (sudorifics) favour sweating, e.g., pilocarpine, Calabar bean, strychnine, picrotoxine, muscarine, nicotine, camphor, ammonia. Others diminish the secretion, e.g., atropine and morphine in large doses. 582 THE SKIN AND ITS APPENDAGES [CH. XXXVIII. Large quantities of water, by raising the blood-pressure, increase the perspiration. Some substances introduced into the body reappear in the sweat, e.g., benzoic, tartaric, and succinic acids readily, quinine and iodine with more difficulty. Compounds of arsenic and mercury behave similarly. Diseases. — Cystin has been found in some cases of cystinuria ; dextrose in diabetic patients ; bile-pigment in those with jaundice (as evidenced by the staining of the clothes); indigo in a peculiar condition known as chromidrosis ; blood or hfematin deriva- tives in red sweat; albumin in the sweat of acute rheumatism, which is often very acid ; urates and calcium oxalate in gout ; lactic acid in puerperal fever, and occasionally in rickets and scrofula. Kidney Diseases. — The relation of the secretion of the skin to that of the kidneys is a very close one. Thus copious secretions of urine, or watery evacuations from the alimentary canal, coincide with dry- ness of the skin ; abundant perspiration and scanty urine generally go together. In the condition known as urozmia (see p. 556), when the kidneys secrete little or no urine, the percentage of urea rises in the sweat; the sputum and the saliva also contain urea under those circumstances. The clear indication for the physician in such cases is to stimulate the skin to action by hot-air baths and pilocarpine, and the alimentary canal by means of purgatives. In some of these cases the skin secretes urea so abundantly that when the sweat dries on the body, the patient is covered with a coating of urea crystals. Varnishing the Skin. — By covering the skin of such an animal as a rabbit with an impermeable varnish, the temperature is reduced, a peculiar train of symptoms set up, and ultimately the animal dies. If, however, cooling is prevented by keeping such an animal in warm cotton-wool, it lives longer. Varnishing the human skin does not seem to be dangerous. Many explanations have been offered to explain the peculiar condition observed in animals ; retention of the sweat would hardly do it ; the blood is not found post-mortem to contain any abnormal substance, nor is it poisonous when transfused into another animal. Cutaneous respiration is so slight in mammals that stoppage of this function cannot be supposed to cause death. The animal, in fact, dies of cold ; the normal function of the skin in regulating temperature is interfered with, and it is animals with delicate skins which are most readily affected. CHAPTEE XXXIX GENEEAL METABOLISM The word metabolism has been often employed in the preceding chapters, and, as there explained, it is used to express the sum total of the chemical exchanges that occur in living tissues. The chemical changes have been considered separately under the headings Alimentation, Excretion, Eespiration, etc. We have now to put our knowledge together, and consider these subjects in their relation to one another. The living body is always giving off by the lungs, kidneys, and skin the products of its combustion, and is thus always tending to lose weight. This loss is compensated for by the intake of food and of oxygen. For the material it loses, it receives in exchange fresh substances. If, as in a normal adult, the income is exactly equal to the expenditure, the body-weight remains constant. If, as in a growing child, the income exceeds the expenditure, the body gains weight; and if, as in febrile conditions, or during starvation, the expenditure exceeds the income, the body wastes. The first act in the many steps which constitute nutrition is the taking of food, the next digestion of that food, the third absorption, and the fourth assimilation. In connection with these subjects, it is important to note the necessity for a mixed diet, and the relative and absolute quantities of the various proximate principles which are most advantageous. Assimilation is a subject which is exceedingly difficult to describe ; it is the act of the living tissues in selecting, appropriating, and making part of themselves the substances brought to them by the nutrient blood-stream from the lungs on the one hand, and from the alimentary canal on the other. The chemical processes involved in some of these transactions have been already dwelt on in connection with the functions of the liver and other secreting organs, but even there our information on the subject is limited ; much more is this the case in connection with other tissues. Assimilation, or the building up of the living tissues, may, to use Gaskell's expression, be spoken of as anabolic. 584 GENERAL METABOLISM [CH. XXXIX. Supposing the body to remain in the condition produced by these anabolic processes, what is its composition ? A glance through the chapters on the cell, the blood, the tissues, and the organs will con- vince the inquirer that different parts of the body have very different compositions ; still, speaking of the body as a whole, Volkmann and Bischoff state that it contains 64 per cent, of water, 16 of proteids (including gelatin), 14 of fat, 5 of salt, and 1 of carbohydrates. The carbohydrates are thus the smallest constituent of the body; they are the glycogen of the liver and muscles, and small quantities of dextrose in various parts. The most important, because the most abundant of the tissues of the body, is the muscular tissue. Muscle forms about 42 per cent, of the body-weight,* and contains, in round numbers, 75 per cent, of water and 21 per cent, of proteids; thus about half the proteid material and of the water of the body exist in its muscles. The body, however, does not remain in this stable condition ; even while nutrition is occurring, destructive changes are taking place simultaneously; each cell may be considered to be in a state of unstable equilibrium, undergoing anabolic, or constructive processes, on the one hand, and destructive, or katabolic, processes on the other. The katabolic series of phenomena commences with combustion ; the union of oxygen with carbon to form carbonic acid, with hydrogen to form water, with nitrogen, carbon, and hydrogen to form urea, uric acid, creatinine, and other less important substances of the same nature. The formation of these last-mentioned substances, the nitrogenous metabolites, is, however, as previously pointed out, partly synthetical. The discharge of these products of destructive metabol- ism by the expired air, the urine, the sweat, and fseces is what con- stitutes excretion ; excretion is the final act in the metabolic round, and the composition of the various excretions has already been con- sidered. An examination of the intake (food and oxygen) and of the out- put (excretion) of the body can be readily made ; much more readily, it need hardly be said, than an examination of the intermediate steps in the process. A contrast between the two can be made by means of a balance-sheet. A familiar comparison may be drawn between the affairs of the animal body and those of a commercial company. At the end of the year the company presents a report in which its income and its expenditure are contrasted on two sides of a balance- sheet. This sheet is a summary of the monetary affairs of the under- taking ; it gives few details, it gives none of the intermediate steps of the manner in which the property has been employed. This is * The following is in round numbers the percentage proportion of the different structural elements of the body: skeleton. 16; muscles, 42; fat, 18; viscera, 9; skin, S; brain, 2; blood, 5. CH. XXXIX.] EXCHANGE OF MATERIAL 585 given in the preliminary parts of the report, or may be entered into by still further examining the books of the company. In the parts of this book that precede this chapter I have endeavoured to give an account of various transactions that occur in the body. I now propose to present a balance-sheet. Those who wish still further to investigate the affairs of the body may do so by the careful study of works on physiology; still, text-books and monographs, however good, will teach one only a small amount ; the rest is to be learnt by practical study and research; and we may compare physiologists to the accountants of a commercial enterprise, who examine into the details of its working. Sometimes, in business undertakings, a deficit or some other error is discovered, and it may be that the source of the mistake is only found after careful search. Under these conditions, the accountants should be compared to physicians, who discover that something is wrong in the working of the animal body ; and their object should be to ascertain where, in the metabolic cycle, the mistake has occurred, and subsequently endeavour to rectify it. The construction of balance-sheets for the human and animal body may be summed up in the German word Stoffwechsel, or " exchange of material." A large number of investigators have applied themselves to this task, and from the large mass of material published, it is only possible to select a few typical examples. The subject has been worked out specially by the Munich school, under the lead of Pettenkofer and Voit. The necessary data for the construction of such tables are : — (1) The weight of the animal before, during, and after the experiment. (2) The quantity and composition of its food. (3) The amount of oxygen absorbed during respiration. (4) The quantity and composition of urine, fasces, sweat, and expired air. (5) The amount of work done, and the amount of heat developed. (The subject of animal heat will be considered in the next chapter.) Water is determined by subtracting the amount of water ingested as food from the quantity lost by bowels, urine, lungs, and skin. The difference is a measure of the katabolism of hydrogen. Nitrogen. — The nitrogen is derived from proteids and albuminoids, and appears chiefly in the urine as urea and uric acid. Minute quantities are eliminated as similar compounds in sweat and fasces. From the amount of nitrogen so found, the amount of proteids which have undergone katabolism is calculated. Proteids contain, roughly, 16 per cent, of nitrogen ; so 1 part of nitrogen is equivalent 586 GENERAL METABOLISM [CIL XXXIX. to 63 parts of proteid; or 1 gramme of nitrogen to 30 grammes of flesh. Fat and carbohydrate. — Subtract the carbon in the metabolised proteid (proteid contains 54 per cent, of carbon) from the total carbon eliminated by lungs, skin, bowels, and kidneys, and the difference represents fat and carbohydrate that have undergone metabolism. The Discharge of Carbon. The influence of food on the rate of discharge of carbonic acid is immediate. The increase after each meal, which may amount to 20 per cent., reaches its maximum in about one or two hours. This effect is most marked when the diet consists largely of carbo- hydrates. About 95 per cent, of the carbon discharged leaves the organism as carbonic acid. The total insensible loss ( = carbonic acid + water given off— oxygen absorbed) amounts in man to about 25 grammes per hour. Of the total hourly discharge of carbonic acid, less than 5 per cent, is cutaneous. The hourly discharge of carbonic acid in a man at rest is about 32 grammes, the weight of oxygen absorbed being 25 to 28 grammes in the same time. The hourly discharge of watery vapour is about 20 grammes. As a volume of carbonic acid (CO.,) contains the same weight of oxygen as an equal volume of oxygen (0. 2 ), it is obvious that, if all the absorbed oxygen were discharged as carbonic acid, the " respiratory quotient " (by volume) = n 2 , i — would be equal to 1. This, however, is not the case, the volume of oxygen absorbed being in excess of the carbonic acid discharged. In animals fed exclusively on carbohydrates (this would only be possible for a short time) equality is approached. The excess of oxygen is greatest when the diet consists largely of fats. On a mixed diet, comprising 100 grammes of proteid, 100 of fat, and 250 of carbohydrates, with a carbonic acid discharge of 770 grammes daily, and a daily assumption of 666 grammes of oxygen, 560 grammes of the oxygen are discharged in the carbonic acid, about 9 in urea, and 97 grammes in the form of water (of which 78 grammes are formed from the hydrogen of the fat); the respiratory quotient is then - 84 In hibernation the respiratory quotient sinks lower than in any other known condition (often less than 0'5), for the animal then lives almost entirely on its own fat. The discharge of carbonic acid is increased by muscular work, and the respiratory quotient also rises. Diminution of the surrounding temperature causes increased discharge of carbonic acid. (These points are all discussed more fully in Chapter XXIV.) CH. XXXIX.] METABOLIC BALANCE-SHEETS 587 The Discharge of Nitrogen. In man the minimum daily allowance of nitrogen is 15 grammes, or 0'02 per cent, of the body-weight; in the carnivora about 0*1 per cent. ; in the ox, as an instance of a herbivorous animal, 0'005 per cent. In certain races of mankind {e.g. coolies) the nitrogen require- ment is less than in Europeans, and evidence has been recently accumulating to show that even Europeans can maintain equilibrium on diets much scantier than what is usually stated to be the minimum (see p. 460). In an animal fed exclusively on flesh, the discharge of nitrogen at first increases pari passu with the absorption of proteid, the absorption of oxygen being proportionately increased at the same time. The animal, however, gains weight from increase of fat, the proteid being split into what is called a nitrogenous moiety, which is burnt off, and a non-nitrogenous moiety which is converted into fat. The discharge of nitrogen is not immediately or markedly influenced by muscular work (see p. 555); the increased combustion that occurs in working as compared with resting muscles falls chiefly on their non-nitrogenous constituents. Balance of Income and Discharge in Health. In Chapter XXVIII. tables are given of adequate diets; these will in our balance-sheets represent the source of income ; the other side of the balance-sheets, the expenditure, consists of the excretions. Exchange of Material ox ax Adequate Diet (Ranke's table). * Income. Expenditure. Foods. Nitrogen. Carbon. Excretions. Nitrogen. Carbon. Proteid . 100 gr. Fat. . 100 ,, Carbohy- drates . 250 ,, 15*5 gr. 53-0 gr. 0-0 „ 79-0 „ 0-0 „ 93-0 „ Urea . 31 - 5 gr. Uric acid 0*5 „ Faeces . Respiration (C0. 2 ) | 14-4 1-1 o-o 6-16 10-84 208-00 15-5 „ 225-0 „ 15-5 i 225-00 * The above table was constructed from data derived from the observations of Prof. Ranke on himself. Though made many years ago, Ranke's tables still serve as typical and standard examples of metabolic balance-sheets. In man the discharge of nitrogen per kilo, of body-weight is 0'21 gramme, and of carbon 303 grammes, the quotient 588 C N ~ GENERAL METABOLISM [CH. XXXIX. 14'5. In carnivorous animals, which, according to Bidder C N 44. and Schmidt, use l - 4 N and 6*2 C per kilo, per diem, Q In the human being on a flesh diet tS= = 5 - 2 ; the exchange thus approaches the condition of the carnivora. This is illustrated by the following balance-sheet (Ranke) : — Income. Expenditure. Nitrogen. Carbon. Nitrogen. Carbon. Food . Disintegration of tissues 62-3 gr. 279-6 45-9 Discharged by excretion Retained in store . 44-0 18-3 62-3 263-0 62'5 32.V5 62-3 „ 325-5 The details of the above experiment may be given as illustrating the method of working out a problem in exchange of material : 1832 grammes of meat used as food yielded 3 - 4 per cent, of nitrogen, i.e. 62 - 3 gr., and 12 - 5 per cent, of carbon, i.e. 229'3 gr. ; 70 gr. of fat added to the food yielded 72 per cent, of carbon, i.e. 50'3 gr. : 229'3 + 50'3 = 279 - 6 = total carbon in food. During the same period 86 - 3 gr. of urea were discharged, containing 46'6 per cent., i.e. 40"4 gr. of nitrogen, and 20 per cent., i.e. 17'3 gr. of carbon, to which must be added 2 gr. of uric acid, containing 33 per cent., i.e. 0"66 gr. of nitrogen, and 35 per cent., i.e. 0"7 gr. of carbon. Further, 2 "9 gr. of nitrogen and 14 gr. of carbon were discharged in the faeces, and 231 gr. of carbon as carbonic acid in the expired air. Hence the total discharge of nitrogen = 40 "4 + '6 6 + 2 -9 = 44 gr., and the total dis- charge of carbon = 17-3 + 07 +14 + 231 = 263 gr. Deducting the quantity of nitrogen discharged from that taken in, 18 - 3 gr. must have been retained in the body, as 108 gr. of proteid, and consequently 53 per cent, of that weight = 62 - 5 gr. of carbon, were also retained. Comparing the quantity of carbon disposed of in the twenty-four hours with the quantity introduced as food, we find the former is in excess by 45 - 9 gr., which must have been derived from the disinte- gration of the fat of the body. Another table of exchange of material on adequate diet may be quoted from the work of Pettenkofer and Voit. This takes into account the elimination of water as well as of carbon and nitrogen. In the first experiment the man did no work. CH. XXXIX.] INANITION 589 Income. Expenditure. Food. Nitrogen. Carbon. Excretions. Nitrogen. Carbon. Water. Proteid . 137gr. Fat. . 117 „ Carbohy- drate. 352 ,, Water . 2016 „ M9-5 j 315-5 Urine . Fasces . Expired air 17-4 2-1 12-7 14-5 248-6 1279 83 828 19-5 275-8 2190 Nitrogen. Carbon. Water. 17'4 12-6 1194 2-1 14-5 94 309-2 1412 Here the body was in nitrogenous equilibrium, and it eliminated more water than it took in by 174 grammes, this being derived from oxidation of hydrogen. It stored 39 - 7 grammes of carbon, which is equivalent to 52 grammes of fat. The next table gives the results of an experiment on the same man on the same diet, but who did active muscular work during the day : — Expenditure. Urine Faeces Expired air . 19-5 336-3 2700 It is important to notice that the discharge of nitrogen was unaltered while that of both carbon and hydrogen was increased. Inanition or Starvation. The income from without is, under these circumstances, nil; expenditure still goes on, as a result of the disintegration of the tissues ; the amount of disintegration is measured by the discharges in the manner already described. The following table from Eanke's experiment on himself represents the exchange for a period of twenty-four hours, twenty-four hours having elapsed since the last meal. Disintegration of Tissue. Expenditure. Nitrogen. Carbon. Nitrogen. Carbon. Proteid Fat 50 gr. 199-6 „ 7-8 o-o 26*5 157-5 Urea . 17 gr. Uric acid 0-2 ,, Respiration (CCX) } 7-8 o-o 3-4 180-6 7-8 184-0 7-8 184-0 590 GENERAL METABOLISM [CH. XXXIX. The discharge of nitrogen per kilo, of body-weight was reduced Q to 01, -rf being 23"5. In carnivorous animals, in prolonged Q inanition, the discharge of nitrogen per kilo, is 09 and ^ = 6'6. During starvation the man or animal gradually loses weight ; the temperature, after a preliminary rise, sinks ; the functions get weaker by degrees, and ultimately, when death ensues, the total weight lost varies from 0'3 to 0"5 of the original body- weight. The as;e of the animal influences the time at which death occurs, old animals withstanding the effects of hunger better than young ones. This statement was originally made by Hippocrates, and was borne out by the experiments of Martigny and Chossat. Young animals lose weight more quickly, and die after a smaller loss of weight, than old ones. The excretion of nitrogen falls quickly at the commencement of starvation ; it reaches a minimum which remains constant for several days ; it then rises when the fat of the animal has been used up, and then quickly falls with the onset of symptoms of approach- ing death. The sulphates and phosphates in the urine show approximately the same series of changes. The discharge of carbonic acid and the intake of oxygen fall, but not so quickly as the body loses weight ; it is not until quite the last stages that these are small in proportion to one another. The fasces become smaller and smaller in quantity until no dis- charge from the rectum occurs at all. The amount of bile secreted also falls ; but bile is found in the gall-bladder and intestine after death. Taking the total loss of weight as 100, the loss due to that of in- dividual organs may be stated as follows (Voit) : — Bone . . 5-4 Pancreas . . o-i Brain and cord o-i Muscle . 42-2 Lungs . 0-3 Skin and hair 8-8 Liver . . 4-8 Heart . o-o Fat . 26-2 Kidneys . 0-6 Testes . o-i Blood 3-7 Spleen . 0-6 Intestines . . 2-0 Other parts 5-0 Some organs, such as heart and brain, thus lose but little weight ; the loss of weight is greatest in the muscles, fat, skin, liver, and blood. Of the muscles, the great pectoral muscles waste most. Death may be delayed somewhat by artificial warmth, but ultimately occurs from asthenia, sometimes accompanied by convulsions. Exchange of Material with various Diets. The reasons why a mixed diet is necessary have been already explained (Chap. XXVIII.). Numerous experiments have, however, been made in the study of metabolism on abnormal diets. Feedin;/ with meat. — As the chief solid in meat is proteid, one must take either CH. XXXIX.] FAT METABOLISM 591 too much nitrogen or too little carbon. The principle that underlies Banting's method of treating obesity is to give meat almost exclusively : the individual then derives the additional supply of carbon necessary for combustion from his own adipose tissue. We have already seen that this may be and often is counteracted by the laying on of fat which comes from the non-nitrogenous moiety of the proteid. Feeding with fat. — If an animal receives fat only, the nitrogenous excreta are derived from the disintegration of tissue without any corresponding supply of nitrogen being supplied in exchange in the food. When fat only is given, or a large excess of fat exists in the food, the respiratory quotient falls. F. Hofmann fed a dog on a mixture of a large amount of fat and a small amount of proteid. After death the quantity of fat found in the body was such that only a small part could have been derived from the proteid, the greater amount being directly derived from the fat of the food. The animal, moreover, lays on fat in which palmitin, stearin, and olein are mixed in a definite proportion ; this proportion is often different in the fat of the food. In addition to this an animal will fatten (laying on fat with its usual composition) on fatty food, such as spermaceti, which contains no glycerides. Feeding with carbohydrates. — The respiratory quotient approaches unity when carbohydrates alone are taken. So far as regards nitrogen the animal is in a state of inanition, as when fat alone is taken. If given in combination with other foods, both carbohydrates and fat act as proteid-sparing foods. The following table is from Pettenkofer and Voit, and illustrates what happens in a dog on a mixed diet of flesh and carbohydrates. 1 Food. Changes in the Body. Fat. roteid sed 'rom ted. 'w to ° =* s o .3 o . <2| ■ 02 u C3 M do ^ fe Amount of p decompo calculated urea excre o . Ph C III o £ O o 8 «« >£ CD O P 379 17 211 -211 379 + 17 24 608 22 193 -193 608 + 22 22 400 210 10 436 - 36 210 + 10 - 8 400 227 393 + 7 227 -25 400 344 6 413 - 13 344 + 6 39 500 167 6 530 - 30 167 + 6 8 500 182 537 - 37 182 16 800 379 14 608 + 192 379 + 14 55 1500 172 4 1475 + 25 172 + 4 43 1800 379 10 1469 + 331 379 + 10 112 2500 2512 + 12 57 Even when the diet consists wholly of carbohydrates, fat is laid on ; the fat laid on when meat and starch are both present in the food comes partly from the proteid and partly from the carbohydrate of the food. When no carbohydrate is given at all, as in the last experiment, the nitrogenous metabolism is raised. Carbohydrate food is thus when given with other foods both fat-sparing and proteid-sparing. The formation of fat from carbohydrates was first observed in pigs by Lawes and Gilbert, and has since been confirmed by numerous investigators. One of the most important instances of the carbohydrate origin of fat is the formation of bees'-wax. Instances of the formation of fat from proteids are (1) the laying on of fat in carnivorous animals; (2) the formation of adipocere, a wax-like material which forms in the muscles of corpses buried in damp soil, or allowed to remain in water ; (3) the gradually increasing quantity of fat in old cheeses. 592 GENERAL METABOLISiM [CH. XXXIX. The most striking examples of the formation of fat by intracellular metabolic processes is seen in fatty degeneration, and in that special form of this degeneration that occurs in the formation of milk. The blood contains a mere trace of fat, so milk formation is no mere filtration process. The food may, as in the case of cows, contain little or no fat. Feeding with gelatin. — A diet containing gelatin alone will not support life. This fact is somewhat remarkable when one considers the closely allied chemical nature of gelatin and proteids. When gelatin alone is given, the body wastes, and the urea excreted is diminished as in inanition. If an enormous amount of gelatin is given the urea increases. Gelatin, however, like carbohydrates and fats, appears to be a " proteid-sparing" food, and if given mixed with proteids seems to proteet the proteids from oxidation. Gelatin can thus be substituted for a part of the pro- teid in the food. Feeding icith "peptones." — In the present day, when artificially digested foods are so much employed, it is of great importance that their nutritive value should be known. Here experimental and clinical evidence coincide in a most favourable way in relation to their nutritive value. Albumoses and the preparations called peptone in commerce, which are in reality mainly albumoses, have the same nutritive value as meat. Concentrated or artificially digested foods of ^this kind (Witte's peptone, plasmon, somatose, etc.) must naturally be distinguished from beef-tea and extracts of meat of which there are so many in the market, but which are mere stimulants and are valueless for nutrition (see p. 469). Effect of Varying External Conditions on Exchange of Material. Effect of atmospheric temperature. — In warm-blooded animals the effect of a low surrounding temperature is to increase katabolisni, or combustion in the body ; the body loses more heat, and therefore more must be produced to keep the animal's temperature within normal limits. The effect of a rise of atmospheric temperature is the reverse. In cold-blooded animals, i.e., animals whose temperature varies with that of the surrounding atmosphere, a rise or fall of the latter is accompanied respec- tively with a rise or fall of combustion in the body. Pembrey has shown that warm- blooded animals in an embryonic condition are practically cold-blooded ; that is, their metabolism, body temperature, and the external temperature vary directly the one with the others. Alterations of hody temperature. — If the changes of the external temperature are so great as to cause a rise (as in steam-baths) or a fall (as in hibernation) of body temperature, the metabolic changes are increased and decreased respectively, as in cold-blooded animals. Effect of removal of blood from /In- body. — The chief effect of a removal of blood from the body is the speedy formation of new blood-corpuscles. The intake of oxygen and discharge of carbonic acid are lessened, and the output of urea is increased. The menstrual flow and epistaxis in strong, healthy people cause no alteration in exchange of material. Exchange of Material in Diseases. Fever. — Fever is a condition in which the temperature of the body is raised above the normal, and the degree to which it is raised is a measure of the intensity of the febrile condition. A rise of temperature may be produced either by increased production of heat, due to the increase of katabolic processes in the body, or to a diminished loss of heat from the body. A mere increase in the production of heat does not necessarily produce fever. By administer- ing an excess of food, combustion is increased in the body ; but in the healthy individual this does not produce a rise of temperature, because pari passu with the increased production there is increased loss of heat. Similarly, diminution in the loss of heat, such as CH. XXXIX.] METABOLISM IN DISEASE 593 occurs on a hot as compared with a cold day, does not produce fever,* because the production of heat within the body is correspondingly diminished. In fever there is increased production of heat, as is seen by the study of exchange of material ; the intake of food is, as a rule, very small ; the discharge of nitrogen and carbon results from the disintegration of tissues, which, as compared with that in simple inanition, is large ; the tissues are said to be in a labile condition, that is, they are easily broken down. In most febrile states, the skin is dry, the sweat-glands, like most of the secreting organs of the body, being comparatively inactive, and so the discharge of heat is lessened. The skin may, however, sometimes be bathed in perspira- tion, and yet high fever be present. The essential cause of the high temperature is neither increased formation nor diminished discharge of heat, but an interference with the reflex mechanism, which in health operates so as to equalise the two. Increased nitrogenous metabolism in fever has been observed in pneumonia, in pyaemia, and in other febrile conditions. Kinger showed the correspondence in temperature and output of nitrogen very clearly in intermittent fever (ague). What is known as the epicritical increase of urea is the greatly increased secretion of urea that occurs at the commencement of the defervescence of a fever. It is probably not due to an increased formation of urea, but to the removal of urea which has accumulated, owing to the fact that the kidneys have been acting sluggishly during the height of the fever. Increased output of carbonic acid also occurs in fever. Other changes noted in fever are a rapid loss of the liver glycogen, a lessening of chlorides in the urine, and often an increase of the urobilin in the urine. The following table illustrates exchange of material in fever, no food being taken : — Income. Expenditure. Disintegration of tissue. Nitrogen. Carbon. Excretions. Nitrogen. Carbon. Proteid . 120 gr. Fat . 205-7 „ 18-6 o-o 63-6 157-4 Urea and uric acid . 40 gr. Respiration (CO..) . 780 „ 18-6 o-o 8-3 212-7 18-6 221-0 18-6 221-0 * A febrile condition does occur on undue exposure to a tropical sun, for instance in soldiers in India ; this is mainly due to their tight-fitting and otherwise unsuitable clothing, which interferes with the proper action of the skin. 2 P 594 GENERAL METABOLISM [CH. XXXIX. ■ Compare this table with that at the bottom of p. 589. Diabetes mellitus. — In addition to the presence of sugar in the urine in this disease, the most marked symptoms are intense thirst and ravenous hunger. As a rule, diabetic patients digest their food well. The thirst is an indication of the necessity of replacing the large quantities of water lost by the kidneys ; the hunger, that of replacing the great waste of tissues that occurs. For not only does the urine contain sugar, but, in addition, a great excess of urea and uric acid. The carbonic acid output is somewhat smaller than in health. In health the carbohydrates, after assimilation, give rise, by oxidation, to carbonic acid ; in diabetes, all the carbohydrates do not undergo this change, but pass as sugar into the urine. Not that all the sugar of the urine is derived from carbohydrates, for many diabetics continue to pass large quantities when all carbohydrate food is withheld ; under these circumstances, it must be derived from the destruction of proteid matter (see also pp. 516, 571). The increased production of organic acids which lessen the alkalinity of the blood should also be remembered (see pp. 518, 559). Luxus Consumption. In former portions of this book we have insisted on the fact that the food does not undergo combustion, or katabolic changes, until after it is assimilated, that is, until after it has become an integral part of the tissues. Formerly the blood was supposed to be the seat of oxidation ; but the reasons why this view is not held now have been already given. When a student is first confronted with balance-sheets, representing metabolic exchanges, it is at first a little difficult for him to grasp the fact, that although the amount of nitrogen and carbon ingested is equal to the amount of the same elements which are eliminated, yet the eliminated carbon and hydrogen are not derived from the food direct, but from the tissues already formed; the food becomes assimilated and takes the place of the tissues thus disintegrated. Let us suppose we have a tube open at both ends and filled with a row of marbles; if an extra marble is pushed in at one end, a marble falls out at the other ; if two marbles are introduced instead of one, there is an output of two at the other end ; if a dozen, or any larger number be substituted, there is always a corresponding exit of the same number at the other end of the tube. This very rough illustration may perhaps assist in the comprehension of the metabolic exchanges. The difficulty just alluded to, which a student feels, was also felt by the physiologists who first studied metabolism ; and Voit formu- lated a theory, of which the following is the gist : All proteid taken into the alimentary canal appears to affect proteid metabolism in two CH. XXXIX.] LUXUS CONSUMPTION 595 ways : on the one hand, it excites rapid disintegration of proteids, giving rise to an immediate increase of urea ; on the other hand, it serves to maintain the more regular proteid metabolism continually taking place in the body, and so contributes to the normal regular discharge of urea. It has been, therefore, supposed that the proteid which plays the first of these two parts is not really built up into the tissues, does not become living tissue, but undergoes the changes that give rise to urea, somewhere outside the actual living substance. The proteids are therefore divided into " tissue-proteids," which are actually built up into Living substance, and " floating or circulating proteids," which are not thus built up, but by their metabolism outside the living substance set free energy in the form of heat only. It was at this time erroneously supposed that the exclusive use of proteid food was to supply proteid tissue elements, and that vital manifestations other than heat had their origin in proteid meta- bolism, the metabolism of fats and carbohydrates giving rise to heat only. Hence, when it was first surmised that a certain proportion of proteids underwent metabolism, which gave rise to heat only, this appeared to be a wasteful expenditure of precious material, and the metabolism of this portion of food was spoken of as a " luxus con- sumption," a wasteful consumption. There were many deductions from this general theory to explain particular points, of these two may be mentioned : (1) In inanition, the urea discharged for the first few days is much greater than it is subsequently : this was supposed to be due to the fact that in the first few days all the floating capital was consumed; (2) the effect of feeding with a mixture of gelatin and proteid was supposed to be due to the fact that gelatin was able to replace " floating proteid," but not " tissue proteid." This theory of Voit's, ingenious and plausible at first sight, has met with but little general acceptance, because so many observed facts are incompatible with it. Sir Michael Foster writes as follows : " The evidence we have tends to show that in muscle (taking it as an instance of a tissue) there exists a framework of what we may call more distinctly living substance, whose metabolism, though high in quality, does not give rise to massive discharges of energy, and that the interstices, so to speak, of this framework are occupied by various kinds of material related in different degrees to this framework, and therefore deserv- ing to be spoken of as more or less living, the chief part of the energy set free coming directly from the metabolism of some or other of this material. Both framework and intercalated material undergo metabolism, and have in different degrees their anabolic and katabolic changes ; both are concerned in the life of the organism, but one more directly than the other. We can, moreover, recognise no sharp break between the intercalated material and the lymph which bathes 596 GENERAL METABOLISM [CH. XXXIX. it ; hence such phrases as ' tissue proteid ' and ' floating proteid ' are undesirable if they are understood to imply a sharp line of demarca- tion between the ' tissue ' and the blood or lymph, though useful as indicating two different lines or degrees of metabolism." Sir John Burdon-Sanderson writes as follows : " The production of urea and other nitrogenous metabolites is exclusively a function of ' living material ' ; and this process is carried on in the organism with an activity which is dependent on the activity of the living substance itself, and on the quantity of material supplied to it. No evidence at present exists in favour of a ' luxus consumption ' of proteid." Professor Hoppe-Seyler, after stating that he can make out no clear distinction between the two varieties of proteid from Voit's own writings, proceeds as follows : " Voit states that the circulating proteid is no other than that which is dissolved in the tissue juice, which is derived from the lymph-stream, and ultimately from the circulating blood. He (Voit) further says : ' As soon as the proteid of the blood-plasma leaves the blood-vessels, and circulates among the tissue elements themselves, it is then the proteid of the nutrient fluid or circulating proteid. It is no longer proteid of the blood- plasma, nor yet is it the proteid of the lymph-stream.' The place where Voit situates his circulating proteid is beyond the ken of the anatomist ; it is in a mysterious space between tissue-elements, blood- vessels, and lymph-vessels ; the chemist meets with equal difficulties, as there is apparently no chemical difference between tissue proteid and circulating proteid. I can, therefore, arrive at no other conclu- sion than that these terms are not only useless, but unscientific, and are the outcome of speculations in a region where there is as yet no positive knowledge. These criticisms on Voit's theories do not, however, by any means lessen the importance and high value of the immense amount of practical research carried on by Voit and his pupils " I have placed Sir Michael Foster's view first because it takes into account certain facts which tend to show that there are degrees in metabolism. The most important of these is the formation of amino-acids in the intestine. It is an undoubted fact that by feeding an animal on leucine and other amino-acids, the urea is increased. This transformation of leucine into urea occurs in the liver. It can hardly be supposed that leucine becomes to any great extent an integral part of the living framework of the liver cells, but like other extractives, and like aromatic compounds absorbed from the ali- mentary canal, it becomes a part of what Foster terms the inter- calated material. Here it undergoes the final change, and is ultimately and apparently very rapidly discharged in the urine. Sheridan Lea, discussing the probable role of the amino-acids in the animal CH. XXXIX.] ROLE OF AMINO-ACIDS 597 economy, compares it to the part played by the salts of the food. Neither salts nor extractives simply pass into the urine without ful- filling a useful purpose on their way ; but the exact and specific use of each, whether on the synthetic or analytic side of metabolic pheno- mena, must be the subject of renewed research. (Eead again in this connection the last paragraph on p. 520, which describes certain recent researches that show that leucine and similar simple substances may be actually synthesised into protoplasm. If this is ultimately found to be correct, the opinions expressed in the first part of the present paragraph will need modification.) CHAPTER XL ANIMAL HEAT Among the most important results of the chemical processes we sum up under the term metabolism, is the production of heat. Heat, like mechanical motion, is the result of the katabolic side of metabolic processes ; the result, or accompaniment, that is to say, of the forma- tion of carbonic acid, water, urea, and other excreted products. As regards temperature, animals may be divided into two great classes : — (1) Warm-blooded or homoiothermal animals, or those which have an almost constant temperature. This class includes mammals and birds. (2) Cold-blooded or poikilothermal animals, or those whose temperature varies with that of the surrounding medium, being always, however, a degree, or a fraction of a degree, above that of the medium. This class includes reptiles, amphibians, fish, embryonic birds and mammals, and probably most invertebrates. The temperature of a man in health varies but slightly, being between 36-5° and 37'5° C. (98° to 99° F.). Most mammals have approximately the same temperature : horse, donkey, ox, 37"5° to 38° ; dog, cat, 38-5 to 39° ; sheep, rabbit, 38° to 39"5° ; mouse, 37"5° ; rat, 3 7 '9°. Birds have a higher temperature, about 42° C. The tempera- ture varies a little in different parts of the body, that of the interior being greater than that of the surface ; the blood coming from the liver where chemical changes are very active is warmer than that of the general circulation ; the blood becomes rather cooler in its passage through the lungs. The temperature also shows slight diurnal variations, reaching a maximum about 4 or 5 p.m. (37'5° C.) and a minimum about 3 a.m. (36"8° C.) ; that is, at a time when the functions of the body are least active. If, however, the habits of a man are altered, and he sleeps in the day, working during the night, the times of the maximum and minimum temperatures are also inverted. Inanition causes the CH. XL.] CALORIFIC VALUE OF FOOD 599 temperature to fall, and just at the onset of death it may be below 30° C. Active muscular exercise raises the temperature temporarily by about 0'5° to 1° C. Diseases may cause the temperature to vary considerably, especially those which we term febrile (see p. 592). Although certain mechanical actions, such as friction, due to movements of various kinds, may contribute a minute share in the production of heat in the body, yet we have no knowledge as to the actual amount thus generated. The great source of heat is, as already stated, chemical action, especially oxidation. Any given oxidation will always produce the same amount of heat. Thus, if we oxidise a gramme of carbon, a known amount of heat is produced, whether the element be free or in a chemical compound. The follow- ing figures show the approximate number of heat-units produced by the combustion of one gramme of the following substances. A heat- unit, or calorie, is the amount of heat necessary to raise the tempera- ture of one gramme of water 1° C. : — Hydrogen .... 34662 Fat . . . . . 9400 Carbon .... 8100 j Cane sugar . . . 3950 Urea 2530 Starch .... 4160 Albumin .... 5600 It is, however, most important to remember that the " physiologi- cal heat-value " of a food may be different from the " physical heat- value," i.e., the amount of heat produced by combustion in the body may be different from that produced when the same amount of the same food is burnt in a calorimeter. This is the case with the pro- teids, because they do not undergo complete combustion in the body, for each gramme of proteid yields a third of a gramme of urea, which has a considerable heat-value of its own. Thus albumin, which, by complete combustion, yields 5600 heat-units, has a physiological heat-value = 5600 minus one-third of the heat -value of urea (2530) = 5600 — 846=4754. Eubner has recently shown that this figure must be reduced to nearly 4000, as some of the imperfectly burnt products of decomposition of proteids escape as uric acid, creatinine, etc., in the urine, and there is a small quantity of similar substances in the faeces. Any difference between the physical and physiological heat-values of fats and carbohydrates may be neglected, provided all the fat and carbohydrate in the food is absorbed. Of the heat produced in the body, it is estimated by Helmholtz that about 7 per cent, is represented by external mechanical work, and that of the remainder about four-fifths are discharged by radia- tion, conduction, and evaporation from the skin, and the remaining fifth by the lungs and excreta. This is only an average estimate, subject to much variation, especially in the amount of work done. The following table exhibits the relation between the production and discharge of energy in twenty-four hours in the human organism 600 ANIMAL HEAT [CH. XL. at rest, estimated in calories.* The table conveniently takes the form of a balance-sheet in which production and discharge of heat are com- pared ; to keep the body-temperature normal these must be equal. The basis of the table in the left-hand (income) side is the same as Eanke's diet (see p. 587) : — Production of heat. Discharge of heat. Metabolism of Calories. Proteid(100 gr.) . 100x4000= 400,000 Warming water in food. Fat (100 gr.) . 100 x 9400= 940,000 2-6 kilos, x 25° C. = 65,000 Carbohydrates \ 9Kn v dififi — i nan onn Warming air in respiration, 16 kilos, x 25° x 0-24 = 96,000 Evaporation in lungs, 630 gr. x582 = 366,660 Radiation, evaporation, etc., at surface, plus the thermal equivalent of mechanical work done accounts for the remainder .... 1,852,340 T o-a V l W250 x 4160 = 1,040,000 ( = 2o0 gr. starch) J 2,380,000 2,3S0.000 The figures under the heading Production are obtained by multi- plying the weight of food by its physiological heat-value. The figures on the other side of the balance-sheet are obtained as follows : The water in the food is reckoned as weighing 2 6 kilos. This is supposed to be at the temperature of the air taken as 12° C. ; it has to be raised to the temperature of the body, 37° C, that is, through 25° C. Hence the weight of water multiplied by 25 gives the number of calories expended in heating it. The weight of air is taken as weighing 16 kilos. ; this also has to be raised 25° C, and so to be multiplied by 25 ; it has further to be multiplied by the relative heat of air (0'24). The 630 grammes of water evaporated in the lungs must be multiplied by the potential or latent heat of steam at 37° C. (582) ; the portion of heat lost by radiation, conduction, and evapora- tion from the skin constitutes about four-fifths of the whole, and is obtained by deducting the three previous amounts from the total. This table does not take into account the small quantities of heat lost with urine and faeces. We are further supposing that the man remains of constant weight, so that there is no storage or loss of material, and, therefore, of energy in the body. He is also supposed to be at rest, and therefore the amount of work clone is only what is called internal work, i.e., maintaining the circulation, respiration, etc. It need hardly be remarked that the above is a mere illustrative experiment. Changes in the diet, in the atmospheric temperature, in the temperature of the food taken, in the activity of the sweat-glands, * The calorie we are taking is sometimes called the small calorie ; by some the word calorie is used to denote the amount of heat necessary to raise one kilogramme of water 1° C. GH. XL.] CALORIMETRY 601 in the amount of moisture in the atmosphere, and in the amount of work done, would considerably alter the above figures. Calorimetry. — Calorimeters employed in chemical operations are not suitable for experiments on living animals. An animal sur- rounded by ice or mercury, the melting and expansion of which respectively are measures of the amount of heat evolved, would be under such abnormal conditions that the results would be valueless. Lavoisier, however, used an ice calorimeter in his experiments on animals. The apparatus often employed is the water calorimeter. This was first used by Crawford (1788). Dulong's instrument is shown in fig. 443. The animal is placed in a metal chamber, surrounded by a Fkj. 443. — Dulong's Calorimeter : C, calorimeter, consisting of a vessel of cold water in which the chamber holding the animal is placed ; G', gasometer from which air is expelled by a stream of water. The air enters the respiratory chamber. G, gasometer receiving the gases of expiration and the excess of air. t, V , thermometers ; a, a wheel for agitating the water. Observe the delivery -tube on the left is much twisted in the water -chamber, so as to give off its heat to the surrounding water. (From McKendrick's " Physiology.") • water-jacket. There are also tubes for the entrance and exit of the inspired and expired gases respectively. The heat given out by the animal warms the water in the jacket, and is measured by the rise of temperature observed in the water, of which the volume is also known. The air which passes out from the chamber goes through a long spiral tube, passing through the water-jacket, and thus the heat is abstracted from it and measured. Air-Calorimeters are now, however, generally used. Fig. 444 is an outline sketch of the one which has been most used in this country. It consists of two precisely similar chambers made of thin sheet copper. Each chamber has two walls between which is an air space ; and the outer is covered by a thick casing of felt (F) to prevent fluctuations in the temperature of the surroundings from affecting the air in the air-space. The chambers are made perfectly air-tight, except for the ventilating tubes AA, A' A'. By means of these, the 602 ANIMAL HEAT [CH. XL. chambers are filled with perfectly dry air before the experiment is commenced. Leading from each air-space is a tube ; the two tubes Fig. 444. — Air Calorimeter of Haldane, Hale White, and Washbourn. C, cage for animal. In order to make the conditions in both chambers as much alike as possible, an empty cage should be placed in the other chamber. are connected to the two limbs of a manometer (M) shaped as in the figure, and containing oil of erigeron. The action of the calorimeter is as follows : — In one chamber the animal, the heat production of which is to be ascertained, is placed within the cage C. In the other, hydrogen is burnt (H). Both chambers are shut, the tubes AA, A'A' being clamped. The heat given off from the animal warms its chamber, and thus increases the pressure of the air in the air-space between the two copper walls of the chamber. This would lead to movement of the fluid in the manometer, but that the heat given off by the burning of the hydrogen increases at the same time the pressure in the air-space between the walls of its chamber. Tnis latter increase of pressure tends to make the fluid in the manometer move in the other direction. If the fluid in the manometer remains stationary, the amount of heat given off by the animal is equal to that produced by the burning hydrogen ; and during an experiment the fluid in the manometer is kept station- ary by turning the hydrogen flame up and down. The amount of hydrogen burnt is estimated by the amount of water formed, and the heat of combustion of hydrogen being known, it is perfectly easy to calculate the calories produced, which equal those given off by the animaL The applicability of the law of the conservation of energy to diverse chemical reactions has been amply demonstrated. In view of the chemical nature of meta- bolism, we might assume that the same law applies to the reactions taking place in the body, that it is in fact one of the fundamental laws of the universe. We have, however, no scientific right to assume in advance that no special laws are operative in living matter. The law therefore here requires experimental verification, and much labour has accordingly been devoted to this problem. The early work of Lavoisier, Crawford, Dulong, and others showed great discrepancies between the heat actually found and that calculated, but with the advance of knowledge and improvements of chemical methods and calorimetry, these have disappeared. It is CH. XL.] REGULATION OF TEMPERATURE 603 to Rubner in particular that we owe the experimental demonstration of the law of the conservation of energy in the living organism. The various tissues of the living body in the performance of their several functions break down and oxidise the proteids, fats, carbohydrates, and other materials of which they are composed, and seize upon the energy previously stored and thus liberated, converting it here into the invisible molecular motion of heat, there into the motion of visible masses of matter in the performance of work, and again into the energy of chemical change as the needs of the organism demand. Of these the liberation of heat is by far the greatest in amount, and for this reason, as well as to simplify calculations, it has become customary to express the available energy in terms of units of heat. The energy expended as work may be divided into (1) external work, i.e. , the work done on masses outside the body ; and (2) internal work, i.e., the physical and chemical changes produced within the body in the processes of breathing, digestion, circulation, and the like. If the law of the conservation of energy applies to the animal organism, the following are its necessary consequences : — 1. If an animal is doing no external work, and is neither gaining nor losing substance, the potential energy of the food (expressed as its heat of combustion) will be equal to that of the excreta, plus that given off as heat, plus that of internal work. 2. If an animal is doing external work, and is neither gaining nor losing substance, the potential energy of the food will be equal to the potential energy of the excreta, plus that given off as heat, plus that of the internal work, plus that of the external work. 3. If an animal is doing no external work, but gaining or losing body substance, the potential energy of the food will equal the potential energy of the excreta, plus that given off as heat, plus that of the internal work, plus that of the gain by the body-substance (a loss by the body being regarded as a negative gain). 4. In an animal doing external work, and gaining or losing body-substance, the potential energy of the food will equal the potential energy of the excreta, plus that given off as heat, plus that of the internal and external work, plus that of the gain (positive or negative) of the body-substance. In actual experimentation it is practically impossible to adjust the food so that there is no gain or loss of body-substance, hence experiments necessarily fall under (3) or (4) ; and the majority under (3). The quantities to be determined, then, are : — i. Potential energy of the food. ii. Potential energy of excreta (faeces, urine, etc). iii. The heat produced (including that into which any mechanical work is converted). iv. The potential energy of the gain or loss of body-substance. If, then, the equality stated under (3) and (4) is found to exist, we shall be justified in the conclusion that the law of the conservation of energy applies to the animal body. This is what the painstaking work of Rubner, Laulanie, Atwater, and others has succeeded in showing is actually the case. Regulation of the Temperature of Warm-blooded Animals. We have seen that heat is produced by combustion processes, and lost in various ways. In order to maintain a normal tempera- ture, both sides of the balance-sheet must be equal. This equalisation may be produced by the production of heat adapting itself to variations in discharge, or by the discharge of heat adapting itself to variations in production, or lastly, and more probably, both sets of processes may adapt themselves mutually to one another. We have, therefore, to consider regulation (1) by variations in loss, and (2) by variations in production. 604 ANIMAL HEAT [CH. XL. Regulation by Variations in Loss. — The two means of loss suscep- tible of any amount of variation are the lungs and the skin. The more air that passes in and out of .the lungs, the greater will be the loss in warming the expired air and in evaporating the water of respira- tion. In such animals as the dog, which perspire but little, respiration is a most important means of regulating the temperature ; and in these animals a close connection is observed between the production of heat and the respiratory activity. The panting of a dog when overheated is a familiar instance of this. A dog also, under the same circumstances, puts out its tongue, and loses heat from the evapora- tion that occurs from its surface. The great regulator, however, is undoubtedly the skin, and this has a double action. In the first place, it regulates the loss of heat by its vaso-motor mechanism ; the more blood passing through the skin, the greater will be the loss of heat by conduction, radiation, and evaporation. Conversely, the loss of heat is diminished by anything that lessens the amount of blood in the skin, such as constriction of the cutaneous vessels, or dilatation of the splanchnic vascular area. In the second place, the special nerves of the sweat-glands are called into action. Familiar instances of the action of these two sets of nerves are the reddening of the skin and sweating that occurs after exercise, on a hot day, or in a hot-air or vapour bath, and the pallor of the skin and absence of sensible perspiration on the application of cold to the body. Regulation by Variations in Production. — The rate of production of heat in a living body, as determined by calorimetry, depends on a variety of circumstances. It varies in different kinds of animals. The general rate of katabolism of a man is greater than that of a dog, and of a dog greater than that of a rabbit. Probably every species has a specific coefficient, and every individual a personal coefficient of heat production, which is the expression of the inborn qualities proper to the living substance of the species and individual. Another factor is the proportion of the bulk of the animal to its surface area, the struggle for existence raising the specific coefficient of the animals in which the ratio is high. Other important con- siderations are the relation of the intake of food to metabolic processes, and the amount of muscular work which is performed. These various influences are themselves regulated by the nervous system, and physiologists have long suspected that afferent impulses arising in the skin or elsewhere may, through the central nervous system, originate efferent impulses, the effect of which would be to increase or diminish the metabolism of the muscles and other organs, and by that means increase or diminish respectively the amount of heat there generated. That such a metabolic or thermogenic nervous mechanism does exist in warm-blooded animals is supported by the following experimental evidence : — CH. XL.] NEEVOUS CONTROL OF TEMPERATURE 605 (1) Though in cold-blooded animals a rise or fall of the surround- ing temperature causes respectively a rise and fall of their metabolic activity, in a warm-blooded animal the effect is just the reverse. Warmth from the exterior demands a diminished production of heat in the interior, and vice versd. For exceptions, see p. 592. (2) That this is due to a reflex nervous impulse is supported by the fact that a warm-blooded animal, when poisoned by curare, no longer manifests its normal behaviour to external heat and cold, but is affected in the same way as a cold-blooded animal. Section of the medulla produces the same effects, as the nerve-channels, by which the impulses travel, are severed. When curare is given, the reflex chain is broken at its muscular end, the poison exerting its influence on the end-plates, and causing a diminution of the chemical tonus of the muscles. The centre of this thermotaxic reflex mechanism must be situated somewhere above the spinal cord ; according to some observers, in the optic thalamus. (3) The reflex mechanism is well exemplified in shivering ; here the muscles are thrown into involuntary contraction, and so produce more heat, as the result of the stimulation of the skin by cold. (4) Various injuries caused by accident, or purposely produced by puncture, or cautery, or electrical stimulation of limited portions of the more central portions of the brain, may give rise to great increase of temperature, not accompanied by other marked symptoms. We thus see that the nervous system is intimately associated with the regulation of the temperature of the body. There is at least one — there may be several centres associated in this action. The centres receive afferent impulses from without ; they send out efferent impulses by at least three sets of nerves : (1) the vaso-motor nerves, (2) the secretory nerves of the sweat-glands, (3) trophic or nutritional nerves. The first two sets of nerves, the vaso-motor and the secretory, affect the regulation of temperature on the side of discharge ; the third set on the side of production. The foregoing account of heat regulation does not take into account what after all is, at any rate in man, a very important factor, namely, the voluntary and arti- ficial means which he employs, such as various kinds of clothing suitable to the climate, heating of rooms, and voluntary muscular exercise. CHAPTER XLI THE CENTRAL NERVOUS SYSTEM We already know sufficient from our preliminary study of nerve- centres to be aware that the central nervous system is divided into the two main parts called the brain and spinal cord. Fig. 445 shows the general arrangement of the cerebro-spinal axis, and some anatomical details concerning the membranes that envelop the brain and cord may here conveniently be added. Membranes of the Brain and Spinal Cord. — The Brain and Spinal Cord are enveloped in three membranes — (1) the Dura Mater, (2) the Arachnoid, (3) the Pia Mater. (1) The Dura Mater, or external covering, is a tough membrane composed of bundles of connective tissue which cross at various angles, and in whose interstices branched connective-tissue corpuscles lie : it is lined by a thin elastic membrane, on the inner surface of which is a layer of endothelial cells. (2) The Arachnoid is a much more delicate membrane, very similar in structure to the dura mater, and lined on its outer or free surface by an endothelial mem- brane. (3) The Pia Mater of the cord consists of two layers between which numerous blood-vessels ramify. In that of the brain only the inner of the two layers is repre- sented. Between the arachnoid and pia mater is a network of fibrous tissue trabecular sheathed with endothelial cells : these sub-arachnoid trabecule divide up the sub-arachnoid space into a number of irregidar sinuses. There are some similar trabecular, but much fewer in number, traversing the sub-dural space, i.e., the space between the dura mater and arachnoid. Pacchionian bodies are growths from the sub-arachnoid network of connective- tissue trabecular which project through small holes in the inner layers of the dura mater into the venous sinuses of that membrane. The venous sinuses of the dura mater have been injected from the sub-arachnoidal space through the intermediation of these villous outgrowths. In the chapters preceding this one we have seen how all-per- vading nervous action is ; in connection with circulation, respiration, secretion, peristalsis, etc., the way in which such functions are regulated by nervous activity has taken up a considerable amount of space. Some of the facts there described will be better understood, or be seen in a clearer light, if the student turns back to them and studies them once more after he has grasped what we are going to consider in the chapters that follow this on the physiology of the central nervous system. It would also be advisable, before he begins this subject, that he eo6 CH. XLI.] THE CENTRAL NERVOUS SYSTEM 607 should once more read Chap. XVII. on nerve-centres, in order to Fig. 445. — View of the cerebrospinal axis of the nervous system. The right half of the cranium and trunk of the body has been removed by a vertical section ; the membranes of the brain and spinal cord have also been removed, and the roots and first part of the fifth and ninth cranial, and of all the spinal nerves of the right side, have been dissected out and laid separately on the wall of the skull and on the several vertebra opposite to the place of their natural exit from the cranio-spinal cavity. (After Bourgery.) refresh his memory concerning the elementary and fundamental problems in relation to nervous activity in these regions. CHAPTER XLTI STRUCTURE OF THE SPINAL CORD The spinal cord is a column of nerve-substance connected above with the brain through the medium of the bulb, and situated in the spinal canal. In transverse section it is approximately circular, but the cord is not of the same size throughout its course. It exhibits two enlargements, one in the cervical, the other in the lumbar region. These are the situations whence the large nerves for the supply of the limbs issue. The cord terminates below, about the lower border of the first lumbar vertebra, in a slender filament of grey substance, the filum terminate, which lies in the midst of the roots of many nerves forming the cauda equina. It is composed of grey and white matter ; the white matter is situated externally, and constitutes its chief portion ; the grey matter is in the interior, and is so arranged that in a transverse section of the cord it appears like two crescentic masses (the horns of each of which are called respectively the anterior and posterior cornua) con- nected together by a narrower portion or isthmus, called the posterior commissure (fig. 446). Passing through the centre of this isthmus in a longitudinal direction is a minute canal ; in a transverse section it appears as a hole ; this central canal of the spinal cord is continued throughout its entire length, and opens above into the space at the back of the medulla oblongata and pons Varolii, called the fourth ventricle. It is lined by a layer of columnar ciliated epithelium, and contains a fluid called cerebrospinal fluid. The spinal cord consists of two symmetrical halves, separated anteriorly and posteriorly by vertical fissures (the posterior fissure being deeper, but less wide and distinct than the anterior), and united in the middle by nervous matter which is usually described as forming two commissures — an anterior commissure in front of the central canal, consisting of medullated nerve-fibres, and a posterior commissure behind the central canal, consisting also of medullated cos CH. XLII.] WHITE MATTER OF THE SPINAL COED 609 nerve-fibres, but with more neuroglia, which gives the grey aspect to this commissure (fig. 446, b). Each half of the spinal cord is marked on the sides (obscurely at the lower part, but distinctly above) by Fig. 446.— Different views of a portion of the spinal cord from the cervical region, with the roots of the nerves (slightly enlarged). In a, the anterior surface of the specimen is shown ; the anterior nerve- root of its right side is divided ; in b, a view of the right side is given ; in c, the upper surface is shown ; in d, the nerve-roots and ganglion are shown from below. 1, the anterior median fissure ; 2, posterior median fissure ; 3, anterior lateral depression, from which the anterior nerve-roots are seen to issue ; 4, posterior lateral groove, into which the posterior roots are seen to sink ; 5, anterior roots passing the ganglion ; 5', in a, the anterior root divided ; 6, the posterior roots, the fibres of which pass into the ganglion 6' ; 7, the united or compound nerve ; 7', the posterior primary- branch, seen in a and d to be derived in part from the anterior and in part from the posterior root. (Allen Thomson.) two longitudinal furrows, which divide it into three portions, columns, or tracts, an anterior, lateral, and posterior. From the groove between the anterior and lateral columns spring the anterior roots of the spinal nerves (fig. 446, B and c, 5) ; and just in front of the groove between the lateral and posterior column the posterior roots enter (b, 6) : a pair of roots on each side corresponds to each vertebra. White matter. — The white matter of the cord is made up of medullated nerve-fibres, of different sizes, arranged longitudinally, and of a supporting material of two kinds, viz. : — (a) ordinary fibrous connective-tissue with elastic fibres, which is connected with septa from the pia mater which pass into the cord to carry the blood- vessels, (b) Neuroglia; the processes of the neuroglia-cells are arranged so as to support the nerve-fibres which are without the usual neurilemmal nerve-sheaths. 