Cli^?'^V \<(p3 Columbia Unibergitp^^ COLLEGE OF PHYSICIANS AND SURGEONS Reference Library Given by i <*«^,^T^. Z^-^ !!;♦' Digitized by tine Internet Arciiive in 2010 witii funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/handbookofphysio1913kirk HALLIBURTON'S HANDBOOK OF PHYSIOLOGY HANDBOOK OF PHYSIOLOGY BY W. D. HALLIBURTON, M.D. LL.D., F.R.C.P., F.R.S. PROFESSOR OF PHTSIOLOGr, KING'S COLLEGE, LONDON ELEVENTH EDITION (being the T\VE>f TY-FOURTH EDITIO>f OF KIRKES' PHYSIOLOGY) WITH NEARLY SIX HUNDRED ILLUSTRATIONS IN THE TEXT, MANY OF WHICH ARE COLOURED, AND THREE COLOURED PLATES PHILADELPHIA P BLAKISTONS SON & CO. 1012 WALNUT STREET 1913 PREFACE TO THE ELEVENTH EDITION Once more this book has been thoroughly revised. The sections dealing with salivary secretion, the formation of urine, and much of the chapter on respiration have been almost entirely rewritten. New matter on the process of conduction in the heart, on the appli- cations of physical chemistry to physiology, on so-called vitamines, and several other subjects has been introduced. The concluding chapter on reproduction and development is a new one, and replaces the two last chapters in previous editions. I am again indebted to several kind friends for assistance in carrying out my task. I would especially thank Mr Barcroft, F.E.S., for his valuable help in the chapters that deal with saliva, respira- tion, and the kidney ; Dr C. S. Myers, who has kindly revised the parts which deal with the special senses ; Dr Hertz of Guy's Hospital, for useful hints in bringing the chapter on the movements of the stomach and intestines up to date ; and Dr F. H. A. Marshall, for similar kind offices in relation to the subject of reproduction. I think, in conclusion, I may congratulate my readers that, although the present edition contains so much that is new both in text and illustrations, I have been successful in introducing this additional information without increasing the bulk of the volume. As a matter of fact, this edition is one page shorter than the last. AV. D. HALLIBUETOX. King's College, London, 1913. CONTENTS CHAPTER I Introductory PaOE 1 The Animal Cell CHAPTER II CHAPTER III Epithelium 20 CHAPTER IV The Coxxective Tissues . 28 CHAPTER V The Connective Tissues — continued .... 37 Cartilage .,,,,,. 37 Bone . ....••• 40 Teeth . ....... 50 The Blood .....•• 60 CHAPTER VI Muscular Tissue 62 Vlll Neuve CONTENTS CHAITEK \II PAOK 73 CHAPTER VJII IumTAllILirV AM) CuNTKAC'ni.nV 81 CHAPTER L\ CllAN(.K IN' Foim I\ A MfSCLK WHEN' IT CoNTHAtTS Instruments used Simple Muscle Curv^e. The Muscle-Wave Effect of two Successive Stimuli Effect of more than two Stimuli Tetanus Voluntary Tetanus . 87 87 96 100 101 101 101 104 CHAPTER X ExTEKsiBiLirv, Elasticity, and Wokk oi Mvscle 108 CHAPTER XI The Electiucal Phenomeka ok Muscle 116 CHAPTER XII Thermal and Ciie^ikal CiiA>r(;Es iv Mitscle . Fatigue ..... Rigor Mortis . . . . . Chemical Composition of Muscle 129 132 136 136 CHAPTER XIII CoMi'AiiisoN OF Voluntary avd Involuntary Muscle 140 CONTENTS IX CHAPTER XIV PnvsroLOnv or Neiive Classification of Nerves Investigation of Nerve Functions Degeneration of Nerve Regeneration of Nerve Roots of the Sjiinal Nerves . Changes in Nerve during Activity Velocity of a Nerve Impulse. Direction of a Nerve Impulse Crossing of Nerves The Nature of the Nerve Impulse Receptive Substances Chemistry of Nervous Tissues PAGE 143 143 14fi 146 148 155 158 159 160 161 163 164 165 CHAPTER XV Electrotovus 169 CHAPTER XVI Nerve CExmES ...... Structure of Nerve-Cells .... The Law of Axipetal Conduction The Significance of Nissl's Granules Classification of Nerve-Cells according to their Function 180 182 191 192 194 CHAPTER XVII The Autonomic Nervous System 196 CHAPTER XVIII Trophic Nerves ....... . 206 CHAPTER XIX The Circulatory Systeji ..... . 208 The Heart . 208 Course of the Circulation ..... . 214 Structure of Arteries ...... . 216 Structure of Veins ...... . 218 Structure of Capillaries and Sinusoids . 222 Structure of Lymphatic Vessels .... . 223 CHAPTER XX The Cibculatiox of the Bi.ood 227 CONTENTS CHAPTER XXI Physiology of the Hkari- The Cardiac Cycle Action of the Valves of the Heart Sounds of the Heart . Coronary Arteries Cardiographs . Intracardiac Pressure The Electro-Cardiogram Frequency of the Heart's Action Work of the Heart Innervation of the Heart Rhythm, Conduction, etc. , in Heart Muscle The Isolated Heart .... PAOK 232 232 234 2:i5 237 238 240 243 247 247 249 254 260 CHAPTER XXn The Circulation ik the Blood-vessels Use of the Elasticity of the Vessels Blood-pressure Velocity of the Blood-How The Time of a Complete Circulation The Pulse The CapUlary Flow The Venous Flow The Vaso-raotor Nervous System Plethysmography Pathological Conditions Local Peculiarities of the Circulation 263 265 266 281 289 290 297 299 300 308 311 312 CHAPTER XXIII Lymph and Lvmphatic GiANns Composition of Lymph Lymphatic Glands Lymph Flow . Relation of Lymph and Blood Formation of Lymph . 315 315 316 318 319 319 CHAPTER XXIV Physical Chemistry and its bearing ox Physiological Pnoni.E.Ms, 322 CONTENTS XI CHAPTER XXV The DrcTLEss Gi.axds Spleen Haeraolyraph Glands Thymus Thyroid Parathyroids . Supra-renal Capsules Pituitary Body Pineal Gland . Coccygeal and Carotid Glands CHAPTER XXVI RESriKATIOX Respiratory Apparatus Respiratory Mechanism Graphic Record of Respirations The Gases of the Blood Solution of Gases in Water . Dalton-Henry Law .... Tension of Gases in Fluids . Measurement of Quantity of Gas in Fluids . Relation between Quantity and Tension The jMechanism of Gaseous Exchange in the Lung 1. Oxygen .... 2. Carbonic Acid Cause and Regulation of Respiration 1. The Respiratory Centre 2. The Nervous Factor in Respiration . 3. The Chemical Factor in Respiration Special Respiratory Acts Artificial Respiration .... Ventilation ..... CHAPTER XXVII The Relation of Respiration to other Processes in the Body Effect of Respiration on the Circulation Asphyxia .... Relation of Respiration to Nutrition Oxygen Want Mountain Sickness Respiration at High Pressures Carbon Monoxide Poisoning. Cheyne-Stokes Respiration . Diabetic Coma CONTENTS CHAPTKI{ XXVIII PAOB Tin: C'liEMu.M Co.Mrosnio.v oi riii HODV . 406 Carbohydrates 406 Fats . . 414 Proteins 416 Lipoids 434 Enzvraes . 438 CHAPTER XXIX The Bi.oon .... Coapfulatinn of tiie Hlood The Plasma and Serum The Hlood-Corpuscles Develo|)raent of the Blnod-Corpustles Chemistry of the Blood-Corimsclcs Haemoglobin . . . , Iramimity .... 444 446 452 454 459 461 461 472 CHAPTER XXX Food ...... . 479 Dietaries ..... 479 Milk 481 The Mammary Glands 485 KgK-s 486 Meat ...... 487 Flour ...... 488 Bread ...... 489 Cooking of Food .... 489 Accessories to Food .... 490 Unknown but Essential Constituents of Food 491 CHAPTER XXXI The Altmentauv Canal; Sechetint. Giaxds . 492 CHAPTER XXXII Sai-Iva ..... The Salivary Glands . The Secretion of Saliva Secretory Nerves of Salivary Glands TheSahva . . . . 498 498 500 502 504 CONTENTS XUl CHAPTER XXXIII TllK GaSIUK JlICE Innervation of the Gastric Glands Action of Gastric Juice PAOK 607 511 513 CHAPTER XXXIV Digestion in the Intestines The Pancreas Composition and Action of Pancreatic Juice The so-called Peripheral Reflex Secretion of the Pancreas The Succus Entericus Bacterial Action ol7 517 518 520 522 525 CHAPTER XXXV The Liver ...... . 527 Bile . 531 Glycogenic Function of the Liver . 536 Diabetes ...... . 538 The Liver and Fat Metabolism 541 CHAPTER XXXVI The Absorption of Food 543 CHAPTER XXXVII The Mechanical Processes of Digestion . 550 Mastication ...... . 550 Deglutition ...... Movements of the Stomach .... . 551 . 553 Vomiting ...... Movements of the Intestines .... . 556 557 CHAPTER XXXVIII The Urinary Apparatus The Nerves of the Kidney ' The Kidne)^ Oncometer The Functions of the Kidney- Extirpation of the Kidneys . Passage of Urine into the Bladder Micturition 565 571 571 572 579 580 580 CONTENTS CHAITER XXXIX PAOK TllK UlUNK. ......... 582 Urea 5.H3 Ammonia .... 588 Creatine and Creatinine 589 Uric Acid .... .',91 Hippuric Acid 594 Inorganic Constituents of Urine 595 Urinary Deposits 598 Pathological Urine . 600 CHAPTER XL Tin: Skin and Its Appendages 604 CHAPTER XLI General Metabolis.m ..... . 612 Balance in Health ..... 613 Metabolism of Carbohydrates . 614 Metabolism of Fat ..... . 616 Metabolism of Protein .... . 621 Growth and Maintenance .... . 626 Inanition or Starvation .... . 628 CHAPTER XLH The Conservation of Energy . CHAPTER XLIII Te."mpehatire ..... CHAPTER XLIV The Central Neuvois Svstem . CHAPTER XLV Stricture ok the Spinal Coud CHAPTER XLVI Struciure ok the Bri.it, Pons, and Mid-Bhain The Cranial Nerves .... 630 636 642 64S 661 673 CONTENTS XV CHAPTER XLVII SfRUCTUIlE Ol' THE CEREBELLUM . PAOK 680 CHAPTER XLVni Structuhe or iiie Ceuehrum ....... 686 The Convolutions ........ 691 Histology of the Cortex ....... 695 The White Matter ........ 698 CHAPTER XLIX Functions of the Si'inal Cord ....... 704 The Cord as an Organ of Conduction . . . . . 704 Reflex Action of the Cord ...... 709 Reflex Action in Man ....... 711 The Principle of the Common Path ...... 716 Reaction Time ........ 720 Spinal Visceral Reflexes ...... 721 CHAPTER L Functions or the Cerebrum ...... 722 Removal of the Cerebrum ...... 722 Localisation of Cerebral Functions ..... . 725 Function and Myeh nation ...... . 739 Association Fibres and Centres ..... . 740 Electrical Variation ....... . 743 Sleep and Narcosis ....... . 744 CHAPTER LI Functions of the Cerebellum . The Semicircular Canals 749 752 CHAPTER LH The Physiology of Conscious States . 757 CHAPTER UIl Cutaneous Sensations Tactile End-Organs . Locahsation of Tactile Sensations Varieties of Cutaneous Sensations 766 766 770 772 XVI CONTENTS CHAPTK1{ MV MOTORIAL AND VlSCKHAL SeKSATIONS PAOK 776 CHAPTER LV Taste avd Smeli. Taste . Smell . 779 779 783 CHAPTER LVI Hearinc Anatomy of the Kar . Physiology of Hearing 788 788 794 CHAPTER LVII LE AND Speech ..... . 799 Anatomy of the Larynx .... . 799 Movements of the Vocal Cords . 804 The Voice ...... . 806 Speech ...... . 807 Defects of Speech ..... . 808 CHAPTER LVIH The Eye and Vision The Eyeball . The Eye as an Optical Instrument Accommodation Defects in the Optical Apparatus The Sliiascoj)e Functions of the Iris . Functions of the Retina The Ojjhthalmoscope The Perimeter Visual Sensations and Colour Vision Changes in the Retina during Activity Movements of the Eyeballs . Nervous Paths in the Optic Nerves . Visual Judgments 810 811 820 824 828 831 832 834 836 839 811 847 849 853 854 CONTENTS xvn CHAPTER LIX RkPUODUCTION, DevEI.OP.MKNT, GUOUTII AND D The New-born Cliild and its Development The Male llejiroductive Organs The Female llejiroduetive Organs . The Physiology of the Reproductive Organs Spermatogenesis . Oogenesis Menstruation Maturation of the Ovum Internal Secretions of Ovary and Testis Fertilisation .... Segmentation The Dccidua and the Foetal Membranes The Festal Circulation Parturition .... Death ..... PAOK 858 862 8G3 867 872 872 873 873 875 878 881 883 887 891 893 895 INDEX 897 COLOURED PLATES Varieties or Colourless Corpuscles . Plate of Absorption Spectra . Simultaneous and Successive Contrast to face page 456 „ 466 „ 845 FAHRENHEIT and CENTIGRADE SCALES. F. 500" 401 892 3S3 374 85G 847 838 329 S20 311 302 284 275 200 248 239 230 212 203 194 170 107 140 122 113 105 104 100 98-5 95 8C 77 68 50 41 32 23 14 + 5 - 4 -13 -22 -40 -76 C. 200- 205 200 195 190 ISO 175 170 165 1()0 155 150 140 135 130 120 115 110 100 95 90 80 75 60 50 45 40-54 40 37 S 36 35 30 25 20 10 5 - 5 -10 -15 -20 -25 -30 -40 -60 1 deg. F. = -54° C. 1-8 „ = 1°C. l-'reezing point 0° C. = 32° F. Boiling point 100° C. = 212° F. To convert de- grees F. into de- grees C, subtract 32, and multiply To convert de- grees C. into de- grees F., multiply by I, and add 32°. MEASUREMENTS. LENGTH. 1 nidtre 10 decinii'tre; ,1 39-37 Englisli 100 continiotres |' ,„, . '"';'','!f , „, .„ s 1000 mUlimetres J ("^ ^ ^^''^ '^'"^ ^J in.) 1 decimetre ^ ^ 3.937 . j 1 centimetre \ = -3937 or about 10 millimetres / (nearly f inch). 1 millimetre = nearly ^\ inch. Or, One Metre = 39-37079 inches. (It is the ten-miUiontli 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 mUe = 4 in. ,^T in. = ^'r in. = 32-80 feet. = 109-36 yds. = 0-62 mile. 2-539 Centimetres. 3-047 Decimetres. 91 of a Metre. 1-60 Kilometre. WEIGHT. (One gramme is the weight of a cubic centimetre of water at 4° C. at Paris.) 1 gramme ^ 10 decigrammes | = 15"432349 grs. 100 centigrammes C (or nearly 15J). 1000 milligrammes J 1 decigramme "i ., 10 centigrammes - = '■''*1??'" ^9^*^ 100 millilrammes j than 14 gram. 1 centigramme "t 10 decigrammes / = rather more than ,^^-, grain. 1 milligramme = rather more than „J!„ grain. Ok, 1 Decagramme = 2 dr. 34 gr. 1 Ilectogrm. = 34 oz. (Avoir.) 1 Kilogrm. = 2"lb. 3oz. 2dr. (Avoir.) A grain equals about 1-16 gram., a Troy oz. about 31 grams., a lb. Avoirdupois about 4 Kilogrm., and 1 cwt. about 50 Kilogrms. CAPACITY. 1,000 cubic di'cimetres \ = 1 cubic 1,000,000 cubic centimetres / metre. litre. 1 cubic decimetre "^ or 1=1 1000 cubic centimetres J Or, One Litre = 1 pt. 16 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.) = 34 oz. Centilitre (10 c.c.) = 2* dr. MillUitre (1 c.c.) = 17 m. Decalitre = 21 gals. Hectolitre = 22 gals. Kilolitre (cubic metre) = 274 bushels. A cubic inch = 16-38 c.c. ; a cubic foot = 28-315 cubic dec, and a gallon = 4-54 litres. CONVERSION SCALE. To convert Grammes to Ounces avoir- dupois, multiply by 20 and divide by 567. To convert Kii.oorammks 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 88 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 scj. 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 kOogrammetre = about 7-24 ft. pounds. 1 foot pound 1 foot ton -1381 kgm. 310 kgms. HEAT EQUIVALENT. 1 kilocalorie = 425-5 kilogrammetres. ENGLISH MEASURES. Apothecaries Weight. Avoirdupois Weight. 7000 grains = 1 lb. Or, 437-5 grains = 1 oz. 16 drams = 16 oz. 28 lbs. 4 quarters = 20 cwt. = 1 oz. 1 lb. 1 quarter. 1 cwt. 1 ton. Measure of 1 decimetre, or 10 centimetres, or 100 millimetres HANDBOOK OF PHYSIOLOGY CHAPTEE I INTRODUCTORY ^/r)^o(;r 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 morphologist or 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. 1. 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 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 furce 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- thing that cannot at present be brought into line with the physical and chemical forces that operate in the inorganic world. 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 sixty or seventy years that active growth has occurred. The en. I.] INTRODUCTORY 3 reasons for this recent progress come umlcr 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 recent times. 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 could possibly have been gained by mere cogitation. Many experi- ments involve the use of living animals, but the discovery of anses- thetics, which renders such experiments painless, has got rid of any objection to experiments on the score of pain. 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 pre- sides over, controls, and regulates the functions of the other systems. If we proceed to make an anatomical analysis, and take any INTRODUCTORY [CH. I. organ, we sec tliat il 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 followin<: four headincrs : — 1. Epithelial tissues. 2. Connective tissues. 4. Muscular tissues. Nervous tissues. Space con- taining liiiuid. Protoplasm. Each of these is again divisible into subgroups. If 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, 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 inter- cellxUar material is much greater, and in this it is that the fil)res 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 deposition 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 con- nective tissues, there is a preponderating amount of intercellular — Cell-wall. Fi^-^- Nuclear matrix. -Nuclear network. Fig. 16.— The non-dividing nucleus. (Waldeyer.) 2. The spirem or skein stage : the nucleoli dissolve, and the nuclear filaments form loops which run from one pole of the nucleus 16 THE ANIMAL CELL [cii. n. to the other (fig. IT). In some colls there is at first one long, much twisted tiiroad, which subsequently breaks up into segments. The loops are called chromosmnes. o. Each loop becomes less convo- luted and splits longitudinally into two sister threads, and the achromatic spindle appears (fig. 18, 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 centrosome. The division of the centrosome of the original cell, and then of the attraction sphere into two, usually precedes the commencement of changes in the nucleus ; the two attraction spheres become prominent in cell division, and the connecting achromatic - i.f. Fio. 17.— Early condition of the skein stage viewed at tlie polar enJ. l.c.f., liooped chromatic filameut; iV-i irre- gular filament. (Rabl.) Achromatic spindle Fio. 18.— Later condition of the skein stage in karyokinesis. a, The chromosomes liecome less con. voluted and the achromatic spindle appears, b, The chrcpnosomes split into two and the achso. matic spindle becomes longitudinal. (Waldeyer.) spindle is probably also formed from them or material of the nucleus. At this stage the nuclear membrane is lost, and thus cell protoplasm and nuclear sap become continuous; the proto- plasmic 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. 20). The V'Shaped chromosomes sink to the equator of the spindle, and arrange themselves from it. from the achromatic Pole of spindle. Outer granular zone. Split fibres. Inner clear zone. ■ Polar corpuscle. la-uT stage of karyokinesis. (Waldeyer.) so as to project horizontally en. II.] KARYOKIXESIS 17 III cells which are the result of the sexual process, the iiumher of chromosomes is always even, an equal uumljcr being contributed by each sex. The number of chromosomes varies with the species from four to twenty-four; in man the PeWcVc/e number is sixteen. 5. The stage of metakinesis. The sister threads separate, one set going towards one pole, and the other to the other pole of the spindle (fig. 21) : these form the two daughter nuclei. The chromo- somes are probably pulled into their new position by the con- traction of the spindle fibres attached to them. 6. Each daughter nucleus goes backwards through the same series of changes; the diaster or double star is followed by the dispirem or double skein, until at last two resting nuclei are obtained (fig. 22). A new membrane forms around each daughter nucleus, the spindle atrophies, and the attraction sphere becomes less prominent. The Pole-boc/y Antipodal zone Fig. 20. — 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 whicli unites them, four chromosomes are seen. Tlie 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.) Fine uniting filaments. Fto. 21. ^Metakinesis. a, Early stage, b, Later stage, c, Latest stage — formation of diaster. B show how the sister threads disentangle themselves from one another. (Waldeyer.) division of the protoplasm into two parts around the nuclei begins in the diaster stage, and is complete in the stage represented in fig. 22. 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 B 18 THE ANIMAL CELL [CU. II. aiupliibians, in iho ogg culls of certain wonua, or in tho growing tips of plants. Line of separation of tho two cells. AntiiKilo of daughter nucleus. l{('iiiaiii.s uf Hiiinille. •->. Lighter substance of the -* uiiclcus. Cell protoplasm. llilus. Fig. 22.— Final stages of karyokinesis. In thu lower daughter nucleus the changes are still more "advanced than in tho upper. (Waldoyor.) The phases may be summarised in a tabular way as follows : — ]. Resting condition of mother nucleus (fig. IG). j 2. Close skein of fine convoluted filaments I (fig. 17). j 3. Open skein of thicker filaments. Spindle 1^ appears (fig. 18 a). 4. iMoveincnt of V-shajicd chromosomes to middle of nucleus, and each splits into two sister tlireads (fig. 18 h). f). Stellate arrangement of V filaments at equator of spindle (fig. 19). 6. Se})aration of cleft filaments and move- ment along fibres of spindle (fig. 21 a and It). 7. Conveyance of V filaments towards poles of spindle (fig. 21 t). , 8. Open skein in dauj^hter nuclei. I 9. Close .skein in dauj,'liter nuclei (fig. 22). . 10. Resting condition of daughter nuclei (fig. 22). The Ovum. The ovary (see Chapter LIX.) 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 i)ollucida. The body of the cell is composed of protoplasm loaded 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 ovum first discharges from its interior a portion of its nucleus, which forms two little globules upon it called the polar globules. Network ou Rkticulu.m Skein ou Spiukm Cleavaoe . SlAll oil MoNASrEll . Divergence ou Metakinesis Do I' RLE Star or Di aster DoruLE Skein or Disi'iuem NprwoRK or Rktruum . en. il] THE OVUM 19 Fertilisation then occurs ; that is to say, the liead or nucleus of a male cell called a spermatozoon penetrates into the ovum, and becomes fused with the remains of the female nucleus. -Nucleus or gormiiial vesicle. •Nucleolus or germinal spot. .Space left by relraction of protoplasm. .Protoplasm containing' yolk spherules. .y. Zona pellucida. Fio. 23. — Representation of a liunian ovum. (Cadiat.) Coll division or segmentation then begins, and the early stages are represented in the next figure. Fig. 24. — Diagram of an ovum (a) undergoing segmentation. In {h) it has divided into two, in (c) into four; and in (li) the process has resulted in the production of the so-called "mulberry-mass." (Frey.) Fluid discharged from the cells accumulates within the interior of the mulberry mass seen in fig. 24 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, nutritive material being derived from the mother in mammals by means of an organ called the placenta. The epiblast forms the epidermis, 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 TIT EPITHELIUM We have seen in the introductory chapter that the elementary tissues of which the organs of the body aro built up may be arranged into four groups : epithelial, connectiv^e, 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 cum- '"^ '&\ 'i1^f'&:_'" ) ^'_ h. (^ "'..■- i^t-^ If '■ ' 'Vl Fio. 25. — From a section of llie lung of a cat, stained witli silvir nitrate. N. AlveoU or air-cells, lined with large flat, nucleated cells, with some smaller polyhedral nucleated colls. (Klein and Noble Smith.) posed 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. Epithelia may be grouped into two great classes, each of which may be again subdivided according to the shape and arrangement of the cells of which it ig composed. 20 CBL riL] EPITHELIUM 21 CiJ^ss 1. — Simjjle epithelium; that is, an epithelium consisting of only one layer of cells. Its subgroups are : — a. Pavement epithelium. This consists of a layer of thin cells arranged in the form of an accurately fitting mosaic ; this is typically seen in the epithelium that lines the air-sacs of the lungs (fig. 25). The endothelium found in the interior of the blood anil lymph vessels and serous sacs is very similar in structure, but differs from other epithelia in being the only one of mesoblastic origin (fig. 26). h. Cubical and columnar epithelium. Here the cells, as their names imply, are thicker. Cubical epithelium is found in the alveoli of the thyroid, in the tubules of the testis, and in the ducts of many glands. Columnar epithelium lines the alimentary canal from the stomach to the anus. The four figures (figs. 27-30) present the very typical columnar cells, each with a bright striated border, which are found lining the intestine, ilg. 28 shows how they are arranged on the surface of a villus, one of the numerous little projections found in the small in- testine. 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 occurs ; these con- sist 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 nucleus being sur- rounded by the remains of the protoplasm in the narrow stem (fig. 30). This transformation is a normal process continually going on throughout life, the discharged mucin being the chief constituent of phlegm or mucus. The cells themselves may recover their original shape after discharge and repeat the process later on. c. Ciliated epithelium ; this form of epithelium presents so many points of physiological interest, that a separate section will be devoted to it later in this chapter. Class 2. — Compound Epithelium; that is, an epithelium con- sisting of more than one layer of cells. It contains two subgroups. a. Transitional epithelium found lining the bladder and ureters. Fig. 2G. — Surface view of au artery from the mesentery of a frog, ensheathed in a perivascular lymphatic vessel. a. The artery, with its circular muscular coat (media) indicated by broad transverse markings, with an indication of the ad\ entitia out- side. I, Lymphatic vessel ; its wall is a simple endothelial membrane. (Klein and Noble Smith.) EPITnELIUM [CH. III. It consists of three or four layers of large cells, the most typical of which are ])car-shapcd (fig. 31). Fig. 27. — Columnar epithelium cells of the rabbit's intestine. The cells have been isolateortion of the substance of cornea. (Klein.) protoplasm being replaced by horny material or keratin. Covering the front of the cornea of the eye is a typical form of stratified epithelium (fig. 32), but the number of layers is not so great as it is in the majority of such epithelia. Ciliated Epithelium. The cells of ciliated epithelium are generally of columnar shape (fig. 33), but they may occasionally be spheroidal (fig. 34). /^^t^' ^ ,i Fig. 33. — Ciliated epithelium from the human trachea, a, Large fully-formed cell ; h, shorter cell ; e, developing cells -nith more than one nucleus. (Cadiat.) Fig. 84. — Spheroidal ciliated cells from the mouth of the frog. X 300 diame- ters. (Sharpey.) Each cell is surmounted by a bunch of fine tapering filaments. They were originally called cilia because of their resemblance in shape to eyelashes. They differ from eyelashes in being extremely small, 24 EPITHKIJUM [CH. III. ;iiul in not' being stiff; Llioy aio During life these move U) and Ulli j)itlu'liuiii of 111',- huiriaii trachea. «, Layer of longituiliiially arraiiyed elastic fibres ; h, basement membrane ; c, deepest cells, circular in form ; d, inter- mediate elon-j'ated cells ; c, outermost layer of cells fully dovi'lopeci and U'aring cilia. X 350. (Kidliker.) the coll proto- plasm as fila- ments or root- lets (fig. 36). According to some observers these rootlets are out^i^p!^^^^i^'i walled small blood - vessels in the ^,i;Wi W^'^^^ff-^ tissues beneath the epithelium, some of its fluid constituents escape. This fluid is called lymph ; it penetrates to ^'^^■i^'^i'TL^f^i^Zx^lZTl all parts of the cellular elements of vertical section of the gum of a new- tissucs and uourishcs them. In the borninfant. (h.lein.) , . , • t.- e •»! t ^i, thicker varieties of epithelium, the presence of the irregular minute channels between the cells (fig. 37) enables the lymph to soak more readily between the cells than it would otherwise be able to do. Epithelium is also destitute of CU. HI.] CHEMISTRY oK EPITHELIUM 27 nerves as a rule, liut in stratified epithelium, particularly that covering the cornea at the front of the eye and in the deeper layers of the epidermis, a plexus of nerve-fibrils is found. Chemistry of Epithelium. There is not much to add to what has been already stated con- cerning cells ; protoplasm and nucleus have the same chemical com- position as has been already mentioned in Chapter II. Two new substances have, however, been mentioned in the foregoing chapter — namely, mucin and keratin. Mucin. — This is a widely distributed substance occurring in epithelial cells or shed out by them (see goblet cells, fig. 30). It also forms the chief constituent of the cementing substance between epithelial cells. We shall again meet with it in the intercellular substance of the connective tissues. The mucins obtained from different sources varies somewhat in composition and reactions, but they all agree in the following points : — (a) Physical character : viscid and tenacious. (b) Precipitability from solutions by acetic acid. They all dis- solve in dilute alkalis, sucli as lime-water. (c) They are all compounds of protein, with a carbohydrate material ; by treatment with mineral acid this is hydrolysed into a reducing but non-fermentable sugar-like substance. The substance mucin, when it is formed within cells (goblet cells, cells of mucous glands), is preceded in the cells by granules of a sub- stance which is not mucin, but is readily changed into mucin. This precursor, or mother-substance of mucin, is called mucigen or mucinogen. 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 other proteins in its high per- centage of sulphur. The silver nitrate reaction of cementing substance. The principal chemical reaction which is employed by histologists for demonstrat- ing the cement or intercellular substance which binds epithelial cells together was formerly supposed to be due to the formation of a silver-protein compound which was reduced by sunlight. Macallum has conclusively shown that this is not the case, but that it is an inorganic reaction. Cementing material is specially rich in chlorides (mainly sodium chloride) ; the addition of silver nitrate leads to the formation of silver chloride, and it is this which is reduced by light. The silver reaction obtained in other tissues is similarly explained : in fact silver nitrate is a micro-chemical reagent for detecting the localities in the body where chlorides occur. According to Mac- allum the nuclei of all cells are entirely free from chlorides. CHAPTER IV THE CONNECTIVE TISSUES The uoiiuecitiv^o tissues aro Llie fulluwing : — 1. Areolar Lissuo. 6. Jelly-like tissue. 2. Fibrous tissue. 7. Cartilage. 3. Elastic tissue. 8. Bone and dentine. 4. Adipose tissue. 9. Blood. 5. lletiform and lymphoid tissues. At first sight these numerous tissues appear to form a very heterogeneous group, including the most solid tissues of the body (bono, dentine) and the most fluid (blood). But on examining a little more deeply, one finds that the group- ing of these apparently different tissues together depends on a number of valid reasons, which may be briefly stated as follows : — 1. They all resemble each other in origin. All are formed from the mesoblast, the middle layer of the embryo. 2. They resemble each other structurally; that is to say, the cellular element is at a minimum, and the intercellular material at a maximum. 3. They resemble each other functionally ; they form the skeleton, and act as binding, supporting, or connecting tissues to the softer and more vital tissues. An apology is sometimes made for calling the blood a tissue, because one's preconceived idea of a tissue or texture is that it must be something of a solid nature. But all the tissues contain water. Muscular tissue contains, for instance, at least three-quarters of its weight as water. Blood, after all, is not much more liquid than muscle. Blood, moreover, contains cellular elements analogous to the cells of other tissues, but separated by large quantities of a fluid intercellular material called blood-plasma. Blood is also mesoblastic, and thus the two first characteristics of a connective tissue are present. It does not fulfil the third condition by contributing to the support of the body as part of the skeleton, but it does so in another sense, and serves to support the body by convoying nutriment to all parts. en. 17.] AKKOLAE TISSUE 29 Areolar Tissue. This is a vory typical connective tissue. It has a wide distribu- tion, and constitutes the subcutaneous, subserous, and submucous tissues. It forms sheaths (fasciae) for muscles, nerves, blood-vessels, glands, and internal organs, binding them in position and penetrat- ing into their interior, supports and connects their individual parts. Fto. 3S. — Loose areolar tissue from the subcutaneous tissue of the cat. x 300. Tliis shows the two varieties of libres, and two of the varieties of connective-tissue"corpuscle.s, namely, the lamellar cells or fibroblasts, and a wander cell. 1, Lamellar cell; 2, wander cell; 3, elastic fibres; 4, bundles of white fibres. (After Szymonowicz.) On microscopic examination it is seen that this typical connective tissue consists of four different kinds of material, or, as they may be termed, histological elements. They are : — (a) Cells, or connective-tissue corpuscles. (b) A homogeneous matrix, ground substance, or intercellular material. ),< ,7- ,, , ,. nr These are deposited in the matrix, (d) Yellow or elastic fibres j ^ In considering these four histological elements we may first take the fibres, because they are the most obvious and abundant of the structures observable. The white fibres. These are exquisitely fine fibres collected into bundles which have a wavy outline. The bundles run in different directions, forming an irregular network, the meshes between which are called areolce ; hence the name areolar. They are composed of the chemical substance called collagen. On boiling they yield gelatin; some chemists regard collagen as the anhydride of gelatin ; but whether this is so or not, the gelatin is undoubtedly derived from the collagen. Gelatin is a protein though 30 THE COKNECTIYE TISSUES [CH. IV. it has cortain characters which distiuguisli it from most members of tlie large protein family. Its most characteristic property is its power of jellying or gelatinising ; that is, it is soluble in hot water, and on cooling the solution it sets into a jelly. The yellow or elastic fibres. Those are seen readily after the white fibres are rendered almost invisible by treatment with dilute acetic Fio. 39. — Ilorizontal preparation of the cornea of frog, staine/) Q ^ Fr;. 4G.— Transverse section of a portion of lig. nuch*, showing the angular out- line of the fibres. (After Stohr.) Fig. 45.— Elastic fibres from the ligamenta subflava. x 200, (Sharpey.) 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 nuchse 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. 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 are the subcutaneous tissue of the eyelids, penis and scrotum, the nymphae, 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 lohiles is applied. 34 TIIK CONNECTIVK TISSUES [CH. IV. Under Lho niicrosco})0 oacli lubiilc is found to consist of little vrtsiclos or cells which jjresont dark, sharply-dofinod edges when viewed with transmitted light: they are about j^.j or ^rj^ 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 i)art solidilied (or sometimes crystallised) after death. A nucleus is always i)resent in some part or other of the cell proto- plasm, but it is not easily visible unless the tissue is stained. The oily matter contained in the cells is com})os6d of the com- pounds of fatty acids with glycerin, which are named olein, stearin, and palmitin. On the addition of osmic acid, fat-cells are stained black; this is duo to tiic olein ])rosont, which reduces the osmium tetroxide to a lower oxide, which has a black colour. Fat is stained deep yellow by Sudan III. and red by Scharlach li. Fat-cells are developed from connective-tissue corpuscles; these colls may be fourul oxliibiting every intermediate gradation between an ordinary corpuscle and a mature fat- cell. The process of development is as follows : a few small drops of oil make their ajjpearance in the protoplasm, and by their confluence a larger drop is jtroduced: this gradually increases in size at the expense of the original protoplasm of the cell, which becomes corresjjondingly diminished in quantity till in the mature cell it only forms a thin film, with a Fio. 47.-Fai-ceiis from tiio flattonod nuclous imboddcd in its substance omeutuni of a rat. (Klein.) ,„ ,, ^ i^^ (figs. 41 and 4/). A large number of blood-vessels are found in adi])Ose tissue, which subdivide until each lobule of fat contains a fine mcshwork of ca])il- laries enshoathing each individual fat-coll. Among the uses of adii)Ose tissue these are the chief : — a. It servos 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. h. 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 bo CH- IV.] RETIFORM TISSUE 35 mentioned the palms of tho liands, ilie solos of the feet, and the orbits. Retiform Tissue. Retiforni or roticular tissue is a kind of connective tissue in which the ground-substance is of more lluid consistency than elsewhere. Flo. 4S. — Hctiform tissue from a lynipliatie glanii, from a section which has been treated witli dilute pota.sli. (Schafer.) There are few or no elastic fibres in it, and the white fibres run in very fine bundles forming a close network. The bundles are covered and concealed by flattened con- nective-tissue corpuscles. When these are dissolved by dilute potash, the fibres are plainly seen (fig. 48). 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 indistin- guishable microscopically, and in many places continuous with eacii other. Mrs Rosenheim 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 resistant 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 cor- puscles. These are in certain foci actively multiplying ; they get into the lymph stream, which washes them into the blood, where they become the variety of colourless Fig. 49, Part of a section of a lymphatic glaud, from which the corpuscles have been for the most part removed, showing the supporting retiform tissue. (Klein and Noble Smith.) 36 THK CONNECTIVK TISSUES [CH. TV. corpuscles called lymphocytes. It is found in the lymphatic glands, the thymus, the tonsils, in the follicular glan " ■ ,^-i\,.:.:'.... Colls of car- n .:k «■■'»-'•• 1 ;\ V,-C I'ibrous inatrix. Fici. 62.— Yellow or elastic flbro-cartilage. Fio. 51.— White nbro-cartilagp. (Cn'liat.) (Cadiat.) White fibro-cartilage (fig. 51) is composed of cells and a matrix. The latter is ])ermcated by fibres of the white variety. In this kind of fibro-cartilage it is not unusual to find portions so CH. v.] CARTILAGE 39 (lonsoly fibrous that no cells can be seen ; but in other parts con- tinuous with those, cartilai^o-colls are freely clistril)ute(l. Yellow or Elastic Fibrc-Cartila^e is found in the pinna of the 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. 52). 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 Fio. 53.— Plan of multiplication of cells in cartilage. a, Cell in its capsule ; h, 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 Sharppy.) disposition of the cells in fully formed cartilage in gronps of two, four, etc., is due to the fact that each group has originated from the division of a sincrle cell, first into two, each of these as:ain into two, and so on. This process of cell division is accompanied with the usual karyokinetic changes. 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. 53). 40 THK COXNKCTIVE TISSUKS [CH. V. 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 l)e seen in fully formed cartilage by the presence of faint concentric lines around the cells. In a variety of cartilage found in the ears of rats and mice, called 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, for intercellular material accumulates outside the capsules and still further separates the cells. 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 mucoid 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, however, the collagen does not become precipitated to form fibres, but in white fibro-cartilage it does. In yellow fibro-cartilage the matrix is per- vaded 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 Jiuoride, and mugnesium 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 CH. v.] BONE 41 articular extremities are found capped on their surface by a thin shell of compact bono, 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 (diploo) 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. Marro-w. — There are two distinct varieties of marrow — the red and yellow. lied marrow is the connective tissue which occupies the spaces in the cancellous tissue ; it is highly vascular, and thus maintains the Fig. 54. — Cells of the red marrow of the goinea-pig, highly magnified, a, A large cell, the nucleus of which appears to be partly divided into three by constrictions ; h, 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. Sch.ifer.) 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 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 smaller 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 myeloplaxes (fig. 54). Yellovj 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 just mentioned. 42 TTIK COKSECTITE TISSUES [CII. V. Periosteum and Nutrient Blood-vessels. — The surfaces of bones, except the part covered with articular cartila<,'e, are clothed by a tough, fibrous membrane, the periosteum ; ami it is from the blood-vessels which are distributed in this niendminc, 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 t^ the Haversian canals, to be immediately descril>ed. 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 tlie 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. Fio. 55. — Transv<>rs'> >••«; seen, with their ojrn-- the direction of tV" down the with trat.- any int/' •. rmnals are '^K-m across in grinding ire. w.M'h r-;r--.T. !-:<..• ..:^;^^N '"''' ' ^^ tindtMi to represent the '•,'/^si,\^^ ^ ri-ticiilar structure of a ' '^ lamella, ,i;ives a better Fi(i. 59.— Lamellic torn oil from a decalcified human i(l(;a of tlie object when parietal bono at some depth from the surface, held rather farther olf «, «, Lamelhe, showing iiitercrossin^c fibres; than usual from the eye. h, darker part, where several lamelhe are super- X 400. (Sharpey.) poseenetnted the sub- periosteal bony crust. (Alter LawTence.) 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 comj)letely boxed up ; so they waste and disappear, leaviny the absorp- tion of the bony tissue that originally occupied the centre of tlie 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 Ijono is thus, after all, a formation of bono 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 long before the histological details which we have descri])ed were made out by Sharpey. Silver rings were placed by Duhamel around the Ijones 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 was performed upon pigs. 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 has always been recognise'! 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. MaoEwen lias recently shown that minute fragments of living bone are even more efficacious in virtue of the bone-cells they contain. The Teeth. During the course of liis life, man, in common with most other mammals, is provided with two sets of tooth; the first sot, called the temporary or milk teeth, makes its appearance in infancy, and is in CH. v.] THE TEETH 51 the course of a few years shed and replaced by the second or per- manent set. The temporary or milk teeth 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 teeth in each jaw is, however, increased to sLxteen by the development of three molars on each side of the jaw, which are called the permanent or true molars. 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. INCISORS. DECIDUOUS FIRST MOLARS. CANINES. DECIDUOUS SECOND ; MOLARS. 6 12 18 24 Permanent Teeth. Tlie aiire at which each tooth is cut is indicated in this table in years. FIRST MOLARS. CENTRALS. LATERALS. BICUSPIDS OR PRE- MOLARS. 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 the other teeth ; cases of whole families in which their absence is a characteristic feature are occasionally met with. 52 THE CONNECTIVK TISSUES [CH. V. 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 bicus])ids 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. Structvire of a Tooth. A tooth is generally described as possessing a croum, neck, and root. The crown is the portion which projects beyond the level of the gum. The neck is that constricte 'Vl-^MiV>^- Fin. 70. sac (fig. 71, s); and the nidimGnt of tlio jaw sends up processes forming partitions between the teeth. In this way small chamhers 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 ar- ranged in a meshwork of connective tissue, the outer or peripheral part being covered with a layer of columnar nucleated cells called odonto- blasts. These cells, either by secretion, or as some think by direct transformation 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 numer- ous, blend into the first cap of dentine. In the mean- while the odontoblasts have formed a second layer of odontogen within this (fig. 72), and this in turn becomes calcified; thus layer after layer is formed, each extend- ing 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. 66), 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 •^ W}^ Fio. 71. Figs. f)9, 70, 71.— Sections of the upper jaw of a fcetal sheep. Fio. 69. — 1, common enamel germ dipping down into the mucous membrane ; 2, palatine pro- cess of jaw ; 3, Rate Malpighi. Fio. 70.— Here the section passes through one of the special enamel germs which is becoming flask-shaped ; c, c', epi- thelium of mouth ; /, neck ; /, body of special enamel germ. Fig. 71. — Alaterstage; c, outline ot epithelium of gum; /, neck of enamel germ; /, enamel organ; p, papilla ; s, dental sac forming ; / p, the enamel germ of permanent tooth ; m, bone of jaw ; v, vessels cut across. (Waldeyer and K/illiker.) 58 THE CONNECTIVE TISSUES [CH. V. protoplasm around which the calcareous deposit is moulded ; thus the dentinal tubules occupied by the processes of the odontoblasts are formed. The other cells of the dental papilla form the cells of the pulp. Fio. 72. — Part of section of developing tooth of a young rat, showin;,' the mode of deposition of tlie dentine. HiL;hly inairnilied. n, Outer layer of fully formed di>ntine ; h, uncalcitied matrix with one or two nodules of calcareous matter near the calcified parts ; c, odonto- blasts sending; processes into the dentine ; d, pulp ; f, fusiform or wedge-shape cells found between odontoblasts ; /, stellate cells of pulp in fibrous connective tissue. The section is stained with cannine, which colours the uucalcified matrix but not the calcified part. (E. A. Schafer.) 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. 73 and 74). 1. Fio. 73. — Vertical transverse section of the dental sac, pulp, etc., of a kitten, a. Dental papilla or pulp ; '), the cap of , if Plasma I Fibrin ) m 4. Blood , r> ^ c Clot. ( Corpuscles j The corpuscles are of two chief kinds, the red and the white. The white corpuscles are typical amoeboid, nucleated cells. 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 tjt^Vtt iiich 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 ampliibia. The most important and abundant of the constituents of the red corpuscles is the pigment which is called hcemoglohin. This is a protein-Hke 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 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 acti^ity. The lymph is collected by lymphatic vessels, which converge to the main lymphatic, called the tharacic duct. This opens into the large veins near to their entrance into the heart ; and thus the Ijnnph 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 oxyhcemoglobin. 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 oxyhgemoglobin, and this removal of oxygen changes the colour of blood to the darker tint it has in the veins. The veins take the blood {minus a large quantity of oxygen and pltts 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. It should, however, be noted that haemoglobin is not a carrier of carbonic acid ; that gas is carried mainly as carbonates in the blood-plasma. CHAPTKU 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 tlieir movements are executed. The muscles may 1)6 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 whicli controls the activity of the voluntary muscles. Wlien muscular tissue is examined with the microscope, it is seen to be made up of small, elongated, thread-Uke structures, which are called muscular fibres ; these are bound into bundles l)y 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 hght 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 tliis rule, namely, in the case of the lieart, the muscular fibres of which are involuntary, but transversely striated. There are, however, liistological differ- ences between cardiac muscle and the ordinary voluntary striated muscles. The unstriatod 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, tliree 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 62 en. VI. ] VOLUNTABY MUSCLE 63 classification into voluntary and involuntary is sliowii in the follow- ing table : — 1. Transversely striated muscular fibres : <(. In skeletal muscle . . . Voli'ntahy. /'. In cardiac muscle . . . "l 2. I'lain muscular fibres : In blood-vessels, intestine, uterus, 1) ladder, etc. . . . , Invomntakv. 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 the fibres are developed in the intercellular material; 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.* The fibres vary in thickness and length a good deal, but they average 3^ inch in diameter, and about 1 inch in length. Each Fig. 75.— a branched muscular fibre from the frog's tougue. (Kulliker.) fibre is c}'lindrical in shape, with rounded ends ; many become pro- longed into tendon bundles 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 to the .under surface of the skin, or mucous membrane (fig. 75). The fibres in these situations are also finer than in the majority of the voluntary muscles. Each fibre consists of a sheath, called the sarcolemina, enclosing a soft material called the contractile substance. The sarcolemma is * The muscular fibres of the pharynx, part of the a'.soj)hagus, and of the muscles of the external ear, thouu,h not under the control of the will, have the same structure as the voluntary nmscular fibres. 64 MUSCUIJ^R TISSUE [CH. VT. homogeneous, elastic in nature, and especially tough in fish and ampliibia. It may readily be demonstrated in a microsco])ic prejiara- tion of fresli muscular fibres by applying gentle pressure to the cover slip; the contractile substance is thereby ruptured, leaving the sarcolemma bridging the space (fig. 76). To the sarcolemma are seen adhering some nuclei Fig. 76.— Muscuhir fibre torn across, the sarcolemma still connecting,' the two parts of the iibre. (Todd and Bow- man.) Fig. 77. — Muscular fibre of a mammal highly mag- nified. The surface of the fibre is accurately focussed. (Schafer.) The contractile substance within the sheath is made up of alternate discs of dark and light substance. Muscular fibres contain oval nuclei. In mammaUan muscle these are situated just beneath the sarcolemma ; but in frog's muscle they occur also in the thickness of the mus- cular fibre. The chromoplasm of the nucleus has generally a spiral arrange- ment, and often there is a httle granular protoplasm (well seen in the muscular fibres of the diaphragm) around the poles of each nucleus. If the surface of a fibre is carefully focussed with a high power, 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. 77). 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. 78), with its longitudinal and transverse meshes, is composed of an interstitial substance lying between the essentially contractile portions of the muscle. A muscular fibre is thus made Fio. 78. — Portion of muscle-fibre of water-beetle, showing networlc very plainly. One of the trans- verse networks is split off, and some of the longitutlinal liars are shown broken oil. (AfliT Mt-l- land. ) cri. VI.] VOLUNTARY MUSCLE 65 Fig. 79.— Transverse section through muscular fibres of human tongue. Tlie nuclei are deeply stained, situated at the inside of the sar- colemnia. Each muscle fibre shows "Cohnheim's areas." X 450. (Klein and Noble Smith.) up of what are called fibrils or sarcostyles ; and the lougitudinal 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 fibrils may be com- pletely separated from one another. A transverse section of a muscular fibre (fig. 79) shows the sections of these fibrils; the interstitial sarcoplasm is re- presented 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 depth, a fine dotted line is seen bisecting each light stripe ; this has been variously termed Dobie's line, or Krause's membrane (fig. 80). At one time this was beheved to be an actual membrane continuous with the sarcolemma. It is prob- ably very largely an optical effect, caused by light being transmitted between discs of different refrangibility. If cross membranes do exist they are not very resistant ; this was well shown by an accidental observation first made by Klihne, and subsequently seen by others. A minute thread-worm, called the Myorectes, was observed crawling up the interior of the contractile 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 disc. A muscular fibre may not only be broken up into fibrils, but under the influence of some reagents, such as dilute hydrochloric 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- E 66 MUSCULAR TISSUK [CII. VI Gvor much rarer iliaii Lho soparatiou into fibrils; indeed, indications of tlie fibrils are soon in perfectly frosh luuscle before any reagent has boon added, and this is markedly evident in the wing muscles of many insects. It is now believed tliat 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 M -♦' iiii \'^ ■B ~l ^m Fio. SO.— A. Porlion of a liuinaii muscular fibre, x SoO. U. Separated bundles of fibrils equally magnified; a, a, larger, and h, h, smaller collections; c, still smaller; d, d, the smallest which could be detached, possibly representing a single series of sarcous elements. (Sharpey.) phenomena. The fibrils are varicose, and whore they are en- larged different refractive efTects will be produced from those caused by the intermediate narrow portions. This view lie has very ingeniously supported by taking negative casts of muscular fibres by pressing them on to tlie surface of collodion films. The collodion cast shows alternate dark and light bands like the muscular fibres. Most histologists have rejected this view, for the behaviour of the dark stripes to various micro-chemical and staining reagents, and to polarised light, is different from that of the liglit stripes. The difference is therefore not merely one of diameter, but of chemical composition. The rapidity of muscular contraction seems to be proportional to the clearness of the cross-striation, and insects' muscles whicli arc CH. VI.] VOLUNTARY MUSCLE 67 remarkable for perfection of mechanism ha\'o consequently been the subject of many researches. In the wing muscles of these animals the sarcostyles are separated by a considerable quantity of interstitial sarcoplasm, which may be of nutritive importance; at any rate it allows the intimate structure of the individual sarcostyles to be worked out very thoroughly. As the result of such work, Schiifer has arrived at the following conclusions : — 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 (iiiiiiiii PIIHIII IIIIIIIIUI MUllllll) Pllllll) (iillllllll^ lllllllllli lllllllllll Fig. 81, — SaiLOstylcs from tlie 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.K. Fig. 82. — Diagram of a sarcomere in a moderately extended con- dition, A, and in a contracted condition, B. K, K, Krause's membranes ; ii, plane of Hensen ; s.e., poriferous sarcous ele- ment. (E. A. Schiifer.) is really double, and in the stretched fibre (fig. 81, 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 memljrane; this clear interval is more evident in the extended sarcomere (fig. 81, b), and diminishes on contraction (fig. 81, 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 at Hensen'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 "^ Notice that this expression has a different meaning from what it originally- had when used by Bowman. 68 MUSCULAR TISSUE [CH. VI. between it and the membrane of Krause ; this lengthens and narrows the sarcomere.* This is shown in the diagrams (fig. 82). It may be added that the sarcous element does not lie free in the middle of the sarcomere, 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. 82, A). This view is interesting, because it brings into harmony amoeboid, ciliary, and muscular movement. In all three instances we have 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. 26). 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 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 accumulates opposite the membranes of Krause, and diminishes in amount oppo- site the sarcous elements ; the accumulation of sarcoplasm in the previously Hght stripes makes them appear darker by contrast than the dark stripes proper. This is shown in fig. 83. There is no true reversal of the stripings in the fibrils themselves. 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 microscope which polarises the light passing through the object placed on the stage. The eye- piece contains another Xicol's prism, which detects this fact. If the two Nicols are parallel, the light passing 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 ai)pears dark. If an object on tlie microscope stage is doubly refracting it will appear bright in this dark field ; if it remains dark it is singly refracting. The sarco- * The existence of open pores is not admitted by all oliservers. These regard the passage of fluid in and out of the sareous element as due to diffusion through its membrane. en. VI.] VOLUNTARY MUSCLE 69 plasm is sin.^ly refracting or isotropous; dark field of the polarising niicroscot)e. are in great measure doubly re- fracting or anisotropous, and ap- pear bright in the dark field of the polarising microscope. The sarc(.)- style, however, is not wholly doubly refracting; the aarcous elements it remains dark in the The fibrils or sarcostyles ■ wttuincMatt,' Fif;. 83.— Wave of contraction passing over a mus- cular fibre of water-beetle, r, k, Portions of the fibre at re.st ; c, contracted part ; i, i, inter- mediate condition. (Scliiifer.) Fig. 84.— This figure (after Engelniann) illus- trates the appearance of a muscular fibre as examined in ordinary light (left-hand side) and in polarised light (right-hand side). In the upper part of the diagram the fibre is not contracted, in the lower part it is contracted. The nark bands are seen to be bright by polarised light, owing to their being doubly refracting or anisotropous; during contraction, fluid passes from the singly refracting or i.^otropous light band into the doubly refracting dark band, which, in conse- quence, becomes widened out. 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 (see fig. 84). _ Tiie meaning and causation of the optical appearances of striated 70 MUSCULAR TISSUE [Cll. VI. musclo fibres, .ind the changes they undergo during contraction have Iiecn tlio subjects of numerous hypotheses. One of two only of tlieso theories liave been mentioned in the preceding paragrajjlis, and it should be recog- nised that even experts arc content to leave the matter very largely an open question at present. Blood-vessels of Muscle. — The arteries break up into capillaries, which run longitudinally in the intervening connective tissue, trans- verse ])raiiches connecting them (fig. 85). No blood-vessels ever penetrate the sarcolemma. The muscular fibres are thus, like other tissues, nourished liy the exudation from the blood called lym2)h. The motor nerves of voluntary muscle pierce the sarcolemma, and terminate in expansions called end-plates, to be described on p. 78. The sensory nerves of voluntary muscle terminate in structures known as the n euro-muscular spindles, which will be dealt with in the chapter on jMotorial Sensations. Fio. 85. — Three muscular (ibres running longitudinally, and two bundles of fibres in trans- versa section, m, from the tongue. Th(! capillaries, <■, are iii.jected. x 150. (Klein and .Noble Smith.) Red Muscles. In many animals, such as the rabbit, and some fishes, most of the muscles are pale, but some few (like the diajjhragm, 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 dififerences between them and ordinary striped muscle, viz. : — 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 other in- voluntary muscles, are striated ; but although in this respect they resemble the skeletal muscles, they have distinguishing character- istics of their own. The fil)res which lie side by side are united at CH. VI.] CAHDIAC AND I'LAIX MUSCLE 71 frequent intervals by short branches (fig. 8G). The fibres are smaller than those of the ordinary striated muscles, and their transverse striation is less distinct. No sarcolemma can be discerned. 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 cement- ing material, stainable by silver nitrate. This is bridged across by fine fibrils from cell to cell. The above is a general description of the fibres in the great mass of the cardiac musculature. But immediately beneath the lining membrane of the ventricles, and in the main connecting strand which links the auricles to the ventricles (the auriculo-ventricular bundle) are found peculiar fibres known after their discoverer as Purkinjes fibres ; these are large, clear, quadrangular cells with granular protoplasm containing several nuclei, and striated only on their margins. The special meaning and function of these fibres will be described in the chapter on the heart. Fig. 86.— Muscular fibre-cells from the heart. (K. A. Schiifer.) Fio. S" -Muscular fibre-cells from the muscular coat of intestine — highly magnified, tuiiinal striation, and in the broken fibre the sheath is visible. Note the longi- Plain Muscle. Plain muscle forms the proper muscular coats (1.) of the digestive 72 MUSCULAR TTS8UE [CH. VI. canal from the midJlo of the oesophagus to the internal sphincter ani ; (2.) of the ureters and urinary l)lad(lor; (3.) of the trachea and bronchi ; (4.) of the ducts of glands ; (5.) of the gall-bladder ; (6.) of the vesiculiE seniinales ; (7.) of the uterus and Fall()j)ian 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 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 attaclied to the hair follicles ; it also occurs in the areola of the nipple. It is composed of long, fusiform cells (fig. 87), which are not as a rule more than ^i^ inch long. Each cell has an oval or rod-shaped nucleus. The cell substance is longitudinally but not transversely 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, and 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 fil^res. 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 muscle, the Likeness to the original cells from which the fibres are formed is not altogether lost, and this is specially the case for the Purkiuje's fibres alluded to on the preceding page. 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- tions appear first along one side, and extend round the fibre (fig. 88), 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 (Hail- (jQiig (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 preg- nancy. After parturition the fibres shrink to their original size, but many disappear and are removed by absorption. 'm Fio. 88. — Develop- ing muscular libro from fivtus of Iwo months vier.) CHAPTEK 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 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 nervous impulse starts in the brain and passes down the efferent or motor nerve-tracts to the muscles of the hand, which contract; when 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 communication 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 physio- logical one, which we shall work out move thoroughly later on. No histological distinction 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-ff^hres. These become sheathed in a manner to be immediately described, and are contained in the nerves, and in the white matter of brain and 73 74 NKRvn; [CIl. VII. spinal cord. Tho bodies of iiorvo-colls diffor in sizo, shape, and arrangement, and wo shall discuss those fully when we get to the nerve-centros. For tho prosont it will bo convenient to confine ourselves to tho nerve-fibres as they are found in a nerve. Nerve-fibres are of two histological kinds, medul- latcd and non-medullatcd. Medullated nerve-fibres are found in the white matter of the nerve-centres and in the nerves originating from tho brain and spinal cord. Non-meduUated norve-fibres occur in the sympathetic nerves. The medullated or ■white fibres are characterised IF Fio. 89. — Nervo- fibre stained with osniic aciil. A, Tioiie ; li, mu'lous. (Key an.l lict- zius.) 1% Fio. 90.— a node of Ranvior in a medullated nervc-llbre, viewed from atove. The medullary slieath is in- terrupted, and the prinii- tive sheath thickened. Copied from Axel Key and Hctzius. X 750. (Klein and Noble Smith.') Fio. 91. — Axis cylinder, highly magnilied, showing its com- ponent fibrils. (M. Schultze.) by a sheath of white colour, fat-like in nature, and stained black by osmic acid ; it is called the medullary sheath or white substance of Schwann ; 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. CIl. VII. MEDULLATED NEUVE Tlie axis cylinder is a soft transparent thread in the middle of the fibre; it is made up of exceedingly fine fibrils (fig. 91) 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 lianvier. The stretch of a nerve- fibre between two nodes is called an inter-node, and in the middle of each inter-node is a nucleus which belongs to the primitive sheath. Besides these interruptions, a variable number of oblique clefts are also seen dividing the sheath into medullary seg- ments (fig. 89) ; 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 fat- like matter consists largely of cholesterin, a monatomic alcohol, and phosphorised fats, such as lecithin. Near their terminations the nerve-fibres branch : the branching occurs at a node (fig. 92). Fio. 92. — Small branch of a muscular nerve of the frog, near its termination, showing division of the fibres — a, into two ; h, into three, x 350. (Kiilliker.) 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 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 transverse bands in the axis cylinder {Fromann's lines), which is here 76 NHTRVE [CH. VII. not closely invested by the medullary sheath (fig. 93). Macallum has shown that tliis apiiearancn of transverse striping is an artifact •liilft Fio. 03. — .Several libres of a buiuUe of merlullated 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.) and can be obtained in any exposed portion of an axis cylinder, that is, wherever the silver nitrate can penetrate to it. The arrangement of the nerve-fibres in a nerve is best seen in a transverse section. Fio. 94.— Transverse section of the sciatic nerve of a cat about x 100. — It consists of bundles (funiculi) of nerve-fibres ensheathed in a librous sheath, rpincurivm, A ; each bundle has a si>ecial sheath (not sufficiently marked out from the epineurium in the figure) or perineurium U; 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.) The nerve is composed of a number of bundles or funiculi of nerve- fibres bound together by connective tissue. The sheath of the whole en. VII.] NON-MEDULLATED FIBRES 77 nerve is called the epineurium ; that of the funiculi the perineurium ; that wliich passes between the fibres in a funiculus, the endoneuri^im (fig. 94). Single nerve-fibres passing to their destination are sur- rounded by a prolongation of the perineurium, known as the Sheath of Hcnle. The nerve trunks themselves receive nerve-filjres wliich ramify and terminate as end-bulbs in tlie epineurium. The size of the nerve-fibres varies ; the largest fibres are found in the spinal nerves, where they arc 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 gangha, whence they emerge as non-medullated fibres, and are distri- buted to involuntary muscle. They are well seen in sections stained by osmic acid, the black rings being the stained medullary sheaths (fig. 95). 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 imaffected in appearance by osmic acid. They Fig. 95. — Section across a nerve bundle in the second thoracic anterior root of the dog, stained with osmic acid. (Gaskell.) Fjg. 96.— Grey, or non-medullated nerve-fibres. A. From a branch of the olfactory nen-e 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 Schultze.) consist of an axis cylinder covered by a nucleated sheath. They branch frequently. /M = micro-millimetre = j,-^,-,r, millimetre. 78 NERVK [CH. VII. Termination of Nerves in Muscle. In the voluntary muscles the motor nerve-fibres have special ond-organs callod end-plates (fig. 97). The fibre branches two or three times, and each branch goes to a muscular fibre. Here the 't^- Fio. 97.— End -plates ; chluride of gold preparation to show the axis cylinders and their Uual ramificalions of librillii'. x 170. (Szymonowicz.) neurilemma becomes continuous with the sarcolemma, the medullary sheath stops short, and tlie axis cylinder branches several times. Fig. 9S.— Termination of mcilullati.-il nerro-fibres in tendon near the mus- cular insertion. (Golgi.) Fiart of an amoeboid coll, and in any direction. Ciliary and muscular movement are limited to one direc- CII. VIII.] RIIYTHMICALITY 83 tioii ; but thoy aro all essentially similar, cuiisistiiic? 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. 68). Rhythviicality. — 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 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 discharges; potential energy is converted into kinetic energy or movement. When contraction travels as a wave along muscular fibres, or from one 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 contraction is a more complicated peristalsis occurring in a rhythmic manner. 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- bility was enunciated by Haller more than a century ago, and was afterwards keenly debated. It was finally settled by the following experiment of Claude Bernard. 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 South American 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 * 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. A solution of pure sodium chloride (O'tJo per cent.) has a similar action. 84 IRRITABILITY AND CONTRACTILITY [CH. VIII. to muscle is dissected out and stimulated, no movement occurs in the muscles to wliich it is distributed. Curare paralyses the end-])lates, so that nervous impulses cannot get past them 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 these parts 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 l^etween 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 ligatvu'ed 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- 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 m-.iscles 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. CH. VIII.] VARIETIES OF STIMULI 85 Fk;. 104. -Muscle-nerve preparation, f, Femur; N, nerve ; j, tendo Achillis. (M'Ken'lrick.) 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 gracihs 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 stimidus 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. Electrical ; the constant or the induced current may be used. In all cases the result of the stimulation is 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 afi'ect muscle do not affect nerve, and vice versa ; thus glycerin stimulates nerve, but not muscle ; ammonia stimulates muscle, but not motor nerves. We may regard stimuli as liberators of energy ; muscle and nerve 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. 86 IRRITABILITY AND CONTRACTILITY [CH. VIIL Contraction of Muscle. Muscle undergoes the following changes when it contracts : — 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 proteins, 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 filDres which require a microscope for their investigation ; these have been already considered (see p. 68). 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 variation in its electrical condition. 5. Chemical changes. — These consist in an increased consumption of oxygen, and an increased output of waste materials such as car- bonic acid, and sarcolactic 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 IX CHANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS Though it has been known since the time of Erasistratus (B.C. 804) 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 apphed to the nerve, and the form of stimidus 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. 105) 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 caUed the positive element, the copper the tiegative eUvient. The distal ends of the wires S7 88 CnANGE IN FORM IN A MUSCLE WHEN IT CONTRACTS [CH. IX. uSd 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 attaclied to the positive element (zinc) is called the negative pole or kathode ; that attached to the nefjative 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 Hows 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 : figs. 106 and 107 represents two common forms of key. A key is a piece of apparatus by which the current CuSO: Fio. 105. — Diagram of a Uaniells Battery. Fio. 100.— Du Bois Reymoml's Key. Km. 107.— MiTcury 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. 108); 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 Toake. A contraction occurs only at make and break, not while the current is quietl}' traversing the nerve or mu'*ole. CH. IX.] THE INDUCTION COIL 89 But it will be seen in the Du Bois Reymond 'kej'(fig. 106) 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. 109) 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. 108. Fig. 109. 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. 90 CHANGE IN FORM IN A MUSCLK WHEN IT CONTRACTS [CH. IX. Fig. 110 roprcsonts the Du Bois licymoiid 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 Fio. 110.— 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 liim. It consists in bridging the current by a side wire, so that the current never en. IX.] THE INDUCTION COIL 91 next diagrams 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, wliich 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 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. 111). 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. 112) the battery wires are connected as before. The interrupter is bridged by Fig. 112. a wire from B to C (also shown in fig. 110, 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 92 CHANGE IN FORM EN A MUSCLE WIIKN IT CONTRACTS [CH. IX. 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 laboratory with an induction coil and cell will teach the student Fio. 113.— Myograph of von Helmholtz, shown in an incomplete form, a, Forceps for hoMiiig frog's femur; h, gastrocnemius; c, sciatic nerve ; d, scale -pan; e, 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. 113 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 upstroke; when it falls it will mark a CH. IX.] MYOGRAPHS 93 downstroke, and if the cylinder is travelling, the downstroke will be written on a different part of the paper than the upstroke; thus a muscle curve or myogram is obtained. The paper may then be removed, varnished, and preserved. Fig. 114 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. 114.— Arrangement of the apparatus necessary for recorrling muscle contractions with a revohing cyliuder carrj'ing 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 pre\"iously strained by the weight. This arrangement is callecl after- loading. The writing surface is again a travelling cylinder tightly covered with smoked glazed paper. The rest of the apparatus shows how 94 CHANGE IN' FORM IN A MUSCLE WHEN IT CONTRACTS [CH. IX. cell, coil, keys, and oloctrodus 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 Fio. 115. -Du Bois Reymoiid's Spring M.vut:rai)h. (M'Keiidrick.) surface. Thus fig. 115 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. 116) 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 key is shown on an enlarged scale inBC (fig. 116). 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 cn. IX.] MYOGRAI'IIS 95 of wet blotting-paper. One form of moist chamher is shown in fici. 117. Fui. 116.— Pendulum Myograph and accessory parts (Pick'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 wliich 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 KiG. 117.— Jloist Chamber. 96 CHANGE IN FORM IN A MUSCLE WUEN IT CONTRACTS [CH. IX. time-marker is a tuning-fork vibrating 100 times a second. This is struck, and by moans 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 nmscle. This causes a single or simjde muscular contraction, or, as it is often called, a twitch. The graphic record of such a contraction is called the simple micscle curve. One of these is shown in the accompanying figure (fig. 118). Fii:. lis. — ^Simple muscle curve. The muscle was stimulated by a single induction-shock, at the instant marked P upon the base-line. The lower wavy line is traced by a tuning-fork vibrating 100 times a second, and serves to measure the time occupied in each part of the contraction. It will be observed that after the stimulus has been applied there is an interval before the contraction commences. This interval, termed the latent period, when measured by the tuning- fork tracing is seen 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. The next stage is the stage of elongation. After reaching its highest point, the lever descends in consequence of the elongation of the muscle. The small waves which follow the main curve are simply due to the elasticity of the muscle and recording apparatus, and are most marked when the contraction is rapid and vigorous. en. IX.] THE SIMPLE MUSCLE CURVE 97 The whole contraction occupies about ,V 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 -f^ 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. Infiucnce of strength of stimulus. — A mining,! stimulus is that which is just strong enough to produce 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. — Increase of load decreases the amount of contraction, 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. Yig. 119 shows the result. At first the contractions 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 curves are much more prolonged ; the latent period gets longer ; the period of contraction gets longer ; and the period of relaxation gets very much longer ; this condition is 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. Contracture is often absent in fatigue of mammalian muscle. 4. Effect of temperature. — Cold at first increases the height of contraction, then diminishes it ; otherwise the effect is very Hke 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 salt solution* at different tempera- * Physiological saline solution used for bathing living tissue is a 0*9 per cent, solution of sodium chloride in ordinary tap water. G ^8 CHANGE TS FORM IN A MUSCLE WHBN IT CONTRACTS [cn. IX. en. IX.] THE SIMl'LK MUSCLE CURVE 99 lures on to llio muscle before taking its curve. Fig. 120 shows the result of such an experiment. Too great heat (above 42^ G.) induces heal riijor, due to the coagulation of the muscle proteins. Fio 120 -Etiect of tem,>erature on the simple muscle curve. The various t«niperauu^es are marked on the curves. P is the point of stimulation ; and the time-tracn.g again indicates hundredths of a second. 5. Efftxt of veratrine.—U this is injected into the frog-, before the muscle-nerve preparation is made, the very remarkable result seen l.'io 1-n -Veratrine curve, taken on a very slowly travelling cylinder ; the time-tracing indicates seconds, not hundredths of a second as in the previous diagrams. iu fif. 121 is produced on stimulation; there is an enormous 100 CFIANOK IN FORM IN A MUSCLE WHEN IT CONTRACTS [CH. IX, prolongation of the period of relaxation ; marked by a secondary rise, and sometimes by tremors. The second rise has received various explanations, none of which can be regarded as satisfactory. After repeated stimulation the veratrine effect passes off, but returns after a period of rest. The Muscle-Wave. The fust ])art of a muscle which contracts is the part where the nerve-fibres enter ; the nerve impulses, however, are so rapidly carried to all the fibres that for practical j)urposes they all contract together. But in a nerveless muscle, that is one rendered physiologically nerve- 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. 122) represents one of the numerous methods Kio. 122.— Arrangement for traciiij; the muscle-wave. (IU'Rundrick.) that have been devised for this purpose. A muscle with long parallel fibres, like the sartorius, is taken ; it is represented diagrammatical ly 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 (T), and this lever goes up first; the 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 Clf. IX] EFFECTS OF SUCCESSIVE STIMULI 101 of the second lever is ascertained, we have the arithmetical data for calculating the rate of propagation of the muscle-wave. It is ahout 3 metres per second in frog's muscle, but is hastened by warmth and delayed by cold and fatigue. The Effect of T-wo successive Stimuli. If a second stimulus follows the first stimulus at a sufficient interval of time, each will cause a twitch and two simple muscle curves will be written (fig. 123, A); the second is a little bigger than the first (beneficial effect of contraction). If the second stimulus arrives before the muscle has finished contracting under the influence of the first, a second curve will be added to the first, as shown in fig. 123, B. This is called superposition, 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 ; but if submaximal, 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 (fig. 123, C). Effect of More than Two Stimuli. If a succession of stimuli are sent into a muscle, or its nerve, the results obtained depend on the rate at which the stimuli follow one another. If the time intervals between the stimuli are sufficiently great, each stimulus will produce a simple muscular contraction, and one records a succession of twitches, and the beneficial effect of previous action is exhibited in what is known as a staircase (fig. 124, A and B). If the induction shocks follow each other more rapidly, the effect is a continuation of the superposition curve already described in connection with two successive 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 second ; a fourth on the third, and so on. Each successive increment is, however, smaller than the preceding, and at last the muscle remains at a maximum con- traction, 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. 92). This method of stimulation is called faradisation. Fig. 124, C to F, shows the kind of tracings one obtains. The number of contractions corresponds to the number of stimulations ; the condition of prolonged contraction Fiii 1-^3 — Elf>-<-C of two 8urc>-s.sivf exciUlioiis. Th«- two poihls of .-TCiiation (Pj ans. These six tracings were obtained ^^.^f^^'yj^'''''^^ a mecSa'l 104 CHANOK IN FOUM IN A MU8CLK WHKN IT CONTRACTS [CIT. IX, 80 produced, the muscle never relaxing completely between the individual contractions of which it is made uj), is called tetanus: incomplete tetanies, when the individual contractions are discernible (fig. 124, C, 1), and E) ; complete tetaniis, as in fig. 124, F, when the contractions are so rapid as to be com[)lotcly fused to form a con- tinuous lino witliout 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 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 as the period of relaxation becomes pro- longed, 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 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 i.s hoard. 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 membrana 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 inappHCable to the investigation of such a CII. IX.] VOLUNTARY TETANUS 105 problom 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 Mare/s Tambour. It consists of a drum, on the membrane of which is a metallic disc fastened near one end of a lever, the far extremity of wliich 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 Screw to retaliate elevation of lever Writing lever. Tambour. Tube to receiving tambour. Fig. 125. — 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. 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 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 that of an incomplete tetanus, which by a Fig. \i6. — Tracing of a voluntary contraction of the oppouens poUicis on a slowly moving drum, by means of the transmission myograph. The vertical lines indicate seconds. (Schafer, Canney, and Tunstall.) time-marker can be seen to be made up of 10 to 12 vibrations a second. A typical tracing is shown in the above figure (fig. 126). 100 CHANOK IN FOIIM IN A MUSCLE WHEN IT CONTRACTS [CII. IX. lu 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 1)0 obtained in an anaesthetised animal 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 stimulation 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 stimulatal, 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 stimulation then makes no difference; the reflex contraction occurs at the same rate, 10 or 12 per second. But now a difficulty arises ; if a twitch only occupies yV of a second, there would be timposite direction to the upper. Attached to the upper set of needles is a small mirror about i inch in diameter; the light from the lamp at B is thrown uiton this little mirror, ane feet from the galvanometer, which is arranged east and west, the lamp is lighted, the mirror is ma^le 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-jiolarisatile electrodes touching the muscle are attached to the outer bimling screws of t: . . :;.';ler, a key intervening for short circuiting, or if a portion only of the current is Uj p.i.so iiilu the galvanometer, the shunt should interv.-iie as well with the appropriat* plug in. When a current ]>asses into the galvanometer the iit^?.ile> and, with them, the mirror, are tunied to the right or left according to the direction of the current. The amount of the iloHec- tion of the needle is marked on the scile by the spot of light travelling along it. Non-polarisable Electrodes. — If a galvanometer is connected CII. XT.] NOX-rOLAniSABI.K ELECTRODES 119 with a muscle by wires which touch the muscle, electrical currents are obtainctl 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 wliicli are non-polarisable. Fig. 136 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"9 per cent, sodium chloride) ; 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 Fig. 13C Non-polarisable elec- trode of Du Bois Keynioiid. (M'Kendrick.) Fig. 137. — Diagram of Du Bois Reymond's non-polarisable electroiies. 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 physiological salt solution ; in the solution of zmc sulphate 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. potential (that is, difference in amount of positive or negative elec- tricity) between the tw^o parts of the muscle thus led oft", there will be a swing of the galvanometer needle ; the galvanometer detects the existence and direction of any current that occurs. 120 THE ELECTRICAL PHENOMENA OF MUSCLE [Cn. XI. Fig. 137 shows a more convenient form of non-polarisable elec- trodes. In order to nu-a^iirc the strength (elec- tromolivc force) of such currents, the mere amount of swinj,^ of the needle is only a very ronffli indication, and in accurate work the arranj^enient shown in fii;. 138 nnist be used. The electromotive force is usually me.isured 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, l> of a long platinum wire of high resistance, called the compen- sator ; r is a slider on this wire ; ii and c are c-onnected to the galvanometer, the com- mutator C enabling the observer to ensure that the current from the Daniell passes in the opposite direction to that produced by the muscle. If the slider r is placed at the end /- of the compensator, the whole strength of the Daniell will be seivt through the galvanometer and will more than Fio. 188. — Arrangement for measuring the elec U-omotive force of muscle. Fio. 139.— Lippmann's Capillarj- Eloctrompter. (After Waller.) 1. Pressure apparatus and microscope on slanil of wliicli the capillary tulje is fixed. '2. Capillary tube, fixed in outer tube containing 10 per cent, sulphuric acid ; the platiaum >^res arc also shown. 8- Capillary and column of mercury as seen in the field of the microscope en. XI.] THE ELECTROMETER 121 neutralise the niusclc current; if c is halfway between a and I>, lialf tlic Daniell's strenj^h will be sent in ; but this is also too much ; (ic will be found to be only ?|uite a small fraction of ah ; and this fraction will cfjrrespond to a j)roportional paction of the electromotive force of the Daniell cell. lilppmann'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 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. 1.39). The surface of the mercury is in a state of tension whic-h 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 in a living tissue in a graphic manner. The instrument is exceedingly sensitive, and its indications are practically instantaneous. The instrument has been much used in investigating the electrical changes of the heart, as will be more fully discussed when we are considering that organ. The String Galvanometer. — This is even more sensitive than the capillary electrometer, and we owe its introduction to Professor Einthoven of Leiden. In the ordinary galvanometer, as we have seen, the current passes through a fixed coil of wire, and deflects a small magnet suspended in the centre. This arrange- ment can be inverted, the magnet being made large and fixed and the coil small and movable. The Einthoven galvanometer is a development of this type. The magnet is large, and shaped so as to give a very intense field, and the "coil" is reduced to a single thread of quartz, silvered on the surface so as to conduct the current. The movements of this thread are too small to be followed by the unaided eye, so the poles of the magnet are pierced by a hole in which a microscope magnifying 600 diameters is arranged, so as to cast the image of the string on a moving photographic plate. We have already seen one use of this instrument in the study of voluntary muscular contraction (see p, 106) ; M'e shall have to return to it in our study of the heart, and respiration, in later chapters. "We can now pass on to a consideration of results. In muscles that are removed from the body, it is found that on leading off two parts of their surface to a galvanometer, the galvan- ometer needle generally swings. The most marked result is obtained with a piece of muscle in which the fibres run parallel to one another, and the longitudinal surface is connected with one of the cut ends by a wire (2 in fig. ]40). On the course o' .he wire a galvanometer indicates that a current flows from the centre to the cut end outside the muscle, and from the cut end to the centre inside the muscle. If, now, the muscle is thrown into tetanic contraction, the needle returns more or less completely to the position of rest. Du Bois Reymond, who first de.=!cribed these facts, called the first current the current of rest, and the second current the current of action; the change in direction is indicated by the expression negative variation ; this means that the current of action is in the opposite direction to the current of rest, and therefore lessens or neutralises it. The word negative is therefore used in its arithmetical, 122 TIIF. KLFXTUICAL PHENOMENA OF MUSCLE [CIl. XI. not its electrical sense. Dii Bois Reymond oxplaineil lliis by sup- posing that a muscular fibre is built up of molecules, each of which Fio. HO.