2 Q 610 STRUCTURE OF THE SPINAL CORD [CII. XLII. The general rule respecting the size of different parts of the cord is, that each part is in direct proportion to the size and number of nerve-roots given off from it. Thus the cord is very large in the middle and lower part of its cervical portion, whence arise the large nerve-roots for the formation of the brachial plexuses and the supply of the upper extremities ; it again enlarges at the lowest part of its dorsal portion and the upper part of its lumbar, at the origins of the large nerves which, after forming the lumbar and sacral plexuses, are distributed to the lower extremities. The chief cause of the greater size at these parts of the spinal cord is increase in the quantity of grey matter ; the white part of the cord (especially the lateral columns) becomes gradually and progressively smaller from above downwards, because a certain number of fibres coming down from the brain pass into the spinal grey matter at different levels. Grey matter. — The grey matter of the cord consists of nerve- fibres, most of which are very fine and delicate, of nerve-cells with branching processes, and of an extremely delicate network of the primitive fibrillae of axis -cylinders and of dendrites. This fine plexus is called Gerlach's network, and is mingled with the meshes of neuroglia. The neuroglia of the grey matter resembles that of the white, but instead of everywhere forming a close network to support the nerve-fibres, here and there it is in the form of a more open sponge-work to support the nerve-cells. It is especially developed around the central canal, which is lined with columnar ciliated epithelium, the cells of which at their outer end terminate in fine processes, which join the neuroglia network surrounding the canal, and form the substantia gelatinosa centralis. It is also developed at the tip of the posterior cornu of grey matter, forming what is known as the substantia gelatinosa lateralis of Eolando, which is much enlarged in the upper cervical region. Groups of cells in the grey matter. — The multipolar cells of the grey matter are either scattered singly or arranged in definite groups. (1) Anterior horn cells. — In the cervical and lumbar enlargements there are several groups of large multipolar cells in the anterior horn ; in the thoracic region these are reduced to two, a mesial and a lateral group. The larger groups correspond with segments of the limbs, and in the cervical cord there is one special group from which . the phrenic nerve arises for the supply of the diaphragm. The axons pass out by the anterior nerve-roots of the same side, but a few axons pass to the antero-lateral column of the same side, and by the white -commissure to that of the opposite side. In birds, a few axons are stated to pass to the posterior roots. (2) Posterior vesicular column of Lochhart Clarke ; generally known as Clarke's column. — This is a group of large nerve-cells with their long CH. XLII.] GREY MATTER OF THE CORD 611 axis vertical. It lies at the base of the posterior horn, and is best marked in the thoracic region. Their axons pass into the direct cerebellar tract. (3) Intermedio-lateral group. — This is seen in the outer part of the grey matter of the lateral horn, and is most distinct in the upper thoracic and lower cervical regions. (4) The middle cell column lies in the middle of the crescent. (5) The cells of the posterior horn are usually small; they are numerous, but are not disposed in special groups. Columns and tracts in the white matter of the spinal cord. — The columns of the white matter which are marked out by the points from which the nerve-roots issue, are called the anterior, the lateral, and the posterior columns ; the posterior is further divided by a septum of the pia mater into two almost equal parts, constituting the postero- external column, or column of Burdach, and the postero-median, or column of Goll (fig. 449). In addition to these columns, however, it has been shown that the white matter can be still further subdivided. These tracts in the white matter perform different functions in the con- duction of impulses. The methods of observation are the follow- ing: Fig. 447.— Section of half the spinal cord to show the principal groups of cells in the grey matter ; o, groups of cells in the anterior horn ; c, Clarke's column ; i, intermedio-lateral group ; m, middle cell column ; p, scattered cells of the pos- terior horn. (Diagrammatic after Schiifer.) (a) The emoryological method. It has been found by exa mini ng the spinal cord at different stages of its development that certain groups of the nerve-fibres put on their myelin sheath at earlier periods than others, and that the different groups of fibres can therefore be traced in various directions. This is also known as the method of Flechsig. (b) Wallerian or degeneration method. — This method depends upon the fact that if a nerve-fibre is separated from its nerve-cell, it wastes or degenerates. It consists in tracing the course of tracts of degenerated fibres, which result from an injury to any part of the central nervous system. "When fibres degenerate below a lesion, the tract is said to be of descending degeneration, and when the fibres degenerate in the opposite direction, the tract is one of ascending degeneration. By the modern methods employed in staining the central nervous system, it has proved comparatively easy to distinguish degenerated parts in sections of the cord and of other portions of the central nervous system. Degenerated fibres have a different staining reaction when the sections are stained by what are called Weigert's and Pal's methods ; this consists in subjecting them to a special 612 STRUCTURE OF THE SPINAL CORD [CH. XLI1. solution of hematoxylin, and then to certain differentiating solutions. The degeuerated fibres appear light yellow, whereas the healthy fibres are a deep blue. Marchi's method is even better. After hardening in Miiller's fluid, Marchi's solution (a mixture of Miiller's fluid and osmic acid) stains degenerated fibres black, and leaves the rest of the tissue unstained. Accidents to the central nervous system in man have given us much information upon this subject, but this has of late years been supplemented and largely extended by experiments on animals, particularly upon monkeys ; and considerable light has been shed upon the conduction of impulses to and from the nervous system by the study of the results of section of different parts of the central nervous system, and of the spinal nerve-roots. By these methods the tracts in the white matter have now been mapped out, and the principal ones are shown in the succeeding diagrams. It will be convenient to begin by considering the result of cutting through the roots of the spinal nerves. Cutting the anterior roots produces chromatolysis of the cells of the anterior horn from which they originate ; this slow atrophy is the result of disuse of the axons which are cut and still remain attached to the cell-bodies. Wallerian degeneration is limited to the motor nerve- fibres on the distal side of the point of section. The fact that chro- matolysis (see p. 202) occurs when the axon of a nerve-cell is cut through, furnishes us with a valuable method as ascertaining what nerve-cells various tracts originate from. Cutting the posterior roots between the spinal ganglia and the cord leaves the peripheral part of the nerve healthy, and degeneration occurs in the portion of the root which runs into the cord, because the fibres are cut off from the cells of the spinal ganglion from which they grew. These degenerated nerve-fibres may be traced up the cord for a considerable distance. Each posterior root-fibre when it enters the cord bifurcates, the main branch passing upwards, and the shorter branch downwards, so that the degeneration is seen in a small tract called the comma tract (fig. 450) immediately below the point of entrance of the cut posterior root. The upgoing fibre is contained in the posterior column of white matter, and it terminates in the grey matter either in the cord itself at a higher level, or in the medulla oblongata. Tig. 448 represents in a schematic way the manner in which the fibres of the two roots of a spinal nerve are connected to the grey matter in the cord. 1, 2, 3, 4 represent four cells of the anterior horn. Each gives rise to an axis-cylinder, process A, one of which is shown terminating in its final ramification in the end -plate of a muscular fibre M. Each of these four cells is further surrounded by an arborisation (synapse) CH. XLII.] ROOTS OF THE SPINAL NERVES 613 derived from the fibres of the pyramidal tract P, which comes down from the brain. According to Schafer's recent work, the pyramidal fibres really terminate around the cells at the base of the posterior horn ; these cells therefore act as intermediate cell-stations on the way to those in the anterior horn. This is not shown in the diagram. A fibre of the posterior root is also shown ; this originates from the cell G of the spinal ganglion ; the process of this cell bifurcates, Fig. 44S.— Course of nerve-fibres in spinal cord. (After Schafer.) one branch (B) passing to the periphery, where it ends in an arbor - escence in the skin (S) ; the arrow by the side of this branch represents the direction of conduction of the sensory impulses from the skin. An arrow in the opposite direction would indicate the direction of its growth. The other branch G passes into the spinal cord, where it again bifurcates ; the branch E, a short one, passes downwards and ends in an arborisation around one of the small cells P x of the posterior cornu; from which a new axis-cylinder arises, and terminates around one of the multipolar cells (4) of the anterior horn. The main division D travels up in the posterior column of the cord, and ends in grey matter at various levels. Some collaterals (5) 614 STRUCTURE OF THE SPINAL CORD [CH. XLII. terminate by arborising directly around the anterior cornnal cells, principally of the same side ; others (6) do so with an intermediate cell station in a posterior cornual cell P., ; others (7) arborise around the cells of Clarke's column (C) in the thoracic region of the cord, and from these cells fresh axis-cylinders carry up the impulse to the cerebellum in what is called the direct cerebellar tract, while the main fibre (8) may terminate in any of these ways at a higher level in the cord, or above the cord in the medulla oblongata. When we become acquainted with the structure of the medulla oblongata, we shall be able to trace these fibres further. In general terms the anterior root-fibres pass out of the grey matter of the anterior horns, and after a short course leave the spinal cord in the anterior spinal nerve-roots. The posterior roots, on the other hand, do not pass to any great extent into the grey matter immediately, but into the white matter on the inner side of the posterior horn ; in other words, they go into the column of Burdach (fig. 449) ; they pass up in this column, but gradually approach the middle line, and are continued upwards to the medulla in the column of Goll; but as they go up they become less numerous, as some terminate in the grey matter of the cord on the way in the manner described. A few fibres of the posterior root, however, travel for a short distance in a small tract on the outer side of the posterior horn ; this is called the tract of Go " Lissauer (fig. 451) ; the comma tract (fig. 450) has been already explained. Suppose now one cuts through several posterior roots between the spinal ganglia and the cord, so that the course of degenera- tion may be more readily traced. Immediately below the points of entrance of these nerve-roots, the comma tract will be found degenerated ; immediately above, the degenerated fibres will be found in the column of Bur- dach ; higher up in the cord they will be less numerous, and have approached the middle line; the fibres which enter the cord lowest get ultimately nearest the middle line, so that the greater part of the column of Goll is made up of sensory fibres from the legs ; the fibres which enter the cord last, for instance those from the upper limbs and neck, pursue their course in the inner part of the column of Burdach. The preceding figure (fig. 449) shows the degeneration in a section Fig. j-h). —Degeneration in column of Goll after section of posterior nerve-roots. CH. XLII.] degeneration teacts 615 of the spinal cord, after the division of a number of nerve-roots on one side. The microscopic section is taken high up, so that all the degenerated fibres have passed into the column of Goll on the same side ; the inner set (1) are shaded differently from the outer set (2), indicating that those nearest the middle line come from the lowest nerve-roots. "We mav pass from this to consider the tracts of degeneration that occur when the spinal cord is cut right across in the thoracic region. Some tracts will be found degenerated in the piece of cord below the lesion ; these consist of nerve-fibres that are connected with the nerve-cells in the brain ; the principal ones are the pyramidal tracts. Other tracts are found degenerated in the piece of cord above the lesion; these consist of nerve-fibres that are connected with the nerve-cells of the spinal ganglia, or with the cells of the spinal cord itself below the lesion and are passing upwards. In general terms we may say that the tracts which degenerate downwards are the motor tracts, and those which degenerate upwards are the afferent or sensory channels. "We must also take into account groups of association fibres which unite together different regions of the cord ; these are generally short tracts in which, there- fore, degeneration can only be traced a short distance up or clown. The long tracts are those which connect cord or spinal nerves with brain, like those of Goll and Burdach just mentioned, or the pyramidal tracts the main efferent pathways. Tracts of Descending Degeneration (fig. 450). (1.) The crossed pyramidal tract. — This is situated in the lateral column on the outer side of the posterior cornu of grey matter. At the lower part of the spinal cord it extends to the margin, but higher up it becomes displaced from this position by the interpolation of another tract of fibres, to be presently described, viz., the direct cerebellar tract. The crossed pyramidal tract is large, and may touch the grey matter at the tip of the posterior cornu, but is separated from it elsewhere. Its shape on cross section is somewhat like a lens, but varies in different regions of the cord, and diminishes in size from the cervical region downwards, its fibres passing off as they descend, to arborise around the nerve-cells and their branchings in the grey matter of the cord. The fibres of which this tract is composed are moderately large, but are mixed with some that are smaller. (2.) The direct or uncrossed pyramided tract, or column of Turck. — This tract is situated in the anterior column by the side of the anterior fissure. It ends in the mid or lower thoracic region of the cord. 616 STRUCTURE OF THE SPINAL CORD [CH. XLII. The two pyramidal tracts come down from the brain ; in the medulla oblongata, the greater number of the pyramidal fibres cross over to the other side of the cord which they descend ; hence the term crossed pyramidal tract ; a smaller collection of the pyramidal fibres goes straight on, on the same side of the cord, and these cross at different levels in the anterior commissure of the cord lower down ; hence the disappearance of the direct pyramidal tract in the lower part of the cord. The fact that the crossed pyramidal tract of one side is the fellow of the direct pyramidal tract of the other side, is indicated in the diagram by the direction of shading (see fig. 450). Comma tract Septomarginal Crosse pyrami ry tract Pre pyramided tract Antero-late descendin tract bundle Bundle of Helweg Direct pyramidal tract Fig. 450. — Tracts of descending degeneration. For the sake of clearness each is shown on only one side. (After Schafer). Mingled with the fibres of the crossed pyramidal tract are a few fibres of the pyramid which have not crossed in the medulla oblongata, and are therefore derived from the same side of the cerebrum (uncrossed lateral pyramidal fibres). The pyramidal fibres are not found at all in vertebrates below the mammals. In the lower mammals they are very small, and in some rodents (rat, mouse, guinea-pig) they are placed in the posterior columns. The direct pyramidal tract is found only in man and the higher apes. The paralysis that results from the section of the pyramidal tracts passes off very soon in many animals, whereas that which results from section of the anterior column and the adjacent part of the lateral column is more permanent. It is probable that the two tracts next to be described may be the second path for volitional impulses, and perhaps derive their importance from the fact that the impulses which travel down them are necessary in the maintenance of the tone of the anterior horn cells. (3.) Antero -lateral descending tract, or tract of Loewenthal, lies by the side of the anterior median fissure, and extends along the margin CII. XLTT.] DEGENERATION TRACTS G17 of the cord towards the lateral column. These originate from the posterior longitudinal bundle of the medulla oblongata, and from other sources to be described later. They end by synapses in the anterior horn. (4.) The prepyramidal tract (Monakow's bundle). — This is situated just in front of the crossed pyramidal tract. Its origin is in the cells of the red nucleus in the mid-brain. Its fibres end by arborisations in the grey matter about the middle of the crescent. (5.) Bundle of Helweg. — The exact origin and destination of these fibres are not known : they can be traced from the neighbourhood of the olivary body in the medulla oblongata, and pass down in the anterior part of the lateral column in the cervical region. (6.) Short tracts in the posterior column. — These are (a) the Comma tract ; though this degenerates downwards, it is in reality a sensory tract, being composed, as we have already seen, of the branches of the entering posterior root-fibres which pass downwards on entering the cord. It is only found for a comparatively short distance below the actual lesion. (b) Septo-marginal fibres; these are few in number, and are mainly found near the median fissure, where they constitute the oval bundle, and near the posterior surface, where they form the median triangle bundle. These are doubtless short associa- tion tracts, and are mixed with others, especially in the ventral part of the posterior column, which have an " ascending " course. Tracts of Ascending Degeneration (fig. 451). (1.) Postero-medial column, or column of Q-oll. — This consists of fibres derived from the posterior roots of the sacral, lumbar, and lower Direct cerebellar tract V Fig. 451.— Tracts of ascending degeneration, shown on one side of the cord only. (After Schafer). thoracic nerves. These fibres enter the postero-lateral column, and gradually pass towards the mid-line, as already explained. They 618 STRUCTURE OF THE SPINAL CORD [CII. XLII. end in the grey matter of the nucleus gracilis of the medulla oblongata. (2.) Postero -lateral column, or column of Burdock. — Many of the fibres of this tract, which is also composed of the entering posterior nerve-roots, pass into the grey matter of the cord either immediately on entrance, or in their course upwards. The rest continue upwards to the medulla oblongata, but those from the lower roots pass into the column of Goll, as just stated ; those from the upper roots continue to travel upwards in ihe column of Burdach, and end in the grey matter of the nucleus euneatus in the medulla oblongata. (3.) Dorsal or direct cerebellar tract, or tract of Flechsig. — This is found in the cervical and thoracic regions of the cord, and is situated between the crossed pyramidal tract and the margin. It degenerates on injury or section of the cord itself, but not on section of the posterior nerve-roots. In other words, its fibres are endogenous, i.e., arise from cells within the grey matter of the cord ; these cells are those of Clarke's column of the same side; the fibres are large ones. (4.) Venial cerebellar or antero-lateral ascending tract, or tract of Goivers. — This is situated in front of the crossed pyramidal and direct cerebellar tracts in the lumbar region, while in the thoracic and cervical regions it forms a narrow band at the margin of the cord, curving round even into the anterior column. Its fibres intermingle with those of the antero-lateral descending tract. Both of these tracts, as their names indicate, go to the cerebellum ; the dorsal cerebellar enters the cerebellum by its lower peduncle, while the ventral cerebellar enters by its superior peduncle. The fibres terminate by arborising around the cells of that part of the cerebellum known as the vermis or middle lobe. V. Gehuchten states that the ventral tract gives off a few fibres that enter the opposite cerebellar hemisphere by its middle peduncle. (5.) Tract of Lissauer, or posterior marginal zone. — This is a small tract of ascending fibres situated at the outer side of the tip of the posterior horn. These are fine fibres from the posterior roots ; they subsequently pass into the posterior column. (6.) A number of association tracts have been differentiated by Flechsig's and Sherrington's method (see next paragraph). Association fibres in the Spinal Cord. The numerous short traets already mentioned as demonstrable in the spinal cord are doubtless bundles of association fibres which connect its different levels together. The main difficulty of investigating them by the degeneration method has arisen from the fact that they are largely intermingled with, and so are hard to distinguish from the long tracts which connect brain and cord together. In 1853 Pfliiger stated that reflex irradiation within the spinal cord always took place in an upward direction, but Sherrington in his work found many exceptions to this rule, and he sought for the paths which are capable of carrying the impulses down the cord by a very ingenious method. The spinal cord of a dog was completely divided across, and the animal was kept alive for a considerable time afterwards ; CH. XLII.] hemisection of the cord 619 sufficient time was allowed to elapse (roughly about a year) for all traces of the degeneration due to this lesion to have disappeared. The cord is then left, as it were, like a cleaned slate, on which once more a new degeneration can be written without fear of confusion with a previous one. The second degeneration produced by such an operation as hemisection would then affect the intra-spinal fibres only, all the long tracts from brain to cord having been wiped out by the first operation. The complete topography of all these fibres, which are very numerous, has not yet been worked out. The degenerated fibres are scattered throughout the white matter, but are most numerous at the margins of the cord. This is especially true for the longer fibres, and some of them appear to be very long indeed. In the case of the longer fibres there is no evidence of decussation ; in the case of the shorter fibres there is some but not very conclusive evidence that they in part cross to the other side. Complete transverse section of the spinal cord leads to : — 1. Loss of motion of the parts supplied by the nerves below the section on both sides of the body. The paralysis is not confined to the voluntary muscles, but includes the muscular fibres of the blood-vessels and viscera. Hence there is fall of blood-pressure, paralysis of sphincters, etc. 2. Loss of sensation in the same regions. 3. Degeneration, ascending and descending, on both sides of the cord. Hemisection. — If the operation performed is not a complete cut- ting of the spinal cord across transversely, but a cutting of half the cord across, it is termed hemisection, or semi-section. This operation leads to : — 1. Loss of motion of the parts supplied by the nerves below the section on the same side of the body as the injury. 2. Loss of sensation in the same region. The loss of sensation is not a very prominent symptom, and is limited to the sense of localisa- tion and the muscular sense. The animal can still feel sensations of pain and of heat and cold. 3. Degeneration, ascending and descending, nearly entirely con- fined to the same side of the cord as the injury. The most important of these are shown in the photo-micrographs (fig. 452) on the opposite page, the small text beneath which should be carefully studied. Differences in different, regions of the spinal cord. — The outline of the grey matter and the relative proportion of the white matter varies in different regions of the spinal cord, and it is, therefore, possible to tell approximately from what region any given transverse section of the spinal cord has been taken. The white matter increases in amount from below upwards. The amount of grey matter varies ; it is greatest in the cervical and lumbar enlargements, viz. , at and about the oth lumbar and 6th cervical nerve, and least in the thoracic region. The greatest development of grey matter corresponds with greatest number of nerve-fibres passing from the cord. In the cervical enlargement the grey matter occupies a large proportion of the section, the grey commissure is short and thick, the anterior horn is blunt, whilst the posterior is somewhat tapering. The anterior and posterior roots run some distance through the white matter before they reach the periphery. At the extreme upper part of the cervical region, the end of the posterior horn is swollen out by 620 STRUCTURE OF THE SPINAL CORD [CH. XLII. excess of neuroglia into a rounded mass called the substantia gelatinosa of Rolando. The cervical cord is wider from side to side than from before back ; this is owing to the great width of the lateral columns. In the dorsal region the grey matter bears only a small proportion to the white, and the posterior roots in particular run a long course through the white matter after they enter the cord ; the grey commissure is thinner and narrower than in the cervical region. The intermedio-lateral tract is here most marked, and forms a Fig. 452. — The above diagrams are reproductions of photo-micrographs from the spinal cord of a monkey, in which the operation of left hemisection had been performed some weeks previously (Mott.) The sections were stained by Weigert's method, by which the grey matter is bleached, while the healthy white matter remains dark blue. The degenerated tracts are also bleached. A is a section of the cord in the thoracic region below the lesion ; the crossed pyramidal tract is degenerated. B is a section lower down in the lumbar enlargement : the degenerated pyramidal tract is now smaller. C is a section in the thoracic region some little distance above the lesion. The degenerated tracts seen are in the outer part of Goll's column, and in the direct cerebellar tract. D is a section higher up in the cervical region ; the degeneration in Goll's column now occupies a median position ; the degenerations in the direct cerebellar tract, and in the tract of Gowers, are also well shown. Xotice that in all cases the degenerated traces are on the same side as the injury. prominence often called the lateral horn. This is shown in fig. 452 C. Clarke's column is also confined to this region of the cord. In the lumbar enlargement the grey matter again bears a very large proportion to the whole size of the transverse section, but its posterior cornua are shorter and blunter than they are in the cervical region. The grey commissure is short and extremely narrow. The cord is circular on transverse section. ^1/ the upper part of the conns medullaris, which is the portion of the cord im- mediately below the lumbar enlargement, the grey substance occupies nearly the whole of the transverse section, as it is only invested by a thin layer of white sub- CII. XLII.] regional diffeeences in cord 621 stance. This thin layer is wanting in the neighbourhood of the posterior n: rve-roots. The grey commissure is extremely thick. At the level of the fifth sacral nerve the grey matter is also in excess, and the central canal is enlarged, appearing T-shaped in section ; whilst in the upper portion of the filum terminale the grey matter is uniform in shape without any central canal. CHAPTER XLlll THE BRAIN A student's first glance at a brain, or at such a drawing of it as is given in fig. 453, will be sufficient to convince him of its complicated Flo. 453.— Base of the brain. 1, superior longitudinal fissure ; 2, 2', 2", anterior cerebral lobe ; 3, fissure of Sylvius, between anterior and 4, 4', 4", middle cerebral lobe ; 5, 5', posterior lobe ; 6, medulla oblongata ; the figure is in the right anterior pyramid ; 7, 8, 9, 10, the cerebellum; +, the inferior vermiform process. The figures from I. to IX. are placed against the corresponding cerebral nerves ; III. is placed on the right eras cerebri. VI. and VII. on the pons Varolii ; X. the first cervical or suboccipital nerve. (Allen Thomson.) J. structure. We shall devote this and a few succeeding chapters to anatomical considerations, before passing on to the study of its physiology. CH. XLIII.] THE BKAIN 623 At the lowest part of the brain (fig. 454), continuing the spinal cord upwards, is the medulla oblongata or bulb (D). Next comes the pons Varolii (C), very appropriately called the bridge, because in it are the connections between the bulb and the upper regions of the brain, and between the cerebellum or small brain (B) and the rest of the nervous system. The mid-brain comes next (a, b), and this leads into the peduncles -or crura of the cerebrum (A), the largest section of the brain. Through the brain runs a cavity filled with cerebro-spinal fluid (see p. 178), and lined by ciliated epithelium ; this is continuous with the central canal of the spinal cord. In the brain, however, it does Fig. 454.— Plan in outline of the brain, as seen from the right side. A. The parts are represented as separated from one another somewhat more than natural, so as to show their connections. A, cerebrum ; /, g, h, its anterior, middle, and posterior lobes ; e, fissure of Sylvius ; B, cerebellum ; C, pons Varolii ; D, medulla oblongata ; a, peduncles of the cerebrum ; 6, c, d, superior, middle, and inferior peduncles of the cerebellum. (From Quain). not remain a simple canal, but is enlarged at intervals into what are called the ventricles. There is one ventricle in each half or hemisphere of the cerebrum ; these are called the lateral ventricles, they open into the third ventricle, which is in the middle line ; and then a narrow canal {aqueduct of Sylvius) leads from this to the fourth ventricle, which is placed on the back of the bulb and pons, which form its floor; its roof is formed partly by the overhanging cere- bellum, partly by pia mater. This piece of pia mater is pierced by a hole {Foramen of Magendie), and so the cerebro-spinal fluid in the interior of the cerebro-spinal cavity is continuous with that which bathes the external surface of brain and cord in the sub-arachnoid space. The fourth ventricle leads into the central canal of the spinal 624 THE BRAIN [CII. XLIII. cord. The fifth ventricle in the central structures of the brain does not communicate with the others. Speaking generally, there are two main collections of grey matter — that on the surface, and that in the interior bordering on the cerebro-spinal cavity, and subdivided into various masses (floor of fourth ventricle, corpora striata, optic thalami, etc.), whose closer acquaint- ance we shall make presently. In the foetus the central nervous system is formed by an infolding of a portion of the surface epiblast. This becomes a tube of nervous matter, which loses all connection with the surface of the body, though later in life this is in a sense re-established by the nerves that grow from the brain and cord to the surface. The anterior end of this tube becomes greatly thickened, to form the brain, its cavity becoming the cerebral ven- tricles; the rest of the tube becomes the spinal cord. The primitive brain is at first subdivided into three parts, the primary cerebral vesicles ; the first and third of these again • subdivide, so that there are ultimately five divisions, which have received the following names : — 1. Pros-encephalon, or fore brain. This is developed into the cerebrum with the corpora striata. It encloses the lateral ventricles. 2. Thalam-encephalon, or twixt brain. This is developed into the parts including the optic thalami, which enclose the third ventricle. 3. Mes-encephalon, or mid brain, con- sists of the parts which enclose the aque- duct of Sylvius — namely, the corpora quadrigemina, which form its dorsal, and the crura cerebri, which form its ventral aspect. 4. Ep-encephalon, or hind brain, which forms the cerebellum and pons. 5. Met-encephalon, or after brain, which forms the bulb or medulla oblongata. Fig. 455. — Diagrammatic hori- zontal section of a vertebrate brain. The figures serve botli for this and the next diagram. Mb, mid-brain : what lies in front of this is the fore-, and what lies behind, the hind- brain ; Lt, lamina terminalis ; Olf , olfactory lobes ; Hvip, hemispheres ; Th. E, thala- mencephalon ; Pn, pineal gland ; Py, pituitary body ; F.M., foramen of Munro; ex, corpus striatum ; Th, optic thalamus ; CC, crura cerebri : the mass lying above the canal represents the corpora quad- rigemina ; Cb, cerebellum ; M.o., medulla oblongata; / — IX, nine pairs of cranial nerves ; 1, olfactory ventri- cle ; 2, lateral ventricle ; 3, third ventricle ; 4, fourth ventricle; +, iter a tercio ad quartum ventriculum, or aqueduct of Sylvius. (Huxley.) CH. XLIII.] PKIMAEY DIVISIONS OF BEAIN 625 Figs. 455 and 456 represent a diagrammatic view of a vertebrate brain; the attachment of the pineal gland, pituitary body, and olfactory (I) and optic (II) nerves is also^shown. IX v Fi<;. 456. — Longitudinal and vertical diagrammatic section of a vertebrate brain. Letters as before PV, pons Varolii. Lamina terminalis is represented by the strong black line joining Pn and Py. (Huxley.) 2 R CHAPTER XLIV STRUCTURE OF THE BULB, PONS, AND MID-BRAIN We may study the bulb and pons by examining first the anterior or ventral, then the posterior or dorsal aspect, and last of all the interior. Anterior Aspect. The bulb is seen to be shaped, like an inverted truncated cone, larger than the spinal cord, and enlarging as it goes up until it terminates in the still larger pons (fig. 457, p). In the middle line is a groove, which is a continuation upwards of the anterior median fissure of the spinal cord; the columns of the bulb are, speaking roughly, continuations upwards of those of the cord, but there is a considerable rearrangement of the fibres in each. Thus the prominent columns in the middle line, called the pyramids {a a), are composed of the pyramidal fibres, which in the spinal cord are situated princi- pally in the lateral columns of the opposite side (crossed pyramidal tracts). The decussation or crossing of the pyramids (b) occurs at their lower part: a small collection of the pyramidal fibres is, however, continued down the cord in the anterior column of the same side of the cord (direct pyramidal tract): these cross at different levels in the cord. On the outer side of each pyramid is an oval prominence (c c), which is not represented in the spinal cord at all. These are called the olivary bodies or olives ; they consist of white matter outside, with grey and white matter in their interior. The restiform bodies at the sides (d d) are the continuation upwards of those fibres from cord and bulb which enter the cerebellum, and the upper part of each restiform body is called the inferior peduncle of the cerebellum* * Each half of the cerebellum has three peduncles : inferior, middle, and Superior. CH. XL! V.] STRUCTURE OF BULB AND PONS 627 Posterior Aspect. Fig. 458 shows a surface view of the back of the bulb, pons, and mid-brain. Again we recognise some of the parts of the spinal cord continued upwards, though generally with new names, and again we see certain new structures. The posterior median fissure is continued upwards, and on each side of it is the prolongation upwards of the posterior column of Fig. 457. — Ventral or anterior surface of the pons Varolii, and medulla oblon- gata, a, a, pyramids ; 6, their decus- sation ; c, e, olivary bodies ; d, d, restiform bodies ; e, arcuate fibres ; /, fibres passing from the anterior column of the cord to the cere- bellum ; g, anterior column of the spinal cord ; h, lateral column ; p, pons Varolii ; i, its upper fibres ; 5, 5, roots of the fifth pair of nerves. Fig. 458. —Dorsal or posterior surface of the pons Varolii, corpora quad- rigemina, and medulla oblongata. The peduncles of the cerebellum are cut short at the sides, a, a, the upper pair of corpora quadri- gemina ; b, b, the lower ; /, /, supe- rior peduncles of the cerebellum ; c, eminence connected with the nucleus of the hypoglossal nerve : e, that of the glosso-pharyngeal nerve ; i, that of the vagus nerve ; d, d, restiform bodies ; p, p, poste- rior columns ; v, v, groove in the middle of the fourth ventricle, ending below in the calamus scrip- torius ; 7, 7, roots of the auditory nerves. the cord. The column of Goll is now called the Funiculus gracilis, and the column of Burdach the Funiculus cuneatus. The two funiculi graciles He at first side by side, but soon diverge and form the two lower boundaries of a diamond-shaped space called the floor of the fourth ventricle ; this is made of grey matter: the central canal of the cord gets nearer and nearer to the dorsal surface of the bulb, till at last it opens out on the back of the bulb, and its surrounding grey matter is spread out to form the floor of the fourth ventricle. The two upper boundaries of the diamond-shaped 628 STRUCTURE OF THE BULB, PONS, AND MID-BRAIN [CH. XLIV. space are made by the superior peduncles of the cerebellum, which contain fibres going up through the mid-brain to the cerebrum. The middle peduncles of the cerebellum are principally made up of fibres running from one cerebellar hemisphere towards the other through the pons. Banning down the centre of the floor of the fourth ventricle is a shallow groove; on each side of this is a rounded longitudinal eminence called the eminentia teres ; running across the middle of the floor are a number of fibres (the stricc acousticaz), which join the auditory nerve. In the upper part of the diagram, the mid-brain, with the corpora quadrigemina (a a, b b), is shown. Here there is once more a canal which penetrates the substance of the mid-brain, and is called the aqueduct of Sylvius, or the iter a tertio ad quartum ventriculum ; it leads, as its second name indicates, from the third to the fourth ventricle. The Internal Structure of the Bulb, Pons, and Mid-Brain. The structure of the interior of these parts is complex, and the complexity arises from the circumstance that here we have to deal not only with parts running upwards from cord to brain, or down from brain to cord, but also with a considerable amount of grey matter in which some of the white tracts terminate, or from which new tracts issue. The most important stretch of grey matter is that which appears on the floor of the fourth ventricle, and which is continued upwards around the Sylvian aqueduct, and downwards into the spinal cord ; here are situated groups of nerve-cells, which are spoken of as centres, or nuclei. The most important of these are those which are connected to the cranial nerves. There are altogether twelve pairs of cranial nerves, and of these the last ten pairs originate from the floor of the fourth ventricle or the neighbouring grey matter. The following is a list of the cranial nerves : — 1. Olfactory. — This is the nerve of smell. 2. Optic. — This is the nerve of sight. ," m -,-, These three nerves supply the muscles of the 4. Trochlear V Ml] 6. Abducens ) ^ 5. Trigeminal. — This is the great sensory nerve of the face and head. Its smaller motor division supplies the muscles of mastication and a few other muscles also. 7. Facial. — This is mainly the motor nerve of the face muscles. 8. Auditory. — This is divided into two parts, one of which, called the cochlear nerve, is the true nerve of hearing, and is distributed to CH. XLIV.] CRANIAL NERVES 629 the cochlea of the internal ear ; the other division, called the vestibular nerve, is distributed to the vestibule and semi-circular canals of the internal ear. 9. Glossopharyngeal. — This is a mixed nerve ; its motor fibres pass to certain of the pharyngeal muscles ; its sensory fibres are mainly concerned in the sense of taste. 10. Vagus or pneumogastric. — This is a nerve with varied efferent and afferent functions ; its branches pass to pharynx, larynx, oeso- phagus, stomach, lungs, heart, intestines, liver and spleen. Most of these functions we have already studied in connection with these organs. 11. Spinal accessory. — The internal branch of this nerve blends with the vagus, and its larger external division supplies the trapezius and the sterno-mastoid muscles. 12. Hypoglossal. — This is the motor nerve to the tongue muscles. A mere enumeration of the nerves connected to the bulb shows how supremely important this small area of the brain is for carrying on the organic functions of life. It contains centres which regulate deglutition, vomiting, the secretion of saliva, etc., respiration, the heart's movements, and the vaso-motor nerves. When we further consider that the various centres are connected by groups of association fibres, we at once realise the reason for the complexity of the structures where all this busy traffic takes place. In the enumeration of the cranial nerves, it will be noticed that many of them are either wholly motor or wholly sensory, and that some of them, like the spinal nerves, have a double function. The motor nerve fibres start as axons from the groups of nerve-cells in the grey matter of this region, just as the motor fibres in the spinal nerves originate from the cells of the spinal grey matter. There is a corresponding resemblance in the origin of the sensory fibres of the cranial and spinal nerves. In the latter, it will be remembered, they originate as outgrowths from the cells of the spinal ganglia, one branch growing to the periphery, and the other to the spinal cord, where it terminates after a more or less extended course by forming synapses with the cells of the grey matter. In the cranial nerves they have a corresponding origin in peripheral ganglia, and those branches which grow towards the bulb terminate by arborising around special groups of cells spoken of as the sensory nuclei. The following diagram (fig. 456) roughly indicates the position of these nuclei ; the motor nuclei are coloured blue, and the sensory red. It must, however, be clearly recognised that while the motor nuclei are true centres of origin, that the so-called sensory nuclei are groups of cells around which the entering sensory fibres arborise ; these cells do not give origin to the axons of the sensory nerves. After we have studied the internal structure of the bulb we shall be able to 630 STRUCTURE OF THE BULB, PONS, AND MID-BRAIN [cil. XLXV. return once more to the cranial nerves, in order that we consider their origin and function in greater detail. But this diagram will give a general idea of the positions of the 3rd. Ventricle C.G. Sir. A Lateral column Funiculus cuneatus Funiculus gracilis PlQ. 459. — Diagram to show the position of the nuclei of the cranial nerves (after Sherrington). The medulla and pons are viewed from the dorsal aspect, the cerebrum and cerebellum having been cut away. The nuclei (sensory coloured red, and motor blue) are represented as being seen through transparent material. C.Q. a., anterior corpus quadrigeminum ; C.Q. p., posterior corpus quadri- geminum ; C.G., corpus geniculatum ; i-.v., value of Vieussens ; I.e., locus cteruleus ; e.t., eminentia teres; str. A., strife acoustics. S.P., M.P., and LP., superior middle and inferior cerebellum peduncles respectively cut through. The numerals III. to XII. indicate the nuclei of the respec- tive cranial nerves, all shown on the left side except the aeeessory-vago-glossopharyngeal IX., X., XI., which to avoid confusion is placed on the right side. Vm. is the motor nucleus of the fifth nerve ; Vd., the sensory nucleus of the same nerve with its long descending root; VHIm., the median nucleus of the auditory nerve; N.D. Nucleus of Deiters ; n. amh. nucleus ambiguus. The position of the descending root of the ninth and tenth (fasciculus solitarius) is also indicated (J. s). nuclei. It will be noticed that the so-called sensory nuclei (coloured red) are in the minority ; they comprise the sensory nucleus of the fifth nerve with its long descending (formerly called ascending) root, CH. XLIV.] CEANIAL NEEVES 631 the nuclei of the eighth nerve (only one of which, VHIm., is seen in the diagram), and the glossopharyngeal and vagal portions of a long strand of nerve-cells called the combined nucleus of the ninth, tenth, and eleventh nerves. The remaining nuclei (coloured blue) are efferent, and may be principally arranged into two groups : — (1) the nuclei of the third, fourth, sixth, and twelfth nerves, which are close to the middle line ; and (2) the motor nucleus of the fifth, the nucleus of the seventh, and the nucleus ambiguus (motor nucleus of the ninth and tenth nerves) which form a line more lateral in position. It should be added that van Gehuchten has shown that, except a few fibres of the third, and the whole of the fourth nerves, none SUP. PED. OF CERESELLUM DDLE „ ,, CEREBELLAR 4 HEMISPHERE Fig. 460. — Diagrammatic representation of dorsal aspect of medulla, pons, and mid-brain. of the fibres of the cranial nerves cross to the opposite side. The first two pairs of cranial nerves, the olfactory and the optic, will be studied in connection with smell and vision later on. We can now pass to the consideration of transverse sections of this part of the central nervous system. We will limit ourselves to seven, the level of which is indicated in the above diagram (fig. 460). The cerebellum has been bisected into two halves and turned out- wards, its upper peduncles having been cut through to render the 632 STRUCTURE OF THE BULB, PONS, AND MID-BRAIN [CH. XLIV. parts more evident. The position of our seven sections is indicated by the transverse lines numbered 1 to 7. First section. — This is taken at the lowest level of the bulb, through the region of the decussation of the pyramids. The similarity to the cervical cord will be at once recognised; the passage of the pyra- midal fibres (P) from the anterior part of the bulb to the crossed pyramidal tract of the opposite side of the cord cuts off the tip of anterior horn (A), which in sections higher up appears as an isolated mass of grey matter, called the lateral nucleus (fig. 462, nl). The V formed by the two posterior horns is opened out, and thus the grey matter with the central canal is brought nearer to the dorsal aspect of the bulb ; the tip of the cornu swells out to form the substantia gelatinosa of Ro- lando (E), which causes a prominence on the surface called the tubercle of Rolando; G and C are the funiculi gracilis and cuneatus respectively, the continuations upwards of the columns of Goll and Burdach. Many of the fibres of the pyramidal tract terminate in the mid-brain and pons, hence this tract is reduced in size when it reaches the bulb. The pyramidal fibres on their long journey give off collaterals to the cortex cerebri, the basal ganglia of the cerebrum, the substantia nigra of the raid-brain, the nuclei pontis of the pons, and lower down in the cord to the base of its posterior horn. They, however, do not give off collaterals to the motor nuclei of the cranial nerves on their passage through the bulb (Schafer). The only collaterals given off in this region are a few to the olivary nuclei. Second section (fig. 462). — This is taken through the upper part of the decussation. Beginning in the middle line at the top of the diagram, we see first the posterior median fissure (p.m/.), below which is the grey matter enclosing the central canal (c.c), and con- taining the nuclei of the eleventh and twelfth nerves ; the funiculus gracilis (f.g.) comes next, and then the funiculus cuneatus (f.c.) ; these two funiculi have now grey matter in their interior : these masses of grey matter are called respectively nucleus gracilis (n.g.) and nucleus cuneatus (n.c.) ; the fibres which have ascended the posterior columns of the cord terminate by arborising around the cells of this grey matter ; the fibres from the lower part of the body end in the nucleus gracilis, and those from the upper part of the body in the p P Fig. 461. — Section through the bulb at the level of the decussation of the pyramids, o, funiculus gracilis, con- tinuation of column of Goll ; c, funiculus cuneatus, continuation of column of Burdach ; r, substantia gelatinosa of Rolando, continuation of posterior horn of spinal cord ; l, continuation of lat- eral column of cord ; a, remains of part of the anterior horn, separated from the rest of the grey matter by the pyramidal fibres p, which are crossing from the pyramid of the medulla to the posterior part of the lateral column of the opposite side of the cord. (After L. Clarke.) CH. XLTV".] INTEENAL STBUCTUBE OF BULB 633 nucleus cuneatus. These nuclei form a most important position of relay in the course of the afferent fibres from cord to brain. The new fibres (the second relay of the sensory spinal path) arising from the cells of these nuclei pass in a number of different directions, and n-M- Fig. 462. — Transverse section of the medulla oblongata in the region of the superior decussation, a.m./., anterior median fissure ;/.o., superficial arcuate fibres; py., pyramid; n.a.r., nuclei of arcuate fibres ; f.a 1 , deep arcuate fibres becoming superficial ; o, o', lower end of olivary nucleus ; n.l., nucleus lateralis ; f.r., formatio reticularis ; f.a! 2 , arcuate fibres proceeding from the formatio reticularis; g, substantia gelatinosa of Rolando; d.V., descending root of fifth nerve; f.c, funiculus cuneatus; n.c, nucleus cuneatus; n.c.', external cuneate nucleus; n.g., nucleus gracilis ; /.l peduncle and superior medullary velum. Some crusta; s.n. , substantia f fch e fibres of the tract are continued, how- nigra ; T, tegmentum. . . , . . ever, into the corpora quadngemma. The Tracts of the Bulb, Pons, and Mid-Brain. In the preceding description we have had occasion to mention the main tracts which are seen in transverse section. It will now be convenient to summarise matters by enumerating them again as well as certain others which are of less importance, or concerning which we know less. The tracts may be divided into two main groups, those which are descending and those which are ascending. Descending tracts. — The principal descending tract is (a) the pyramidal tract. This has already been sufficiently described, so also have (b) the posterior and (c) the ventral longitudinal bundles. The remaining tracts are : — (d) Monakow's bundle. — These fibres start from the cells of the red nucleus, cross the raphe in F Orel's fountain decussation ; they eventually pass into the lateral column of the cord as the prepyramidal tract. (e) The ponto-spinal lateral tract starts from the large cells of the formatio reticularis, and runs down the lateral portion of this formation through the pons and bulb. In the spinal cord the fibres, mixed with many others of different origin, lie in the lateral column between the grey matter and the tracts of Gowers and Monakow. They pass like the fibres of the posterior and ventral longitudinal bundles into the grey matter of the anterior cornu. (/) The vestibulospinal tract fibres are similar in origin to those of the posterior longitudinal bundle ; its fibres lie mixed with those of the two last-mentioned tracts, and their destination is the grey matter of the anterior horn. {(/) The central tract of the tegmentum; this is a distinct bundle which lies in the middle of the reticular formation, but its origin and destination are both unknown. (h) Other longitudinal fibres of the tegmentum are (1) the fasciculus retroflexus, which passes obliquely from the ganglion of the trabecula (a collection of cells near the middle of the optic thalamus) to the interpeduncular ganglion of the opposite side (a collection of cells just where the peduncles diverge from the transverse fibres of the pons) ; (2) Von Guddens bundle, which runs from the corpora mammillaria to end in the tegmentum ; these fibres decussate, and their intercrossing together with that of Monakow's bundle constitutes the fountain decussation of Fore). G40 ' STRUCTURE OF THE BULB, PONS, AND MID-BRAIN [CH. XLIV. Ascending Tracts. — The most important of these are — (a) the tract of the fillet, and (b), the central tract of the cranial sensory nerves. We must also remember the fibres that connect the cord to the cerebellum ( (c) dorsal and (d) ventral cerebellar tracts), and (er of depres- sions which are called fissures or sulci, and it is this folding of the surface that enables a very large amount of the precious material Fig. 4S3. A. Cerebral Hemisphere of adult Macacque monkey. B. Cerebral Hemisphere of child shortly before birth. The two brains are very much alike, but the growth forwards of the frontal lobes even at this early stage of development of the human brain is quite well seen. S, Assure of Sylvius ; R, fissure of Rolando. called the grey matter of the cortex to be packed within the narrow compass of the cranium. In the lowest vertebrates the surface of the brain is smooth, but going higher in the animal scale the fissures make their appearance, reaching their greatest degree of complexity in the higher apes and in man. In an early embryonic stage of the human foetus the brain is also, smooth, but as development progresses the sulci appear, until the climax is reached in the brain of the adult. The sulci, which make their appearance first, both in the animal scale and in the development of the human foetus, are the same. They remain in the adult as the deepest and best marked sulci ; they are called the primary fissures or sulci, and they divide the brain into lobes; the remaining sulci, called the secondary fissures or sulci, further subdivide each lobe into convolutions or gyri. A first glance at an adult human brain reveals what appears to be a hopeless puzzle ; this, however, is reduced to order when one studies the brain in different stages of development, or compares the CH. XLVI.] THE CEEEBEAL CONVOLUTIONS 663 brain of man with that of the lower animals. The monkey's brain in particular has given the key to the puzzle, because there the primary fissures are not obscured by the complexity and contorted arrangement of secondary fissures. The preceding figure, comparing the brain of one of the lower monkeys with that of the child shortly before birth, shows the close family likeness in the two cases. Fig. 484 gives a representation of the brain of one of the higher monkeys, the orang-outang, where there is an intermediate condition of complexity by which we are led lastly to the human brain. Fig, 4S4. — Brain of the Orang, § natural size, showing the arrangement of the convolutions Sy, fissure of Sylvius; R, fissure of Rolando; EP, external parieto-occipital fissure; Olf, olfactory lobe; Cb, cerebellum; FV, pons Varolii; MO, medulla oblongata. As contrasted with the human brain, the frontal lobe is short and small relatively, the fissure of Sylvius is oblique, the temporo-sphenoidal lobe very prominent, and the external parieto-occipital fissure very well marked. Note also the bend or genu in the Rolandic fissure. This is found in all anthropoid apes. Let us take first the outer surface of the human hemisphere ; the primary fissures are — 1. The fissure of Sylvius ; this divides into two limbs, the posterior of which is the larger, and runs backwards and upwards, and the anterior limb, which, passing into the substance of the hemisphere, forms the Island of Ecil. 2. The fissure of Rolando, running from about the middle of the top of the diagram (fig. 485) downwards and forwards. 3. The external parieto-occipital fissure (Pae. oc. f) parallel to the fissure of Kolando but more posterior and much shorter ; in monkeys it is longer (see fig. 484). These three fissures divide the brain into five lobes : — 1. The frontal lobe; in front of the fissure of Rolandq, 664 STRUCTURE OF THE CEREBRUM [Gil. XLVI. Of 2. TJie parietal lobe ; between tho fissure of Eolando and the external parieto-occipital fissure. 3. The occipital lobe ; behind the external parieto-occipital fissure. 4. The tcmporo-sphcnoidal lobe ; below the fissure of Sylvius. 5. The Island of Reil. It will be noticed that the names of the lobes correspond to those the bones of the cranial vault which cover them. There is no exact correspondence between the bones and the lobes, but the precise position of the various convolutions in relation to the surface of the skull is a matter of anatomy, which, in these days of brain-surgery, is of overwhelming importance to the surgeon. The position of a localised disease in the brain can be determined very accurately, as we shall see later, by the symptoms exhibited by the patient, and it would be obviously inconvenient to the patient if the surgeon was unable to trephine over the exact spot under which the diseased con- volution lies, but had to make a number of exploratory holes to find out where he was. Each lobe is divided into convolutions by secondary fissures. 1. The frontal lobe is divided by the central frontal or prefrontal sulcus, which runs upwards parallel to the fissure of Rolando, and two F B O N T A /. LODE : £MP3^rT^B e Fig. 485. — Right cerebral hemisphere, outer surface. transverse frontal sulci, upper and lower, into four convolutions ; namely, the ascending frontal convolution in front of the fissure of Rolando, and three transverse frontal convolutions, upper, middle, and lower, which run outw T ards and forwards from it. 2. The parietal lobe has one important secondary sulcus, at first running parallel to the fissure of Rolando and then turning back parallel to the margin of the brain. It is called the intra-parietal sulcus. The lobe is thus divided into the ascending parietal convolu- tion behind the fissure of Rolando, the supra-marginal convolution between the intra-parietal sulcus, and the fissure of Sylvius ; the angular convolution which turns round the end of the Sylvian fissure. CF. XLVI.] LOBES OF THE BRAIN 665 and the superior parietal convolution, or parietal lobule, in front of the external parieto-occipital fissure. 3. The occipital lolbe is divided into upper, middle, and lower occipital convolutions by two secondary fissures running across it. 4. The temporal or temporo-sphenoidal lobe is similarly divided into upper, middle, and lower temporal convolutions by two fissures running parallel to the fissure of Sylvius ; the upper of these fissures is called the parallel fissure. 5. The Island of Reil is divided into convolutions by the break- ing up of the anterior limb of the Sylvian fissure. LOBC r £MPOBAU LC Fig. 4S6.— Eight cerebral hemisphere, mesial surface. Coming now to the mesial surface of the hemisphere (fig. 486), its subdivisions are made evident by cutting through the corpus callosum which unites the hemisphere to its fellow. The sub- division into lobes is not so apparent here as on the external surface of the hemisphere, so we may pass at once to the con- volutions into which it is broken up by fissures. In the middle the corpus callosum is seen cut across ; above it and parallel to its upper border is a fissure called the calloso-marginal fissure which turns up and ends on the surface near the upper end of the fissure of Eolando. The convolution above this is called the marginal convolution, and the one below it the callosal convolution or gyrus for nicatus. The deep fissure below the corpus callosum running from its posterior end forwards and downwards is called the dentate fissure; this forms a projection seen in the interior of the lateral ventricle, and called there the hippocampus major ; it is sometimes called the hippocampal convolution which, together with the gyrus fornicatus above the corpus callosum, constitutes the limbic lobe. Below the dentate fissure is another called the collateral fissure, above which is the uncinate convolution, and below which is the inferior temporal convolution which we have previously seen on the external surface of the hemisphere (see fig. 485). In the occipital region the. 666 STRUCTURE OF THE CEREBRUM [CH. XLVI. internal parieto-occipital fissure, which is a continuation of the external parieto-occipital fissure, passes downwards and forwards till it meets the calcarine fissure ; these two enclose between them a wedge-shaped piece of brain called the cuneus or cuncate lobule; the square piece above it is called the precuneus or quadri- lateral lobule. The only convolutions now left are those which are placed on the surface of the frontal lobe that rests on the orbital plate of the frontal bone ; they are shown in fig. 453, 2 2' 2" (p. 622), and may be seen diagrammatically in fig. 487, the end of the temporal lobe being cut off to expose the convolutions of the central lobe or Island of Eeil. Along the edge is the continuation of the marginal convolution (m) ; next comes the olfactory sulcus (o) in which the olfactory tract and bulb lie ; then the triradiate orbital sulcus (o.s.) which divides the rest of this surface into three convolutions. A.P.S —Orbital surface of frontal lobe. M, marginal convolution. 0, olfactory sulcus. ( >.S., orbital sulcus. 1, island of Reil. ■ S.a., anterior limb of Sylvian fissure. S.p., posterior limb of Sylvian fissure. A.L'.s., anterior perforated spot. CHAPTER XLVII FUNCTIONS OF THE SPINAL CORD The functions of the spinal cord fall into two categories : functions of the grey matter, which consist in the reflection of afferent im- pulses, and their conversion into efferent impulses {reflex action) ; and functions of the white matter, which are those of conduction. The Cord as an Organ of Conduction. We have studied at some length the various paths in the white matter, and so we have the materials at hand for recapitulating the main facts in connection with the physiological aspect of the problem. Complete section of the spinal cord in animals, and diseases or injuries of the cord or spinal canal in man, which practically cut the cord in two, lead to certain histological changes of a degenerative nature, which we have already studied, and to physiological results, which are briefly — (1) paralysis, both motor and sensory, of the parts of the body supplied by spinal nerves which originate below the point of injury; and (2) increased reflex irritability of the same parts, the reason for which we shall study immediately. Hemisection of the cord leads to degenerative changes on the same side of the cord, and loss of motion and sensation on the same side of the body below the lesion (see p. 619). The main motor path in the cord from the brain is the pyramidal tract ; the anatomy of this tract is described in Chapters XLII. to XLVL, and we need do no more here than remind the reader that it originates from the pyramidal cells of the cortex of the opposite cerebral hemisphere, and that the principal decussation occurs at the lower part of the bulb. The sensory tracts are more complex, on account of the numerous cell-stations on their course. The path for tactile and muscular sense impressions is up the posterior columns to the nucleus gracilis and nucleus cuneatus ; thence by the internal arcuate fibres and fillet 6 ^'^''^'^^^^wV^P'^t' 5 ^ v c; the myelination of the two optic ^K^'^^ ^^^^t^ aj?k*^T "^ nerves is observable. Flechsig ^-"^"^m .-^^ ""-^feci •is*'' '^^vK^m also showed that a child born RA r ..l_>~^.