— Diagram of tlie currents in a muscle prism. (Du Bois Iteymond.) is galvanometrically positive in the centre and galvanometrically negative at both ends. So when a muscle is cut across, a number of the galvanometrically negative ends of these molecules is exposed. On contraction the difference between the centre and ends of each molecule is lessened, and the resultant effect on the whole mu.scle (made up of such molecules) is similar. In tlie foregoing sentence I have employed the rather cumbrous adjectives, qalvanometrtrulli/ pu.sitive and (/alvanomet riralfi/ nf(/afii'e, instead of the terms positive and negative which are usually employed by physiologists. If we take a Daniell cell and connect it to a galvanometer, the zinc, jxs we have seen, is the electro-positive element, and the copper the electro-negative element, but the ends of the wires which connect these metals to the galvanometer have the reverse names ; the kathode or negative pole is connected to the zinc or positive metal ; the anode or positive pole is connected to the copper or negative metal. The current enters the galvanometer by the anode, and leaves it on its way back to the zinc by the kathode. Therefore, although the copper is electro- negative, it may be spoken of as galvanometrically j)ositive, and the zinc though electro-positive, as galvanometrically negative. If we apply this to a muscle, we have seen that the current flows (in the wire that connects the uninjured longitudinal surface to the c-ut end) from the longi- tudinal surface to the cut end; the longitudinal surface thus corresponds to the copper of the Daniell cell, and is therefore electro-negative, though galvanometrically positive ; similarly the cut end corresponds to the zinc, and is electro-positive though galvanometrically negative. The omission of the qualifying prefix to positive and negative has Ud to a good deal of confusion in physiological writings. A physicist uses the terms positive and negative as meaning electro-positive and electro-negative resj)ectively, and as Dr Waller has pointed out, it is time that physiologists adopted the same nomenclature. In what now follows, I propose to adopt Dr VV'aller's suggestion. There is no doubt about the facts as described by Du Bois Eeymond. We now adopt, however, an entirely different view of their meaning : in causing this revolution of ideas the principal part has been played by Hermann. Hermann showctl that the so-called CIT. XT.] THE DIPHASIC VARIATION 123 current of rest docs not exist; it is really a current produced by injury, and is now generally called a dcviarcation current : the more the ends of the muscle are injured the more positive they become; and when they are connected to the uninjured centre, a current naturally is set up as described by iJu Lois lleymond. If a muscle is at rest and absolutely uuinjuretl it is iso-elcctric ; that is, it gives no current at all when two parts of it are connected together by a wire. Since Du Bois Eeymond's researches, the electrical changes which occur during a single twitch have been studied also, and before wo can understand the "negative variation" of tetanus, it is obviously necessary to consider the electrical variation which takes place during a twitch, for tetanus is made up of a fused series of twitches. The electrical change during a twitch is called a diphasic variation. The contracting part of a muscle becomes first more positive than it was before ; it then rapidly returns to its previous condition. The increase of positivity indicates a disturbance of the stability of the tissue ; the disappearance of this increased positivity is the result of a return of the muscular tissue to a state of rest. If the muscle is stimulated at one end, a wave of contraction travels along it to the other end. This muscle-wave (see p. 100) may be most readily studied in a curarised muscle, that is, in a muscle which is physiologically nerveless. The electrical variation travels at the same rate as the visible contraction, but precedes it. Suppose two points {p and d) of the muscle (fig. 141) are connected by non- polarisable electrodes to a galvanometer, and that the muscle-wave is started by a single stimulus applied at A ; as soon as the wave reaches p this point be- comes positive to d, and therefore a current Hows from d to p through the galvanometer G. A moment later the two points are equi-potential and no current flows; a minute fraction of a second* later this balance is upset, for when the wave reaches the point d, that point is positive to p, and the galvanometer needle moves in the opposite direction. Fig. 141. The time will vary with the distance between /< and d. 124 THE ELECTRICAL PHENOMENA OF MUSCLE [CH. XL The galvanometer is not the best instrument to employ to demonstrate these facts; the inertia of the needle may be so great that it is impossible for it to catch and respond to the two phases. Wedenski has made extensive use of the telephone instead, and the Fio. 142. — Diphasic cuire (black) of the normal sartorius. The grey curve is the monophasir cur\'e of the same muscle when one electrometer contact was placed on the injured end. The two photo- graphic curves are placed one over the other so that the b^nnings coincide. (Burdon Sanderson.) sounds produced in it by the electrical changes in the muscle are distinctly audible. An appeal to the eye, however, is generally regarded as more satisfactory than one to the ear, and for this purpose the capillary electrometer is the instrument most frequently em- ployed, as its responses are immediate ; the mercury moves first in one direction, and then in the other. The deep black curve in the next figure (fig. 142) shows the record obtaining by photographing the movement of the column of mercury on a rapidly travelling photographic plate. The capillary electrometer has the advantage of giving us the means of measur- ing the time of onset and duration of the electrical disturbance, and experiments made with this instrument G show that the change only lasts a few thousandths of a .second, and is over long before the other changes in form, etc, are com- pleted. Sir J. Burdon Sanderson gives the follow- ing numbers from experi- ments with the frog's ga.stro<'nemius. When the muscle was excited through its nerve the electrical respon.se began ^^*,-^ and the change of form ir.'s-, second after the stimula- tion ; the second phase of the electrical response began fjjn second after excitation. When the mu.scle was directly excited, the latent period was much shorter, the change in form beginning TTi*Mf. and the electrical change in less than ,;',,„ .second after excitation. If, however, instead of examining the electrical change in the muscle in the manner depicted in fig. 141, one electrode is placed on Fir,. 143. CH. XI.] THE KLECTKOMETEIi RECORD 125 the uninjured surface and the other on the cut end (see fig. 14o), tlie electrical response is a different one. Under these circumstances, the electrical change is a monophasic variation, for when the muscle-wave reaches d, this part of the muscle, owing to its injured state, does not respond to the excitatory condition, and the electrical re- sponse is also extinguished. The grey curve in figs. 142 and 144 is the graphic record of the change as revealed by the capillary electrometer. It will be seen that the ascending limb of the curve is iden- tical in the two cases, but that the second phase is absent. From the point at which the diphasic curve approaches its culmination the injury curve diverges from it, continuing to ascend; the line soon after becomes hori- zontal, and then begins slowly to decline. This long tail denotes only the gradual dis- appearance of polarisation of the mercury meniscus. The meaning of such photographic records be- comes clear by testing the electrometer with known differences of potential, and from such data it is possible to construct what may be called an interpre- tation diagram (fig. 144). The horizontal line is that of equipotentiality of the two surfaces of contact /* and d. The curve P' expresses the relative positivity of the surface p ; the curve D', the corresponding relative positivity of the surface d. S' is a curve of which the ordinates are the algebraic sums of the corresponding ordinates of P' and D'. S is the photographic curve which expresses S' ; P is the photographic curve which expresses P' (monophasic variation). The numbers under the horizontal line indicate hundredths of a second ; the distance t t' expresses the time taken by the wave in its progress from p to d. From these considerations we can now pass to study what occurs when the muscle enters into tetanus. The simplest case is that which was first observed by Du Bois Eeymond. He placed his non- polarisable electrodes in the positions indicated in fig. 143, one {jp) on the comparatively uninjured surface, the other (fZ) on the devital- ised cut end. He sent in the tetanising series of shocks at A. The electrical response is under these circumstances a summation of the individual electrical responses evoked by instantaneous stimuli ; and the monophasic character of the single response explains easily what occurs during tetanus ; the centre of the muscle becomes more positive than it was before, and so the electrical difference of potential Fig. 144. — Interpretation dia- gram. (Burdon Sanderson.) 126 TMK Kr.ECTPJCAL niEXOMENA OF MUSCLE [CH. XI. between the centre and tlie injured end is lessened. But with regard to uninjurod muscle the problem is not so easy. It is at first sight diflicult to see why the summed cfrocts of a scries of dipiiasic varia- tions shoulil take the direction of the first j^liase, as was found to be the case by ]Ju Buis Eciymond in experiments with the frog's gastroc- nemius. One would have anticipated that "negative" variation in the arithmetical sense would be absent altogether, and this is the case in absolutely normal muscles; Hermann has shown that it is so during tetanus of the human forearm. But a muscle removed from an animal's body cannot be considered al)solutely normal, and if the two contacts be placed on the comparatively uninjured longitudinal surface, as in fig. 142, a negative variation is observed, each excitatory phase becoming weaker as it progresses, and the second phase of each diphasic effect is weaker than the first. The following figure (fig. 145) illustrates the record obtained by the capillary electrometer Fio. 145. -Electrometer record of injured sartorius during tetanus. (Burdnii Sander-ion.) from an injured sartorius excited 14 times a second; each oscillation represents a single monophasic variation. The individual oscillations can, however, be seen when the excitations follow one another more rapidly, even up to 80 or 100 per second. Muscle is not the only tissue which cxliibits electrical i)lienomena. A nerve which is uninjured is iso-electric ; injury causes a demar- cation current ; activity is accompanied with a similar diphasic wave travelling along the nerve simultaneously with the nervous impulse. Tlie activity of secreting glands, vegetable tissues, retina, etc., is accompanied with somewhat similar electrical changes, which we shall study in detail later. But the most prominent exhibition of animal electricity is seen in the electric organs of electric fishes. In som'e of these fishes the electric organ is modified muscle, in which a series, as it were, of hypertrophied end-plates correspond to the jtlatcs in a voltaic pile. CII. XI.] THE RHEOSCOPIC FROO 127 In other fishos the electric organ is composed of modified skin glands. But in each case the electric discharge is the principal phenomoncjii that accom])anies activity. The Rlieoscopic Prog. The electrical changes in muscle can be detected not only by the galvanometer and electrometer, but also by what is knov^^n as iho physiological rheoscope ; this consists of an ordinary muscle-nerve preparation from a fresh and vigorous frog. The nerve is stimulated by the electrical changes occurring in muscles, and the nervous impulse so generated causes a contraction of the muscles of the rlieo- scopic preparation. The following are the principal experiments that can be shown in this way : — 1. Contraction witJwut metals. If the nerve of a nerve-muscle preparation A is dropped upon another muscle B (fig. 146) or upon Fio. 14(3. — Galvaui's experiment without metals. its own muscle, it will be stimulated by the injury current of the muscle on which it is dropped, and this leads to a contraction of the muscle (A) which it supplies. The experiment succeeds best if the nerve is dropped across a longitudinal surface and a freshly made transverse section. 2. Secondary contraction. This is caused by the current of Fig. 147. — Secondary contraction. (After Waller.) action. If, while the nerve of A is resting on the muscle B (fig. 147), the latter is made to contract by the stimulation of its nerve, the nerve of A is stimulated by the electrical variation which accompanies the contraction of the muscle B, and so a con- traction of muscle A is produced. This is called secondary con- 128 . THE KLKCTKICAL PUKNOMENA OF MUSCLE [CH. XI. traction. It may 1)0 ciLhur a accondary twitch or secondary tetanus, according as to whether the muscle li is made to contract singly or tetanically. 3. Secondary coiitraction from the heart. If an excised but still beating frog's heart is used instead of muscle B, and the nerve of A laid across it, each heart's beat, accompanied as it is by an electrical variation, will stimulate the nerve and cause a twitch in the rheo- scopic muscle A. CHAPTER XII THERMAL AND CHEMICAL CHANGES IN MUSCLE In muscular contraction there is a transformation of the potential energy of chemical affinity into other forms of energy, especially molar motion and heat. Heat is a form of motion in which there is movement of molecules ; in molar motion there is movement of masses. The fact that when a blacksmith hammers a piece of iron it becomes hot is a familiar illustration of the transformation of one mode of movement into the other. Heat is measured in heat-units or calories. One calorie is the energy required to raise the temperature of 1 gramme of water from 0" to I'' C. ; and this in terms of work is equal to 425'5 gramme-metres, that is, the energy required to raise^ the weight of 42 5 "5 grammes to the height of 1 metre. A muscle when uncontracted is nevertheless not at absolute rest. We have already seen that it possesses tonus or tone ; it also possesses what we may call chemical tone ; that is, chemical changes are occurring in it, and consequently heat is being produced. But when it contracts, the liberation of energy is increased ; work is done, and more heat is produced; the heat produced represents more of the energy than the work done. The more resistance that is offered to a muscular contraction, the more is the work done relatively increased and the heat diminished. The amount of heat produced is increased by increasing the tension of the muscle. It diminishes as fatigue comes on. On increasinn- the strength of the stimulus the amount of heat increases faster, proportionately, than the work performed. If work is done by a few large contractions, more heat is produced than if the same work is done by a larger number of smaller contrac- tions ; that is, more chemical decomposition occurs, and fatigue ensues more rapidly in the first case. This fact is within the personal experience of everyone. If one ascends a tower, the work done is the raising of the weight of one's body to the top of the tower. If the staircase in the tower has a gentle slope, each step being low, far less fatigue is experienced than if one ascended to the same height by a smaller number of steeper steps. I 130 THRTIMAL ANli CHEMICAL CnANGES IN MUSCLE [CH. XIL On a cold flay one keeps oneself warm by muscular exercise ; this common fact is confirmed by more accurate experiments on isolated muscles, the heat produced being sufficient to raise temporarily the temperature of the muscle. This can be shown in large animals by in- serting a thermometer between the thigh muscles and stimulating the spinal cord. The rise of temperature may amount to several degrees. In the case of frog's muscles, Helmholtz found that, after tetanis- ing them for two or three minutes, the temperature rises 0'14' to 018' C. ; and for each single twitch Heidenhain gives a rise of temperature of from 0001' to 0005' C. For the detection of such small rises in temperature, a thermopile, and not a thermometer, is employed. A thermopile consists of a junction of two different metals; the metals are connected by wires to a galvanometer. If the junction is heated an electrical current passes round the circuit, and is detected by the galvanometer. The metals usually employed are \\ ftr^ B-^A A«-B D-A A-^^B B-»->--A 7 Couple. 2 Cnaples. 3 Couples. Fig. 148. Fig. Ii9. Fio. 150. Figs. HS-150.— .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 galvan- ometer. The arrangement is shown in the fig. 148, 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 ^thjij 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 fig. 149, and they are heated equally, no current will pass through the galvanometer, 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 (tig. 150) 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 the other direction, indicating the production of heat first on one side, then on the other. CH. XII.] CHEMICAL CHANGES IN MUSCLES 131 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. Sarcolactic 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 When a muscle contracts, the quantity of oxygen consumed is increased, and the discharge of carbonic acid is increased also. This is the cause of the rise in heat-production just described. It is important to note, however, that this change follows rather than accompanies the increase of work, as we shall see more at length when we are studying tissue-respiration (p. 397). For a certain time after its removal from the body, an excised muscle can be made to contract and give off oxidation products such as carbonic acid in an atmosphere containing no oxygen at all. The oxygen used has thus been 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. Excised muscles, however, must be regarded as partially asphyxiated, for their individual fibres are largely cut off from that ready supply of oxygen which normally reaches them by the blood. During life (and the living condition can be imitated by placing an excised muscle in an atmosphere of pure oxygen) the muscular substance breaks down into a number of simpler substances ; one of these is carbonic acid. The others, however, or some of them, are at once built up again with the inclusion of oxygen and some carbon-containing substance, perhaps sugar, into living material. The muscle, therefore, does not contain any of the by-products of its own metabolism. In excised muscle, when the oxygen supply is deficient the by - products accumulate, as a result of which very striking alterations take place: — (1) The reaction of the muscle changes and the phenomena of fatigue and functional death set in. (2) The proteins become coagulated, and this is the physical basis of rifjor mortis. There are other chemical changes in the muscle when it contracts, for instance, a change of glycogen into sugar. The question whether nitrogenous waste is increased during muscular activity has been a much debated one. It has now, however, been finally proved that an increased consumption of carbon (in large measure derived from the carbohydrate stored in the muscle) is a marked and immediate feature of muscular activity. Any increase in the consumption of 132 TITEKMAL AND CHEMICAL CHANGES IN MUSCLE [CH. XH. nitrogen is negligible, and only occurs when the muscles do not receive a due share of non-nitrogenous food. (See more fully chapter on Metabolism.) Fatigue. If the nerve of a nerve-muscle preparation is continually stimu- lated, the muscular contractions become more prolonged (see p. 97), smaller in extent, and finally cease altogether. The muscle is said to be fatigued : this is duo to the consump- tion of the substances available for the supply oi energy in the muscle, but more particularly to the accumulation of waste i)ro- ducts of contraction ; of these, sarcolactic acid is 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 prei)aration 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 the peripheral end 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 mu.scles 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. 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 registered by a marker on a blackened surface. By the use of this and similar instruments it has been shown that the state of the brain and central nervous system generally is a * Another convonitnt block which is .sometimes used is to throw a consbint current into the nerve between tlie j)oint of excitation and tlic muscles. This pre- vents the nerve impulses from reachinj^ the muscles. en. XII.] FATIGUE 133 most important factor in fatigue, and that the fatigue products pro- duced in the nuusclos during work cause part of their injurious otfects 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. 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. It should, however, be mentioned that some physiologists (Lee, loteyko, etc.), still regard the effect on the end plates as the most important factor in fatigue. 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 shght, 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-meduUated nerve with which to try the experiment, and her results confirmed Dr Waller's expectation ; the galvano- metric replies of the nerve became somewhat feebler after repeated stimulation. 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 (li 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 stinmlating the nerve with a weak faradic current the organ contracts, and the recording lever falls. 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 134 TRKKMAL AND CHEMICAL CHANGES IN MUSCLE [CH. XII. nirrents will coiiiplctcly block the transmission of impiilsrs, and not only that, but tilt' nerve remains blocked after the current is removed. After the current has been allowed to flow for two iniruites the nerve remains impassable to nerve impulses for an hour or more, and then slowly recovers. If, therefore, faradic excitation of tlie nerve is kei)t up all this time arid fails to excite the contraction of the S})leen after the removal of the constant current, it is impossible to say whether r> N Fio. 151. — Apparatus for obtaining splenic curves, s, Spleen in oncometer o, whicli is made of gutta perclia, and covered with a glass plate (o. p.) luted on with vaseline, si is the splenic niesentery containing vessels and ner^'es ; this passes through a slit in the base of the oncometer which is made air-tight with \aseline. The oncometer is connected to the flexible bellows (b) 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. 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 (due to electrolytic changes caused constant current) is still effective. Our best results were obtained by using cold instead of a constant current as our blocking agent. Fig. 1.51 is an outline draw-ing of the apparatus used, and fig. 152 shows the arrangement adopted in connection with the nerve. The nerve (x) rests on a metal tube (i) through which water can be kept flowing, k is the situation of the electrodes. If the nerve is excited, the spleen con- tracts, and the recording lever (in fig. 151) 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 :!0 C, the nerve again becomes passable by nerve impulses, and the spleen contracts once more. While the fluid in t is kept at the low temperature mentioned, the nerve is excited with strong induction shocks all the time, and 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 f. and t has been fatigued. But our experiments have shown us that non-mcdullated nerve is just as difficult to fatigue as meduUatcd 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. DT I. 152. — Arrangement of ap- paratus in connection with the splenic nerve, s is the spleen, and N the main bundle of ner\'es. The ner\'e rests on the metal tube (T)through which fluid at the required temperature is kept flowing, and on the electrodes (k) which come from the secondary coil of an inductoriuni. CII. XII.] FATIGUE IN NERVE 135 We havf made similar experiments witli vaso-motor nerves, such as tlie cervical sympathetic nerve in tlie rabbit, tiie splanchnic nerve of the dof?, and the sciatic nerve in a eurarised dog, and have obtained corresponding results. This confirms the work previously pul)lished 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 upjjcr 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 eflFect of this alkaloid is increase of refiex 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 cannot be shown to occur in nerve-fibres of either the medullated or non-medullated variety by these methods. 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 sfimuJation fatUjuf, ; 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 test the 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 that many of them, such as the vaso- con- strictors, are in constant action throughout life. It should be clearly understood that all these experiments prove only that nerve-fibres are not fatiguable under ordinary conditions of stimulation. If we assume that nerve is entirely "unfatiguable," we must assume also that its activity is not associated with the consumption of material and the production of waste products. This would render nerve unique among all the other tissues of the body, and is, moreover, contradicted by recent discoveries of evidence of metabolic changes in a nerve during its activity. We are therefore driven to the conclusion that repair is exceedingly rapid and perfect, although it is impossible to agree with Waller that the repairing process is definitely associated with the presence of a medullary sheath. The interval between successive induction shocks is certainly short, but it is apparently long enough to allow the nerve to recover completely before the next stimulus arrives. If, however, the interval between two successive stimuli is made very brief indeed (O-OOG sec), the second stimulus is ineffective because of the fatigue due to the first. If the irritability of the nerve is depressed by cold, by asphyxia, or by an anaesthetic (such as yohimbine), the irresponsive period may be lengthened to as much as one to two tenths of a second. In one of the foregoing paragraphs the following sentence occurs : "fatigue is demonstrable in nerve-cells." M-Dougall has recently adduced evidence that fatigue in the central nervous system has its seat not so much in the bodies of the nerve-cells as in their synaptic junctions, which are the points of highest resistance (that is, where impulses pass with greatest difficulty) in all mental and other operations in which the brain and spinal cord share, even when no fatigue exists. 136 THEHMAL AND CHEMICAL CUANGES IN MUSCLE [CII. XII. Rigor Mortis. After death, the muscles gradually Icjse their irritability and ]*ass 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. Tiie 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 sarcolactic 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 there is very little doubt that it is really the first stage in the self-digestion or autolysis which occurs in all tissues after death, owing to the presence of intracellular enzymes or fer- ments. It is known that a pepsin-like or proteolytic enzyme is present in muscle, as in many other animal tissues, kidney, spleen, etc. (Hedin), and that such enzymes act best in an acid medium. The conditions for the solution of the coagulated myosin are there- fore 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 com- mences 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 paro.xysnis 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-S<'*quard make it probable that the rigidity may supervene immediately after death, and then pass away with such rapidity as to be .s.sln() V. Fiirth took up the subject. On the main que.stion we are in substantial agreement, namely, that in the muscle-plasma there are the two i)r()teins just alluded to, and that these both contribute to the formation of the muscle-clot. The main points of ditference between us are in thi- names of the proteins. He uses physio- logical saline .solution to extract the muscle-j)lasma, and this extract coagulates spontaneously on standing; he is doubtful whether a specific myosin-ferment brings about the change. Paramyosinogen he terms mi/uxin, and this passes directly into en. XII.] PROTEINS OF MUSCLE 139 the clottt'd coiulition ; but myosinogcn, called myoyt'/n by v. Fiirtli, first pusses into ji soluble eouiiition (co.igulable by heat at the remarkably low temperature of 40" C. ) bi'fore it clots : t he soluble stage he calls sdIkIiIi'. mi/orin ; a better name is soliihli' mi/o.sin. We may put this in a (liiigr.inHuatic way as follows: — Proteins of the living muscle. Paramyosinogen. Myosinogen. I Soluble myosin. Myosin (the protein of the Muscle-clot). V. Fiirth also calls attention to some characters of myosinogen which separate it from the typical globulins ; e.;/., it is not precipitable by dialysingthe salts away from its solutions. It may be therefore called an att/plcal globulin. In mammalian muscle, soluble myosin is only found as a stage in the process of rii/or mortis, but in the nuiscles of the frog and other amphibia it is present as such in the living muscle. The muscle-plasma from fishes' muscle contains another protein termed mi/o- prote'm by v. Fiirth. It is precipitable by dialysis, but not coagulable by heat. Brodie, and later, Vernon, did some interesting experiments on heat riyor. 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 proteins. 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 myosin), 47% and 56°. This work of Brodie's is especially valuable because it teaches us that the proteins 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 proteins, but that when one of the muscular proteins has been coagulated, the living substance as such is destroyed ; the proteins 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-proteins ; his conclusions are based on the examination of only thirty species of animals, ana may require revision in the future, but such as they are, they are as follows : — Invertebrates : paramyosinogen present ; myosinogen absent. Vertebrates : paramyosinogen and myosinogen both present. Fishes : in addition to these two principal proteids, soluble myosin and myo- protein (in large quantities) occur.^ Amphibians : like fishes, except that myoprotein is only present in traces. Reptiles, birds, mammals : myoprotein is absent, and soluble myosin is only present when rigor mortis commences. CHAPTEli XIII COMPARISON OF VOLUNTARY AND INVOLUNTARY MUSCLE The main differonce 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, es[)ecially 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 })arts. 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, 140 CH. XIII.] CONTRACTION OF INVOLUNTARY MUSCLE 141 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 he douhtod that under normal conditions the contraction of involuntary muscle is influenced and controlled by nervous agency. As instances of nerveless involuntary muscles which possess the property of rhythmical action, we may take the ventricle apex of the frog's or tortoise's heart. If this is cut off and fed with a suitable nutritive fluid at considerable pressure it will beat rhythmically (Gaskell). The middle third of the ureter is another instance of muscular tissue free from nerves, but which nevertheless executes peristaltic movements. Perhaps, however, the most striking example is that of the foetal heart, which begins to beat directly it is formed, long before any nerves have grown into it. The artificial stimuli employed for involuntary are the same as those used for voluntary muscle ; single induction shocks are, however, 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. It is possible to render the frog's heart quiescent by tying a ligature tightly around the junction of the sinus with the right auricle, but the heart can be made to contract on stimulating it. It is then found that the latent period is much longer than in voluntary muscle ; if a series of stimuli are applied, say, at intervals of a second or two, each produces a single heart-beat ; the successive contractions so obtained show a well-marked staircase (beneficial effect of contraction, see p. 101). The strength of the stimulus in such an experiment does not matter ; a minimal stimulus elicits a maximum effect (" all or nothing " — Waller). 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 dm-ation. It does not obey the " all or nothing " law. The normal contraction of voluntary muscle is a kind of tetanus (see p. 104) ; 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 physiokjgical rheoscope (see p. 128). Each time the heart contracts the rheoscopic preparation executes a single twitch. 142 COMPARISON OF VOLUNTARY AND INVOLUNTARY MUSCLE [CH. XIIL not a tetanus. This is an indication that the electrical change is a sinffle one, and not a succession of chanties such as occurs in tetanus. But thougii involuntary muscle cannot be thrown into tetanus, it has the property of entering into a condition of sustained contrac- tion called to7i2is. 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 witli in the case of the vohmtary muscles. Involmitary 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 sarcolactic 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 proteins (paramyosinopren and rayosinogen) occur in both striped and unstriped muscle, and the iieat rigor curves of involuntary muscle are jiractically identical with those obtained by Brodie (see p. 131I)- He is inclined to think that the two proteins are formed by the breaking down of a compound protein which in living muscle mainly coagulates at 17 C. This view is taken by Stewart in reference to stri])ed nmscle also, l)nt has been very seriously cjuestioned by v. Fiirth. The most striking cliemic-al difference between unstriped and striped muscle is seen in the amount of nucleo-protein wiiich they contain. Plain muscle contains six to eight times tiie amount found in voluntary muscle ; cardiac muscle contains an intermediate cpiantity. CHAPTER XIV PHYSIOLOGY OF NERVE 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 hi 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. A list of the classes of efferent nerves is as follows : — a. Motor. h. 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 wliich supply the muscular tissue in the walls of arteries. 144 PHYSIOLOGY OF NRRVB [CH. XIV. b. Accelerator iiorves aru tliose which produco an increase in the rate of rhythmical action. An instance of tliese is seen in tlie synipatlietic nerves that supply the heart. c. InJiihitory nerves are those which cause a slowing in the rate of rhytiunical action, or it may be its complete cessation. InhiliiLory nerves are found supplying many kinds of involuntary muscle; a very typical instance is found in the iidiibitory 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, 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 tlio nutrition of the part they supply. 2. Atferent 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 ; such as, of sight, hearing, taste, smell, and touch. h. The nerves of general sensibility ; that is, of a vague kind of sensation not referable to any of the special senses ; as an instance, wo 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 those are anatomi- cally distinct from the others, but there is some evidence that this is the case (see more fully chapters on Sensation) The words " sensory " and " afferent," however, are not quite synonymous. Just as we may have efferent impulses leaving the brain for the heart or blood-vessels of which we have no con- * The (jut'stioii lias bci-ii iiiucli dihalitl vvlictluT volunlaiy miisilc is provitk-d with inhibitory lurvfs ; tiny do. lunMvcr, ai)|)(ar to be present in i-ertain nerves supplying the nuiseles of the elaws of lobsters and similar crustaceans. CH. XiV.] REFLEX ACTION 145 scious knovvlodge, 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 spinal 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 the 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. Inter-central nerve-fibres 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. K 14G PHYSIOLOGY OF NKKVK [CII. XIV. 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 supj)lies can no longer be produced Ijy 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 2Je'>'iphe7-al end, is still connected with some peripheral part of the body. Both the central and the jjeripheral 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 (Eitter-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 approximately healthy both in structure and functions ; but the peripheral piece of the nerve loses its functions and undergoes what is generally called, after the discoverer of the process, Walleriaji 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 portions of the CH. XIV.] DEGENERATION OF NERVE 147 axis cylinders which are cut off from their parent cells die, 1 breaking up into fragments; the medullary sheath of each undergoes a 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 begins to be visible microscopically two or three days !)--- Fio. 153.— Degeneration and regeneration of nervo-tibres. A, nerve-tibre, fifty hours after operation. m\j, Medullary sheatli breaking up into myelin drops, p, Granular protoplasm, w, Nucleus, g, Primitive sheath or neurilemma. 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 Hbres (£', t") have sprouted from the somewhat bulbous cut end (h) 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.) 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 nuclei of the sheath do not multiply ; there is simply death of the axis cylinder. The degenera- tion occurs simultaneously throughout the whole extent of the nerve. Eanvier's original diagram is reproduced in fig. 153. Fig. 154 is drawn from a specimen of degenerated fibres stained by osmic acid ; the myelin droplets are coloured black by this method. 148 PHYSIOLOGY OF NERVE [CH. XIV. A great amount of attention has been directed to this process of degeneration, because it has formed a valuable method of research in tracinrr nervous tracts, and ascertaining the nerve-cells from which they originate. It must nut, however, be regarded as an isolated phenomenon in physiology ; it is only an illus- tration of the universal 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. Regeneration of Nerve-Pibres. If a nerve is cut and allowed to heal, restoration of function occurs after the lapse of a variable time, which can be shortened if the cut ends of the nerve are sutured together. This surgical assistance is of special import- ance when the nerve is a large one, and the formation of dense cicatricial tissue between the ends is thus minimised. The restoration of function is due to regeneration of nerve- fibres, which sprout out from the central end of the cut nerve and grow distal wards, replacing those which have degenerated. The now fibres, which are the earliest to appear, are of a much narrower diameter than those they replace ; this is illustrated in fig. 153, D. Later the It is obvious that a mass of dense scar tissue S^rowth of the nerve-fibres. When regene- F.G. 154. — Di'generateil nerve- fibres at an early stage, where tlie frajjmentation of tlie medullary sheath into myelin droplets is well shown. Stained by osmic acid. (S. Martin.) new fibres are larger. will hinder the successful ^ ration does not take place, the central ends of the cut fibres and the cells from which they originate undergo slow atropic changes (disuse atrophy). The view that in the embryo each nerve-fibre develops as an outgrowth from a nerve-cell, and grows in a distal direction, finally becoming united to other tissues in the periphery of the body, is associated especially with the name of His, and has been accepted by the majority of embryologists. There have been other views held, but it will bo sufficient to mention only one of these, for it is the one which, next to that of His, has been favoured l)y investigators. Briefly it is as follows : the nerve-fibre is not a secondarily formed bridge between the central nervous system and the peripheral organs, but exists from the very first, and in subseijuent develop- ment it merely undergoes elaboration, and increases in bulk and in length as the distance from the central nervous system and CH. XIV.] REGENERATION OF NERVE 149 the periphery increases with the increasing size of the developing animal. T shall not fully discuss the pros and cons of this controversy, hut only say that the available evidence appears to mo strongly in favour of the first of the two views, and it has within the last few years been supported by a very remarkable ocular demonstration of its truth. Mr Eoss Harrison of the Johns Hopkins University, Balti- more, has actually seen the fibres growing outwards in embryonic structures. Pieces of the primitive nervous tube which forms the central nervous system were removed from frog embryos, and kept alive in a drop of lymph for a considerable time ; the cilia of the neighbouring epidermic cells remained active for a week or more ; embryonic mesoblastic cells in the vicinity were seen to become transformed into striated muscular fibres, and there was therefore no doubt that even under artificial conditions of this kind — rendered necessary for microscopic purposes — life and growth were continuing. From the primitive nerve-cells, and from these alone, nerve-fibres were observed growing and extending into the surrounding parts. Each fibre shows faint fibrillation, but its most remarkable feature is its enlarged end, which exhibits a continual change of form. This amoeboid movement is very active, and it results in drawing out and lengthening the fibre to which it is attached, and the length of the fibre increases at the rate of about a micro-millimetre in one or two minutes. Similar observations have since this been made in the embryos of other animals. I think these observations show beyond question that the nerve- fibre develops by the overflowing of protoplasm from the central cells, and thus give us direct evidence in favour of the view which most embryologists previously held mainly as the result of circum- stantial evidence. Such, then, being the general state of our knowledge regarding the way in which nerve-fibres grow in the developing animal, it is not surprising to find that the prevalent idea regarding their regeneration after injury follows the same lines. The original teaching of the elder Waller (1852), that regeneration occurs by fibres growing out from the central stump into the peripheral segment of the nerve, was formulated at a time when the relationship of nerve-fibres to nerve-cells was not so fully recognised as it is at present ; and the Wallerian doctrine may be accepted with confidence to-day. It has, however, been questioned from time to time, and the earliest to hold an opposite view was Vulpian. Vulpian, working with Philippeaux, cut nerves in young animals, excising long portions so as to prevent the two ends uniting. Some months later they were surprised to find that a number of new perfectly formed nerve-fibres had appeared in the peripheral segment, and that this segment possessed the physiological properties of being excitable and capable of conducting nerve impulses. To this 150 PHYSIOLOGY OF NKRVK [CB. XIV. phenomenon they gave the name of "autogenetic regeneration." The publication of these results ]»rovoked a long controversy, which lasted from 1859 to 1874, and was closed at the latter date by Vulpian withdrawing his new idea. He did so because in the meanwhile he had repeated his experiments more carefully, and so discovered that, although the ends of the divided nerve had not joined up, connection with the central nervous .system had neverthe- less been re-established l)y means of fibres growing into the peripheral segment from other nerves cut through in skin and muscle in the course of the operation. The controversy has been revived within the last few years, and the position of the disputants has been almost exactly the same as that occupied by Waller and Vulpian half a century ago. Modern investigators have, however, the advantage of being able to apply new methods of research, and are provided with many histological reagents of which the older workers were destitute. It is, however, never safe to argue entirely from microscopic appearances, for nerve- fibres may be simulated by non-nervous structures, and a strand that looks like a nerve-fibre is not really such unless it can be experimentally shown to be both excitable and capable of conducting nerve impulses. Vulpian's old doctrine of auto-regeneration has been revived in this country by Ballance and Purves Stewart, and in Scotland by Kennedy. The most prominent and persistent supporter of the autogenetic theory is, however, a German neurologist named Bethe. But none of these investigators have excluded the fallacy which underlay the work of Vulpian and Philippeaux, as has been recently pointed out by Langley and Anderson. These two workers at first thought they also had obtained evidence of purely peripheral regeneration, and it was not until they carried out careful dissections that they convinced themselves that union with the central nervous system had really occurred. The new nerve-fibres which grow into the peripheral segment from other nerves divided in the operation, often do so by a devious and contorted course. If the number of medullated nerve-fibres in the peripheral end is small, then the connection with central fibres was found to be slight ; and in cases where no connection occurred then medullated nerve-fibres were entirely absent. Bethe admits a variability in the number of medullated fibres, and this, though easily explicable on the view that such fibres come by accident from the central ends of divided nerves, is not accounted for at all by the autogenetic theory. Bethe's views have been contested not only by Langley and Anderson, but also by Lugaro, by Kttlliker, by Cajal, by Marinesco, by Mott, and Edmunds in conjunction with myself, and by numerous others. CH. XIV.] REGENERATION OF NERVE 151 I may mention a few of the experimental results which have come out of the renewed work elicited by the promulgation of the autogenetic theory. (1) It is possible entirely to prevent reunion with the central ends of divided nerves. In our own work we accomplished this by removing a long stretch of the main nerve experimented with, by making the skin incision as small as possible, and by inclosing the top end of the peripheral segment in a cap of sterilised gutta-percha. Under such circumstances no auto-regeneration occurs. (2) Pieces of nerve may be transplanted under the skin, and in time a few fully formed medullated fibres appear within the degener- ated bundle of fibres. This is adduced by Kennedy as undoubted evidence of auto-genesis, but, again, is easily explicable on the hypothesis that the new fibres had wandered in from cutaneous nerves divided in the course of the operation, and we showed that if this fallacy is excluded by transplanting the nerve, not into the subcutaneous tissues, but on to the stomach wall in a sheath of peritoneum, where invasion by nerves is practically impossible, no regeneration occurs at all. (3) The late appearance of the medullary sheath in those portions of the regenerating fibres which are most distant from the place where the nerve is originally cut and sutured, is a conclusive piece of evidence that the new nerve-fibres grew from the central end in a peripheral direction. (4) After regeneration has occurred, the nerve may be again cut across, either on the central side of the original point of section (as in Langley and Anderson's work), or on the peripheral side of the original seat of operation (as in our own work). In the former case Wallerian degeneration occurs in all the new fibres, showing that they were all under the nutritive control of the cells of the central nervous system In the latter case the degeneration took place solely on the peripheral side of the second cut. The direction of degeneration is always the direction of growth, so this experiment shows that the growth of the new fibres had not started from the periphery centralwards, but in the reverse direction. On looking up the literature of the subject, I found that Vulpian also did this experiment with the same result, and it can hardly be doubted that this formed one of the factors that later led him to abandon the autogenetic theory. An experiment on somewhat the same lines has been carried out recently by Lugaro : he has shown that regeneration of the cut nerves connected with the lower part of the spinal cord does not occur after that part of the spinal cord has been extirpated. This is a very striking piece of evidence, showing the dependence of the growth of fibres on the activity of the cells of the central nervous system with which they are originally connected. 152 PHYSIOLOGY OF NERYE [CH. XIV. Cajal, by the help of his new silver metliod, has come to the conclusion that the new formation of nerve axons in the peripheral stump is exclusively due to growth from tlie central end. He Fig. 155. — Olive-shapeJ swellings at tlie mils of nerve-tibres growini; distahvards from the central ends twenty-one days after the nerve had been divided. (Marinesco.) Fio. 150. — Spiral forms often seen in rfKenerating norve-libres : the fibres are seen to be of varying thickness, and each is provided with a torminal swellinj;. (Marioesco.) figures the long and often contorted course of those growing fibres in the swelling at the cut central end, and shows that they ultimately reach their goal — the peripheral segment — in time and in spite of all hindrances. The greater the obstacles interposed the later does the CH. XIV.] REGENERATION OF NERVE 153 union and consequent regeneration in the peripheral end occur. Ho also draws attention to the olive-shaped swelling at the free end of each growing axis-cylinder. These are also figured hy Marinesco, who calls attention to the fact that these terminal swellings, although they may roughly be described as olive-shaped, vary a good deal in external form; this is shown in the accompanying drawings (figs. 155 and 156), and is quite intelligible now that we have Eoss Harrison's description of the constant changes of form they exhibit in embryonic history. The two next figures (157 and 158) are drawn from preparations stained by Cajal's new method, and they require but little comment. They show the new fibres penetrating the cicatricial tissue of the junction from the central end in a peripheral direction ; they show the absence of any new axons developed autogenetically in the peripheral end. Such preparations ought to carry conviction to those who have any lingering belief in auto-regeneration, that the Wallerian view is the only possible one to adopt. It must not, however, be supposed that the peripheral end is entirely inactive ; for while degeneration is progressing in the axons and their fatty sheath, an active multiplication of the cells of the primitive sheath or neurilemma is taking place. These neuri- lemmal cells probably play a nutritive action towards the more important structures within them, and Graham Kerr, in a recent study of nerve growth in the fish Zepidosiren, has supported in a very conclusive and entirely independent way the view that Mott and I advanced some years ago of the value of the neurilemma in maintaining the nutrition of the axis cylinder. There is but little doubt also that these cells act as phagocytes in the removal of the degenerated products of the other portions of the nerve-fibre. But after this is accomplished they elongate and unite into long chains. It is this appearance that has led some observers into regarding them as true nerve-fibres ; they have jumped to the conclusion that the neurilemmal cells are also able to form a conducting core, and so have regarded auto-regeneration as a histological possibility. But all recent observations by the best methods, as I have already stated, have failed to discover either an axial core or a fatty sheath in these " embryonic fibres," as they have been termed. Howell and Huber put it very well twenty years ago, when they said the peripheral structures are able to prepare the scaffolding, but the axon, the essential conducting core of the fibre, has an exclusively central origin. The change in the neurilemmal cells which occurs in the peri- pheral segment is even more vigorous at the central termination of the cut nerve ; here its nutritive function (or apotrophic function, as Marinesco calls it) is effective, and provides for the nourishment of the actively lengthening axis cylinders. At the peripheral end, Fio. 157. — Longitudinal section of sciatic nerve of new-bom dog ei^'lit days aftftr tlio nervo had been divideil. Union bad already taken placo. At the extremity of the central fiid (A) crow- ing fibres are seen ninniiif; in various direc- tions towards the cicatrix (HI; C is the peripheral end, into which a few llbres are already penetrating. (Mannesco.) Ar^ ifi|ii .-TTl iliiiisi^i'iiiyii'^lifiiJ) ^1 Fio. 158.— Longitudinal section of dog's nerve, twenty-one days after the nerve liad been divided. A more advanced condition is seen than that shown in lig. 157. A is tlie central end ; li the cicatrix of union, where the nerve- tibres are seen in Rreat numbers taking an irrej;ular course. Into C, the peripheral end, many libres liave already successfully pene- trated ; m, to', to", etc., are the terminal swellings of libres growing from the central stump and directed towards tlie periphery, I'xcept in tlie case of to", where the twisting of the new llbre in its eflorts to gmw liad, at the time when tlie animal was killed, directed tlie termination backwards. (Marinesco,) CH. XIV.] SPINAL NERVE ROOTS 155 unless tho axons reach it, it is ineffective in so far as any real new formation of nerve-fibres is concerned. If, however, the axons reach the peripheral set^ment, the work of the neurilemmal cells has not been useless, for they provide the supporting and nutritive elements necessary for their continued and successful growth. Moreover, the neurilemmal activity appears to be essential. In the white fibres of the central nervous system the neurilemma is absent; in this situation not only is the removal of the products of degeneration a very slow process, but regeneration does not occur, Pixncticns 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 fibres of the blood-vesssels 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, 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. 159, A), one of which grows to the spinal cord, where it terminates by branching around the multipolar cells of the grey matter ; the other 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 (fig. 159, B). Fig. 159. — A, bipolar cell from spinal ganglion of a 4A 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 aUilii and roiKlurtiri/i/. — It is necessary to distinguish between these two properties of nerve. Chan.i:;i's in excitability, and in the power of conducting nerve impulses, do not necessarily go together, as shown in the following experiment : — The nervi- of a frog's leg is led through a glass tui)e, the ends of which are sealed with clay, care being taken that the nerve is not coni])ressed. 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 chamlier. 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 stinmlated 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 impidses. 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 stimuli. Velocity of a Nerve Impulse. This may be measured, as was first done by Helmholtz, 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. 105). 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. The same method may be employed in man for determining the rate of transmission in sensory nerves. A man is told to make a given signal, such as to open a key in an electrical circuit, when he receives a stimulus such as an induction shock appUed to one of his toes; the time between the excitation and the reply is easily measured. A second experiment is then performed in the same way, except that the stimulus is applied to another part of his body ; for instance, his knee. The time interval is again measured, and found 160 PHYSIOLOGY OK NKKVK [cO. XIV. to bo shorter ; the differencG between the time intervals in the two experiments will obviuusly measure the time occupied by the impulse in traversing a stretch of nerve equal to the distance between his toe and his knee. Another method, largely employed by Bernstein, is to take the electrical change as the indication of the impulse. A stimulus is applied to one end of a long nerve, and the change in the electrical condition of the nerve is recorded by a galvanometer connected to the other end of the nerve. The time between the application of the stimulus and the galvanometric reply is measured. The velocity of the nerve impulse has l)y such experiments been found to vary with temperature, and to be approximately the same in both motor and sensory nerves. In cold-blooded animals it is thus slower than in warm-blooded animals. In the frog, for instance, at ordinary room temperature it averages 27 metres per second. In man, at normal body temperature it is 120 metres per second. In the case of non-meduUatcd fibres the velocity is much slower; these ol)servations have been chiefly made on invertebrate animals; in the non-medullated nerves of the lobster it is 6, and in the octopus only 2 metres per second, and values lower than these have been recorded in other cases. 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 galvanometer experiment just .described, if the nerve is stimulated in the middle instead of at one end, the electrical change (the evidence of an impulse) 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. 103) 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 ''^'"' ^Sfte? waner°r'°"" ^^^^^^ cau be performed with the nerve that 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 tlie " discharge " of the electrical CU. XIV.] CKOSSING OF NERVES 161 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 which the 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 suppl}dng 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 versa. A series of equally important experiments have also 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 * The meaning of the term " synapse " is fully explained in Chapter XVI. (p. ISS). 162 I'llVSIOLOGY OV XKKVK [cil. XIV. cut. symiiatlicLic, in llio course of some weeks the vaj^us fibres grow into the sympathetic and form synapses around the cells of the superior cervical L!;angli(jn, and stimulation of the united nerve now produces such elFects 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. 164.) Such experiments as these are important because they teach us that though the action of nerves may be so diflerent in different cases (some being motor, so^ue inhibitory, some secretory, some 5~~| Superior f^ Cervical I I Ganglion Vy a: c ^° Fici. 1G4.— Diagram to illuslrale Laii^loy's exporiment on va;;us and cervical .syin|»aLhetic nerves. In A, the two nerv's are sliown intact ; the direction of the impulses they noinially carry is shown by arrows, and tlic names of some of the pirts they supply are mentioneii. In IJ, both nerves arc cut throii<;li. The dej;enerated portions are repn^sented by discontinuous lines. In C, the union d(?scril)ed in the text has lieon accomplished, anil stimulation at tlic point «' now produces the sama results as were in the intact nerves (A) proiluced by stimulation at a. sensory, etc.), after all what occurs in the nerve trunk itself is always the acme; the difTerence of action is due to difTerence eitlier in the origin or distribution of the nerve-fibres. If we remember the familrar 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 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 results as though the impulse had reached its destination by the usual channel. Cfl. XIV.] NATURE OK THE NERVE IMPULSE 163 The Nature of the Nerve Impulse. What ia the nature uf this change which we have proviyioiially been alluding to as a molecular disturbance ? The ancients imagined the nerves were tubes along which a flow of a spiritual essence (animal spirits) took place. We know that this is not the case, but we do not know anything else about it for certain. Theories there are in plenty, but none of tliem are adequate to explain the pheno- menon. The theories fall under two main headings, chemical and physical. In a chemical theory we may compare the transmission of the impulse to the propagation of a flame along a train of gunpowder ; but such an analogy is very imperfect, for the gunpowder is entirely consumed, and has not the power to repair itself as a nerve has. Nevertheless there are certain facts which make a chemical theory acceptable ; these are : — (1) Analogy with muscle, where the propagation of the muscular impulse is undoubtedly largely due to the propagation of chemical disturbances. (2) Evidence that the nerve does undergo metabolic changes, as shown by the necessity for oxygen, and the production of minute amounts of carbon dioxide. (3) Arrhenius and van 't Hoff showed that a rise of 10"' in tem- perature increases the velocity of a chemical reaction to two or three times its original rate. Purely physical changes are not accelerated nearly so greatly by the same rise of temperature. Maxwell's recent experiments show that a rise of 10' C. approximately doubles the velocity of nerve conduction, and the conclusion is drawn that, therefore, the nerve impulse is a chemical phenomenon. Keith Lucas confirmed this observation. Woolley obtained the same figure from the influence of temperature on the rate of conduction in muscle, so probably the conduction process is of a similar nature in both tissues. The physical theories in relation to this question compare the nerve impulse to the way in which an electrical change is projDagated along a wire. When the electrical accompaniment of nervous activity was first discovered this view was unhesitatingly accepted by many physiologists, and the current of action was regarded not as an accidental concomitant of the impulse, but as the change which really constitutes the essence of the impulse, and which serves to excite the chemical and other changes in the tissues to which the nerve is distributed. Two facts, however, stood out at once which rendered the adoption of this simple view difficult ; one of these is the slow rate of conduction in nerve ; and the other is the pheno- menon of inhibition ; it is quite conceivable that an electrical dis- turbance, feeble though it be, can fire off an excitable tissue and lead 164 PHYSIOLOGY OF NERVE [CU. XIV. to increase in its activity; it is much more difficult to understand how it can ])ossibly produce a lessening of action such as occurs in iiihihition. Nevertiieless the "discliarge hyi)otliesi.s," as it used to be called, has been revived of late in modified form, and electrolytic changes with liberatireak-up of phosphatides, and the liberation of phosphoric acid which is carried away as phosphates by the lymph and blood. The staining reactions of a degenerated nerve also indicate that the appearances are not only due to a breakdown in an anatomical sense, but in a chemical sense also. Of these staining reactions the one most often employed is that which is associated with the name of Marchi. This is the black staining which the medullary sheaths 168 riiYSinLOGv of nerve [cii. xiv. of degenerated ncrvc-filjres sliow when after hcing hardened in ^liiller's fluid they are treated with Marchi's reagent, a mixture of ^Killer's fluid, and osmic acid. Healthy nerve-fibres are not blackened by this reagent, because the nidre rapidly penetrating chromic acid of the Miiller's fluid lias already supplied the unsaturated oleic acid radical in the lecithin and other phosphatides with all the oxygen they can take up. But when the nerve is degenerated, the oleic acid is either increased in amount, or so liberated from its previous combination in the lecithin molecule, that it is then able also to take oxygen from osmic acid and reduce it to a lower Itlack oxide. In the later stages of degeneration the Marchi reaction is not obtained, because the fat globules have then been absorbed. In certain diseases of the central nervous system, such as general paralysis of the insane, degeneration occurs on a large scale, and the products of the chemical disintegration of the cerebral tissue have been sought for in the blood, but with more profitable results in the cerebro-spinal fluid. This fluid under those circumstances shows an excess of protein which is mainly iiucleo-protein ; cholesterin can also be usually detected in the fluid, and so also can choline or some similar base which originates from the decomposition of phosphatides. Although many physiologists have taken up the choline question and the methods for identifying this base, it must be admitted that the tests hitherto devised are not absolutely conclusive, for sufficient of the base cannot be collected for a complete analysis. The base which is present if not choline is a nearly related substance, perhaps a derivative of choline, and according to the latest researches the questionable material is trimethylamine, which we have already seen is a cleavage product of choline. Cerebro-spinal fliiid. This plays the part of the IjTiiph of the central nervous system, but it 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 protein matter (globulin) and a small amount of sugar. Normally it contains neither nucleo -protein, cholesterin, or choline, and practically no cells. Colourless corpuscles, however, occur in it in inflammatory conditions. There is no doubt that the fluid is a true secretion, and that the cells which secrete it are the cubical epithelial cells which cover the choroid plexuses. The choroid structure may indeed be spoken of as the choroid f/lanJ ; only it differs from other glands in having the secreting epithelium on its outer surface. Injection of an extract of the choroid plexuses into the circulation causes a very rapid increase in the flow of the cerebro-spinal, fluid which can be collected from a cannula thrust into the subcerebellar space, or into the lumbar regirtions of a nerve, or to two dilferent nerves, and by tilting the cradle to ri,n:lit or lei I the current can be sent tliroufili one or the other pair of electrodes. Tlic 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 is placed as a bridge on the course of the battery current. (See fig. 166.) The current is thus divided into two parts: one part through Simple Kheochord. 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 -"'>X Hr^;; ':-"":■ t y - HL' U,l-yLMJd Fio. 107. — roggenilorfs Rlifoclionl. that the resistance can be varied to a much greater extent than in the simpler form of the instrument. CH. XT.] KLECTROTONIC CURRENTS 171 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 cvirrents. — The constant current is passed through the nerve from a battery, non-pularisable 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. 168) 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 hateledrotonic current ; and that in the neighbour- hood of the anode is called the aneledrotonic cui^rent. In both cases the electrotonic current has the same direction as the polarising current. These currents are dependent on the physical integrity of medullated Aneledrotonic rh ^ Katelectrotonic Current \ \ > \ | Current Polarising Current Fio. 108.— Electrotonic currents. nerve; they are not found in muscle, tendon, or non-medullated 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-elcctrotonic currents occur in different directions in the three regions tested. (eriment the nerve-fibres themselves liranr/i, 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 slilf l>i/ side in the sciatic trunk ; there is therefore no possibility of conduction of a nerve impulse in^both directions; the stimulus, moreover, must be an electrical one. Electrotonic alterations of excitability and conductivity. — When a constant current is passed through a nerve, the excitaViility 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 V)e shown in the case of a motor nerve by the following experiment. The next diagram represents the apparatus used. ^ >:> ./ ■■■^ % Cells' ^ fxk: 'Cei/ -f — r O Reverser ■jj O c cv// " vV EXCITING CIRCUr Sen., _ f^iiscle Fig. 1C9.— 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 CH. XT.] CHANGES IN EXCITABILITY 173 may be recorded on a stationary blackened cylinder. The cylinder is moved on a short distance, and this is rei)eaicd. The height of the lines drawn may be taken as a measure of the excitability of the ner\'o. The polarising current is then thrown in, in a descending direction {i.e. towards the muscle) ; the katlwule 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 kat- electrotonic, A when it is anelectrotonic. Exactly similar results are obtained if one uses mechani- cal stimuli instead of in- duction shocks. The best mechanical form of stimulus is to allow drops of mercury to fall on the nerve. The same is true for chemical stimuli. If the ex- citing electrodes are removed, and salt sprinkled on the nerve near the muscle, the latter soon begins to quiver ; its con- tractions are increased by throwing in a descending and diminished by an ascending polarising current. The increase in irritability is called katelectrotonus, and the decrease is called anelectrotonus. The accompanying diagram (lig. Fig. 170.— Electrotouus. M, make. B, break. 174 ELECTUOTONUS [CII. XV. 171) shows how Iho oflbct is iiiost intense ul, the jtoints (a, k) where the electrodes are applied, and extends in f^radually diminisliing intensity on each side of them, between the electrodes the increase shades off into the decrease, and it is evident that there must be a A \ Fig. 171. — Diaj;rani illustrating the effects of various intensities of the polarising current, v, n', Nervo, o, anode ; A', kathode ; the curvi's 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 (I, and as the current is increased in strength, the changes in irritability are greater, and the neutral point approaches k. neutral point where there is neither increase nor decrease of irritability. The position of this neutral point is found to vary with the intensity of the polarising current — when the current is weak the point is nearer the anode, when strong nearer the kathode. Pfliiger'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 maybe demonstrated in the following way (fig. 172); Flo. 172. — Arrangement of apparatus for demonstrating Pfliigcr'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 load wdres 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 CII. XV. PFLUGEIiS LAW OF CONTRACTION 175 is vurioil by llie slider S. The nearer S is to llie biiuling screws tlio 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. With a stronger current (ascending or descending) contraction occurs both at make and break. With a very strong current (six Groves), 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 Pfliiger's Law of Contraction. Strength of cobrest dsed. Weak . Moderate Strong . Descendikq Current. Ascending Cdrrent. Make. Break. Make. Break. Yes. Yes. Yes. No. Yes. No. 1 Yes. Yes. No. No. Yes. Yes. 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 cases 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 niuscle 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 methods he adopted. Gotch's much more trustworthy experiments with the 176 ELECTR0T0NU8 [CIL XT. electrometer iire directly opposed to those of Stewart. The foUowin;^ simple experiment devised by Ciotcli appears to be (]uite conclusi\ e that conductivity like excitability is lessened at tlie anode when tiie current is made, 'three non-polaris- able electrodes arc employed (fi;;. 173). 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 (A, to K) is longer, because in tiiat case tiie nerve impulse has to traverse a region of nerve at A, in which the power of conduction is lessened. • 1 1 1 — Fig. 173. — Diatjr.im lo illuslruto Gotch's oxijerimunt willi 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 stimidating electrode at the make, and the anode at the break, may be easily 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. 122, p. 100), 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 it starts 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 bo the more effective in causing contraction. Eesponse of Human Muscles and Nerves to Electrical Stimulation. Perhaps the most imj)ortant outcome of this study of the response of muscle and nerve to electrical stimulation is its application to the muscles and nerves of the human body, ])ecau8e here it forms a most valuable method of diaunosis in cases of disease. en. XV.] LAW OF CONTRACTION IN MAN 177 In the normal state, nerves can be stimulated through the moistened skin 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. When the motor nerve is degenerated, and will not respond to any form of electrical stimulation, the muscle also loses all its power of M 178 KLECTROTONUS [CFl. XT. response to induction shocks. The nerve-degeneration is accompanied by changes in tlie 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 of the muscle 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-contraction 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 imtient. 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 \y\\\ 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 PHiiirir's law of contraction, a.s formulated for frogs' muscles and nerves, is true for human nmsdes and nerves in the main, but there are certain discrepancies. These arise from tlie method necessarily employed in man being different from those used with a muscJe-nerve preparation. In a muscle-nerve preparation the nerve is dissected out, the two electrodes })laied on 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 ClI. XV.] REACTION OF DEGENERATION 179 which consist of metal discs covered with wasli leather, and soaked in brine. One of these is plaied on the moistened skin over the nerve, and the other on some indifferent point, such as the baek. Tiie 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 readies 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 eflfect will predominate, the points being more concentrated, the hitter effect may prevent a pure anelectrotonic effect being observed (fig. 174). 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. 174. — 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 investigated this question afresh, and found 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. 174 ; 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 XVI NERVE-CENTRES The nerve-centres consist of the brain ami 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, such as 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 tentli), 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 o])tic) 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. 155-158). 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. Tiiey are called respectively white matter and grey matter. en. XVI.] WHITE AND GT^EY MATTER 181 Mec'.'jlL Odloiia^^ r//>/,.cr £-:fi-e},U( of S/'.bial Cord Vei-{ebrc,^ 'mm \Vhite. matter is composed of modullated nerve-fibres, which differ in structure from the medul- lated 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 LoimvExh-einttu . .\J -ist Lam.hn'.r Verfehc. i..:x ^ Fh;. 175.— View ol' the cerebro-spiiial axis of the uervuus 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 lirst part of the lifth and ninth cranial, and of all tlie spinal nerves of the right side, have been dissected out and laid separately on the wall of the skull and on the several vertebrse opjiosite to the place of their natural exit from the cranio-spinal cavity. (After Bourgery.) 182 NFRVE-CKNTRKS [cn. XVT. the pia mater. Tlie other fibres of tlie tissue are cell processes of the neuroglia or glia cells projicr, or spider cells as they are some- times termed (see fig. 176). Neuroglia is thus a connective tissue in function, but it is not one in origin. Like the rest of the nervous system, it originates horn the outermost layer of the embryo, the epiblast. All true connective tissues are mesoblastic. Chemically, it is very difTerent from connective tissues. It con- Fio. 170.— Branched neuroglia-cell. (After Str.lir.) sists of an insoluble protein material called neuro-keratin, or nerve- horn, similar to the horny substance, keratin, which is found in the surface layers of the epidermis. Structiire 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. 177). en. XVI.] NERVE-CELLS 183 Tlic simplest ncrve-cclls known arc termed hpolnr. Tn 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. 178 (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 bo unipolar. This is shown in a more diagram- matic way in fig. 159, p. 155. The bifurcation of the nerve-fibre is Fio. 177. — Diagram after Ramon y Cajal to show the ontogenetic (or embryological) and pliylogenetic (i.e. in the animal seriS) development of a neuron. A, cerebral cell of frog ; B, newt ; C, mouse ; l), man. As the place in the zoological series rises, the neuron increases in complexity and in the number of poiats of contact ; this is produced partly by an increase of the dendroiis, 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. 178 (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. The majority of nerve-cells found in the body are multipolar. Here the cell becomes angular or stellate. Fig. 179 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 ; 184 NFTRVE-CENTIIKS [CIT. XVI. but one process, and one process only, of eacli coll 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. N.S. Via. 17S. — Bipolar ner\-e-cell3. A. From the Gassprian ganglion of tlie pike (after Bidder). B. From a spinal gant,'lion of a 41 weeks' human f-mbryo (after His). C. Adult condition of the mammalian spinal ganglion cell : X. S. nucleated sheath ; only the nuclei seen in prolile are represent**'!. T. is the T-shaped junction (after Retzius). Fig. 180 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 contains a number of angular or spindle-shaped masses, which have a great affinity for basic aniline dyes like methylene blue. They are 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. CU. XVT.] NERVE-CELLS 185 In preparations made by Golgi's chromate of silver method, the cells and their processes are stained an intense lilack by a deposit of Fir.. 179. — An isolated sympathetic ganglion cell of man, showing sheath with nucleated cell lining, 13. A. Ganglion cell, with nucleus and nucleolus. C. Branched process. D. Axis cylinder process (Key and lietzius.) x 750. silver. The various structures in the cells (nucleus, granules, fibrils, etc.), are not visible in such preparations, but the great advantage of Fio. ISO. — Multipolar nerve-cell from anterior horn of spinal cord ; a, axis cylinder process. (Max Schultze.) 18G NERVE-CENTRES [cii. xvr. the method is that it enables one to follow the branches to their finest ramifications. It is thus found that the axis cylinder process is not un branched, as represented in fig. 180, 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 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 envelop- ing other nerve-cells ; the col- laterals also terminate in a similar way. The longest type of axis cylinder is that which Fio. 181. — Pyramidal cell of human cerebral cortex. Golgi's method. passes away from the nerve-centre, and gets bound up with other similarly sheathed axis cylinders to form a nerve; but all ulti- mately terminate in an arbor- escence 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 1S2. — Ci-rebral cortex of mammal, prejjared by Golj;i's method. A, B, C, 1), V, iier\'e* cells; E, neuroglia-cell. (Hamoii y Cajal.) CIT. XVI.] NERVE-CELLS 18? shape. Thoy arc especially larf,re and numerous in what are called the motor areas of the brain. The apox of the cell is directed to the surface ; the ajncal 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 originate ; the axis cylinder comes off from the base of the pyramid. (See figs. 181, 182). The grey matter of the ceretellum contains a large number of small nerve-cells, and one layer of large cells. These are flask-shaped, and are called the cells of Furkinje. The neck of the flask breaks up Pin. 183.— Cell of Purkinje from the human cerebellum. Golgi's method. (After Szymonowicz.) into branches, and the axis cylinder process comes off from the base of the flask (fig. 183). 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 called protoplasmic processes, are now termed dendrons. 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 188 NERVE-CENTRES [CIT. XVI. the complete nerve-imit, that is, the Ijody of the coll, and all its branches. The fibrils of the axon may be traced through the body of the cell from the dendrons. The next idea which it is necessary to grasp is, that each nerve- unit (cell j9/«s branches of both kinds) is anatomically independent of every other nerve-unit. There is no true anastomosis 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 con- tinuous structures. A convenient expression for the intermingling of arborisations is synapse (literally, a clasping). Fig. 184 is a diagram of the nervous path in a spinal reflex action. Excitation occurs at S, the skin or other sensory surface, and the A.C.C Fiii. 184. -Reflox action. impulse is transmitted by the sensory nerve-fibre to the central nervous system. It does not become anatomically connected to any of the cells of the central nervous system. The only cell-body in actual continuity with the sensory nerve-fibre is the one in the spinal ganglion (G) from which it grew. On entering the spinal cord, the main fibre conveys impulses upwards which ultimately reach the brain, but in the spinal cord it gives off fine side branches or collaterals which terminate in branches that arborise around one or more cell l)odies and their dendrons; these cells are small ones situated in the posterior cornu of the spiiuil grey matter ; one only (P.C.C.) is shown in the diagram. The short axon of this cell similarly terminates by a synaptic junction with one or more of the large CII. XVI.] SYSTEMS OF RELAY 189 multipolar cells of the anterior cornu of the spinal grey matter; one of these sliown in the figure is labelled A.C.C. This motor-cell is thus stirred up to action and sends an impulse by its axon to the muscular fibres (M) it supplies. Thus excitation of the skin will cause, by this spinal reflex arc, the contraction of muscles. In some cases severe excitation will cause contraction of the muscles of the opposite side of the body (crossed reflex); under such circumstances the intermediary neuron (P.C.C.) sends its axon to the anterior horn-cells of the opposite side. The synaptic junctions a-re naturally the places which the impulse has the greatest difficulty in traversing ; and some observers believe that at the points of contact there is a kind of undifferentiated interstitial protoplasm which the impulse has to get through. This example illustrates a most important general truth, namely, 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 remembered that a nervous impulse travels more slowly than electricity. Suppose, now, one wishes to send a message from the metropolis, which will represent 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 messenger on foot or horseback. There are at least two relays on the journey. We may take another illustration of this. Suppose one wishes to move the arm ; the impulse 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 from these cells fresh nerve- fibres pass on the impulse to the arm-muscles. This is shown in the accompanying diagram (fig. 185). The cell of the cerebral grey matter is represented by C.C., and its axon (pyramidal fibre) by P.F. This passes into the white matter of the brain, and in the medulla oblongata it crosses over, and then travels down the opposite side of the spinal cord. It enters the grey matter in the 190 NERVE-CENTRES [CH. XVI. part of the cord which controls the arm moveinonts, and terminates by arborising around small cells at the base of the posterior cornu (I'.C.C.); thence the im- pulse is transferred to the large motor cells of the anterior cornu (A.C.C.), and the final link in the chain is formed by the motor nerve-fibres to the muscular fibres (M). The spinal cord cells are thus surrounded by arborisa- tions (synapses), derived not only from the sensory nerves 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 im- pulses from the brain. The system of relays is still more complicated in the case of sensory im- pulses, as we shall see later on; the same is true for the motor path to involun- tary 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 ofif from its connection with the spinal nerve-cell, the peripheral end degenerates as far as the muscle. Suppose, now, the pyra- midal fibre were cut across, the piece still attached to the brain-cell would remain in a compara- tively normal condition, but the peripheral end would degenerate as far as the next synapse. 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 KUJ. 185.— Diagram of the neurons of the motor path. CII. XVI.] LAW OF AXIPETAL CONDUCTION 191 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 overgrowth of neuroglia. Degenerated tracts conse- quently stam differently from healthy white matter, and can by this means be easily detected. 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 indivi- dual 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 Law af 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 refiexes 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 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 0'150 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 192 NERVE-CENTRES [Cll. XVI. synapses throii^li which it has to travel (see later, on the structure of the visual and auditory mechanisms). The valved condition of nervous paths also explains another difficulty. We have seen on p. 160 that under certain circumstances a nervous impulse will travel in both directions along a nerve. Yet wlien 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 fe 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 neurons of the spinal ganglia; 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 centripetally, is simply arguing in a circle. The Significance of Nissl's Granules. If portions of the brain or spinal cord arc fixed in absolute alcohol, and sections obtained from the liardened pieces are stained by means of methylene blue, the nerve-cells exhibit a characteristic appearance. The nucleus and nucleolus take up the blue stain, but the total amount of chromatin present in the nucleus is not large, except in embryonic nerve-cells ; throughout the cell body a number of angular- shaped masses, which are termed Nissl's granules, are also stained blue. These extend some distance 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 such as 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 Nissl granules is an iron-containing nucleo-protein. 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 conii)ared it to the granular material wliich is present in secreting cells; in these cells before secretion occui's, the granules accumulate, CH. XVI.] nissl's gkanules 193 and during the act of secretion they are discharged and converted into constituents of the secretion. It is stated by some observers that the Nissl 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 Nissl granules have disappeared, or at least broken up into fine dust-like particles, so that the cell presents a more uniform blue staining. This is called chromatolysis (see fig. 186). It is, however, doubtful whether this is due to a transfor- mation associated with intense activity, or whether it may not be Fio. 186. — -Nissl's granules. A. Normal pyramidal cell of human 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 anajmia. Notice great swelling of the nucleus, and advanced chromatolysis, most marked at the periphery of the cell. 700 diameters. (After Mott.) caused by venosity of the blood. The cells are very sensitive to altered vascular conditions ; anaemia, for instance, produces a similar change accompanied with swelling of the cell, and swelling and in extreme cases extrusion of the nucleus. The most convincing observations in reference to the influence of fatigue in producing chromatolysis have been made on bees ; their nerve-cells are rich in chromophilic material when they are about to leave the hive in the morning. In the evening, after a hard day's work, this material is much reduced in quantity. By this sensitive method neurologists have 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, or after being subjected to the action of certain poisons, and N 1!)4 NERVE-CENTRES [CH. XVI. valuable results liave been obtained. AVe will, however, be content with alluding to only one pathological condition, namely, that pro- duced by extremely higli fever (hyperpyrexia); in this condition chromatolysis i.s very marked and is produced by the coagulation of the proteins of the cell-protoplasm by the high temperature. The questi(jn has arisen whether the Nissl granules are present as such in the living coll, or whether they are artifacts produced by the fixative action of strong alcohol. 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. The view most generally held is that the granules are artifacts, and that the actual Xissl substance in the living nerve-cell is a fluid plasm of rich nutritive value to the fibrils. 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 between which the Nissl substance lies 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 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 chromatolysis. Classification of Neurons according to their Function. In addition to the anatomical classification of the nerve-cells already given, they may be grouped into four chief classes on a physiological basis : — 1. Afferent neurons. 2. Efferent neurons. 3. Intermediary neurons. 4. Distributing m-urons. 1. Aj^creiit neurons. — Originally tlie cell bodies are situated at the periphery, and are connected with a process or afferent fiVire which passes to and arborises among the nerve-cells of the central nervous CH. XVI.] CLASSIFICATION OF NERVE-CELLS 195 system. This primitive coudition 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. 187). Ultimately in the vertebrates the body of the Earth -worm N ereis Vertebrate Fio. 187.— Diagram to illustrate the primitive conditions of the afferent 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. cell approaches close to the central nervous system, in the spinal ganglion of the posterior root, and the peripheral sensory nerve-fibre is correspondingly longer. The afferent neurons such as those of the spinal ganglia and the corresponding ganglia of the cranial nerves, are peculiar in possessing no dendrons. 2. Efferent neurons. — The anterior horn-cells of the spinal cord are instances of these ; their axons go directly to muscle fibres. 3. Intermediary neutrons. — 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 coiirdination, and thus their activity underlies psychical phenomena. 4. Distributing neurons. — These are the cells of the sympathetic 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. CHAPTER XVII THE AUTONOMIC NERVOUS SYSTEM Allusion has frequently been made in the foregoing chapters to sympathetic nerves. These nerves govern the processes in the body over which we have no voluntary control. They innervate cardiac muscle, the plain muscle in the walls of blood-vessels, and in the walls of other contractile viscera such as the stomach and intestine, the bladder, and the organs of generation. Secretorv nerve-fibres also come into the same category. In the chapters which im- mediately follow this one, we shall be studying such organs, organs which carry on the vegetative functions of life as it was formerly the custom to call them. It is therefore desirable that, at the outset, we should obtain some general idea of the nervous mechanism involved in controlling and regulating these functions. The sympathetic system proper consists of a chain of ganglia or collections of nerve-ceUs, situated on each side of the vertebral column. These ganglia correspond roughly with the spinal seg- ments ; the uppermost is called the superior cervical ganglion, and the next the inferior cervical ganglion ; these are the only two ganglia in the cervical region in the dog; in man there is a middle cervical ganglion in addition. The inferior cervical ganglion is connected to the first thoracic ganglion (a large ganglion sometimes caDed the ganglion stellatum) by fibres, some of which go in front of, and others behind the suljclavian artery ; this ring around the artery is called the annulus of Vieussens ; after this the correspondence of the ganglia to the spinal nerve roots is more exact, and we finally reach the ganglion at the end of the chain, the ganglion coccygeum. AH these ganglia (with the possible exception in some animals of the inferior cervical ganglion) send bundles of nerve-fibres to the spinal nerves, and the communicating strands between the ganglia and the spinal nerves are termed the rami communicant cs. The rami communicant^s are divided into white and grey. The white rami consist of meduUated fibres of small diameter; the grey rami consist mainly of non-meduUated nerve-fibres. The sympathetic chain, then, is a system of ganglia longitudinally CIT. XVII.] THE AUTONOMIC NERVOUS SYSTEM 197 arranged, and these ganglia are called the vertebral or the lateral giinglia. In connection with the lateral chain are other outlying ganglia, such as the semilunar ganglion, froni which the coeliac plexus takes origin ; the superior mesenteric ganglion, and the inferior mesenteric ganglion, f«)m which the hypogastric nerve takes origin. These outlying ganglia are called the collateral or the prevertebral ganglia. These differ from the lateral ganglia in not sending any fibres back to the spinal nerves ; their fibres pass onwards to the thoracic, abdominal, and pelvic viscera. Finally, there are ganglia situated in the walls of the organs themselves, as, for instance, those in the heart wall, and those in the plexuses of the wall of the alimentary canal Tthe plexuses of Auerbach and of Meissner). By some, these ganglia are included with the collateral ganglia, but it appears better for descriptive purposes to speak of them as Gaskell does, as a third group, and name them the terminal gamglia. The sympathetic system thus consists of three sets of ganglia with strands connecting them together, and all come into ultimate connection with fibres which leave the spinal cord. There is, however, another set of ganglia which are related anatomically in a similar way to some of the cranial nerves, and physiologically with the involuntary muscles and glands in the head region as well as with some of the thoracic and abdominal organs. Thus we have the ciliary ganglion in connection with the third cranial nerve; then there are such ganglia as the spheno-palatine, otic, and submaxillary, in connection with other cranial nerves. It has been considered wise not to extend the term sympathetic to these, but to include both them and the sympathetic system under one common term, and Langley's suggestion that this word should be autonomic has been very generally adopted. The word indicates that they possess a certain power of self-government, and are to some extent, at any rate, independent of the central nervous system. The impulses that pass to the involuntary musculature of the body arise in the central nervous system, and travel to the ganglia of the autonomic system by means of fine medullated nerve-fibres; the diameter of these fibres varies from 1-8 to 3-6 /x; the fibres therefore contrast with the motor fibres which pass to voluntary muscles; the diameter of these being 14 to 19 ix (see fig. 95, p. 77). There is a further contrast in the two cases; the motor fibres to voluntary muscles pass uninterruptedly from the brain or cord until they terminate in the end-plates of the voluntary muscles. The autonomic fibres, on the other hand, terminate by arborising around cells in one or other of the autonomic ganglia, and from the ganglion cells a fresh relay of nerve-fibres carries on the impulse to the 198 THE AUTONOMIC NERVOUS SYSTEM [CH. XVII. iiivoluiitary musclos. Thoro is thus an oxfcra cell-station or synaptic junction outside the central nervous syst(,'ni altogether. The autonomic path, in other words, consists of two neurons; one from the central nervous system to the f^anglion, and a second from the ganglion to the peripheral tissue. The first a.xon is termed the prc- (langUonic fibre; the second, the po^/-ganfjlio7nc fibreT The pre- ganglionic fihres are fine medullated ones, and the postganglionic fibres are usually non-medullated, but there are exceptions to this rule. The small medullated or pre-ganglionic fibres arise from the following four regions of the central nervous systeni. 1. From the mid-brain, issuing therefrom liy the third cranial nerve (motor oculi). 2. From the medulla oblongata, issuing therefrom in the seventh (facial), ninth (glosso- pharyngeal), tenth (vagus), and eleventh (spinal accessory) nerves. 3. From the thoracic region of the spinal cord, issuing therefrom in the anterior roots of tlie spinal nerves and jiassing from these by the white rami communicantes to the sympathetic ganglia. These occur in all the nerves from the first or second thoracic, as far down as the second, third, or fourth lumbar nerves. 