- ; \ ^^f^-^^i^-S^M at 8 months had more marked ' ' ' \" ■ j^ ' j^^y). ,< '/ • r K j_>**\ myehnation of its optic nerves, ^Jl^Ow* hjjJ /()fi/!MJ__£w a month later, than a child born C'C^IP^s? ^ c - in the usual way at the ninth ^^<07. — Inner surface of same. (Flechsig.) inferior fornix is connected with Nos. 2 and 3. The inner bundle of the pes springs from 1 b, 6, 12, 14 and 15; the origin of the outer bundle of the pes is doubtful. From the visual area (No. 4) a tract arises which passes mainly into the anterior corpus quadrigeminum ; the auditory zone (No. 5), towards which a tract proceeds * This coincides well with the work of Sherrington and Griinbaum (p. 686). CH. XLVIII.] ELECTRICAL CHANGES IN BRAIN 697 that leads from the internal corpus geniculatum, sends an outgoing tract into the column of Tiirck, and thus motor functions of the upper part of the body are possible as a direct result of auditory, impressions. In fact in every case each primordial sensory zone is connected with a well-defined pair of tracts, one proceed- ing to it (cortico-petal) and the other from it (cortico-fugal). It is thus impossible to speak of a purely motor or a purely sensory area. The terminal areas (Nos. 31 to 36, unshaded in the diagrams) do not begin to be myelinated until at least a month after birth. These and the majority of the intermediate areas (Nos. 11 to 31, lightly shaded in the diagrams) show few or no projection fibres * even 8 months after birth. They comprise, in fact, the association centres, and are rich in long association fibres. The view of Monakow, Dejerine, and others, that the fasciculus longitudinalis inferior (e in fig. 503, p. 694) and the cingulum (c in the same figure) are long associa- tion tracts is denied by Flechsig; they connect primordial zones, and are regarded by him as projection fibres, the former connecting the lateral corpus geniculatum with the cortical field of vision, and constituting the real optic radiation. Electrical Variation in Central Nervous System. Du Bois Keymond found that the spinal cord, like a nerve, exhibits a demarcation current between its longitudinal surface and a cross-section, and that a diminution of this current occurs on excitation (negative variation). Gotch and Horsley investigated the currents of the cord very thoroughly. If the Eolandic area of the cortex is stimulated, and a portion of the thoracic region of the spinal cord is led off to a galvanometer, a persistent negative varia- tion followed by a series of intermittent variations is observed ; this exactly corresponds to the tonic spasm followed by clonic con- tractions which occur in the muscles excited by this means. The galvanometer in the hands of these observers also proved to be a valuable instrument for determining the paths taken by nervous impulses in the cord. One example will suffice : If the central end of one sciatic nerve is stimulated, the chief electrical variation in the cord is noticed to be obtained when the same side of the cord is led off to the galvanometer, but a certain amount of electrical variation is obtainable from the opposite side of the cord. This coincides with the fact ascertained by other methods, that the main sensory channel is on the same side of the cord as the entering nerves, but that there is a certain small amount of decussation below the level of the bulb. Electromotive changes also occur during activity in the cortex cerebri, but they have not been much studied, and we do not know whether they have their seat in the grey or in the underlying white matter. Sleep. The conditions that favour sleep are : — (1) A diminution of the impulses entering the central nervous system by the afferent channels. This is under our voluntary * That they never have any projection fibres at all is denied by most observers, 698 FUNCTIONS OF THE CEREBRUM [CH. XLVIII. control, as, for instance, in closing the eyes, or retiring to a qniet room. (2) Fatigue. This diminishes the readiness of the central nervous system to respond to stimuli. The first two hours of sleep are always the most profound ; later on, relatively weak stimuli will cause awakening. Of the parts of the central nervous system, the spinal cord is always less profoundly affected than the brain, but even the brain is never entirely irrespon- sive, and unless slumber is very profound, dreams are the subjective result of external stimuli. Sleep has been attributed by some to changes in the blood-supply of the brain, and ultimately referred to fatigue of the vaso-motor centres. The existence of an effective vaso-motor mechanism in the cerebral blood-vessels themselves is problematical (see p. 312); so that if changes occur in the cerebral blood-pressure or rate of flow, they are mainly secondary to those which are produced in other parts of the body. Plethysmographic records from the arm of a sleeping man show a diminution in its volume every time he is disturbed, even though the disturbance may not be sufficient to awaken him. This is interpreted as meaning a diminution in the blood of the body, and a corresponding increase in the blood-flow through the brain. It is, however, quite possible that the vascular condition is rather the concomitant or consequence of sleep than its cause. Some of the theories to account for sleep have been chemical. Thus certain observers have considered that sleep is the result of the action of chemical materials produced during waking hours, which have a soporific effect on the brain; according to this theory awakening from sleep is due to the action of certain other materials produced during rest, which have the opposite effect. Obersteiner has gone so far as to consider that the soporific substances are reducing in nature, and others regard them as alkaloidal. These theories all rest upon the slimsiest foundations, and none has yet been found to stand experimental tests. Then there are what we may term histological theories of sleep, and these are equally unsatisfactory. The introduction of the Golgi method opened a fresh field for investigators, and several have sought to find by this method a condition of the neurons produced by narcotics like opium and chloroform, which is different from that which obtains in the waking state. Demoor and others found that in animals in which deep anaes- thesia has occurred, that the dendrites exhibit moniliform swellings, that is, a series of minute thickenings or varicosities. On the strength of this observation, he has formulated what we may call a bio-physical theory of sleep. In the waking state, the neighbouring CH. XLVIII.] sleep and naecosis 699 nerve units are in contact with each other ; transmission of nerve impulses from neuron to neuron is then possible, and the result is consciousness ; during sleep the dendrites are retracted in an amoeboid manner ; the neurons are therefore separated, and the result is unconsciousness. Lugaro, on the other hand, takes the precisely contrary view. He was not able to discover moniliform enlargements, and his bio- physical hypothesis is that the interlacing of dendrites is much more intimate during sleep than during consciousness. He therefore explains sleep by supposing that the definite and limited relation- ships between neurons no longer exists, but are lost and rendered ineffective by the universality of the connecting paths. It is not very difficult to explain such divergence of views, for they both depend mainly on observations made by a single method ; and the method itself is open to objection. It is one which gives even in the same brain most inconstant results, and is not calculated to show much more than a mere outline of a few of the cells and their branches. So much doubt has arisen of late in regard to the trust- worthiness of the method, that many neurologists are beginning to doubt whether the neuron theory implying absolute non-continuity of nerve units has been satisfactorily proved, and there is a tendency to return to the idea of a connecting network not very different from that originally put forward by Gerlach. A more satisfactory investigation of the effect of anaesthetics on nerve-cells was carried out by Hamilton Wright. He used rabbits and dogs, and subjected them to ether and chloroform narcosis for periods varying from half an hour to nine hours. In both animals he found that the nerve-cells are affected, but in rabbits much more readily. This accords quite well with what is known regarding the susceptibility of rabbits as compared to dogs towards the influence of these narcotising agents. In a rabbit, the nerve-cells, especially of the cerebrum, show changes even after only half an hour's anaesthesia, but in dogs at least four hours' anaes- thesia must be employed. By the G-olgi method the moniliform enlargements can be seen. These become more numerous, larger, and encroach more and more on the dendritic stems, the longer the anaesthesia is kept up. The accompanying illustrations show the appearances seen (fig. 508). Lugaro's failure to find these appearances is doubtless due to his not having maintained the anaesthesia long enough in his dogs. Wright started his work with a bias in favour of Demoor's bio- physical theory, but he soon found that the theory was untenable ; the results of his observations have shown him that the action of anaesthetics is bio-chemical rather than bio-physical, and he has been led to this conclusion by the employment of other histological '00 FUNCTIONS OF THE CEREBRUM [CH. XLVIII. methods, particularly the most sensitive one we possess, namely, the methylene-blue reaction. Owing to the chemical action of the anaesthetic on the cells, the Nissl bodies have no longer an affinity for methylene-blue, and the Fio. 508. — Mouiliform enlargements on dendrites of nerve-cells, rendered evident by Cox's modification of Golgi's method, a, in a cortical cell of a rabbit ; B, in a corresponding cell oi' a dog's brain, after six hours' anaisthotisation with ether in each case. (Hamilton Wright.) cells consequently present what Wright calls a rarefied appearance ; when this becomes marked the cells appear like the skeletons of healthy cells. In extreme cases the cells look as though they had undergone a degenerative change, and after eight or nine hours' anaesthesia in dogs, even the nucleus and nucleolus lose their affinity for basic dyes. The change, however, is not a real degeneration, and passes off when the drug disappears from the circulation. Even after nine hours' anaesthesia the cells return rapidly to their normal condition, stain normally, moniliform enlargements have disappeared, and no nerve-fibres show a trace of Wallerian degeneration. The pseudo-degenerative change produced by the chemical action of the anaesthetic no doubt interferes with the normal metabolic activity of the cell-body, and this produces effects on the cell-branches. In the early stages of Wallerian degeneration, the branch of the nerve- cell which we call the axis-cylinder presents swellings or varicosi- ties, produced by hydration or some similar chemical change. The moniliform enlargements seen during the temporary pseudo-degenera- tive effects produced by anaesthetics are comparable to this.* These * Some observers look upon the varicosities as artifacts. If they are, they ought to have been found in all Wright's specimens, for the method of preparation was the same throughout. CH. XLVIII.] SLEEP AND NAUCOSlS 701 enlargements are therefore not the primary cause of loss of conscious- ness, but are merely secondary results of changes in the cell-body. "When a tree begins to wither the earliest apparent change is noticed in the branches most remote from the centre of nutrition, the root ; as the changes in the centre of nutrition become more profound, the larger branches become implicated, but the seat of the mischief is not primarily in the branches. This illustration may serve to render intelligible what is found in nerve-cells and their branches. Whether the appearances found in dogs and rabbits are appli- cable to the human subject is another question. I am inclined to think that we may safely regard them as such ; there is no reason why an anaesthetic should act differently in different animals. The resistance of the animal is a variable factor, and this causes a varia- tion in degree only ; the effect is probably the same in kind for all animals, man included. But I feel that we should be very chary in concluding that the artificial sleep of a deeply-narcotised animal is any criterion of what occurs during normal sleep. The sleep of anaesthesia is a pathologi- cal condition due to the action of a poison. The drug reduces the chemico-vital activities of the cells, and is, in a sense, dependent on an increasing condition of exhaustion, which may culminate in death. Normal sleep, on the other hand, is not produced by a poison, or at any rate we have no evidence of any poison ; it is the normal mani- festation of one stage in the rhythmical activity of nerve-cells, and though it may be preceded by fatigue or exhaustion, it is accom- panied by repair, the constructive side of metabolic activity. Loss of sleep is more damaging than starvation. Dogs will recover after being starved for three weeks, but they die from loss of sleep in five days. The body temperature falls, reflexes disappear, and post-mortem the brain is found to contain capillary haemorrhages, the cord is dry and anaemic, and fatty degeneration is found in most of the tissues. In man, loss of sleep curiously enough causes a slight rise in weight ; the body temperature falls ; the excretion of nitrogen and still more so that of phosphoric acid increases ; the reactions of the muscular, and later those of the nervous, system diminish in intensity, except that in all cases there is an increase in acuteness of vision. These experiments were made by Patrick and Gilbert on three young men, who voluntarily went without sleep for ninety hours. At the end of the experiment a very small extra amount of sleep beyond the normal caused complete restoration, and all the symptoms, including the increase of weight, disappeared. CHAPTER XLIX FUNCTIONS OF THE CEREBELLUM In past times there have been several views held as to the functions of the cerebellum. One of the oldest of these was the idea that the cerebellum was associated with the function of generation ; another view, first promulgated by Willis, was that the cerebellum contained the centres which regulate the functions of organic life ; this arose from the circumstance that diseases of the cerebellum are often associated with nausea and vomiting; it is a familiar fact that in displacements of equilibrium such as occur on board ship in a rough sea, or in the disease called Meniere's disease, sickness is a frequent result ; it appears from this that the cerebellum does receive from or send to the viscera certain impulses. The third and last of these older theories was that the cerebellum was the centre for sensation. This arose from the fact that certain of the afferent channels of the spinal cord were traced into the cerebellum. The impulses that travel along these, however, though afferent, are not truly sensory, and their reception in the cerebellum is not associated with consciousness. The true function of the cerebellum was first pointed out by Flourens, and our knowledge about it has not advanced much from the condition in which Flourens left it. He showed that the cere- bellum is the great centre for the co-ordination of muscular movement, and especially for that variety of co-ordination which is called equili- bration — that is, the harmonious adjustment of the working of the muscles which maintain the body in a position of equilibrium. It must not be supposed from this that the cerebellum is the sole centre for co-ordination. We have already seen that all the machinery necessary for carrying out very complicated locomotive movements is present in the spinal cord. The higher centres set this machinery going, and the work of arranging what muscles are to act, and in what order, is carried out by the whole of the grey matter from the corpora striata to the end of the spinal cord, including such out- growths as the corpora quadrigemina and cerebellum. An instance of a complex co-ordinated movement is seen in what we learnt to call 702 CH. XLIX.] FUNCTIONS OF CEKEBELLUM 703 in the last chapter conjugate deviation of head and eyes. The higher cortical centre gives the general word of command to turn the head and eyes to the right : the subsidiary centres or subordinate officials arrange that this is to be accomplished by the external rectus of the right eye supplied by the right sixth nerve, the internal rectus of the left eye supplied by the left third nerve, and numerous muscles of neck and back of both sides supplied by numerous nerves. We thus see how the complicated intercrossing of fibres and connections of the centres of the various nerves are brought into play. The functions of the cerebellum are investigated by the same two methods of experiment {stimulation and extirpation) that are employed in similar researches on the cerebrum. The anatomical connections of the cerebellum with other parts of the cerebro-spinal axis (see p. 651) have been chiefly elucidated by the degeneration method. Fig. 509. — Pigeon after removal of the cerebellum. (Dalton.) Each side of the cerebellum has three peduncles : the superior peduncle connecting it to the opposite hemisphere of the cerebrum, the inferior peduncle connecting it mainly to the same side of the spinal cord, and the middle peduncle contains fibres which link the two halves of the cerebellum together in a physiological though not in an anatomical sense. The upper end of the inferior peduncle terminates in the vermis ; in some of the lower animals the vermis is practically the only part of the cerebellum which is present, and it is this part of the cerebellum which is principally concerned in the co-ordination of the bodily movements. The cerebellar hemispheres are especially connected with the opposite cerebral hemispheres ; and possibly just as the different regions of the body have corresponding areas in the cerebrum, so also they are similarly represented in the cerebellum ; but localisation of function in the cerebellum has not gone sufficiently far yet to make this a certainty. 704 FUNCTIONS OF THE CEREBELLUM [CH. XLIX. If the cerebellum is removed in an animal, or if it is the seat of disease in man, the result is a condition of slight muscular weak- ness ; but the principal symptom observed is inco-ordination, chiefly evidenced by a staggering gait similar to that seen in a drunken man. It is called cerebellar ataxy. This condition is well illustrated in the figure on p. 703 (fig. 509) ; the disturbed condition of the animal contrasts very forcibly with the sleepy state produced by removal of the cerebrum (see fig. 492). In order that the cerebellum may duly execute its function of equilibration, it is necessary that it should send out impulses ; this it does by fibres that leave its cells and pass out through its peduncles ; they pass out to the opposite cerebral hemisphere, and so influence the discharge of the impulses from the cortex of the cerebrum. It is also probable that impulses pass out to the cord (see dotted line in fig. 482), but the exact course of these fibres, if they do exist, has still to be worked out. The cerebellum thus acts upon the muscles of the same side of the body in conjunction with the cerebral hemi- sphere of the opposite side. The close inter-relation of one cerebral with the opposite cerebellar hemisphere is shown in cases of brain disease, in which atrophy of one cerebellar hemisphere follows that of the opposite cerebral hemisphere (see fig. 510). In order that the cerebellum may send out impulses in this way, it is impulses which guide it by keeping it These afferent im- Fio. 510. — This is a reproduction of a photograph of a lunatic's brain lent me by Dr Fricke. One cerebral and the opposite cerebellar hemisphere are atrophied. necessary that it receive informed of the position of the body in space. pulses are of four kinds, namely : — 1. Tactile. 2. Muscular. 3. Visual. 4. Labyrinthine. We will take these one by one : — 1. Tactile impressions. — The importance of impulses from the skin is shown in those diseases of the sensory tracts (especially locomotor ataxy) where there is diminution in the tactile sense in the soles of the feet. In such cases the patient cannot balance himself while standing with his eyes shut. The same effect may be produced experimentally by freezing the soles of the feet. Again, if the skin is stripped from the hind limbs of a brainless frog, it is unable to execute such reflex actions as climbing an inclined plane, which it can do quite well when the skin is uninjured. CH. XLIX.] LABYRINTHINE IMPRESSIONS 705 2. Muscular impressions. — Quite as important as the tactile sense from the skin is the muscular sense, the sense which enables us to know what we are doing with our muscles. We have hitherto chiefly spoken of the muscular nerves as being motor; they also contain sensory fibres ; these pass from the muscles, and their tendons to the posterior roots of the spinal nerves, and the impulses ascend the sensory tracts through cord and brain to reach the cerebellum and the Eolandic area. In some cases of locomotor ataxy there is but little loss of tactile sensibility, and the condition of inco-ordination is then chiefly due to the loss of the muscular sense. 3. Visual impressions. — The use of visual impressions in guiding the nervous centres for the maintenance of equilibrium is seen in those cases of locomotor ataxy where there is loss of equilibrium when the patient closes his eyes. Destruction of the eyes in animals often causes them to spin round and lose their balance. The giddiness experienced by many people on looking at moving water, or after the onset of a squint, or when objects are viewed under unusual circum- stances, as in the ascent of a mountain railway, is due to the same thing. The importance of keeping one's eyes open is brought home to one very forcibly when one is walking in a perilous posi- tion, as along the edge of a precipice, where an upset of the equilibrium would be attended with serious con- sequences. 4. Labyrinthine impressions. — These are the most important of all ; they are the impressions that reach the central nervous system from that part of the internal ear called the labyrinth. Here, how- ever, we must pause to consider first some anatomical facts in connection with the semicircular canals that make up the labyrinth. Fig. 511 is an external view of the internal ear ; it is enclosed within the petrous portion of the temporal bone; and consists of three parts — the vestibule (1), the three semicircular canals (3, 4, 5) which open into the vestibule, and the tube, coiled like a snail's shell, called the cochlea (6, 7, 8). The cochlea is the part of the apparatus which is concerned in the reception of auditory impressions ; it is supplied by the cochlear division of the eighth or auditory nerve. The 2 Y Fig. 511. — Eight bony labyrinth, viewed from the outer side. The specimen here represented was prepared ~ by separating piecemeal the looser sub- stance of the petrous bone from the dense walls which immediately en- close the labyrinth. 1, the vestibule ; 2, fenestra ovalis ; 3, superior semi- circular canal ; 4, horizontal or ex- ternal canal ; 5, posterior canal ; *, ampullae of the semicircular canals ; 6, first turn of the cochlea ; 7, second turn ; 8, apex ; 9, fenestra rotunda. The smaller figure in outline below shows the natural size. (Sommering.) 706 FUNCTIONS OF THE CEREBELLUM [CH. XLIX. remainder of the internal ear is concerned not in hearing, but in the reception of the impressions we are now studying. Within the vestibule are two chambers made of membrane, called the utricle and the saccule; these com- municate with one another and with the canal of the cochlea. Within each bony semicircular canal is a membranous semi- circular canal of similar shape. Each canal is filled with a watery fluid called endohjmph, and separated from the bony canal by another fluid called perilymph. Each canal has a swelling at one end called the ampulla. The membranous canals open into the utricle ; the horizontal canal by each of its ends ; the superior and pos- terior vertical canals by three openings, these two canals being connected at their non-ampul- lary ends. Fig. 512 shows in transverse section the way in which the membranous is contained within the bony canal ; the membranous Fig. 512. — Section of human semicircular canal. (After Rudinger.) 1, Bone; 2, periosteum; 3, 3, fibrous bands connecting the periosteum lo 4, the outer fibrous coat of the membranous canal ; 5, tunica propria ; 6, epithelium. Fig. 513. — Section through the wall of the ampulla of a semicircular canal, passing through the crista acoustica. i, Epithelium ; 2, tunica propria ; 3, fibrous layer of canal ; X, bundles of nerve-fibres ; C, cupula, into which the hairs of the hair-cells project. (After Schafer). canal consists of three layers, the outer of which is fibrous and continuous with the periosteum that lines the bony canal ; then comes the tunica propria, composed of homogeneous material, and thrown into papillse except just where the attachment of the membranous to CH. XLIX.] SEMICIKCULAK CANALS 707 the bony canal is closest; and the innermost layer is a somewhat flattened epithelium. At the ampulla there is a different appearance ; the tunica propria is raised into a hillock called the crista acoustica (see fig. 513) ; the cells of the epithelium become columnar in shape, and to some of them fibres of the auditory nerve pass, arborising round them ; these cells are provided with stiff hairs, which project into what is called the cupula, a mass of mucus-like material containing otoliths or crystals of calcium carbonate. Between the hair-cells are fibre- cells which act as supports (fig. 514). When the endolymph in the interior of the canals is thrown into vibration, the hairs of the hair- cells are affected, and a nervous im- pulse is set up in the contiguous nerve-fibres, which carry it to the central nervous system. The walls of the saccule and utricle are similar in composition, and each has a similar hillock, called a macula, to the hair-cells on which nerve-fibres are distributed. The macula of the utricle and the cristas of the superior and hori- zontal canals are supplied by the vestibular division of the eighth or auditory nerve. The macula of the saccule and the crista of the posterior canal are supplied by a branch of the cochlear division of the same nerve (see p. 643). When these canals are diseased man, as in Meniere's disease, m Fig. 514. — 1, Hair-cell ; 3, hair-cell, showing the hair broken, and the base of the hair split into its constituent fibrils ; 2, fibre- cell; N, bundle of nerve-fibres which have lost their medullary sheath, and terminate by arborising round the base of the hair-cells ; A.B., surface of tunica propria. (After Eetzius). there are disturbances of equili- brium : a feeling of giddiness, which may lead to the patient's fall- ing down, is associated with nausea and vomiting. In animals similar results are produced by injury, and the subject has been chiefly worked out on birds by Flourens, where the canals are large and readily exposed, and more recently in fishes, by Lee. Thus, if the horizontal canal is divided in a pigeon, the head is thrown into a series of oscillations in a horizontal plane, which are increased by section of the corresponding canal of the opposite side. After section of the vertical canals, the forced movements are in a vertical plane, and the animal tends to turn somersaults. "When the whole of the canals are destroyed on both sides the disturbances of equilibrium are of the most pronounced character. G-oltz describes a pigeon so treated which always kept its head with 708 FUNCTIONS OF THE CEREBELLUM [CU. XLIX. the occiput touching the breast, the vertex directed downwards, with the right eye looking to the left and the left looking to the right, the head being incessantly swung in a pendulum-like maimer. Cyon says it is almost impossible to give an idea of the perpetual movements to which the animal is subject. It can neither stand, nor lie still, nor fly, nor maintain any fixed attitude. It executes violent somersaults, now forwards, now backwards, rolls round and round, or springs in the air and falls back to recommence anew. It is necessary to envelop the animals in some soft covering to prevent them dashing themselves to pieces by the violence of their move- ments, and even then not always with success. The extreme agitation is manifest only during the first few days following the operation, and the animal may then be set free without danger ; but it is still unable to stand or walk, and tumultuous movements come on from the slightest disturbance. But after the lapse of a fortnight Fig. olj.— Diagram of semicircular canals, to show their positions in three planes at right angles to each other. It will be seen that the two horizontal canals (H) lie in the same plane : and that the superior vertical of one side (S) lies in a plane parallel to that of the posterior vertical (P) of the other. (After Ewald.) it is able to maintain its upright position. At this stage it resembles an animal painfully learning to stand and walk. In this it relies mainly on its vision, and it is only necessary to cover the eyes with a hood to dispel all the fruits of this new education, and cause the reappearance of all the motor disorders." (Ferrier.) It is these canals which enable all of us to know in which direc- tion we are being moved, even though our eyes are bandaged, and the feet are not allowed to touch the ground. On being whirled round, such a person knows in which direction he is being moved, and feels that he is moving so long as the rate of rotation varies, but when the whirling stops he seems, especially if he opens his eyes, to be whirling in the opposite direction, owing to the rebound of the fluid in the canals. The forced movements just described in animals are due both to the absence of the normal sensations from the canals and to delusive sensations arising from their irritation, and the animal makes efforts to correct the movement which it imagines it is being subjected to. CH. xldl] semicieculae canals 709 Artificial stimulation of the canals produces movements of the head and orbits, and giddiness. Similar movements occur during bodily rotation, and giddiness is the result of a rivalry of sensations which afford conflicting ideas of the position of the body relatively to external objects. A certain proportion of deaf mutes lose their sense of direction under water, cannot maintain their equilibrium when their eyes are shut, exhibit no orbital movements when rotated, and never suffer from sea-sickness or giddiness. This proportion (36 per cent.) is approximately the frequency in which abnormal conditions of the canals have been found post-mortem in deaf mutes. It will be noticed that the canals of each side are in three planes at right angles to each other, and we learn the movements of our body with regard to the three dimensions of space by means of impressions from the ampullary endings of the auditory nerve ; these impressions are set up by the varying pressure of the endolymph in the ampullae. Thus a sudden turning of the head from right to left will cause movement of the endolymph towards, and therefore increased pressure on, the ampullary nerve-endings of the left horizontal canal, and diminished pressure on the corresponding nerve-endings of the right side. It is probable that resulting from such a movement two impulses reach the brain, one the effect of increased pressure in one ampulla, the second the effect of decreased pressure in its fellow. " One canal can be affected by, and transmit the sensation of rotation about one axis in one direction only; and for complete perception of rotation in any direction about any axis, six canals are required in three pairs, each pair being in the same or parallel planes, and their ampullae turned opposite ways. Each pair would thus be sensitive to any rotation about a line at right angles to its plane or planes, the one canal being influenced by rotation in one direction, the other by rotation in the opposite direction." (Crum-Brown.) The two horizontal canals are in the same plane ; the posterior vertical of one side is in a plane parallel to that of the superior vertical of the other side (see fig. 515). These four sets of impressions (tactile, muscular, visual, and labyrinthine) reach the cerebellum by its peduncles ; from the eyes through the superior peduncle, from the semicircular canals through the middle and inferior peduncles, and from the body generally through the restiform body or inferior peduncle. Section and stimulation of the peduncles cause inco-ordination, chiefly evidenced by rotatory and circus movements similar to those that occur when the nerve-endings in the semicircular canals are destroyed or stimu- lated. Stimulation of the cerebellum itself — and this has been done through the skull in man — causes giddiness, and consequent muscular efforts to correct it. The results of stimulation, indeed, are precisely analogous to those of extirpation, only in the reverse direction. Loss of muscular tone which follows extirpation of the canals is probably the result of secondarv changes in the brain. CHAPTER L COMPARATIVE PHYSIOLOGY OF THE BRAIN It will have been noticed in the preceding chapters how much of our knowledge of cerebral functions is derived from observations and experiments performed upon the lower animals. I propose in this chapter to expand this part of the subject. It is important not only because of its intrinsic interest, but also because a wider survey of the conditions in various animals throws considerable light on what is found in man.* The brain in the lower vertebrata is composed of a smaller number of cells than is found in the human brain ; one notices also that the massing of the nerve units towards the cerebral cortex and in relation to the principal sense organs has gone on to a less extent. The doctrine of cerebral localisation is not accurately expressed by the statement that a cortical centre is one, the stimulation of which produces a definite response, and the extirpation of which abolishes the response. We have, for instance, seen that the stimu- lation of certain areas in the .dog's brain produces certain movements, but Goltz showed that in his dogs, the removal of an entire hemi- sphere did not cause paralysis of the opposite side of the body. In the central nervous system there are few or no places, where only one set of nerve units are situated, with fibres passing to and from them. Almost every locality has several connections with other parts, and also fibres passing through it which connect together the parts on all sides of it. Hence in extirpating even a limited area, numerous pathways are interrupted, and the damage is con- sequently widespread. Much of the disturbance produced at first gradually passes away, and the temporary effects must be distinguished from those which are permanent ; the permanent effects have the greater significance of the two. Moreover, it is clear that the relative * This subject is treated at some length in Dr Donaldson's article on the Central Nervous System in the American Text-book of Physiology edited by HowelL I am indebted to this article for much contained in the present chapter. CH. L.] COMPARATIVE PHYSIOLOGY OF THE BRAIN 7 1 1 and absolute value of any locality in the central nervous system depends largely on the degree to which centralisation has progressed, and on the amount of connection between the various areas. The closer the connection, the more numerous and intricate the path- ways, the greater will be the permanent effects of an extirpation, and the recovery of function the more remote. The lower the animal in the zoological series, or the less the age of the animal, the more imperfectly developed will be the connecting strands, and so the possibility of other parts taking up to some extent the functions of those that are removed will be increased. If the cerebral hemispheres are removed in a teleostean or bony fish (and in such animals there is practically no cortex), the animal is to all intents and purposes unaffected ; it can distinguish between a worm and a piece of string, and will rise to red wafers in preference to those of another colour. The operation does not damage the primary centres of vision, and in these fishes the eye is the most important sense organ. A shark, however, subjected to the same operation, is reduced to a condition of complete quiescence ; this is due to the circumstance that in this fish the principal sense organ is that of smell, and sever- ance of both olfactory tracts produces the same result as removal of the entire hemispheres. In either case the path between the olfactory bulbs and the centres that control the cord are interrupted. G-oing a little higher in the animal scale to the frog, we find that removal of the hemispheres only does not entirely abolish its apparent spontaneity ; it still continues to feed itself, for instance, by catching passing insects. It is not until the optic thalami are removed also that it becomes the purely reflex animal described on p. 678. If the brain and the anterior end of the bulb are removed the frog becomes incessantly active, creeping and clambering about the room ; but if the whole bulb is removed strong stimulation is required to produce movements ; these, however, remain co-ordinated. If the frog's cerebellum is removed there is some tremor of the leg muscles, and a loss of co-ordination in jumping. If the removal is confined to one side of the twixt-brain, mid-brain, or bulb, there is a tendency to forced positions and movements, action being most vigorous on the side of the body associated with the uninjured portions. We thus see that a progressive removal of portions of the brain is followed by a progressive loss of responsiveness, until we reach the anterior end of the bulb, the removal of which sets free the lower centres of the cord, and the result is incessant movement provoked by slight stimuli. Further removal, however, lessens responsiveness, and this is not easy to explain. 712 COMPARATIVE PHYSIOLOGY OF THE BRAIN [CH. L In the bird, removal of the hemispheres and basal ganglia pro- duces the sleepy condition already described (p. 679); when the animal is made to fly its movements are directed by the sense of sight, and it will select a perch to settle on in preference to the floor. It will start at a noise ; it will not eat voluntarily ; it exhibits no emotions such as fear, sexual feeling, or maternal instincts. In mammals, the difficulty of the operation has been overcome by G-oltz in dogs by removing the cerebrum piecemeal. One dog treated in this way lived in good health for eighteen months, when it was killed in order that a thorough examination of the brain might be made. It was then found that not only the hemispheres but the main parts of the optic thalamus and corpus striatum had been removed also. Though it could still carry out co-ordinated move- ments, its reactions were entirely reflex, and emotions, feelings, or the capacity to learn were entirely absent. If we now compare these effects, it is seen that the results of the operation becomes progressively greater as we ascend the scale. The higher the animal, the more fatal the effects, the immediate disturb- ance more severe, the return of function slower, and the permanent loss greater. The long life of Goltz's dog was doubtless due to the fact that the removal was accomplished by several operations. The higher animal loses just those characters which distinguish it from the lower ones. It is difficult to prophesy what would happen if as extensive operations were carried out in a monkey or a man. But so far as extirpation has been observed, the initial paralysis (which is seen also in the dog) does not disappear so rapidly or so completely. In man, the tendency to recover is least. F§ This is anatomically explicable when we remember that the anterior horn cells are influenced chiefly by two sets of impulses, those which enter the cord by the posterior roots, and those which come down from the cerebrum by the pyramidal tracts. In the lower animals the pyramidal pathway is insignificant, and when it is inter- rupted the disturbance is consequently slight. In animals below the mammals it is absent, and going up the mammalian scale it becomes more and more important as the following figures show : — In the mouse the pyramidal fibres constitute ] "14 per cent, of those in the cord. „ guinea-pig „ „ 3"0 „ rabbit ,, „ 5-3 ,, ,, „ cat „ „ 7-76 »» man „ ,, 11*87 ,, ,, We can therefore quite readily understand that in the apes and in man, a damage to the cortex which causes degeneration of these tracts will cut off many impulses to the anterior cornual cells, and produce a greater or less degree of paralysis. We have already pointed out (p. 686) that the size of the cortical areas does not vary"with the mere mass of the muscles under control, CH. L.] COMPAKATIVE PHYSIOLOGY OF THE BEAIN 713 but with the increasing complexity and delicacy of the movement ; (compare in fig. 498 the relative size of the areas which control the trunk muscles and the finger movements). It is just these move- ments which are most affected by a cortical injury, and which exhibit least recovery ; in the upper limb, for instance, the shoulder muscles will be the least, and the hand the most, paralysed. On the sensory side of the cortex, vision alone can be analysed with sufficient accuracy. The lower the animal in the series, the more readily can its actions be controlled by sensory impulses which have not passed through the cortex cerebri. A decerebrated bony fish can distinguish colours, a frog can catch flies, even a pigeon will select its perch, though it takes no notice of food or of people who try to frighten it. A dog similarly operated on is practically blind, though it will blink at a bright flash of light. In the lower animals the impulses pass in to the primary visual centre which acts as the centre for the reflex; the higher we ascend the animal scale, the path via the cortex becomes more permeable, of greater value or even indispensable, and the reflexes through the lower centres of less importance; not only so, but there are subdivisions of the visual cortical area, which correspond to different regions of the retinae. In the fishes which have no cortex cerebi, the optic lobes, analogous to the C. quadrigemina, are the centres for vision. In some fishes, a small number of the fibres of the optic nerve pass into the geniculate body, which forms a cell station on the road to the posterior region of the cerebrum, where a primitive cortex begins to appear. On ascending the animal scale, this group of fibres becomes more and more abundant, and this part of the cortex becomes more elaborate in structure. When we reach the monkeys, this part of the brain is cut off from the rest to form a dis- tinct occipital lobe by the parieto-occipital fissure, which is frequently called the Affenspalte (ape's split). At first this lobe is smooth (fig. 497, p. 685), but as the great parietal association centres get larger with increase of intelligence, the visuo- sensory area is pushed back, and is thus thrown into folds. In the highest apes, and in the lower races of mankind, a good deal of the visuo-sensory sphere is still seen on the external cerebral surface ; but in the higher races, most is pushed round on to the mesial surface (area 4, figs. 506, 507, p. 696). This calcarine area is better named the striate area, because it is characterised by the white stripe called the line of Gennari (see p. 689). Some animals have panoramic and others stereoscopic vision. The former (mainly vegetable feeders) have eyes set laterally; each eye receives a different picture, and the decussation of the optic nerves is complete ; each eye sends impulses to the opposite hemisphere. Animals with stereoscopic vision have the eyes, as in man, in front, and the optic axes can be converged so that an object is focussed with both eyes. This becomes necessary in carnivora, which have to catch moving prey; the more complex the movements of the fore-limb, the greater becomes the necessity for fixation of the eyes to guide them. In such animals each visual area corresponds with the same half of both retinas, that is, with the opposite half of the visual field ; the lower half of each area corresponds with the upper half of each half field of vision, and vice versa. The appearance of the macula lutea (with cortical representation in both hemispheres) in the primates is the culminating point in visual development. A man or an animal who loses both eyes is blind, but in time manages to find his way about. This is not the case when blindness is produced by removal or disease of both occipital lobes ; here, the sense of orientation is lost also, for the association of many essential sensory and motor impulses is then impossible. CHAPTEE LI SENSATION Before passing to the study of the various special senses, there are a number of general considerations in connection with the subject of sensation that demand our attention. The psychologist divides the mental phenomena, which the physiologist localises in the brain, into three main categories : — 1. Intellectual : perceiving, remembering, reasoning, etc. 2. Emotional : joy, love, hate, anger, etc. 3. Volitional : purposing, deliberating, doing. These are all closely connected together, and are all present in each healthy brain ; but according as one or other may predominate, we speak of intellectual, emotional, or strong-willed individuals. The connection is especially close between intellect and will, which represent as it were the two sides of what we may call a conscious reflex action ; the intellect gives the reason or stimulus for the exercise of the volitional power. The emotions are more complex, and we shall not discuss them ; they are elaborate mental processes, in which sensations predominate. The intellectual faculties are derived from the senses ; sensations form the materials for intellect ; in other words, we know and learn from what we see, feel, hear, taste, and smell. People born blind or deaf thus labour under the great disadvantage of having one or the other channel of knowledge closed ; they can, however, make up for this in some measure by an education, and consequent increased sensitiveness of the channels that remain open. The simplest mental operation is a sensation — that is, the conscious reception of an impression from the external world. For this the following things are necessary : — 1. A stimulus. 2. A nerve-ending to receive it. 3. A path to the brain. 4 A part of the brain to receive the impulse. CH. LI.] SENSATION 715 Partly through congenital, partly through acquired experience, the brain refers the sensation to the nerve-ending which received the stimulus ; thus pain in the finger is referred to the finger, the sight of an object to the eyes, etc. If the ulnar nerve is stimulated by a knock on the elbow, the sensation is referred to the fingers where the nerve is distributed ; if the stump of a recently amputated leg be stimulated, the brain not having got used to the new condition of things, refers the sensation to the toes, which still seem to be present. Perception is a more complicated mental process ; it consists in the grouping of sensations, and the imagining of the object from which they arise, and which is called the percept. The smell, the taste, the colour, etc., of an orange are all sensations ; the grouping of these together constitutes the perception of an orange. Each mental process leaves an impress on the mind ; these impressions build up memory, or representative imagination ; this may be repro- ductive, as in recalling a friend's face ; or constructive, as in picturing the face of an historical person. During the whole operation, moreover, there must be attention ; it is quite possible, for instance, in a dreamy person, that he may look at a thing without seeing it, or be present at a lecture without hearing it. The more complex intellectual operations consist in the forma- tion of concepts, and reasoning the grouping and discrimination of conceptions. Just as perception is built up of sensations, so conception is built up of perceptions. Thus the orange of our previous example is learnt to be one of similar substances called fruits ; fruits to be products of the vegetable, as distinguished from the animal world, and so on. This is seen in the education of a child : at first scattered sensa- tions only are perceived, and by education he learns what these sensa- tions correspond to in the external world, and how they may be classified. The other mental faculties are in the same way built of simpler material ; from the first, perceptions and conceptions find an outlet in motor activity ; at length the conscious realisation of ideas of movement culminate in the purposeful actions of volition. More- over, every experience contains its own quantum of pain or pleasure, and produces reflex contractions or relaxations in vascular and other tissues, which in their turn possess a painful or pleasurable com- ponent. So, too, ideas acquire their colouring of pain or pleasure, ultimately elaborating the complex emotions of sorrow, joy, etc. The nerve-endings that receive the impression from the external world are of various kinds. They may be simply ramifying and interlacing plexuses of nerve-fibrils, as in the cornea, parts of the skin, and in the interior of the body ; this kind of nerve-ending is 716 SENSATION [CH. LI. chiefly associated with general sensibility, that vague kind of sensa- tion which cannot be put under any of the special headings — taste, sight, hearing, touch, and smell. The nerve-endings of the nerves of special sense are usually end-organs of a specialised kind. The most frequent kind of sensory end-organ is made of what is called nerve-epithelium, ; certain epithelial cells of the surface of the body become peculiarly modified, and grouped in special ways to receive the impressions from the outer world ; these send an impulse into the arborisations at the termination of the axis-cylinders of the nerves which envelop the cells. One of these varieties of nerve- epithelium we have already made the acquaintance of, in the hair- cells of the semicircular canals ; we shall find other kinds in the hair-cells of the cochlea, in the rods and cones of the retina, etc. Pain is due to an excessive stimulation of the other sensory nerves, but there is some evidence that it may be a distinct sensation. Thus in some cases of diseases of sensory channels, tactile sensation may be intact, but sensitiveness to pain absent, and vice versd ; see also p. 668. The other essential anatomical necessities for a sensation are the channels to the brain with their numerous cell-stations on the road, and the parts of the brain to which these tracts pass. Blindness, for instance, may not only be due to disease of the eye, but also to disease of the optic nerve, or of the parts of the brain to which the optic nerve passes. A small stimulus, or a small increase or decrease in a big stimulus, will have no effect ; a light touch, a feeble light, a gentle sound, may be so slight as to produce no effect on the brain. The smallest stimulus that produces an effect is called the lower limit of excitation or the liminal (from limen, a threshold) intensity of the sensation. The height of sensibility or maximum of excitation is a stimulus, so strong that the brain is incapable of recognising any increase in it ; a bright light, for instance, may be so intense that any increase in its brightness is not perceptible. Between these two extremes we have what is called the range of sensibility. Most of our ordinary sensations fall somewhere about the middle of the range, and Weber's law (as expanded by Fechner) is a law that regulates the proportion between the stimulus and the sensation, and which is operative for this region of the range of sensibility. In general terms it may be stated that sensations increase as the logarithm of the stimuli ; or, in order that the intensity of a sensation may increase in arithmetical progression, the stimulus must increase in a geometrical progression. A definite example will help us to understand these mathemati- cal terms a little better. We will select our example from the sense of vision, because the intensity of the cause of visual sensa- CH LI.] DISCRIMINATIVE SENSIBILITY 717 tions, light, is easily measurable. Suppose a room lighted by 100 candles, and one candle more is brought in, the increase of light pro- duced by the extra candle is quite perceptible to the eye ; or if a candle were removed, the decrease in light would be perfectly appreciable. Next suppose the room lighted by 1000 candles, and one extra was brought in, no difference would be seen in the amount of illumination ; in order to notice increase or decrease in the light it would be necessary to bring in ten extra candles, or take away ten of the candles, as the case might be. In each case an increment or decrease of one-hundredth of the original light is necessary to cause an increase or diminution in the sensation. This is after all a perfectly familiar fact ; a farthing rushlight will increase the illumination in a dimly-lighted cellar, but it makes no apparent difference in the bright sunshine. The magnitude of the fraction representing the increment of stimulus necessary to produce an increase of sensation determines what is called the discriminative sensibility. This fraction differs considerably for different sense-organs ; thus : — For light it is y^-g-. For weight it is -^ to -^ for different muscles. For tactile pressure -fa to yV in different parts of the body. Another general consideration in connection with sensation is that the sensation lasts longer than the stimulus ; a familiar instance of this is the sting after a blow. The after-sensations, as they are called, have been specially studied in connection with the eye (see After-images). Subjective sensations are those which are not produced by stimuli in the external world, but arise in one's own inner consciousness ; they are illustrated by the sensations experienced during sleep (dreams), and in the illusions to which mad and delirious people are subject. Homologous stimuli. — Each kind of peripheral end-organ is speci- ally suited to respond to a certain kind of stimulus. The homo- logous stimuli of the organs of special sense may be divided into : — 1. Vibrations set up at a distance without actual contact with the object; for instance, light and radiant heat. 2. Changes produced by actual contact with the object; for instance, in the production of sensations of taste, touch, weight, and alteration of temperature by conduction ; in the case of the olfactory end-organs, the sensation is also excited by material particles given off by the odoriferous body, and borne by the air to the nostrils. In sound also, though there is no actual contact of the ear with the vibrating body which emits the sound, the organ of hearing is excited by waves of material substance, first of air, then of bones, then of endolymph, and these excite the nerve-endings of the internal ear. 718 SENSATION [CH. LI. When the eye is excited by any other kind of stimulus than by light, which is its adequate or homologous stimulus, the sensation experienced is light all the same ; for instance, one sees sparks when the eyeball is struck ; singing in the ears, the result of an accumula- tion of wax against the membrana tympani, is a similar example. It has been inferred that there are separate nerve-fibres for the conveyance of each kind of sensation, and Johannes Miiller expressed this idea in what is known as the law of specific nerve energy. He pointed out that the same nerve may be stimulated by mechanical or electrical means as well as in the normal physiological manner, and that in all cases the sensation — light, sound, taste, contact, etc., as the case might be — is the same. Hence it was argued that the psychical effect or sensation is independent of the nature of the stimulus, but dependent on the nature of the activity of the central cells among which the afferent fibres terminate. We have no observa- tions which can decide whether the nerve impulses passing along the optic fibres are, for instance, similar to or different from those which are transmitted by the auditory fibres. The experiments of Langley and others on nerve-crossing (p. 173) would seem to indicate that the nervous impulse is an identical process in all nerves ; and if this is so, we are obliged to infer that separate nerve-fibres convey the impulses destined to give rise to different sensations. It is, however, possible that in the nerves of cutaneous sensation, the psychical process is determined by the nature of the peripheral stimulus, and consequently different branches of the same nerve-fibres may be imagined to be susceptible to different forms of stimulation, and thus two different sensations follow from the partial stimulation of the same nerve-fibres. Hering even argues in favour of the view that the nerve impulse has different characters in different afferent nerves, and further that it may be modified by the nature of the normal stimulus {e.g. in the skin, heat, cold, pain, or pressure). In the absence of direct experimental proof of such an idea, it is difficult to see upon what grounds it can rest. CHAPTEE LII CUTANEOUS SENSATIONS The tactile end-organs are of numerous kinds, but the following are the principal ones : — Pacinian Corpuscles. — These are named after their discoverer Pacini. They are little oval bodies, situated on some of the cerebro- spinal and sympathetic nerves, especially the cutaneous nerves of the hands and feet, where they lie deeply placed in the true skin. They also occur on the nerves of the mesentery of some animals like the cat. They have been ob- served also in the pancreas, lymphatic glands and thyroid glands, as well as in the penis. They are about -^ inch long. Each corpuscle is attached by a narrow pedicle to the nerve on which it is situated, and is formed of several concentric sheaths of con- nective-tissue, each layer being lined by endothelium (figs. 517, 518); through its pedicle passes a single nerve-fibre, which loses its medullary sheath and enters a central core, at or near the distal end of which it terminates in an arborisation. Some of these layers are continuous with those of the perineurium, but some are super-added. In some cases two nerve-fibres have been seen entering one Pacinian body, and in others a nerve-fibre after passing unaltered through one has been observed to terminate in a second. The corpuscles of Herbst (fig. 519) are closely allied to Pacinian corpuscles, except that they are smaller and longer, with a row of nuclei around the central termination of the nerve in the core. They have been found chiefly in the tongues and bills of ^ducks. Fig. 516. — Extremities of a nerve of the finger with Pacinian cor- puscles attached, about the natural size. (Adapted from Henle and Kolliker.) 720 CUTANEOUS SENSATIONS [CH. LII. End-bulbs are found in the conjunctiva (where in man they are spheroidal, but in most animals oblong), in the glans penis and clitoris, in the skin, in the lips, in the epineurium of nerve-trunks, and in tendon ; each is about -^^ inch in diameter, oval or spheroidal, Fig. 517. — Pacinian corpuscle of the cat's mesen- tery. The stalk consists of a nerve-fibre (N) with its thick outer sheath. The peripheral capsules of the Pacinian corpuscle are con- tinuous with the outer sheath of the stalk. The intermediary part becomes much nar- rower near the entrance of the axis-cylinder into the clear central core. A hook-shaped termination (T) is seen in the upper part. A blood-vessel (V) enters the Pacinian corpuscle, and approaches the end ; it possesses a sheath which is the continuation of the peripheral capsules of the Pacinian corpuscle, x 100. (Klein and Noble Smith.) Fir,. 518. — Summit of a Pacinian cor- puscle of the human finder Bhowing the endothelial membranes lining the capsules, x 220. (Klein and Noble Smith.) and is composed of a medullated nerve - fibre, which terminates among cells of various shapes. Its capsule contains a transparent or striated core, in the centre of which terminates the axis-cylinder of the nerve-fibre, the ending of which is somewhat clubbed (fig. 520). Touch-corpuscles (Meissner's corpuscles), (figs. 521, 523), are found in the papillae of the skin of the fingers and toes. They are small oblong masses, about ^j- inch long, and -gfo inch broad, com- posed of connective-tissue, surrounded by elastic fibres and a capsule of more or less numerous nucleated cells. They do not occur in all the papillae of the parts where they are found, and, as CH. LII.] TACTILE END OEGANS 721 a rule, in the papillae in which they are present there are no blood- vessels. The peculiar way in which the medullated nerve winds round and round the corpuscle before it enters it is shown in fig. 523. It loses its sheath before it enters into the interior, and then its axis- Fig. 519. — A corpuscle of Herbst, from the tongue of a duck, a, Medullated nerve cut away. (Klein.) Fig. 520.— End-bulb of Krause. a, Me- dullated nerve-fibre; 6, capsule of corpuscle. cylinder branches, and the branches after either a straight or con- voluted course terminate within the corpuscle. The corpuscles of Grandry (fig. 522) form another variety, and \ Fig. 521.— Papillae from the skin of the hand, freed from the cuticle and exhibiting Meissner's corpuscles. a. Simple papilla with four nerve-fibres ; a, tactile corpuscle ; 5, nerves with winding fibres c and e. b. Papilla treated with acetic acid ; a, cortical layer with cells and fine elastic filaments ; b, tactile corpuscle with transverse nuclei ; c, entering nerve ; d and e, nerve-fibres winding round the corpuscle, x 350. (Kolliker.) have been noticed in the beaks and tongues of birds. They consist of oval or spherical cells, two or more of which compressed vertically 2 Z 722 CUTANEOUS SENSATIONS [CII. LII. are contained within a delicate nucleated sheath. The nerve enters on one side, and, laying aside its medullary sheath, terminates between the cells in flattened expansions. Sensory nerve - endings in muscle. — Nerve terminations, sensory in function, are found in tendon. These appear very much like end-plates, and are represented in figs. 524 and 525. The Fig. 522.— A^corpuscle of Grandly, from the tongue,.of a duck. Fig. 523. — A touch-corpuscle from the skin of the human hand, stained with gold chloride. neuro-muscular spindles, which are described on p. 86, are principally found in muscles in the neighbourhood of tendons and aponeuroses. . 524. — Termination of medullated nerve-fibres in tendon near the mus- cular insertion. (Golgi.) Fig. 525.— One of the reticulated end-plates of rig. 524, more highly magnified, c, Medullated nerve-ribre; 6, reticulated end-plate. (Golgi.) One of these spindles is shown in the accompanying drawing (tig. 526). The principal grounds for believing the neuro-muscular spindles to be sensory are, first, that the nerve-fibres that supply them do not degenerate when the anterior roots of the spinal nerves are cut, and secondly, that they do degenerate when the posterior roots are divided (Sherrington). They also undergo degenerative changes i n CII. LII.] TACTILE LOCALISATION 723 locomotor ataxy, which is a disease of the sensory nerve-units, and remain healthy in infantile paralysis, which is a disease of the m.'n.b. Fig. 526.— Neuromuscular spindle, c, Capsule; n.tr., nerve trunk; m.n.b., motor nerve bundle; pl.e., plate-ending; pr.e., primary nerve-ending; s.e., secondary ending. (After Ruffini.) motor cells of the anterior horn of the cord (Batten). In addition to the special end-organs, sensory fibres may terminate in plexuses of fibrils, as in the sub-epithelial and the intra-epithelial plexus of the cornea (tig. 527) and around the hair follicles in the skin generally. In some cases the nerve-fibrils within a stratified epithelium end in crescentic expansions (tactile discs) which are applied to the deeper epithelium cells. These are well seen in the skin of the pig's snout. Localisation of Tactile Sensations. The ability to localise tactile sensa- tions on different parts of the surface is proportioned to the power which such parts possess of distinguishing and iso- lating the sensations produced by two points placed close together. This power depends in part on the number of nerve- fibres distributed to the part; for the fewer the fibres which any part receives, the more likely is it that several im- pressions on different contiguous points will act on only one nerve-fibre, and hence produce but one sensation. The experiments which have been made to determine the spatial relationships of the cutaneous sense consist in touching the skin, while the eyes are closed, with the points of a pair of compasses, and in ascer- Fig. 527. — Vertical section of rabbit's cornea, stained vath gold chloride. The nerves n, terminate in a plexus under and within the epithelial layer, e. 724 CUTANEOUS SENSATIONS [CH. LI1. taining how close the points may be brought to each other, and still be felt as two points. (Weber). A few results are as follow : — Tip of tongue .,y-inch 1 mm. Palmar surface of third phalanx of forefinger . p, ligamentum spirale. (Quain.) CH. LIV.] THE OKGAN OF COETI 745 above, the organ of Corti shows a remarkable resemblance to the keyboard of a piano. The top of the organ is roofed by the membrane/, tectoria (fig. 547, t) that extends from the end of the limbus (Us, fig. 547), a connective tissue structure on the spiral lamina. The spiral ganglion from which the cochlear nerve-fibres originate is situated in the spiral lamina. The peripheral axons of its bipolar cells arborise around the hair-cells of the organ of Corti : the central axons pass down the modiolus, and thence to the pons (see p. 642). Physiology of Hearing. Sounds are caused by vibrations ; when a piano-string is struck, it is thrown into a series of rapid regular vibrations ; the more Fig. 548. — Vertical section of the organ of Corti from the dog. 1 to 2, Homogeneous layer of the membrana basilaris ; u, vestibular layer; v, tympanal layer, with nuclei and protoplasm ; a, pro- longation of tympanal periosteum of lamina spiralis ossea ; c, thickened commencement of the membrana basilaris near the point of perforation of the nerves h ; d, blood-vessel (vas spirale) ; e, blood-vessel; /, nerves ; g, the epithelium of the sulcus spiralis intermis; i, internal hair-cell, with basal process k, surrounded with nuclei and protoplasm (of the granular layer), into which the nerve-fibres radiate ; I, hairs of the internal hair-cell ; n. base or foot of inner pillar of organ of Corti ; m, head of the same uniting with the corresponding part of an external pillar, whose under half is missing, while the next pillar beyond, o, presents both middle portion and base; r, s, d, three external hair-cells ; t, bases of two neighbouring hair or tufted cells ; x, supporting cell of Deiters ; w, nerve-fibre arborising round the first of the external hair-cells ; I I to I, lamina reticularis. x 800. (Waldeyer.) rapidly the vibrations occur the higher is the pitch of the musical note; the greater the amplitude of the vibration, the louder or more intense is the tone; if the vibrations are regular and simple (pendular), the tone is pure ; if they are regular but compound, the tone is impure, and its quality or timbre is dependent on the rate and amplitude of the simple vibrations of which the compound vibrations are composed. The vibrations are transmitted as waves, and ultimately affect the hair-cells at the extremities of the auditory nerve in the cochlea. The semicircular canals are not concerned in the sense of hearing ; their function in connection with equilibration is described in Chapter XLIX. The external and 746 HEARING [CH. LIY. middle ears are conducting; the internal ear is conducting and receptive. In the external ear the vibrations travel through air ; in the middle ear through solid structures — membranes and bones ; and in the internal ear through fluid, first through the perilymph on the far side of the fenestra ovalis ; and then the vibrations pass through the basilar membrane, and membrane of Eeissner, and set the endo- lymph of the canal of the cochlea in motion. This is the normal way in which the vibrations pass, but the cndolymph may be affected in other ways, for instance through the other bones of the head ; one can, for example, hear the ticking of one's watch when it is placed between the teeth, even when the ears are stopped. From this fact is derived a valuable practical method of distinguishing in a deaf person what part of the organ of hearing is at fault. The patient may not be able to hear a watch or a tuning-fork when it is held close to the ear ; but if he can hear it when it is placed between his teeth, or on his forehead, the malady is localised in either the external or middle ear ; if he can hear it in neither situation, it is a much moie serious case, for then the internal ear or the nervous mechanism of hearing is at fault. In disease of the middle ear the hearing of low tones is especially affected ; high tones appear to be transmissable by bone- conduction more readily than low. In connection with the external ear there is not much more to be said ; the pinna in many animals is large and acts as a kind of natural ear-trumpet to collect the vibrations of the air ; in man this function is to a very great extent lost, and though there are muscles present to move it into appropriate postures, they are not under the control of the will in the majority of people, and are functionless, ancestral vestiges. In the middle ear, however, there are several points to be con- sidered, namely, the action of the membrana tympani, of the ossicles, of the tympanic muscles, and of the Eustachian tube. The Membrana Tympani. — This membrane, unlike that of ordinary drums, can take up and vibrate in response to, not only its own fundamental tone, but to an immense range of tones differing from each other by many octaves. This would clearly be impos- sible if it were an evenly stretched membrane. It is not evenly nor very tightly stretched, but owing to its attachment to the chain of ossicles it is slightly funnel-shaped : the ossicles also damp the con- tinuance of the vibrations. When the membrane gets too tightly stretched, by increase or decrease of the pressure of the air in the tympanum, then the sense of hearing is dulled. The pressure in the tympanic cavity is kept the same as that of the atmosphere by the Eustachian tube, which leads from the cavity to the pharynx, and so to the external air. The Eustachian tube is not, however, always open ; it is opened by the action of the tensor pa lati during swallowing. Suppose it were closed owing to swelling of its mucous membrane — this often happens in inflammation of the throat — the result would be what is called Eustachian or throat deafness, and this is relieved by passing a catheter so as to open the tube. When the tube is closed, an CH. LTV.] MECHANISM OF THE TYMPANUM 747 interchange of gases takes place between the imprisoned air and the blood of the tympanic vessels. In time, as in the aerotomometer (see p. 381), equilibrium is established and the tension of the imprisoned gases becomes equal to that of the blood-gases, not to that of the atmosphere. The membrane is therefore cupped inwards by the atmospheric pressure on its exterior ; it is this increased tightening of the membrane that produces deafness. There is also an accumulation of mucus. When one makes a violent expiration, as in sneezing, some air is often forced through the Eustachian tube into the tympanum. The ears feel as though they were bulged out, as indeed the membrana tympani is, and there is again partial deaf- ness, which sensations are at once relieved by swallowing so as to open the Eustachian tube and thus re-establish equality of pressure once more. The ossicles communicate the vibrations of the membrana tympani (to which the handle of the malleus is fixed) to the mem- brane which closes the fenestra ovalis (to which the foot of the stapes is attached). Thus the vibrations are communicated to the fluid of the internal ear which is situated on the other side of the oval window. The accompanying diagram will assist us in understanding how this is brought about. The bones all vibrate as if they were one, the slight movements between the individual bones being inappreci- able. The utility of there being several bones is seen when the vibrations are excessive ; the small amount of " give " at the articulations is really protective and tends to prevent fractures. The handle of the malleus is inserted between the layers of the tympanic membrane ; the processus gracilis (p. g.) has its end A attached to the tympanic wall on the inner aspect of the Glaserian tissure ; the end B of the short process (s. p.) of the incus is fastened by a ligament to the opposite wall of the tympanic cavity ; the end D of the long process of the incus articulates with the stirrup, the base of which is turned towards the reader. The handle vibrates with the membrana tympani ; and the vibrations of the whole chain take place round the axis of rotation AB. Every time C comes forwards D comes forwards, but by drawing perpendiculars from C and D to the axis of rotation, it is found that D is about § of the distance from the axis that C is. So in the transmission of the Foot of Stapes Fig. 549. — Diagrammatic view of ear ossicles. 