4. From the sacral region of the spinal cord, issuing therefrom by the anterior roots of the second, third, and fourth sacral nerves, and thence passing by white rami communicantes to sympathetic ganglia; these fibres supply the descending colon, rectum, anus, and urino-genital organs in the pelvis, and they constitute the nervi erigentes. It will be noticed that in the spinal district white rami com- municantes only occur in certain regions: but all the spinal nerves have grey rami which consist of post-ganglionic fibres returning to the spinal nerves for distribution to the blood-vessels of the body wall, to the muscles which erect the hairs (pilo-motor nerves), and to the sweat glands of the skin. The general arrangement of such nerves is represented in fig. 188. The cell-station of any particular pre-ganglionic fibre is not necessarily situated in the first ganglion to which it passes; the fibres of the white ramus communicantes of the second thoracic nerve, for instance, do not all have their cell-stations in the second thoracic ganglion, but may pass upwards or downwards in the chain to a more or less distant ganglion before they terminate by arborising around its cells. It therefore follows that fibres that leave any given spinal nerve by its white ramus, do not necessarily return as post-ganglionic fibres by the grey ramus to the same spinal nerve, although, for the sake of simplifying the diagram, they arc repre- sented as doing so in fig. 188. en. XVII. ] THE AUTONOMIC J'ATI! 199 SPINAL GANGLION Fio. 188. — Diagram of tlie autonomic patli in the spinal region. A.C.C. anterior comual cell giving rise to a large motor nerve-fibre which is distributed to voluntary muscle (V.M.). I.L.T. a small cell of the intermedio-lateral tract giving rise to a small medullated nerve-Bbre which leaves the eord by an anterior root, and leaves the anterior root by the while ramus (W.B.) ; it terminates by arborising around cells in a ganglion of the sympathetic chain. From these cells fresh non-medullateil axons continue the impulse, and return to the spinal nerve by the grey ramus (G.R.) being finally distributed to involuntary muscular fibres (I.M.). The pre-ganglionic path is coloured red, the post-ganglionic blue. To complete the diagram, a posterior root-fibre is also shown with its parent coll in a spinal ganglion. SPINAL CORD LATERAL GANGLION Pre- ganglionic — -* ) Post-ganglionic fibres A. SPINAL CORD LATERAL GANGLlCN SOLAR GANGLlOri Pre''-gang(/on/c fibre ''/e2>-T- ■j>-f- Post-gang/ionic fibres ^3>-»r; B. '^-^^ '"Pre- qanq. fibref - \PosC-gang fib res Pes t-ga ng I ionic fibre ~ ' Fig ISO.- Arrangement of pre- and post-ganglionic fibres in splanchnic and inferior splanchnic nerves. (After Langley.) 200 THE AUTONO>nC NERVOUS SYSTEM [CM. XVII. Furthermore, there are many fibres of the white rami which enter the lateral chain of ganglia and pass through them witliout com- municating with their cells at all, and never return to the spinal nerves by grey rami. They pass out of the lateral chain either to collateral or even terminal ganglia before reaching their cell-stations, whence they emerge as post-ganglionic fibres. This is the case for the sympathetic supply of the blood-vessels of and involuntary muscular fibres of the thoracic, abdominal, and pelvic viscera, and is therefore true for such important nerves as the cardiac accelerators, the splanchnics, and the nervi erigentes. Fig. 189 shows the course of the splanchnic fibres, and will assist the student in grasping this method of distribution. The great majority are arranged as in A, that is to say they have their cell-stations in the solar ganglion. Comparatively few are arranged as in B, where some fibres do not reach their cell-stations until they arrive at the terminal ganglion situated in the walls of the viscus (for instance, the pancreas) to which they are distributed. A few possibly and occasionally are arranged as in C, with a cell-station for some of their branches in the lateral sympathetic chain. It will be noticed that if any post-ganglionic fibre is traced back- wards, there is one and only one cell-station between the central nervous system and the ultimate distribution of the nerve fibrDs. The next question that arises is, how have all these facts been ascertained ; for it is obviously impossible to follow the individual fibres with the microscope, and still less with the naked eye. The method above all others which has proved successful in solving the problem is the nicotine method, originally introduced by Langley and Dickinson, and employed since by Langley mainly in conjunc- tion with H. K. Anderson. The Nicotine Method. — Nicotine in small doses paralyses nerve- cells, but not nerve-fibres. Before the paralytic effect of nicotine comes on, it excites the nerve-cells, and this in the case of the blood- vassels causes a general constriction of the arterioles, and a con- sequent rise of arterial pressure. It is still a matter of uncertainty whether the drug produces these effects on the nerve-cells themselves or on the terminal arborisations (synapses) of the fibres that sur- round them, or on receptive substances (see p. 164) either in the cells or present at the synaptic junctions. But whichever of these modes of action is the correct one, the main result is the same; a nervous impulse which reaches a ganglion by a pre-ganglionic fibre cannot get across to the corresponding post-ganglionic fibres if the animal is poisoned with nicotine. Stimulation of the anterior nerve- roots, or of the white rami no longer produces movements of the involuntary muscular tissues, because the paralysed cell-stations act as blocks to the propagation of the impulses. If, however, post- CH. XVII.] AUTONOMIC PATHS 201 ganglionic fibres are stimulated, the usual effects (for instance, constriction of blood-vessels, erection of the hairs, etc.) take place. If instead of injecting nicotine into the circulation, and so producing a general effect, the nicotine is painted over one or more ganglia, there will be a block in those fibres only which have their cell- stations in those particular ganglia. By patiently examining all the ganglia in this way in turn, stimulating the fibres that enter it and those that leave it, Langley and his colleagues, after years of work, have been successful in localising the cell-stations on most of the autonomic paths in the body. We shall in later chapters be considering the autonomic nerve supply of the individual organs, but it will be convenient here to state in a general way the main course of the distribution of these nerves; we have seen that the outflow from the central nervous system occurs in four regions, and therefore we may take these seriatim. 1. The autonomic nerve-fibres which arise from the mid-brain. — These emerge by the third nerve ; the pre-ganglionic fibres pass to the ciliary ganglion; the post-ganglionic arising from the cells of this ganglion run in the short ciliary nerves to supply the intrinsic muscles of the eyeball (sphincter iridis and ciliary muscle). 2. The autonomic nerve-fibres which arise from the medulla oblongata. — These emerge by the following nerves : — (a) Seventh and ninth nerves. These supply the blood-vessels with vaso-dilator fibres and also the secreting glands in the nose and mouth region. Many of these fibres (for instance, those in the chorda tympani) get bound up with branches of the fifth nerve, and are distributed with them. The ganglia on the course of these fibres are the spheno-palatine, otic, submaxillary, and sublingual ganglia. {b) Tenth and eleventh nerves. These are distributed by the branches of the tenth or vagus nerve to the oesophagus, stomach, and part of the intestine, to the bronchial muscles, to the heart, and to the gastric and pancreatic secretory mechanism. Here our know- ledge of the localisation of the cell-stations is not so exact as it is in other parts ; some of the fibres appear to have their cell-stations in the ganghon on the trunk of the vagus, but in most cases they do not become post-ganglionic until the terminal ganglia in the walls of the various organs mentioned are reached. 3. The autonomic fibres which arise from the thoracic region of the spinal cord. — These constitute the best known of the autonomic fibres, and we may describe them according to their distribution under the following two headings : — (a) The white rami leave the spinal nerves and find their cell- stations in lateral ganglia, returning by the grey rami for distribution 202 TIIK AUTONOMIC NKKVOUS SYSTEM [OII. XVII. to the iuvolunLiiry muscular tissue ami ene(l, and a jian .t lii'ir rigiil and anterior walls rpmoved, so as to show their interior. A. — 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 ; -f +, placed in the auriculo-ventricular groove, where a narrow portion of the adjacent walls of the auricle and ventricle has been preservecl ; 4, 4, cavity of the right ventricle, the uiiper figure is immediately below the sendlunar valves ; 4', large columna carnea or musculus papillaris; 5, 5', 5", tricuspid valve ; 6, placed in the interior of the pulmonary arterj', a part 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, conca\ity of the aortic arch close to the cord of the ductus arteriosus ; S, ascending i)art 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.) The left auricle is best seen from behind. It receives on either side two pulmonary veins. The left auricle is somewhat thicker than the right. The left auriculo-ventricular orifice is oval, and a little smaller than that on the rijjht side. CH. XIX.] THE HEART 211 77i6 left ventricle occupies the chief part of the posterior surface. In it are two openings very close together, viz., the auriculo-ventrj- Fiii. 192. — Tlie left auricle and ventricle opened and a part of tlioir anterior and left walls removed. A. — The pulmonary artery lias 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', jjlaced 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 iiarrow 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 ; 6, 6', 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 pulmonarj- 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.) cular and the aortic, guarded by the valves corresponding to those of the right side of the heart, viz., the hicuspicl or mitral and the semi- 212 THE CIRCULATORY SYSTEM [CII. XIX. lunar. The walls of the left ventricle, which in man are nearly half an inch in thickness, are about three times as thick as those of the right. Cavity of right ventricle. . Cavity of left ventricle. Fig. 193. — Transverse section of bullock's heart in a state of cadaveric rigidity. (Ualton.) Capacity of the Chambers. — During life each ventricle is capable of containing about three ounces of blood. The capacity of 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 that the ventricles are partly filled with blood before the auricles contract. Size and Weight of the Heart. — The heart is about 5 inches long (about 12'6 cm.), 3^1 inches (8 cm.) greatest width, and 2i- 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. Structiire. — The main thickness of the heart-wall is composed of muscular tissue ; but a ring of connective tissue, to which many of the muscular fibres are attached, lies between each auricle and ventricle at the auriculo-ventricular orifice. The embryonic origin of the heart from a single tube is indicated by the fact that the superficial layers of muscle of the auricles and also of the ventricles encircle the chambers of the two sides ; this ensures their simul- taneous contraction. Very varying accounts are given of the arrange- ment of the layers of fibres especially in the ventricles, but the best appears to be the following : in the interior we have muscular fil)res which are thrown into the columnse carnepe, and papillary muscles ; it may be called the papillary layer. Next come fibres arranged circularly, some round the left, and others round the right ventricle; this layer called the circular layer comprises the main thickness of the ventricular wall, and the act of propelling the blood into the arteries is chiefly performed by it. External to this, arranged in three principal bands, are fibres which spirally encircle one ventricle, and CH. XIX.] VALVES OF THE HEART 213 then pass by the septum around the other ventricle, and finally terminate at the base of the heart : this is called the spiral layer. In the amphibian heart there is an obvious muscular con- nection between the auricle and ventricle. A similar muscular link mingled with nou-medullated nerve-fibres also occurs in the mammal. This bundle passes down from the interauricular septum to the interventricular septum, where it divides into two bundles, one for each ventricle : its fibres are peculiar in structure and are known as Purkiuje's fibres (p. 71). It is called the auriculo- ventricular bundle. At the junction of the superior vena cava and the right auricle is a focus of tissue known as the sino-auricular node which corresponds to the sinus venosus of the embryo and lower mammals. The special significance of these structures will be discussed later (see p. 257). Valves. — The arrangement of the heart's valves is such that the blood can pass only in one direction (fig. 194). The tricuspid valve (5, fig. 191) presents three principal cusps or subdivisions, and the mitral or bicuspid valve has two such portions (6, fig. 192). But in both valves there is between each two principal portions a smaller one : so that more properly, the tri- cuspid may be described as consisting of six, and the mitral of four, portions. Each portion is of triangular form. Its base is continu- ous with the bases of the neighbouring portions, so as to form an annular mem- brane around the auriculo- ventricidar opening, and is fixed to the tendinous ring which encircles the orifice. While the bases of the cusps of the valves are fixed to the tendinous rings, their borders are fastened by slender tendinous 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 columnce 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 Fio. 194.— Diagrrm of the circulation through the heart. (Dalton.) 214 THE CIRCULATORY SYSTEM [CH. XIX. name rmiscvH papUlares \ms been given, arc attached to the wall of the ventricle by one extremity only, the other projecting, papilla- like, into the cavity of the ventricle (5, fig. 192), and having attached to it chordre tendineae. 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 tliicker portions of the cusps. The ends of these cords are spread out in the substance of the valve, giving its middle part its peculiar strength and toughness. 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 tliicker 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 more strongly constructed than the pul- monary valves, in accordance with the greater pressure wliich 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. 192). In the centre of the free edge of the pouch, which contains a fine cord 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 aroimd 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 prevent any return. 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 simises of Valsalva. Course of the Circulation. The blood is conveyed away from the left ventricle (as in the diagram, fig. 195) by the aorta to the arteries, and returned to the ricrht 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 CII. XIX.] COURSE OF THE CIRCULATION 215 by the pulmonary artery, which divides into two, one for eacli 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 longer 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 Pulmonary capillaries. Pulmonai-y artery. Superior cava or vein from head and neck. Right auricle. Inferior vena cava- Right ventricle. Portal circulation. Second renal circu- lation. Pulmonary veins. Aorta. Arteries to head and neck. Left auricle. I>eft ventricle. Gastric and intestinal vessels. First renal circulation. .Systemic capillaries. Fio. 105.— Diagram of the circulation. 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 subordinate 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. 195 indicates roughly the difference between arterial and venous blood. 21G THE CrRCULATORY SYSTKM [CH. XIX. The blood is oxy^renated in the lun(,'s, and the formation of oxy- hsenioglobin 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 deoxygonated hoemoglobin is darker in tint tlian the oxy- ha3ni(|globin ; 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 hinfrs, like the rest of the body, are also supplied with arterial blood, which reaches them by the bronchial arteries. The Arteries. The arterial system begins at the left ventricle in a single large trunk, the aorta, which almost immediately after its origin gives ofif 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 r.y '^^=>■ r^-r Fio. 196.— Transverse section through a large branch of the inferior mesenteric artery of a pig. c, Eiiflotliolial mem- brane; t, tunica elastica interna, no subendothelial layer is seen ; m, mus- cular tunica media, containing only a few wav-y elastic fibres; c, e, tunica elastica externa, dividing the media from the connective-tissue adventitia, a. (Klein and Noble Smith.) x 350. Fio. 197. — Minute artery viewed in longitudinal section, e, Nucleated endothelial membrane, with faint nuclei in lumen, looked at from above; t, eliistic mem- brane ; m, muscular coat or tunica media; o, tunica adventitia. (Klein and Noble Smith.) X 2r.O. 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 CH. XIX.] THE ARTERIES 217 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 inosculate) with other arteries. The branches are usually given off at an acute angle, and the sum of the sectional 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 {aprtjpia, 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 distributed much as the arteries belonging to the general systemic circulation. Structure. — The arterial wall is composed of the following coats : — (a) The external coat or tunica adventitia (figs. 196 and 197, 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. 196, e). (h) The middle coat (fig. 196, m) is com- posed of both muscular and elastic fibres, with a certain proportion of areolar tissue. In the larger arteries (fig. 196) its thickness is comparatively as well as absolutely much greater than in the small ones ; it consti- tutes the greater part of the arterial wall. The muscular fibres are unstriped (fig. 198), and are arranged for the most part trans- versely to the long axis of the artery; while the elastic element, taking also a transverse 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 proportion of the muscular and elastic element, elastic tissue preponderating 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. 196, e), which make it smooth, so that the blood may flow with the smallest possible Fig. 198, Muscular fibre-cells from human arteries, magni- fied 350 diameters. (Kiilliker.) a. Nucleus, h. A fibre-cell treated with acetic acid. 218 THE CIRCULATOKY SYSTEM [CII. XIX. amount of resistance from friction. Immediately external to tlio endothelial lining of the artery is fine connective tissue (sub- endothelial layer) with branched corpuscles. Thus the internal coat consists of three parts, (a) an endothelial lining, (h) the subendo- thelial 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 surrounded by a plexus of sympathetic nerves, which terminate in a plexus between the muscular fibres. f Kiuiotheliuin. •Subi'iidotbelial layer. Elastic layer. .Middle coat. \3 Via. 19U — Transverse section of aorta thro\i>'h tin' inti'nial aud about ball' tbo middle coat. The Veins. The venous system begins in small vessels which are shghtly 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 venaB cavce and the CH. XIX.] THE VEINS 219 a ^% coronary veins, which enter the right auricle, and (as regards tlie puhnonary circidation) in four puhnonary 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 the 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 collapsed, owing to their want of elasticity. They are usually distributed in a superficial and a deep set which communicate frequently in their course. Struchcre. — In structure the coats of veins bear a general resemblance to those of arteries (fig. 200). Thus, they possess outer, middle, and in- ternal 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. (l) The middle coat is consider- ably thinner than that of the arteries ; it contains circular unstriped mus- cular 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 pulmonary veins, the middle coat is replaced, for some distance from the heart, by circularly arranged striped muscular fibres, con- tinuous 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 membrane, which may be absent endothelium is made up of cells elongated vessel, but wider than in the arteries. Valves. — One main distinction between arteries and veins is the presence of valves in the latter vessels. The general construc- FiG. 200. — 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. Tlie muscular coat of the vein (m) is seen to be much thinner than that of the artery. x 350. (Klein and Noble Smith.) has a very thin fenestrated the smaller veins. The in the direction of the 220 THK CIKCULATORY SYSTKM [CH. XIX. tion 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 l)ackward. Tiiey are commonly placed in pairs, at various distances in different veins, but almost uniformly in each (fig. 201). In the smaller veins single valves Fio. 201. — Diagram showing valves of veins. A, part of a vein laid open ami spread out, with two pairs of valves. B, longitudinal section of a vein, showing the appcjsition 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. are often met with; and three or four are sometimes placed together, or near one another, in the largest veins, such as the Fio. 202.— a, vein with valves oijen. B, uith valves closed; strciini c,r M.h.,1 passing oil bj lateral channel. (Ualtoii.) subclavian, at their junction with the jugular veins. They are com- posed of an outgrowth of the subeudothelial tissue covered with en. XIX. ] THE VEINS 221 endothelium. Their situation in the superficial veins of the fore- arm 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. 201, 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 canal, 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 in the coats of both arteries and veins. In the external coat of large Fig. 203.— Surface view of an artery from the mesentery of a frog, ensheatlied in a perivascular lym- phatic vessel, a, The artery, with its circular muscular coat (media) indicated liy broad transverse markings, with an indication of the adventitia outside. I, Lymphatic vessel ; its wall is a simple endothelial membrane. (Klein and Noble Sn ith.) vessels they form a plexus of more or less tubular vessels. In smaller vessels they appear as spaces lined by endothelium. Sometimes, as 222 THE CIRCULATORY SYSTEM [CII. XIX, in the arteries of the omentum, mesentery, membranes of the brain, hmg, liver and spleen, the spaces are continuous with vessels which distinctly ensheath them — perivascular lymphatics (fig. 203). The Capillaries. In most cases the blood finds its way from the small arteries to the small veins through a network of minute cylindrical vessels called capillaries. But in certain cases (parathyroid, spleen, the thyroid of some animals, erectile tissue, the placenta, and the embryonic liver and kidney) the connecting system of vessels are larger and have an irregular shape ; these vessels are termed sinusoids. The walls of both capillaries and sinusoids are composed of endothelium — a single layer of elongated flattened and nucleated cells, 80 joined and dovetailed together as to form a continuous Fio. 204.— Capillary blood -vo.ssels from the omentum of rabbit, showing the nucleated endothelial membrane of which they are composed. (Klein and Noble Smith.) transparent membrane (fig. 204). Here and there the endothelial cells do not fit quite accurately ; the space is filled up with cement material ; these sj)ots 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 MTToirth of an inch (12 ^). Among the smallest may be mentioned those of the brain, and of the follicles of the mucous membrane of 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 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 CH. XIX.] LYMPHATIC VESSELS 223 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. 205), most glands and mucous membranes, and the 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. 206), the short sides of which may be from three Kii;. 205. — Network of capillary vessels of the air-cells of the horse's lung magnified, a, a, Capillaries proceeding from h, b, terminal branches of the puhnonarj- artery. (Frey.) Fig. 206. — Injected capil- lary vessels of muscle seen with a low mag- nifying power. (Sharpey.) 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 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 224 THE CIRCULATORY SYSTEM [Cn. XIX. called lymph, is gathered up and carried back again into the blood by a system of vessels called lymphatics 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. 208 and 209 is due to the presence of these valves. They commence in fine microscopic lymph-capillaries, in the orcrans and tissues of the body. Lymphatics of head and neck, right. Uight internal jugular vein. lUght subclavian vein. Lymphatics of right arm Ueceptaculum chyli. Lymphatics of lower ex- tremities. Lymphatics of bead and neck, left. Thoracic duct. I .eft subclavian vein. Thoracic duct. I.actcals. Lymphatics of lower ex- tremities. Fio. 207.— Diagram of the principal gruups of lymphatic vessels. (From Quain.) and they end in two trunks which open into the large veins near the heart (fig. 2Q7). 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. 207 the greater part of the contents of the lymphatic system of vessels will be seen to pass through a com- paratively large trunk called the thoracic duct, wliich finally empties its contents into the blood-stream, at the junction of the internal CH. XIX.] LYMPHATIC VESSELS 225 jugular and subclavian veins of the left side. There is a smaller duct on the right side. The lymphatic vessels of the intestinal canal Flu. 208. — Lymphatic vessels of the head and neck and the upper part of the trunk (Mascagni). J. — The chest and pericardium liave been opened on the left side, and the left inamma detached and thrown outwards over the left arm, so as to expose a great part of its deep surface. The principal lynijdiatic vessels and glands are shown on the side of the head and face and iu the neck, axilla, and medi- astinum. Between the left internal jugular vein and tlie common carotid arterj', the upper ascending part of tlie 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. /\if^;^ \ Fig. 200. — Superlicial lymphatics of the forearm and palm of the hand. i. — 5. Two small glands at the bend of the arm. 0. Radial lymphatic vessels. 7. Ulnar lymphatic vessels. S, S'. 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.) are called ladeals, because during digestion (if the meal contains- fat) the fluid contained in them resembles milk in appearance ; and the lymph in the lacteals during the period of digestion is called chyle. 226 THE CIRCULATOKY SYSTEM [CH. XIX. Chyle is lymph containing finely Jivdded fat-globules. In some parts of its course the lymph-stream passes tlirough lymphatic glands, to be described later on. Origin of Lymph Capillaries. — The lymphatic capillaries com- mence most commonly either (a) in closely-meshed networks (see fig. 210), or (Jb) in irregular lacunar spaces, lined l)y endothelium, between the various structures of which the different organs are composed. These spaces freely communicate with the cell spaces (Saft Kaniilchen, see p. 31) of the tissues. Fig. 210. — 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 i; valves at frequent intervals. (Schotield.) The lacteals offer an illustration of another mode of origin, namely, as blind dilated extremities in the villi of the small intestine (see fig. 28, p. 22). 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. They differ from blood capillaries mainly in their larger and very variable calibre, in the presence of valves, and in their numerous communications with the spaces of the tissues. 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 many serous membranes ; a serous cavity thus forms a large lymph-sinus or widening out of the lymph-capillary system with which it directly communicates. CHAPTEli XX 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 Wilham 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 rehed 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 data 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. 4. That if the large veins near the heart are tied, the heart 227 228 THE CIRCULATION OP THE BLOOD [CH. XX. 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. 8. If an artery is wounded, haemorrhage may he stopped by pressure applied between the heart and the womid ; but in the case of a wound in a vein, the pressure must be applied beyond the seat of injury. Since Harvey's time many other proofs have accumulated ; for instance : — 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 j^roof 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 sufflciently 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 l)lood 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 circulatory system is shown in fig. 211 A. Here there is a closed CH. XX.] SIMPLE SCHEMA OF CIRCULATION 220 ring containiiio; 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. This, however, would be merely a to-and-fro movement, not a circula- Fio. 211. — Simple schema of the circulation. tion. Fig. 211 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 hsemolymph system, that is, there is no distinction between blood 230 THE CIRCULATION OF TlIK lU.OOD [cn. XX. and lymph. The heart pumps the circulating fluid along a system of vessels which distribute it over tlie ])ody ; there are no capillaries, and the luemulyiuph is discharged into the tissue spaces; it is thence drained into channels wiiich convey it to the gills, and after it is aorated 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 h;x3molymph 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, wliich 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 heart is divided into a number of chambers placed in single file, one in front of the other; the most posterior which receives the veins is called the 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 aorated : 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 passes into the systemic capillaries, then into 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 tlie hearts of worm and fish, becomes correspondingly modified. There is only one ventricle, but there are two auricles, right and left. The ventricle contains mixed blood, since it receives arterial Fio. 212. — Tlioheartof a fro;^(I{anacsculenLa) from tlie front. I', vontricle; Ad, rit;ht auricle; ^Is, left auricle ; 7,', bulbus arteri- osus, dividing into right and left aort.T. (Kckor.) CH. XX.] HEART OF FROG 231 blood 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 T.p. a. ■ A.^. 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 supplv of the head (fig. 212, 1), lungs and skin (fig. 212, 3), and the third branch (fig. 212, 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 (except in a very early fcetal stage), but is represented by that portion of the right auricle at which the large veins enter. Fig. 213. — 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. y2*-3. (Ecker.) CHAPTER XXI PHYSIOLOGY OF THE HEART The Cardiac Cycle. The series of changes which occurs 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 ^V 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 O'l + Auricular diastole . 0*7 - 0*8 Ventricular .systole . ,, 0*3 + Ventricular dia.stok' . 0*5 = 0*8 Total systole . . ,, 0-4 + Joint diastole . . 0*4 = '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 in 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 ?32 CH. XXI.] THE CATIDIAC CYCLR 233 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 234 PHYSIOLOGY OF THE HEART [CH. XXI. ventriclo 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 tlu- right and forwards, twisting on its long axis and exposing more of the k-ft ventricle anteriorly than when it is at rest. These movements, which were first described by Harvey, have been since llarviy'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 (li) that of the vertebr.e 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 sj)ace, because the heart surface is much more curved than the internal thoracic wall. The forward movement this pressure causes is the ai)ex 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 occurs 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 tendinece 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 chorda tendineoe 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 to the auriculo-ventricular orifice, the musculi papillares more than compensate for this by their own contraction ; they hold the cords CH. XXT.] THE SOUNDS OF THE HEART 235 ticjht, and, by pnllinc^ 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 which 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 intraventricular 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 it lasts during the greater part of the ventricular systole ; it 236 PHYSIOTX)GY OF TIIK HEART [Cn. XXI. just precedes the pulse at the wrist. The second or diastolic sound is shorter and sharper, with a somewhat flapping character, and follows the end of ventricular systole, and is audible just after the radial pulse is felt. The sounds are often but somewhat inaptly compared to the syllables, luhb — di'qo. 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 tendinece. 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 con- traction, may have some part in producing the first sound. The second factor is a 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 contrac- tions or tetanus, it is at first sight difficult to see why there should be any miiscular sound at all when the heart contracts, as a single muscular contraction docs 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 as 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 contrilnition to the first sound is audible, but it is very faint. It is stated to have a somewhat lower pitch than the valvular sound. Fin. 214. — Scheme of caniiac cycle. The inner circle .shows the events which occur within the heart ; the outer the relation of the sounds and pauses to these events. (iSharpey and Gairdnor.) CH. XXI.] THE CORONARY ARTERIES 237 There is, ou the other hand, much to bo said agaiust the view that the cause of the lirst sound is entirely due to vibra- tion 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 imder 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 stretcliing 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 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. Tlie 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. 209). Ligature of the coronary arteries causes almost immediate 238 PHYSIOLOGY OF THE HEART ,',^!.l;j [CH. XXI. 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. SelJ-xtefrimi Arlion uf tlic Ht^art. — This expression was orifrinatcd 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 jiressure. 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, and levers connected to its various parts may be employed to write on a revolving blackened surface. A simple instrument for the frog's heart is the following : — XF Fu;. 215. — Simple Carrliograph for frog's heart. The sternum of the frog having been removed, the pericardium opened, and the fraeuum (a small band from the back of the heart to the pericardium) di%nded, the heart is pulled through the open- ing, 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 contraction starts at the sinus, this is followed by the auricidar systole, and that by the ventricular systole and pause. Tins is CH. XXI.] CARDIOGKAPHS 239 recorded as in the next figure (fig. 216) by 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 cardio- graph devised for this purpose are modi- fications of Marey's tambours. One of those most frequently used is depicted in the next two diagrams. It (fijJC- 217) consists of a cup-shaped metal box over tlie open front of which is stretclied 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 communi- cates 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 etfect is at once transmitted by the column of air in the elastic tube to the interior of the second tambour (fig. 218), also closed, and through the elastic and movable lid of the latter to the lever, which is placed in connection with a registering apparatus, which consists of a cylinder covered with Tube to communicate with tambour. Fig. 216. — Cardiogram of frog's heart C, .showing auricular, followed by ventricular beat ; T, time in half seconds. Tambour. Ivory Tape to attach the instru- knob. ment to the chest. Fig. 217. — Cardiograph. (Sanderson's.) 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. Fig. 219 represents a typical tracing obtained in this way. The first small rise of the lever is caused by the auricular, the second larger rise by the ventricular systole ; the downstroke represents the 240 PHYSIOLOGY OF THE IIKAKT [cH. xxr; pause, the tremors at the coimaeiiceinent of whicli are partly instru- mental and partly caused by the closure of the semilunar valves. Screw to|regulate elevation of lever. WriliiiL; lever. Tambour. Tube of cardiograph. Flo. 218. — Marey's Tambour, to which the movement of the column of air in the first tambour is con- ducted by a tube, and from whicli it is communicated by the lever to a revolving cylinder, so that the tracing of the movement of the impulse beat is obtained. Another method of obtaining a tracing from one's own heart consists in dispensing with the first taml)our, and placing the tube of the recording tambour in one's mouth, and holding the breath Fig. 219. — Cardiogram from human heart. The variations in the individual boats are due to the influence of the respiratory movements on the heart. To be read from left to right. 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 apparatus. There are several methods by which the intracardiac pressure may be recorded. By placing two small india-rubber air-bags or cardiac sounds down 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 CH. XXI.] INTRACAKDIAC PEESSURE 241 long narrow tubes, in communication with three tambours with levers, arranged one over the others in connection with a registering apparatus (fig. 220), Chauveau and Marey were able to record and Fig. 220. — Apparatus of MM. Chauveau and Marey for estimating the variations of endocardiac pressure, and the production of the impulse of the heart. 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. 221), the inter- vals between the vertical lines represent periods of a tenth of a second. The parts on which any 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 im- pvdse, which is indicated by a" in the third tracing. The large curve of the ventricular and the impulse tracings, between a' and d', and a" and d", are caused by the ventricular contraction ; while the smaller undulations, between B and c, b' and c', b" and c", 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 Fig. 221.— Tracings of (1), Intra-auricular, and (2), Intraventricular 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. XXI. 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 tendency to record inertia vibrations. Rolleston reinvestigated the subject with a more suitable but rather complicated apparatus. The principle of his 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 varjdng pressures exerted on the blood by the contraction and dilatation of the heart. Another and still better method of overcoming the imperfections of Marey's tambour is by the use of Hiirthle's manometer (fig. 222). Fig. 222.— Hiirthle's Manometer. In this the tambour is very small, the membrane is made of thick rubber, and the 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. Fig. 223.— Curve of intraventricalar pressure. (After Hiirthle.) 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 second). At D the ventricle relaxes. The flat top of the curve is spoken of as the systolic plateau, and according to the state of the CH. XXI.] THE ELECTRO-CARDIOGRAM 243 heart and the peripheral resistance may present a gradual ascent or descent ; it occupies about 18 second. Almost immediately after the 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 actual amount of pressure in the heart is measured by a mercurial manometer, which is connected to the heart by a tube con- taining 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 pressure 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 a pressure less than that of the atmosphere, so 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 cannulse are brought into connection with tambours (a and b) which work on points of a lever at equal distances from and on Maximum Jliiiimum pressure. pressure. 140 mm. - 30 to 40 mm 60 mm. - 15 mm. 20 mm. - 7 to 8 ram. Fig. 224. B A -Diai;rani uf Iliirthle's differential Manometer. opposite sides of its fulcrum (i). 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 u 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. The Electro-Cardiogram. The muscular tissue of the heart gives rise on action to an electrical disturbance which is in all essential features the same as the diphasic variation we have already studied in Chapter XI. in connection with voluntary muscle. The excised beating heart of a frog can be readily connected either to a galvanometer or 244 PHYSIOLOGY OF THE HEART [CH. XXI. electromoter, and the (lifferent ])hases of the action current can in tlio former case bo asccrUuned by watching tho movements of the magnetic needle, and in the latter case by watching under the microscope the movements of the meniscus of mercury in the capil- lary tube. If the eyepiece of the microscope is removed, and the image of the mercurial column alhjwed to fall on a moving photo- graphic plate, a graphic record is obtained, in which the to-and-fro movements of the mercury are shown as waves. Such a graphic record is termed an electro-cardiogram, and one of these is shown in the next figure (fig. 225). KlG. 225. — Electro-uaiiliograni from Irog's vi^uli icle. Uiphasiu varialiuii. .Siiiiullaiicuu.s pliutograph of a single beat (upper blauk line), and the accompanying electrical change indicated by the levei of the black area, which shows the varying level of mercury in a capillary electrometer. The time- tracing at the top marks tenths of a second. (Waller.) It is, however, possible (as Waller first demonstrated) to obtain an electro- cardiogram in the intact animal, and even in man. If a dog is placed with a fore paw in a basin of salt solution, and a hind paw in another, and the two basins are led off to the electrometer, the electrical changes produced by the beating heart will be con- ducted through the body of the animal and through the electrometer, and the movements of the mercury can be watched with a microscope or recorded on a travelling photographic plate. By the use of this method Miss Buchanan has succeeded in performing what otherwise would have been the impossible task of counting the heart rate of small mammals such as mice. The photographic plate must travel at great speed, and the notches in the shadow of the mercurial column, which correspond to the heart-beats, were found in the mouse to occur at the rate of 700 per minute. In a corresponding way the human electro-cardiogram can be registered, as shown in fig. 226. In that particular experiment, the "lead-offs" were from mouth and left foot. It is more usual to employ one hand and one foot. We must, liDwever, i-ecognise that tho heart muscle is not a simple longitudinal strip like a sartorius, but is arranged in a com- plex way, and in the mammalian heart is arranged around four CH. XXT.] THE ELECTRO -C AUDIOGRAM 245 chambers, and that the left and right sides are contracting simultaneously. One would therefore anticipate that there would be a corresponding complexity in the electrical record of the intact organ. This ex[iectation has been verified by later work in which investigators have used more sensitive instruments. But there was some indication of this even in the records of the earlier workers who employed the capillary electrometer. Thus Bayliss and Starling described in the mammalian heart a triphasic variation, and Gotch by means of careful experiments on both cold and warm blooded animals, has shown that this is explicable in the following PlO. 226. — niiman heart. Electro-cariiiuKram, EE, and simultaneous cardiogram, CO. Time, tt, is marked in I'.-jth second. The lead-ofls to the capillary electrometer were from the mouth to tlie sulphuric acid, and from the left foot to the mercury. (Waller.) way. Leaving out of account complications due to auricular activity, he has shown that the contraction process in each ventricle and its electrical concomitant commences at the part of the base of the ventricle where it is continuous with its respective auricle ; the contraction wave travels to the apex and returns to the part of the base from which the aorta on one side and the pulmonary artery on the other side arise. An electrode placed on the base will therefore record the increased positivity at the beginning and the end of the ventricular contraction ; the electrode on the apex will record the middle phase when the contraction wave reaches that point, and causes an increase of positivity there. By far the most delicate instrument now in use is Einthoven's String Galvanometer (see p. 121), and during the last few years it has been much employed, not only by Einthoven himself, but by numerous other observers, including Dr T. Lewis, in this country. The excursions of the thread or string can be photographed, and the followino; diagram is a cardio-electroQ;ram obtained from the human heart during a single beat, the electrodes being connected with the right and left hands. It will be seen that there is a small movement due to the auricular systole, and several large ones which accompany ventricular contraction. The exact meaninsj; of these different waves is still far 246 PHYSIOLOGY OF THE HEART [CH. XXI. from clear, and the extent of each varies considerably even in liealth, Ijiit in heart disease the electro-cardiogram shows very marked (Hfferences from the normal, especially in cases of "heart-ldock." When in the future the meaning of each part of the record is under stood, the physician will be provided with a new help to diagnosis. Fio. 227.