748 HEARING [CH. LTV. vibrations from membrane to membrane across the bony chain, the amplitude of the vibration is decreased by about J, and the force is correspondingly increased. This increase of power is augmented by the fact that the tympanic membrane concentrates its power upon an area (the membrane of the oval window) only one-twentieth of its size. The final movement of the stapes is, however, always very small ; it varies from -jV to less than l0o oo of a millimetre. The action of the tensor tympani, by pulling in the handle of the malleus, increases the tension of the membrana tympani. It is supplied by the fifth nerve. It is opposed by the strong external ligament of the malleus. The stapedius attached to the neck of the stapes tilts it backwards and diminishes the intra-tympanic air- pressure. It is supplied by the seventh nerve. The next very simple diagram (fig. 550) will explain the use of the fenestra rotunda. The cochlea is supposed to be uncoiled ; the scala vestibuli leads from the fenestra ovalis, to the other side of which the stapes is F. Ovalis Stapes I Scale Vestibuli (Perilymph) -C anal of Covhlea (Endotumohl Scala Tympani (Perilymph) Helicotrema F. Rotunda Fig. 550.— DiagTam to illustrate the use of the fenestra rotunda. attached ; the scala tympani leads to the fenestra rotunda ; the two scalse communicate at the helicotrema, and are separated from the canal of the cochlea by the basilar membrane, and the membrane of Eeissner. C.E. is the canalis reuniens leading to the saccule. The cochlea is filled with incompressible fluid in an inexpansible bony case, except where the windows are closed by membranes. Hence every time the membrane of the oval window is bulged in by the stirrup, the membrane of the round window is simultaneously bulged out to the same extent, and vice versd. These changes of pressure are transmitted from one scala to the other directly through the cochlear canal, setting it into vibration, and through the helicotrema. The range of hearing extends over 10 or 11 octaves; the lowest audible tone having about 20, the highest about 25,000, vibrations per second. The range varies in different people, and diminishes from childhood onwards. The upper limit of hearing may lie tested by minute forks, metal rods, or by G-alton's whistle. Many animals appear to be able to detect high tones which lie beyond the human limit. The lower limit may be determined by very large forks, or by employing very low difference-tones. CH. LIV.] THEOEIES OF THE COCHLEA 749 Difference-tones are produced when two tones of different pitch, to and n, are sounded together. A tone having the pitch to minus n is then heard in addition to the tones m and n : also a summation tone of pitch m plus n may be heard, but with greater difficulty. When to and n are nearly equal, a beating tone, instead of a difference- tone, results, having a pitch somewhere intermediate between to and n. If the difference between to and n is exceedingly small, this beating- tone alone is heard. The frequency of the beats corresponds to the difference in vibration-rates, to and n. Under certain conditions the difference and summation-tones (which are collectively called combina- tion-tones) exist in the air; their presence being demonstrable by their re-inforcement before appropriate resonators. More generally, however, they appear to be produced within the ear, i.e., they have merely a subjective origin. The smallest perceptible difference in pitch between two successive tones is about 0'2 vibrations in the middle region of the piano for trained subjects. Practice effects extraordinary improvement, even among the most unmusical. There can be little doubt that the cochlea is the organ specially concerned in hearing. It first appears among vertebrata in certain fishes as a very rudimentary structure. If the cochlea is removed from dogs, they become deaf. The utricle and saccule are probably only stimulated by gross disturbances in the siirrounding media (see the functions of the semicircular canals in Chapter XLIX.). There are two classes of theories of hearing, in both of which the basilar membrane of the cochlea plays the essential part. The one class comprises the many "sound-picture" theories which have been advanced in very various forms by Rutherford, Waller, Hurst, Ewald, and Meyer. The entire basilar membrane is supposed to vibrate either as a telephone plate, or as an elastic mem- brane, different tones or combinations of tones giving rise to different patterns of vibrations which are communicated to the hair-cells and thence carried by the auditory nerve-fibres to the brain, where (in Rutherford's theory) the analysis of these patterns is held to take place. The other is the resonance-theory of Helmholtz, in which the pitch of a tone, or the analysis of a complex sound into its constituent tones, is determined not in the brain but in the cochlea, It depends on the principle of sympathetic vibration. As is well known, if a tone is sung in front of a piano (best with the loud pedal held down), the string of the piano which is attuned to that tone will immediately respond; another tone will elicit response from another string. So in the cochlea the appropriate fibre of the basilar membrane is thrown into vibration when the tone to which it is attuned reaches it. The fibre thus stimulated affects the hair-cells above it, whence the 750 U EARING [CH. L1V. stimulus is conducted to the brain. If two tones are sounded together, the two appropriate fibres respond, and the analysis of the now more complex stimulus is performed in the cochlea. The fibres of the basilar membrane increase in radial length from the base towards the apex of the cochlea. According to the resonance-theory, the upper part of the organ would thus be affected by low tones, the lower part by high tones. The first of these two classes of theory makes it difficult or impossible for us to explain our ability to analyse complex chords into their component tones. The full acceptance of the second is difficult in the face of the small difference of length (at most 1 : 12) between the shortest and the longest of the basilar fibres. On the other hand, it accounts for nearly all the phenomena which require explanation, and gains support from the effects of experiment on, and disease of, different portions of the cochlea. For instance, the deafness to high pitched tones (seen in boiler makers) is associated with disease of the lower whorl of the cochlea. C H A P T E R L V VOICE AND SPEECH The fundamental tones of the voice are produced by the current of expired air causing the vibration of the vocal cords, two elastic bands contained in a cartilaginous box placed at the top of the wind-pipe or trachea. This box is called the larynx. The sounds produced here are modified by other parts like the tongue, teeth, and lips, as will be explained later on. Anatomy of the Larynx. The cartilages of the larynx are the thyroid, the cricoid, the two arytenoids. These are the most important for voice production ; they are made of hyaline carti- Cornu min. Coruu maj. Cornu sup. Lig. crico-thyr. med Cart, cricoidea Lig. crico-trachese .. m. Sterno-hyoideus. -- m. Thyro-hyoideus. to. Sterno-hyoideus. m. Crico-thyroideus. Cart, tracheale ^ Fig. 551.— The larynx, as seen from the front showing the cartilages and ligaments. The muscles, with the exception of one crico-thyroid, are cut oS short. (Stoerk.) lage. Then there are the epiglottis, two cornicular, and two cuneiform cartilages. These are made of yellow fibro-cartilage. The thyroid cartilage (fig. 552, 1 to 4) does not form a complete ring around the larynx, but only covers the front portion. It forms the prominence in front of the 751 752 VOICE AND SPEECH [CU. LV. throat known as Adam's apple. The cricoid cartilage (fig. ">52, 5, 6), on the other hand, is a complete ring; the back part of the ring is much broader than the front. On the top of this broad portion of the cricoid are the arytt noid cartilages (fig. 552, 7); the connection between the cricoid below and arytenoid cartilages above is a joint with synovial membrane and ligaments, the latter permitting tolerably free Fio. 552. — Cartilages of the larynx seen from the front. 1 to 4, Thyroid cartilage; 1, vertical ridge or pomum Adami ; 2, right ala ; 3, superior, and 4, inferior cornu of the right side ; 5, 6, cricoid carti- lage ; 5, inside of the posterior part ; 6, anterior narrow part of the ring ; 7, arytenoid cartilages, x |. motion between them. But although the arytenoid cartilages can move on the cricoid, they accompany the latter in all its movements. The base by means of which each arytenoid cartilage sits on the cricoid is triangular ; the anterior angle is often called the vocal process : to it the posterior ends of the true vocal cords are attached. The outer angle is thick and called the muscular process. The cornicular cartilages, or cartilages of Santorini, are perched on the top of Lig. ary-epiglott. .. Cart. Wrisbergii. -J- Cart. Santorin Lig. crico-ary ten. --'''I Lig. cerato-crico. post. sup. * Cornu infer. Lig. cerato-crieo. post, inf Cart, tracheae. -:->• — Pars membraii. Fig. 553.— The larynx as seen from behind after removal of the muscles. The cartilages and ligaments only remain. (Stoerk.) the arytenoids ; the cuneiform cartilages, or cartilages of Wrisberg, are in a fold of mucous membrane ; the epiglottis looks like a lid to the whole (fig. 553). The thyroid cartilage is connected with the cricoid, by the crico-thvroid mem- brane, and also by joints with synovial membranes ; the lower comma of the thyroid clasp the cricoid between them, yet not so tightly but that the thyroid can revolve, CH. LV.] MUSCLES OF THE LAEYNX 753 F.V.C.- within a certain range, around an axis passing transversely through the two joints at which the cricoid is clasped. The vocal cords are attached behind to the front portion of the base (vocal process) of the arytenoid cartilages, and in front to the re-entering angle at the back of the thyroid ; it is evident, therefore, that all move- ments of either of these cartilages must produce an effect on them of some kind or other. Inasmuch, too, as the arytenoid cartilages rest on the top of the back portion of the cricoid cartilage, and are connected with it by capsular and other ligaments, all movements of the cricoid cartilage must move the arytenoid cartilages, and also produce an effect on the vocal cords. Mucous membrane. — The larynx is lined with a mucous membrane continuous with that of the trachea ; this is covered with ciliated epithelium except over the vocal cords and epiglottis, where it is stratified. The Vocal cords are thickened bands of elastic tissue in this mucous membrane which run from before back. They are at- tached behind to the vocal processes of the arytenoid cartilages, and in front to the angle where the two wings of the thyroid meet. The chink between them is called the rima glottidis (see fig. 554). Two ridges of mucous membrane above and parallel to these are called the false vocal cords: between the true and false vocal cord on each side is a recess called the ventricle. Muscles. — The muscles of the larynx are divided into intrinsic and extrinsic. The intrinsic are named from their attachments to the various cartilages ; the extrinsic are those which connect the larynx to other parts like the hyoid bone. The intrinsic muscles of the larynx are as follows : — 1. Crico-thyroid. 2. Posterior crico-arytenoid. 3. Lateral crico-arytenoid. 4. Thyro-arytenoid. 5. Arytenoid. All these muscles except the arytenoid are in pairs. Their attachments and actions are as follows : — 1. Crico-thyroid. — This is a short, thick triangular muscle, at- tached below to the cricoid cartilage ; this attachment extends from the middle line backwards. The fibres pass upwards and outwards, diverging slightly to be attached above to the inferior border of the thyroid cartilage, and to the anterior border of its lower cornu. In the latter portion of the muscle, the fibres are nearly horizontal. Some of the superficial fibres are continuous with those of the inferior constrictor of the pharynx. The thyroid cartilage being fixed by extrinsic muscles, the contraction of this muscle draws upwards the anterior part of the cricoid cartilage, and depresses the posterior part, and with it the arytenoid cartilages, so that the vocal cords are stretched. Paralysis of these muscles therefore causes an inability to produce high- pitched tones. 2. Posterior crico-arytenoid. — This arises from the broad depression on the corresponding half of the posterior surface of the cricoid cartilage ; its fibres con- 3 B CM. Fig. 554. — Vertical section through the larynx, passing from side to side. H, Hyoid bone ; T., thyroid carti- lage ; T.C.M., thyro-cricoid membrane ; C, cricoid cartilage; Tr., first ring of trachea; T.A., thyro- arytenoid muscle ; R.G., rima glottidis ; V.C., vocal cord ; V., ventricle ; F.V.C., false vocal cord. (After Allen Thomson.) 754 VOICE AND SPEECH [CH. LV. verge upwards and outwards, and are inserted into the outer angle of the base of the arytenoid cartilage behind the attachment of the lateral crico-arytenoid muscle. Near their insertion the upper fibres are blended with the lower fibres of the ary- tenoid muscle. These muscles draw the outer angles of the arytenoid cartilages backwards and inwards, and thus rotate the anterior or vocal processes outwards, and widen the rima glottidis. They come into action during deep inspiration. If they are paralysed, the lips of the glottis approach the middle line and come in contact during each inspiration, so that dyspnoea is produced. 3. Lateral crico-arytenoid. — This arises from the sloping upper border of the cricoid cartilage, and is inserted into the muscular process of the arytenoid carti- lage, and the adjacent part of its anterior surface. Its upper part is more or less blended with the thyro-arytenoid, and a few of its fibres are continuous round the outer side of the arytenoid cartilage with the arytenoid muscle. These muscles draw the muscular processes of the arytenoid cartilages forwards and downwards, and thus ap- proximate the vocal cords. They are antagonistic to the posterior crico-arytenoids. 4. Thyro - arytenoid. — This consists of two portions, inner and outer. The inner portion arises in the lower half of the angle formed by the alae of the thyroid cartilage, and passing backwards is attached behind to the vocal process and to the ad- jacent parts of the outer surface of the arytenoid cartilage. These fibres are joined internally by short fibres which are attached in front to the vocal cord, and behind to the vocal process. Some oblique fibres pass from the sloping portion of the crico- thyroid membrane below the vocal cord, upwards, outwards, and somewhat backwards, to end in the tissue of the false vocal cord. The fibres of the outer portion arise in front from the thyroid cartilage close to the origin of the inner portion and from the crico-thyroid membrane. They pass back- wards to be inserted in part into the lateral border and muscular process of the arytenoid cartilage, and in part they pass obliquely upwards towards the aryteno- epiglottidean fold, ending in the false vocal cord. The portion of this muscle which extends towards the epiglottis is often described as a separate muscle (thyro- epiglottidean) ; it resembles the crico-arytenoid in that some of its fibres are con- tinuous with those of the arytenoid muscle. The antero-posterior fibres will tend to draw forward the arytenoid cartilage, and with it the posterior part of the cricoid cartilage, rotating the latter upwards and antagonising the action of the crico-thyroid muscle, the effect being to relax the vocal cords. But if the latter are kept stretched those fibres of the inner portion of the muscle which are inserted into the vocal cord may serve to modify its elasticity, tightening the parts of the cord in front of, and relaxing those behind, its attach- ment. The vertical fibres of the muscle which extend from the crico-thyroid mem- b rane across the base of the vocal fold and over the ventricle into the false vocal cord, render the free edge of the former more prominent Then the fibres which are inserted into the muscular process and outer surface of the arytenoid cartilage will tend to draw the arytenoid cartilage forwards and rotate it inwards ; finally, the Lig. ary-epiglott. Cart. Wrisbergii Cart. Santorini mm. Aryten. obliqu. Crico-arytenoid. post. Cornu inferior Lig. cerato-cric. Pars post. inf. membrani Pars cartilag. Fio. 555.— The larynx as seen from behind. To show the intrinsic muscles posteriorly. (Stoerk.) CH. LV-] THE LARYNGOSCOPE 755 fibres which pass into the aryteno-epiglottidean fold may assist in depressing the epiglottis. If these muscles are paralysed, the lips of the glottis are no longer parallel, but are curved with the concavity inwards, and a much stronger blast of air is required for the production of the voice. 5. Arytenoid. — When the mucous membrane is removed from the back of the arytenoid cartilages, a band of transverse fibres is exposed, on the dorsal surface of which are two slender decussating oblique bundles. These are often described as separate muscles (arytenoid and aryteno-epiglottidean), but they are intimately blended together. The ventral fibres (arytenoid proper) pass straight across from the outer half of the concave surface on the back of one arytenoid cartilage to the corresponding surface of the other. The dorsal fibres can be followed to the lateral walls of the larynx, the uppermost ones to the cartilage of Santorini, the intermediate ones run with the uppermost fibres of the thyro-arytenoid muscle forming the so- called aryteno-epiglottidean muscle, and the lowest fibres blend at the level of the true vocal cords with the thyro-arytenoid and lateral crico-arytenoid muscles. The arytenoid muscle draws the arytenoid cartilages together. If it is paralysed, the intercartilaginous part of the glottis remains open, although the membranous lips can still be approximated during vocalisation. It has been generally supposed that the epiglottis is depressed as a lid over the glottis during swallowing. This may be so in some animals, but in man it is not the case ; the epiglottis projects upwards in close contact with the base of the tongue. The necessary closure of the glottis during swallowing is brought about by the con- traction of the arytenoid and thyro-arytenoid muscles ; by this means the arytenoid cartilages are drawn towards each other, and also forwards into contact with the posterior surface of the epiglottis (Anderson Stuart). Henle remarks that "the muscles which he in the space enclosed by the laminae of the thyroid cartilage and above the cricoid may be regarded in their totality as a kind of sphincter such as is found in its simplest form embracing the entrance of the larynx in reptiles " (Quain's Anatomy). Nerves. — The larynx is supplied by two branches of the vagus ; the superior laryngeal is the sensory nerve ; by its external branch, it supplies one muscle, namely, the crico-thyroid. These fibres, however, probably arise from glosso- pharyngeal rootlets (see p. 645). The rest of the muscles are supplied by the inferior laryngeal nerve, the fibres of which come from the spinal accessory, not the vagus proper. The laryngoscope is an instrument employed in investigating during life the condition of the pharynx, larynx, and trachea. It consists of a large concave mirror with perforated centre, and of a smaller mirror fixed in a long handle. The patient is placed in a chair, a good light (argand burner, or electric lamp) is arranged on one side of, and a little above, his head. The operator fixes the large mirror round his head in such a manner, that he looks through the central aperture with one eye He then seats himself opposite the patient, and so alters the position of the mirror, which is for this purpose provided with a ball-and-socket joint, that a beam of light is reflected on the lips of the patient. The patient is now directed to throw his head slightly backwards, and to open his mouth ; the reflection from the mirror lights up the cavity of the mouth, and by a little alteration of the distance between the operator and the patient the point at which the greatest amount of light is reflected by the mirror — in other words, its focal length— is readily discovered. The small mirror fixed in the handle is then warmed, either by holding it over the lamp, or by putting it into a vessel of warm water ; this is necessary to prevent the condensation of breath upon its surface. The degree of heat is regulated by applying the back of the mirror to the hand or cheek, when it should feel warm without being painful. After these preliminaries the patient is directed to put out his tongue, which is held by the left hand gently but firmly against the lower teeth by means of a handkerchief. The warm mirror is passed to the back of the mouth, until it rests upon and slightly raises the base of the uvula, and at the same time the light is directed upon it : an inverted image of the larynx and trachea will be seen in the mirror. If the dorsum of the tongue is alone seen, the handle of the mirror must 756 VOICE AND SPEECH [CH. LV. be slightly lowered until the larynx comes into view ; care should be taken, how- ever, not to move the mirror upon the uvula, as it excites retching. The observa- tion should not be prolonged, but should rather be repeated at short intervals. Fig. 556.— The parts of the Laryngoscope. The structures seen will vary somewhat according to the condition of the parts as to inspiration, expiration, phonation, etc. ; they are (fig. 558) first, and apparently Fro. 557.— To show the position of the operator and patient when using the Laryngoscope. at the posterior part, the base of the tongue, immediately below which is the arcuate outline of the epiglottis, with its cushion or tubercle. Then are seen in the central CH. LV.] MOVEMENTS OF THE VOCAL CORDS 757 line the true vocal cords, white and shining in their normal condition. The cords approximate (in the inverted image) posteriorly ; between them is left a chink, narrow whilst a high note is being sung, wide during a deep inspiration. On each side of the true vocal cords, and on a higher level, are the \)\nk. false vocal cords. Still more externally than the false vocal cords is the ari/teno-epiglottidean fold, in which are situated upon each side three small elevations ; of these the most external is the cartilage of Wrisberg, the intermediate is the cartilage of Sanlorini, whilst the summit of the arytenoid cartilage is in front, and somewhat below the preceding, being only seen during deep inspiration. The rings of the trachea, and even the bifurcation of the trachea itself, if the patient be directed to draw a deep breath, may be seen in the interval between the true vocal cords. Movements of the Vocal Cords. In Respiration. — The position of the vocal cords in ordinary tranquil breathing is so adapted by the muscles, that the opening of the glottis is wide and triangular (fig. 558, b). For all practical purposes, the glottis remains unaltered during ordinary quiet breath- ing, though in a small proportion of people it becomes a little wider at each inspiration, and a little narrower at each expiration. In the cadaveric position the glottis has about half the width it has during ordinary breathing ; during life, therefore, except during vocalisation, the abductors of the vocal cords (posterior crico-arytenoids) are in constant action. (F. Semon.) On making a rapid and deep inspira- tion the opening of the glottis is widely dilated (fig. 558, c), and somewhat lozenge-shaped. In Vocalisation. — At the moment of the emission of a note, the chink is narrowed, the margins of the arytenoid cartilages being brought into contact, and the edges of the vocal cords approximated and made parallel (fig. 558, a); at the same time their tension is much increased. The higher the note produced, the tenser do the cords become; and the range of a voice depends, in the main, on the extent to which the degree of tension of the vocal cords can be thus altered. In the production of a high note the vocal cords are brought well within sight, so as to be plainly visible with the help of the laryngoscope. In the utterance of low-pitched tones, on the other hand, the epiglottis is depressed and brought over them, and the arytenoid cartilages look as if they were trying to hide themselves under it (fig. 559). The epiglottis, by being somewhat pressed down so as to cover the superior cavity of the larynx, serves to render the notes deeper in tone and at the same time somewhat duller. The degree of approximation of the vocal cords also usually corresponds with the height of the note produced ; but the width of the aperture has no essential influence on the pitch of the note, as long as the vocal cords have the same tension : only with a wide aperture the tone is more difficult to produce and is less perfect, the 758 VOICE AND SPEECH [CH. LV. rushing of the air through the aperture being heard at the same time. No true vocal sound is produced at the posterior part of the 1 to. 558.— Three laryngoscopy views of the superior aperture of the larynx and surrounding parts. A, The glottis during the emission of a high note in singing ; B, in easy and quiet inhalation of air ; C, in the state of widest possible dilatation, as in inhaling a very deep breath. The diagrams A', B', and C', show in horizontal sections of the glottis the position of the vocal curls and arytenoid cartilages in the three several states represented in the other ligures. In all the figures so far as marked, the letters indicate the parts as follows, viz. : I, the base of the tongue ; e, the upper free part of the epiglottis; <', the tubercle or cushion of the epiglottis; ph, part of the anterior wall of the pharynx behind the larynx ; in the margin of the aryteno-epiglottidean fold, ;/-, the swelling of the membrane caused by the cartilages of Wrisberg ; s, that of the cartilages of iSantorini ; a, the tip or summit of the arytenoid cartilages ; c v, the true vocal cords or lips of the rima glottidis ; c v s, the superior or false vocal cords ; between them the ventricle of the larynx; in C, tr is placed on the anterior wall of the receding trachea, and 6 indicates the commencement of the two bronchi beyond the bifurcation which may be brought into view in this state of extreme dilatation. (Quain, after Czermak.) aperture of the glottis, that, viz., which is formed by the space between the arytenoid cartilages. The Voice. The human musical instrument is often compared to a reed organ- pipe : certainly the notes produced by such pipes in the vox humana stop of organs is very like the human voice. Here there is not only the vibration of a column of air, but also of a reed, which corre- CH. LV.] THE VOICE 759 sponds to the vocal cords in the air-chamber composed of the trachea and the bronchial system beneath it. The pharynx, mouth, and nasal cavities above the glottis are resonating cavities, which, by alterations in their shape and size, are able to pick out and emphasize certain component parts of the fundamental tones produced in the larynx. The natural voice is often called the chest voice. The falsetto voice is differently explained by different observers ; on laryngoscopic examination, the glottis is found to be widely open, so that there is an absence of chest resonance ; some have supposed that the attachment of the thyro-arytenoid muscle to the vocal cord renders it capable of acting like the finger on a violin string, part of the cord being allowed to vibrate while the rest is held still. Such a shortening of a vibrating string would produce a higher pitched note than is natural. Musical sounds differ from one another in three ways : — 1. In pitch. — This depends on the rate of vibration; and in the case of a "'TJIP^ string, the pitch increases with the ten- FlG . 5 59.-view of the upper part of the Sion, and diminishes With the length Of larynx as seen by means of the laryngo- . ' - tip scope during the utterance of a bass the String. Ihe VOCal COrdS Of a WOman note, e, Epiglottis ; s, tubercles of the i_ , ,i , t_ n -i cartilages of Santorini ; a, arytenoid are shorter than those or a man, hence cartilages ; z, base of the tongue ; the higher pitched voice of women. fcz. In slight disease of the auditory word-centre, he is unable to do this, but if his mind is set into a certain groove he will speak ; thus if the alphabet or a well- known piece of poetry be started for him he will finish it by himself. c. Mimetic. In more severe cases, a more powerful stimulus still is needed ; he will repeat any words after another person, but forget them immediately afterwards. With regard to the visual word-centre as tested by writing, there are also three ways of reviving impressions for written words or letters. («) Spontaneous or normal (b) A train of thought must first be set going; as, for instance, converting printed words into written characters. (c) Mimetic ; he can only write from a copy. Two operations require the combined activity of both centres ; the first of these is reading aloud, the second is writing from dictation. These, however, we have previously considered in connection with the subject of association in the brain (see p. 695). In the investigation of any case of defective speech there are always the follow- ing six things to be inquired into : — 1. Can the patient understand spoken words? (The patient, of course, not being deaf. ) If he cannot, the auditory word-centre is deranged. 2. Can he repeat words when requested ? This tests the emission fibres from the auditory word-centre which pass through the motor-centres for speech in Broca's convolution. If he cannot do this, the patient has aphasia. CH. LV.] DEFECTS OF SPEECH 763 3. Can he write from dictation? If he cannot, either the auditory or visual word-centre, or the fibres passing from the one to the other, are injured. 4. Does he understand printed matter, and can he point out printed letters and words? Can he read to himself? (The patient, of course, not being blind.) This tests the visual word-centre. 5. Can he copy written words ? This tests the channels from the visual word- centre to the motor-centres for movements of the hand in writing. 6. Can he read aloud, or, what is the same thing, name objects he sees ? This is the opposite to writing from dictation, and tests the healthiness of the word-centres or the fibres which connect the visual to the auditory word-centre. CHAPTER LVI THE EYE AND VISION The eyeball is contained in the cavity of the skull called the orbit; here also are vessels and nerves for the supply of the eyeball, muscles to move it, and a quantity of adipose tissue. In the front of the eyeball are the lids and lacrimal apparatus. The eyelids consist of two movable folds of skin, each of which is kept in shape by a thin plate of fibrous tissue called the tarsus. Along their free edges are inserted a number of curved hairs {eye- lashes), which, when the lids are half closed, serve to protect the eye from dust and other foreign bodies : the tactile sensibility of the lids is very delicate. Imbedded in the tarsus are a number of long sebaceous glands {Meibomian), the ducts of which open near the free edge of the lid. In the loose connective tissue in front of the tarsus, the bundles of the orbicularis muscle are situated. The orbital surface of each lid is lined by a delicate, highly sensitive mucous membrane {conjunctiva), which is continuous with the skin at the free edge of each lid, and after lining the inner surface of the eyelid is reflected on to the eyeball, being somewhat loosely adherent to the sclerotic coat. Its epithelium, which is columnar, is continued over the cornea as its anterior epithelium, where it becomes stratified. At the inner edge of the eye the conjunctiva becomes continuous with the mucous lining of the lacrimal sac and duct, which again is continuous with the mucous membrane of the nose. The eyelids are closed by the contraction of a sphincter muscle {orbicularis), supplied by the facial nerve ; the upper lid is raised by the levator palpebral superioris, supplied by the third nerve. The lacrimal gland, composed of lobules made up of acini resembling the serous salivary glands, is lodged in the upper and outer angle of the orbit. Its secretion, which issues from several ducts on the inner surface of the upper lid, under ordinary circumstances just suffices to keep the conjunctiva moist. It passes out through two small openings (puncta lacrimalia) near the inner angle of the eye, CH. LVI.] THE EYEBALLS 765 one in each lid, into the lacrimal sac, and thence along the nasal duct into the inferior meatus of the nose. The excessive secretion poured out under the influence of an irritating vapour or painful emotion overflows the lower lid in the form of tears. The secretory nerves are contained in the lacrimal and subcutaneous malar branches of the fifth nerve, and in the cervical sympathetic. The Eyeball. The eyeball (fig. 561) consists of the following structures : — Ciliary muscle- Ciliary process — Canal of Petit- Cornea— Anterior chamber- Lens — Iris- Ciliary process- Ciliary muscle— — Sclerotic coat. — Choroid coat. — Retina. — Vitreous humour. Fig. 561. — Section of the anterior four-fifths of the eyebalL The sclerotic, or outermost coat, envelops about five-sixths of the eyeball : continuous with it, in front, and occupying the remaining Fig. 562.— Vertical section of rabbit's cornea, a, Anterior epithelium, showing the different shapes of the cells at various depths from the free surface ; 6, portion of the substance of cornea. (Klein.) sixth, is the cornea. Immediately within the sclerotic is the choroid coat, and within the choroid is the retina. The interior of the 766 THE EYE AND VISION [CH. LVI. eyeball is filled by the aqueous and vitreous humours and the crystalline lens; but, also, there is suspended in the interior a contractile and perforated curtain, — the iris, for regulating the admission of light, and behind at the junction of the sclerotic and Fiq. 563. — Horizontal preparation of cornea of frog ; showing the network of branched cornea-corpuscles. The ground substance is completely colourless, x 400. (Klein.) cornea is the ciliary muscle, the function of which is to adapt the eye for seeing objects at various distances. The sclerotic coat is composed of white fibrous tissue, with some elastic fibres near the inner surface, arranged in variously disposed and interlacing layers. Many of the bundles of fibres cross the Fig. 564. — Surface view of part of lamella of kitten's cornea, prepared first with caustic potash and then with nitrate of silver. (By this method the branched cornea-corpuscles with their granular proto- plasm and large oval nuclei are brought out.) x 450. (Klein and Noble Smith.) others almost at right angles. It is separated from the choroid by a lymphatic space (perichoroidal), and this is in connection with smaller spaces lined with endothelium in the sclerotic coat itself. There is a lymphatic space also outside the sclerotic, separating it from a loose investment of connective tissue, containing some smooth CH. LVI.] THE COENEA 767 muscular fibres, called the capsule of Tenon. The innermost layer of the sclerotic is made up of loose connective tissue and pigment-cells, and is called the lamina fusca. The cornea is a transparent membrane which forms a segment of a smaller sphere than the rest of the eye- ball, let in, as it were, into the sclerotic, with which it is continuous all round. It is covered by stratified epithelium (a, fig. 562), consisting of seven or eight layers of cells, of which the superficial ones are flattened and scaly, and the deeper ones more or less columnar. Immediately beneath this is the anterior homogeneous lamina of Bowman, which differs, only in being more condensed tissue, from the rest of the cornea. The rest of the cornea consists of many layers of connective tissue fibres arranged parallel to the free surface, the direction of the fibres crossing one another at right angles in the alternate laminae. The corneal corpuscles lie in branched anasto- mosing spaces between the laminse. They have been seen to execute amoeboid move- ments. At its posterior surface the cornea is limited by the posterior homogeneous lamina, or membrane of Descemet, which is elastic in nature, and lastly a single stratum of cubical epithelial cells (fig. 565, d). The nerves of the cornea are both large and numerous : they are derived from the ciliary nerves. They traverse the sub- stance of the cornea, in which some of them near the anterior surface break up into axis cylinders, and their primitive fibrillse. The latter form a plexus im mediately beneath the epithelium, from which delicate fibrils pass up between the cells anastomosing with horizontal branches, and forming an intra-epithelial plexus. Most of the primitive fibrillse have a beaded or varicose appearance. The cornea has no blood-vessels or lymphatics, but is nourished|by the circulation of lymph in the spaces in which the corneal corpuscles lie. These communicate freely and form a lymph-canalicular system. Fig. 565. — Vertical section of rabbit's cornea, stained with gold chloride, e, Stratified anterior epithelium. Immediately beneath this is the anterior homogeneous lamina of Bowman, n, Nerves forming a delicate sub-epithelial plexus, and sending up fine twigs between the epithelial cells to end in a second plexus on the free surface; d, Descemet's membrane, consisting of a fine elastic layer, and a single layer of- epithelial cells ; the sub- stance of the cornea, /, is seen to be fibrillated, and contains many layers of branched corpuscles, ar- ranged parallel to the free surface, and here seen edgewise. (Schofield.) 768 THE EYE AND VISION [CH. LVI. The Choroid Coat {tunica vasculosa) is attached to the inner layer of the sclerotic in front at the corneo-scleral junction and behind at the entrance of the optic nerve ; elsewhere it is connected to it only by loose connective tissue. Its external coat is formed chiefly of elastic fibres and large pigment cor- puscles loosely arranged; it contains lym- phatic spaces lined with endothelium. This is the lamina suprachoroidea. More inter- nally is a layer of arteries and veins arranged in a system of venous whorls, together with elastic fibres and branched pigment cells. The lymphatics, too, are well developed around the blood-vessels, and there are besides distinct lymph spaces lined with endothelium. Internal to this is a layer of fine capillaries, very dense, and derived from the arteries of the outer coat and ending in veins in that coat. It contains corpuscles without pigment, and lymph spaces which surround the blood-vessels {membrana chorio-e axillaris). It is separated from the retina by a fine elastic membrane {membrane of Fio. 566. — Section through the choroid coat of the,human eye. 1, Membrane of Bruchr; 2, chorio-capillaris or tunica Ruy- schiana ; 3, proper substance of the choroid with large vessels cut through; 4, suprachoroidea; 5, sclerotic. (Schwalbe.) Fig. 567. — Section through the eye carried through the ciliary processes. 1, Cornea; 2, membrane of Descemet; 3, sclerotic; 3', corneo-scleral junction; 4, canal of Schlemm ; 5, vein; 6, nucleated network on inner wall of canal of Schlemm ; 7, lig. pectinatum iridis, abe ; 8, iris ; 9, pigment of iris (uvea); 10, ciliary processes ; 11, ciliary muscle; 12, choroid tissue; 13, meridional, and 14, radiating fibres of ciliary muscle; 15, ring-muscle of Miiller; 16, circular or angular bundles of ciliary muscle. (Schwalbe.) Bruch), which is either structureless or finely fibrillated. (Fig. 566, 1.) The choroid coat ends in front in what are called the ciliary processes (figs. 567, 568). These consist of from 70 to 80 meridion- ally arranged radiating plaits, which consist of blood-vessels, fibrous OH. LVI.] THE IRIS AND LEXS '69 They are lined by a The ciliary processes [G. 56S. — Ciliary processes, as seen from behind. 1, Posterior surface of the iris, -n-ith the sphincter muscle of the pupil ; 2, anterior part of the choroid coat ; 3, one of the ciliary processes, of which about seventy are represented. connective tissue, and pigment corpuscles continuation of the membrane of Bruch. terminate abruptly at the margin of the lens. The ciliary muscle (13, 14, and 15, fig. 567), takes origin at the corneo-scleral junction. It is a ring /. of muscle, 3 mm. broad and 8 mm. thick, made up of fibres running in three directions. (a) Meridional fibres near the sclerotic and passing to the choroid; (b) radial fibres in- serted into the choroid behind the ciliary processes ; and (c) circular fibres (muscle of Miiller), more in- ternal ; they constitute a sphincter. The Iris is a continuation of the choroid inwards beyond the ciliary processes. It is a fibro-muscular membrane perforated by a central aperture, the pupil. Posteriorly is a layer of pigment cells {uvea), which is a con- tinuation forwards of the pigment layer of the retina. The structure of the iris proper is made of connective tissue in front with corpuscles which may or may not be pigmented, and behind of similar tissue supporting blood - vessels. The pigment cells are usually well developed here, as are also many nerve-fibres radiating towards the pupil. Surrounding the pupil is a layer of circular unstriped muscle, the sphincter pupillce. In some animals there are also muscle-fibres which radiate from the sphincter in the substance of the iris forming the dilator pujoillce. The iris is covered anteriorly by a layer of epithelium continued upon it from the posterior surface of the cornea. The Lens is situated behind the iris, being enclosed in a distinct capsule, the posterior layer of which is not so thick as the anterior. It is supported in place by the suspensory ligament, fused to the anterior surface of the capsule. The suspensory ligament is derived from the hyaloid membrane, which encloses the vitreous humour. The lens is made up of a series of concentric laminae (fig. 569), which, when it has been hardened, can be peeled off like the coats of an onion. The laminse consist of long ribbon-shaped fibres, which in the course of development have originated from cells. The fibres near the margin have nuclei and are smooth, those near the centre are without nuclei and have serrated edges. They are hexagonal in transverse section. The fibres are united together 3C 770 THE EYE AND VISION [CII. LVI; by a scanty amount of cement substance. The central portion (nucleus) of the lens is the hardest. The epithelium of the lens consists of a layer of cubical cells anteriorly, which merge at the equator into the lens fibres. The development of the lens explains this transition. The lens at first consists of a closed sac composed of a single layer of epithelium. The cells of the posterior part soon elongate forwards and obliterate the cavity ; the anterior cells do not grow, but at the edge they become continuous with the posterior cells, which are gradually developed into fibres (fig. 570). The principal chemical constituent of the lens is a proteid of the globulin class called crystal! i /i. Corneoscleral junction. — At this junction the relation of parts (fig. 567) is so important as to need a short description. In this neigh- bourhood, the iris and ciliary processes join with the cornea. The proper substance of the cornea and the posterior elastic lamina become continuous with the iris, at the angle of the iris, and the iris sends forwards processes towards the posterior elastic lamina, form- Fig. 569. — Laminated structure of the crystalline lens. Thelaminre are split up after hardening in alcohol. 1, The denser central part or nucleus ; 2, the succes- sive external layers. }. (Arnold.) Fig. 570. — Meridional section through the lens of a rabbit. 1, Lens capsule ; 2, epithelium of lens; 3, transition of the epithelium into the fibres ; 4, lens fibres. (Bubuchin.) ing the ligamenhim pectinatu??i iridis, and these join with fibres of the elastic lamina. The epithelial covering of the posterior surface of the cornea is, as we have seen, continuous over the front of the iris. At the iridic angle, the compact inner substance of the cornea is looser, and between the bundles are lymph spaces called the spaces of Fontana. They are little developed in the human cornea. The spaces which are present in the broken-up bundles of corneal tissue at the angle of the iris are continuous with the larger lymphatic space of the anterior chamber. Above the angle at the corneo-scleral junction is a canal, which is called the canal of Schlemm. It is a lymphatic channel. The retina (fig. 571) apparently ends in front, near the outer part of the ciliary processes, in a finely-notched edge, — the ora CII. LVT.] THE RETINA 771 O O 0= " ,( ^ ex of refraction. mean curved surface of known curvature, and the differently refract- ing media into one mean medium the refractive power of which is known. The simplest so-called schematic eye formed upon this principle, CH. lvl] refraction of light 779 suggested by Listing as the reduced eye, has the following dimen- sions : — From anterior surface of cornea to the principal point = 2*3448 mm. From the nodal point to the posterior surface of lens = '4764 ,, Posterior chief focus lies behind cornea . . . = 22*8237 ,, Anterior chief focus in front of cornea . . . = 12*8326 ,, Radius of curvature of ideal surface . . . . = 5*1248 ,, The term index of refraction means the ratio of the sine of the angle of incidence to that of the angle of refraction ; this is explained in the small text beneath fig.. 579. In this reduced or simplified eye, the principal posterior focus, about 23 mm. behind the spherical surface, would correspond to the position of the retina behind the anterior surface of the cornea. The refracting surface would be situated about midway between the posterior surface of the cornea and the anterior surface of the lens. The optical axis of the eye is a line drawn through the centres of curvature of the cornea and lens, prolonged backwards to touch the retina between the porus opticus and fovea centralis, and this differs from the visual axis which passes through the nodal point of the reduced eye to the fovea centralis ; this forms an angle of 5° with the optical axis. But for practical purposes the optical axis and the visual axis may be considered to be identical. The visual or optical angle (fig. 580) is included between the lines drawn from the borders of any object to the nodal point; if the lines are prolonged backwards they include an equal angle. It has been shown by Helmholtz that the smallest angular distance between two points which can be appreci- ated as two distinct points = 50 seconds, the size of the retinal image being 3 , 65 / u ; this is a little more than the diameter of a cone at the fovea Centralis which = 3/A, fig. 5S0.-Diagram of the optical angle. the distance between the centres of two adjacent cones being = 4/a. If the two points are so close together that they subtend a visual angle less than 50 seconds, both images will fall upon one cone, and the two points will therefore appear as one. Any object, for example, the arrow A B (fig. 581), may be con- sidered as a series of points from each of which a pencil of light diverges to the eye. Take, for instance, the rays diverging from the tip of the arrow A ; C represents the curvature of the schematic or reduced eye ; the ray which passes through the centre of the circle of which C C is part is not refracted ; this point is represented as an asterisk in fig. 581 ; it is near the posterior surface of the crystal- 780 THE EYE AND VISION [CII. LVI. line lens ; the ray A C, which is parallel to the optic axis 0', is refracted through the principal posterior focus P, and cuts the first ray at the point A' on the retina. All the other rays from A meet at the same point. Similarly the other end of the arrow B is focussed at B', and rays from all other point;? have corresponding focusses. It will thus be seen that an inverted image of external objects is Fio. 5S1.— Diagram of the course of the rays of light, to show how an Image is formed upon the retina. The surface C C should be supposed to represent the ideal curvature. formed on the retina. The retina is a curved screen, but the images fall only on a small area of the retina under normal circumstances ; hence, for practical purposes, this small area may be regarded as flat. The question then arises, Why is it that objects do not appear to us to be upside down ? This is easily understood when we remember that the sensation of sight occurs not in the eye, but in the brain. By education the brain learns that the tops of objects excite certain portions of the retina, and the lower parts of objects other portions of the retina. That these portions of the retina are reversed in position to the parts of the object does not matter at all, any more than it matters when one's photograph arrives home from the photographer's that it was wrong way up in the photographer's camera — one puts it right way up in the photograph album. Accommodation The power of accommodation is primarily due to an ability to vary the shape of the lens ; its front surface becomes more or less convex, according as the distance of the object looked at is near or far. The nearer the object, the more convex, up to a certain limit, the front surface of the lens becomes, and vice versd ; the back surface takes no share in the production of the effect required. The posterior surface, which during rest is more convex than the anterior, is thus rendered the less convex of the two during accommodation. The following simple experiment illustrates this point : If a lighted CH. LVI.] ACCOMMODATION 781 candle be held a little to one side of a person's eye an observer looking at the eye from the other side sees three images of the flame (fig. 582). The first and brightest is (1) a small erect image formed by the anterior convex surface of the cornea ; the second (2) is also erect, but larger and less distinct than the preceding, and is formed at the anterior convex surface of the lens; the third (3) is smaller, inverted, and indistinct; it is formed at the posterior surface of the lens, which is concave forwards, and therefore, like all concave mirrors, gives an inverted image. If now the eye under observation is made to look at a near object, the second image becomes smaller, clearer, and approaches the first. If the eye is now adjusted for a far point, the second image enlarges again, becomes less distinct, and recedes from the first. In both cases the first and third images remain unaltered in size, distinct- ness, and position. This proves that during accommodation for near objects the curva- ture of the cornea, and of the posterior surface of the lens, remain unaltered, while the anterior surface of the lens becomes more convex and approaches the cornea. The experiment is more striking when two bright images (repre- sented by arrows in fig. 583) are used ; the two images from the front Fig. 5S2. — Diagram showing thiee reflections of a candle. 1, From the anterior surface of cornea ; 2, from the anterior surface of lens ; 3, from the posterior sur- face of lens. Fio. 583. — Diagram of Sanson's images. A, When the eyes are not, and B, when they are focussed for near objects. The fig. to the right in A and B is the inverted image from the posterior surface of the lens. surface of the lens during accommodation not only approach those from the cornea, but also approach one another, and become some- what smaller. (Sanson's Images). Helmholtz's Phakoscope (fig. 584) is a triangular box with arrangements for demonstrating this experiment. Mechanism of Accommodation. — The lens having no inherent power of contraction, its changes of outline must be produced by 782 THE EYE AND VISION [CH. LVI. some power from without; this power is supplied by the ciliary muscle. Its action is to draw forwards the choroid, and by so doing to slacken the tension of the suspensory ligament of the . ".St.- Phakosc pe of llelmhultz. At V, If are. two prisms, by which the light of a candle is con- e. nitrated on Llie eye of the person experimented with, which is looking through a hole in the third angle of the box opposite to the window C. A is the aperture for the eye of the observer. The observer notices three double images, represented by arrows, in fig. 533, reflected from the eye under ex tmination when the eye is fixed upon a distant object ; the position of the images having been noticed, the eye is made to focus a uear object, such as a reed pushed up at C ; the images from the anterior surface of the lens will be observed to move as described in the text. lens which arises from it. The anterior surface of the lens is kept flattened by the action of this ligament. The ciliary muscle during accommodation, by diminishing its tension, diminishes to a proportional degree the flattening of which it is the cause. On diminution or cessation of the action of the ciliary muscle, the lens returns to its former shape, by virtue of the elasticity of the suspen- sory ligament (fig. 585). From this it will appear that the eye is usually focussed for distant objects. In viewing near objects the ciliary muscle contracts ; the ciliary muscle relaxes on withdrawal of the attention from near to distant objects. It is possible to calculate the curvature of the lens or cornea in the body, by measuring the size of the image of an object upon it. The radius (>•) of curvature of a convex reflecting surface is given by the formula r= — ; a is the distance of the object from the surface, b the diameter of the image, and c that of the object. a and e are easily measured ; l> is measured by Helmholtz's ophthalmometer, the principle of which is as follows : — If a line is looked at through a plate of glass placed obliquely between it and the eye, the line is shifted sideways to either right cir. lvl] RANGE OF VISION 783 or left ; if the glass plate is then placed obliquely at right angles to its previous position, the line is shifted in the opposite direction. In the ophthalmometer there are two glass plates intersecting each other at an angle ; the image of a bright horizontal line upon the lens or cornea is looked at through the junction between the two plates ; one plate shifts the image to the right, the other to the left ; the angle between the two plates is altered until the line appears as two distinct lines just touching each other. The amount of shifting of each, which must therefore be half the length of the image of the line, can be easily calculated if the thickness of the glass plates, their refractive index, and the angle between them are known. Double this result gives the size of the image on the surface under investigation. Range of Distinct Vision. Near-point. — In every eye there is a limit to the power of accommodation. If a book be brought nearer and nearer to the eye, the type at last becomes indistinct, and cannot be brought into focus by any effort of accommodation, however Fig. 5S5. -Diagram representing by dotted lines the alteration in the shape of the lens on accommo- dation for near objects. (E. Landolt.) strong. This, which is termed the near-point, can be determined by the following experiment {Scheiner). :./Two small holes are pricked in a card with a pin not more than a twelfth of an inch (2 mm.) apart ; at any rate their distance from each other must not exceed the diameter of the pupil. The card is held close in front of the eye, and a small needle viewed through the pin-holes. At a moderate distance it can be clearly focussed, but when brought nearer, beyond a certain point, the image appears double, or at any rate blurred. This point where the needle ceases to appear single is the near-point. Its distance from the eye can of course be readily measured. It is usually about 5 or 6 inches (13 cm.). In the accompanying figure (fig. 586) the lens b represents the refractive apparatus of the eye; e and/ the two pin-holes in the card, nn the retina ; a represents the position of the needle. When the needle is at a moderate distance, the two pencils of light coming from e and/ are focussed at a single point on the retina nn. If the needle is brought nearer than the near-point, the strongest effort of accommodation is not sufficient to 784 THE EYE AND VISION [CII. LVI. focus the two pencils, they meet at a point behind the retina. The effect is the same as if the retina were shifted forward to mm. Two images h.g. are formed, one from each hole. It is interesting to note Fig. 586. — Diagram of experiment to ascertain the minimum distance of distinct vision. that when two images are produced, the lower one g really appears in the position q, while the upper one appears in the position p. This may be readily verified by covering the holes in succession. During accommodation two other changes take place in the eyes : (1) The eyes converge owing to the action of the internaLrectus muscle of each eyeball. (2) The pupils contract. The contraction of all of the muscles which have to do with accommodation, viz., of the ciliary muscle, of the internal recti muscles, and of the sphincter pupillae, is under the control of the third nerve. It should further be noted that although the act is a voluntary one, the fibres of the ciliary muscle and of the sphincter pupillae are of the plain variety. The account of accommodation v.. given in the preceding pages is true for man and other mammals, birds, and certain reptiles. Beer has, however, shown that in many animals lower in the scale, the mechanism of accommodation varies a good deal, and is often very different from that just described, consisting, in fact, in a power of altering the distance between the lens and the retina. In bony fishes, the eye at rest is accommodated for near objects ; in focussing for distant objects the lens is drawn nearer to the retina by a special muscle called the retractor lentis. In cephalopods the same occurs, but the retractor lentis is absent ; here the approach of the lens to the retina is brought about by an alteration of intra-ocular tension. In Amphibia and most snakes, the eye at rest is focussed for distant objects ; in accommodating for near objects the lens, by alteration of intra-ocular tension, is brought forward, that is, the distance between it and the retina is increased. There appear to be not a few animals in all classes which do not possess the power of accommodation at all. Indeed, Barrett states this is so for most mammals. Defects in the Optical Apparatus Under this head we may consider the defects known as (1) Myopia, (2) Hypermetropia, (3) Astigmatism, (4) Spherical Aber- ration, (5) Chromatic Aberration. The normal {emmetropic) eye is so adjusted that at rest parallel CH. LVI.] ERRORS OF REFRACTION 785 rays are brought exactly to a focus on the retina (1, fig. 587). Hence all objects except near ones (practically all objects more than twenty feet off) are seen without any effort of accommodation ; in other words, the far-point of the normal eye is at an infinite distance. Fig. 587. — Diagram showing — 1, normal {emmetropic') eye bringing parallel rays exactly to a focus on the retina ; 2, normal eye adapted to a near-point ; without accommodation the rays would be focussed behind the retina, but by increasing the curvature of the anterior surface of the lens (shown by a dotted line) the rays are focussed on the retina (as indicated by the meeting of the two dotted lines) ; 3, hypermetropic eye ; in this case the axis of the eye is shorter than normal ; parallel rays are focussed behind the retina ; 4, myopic eye ; in this case the axis of the eye is abnormally long ; parallel rays are focussed in front of the retina. The figure incorrectly represents the refraction as occurring only in the crystalline lens; the principal refraction really occurs at the anterior surface of the cornea. In viewing near objects we are conscious of the effort (the contraction of the ciliary muscle) by which the anterior surface of the lens is rendered more convex, and rays which would otherwise be focussed behind the retina are converged upon the retina (see dotted lines, 2, fig. 587). 1. Myopia (short-sight), (4, fig. 587).- — This defect is due to an 3D 786 THE EYE AND VISION [CII. LV1. abnormal elongation of the eyeball. The retina is too far from the lens, and consequently parallel rays are focussed in front of the retina, and, crossing, form little circles on the retina ; thus the images of distant objects are blurred and indistinct. The eye is, as it were, permanently adjusted for a near-point. Kays from a point near the eye are exactly focussed on the retina. But those which issue from any object beyond a certain distance {far-point) cannot be distinctly focussed. This defect is corrected by concave glasses which cause the rays entering the eye to diverge : hence they do not come to a focus so soon. Such glasses, of course, are only needed to give a clear vision of distant objects. For near objects, except in extreme cases, they are not required. 2. Hypermctropia (3, fig. 587). — This is the reverse defect. The eyeball is too short. Parallel rays are focussed behind the retina : an effort of accommodation is required to focus even parallel rays on the retina ; and when they are divergent, as in viewing a near object, the accommodation is insufficient to focus them. Thus, in well- marked cases, distant objects require an effort of accommodation, and near ones a very powerful effort, and the ciliary muscle is, therefore, constantly acting. This defect is obviated by the use of convex glasses, which render the pencils of light more convergent. Such glasses are, of course, especially needed for near objects, as in reading, etc. They rest the eye by relieving the ciliary muscle from excessive work. 3. Astigmatism. — This defect, which was first discovered by Airy, is clue to a greater curvature of the eye in one meridian than in others. The eye may be even myopic in one plane, and hyper- metropic in others. Thus vertical and horizontal lines crossing each other cannot both be focussed at once; one set stand out clearly, and the others are blurred and indistinct; This defect, which is present in a slight degree in all eyes, is generally seated in the cornea, but occasionally in the lens as well ; it may be corrected by the use of cylindrical glasses (i.e., curved only in one direction). 4. Spherical Aberration. — The rays of a cone of light from an object situated at the side of the field of vision do not meet all in the same point, owing to their unequal refraction ; for the refraction of the rays which pass through the circumference of a lens is greater than that of those traversing its central portion. This defect is known as spherical aberration, and in the camera, telescope, microscope, and other optical instruments, it is remedied by the interposition of a screen with a circular aperture in the path of the rays of light, cutting off all the marginal rays, and only allowing the passage of those near the centre. Such correction is effected in the eye by the iris, which prevents the rays from passing through any part of the refractive apparatus but its centre. The image of an CH. LVI.] ERRORS OF REFRACTION 787 object will be most defined and distinct when the pupil is narrow, the object at the proper distance for vision, and the light abundant ; so that, while a sufficient number of rays are admitted, the narrow- ness of the pupil may prevent the production of indistinctness of the image by spherical aberration. Distinctness of vision is further secured by the pigment of the outer surface of the retina, the posterior surface of the iris and the ciliary processes, which absorbs most of the light which is reflected within the eye, and prevents its being thrown again upon the retina so as to interfere with the images there formed. 5. Chromatic Aberration. — In the passage of light through an ordinary convex lens, decomposition of each ray into its elementary colours commonly ensues, and a coloured margin appears around the image, owing to the unequal refraction which the elementary colours undergo. In optical instruments this, which is termed chromatic aberration, is corrected by the use of two or more lenses, differing in shape and density, the second of which continues or increases the refraction of the rays produced by the first, but by recombining the individual parts of each ray into its original white light, corrects any chromatic aberration which may have resulted from the first. It is probable that the unequal refractive power of the transparent media in front of the retina may be the means by which the eye is enabled to guard against the effect of chromatic aberration. The human eye is achromatic, however, only so long as the image is received at its focal distance upon the retina, or so long as the eye is properly accommodated. If these conditions are interfered with, a more or less distinct appearance of colours is produced. From the insufficient adjustment of the image of a small white object, it appears surrounded by a sort of halo or fringe. This phenomenon is termed Irradiation. It is partly * for this reason that a white square on a black ground appears larger than a black square of the same size on a white ground. The phenomenon is naturally more marked when the white object is a little out of focus. Defective Accommodation — Presbyopia. — This condition is due to the gradual loss of the power of accommodation which is an early sign of advancing years. In consequence, the person is obliged in reading to hold the book further and further away in order to focus the letters, till at last the letters are held too far for distinct vision. The defect is remedied by weak convex glasses. It is due chiefly to the gradual increase in density of the lens, which is unable to swell out and become convex when near objects are looked at, and also to a weakening of the ciliary muscle, and a general loss of elasticity in the parts concerned in the mechanism. * The phenomenon is also partly due to what is called " spatial induction." 788 THE EYE AND VISION [CH. I.V1 Functions of the Iris. The iris has three uses : — 1. To act as a diaphragm in order to lessen spherical aberration in the manner just described. 