— Electro-cardiogram obtained by photographing the mOTements of the thread of a String Galvanometer. The electrodes were connected to a man's right and left hands. Waves upwards indicate tliat the base (right ventricle) is galvanometrically negative to the ai>ex (left ventricle); do\%n»ard waves have the opposite meaning. Wave P accompanies auricular systole ; waves Q, R, S, and T occur during ventricular systole. The time-tracing (T) shows tenths of a second. (After Einthoven.) The Cardiophonogram. — An interesting extension of this work consists in the registration of the heart sounds. This was first done by Hiirthle some years ago, but Einthoven's string galvanometer, as an instrument of precision far exceeding these previously used, has enabled him to repeat this work with much greater accuracy. A stethoscope is placed over the chest and connected to a microphone, which magnifies the heart sounds ; the vibrations in the microphone are communicated as electrical changes by a transformer to the string galvanometer, the movements of the quartz fibre being finally photographed on a travelling plate. If simultaneously an electro- cardiogram is taken, the simultaneity of the first heart sound with the ventricular systole, and of the second heart sound with the com- mencement of ventricular diastole, are very conclusively demon- strated. In heart disease where the adventitious sounds called murmurs are present, their time relationships in the cardiac cycle are most clearly seen. Einthoven has further found the presence of a thinl ht-arf sound, which is inaudible to the unaided ear, although it was first described by Dr A. G. Gibson of Oxford, in a patient in whom it was very pronounced, by means of ordinary auscultation. It seems, however, to be present in all human hearts in varying degrees of intensity when the cardiophonogram is examined. It occurs during diastole, and follows the second sound after a short pause. It is not due to a reduplication of the second sound, nor is it a presystolic murmur such as can be heard in man when there is obstruction at the auriculo-ventricular orifices. PLinthoven adduces evidence against both these views, and believes it is produ;-ed at the aortic orifice; the semilunar valves and the neighl)ouring portion of the aortic wall being thrown for a second time and for a short period into vibration by the changes in the aortic pressure which occur during diastole. CH. tkl] work of the heart 247 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 to vary even in health. The chief are age, temperament, sex, food and drink, e-xercise, 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, thus : — Before birth the average number About the seventh year . from 90 to 85 of pulsations per minute is . 150 About the fourteenth Just after birth . . from 140 to 130 1 year . . . . ,, 85 to 80 During the first year . ,, 130 to 115 { In adult age . . . „ 80 to 70 During the second year ,, 115 to 100 | In old age . , . ,, 70 to 60 In health there is a uniform relation between the frequency of the heart - beats and of the respirations ; the proportion being 1 respiration to 3 or 4 beats. The same relation is generally main- tained in 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 a day to that done by an able-bodied labourer working hard for two hours. The heart's work consists in discharging blood against pressure, and in imparting velocity to it. It is therefore necessary to know how much blood is expelled from the heart at each beat, the time occupied in such expulsion, the velocity with which the blood is expelled, and the pressure against which the heart has to act. Without going into the somewhat elaborate calculations obtained from these and other data, it will be sufficient to say that about ■j^g- of the total energy of the heart is used in imparting velocity to the blood, but when the blood reaches the aorta the velocity is checked, and that the kinetic energy of the blood in the aorta is only about ■g^ of the total energy imparted to the blood by the heart. The Outpiit of the Heart. — Direct measurements of the heart's output have been made by Stolnikow and Tigerstedt. The former cut oflF the whole of the systemic circiilation in the dog, and then measured the amount of blood passing through the simplified circulation, which consisted only of the pulmonary and coronary vessels by means of a cylinder interposed on the course of the vessels, (see fig. 228). Tigerstedt made his observations by means of a Stromuhr (see next chapter) inserted into the aorta. Severe operative measures of this kind, however, interfere with the circulation a good deal. G. N. Stewart has introduced an ingenious method, the principle of which is the following : — A solution of an innocuous substance, which can be easily recog- nised and estimated, is allowed to flow for a definite time and at a uniform rate into the heart ; the substance selected was sodium chloride. This mingles with the 248 PHYSIOLOGY OF THE HEART [cn. XXI. f^> o o \ B / blood and passes into the circulation. At a convenient point of the vascular system, a sample of blood is drawn off just before the injection, and an equal amount durinj;- the passage of the salt; the (juantily of the sodium chloride solution which nmst be added to the first sample in ordir that it may contain as much as the second sample is determined. This determination j^ives the extent to which the salt solution has been mixed with the i)lood in the heart, and knowing the quantity of the solu- tion which has run into the heart, the output in a given time can be calculated. All these experiments have been on animals. The results obtained neces- sarily vary with the size of the animal used, and with the rate at which the heart is beating. If the same relation- ship holds for man as for animals, Stewart calculates that in a man weigh- ing 70 kilos the output of each ventricle per second is less than 0"002 of the body weight, i.e., about 10,5 grammes of blood per second, or 87 grammes (about 80 c.c.) per heart-beat with a pulse rate of 72. An instrument called the cardl- omel.ar was invented by Roy for regis- tering the output of the heart. His instrument was made of metal, and oil was used as the transmitting medium in its interior. A simple modification of this applicable to the heart of a small mammal like a cat has been devised by Barnard. It consists of an india-rubber tennis ball with a circular orifice cut in one side of it large enough to admit the heart ; a glass tube is securely fixed into a small <)j)ening on the opposite side of the ball. The animal is an;esthetised, and its thorax opened. The animal is kept alive by artificial respiration. The pericardium is then opened by a crucial incision, the heart is slipped into the ball ; the pericardium overlaps the outside of the ball, and the apparatus is rendered air-tight by smearing the edges of the hole with vaseline. The four corners of the ])cricardium are then tightly tied by ligatures round the glass tube just mentioned. This tube is con- nected by a stout india-rubber tube to a Marey's tambour or a piston-recorder, the writing-point of which is applied to a moving blackened cylinder. When the heart contracts, air will be with- I. 228. — Stolnikow'.s apparatus. A and B are two cylinders fitted with lloats provided with writing-points at their upper ends. The tube from the lower end of each bifurcates into two, a and v from A ; a' and v' from B. a and a' are united together and enter the right carotid artrry ; jjand v' unite aTid are inserted into the superior vena cava. The remaining branches of the aorta and the inferior vena cava are tied. B is tirst tilled with defibrin- ated blood, which passes down v' into the right auricle, thence to the right ventricle, lungs (where it is oxygenated), and then enters the left side of the heart ; the left ventricle exp(ds it by the tube o into A, so that the float in A rises while that in B falls. As soon as B is enijity the tubes v and a' which were previously clamped are released, and v' and a are clamped instead. Tlie left ventricle now exptds its blood by the tube a' into the cylinder B ; sitnultaneously A empties itself through v into tht! right side of the heart, iiigzag lines are tluis traced by the wriliiig-points on tho toji of the floats, and their 1rc(iu''iicy enables one to estimate the output of the left ventricle in a given time. (After Starling.) drawn from the tambour to the cardi- ometer; when the heart expands, the air will move in the reverse direction. These movements are written by the end of the lever of the tambour, and varia- tions in the excursions of this lev^r corrcs]>ond with variations in the amount of blood ex|)elled from or dr.iwn into the heart witli systole and diastole respec- tively. By calibrating the instrument the actual volume of the blood expelled can be ascertained. CH. XXI.] INNERVATION OF THK HEAT^T 249 Innervation of the Heart. The nerves of the heart, wliich under normal circumstances control its movements, are : — 1. Cardiac branches of the vagus (inhibitory fibres). 2. Cardiac branches of the sympathetic (augmentor and acceler- ator fibres). These pass to the heart and terminate in certain collections of ganglion cells in its wall (terminal ganglia) ; from these cells post- ganglionic fibres are distributed among the muscular fibres. In addition to these nerves, which are efferent, we have to mention : — The sensory or afferent nerves of the heart, the best known of which is called the depressor nerve. This nerve, starting from the cardiac tissue, joins the vagus trunk ; it passes to the bulb, especially to the vaso-motor centre. We shall therefore postpone its study until we are considering the vaso-motor nerves. The Vagus. — The ninth, tenth, and eleventh cranial nerves arise close together from the grey matter in the floor of the fourth ventricle, and leave the bulb by a number of rootlets. These rootlets are divided by Grossmann into three groups, a, b, and c ; there is a good deal of blending of the rootlets before they ultimately emerge from the skull, but the a (the uppermost) group corresponds fairly well with the fibres of the glossopharyngeal, h with those of the vagus, and c (the lowermost) with those of the spinal acces- sory. The rootlets of the tenth nerve pass through two ganglia called respectively the jugular ganglion, and the ganglion trunci vagi. The fibres of the spinal accessory nerve which join the vagus are chiefly motor, especially to the larynx, but some go to the heart. The vagus gives off branches to many organs, pharynx, larynx, heart, lungs, oesophagus, and various abdominal organs. We have, however, in this place only to deal with its cardiac fibres. It has been known since the experiments of the Brothers Weber in 1845 that stimulation of one or both vagi produces slowing or stoppage of the beats of the heart. It has since been shown that in all vertebrate animals, this is the normal result of vagus stimulation ; the pheno- menon is called inhihition, and the nerve-fibres cardio-inhihitory. Section of one vagus produces slight acceleration of the heart ; this result is better marked when both vagi are divided. This shows that the restraining influence of the vagus is being continuously exercised ; it is, however, found that the amount of vagus control varies a good deal in different animals. The most potent artificial stimulus which can be applied to the vagus nerve to produce inhibition of the heart is a rapidly interrupted induction current ; severe mechanical stimuli have a slight effect, but chemical and thermal stimuli are ineffective. 250 PHYSIOLOGY OF THE HEART [Cn. XXI. A certain amount of confusion has arisen as to the effect of vagus stimulation, because so many experiments liave been made on the frog. In this animal the sympathetic fibres join the vagus after it loaves the skull, and so what is usually called the vagus in this animal should more properly be termed the vago-symjjathetic. It will readily be understood that l3y stimulating a mixed nerve, one obtains Fig. 229.— Tracing showing the actions of the vagus on the heart. Aur., auricular ; Vent., ventricular tracing. The part between the perpendicular lines indicates the period of vagus stimulation. C8 indicates that the secondary coil was 8 cm. from the primary. The part of the tracing to the left shows the regular contractions of moderate height before stimulation. During stimulation, and fur some time after, the beats of auricle and ventricle are arrested. After they commence again they are small at lirst, but soon acquire a much greater amplitude than before the application of the stimulus. (Prom Brunton, after Gaskell.) an intermixture of effects. If, however, one stimulates the intra- cranial vagus before the sympathetic blends with it, a pure inhibitory effect is obtained. Figs. 229 and 230 show the common effect of stimulating the mixed trunk ; the inhibitory effect is usually mani- fested first, and this is followed by the augmentor effect due to Vend '^'-J^- .MUmKIWillUM Fio. 280. — Tracing showing diminished amplitude and slowing of the pulsations of the auricle and ventricle without complete stoppage during stimulation of the vagus. (From IJrunlon, after Gaskell.) sympathetic action. But it is by no means infrequent to obtain the phenomena in the reverse order. It is often stated that the right nerve contains more inhibitory fibres than the left, but this is by no means a constant rule. One can always obtain good inhibition if the stimulus is applied to the wall of the sinus ; here one stimulates the post-ganglionic fibres which originate from the nerve-cells in the sinus ganu;lion around which the vagi terminate. CH. XXI.] CAIIPIAC SYMPATHETIC NERVES 251 Tho effect of the stimulus is not immodiately seen; one or more beats may occur before stoppage of tho heart takes place, and slight stimulation may produce only slowing and not complete stoppage of the heart (fig. 230). The stoppage may be due either to prolongation of the diastole, as is usually the case, or to diminution of the systole. Vagus stimulation lessens the conductivity of the cardiac tissue, but it does not abolish the irritability of the heart-muscle, since direct mechanical stimulation may bring out a beat during the standstill caused by vagus stimulation. The inhibition of the beats varies in duration, but if the stimulation is a prolonged one, the beats reappear before the current is shut off. This is known as " vagus escape," and is probably due to fatigue of the vagal endings. The Sympathetic. — The influence of the sympathetic is the Stimulation of the sympathetic Roots of Vagus reverse of that of the vagus, produces acceleration of the heart-beats, and as a rule, sec- tion of the nerve produces slowing. Hence the nerve is also in constant action like the vagus. The acceleration produced by stimulation of the sympathetic fibres is accom- panied by increased force, and so the action of the nerve is also termed augmentor. It is probable that the augmentor fibres are distinct from the accelerator fibres, because in mammals one or two of the small nerves leaving the stel- late ganglion on stimulation produce augmentation without acceleration. The fibres of the sympa- thetic system which influence the heart- beat in the frog, leave the spinal cord by the anterior root of the third spmal nerve, and pass by the ramus communicans to the third sympathetic ganglion, then to the second sympathetic ganglion, then by the annulus of Vieussens (round the subclavian artery) to the first sympathetic ganglion, and finally in the main trunk of the sympathetic, to near the exit of the vagus from the cranium, where it joins that nerve Ant. root Post, root Fig. 231.— Heart nerves of frog. (Diagrammatic.) 252 PnTSIOLOGY OF TTTE ITKART [Cn. XXI. JiigtilarGaiHjIion Ganglion triinci Vagi Roots of X Naroe Roots of XI Nerue and runs down to tho hnavt witliin its slioatli, formini:^ tlio joint vago- sym])atliotic trunk. Those filires aro indicated by tho dark lino in fig. 231. The tibros of tho syuipathotic seen running up into the skull aro for the supply of blood-vessels there. It should be noted that the frog has no spinal accessory nerve. In tho mammal the sympathetic fibres leave the cord by the second and third dorsal nerves, and possibly by an- terior roots of two or more lower nerves ; they pass by the rami communicantes to the ganglion stellatum, or first thoracic ganglion, and thence by the annulus of Vieussens to the inferior cervical ganglion of the sym- pathetic ; fibres from the an- nulus, or from the inferior cervical ganglion, proceed to the heart (see fig. 232). In man, the cardiac branches of the sympa- thetic travel to the heart from the annulus of Vieus- sens and cervical sympa- thetic in superior, middle, and lower bundles of fibres. These pass into the cardiac plexus, and surrounding the coronary vessels ultimately reach the heart. Cardiac branches Third Thoracic Ganglion Fia. 232.— Heart nerves of mammal, (l)ia^ammatic.) By stimulating each rootlet in his tiirec groups, Grossmann found the cardio-inhibitory filires in tho lower two or tiiree rootlets of group /) aiul the upper rootlet of group r. There are probably difTerences in dilfcrent animals. In the cat and dog Cadman finds that the rot)tletH in the a group are respiratory and afferent inhibitory, and that all the efferent inhibitory fibres are in group c. The inhibitory fibres are medullated. and only measure 2 /< to :? n in diameter ; they pass to the "heart and have their cell-stations in the ganglia of that organ. Some of the sympatlietie fil)res, on the otlier hand, reacii the heart as non- meduUated fibres ; having their cell-stations in tiie symjiathetic (inferior cervical and first tlioracic) ii-anglia ; but the majority do not reaeii their cell-stations until they reach terminal ganglia in the heart wall. The augiuentor and accelerator centres in the central nervous system have not yet been accurately localised. CU. XXI.] CARDIAC SYMPATHETIC NERVES 253 Injiuoice of Drugs. — The question of the action of drugs on the heart forms a largo branch of pharniacohjgy. Wo shall bo content here with mentioning two only, as they are largely used for experi- mental purposes by physiologists. Atrojyine produces consider- able augmentation of the heart-beats by paralysing the inhibitory mechanism. Muscarine (obtained from poisonous fungi) produces marked slowing, and in larger doses temporary stoppage of the heart. Its effect is a prolonged inhibition, and can be removed by the action of atropine. The action of atropine cannot, however, bo easily antagonised by muscarine ; a large dose is necessary. That these drugs act on the nerves, and not the muscular substance of the heart, is shown by the fact that in the hearts of early embryos, so early that no nerves have yet grown to the heart, these drugs have little or no effect. (Pickering.) Reflex Inhibition. — Thus there is no doubt that the vagi nerves are simply the media of an inhibitory or restraining influence over the action of the heart, which is conveyed through them from the centre in the medulla oblongata, which is always in operation. The restraining influence of the centre in the medulla may be reflexly increased by stimulation of many afferent nerves, particularly those from the nasal mucous membrane, the larynx, and the lungs. A blow on the abdomen causes inhibition and fainting ; a blow on the larynx, even a moderate one, will kill. There is no comparison between the ease with which stimulation of the laryngeal or pul- monary fibres produces inhibition, as compared to the difficulty of obtaining inhibition from the alimentary tract. Tobacco smoke in some people and animals, by acting on the terminations of the vagi or their branches in the respiratory system, may also produce reflex inhibition of the heart. Some very remarkable facts concern- ing the readiness by which reflex inhibition of the fish's heart may be produced were made out by M'William ; any irritation of the tail, gills, mucous membrane of mouth and pharynx, or of the parietal peritoneum, causes the heart to stop beating. In connection with the subject of reflex inhibition, it may be mentioned in conclusion that though we have no voluntary control over the heart's movements, yet cerebral excitement will produce an effect on the rate of the heart, as in certain emotional conditions. Action of Gkloroform on the Cardiac Mechanism. — The mammalian heart is more difficult to stop by stimulation of the vagus than the frog's heart ; commonly it is only slowed, and the amplitude of the beat reduced, yet it is most important for the student of medicine to recollect that vagus inhibition may have far-reaching results. One of the most familiar causes of heart stoppage in surgical practice is that produced by chloroform ; chloroform acts directly on the cardiac tissue when it is administered incautiously, or in too large 254 PITYSIOLOGY OF THE HEART [CH. XXI. doses over long peii(jJ.s of time; the term inhibition is not apphcable in this case, and the effects of the poisonous action of chloroform on the heart itself can be avoided by keeping the proportion of chloro- form in the inspired air at 2 per cent, or less. But in other cases which are seen both in animals and human beings who may be peculiarly susceptible to the influence of chloroform, heart stoppage occurs during the onset of anaesthesia long before the percentage of chloroform in the blood has reached a value which is toxic to the heart. Some have considered that death during the induction of chloroform anaesthesia is due to the vapour irritating the vagal terminations in the lung, and so leading to reflex inhibition of the heart. Embley's experiments, however, lead to the conclusion that the chloroform acts on the vagus centre in the medulla oblongata. In animals, cutting the vagi immediately sets the heart going again. In man this operation cannot be performed, and it is therefore a wise precaution, whenever it is necessary to administer chloroform, to give beforehand a small dose of atropine under the skin so as to temporarily paralyse the vagus endings in the heart. Gaseous Exchanges in the Heart. — The using up of oxygen by the living heart was well illustrated by an old experiment of Yeo's. He passed a weak solution of oxyhaemoglobin through an excised beat- ing frog's heart, and found that after it had passed through the heart, the solution became less oxygenated and venous in colour. This is still better shown by the following numbers, obtained by Barcrof t and Dixon by estimating the gases in the blood entering and leaving the coronary vessels of a cat. It will be seen that the metabolism in the heart tissue is reduced during inhibition; this is followed by increased metabolism during the subsequent period, which corresponds with the increase of visible activity which then occurs, and which is seen in the tracings given in figs. 229 and 230. Oxygen used up per minute Carbonic acid given out per minute Normal Heart. D»™.'«.^>g»'^ ^ff'.^'^e"^ Iniiibitioii. Inlubiliou. 0-21 C.C. 0-13 c.c. 0-34 cc. 0-45 cc. 0-07 cc 0*22 cc Rhythm, Conduction, etc., in Cardiac Muscle. In one time, the rhythm which cardiac muscle exhibits was supposed to be due to the action upon it of the nerves which are present. We now know that the property of rhythmical peristalsis resides in the muscular tissue itself, though normally dtiring life it is controlled and regulated by the nerves that supply it. This conclusion may be expressed by saying that cardiac rhythm is myogenic, not CH. XXr.] CARDIAC lUIYTHM AND CONDUCTION 255 neurogenic. There are still a few physiologists who maintain the older neurogenic theory, but these are mainly those wlioso chief work has been performed on the hearts of invertebrate animals, and it is quite possible that the mechanism there is a different one. But so far as the vertebrate heart is concerned, the myogenic theory is now held, because (1) the foetal heart manifests rhythm long before any nerves reach it ; (2) the apex of the ventricle of such animals as frogs and tortoises can be made to beat rhythmically by perfusing it with suitable fluids at high pressure ; and this part of the heart has few nerves and no ganglion cells ; and (3) the rate of conduction of the peristaltic wave is slow, and corresponds to the rate of muscular rather than of nervous conduction. The older observers, who first made the striking observation that a heart will continue to beat after its removal from the body for a considerable period, and who at the same time were imbued with the neurogenic theory, naturally placed the seat of rhythm in the intracardiac ganglia. They were not at the time aware of the general arrangements of autonomic nerves, and therefore did not recognise that the ganglia were terminal cell-stations on the course of the nerves which reach the heart via vagus and sympathetic. The intracardiac nerves have been chiefly studied in the frog ; in this animal the two vago-sympathetic nerves terminate in various groups of ganglion-cells ; of these the most important are Remah's ganglion, situated at the junction of the sinus with the right auricle; and Bidder s ganglion, Sit the junction of the auricles and ventricle. A third collection of ganglion cells (von Bezold's ganglion) is situated in the interauricular septum. From the ganglion - cells, post- ganglionic fibres spread out over the walls of the sinus, auricles, and upper part of the ventricle. Remak's ganglion used to be called the local inhibitory centre of the heart ; it is really the chief cell-station of the inhibitory fibres, and stimulation of the heart at the sino- auricular j unction is the most certain way of obtaining stoppage of the heart. Bidder's ganglion was called the local accelerator centre for a corresponding reason. The intracardiac ganglia have been examined in a few other cold- blooded animals (for instance the tortoise), but any precise knowledge of their arrangement and position in the mammalian and human heart is unfortunately lacking. Conduction in the Heart. — As already stated, the slow rate of propagation of the wave points to the link being muscular rather than nervous, and histology lends support to this view, the muscular fibres being connected to each other by intercellular bridges of proto- plasm (see p. 71). An experimental proof of the same view is the following: if a strip of the heart wall is taken and a number of cuts going nearly completely across it, be made first from one side. 256 PHYSIOLOGY OF THE HEART [CH. XXI. then from the otlier, all the nerves must be cut throuf,'h at least once, and the only remaining tissue not severed is muscular, yet' the strip still continues to beat ; in other words, the propagation is myodromic. The passage of the wave from one chamber to another is also myo- dromic. The slow rate of propagation indicates that this is so, and the view has been fully proved by the discovery of muscular strands, passing across from one chaml>er to the next. It appears that under normal conditions the wave of contraction in the heart starts at the sinus, and travels over the auricles to the ventricle ; the irritability of the muscle and the power of rhythmic contractility is greatest in the sinus, less in the auricles, and still less in the ventricles. Under ordinary conditions the apical portion of the ventricles exhibits very slight power of spontaneous contraction. The importance of the sinus as the starting-point of the peristalsis can be shown by warming it. If a frog's heart is warmed by bathing it in warm salt solution at about body temperature, it beats faster ; this is due to the sinus starting a larger number of peristaltic waves ; that this is the case may be demonstrated by warming localised portions of the heart by a small galvano-cautery ; if the sinus is warmed the heart beats faster, but if the auricles or ventricles are warmed there is no alteration in the heart's rate. The sinus in the frog's heart, and that portion of the right auricle in the mammal's heart which corresponds to the sinus, is always the last portion of the heart to cease beating on death, or after removal from the body {ultima moriens, Harvey). This is an additional proof of the superior rhyth- mical power which it possesses. The fojtal remnant of the sinus in the mammal's heart has been called the sino-atiricular lude (Keith and Flack), and this has been believed to act as the " pace-maker " of the heart. But after its removal other parts in the same region which contain no Purkinje's fibres have been found quite capable of maintaining the ordinary cardiac rhythm. The sino-auricular node cannot therefore be the specific or exclusive pace-maker, and some observers regard the final part of the large veins outside the heart altogether as more important from this point of view. It is supposed that the wave starting at the sinus is more or less blocked by a ring of lower irritaiiility at its junction with the auricle ; again, the wave in the auricle is similarly delayed in its passage over to the ventricle by a ring of lesser irritability, and thus the wave of con- traction is delayed at its entrance into both auricular and ventricular tissue. By an arrangement of ligatures, or, better, of clamps, one part of the heart may be isolated from the other portions, and the contrac- tion when aroused by an induction shock may be made to stop in the portion of the lieart muscle in which it begins. It is not unlikely that the contraction of one portion of the heart acts as a stimulus to the next portion, and that clamps and ligatures prevent or " block " en. XXI.] HEART-BLOCK 257 this normal propagation of stimuli. It must not, however, be thought that the wave of contraction is incapable of passing over the heart in any other direction than from the sinus onwards; for it has been shown that by the application of appropriate stimuli at appropriate instants, the natural sequence of beats may be reversed, and the con- traction starting at the arterial part of the ventricle may pass to the auricles and then to the sinus. If clamps or ligatures are not applied sufficiently tightly one often sees partial blocking ; a few waves get tliroucrh but not all ; or if the ventricular wall is left connected with other parts of the heart by only a small portion of undivided muscular tissue, the effect is much the same, the wave is only able to pass the block every second or thii'd beat. Heart-Bloch. — The phenomena of blocking just described were made out by Gaskell many years ago in his study of the hearts of cold-blooded animals. But the same sort of thing occurs also in the mammalian heart. The starting-point in our knowledge of this branch of the subject was the discovery by Stanley Kent of bands of muscular tissue passing across from auricles to ventricles, and the principal one was subsequently and independently re-discovered by His, and is known as Kent's bridge or the Bundle of His, or better as the auriculo-vcntricular bundle. It arises in close con- nection with the fibres of the interauricular septum, and with the tissue of the sino-auricular node at the junction of the superior vena cava and right auricle. It comes also into relationship with another similar mass or foetal residue known as the auriculo- ventricular node which lies at the base of the auricular septum on the right side below the coronary sinus. From here the bundle rims along the top of the intraventricular septum and divides into right and left sub-divisions which run down to their respective ventricles along the septum which separates them, and into the papillary muscles arising from the septum. From the papillary muscles fine strands run to other parts of the ventricle immediately under the endocardium, and finally reach the apex. All these structures are made of the peculiar muscular fibres known as Purkinje's fibres (see p. 71). There is no doubt that this is the main conducting path from auricles to ventricles, and although there are nerve-fibres mingled with the muscular fibres of Purkinje there is no reason for modifying the view already expressed that con- duction is myodromic. The conclusion that the auriculo-ventricular bundle is the important link which propagates the rhythmic wave has been reached first by experiments on animals, and secondly, by observa- tions in disease in man. In animals, cutting through the bundle abolishes the ordinary sequence of cardiac events. The auricles go on beating, but the ventricles stop altogether, and later when they K 258 PHYSIOLOGY OF THE HEART [CH. XXI, do begin to beat again, the ventricular l)eat is much less frequent than the auricular, and bears no relationship to it. This lack of correspondence in auricular and ventricular rhythm is known as arhythmia. When the l)undle is destroyed by disease in man (Stokes-Adams* disease) there is a simihxr dissociation Ijetwoen the auricular and ventricular rhythm, the ventricles beating slowly and the auricles rapidly. Sometimes the "heart-block" is incomplete. This is seen in the early stages of the disease ; then one out of every two or three auricular waves gets over to the ventricle, just as in Gaskell's experiments on the frog's heart when the clamp is not sutliciently tight. These recently discovered facts throw a good deal of light on the propagation of the normal heart wave. It starts in the sino- auricular node, and spreads thence to both auricles; it also travels to the ventricles by the auriculo-ventricular bundle, reaching first the papillary muscles, and thence the rest of the heart until it arrives at the apex, and finally returns by the spiral fibres (see p. 212) to the base of the heart in the region of the origin of the pulmonary artery, which is the representative of the bulbus aortse of the primitive heart. It is therefore not surprising that the electro- cardiogram (p. 246) is complex. The wave P due to auricular activity is followed by a pause before the waves which accompany ventricular systole occur. During this pause it is supposed that the excitatory wave is travelling along the auriculo-ventricular bundle, the mass of which is too small to affect the galvanometer. The pause which intervenes after the wave E, which is the sign of commencing ventricular activity, is supposed to be due to a state of oquipotentiality when the great mass of the circular muscles of the ventricle are contracting ; the final wave T indicates the arrival of the contraction wave at the base by the spiral fibres. The Stannius Experiment. — This consists in applying a tight ligature to the heart between the sinus and the right auricle ; the sinus continues to beat, but the rest of the heart is quiescent. The quiescent parts of the heart may be made to contract in response to mechanical or electrical stimulation. If a second ligature is applied to the junction of the auricles with the ventricle, the ventricle begins to beat again ; the auricles may also beat, but they usually do not. According to Gaskell, the effect of the first ligature is simply an example of blocking ; it is, however, difficult to wholly accept this view, for if instead of applying a ligature at the sino-auricular junction, the heart wall is simply cut through at this spot, the auricles and ventricle are not thereby always rendered quiescent. It appears probable, therefore, that there is some truth in the older view that the ligature acts as a stimulus irritating the vagal termi- nations in Remak's ganglion, and so eliciting a condition of prolonged CH. XXI.] THE 8TANNIUS EXPEKIMENT 259 inhibition ; this, however, passes off after a variable time, and the auricles and ventricle once more beat rhythmically. It is impossible to explain the effect of the second Stannius ligature except on the hypothesis that it acts as a stimulus, and there is no a 'priori reason why the two ligatures should act in opposite ways. The fact that the Stannius heart is quiescent has enabled physiologists to study the effects of stimuli upon heart muscle. A single stimulus produces a single contraction, which has a long latent period, is slow, and propagated as a wave over the heart at the rate of t to |- inch, or 10 — 15 mm. a second. A second stimulus causes a rather larger contraction, a third one larger still, and so on for some four or five beats, when the size of the contraction becomes constant. This staircase phenomenon, as it is called, is also seen in voluntary muscle, but it is more marked in the heart. The accom- panying tracing (fig. 233) shows the result of an actual experiment. Fn;. 233. — Staircase from frog's heart. This was obtained from a Stannius preparation; an induction shock being sent into it with every revolution of the cylinder (rapid rate). The contractions became larger with every beat. To be read from right to left. There are, however, more marked differences than this between voluntary and heart muscle. The first of these is, that the amount of contraction does not vary with the strength of the stimulation. A stimulus strong enough to produce a contraction at all brings out as big a beat as the strongest. The second is, that the heart muscle has a long refractory period ; that is to say, after the application of a stimulus, a second stimulus will not cause a second contraction until after the lapse of a certain interval called the refractory 'period. The refractory period lasts as long as the contraction period. The third difference depends on the second, and consists in the fact that the heart-muscle can never be thrown into complete tetanus by a rapid series of stimulations ; with a strong current there is a partial fusion of the beats, but this is entirely independent of the rate of faradisa- tion. Indeed, as a rule, the heart responds by fewer beats to a rapid than to a slow rate of stimulation. Although nearly all our information on this subject is derived ■from the examination of the hearts of cold-blooded animals, and mainly from the heart of the frog, there is no reason to suppose that what is true for one vertebrate is not true for all ; such differences 260 PHYSIOLOGY OF THE HEART [CH. XXI, as do occur are differences of degree and detail rather than of kind, and Wooldridge, many years ago, succeeded in performing the Stannius experiment on the heart of a mammal. The Isolated Heart. If a frog's heart is simply excised and allowed to remain without being fed, it ceases to beat after a time varying from a few minutes to an hour or so. But if it is fed with a nutritive fluid, it will con- tinue to beat for many hours. Other substances such as drugs may bo added to the perfusion fluid, and their effects noted. The fluid may be passes! through the heart, and the apparatus employed may be oxemplifieil by the following diagram of Schdfer's heart -pleihys- mograph (fig. 234). A frog's heart is tied on to the end of a perfusion Fig. 234. — Schafer's Heart-plethysmograph. cannula, one tube of which serves for the fluid to enter, the other for it to leave. The end of the cannula projects into the ventricle ; the frog's heart, it should be remembered, possesses no coronary vessels ; the spongy texture of the cardiac tissue enables it to take up what it requires from the blood in its interior. The cannula passes through the well-fitting stopper of an air-tight vessel containing oil. On one side of the vessel is a tube, in which a lightly moving piston is fitted ; to this a writing-point is attached. The piston is moved backwards and forwards by the changes of volume in the heart causing the oil to alternately recede from and pass into this side tube. The corresponding tube on the other side can be opened and the tube with the piston closed when one wishes to cease recording the movements. It is with instruments of this kind that a vast amount of valuable work was performed, and the name of the late Dr Sydney Ringer is specially connected with investigations of drug action by means of this method. The best nutritive fluid to employ is undoubtedly the natural fluid, the blood. But in order to use blood there are practical difficulties ; it is difficult, for instance, to obtain much blood from a frog; it is difflcult to prevent it from clotting, and if agents are added to check clotting, such agents usually act deleteriously in the cardiac tissue. The blood of another animal may not be altogether CTT. XXT.] TIIR EXCISED MAMMATJAN HEART 2G1 innocuous, and this is specially the case if thai, blood has l)oen pre- viously whipped, and the li))rin removed. Physiologists therefore owe Dr Kinger a deep debt of gratitude for his discovery of the solution now known as Bi7i(/er's solution. This is physiological salt- solution to which minute quantities of calcium and potassium salts have been added. In other words, the inorganic salts in the propor- tion occurring in the blood will maintain cardiac activity for a long time without the addition of any organic material. These salts are not nutritive in the strict sense, but they constitute the stimulus for the heart's action. Howell of Baltimore has shown that such an inorganic mixture is especially efficacious in throwing the sinus or venous end of the heart into rhythmical action. The normal stimulus for the starting of the heart-beat is thus to be sought in the mineral constituents of the blood. These mineral compounds in solution are broken up into their constituent ions; and of these, sodium ions are the most potent in maintaining the osmotic con- ditions that lead to irritability and contractility. A solution of pure sodium chloride, however, finally throws the heart into a condition of relaxation; hence it is necessary to mix with it small amounts of calcium ions to restrain this effect. Potassium is not absolutely necessary, but it also favours relaxation during diastole. Calcium, on the other hand, is the element which produces contraction, and if present alone or in excess, will produce an intense condition of tonic contraction known as calcium rigor. Some physiologists have manifested a hesitation in accepting the simple view that the various kations mentioned actually originate the heart-beat, and have advanced the hypothesis that they influence a mysterious factor they have named the inner stimulus. What this inner stimulus is, is entirely unknown, and whether or not it is connected with one or more of Langley's receptive substances is equally a matter of speculation. If it exists it is not able to originate cardiac rhythm in the absence of the appropriate inorganic salts. The Excised Mavimalian Heart. — During the past few years it has been shown that the mammalian heart can also be kept alive and active after it has been excised. Valuable as the results have been from a study of the frog's heart, one can hardly doubt that those which one hopes to obtain in the future from a similar study of the mammal's heart will be still more important, and still more trustworthy for the drawing of deductions useful to man. Already the new method has shown its usefulness not only in reference to the metabolism occurring during normal cardiac activity, but also from the pharmacological point of view. In order to maintain the action of the excised mammalian heart certain precautions must be taken — 1. The perfusion fluid must be maintained at or about body temperature (37° C). 262 riTYSioLooY of the heart [CTT. XXI. 2. It must circulate through the coronary vessels. 8. It must be well oxygenated. As before, living blood is the ideal lluid for perfusion, but the practical difficulties in its use are so great, that a modification of Ringer's fluid is usually employed. On this fluid the heart will continue to beat for many hours, but it will beat longer (sometimes several days) if a little dextrose is added to the solution. We owe this addition, and the oxygenation alluded to above, to Dr Locke ; and the perfusion fluid now universally employed is consequently called Locke's solution. This has the following CDUiposition: — Pure distilled water Sodium chloride Potassium chloride Calcium chloride Sodium bicarbonate Dextrose 100 c.c. 9 grammes. 0-048 „ 0-02 0-2 Dr Locke has tried other sugars besides dextrose, but no other has the same favourable effect ; Itevulose is better than most other sugars, but not nearly so good as dextrose. Locke and Eosenheim have further shown that the dextrose is used up during cardiac activity, and this lends support to the view already expressed on the importance of this kind of sugar as a source of muscular energy (see p. 131). A mammal such as a cat or rabbit is killed by bleeding or pithing. The heart enclosed in the pericardium is quickly cut out, and gently kneaded to free it from blood, in some warm Einger's solution. The pericardium is then dissected off, and a cannula tied into the aorta ; this is connected to a burette which is kept full of Locke's solution. The solution must be maintained at body tempera- ture, by a warm water-jacket, and must be well oxygenated by letting oxygen bubble through it. The fluid is then allowed to flow, and its pressure closes the aortic valves, and so the fluid enters the coronary arteries, and escapes from the right auricle, which should be freely opened. Under these circumstances the heart will continue to beat for many hours. A graphic record may be obtained by putting a small hook into the apex, and attaching this by a thread to a record- ing lever beneath it. A very good illustration of the usefulness of the method for demonstrating the action of drugs consists in adding a small amount of chloroform to the circulating fluid, and one notices its immediate depressant effect ; on the other hand, a minute dose of adrenaline markedly increases the rate and force of the heart. CHAPTER XXII THE CIRCULATION IN THE BLOOD-VESSELS The movement of the blood from the heart through the arteries, capillaries, and veins back to the heart again, depends on a number of physical factors ; and in the consideration of this important subject we shall have to take into account the general laws which regulate the movement of fluids in tubes, as well as their special application to the flow of the blood in the blood-vessels. The contraction of the heart is the primary propelling force, and the increase of pressure which is thus communicated to the blood it contains causes that blood to enter the arteries ; the arterial blood- pressure is higher than that in the capillaries, and the capillary pressure is higher than that in the veins; the venous pressure gradually falls as we approach the heart ; it is lowest of all in the heart cavities during diastole ; fluid moves in the direction of lower pressure, hence the flow of blood is from the heart through the vessels back to the heart again. The vessels are not rigid tubes, but possess marked elasticity ; it is owing to this that the intermittent force of the heart is modified in such a way that the stream of blood in the capillaries is a constant one, and under normal circumstances exhibits no pulsation ; the p^dse is one of the main characters of the arterial flow. A further com- plication is due to the fact that the vessels through which the blood flows are of varying calibre, and this is the main factor in determin- ing its velocity. Every time an artery divides, the united sectional area of its branches is greater than that of the parent artery, although, of course, each of the individual branches is of smaller calibre. The total bed of the stream is thus becoming greater, until when we reach the capillaries the bed is increased suddenly and enormously, being several hundred times greater than that of the aorta from which they all ultimately spring. In the case of the veins the same is true in the reverse direction ; the sectional area of a vein is less than that of the total sectional area of its tributaries ; hence as we approach the heart the total bed of the stream is becoming continually ?63. 