2. To regulate the amount of light entering the eye. In a bright light the pupil contracts ; in a dim light it enlarges. This may be perfectly well seen in one's own iris by looking at it in a mirror while one alternately turns a gas-light up and down. 3. By its contraction during accommodation it supports the action of the ciliary muscle. The muscular fibres (unstriped in mammals, striped in birds) of the iris are arranged circularly around the margin of the pupil, and radiatingly from "its margin. The radiating fibres are best seen in the eyes of birds and otters; some look upon them as elastic in nature, but there is little doubt that they are contractile. Those who believe they are not contractile explain dilatation of the pupil as due to inhibition of the circular fibres. But if the iris is stimu- lated near its outer margin at three different points simultaneously the pupil assumes a triangular shape, the angles of the triangle corresponding to the points stimulated ; this must be clue to con- traction of three strands of the radiating muscle ; inhibition of the circular fibres would occur equally all round. The iris is supplied by three sets of nerve-fibres contained in the ciliary nerves. (a) The third nerve via the short ciliary nerves supplies the circular fibres. (b) The cervical sympathetic supplies the radiating fibres. The cilio-spinal centre which governs them is in the cervical region of the cord (see p. 676). The fibres leave the cord by the anterior root of the second thoracic nerve, pass into the cervical sympathetic, and reach the eyeball via the ophthalmic branch of the fifth, and long ciliary nerves. (c) Fibres of the fifth nerve which are sensory. The experiments on these nerves are those of section and stimula- tion of the peripheral ends; the usual experiments by which the functions of a motor nerve are discovered. Experiment. EH'ect on pupil. Third Third Sympathetic Sympathetic Both nerves together Section . Stimulation Section . Stimulation Stimulation Dilatation. Contraction. Contraction. Dilatation. | Contraction overcomes \ the dilatation. ch. lvl] uses of the ieis 789 Certain drugs dilate the pupil. These are called mydriatics; atropine is a well-known example. Others cause the pupil to contract. These are called myotics ; physostigmine and opium (taken internally) are instances. Different myotics and mydriatics act in different ways, some exerting their activity on the muscular, and others on the nervous structures of the iris. Reflex actions of the iris. — When the iris contracts under the influence of light, the sensory nerve is the optic, and the motor the third nerve. The central connection of the two nerves in the region of the mid-brain we shall see later on. The iris also contracts on accommodation ; and the reflex path concerned in this action is a different one from that concerned in the light reflex, as this reflex often remains in cases of locomotor ataxy, after there is an entire loss of the reflex to light (Argyll-Bobertson pupil). On painful stimulation of any part of the body, there is reflex dilatation of the pupil. This is accompanied by starting of the eyeballs, due to contraction of the plain muscle in the capsule of Tenon, which, like the dilator fibres of the iris, is supplied by the cervical sympathetic nerve. We may sum up the principal conditions under which the pupil contracts and dilates in the following table : — Causes of — Contraction of the Pupil. Dilatation of the Pupil. 1. Stimulation of third nerve. 1. Paralysis of the third nerve. 2. Paralysis of cervical sympathetic. 2. Stimulation of the cervical sympa- 3. When the eye is exposed to light. thetic. 4. When accommodation occurs. 3. In the dark. 5. Under the local influence of 4. When the accommodation is physostigmine. relaxed. 6. Under the influence of opium. ' 5. Under the local influence of atro- 7. During sleep. pine. This drug also paralyses the ciliary muscle. 6. In the last stage of asphyxia. 7. In deep chloroform narcosis. 8. Under the influence of certain emotions, such as fear. 9. During pain. There is a close connection of the centres that govern the activity of the two irides. If one eye is shaded by the hand, its pupil will of course dilate, but the pupil of the other eye will also dilate. The two pupils always contract or dilate together unless the cause is the local injury to the nerves of one side or the local action of drugs. Functions of the Eetina. The Eetina is the nervous coat of the eye ; it contains the layer of nerve-epithelium (rods and cones) which is capable of receiving 790 THE EYE AND VISION [CM. LY1. the stimulus of light, and transforming it into a nervous impulse which passes to the brain by the optic nerve. The bacillary layer, or layer of rods and cones, is at the back of all the other retinal layers, which the light has to penetrate before it can affect this layer. The proofs of the statement that it is the layer of the retina which is capable of stimulation by light are the following : — (1) The point of entrance of the optic nerve into the retina, where the rods and cones are absent, is insensitive to light, and is called the Mind spot. This is readily demonstrated by what is known as Mariotte's experiment. If we direct one eye, the other being closed, upon a point at such a distance to the side of any object, that the image of the latter must fall upon the retina at the point of entrance of the optic nerve, this image is lost. If, for example, we close the left eye, and look steadily with the right eye at the dot here represented, while the page is held about six inches from the eye, both dot and cross are visible. On gradually increasing the distance between the page and the eye, still keeping the right eye steadily on the dot, it will be found that suddenly the cross dis- appears from view, because its image has fallen on the blind spot ; on removing the book still farther, it comes in sight again. The question has arisen why we are not normally conscious of a gap in the image. The gap is not felt for the reason that a defect of light sensations at a spot blind from the beginning can no more be per- ceived as a gap in the image than the blindness, say, of the skin of the back or foot can be so perceived. (2) In the fovea centralis which contains rods and cones but no optic nerve-fibres, and in which the other layers of the retina are thinned down to a minimum, light produces the greatest effect. In the macula lutea, cones occur in large numbers, and in the fovea centralis cones without rods are found, whereas, in the rest of the retina which is not so sensitive to light, there are fewer cones than rods. (3) If a small lighted candle is moved to and fro at the side of and close to one eye in a darkened room, while the eyes look steadily forward on to a dull background, a remarkable branching figure (Purkinje's figures) is seen floating before the eye, consisting of dark lines on a reddish ground. As the candle moves, the figure moves in the opposite direction, and from its whole appearance there can be no doubt that it is a reversed picture of the retinal vessels pro- CH. LVI.] functions of the eetina 791 jected before the eye.* This remarkable appearance is due to shadows of the retinal vessels cast by the candle ; and it is only when they are thrown upon the retina in an unusual slanting direction that they are perceived. The branches of these vessels are distributed in the nerve-fibre and ganglionic layers ; and since the light of the candle falls on the retinal vessels from in front, the shadow is cast behind them, and hence those elements of the retina which perceive the shadows must also lie behind the vessels. Here, then, we have a clear proof that the light-perceiving elements are not the inner, but one of the external layers of the retina ; further than this, calculation has shown it is the layer of rods and cones. The data for such a calculation are — the dimensions of the eyeball, the distance of the screen from the eye, the angle through which the candle is moved, and the displacement of the figure seen. Duration of Visual Sensations. — The duration of the sensation produced by a luminous impression on the retina is always greater than that of the impression which produces it. However brief the luminous impression, the effect on the retina always lasts for about one-eighth of a second. Thus, supposing an object in motion, say a horse, to be revealed on a dark night by a flash of lightning. The object would be seen apparently for an eighth of a second, but it would not appear in motion ; because, although the image remained on the retina for this time, it was really revealed for such arj extremely short period (a flash of lightning lasting only a millionth of a second) that no appreciable movement on the part of the object could have taken place in the period during which it was revealed to the retina of the observer. The same fact is proved in a reverse way. The spokes of a rapidly revolving wheel are not seen as distinct objects, because at every point of the field of vision over which the revolving spokes pass, a given impression has not faded before another replaces it. Thus every part of the interior of the wheel appears occupied. The stimuli which excite the retina are exceedingly slight ; for instance, the minimum stimulus in the form of green light is equal in terms of work to that which is done in raising a ten-millionth part of a milligramme to the height of a millimetre, and even some of this is doubtless wasted in the form of heat. The time during which the stinmlus acts may be excessively small, thus light from a rapidly rotating mirror is visible even when it only falls upon the retina for one eight-millionth part of a second. Some physiologists have drawn an analogy between retinal and muscular excitations. There is no complete analogy, but the following points of resemblance may be noted : — 1. The retina like the muscle possesses a store of potential energy, which the stimulus serves to fire off. 2. Fatigue on action, and recovery after rest are noticeable in both. * Purkinje's figures can be much more readily seen by simply looking steadily down a microscope, and moving the whole instrument backwards and forwards, or from side to side, while so doing. 792 THE EYE AND VISION [CH. LVI. 3. The curve of retinal excitation, like the muscle curve, rises not abruptly but gradually to its full height, and on the cessation of the stimulus takes a measurable time to fall again, the retinal impression outlasting the stimulus by about one-eighth of a second. 4. With comparatively slow intermittent excitation, the phenomenon known as flicker takes place ; this may be shown by the slow rotation on Maxwell's machine of a disc painted with alternate black and white sectors. This roughly corresponds with what in a muscle is called incomplete tetanus. 5. When the rate of stimulation is increased, as by increasing the speed of rota- tion of the disc just alluded to (say to twenty or thirty times a second) the resulting sensation is a smooth one of greyness. This fusion of individual stimuli into a con- tinuous sensation, does not by any means correspond to the complete tetanus of muscle, for the resultant sensation has a brightness corresponding not to a summa- tion of the individual fusing sensations, but to a brightness which would ensue if the stimuli were spread evenly over the surface of the disc (Talbot's Law). The Ophthalmoscope. Every one is perfectly familiar with the fact, that it is quite im- possible to see W\q fundus or back of another person's eye by simply looking into it. The interior of the eye forms a perfectly black background.* The same remark applies to the difficulty we experi- ence in seeing into a room from the street through the window unless the room is lighted within. In the case of the eye this fact is partly due to the feebleness of the light reflected from the retina, most of it being absorbed by the retinal pigment ; but far more to the fact that every such ray is reflected straight to the source of light {e.g., candle), and cannot, therefore, be seen by the unaided eye without intercepting the incident light from the candle, as well as the reflected rays from the retina. This difficulty is surmounted by the use of the ophthalmoscope. The ophthalmoscope was invented by Helmholtz ; as a mirror for reflecting the light into the eye, he employed a bundle of thin glass plates ; this mirror was transparent, and so he was able to look through it in the same direction as that of the rays of the light it reflected. It is almost impossible to over-estimate the boon this instrument has been to mankind ; previous to this in the examina- tion of cases of eye disease, the principal evidence on which the surgeon had to rely was that derived from the patient's sensations ; now he can look for himself. The instrument, however, has been greatly modified since Helm- holtz's time ; the principal modification is the substitution of a con- cave mirror of silvered glass for the bundle of glass plates ; this is * In some animals (/>.;/■, the cat), the pigment is absent from a portion of the retinal epithelium ; this forms the Tapetum luridum. The use of this is supposed to be to increase the sensitiveness of the retina, the light being reflected back through the layer of rods and cones. It is certainly the case that these animals are able to see clearly with less light than we can, hence the popular idea that a cat can see in the dark. In fishes a tapetum lucidum is often present ; here the brightness is increased by crystals of guanine. en. lvl] THE OPHTHALMOSCOPE 793 mounted on a handle, and is perforated in the centre by a small hole through which the observer can look. The methods of examining the eye with this instrument are — the direct and the indirect : both methods of investigation should be employed. A drop of a solution of atropine (two grains to the ounce) or of homa- tropine hydrobromate, should be instilled about twenty minutes before the examination is com- menced ; the ciliary muscle is thereby paralysed, the power of accommodation is abolished, and the pupil is dilated. This will materially facili- tate the examination ; but it is quite possible to observe all the details to be presently described without the use of such drugs. The room being now darkened, the observer seats himself in front of the person whose eye he is about to examine, placing himself upon a somewhat higher level. Let us suppose that the right eye of the patient is being examined. A brilliant and steady light is placed close to the left ear of the patient. Taking the mirror in his right hand, and looking through the central hole, the operator directs a beam of light into the eye of the patient. A red glare, known as the reflex, is seen; it is due to the illumination of the retina. The patient is then told to look at the little finger of the observer's right hand as he holds the mirror ; to effect this the eye is rotated somewhat inwards, and at the same time the reflex changes from red to a lighter colour, owing to the reflection from the optic disc. The observer now approximates the mirror, with his eye to the eye of the patient, taking care to keep the light fixed upon the pupil, so as not to lose the reflex. At a certain point, which varies with different eyes, but is usually reached when there is an interval of about two or three inches between the observed and the observing eye, the vessels of the retina become visible. Examine carefully the fundus of the eye, i.e., the red surface — until the optic disc is seen ; trace its circular outline, and observe the small central white spot, the porus opticus, or physi- ological pit : near the centre is the central artery of the retina breaking up upon the disc into branches ; veins also are present, and correspond roughly to the course of the arteries. Trace the vessels over the disc on to the retina. Somewhat to the outer side, and only visible after some practice, is the yellov) spot, with the smaller lighter-coloured fovea centralis in its centre. This constitutes the direct method of examination ; by it the various details of the fundus are seen as they really exist, and it is this method which should be adopted for ordinary use. If the observer is myopic or hypermetropic, he will be unable to employ the direct method of examination until he has remedied his defective vision by the use of proper glasses. In the indirect method the patient is placed as before, and the operator holds the mirror in his right hand at a distance of twelve to eighteen inches from the patient's right eye. At the same time he rests his left little finger lightly upon the patient's right temple, and holding a convex lens between his thumb and forefinger, two or three inches in front of the patient's eye, directs the light through the lens into the eye. The red reflex, and subsequently the white one, having been gained, the operator slowly moves his mirror, and with it his eye, towards or away from the face of the Fig. 5SS.— The Ophthalmoscope. The small upper mirror is for direct, the larger for indirect, illumination. ■94 THE EYE AND VISION [CII. LVI. patient, until the outline of one of the retinal vessels becomes visible, when very slight movements on the part of the operator will suffice to bring into view the details of the fundus above described, but the image will be much smaller and in- verted. The appearances seen are depicted in fig. ")74. The lens should be kept fixed at a distance of two or three inches, the mirror alone being moved until the disc becomes visible : should the image of the mirror, however, obscure the disc, the lens may be slightly tilted. The two next figures show diagrammatically the course of the rays of light. Fig. 589 represents what occurs when employing the direct method. S is the Fig. 589.— The course of the light intexaminingjtbeeye by the direct method. (T. G. Brodie.) source of light, and M M the concave mirror with its central aperture, which reflects the rays ; these are focussed by the eye E, which is being examined, toapointin the vitreous humour, and this produces a diffuse lighting of the interior of the eyeball. Rays of light issuing from the point p emerge from the eye parallel to one another, and enter the observer's eye E 1 ; they are brought to a focus p 1 on the retina as the eye is accommodated for distant vision. Similarly the point m and n will give rise to images at m 1 and n 1 respectively. Fig. 590 represents what occurs in examining the eye by the indirect method. Fig. 590. — The course of the light in examining the eye by the indirect method. (T. G. Brodie.) S is the source of light, M M the mirror, E the observed, and E 1 the observing eye as before. The rays of light are reflected from the mirror and form an image at o 1 ; they then diverge and are again made convergent by the lens L held in front of the eye by the observer; by this means a second image is focussed just behind the crystalline lens of the eye E. They then again diverge and diffusely light up CH. LYI.] THE PERIMETER 795 the interior of the eyeball. The rays of light reflected from two points i and m on the retina diverging from the eye are refracted to the glass lens L, and give an inverted real image i 1 m 1 larger than the object i in. These latter rays then diverge, and are collected and fooussed by the observing eye E 1 to give an image i 2 rri 1 on the retina. (T. G. Brodie.) The Perimeter. This is an instrument for mapping out the field of vision. It consists of a graduated arc, which can be moved into any position, Fig. 591.— Priestley Smith's Perimeter. and which when rotated traces out a hollow hemisphere. In the centre of this the eye under examination is placed, the other eye being closed. The examiner then determines on the surface of the hemisphere those points at which the patient just ceases or just begins to see a small object moved along the arc of the circle. These points are plotted out on a chart graduated in degrees, and by con- necting them the outline of the field of vision is obtained. Fig. 591 shows one of the forms of perimeter very generally employed, and fig. 592 represents one of the charts provided with the instrument. The blind spot is shown, and the dotted line represents the normal average field of vision for the right eye. It will be seen that the field of vision is most extensive on the outer side ; it is less on the inner side because of the presence of the nose. By the use of the same instrument, it is found that the colour of a coloured object is not distinguishable at the margin, but only towards the centre of the field of vision, but there are differences 796 THE EYE AND VISION [CH. LVI. for different colours ; thus a blue object is seen to be blue over a wider field than a red, and a red over a wider field than a green object. 100 180 Fig. 592. — Perimeter chart for the right eye. In disease of the optic nerve, contraction of the field of vision for white and coloured objects is found. This is often seen before any change in the optic nerve is discoverable by the ophthalmoscope. The yellow spot of one's own eye can be rendered evident by what is called Clerk-Maxwell's experiment : — On looking through a solution of chrome-alum in a bottle with parallel sides, an oval purplish spot is seen in the green colour of the alum. This is due to the pigment of the yellow spot. Colour Sensations. Colours may differ (1) in hue, for instance, blue, red, yellow ; (2) in saturation, for instance, pale green and full green ; this depends upon the degree of admixture with white light; and (3) in intensity, CH. LVI.] COLOUR SENSATIONS 797 i e., the amount of light per unit area of surface. These differences are dependent respectively on the length, the purity, and the ampli- tude of the light-wave. Colours also differ (4) in brightness or luminosity; this is a purely physiological quality devoid of any known physical counterpart. The brightness of a colour may be measured by determining the shade of grey to which it appears equivalent. Even the most saturated colours (for instance, yellow and blue) have different degrees of brightness varying with change of illumination (see also p. 803). If a ray of sunlight is allowed to pass through a prism, it is decomposed by its passage into rays of different colours, which are called the colours of the spectrum ; they are red, orange, yellow, green, blue, indigo, and violet. The red rays are the least turned out of their course by the prism, and the violet the most, whilst the other colours occupy in order places between these two extremes. The differences in the colour of the rays depend upon the rapidity of vibrations producing each, the red rays being the least rapid and the violet the most. In addition to these, there are others which are invisible but which have definite properties ; those to the left of the red are less refrangible, being the calorific rays which act upon the thermometer, and those to the right of the violet, which are called the actinic or chemical rays, have a powerful chemical action. "White light may be built from its constituents in several ways, for instance, by a second prism reversing the dispersion produced by the first, or by causing the colours of the spectrum to fall on the retina in rapid succession. The best way to study the effects of mixing colour sensations is by means of a rapidly revolving disc to which two or more coloured sectors are fixed. Each colour is viewed in rapid succession, and owing to the persistence of retinal impressions, the constituent colour impressions blend and give a single sensation of colour. (Maxwell.) White light can be produced by the mixture of the three primary colours, or even of two colours in certain hues and proportions. These pairs of colours, of which red and greenish-blue, orange and blue, and violet and yellow are examples, are called complementary. The colours are not of equal stimulation energy, otherwise they might be arranged around a circle ; they are more properly arranged in a triangle, with red, green, and violet at the angles (fig. 593). The red, green, and violet are selected on the theory of Helmholtz that they constitute the three primary colour sensations ; other colour sensations are mixtures of these. Thus, the orange and yellow between the red and green are mixtures of the red and green sensations ; the blue a mixture of green and violet ; and the purples (which are not represented in the spectrum) of red and violet. 798 THE EVE AND VISION [CII. LVL Join the three angles red, green, and violet, and one gets white light; or join the bine and orange, which comes to the same thing, and one also gets white. Blue and orange on Maxwell's disc give white ; but it is well known that a mixture of blue and orange paint gives green ; how can om explain this ? Suppose the paint is laid on white paper; the white light from the paper on its way to the eye passes through transparent particles of blue and orange pigment ; the blue particles only let the green and violet sensations reach the eye, and cut off the red ; the yellow particles only let the red and green through, and cut off the violet. The red and violet being thus cut off, the green sensation is the only one which reaches the eye. The experiments which led Helmholtz and others to the selection of green, red, and violet as the three fundamental colour sensations were performed in this way : the eye undergoes exhaustion to a colour when exposed to it for some time ; suppose, for instance, the eye is fatigued for red, and is then exposed to a pure yellow light, such as that given off by the sodium flame, the yellow then appears greenish ; or fatigue the eye for green and then expose it to blue, the blue will have a violet tint. By the repetition of numerous experiments of this kind, it was found that the fatigue experienced manifested itself in three colours, red, green, and violet, which were therefore selected as the three fundamental colour sensations. It was also found that these three colour sensa- tions could not be produced by any combination of other colour sensations, and further that all other colour sensations can be obtained by mixing these three in various proportions. The theory of colour vision constructed on these data was originated by Thomas Young, and independently discovered and elaborated by Helmholtz. It is consequently known as the Young- Helmholtz theory. This theory teaches that there are in the retina certain elements (? cones) which answer to each of these primary colours, whereas the innumeiable intermediate shades of colour are produced by stimulation of the three primary colour terminals in different degrees, the sensation of white being produced when the three elements are equally excited. Thus, if the retina is stimulated by rays of certain wave length, at the red end of the spectrum, the terminals of the other colours, green and violet, are hardly stimulated at all, but the red terminals are strongly stimulated, the resulting sensation being red. The orange rays excite the red terminals con- Fig. 593. — Colour triangle. MI. LVI.] THEORIES OF COLOUR VISION 799 siderably, the green rather more, and the violet slightly, the result- ing sensation being that of orange, and so on (fig. 594). Another theory of colour vision (Hering's) supposes that there are six primary colour sensations, viz. : three pairs of antagonistic colours, black and white, red and green, and yellow and blue ; and that these are produced by the changes either of disintegration or of assimilation taking place in certain substances, somewhat, it may be supposed, of the nature of the visual purple, which (the theory supposes) exist in the retina. Each of the substances corresponding to a pair of colours is capable of undergoing two changes, one of construction and the other of disintegration, with the result of pro- ducing one or other colour. For instance, in the white-black substance, when disintegration is in excess of construction or assimi- lation, the sensation is white, and when assimilation is in excess of disintegration the reverse is the case ; and similarly with the red- green substance, and with the yellow-blue substance. When the repair and disintegration are equal with the first substance, the visual sensation is grey ; but in the other pairs, when this is the case, no sensation occurs. The rays of the spectrum to the left produce changes in the red-green substance only, with a resulting sensation of red, whilst the (orange) rays further to the right affect both the red-green and the yellow-blue sub- stances ; blue rays cause construc- tive changes in the yellow-blue substances, but none in the red-green, and so on. These changes produced in the visual substances in the retina are perceived by the brain as sensations of colour. Neither theory satisfactorily accounts for all the numerous complicated problems presented in the physiology of colour vision. One of these problems is colour blindness, a by no means uncommon visual defect. Some people are completely colour blind, but the commonest form is the inability to distinguish between red and green. Helmholtz's explanation of such a condition is, that the elements of the retina which receive the impression of red, etc., are absent, or very imperfectly developed, and Hering's would be that the red-green substance is absent from the retina. Other varieties of colour-blindness in which the other colour-perceiving elements are absent, have been shown to exist occasionally. Hering's theory appears to meet the difficulty best, for if the red Fig. 594. — Diagram of the three primary colour sensations. (Young-Helmholtz theory.) 1 is the red ; 2, green, and 3, violet, primary colour sensation. The lettering indicates the colours of the spectrum. The diagram indi- cates by the height of the curve to what extent the several primary sensations of colour are excited by vibrations of different ■wave lengths. 800 THE EYE AND VISION [CH. LVI. element of Helmholtz were absent, the patient ought not to be able to perceive white sensations, of which red is a constituent part ; whereas, according to Hering's theory, the white-black visual sub- stance remains intact. It likewise explains to some extent the phenomena of total colour blindness, which is an almost inconceiv- able condition, if the Young-Helmholtz theory is accepted. These two theories have been for a long time before the scientific world. As facts have accumulated, it has been for some years recognised that many facts could not be reconciled with either ; and modifications of one or the other have been from time to time introduced. The observations made by C. J. Burch are of considerable importance ; the following is a brief account of his methods and results. He finds that by exposing the eye to bright sunlight in the focus of a burning glass behind transparent coloured screens, it is possible to produce temporary colour blindness. After red light, the observer is for some minutes red-blind, scarlet geraniums look black, yellow flowers green, and purple flowers violet. After violet light, violet looks black, purple flowers crimson, and green foliage richer than usual. After light of other colours, corresponding effects are pro- duced. If one eye is made purple-blind, and the other green-blind, all objects are seen in their natural colours, but in exaggerated per- spective, due to the difficulty the brain experiences in combining the images from the two eyes. By using a brightly-illuminated spectrum, and directing the eye to certain of its colours, the eye in time becomes fatigued and blind for that colour, so that it is no longer seen in the spectrum. Thus, after green blindness is induced the red appears to meet the blue, and no green is seen. If, however, the eye is exposed to yellow light, it does not similarly become blind for yellow only, but for red and green too. This supports the Young-Helmholtz theory, that the sensation yellow is one compounded of the red and green sensations. By an exhaustive examination of the different parts of the spectrum, in this way it thus becomes possible to differentiate between the primary colour sensations and those which are compound. By a study of this kind, Burch concludes that the phenomena of colour vision are in accordance with the Young-Helmholtz theory, with the important addition that there is a fourth primary colour sensation, namely, blue. He could not discover that colour sensations are related to each other in the sense indicated by Hering. Each may be exhausted without .either weakening or strengthening the others. These observations were confirmed by examining in a similar way the colour sensations of seventy other people, but there are individual differences in the extent to which the colour sensations overlap. CH". LVI.] AFTER-IMAGES 801 After-Images. — These are the after-effects of retinal excitation, and are divided into positive and negative. Positive after-images resemble the original image in dis- tribution of brightness and colour. In negative after-images bright parts appear dark, dark parts bright, and coloured parts in the complementary or contrast colours. If a bright white object is looked at, and the eyelids are then closed, a positive after-image is seen which fades gradually, but as it fades it passes through blue, violet or red, to orange ; according to the Young-Helmholtz theory, this is explained on the hypothesis that the excitation does not decline with equal rapidity in the three colour terminals. Further details of these after-images are given on p. 803. A positive after-image is readily obtained by momentarily looking at a bright object, e.g. a window, after waking from sleep. Negative after-images develop later than positive images, and may be seen either by closing the eyes or by turning them to a uniform grey surface after viewing an object steadily. If the object looked at is coloured, the negative after-image seen upon such a background is in its complementary colour ; this is explained by the Young-Helmholtz theory, by the supposition that the colour perceiving element for the colour looked at is the most fatigued, and the terminals for its complementary colour least fatigued. On the Hering theory, one colour produces anabolic or katabolic effects as the case may be ; on withdrawing the eye from stimulation by that particular colour, the opposite phase of metabolism takes place and produces the complementary colour. One has an analogy to this in the case of the heart ; when that organ has been thrown into an anabolic state by the stimulation of the vagus, it will beat better when the stimulation stops owing to increase of katabolic processes. Negative after-images are frequently spoken of as phenomena of successive con- trast. Somewhat more complex than these are the phenomena of simultaneous con- trast. A white object looks whiter when viewed against a dark background than when seen against a white background ; the colour of an object is intensified by viewing it against a background of its complementary hue. Another familiar experiment is the following ; — A piece of grey paper is placed on a green sheet, and the whole covered with tissue paper; the grey patch then appears to be reddish, that is, of the colour complementary to green. Helmholtz regarded such phenomena as the result of false judgment, and not of changes in excitability of the different parts of the retina.* It certainly appears easier to explain contrast by the Hering theory ; excitation by one colour induces an opposite metabolic process in neighbouring areas of the retina ; if two stimuli of opposite character are presented simultaneously side by side, the con- trast effect will be most marked. In the experiment wiih tissue paper, the greater part of the retina is being excited by green, and the part of the retina stimulated by the feeble white light from the grey paper will undergo the opposite change and pro- duce a sensation of red. By means of the stereoscope, binocular combinations of colour can be obtained. Thus, if one eye is exposed to a red disc, and the corresponding portion of the olher eye to a yellow one, the mind usually perceives one disc of an orange tint ; but frequently, especially if there be differences of brightness or of form in the two objects, we notice that "rivalry of the fields of vision" occurs, first one then the other disc rising into consciousness. A stereoscopic combination of black and white produces the appearance of metallic lustre ; this is very beautifully shown with figures of crystals, one black on a white ground, the other white on a black ground. Probably the combination of black and white is interpreted as indicating a polished surface, because a polished surface reflects rays irregularly so that the two eyes re- ceive stimuli of unequal intensity. Changes in the Retina during Activity. The method by which a ray of light is able to stimulate the endings of the optic nerve in the retina in such a manner that a * By "retina" here and elsewhere we mean " cerebro-retinal apparatus." We have no knowledge of the precise share of retina and brain in the development of visual sensations and after-sensations. 3 E 802 THlE EYE AND VISION [CH. LVt. visual sensation is perceived by the cerebrum, is not yet understood. It is supposed that the change effected by the agency of the light which falls upon the retina is in fact a chemical alteration in the protoplasm, and that this change stimulates the optic nerve-endings. The discovery of a certain temporary reddish-purple pigmentation of the outer limbs of the retinal rods in certain animals {e.g., frogs) which had been killed in the dark, forming the so-called rhodopsin or visual purple, appeared likely to offer some explanation of the matter, especially as it was also found that the pigmentation dis- appeared when the retina was exposed to light, and reappeared when the light was removed, and also that it underwent distinct changes of colour when other than white light was used. It was also found that if the operation were performed quickly enough, the bleached image of a bright object {optogram) might be fixed on the retina by soaking the retina of an animal which has been killed in the dark, in alum solution. The rhodopsin is derived in some way from the black pigment (melanin or fuscin) of the polygonal epithelium of the retina, since the colour is not renewed after bleaching if the retina is detached from its pigment layer. Certain pigments, not sensitive to light, are contained in the inner segments of the cones. These are oil globules of various colours, red, green, and yellow, called chromop>hanes, and are found in the retinte of marsupials (but not other mammals), birds, reptiles, and fishes. Nothing is known about the yellow pigment of the yellow spot. Another change produced by the action of the light upon the retina is the movement of the pigment cells. On being stimulated by light the granules of pigment in the cells which overlie the outer part of the rod and cone layer of the retina pass down into the processes of the cells, which hang down between the rods: these melanin or fuscin granules are generally rod-shaped, and look almost like crystals. In addition to this, a movement of the cones and possibly of the rods occurs, as has been already mentioned ; in the light the cones shorten, and in the dark they lengthen (Engelmann). Dewar and McKendrick were the first to show that the chemical changes in the retina are accompanied with an electrical change. Red light has no action on visual purple ; the maximum bleaching effect takes place in greenish-yellow light. Now, when the living eye is brought into a condition of "dark adaptation," that is, when the retina has become adapted to light of low intensity, the colours of the spectrum alter in brightness ; the red end becomes shortened and much darker ; the blue end becomes brighter, and the region of maximum brightness is in the green. This change of brightness with change of adaptation is absent in the fovea, where there are no rods. The selective action of the colours of the spectrum on the visual purple is so strikingly similar to the altered conditions of brightness just described, that changes in the visual purple of the rods have been supposed to be the cause of sensations excited by feeble illumination {i.e., CH. lvl] electeical changes in retina 803 in the "dark-adapted" eye), while the cones are affected under more ordinary con- ditions of illumination. This conclusion gains support from several interesting facts. Visual purple is specially abundant in the retinae of almost all animals whose habits are nocturnal, or who live underground. Further, if the intensity of a colour stimulus is gradually increased, it at first is too faint to produce any sensation ; then it pro- duces a sensation of greyness, and at last the colour itself is seen ; the interval between the appearance of the grey or white-black effect and of the true colour effect of the stimulus is spoken of as the "photo-chromatic interval." Red light has no effect on visual purple, and has no photo-chromatic interval (that is, it appears either red or nothing), and according to several observers, there is no such interval at the fovea, where the rods and therefore visual purple, are absent. Thirdly, a very similar effect has been described by M'Dougall, when the retina is momentarily stimulated by a coloured light ; the sensation arising from the stimulus is followed by a series of "primary responses" or after-sensations; the first members of the series have the same colour as the stimulus, and these are sometimes followed by a series of colourless (grey) sensations ; these grey sensations are only present outside the fovea, and under conditions of " dark adaptation " are absent with red and bright- est with green stimuli. Here again we are able to differentiate between a visual- purple (rod) effect, and a cone effect, the former, active under conditions of feeble illumination, affected most by green, and unaffected by red light, and yielding colour- less sensations ; the latter being more specially concerned in developing sensations of colour under conditions of adaptation to ordinary light. The fovea centralis thus becomes the region where the colours of objects are best distinguishable, and where with ordinary illumination visual acuity is most marked. In the dark, however, extra-foveal (rod) vision is more sensitive than foveal (cone) vision ; astronomers see faint stars more readily in the periphery of the field of vision. Two abnormal conditions may be described here, for they throw light on these phenomena. In cases of achromatopsia (total'colour blindness) the spectrum is seen as a band of light differing only in brightness ; the region of maximum brightness is the same as in extra-foveal vision of the normal eye ; in many of these cases there is a central scotoma (blind spot), that is, the rod-less fovea is blind ; there is reduced acuity of vision as in the " dark-adapted " eye, and photophobia (fear of strong light); nystagmus (oscillating movements of the eye) also occurs due to absence of an area of distinct vision. We are thus in typical cases of achromatopsia dealing with cases of cone blindness. In nyctalopia (night blindness) on the other hand, we meet the converse condition. Here there is an abnormal slowness of " dark adaptation," and a pathological change known as retinitis pigmentosa is present, suggesting an im- paired function of the visual purple. Pilocarpine has been found an effective drug in such cases, and this is also interesting because it hastens the regeneration of visual purple in the extirpated eye. The electrical variations in the retina under the influence of light have been recently reinvestigated by Waller. The excised eyeball of a frog is led off by non- polarisable electrodes to a galvanometer. One electrode is placed on the front, the other on the back of the eye. If the eyeball is quite fresh, a current is observed passing through the eyeball from back to front. When light falls on the eye this current is increased ; on shutting off the light there is a momentary further increase, and then the current slowly returns back to its previous condition. Waller explains this by supposing that anabolic changes in the eye predominate during stimulation by light. With the onset of darkness, the katabolic changes cease at once, and the anabolic more slowly ; hence a further positive variation. As already stated, the current in a fresh eyeball passes from back to front before the stimulus is applied, but this cannot be regarded as a true current of rest, but as a current due to previous action which very slowly subsides. When this has subsided, the true current of rest is from cornea to fundus, i.e., it is like that of the skin (see p. 473) ingoing — the response to stimulation is like that of the skin out- going. Waller has also studied the electrical responses of the eyeball to other methods of stimulation ; if electrical currents are employed, and the eyeball is still healthy, the response is always an outgoing current, whatever may be the direction of the electrical current used as the stimulus. These currents of action are no doubt mainly of retinal origin, but later Waller showed that the anterior portions of the 804 THE EYE AND VISION [CH. LVI. eye, especially the crystalline lens, participate in their causation. The response of the eye to non-luminous stimuli lasts sometime, and is spoken of as a " blaze current." An analogous response has been seen in skin, plant-tissues, etc. Gotch has studied the photo-electric changes in the frog's eyeball with the capillary electrometer. He, like Waller, draws attention to the long latent period and sustained character of the response. The photo-electric changes are all monophasic effects, whether produced by illumination, or by shutting off the light. Gotch suggests there are two chemical substances in the retina, one of which reacts to light, the other to darkness. Each reaction is a change of the same type, but for the change to occur markedly, the eye must be previously adapted, Le., the substances must undergo a phase of metabolism under conditions opposite to those which evoke the reaction effects. Observations with red and green light do not support the view that the photo-chemical changes are of opposite characters, for the photo-electric change is always in the same direction, differing only in period of latency, that for red being the longer. Movements of the Eyeball Protrusion of the eyeballs occurs (1) when the blood-vessels of the orbit are congested ; (2) when contraction of the plain muscular fibres of the capsule of Tenon takes place ; these are innervated by the cervical sympathetic nerve ; and (3) in the disease called exophthalmic goitre. Retraction occurs (1) when the lids are closed forcibly; (2) when the blood-vessels of the orbit are comparatively empty; (3) when the fat in the orbit is reduced in quantity, as during starvation; and (4) on section or paralysis of the cervical sympa- thetic nerves. The most important movements, however, are those produced by the six ocular muscles. The internal rectus turns the eyeball inwards, the external rectus turns it outwards. If the superior rectus acted alone, it would turn the eyeball not only upwards, but owing to the sloping direction of the muscle, the eyeball would be turned inwards also ; in turning the eyeball directly upwards, this inward movement is arrested by the outward tendency of the inferior oblique. Similarly, in turning the eyeball directly downwards, the inferior rectus acts in conjunc- tion with the superior oblique. Movements in intermediate directions are produced by other combinations of the muscles. These muscles are all supplied by the third nerve except the superior oblique, which is supplied by the fourth and the external rectus by the sixth nerve. (See p. 640.) The muscles of the two eyes act simultaneously, so that images of the objects looked at may fall on corresponding points of the two retinse. The inner side of one retina corresponds to the outer side of the other, so that any movement of one eye inwards must be accompanied by a movement of the other eye outwards. If one eyeball is forcibly fixed by pressing the finger against it so that it cannot follow the movement of the other, the result is CH. LVI.] POSITIONS OF THE EYEBALLS 805 double vision (diplopia), because the image of the objects looked at will fall on points of the two retinae which do not correspond. The same is experienced in a squint, until the brain learns to disregard the image from one eye. If the external rectus is paralysed, the eye will squint inwards ; if this occurs in the right eye the false image will lie on the left side of the yellow spot, and appear in the field of vision to the right of the true image. If the third nerve is paralysed, the case is a more complicated one: owing to the paralysis of the levator palpebree superioris, the patient will be unable to raise his upper lid (ptosis), and so in order to see will walk with his chin in the air. If the Fig. 5 l J5. -Diagram of the axes of rotation to the eye. The thin lines indicate axes of rotation, the thick the position of muscular attachment. paralysis is on the right side, the eyeball will squint downwards and to the right ; the false image will be formed below and to the right of the yellow spot, and the apparent image in the field of vision will consequently appear above and to the left of 'the true image, and owing to the squint being an oblique one, the false image will slant in a corresponding direction. Various Positions of the Eyeballs. All the movements of the eyeball take place around the point of rotation, which is situated 177 mm. behind the centre of the visual axis, or 10'9 mm. behind the front of the cornea, 806 THE EYE AND VISION [CH. LVI. The three axes around which the movements occur are : — 1. The visual or antero-posterior axis. (A P, fig. 595). 2. The transverse axis, which connects the points of rotation of the two eyes. (Tr, fig. 595). 3. The vertical axis, which passes at right angles to the other two axes through their point of intersection. The line which connects the fixed point in the outer world at which the eye is looking to the point of rotation is called the visual line. The plane which passes through the two visual lines is called the visual plane. The various positions of the eyeballs are designated primary, secondary, and tertiary. The primary position occurs when both eyes are parallel, the visual lines being horizontal (as in looking at the horizon). Secondary positions are of two kinds: — (1) The visual lines are parallel, but directed either upwards or Fig. 596. — Identical points of the retina-. downwards from the horizontal (as in looking at the sky). (2) The visual lines are horizontal, but converge towards one another (as in looking at a small object near to and immediately on the same level as the eyes). Tertiary positions are those in which the visual lines are not horizontal, and converge towards one another (as in looking at the tip of the nose). It is possible to conceive positions of the eyeballs in which the visual lines diverge from one another; but such positions do not occur in normal vision in man. Both eyes are moved simultaneously, even if one of them happens to be blind. They are moved so that the object in the outer world is focussed on the two yellow spots, or other corre- sponding points of the two retinae. The images which do not fall on corresponding points are seen double, but these are to a great extent disregraded by the brain, which pays particular attention to those images which fall on corresponding points. CH. LVI.] NEEVOUS PATHS IN THE OPTIC NERVES 807 The accompanying diagrams will assist us in understanding what is meant by corresponding or identical points of the two retina. If E and L (fig. 596) represent the right and left retina respectively, and 0' the two yellow spots are identical ; so are A and A', both being the same distance above and 0'. But the corresponding point to B on the inner side of in the right retina, is B', a point to the same distance on the outer side of 0' in the left retina ; similarly C and C are identical. The two blind spots X and X' are not identical. Fig. 597 shows the same thing in rather a different way; A and B represent a horizontal section through the two retinEe ; the points a a', b b', and c c', being identical. In the lower part of the diagram Fig. 597. — Diagram to show the correspond- ing parts of both retinae. Fig. 598. — The Horopter, ivhen the eyes are convergent. is shown the way in which the brain combines the images in the two retinas, one overlapping so as to coincide with the other. The Horopter is the name given to the surface in the outer world which contains all the points which fall on the identical points of the retinas. The shape of the horopter will vary with the position of the eyeballs. In the primary position, and in the first variety of the secondary position, the visual lines are parallel; hence the horopter will be a plane at infinity, or at a great distance. In the other variety of the secondary position, and in tertiary positions in which the visual lines converge, as when looking at a near object, the horopter is a circle (fig. 598) which passes through the nodal points of the two eyes, and through the fixed point (I) in the outer world at which the eyes are looking, and which will con- sequently fall on the two yellow spots (0 and 0'). All other points in this circle (II, III) will fall on identical points of the retina?. The image of II will fall on A and A'; of III on B and B'; it is a 808 THE EYE AND VISION [CH. LVI. simple mathematical problem to prove that OA = 0'A', and OB = 0'B'. This, however, applies to man only, or to animals with both eyes in front of the head ; in those animals in which the eyes are lateral in position, and the visual lines diverge, the problem of binocular vision is a very different one (see also p. 713). Nervous Paths in the Optic Nerves. The correspondence of the two retince and of the movements of the eyeballs is produced by a close connection of the nervous centres controlling these phenomena, and by the arrangement of the nerve- fibres in the optic nerves. The crossing of the nerve-fibres at the optic chiasma is incomplete, and the next diagram (fig. 599) gives a simple idea of the way the fibres go. It will be seen that it is only the fibres from the inner portions of the retinas that cross ; and that those Left Retina Right Retina represented by continuous lines from the right side of the two retinas ultimately reach the right hemisphere, and those represented by interrupted lines from the left side of the two retinae ultimately reach the left hemi- sphere. The two halves of the retinas are not, however, separated by a hard-and-fast line from one another; this is represented by the two halves being depicted as slightly overlapping, and this comes to the same thing as saying that the central region of Hemisphere Hemisphere , ° , . ." ° , -i • 1 1 • t each retina is represented m each hemisphere. Fig. 593.— Course of fibres at „,, p *;, , . , •*•,. optic cMasma. llie part or the hemisphere concerned in vision is the occipital lobe, and the reader should turn back to our previous consideration of this subject in connection with cerebral localisation, the phenomena of hemian- opsia (p. 689) and the conjugate deviation of head and e} r es (pp. 689, 703). Fig. 600, though diagrammatic, will assist the reader in more fully comprehending the paths of visual impulses, and the central connections of the nerves and nerve-centres concerned in the process. The fibres to the external geniculate body end there by arborising around its cells, and a fresh relay of fibres from these cells passes in the posterior part of the internal capsule to the cortex of the occipital lobe. Those to the anterior corpus quadrigeminum are continued on by a fresh relay to the nuclei of the nerves concerned in eye-movements (represented by the oculo-motor nucleus in the diagram); the axons of the cortical cells pass to the tegmentum, CI1. LVI.] VISUAL JUDGMENTS 809 whence a fresh relay continues the impulse to the oculo-motor nucleus. Visual Judgments. The psychical or mental processes which constitute the visual sensation proper have been studied to a far greater degree than is possible in connection with other forms of sensation. We have already seen that in spite of the reversion of the imaye Fig. GOO —Relations of nerve cells and fibres of visual apparatus. (Schafer.) in the retina, the mind sees objects in their proper position ; this is explained on p. 780. We are also not conscious of the blind spot. This is partly due to the fact that those images which fall on the blind spot of one eye are not focussed there in the other eye. But even when one looks at objects with one eye, there is no blank, for the reason explained on p. 790. Our estimate of the size of various objects is based partly on the visual angle (p. 779) under which they are seen, but much more on the estimate we form of their distance. Thus a lofty mountain many miles off may be seen under the same visual angle as a small hill near at hand, but we infer that the former is much the larger object because we know it is much farther off than the hill. Our 810 THE EYE AND VISION [CII. LVT. estimate of distance is often erroneous, and consequently the estimate of size also. Thus persons seen walking on the top of a small hill against a clear twilight sky appear unusually large, because we over-estimate their distance, and for similar reasons most objects in a fog appear immensely magnified. The same mental process gives rise to the idea of depth in the field of vision ; this idea is fixed in our mind principally by the circumstance that, as we ourselves move forwards, different images in succession become depicted on our retina, so that we seem to pass between these images, which to the mind is the same thing as passing between the objects themselves. The action of the sense of vision in relation to external objects is, therefore, quite different from that of the sense of touch. The objects of the latter sense are immediately present to it ; and our own body, with which they come in contact, is the measure of their size. The part of a table touched by the hand appears as large as the part of the hand receiving an impression from it, for the part of our body in which a sensation is excited, is here the measure by which we judge of the magnitude of the object. In the sense of vision, on the contrary, the images of objects are mere fractions of the objects themselves, realised upon the retina, the extent of which remains constantly the same. But the imagination, which analyses the sensations of vision, invests the images of objects, together with the whole field of vision in the retina, with very varying dimensions ; the relative size of the image in proportion to the whole field of vision, or of the affected parts of the retina to the whole retina, alone remains unaltered. The estimation of the form of bodies by sight is the result partly of the mere sensation, and partly of the association of ideas. Since the form of the images perceived by the retina depends wholly on the outline of the part of the retina affected, the sensation alone is adequate to the distinction of superficial forms from each other, as of a square from a circle. But the idea of a solid body like a sphere, or a cube, can only be attained by the action of the mind construct- ing it from the different superficial images seen in different positions of the eye with regard to the object, and, as shown by Wheatstone and illustrated in the stereoscope, from two different perspective pro- jections of the object being presented simultaneously to the mind by the two eyes. Thus, if a cube is held at a moderate distance before the eyes, and viewed with each eye successively while the head is kept perfectly steady, a (fig. 601) will be the picture presented to the right eye, and B that seen by the left eye. Wheatstone has shown that on this circumstance depends in a great measure our conviction of the solidity of an object, or of its projection in relief. If different CH. LVI.] THE STEREOSCOPE 811 perspective drawings of a solid body, one representing the image seen by the right eye, the other that seen by the left (for example, the drawing of a cube, A, B, fig. 601) be presented to corresponding parts of the two retinae, as may be readily done by means of the P \ Fig. 601. — Diagrams to illustrate how a judgment of a figure of three dimensions is obtained. stereoscope, the mind will perceive not merely a single representa- tion of the object, but a body projecting in relief, the exact counter- part of that from which the drawings were made. By transposing two stereoscopic pictures a reverse effect is pro- duced; the elevated parts appear to be depressed, and vice versa. An instrument contrived with this purpose is termed a pseudoscojpe. Viewed with this instrument a bust appears as a hollow mask, and as may readily be imagined the effect is most bewildering. The clearness with which the details of an object is perceived irrespective of accommodation, would appear to depend largely on the number of rods and cones which its retinal image covers. Hence the nearer an object is to the eye (within moderate limits) the more clearly are all its details seen. Moreover, if we want carefully to examine any object, we always direct the eyes straight to it, so that ABC D Pig. 602.— Diagrams to illustrate visual illusions its image shall fall on the^two yellow spots, where an image of a given area will cover a larger number of cones than anywhere else in the retina. Moreover, as previously pointed out, each cone in the macula lutea is connected to a separate chain of neurons. 812 THE EYE AND VISION [CH. LVI. The importance of binocular vision is very great. If an object is looked at with one eye only, it is impossible to estimate its distance by the sense of vision alone. For instance, if one eye is closed and the other looks at a wire or bar, it is impossible to tell whether, if some one drops a small object, it falls in front of or behind the bar. Visual judgments are not always correct; there are a large number of puzzles and toys which depend on visual illusions. One or two of the best known are represented in the accompanying diagrams. Fig. G03.— Parallel puzzle. In fig. 602, a, B, and c are of the same size ; but a looks taller than b, while c appears to cover a less area than either. The sub- division of a space or line increases its apparent size or length. In fig. 602 d, ab is equal to he. Vertical distances also are usually over-estimated. In fig. 603, the horizontal lines are parallel, though they do not appear so, owing to the mind being distracted by the intercrossing lines. CUAPTEK LVli TEOPHIC NERVES Nerves exercise a trophic or nutritive influence over the tissues and organs they supply. Some nerves increase the building-up stage of metabolism ; these are termed anabolic. Such a nerve is the vagus in reference to the heart; when it is stimulated the heart beats more slowly or may stop, and is thus enabled to rest and repair its Waste. The opposite kind of nerves (katabolic) are those which lead to increase of work, and so increased wear and tear and formation of waste products. Such a nerve in reference to the heart is the sympathetic. There has been considerable diversity of opinion as to whether trophic nerve-fibres are a distinct anatomical set of nerve-fibres, or whether all nerves in addition to their other functions exercise a trophic influence. When a nerve going to an organ is cut, the wasting of the nerve itself beyond the cut constitutes what we have learnt to call Wallerian degeneration, but the wasting process continues beyond the nerve ; the muscles it supplies waste also, and waste much more rapidly than can be explained by simple disuse. The same is seen in the testicle after section of the spermatic cord ; and in the disease of joints called Charcot's disease, the trophic changes are to be explained by disease of the nerves supplying them. From these, and numerous other instances that might be given, there is no question that nerves do exert a trophic influence ; the question, however, whether this is due to special nerve-fibres has been chiefly worked out in connection with the fifth cranial nerve. After the division of this nerve there is loss of sensation in the corresponding side of the face: the cornea in two or three days begins to get opaque, and this is followed by a slow inflammatory process which may lead to a destruction not only of the cornea, but of the whole eyeball. The same is seen in man ; when the fifth nerve is diseased or pressed upon by a tumour beyond the G-asserian 814 TROPHIC NERVES [CH. LVII. ganglion, the result is loss of sensation in the face and conjunctiva, an eruption {herpes) appears on the face, and ulceration of the cornea leading in time to disintegration of the eyeball may occur too. In disease such as hsemorrhage in the spinal ganglia there is a similar herpetic eruption on the skin {shingles). In the case of the fifth nerve the evidence that there are special nerve-fibres to which these trophic changes are due, is an experiment by Meissner and Biittner, who found that division of the most internal fibres is most potent in producing them. Those, however, who do not believe in special trophic nerves, attribute the changes in the eyeball to its loss of sensation. Dust, etc., is not felt by the cornea, and is therefore allowed to accumulate and set up inflammation. This is supported by the fact that if the eyeball is protected by sewing the eyelids together the trophic results do not ensue. On the other hand, in paralysis of the seventh nerve, the eyeball is much more exposed, and yet no trophic disorders follow. Others have attributed the change to increased vascularity due to disordered vaso-motor changes ; against this is the fact that in disease of the cervical sympathetic, the disordered vaso-motor phenomena which ensue do not lead to the disorders of nutrition we have described. Nevertheless in trophic disorders, it is very difficult to be sure that the disordered metabolism is not in part due to vascular disturbances. There can, therefore, be but little doubt that we have to deal with the trophic influence of nerves ; * but the dust, etc., which falls on the cornea must be regarded as the exciting cause of the ulceration. The division or disease of the nerve acts as the predisposing cause. The eyeball is more than usually prone to undergo inflammatory changes, with very small provocation. The same explanation holds in the case of the influence of the vagi on the lungs. If both these nerves are divided, the animal usually dies within a week or a fortnight from a form of pneumonia called vagus pneumonia, in which gangrene of the lung substance is a marked characteristic. Here the predisposing cause is the division of the trophic fibres in the pneumogastric nerves ; the exciting cause is the entrance of particles of food into the air passages, which on account of the loss of sensation in the larynx and neighbouring parts are not coughed up. Another trophic disturbance that follows division of the vagi is fatty degeneration of the heart. Many bedsores are due to prolonged confinement in bed with bad nursing ; these are of slow onset. But there is one class of bed- sores which are acute; these are especially met with in cases of * The proof, however, that there are distinct nerve-fibres anatomically is not very conclusive. Cft. LVII.j tEOPHiC NEKVES 815 paralysis, due to disease of the spinal cord ; they come on in three or four days after the onset of the paralysis in spite of the most careful attention ; they cannot be explained by vaso-motor disturbance, nor by loss of sensation ; there is, in fact, no doubt they are of trophic origin ; the nutrition of the skin is so greatly impaired that the mere contact of it with the bed for a few days is sufficient to act as the exciting cause of the sore. It will be noticed that in some instances of trophic disorder the nerves which are injured are efferent ; the muscular wasting that occurs when a muscular nerve is cut is the best marked example of this. In nerve itself Wallerian degeneration follows the direction of growth, which, as a rule, is the direction in which the nerve transmits impulses. The acute Wallerian change does not actually leap synapses, still the trophic influence of one set of neurons upon a second set among which the axons of the first set terminate is shown by a slow wasting process, of which chromatolysis is the principal visible sign. In the peripheral axons of the cells of the spinal and corresponding cranial ganglia, the trophic disorder follows a peripheral direction, while impulses are carried in the opposite or afferent direction. The trophic influence here travels against the stream of impulse. It cannot fail to be a striking fact that the most marked trophic disorders with which we are acquainted, herpes, acute bedsores, Charcot's disease, eye changes after division or injury to the fifth nerve, vagus pneumonia, etc., are due to interference with sensory channels. Loss of sensation is the great predisposing cause of nutritive mischief. CHAPTER LVItl THE REPRODUCTIVE ORGANS The reproductive organs consist in the male of the two testes which produce spermatozoa, and the ducts which lead from them, Fig. 604.