264 THE CIRCULATION IN THE I5L00D-VESSELS [CH. XXII. smaller, but never so small as in tlie corresjjonding arteries; a vein is always twice the size, often more than twice the size, of the cor- responding artery. Velocity of flow varies inversely with the bed of the stream ; the velocity is therefore greatest in the aorta, slows down in the small arteries, and becomes slowest of all in the capil- laries where the total bed is widest ; we may compare the combined capillaries to a vast lake into which the arterial river flows. On leaving the capillaries, the blood, in traversing the veins once more, becomes accelerated because the bed of the stream becomes narrower, but its speed in a vein is only about half that in the corresponding artery because the bed is twice as great. In connection with the variation in the bed of the stream we must also consider the question of resistance. If the increase in sectional area took place without division of the stream into numerous branches, the main effect would be to lower resistance to the flow of fluid ; but the friction-lowering effect of increased area is much more than counterbalanced by the increased surface of the numerous branches, and there is increased friction on this account. The resist- ance of the capillaries would be large even for a stream of water, and when we consider that the blood is much more viscid than water, we see the effect must be much greater. The resistance to the flow of fluid along a small tube is in inverse proportion to the fourth power of the diameter, i.e., if the diameter of the tube is halved, the resistance is increased sixteen-fold. Between the arteries and the capillaries are the small arteries or arterioles ; these vessels are always in a state of moderate or tonic constriction ; they may roughly be compared to narrow inlets into the wide capillary lake. The main resistance to the passage of blood through the tissues is situated in the arterioles, and not in the capillaries ; this is usually spoken of as the peripheral resistance, and it is variable by alterations in the calibre of the arterioles, their muscular tissue being under the control of nerves which are termed vaso-motor. The main resistance is in the arterioles and not in the capillaries for the following reason : each individual capillary is small, and its resistance therefore great, but their number is so immense, and the total bed so large, that the resultant resistance offered is com- paratively small. This is well brought out by a com^^arison of the velocity in the two cases ; in the arterioles the velocity has to be high in order to supply with l)lood the large capillary areas spring- ing from them; in the capillaries, as we have already seen, the velocity is low. After this general account of the main features of the circulation, we can now pass to a detailed description of the various points raised. CH. XXTI.] ELASTICITY OF THE BLOOD-VESBELS 265 Use of the Elasticity of the Vessels. If a pump is connected to a rigid tube, such as a glass tube, filled with water, and a certain amount of water is forced into the tube, an exactly eijual amount of water is driven out from the open end. During the intervals of pumping the flow ceases, accurately at the instant the inflow stops. If in the next place the open orifice is constricted and the pumping continued as before, the outflow is still restricted to the time during which water is being driven into the tube. The only difference is that a greater force of pumping will be required if the pump is to empty itself in the same time as before, and the force required will increase in proportion to the degree of constriction of the orifice, until with a fairly considerable constriction the force required will be enormous. If the rigid tube is replaced by an elastic one with a wide free opening, the outflow will again be intermittent but not quite restricted to the time of the pumping. This latter difference is because the elastic wall of the tube will stretch a little at each output of the pump, and this continues after the pump has ceased to discharge, and will then recover, at the same time driving out the extra small amount of fluid it contained, after the pump has ceased to act. The flow will thus be intermittent, but the outflow will last for a short time longer than the inflow. If now the orifice be diminished, the dura- tion of the outflow will begin to increase still further, and, as the constriction is increased more and more, will gradually extend over the diastolic period of the pumping. The amount of work required to drive the fixed volume of fluid through the constricted orifice is the same with a rigid and with an elastic tube. In the former case, however, the duration of the outflow is of necessity the same as that of the inflow, whereas in the second case this time is prolonged. If the constriction of the orifice of the elastic tube is sufficiently increased, a point is at last reached at which the outflow lasts throughout the whole cycle of the pump, and here therefore some of the energy imparted to the fluid by the pump is converted into a pressure energy represented by the tension of the elastic walls of the tube, and this energy is given out again after the fluid has ceased to enter the tube and is just sufficient to exactly drive out the stored fluid during the resting period, and a point will ultimately be reached at which the outflow will become not only continuous but also constant. The degree of constriction necessary to produce this effect will depend upon the distensibility of the elastic tube. The more distensible this is, the earlier will tliis stage be reached, and the lower will be the mean pressure. This is the condition we find in the circulatory system. Let us now apply this to the body. 266 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXII. At each beat the left ventricle forces about three ounces of blood into the already full arterial system. The arteries are elastic tubes, and the amount of elastic tissue is greatest in the large arteries. The first effect of the extra three ounces is to distend the aorta still further ; the elastic recoil of the walls drives on another portion of blood, which distends the next section of the arterial wall, and this distension is transmitted as a wave along the arteries, but with gradually diminishing force as the total arterial stream becomes larger. This wave constitutes the pulse-wave. Between the strokes of the pump, or, in other words, during the periods of diastole, the energy imparted to the elastic arterial walls by the heart, and which has produced distension of the arteries, comes into play ; their recoil drives the blood onwards and the arteries return to their original size. The flow, therefore, does not cease during the heart's inactivity, so that although the force of the heart is an intermittent one, the flow through the capillaries and the veins beyond is a constant one, all trace of pulsation having disappeared. The peripheral resistance which keeps up the blood-pressure in the arteries, and like the con- striction at the end of our india-rubber tube, assists in the conversion of the intermittent into a continuous and constant stream, is to be found in the arterioles or small arteries, just before the blood passes into what we have termed the vast capillary lake. These small arteries with their relative excess of muscular tissue, are in health always in a state of moderate tonic contraction. The large arteries contain a considerable amount of muscular as well as elastic tissue. This co-operates with the elastic tissue in adapting the calibre of the vessels to the quantity of blood they contain. For the amount of blood in the vessels is never quite constant, and were elastic tissue only present, the pressure exercised by the walls of the containing vessels on the contained blood would be sometimes very small, sometimes too great. The presence of a contractile element, however, provides for a certain uniformity in the amount of pressure exercised. There is no reason to suppose that the muscular coat assists in propelling the onward current of blood, except in virtue of the fact that muscular tissue is elastic, and there- fore co-operates in the large arteries with the elastic tissue in keeping up the constant flow in the way already described. The contractility of the arterial walls fulfils a useful purpose in checking haemorrhage should a small vessel be cut, as it assists in the closure of the cut end, and this in conjunction with the coagulation of the blood arrests the escape of blood. Blood-pre ssure . The circulation of the blood depends on the existence of different degrees of pressure in different parts of the circulatory system ; CH. XXII.] BLOOD-PRESSURE 267 there is a diminution of pressure from the heart onwards through arteries, capillaries, and veins, back to the heart again. Fig. 235 represents roughly the fall of pressure along the systemic vascular system. It falls slowly in the great arteries and manifests oscillations corresponding with the alternate systole and diastole of the heart ; at the end of the arterial system it falls suddenly and extensively in the course of the arterioles ; it /^ /, ^ ^ again falls gradually through the capillaries and veins till in the large veins near the heart it is negative. Such a diagram of blood-pressure is thus very different from one of velocity ; the velocity like the pressure falls from the arteries to the °lv a c v capillaries, but unlike it, rises ^^^, .so.-ueigbt .of biood-pressure (bp) m lv, left a^ain in the veins ventricle, a, arteries ; C, capillaries ; V, veins ; * ,TT , ' i 1 j_i RA, right auricle ; 00, line of no pressure. We must now study the methods by which blood-pressure is measured and recorded, and the main causes that produce variations in its amount. In order that we may understand the methods that are used for this purpose, it will be first necessary for us to consider some of the general laws of fluid pressure, and then to study the methods that are employed in an artificial schema of the circulation. Fluid pressure is a different thing from the pressure of a solid, and is exercised equally in all directions. If a cylindrical vessel, placed vertically, is filled with a cylinder of ice, the pressure of the ice will be exercised on the bottom of the cylinder, but not on its sides. When the ice melts, the water presses on the sides also, and if a hole is made in the cylinder below the level of the upper surface of the water, the water will flow out of the hole, and the force with which it escapes will be proportional to the depth of the hole beneath the surface. If we take a square centimetre as the unit of area, the actual pressure exerted on it is hxdxg, where h is the height of the free surface above the level where we are measuring the pressure, d the density of the fluid, and g the acceleration of gravity (981). Suppose a gramme of water to flow out, we may consider that this gramme has fallen through a height or head h in centimetres from the free surface to the opening ; it comes practically from the top, because it is there that the liquid disappears from inside the vessel. In falling the height h, it gives out hg ergs of work. The unit of force is called a di/np, : a moving body is said to possess momentum : this is measured by the product of its mass and its velocity ; thus the effective quantity of motion of a body may be large on account of its having a large 268 TTIK CmCULATION IN TTTK BLOOD-VESSELS [CTI. XXIL mass (tor instanci-, a lic.ivy wafjffoii rolliii;; down aliill), or larprc- velocity (for instance, a bullet sjiccdinfj tliroiitili the air). A force continuously applied to a ni(jvinj< mass produces a continuous increase in its rate of movement ; this is termed arrelcratpjn, and force may be defined as the rate of change of momentum ; it can be measured, therefore, by observinj;- the amount of momentum it ffcneratcs in a measured time, and dividintr by that time. If a frramme is taken as the unit of mass, a centimetre as the unit of length, ;ind a second us tiie unit of time, the unit of force ^ _ momentum _ gramme-centimetre per second Time. Time in seconds. = gramme-<'entimetre per second, per second = 1 dyne. The unit wliich corresjionds to the dyne in the measurement of work is called an en/, that is, the work done in lifting a gramme weiglit through the height of one centimetre ; tlie weight of a gramme is ItSl dynes, and the work done in Ufting it one centimetre is 981 ergs. The kinetic energy of a body moving with velocity v is ', x mass XV-, or for one gramme i-y'; hence if all the work that liquid can do is spent in giving kinetic energy to it, the velocity with which it will flow out is given by putting the kinetic energy = work done. In other terms : — lv2 = sh ; hence *' = J2ph or /' = |r- A liquid, however, has not necessarily a free surface, but may be completely enclosed, as is the water in a system of hydraulic pressure mains, or the blood in the circulatory system. The pressure in such a system at any point may be measured by inserting at that point a vertical tube at right angles to the blood-vessel ; the blood would rise in it to a point, and would form a free surface a certain distance up this tube ; the head h in the above calculation must be reckoned from this free surface downwards. If, instead of using a tube of fine bore for this purpose, we employ a wider tube, say of ten times greater area, the height or head to which the fluid rises will be the same as in the narrow tube, though naturally the actual weight of fluid supported will be ten times greater ; but the weight per unit of area is the same in both cases. When, therefore, we measure the pressure of fluid in terms of the height of a column of fluid, such as mercury, which it will balance, we really moan that the force of the blood is equal to the weight of the mercury it supports per unit of area, and this will naturally be proportional to the height of the column. Let us next consider the simple case of a fluid flowing from a reservoir, E (fig. 236), along a tube, which wo will imagine is open at the other end. In the course of the tube we will suppose three upright glass tubes (A, B, and D) are inserted at equal distances. Between B and D there is a bladder, which may be divided into a number of channels by packing it with tow to represent the capillaries, and between B and CH. XXII.] SCHEMA OF THE CIRCULATION 269 C, a clip E, which can he tightened or loosened at will, and which will roughly represent the peripheral resistance produced hy the arterioles. The far end of the tube is provided with a stop-cock. If this stop-cock is closed there will naturally be no flow of fluid, and the fluid will rise to equal heights indicated by the dotted line in all the upright tubes. This shows that the pressure in all parts of the tube is the same. The upright tubes which measure the lateral pressure exerted by the fluid on the wall of the main tube, are called pizometers, manometers, or pressure measurers. If now the stop-cock is opened, the fluid flows on account of the difference of pressure brought about Ijy gravitation ; the height of the — Schema to illustrate blood-pressure. fluid in the manometers indicates that the pressure is greatest in K, less in A, less still in B, and least of all in D. On account of the peripheral resistance of the arterioles and capillaries, the pressure is very small in the veins, as indicated by the height of the fluid in the manometer D. The difference between D and B is much more marked than the difference between B and A. If the fluid which flows out of the end of the tube is collected in a jug and poured back into E, we complete the circulation. But the schema is an extremely rough one, and is especially faulty in that the pressure which starts at E is nearly constant and not intermittent. This may be remedied by taking E in the hand, and raising and lower- ing it alternately. The fluid in the manometers bobs up and down with every rise and fall of E : this is least marked in D. The greater and the faster the movement of E, the greater is the rise of arterial pressure. This is a rough illustration of the fact that increase in 270 THE CIRCULATION IN THE BLOOD-VESSELS [CH, XXIL the force and frequency of the lieart's beat causes a rise of arterial pressure. Again, if more fluid is poured into K, there is a correspond- ing rise in fluid in the manometers. This illustrates the rise of pressure produced by an increase in the contents of the vascular system. And this schema, rough thougli it is, also serves to illustrate the third important factor in the maintenance of the blood-pressure, namely, the peripheral resistance. This is done by means of the clip E ; if the clip is tightened, one imitates increased constriction of the arterioles ; if it is loosened, one imitates dilatation of the arterioles. If it is closed entirely, the fluid in A and B rises to the same level as that in K ; the pressure of E is not felt at all by C and D, which empty themselves, and the flow ceases. If the clip E is only tightened so as not to be quite closed, the arterial pressure (in A and B) rises, and the venous pressure (in D) falls ; if the clip is freely opened, the arterial pressure falls, and the venous pressure rises. These same facts can be demonstrated by a more perfect circula- tion schema, such as is represented in fig. 237. Fio. 237. — Schema of tlie circulation. The heart (H) is represented by a Higginson's syringe, which is worked with the hand ; the tube from it represents the arterial system, the clip E the resistance of the arterioles ; C is the capillary lake, from which the vein (larger than the artery) leads back to the heart H. A and B are two manometers wliich respectively indicate arterial and venous pressures. Only in place of straight tubes mercurial manometers are used. Each of these is a U-tube about half filled with mercury, and united to the artery or vein by a tube containing fluid. If the mercury in the two limbs of the (J i.s at the same level, the pressure of the fluid in connection with one limb is exactly equal to Cll. xxu.] STEPHEN HALES EXPERIMENTS 271 that exerted by the atmospheric pressure on the other. The mercury, however, is pushed up in the far limb of the manometer connected to the artery, the pressure there being greater than that of the atmos- phere ; this is therefore called positive pressure, and the total amount of pressure is measured by the difference between the levels a and a. The manometer B attached to the vein, however, indicates a negative pressure (b h'), that is a pressure less than that of the atmosphere, so that the mercury in the limb nearest the vein is sucked up. Anderson Stuart's kymoscope (iig. 238) is a more complete schema. It consists of a long leaden tube filled with fluid, the two ends of which are connected by an india-rubber tube on which is a valved syringe to represent the heart On the course of the tube are a large number of open- mouthed upright manometers which indicate the pressure when the syringe is worked, and confer on the tube the elasticity necessary to cause the dis- appearance of the pulse in the middle region which represents the capillaries. The long leaden tube is twisted round a cylinder, so that the manometers are placed closely side by side. We can now pass on to the methods adopted in the investigations of blood- pressure in animals. The fact that the blood exerts considerable pressure on the arterial walls may be readily shown by puncturing any artery; the blood is propelled with great force through the opening, and the jet rises to a considerable height; in the case of a small artery, where the pressure is lower, the jet is not so high as in a large artery : the jerky character of the outflow due to the intermittent action of the heart is also seen. If a vein is similarly injured, the blood is expelled with much less force, and the flow is continuous, not intermittent. The first to make an advance on this very rough method of demonstrating blood-pressure was the Eev. Stephen Hales, vicar of Teddington (1702). He inserted, using a small brass tube as a cannula, a glass tube at right angles to the femoral artery of a horse, and noted the height to which the blood rose in it. This is a method like that wliich we used in the first schema described (fig. 236). The blood rose to the height of about 8 feet, and having reached its highest Flo. 23S. — Anderson Stuarl's Kymoscoiie. 272 THE CIRCULATION IN THK BLOOD-VESSELS [CH. XXII. point, it oscillated with the hoart-beats, each cardiac systole causing a rise, each diastole a fall. Hales also noted a general rise during each inspiration. The method taught Hales these primary truths in connection with arterial pressure, but it possesses many disadvan- tages ; in the first place, the blood in the glass tube very soon clots, and in the second place, a column of liquid 8 feet high is an inconvenient ono to work with. The first of these disadvantages was overcome to a great extent by Vierordt, who attached a tube filled with saturated solution of sodium carbonate to the artery, and the blood-pressure was measured by the height of the column of this saline solution which the blood would support. The second disadvantage was overcome by Poiseuille, who intro- duced the heavy li(]uid, mercury, as the substance on which the blood exerted its pressure; and the U-shaped mercurial manometer was connected to the artery by a tube filled with sodium carbonate solution to delay clotting. The study of blood-pressure cannot, however, be considered to have been in a satisfactory condition until the introduction by Carl Fid. 231). Oiugraiii of iiRTi-iii i;U Kyiiiogniiih. Ludwig of the Kymograph ; that is to say, Poiseuille's hcemodyna- mometer was combined with apparatus for obtaining a graphic record of the oscillati(ms of the mercury. The name kymograph or wave- writer, we shall sec immediately, is a very suitable one. A skeleton sketch of the apparatus is given in fig. 239. CH. XXII.] TUK KYMOGRAPH 273 The artery is exposed and clamped, so that no haemorrhage occurs ; it is then opened, and a glass cannula is inserted and firmly tied in. The form of cannula usually employed (Fran('ois Franck's) is shown on a larger scale at A ; the narrow part with the neck in it is tied into the artery towards the heart ; the cross piece of the T is united to the manometer; the third limb is provided with a short piece of india-rubber tubing which is kept closed by a clip and only opened on emergencies, such as to clear out a clot with a feather should one form in the cannula during the progress of an experiment. The tube by means of which the cannula is united to the man- FiG. 240.— The manometer of Ludwifi's Kymograph. It is also shown in fig. 241, D, 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. ometer is not an elastic one, but is made of flexible metal or thick rubber, so that none of the arterial force may be wasted in expanding it. The tube, cannula, and proximal limb of the manometer are all filled with a saturated solution of sodium carbonate, sodium sulphate, or other salt which will mix with blood and delay its clotting. Before the clip is removed from the artery, the pressure is first got up by a syringe (or pressure bottle containing the same saline solution sus- pended at a good height above the apparatus and connected to it by a tu-be), so that the mercury rises in the distal limb to a height greater than that of the anticipated blood-pressure ; this prevents blood pass- ing into the cannula when the arterial clip is removed. In the distal limb of the (J -tube, floating on the surface of the S 274 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXIL mercury, is an ivory float, from which a long steel wire extends upwards, and terminates in a stiff piece of parchment or a bristle wliich writes on a moving surface covered with smoked paper. 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. 241. — Dia}:ratn of merrurial Kymograph. A, revolting cylinder, workwl by a clockwork arrange- ment contained in the box (B),"the .speed beintc regulated by a fan aUjve the box ; the cylinder is supported by an upright (b), 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. 240. (fig. 239), the large waves corresponding to respiration (the rise of pressure in most animals accompanying 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 Ijy the difference of level between a and a' (fig. 239). * The explanation of the respiratory curves on the tracing is postponed till after we have studied Respiration. CH. XXII.] VENOUS BLOOD-PRESSURE 275 Fig. 240 shows a more complete view of the manometer, and fig. 241 is a diagram of the arrangement by means of whicli it is made into a kymograph. Fig. 242 shows a typical normal arterial blood-pressure tracing on a larger scale. I''i(i. '242. —Normal tracing, somewhat magnilieil, 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.) In taking a tracing of venous Uood-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 Fig. 243.— a form of Kick's Spring Kymograph, u, Tube to be Lduiu lU d \\\t\\ artery ; c, hollow spring, the movement of which moves 6, the writing lever ; c, screw to regulate height of b ; d, outside protective spring ; g, screw to fix on the upright of the support. is investigated is near the heart, a venous pulse is exhibited on the tracing, with small waves as before corresponding to heart-beats, and 276 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXII. larger waves to respiration, only the respiratory rise in pressure now accompanies expiration. The capillary pressure is estimated by the amount of pressure necessary to blanch the skin ; this has l)een done in animals and men (v. Kries, Roy and Brown). Other manometers are often employed instead of the mercurial one. Fick'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 Fig. 244. — Fick's Kymograph, improved by Hering (after M'Kendrick). a, Hollow spring tilled with alcohol, bearing lever arrangement h, 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; (J, syringe for tilling the leaden tute h with saturated sulphate of sodium solution, and to apply sufljcient pressure as to prevent the blood from jiassinp into the tube h at i, the cannula inserted into the vessel; /, 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/. (which is seen in fig. 244, g), before the clip is removed from the artery. The manometer itself is a hollow C-shapcd 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 extent of each pressure change is much better seen. In a mercury en. xxiT.] VARIATIONS OF BLOOD-PPtESSURE 21\ 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. 245). These instruments, though useful for recording the complete Fio. 245.— Normal arterial tracing obtained with Pick's Kymograph in the (log. (Burdon-Sanderson.) changes in pressure, require calibration : that is, the extent of move- ment that corresponds to known pressures must be ascertained by actual experiment. They teach us that the highest pressure reached during systole may be twice or thrice the lowest attained during diastole. 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 : — Large arteries {e.g. carotid) Medium arteries {e.g. radial) / + 140 mm. (about 6 inches) t mercury. + 110 mm. mercury. Capillaries . + 15 to + 20 Small veins of arm . + 9 Portal vein + 10 Inferior vena cava . + 3 Large veins of neck from to — 8 (Starling.) These pressures are, however, subject to considerable variations ; the 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 hcemorrhage). The above is true for general arterial pressure; but if we are investigating local arterial pressure in any organ, the increase or 278 THE CIRCULATION IN THE HLOOD-VESSELS [CH. XXIL decrease in the size of the arterioles of other areas may make its effect felt in the special area under investigation. Venous jjresstcre 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 fore- going table, venous pressure varies in the opposite way to arterial pressure. 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 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 into the cai^illaries is cut down. More blood is therefore retained in the arteries ; 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. The flow into the veins is thus 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 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 CH. XXII.] EFFECT OF GRAYITY 279 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 ansesthetised, 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-cavities once more fill with blood during every diastole. Another experiment was originally performed by Salathe 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 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. We shall, a few pages later, be considering the methods by which blood-pressure may be estimated in man. The effects of gravity on the pressure in various parts can be well shown by alterations of posture. This is an important practical question, especially during 280 THE CIRCULATION IN THE BLOOD-VESSELS [CH XXII Fig. 246.— Effect of weak stimulation of the peripheral end of vagus on arterial blood-pressnre (carotid of rabbit). BP, blood-pressure; A, abscissa or base-line ; T, lime in seconds. Note fall of blood- pressure and slow heart-beats. Fig. 247. — Effect of strong stimulation of the peripheral end of vagus on arterial blood-pressnre (carot of rabbit). Note stoppage of heart and fall of blood-pressure nearly to zero ; after the recommenc ment of the heart, the blood-pressure rises, as in fig. 246, above the normal for a short time. CH. XXn.] VELOCITY OF BLOOD-FLOW 281 anaesthesia, when the forces which counteract the bad effects of gravity may not be working efficiently; if the legs are hanging down, the result may be serious. The pressure in the Pulmonary Circulation varies from i to ^ (mean J) 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 vagv^ 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 on arterial pressure is shown in the two accompanying tracings ; fig. 246 represents the effect of partial, and fig. 247 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 fibres) 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 be 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 amoimt 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 mms. per minute in the systemic capillaries. In warm-blooded animals the velocity is somewhat greater ; in the dog it is Jg- to -j-J^ inch (0"5 to 075 mm.) per second. It must be remembered that the total length of capillary vessels through which any given portion of 282 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXIL blood has to pass probably does not exceed from ^V to ^V 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 hccmodromometer, as it was termed, is shown in the accompanying diagram (fig. 248); this is filled with fr^ Fio. 248. -Volkmann's Hiemoilroniom ler. Fio. 249.— Ludwig's Stromuhr. salt solution, and provided with a stop-cock a ; this tap is so arranged 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 CH. XXII.] THE STROMUHR 283 U-shaped n;lass tubo dilated at a and a, the ends of which, h and i, are of known calibre. The bulbs can be tilled by a coninion opening at k. The instrument is so contrived that at h and 6', the glass part is firraly 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. 249, corresponds exactly with those \\\.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 is divided and connected with two cannulse and tubes which fit it accurately with h and *; ^ is the central end, and i 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 defibrinatcd 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 Veloeitv = t- 1 = "S"- •' sectional area o 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 7rr-; r is the radius (2 mm.), and 7r = 31416. From these data we get ,, , V 0-5 c.c. 500 cubic millimetres Velocity =.^=3.j^^g^ 2-3 = STiTG^Vl = ^^'^ "^"^- P"^' '""• Many modifications of Ludwig's original instrmnent have been devised. Fig. 250 shows Tigerstedt's. The tubes A and B are placed in connection with the two ends 284 THE CIRCULATION IN THE niX)OD-VESSELS [cn. XXII. Fin. 250.— Tigerstcdfs Stromuhr. of tho cut artery as before ; there is also a turntable arrangement at F, by means of which the two upper tubes and I) may be connected as in the liguro ; or by twisting it through two right angles, D can bo made to communicate with A, and 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 instrument 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 numl)er of revolutions during a given period is noted. The capacity of the cylinder minus that of the ball is ascertained, and the velocity is calculated by the same formula as that already given. Tlie Stromuhr has one advantage over the hremodromometer, in that it enables one to note changes in viean 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 neces- sary 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 hydrostatic. Thus, if we consider the flow from one point in the tube to another (say, for example, at 1 cm. dis- tance), the forces producing the flow are (1) the kinetic energy pos- sessed by the blood when it enters the first spot {i.e. ^- dynes, CH XXII.] THE PRESSURE GRADIENT 285 or -_ grainine-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, 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 286 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXIL D vessel wall as the pressure-head, aud 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 difierence between the two pressure-lieads 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. 251). 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 reach a height sufficient to balance the pressure-head; the difiference 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 compressed, 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-haemata- 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 velo- city 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 Fio. 251. — Diagram to illustrate the principle of Pitot's Tube and Cybulski's rhoto-ha;mata- chometer. CHAUVEAU S DROMOGRAPII 287 CH. XXII.] carotid are practically identical, but that the maximuni 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, wliile the crural, to a considerable extent, faces the stream, and 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 in- vented a hsemo - tachometer, employing the principle of the hydrometric pendulum ; liis instrument was improved by Chauveau. Chauveau's in- strument is shown in fig. 252. It consists of a thin brass tube, a, in one side of which is a small per- foration closed by thin vulcanised india-rubber. Passing through the rubber is a fine lever, one end of which, slightly flattened, extends into the lumen of the tube, while the other moves over the face of a dial. The tube is inserted into the interior of an artery, and ligatures applied to fix it, so that the ''velocity pulse,'' i.e., 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 movements in terms of velocity, the instrument must be calibrated beforehand. The next diagram, fig. 253, shows how the instrument may be adapted to give Fig. 252.— 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. Fio. 253.— Chauveau's Dromograph connected with tambours to give a graphic record. a graphic record. The movements of the pendulum are brought to bear upon a tambour, B, which communicates by a tube with the 288 THE CIRCULATION IN TllK BLOOD-VESSELS [CIL XXII. recording tambour 0. If the mass of the pendulum is small, the accuracy of the instrument is considerable. Fig. 254 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 corresponding to one cardiac cycle. On both curves the upstroke is the 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 are due to elastic vibrations. We shall be studying all those 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 maximum before the pressure curve ; this Fiu. 254.— Velocity curve (V), and pressure curve (P) from the carotid artery of the liorse ; no, abscissa of velocity curve; 1, 2, 3, 4 show simultaneous points on both curves. (Cliauveau and Marey.) 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 bo noticed that during the dicrotic notch the pressure falls comparatively little, but in the velocity curve the fall is considerable, and the curve may sink below the base line oo. This negative effect is naturally much more marked in the aorta and its first large branches than in situations farther 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 en. XXII.] TIME OF A COMPLETE CIRCULATION 289 changes has also been observed. Thus Lortot found that the carotid flow is live 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 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 compart- ment, and the ferrocyanide was 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, doc 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 dof'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 reinvestigated 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 carotid. 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. T 290 THE CIRCULATION IX TlIK BLOOD-VESSELS [cil. XXII. The second method used is even simpler, and gives practically the same results; a solution of methylene blue is injected into a vessel. The corresponding vessel 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 vessel under observation. Stewart has applied these methods also for determining the time occupied by the passage of blood through various districts of the circulation ; the longest circulation times were found in the portal system and the lower limbs. He calculates that the total circulation time in man is about 15 seconds. 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 three 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 Pvdse. 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 -boat. 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 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 freqitency ; that is the number of pulse-beats per minute. This gives tlio 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. 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 CII. XXII.] THE rULSE 291 heart missing a beat every now anil 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 Fro. 255.— Marey'.s Sphygmograph, modified by Mahomed. 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 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 T ^ Fio. 256.— Diagram of the lever of the Sphygmograph. 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 292 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXII. inscribe tho magnified record of the arterial movement on a travelling surface. The instruments most frequently used are those of Marey, one of the numerous modifications of which is represented in figures 255, 256, and 257, and of Dudgeon (fig. 258). Fio. 2a7.— Tho Siihygmogiapli applied to thf arm Each instrument is provided with an arrangement by which tlie pressure can be adjusted so as to obtain the best record. The measurement of the j^ressure is, however, rough, and both instruments have tho disadvantage of giving oscillations of their own to tho Fic. 25S.— Dudgeon's Spliygmoj,'raph. The doited outliiin represents the piece of l)lackened paper on which tlie spliygmograni is written. sphygmogram ; this is specially noticeable in Dudgeon's sphygmo- graph. But these defects may be overcome by the use of some form of sphygmometer. (See later, p. 295.) It is also important to remember that the pad or button placed upon the artery rests partly on the venae comites, so that not only arterial tension but any CH. XXII.] SPHYGMOGRAMS 293 turgidity arising from vouous congestion, will affect the height and form of the sphygniographic record. Fig. 259 represents a typical sphygmographic tracing obtained from the radial artery. It consists of an upstroke due to the expansion of the artery, and a down- stroke due to its retraction. The descent is more gradual than the upstroke, because the elastic recoil acts more constantly and steadily than the heart-beat. On the descent are several secondary (katacrotic) 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. 260). 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 Fio. 259. — Diagram of pulse-tracing. A, up- strol^e; B, downstroke; C, pre-dicrotic wave; D, dicrotic; E, post-dicrotic wave. Fio. 260.— Anacrotic pulse. arteries, and are increased in number when the tension of the arteries 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, showing that it has its origin in the commencement of the arterial system. 294 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXII. 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. 288), 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 Fio. 2.;i.— Dicrotic pulse wave rcbouuds from these and is propagated through the arterial system as the dicrotic 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. 261), 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 con- tinuous line in the accompanying figure (fig. 259). The apex of the tidal wave, B, marks the end of the ventricular systole. T ,1 p • J T Fifi. 262. — Uiaiirani of In our study of intracardiac pressure, we puise-traoinf,-; A.per- saw that the systolic plateau sometimes has an drcrot"c • aAd^D^pLs^t- ascending, sometimes a descending, slope (see dicrotic 'waves. ' p. 243) ; we now come to the explanation of this fact. If after the first sudden rise of pressure in the aorta the peri- pheral 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 Bright'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. The main waves of the pulse can bo demonstrated without the CIl. XXII.] BLOOD-rRESSURE IN MAN 295 Hae in auto- graph, to be read from right to left. use of any instrument at all, by allowing the blood to spurt from a cut artery on to the surface of a large sheet of white paper travel- ling past it. Wo thus obtain what is very appropriately called a hcemautograph (fig. 2G3). A distinction must be drawn between ilie pulse as felt at any one spot in the course of an artery, and the pulse-wave which is propagated through- out the arterial system. This wave of expansion travels along the arteries, and is started by the pro- pulsion 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 small fraction 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 Rate of Propagation of the Pulse-Wave.— 1h& 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 ri»e 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 distanc-es from the heart ; their levers are arranged to write immediately under one another, as in fig. 220, p. 241. The difference in time between the commencement of their upstrokes 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 is effected by instruments which may be applied to the vessels without any dissection. These instruments are termed sphygmometers, and the best of them are modifications of one originally introduced by Eiva Rocci. C. J. Martin's pattern consists of a four-sided elastic bag about four and a half inches wide, and long enough to encircle the arm. It is wrapped round the arm, and outside of it a cuff of strong canvas is firmly strapped. Air is forced into the bag by a tube leading from a ball syringe; this tube is also connected by a side branch to a mercury manometer. As one continues to pump and distend the bag, the pulse-beats are transmitted to the mercury which is seen to rise in the manometer and oscillate with the pulse-beats. As the 296 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXII. pressure rises the oscillations become more pronounced, and at a certain point they exhibit a greater excursion than they do at any other height; beyond this point of maximal pulsation, the oscilla- tions diminish in amplitude, and as the distension of the bag is increased still more, the pressure is at last reached, when it is sufficient to obliterate the pulse, and the oscillations of the mercurial column cease, and the })ulsc is no longer to be felt at the wrist. The pressure necessary to do this is equal to the systolic j^rcssure, and the height of the mercurial column should bo noted when the pulse just disappears. The point of maximal pulsation gives a reading of the Fio. 204.— Martin's Sijliy^jmometer (made by Hawskloy, 357 Oxford Street). diastolic pressure. The systolic pressure is more easily read than the diastolic pressure, for it is by no means easy to judge accurately where the pulsations are greatest. Moreover, the amount of systolic pressure gives one more useful information of the condition of the circulation than does the diastolic pressure. 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. The pressure in the lower limbs is greater than that in the upper limbs in the standing posture owing to the effect of gravity. 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 en. XXII.] TIIK CAPILLARY FLOW 297 of food produces no noteworthy effect. In disease there are naturally great variations, and the study of those has yielded valuable results. The Capillary Plo-w. 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 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, which moves more slowly than the blood in the centre. Anyone who has 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 298 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXII. 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 bo seen before their escape, so none could be observed afterwards — so rapidly was the part healed. But these observations did not attract much notice until the phenomenon was rediscovered by Cohnheim in 1867. Cohnheira's experiment was performed in the following manner : A frog is anaesthetised ; and the abdomen having been opened, a portion 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 cor- puscles, 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 corpuscles) 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 emigrat- ing leucocytes do not close up immediately, and so the red corpuscles escape too. The real moaning 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 the process. Metschnikoff teaches that the vascular phenomena of inflammation have for their object an in- crease in the emigration of leucocytes, which have the power of devouring the irritant substance, and removing the tissues killed by the lesion. They are therefore called phagocytes (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 leuco- cytes become pus corpuscles; but if the leucocytes are successful in destroying the foreign body, micro-organisms, and disintegrated tissues, they disappear, wandering back to the blood-vessels, and Fio. 265.— A large capillary from the frog's mesentery oight liours after irrita- tion had been set up, showing emigration of leucocytes, a, Cells in the act of traversing the capillary wall ; 6, some already escaped. (Frey.) important part in en. XXII.] THE VENOUS FLOW 299 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- 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 clilatation in blushing, may be referred primarily to the action of the small arteries. The Venous Flo-w. The blood-current in the veins is maintained primarily by the vis a tergo, that is, the force behind, which is the blood-pressure transmitted from the heart and arteries; but very effectual assist- ance 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. 202, 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 circula- tion. 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, * This question is closely related to that of immunity, which is discussed in the chapter on the Blood (Chapter XXIX. ). 