— Plan of a vertical section of the testicle, showing the arrangement of the ducts. The true length and diameter of the ducts have been disre- garded, a «, Tubuli semi- niferi coiled up in the separate lobes ; b, tubuli recti ; c, rete testis ; d, vasa eflerentia ending in the coni vasculosi ; I, e, g, convo- luted canal of the epidi- dymis ; h, vas deferens; /, section of the back part of the tunica albuginea ; i I, fibrous processes run- ning between the lobes; g, mediastinum. ^^ — ■ , Fig. COS. — Section of the epididymis of a dog. — The tube is cut in several places, both transversely and ob- liquely ; it is seen to be lined by a ciliated epithelium, the nuclei of which are well shown, c, Connec- tive tissue. (Schofield.) and in the female of the two ovaries which produce ova, the Fallopian tubes or oviducts, the uterus, and the vagina. Male Organs The testis is enclosed in a serous membrane called the tunica vaginalis, originally a part of the peritoneum. It descends into the 816 CU. LVIII.] THE TESTIS 817 scrotum before the testis and subsequently gets entirely cut off from the remainder of the peritoneum. There are, however, many animals in which the testes remain permanently in the abdomen. The external covering of the testicle itself is a strong fibrous capsule, called, on account of its white appearance, the tunica albuginea. Passing from its inner surface are a number of septa or trabecule, which divide the organ imperfectly into lobules. On the posterior aspect of the organ the capsule is greatly thickened, and forms a mass of fibrous tissue called the Corpus Highmorianum (body ^.-^v s I, 7'' '>■-._ of Highmore) or mediastinum testis. Attached to this is a much convoluted tube, which forms a mass called the epi- didymis. This receives the ducts of the testis, and is prolonged into a thick walled tube, the vas deferens, by which the semen passes to the urethra. Each lobule of the testicle contains several convoluted tubes. Every tube commences near the tunica albuginea, and terminates after joining with others in a straight tubule, which passes into the body of Highmore, where it ends in a network of tubes, the rete testis. From the rete about fifteen efferent ducts (vasa efferentid) arise, which become convoluted to form the coni vasculosi, and then pass into the tube of the epididymis. The convoluted or semi- niferous tubes (fig. 607) have the following structure : each consists of (1) an outer boundary of flattened connective tissue cells inter- mingled with elastic fibres; (2) a fine membrana propria; (3) a lining epithelium of many layers of germinal cells. Next the membrana propria is a layer of cells, some of which are prim- ordial germinal cells, others are spermatogonia produced from the primordial germinal cells, but differing from them in structure, and the remainder are supporting or nurse cells which provide nutri- ment for the developing spermatozoa. More internally, between the A F Fig. 606. — Dissection of the base of the bladder and pro- state gland, showing the vesiculee seminales and vasa deferentia. a, Lower surface of the bladder at the place of reflexion of the peritoneum ; I, the part above covered by the peritoneum ; i, left vas deferens, ending in e, the ejaculatory duct; the vas deferens has been divided near i, and all except the vesical portion has been taken away ; s, left vesicula semi- nalis joining the same duct ; s s, the right vas de- ferens and right vesicula seminalis, which has been unravelled ; p, under side of the prostate gland ; m, part of the urethra ; v. u, the ureters (cut short), the right one turned aside. (Haller.) 818 THE REPRODUCTIVE ORGANS [CH. LYIII. projecting processes of the nurse cells, are large spermatocysts of the first order, derived from the spermatogonia by karvokinesis and growth. Still nearer the lumen of the tube lie the spermatocysts Fig. GO". — Diagram of a portion of a seminal tubule showing development of spermatozoa. 1, Primi- tive germ cell ; 2, spermatogonia ; 3, spermatocysts of the first order ; 4, spermatocysts of the second order ; 5, spermatids, some with commencement of axial filament ; ti, a nurse cell with spermatids and spermatozoa in various stages of development ; 7, free spermatozoa in lumen of tube ; 8, por- tions of nurse cells. (After Waldeyer.) of the second order, which are the daughter-cells of the spermato- cysts of the first order, and the spermatocysts of the second order give rise by divisions to the spermatids which lie next the lumen. The spermatids become embedded in the inner ends of the nurse cells, where they lose their distinct cellular characters and become Fig. COS. — A spermatid largely magnified. 1, nucleus; 2, nucleolus ; 3, chromatoid body ; 4, idiosome ; 5. centro- somes ; 0, commencement of axial filament. (After Meves.) Fig. 609.— Cells of the interstitial tissue of the testis with crystal- loid bodies. converted into spermatozoa. Every spermatid consists of a cell body and a nucleus with a nucleolus. In the cell body near the nucleus CH. LVIII.] SPERMATOZOA 819 is another structure called au idiosome, containing a number of microsomes. There are also a coloured or chromatoid body whose function is not known, and two centrosomes (see fig. 608). The straight tubules consist of basement membrane and lining cubical epithelium only. The interstitial connective tissue of the testis is loose, and con- tains numerous lymphatic clefts. Lying in it, accompanying the blood-vessels, are strands of polyhedral epithelial cells, of a yellowish colour (interstitial cells), which frequently contain crystalloid bodies. The tubules of the rete testis are lined by cubical epithelium ; the basement membrane is absent. The vasa efferentia, coni vasculosi, and epididymis are lined by columnar cells, some of which are ciliated, whilst others are devoid of cilia, and probably possess secretory functions. There is a good deal of muscular tissue in their walls. The vas deferens consists of a muscular wall (outer layer longi- tudinal, middle circular, inner longitudinal), lined by a mucous membrane, the inner surface of which is covered by columnar epithelium. The vesicula? seminales (fig. 606) are outgrowths of the vasa deferentia. Each is a much convoluted, branched, and sacculated tube of structure similar to that of the vas deferens, except that the wall is thinner, and the lining epithelium is often of transitional character. The penis is composed of cavernous tissue covered by skin. The caver- nous tissue is collected into three tracts, the two corpora cavernosa and the corpus spongiosum in the middle line inferiorly. All these are en- closed in a capsule of fibrous and plain muscular tissue ; the septa which are continued in from this capsule, form the boundaries of the cavernous venous spaces of the tissue. The arteries run in the septa ; the capil- laries open into the venous spaces. The arteries are often called helicine, as in injected specimens they form twisted loops projecting into the cavernous spaces (see also p. 313). The structure of the urethra and prostate is described on pp. 541-543. The Spermatozoa, suspended in a richly albuminous fluid, con- stitute the semen. Each spermatozoon consists of a head, a very short neck, a body, a tail, and an end-piece. The head is of flattened Fig. 610.— Erectile tissue of the human penis. a, Fibrous trabeculee with their ordinary capillaries ; b, section of the venous sinuses ; c, muscular tissue. (Cadiat.) 820 THE REPRODUCTIVE ORGANS [CH. LVIII. ovoid shape, and in the anterior two- thirds of its extent is surmounted by a bead-cap which, sharpened at its extremity, forms a cutting edge. The neck is very short, but contains two centrosomes. The body is about the same length as the head ; it is traversed by an axial filament and a spiral fibril wound round the sheath of the axial filament. More externally is a layer of punctiform substance Fig. 611.— Semi-diagrammatic representation of human spermatozoa. A, front view ; B, side view. 1, Head cap surrounding head; 2, neck ; 3, body ; 4, tail ; 5, end-piece. The axial filament runs through the body and taU into the end-piece. Fig. 612.— Diagram of part of a human sper- matozoon highly mag- nified (after Meves). 1, Head cap ; 2, head ; 3, anterior centrosome in neck ; 4, posterior centrosome in neck ; 5, axial filament; 6, spiral sheath ; 7, sheath of axial filament in body ; 8, mitochondrial sheath; 9, annulus ; 10, thick sheath of axial filament in tail. called the mitochondrial sheath which terminates at the junction with the tail on an annular disc. The axial filament is continued through the tail into the end - piece, and in the tail is sur- rounded by thick sheath. In some animals, newts and sala- manders, the tail is surrounded by a spiral membrane, but this is not present in the human spermatozoon. The head of the spermatozoon is formed from the nucleus of the spermatid, the head-cap from the idiosome ; the centrosomes of the spermatid CS. LVIII.] THE OVARY 821 pass to the neck of the spermatozoon, and the cytoplasm of the spermatid is transformed into the parts of the body and tail of the spermatozoon. Female Organs The Ovary is a solid organ composed of fibrous tissue (stroma), containing near its attachment to the broad ligament a number of plain muscular fibres. It is covered by a layer of cubical cells, the so-called germinal epithelium, which, in young animals, is seen dipping down, here and there, into the stroma. The stroma contains a number of yellow polyhedral cells similar to the interstitial cells of the testicle. Sections of the ovary show that the stroma is crowded with a Fig. 613. — Diagrammatic view of the uterus and its appendages, as seen from behind. The uterus and upper part of the vagina have been laid open by removing the posterior wall ; the Fallopian tube, round ligament, and ovarian ligament have been cut short, and the broad ligament removed on the left side ; u, the upper part of the uterus ; c, the cervix opposite the os internum ; the triangular shape of the uterine cavity is shown, and the dilatation of the cervical cavity with the rugae termed arbor vitas ; v, upper part of the vagina ; od, Fallopian tube or oviduct ; the narrow communication of its cavity with that of the cornu of the uterus on each side is seen ; I, round ligament ; lo, liga- ment of the ovary ; o, ovary ; i, wide outer part of the right Fallopian tube ; fi, its fimbriated extremity ; po, parovarium ; h, one of the hydatids frequently found connected with the broad liga- ment. J. (Allen Thomson.) number of rounded cells, the oocytes, derived from primitive germ cells, which, in the early stages, were intermingled with the cells of the germinal epithelium. There are also numerous vesicles of differ- ent sizes which are called Graafian follicles. The smallest follicles are near the surface, the largest are deeply placed, but as they ex- pand they again approach the surface, and ultimately rupture upon it. A Graafian follicle has an external wall formed by the stroma ; this is lined internally by a layer of cells derived from the germinal epithelium which surrounds the oocyte. At a later stage there are two layers of cells, one lining the cavity, and the other surrounding the oocyte, but the two are close together. A viscid fluid collects between the two, and as the follicle grows, separates them. 822 THE REPRODUCTIVE ORGANS [ch. Lvttt. The cells in each layer multiply, and are eventually arranged|in several strata. The lining epithelium of the follicle is then called Fig. G14. — View of a section of the ovary of the cat. 1, Outer covering and free border of the ovary ; 1 ', attached border ; 2, the ovarian stroma, presenting a fibrous and vascular structure ; 3, granular substance lying external to the fibrous stroma ; 4, blood-vessels ; 5, ovigerms in their earliest stages occupying a part of the granular layer near the surface ; (5, ovigerms which have begun to enlarge and to pass more deeply into the ovary ; 7, ovigerms round which the Graafian follicle and tunica granulosa are now formed, and which have passed somewhat deeper into the ovary and are surrounded by the fibrous stroma; 8, more advanced Graafian follicle with the ovum imbedded in the layer of cells constituting the proligerous disc; 0, the most advanced follicle containing the ovum, etc.; 9', a follicle from which the ovum has accidentally escaped ; 10, corpus luteum. (Schrdn.) the membrana granulosa, and the heaped mass of cells around the ovum, the discus proligerus. The fluid increases in quantity, the Pig. tilu.— Section of the ovary of a cat. A, germinal epithelium; B, immature Graafian follicle; C, stroma of ovary ; D, vitelline membrane containing the ovum ; E, Graafian follicle showing lining cells; F, follicle from which the ovum has fallen out. (V. D. Harris.) follicle becomes tenser, and finally it reaches the surface of the organ and bursts ; the ovum is thus set free, and is seized by the fringed CH. LVIII.] THE CORPUS LUTEUM 823 ends of the Fallopian tube and thence passes to the uterus. The bursting of a Graafian follicle usually occurs about the time of men- struation. After the bursting of a Graafian follicle, it is filled up with what is known as a corpus luteum. This is derived from the wall of the Fig. 616.— Corpora lutea of different periods. 13, Corpus luteum of about the sixth week after impreg- nation, showing its plicated form at that period. 1, Substance of the ovary; 2, substance of the corpus luteum ; 3, a greyish coagulum in its cavity. (Paterson.) A, Corpus luteum two days after delivery ; D, in the twelfth week after delivery. (Montgomery.) follicle, and consists of columns of yellow cells developed from the yellow cells of the membrana granulosa ; it contains a blood-clot in its centre. These cells multiply, and their strands get folded and converge to a central strand of connective tissue; between the columns there are septa of connective tissue with blood-vessels. The corpus luteum after a time gradually disappears ; but if pregnancy supervenes it becomes larger and more persistent (see fig. 616). The following table gives the chief facts in the life-history of the ordinary corpus luteum of menstruation, compared with that of pregnancy : — Corpus Luteum of Menstruation. At the end of three weeks. One month . Two months Six months Nine months . Corpus Luteum of Pregnancy. hree-quarters of an inch in diameter ; central clot reddish ; convoluted wall pale. Larger ; convoluted wall bright yellow ; clot still reddish. Smaller ; convoluted wall bright yellow ; clot still reddish. Reduced to the condition of an insignificant cica- trix. Absent. Seven-eighths of an inch in dia- meter; convoluted wall bright yellow ; clot perfectly de- colorised. Still as large as at end of second month ; clot fibrinous ; convo- luted wall paler. One half an inch in diameter ; central clot converted into a radiating cicatrix ; the external wall tolerably thick and con- voluted, but without any bright yellow colour. 824 THE REPRODUCTIVE ORGANS [CH. LVIII. It has been suggested that the corpus luteum yields an internal secretion, the effect of which is to assist gestation in some at present unknown way. Many of the Graafian follicles never burst ; they attain a ... Nucleus or germinal vesicle. — Nucleolus or germinal spot. ... space left by retraction of protoplasm. — Protoplasm containing yolk spherules. — Zona pellucida. Fig. 617. — A human ovum. (Cadiat.) certain degree of maturity even during childhood, then atrophy and disappear. The ovarian ovum or oocyte of the first order (fig. 617) is a large Fig. CIS. — Diagram showing mode of development of oocytes of the first order from primitive germ cells in mammalian ovary. 1, germinal epithelium ; 2, primitive germ cells ; 3, oogonia ; 4, oocytes ot the first order. In A, two primitive germ cells are seen imbedded in the germinal epithelium. In B, a primitive germ cell has descended into the stroma of the ovary accompanied by cells proliferated from the germinal epithelium which will become the cells of the membrana granulosa. In C, the oogonia derived from primitive germ cells, and oocytes of the first order produced by division of the oogoniaj are seen. (After Buhler.) spheroidal cell surrounded by a transparent striated membrane called the zona pellucida, or zona striata. The protoplasm is filled with large CH. LVIII.] THE UTERUS 825 fatty and albuminous granules (yolk spherules), except in the part around the nucleus, which is comparatively free from these granules. It contains a nucleus which has the usual structure of nuclei ; there is generally one very well-marked nucleolus. The nucleus and nucleolus are still often called by their old names, germinal vesicle and germinal spot respectively. An attraction sphere, not shown in the figure, is also present, and a fine membrane, the vitelline membrane, is said to lie between the protoplasm and the zona pellucida. The oocytes are developed from the primitive germ cells which in the earliest stages are interspersed between the cells of the germinal epithelium. The primitive germ cells divide and produce oogonia ; and by the division of the oogonia, oocytes are formed (fig. 618). As the oogonia and oocytes are developed they sink into the stroma, surrounded by cells, produced by the proliferation of the germinal epithelium, which are destined to form the membrana granulosa and the discus proligerus. Fig. 619. — Section of the lining membrane of a human uterus at the period of commencing pregnancy, showing the arrangement of the glands, d, d, d, with their orifices, a, a, a, on the internal surface of the organ. Twice the natural size. The Fallopian tubes have externally a serous coat derived from the peritoneum, then a muscular coat (longitudinal fibres outside, circular inside), and most internally a very vascular mucous mem- brane thrown into longitudinal folds, and covered with ciliated epi- thelium. The uterus consists of the same three layers. The muscular coat is, however, very thick and is made up of two strata imperfectly separated by connective tissue and blood-vessels. Of these the thinner outer division is the true muscular coat, the fibres of which are arranged partly longitudinally, partly circularly. The inner division is very thick ; its fibres run chiefly in a circular direction ; the extremities of the uterine glands extend into its internal surface. It is in fact a much hypertrophied muscularis mucosae. The mucous membrane is thick, and consists of a corium of soft connective tissue, lined with ciliated epithelium ; this is continued down into long tubular glands which have, as a rule, a convoluted course. In the cervix the glands are shorter. Near the os uteri the 826 THE REPRODUCTIVE ORGANS [ciI. LVIII. epithelium becomes stratified ; stratified epithelium also lines the vagina. At each menstrual period the uterus becomes congested, and some of the blood-vessels of the mucous membrane are ruptured ; the blood, together with the secretion of the glands and some epithelial dtbris from the surface, constitutes the menstrual flow, which usually lasts two or three days. The amount of destruction of the surface epithelium is not, however, a marked phenomenon ; still less is there any disintegration of the deeper parts of the mucous membrane. For Parturition (see p. 677), and for a description of the mammary glands (see p. 464). CHAPTEK LIX DEVELOPMENT The description of the origin and formation of the tissues and organs constitutes the portion of biological science known as embryology. All one can possibly attempt in a physiological text-book is the merest outline of the principal facts of development. In our descriptions we shall speak principally of the develop- ment of the mammal ; it will not be possible to do so altogether, for many of the facts which are believed to be true of the mammal (man included) have only been actually seen in the lower animals. That they occur in the higher animals is a matter of inference. It will, however, add interest to the subject to draw some of our descriptions from the lower animals ; for the scientific discussion of embryology must always start from a wide survey of the whole animal kingdom, because the changes which occur in the embryo- logical history of the highest animals, form a compressed picture of the changes which have taken place in their historical develop- ment from lower types. The Ovum. The human ovum is like that of other mammals, a small cell about T ^ T to y^q- inch in diameter. The changes by which the ovum, or a portion of the ovum, is transformed into the young animal may take place either inside or outside the body of the parent. If they take place inside the parent, as in mammals, including the human subject, the ovum is small, and the nutriment necessary for its growth and development is derived from the surrounding tissues and fluids of the mother. If the development takes place outside the parent's body, as in birds, the egg is larger; it contains a large amount of nutritive material called the yolk, and it may, in addition, be surrounded by sheaths of nutritive substance. Thus, in the hen's egg, the yellow part alone is comparable with the mammalian ovum, and the larger part of that is merely nutritive substance ; upon it is a whitish speck, the 828 DEVELOPMENT [CH. LIX. B Fig. 620.— Diagram showing the formation of the polar bodies (maturation of the ovum). A, B, and C show stages in the formation of the first polar body by heterotype mitosis. A is the ooycte of the first order at the commencement of mitosiSj when only half the usual number of chromosomes appear. C is the oocyte of the second order ; it has no distinct nucleus, because no resting-stage occurs ; after the separation of the first polar body, the chromo- somes which remain in the oocyte of the second order at once rearrange themselves on a new spindle. I» is the mature ovum, with the female pronucleus and the two polar bodies. 1, First polar bud; 2, first polar body; 3, second polar body ; 4, chromosomes on spindle of oocyte of first order ; 5, zona striata ; 6, vitelline membrane; 7, daughter chromosomes in first polar bud ; S, female pronucleus. cicatricula, about }• of an inch in diameter. In the cicatricula lies the nucleus or germinal vesicle, and it is this small mass of proto- plasmic substance which divides and grows to produce the chick ; the yolk and the surrounding white being used as food. Ova like the hen's, in which only a small part, the cicatricula, divides and grows, are called mero- blastic. Small ova, with little food yolk, such as the human ovum, divide completely during develop- ment, and are called holoblastic, but numerous gradations occur between the two extreme types. The structure of the mammalian ovum and its mode of formation have already been considered (p. 824), but before such an ovum can develop it must first become mature, and then it must be im- pregnated by the entrance of a spermatozoon. Maturation of the Ovum. It will be remembered that the germ cells which form the ova are at first embedded in the ger- minal epithelium, from which they pass into the stroma of the ovary, and then by division and growth they form oogonia ; from the oogonia, oocytes of the first order are developed, and the oocytes of the first order become enclosed in Graafian follicles. It is the process by which the oocytes of the first order become converted into mature ova, which is known as maturation, and it consists essentially of a double mitotic division of the oocyte, each division producing two CTT. LIX.] THE POLAK BODIES 829 unequal parts. The first division produces an oocyte of the second order and the first polar body, and the second, which takes place without any resting-stage, results in the formation of the mature ovum and the second polar body. Thus, when the two divisions are completed, the mature ovum and two polar bodies lie inside the zona pellucida. In some cases, only one polar body is formed, that is, only one division occurs. The unequal division is naturally associated with an eccentric position of the spindle. At each division one end of the spindle projects in the surface with a little surrounding protoplasm, and it is the small process which becomes the polar body. One of the essential features of maturation is the reduction of the number of chromosomes in the nucleus. It is well known that 2a2 Fig. 621. — Diagram showing the stages in the maturation of the ovum when the first polar body divides. A similar diagram would represent the formation of spermatids from a spermatocyst of the first order. 1, Oocyte of the first order ; 2, oocyte of the second order ; 2a, first polar body ; 3, mature ovum ; 3a, second polar body ; 2al, and 2a2, daughter cells of the first polar body. All the last generation in the male would be spermatids of equal value. the nuclei of all animal cells, including germ cells and oogonia, con- tain a definite number of chromatic particles. When maturation commences in the oocytes of the first order, an achromatic spindle is formed in the usual way; but instead of the ordinary number of chromosomes appearing at its equator, only half that number are seen : for example, if eight be the normal number of chromosomes, only four appear. Further, each chromosome is not a slender V-shaped loop, but a short, thick rod, or ring, or group of four particles. Neither does it split longitudinally in the usual way, but transversely ; and at the end of the process the oocyte of the second order and the first polar body both contain four chromosomes. This form of mitosis is known as heterotype, whilst the ordinary form is called homotype. The second division which produces the mature ovum and the second polar body is of the homotype form, and the final result is that each of the segments into which the oocyte of the first order has divided 830 DEVELOPMENT [CII. LIX. ZONA PELLUCIDA — the mature ovum and the two polar bodies — contains half the number of chromosomes present in the parent germinal cell. In some cases the first polar body divides at the same time that the second polar body is formed, and the process may be represented by the schema in fig. 621. The nucleus of the mature ovum is known as the female inn- nucleus. Impregnation. By impregnation is meant the union of a spermatozoon with an ovum. The spermatozoon, moving by the flagellar movement of its tail meets ' the mature ovum in the upper part of the Fallopian tube, and by means of its sharp head cap it pierces the zona pel- lucida, and the head, neck, and possibly part of the body, enter the substance of the ovum, where they undergo transforma- tion, and are converted into a nialepn (nucleus with an attendant attraction sphere and its centro- sorne. The male pronucleus con- tains the same number of chromo- somes as the female pronucleus, for the mitosis which occur when the spermatoeyst of the first order divides to form the two spermatocysts of the second order, is a heterotype mitosis, in which only half the usual number of chromo- somes appear ; and consequently the spermatocysts of the second order, and their descendants the spermatids, also contain only half the typical number of chromosomes. These are retained in the spermatozoa, which are produced by modification of the spermatid, and they reappear in the male pronucleus. After the male pronucleus has formed in the substance of the mature ovum, it approaches the female pronucleus, and when the two pronuclei fuse, fertilisation is completed. The nucleus which results from the fusion — the first segmentation nucleus — contains the typical number of chromosomes, half being derived from the female and half from the male germinal element. When the fertilisation is completed, the segmentation nucleus is accompanied by two attrac- tion spheres with their centrosomes (see fig. 622) ; one of these spheres is that associated with the male pronucleus, but the origin of the other is uncertain. It may belong to the ovum, though it was not apparent during the maturation, or it may have been produced by the division of the centrosome and attraction sphere which accompany the male pronucleus. J POLAR LGLOBULES Fig. 622. — The fertilised ovum or blastospkere, showing its new nucleus and attraction spheres ; the yolk granules have been omitted. CU. LIX.] SEGMENTATION Segmentation. After fertilisation is completed, the ovum divides into two parts ; each of these again divides, and so on till a mulberry-shaped mass — the morula — is formed. It consists of a large number of small cells, and it is enclosed together with the polar bodies, in the zona pellucida. The polar bodies soon disappear ; indeed in niairy cases they have vanished long before the morula is completed. A cavity soon appears in the morula, which thus becomes converted into a blastula or blastocyst. The cells which form the peripheral wall of the blastula assume a more or less cubical form, whilst those which lie in the interior and form the inner cell mass are irregular in outline, and they are grouped together at one pole of the blastula. At this period the blastula is unilaminar, except at the region where the inner cell mass is situated ; but soon the cells of the inner mass extend round the cavity and the wall of the cyst becomes bilaminar. In amphioxus and in many in- vertebrates the blastula is at first entirely unilaminar, no inner cell mass being present. In these cases the inner layer is formed by the invagination of a part of the wall of the vesicle, and the opening at which the in- vagination occurs is known as the blastopore or primitive mouth. If the surface of a bilaminar mammalian blastoderm is examined, an area is found which is darker or more opaque than the rest; this is the area where the embryo will be formed, and it is known as the germinal or embryonic area (fig. 624). It region where the inner mass is adherent to Fig. 623. — Diagrams of various stages of cleava; the ovum. (Daltoa.'* the of corresponds with the the outer layer, and in it the epiblast cells are of cubical or columnar form, whilst over the remainder of the wall of the vesicle they have been transformed into flattened plates (fig. 625). At first the germinal area is circular, then it becomes ovoid, and ultimately pear-shaped, the narrow part of the pear-shaped area indicating the region of the posterior end of the body of the future embryo (fig. 626). A linear streak — the primitive streak — quickly appears in the narrow part of the area, and after a time, a groove — the primitive groove — appears on its 832 DEVELOPMENT [CH. LIX. surface. In the meantime, a second groove has appeared on the surface of the ovum in front of the primitive streak. This is the Fra. 624. — Diagram of a surface view of a young mammalian blastula. 1, Germinal area. A, line of section represented in tig. 625. Pig. 625. —Diagram of a section of the mammalian blastula shown in fig. 024 along the lme A. 1, Ger- minal area ; 2, epiblast ; 3, inner cell mass. neural groove or rudiment of the central canal of the brain and spinal cord. It is bounded by two folds — the neural folds, which are united together at their anterior ends, but their posterior ends which embrace the anterior end of the primitive streak do not unite until after the appearance of the opening at the anterior end of the primitive streak. This opening therefore connects the neural groove with the cavity in the interior of the blastodermic vesicle, which is called the archenteric cavity, and through it the epiblast be- comes continuous with the hypoblast. Therefore it evidently represents a part of the blastopore of more primitive forms, but it is called the neurenteric canal. It soon closes, and all traces of it are lost. A— Fig. 626. — Diagram of a surface view of a mammalian blastoderm after the formation of the neural groove. 1, Germinal area ; 2, neural ridge ; 3, neural groove ; 4, neuren- teric canal (part of blastopore) ; 5, primitive groove and streak. A, line of section shown in fig. 627 ; B, line of section shown in fig 628. Fio. 627. — Diagram of a transverse section through a mammalian blastoderm along line A in fig. 626. 1, primitive groove; 2, primitive streak ; 3, epiblast ; 4, mesoblast ; 5, hypoblast ; 6, cadom ; 7, archenteron. Fio. 623. — Diagram of a transverse section through a mammalian blastoderm along line IS in tig. 626. 1, neural groove; 2, neural ridge ; 3, epiblast ; 4, somatic mesoblast ; o, splanchnic mesoblast ; 6, hypoblast ; 7, somatopleur : 8, splanch- nopleur ; 9, notochord ; 10, coelom ; 11, archenteron. The primitive streak itself is due to a down-growth of a linear CH. LIX.] THE MESOBLASTIC SOMITES 833 ridge of epiblastic cells, and soon after its formation a layer of cells, the mesoblast, or third layer of the blastoderm, grows out from its sides and posterior end, and extends between the epiblast and hypoblast over the whole area of the vesicle. That portion of the mesoblast which lies immediately at the sides of the neural groove becomes partially separated from the rest, and at the same time divided into cuboidal blocks, the protovertebrae or mesoblastic somites. The more laterally situated part of the mesoblast constitutes the lateral plates, and the narrow strand of mesoblastic cells which connects the lateral plate on each side with the pro- tovertebral somites is the intermediate cell mass. Soon after its formation the lateral mesoblast is cleft into two layers, and the space which appears between the two layers is called the coelom (figs. 627, 628). The outer or somatic layer of the meso- blast adheres to the epiblast; the two together form the somatopleur. The inner or splanchnic layer fuses with the hypo- blast to form the splanchnopleur. Cavities also appear in the mesoblastic somites. Whilst the mesoblast is extending and cleaving, the neural folds gradually grow in height, and their free margins turn inwards and fuse together. This fusion commences in the cervical region, and extends forwards and backwards, and when it is completed the neural groove is con- verted into a closed tube, the neural tube, and the original groove is now the central canal of the nervous system. In the ovum at this period there are, therefore, three cavities : (1) The neural or central canal confined to the embryonic region ; (2) The ccelom or space in the mesoblast ; (3) The archenteron within the hypoblast. The embryonic area is still outspread on the surface of the ovum. When the changes to which reference has been made are well advanced, and in many cases before the neural groove is closed, the embryonic area begins 3G to. 629.— Embryo chick (36 hours), viewed from beneath as a trans- parent object (magnified), pi, Out- line of pellucid area ; FB, fore-brain, or first cerebral vesicle : from its sides project op_, the optic vesicles ; SO, backward limit of somatopleur fold, " tucked in " under head ; a, head-fold of true amnion ; a', re- flected layer of amnion, sometimes termed " false amnion " ; sp, back- ward limit of splanchnopleur folds, along which run the omphalo- mesenteric veins uniting to form h, the heart, which is continued forwards into ha, the bulbus arte- riosus ; d, the fore-gut, lying behind the heart, and having a wide cres- centic opening between the splanch- nopleur folds ; HB, hind-brain ; MB, mid-brain ; pv, protovertebrae lying behind the fore-gut ; mc, line of junction of medullary folds and ofnotochord; ch, front end of noto- chord ; vpl, vertebral plates ; pr, the primitive groove at its caudal end. (Foster and Balfour.) 834 DEVELOPMENT [CH. LIX. to fold off from the rest of the ovum. A sulcus appears all round the margins of the area, and over this sulcus the area bends forwards, backwards, and laterally. It looks as if some constricting agent had been placed round the margin of the area, and that afterwards the area above the constriction, and the area below had gone on growing rapidly. In tin's way, the ovum is clearly separated into two parts, an upper, the embryo, and a lower, which becomes the appendages of the embryo. The anterior part of the folded embryonic area is known as the head fold, the posterior as the tail fold, and the two are connected together on each side by the lateral folds. As the constric- tion between the embryonic and non-embryonic parts affects the 5 14- 7 13 Fio. 630. — Diagram of a transverse section through a mammalian ovum at the period when the folding off of the embryo has commenced. 1, Neural tube ; 2, proto- vertebral somite ; 3, epiblast ; 4, somatic mesoblast ; 5, splanchnic mesoblast ; 6, hypoblast ; 7, notochord ; 8, primitive alimentary canal ; 9, ccelom ; 10, vitello- intestinal duct; 11, yolk sac ; 12, lateral fold of amnion. Fig. 631. — Diagram of a longitudinal section of a mammalian ovum at the period when the folding off of the embryo has commenced. 1, Neural tube; 2, epiblast ; 3, notochord ; 4, stomadreal space ; 5, head fold of amnion ; 6, tail fold of amnion ; 7, hypoblast ; 8, somatic mesoblast ; 9, splanchnic mesoblast ; 10, yolk sac ; 11, ccelom ; 12, allantois ; 13, hind-gut; 14, mid-gut ; 15, fore-gut; 16, peri- cardium. interior as well as the exterior of the ovum, it follows that three cavities are present in the embryo. (1) The central canal of the neural tube, which is of course lined by epiblast. (2) A portion of the archenteron lined by hypoblast. (3) A portion of the ccelom or cavity of the mesoblast (fig. 630). The central canal of the neural tube, as before stated, becomes the cavity of the permanent central nervous system, and it forms the central canal of the spinal cord, the lateral, third and fourth ventricles, and the aqueduct of Sylvius which connects the third and fourth ventricles together. The portion of the archenteron enclosed in the embryo forms the primitive gut. The part contained in the head fold is the fore-gut, CH. LIX.] THE NOTOCHOED 835 that in the tail fold is the hind-gut, and the remainder is the mid-gut (fig. 631). The constriction where the body of the embryo becomes con- tinuous with the remainder of the ovum, is known ultimately as the umbilicus. It remains pervious till birth, when the embryo is separated from the rest of the ovum, and through it the mid-gut is connected with the remainder of the archenteron (which is henceforth called the yolk sac) by a narrow hypoblastic tube, the vitello -intestinal duct (fig. 630, 10). The portion of the mesoblastic cavity enclosed in the embryo is called the body cavity. It gradually differentiates into the pericardial pleural and peritoneal cavities, which are eventually entirely separated from each other. In the early stages the gut is close to the posterior wall of the body, but after a time it advances into the body cavity ; it remains connected, however, with the dorsal wall by a fold of the splanchnic portion of the mesoblast, which is called the dorsal mesentery. A similar mesentery is found connecting the ventral wall of that portion, fore-gut, which becomes stomach and duodenum, with the ventral wall of the body. Before the neural groove is closed and becomes the neural canal, the hypoblast beneath the middle of the groove becomes thickened to form a longitudinal ridge (fig. 628). This ridge is the notochord or primitive skeletal axis. It soon separates from the remainder of the hypoblast, and forms a round cord, which lies at first immediately beneath the neural groove, and afterwards beneath the neural tube, extending from the anterior end of the primitive gut, which lies beneath that region of the neural tube which afterwards becomes the mid-brain, to the caudal end of the embryo (figs. 630, 631). It follows from what has already been stated, that the embryo attains its distinct form by a process of folding ; but for some time after it is separated off from the remainder of the ovum (except at the margins of the umbilical orifice), it has no limbs. After a time a ridge appears on each side of the body, along the line of the intermediate cell mass in the interior ; this is the "Wolffian ridge, and from its anterior and posterior parts, the limbs grow out as small horizontal ledges. The differentiated embryo contains parts of all the layers of the blastoderm, and from each of these certain organs are formed as indicated in the following list. 1. From Epiblast. — a. The epidermis and its appendages. b. The nervous system, both central and peripheral. c. The epithelial structures of the sense-organs. d. The epithelium of the mouth, the enamel of the teeth. 836 DEVELOPMENT [CH. LIX. c. The epithelium of the nasal passages. /. The epithelium of the glands opening on the skin and into the mouth, and nasal passages. g. The muscular fibres of the sweat-glands. 2. From Mesoblast. — a. The skeleton and all the connective tissues of the body. b. All the muscles of the body. c. The vascular system, including the lymphatics, serous mem- branes, and spleen. d. The urinary and generative organs, except the epithelium of the bladder and urethra. The Somatic mesoblast forms the osseous, fibrous, and muscular tissues of the body-wall, including the true skin. The Splanchnic mesoblast forms the fibrous and muscular wall of the alimentary canal, the vascular system, and the urino-genital organs. 3. Prom Hypoblast. — a. The epithelium of the alimentary canal from the back of the mouth to the anus, and that of all the glands (including liver and pancreas) which open into this part of the ali- mentary tube. b. The epithelium of the respiratory cavity. c. The epithelium of the Eustachian tube and tympanum. d. The epithelium lining the vesicles of the thyroid. e. The epithelial nests of the thymus. /. The epithelium of the bladder and urethra. The Decidua and the Foetal Membranes. When the uterus is ready for the reception of an ovum it is lined by a greatly hyper trophied mucous membrane, called the decidua, because, after the delivery of the child, a portion of it comes away from the uterus with the other membranes. When the ovum, which has been fertilised in the upper part of the Fallopian tube, reaches the uterine cavity, it is usually in the stage of a morula or blastula. It rapidly eats its way into the substance of the decidua which closes over it, obliterating the opening through which it passed, and thus the ovum becomes embedded in the membrane, winch thereupon becomes separable into three parts. 1. The part between the ovum and the muscular wall of the uterus, the decidua basalis. 2. The part between the ovum and the uterine cavity, the decidua capsularis or refiexa, 3. The remaining part is called the decidua vera. Between the decidua capsularis and the decidua basalis lies the ovum, which speedily becomes differentiated into embryo, membranes, and appendages. The outermost of the f cetal membranes is the chorion ; this is covered with vascular villi, CH. LIX.] THE DECIDUA 837 Fig. 632. — Diagram representing the relation of the developing ovum to the decidua at a very early stage. 1, Uterine muscle ; 2, epiblast of ovum ; 3, inner cell mass of ovum (hypo- blast) ; 4, decidua basalis ; 5, decidua cap- sularis ; 6, decidua vera ; 7, cavity of uterus. which dip into the decidua capsularis and basalis. Inside the chorion is the amnion, a closed sac, which surrounds the embryo and is attached to its ventral wall at the 4 umbilicus. The amnion also forms a sheath for the umbilical cord by which the embryo is attached to the inner surface of the chorion; it is filled with fluid, the amniotic fluid, in which the foetus floats; the umbilical cord contains not only the blood-vessels which pass between a specialised portion of the chorion, which forms the foetal part of the placenta, and the em- bryo, but also the remains of the yolk-sac, and the duct by which it is connected with the intestine of the embryo. As the ovum grows, the decidua capsularis is expanded over its surface, and as the growth con- tinues the uterine cavity is gradu- ally obliterated, and the decidua capsularis is forced into contact with the decidua vera, with which it fuses. As the decidua is merely thickened mucous mem- brane, it naturally contains glands which become en- larged as the decidua thickens. It was believed, at one time, that the villi of the chorion entered the glands, but this is now known to be incorrect. The villi enter theinterglandular substance, and, in the human subject, the glands of the decidua capsularis eventu- ally disappear entirely. In the decidua basalis and the decidua vera the superficial portions of the glands also disappear ; their deep portions remain in an almost unchanged condi^ tion, and furnish the epithelium for the regeneration of the glands Fig. 633. — Diagram representing a later stage of develop- ment than that shown in fig. 632. 1, Uterine muscle ; 2, villi of chorion of ovum ; 3, coelom ; 4, decidua basalis ; 5, decidua capsularis ; 6, decidua vera ; 7, cavity of uterus ; 8, allantois ; 9, amnion cavity ; 10, primitive intestine ; 11, yolk-sac. 838 DEVELOPMENT [CH. LIX. and the lining of the uterine cavity after parturition. The inter- mediate parts of the glands in the decidua vera and the decidua basalis become very much enlarged, and form a stratum of the decidua called the spongy layer, and ultimately this layer is converted into a series of clefts, and it is along the line of these clefts that the decidua is separated at birth. In some mammals in which the connection between the chorion and the decidua is less intimate than in the human subject, the Fig. 634.— Diagrammatic view of a vertical transverse section of the uterus at the seventh or eighth week of pregnancy, c, c, c', cavity of uterus, which becomes the cavity of the decidua, opening at c, c, the cornua, into the Fallopian tubes, and at d into the cavity of the cervix, which is closed by a plug of mucus ; dv, decidua vera ; dr, decidua reflexa, with the sparser villi embedded in its substance ; ds, decidua basalis or serotina, involving the more developed chorionic villi of the commencing placenta. The foetus is seen lying in the amniotic sac ; passing up from the umbilicus is seen the umbilical cord and its vessels passing to their distribution in the villi of the chorion ; also the pedicle of the yolk-sac, which lies in the cavity between the amnion and chorion. (Allen Thomson.) glands persist to a greater or less extent, and secrete a fluid called uterine milk, which is absorbed by the chorion. The portion of the decidua which undergoes the greatest change is the decidua basalis, formerly called the decidua serotina. In it a number of large blood spaces are formed, and these are separated into masses or cotyledons by fibrous strands. The cotyledons are penetrated by chorionic villi, and it is this conjunction of chorionic villi and CH. LIX.] THE FCETAL APPENDAGES 839 decidua basalis which produces the placenta, which, at full term, is seven or eight inches across, and weighs nearly a pound. The placenta is the organ of foetal nutrition and excretion. Its blood sinuses are filled with maternal blood, which is carried to them by the uterine arteries and away from them by the uterine veins. Into these blood-filled spaces the vascular foetal villi project; hence it is easy for exchanges to take place between the foetal and the maternal blood, though the two blood-streams never mix together. Oxygen and nutriment pass from the maternal blood through the coverings of the foetal vessels into the foetal blood, and carbonic acid, urea, and other waste pro- 2 ducts pass in the contrary -— direction. The foetal blood is carried to the placenta by the umbilical arteries, which are the terminal branches of the aorta of the foetus ; these pass to the placenta by the umbilical cord, and the blood is returned, through the cord, by the umbilical vein. Development of the Foetal Appendages and Membranes. The manner in which the primitive intestinal canal is separated from the yolk-sac during the folding off of the embryo from the ovum, has already been con- sidered (p. 834). In birds the yolk-sac affords nutriment till the end of incubation, and the omphalo-mesenteric blood-vessels which convey the nutriment to the embryo, are correspondingly well developed. In mammalia, the office of the umbilical vesicle ceases at an early period, for the quantity of yolk is small, and the embryo soon becomes independent of it, on account of the intimate relations established with the maternal blood in the placenta. In birds, moreover, as the yolk-sac empties, it is gradually withdrawn into the abdomen of the chick through the umbilical opening which then closes over it. In mammals it remains outside the embryo, and in man its remnants, in a con- tracted and shrivelled condition, are found in the umbilical cord. In some mammals, however, it plays a much more important part than it Fig. 635. — Diagram representing a later stage of develop- ment of membranes and placenta than that shown in fig. 633. 1, Uterine muscle ; 2, placenta ; 3, yolk-sac ; 4, fused decidua vera and capsularis ; 5, primitive blood- vessel of embryo ; 6, amnion cavity (outer surface of amnion is fused with inner surface of chorion) ; 7, um- bilical cord ; 8, fostal villus in placenta. For blood- vessels see subsequent figures. 840 DEVELOPMENT [CH. LIX. does in man, and the time and mode of its disappearance differ in different orders of mammals. At an early stage, and whilst the changes to which reference has been made are proceeding, three important structures, the amnion, the chorion, and the allantois, are developed. Amnion. — As the embryo is differentiated, the surface of the ovum beyond its margins, formed by somatopleur, is gradually raised as a circular fold which is looked upon as consisting of head, tail, and lateral portions. The various parts of the fold rise quickly Fig. 636.— Diagram of a longitudinal section of an ovum showing mode of formation of amnion, allantois, and the primitive blood-vessels. 1, Amnion cavity ; li, villi on placental part of chorion ; 3, allan- tois ; 4, epiblast of chorion ; 5, somatic mesoblast ; 6, splanchnic mesoblast ; 7, yolk-sac ; S, coelom : 9, vascular area on yolk-sac ; 10. pericardium ; 11, heart ; 12, allantois diverticulum from cloaca; 13, chorion. and converge over the embryo, which, at the same time, passes towards the interior of the ovum. Finally the folds meet and fuse together at a point which is called the amnion navel. As soon as the folds fuse, the inner parts separate from the outer and form a closed sac (figs. 630 to 639). The inner wall of the sac is formed by epiblast, the outer by mesoblast, and both are continuous with the same layers of the embryo at the umbilical orifice. At first the amnion closely invests the embryo, but soon the space between the two, the amniotic cavity, becomes filled with fluid, and this increases in amount, till at the end of pregnancy it is present in very considerable quantity. CH. LIX.] THE AMNION AND CHORION 841 The amniotic fluid consists of water containing small quantities of albumin, urea, and salts. It is an exudation from the foetal and the maternal blood, and the urea in it comes from the foetal urine which is passed into the amniotic cavity in the later part of pregnancy. The function of the fluid appears to be purely mechanical. It supports the embryo on all sides, and protects it from blows and other injuries to the abdomen of the mother, and from sudden irregular contractions of the abdominal walls. Chorion. — The chorion is that portion of the surface of the ovum Fig. 637. — Diagram of a longitudinal section of an ovum, showing later stage of formation, amnion and foetal part of placenta than that shown in fig. 636. 1. Amnion cavity almost completely 3. Allantoic diverticulum from cloaca. 7. Yolk sac. closed in. 4. Epiblast of chorion 1 Q a nTn -t nT ,i 01 „. S. Ccelom. 2. Placental villi of chorion. 5. Somatic mesoblast / J - ™ m ' ltl, P leur ' io. Pericardium. which does not enter into the formation of the embryo or amnion, and after the separation of the amnion, it forms the whole of the outer surface of the ovum, completely surrounding the embryo, the amnion, and the allantois. At a very early period its surface is set with fine processes, the chorionic villi, which at first consist of epiblastic cells, alone, but very soon they acquire cores of somatic mesoblast, which becomes vascu- larised by the allantoic vessels which rapidly extend throughout the whole of the chorionic mesoblast. 842 DEVELOPMENT • [CH. LIX. At first the villi are small, but, as they project into the decidua capsularis and decidua basalis, they grow rapidly and branch repeatedly. Their function is to obtain nutriment from the uterine tissues. In the higher mammals, including man, they destroy and eat up many of the cells of the decidua, and gases and fluids pass through them from the maternal to the fcetal blood, and vice versd. In some mammals, however, they do not destroy the uterine tissues, and in those cases they absorb the uterine milk, which is secreted by the enlarged uterine glands. The chorionic villi which penetrate the decidua capsularis gradu- ally disappear as the capsularis fuses with the vera, and is reduced to a thin membrane ; but the villi which enter the decidua basalis increase enormously in size and complexity, to form the foetal part of the placenta, and their branches hang free in the interiors of large blood sinuses which are filled with maternal blood (fig. 634). Allantois. — The allantois is an outgrowth from the ventral portion of the posterior part of the primitive alimentary canal, and it consists of a hollow process of hypoblast covered with mesoblast (fig. 631, 12). In the human embryo it appears at a very early period, before the amnion folds have separated from the chorion, and it conveys the allantoic arteries from the embryo to the chorion, and the allantoic vein from the chorion to the embryo. As development proceeds, and that part of the chorion in contact with the decidua basalis is converted into the foetal part of the placenta (figs. 634 to 637), the allantoic blood- vessels in the chorion gradually disappear except in the placental area where they grow larger till birth. At first the allantois is very short, but, as the amnion distends and the embryo passes further and further into the interior of the enlarg- ing ovum, it is elongated into a cord which, together with the remains of the yolk-sac is surrounded and ensheathed by the amnion ; this cord is called the umbilical cord (fig. 634). In the human subject that portion of the allantois which lies in the umbilical cord consists entirely of vascular mesoblast, for the hollow pouch of hypoblast ends near the umbilicus; but in some mammals the hypoblastic diverticulum is prolonged to the inner surface of the chorion/ In man, therefore, the umbilical cord consists of — 1, An outer covering of amnion ; 2, a core of modified mesoblast derived from the mesoblast of the allantois and the wall of the yolk- sac ; 3, the remains of the hypoblastic portion of the yolk-sac, and 4, the two allantoic arteries and the allantoic vein. In the early stages immediately after the separation of the amnion from the chorion, the embryo and its amnion are attached to the chorion by the allantois, and they are situated in a space which is part of the original coelomic space between the somatic and splanchnic mesoblast (figs. 635 to 637). This space is continuous with the ccelum CH. LIX.] THE ALLANTOIS 843 in the embryo at the umbilical orifice. In the later* periods it is entirely obliterated, for the amnion is distended till its outer surface fuses with the inner surface of the chorion ; and at the same time the umbilical cord is differentiated as the distending amnion surrounds and presses together the allantoic stalk and the remains of the yolk- sac (fig. 634). At birth, on account of the contraction of the walls of the uterus and the pressure of the surrounding muscles, the liquor amnii forces part of the membrane formed by the fused amnion and chorion through the cervix uteri, which is gradually distended. When the distension is sufficient, the membrane ruptures, the liquor amnii escapes, and afterwards the child is forced out. It still remains con- nected with the placenta by the umbilical cord, and this connection should not be severed for a few minutes, in order that as much blood as possible may be aspirated from the foetal part of the placenta into the child as breathing commences. After' the child is expelled the contraction of the uterine wall con- tinues and the placenta is separated and forced out. The separation gradually extends through the decidua, along the line of the stratum spongiosum, and the fused chorion amnion and decidua turned inside out, follow the placenta to which they are attached, constituting, with the placenta, the after-birth. After the umbilical cord is tied and separated, the umbilical arteries inside the child become filled with blood-clot, and ultimately they are converted into fibrous cords, the so-called obliterated hypo- gastric arteries, and at the same time the allantois is also converted into a fibrous strand, the urachus, which extends from the apex of the bladder to the umbilicus. Development of the Framework of the Body. In the early stages of development, the only indication of a frame- work or skeleton is the notochordal rod of hypoblastic cells, which extends along the whole length of the dorsal wall of the primitive intestine beneath the neural tube, its anterior end being situated immediately behind the position where the pituitary body is after- wards formed. In mammals the notochord disappears, except in the centres of the intervertebral discs, but in amphioxus and lampreys it persists as a permanent skeletal support, and in these cases it closely resembles cellular cartilage enclosed in a fibrous sheath. It is com- posed of a very insoluble proteid-like substance, which, however, is not collagen. Collagen and gelatin (which is formed from collagen by boiling), are characteristic of true connective tissues which are formed from mesoblast ; the notochord is hypoblastic. The notochord contains also, like all embryonic tissues, a large quantity of glycogen. 844 DEVELOPMENT [CH. LIX. The rudiments from which the axial skeleton of the body is formed are the protovertebrse or mesoblastic somites (see p. 833). Each protovertebra separates into three parts : — 1. An outer, the cutaneous lamella, from which the deeper parts of the skin and the subcutaneous tissues of the body are developed. 2. A middle portion, the muscle plate. From the muscle plates all the striped muscles of the body, with the exception of those of the heart, are formed. Hypoblast S. Yolk-sac. Diagram of a transverse section of an ovum showing differentiation of protovertebra and formation of amnion folds, primitive intestine, and yolk-sac. 10. Primitive intestine. 11. Ccelom (extra-embryonic). 12. Co.'lom (intra-embryonic). 14. Primitive dorsal blood-vessel. 15. Scleratogenous part of protovertebra. 16. Muscle plate part of protovertebra. 17. Cutaneous lamella of protovertebra. 18. Amnion folds. Fio. 038. 1. Spinal cord. 2. Notochord. 3. Amnion cavity. 4. Epiblast | ,, somatopleur. 5. Somatic mesoblast / r 6. Splanchnic mesoblast |. ig Bplanchnopleur . J 3. A scleratogenous segment. The scleratogenous segments fuse together round the neural tube and the notochord, and in this way a continuous membranous vertebral column is formed. This is cleft on each side in every segment, for the passage of the nerve-roots and the accompanying blood-vessels. Part of the membranous column is converted first into cartilaginous and afterwards into bony vertebrae ; other parts are transformed into intervertebral discs and ligaments, and the remainder forms the membranes which line the spinal canal and surround the spinal cord. From the sides of the vertebras the CH. LIX.] FOEMATION OF LIMBS AND HEAD 845 ribs grow outwards and forwards in the thoracic region, and some of them meet together in front, and enter into the formation of the sternum or breast-bone. The Limbs. — At first there are no limbs, and then they jut out as buds from the sides of the body. Each consists of an epiblastic covering and a core of mesoblast. The central part of the mesoblast condenses and forms the cartilaginous rudiments of the bones which afterwards become ossified, and it also forms the ligaments which connect the bones together. Buds from the muscle plates, opposite the limbs, grow into them to form the muscles, and nerves from the corresponding segments of the spinal cord enter the buds (fig. 639). Blood-vessels connected with the vessels of the body also appear. Fig. 639. — Diagram of a transverse section of embryo and amnion, showing extension of mnscle plates, rudimentary limbs, and membranous vertebral column. 1, Spinal cord with nerve-roots ; 2, membranous vertebral column, formed from fused scleratogenous segments of protovertebrse ; 3, descending aorta ; 4, ccelom ; 5, amnion cavity ; 6, primitive intestine ; 7, muscle plate extending into body wall ; 8, bud of muscle plate into limb ; 9, muscle plate. The Read. — In the early stages the head is merely a rounded projection developed in the head fold of the embryo. Its anterior part is bent sharply downwards in front of the anterior end of the body in which the pericardium has been formed, and the cleft between the front of the head and the pericardium is the stomadoeal space or primitive mouth cavity (figs. 640, 641, 642). At tin's time there is no neck, but from the posterior part of the head to the side of the pericardium, a series of five visceral arches, with four intermediate clefts, extend round the sides of the foregut. As the neck forms, the visceral arches move forward with the head, and their lower ends meet in the middle line of the neck in front of the anterior end of the body ; thus it comes about that the stomadceal space is now bounded laterally and below by the first or mandibular arches, and above by the 846 DEVELOPMENT [CH. LIX anterior part of the head which is called the fronto-nasal process. The back of the space is bounded for a time by a thin membrane which separates the foregut from the stomadaeum. Just in front of the upper end of this membrane a diverticulum projects from the stomadseum towards the brain — this is Rathke's pouch ; it meets a downgrowth from the brain called the hypophysis, and the two structures unite to form the two lobes of the pituitary body. The membrane soon disappears, and the primitive mouth and the foregut form a con- tinuous cavity. In the meantime two olfactory fig. 64o.-Diagram representing pits have appeared on the under surface of a 0n ve^ ie youn^embr/o 116 ?! the fronto-nasal process, and they grow back Fronto-nasai process of head • into the roof of the stomadaeum. These pits 2, lolfactory pit ; 3, stoma- , „ . . . ., *• , (teum ; 4, umbilical orifice ; 5, cut the ironto-nasal process into three parts, a?cirrv! u eye ; . 6> mandibular the mesial nasal process between them, and the lateral nasal processes at the sides. Moreover, two little projections, the globular processes, grow down on each side of the middle line from the mesial nasal process. At this period the Fig. 641. — Diagram of anterior view of an embryo older than that shown in fig. 640. 1, Mid-brain ; 2, fore-brain ; 3, eye ; 4, olfactory pit ; 5, stomadajum; 6, pericardium; 7, umbilical orifice; 8, third visceral arch ; 9, second visceral arch ; 10, first or mandibular arch ; 11, max- illary process of mandibular arch ; 12, globular process ; 13, mesial nasal process ; 14, lateral nasal process. Fig. 642. — Diagram representing a later stage of development of the face than that shown in fig. 641. 1, Mid-brain ; 2, fore-brain ; 3, eye ; 4, anterior nasal orifice ; 5, globular process ; 6, mouth ; 7, pericardium; 8, second visceral arch ; 9, first visceral arch ; 10, maxillary pro- cess of first arch ; 11, lateral nasal process. upper boundary of the orifice of the stomadseum is formed by the two globular processes separated by a small cleft, and the two lateral nasal processes separated from the globular processes by the olfactory CH. LIX.] FOKMATION OF FACE AND SKULL 847 pits, and the sides and the lower boundary of the orifice are formed by the first or mandibular arches. From the upper ends of the mandibular arches the maxillary processes grow forwards immediately beneath the eyeballs (which have appeared on the sides of the head), and as they grow they pass beneath the lateral nasal processes, and beneath the anterior ends of the olfactory depressions, and fuse with the globular processes which also fuse together. Thus the orifice of the stoinadseal space is cut into three parts, the two nasal orifices and the mouth. The upper lip is formed by the fused globular and maxillary processes, and contains three lines of fusion — one in the middle line between the globular processes, and two more laterally placed between the maxillary processes and the globular processes. In certain cases the fusions do not take, and then clefts are left in the upper lip, and constitute the various forms of hare- lip. From the inner parts of the maxillary processes of opposite sides, palatal ledges grow across the stomadaeal space; and meeting in the middle line, they fuse together and separate the space into an upper or nasal and a lower or buccal space. If the palatal ledges fail to meet, cleft palate results. A cleft may also appear between the nasal orifice and the conjunctival sac, as a result of the absence of fusion between the maxillary process and the lateral nasal process. The lower boundary of the mouth orifice is formed by the mandibular arches. Both the tissues of the fronto-nasal process and those of the mandibular arches take part in the formation of the skeleton of the head. The notochord extends forwards as far as the pituitary body in all vertebrates, and in some, protovertebral somites can be traced forwards to a similar point; but in mammals they are only distinct behind the ear in the occipital region, and even there they entirely disappear at an early period. In the lower vertebrates a bar of cartilage appears at each side of the notochord in the head ; these are the parachordal cartilages, and they soon fuse to form a basilar plate in which the notochord is embedded. It becomes the basi-occipital and basi-sphenoid bones. In mammals, the parachordal stage is eliminated, and a basilar plate is formed at once. In front of the basilar plate two trabecule cranii embrace the pituitary body and extend forward into the fronto-nasal process, where they blend together to form an ethmo- vomerine plate ; and from this, processes extend down on each side, the Fig. 643. — Diagrams of the cartilaginous cranium. A, first stage. Ch, Notochord ; Tr, trabecules cranii ; P.ch., parachordal cartilages ; P, situa- tion of pituitary body ; N, E, 0, situations of olfactory, visual, and auditory organs. B, later stage. B, Basilar cartilages ; S, nasal septum and ethmoidal cartilages ; Eth, Eth', prolongations of ethmoid around olfactory organ, completing the nasal capsule ; N, E, 0, Ch, Tr, P. as before. (After Wiedersheim.) 848 DEVELOPMENT [CH. LIX. nasal part of the stomadseal space forming the rudiments * of the ethmoid and inferior turbinal bones, and a mesial process descends into a septum which has grown down from the under surface of the fronto- nasal process, and united with the palate dividing the nasal chamber into right and left halves. In this the vertical plate of the ethmoid and the vomer are ossified. The posterior parts of the trabecule fuse with the basilar plate and form the rudiment of the presphenoid. Posteriorly, and at the sides, cartilaginous plates grow over the cerebral vesicles; but in mammals the occipital region alone is roofed in by cartilage; the rest of the cranial vault being formed of membrane bones. From the sides of the presphenoid, the lesser wings or orbito- sphenoids containing the optic foramina are developed, and from the sides of the basi-sphenoid the greater wings or alisphenoids. A cartilaginous capsule invests the auditory vesicle, and becomes con- nected to the parachordal cartilage on each side. It is called the periotic capsule ; it is replaced by bone, which constitutes the petrous and mastoid portions of the temporal bone. Cartilaginous bars appear in the visceral arches, and from that in the mandibular arch on each side — Meckel's cartilage ; — the symphysis of the jaw, the malleus, and possibly the incus are formed. The stapes is the result of a separate ossification round the stapedial artery. The remainder of the mandible is ossified in the membrane around the mandibular cartilage. From the second bars the anterior part of the body of the hyoid bone, its small cornua, the stylo-hyoid ligaments, and the styloid pro- cesses are developed. The cartilages of the third arches give rise to the posterior part of the body of the hyoid, and its great cornua; the cartilages of the remaining arches take part in the formation of the cartilages of the larynx. In mammals the clefts between the arches are merely grooves which do not communicate with the cavity of the foregut, as they do in fishes and amphibians. The outer depression of the first cleft forms the external auditory meatus, and the inner depression is converted into the tympanic cavity and the Eustachian tube. The remaining clefts disappear. The cranial nerves are also associated with the arches and clefts. The third division of the fifth is distributed to the mandibular arch, its second division goes to the maxillary process, and its first division to the fronto-nasal process. The seventh is the nerve of the second arch, the ninth belongs to the third arch, and the remaining arches are associated with the tenth nerve. CH. LIX.] DEVELOPMENT OF VASCULAE SYSTEM 849 Development of the Vascular System. We have already seen that at an early stage of development, blood- vessels begin to form in the splanchnic mesoblast on the wall of the yolk-sac, outside the embryo, in an area called the area vasculosa. From the cephalic end of this area two longitudinal vessels run back- wards through the embryonic region, and they terminate posteriorly in the caudal part of the area vasculosa (fig. 644). As they run through the embryonic region, which is still outspread on the surface of the ovum, they pass beneath the pericardium, and then beneath the inner parts of the protovertebrse, not far from the sides of the notochord. As the Fig. 644.— Diagram representing the arrangement of the primitive blood-vessels before the embryo is folded off from the ovum. 1, Primitive vessel of left side ; 2, protovertebra ; 3, primitive streak ; 4, vascular area of yolk-sac; 5, non-vascular area of yolk-sac; 6, splanchnic mesoblast ; " mesoblast ; S, epiblast ; 9, pericardium. somatic head and the tail folds of the embryo form, these longitudinal vascular tubes are bent, both in front and behind, and, after the bending, each consists of five parts. A dorsal part which extends along the dorsal wall of the alimentary canal ; two ventral parts, one in front of the umbilicus and one behind that orifice, and two arches, a cephalic and a caudal, connecting the dorsal portion of each vessel with the anterior and posterior ventral portions respectively (fig. 645). The blood flows from the anterior part of the yolk-sac wall into the anterior ventral parts of these primitive embryonic vessels by two channels, which are called the omphalo-mesenteric veins. The anterior ventral vessels into which the omphalo-mesenteric veins pass, lie, now that the folding of the embryo has taken place, in the dorsal wall of the 3 H 850 DEVELOPMENT [CTI. LIX. pericardium and on the ventral wall of the foregnt ; they are the primitive heart tubes, and their anterior ends run into the first cephalic aortic arches, which pass round the sides of the anterior end of the foregut into the primitive dorsal vessels. A little later the parts of the anterior ventral vessels in front of the heart are con- nected with the dorsal vessels by four additional arches, one in eacli visceral arch — that is, there are now five aortic arches on each side connecting the anterior parts of the ventral with the anterior parts of the dorsal vessels. The portions of the ventral vessels winch lie behind the arches in the dorsal wall of the peri- cardium rapidly enlarge, and they fuse together to form the single heart, which is thus for a time a single longitudinal vessel. The parts of the ventral and dorsal vessels immediately behind each arch are called the roots of the arch. In mammals, the first and second arches disappear, and their ventral roots become the external carotid artery. The third arches and the dorsal roots of the first and second arches form the internal carotids. The dorsal root of the third arch disappears on each side, and the ventral root forms the common carotid artery. The ventral root of the right fourth arch becomes the innominate artery, and the arch itself takes part in the formation of the right subclavian artery. The dorsal roots of the right fourth and fifth arches and the dorsal part of the fifth arch itself disappear, and the ventral part of the fifth arch becomes the right pulmonary artery. The left fourth arch, with its dorsal and ventral roots, and the dorsal root of the left fifth arch, take part in the formation of the arch of the aorta. The left fifth arch persists till birth, then its dorsal part becomes a fibrous cord, the ligamentum arteriosum, and its ventral part forms the left pulmonary artery (fig. 647). The five aortic arches correspond with the gill arteries of fishes, but in mammals they never break up into capillaries, as in the fishes' gills. In amphibia three pairs persist throughout life. In reptiles the fourth pah* remains throughout Life as the permanent right and left aortse. In birds the right fourth remains as the permanent aorta, curving over the right bronchus, whereas in mammals, the left Fio. 045. — Diagram representing the primitive blood-vessels of the embryo. 1, First cephalic aortic arch ; 2, anterior ventral part of primitive vessel ; 3, dorsal part of primitive vessel ; 4, vascular area of yolk-sac ; 5, posterior ventral part of primitive vessel ; 6, caudal aortic arch ; 7, allantoic or umbilical branch ; 8, umbilical or allantoic vein; 9, placenta. CH. LIX.] THE PRIMITIVE ARTERIAL SYSTEM 851 fourth arch becomes the permanent aorta, curving over the left bronchus. Behind the dorsal roots of the fifth arches the dorsal longitudinal vessels fuse together, as far back as the lumbar region, to form the descending aorta, and the lower or posterior end of this vessel is con- tinued at first through the caudal arches into the posterior ventral portions of the longitudinal vessels which end on the yolk-sac (fig. 646). As soon as the allantois forms, each of the posterior ventral vessels gives off a large branch to it, and in front of the origin of tins vessel it "atrophies so that now the dorsal vessels are continued through the caudal arches into the allantoic or umbilical arteries, Fig. 646. — Diagram representing arrangement of primitive blood-vessels of left side of embryo. 1, Left primitive jugular vein ; 2, left duct of Cuvier ; 3, left cardinal vein ; 4, protovertebra ; f., primitive intestine ; 6, caudal aortic arch ; 7, allantoic or umbilical artery ; S, placenta ; 9, atrophied posterior ventral part of primitive vessel ; 10, yolk-sac artery ; 11, yolk-sac ; 12, vascular area on yolk-sac ; 13, pericardium ; 14, heart ; 15, cephalic aortic arch ; 16, brain. which carry blood to the placenta, and new vessels of small size are given off from the descending aorta to the yolk-sac. A little later the primary caudal arches, which lie inside the posterior ends of the Wolffian duets, are replaced by new arches, which pass outside the ducts, and connect the posterior ends of the dorsal longi- tudinal vessels with the allantoic arteries. At the same time the hind limbs appear, and each receives a branch from the corresponding dorsal vessel ; this is the external iliac artery. After its appearance the part of the dorsal vessel between it and the aorta is the common iliac artery, and the portion of the dorsal vessel behind it, together 852 DEVELOPMENT [CH. LIX. with the caudal arch, becomes the internal iliac or hypogastric artery. This is continued in the embryo along the ventral wall of the body as the umbilical arteries to the placenta. The Heart. — The simple longi- tudinal heart soon becomes separated by three transverse constrictions into four chambers, which are, from behind forwards, the sinus venosus, the auricle, the ventricle, and the aortic bulb (figs. 648 and 649). The sinus venosus receives the omphalo-mes- enteric and other veins, and the aortic bulb terminates in the fifth arches and the ventral roots of the fourth arches. The sinus venosus is gradu- ally absorbed into the auricle, and at the same time the heart tube bends so that the auricle is placed behind the ventricle and the aortic bulb — that is, between them and the wall of the foregut (figs. 650 and 651). As soon as the bending is completed each chamber is divided by septa into right and left halves, but an opening, the foramen ovale, remains in the interauricular septum till after birth. The aortic bulb is also divided into two parts : one of these is con- nected above with the fifth arches, which become the pulmonary arteries, and below with the right ventricle ; it becomes, therefore, the stem of the pulmonary artery. The other part, which is connected with the roots of the fourth arches above and the left ventricle below, forms the ascending part of the aorta. The Veins. — 1. The veins of the embryo are the omphalo-mes- enteric, which carry blood from the yolk-sac to the heart. 2. The umbilical or allantoic, bearing oxygenated blood from the placenta to the heart. 3. The primitive jugular veins, one on each side returning blood from the head, neck, and upper extremities. 4. The cardinal veins returning blood from the body walls, the Fio. 647.— Diagram of the aortic arches in a mammal, showing transformations which give rise to the permanent arterial vessels. A, Primitive arterial stem or aortic bulb, now divided into A, the ascending part of the aortic arch, and p, the pulmonary a a', right and left aortic roots; A', de scending aorta; 1, 2, 3, 4, 5, the five primi tive aortic or branchial arches ; I, II, III. IV, the four branchial clefts which, for the sake of clearness, have been omitted on the right side. The permanent systemic vessels are deeply, the pulmonary arteries lightly, shaded ; the parts of the primitive arches which are transitory are simply outlined ; c, placed between the permanent common carotid arteries ; c c, external carotid arte- ries ; c i, internal carotid arteries ; s, right subclavian, rising from the right aortic root beyond the fifth arch ; v, right vertebral from the same, opposite the fourth arch ; v' s', left vertebral and subclavian arteries rising together from the left, or permanent aortic root, opposite the fourth arch ; p, pulmonary arteries rising together from the left fifth arch ; d, outer or back part of left fifth arch, forming ductus arteriosus ; p n, p n', right and left pneumogastric nerves descending in front of aortic arch, with their recurrent branches represented diagrammatically as passing behind, to illus- trate the relations of these nerves respec- tively to the right subclavian artery (4) and the arch of the aorta and ductus arteri- osus (d). (Allen Thomson, after Rathke.) OH. LIX.] FOKMATION OF THE VEINS 853 Wolffian bodies, and the hind limbs. 5. The ducts of Cuvier, each of which receives a primitive jugular and a cardinal vein, and ends in the Fig. 648. — Diagram representing an anterior view of the primitive heart, aortic arches, and their roots. 1, Bulbus arteriosus ; 2, ventricle ; 3, auricle ; 4, sinus venosus ; 5, descending aorta ; 6, omphalo-mesenteric vein ; 7, um- bilical vein ; 8, duct of Cuvier ; 9, dorsal roots of aortic arches ; 10, ventral roots of aortic arches. Fig. 649.— Diagram representing a side view of the primitive heart with the cephalic aortic arches and their roots. 1, First cephalic aortic arch ; 2, second cephalic aortic arch ; 3, third cephalic aortic arch ; 4, fourth cephalic aortic arch ; 5, fifth cephalic aortic arch ; 6, bulbus arteriosus ; 7, ventricle ; 8, auricle ; 9, sinus venosus ; 10, omphalo-mesenteric vein (left) ; 11, ventral roots of aortic arches ; 12, dorsal roots of aortic arches ; 13, descending aorta. auricle. Thus six veins terminate in the sinus venosus, and through it in the auricle (fig. 648). Both ducts of Cuvier retain their con- Fig. 650. — Diagram representing a side view of heart after it has folded on itself. 4, Ventral root of fourth aortic arch ; 5, fifth aortic arch ; 6, bulbus arteriosus ; 7, ventricle ; 8, auricle ; 9, sinus venosus ; 10, left omphalo- mesenteric vein. Fig. 651. — Diagram representing an anterior view of the heart after it has folded on itself. 4, Ventral root of fourth aortic arch ; 5, fifth aortic arch ; 6, bulbus arteriosus ; 7, ventricle ; S, auricle. nection with the auricle, the right forming the lower part of the superior vena cava, and the left the oblique vein of Marshall in man, and the lower part of the left superior cava in some mammals. 854 DEVELOPMENT [Oil. LIX. The upper part of the primitive jugular vein on each side becomes the internal jugular. The lower part on the right side becomes the right innominate vein, and the upper portion of the superior vena cava. On the left side the lower part helps to form the left superior intercostal vein. The left innominate vein is a transverse anastomosis between the Fig. 652. — The dark are the primitive, the light the secondary veins, with the exception of tin 1 external and internal jugular veins. The dark portions entering the auricles are the remains of the primi- tive ducts of Cuvier. The dark portion above each duct of Cuvier, as far as the external and internal jugular veins, is the primitive jugular vein, and the dark portion below the duct of Cuvier is the cardinal vein. 1, External jugular vein ; 2, internal jugular vein ; 3, subclavian vein ; 4, right innominate vein ; 5, superior vena cava ; 6, right superior intercostal vein ; 7, vena azygos major; 8, right hepatic vein ; 9, upper part of inferior vena cava; 10, renal vein; 11, right common iliac vein; 12, right external iliac vein; 13, right internal iliac vein; 14, left innominate vein; 15, left superior intercostal vein ; lti, oblique vein of Marshall ; 17, vena azygos minor superior ; 18, vena azygos minor inferior ; 19, atrophied part of left cardinal vein ; 20, left common iliac vein ; 21, auricle ; 22, duct of Cuvier. primitive jugular veins. The subclavian veins and the external jugular veins are new formations, the former being developed in association with the growth of the upper limbs. The cardinal veins receive the intercostal and lumbar veins from the walls of the body, and the veins from the Wolffian bodies and kidneys. Below the point of union with the external iliac vein from the hind limb the cardinal vein becomes the internal iliac vein. Above the external iliac vein the right cardinal vein forms the right CH. LIX.] THE LIVEK VEINS 855 common iliac vein, and the lower part of the inferior vena cava below the right renal vein. Above the right renal vein it becomes the vena azygos major. The parts of the left cardinal between the left lumbar veins disappear, and blood from the left lumbar veins and the left common iliac vein is carried across to the right cardinal, and subse- quently to the inferior vena cava by a series of transverse anastomosing channels, of which the lowest becomes the left common iliac vein. The upper part of the left cardinal vein is also broken up, and its remains form the vertical parts of the minor azygos veins and lower part of the left superior intercostal vein. The transverse parts of the minor azygos veins are also developed from transverse anastomosing channels (fig. 652). Fig. 653. — Diagram showing the arrangement and transformation of some of the primitive veins. A, Early stage ; B, later stage. 1, Primitive jugular vein ; 2, duct of Cuvier ; 3, cardinal vein ; 4, right umbilical vein ; 5, right omphalo-mesenteric vein ; 6, common umbilical vein ; 7, sinus venosus ; S, liver ; 9, left umbilical vein ; 10, right vena revehens ; 11, left vena revehens ; 12, right vena advehens ; 13, left vena advehens. In the early stages both the omphalo-mesenteric and the right and left terminal branches of the umbilical vein end in the heart. When the liver forms, the omphalo-mesenteric veins end in venge advehentes, which break up into capillaries in the liver, and the capillaries end in venae revehentes, which become the hepatic veins (fig. 653). The left hepatic vein joins the right hepatic vein to form a common trunk, which becomes the upper end of the inferior vena cava, and this is prolonged down to unite with the right cardinal at the level of the right renal vein ; but before joining the right cardinal it gives off a branch to join the left cardinal at the level of the left renal vein, and thus the blood from both kidneys enters the inferior vena cava. In the meantime two transverse anastomoses have formed between the omphalo- mesenteric veins below the liver, and still lower the two veins fuse 856 DEVELOPMENT [CH. LIX. together; thus two loops are formed through which the duodenum passes. The veins from the intestine open into the fused trunks, and the splenic vein enters the left vein at the level of the lower transverse anastomosis. Subsequently the left side of the upper and the right side of the lower loop disappear, and the portal vein is produced from the remains. In the meantime the right umbilical vein has disappeared, and the left has united with the left omphalo-mesenteric vein at the point where the latter ends in the left vena advehens. From this r=r Flo. 654. — Diagram representing a later stage in the development of the veins than that shown in tig. 053. 1, Primitive jugular vein ; 2, duct of Cuvier ; 3, upper part of cardinal vein, now vena azygos major ; 5, remains of light lower limb of loop formed by fusion of omphalo-mesenteric veins ; 6, common umbilical vein ; 7, sinus venosus ; 8, liver ; 9, left branch of umbilical vein ; 10, right hepatic vein ; 11, left hepatic vein ; 12, right vena advehens ; 13, left vena advehens ; 14, upper part of inferior vena cava ; 15, right renal vein ; 16, lower part of inferior vena cava (cardinal vein) ; 17, fused part of omphalo-mesenteric vein ; 18, vein from alimentary canal ; 19, splenic vein ; 20, remains of left upper limb of loop formed by fusion of omphalo-mesenteric veins ; 21, ductus venosus. point a direct channel opens up beneath the liver to the upper part of the inferior vena cava; this is the ductus venosus, and it conducts the greater part of the oxygenated blood from the umbilical vein directly to the inferior vena cava, and so to the right auricle ; but part of the umbilical blood passes into the liver with the omphalo-mesenteric blood. A pulmonary vein forms and carries blood from the lungs to the left auricle. It is subsequently replaced first by two veins, one from each lung, and afterwards four veins, two from each lung. CH. LIX.] THE FCETAL CIRCULATION 857 Circulation of Blood in the Fcetus The circulation of blood in the fcetus differs considerably from that of the adult. It will be well, perhaps, to begin its description by tracing the course of the blood, which, after being carried to the Fig. 655. — Diagram of the Festal Circulation. placenta by the two umbilical arteries, has returned, oxygenated and replenished, to the fcetus by the umbilical vein. It is at first conveyed to the under surface of the liver, and there 858 DEVELOPMENT [CII. LIX. the stream is divided, — a part of the blood passing straight on to the inferior vena cava, through a venous canal called the ductus venosus, while the remainder passes into the portal vein, and reaches the inferior vena cava after circulating through the liver. Whether, however, by the direct route through the ductus venosus or by the roundabout way through the liver, — all the blood which is returned from the placenta by the umbilical vein reaches the inferior vena cava at last, and is carried by it to the right auricle of the heart, into which cavity is also pouring the blood that has circulated in the head and neck and arms, and has been brought to the auricle by the superior vena cava. It might be naturally expected that the two streams of blood would be mingled in the right auricle, but such is not the case, or only to a slight extent. The blood from the superior vena cava — the less pure fluid of the two — passes almost exclusively into the right ventricle, through the auriculo-ventricular opening, just as it does in the adult ; while the blood of the inferior vena cava is directed by the fold of the lining membrane of the heart, called the Eustachian valve, through the foramen ovale into the left auricle, whence it passes into the left ventricle, and out of this into the aorta, and thence to all the body, but chiefly to the head and neck. The blood of the superior vena cava, which, as before said, passes into the right ventricle, is sent out thence in small amount through the pulmonary artery to the lungs, and thence to the left auricle, by the pulmonary veins, as in the adult. The greater part, however, does not go to the lungs, but instead, passes through a canal, the ductus arteriosus, leading from the pulmonary artery into the aorta just below the origin of the three great vessels which supply the upper parts of the body ; and there meeting that part of the blood of the inferior vena cava which has not gone into these large vessels, it is distributed with it to the trunk and other parts — a portion passing out by way of the two umbilical arteries to the placenta. From the placenta it is returned by the umbilical vein to the under surface of the liver, from which the description started. Changes after Birth. — Immediately after birth the foramen ovale begins to close, and so do the ductus arteriosus and ductus venosus, as well as the umbilical vessels ; the closure is completed in a few days, so that the circulation then takes the course it traverses for the rest of life. Development of the Nervous System. The nervous system originates from the thickened walls of the medullary groove, which by the meeting of the dorsal ridges is con- verted into the medullary canal. These walls are composed entirely of epiblast. The anterior part of this mass becomes the brain, the CH. LIX.] THE NERVOUS SYSTEM 859 rest of it the spinal cord ; the canal itself is seen in the adult as the ventricles of the brain and central canal of the spinal cord. The nerves are formed of epiblast too ; they are outgrowths from masses of cells called neuroblasts, the primitive nerve-cells. In the case, however, of the olfactory and optic nerves we have not to deal with solid outgrowths, but with hollow protrusions from the brain, which become solid at a later stage. The Spinal Cord. — The cavity formed by the closure of the neural canal soon becomes a cleft running from before backwards. It is bounded at first by columnar epithelium ; these cells afterwards become ciliated ; on their exterior is a homogeneous basement mem- brane. The wall soon becomes thicker, and the basement membrane is thus separated further and further from the central canal. This increase in thickness is due in part to the increase in length of the columnar cells: in part to The inner retains its the appearance of new cells, part of the columnar lining palisade-like character, and forms ultimately the lining epithelium of the central canal. The cells are called spongioblasts. The external ends of the cells break up into a reticulum called the my- elospongium, and this is limited externally by the basement membrane at the circum- ference. The myelospongium forms the neuroglia. Between the inner ends of the spongio- blasts (fig. 656, S) numerous rounded cells called germinal cells (G) next appear. These rapidly divide, and so form neuroblasts (N). The neuroblasts are pear-shaped; each has a large oval nucleus, and its tapering stalk is directed towards the outer surface of the cord ; the process ultimately pierces the basement membrane (fig. 657). These are the primitive nerve-cells ; their processes are the axis cylinder processes which grow out as nerve-fibres. The nerve sheaths are formed later (see pp. 692-697). The neuroblasts collect into groups, one of which, especially large, is at the situation of the future anterior horn ; the processes of the primitive nerve-cells pass out of the cord as the beginnings of the anterior roots (fig. 658). The somewhat oblique coursing of these fibres before they leave the cord forms the beginning of the anterior white column. The posterior white Fig. 656.— Inner ends of spongio- blasts (S), with germinal cells (G) between them. NX, neuro- blasts which have resulted from the division of a germinal cell ; M, myelospongium formed by the branching outer ends of the spongioblasts. (After His.) Fig. 657.— Three neuroblasts, each with a nerve-fibre pro- cess, growing out beyond the basement membrane of the embryonic spinal cord. (After His.) 860 DEVELOPMENT [CII. LIX. columns simultaneously begin to appear on each side of the narrow dorsal part of the canal. They are formed by the posterior roots entering the cord. As the cornua of grey matter grow out from the central mass, the anterior fissure and the posterior septum of the cord begin to appear. The anterior or ventral fissure is simply a cleft between the enlarg- ing lateral halves of the cord. The posterior septum is formed by a condensation of the neuroglia in the dorsal wall of the neural canal. Fio. 658. — Section of spinal cord of a four weeks human embryo. The posterior roots are continued within the cord into a small longitudindal bundle, which is the rudiment of the posterior white column. The anterior roots are formed by the convergence of the processes of the neuroblasts. The latter, along with the elongated cells of the myelospongium, compose the grey matter. (His.) The cylindrical form of the cord is attained by the development of the lateral columns, which are formed by the processes from neuro- blasts in the brain growing; down the sides of the cord, and these become medullated at a later period. The membranes and blood- vessels are formed from mesoblast. Up to the fourth month the cord and vertebral canal increase in length pari passu, but after that, the vertebral canal grows faster, so that at birth the coccygeal end of the cord is opposite the third lumbar, and in the adult opposite the first lumbar vertebra. This gives an obliquity to the lower nerve roots, which, together with the filum terminate, form the cauda equina. The Nerves. — Some fibres grow from the spinal cord and form CH. LIX.] FORMATION OF SPINAL CORD AND BRAIN 861 the anterior roots which we have already considered. The posterior roots are formed in the following way : — Along the dorsal aspect of the primitive cord a crest of epiblast appears, and is called the neural crest. Special enlargements of this appear opposite the middle of each pair of protovertebrse ; these grow downwards on each side, and their attachment to the cord is then entirely lost. These little islands of epiblast contain numerous neuroblasts ; each island forms a spinal ganglion, and the neuroblasts within it become the cells of that ganglion. Two processes grow from each cell ; one directed towards the spinal cord, where it con- Fig. 659.— A, Bipolar cell from spinal ganglion of a 4J weeks embryo (after His), n, Nucleus ; the arrows indicate the direction in which the nerve processes grow, one to the spinal cord, the other to the periphery. B, a cell from a spinal ganglion of the adult ; the two processes have coalesced to form a T-shaped junction. (Diagrammatic.) tributes to the formation of the posterior white column, and ultimately arborises around the cells of the grey matter at a higher level. The other grows to the periphery. The two processes become blended in the first part of their course, and so the T-shaped junction is formed (fig. 659). Small portions segmented off from the spinal ganglia form the sympathetic ganglia. The Brain. — The histological details of the formation of the epithelium of the ventricles from spongioblasts, of neuroglia from the myelospongium, of nerve-cells from neuroblasts, and of the nerve-fibres of the white matter and of the nerves as the out- growths from the neuroblasts, are all essentially the same, as already described in connection with the spinal cord. But the grosser anatomical details differ. The front portion of the medullary canal is almost from the first widened out and divided into three vesicles. From the anterior 8G2 DEVELOPMENT [CII. LIX. vesicle the two primary optic vesicles are budded off laterally : their further history will be traced in the next section. Somewhat later the same vesicle divides into two, and thus the telencephalon and diencephalon are formed. In the walls of the posterior (third) cerebral vesicle, a thickening appears (rudimentary cerebellum) which becomes separated from the rest of the vesicle by a deep inflection. At this time there are two chief curvatures of the brain (fig. 660). Fig. 600. — Early stages in development of human brain (magnilied). 1, 2, 3, are from an embryo about seven weeks old ; 4, about three months old. m, Middle cerebral vesicle (mesencephalon) ; c, cere- bellum ; m o, medulla oblongata; i (in tig. 3), diencephalon; h, telencephalon; i', infundibulum ; fig. 3 shows the several curves which occur in the course of development ; fig. 4 is a lateral view, showing the great enlargement of the cerebral hemispheres which have covered in the thalami, leaving the optic lobes, m, uncovered. (Kolliker.) N.B.— In fig. 2 the line i terminates in the right hemisphere ; it ought to be continued into the diencephalon. (1.) A sharp bend of the whole cerebral mass downwards round the end of the notochord, by which the anterior vesicle, which was the highest of the three, is bent downwards, and the middle one comes to occupy the highest position. (2.) A sharp bend, with the convexity forwards, which runs in beneath the rudimentary cere- bellum separating it from the medulla. Thus, five fundamental parts of the foetal brain may be distin- guished, which, together with the parts developed from them, may bo presented in the following tabular view : — • OIL LTX.] THE CEREBRAL IIEMISPHEEES 863 Table of Parts developed from Fundamental Parts of Brain. I. Anterior Primary Vesicle. First Secondary Vesicle, Telencephalon, or Fore- brain. Second Secondary Vesicle, Diencephalon, or Twixt--! brain. Anterior end of third ventricle, foramen of Monro, lateral ven- tricles, cerebral hemispheres, corpora, striata corpus callosum, fornix, lateral ventricles, olfac- tory bulb. Thalami optici, pineal gland, part of pituitary body, third ven- tricle, optic nerve and retina, infundibulum. II. Middle f Third Secondary Vesicle, Primary Vesicle. Mesencephalon, or Mid- l Cor P ^. quadrigemina, crura k ram r cerebri, aqueduct of Sylvius. and III Posterior [Fourth Secondary Vesicle, \ Fourth ven- (Cerebellum Prima J or Metencephalon. / tricle. \ Pons. Vesicle I Fifth Secondary Vesicle,) Fourth ven-/ Medulla oblon- \ or Myelencephalon. J tricle. \_ gata. The cerebral hemispheres formed by bifurcation of the telence- phalon grow rapidly upwards and backwards, while from their inferior surfaces the olfactory bulbs are budded off. The middle cerebral vesicle (mesencephalon) for some time is the most pro- minent part of the foetal brain, and in fishes, amphibia, and reptiles, it remains uncovered through life as the optic lobes. But in birds the growth of the cerebral hemi- spheres thrusts the optic lobes down laterally, and in mammalia completely overlaps them. In the lower mammalia the backward growth of the hemi- spheres ceases, but in the higher groups, such as the monkeys and man, they grow still further back, until they completely cover in the cerebellum, so that on looking down on the brain from above, the cerebellum is quite concealed from view. The surface of the hemispheres is at first quite smooth, but as early as the third month the great Sylvian fissure begins to be formed (fig. 661). The next to appear is the parieto-occipital fissure ; these two great fissures, unlike the rest of the sulci, are formed by a curving round of the whole cerebral mass. In the sixth month the fissure of Eolando appears : from this time till the end of foetal life the brain grows rapidly in size, and the Fig. 661. — Side view of foetal brain at six months, showing commencement of formation of the principal fissures and convolutions. F, Frontal lobe ; P, parietal ; 0. occipital ; T, temporal ; a a a, commencing frontal convolutions ; s, Sylvian fissure ; s', its anterior division ; c, within it the central lobe or island of Eeil ; r, fissure of Rolando ; p, parieto-occipital fis- sure. (R. Wagner.) 864 DEVELOPMENT [CH. LIX. convolutions appear in quick succession ; first the great primary ones are sketched out, then the secondary ones. The commissures of the A Fio. 662.— Longitudinal section of the primary optie vesicle in the chick, magnified (from Remak).— A, from an embryo of sixty-five hours ; B, a few hours later ; C, of the fourth day ; c, the corneous layer or epidermis, presenting in A the open depression for the lens, which is closed in B and C ; I, the lens follicle and lens ; pr, the primary optic vesicle ; in A and B, the pedicle which forms the optic nerve is shown ; in C, the section being to the side of the pedicle, the latter is not shown ; v, the secondary optic vesicle and vitreous humour. brain, and the corpus callosum, are developed by the growth of fibres across the middle line. The Hippocampus major is formed by the folding in of the grey matter from the exterior into the lateral ventricles. The Eye. — Soon after the first three cerebral vesicles have become distinct from each other, the anterior one sends out a lateral Via. 663. — Diagrammatic sketch of a vertical longitudinal section through the eyeball of a human fietus of four weeks. The section is a little to the side, so as to avoid passing through the ocular cleft ; c, the cuticle where it becomes later the corneal epithelium ; 1, the lens ; op, optic nerve formed by the pedicle of the primary optic vesicle ; vp, primary medullary cavity or optic vesicle ; p, the pigment layer of the retina ; r, the inner wall forming the remaining layers of the retina ; vs, secondary optic vesicle containing the rudiment of the vitreous humour, x 100. (Kolliker.) Fir.. 664.- — Transverse vertical section of the eyeball of a human embryo of four weeks. The anterior half of the section is represented : pr, the remains of the cavity of the primary optic vesicle ; p, the inner part of the outer layer forming the retinal pig- ment; r, the thickened inner part giving rise to the other structures of the retina ; v, the commencing vitre- ous humour within the secondary optic vesicle ; v', the ocular cleft through which the loop of the central blood-vessel, a, projects from below ; I, the lens with a central cavity, x 100. (Kolliker.) vesicle from each side (primary optic vesicle), which grows out towards the free surface, its cavity communicating with that of the CM. LIX.] FORMATION OF THE EYE 865 cerebral vesicle through the canal in its pedicle. It remains con- nected to the diencephalom It is soon met and invaginated by an ingrowing process from the epiblast of the surface (fig. 662). This process of the epiblast is at first a depression, which ultimately becomes closed in at the edges so as to produce a hollow ball, which is thus completely severed from the epidermis with which it was originally continuous. From this hollow ball the crystalline lens is developed. The way in which this occurs has been described in a previous chapter (see p. 770). By the ingrowth of the lens the anterior wall of the primary optic vesicle is forced back nearly into contact with the posterior, and thus the primary optic vesicle is almost obliterated. The cells in the anterior wall are much longer than those of the posterior wall ; from the former all the layers of the retina are developed, except the layer of pigment cells which is formed from the latter. The cup-shaped hollow in which the lens is now lodged is termed the secondary optic vesicle ; its walls grow up all round, leaving, how- ever, a slit below where it meets the lens. This slit is the choroidal fissure. The cavity of the secondary optic cup is filled by processes of the neuroglia cells of the retina. Amidst these a process of vascular mesoblast projects through the choroidal fissure, and by the union of the two the vitreous humour, the lens capsule, and the capsulo-pupillary membrane are formed. In mammals the mesoblastic process projects, not only into the secondary optic vesicle, but also into the pedicle of the primary optic vesicle, invaginating it for some distance from beneath, and thus carrying up the arteria centralis retince into its permanent position in the centre of the optic nerve. This invagination of the optic nerve does not occur in birds, and consequently no arteria centralis retinse exists in them. But they possess an important permanent relic of the original protrusion of the mesoblast through the choroidal fissure, in the pecten, while a remnant of the same fissure sometimes occurs in man under the name coloboma iridis. The cavity of the primary optic vesicle becomes completely obliterated, and the rods and cones get into apposition with the pigment layer of the retina. The inner segments of the rods are the first formed, then the outer. The cavity of its pedicle dis- appears and the solid optic nerve is formed. Meanwhile the cavity in the centre of the primitive lens becomes filled up by the growth of fibres from its posterior wall. The epithelium of the cornea is developed from the epiblast, while the corneal tissue proper is derived from the mesoblast which intervenes between the epiblast and the primitive lens which was originally continuous with it. The sclerotic coat is developed round the eyeball from the general mesoblast in which it is imbedded. The choroid is developed from the mesoblast 3 I 866 DEVELOPMENT [CII. TJX. on the outside of the optic cup, and the iris by the growing forwards of the anterior edge of the optic cup. The ciliary processes arise from the hypertrophy of the edge of the optic cup, which forms folds into which the choroidal mesoblast grows, and in which blood-vessels and pigment-cells develop. The iris is formed rather late, as a circular septum projecting inwards, from the fore part of the choroid, between the lens and the cornea. In the eye of the foetus of mammalia, the pupil is closed by a delicate membrane, the membrana papillaris, which forms the front portion of a highly vascular membrane that, in the foetus, surrounds the lens, and is named the membrana capsulo-pupillaris (fig. 665). It is supplied with blood by a branch of the arteria centralis retina, which, passing forwards to the back of the lens, there subdivides. The arteria centralis is obliterated in the adult, and is then called the canal of Stilling. The membrana capsulo-pupillaris disappears in the human subject a short time before birth. The eyelids of the human subject and mammiferous animals, like those of birds, are first developed in the form of a ring. They then extend over the globe of the eye until they meet and become firmly agglutinated to each other. But before birth, or in the carnivora after birth, they separate. The Ear. — Very early in the development of the embryo a depression or ingrowth of the epiblast occurs on each side of the head, which deepens and soon becomes a closed follicle. This primary otic vesicle, which closely corresponds in its formation to the lens follicle in the eye, sinks down to some distance from the free surface ; from it are developed the epithelial lining of the membranous laby- rinth of the internal ear, consisting of the vestibule and its semicir- cular canals and the scala media of the cochlea. The surrounding mesoblast gives rise to the various fibrous bony and cartilaginous parts which complete and enclose this membranous labyrinth, the bony semicircular canals, the walls of the cochlea with its scala vesti- buli and scala tympani. The Eustachian tube, the cavity of the tympanum, and the Fig. 605.— Blood-vessels of the capsulo-pupillary membrane of a new-born kitten (magnified). The drawing is taken from a preparation injected by Tiersch, and shows in the central part the con- vergence of the net- work of vessels in the pupil- lary membrane. (Kdlliker.)] CH. LIX.] THE ALIMENTARY CANAL 867 external auditory passage, are the remains of the first or hyo- mandibular cleft. The membrana tympani divides the cavity of this cleft into the tympanum, and the external meatus. The mucous membrane of the pharynx, which is prolonged in the form of a diver- ticulum through the Eustachian tube into the tympanum, and the external cutaneous system come into relation with each other at this point; the two structures are separated only by the membrane of the tympanum. The pinna or external ear is developed from a process of integu- ment in the neighbourhood of the first and second visceral arches, and probably corresponds to the gill-cover (operculum) in fishes. The Nose. — The nose originates, like the eye and ear, in a depres- sion of the superficial epiblast at each side of the fronto-nasal process (primary olfactory pit), which is at first in front of the cavity of the primitive mouth, and gradually extends backwards, into its roof (p. 846). The olfactory bulbs of the brain lie in close relation with the roofs of the olfactory pits, and the olfactory nerves are out- growths from special bipolar cells in the epithelium of the pit (see p. 736). Development of the Alimentary Canal. The alimentary canal in the earliest stages of its development consists of three parts — the fore- and hind-gut ending blindly at each end of the body, and a middle segment which communicates freely on its ventral surface with the cavity of the yolk-sac through the vitelline or omphalo-mesenteric duct. From the fore-gut are formed the lower and back part of the mouth, the pharynx, oesophagus, stomach, and first and second parts of the duodenum; from the hind-gut, the lower end of the colon, the rectum, and the bladder. The upper and front part of the mouth, and the nasal chambers are developed from the stoniadseal space (p. 847). At the other end of the alimentary canal the anus is formed by an involution from the free surface, which at length opens into the hind-gut. When the depression from the free surface does not reach the intestine, the condition known as imperforate anus results. A similar condition may exist at the other end of the alimentary canal from the failure of the involution which forms the mouth, to meet the fore-gut. The middle portion of the digestive canal becomes more and more closed in, till its wide communication with the yolk-sac becomes narrowed down to a small duct (vitelline). This duct usually com- pletely disappears in the adult, but occasionally the proximal portion 8G8 DEVELOTMKNT [CII. LIX. remains as a diverticulum from the intestine, Meckel's diverticulum. Sometimes a fibrous cord, attaching some part of the intestine to the umbilicus, remains to represent the vitelline duct. Such a cord has been known to cause, in after-life, strangulation of the bowel and death. The alimentary canal lies in the form of a straight tube close beneath the vertebral column, but it gradually becomes long, con- Fio. 6(30.— Outlines of the form and position of the alimentary canal in successive stages of its develop- ment. A, Alimentary canal, etc., in an embryoof four weeks; 15, at six weeks; C, at eight weeks; I, the primitive lungs connected with the pharynx ; s, the stomach ; d, duodenum ; i, the small intestine; i', the large intestine; c, the cascum and vermiform appendage; r, the rectum; cl, in A, the cloaca ; a, in B, the anus distinct from si, the sinus uro-genitalis ; v, the yolk-sac , vi, the vitello-intestinal duct; u, the urinary bladder and uracil us leading to the allantois; g, genital ducts. (Allen Thomson.) voluted, and divided into its special parts, stomach, small intestine, and large intestine (fig. 666), and at the same time comes to be suspended in the abdominal cavity by means of a lengthening mesentery formed from the splanchnopleur which attaches it to the vertebral column. The stomach originally has the same direction as the rest of the canal ; its cardiac extremity being superior, its pylorus inferior. These changes of position may be readily understood from the accompanying figures (fig. 666). Pancreas and Salivary Glands. — The principal glands in con- nection with the intestinal canal are the salivary glands, pancreas, and the liver. In mammalia, each salivary gland first appears as a simple canal with bud-like processes, lying in a mass of mesoblast, and communicating with the cavity of the mouth. As the develop- ment of the gland advances, the canal becomes more and more ramified (fig. 667). The submaxillary and sublingual glands and CH. LIX.] SALIVARY GLANDS, PANCEEAS, AND LIVEE 869 the pancreas are developed exactly in the same way, and their cells are derived from the hypoblast lining the fore-gut, while those Fig. 6(57. — Lobules of the parotid with the salivary ducts, in the embryo of the sheep, at a somewhat advanced stage. of the parotid glands are formed from the epiblast lining the stomadseum. In both cases the blood-vessels and connective tissues mm Fig. 66S. — Diagram of part of digestive tract of a chick (-1th day). The black line represents hypoblast, the outer shading mesoblast. lg. Lung diverticulum with expanded end forming primary lung- vesicle ; St, stomach ; I, two hepatic diverticula, with their terminations united by solid rows of hypo- blast cells ; p, diverticulum of the pancreas with the vesicular diverticula coming from it. (Gotte.) are formed from the mesoblast into which the glandular structure grows. The Liver. — The liver is developed by the protrusion of a part of 870 DEVELOPMENT [CII. LIX. the walls of the fore-gut, in the form of two conical hollow branches (figs. 668, 669). The inner portion of the cones consists of a number of solid cylindrical masses of cells, derived from the hypoblast, which become gradually hollowed by the formation of the hepatic ducts, and among which blood-vessels are rapidly developed. The secreting cells of the organ and the lining epithelium of the ducts are derived from the hypoblast; the connective tissue, and vessels from the mesoblast. The gall-bladder is developed as a diverticulum from the hepatic duct. The spleen and lymphatic glands are developed from the meso- blast : the thyroid originates from the hypoblast ; it grows as a diverti- W^k BE "^ fm ¥ ^'dK 53ffi38i^B iii 5 W /« |J v^_S ~-'.7>^H L VV fctifl^' ' 2 "^ t^^ ^ Fig. 60: ■».— Rudiments of the liver on the intestine of a chick at the tifth day of incubation. 1, Heart ; 2, intestine; 3, diverticulum of the intestine in which the liver (4) is developed; 5, part of the mucous layer of the germinal membrane. (Muller.) culum from the floor of the fore-gut, opposite the first clefts, and by two diverticula from the fourth visceral clefts. The hypoblastic cells form the lining epithelium of the vesicles ; the stroma of the gland is formed by the surrounding mesoblast. The thymus is formed in a similar way from the third visceral clefts, and its hypoblastic cells form the corpuscles of Hassall; the lymphoid tissue by which they are invaded and ultimately surrounded is mesoblastic. Development of the Respiratory Apparatus. The Lungs first appear as two small diverticula from a groove in the ventral wall of the fore-gut (figs. 608, 670). The groove is gradually separated off to form the trachea and larynx, and the diverticula becomes the bronchi, whilst the dorsal part of the fore-gut in this region forms the oesophagus. These primary bronchial diverticula of the hypoblast of the alimentary canal send off secondary branches into the surrounding mesoblast, and these again give off tertiary branches, forming the air-cells. Thus CH. LIX.] RESPIRATORY AND GENlTO-URlNARY ORGANS 871 we have the lungs formed: the epithelium lining the air-cells, bronchi, and trachea is derived from the hypoblast and all the rest of the lung-tissue, and of the tubes from the mesoblast. The diaphragm is early developed as a partition of mesoblast Fig. 670 illustrates the development of the respiratory organs. A is the oesophagus of a chick on the fourth day of incubation, with the rudiments of the trachea on the lung of the left side, viewed laterally; 1, the inferior wall of the cesophagus; 2, the upper portion of the same tube; 3, the rudimentary lung ; 4, the stomach ; B is the same object seen from below, so that both lungs are visible. C shows the tongue and respiratory organs of the embryo of a horse ; 1, the tongue ; 2, the larynx ; 3, the trachea ; 4, the lungs, viewed from the upper side. (After Rathke.) dividing the original pleuro-peritoneal cavity into thoracic and abdominal serous cavities. Development of the Genito-urinary Apparatus. In the early stage of the development of the urino-genital organs, the most striking thing se en is their resemblance to the segmental Fig. 671.— Diagram of transverse section of embryo dogfish. On the right of the middle line, A B, the primitive segmental tube (A) is seen in transverse section ; on the left side a later stage is repre- sented ; it here forms a well-marked projection into the pleuro-peritoneal cavity, and the section is represented as passing through the trumpet-shaped opening of the tube into that cavity (A"). organs, or nephridia of worms. The subject was first worked out by Balfour in the elasmobranch fishes ; we may therefore first describe what he found here, and then pass on to what occurs in mammals. In the preceding diagram (fig. 671) we have a transverse section through the embryo in which the structures represented will be m ItKVKLOI'.MKNT [(11. 1.1V familiar from our previous studies. About the fifth segment a thickening in the mesoblast occurs, which grows backwards as a solid column of cells; this becomes hollow, and is seen in transverse section at A'; later on the hollow extends at one part into the pleuro- peritoneal cavity by a trumpet-shaped opening, and this is seen cut through at A". This duct is termed the archincphros. The prominence created by this duct grows into the pleuro-peritoneal cavity; and a number of con- voluted tubes, one in each segment, open into the duct, which soon splits into two longitudinally; one division, the pironcpliros or Mullerian duct (fig. 672, M), has the original opening into the body cavity; the other convoluted tubes open into the other division ; they become united together by connective tissue, and form a solid organ called the Wolffian hody, or mesoncphros. The duct is called the mcsoncphric, or Wolffian duct (fig. 672, W). The two ducts open into the cloaca, which also receives the hinder opening of the alimentary canal. The tubules of the Wolffian body become more convoluted, and form the tubules of the primitive kidney ; some of their original openings into the peritoneal cavity can be traced, even in the adult. From the lower end of the Wolffian duct a protrusion or growth takes place, and this also becomes hollow, and a number of segmental tubes develop and form with it an organ similar to the Wolffian body ; this is called the metanephros, and it forms the hind kidney, which represents the true kidney of the higher vertebrates (K, fig. 673) ; the metanepliric duct becomes the ureter. In the female the Mullerian ducts become the oviducts, and, where they join, the uterus. In the male they disappear. The head or Wolifian kidney, and the hind or true kidney both execute renal functions in both sexes ; but in the male, the Wolffian tubules apply themselves to the testis and constitute its efferent ducts; the main Wolffian duct becomes the vas deferens. Thus in fishes and amphibians, the semen passes through tubules which are also renal in function. In the higher vertebrates the duct of the archinephros becomes the Wolffian duct, and the segmental tubules, which are rather more numerous than one to each segment, get bound into the Wolifian body. The Mullerian duct is not split off from this, but is formed i M W. Fig. G7l'. — Diagram re- presenting the splitting of the archinephros into Miillerian (M) and Wolffian (W) ducts. CH. tix] THE WOLFFIAN BODIES separately by a longitudinal folding in of the pleuro-peritoneal cavity; the true kidney is formed in both sexes as before by a growth backwards from the Wolffian duct. The tubules are at first solid columns of cells which are subsequently hollowed out. The Wolffian bodies, or temporary kidneys, as they may be termed, give place at an early period in the human foetus to their successors, the permanent kidneys, which are developed behind them. "U.tf m Wtf M Fig. (373. — Diagram showing tlie relations of the female (the left-hand figure $) and of the male (the right-hand figure £) reproductive organs to the general plan (the middle figure) of these organs in the higher vertebrata (including man). CI, Cloaca ; R, rectum ; Bl, urinary bladder ; U, ureter ; K, kidney ; Uh, urethra ; G, genital gland, ovary, or testis ; W, Wolffian body ; IV d, Wolffian duct ; M, Miillerian duct ; Pst, prostate gland ; Cp, Cowper's gland ; C.sp, corpus spongiosum ; C.c, corpus cavernosum. In the female. — V, vagina; Ut, uterus; Fp, Fallopian tube; Gt, Gaertner's duct; Pv, parovarium; A, anus; C.c, C.sp, clitoris. In the male. — C.sp, C.c 1 , penis; (Huxley.) Ut, uterus masculinis ; V s, vesicula seminalis ; V d, vas deferens. The Wolffian body loses all renal functions. In the male it applies itself to the testis, and is developed into the vasa efferentia, coni vasculosi, and globus major of the epididymis. Its duct forms the body and globus minor of the epididymis, the vas deferens, and the ejacula- tory duct ; the vesicula seminalis is a diverticulum from its lower part. In the female a relic of the Wolffian body persists as the parovarium, a functionless collection of tubules lined with ciliated epithelium near the ovary (see p. 821, fig. 613, po); in the male a similar relic is 874 DEVELOPMENT [oil. Ll.W Fig. 674. — Transverse section of embryo chick (third day), mr, Rudimentary spinal cord ; the primitive central canal has become constricted in the middle; ch, notochord ; uwh, primordial vertebral mass; m, muscle-plate; dr, df, hypoblast and visceral layer of mesoblast lining groove, which is not yet closed in to form the intestines ; ao, one of the primitive aortse ; itn, Wollfian body ; ung, Wolffian duct; v c, vena cardinalis ; h, epiblast ; hp, somatopleur and its reflection to form a f, amniotic fold ; p, pleuro-peritoneal cavity. (KcSlliker.) Fig. 675.— Section of intermediate cell-mass on the fourth day. m, Mesentery; L, somatopleur; a', germinal epithelium, frc 11 which z, the duct of Miiller, becomes involuted; a, thickened part of germinal epithelium, in which the primitive ova and o are lying; E, modified mesoblast, which will form the stroma of the ovary ; WK, Wolffian body ; y, Wolffian duct, x 160. (Waldeyer.) CH. LTX.] THE MULLERIAN DUCTS ' 875 termed the organ of Giraldes. The lower end of the Wolffian duct may remain as the duct of Gaertner, which descends towards, and is lost upon, the anterior wall of the vagina. The Fallopian tubes, the uterus, and the vagina are developed from the Mullerian ducts. The two Mullerian ducts are united below into a single cord, called the genital cord, and from this are developed the vagina, as well as the lower portion of the uterus ; while the ununited portion of the duct on each side forms the upper part of the uterus and the Fallopian tube. In certain cases of arrested or abnormal development, these portions of the Mullerian ducts may not become fused together at their lower extremities, and there is left a cleft or horned condition of the upper part of the Fig. 676. — Diagram of two-horned uterus. The body of the uterus (U) is formed by the fusion of the two Mullerian ducts, the ununited portions of which form the oviducts, Fallopian tubes or horns of the uterus (O, O) ; V, vagina. uterus resembling a condition which is permanent in certain of the lower animals (see fig. 676). In the male, the Mullerian ducts have no special function, and are but slightly developed. The hydatid of Morgagni is the remnant of the upper part of the duct. The small prostatic pouch, uterus masculinus, or sinus pocularis, forms the atrophied remnant of the distal end of the genital cord, and is, therefore, the homologue of the vagina and uterus. Between the Wolffian body and the mesentery, the mesoblast covering the ridge produced by the projecting Wolffian body is converted into a thick epithelium called the germ epithelium (see fig. 675). From this the reproductive gland (ovary or testis as the case may be) is developed. 8/6 DEVELOPMENT [oil. L1X. The manner in which the ovary is formed is described in outline in Chapter LVIII. (p. 825); the testis is formed in a similar way, only the downgrowths of cells which become nests of cells to form ova and Graafian follicles in the female, become hollowed out as seminiferous tubules in the male. For some time it is impossible to determine whether an ovary or testis will be developed ; gradually, however, the special characters belonging to one of them appear, and in either case the organ soon begins to assume a relatively lower position in the body ; the ovaries are thus ultimately placed in the pelvis, and the testicles descend into the scrotum; the testicle enters the internal inguinal ring in the seventh month of fcetal life, and completes its descent through the inguinal canal and external ring into the scrotum by the end of the eighth month. A pouch of peritoneum, the processus vaginalis, precedes it in its descent, and ultimately forms the tunica vaginalis or serous membrane of the organ ; the communication between the tunica vaginalis and the cavity of the peritoneum is closed only a short time before birth. In its descent, the testicle or ovary of course retains the blood-vessels, nerves, and lymphatics, which were supplied to it while in the lumbar region, and which accompany it as it assumes a lower position in the body. Hence it is that these parts originate at so considerable a distance from the organ to which they are distributed. The gubernaculum testis is a cord, partly fibrous, partly muscular, which extends while the testicle is yet high in the abdomen, from its lower part, through the abdominal wall (in the situation of the inguinal canal) to the front of the pubes and lower part of the scrotum. The homologue, in the female, of the gubernaculum testis is the round ligament of the uterus, which extends through the inguinal canal, from the outer and upper part of the uterus to the subcutaneous tissue in front of the symphysis pubis. At a very early stage of foetal life, the Wolffian ducts, ureters, and Mullerian ducts open into the lower extremity of the intestine, which constitutes for the time a common receptacle or cloaca. This opens to the exterior of the body through a part corresponding with the future anus, an arrangement which is permanent in reptiles, birds, and some of the lower mammalia. In the human foetus, how- ever, the intestinal portion of the cloaca is cut off from that which belongs to the urinary and generative organs ; a separate passage or canal to the exterior of the body, belonging to these parts, is called the sinus urogenitals. Subsequently, this canal is divided, by a process of division extending from before backwards or from above downwards, into a "pars urinaria" and a "pars genitalis." The former, continuous with the uraclous, is converted into the urinary bladder. CH. TAX.] SUPRARENAL CAPSULES 877 The external parts of generation are at first the same in both sexes. The opening of the genito-urinary apparatus is, in both sexes, bounded by two folds of skin, whilst in front of it there is formed a penis-like body surmounted by the glans, with a cleft or furrow along its under surface. The borders of the furrows diverge pos- teriorly, running at the sides of the genito-urinary orifice internal to the cutaneous folds just mentioned. In the female, this body becom- Fig. 677. — Diagram of the Wolffian bodies, Mullerian ducts and adjacent parts previous to sexual distinction, as seen from before, sr, The supra-renal bodies ; r, the kidneys ; ot, common blastema of ovaries or testicles; W, Wolffian bodies; w, Wolffian' ducts ; mm, Miillerian ducts; g c, genital cord : ug, sinus uro-genitalis ; ?', intestine ; cl, cloaca. (Allen Thomson.) ing retracted, forms the clitoris, and the margins of the furrow on its under surface are converted into the nymphae, or labise minora, the labia majora pudendae being constituted by the great cutaneous folds. In the male foetus, the margins of the furrow at the under surface of the penis unite at about the fourteenth week, and form that part of the urethra which is included in the penis. The large cutaneous folds form the scrotum, and later receive the testicles. Sometimes the urethra is not closed, and the deformity called hypo- spadias then results. The appearance of hermaphroditism may, in these cases, be increased by the retention of the testes within the abdomen. The supra-renal capsules originate partly from the mesoblast anc [ 878 DEVELOPMENT fCH. LIX. partly from certain special cells of the sympathetic ganglia, called chromofine cells, on account of the yellow colour they acquire when hardened with chromic salts. The chromofine cells form the medullary parts of the suprarenal hodies, and the cortex is de- veloped from buds of mesoblastic cells separated from the peri- toneum on the inner sides of the germinal ridges. INDEX Abdominal muscles, action in respiration, 353 Abducens nerve, 628, 640 centre, 040 Aberration, chromatic, 787 spherical, 786 Abrin, 442 Absorption of carbohydrates, 519 fats, 521 food, 519 et seq. proteids, 520 solutions from the intestines, 523 by the skin, 579 Accelerator nerves, 162 urinae, 549 Accommodation of eye, 7S0 defects of, 7S4 mechanism of, 7S1 Beer's experiments, 7S4 Acetonemia, 517 Acetyl, 394 Achromatin, 11 Achromatopsia, S03 Achroo-dextrin, 392, 480 Acids in gastric juice, 4S4 Acid-albumin, 401, 4S7 Acini of secreting glands, 472, 474 Acrolein, 394 Acromegaly, 341 Acrylic series, 394 Adamantoblasts, 73 Adamkiewicz reaction, 39S Adenine, 335, 403, 562 Adenoid or lymphoid tissue, 47 in intestines, 457 Adipose tissue, 43. See Fat. development, 44 situations of, ib. structure, ib. uses, 46 vessels and nerves, ib. Adrenaline, 340 Aerotononieter, 3S1 .Esthesiometers, 725 Affenspalte (ape's split), 713 Afferent nerves, 90, 162 nerve-cells, 203 After-birth, 843 After-images, 801 Age, influence on capacity of respiration, 359 Agglutinin, 443 Agraphia, 762 Air, atmospheric, composition of, 375 breathing, 357 Amnion. Air — continued changes by breathing, 375 complemental, 358 quantity breathed, 358 reserve, ib. residual, ib. tidal, ib. transmission of sonorous vibrations through, 745, 746 undulations of, conducted by external ear, 746 Air-pumps, 383, 3S4 Air-sacs, 349 Air-tubes. See Bronchi. Alanine, 500 Albumin, 396, 399 acid, 401 alkali, ib. chemical composition, 397 egg, 399 crystallisable, 397 lact-, 399 serum, ib. crystallisable, 397 of blood, 416 Albuminates, 400 Albuminoids, 403 Albuminometer, Esbach's, 571 Albuminous substances, 396 action of gastric fluid on, 492 Albumins, 399 Albumoses, 396 Alcohol as an accessory to food, 469 Alcohols, monatomic, 388 Aldehyde, 387 Aldoses, 3S7 Alimentary canal, 445 et seq. development of, 867 nerves of, 530 Alisphenoids, S4S Alkali-albumin, 401 properties of, ib. Allantoic veins, S52 AUantoiu, 561 Allantois, development of, 842 Alloxan, 561 Alloxuric or purine bases, 403 Allyl alcohol, 394 Amacrine cells, 772 Ammo-acetic acid, 499 Ammonia, 559 cyanate of, isomeric with urea, 552 urate of, 561 Amnesia, 762 Amnion, S37, S40 development of, S40 880 IXDEX AMNIO! [i C vvn v. Ainiiini ic cavity, 8 10 fluid S37, 841 Amoebae, o Amceboid movements, 12 et seq., 421 cells, 6 colourless corpuscles, 422 cornea-cells, 767 protoplasm, 12, 100 Tradescantia, 14, 326 Amyloids or Starches, 392 action of pancreas and intestinal glands, 492 of saliva on, 480 Amylopsin, action of, 492 Amyloses, 3S9 Anabolic phenomena, 583, 813 Anacrotic pulse, 290 Anelectrotonus, 183 Angio-neuroses, 310 Angulus opticus seu visorius, 779 Animal cell, structure of, 8 et seq. Animal heat. See Heat and Temperature. Anions, 321 Ankle-clonus, 672 Auosmatic animals, 730 Ano-spinal centre, 534 Antagonistic muscles, reciprocal action of, 073» Anterolateral ascending tract, 618 Antero-lateral descending tract, 01(i Antihelix, 738 Antitoxin, 441 Antitragus, 738 Aortic arches, 850 Aphasia, 689, 762 Aphemia, 762 Apncea, origin of, 364 Appendices epiploic^, 457 Appendix vermiformis, ib. Aquseductus cochleae, 742 Aqueduct of Sylvius, 623, 628, S34, 863 Aqueous humour, 776 Arachnoid membrane, GOO Archenteron, S32-S34 Arches, visceral, S45 aortic, 850 Archinephros, 872 Area cheiro-kinEesthetic, 095 germinal, or embryonic, 831 glosso-kineesthetic, 695 vasculosa, 849 Areas, of Cohnheim, SI intermediate, 095-697 primary, 695, 696 terminal, 695-697 Areolar tissue, 36 development of, 40 Arginase, 573 Arginine, 404, 492, 557, 573 Arteria centralis retinae, 771, 776, 86j, 866 Arterial tension in asphyxia, 373 Arteiies, 214 allantoic, 851 bronchial, 350 circulation in, velocity of, 27S coronary, 237 development of, S49 distribution, 214 elasticity, 262 hypogastric, 852 muscularity, 263 nerves of, 216 nervous system, intiuence of, 306 pressure of blood in asphyxia, 373 pulse, 287 et seq. renal, ligature of, 548 rhythmic contraction, 263 et seq. Bilaminar Blastoderm, Arteries -continued structure, 215 et *< /. umbilical, S43, 851, 852 velocity of blood-flow in, 278 Arterioles, 260 Articulate sounds, classification of, vowels and consonants, 761 Artifacts, 9 Arytenoid cartilages, 752 effect of approximation, 754 movements of, ib. Arytenoid muscle, 755 Ascending tubule of Henle, 530 Asphyxia, 370 et seq. causes of death in, 371 conditions of the vascular system in, ib. symptoms, ib. Assimilation, 6, 519, 583 Association centres, 693 iibres, 659, 691, 693 Astigmatism, 7S6 Atmospheric air, 374. See Air. composition of, 375 pressure in relation to respiration, 374 Atropine, effect of, on heart, 250 on salivary secretion, 477 Attraction sphere, 12, 825, 830 Auditory area, 690 Auditory nerve, 62S, 042, 743 distribution, 743 origin, 042 Auerbach's plexus, 97, 452 Auricles of heart. See Heart. Auricular diastole, 231 systole, 232 Auriculo-ventricular valves. See Heart valves. Auto-intoxication theory of the ductless glands, 329 Avogadro's law, 325, 375 Axial skeleton, S44 Axipetal conduction, law of, 204 Axis-cylinder of nerve-fibre, 92 B. Bacterial action on intostinal digestion, 49S Bacterio-lysm, 440 Bacterium lactis, 391 Baillarger, line of, 658 Barnard's cardiometer, 246 Basement-membrane, 47, 455 Basilar membrane of ear, 742, 743 plate, 847 Basi-occipital bones, S47 sphenoid bones, ib. Basophile cells, 421 Batteries and keys, 108 Daniel] cell, 107, 108 Bayliss, observations on vaso-dilator nerves of dogs, 303 Bechterew, nucleus of, 643 Beckmann's differential thermometer, 325 Beddard, experiments on renal epithelium, 547 Beer's experiments on accommodation of the eye, 784 Bernard's experiment on independent muscular irritability, 102 on pancreatic secretion, 496 Bezold's ganglion, 252 Bicuspid valve, 211 Bidder's ganglion, 252 Biedermann's fluid, 101, note Bilaminar blastoderm, 831 INDEX 881 Bile. Bile, 508 absorption by lymph, 513 analyses of human, 509 capillaries, 505 characters of, 509 constituents of, ib. digestive properties, 498, 512 doubtful antiseptic power, 512 influence of, on fat absorption, 522 fasting on secretion, 590 mixture with chyme, 512 mucin, 510 pigments, ib. process of secretion, 50S quantity secreted, 509 salts, 510 secretion and flow, 509 specific gravity, ib. uses, 512 Bile-expelling mechanism, 513 Bilirubin, 432, 509, 510 Biliverdin, 511 Binocular vision, 805 Bipolar nerve-cells, 193, 736, 861 Birth, changes after, S58 Biuret test, 398 Bladder, urinary. See Urinary Bladder. Blastema. See Protoplasm. Blastocyst, blastoderm, blastula, bilaminar, S31 Blastopore, 831 Blastosphere, S30 Blind spot, 790, 809 Blocking, 254 Blood, 76, 409 arterial and venous, difference between, 213 buffy coat, 413 carbonic acid in, 378, 379 circulation of, 226 et seq. iu the foetus, 857 local peculiarities, 311 schema of, 228 coagulation, 76, 412 et seq. colour, 76, 409 colouring matter, 428 relation to that of bile, 432 curpuscles or cells of, 76, 41S. See Blood- corpuscles. red, 418 corpuscles, white, 421 crystals, 429 et seq. extractive matters, 417 fatty matters, ib. fibrin, 76, 412 separation of, 413 gases of, 37S haemoglobin, 419, 428 et seq. photographic spectrum of, 435 nitrogen in, 378 odour or halitus of, 409 oxygen in, 378 oxyhemoglobin, 429 et seq. photographic spectrum of, 435 plasma, 409, 414 proteids of, 416 quantity, 409, 410 Haldane's and Ijorrain Smith's experiments, 411 reaction, 409 salts, 417 serum of, 412, 414 specific gravity, 409 splenic, 332 structural composition, 418 taste, 409 temperature, ib. tests for, 439 Brain. Blood — continued transfusion of, 318 venous, 214 Blood-corpuscles, red, 76, 418 action of reagents on, 420 et seq. composition of, 420 development, 425 intracellular, 427 disintegration and removal, 331, 332 methods of counting, 423 origin of matured, 426 rouleaux, 420 specific gravity, 418 stroma, ib. tendency to adhere, 420 varieties, 418 vertebrate, various, 419 Blood-corpuscles, white, 76, 421 action of reagents on, 422 amoeboid movements Of, 421 composition of, 428 emigration of, 295 formation in spleen, 331, 427 locomotion, 422 origin of, 428 varieties, 421 Blood-crystals, 429 et seq. Blood-platelets, 423 Blood-pressure, 263 et seq. ill capillaries, 272 in veins, 271 action of respiratory movements on, 29? measurement in man, 292 et seq. schema to illustrate, 265-267 Blood-vessels, circulation in, 259 effect of gravity, 276 elasticity of, 261 of eyeball, 776 in intestines, 454 of kidney, 538 of muscle, 86 of stomach, 451 influence of nervous system on, 297 Body-eavity, 835 Body, development of framework of, S43 Boiler-makers' disease, 750 Bone, 54 canaliculi, 56 cancellous, 54 chemical composition, ib. compact ib. lamellae of, 57 development, 59 et seq. growth, 64 Haversian canals, 56 lacunae, 57 marrow, 54 medullary canal, ib. microscopic structure, 55 ossification in cartilage, 60 periosteum and nutrient blood-vessels, 55 structure, 54 et seq. Bowman's glands, 734 muscle, 743 Boyle-Mariotte's law for gases, 324 Brain. See Bulb, Cerebellum, Cerebrum, Pons, etc. capillaries of, 311 child's, 662 circulation of blood in, 311 et seq. comparative physiology of, 710 convolutions, 662 development, 861 et seq. dog's, 6S4 extirpation of, in mammals, 579 3 K 882 DfDfiX Brain, Brain— continued in foetus, 624 grey matter, 191 lobes, 663-605 lunatic's, 704 membranes of, 000 monkey's, GS5 motor areas, 6S6 orang's, 603 quantity of blood In, 311, 312 sensori-motor area, 690 sensory areas, 689 ventricles, 623 vertebrate (section), 625 vesicles, Sf'3 white matter, 191 Bread as food, 408 Breathing. See Respiration. Broca's convolution, 0S9, 762 Brodie, on splenic nerve, 151 his bellows-recorder, 151, 310 on heat rigor, 157 Bronchi, arrangement and structure of, 343 Bronchial arteries and veins, 350 Brownian movement, 100 Bruch, membrane of, 708, 709 Briicke on the self-steering action of the heart, 237 Brunner's glands, 455 Bruuton, after Gaskell, tracing of actions of vagus on the heart, 24S Bufi'y coat, formation of, 413 Bulb, ions and mid-brain, 026 anterior aspect, ib. internal structure, 628 et s< q. posterior aspect, 627 tracts of, 639 Bui bus arteriosus, 853 Bundle of llelweg, 617 of Monakow, 617, 639 of von Gudden, 689 Burch's experiments on colour vision, 800 Burdach's column, 611, 614, 018, 627, 032 Burdon-Sanderson's stethograpb, 355 Bursae, synovial, 471 Butyric acid, 391, 499 Cachexia strumlpriva, 337 Caffeine, 469 Caisson disease, 374 Cajal, law of axipetal conduction, 204 Calcification of bone, 61 Calcium carbonate, 54 in urine, 569 fluoride, 54 oxalate In urine, 568 phosphate, 54 Calorimeters, 601, 602 Calyces of the kidneys, 530 Canal, alimentary. See Stomach, Intestines, etc. external auditory, 738 function of, 746 spiral, of cochlea, 744 C '.aal of Schlemm, 770 of Petit, 770 Of Stilling, 867 Canal iculi of bone, 56 Canals, semicircular, of ear, 741 development of, 866 Cancellous tissue of bone, 54 Cane sugar, 390 Cannon, shadow photographs of the stomach, showing peristaltic movements, 529 Cells. Capacity of chest, vital, 358 Capillaries, 219 bile, 505 circulation in, 280, 293 velocity of, 2S0 development, S50 diameter, 219 form, ib. influence on circulation, 294 network of, 219, 220 number, 221 passage of corpuscles through walls of, 295 pressure in, 272 et Si q. resistance to How of blood In, 294 still laypr in, ib. size, 219 structure of, ib. Cap-mle of Bowman, 536 of Glisson, 503 of Tenon, 767, 804 Capsules, Malpighian, 53G Carbamide. See Urea. Carbohydrates, 386 et seq. absorption of, 519 Carbonates in urine, 566 Carbonic acid in atmosphere, 373, 374 in blood, 378, 379 effect of, 3S0 increaso in breathed air, 374 influence of, on nerve, 171, 172 in lungs, 378 Carbonic oxide, poisonous action of, 373 Carbonic oxide luemoglobin, 437 Cardiac cycle, 231 Cardiac glands, 449, 4S1 Cardiac orifice of stomach, action of, 529 sphincter of, 530 relaxation in vomiting, ib. Cardiac sympathetic, 249 Cardiogram from human heart, 239 Cardiograph, 237 et seq. Cardiometer, Barnard's, 246 Roy's, ib. Carotid gland, 342 Cartilage, 49 articular, 50 cellular, 53 chondrin obtained from, 51 classification, 49 costal, 50 development, 52 elastic, 49, 52 fibrous, 51, 52. See Fibro-cartilage. hyaline, 50 matrix, ib. ossification, 00 parachordal, 847 perichondrium of, 51 structure, 49 temporary, 50 transitional, ib. varieties, 49 Cartilages of larynx, 751 Casein, 402. See Milk. Caseinogen, 462 Cauda equina, 608, 860 Caudate nucleus, 054 Cavity of reserve, 75 Cell division, 16 Cells, 5 amoeboid, 6 blood. See Blood-corpuscles. bone, 57 cartilage, 50 et seq. characteristics of, 12 INDEX 883 Cells. Cells— continued chromofine, 878 ciliated, 27 connective tissue, 36 definition of, 6 epithelium, 25. See Epithelium. fission, 16 germinal, 859 gustatory, 731 hepatic, 502 nerve, 192 olfactorial, 734 parietal, 450, 481 pigment, 100 structure, 8 et seq. varieties, 22 et'seq. vegetable, 6, 13 distinctions from animal cells, 6 et seq. Cells of Deiters, 745 of Purkinje, 197, 649-651 Cellular cartilage, 53. bee Cartilage. Cellulose, 392 Cement of teeth, 69, 71, 74 Centres, nervous, etc. See Nerve-centres. of ossification, 59 Centrifugal machine, 415 nerve-fibres, 161 Centripetal nerve-fibres, 162 Centro-acinar sells, 490 Centrosome, 8, 12, 17, 820 Cephalic aortic arches, S50 Cerebellar ataxy, 704 Cerebellum, 648 effects of removal or disease, 704 equilibration, ib. functions of, 702 et seq. grey matter, 197, 624, 64S hemi-extirpation, results of, 710 semicircular canals, 705 extirpation of, 707, 708 sensory impulses, 704 structure, 648 Cerebral cortex, 656 histological structure, ib. Cerebral hemispheres. See Cerebrum. Cerebral nerves, origin of, 629 ct seq. See under names of nerves. Cerebrin, 176 Cerebro-spinal axis, 191, 607 Cerebro-spinal fluid, 17S, 608, 623 Cerebro-spinal nervous system, 191, 606 See Brain, Spinal Cord, etc. Cerebrum, 652 ■ convolutions of, 662 et seq. crura of, 623 degeneration tracts after injury of Kolandic area, 682 development, S61 effects of injury, 682 removal, 67S, 681 external capsule, 655 functions of, 678 et seq. early notions, 67S grey matter, 197, 653 internal capsule, 655 localisation of functions, 679 motor areas, 6S1, 6S6, 690 relation to speech, 762 sensory areas, 682 extirpation, ib. stimulation, ib. structure, 652 et seq. white matter, 655 Ceruminous glands of ear, 579 Chambers of the eye, 776 Chauveau's dromograph, 284 Coagulation of Blood. Cheiro-klnsssthetic area, 695 Chemical composition of the human body, 386 et seq. Chemotaxis, 444 Chest, expansion in inspiration, 351 Chest-voice, 759 Cheyne-Stokes' respiration, 365 Chlorides in urine, 565 Cholagogues, 513 Cholalic acid, 510 Cholesterin, 92, 176, 395, 511 Choletelin, 511 Choline, 176, 17S, 395 Chondrin, 51, 404 Chorda tympani, 476, 642 effects of stimulation of divided, 477 Chordse tendineae. Sec Heart. Chorion, 836, S41 Choroid coat of eye, 765 blood-vessels, 76S development, S65 structure, 7CS Choroidal fissure, 865 Chromatic aberration, 787 Chromatin, 11 (see 402) Cliromatolysis, 202 Chromatoplasm, 201 Chromofine cells, S7S } Chromogen, 339 Chromophanes, S03 Chromoplasm, 10 Chromosomes, 828, 829 Chyle, 223, 315, 521 molecular basis of, 315 Chyme, 50S Cicatricula, 82S Cilia, 28 Ciliary epithelium, 27 function of, 28 Ciliary motion, 29 nature of, ib. Ciliary muscles, 769 action of, m adaptation to distances, 7S2 Ciliary processes, 768 Ciho-spmal centre, 676 Circulation of blood, 206, 226 et tej. action of heart, 206 in brain, 311 capillaries, 294 course of, 213 et seq. erectile structures, 312 in foetus, 857 influence of respiration on, 366 of gravity, 276 peculiarities of, in different parts, 311 portal, 214 pulmonary, ib. renal, ib. systemic, lb. in veins, 216 velocity of, 278 Circulatory system, 206 et seq. Circumvallate papillae of the tongue, 729 Claustrum, 654 Cleft-palate, cause of, S47 Clefts, visceral, S45 Clerk-Maxwell's experiment, 797 Clitoris, 313 development of, S77 Cloaca, S72, 876 Clonus, 121 Colt or coagulum of blood. See Coagula- tion. Coagulated proteids, 400 Coagulation of blood, 76, 412 et seq. conditions affecting, 413 884 INDEX Coagulation ok Blood. Coagulation of blood — continued theories of, 414 of milk, 462 Cocaine, 4G9 Coccygeal gland, 342 Cochlea of the ear, 741 theories in connection with, 74'.) Coelom, 833 Cohnheim, areas of, 81 Cold spots, 72(5 Collagen, 37, 54, 403 Colloids, 323, 39(3 Colostrum, 401 corpuscles, 461, 465 Colour-blindness, 799 Colour-perception, 797 Colour sensations, 797 liurch's experiments, S00 theories of, 79S-S00 Colours, optical phenomena, 797 i Columnar epithelium, 25 Combination-tones, 749 Comma tract, 612, 614, 616, 617 Commissural fibres, 659 Compiemental air, 353 Complementary colours, 798 Compound tubular glands, 472 racemose gland-*, 473 Conception, 715 Condiments as accessories to food, 469 Conducting paths in cord, 667 ct seq. Conduction, law of axipetal, 204 Conductivity, 172 Conical and aliform papillae of tongue, 730 Coni vasculosi, 817, 819, S73 Conjugate deviation of head and eyes, 6S9, 703 Conjunctiva, 764 Connective tissues, 35 classification, ib. corpuscles, 38 elastic, 43 (ibrous, 41 general structure of, 36 jelly-like, 48 retiform, 46 varieties, 35 Conservation of energy, law of, 602 Contractility of muscle, 99 Contraction of pupil, 784 Convolutions, cerebral, 662 ct seq. Cooking, effect of, 468 Co-ordination of muscular movements, 124 Copper sulphate, or Piotrowski's test, 39S Cord, spinal. Sec Spinal Cord. Corium, 471 Cornea, 765 corpuscles, 767 nerves, ib. structure, ib. Corneo-scleral junction, 770 Coronary arteries, 237 Corona radiata, 655 Corpora cavernosa, 312, S19 quadrigemina, 628 Corpus Arantii, 213 callosum, 652 dentatum of cerebellum, 649 of olivary body, ib. Highmorianum, 817 luteum, 823 of human female, ib. of menstruation and pregnancy compared, 823 spongiosum, 312, 819 striatum, 653 Dkb.mis. Corpuscles of blood, 76, 418. See Blood-corpuscles. Corpuscles, Malpighian, 331, 536 Corpuscles, of Granary, 721 of Herbst, 719 of Meissner, 726 Corti's rods, 744 ct seq. office of, 749 Coughing, mechanism of, 364 Cowper's glands, 543 Cranial nerves, 190, 640 ct seq., 848 Crassamentum, 412 Creatine, 55G, 503, 573 Creatinine, 563 Crescents of Gianuzzl, 475 Cretinism, cause of, 336 Crico-arytenoid muscles, 753, 754 Cricoid cartilage, 752 Crico-thyroid muscle, 753 Crista acoustica, 707, 743 Crossed pyramidal tract, 615 Crosses of Uanvier, 93 Crowbar accident, 691 Crura cerebelli, 627, 64S, 649, 653 cerebri, 623, 639, 648, 649 grey matter of, 024 Crusta, 638 petrosa, 71, 74 Crypts of Lieberkuhn, 454 Crystallin, 770 Crystalline leus, 766, 769 in relation to vision at different distances, 780 Crystallisable proteids, 397 Crystalloids, 396 Cupula, 707 Curdling ferments, 402, 480, 493 Currents of action, constant, 108 induced, 109 nerve, 103 Cuticle. See Epidermis, Epithelium. Cutis vera, 574 Cybulski's haematachometer, 283 Cystic duct, 502 Cystin in urine, 569 D. Daniell's battery, 107, 10S Dark-adaptation of eye, 803 Deaf-mutes and equilibrium. 709 Decidua, 836 basalis, 836 development of, S37 menstrualis, 826 reflexa, or capsularis, 836 serotina, S38 vera, 836 Decussation of fibres in medulla oblongata, 632- 634 in spinal cord, 668 of optic nerves, S07 Defecation, mechanism of, 533 influence of spinal cord on, 534 Degeneration method, 164, 169, 011 Deglutition. See Swallowing. Deiters, cells of, 745 nucleus, 036, 643 Demoor's sleep theory, 698 Dental germ, 72 papilla, ib. Dentine, 69 formation of, 73 structure, 69 Depressor nerve, 305 Dermis, 576 INDEX Descf.met's Membrane. Deseemet's membrane, 767 Descending tubule of Henle, 530 Deutero-albumose, 487 Development, 827 et seq. adipose tissue, 44 alimentary canal, 867 allantois, 842 amnion, 840 arteries, 849 blood-vessels, 849 bone, 59 et seq. brain, 861 decidua, 837 ear, 866 extremities, 845 eye, 864 eyelids, 860 face, 846 Fallopian tubes, 875 foetal membranes, S39 framework of body, 843 genito-urinary apparatus, S71 et seq. bead, 845 heart, 852 intestines, 867 limbs, 845 liver, 809 lungs, 870 medulla oblongata, 862 muscle, 88 nerve-fibres, 96 nervous system, 858 et seq. nose, 867 oesophagus, ib. optic nerve, 865 organs of sense, 866, 867 ovum, 827 pancreas, 868 pharynx, 867 respiratory apparatus, S70 salivary glands, 86S spinal cord, 859 stomach, 867 teeth, 71 vagina, 875 vascular system, 849 veins, S52 vertebrae, 844 visceral arches and clefts, 845 et seq. Wolffian bodies, urinary apparatus, and sexual organs, 872 et seq. Dextrin, 392 Dextrose, 389 in urine, 571 tests for determining, 389, 571 Diabetes, 516, 594 artificial production in animals, 516, 517 (see 571) Dialysis, 323, 397 Diapedesis of blood-corpuscles, 295 Diaphragm. See Inspiration, etc. development, 871 Diastase of liver, 515 Diastole of heart, 231 Dicrotic pulse, 291 Diencephalon, S62, 863, 865 Diet, 587 et seq. nutritive value, 450 tables, 460, 461, 587 et seq. Difference-tones, 749 Diffusion and osmosis, distinguished, 322, 397 Digestion, in the intestines, 490 et seq. duration of, 533 mechanical processes, 525 et seq. gee Gastric fluid, Food, Stomach. Bmbryological Method. Dilator pupillas, 769 Diphtheria toxin, 441 Diplopia, 805 Direct cerebellar tract, 61S pyramidal tract, 615 Disaccharides, 388, 389 Discus proligerus, 822 Distributing nerve-cells, 203 Disuse atrophy, 203, 690 Diuretics, 546 Diverticulum, Meckel's, 868 Dobie's line, 82 Dorsal mesentery, S35 ridges, 858 Double vision, 805 Dreser, on kidney, 54S Dromograph, Chauveau's, 284 Drugs, action of, 533 on the eye, 789 on the heart, 250 on perspiration, 581 Duct of Gaertner, S75 Ductless glands, 32S et seq. theories of secretion, 329 Ducts of Bellini, 537, 53S of Cuvier, 853 Ductus arteriosus, S52, 858 closure of, 858 venosus, 856, 858 closure of, S58 Dudgeon's sphygmograph, 289 Dulong's calorimeter, 601 Duodenum, 451 Dupre^s urea apparatus, 554, 555 Dura mater, 606 Dyne, 264 Dyspnoea, 362, 371 Ear, 738 bones or ossicles of, 740 function of, 747 development, 866 external, 73S function of, 746 internal, 741 function of, 746 middle, 738 function of, 746 Eck's fistula, 557 Efferent nerves, 90, 161 nerve-cells, 203 Eggs as food, 459, 465 Ehrlich's experiments with methylene blue, 379 681 side-chain theory, 442 Elastic cartilage, 49, 52 fibres, 41 tissue, 43 Elastin, 38, 404 Electrical currents of retina, S03 nerves, 162 phenomena of muscle, 133 et seq., 186 variation in central nervous system, 697 in glands, 473 Electricity, action on blood-corpuscles, 421 in muscle, 141 et seq., 187 nerve, 1S7 Electrodes, non-polarisable, 135 Electrometer, Lippmann's capillary, 13S Electrotonus, 179 Eleidin, 575 Elementary substances in the human body, 3S6 Embryo, 827 et seq. See Development. Embryological method, 611 886 INDEX Embryonic Arka. Embryonic area, 831, 888 heart anil blood-vessels, 851-858 Emetics, 531 Emulsification, 30.0, 492, ".'-'1 Enamel of teeth, 70 formation of, 78 Enamel organ, ib. Enchylema, 9 Eud-bulbs, 720 End-plates, motorial, B6, 05 Endocardiac pressure, 24ti Endocardium, 207 Endogenous fibres, 692 Endolymph, 706, 741, 744 Endomysium, 79 Endoneurium, 94 Endothelium, 24 distinctive characters, £6. germinating, 46. Energy, law of conservation of, 602 Eosinophile cells, 421 Epencephalon, 624 Epiblast, 21, 832-835 organs formed from, S35 Epicardium, 206 Epidermis, 574 Epididymis, S17, 819, S73 Epiglottis, 756, 757 Epimysium, 79 Epineurium, 94 Epithelium, 22 chemistrv of. 33 ciliated, 27, S25 cogged, 32 columnar, 25 compound, 22 cubical, 25 germinal, 821, 875 goblet-shaped, 26 nutrition of, 33 pavement, 22 renal, 546 simple, 22 spheroidal, 25 stratified, 31 transitional, 30 Erectile structures, circulation in, 312 Erection, 313 cause of, ib. centre, 676 influence of muscular tissue in, 313 Erg, 264 Ergograph, Mosso's, 150 Erythroblasts, 427 Erythro-dextrin, 392, 4S0 Esbach's albuminometer, 571 Ethmoid, 848 Ethmo-vomerine plate, S47 Eustachian tube, 738, 747, 807 function of, 747 valve, 85S Exchange of material, "jSO in diseases, 592 with, various diets, 590 Excitability of nerves, 172 of tissues, 99 Exercise, effects on temperature of body, 599 Exogenous fibres, 692 Expiration, 353 force of expiratory act, 359 influence on circulation, 350, 359 mechanism of, 354 muscles concerned in, ib. relative duration of, 356 External capsule, 655 Fibrils of Mi si i External respiration, 375 sphincter muscle, 532 Intraventricular nucleus, 654 Extremities, development of, 845 Eye, 764 action of drugs on pupil, 7S9 adaptation of vision at different dis- tances, 780 et seg. blood-vessels, 776 causes of dilatation and contraction of pupil, 789 chambers of, 776 development, S64 optical apparatus of, 777 defects in, 7S1 refractive media of, 777 resemblance to camera, 776 Eyeball, 765 blood-vessels of, 776 electrical currents of, 803 muscles influencing movement, S04 various positions of, S05 Eyelids, 764, 765 development of, S06 Eyes, simultaneous action in vision, S05 Face, development of, 846 Facial nerve, 641 effects of paralysis of, ib. origin, 642 relation of, to expression, ib. Fieces, composition of, 524 quantity passed, ib. Fallopian tubes, 825 development of, S75 Falsetto voice, 759 Faradisation, 121 Far-point, 7S6 Fasciculus solitanus, 630, 646 Fasting, influence on secretion of bile, 590 Fat. See Adipose tissue. action of bile on, 512 of pancreatic secretion, 498 situations where found, 43, 44 uses of, 46 Fats, absorption of, 521 action of pancreatic juice on, 492 chemical constitution, 393 decomposition products, 394 emulsification, 395 of milk, 46S saponification, 395 Fatty acids, 393 Fatigue, 697 in nerves, 151 Female generative organs, S21 pronucleus, S2S, 880 Pent strated membraiie of Henle, 216 Fenestra ovalis, 739, 741 rotunda, 739, 742 action of, 74S Ferment coagulation, 398 Ferments, 405, 4S2. Sic also Blood, Milk, Diges- tive juices, classification of, 406 Fibres of Midler, 772 of Remak, 95 Fibrils of muscle, 81 of nerve, 92 INDEX Fibrin. Fibrin, 412, 414, 416 ferment, 414, 41(5, 417 formation, 413, 414 Fibrinogen, 76, 414, 416 Fibrinoplastin, 417 Fibro-cartilage, 51 classification, ib. development, 52 white, 51 yellow, 52 Fibrous tissue, 41 white, ib. yellow, 43 Fick's spring kymograph, 272, 273 Fifth cranial nerve, 628, 641 Filiform papillse of tongue, 730 Fillet, 637 Filtration, 318, 319, 323 Filum terminale, 60S, S60 Fishes, circulatory system in, 229 Flechsig's method, 692 Fleischl's hEemoglobinometer, 438 Flesh of animals, 459 Flicker, 792 Flour as food, 467 Fluids, swallowing, 527 Fluoride of calcium, 54 Focal distance, 7S0 Foetal membranes, 836 development of, 839 Foetus, circulation in, S57 communication with mother, 839 Follicles, Graafian. See Graafian follicles. Food, 459 absorption of, 519 ct seq. accessories to, 469 cooking, 468 digestibility of articles of, 459 value dependent on, ib. heat-value of, 599 of man, 460 too little, 589 proximate principles in, 459 vegetable, ib., 46S Foramen ovale, 852 of Magendie, 623 of Monro, 654, 863 Fore-gut, S34 Formic acid, 393 Fornix, 654 Fourth cranial nerve, 628 Fovea centralis, 771, 775, 793, 796 Fredericq's aerotonometer, 3S1 Fromann's lines, 93 Fronto -nasal process, 846 Fundus of eye, 792 of urinary bladder, 541 Fungiform papillee of the tongue, 730 Funiculus solitarius, 635, 645 Furfuraldebyde, 510 Furth, on muscle proteids, 156, 160 Fuscin granules, 803 G. Galactose, 390 Gall-bladder, 507 development of, S70 structure, 507 Galvanism, 133 Galvanometer, 134 Gamgee, photographic spectrum of hcemog and its derivatives, 435 Ganglia. See Nerve-centres. sympathetic, functions of, 299, 300 obin Graafian Follicxks. Ganglion spirale, 745 Gas analysis, 385 Gases, extraction from blood, 378 in blood, ib. in the lungs, ib. of plasma and serum, 416 Gastric glands, 481 innervation of, 485 Gastric juice, 481 acids in, 4S3 test for, 484 action on bacteria, 498 action on food, 4S7 (see 52S) artificial, 481 composition of, 483 pepsin of, 482, 484 secretion of, 4S3 influence of nervous system on, 485 Gay-Lussac's law for gases, 325 Gehuchten, von, law of axipetal conduction, 204 Gelatin, 37, 403 as a constituent of food, 466 Generative organs of the female, S21 of the male, 816 Genital cord, S75 Genito-urinary apparatus, development of, S71 et seq. Gennari, line of, 659, 6S9, 713 Gerlach's network, 610 Germinal area, 831 cells, 859 epithelium, 821, 875 spot, 20, 825 vesicle, 20, 825 Giant cells, 55 Glands. See names of different. Glisson"s capsule, 503 Globin, 430 Globular processes, 846 Globulins, 176, 396, 399 distinctions from aibumin, 396 Glosso-khiEesthetic area, 695 Glossopharyngeal nerve, 629, 644 communications of, 644 functions, ib. motor filaments, 645 a nerve of common sensation and of taste, ib. Glottis, movements of, 75S, 759 Gluco-proteids, 401 Glucosamine, ib. Glucose, in liver, 514 test for, 392 Glycerides, 393 Glycerin or Glycerol, 394 . Glycocholic acid, 510 Glycine, 499, 563 Glycogen, 392, 514 characters, 392 destination of, 515 preparation, ib quantity formed, ib. source of, 514 variation with diet, 515 Glycosuria, 516 Glycuronic acid and sugar, 517 Gmelin's test, 511 Goblet cells, 26, 732 Goll's column, 611, 614, 617, 627, 632 Gotch, experiments on nerves, 153, 171 Gowers' hemacytometer, 424, 425 hEemoglobinometer, 437 Graafian follicles, 821 formation and development of, ib. et seq. 888 INDEX Qraafi \n Follicles. Graiflan follicles — continm d relation of ovum to, 822 rupture of, changes following, S23 ( I Gradient, pressure, 281, 367 Gramme-molecular solutions, 322 Grandry, corpuscles of, 721 Granular layers of retina, 772 Grape-sugar. Sir Dextrose. Gravity, influence of, on circulation, 27(3 Grehant, output of the heart, 24G Grey matter of cerebellum, 191, 024, 649 of cerebrum, 197, 653 of crura cerebri, 634 of medulla oblongata, 627, 632, 633, 636 of pons Varolii, 636 of spinal cord, 191, G10 Groove, primitive, 831 Grossmann, on the course of the inhibitory fibres in mammals, 250 Growth of bone, 64 Guanine, 403, 562 Gubernaculum testis, 876 Gudden, von, bundle of, 639 Gullet, 446. See Oesophagus. Gustatory cells, 731 II. Hemacytometers, 423, 424 Haemadromometer, Volkmann's, 278 Haematachometer, Cybulski's, 2S3 Vierordt's, ib. Haematin, 430 Haematoblasts, 332, 420 Haernatoidin, 431, 50S Haematoporphyriu, 431, 444 Haem-autograph, 292 Haemin, 431 Haemochromogen, 431 Haemoglobin, 76, 401, 41S, 429 et seq. analysis of, 430 compounds of, 432 crystallisable, 397 distribution, 429 estimation of, 437 photographic spectrum of, 435 Htemoglobinometers, 437, 43S Haemoglobinuria, paroxysmal, 573 Haemolymph glands, 333 Hemolysins, 440 Hair-cells, 745 Hair-follicles, 577 Hairs, 577 structure of, ib. Haldane's apparatus for estimating the carbonic acid and aqueous vapour given off by an animal, 376 carbonic oxide method of estimating oxygen tension of arterial blood, 382 Hamulus, 744 Hardy, microscopic structure of cells, 9 Hare-lip, cause of, 847 Hassall, concentric corpuscles of, 334, 870 Haversian canals, 56 Head, development of, 845 Head and tail folds, 831 Hearing, anatomy of organ of, 738 et seq. influence of external ear on, 746 of middle ear, ib. physiology of, 745 range of, 749 See Sound, Vibrations, etc. Heart, 206 et seq. action of, accelerated, 249 IIknsen's Link op Dihc, Heart — continued force of, 244 frequency, ib. inhibited, 249 self-steering, 237 auricles of, 207, 231 chambers, 207 capacity of, 210 chordae tendineae of, 212 columnar carneae of, ib. conduction in the, 253 course of blood in, 213 cycle, 231 development, 852 endocardiac pressure, 240 endocardium, 207, 211 foetal, 850 force, 244 frog's, 229, 230 instruments for studying, 256 nerves of, 250 ganglia of, ib. influence of drugs, ib. of pneumogastric nerve, 247 of sympathetic nerve, 249 innervation, 247 intracardiac nerves, 252 pressure, 240 investing sac, 206 muscular fibres of, 86 musculi papillares, 212 nervous system, influence on, 247 output of, 245 pericardium, 206 physiology, 231 et seq. reflex inhibition, 251 situation, 206 size and weight, 210 sounds of, 234 causes, 235 structure of, 210 valves, 211 auriculo-ventricular, 210 function of, 233 semilunar, 212 function of, 234 structure, 211 ventricles, their action, 207, 210, S.V2 work of, 244, 245 Heat, animal. See Temperature, influence of nervous system, 004 of various circumstances on, 003 et srq. losses by radiation, etc., 000 variations of, 598 Heat coagulation, 398 Heat-rigor of muscle, 157 of nerve, 17S Heat spots, 726 Heat-value of food, 599 Height, relation to respiratory capacity, 359 Held, experiments on myelination, 693 Helicine arteries, 819 Helicotrema, 744 Helix of ear, 738 Heller's nitric-acid test, 570 Helmholtz'8 induction coil, 111 myograph, 112 phakoscope, 7S2 Helwig's bundle, 617 Hemianopsia, 6S9, SOS Hemiplegia, 655, 683 Hemisection of spinal cord, 619, 607 Hemispheres, cerebral. See Cerebrum. Henle, sheath of, 94 Henry-Dalton law for gases, 325 Hensen's line or disc, 82 INDEX Hepatic Cells. Hepatic cells, 502 colic, 513 Herbst, corpuscles of, 719 Hering's theory of colour, 799 Hetero-albumose, 487 Heterotype mitosis, 829 Hexone bases, 404 Hexoses, 388 Hiccough, mechanism of, 3G5 Hill (Croft) on inverting ferments, 407 Hill (Leonard) on the circulation of blood in the brain, 312 et seq. on the influence of gravity on the circulation, 277 on alterations in atmospheric pressure, 374 Hill's air-pump, 384 Hind-gut, 835 Hippuric acid, 562 Histone, 430 Holoblastic ova, S2S Homotype mitosis, 829 Horopter, 807 Hurthle's manometer, 242, 273, 310 differential manometer, 243 Hyaline cartilage, 50 corpuscle, 421 Hyaloplasm, 9 Hydrobilirubin, 511, 551 Hydro-kinetic force, 281 -static force, 2S1 Hypermetropia, 7S6 Hyperpncea, 371 Hypertonic solutions, 326 Hypoblast, 21, S32-836 organs formed from, 833 Hypoglossal nerve, 646 distribution, 647 origin, 646 Hypophysis, 846 Hypospadias, S77 Hypotonic solutions, 326 Hypoxanthine, 335, 403, 562 presence in the spleen, 332 I. Idiosome, 819 Ileo-caecal valve, 451, 45o, 457 Ileum, 451 Image, formation on retina, 779 Immunity, 439 Impregnation of ovum, S30 Inanition or starvation, 5S9 Incus, 740 development of, 84S Indican, 565 Indigo, ib. Induction coil, 109 et seq. current, 109 Infundibulum, 349 Inhibition, vagus, 247 Inhibitory centre for heart, effect of venous blood on, 373 Inhibitory influence of pneumogastric nerve, 247 Inhibitory nerves, 162 Inoculation, curative, 440 protective, ib. Inogen, 149, 155 Inorganic compounds in body, 3S6 salts in protoplasm, 10 Inosite, 393 Insalivation, 525 Inspiration, 351 elastic resistance overcome by, 353 expansion of chest in, ib, Kabyokinesis. Inspiration— continue d extraordinary, ib. force employed in, ib. mechanism of, 351 et seq. Instruments for demonstrating muscular action, 107 et seq. Intercellular material, 5, 36 passage, 349 Intercentral nerves, 163 Intercostal muscles, action in inspiration, 353 et seq. action in expiration, 354 Intercrossing fibres of Sharpey, 58, 59 Intermediary nerve-cells, 203 Intermediate areas, 695-697 Intermittent pulse, 288 Internal capsule, 655, 6S0 importance of, 655 respiration, 375 Internal secretion theory of the ductless glands, 328, 329 Internal sphincter muscle, 457, 532 Interstitial cells, 819 Intestinal juice, 495, 496, 533 Intestines, 451 absorption of solutions from the, 523 action of drugs, 533 digestion in, 490 et seq. duration of, 533 development, S67 large, 456 glands, 457 structure, ib. movements, 531 nervous mechanism, 534 small, 451 glands, 454 structure, ib. Intracardiac nerves, 252 pressure, 240 Intraventricular nucleus, 654 Inversion, 390, 496 Invertin, 496 Involuntary muscles, 78 (see 15S et seq.) structure of, 78 Iodo-thyrin, 337 Iris, 769 development of, 866 functions, 78S reflex actions, 7S9 Irradiation, 787 Irritability of tissues, 99 Islets of Laugerhans, 490, 491, 501 Iso-cholesterin, 512, 578 Iso-maltose, 391 Isometric contraction, 132 Isotonic contraction, ib. solutions, 326 Jacksonian epilepsy, 683 Jacobsen's nerve, 644 Jaundice, 513 Jecorin, 339 Jejunum, 451 Jelly of Wharton, 40, S43 Jelly-like connective tissue, 4S Juice, gastric, 481 pancreatic, 491 K. Kaiser's views on muscular contraction, 132 Karyokinesis, 16 et seq. phases of, 20. 890 INDEX K.\T \l ' 11,11 I'll VI! N \. Katabolic phenomena, 584, 813 Katelectrotonus, 1S3 Kations, 321 Kennedy, experiment on nerve crossing, 174 Kephalin, 17(1 Keratin, 33, 404, 575, 581 Ketoses, 388 Key, Du Bois Reymond's, 108 Kidneys, 535 blood-vessels of, how distribute I effect of ligaturing, 545 calyces, 530 capillaries of, 540 development of, S73 diseases of, effect on the skin, 5S2 extirpation of, 54S function, 543. See Urine. Malpighian corpuscles of, 530 nerves, 543 pelvis of, 530 structure, 535 tubules of, 530 et seq. weight, 535 work done by, 547 Kinresthetic area, 090 sense, 728 Kinetoplasm, 201 Kjeldahl's method of estimating urea, 555 Klein on the stages of karyokinesis, 17 Knee-jerk, 072, 074 Konig's apparatus for obtaining flame-pictures of musical notes, 7G0 Kossel on protamines, 404 Krause's membrane, S2-87 Kronecker's perfusion cannula, 257 Kiihne's gracilis experiment, 173 (see 301) muscle plasma experiment, 150 Kvmograph, Kick's spring, 272, 273 Ludwig's, 270 tracings, 272, 274 Labia externa and interna, de\elopn ent of, S77 Labyrinth of the ear. See Ear. Lacrimal gland, 704 Lact-albumin, 402 Lactase, 501 Lacteals, 223, 453, 454, 521 fermentation, 391 Lactiferous ducts, 404 Lactose, 390, 403. 071 Lamina cribosa, 771 spiralis, 742 supra-choroidea, 7G8 Langley's experiment on vagus and cervical sympathetic nerve, 174, 175 (see 71S) ganglion, 477 nicotine method, 301, 478 Large intestine. Sec Intestines. Laryngoscope, 755 Larynx, anatomy of, 751 cartilages of, ib. mucous membrane, 753 muscles of, 753 et nerves of, 755 vocal cords, 751, 757 movements of, 757 Lateral sclerosis, ii71 Lateral nasal process. S40 Lateritious deposit, 561 Laugerhans, islets of, 490, 491 Lecithin, 92, 170, 395, 499 Lens, crystalline, 709, 770 Lenticular nucleus, Lymphocytes. I.- pine's theory of the ferment of the pancreatic internal secretion, 517 Leucine, 335, 499 Leucocytes. See Blood corpuscles (white). Levulose, 390 Lewis, on luemolymph glands, 333 Lieberkiihn's glands, 454, 457 jelly, 401 Ligamentum pectinatum iridis, 770 arteriosum, 850 Limbs, development of, 845 Line of Baillargcr, 05S of Gennari, 669, 689, 713 Lippmann's capillary electrometer, 138 Liquor sanguinis, or plasma, 70, 414 Liver, 502 blood-vessels, 503 capillaries, 505 ceLls of, 502 circulation in, 505 development of, S09 extirpation in mammals, 557 in frogs, ib. formation of urea by, 507, 557 functions, 507 glycogenic function of, 514 nerves of, 518 secretion of. See Bile. structure, 503 sugar formed by, 514 (see 515) supply of blood to, 502, 50S Local signature, 724 Localisation of tactile sensations, 723 Locomotor ataxy, 0CS, 074 Loop of Henle, 530 Lortet on the carotid flow, 2S5 Ludwig's air-pump, 3S3 kymograph, 270 Stromuhr, 279 Lugaro's sleep tlieorj Lunatic's brain, 704 Lungs, 347 air-sacs of, 349 blood-supply, 350 capillaries of, 349 changes of air in, 375 circulation in, 350 coverings of, 347 development of, 870 diffusion of gases within, 377 lobes of, 348 lobules of, ib. lymphatics, 350 muscular tissue of, 348 nerves, 351 nutrition of, 350 position of, 343 structure, 347 Luxus consumption, 594 Lymph, 221, 313 composition of, 313 current of, 317 formation of, 31S Lymph capillaries, 222 origin of, 223 structure, 225 Lymph-hearts, structure and action of, 317 relation to spinal cord, 318 l.ymphagogues, 319 Lymphatic glands, 223, 315 development, S70 Lymphatic vessels, 221 of arteries and veins, 218 communication with blood-vessels, 221 structure of, 222 Lymphocytes, 331, 421 INDEX 891 Lymphoid or Retiform Tissue. Lymphoid or retiform tissue, 47. See Adenoid tissue. Lysatinine, 557 Lysine, ib. M. MacMunn, use of the term myo-haematin, 156 Macrosmatic animals, 736 Macula, 707 lutea, 771, 772, 775 Maculse acoustics, 743 Magnesium phosphate, 54 Male organs of generation, 816 pronucleus, 830 sexual functions, 819 Malleus, 740, 848 Malpighian bodies or corpuscles of kidney, 536 See Kidney. corpuscles of spleen, 331 Maltase, 407 Maltose, 391, 480 Mammal, nerves of, 251 Mammary glands, 464 evolution, 465 involution, ib. lactation, ib. structure, 464 Mandibular arch, S47 Manometer, Hiirthle's, 242, 273 Martin's, 372 Marchi reaction, 177 Marey's sphygmograph, 2S7 tambour, 122, 239, 310 Mastication, 525 Mastoid cells, 738 Maturation of the ovum, 828 Maxillary process, 847 Maximal pulsation, 292 May, Page, reaction of degeneration, 189 Meat as food, 466 Meatus of ear, 743 Meckel's cartilage, S48 diverticulum, S6S Meconium, 524 Mediastinum testis, S17 Medulla oblongata, 190, 623, 626 et seq. columns of, 627 decussation of fibres, 632-634 development, S62 fibres of, how distributed, 627 grey matter in, 619 pyramids of anterior, 626 posterior, 627 structure of, 628 Medullary groove, 858 Meibomian follicles, 472, 764 Meissner's corpuscles, 726 plexus, 452 Melanin granules, 803 Membrana eapsulo-pupillaris, S66 chorio-capillaris, 768 decidua, S36 granulosa, 822 development into corpus luteuai, ib. hyaloidea, 776 limitans externa, 773, 775 interna, 77 propria or basement membrane. See Basement Membrane. pupillaris, 866 tectoria, 745 action of, 749 tympani, 739, 746 Membrane, vitelline, S25 Membranes of the brain and spinal cord, 190 Motor Areas of Cerebrum. Membranes, mucous. See Mucous Membranes. semipermeable, 323 serous, 471 Membranous labyrinth, 741, 742. See Bar. Menstruation, 823, S26 coincident with discharge of ova, 823 corpus luteum of, S23 Mercurial kymograph, 269, 271 Meroblastic ova, S28 Mesencephalon, 624, 863 Mesentery, dorsal, S35 Mesial nasal process, 846 Mesoblast, 21, 833 organs formed from, 830 Mesoblastic somites, 833, 844 Mesonephros, 872 Metabolic balance-sheets, 5S7 et.seq. Metabolism, 7, 813 general, 5S3 et seq. Metanephros, 872 Metencephalon, 624, S63 Methsemoglobin, 435 photographic spectrum of, ib. . Mett's tubes, 4S9 Micrococcus urese, 569 Microcytes, 420 Micro-organisms, types of, 405 Microsmatic animals, 736 Micro-spectroscope, 434 Micturition, 549 centre, 549, 676 Middle ear. See Tympanum. Mid-gut, S35 Milk, as food, 461 alcoholic fermentation of, 463 chemical composition, 462 coagulation of, ib. fats of, 463 chemical composition, ib. proteids of, 462 reaction and specific gravity, 461 salts of, 463 secretion of, 461 souring of, 463 (see 391) uterine, S38 Milk-curdling ferment, 493 Milk-globules, 461 Milk-sugar, 390, 463 properties of, 391 Milk-teeth, 65 et seq. Millon's re-agent and test, 397 Mitochondrial sheath, 820 Mitosis, 16, S29 Mitral cells, 736 Modiolus, 742 Molars. See Teeth. Molecular layers, 772, 773 Moleschott's diet table, 461 Momentum, 264 Monakow's bundle, 617, 639 Monaster stage of karyokinesis, IS Monatomic alcohols, 38S Monkey's brain, 6S5 Monoplegia, 683 Monosaccharides, 3SS Monro-Kellie doctrine, 311 Moore's test for sugar, 3S9 Morner and Sjoquist's method of estimating uies , 555 Morphological development, 20 Morula, S31 Mosso's ergograph, 150 experiments on the effects of fatigue, 151 Motor areas of cerebrum, 6S1, 6S6, 690 impulses, transmission in cord, 669 nerve-fibres, 91 892 INDEX Motor Nerves. Motor nerves, 161 Motor oculi nerve, C2S, 040 origin of, 640 Mott and Halliburton, on degenerated nerve, 101 177 Mountain sickness, 374 Mouth, 445 Movements of protoplasm, 12, 100 peristaltic, of intestines, 531 of involuntary muscle, 15S of stomach, 528 Mucic acid, 390 Mucigen or Mucinogen, 20, 33, ■)"."> Mucin, 26, 33, 401, 471 Mucoids, 401 Mucous membrane, 471 digestive tract, ib. epithelium-cells of, 472. .See Epithelium, gastro-pulmonary tract, 472 genito-urinary tract, ib. gland-cells of, ib. of intestines, 452, 457 respiratory tract, 472 of stomach, 448 of uterus, changes in pregnancy, 825 Muller's fibres, 772 Miillerian duct, 872 Multipolar nerve-cells, 104 Murexide test, 500 Muscarine, action of, on the heart, 250 Muscle, 105 blood-vessels of, 86 cardiac, 87 changes in form, when it contracts, 107 et seq. chemical changes in, 149 composition of, 154 clot, ib. columns, 81 contractility, 99 curves, 113, 116-118, 132 development, 88 dynamometer, 131 elasticity, 125 electrical phenomena of, 133 et seq., ISO extensibility of, 125 et seq. fatigue, effect of, 117, 150 curves, 117 Heasen's line, 82 involuntary, 79 (see 158 et seq.) irritability, 99 evidence of, ib. nerves of, 86 plain, 87 plasma, 154, 150 red, 87 response to stimuli, 102 et seq., 186 rigor, 153, 160 sarcolemma, 80 sensory nerve-endings in, 722 serum, 154 shape, changes in, 121 skeletal, 79 sound, developed In contraction of, 122 spindle, S6, 673. See Neuro-muscular spindle. stimuli, 102 striated, structure of, 81 et seq. tetanus, 121 negative variation of, 140 thermal changes in, 147 tonus, 130, 160 twitch, 116 (see 141) voluntary, 79 (see 15S et seq.) wave, 118, 141 work of, 130 Muscles, reciprocal action of antagonistic, 673 Muscular action, conditions of, 131 Nebves, Muscular contraction, 106, 116 ellect of two successive stimuli, 119 of more than two stimuli, 120 voluntary tetanus, 121 Muscular fibres, development, 88 plain, 78 transversely striated, ib. Muscular force, 130 irritability, 99 sense, 72S tissue, 78 et seq. composition of, 155 Muscularis mucosse, 345, 448, 453, 454, 457 Musical sounds, 759 Mydriatics, 789 Myolencephalon, 863 Myelination, 692 Myeloplaxes, 55 Myelospongium, 859 Myogen-fibrin, 156 Myoglobulin, 156 Myohsematin, 156 Myograph, 107 Helmholtz's, 112 pendulum, 114 spring, ib. transmission, 122 (sec 172) Myopia, or short-sight, 785 Myosin, 154, 156 Myosin-fi brin, 156 Myosinogen, 155-157 Myotics, 789 Myxoedema, 336 (see 341) N. Nails, 577 Nasal cavities in relation to smell, 734 et seq. Nasmyth's membrane, 69, 74 Near point, 783 Nerve-cells, classification of, 203 structure of, 192 et seq. Nerve-centres, 190 et seq. See Cerebellum, Cere- brum, etc. ano-spinal, 534 cilio-spinal, 676 (see 788) defalcation, 533 deglutition, 527 erection, 676 micturition, 549, 676 parturition, 676 respiratory, 360 secretion of saliva, 476 speech, 688 vaso-motor, 297, 671 Nerve-corpuscles, 192 et seq. bipolar, 193 unipolar, ib. Nerve epithelium, 716 Nerve-libres, cardio-inhibitory, 247 Nerve-impulse, velocity of, 172 Nerves, 90 accelerator, 162 action of stimuli on, 102, 549 afferent, 90, 162 axis-cylinder of, 92 cells, 91, 192 centrifugal, 161 centripetal, 162 cerebro-spinal, 191, 606 changes in, during activity, 171 classification, 161 conductivity of, 181, 189 cranial, 191, 640 et seq., 848 INDEX 893 Nerves. Nerves— continued degeneration, 164, 200 chemistry of, 177 reaction of, 1SS direction of a nerve impulse, 173 efferent, 90, 161 electrical, 162 stimulation of, 1S6 excitability of, 172 fibres, 91 development of, 96 functions of, 164 funiculi of, 94 grey matter, 91 inhibitory, 162 intercentral, 163 intracardiac, 252 irritability of, 99 laws of conduction, 162 et seq, medullary sheath, 92 medullated, 91 motor, 161 termination of, 95 nodes of Banvier, 92 non-medullated, 91 olfactory, 628, 735 physiology of, 161 et seq. plexuses of, 95 reflex actions, 163, 19S secretory, 162 section of, 164, 477 size of, 94 spinal. See Spinal Nerves. splanchnic, stimulation of, 361 stimulation of cut, 164, 361, 477 structure, 91 sympathetic, influence on heart, 249 taste, 731 terminations of, in corpuscles of Golgi, 722 in corpuscles of Grandry, 722 in corpuscles of Herbst, 719 in end-bulbs, 720 in motorial end-plates, 95 in networks or plexuses, 723 in Pacinian corpuscles, 719 in touch-corpuscles, 720 trophic, 162, 813 Nervous circles, 662, 674 Nervous system, cerebro-spinal, 191, 606 development, S58 et seq. electrical variation in central, 697 influence on the heart, 370 sympathetic, 249 vaso-motor, 297 et seq. Nervous tissues, chemistry of, 175 Neural crest, 861 Neurenteric canal, 832 Neuroblasts, 859 Neuroglia, 191, 609, 859 Neurokeratin, 92, 192, 404 Neuro-muscular spindles, S6, 722, 723 Nicotine, action of, 302, 340, 47S Nissl's granules, 195 et seq., 700 significance of, 200 Nitric oxide haemoglobin, 437 Nitrogen in the blood, 37S eliminated in the form of urea, 459 Nodal point, 777 Nodes of Ranvier, 92 Nose. See Smell. development of, 867 Notochord, 835, 843 Nuclear layers, 772, 773 sap or matrix, 10 Ossicles of the Ear. Nucleic acid, 402 Nuclein, 11, 402, 403, 463 Nuclei pontis, 635 Nucleoli, 10 Nucleo-proteids, 402 Nucleus of animal cell, 6, 10 et seq. chemical composition, 11 division, 16 staining of, 11 structure, ib. Nucleus ambiguus, 634, 645 Nucleus of Bechterew, 643 Nyctalopia, 803 Nystagmus, 803 O. Oblique vein of Marshall, S53 Odontoblasts, 6S, 70, 72, 73 Odontogen, 73 Odours, 737. See Smell. (Esophagus, development, S67 structure of, 446 Oleaginous principles, 393 Oleic acid, 394 Olein, 44, 393 Olfactory bulb, 735 cells, 734 depression, 847 nerves, 628, 735 tract, 735 " ruots " of, ib. Olivary body, 626, 634 Oliver's hsemacytometer, 425 on the sphygmometer, 293 Omphalo-mesenteric veins, 839, 849, S52, S55 Oncograph, Roy's, 309 Oncometer, 310, 545 intestinal, 533 Roy's, 309, 333 Oocytes, 821, S25, 82S, 829 Oogonia, 825 Ophthalmoscope, 792 et seq. Opsonins, 444 Optic disc, 771 Optic nerve, 628 decussation of fibres in, 808 development of, 865 Optic thalamus, 654 vesicle, primary, 864 Optical angle, 779 apparatus of eye, 777 defects in, 784 Optogram, 802 Ora serrata of retina, 771, 776 Orang's brain, 663 Orbito-sphenoids, 848 Organ of Corti, 744 of Giraldes, 875 Organic compounds in body, 386 Organised ferments, 406 Ornithine, 573 Osmosis, 322, 523 distinguished from diffusion, 397 Osmotic pressure, method of estimating, 321, 322 327, 548 calculation of, 325 determination of, ib. of proteids, 326 phenomena, 321 et seq. physiological applications, 326 Ossein, 403 Osseous labyrinth, 741. See Ear. Ossicles of the ear, 740 action of, 747 894 INDEX Ossification'. Ossification, stages of, 59 et seq. Osteoblasts, 59, 63 Osteoclasts, 03 Osteogen, 59 Otic vesicle, primary, S66 Otoliths, 707 Ovary, 821 development of, S27 Graafian follicles in, 821 Oviduct, or Fallopian tube, 825 Ovo-mucoid, 401 Ovum, 20, 822, 827 action of seminal fluid on, S2S ct seq. changes in ovary, 827 previous to fecundation, 82S cleaving of yolk, 831 development, 827 fertilised, 830 formation of, 824 germinal vesicle and spot of, S25 ct seq. impregnation of, S30 maturation, B28 segmentation, S31 structure of, 827 in mammals, 824 subsequent to cleavage, 831 1 1 si ,. Oxidases, 407 Oxygen in the blood, 378, 3S6 Oxyhemoglobin, 77, 429 ct seq., 432 spectrum of, 434, 435 (sec coloured plate) Oxyntic cells, 4S1, 482 Oxyphile cells, 421 P. Pacchionian bodies, 600 Pacinian corpuscles, 719 Pain, 710 (see 60S) Palmitic acid, 394 Palmitin, 44, 393 Pancreas, 490 adaptation of, 501 deveiopmeut of, SOS extirpation of, 500 diabetic condition produced in animals by 501, 510 functions of, 500 secretory nerves of, 493 structure, 490 Pancreatic juice, 491 action on fats, 492 composition and action, 491 ferments in, ib. Panoramic vision, 713 Papillae, of the kidney, 536 of skin, distribution of, 576 of tongue, 729, 730 Parachordal cartilages, 847 Paradoxical contraction, 182 Paraglobulin, 417 Parallel puzzle, 811 Paramucin, 402 Paramyosinogen, 156 Parapeptone, 487 Parathyroids, 337 Parietal cells, 450, 4S1 Parotid gland, 478 Parovarium, 873 Paroxysmal hemoglobinuria, 573 Pars ciliaris retime, 770 Parturition centre, 076 Par vagum. Sec Pneumogastric nerve. Pathological urine, 570 Pavy's views as to the liver being a sugar- forming organ, 510 Pneumogastric N'ekve. Pawlow's method for obtaining pure gastric juice, 482, 493, 490 Pelvis of the kidney, 536 Pendulum myograph, 114 Penis, 819 structure, ib. Pepsin, 481, 485 Pepsinogen, 4S2 Pepsin-hydrochloric acid, 484 Peptones, 396, 400, 4S7 characters of, 4S7 Peptonuria, 571 Perception, 715 Perforating fibres of Sharpey, 58 Perfusion cannula, Kronecker's, 257 Pericardium, 206 Perichondrium of cartilage, 51 Perilymph, or Said of labyrinth of car, 706, 741 Perimeter, 795 Perimysium, 79 Perineurium, 94 Periotic capsule, 848 Peripheral resistance, 260 Peristaltic movements of intestines, 531, 532 of involuntary muscle, 15S, 159 (see 52S) of stomach, 528 Perivitelline fluid, S30 Permanent teeth. See Teeth. Perspiration, cutaneous, 579 insensible and sensible, 5S0 ordinary constituents of, 5S1 Pettenkofer's reaction, 510 Peyer's patches, 456 Pfliiger's law of contraction, 1S4, 1S9 at-rotonometer, 3S1 Phagocytes, 295, 422, 444 Phakoscope, Helmholtz's, 7S2 Pharynx, 445 action in swallowing, ib. development, 867 Pheuyl hydrazine test, 391 (see 572 Phloridzin-diabetes, 517 Phosphates in urine, 500, 569 Photo-chromatic interval, 803 Photographic spectra of haemoglobin, oxyhemo- globin, and methoemoglobin, 435 Photophobia, 803 Phrenograph, 350 Physiological methods, 3 rheoscope, 145, 159 zero, 727 Pia mater, GOO Picric acid test, 571 Pigment cells of retina, 100, 774 movement of, 803 Pineal gland, 341 Piotrowski's reaction, 39S, 404 Piperidine, action of, 340 Pitot's tube, 283 Pituitary body, 341 development, 843 effects of removal, 341 Placenta, maternal, S39 foetal, S42 Plasma of blood, 70, 409, 414 gases of, 410 Plethysmograph, 307 Schiifer's, 25S Pleura, 347 Plexus, terminal, 723 of Auerbach, 97, 452 Pneumogastric nerve, 020, 613 distribution of, 645 functions, 629, 645 influence on deglutition, 527 INDEX 895 Pxeujiogastjeuc Nerve. Pneumogastric nerve— continued influence on gastric digestion, 529 secretion, 4S6 heart, 247 lungs (trophic), 814 muscles of stomach, 530 pancreatic secretion, 493 respiration, 362 vomiting, 531 mixed function of, 645 origin, ib. Poggendorf's rheochord, ISO Polil's commutator, 179 Polar globules, S2S-830 Polariraeter, 404 Polypeptides, 492, 500 Polysaccharides, 3S9 Pons Varolii, 623, 625 grey matter in, 624 Portal canals, 505 circulation, 214 vein, 505. See Liver. Porus opticus, 771 Postero-lateral column, 618 Postganglionic fibres, 301 Precipitin, 443 Preganglionic fibres, 301 Pregnancy, corpus luteum of, 823 Prepynmidal tract, 617 Presbyopia, 787 Presphenoid, 84S Pressor nerves, 305 Pressure gradient, 2S1, 367 Pressure head, 2S2 Pressure-measurers, 264 Primary areas, 695, 696 Primitive groove, 831 germ cells, S21 jugular veins, 852 mouth cavity, 845 nerve-sheath, or Schwann's sheath, 92 streak, S31 Processus gracilis, 740 vaginalis, 876 Projection fibres, 659 Pronephros, S72 Pro-nucleus, female, 828, 830 male, 830 Propeptone, 4S7 Prosencephalon, 624 Prostate gland, 543 Protamines, 404 Proteid metabolism, 7 Proteids, 7, 395 absorption of, 520 action on polarized light, 397 of blood, 416 classification, 399 coagulated, 400 colour reactions, 397 composition, 395 conjugated or compound, 399 crystallisation, 397 indiffusibility of, 396 osmotic pressure of, 326 precipitants of, 39S simple, 399 solubilities, 396 - - Proteoses, 396, 400, 487 characters of, 4S7 Prothrombin, 414, 428 Proto-albumose, 487 Protoplasm, 7, 8, 824, 829 chemical structure, 9 Respiration - . Protoplasm — continued irritability, 15 movements, 12 et scq., 100 Prato-vertebras, 833,' 844 Pseudo-mucin, 402 Pseudo-nuclein, 402 Pseudopodia, 13, 15 Fseudoscope, 811 Pseudo-stomata, 219 Ptosis, 805 Ptyalin, 475, 4S0 Ptyalinogen, 476 Pulmonary artery, S50 Pulsation, maximal, 292 Pulse, anacrotic, 290 arterial, 287 et seq. dicrotic, 291 velocity, 2S1 Purine bases, 403, 562 Purkinje's cells, 197, 649 fibres, S9 figures, 790 phenomenon, 797 Pyloric glands, 450, 4S2 Pyramidal tracts, 615 et seq. Pyramids of medulla obloMgata, 626 of kidney. See Kidney. P/.ibram, Hans, theory of classification by muscle proteids, 157 Quinquand, output of the heart, 246 R. Racemose glands, 472 Ranke's metabolic balance-sheet, 587. diet table, 461, 5S7 Rathke's pouch, 846 Raynaud's disease, 311 Reaction time in man, 675 Reluced eye, 779 Reflex arc, 671 actions, 667 inhibition of, 670 in frog, 669, 679 in man, 671 superficial, ib. tendon, 672 of nerves, 163, 198 of spinal cord, 669 et seq. Reflexes, uterine, 677 Refraction, laws of, 777 Refractive media of eye, ib. Regions of body. See Frontispiece. Reid, Waymouth, experiments on absorption from the intestines, 523 Remak, fibres of, 95 ganglion of, 252 Renal circulation, 214 epithelium, activity of, 546 oncometer, 545 Rennet, 462 Reproductive organs, S16 et scq. Requisites of diet, 5S7 Reserve air, 358 Residual air, ib. Resistance, peripheral, 260 Respiration, 343 abdominal type, 354 alteration in atmospheric pressure, 374 breathing or tidal air, 357 chemistry of, 374 effect on circulation, 366 896 INDEX Respiration. Respiration— continued gases m relation to, 873, 377 influence of nervous system, 300 mechanism of, 351 et seq. nervous, 300 movements, 354 of vocal cords in, 757 nuantity of air changed, 357 Respiratory acts, special, 364 apparatus, 343 development of, 870 capacity of chest, 35S circumstances affecting, 359 movements of glottis, 357 methods of recording, 354 muscles, 351 et seq. nerve-centre, 300 rate, 359 relation to pulse-rate, ib. size of animal, ih. relation to will, 301 et seq. rhythm, 353 sounds, 350 Restiform bodies, 035, 040-051 Rete testis, 817 Reticulum, 9 Ratiform tissue, 40 Retina, 770 blind spot, 790 blood-vessels, 770 changes in, during activity, 802 duration of impression on, 791 of after-sensations, 801 electrical variations in, 803 excitation of, 790 focal distance of, 7S0 fovea centralis, 771 functions of, 789 image on, how formed distinctly, 779 layers, 771 ora serrata, ib. pigment-cells, 100, 774 movement of, S03 pigments of, 803 in relation to single vision, 805 structure of, 770 visual purple, 773, S02 Retinitis pigmentosa, 803 Retractor lentis muscle, 7S4 Rheochord, 180 Poggendorfs, ib. Rheoscope, physiological, 145, 159 Rheoscopic frog, 145 Rheotome, 13S Rhodopsin or visual purple, 802 Rhythmicality of movement, 101, 158 Ricin, 442 Rigor mortis, 153, 154, 150 affects all classes of muscles, 153, 151 phenomena and causes of, 154 Hitter's tetanus, ISO Rods and cones, 773, 790, 803 Rolandic area, 081, GS5, 090 injury of, 082 Roy's cardiometer, 240 oncograph, 309 oncometer, 309, 333 tonometer, 257 Rubner, law of conservation of energy, 003 Rumination, 525 Saccharic acid, 390 Saccharoses, 3S9 St Martin, Alexis, case of, 4S1, bij Sensory Impressions. Saccule, 743 Salathe, effect of gravity on the circulation, 270 Saliva, 474 action of, 4S0 composition, 479 process of secretion, ib. reflex secretion, 478 secretion following stimulation of nerves, 300, 477 et seq. Salivary glands, 474 development of, SOS extirpation of, 479 influence of nervous system, 477 secretory nerves of, 470 effect of section of, 477 structure, 474 Sanderson's cardiograph, 239 Sanson's images, 781 Saponification, 395, 492 Sarcolemma, 80 Sarcomeres, 83 Sarcoplasm, 81 Sarcosine, 503 Sarcostyles, 81 Senator, heart plethysmograph, 258 researches on the structure of a sarcostylc, 83 views regarding the function of the Roland it- area, 091 Schemer's experiment, 783 Schematic eye, 778 Schenk on muscular contraction, 132 Schutz' law, 489 Schwann, white substance of, 170 Scleratogenous segment, 844 Sclerotic, 705 development of, S65 Sebaceous glands, 57S Sebum, 57S, 579 Secreting glands, 470 et seq. classification of, 472 Secreting membranes. See Mucous and Serous membranes. Secretion, internal, 328 of kidney, 548 pancreas, 493 suprarenal, 3d9 thyroid, 330 Secretory nerves, 102 of pancreas, 493 of salivary glands, 47>« effect of section of, 477 Segmentation of cells, 831 in chick, S33 ovum, 831 Semen, 819 spermatozoa, S19 Semicircular canals of ear, 741 development of, 800 structure, 705 et seq. Semilunar valves. See Heart valves. Seminiferous tubules, 817 Semipermeable membranes, 323 Sensation, 714 et seq. conception, 715 homologous stimuli, 717 nerves of, 102 pain, 710 (see 008) perception, 715 subjective, 717 tactile, 090, 723 S^nse, organs of, development, 860, 867 Sonsori-motor area, 690 Sensory areas in cerebral cortex, ('82 Sensory 7 impres-uons, conduction of, by sp.nal cord, 067 In brain, GS9-091 INDEX 897 Sessoby Neeve-Endings in Muscle. Sensory nerve-endings in muscle, 722 Serous membranes, 206, 471 Serum, albumin, 399, 416 of blood, 413, 414 globulin, 416 Seventh cerebral nerve, 62S, 641 Sex, influence on respiratory capacity, 359 Sexual organs in the female, S21 in the male, 816 Sherrington, reciprocal action of antagonistic muscles, 673 Side-chain theory, 442 Sighing, mechanism of, 365 Sight. See Vision. Simple tubular glands, 472 Sinus pocularis, 875 uro-genitalis, 876 venosus, 852 Sinuses of Valsalva, 213 Sixth cerebral nerve, 62S, 640 Skeletal muscles, 79 Skeleton. See Frontispiece. Skin, 574 absorption by, 579 dermis, 576 epidermis of, 574 functions of, 579 papillae of, 576 respiration, 579 rete mucosum of, 574 sebaceous glands of, 578 secretions, 579 sensory nerves of, 361 sweat, 579 sweat-glands, 578 varnishing the, 582 Sleep, 697 Small intestine, 451 et seq. See Intestines. Smell, sense of, 730 (see 690) anatomy of regions, 734 delicacy of sense of, 737 tests for, 736 varies in different animals, 734 Smith, Lorrain, carbonic oxide method of esti- mating oxygen tension of arterial blood, 382 experiments on quantity of the blood, 411 Smith's perimeter, Priestly, 795 Sneezing, mechanism of, 365 Snoring, mechanism of, ib. Soap, 395 Sobbing, 365 Sodium chloride method, 402 Solitary glands. See Peyer's patches. Solutions, gramme-molecular, 322 Somatic mesoblast, 836 Somatopleur, 832, S33 Somites, mesoblastic, 833, 834 Sonorous vibrations, how communicated in ear, 745 et seq. in air and in water, 746. See Sound. Soret's band, 435 Sound, conduction by ear, 746 heart, 234 production of, 758 Soup, value as food, 469 Spaces of Fontana, 770 Speaking, mechanism of, 760 Special senses, 719 et seq. Spectroscope, 432 et seq" Speech, 751, 760 centre, 688 defects of, 761 (see 689) Spermatids, 818 Spermatocysts, 81S Stabvation. Spermatogonia, 817 Spermatozoa, 819 form and structure of, ib. Spherical aberration, 7S6 correction of, ib. Sphincter ani. See Defaecation. pu pill 33, 769 Sphygmographs, 2S8, 289 tracings, 2S9 et seq. Sphygmometer, Hill and Barnard's, 292 Sphygmoscope, Anderson Stuart's, 26S Spinal accessory nerve, 629, 645 functions of, 646 origin, ib. Spinal cord, 608 canal of, ib. centres in, 676 columns of, 609 commissures of, 608 conduction of impressions by, 667 et seq. course of fibres in, 613 development of, 859 fissures and furrows of, 608 functions of, 667 et seq. of columns, 615 grey matter, 191, 610 cells in, 610 hemisection, 619, 667 injuries of, 667, 670 membranes of, 606 morbid irritability of, 673 nerves of, 613 reflex action of, 669 et seq. inhibition of, 670 in frog, ib., 678 in man, 671 superficial, ib. regions of, 619 special centres in, 676 structure of, 608 et seq. tracts, 611, 615, 667, 60S transverse section of, 619 white matter, 191, 609 tracts in, 611 Spinal nerves, 16S functions of roots of, 16S origin of, 168 et seq. physiology of, 16S Spindle-shaped cells, 490 Spirem, 17 Spirometer, 358 Splanchnic mesoblast, 836 Splanchnopleur, 833 Spleen, 329 apparatus for splenic curves, 152 development, 870 functions, 331 influence of nervous system upon, 332 Malpighian corpuscles of, 331 pulp, 330 structure of, 329 trabeculae of, ib. Spongioblasts, 772, 859 Spongioplasm, 9 Spot, germinal, 825 Spring myograph, 114 Staircase phenomenon, 117, 159, 255 Stannius' experiment, 255 Stapedius muscle, 740, 748 Stapes, 740 development of, 848 Starch, 392 Starling, on swaying or pendulum movement of intestines, 533 Starvation, 5S9 effects of, 590 898 INDEX StE.U'SIN. Steapsin, 491 Stearic acid, 394 Stearin, 44, 393 Stercobil in, 511,551 Stereoscopic vision, 713, Sll Stethographs, 354, 355 Stewart's diet-table, 4G1 experiments on the circulation of the blood, 2S0 on muscle proteids, 160 on the output of the heart, 21(5 Steyrer on paramyosinogen, 157 Stimulants as accessories to food, 469 Stimulation fatigue, 153 Stimuli, varieties of, 15, 102 Stolnikow, measurement of the heart's output, 245 St >mach, 448 blood-vessels, 451 development, 867 digestion in, 49S, 533 glands, 449 lymphatics, 451 movements, 52S influence of nervous system on, 529 mucous membrane, 44S muscular coat, ib. nerves, 451 peritoneal coat, 448 secretion of. See Gastric juice shadow photographs of, 529 submucous coat, 448 structure, ib. Stomadaeum, 846 Stomata, 24 Stratum granulosum, 575 intermedium of Hannover, 73 lucidum, 575 Striated border, 455 (see 25-27) Striated muscle, 81 ct seq. See Muscle. Stroma, 418, 821 Stromuhr, Lud wig's, 279 Tigerstedt's, 2S0, 281 Structure of cells, 9 et seq. Stuart's kymoscope, 268 Submaxillary gland of dog, 478 Submaxillary and sublingual glands, 476, 868 Substantia gelatinosa of Rolando, 610, 632, 634 nigra, 639 Subthalamic area, 655 Succus entericus, 495, 496, 532 functions of, 496 Sucroses, 3S9 Sugar. See Dextrose. Sulphates in urine, 565 Summation -tones, 749 Superior laryngeal nerve, effects of stimulation of cut, 361 olivary nucleus, 635 Supra-renal capsules, 33S development, 877 (sec 340) fanction, 339 structure, 338 Swallowing, 526 centre, 527 fluids, ib. nerves engaged, ib. Sweat-glands. See Skin. Swim-bladder of fishes, 381 Symphysis of jaw, 84S Synovial fluid, secretion of, 471 membranes, ib. Syntonin, 401 Syringomyelia, 66S Systemic circulation, 214. Sec Circulation. Systole of heart, 231 Tactile end organs, 719 sensibility, 690, 723 variations in, 724 Talbot's law, 792 Taste, sense of, 729 classification of, 732 connection with smell, 729 delicacy of, 734 nerves of, 731 Taste-buds, ib. Taurine, 510 Taurocholic acid, ib. Taxis, positive and negative, 16 Teeth, 64 development, 71 eruption, times of, 66 structure, 67 it seq. temporary and permanent, 06 et seq. Tegmentum, 637 Telencephalon, 862, 863 Temperature, 59S average of body, ib. changes of, effects, 598 et nq. circumstances modifying, 603 effect on muscular contraction, 117 of cold-blooded and warm-blooded animals, 598 in disease, 599 loss of, 603 maintenance of, 598 of Mammalia, birds, etc., ib. regulation of, 603 et seq. sensation of variation of, 725. See Heat. Tendon-reflexes, 672 Tension, arterial, in asphyxia, 3S2 Tensor palati muscle, 747 tympani muscle, 740 action of, 74S Terminal areas, 095-697 Testicle, 816 development, 876 descent of, ib. structure, 816 et seq. Tetanus, 121 (see 141) Hitter's, 186 voluntary, 122, 159 Thalamencephalon, 024 Thalami optici, 654 Theine, 469 Theobromine, ib. Thoma-Zeiss hemacytometer, 424, 425 Thoracic duct, 77, 223 innervation of, 31S Throat deafness, 747 Thrombin, 414, 428 Thymus gland, 334 development, 870 effects of removal, 335 function, ib. structure, 334 Thyro-arytenoid muscle, 754 Thyro-epiglottidean muscle, 754 Thyroid cartilage, 751 Thyroid gland, 335 development, 870 function, 336 structure, 335 Thyro-iodin, 337 effect of intravenous injection of, on blood- pressure, 337, 341 Tigerstedt, measurement of the heart's output, 245 Stromuhr, 2S0, 2S1 Timbre of voice, 759 INDEX 89U • Tissde Fibrinogen. Tissue fibrinogen, 402 Tissue-respiration, 375, 382 Tongue, 729 action in deglutition, 526 epithelium of, 731 muscles of, 729 papillae of, 729, 730 parts most sensitive to taste, 731 structure of, 729 Tonometer, Roy's, 257 Tonsils, 446 Tonus, 130, 160, 673 Torsion, 825 Touch, 719 et seq. muscular sense, 72S sense of locality, 723 of pressure, 725 of temperature, 725 tactile end organs, 719 Touch-corpuscles, 720 Toxin, 441 Trabecules cranii, S47 Trachea, 343 Tract of Flechsig, 61S of Gowers, 618, 66S of Lissauer, 614, 618 of Loewenthal, 616 Tracts in the spinal cord, 611, 615, 667. 668 of bulb, pons, and mid-brain, 639 et seq. Tragus, 73S Transfusion of blood, 31S Transmission myograph, 122 (see 172) Traube-Hering curves, 303, 304, 546 Tricuspid valve, 211 Trigeminal nerve, 628, 641 function, 641 origin of, ib. Trochlear nerve, 62S, 640 origin of, 640 Trommer's test, 389 Trophic nerves, 162 influence of, 813 Trypsin, action of, 492 Trypsin ogen, 490 Tryptophan, 492 Tschistovitch's test, 443 Tubercle of Rolando, 632 Tubuli seminiferi, 816, SI 7 uriniferi, 536 et seq. Tubulo • racemose or tubulo - acinous glands, 473 Tunica albuginea of testicle, S17 dartos, SS propria, 706 vaginalis, 816, 876 vasculosa, 768 Tiirck's column, 615 Tympanum or middle ear, 73S development, 866 membrane of, 738, 739 muscles of, 740 structure, 739 Tyrosine, 500 U. Umbilical arteries, S39, S43, 851, S52 cord, 839, 842 vesicle, 839 Umbilicus, 835 Unicellular organisms, 6 Unilaminar blastodeim, S31 Unipolar nerve-cells, 1P3 Utricle. Unorganised ferments, 406 Urachus, 843, 876 Ureemia, 556, 582 Urate of sodium, 56S Urea, 552 apparatus for estimating quantity, 554, 555 chemical composition of, 552 formation of, by liver, 507, 557 isomeric with ammonium cyanate, 552 quantity. 555 Ureters, 540 Urethra, 541 Uric acid, 560-562 condition in which it exists in urine, 562 deposit of, 568 forms in which it is deposited, 5C0, 567 origin of, 552 presenca in the spleen, 332 proportionate, quantity of, 561 tests, 560 Urina potus, 552 Urinary apparatus, 535 et seq. Urinary bladder, 541 development, 876 nerves, 541 structure, ib. Urinary deposits, 567 et seq. Urine, 551 analysis of, 552 bile in, 572 blood in, ib. chemical sediments in, 569 colour, 551 composition, 552 cystin in, 569 expulsion, 549 flow into bladder, 548 hippuric acid in, 562 inorganic constituents, 564 mineral salts in, 565 mucus in, 566 pathological, 570 phosphates in, 566, 569 physical characters, 551 pigments, ib. pus in, 573 quantity, 551 varies with blood-pressure, 544 reaction of, 551 in different animals, 552 made alkaline by diet, ib. saline matter, 552, 559 solids, 551 specific gravity of, 552 variations of, ib. sugar in, 571 et seq. tests for estimating, 571 tests for inorganic salts of, 567 urates, 56S urea, 552 uric acid in, 560 Urobilin, 511, 513, 551 Urobilinogen, 551 Urochrome, 551 Uro-erythrin, 568 Uterine milk, 838 reflexes, 677 Uterus, S25 change of mucous membrane of, S25 development in pregnancy, ib. follicular glands of, ib. round ligament of, 876 structure, 825 Uterus masculinus, S75 Utricle, 743 900 INDEX Vagina, development of, 875 Yago-sympathetic of frog, 248 Vagus escape, '249 nerve. See Pneumogastric. pneumonia, 361, 814 Valsalva's experiment, 370 Valves of heart, 211. See Heart. Valvulae conniventes, 453 Vas deferens, 817, 819 Vasa eflerentia of testicle, 817, 810, 873 Vasa vasorum, 216 Vascular system, development of, 84!) in asphyxia, 371 Yaso-constrictor nerves, 299 Vaso-dilator nerves, 300, 300, 477 Vaso-motor nerves, distribution of, 29S effect of section, 298 et seq. experiments on, 305 influence upon blood-pressure, 303 stimulation fatigue, 153 Vaso-motor nerve-centres, 297, 071 nervous system, 297 et seq. reflex action, 303 Vegetables as food, 459, 467, 469 Vegetable cells, 6 protoplasmic movement in, 13, 14 Veins, 216 allantoic, 852 cardinal, 852, 854, 855 circulation in, 296 et seq, velocity of, 285 collateral circulation in, 217 development, S52 distribution, 216 hepatic, 855 iliac, 852 innominate, 854 intercostal, 854 jugular, 852, 854 lumbar, 854 omphalo-mesenteric, 839, 849, 852, 855 pulmonary, 856 pressure in, 273 rhythmical action in, 296 structure of, 217 subclavian, S54 umbilical, S43, S52 valves of, 218 et seq. Velocity head, 282 pulse, 281 Velocity of blood in arteries, 278 in capillaries, 280 in veins, ib. of circulation, ib. of ferment action, 489, 402 of nervous impulse, 172 Vena azygos, S55 Vena cava, 854, 855, 85S Venae advehentes, 855 revehentes, ib. Ventilation, 383 Ventral cerebellar tract, 618 Ventricles of heart. See Heart. Ventricular diastole, 232 systole, ib. Ventriloquism, 760 Veratrine, effect of, on muscular contraction, IIS Vermicular movement of intestines, 531 Vernon, heat rigor experiment, 157 pancreatic secretion, 496 Vertebra, development of, 844 Verworn, Max, strychnine and fatigue, 158 Vesicle, germinal, 20, 825 Vesiculas seminales, 819 White Fihro-Cartilaoe. Vibrations, conveyance of, to auditory nerve, 740 et seq. Vierordt's hiematachometer, 2S3 Villi in chorion, function of, 836, 841 of intestines, 453 Vincent, Swale, muscle proteids, 160 Visceral clefts and arches, development of, 817 et seq. connection with cranial nerves, 84S Visceral mesoblast, 833 pain, 727 Vision, 760 angle of, 779 at different distances, adaptation of eye to, 780 et seq. corpora quadrigemina, the principal nerve- centres of, 628 correction of aberration, 786 ct seq. of inversion of image, 809 defects of, 784 et seq. distinctness, how secured, 811 ct seq. duration of sensation in, 791 estimation of the size and form of objects. S09- 811 focal distance of, 780 impaired by lesion of fifth nerve, S13 single, with two eyes, 805 ct seq. Visual area, 689, 713 judgments, 809 ct seq. Visual purple, 773, 802 Visual word centre, 695 Vital action, 326 Vitellin, 466 Vitelline duct, 867 membrane, 825 spheres, ib. Vitello-intestinal duct, 835 Vitreous humour, 766, 776 Vocal cords, 751, 757 action in respiratory actions, 757 approximation of, effect on height of note, ib. vibrations of, cause voice, 757, 758 Voice, 751, 75S range of, 760 Volkmann's hsemadromometer, 27S Voluntary muscle, 79 et seq. nerves of, 86 Voluntary tetanus, 122, 159 Vomer, 848 Vomiting, 530 action of stomach in, ib. centre, 531 nerve actions in, ib. voluntary and acquired, ib. Vowels and consonants, 761 W. Waldeyer, stages of karyokinesis, 17 et seq. Wallerian degeneration method, 164, 169, 611 Waller, apparatus for gas analysis, 384 fatigue theory, 151-153 on the electrical currents of the eyeball, 803 variation iu nerve action, 171 Water-hammer pulse, 288 Wave of blood causing the pulse, ib. velocity of, ib. Weber- Fechner law, 716, 725 Weber's paradox, 129 Weight, influence on capacity of respiration, 359 Whey proteid, 462 White corpuscles. See Blood-corpuscles, white; and Lymph-corpuscles. White fibro-cartilage, 51 fibrous tissue, 41 spot, 771 INDEX 901 Wolffian Bodies. Wolffian bodies, S72 et seq. duct, 872 ridge, S35 Wooldridge's method of preparing tissue-fibrino- gen, 402 Word-centres, 762 Worms, circulatory system in, 229 Wright, Hamilton, sleep theoiy, 699 Xanthine, 332, 335, 403, 562 presence in the spleen, 332 Xantho-proteic reaction, 397 Yawning, mechanism of, 365 Yellow elastic fibre, 43 fibro-cartilage, 52 spot of Sommering, 771, 793 Yolk-sac, 835, S49, 839 et seq. Yolk-spherules, 825 Young-Helmholtz theory, 800, S01 Z. Zona peUucida, 20, S24, 830 Zonule of Zinn, 776 Zuntz, output of the heart, 246 Zymogen, 475, 4S2 Printed by Oliver & Boyd Edinburgh QP34 WalliLurton - K6S 1905