300 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXIL about teu times in a miuuto ; tho existence of valves prevents regur- gitation, so the entire effect of the contractions is auxiliary to the onward current of blood. Analogous phononiena arc occasionally found in other animals. A venous pulse is observed under the conditions previously described (p. 297), 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 tho heart ; this corresponds to varia- tions of the pressure in the right auricle. When the ventricle is con- 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-constridor nerves ; (h) those the stimulation of which causes dilatation of the vessels ; these are called vaso-dilator nerves. The muscular structure of arteries was first described by Henle in 1841 ; but it was not until twelve years later that the nerves supplying this muscular tissue were discovered. The names of Claude Bernard, Brown-Sequard, and Schiff are specially connected with this discovery. These nerves 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 Hows 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 CII. XXII.] THE VASO-MOTOn NERVOUS SYSTEM 301 area, and therefore a correspondingly small amount 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 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, heart itself, 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 acceleration of the heart, which is another result of stimu- lating 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 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 302 THE CIRCULATION IN THE RI.OOD-VESSELS [CH. XXII. higher and liigher, and tho 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- 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 exact position of the vaso-motor centre in the bulb is far from clear ; there is no special group of cells there which an anatomist can point to as exercising this function, in the same way as he can point to the respiratory or the cardio- inhibitory centre. Possibly the cells are scattered over a large area and do not occur in definite groups. The fibres that leave these cells to pass down the spinal cord probably travel along the lateral columns ; but here again exact information is lacking, and we do not know whether or not they decussate in the bulb or elsewhere. They terminate by arborising around the cells in the grey matter of the subsidiary vaso-motor centres, the anatomical position of which 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 general arrangement of the vaso-motor nerves will have been already gathered from our description of the Autonomic Nervous System (Chapter XVII.); but we may briefly recapitulate the main facts. Tho vaso-constridor 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 of the vertebral column. That is to say, the small medullated or 'pre-ganglionic 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. Those which are destined for the supply of the vessels of the head pass into the ganglion stellatum or first thoracic ganglion, thence through the annulus of Vieussens to the inferior cervical ganglion, and thence along the sympathetic trunk to their destination. Their cell-station is in the superior cervical ganglion. en XXII.] VASO-DILATOK NERVES 303 The new fibres which arise in the ganglia are usually non-niedul- lated, and are termed post-ganglionic. 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 samrlion 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 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 collateral ganglia. The vaso-dilator nerves have been stated to 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 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. Our knowledge of vaso-dilator nerves is limited, except in such instances as the two nerves just mentioned. Equally deficient is our information concerning vaso-dilator centres in the central nervous system. AV. M. Bayliss, in his search for vaso-dilator fibres in the dog, was not successful in finding any for 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, or electrical 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. 160), 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 Vaso -motor centre can be excited directly by induc- tion currents; the result is an increase of arterial blood-pressure owing to an increase of the contraction of the peripheral arterioles. 304 THE CIRCULATrON IN THE BLOOD-VESSELS [CH. XXII. Kl<:. 'Ji'iO. -Aitdial M(ji)il-iiri'.ssure lr;icii]i; from dn^ slmwin- Mayci- wavi's. (Sliorringtcjn.) aamfe (' \ ■■;.. ,/ \^^ "X '^ "^ %m Br ^t 'wft^dww B.P. ^^■■■r'^^'^y.^^H'; ': ^'■Nr™ ■ill: 1 B A T P '^L^ —i-J Fio. 2(57. — Hise in arterial blood-pressvire iiroduced by stiniulatiiiK tlie central end of a sensory nerve (external popliteal) in a cat under the influence of morphine and curare. BP, blood-pre.s3urc ; A, abscissa or base-line; T, time intervals of 5 seconds ; E, signal line, the lowering of which indicates the period of stimulation of the nerve. The size of the U;iure is slightly reduced in reproduction. (Sherrington.) CII. XXII.] PRESSOIt AND DKPRKSSOR XKRVKS 305 It can also be excited by tbo action oi poisons in tlio blnod 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 asphyxia ; 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. When asphyxia is brought about by the cessation of artificial respiration in a curarised animal, waves are often observed on the blood-pressure curve synchronous with the normal rate of respiration. The respiratory centre is making ineffectual efforts to produce breathing movements, and thus it affects its neighbour, the vaso-motor centre, in a parallel manner. Such waves are known as Trauhe-Hering waves. One, however, frequently sees in tracings of blood-pressure in anoesthetised animals larger waves which arise from a slow rhythmic action of the vaso- motor centre, and which are much slower in their rhythm than those due to respiration. Fig. 266 represents a tracing from a dog which shows tliese waves {Mayers uave.^). The tracing shows three sets of waves, first the oscillations due to the heart-beats, next in size those produced by the respiratory movements, which in their turn are superposed on the prolonged Mayer waves. The Vaso-motor centre may be excited, reflexly. — The afferent 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. 267 shows the result of such an experiment. It is necessary in performing the 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 ; these produce the opposite effect. The most marked bundle of these is known a& the depressor nerve. In most animals this is bound up in the trunk of the vagus ; but in some, such as 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-pressui'e is produced (see fig. 268). U 306 THE CIRCULATION IN THE BLOOD-VESSELS [CII. XXIL Stimulation of this nerve affects the vaso-motor centre in such a way tliat the normal constrictor ini])ulscs that pass down the vaso-con- strictor nerves are inhibited. The fall of ])ressiire is very slight after section of the splanchnic nerves, showin.ii; that the splanchnic area is the part of the body most affected. Tlie normal function of this Fio. 263.— Tracing of ai-terial blood-pressun- sliowin^ tlie ellVct of stiniulatin a cat. The letters pretixed to the various linos liavo the same meaning a :tliec > in li; entral end of the Depressor nervi ;. 'JOT. (tjherriiigton.) 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. JY. R— 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. 24:6 and 247) ; stnnulation of the central end of the CH. XXII.] EXPEKIMENTS ON VASO-MOTOR NERVES 307 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 the ear of an antesthetised 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 excessive constriction of the vessels. 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 may be so rapid that the blood is 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. 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 miless 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. ITie 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. 308 THE CIRCULATION IN TIIK HLOOD-VESSELS [CII. XXII 2. The method of slowly interrupted shocks. — If a mixed nerve is stimulated witli 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 tho blood through the submaxillary gland, in which tho vaso-constrictor and dilator fibres run separate courses, it has been shown that if both sots of fibres are simultaneously 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 wull be summed up to produce a marked effect. 3. The injluence 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 bv the use of various forms of manometer, which is the only Fio. 269.— PleUiysmo^;rai)li. IJy nifians of tliis apparatus, the alteration in volume of the arm e, which is enclosed in a glass tube a, tilled with fluid, the openiiiR throut;h which it passes being lirnily closed by a thick gutta-percha band v, is communicated to the lover r>, and rogisti-red by a recording apparatus. The fluid in a communicates with that in n, the upper limit of which is above that in A. The alterations in volume are due to alterations in tho 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 wdien 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. 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 liml), or CI I. XXII.] THE ONCOMETEK 309 organ of au animal. Such an instrument is called a plethysmograph. One of these instruments applied to the human ai'm is shown in the accompanying figure (fig. 269). Every time the arm expands with the heart's systole, a little of the fluid 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. A study of the volume pulse shows it to possess the same main characters (for instance, a dicrotic wave on the downstroke) which we have already described in connection with the velocity pulse, and the pressure pulse (see p. 288). When the same method in a modified form is applied to such viscera as the kidney or spleen, the instrument is generally called an oncometer. The earliest oncometers were made by Roy. Eoy's oncometer (figs. 270 and 271) 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 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 recorder by a tube also containing oil. An increase in the volume of the organ squeezes the oil out of the oncometer into the recorder, and so produces a rise of its piston and lever ; a contraction of the organ produces a fall of the lever. These elaborate instruments have now been entirely superseded by air oncometers, and Schafer was the first to employ an air oncometer in his work on the spleen. If now we are investigating the action of the anterior root of eleventh thoracic nerve on the vessels of the kidney, a tracing is taken simultaneously of the arterial blood-pressure in the carotid, and of the volume of the kidney by the oncometer. On stimulating the nerve rapidly, there is a slight rise of arterial pressure, but a large fall of the recording 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, 310 THE CIRCULATION IN THE BLOOD-VESSELS [CH. XXIL or of a nerve, ou any organ, to record its volume changes by the plethysniographic method. Thus, the salivary glands, lobes of the Fig. 270. — Diagram of Roy's Oncometer, a represents the kidney enclosed in a metal box, whicli opens by hinge /.- h, 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 hrmly screwed together by screws at h, and below. The membninous chamber below is filled with a varj-ing amount of warm oil, according to the size of the kidney experimented with, through the opening, then closed with the 7)lug i. After the kidney has been enclosed in the capsule, the membranous chamber above is tilled with warm oil through the tube e, 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. 5571. Fiu. 271 — Roy's Oncograph, or apparatus for recording alterations in the volume of the kidney, etc., as shown by the onconieler — a, upright, supporting recording lever I, which is raised or lowered by needle '), which works through/, and which is attached to the jiiston e, working in the chamber d, with which the tube from the oncometer communicates. The oil is prevented from being S4|ueezed 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. liver or lung, the limbs, the kidney, spleen, a coil of intestine, etc., can each be easily enclosed in an appropriately shaped gutta-percha en. xxir.] PATHOLOGICAL CONDITIONS 311 box, covorod with a glass plato mado 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 i.s filled up with a piece of glass tubing which is connected by an india-rubber tube to the recording apparatus (see fig. 272). The most delicate of Fig. 272. — Apparatus for obtaining splenic curves, s, Spleen in oncometer o, which is made of gutta- percha, and covered with a glass plate (o.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 (n) by the india- rubber tube (r), the side tube (r) being closed during an experiment by a piece of glass rod. The recording lever (l) writes on a revolving drum. the volume recorders is the bellows-recorder of Brodie or the piston recorder of Hiirthle. 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 ccrcbrale is duo to abnormal sensitiveness of the vascular 312 THE CIi;CULATION IN THE BLOOD-VESSEIJs [CII. XXII. nerves ; drawinrf the finrrer-nail across the skin causes an immediate wheal, or at least a red mark that lasts a considerable time. At one time this was considered characteristic of affections of the cerebral meninges such as tubercular meningitis, and was consequently called the " meningeal streak." It, however, occurs in a variety of patho- logical 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 such drugs as amyl-nitrite or nitroglycerin, 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 attendinj? the circulation of blood through different organs are observed in the cases of the hniln, crertUf or(/a».<<, luru/s, lirer, spleen, and kidneijs. In the Brdin. — The brain must alway.s 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 arterj' 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. 5fo 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 expiratorj- 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 CII. XXri] THK CIKCUIATION IN THE BKAIN 313 to advance the opinion that tlie 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- ous diminution or increase of the cerebrospinal fluid, so that the contents of the cranium are kept imiform 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 are nuiscular, 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 c-irculation passively follows the slightest changes in aortic and, more especially, vena cava pressure, and no active vaso-motor change has been conclusively proved. 'Jhe velocity of lilood-flow through the brain is thus influenced markedly by the con- dition of the vessels of the splanchnic area. If these are unduly dilated, the blood- flow through the brain may be so reduced as to lead to fainting. 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 lymphatics, and possibly also into the veins, at any pressure above the cerebral venous pressure ; the tension of this fluid and the pressure in the veins are therefoie always the same. The fluid is secreted by the epithelium covering the vascular fringes of the choroid plexuses in the ven- tricles of the brain (see p. 172), and is absorbed mainly by the lymphatics. 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 reabsorbed. 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 by it, and pass into the state which has been termed erection. Such structures are the corpora carernosd 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 31-i THE CmCULATION IN THE BLOOD-VESSEIJ? [cn. XXII. both sexes. The corpus cavernosiim 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 lamell.TP 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 fibronB 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 urethnp, 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 sjjjnal 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. Tlif rirrn/a/ioH in (he Lunr/s, Liver, Spleen, and Kidnei/s will be described in our study of those organs. CHAPTER XXIII LYMPH AND LYMPHATIC GLANDS As tliG 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 protein constituents are concerned. This is due to the fact that proteins do not pass readily through membranes. The proteins present are called fibrinogen, serum globulin, and serum albumin; these we shall study w4th the blood-plasma. The salts are similar to those of blood-plasma, and are present in about the same propor- tions. Chlorides, however, are more abundant in lymph than in blood. The waste products, such as carbonic acid and urea, are also more abundant. The amount of solids dissolved in lymph is about 6 per cent., more than half of which is protein 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, and constitute there one of the varieties of colourless blood corpuscles. All the lymphatics pass at some point of their course through 316 LVMI'II AND LYMPHATIC (JLAN'DS [CII. XXIIL 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, Mal])ighian bodies of the spleen, Foyer's patches, and the solitary glands of the intestine. The lymph that leaves those tissues is richer in lymph-cells than that which enters thoni. When lymph is collected from tho 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. Tho fat particles constitute what used to be called the molecular basis 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 XIX., 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 Flu. 273.— Diagrammatic suction of lyiiii)liatic glaml. a.L, Atloroiit; r.l., pllerent lymphatics; C, cortical substance; J.h., lymphoid tissue; l.s., lymiih-i>ath ; c, librous capsule sending in trabeculse tr. into the substance of the gland. (Sliarpey.) 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 en. xxTii.] LYMPHATIC OLANPS 317 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 down the leg, and in the arm as far down 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), the capsule sends inwards processes called traheculce in which the blood- vessels are contained, and these join with other processes prolonged from the inner surface of the y Mm ^mjiflitly't^^'if'f 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, and an inner or medullary por- tion of redder appearance (fig. 273). In the cuter part, or cortex, of the gland the intervals between the trabeculse 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 tra- becular processes. Within the alveoli of the cortex and in the meshwork formed by the trabec- ulse 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 trabeculse, is a more open meshwork of retiform tissue 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. 274 1), are left within those anastomosing cords, in which are found portions of the trabecular meshwork and the continuation of the lymph-path. Fig. 274.— a small portion of medullary substance from a mesenteric gland of the ox. d, d, Trabe- culse ; o, part of a cord of lymphoid tissue from which aU 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); li, h, lymph-path, of which the retiform tissue is represented only at c, c. X 300. (Kijlliker.) 381 LYMPH AND LYMPHATIC GLANDS [CII. XXIIL 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 endothehal lining, which is continuous with the lining of the lymph-path. The efferent vessels begin in the medullary part of ihe gland, and are continuous with 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 trabecular and lymphoid tissues. The Lymph Plow. 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 propels 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 propelling the chyle ; in the small intestine of many animals the chyle has been seen mov'ing with intermittent propidsions that correspond with the peri- staltic movements of the intestine. For the general propulsion of the lymph and chyle, it is probable that, in addition to external pressure, some of the force is derived from the contractility 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 h/mplt-hearls, and it has been shown that the caudal heart of the eel is a lymph- lieart 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. The muscular coat of these hearts is of variable thickness ; in some cases it can only be discovered bv means of the microscope ; but in every case it is composed of striped fibres. The" contrac-tions of the hearts are rhythmical, occurring about sixty times in a minute. The pulsations of the c-ervical 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-lieart, 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 c-ord corresponding to the third vertebra of the frog was uninjured, the cervical pair of lymph-hearts en. XXIII.] FORMATION OV LYMTII 319 coiitimu'd pulsatiiif; aftrr all tlic rest of the spinal cord and the brain were destroyed ; while destriietion of this portion, even thoufih all other |)art.s 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 the portion of the 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. /inifrrafion of tJie TItorarir hurt. — Hy determining the rate of outflow of a fluid at constant pressure passing through the thoracic- duct. Cannjs 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 htemorrhage) is soon remedied by a transfer of water from the tissues to the blood through the intermediation of the lymph. In severe hemorrhage 'life has often been saved hy transfusion of blood from another person. The transfer of the blood of another animal to the human vascular system is usually dangerous, especi- ally 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 (htemolysis) is the most constant sign. It is, however, quite unnecessary to use blood at all for this purpose; saline (preferably Einger's) solution should be used instead. 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 a, filtration of fluid through the capillary walls ; and secondly, chemical differences between these two fluids, setting up osmotic interchanges through the wall of the blood-vessel. (See further, next 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 320 LYMPH AND LYMPHATIC GLANDS [CIL XXIIL 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 IjTnph 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. The excess of chlorides in lymph is also in favour of ihe same view. Heidenhain was the inventor of the term b/mj^hagogues (literally, lymph drivers). These are substances like curare, which have a specific action in causing an increased lymph flow. Heidenhain considered that the majority of these act by stimulating the endo- thelial 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 supposed it to be, but that most of the phenomena in connection with lymph formation can be explained by the simpler mechanical theory. Starling considers that ihe 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 justly, that this is incorrect, as there is between the arteries and the capillaries the unknown 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 limbs. Liver lymph is also richer ju protein than lymph from the limbs. The flow of lymph may therefore be increased in two ways : — 1. By increasing the intracapillary pressure. This may be done locally by ligaturing the vems of an organ ; or generally by injecting a large amount of fluid into the circulation, or by the injection of CH. XXIII.] LYMPHAGOGUES 321 such substances as sugar and salt (Heidenhain's second 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 first class of lymphagogues). These act chiefly on the liver capillaries; curare acts chiefly on the limb capillaries. There is no doubt that in pathological conditions which lead to the production of a great increase of lymph (dropsy) this second factor is the more important of the two ; the increased permeability of the capillaries may be the result of malnutrition, or due to the action of poisons produced by the disease. In reference to the action of the endothelial cells, it is necessary to recognise that they are alive, and are therefore capable of exerting a selective action which may mask or counteract or assist 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 always found to be the case. Lymph formation is doubtless 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 has been a similar difference of opinion, but that recent research has confirmed the theory of selective activity of the absorptive epithelium. Dr Martin H. Fischer has advanced a new theory of dropsy or oedema within the last few years. He believes that circulatory conditions are of minor importance, but that the main factor leading to transudation of water into the tissues is to be found in the tissues themselves. He finds that colloids imbibe more water from an acid solution than under other conditions. He therefore believes that it is the accumulation of acid products (such as lactic acid) in the tissues that determines their increased affinity for water, and thus they attract it out of the blood. The theory has met with much adverse criticism, and it is too early at present to state whether Fischer or his critics are correct. CHAPTER XXIV i'UYSICAL CIIK.MISTKV AND ITS BEARING ON I'lIYSIOLOGICAL PROBLEMS The investigations of physical cheiiiists during recent years have given us new conceptions of the nature of sohitions, and these have important bearings on the exphmation of osmotic j)heiu)Miena, and so are interesting to the jjliysiologist. Water is the Huid in wliich soluble materials are usually (hssolved, and at ordinary temperatures it is a (iuid 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 with the formula H.^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 ionx. Thus, if sodium chloride is dissolved in water a certain number of its molecules become dissociated into sodium ions, which are charged with positive electricity, and chlorine ions, which are charged witii negative 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 SO4. The term ion is thus not equivalent to atom, for an ion may be a group of atoms, such as SOj, 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 tlie SO, ion is cipial to the positive charge of two hydrogen ions. We can thus speak of monovalent, divalent, trivalent, etc., ions. Ions positively charged are called kat-ioiis because they move towards the kathode or negative pole ; those which are negatively charged are called a)i-l<)ns because they move towards the anode or positive j)ole. The following are some examples of each class : — Kat-ions. Monovalent :— H, Na, K, NH4, 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, NO,, etc. Divalent :— S, Se, SOj, 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 3-J2 CH. XXIV.] OSMOTIC PIIKNOMENA 323 thri)Uf>h the solution by tlie movi'inciit of tlie ions. Substancrs wliicli e.xliibit the properly of dis.sociation are known as eleitrolytes. Tht' liquids of the body contain electrolytes in sohition, and it is owing to this fact that they ajrc able to c-onduct 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 iiunend salts in solution on living organisms and i)arts of organisms. Many years ago Kinger showed that contractile tissues (heart, cilia, etc.) continue to manifest their activity in I'ertain saline solutions. Locb aiid 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 (such as sugar, urea, albumin). But different contractile tissues differ in the nature of the ions which are most favourable stimuli. Thus cardiac niuscle, cilia, amoeboid nujvement, karyokinesis, 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. Loeb at one time considered that the process of fertilisation was mainly ionic action, but since then he has modified his views ; the action of ions is only one of many factors. Howell's work, however, on the action of ions in the causation of the heart-beat (see p. 261) may be taken as one of the best-proved instances of the importance of this branch of study. 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 .58-46 grammes of sodium chloride (Na = 2:3-00: Cl==3f.-46) in a litre. A gramme-molecular solution of grape sugar (QHi.jO,;) is one which contains 180 grammes of grape sugar in a litre. A gramme-molecule of hydrogen (H.,) is 2 grammes by weight of hydrogen, and if this was compressed to the volunie 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 if as a litre of a solution containing 58-46 grammes of sodium chloride, or one containing ISO 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 spa,ce, and the process is called cU fusion. 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 cri/stalloiils. Substances which have such large molecules (starch, pro- tein, 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 324 PHYSICAL CHEMISTRY [CH. XXIV. M fi^ is usually called f/j((///.vi.v. The process oi fllrnllon (/.^., the passafje of materials throufi;h tlu- jiores of a membrane under the influence of mechanical pressure) may be excluded in such experiments by placing the raemDrane (M) vertically as shown in the diagram (fig. 275), 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 subsbinces dis- solved in the water. But very few or no membranes are equally permeable to water and to molecules of the sub- stances dissolved in the water. If in the accomj)anying diagram the comjiartment A is filled with pure water, and B with a sodium chloride solution, the liquids in the two compartments will ultimately be found to be equal in bulk as they were at the start, ami each will be a solution of salt of half the strength of that originally in the compartment Vu.. jT.j. 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 terra (lidli/sis- is applied to the passage of the molecules in solution in the water. The osmotic stream of water is especially important, and in connection with this it is necessary to explain the term osmotic pressure. At II 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 : 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 imchanged. If now we imagine the mem- brane M is not permeable except to water, and the compartment A contains water, and the compart- ment B contains a solution of salt or sugar ; under these circumstances water will j)ass 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 con- tinue to decrease, until at last a limit is reached. The determination of this limit, as measured by the height of a coluiim 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. B -A — Fio. 27(5. — A, outer vessel, con- taining distilled water ; U, inner semi-permeable vessel, containing 1 per cent, salt solution ; M, mercurial manometer. (After Star- ling.) CH. XXTV.] OSMOTIC PRESSURE 325 It is therefore necessary to use a membrane which will not allow salt to pass out either by dialysis or hltration, thoufrii it will let tlic water pass in. Such membranes are called semi-iitfrmfdlilf membranes, and one of the best of tliese is ferroryanide of copper. This may be made by taking a cell of porous earthenware and washing it out tirst with copper sulphate and then witii potassium ferrocyanide. An insoluble precipitate of copper ferrocyanide is thus deposited in the j)ores of the earthenware. If such a cell is arranged as in fig. 276, 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 oOnQ mm. of mercury. If the pressure in the cell is increased beyond this artificially, water will be pressed through the semi-permeable 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 concentration than 1 i)er 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 ditlieult to construct a membrane which is absolutely semi- permeable ; they are nearly all permeable in some degree to the molecules of the dissolved crystalloid. 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 explanation is perhaps the best, and may be rendered most intelligible by an illustration. Suppose we have a solution of sugar separated by a serai-permeable membrane from water ; that is, the membrane 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 versa. 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 proportional to the number of sugar molecides 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 HofTs hypothesis). The nature of the substance makes no difference ; it is only the number of mole- cules which causes osmotic pressure to vary. The osmotic pressure, however, of substances like sodium chloride, which are electrolytes, 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). 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 326 PHYSICAL CHEMISTRY [CH. XXIV. of the pressures which tlie individual substances would exert if they were alone in the solution (Heiiry-Daltoii law for partial pressure of gases). 1. The osmotic pressure is independent of the nature of the substance in solution, and depends only on the number of raolceuies 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 tlie case of a non-electrolyte sucii as sugar. We shall then not have to take into account any electrolytic dissocia- tion of the molecules into ions. We will sup|)Ose 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. occui)ies a volume of 11 "2 litres; two grammes of hydrogen will therefore occupy a volume of 22 "4 litres. A gramme-molecule of iiydrogen — that is, 2 grammes of liydrogen — when brought to tlie volume of 1 litre, will exert a gas pressure equal to tliat of 22'4 litres compressed to 1 litre — that is, a pressure of 22 "4 atmospheres. A gramme-mole- cular solution of cane sugar, since it contains the same numl)er of molecules in a litre, must therefore exert an osmotic pressure of 22 4 atmospheres also. A gramme-molecular solution of cane sugar (C'|,jH..jO|,) contains 312 grammes of cane sugar in a litri' of water. 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 ~— x22'4 atmospheres, or 0'65 of an atmosphere, o42 which in terms of a colutim of mercury = TtiO x 0'6."> = 491 mm. It would not be ])Ossible 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 is seldom directly measured by a manometer, because of the difficulty in obtaining perfect semi- permeable membranes ; 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 aj>paratus (Beckmann's differential tliermoMu-t6 C. A 09 per cent, .solution of sodium chloride has the same A ; hence serum and a 0-9 per cent, solution of common salt have the same osmotic jjressure, or are isotonic The osmotic pressure of blood serum is — — - — '—— -5000 nmi. of mercury a|)proximately, or a pressure of nearly 1 'o7 7 atmospheres. 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. en. XXIV.] OSMOTIC ri:Essui:E 327 If the solution is hi/iier/otiir, i.e., has a greater osmotic pressure tlian the cell con- tents, the protoplasm shrinks, and loses water, or if red hr asserts \ . c\*X^^^^ that it is not true lymphoid tissue. V?'^ *^^^^^*y It has boon stated that in hibernating i) '^;*' ^^%s, 'x animals, in which it undoubtedly persists ° <^" A^If^"^"^^^,^- ? throughout life, that as each hibernating .'s-^^ '':"'■ period approaches the gland enlarges, and its ^^C^^rf/ 'e* cells become laden with fat. In this case, the store of fat will serve to maintain combustion '''''\he'''ti7j^ms.'^'''^rt?'L™mp°h processes during the winter sleep. ??^^® •,,''', p':°[.PV*f''^^ °^ Eemoval of the gland in the frog is stated to be followed by muscular weakness, paralysis, and finally death ; but later observations have failed to confirm this result, either in frogs or mammals. Intravenous injection of extracts of thymus lowers arterial blood-pressure and accelerates the heart, but extracts of most organs produce similar effects, especially on the blood-pressure. Lately it has been suggested that there is some relationship between the thymus and the generative organs ; and this view is supported by the circumstance that castration retards the atrophy of the thymus, whilst removal of the thymus hastens the growth of the testes. The Thyroid. The thyroid gland is situated in the neck. It consists of two lobes, one on each side of the trachea ; 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 trabeculse, which enclose the thyroid vesicles — which are rounded or oblong sacs, consisting of a wall of thin hyaline membrane lined by a single layer of short cylindrical or cubical cells. These vesicles are filled with transparent colloid nucleo-protein material. The colloid substance increases with age, and the cavities appear to coalesce. In the interstitial connective- 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 sometimes, in addition to the yellowish glassy colloid material, epithelium cells, colourless blood-corpuscles, and also coloured corpuscles undergoing disintegration. It is diffiicult to state definitely the function of the thyroid body ; 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 Y 338 THE DUCTLESS OLAXDS [CIT. XXV, 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 myxedema ; 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 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 1 i^^sjm^^^ Fio. SSO.— Spctiun uf liuniaii thyroid ; tlie few vesiclos shown are lined by cubical epithelium, and con- tain a colloid material. (After Schafcr.) surgically; this is called cachexia strumipriva ; this operation, which was performed previous to our knowledge of the importance of the thyroid, is of course not performed 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 MyxcEdema 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. CU. XXX.] THE rAIv'ATIIYJJOIDS 339 The discovery of the relationships between the thyroid and tliese 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 tliese 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, ia 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 mainly though not entirely 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 lodo-thyrin, as this substance has been called, is present in combination with protein 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. In healthy animals and men, administration of thyroid produces an increase in nitrogenous metabolism. Parathyroids. These are small bodies, usually four in number, situated near or imbedded in the substance of the thyroid. They are made up of elongated groups of polyhedral cells, bound together by connec- tive tissue, and well supplied with blood-vessels. Some have supposed that parathyroid is only immature thyroid tissue, but a study of development shows that the parathyroids have a different embryonic origin from the thyroid, and in the lower vertebrates the two organs are entirely distinct. It is only in the mammals that they are so closely associated anatomically. They are probably associated physiologically also, and it has been by no means easy to determine the role of each. Most of the facts described in the preceding section on the thyroid were discovered previous to the recognition of the parathyroids, and since then the view has been advanced that in removing the thyroid it is really the simultaneous removal of the parathyroids which causes the nervous symptoms. Certainly the most prominent symptom after extirpation of the parathyroids is tetany (muscular spasms and twitchings). The parathyroids contain no iodine, and it is doubtful if they form an internal secretion. If they do not, their function must be to neutralise poisonous substances formed elsewhere, and 310 THE DUCTLESS OLAl^DS [cn. XXV. the symptoms after extirpation will then be due to the toxic effect of an accumulation of the poison. It has further been shown that tetany produced in animals and men by parathyroidectomy can be relieved by the administration of calcium salts, and so it is possible that the parathyroids may be related in some way to calcium metabolism. The Suprarenal Capsules. These are two triangular or cocked-hat-shaped Ixxlies, each resting by its lower border upon the upper border of the kidney. The gland is surrounded by an outer sheath of connective tissue, 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. 281) columnar groups :s a 3 0" "© Kco ■ s ■ '^ ' - • - '■ • -" '■■ c> G ■ ? [t: ;• <■■/ . c- M Fill. 281.— Vertical section through part of the cortical portion of suprarenal of guinca-pij;. n, Cap- sule ; li, zona glomerulosa ; c, zona fasciculata ; d, connective tissue supporting the cohimiis of the cells of the latter, and also indicating the position of the blood-vessels. (S. K. Alcock.) of cells (zona fasciculata). Immediately under the capsule, however, the groups are more rounded {zona glovierulosa), while next to the medulla they have a reticular arrangement (zona reticularis). The cells themselves are polyhedral, each with a clear round nucleus, and contain lipoid globules. (2) The medullary substance consists of a coarse rounded or irregular meshwork of fibrous tissue, in the alveoli of which are CH. XXV.] THE SUPRARENAL CAPSULES 341 masses of multinucleated protoplasm (fig. 282), numerous Llood-vessels (sinusoids, see p. 222), and an abundance of nerve-fibres and cells. The cells of the medulla are clmracterised 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 united to glucose also found in the liver, spleen, and other organs. The immense importance of the suprarenal bodies was first in- dicated by Addison, who, in 1855, pointed out that the disease now known by his name is associated with pathological alterations of these Fig. 2S2. — Section through a portion of the medullary part of the suprarenal 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.) glands. This was tested experimentally by Brown-Sequard, who found a few years later that removal of the suprarenals 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 for many years, until they were confirmed by Abelous, Langlois, Schiifer, 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 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- 342 TTIE DUCTLESS GLAXDS [CH. XXV. longation of the period of relaxation. The efiect on involuntary muscle is even more 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 arterioles, not an indirect one through the vaso-motor centre.* The substance in the extract that produces the effect is known as adrenaline; it is confined to the medulla of the capsules, and is absent in cases of Addison's disease. The suprarenal bodies, therefore, form something which is dis- tributed to the muscles and is essential for their normal tone ; when they are removed or diseased, the 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 physio- logical effects. Its composition is shown by the following formula: — OH CH.OH.CHo.XH.CH, and it is therefore a methyl-amino derivative of catechol (Pauly, Jowett). Recently, compounds closely allied to it in composition and action have been made synthetically (Stolz, Friedmann, l)akin). "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 suprarenal 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 subdue the congestion of inflammation and even arrest haemorrhage. The splanchnic nerves have been shown to contain secretory fibres which control the amount of adrenaline poured into the circulation. The use of the suprarenal cortex is still unknown. It has been suggested that it has some effect on the development of the organs of generation, but these views are quite hypothetical. The cortex, how- ever, contains large quantities of lipoid material (cholesterin, lecithin, and similar substances), and the droplets seen in the fresh cells consist of these compounds ; the suggestion that the suprarenal cortex plays a part in the metabolism of these substances appears to be the only feasible one at present. * It is the sympathetic nerve terminals which are really affected. Any muscular tissue supplied by sympathetic nerves contracts under the intiuence of adrenaline. Vessels destitute of constrictor fibres (coronary, pulmonary and cerebral) are not contracted by adrenaline. CH. XXV.] THE PITUITARY BODY 343 Thoro are some points of interest in the development and com- parative physiology of the suprarenals. In mammals the medullary portion is developed in connection with the sympathetic, and is at tirst distinct and outside the cortical portion which is developed in connection with the ui)})er part of the Wolffian body; it gradually insinuates itself within the cortex (Mitsukiri). In Elasmobranch fishes the suprarenals 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 suprarenal ; extracts of this are inactive, and in the Teleostean fishes, where it is the sole repre- sentative of the suprarenal, it may be removed without any harm to the animal. The other portion of the Elasmobranch suprarenal is paired, and derived from the sympathetic ganglia. This corresponds to the medulla ; it contains the same chromogen as the medulla of the mammalian suprarenal, and extracts of it have the same physio- logical action (S. Vincent). The tissue of the suprarenal medulla is often ealled chroinophU tissue, on account of the ready way in which it stains with chromic salts. Such tissue is, moreover, not confined to the suprarenal, but is found in scattered patches in the retro-peritoneal region and in many sympathetic ganglia, especially in the abdomen. The histological resemblance is accentuated by the presence of numerous sympathetic cells in the suprarenal medulla. The chromophil tissue wherever found always yields adrenaline. The Pituitary Body. This occupies the sella turcica of the sphenoid bone. It may be divided into three parts, which show developmental, structural and functional differences. (1) The anterior lohc is developed as a tubular prolongation from the epiblast of the buccal cavity, but the growth of intervening tissue soon cuts off all connection with the mouth. It consists of large granular cells and numerous blood-vessels. Its precise function is undetermined, although probably it is a vascular gland pouring an internal secretion into the blood, which influences growth. Abnormal hypertrophy of the pituitary produces the condition known as acromegaly, in which the bones of the face and limbs hypertrophy ; and if the view advanced above of the anterior lobe is correct, the condition is caused by an increase of the internal secretion. Feeding young animals and children in the anterior lobe hastens the growth of their skeletal tissues. f s,-:-.^ (2) The pars intermedia. — This lies between the anterior and posterior lobes, and forms a closely fitting investment of the latter lobe. It is developed in association with the anterior lobe, and consists of finely granular cells arranged in layers closely applied to the body and neck of the posterior lobe and the under surface of adjacent parts of the brain. Colloid material occurs between the 344 THE DUCTLESS GLANDS [CH. XXV. cells, which passes into the adjacent nervous substance, to be absorbed by lymphatics which carry it to the cavity of the posterior lobe, and so into the third ventricle of the brain. The existence of colloid cysts in the pituitary closely reseniljling those of the thyroid has led many observers to the conclusion tliat tlie function of the two glands is similar, and that after removal of the thyroid the pituitary may take on its work vicariously. After extirpation of the thyroid gland, the cells of the pars intermedia do manifest increased activity, and the colloid matter increases but this is all that can be said at present in favour of such a view; the removal of the two organs produces very different symptoms ; injection of extracts produces different effects; moreover, the pituitary contains no iodine, therefore the colloid material is a different substance in the two cases. (3) The posterior lobe. — This is connected to the floor of the third ventricle, of which it forms a developmental outgrowth ; in some animals (cat) it remains hollow throughout life, in others (dog) the neck alone remains hollow, and in most (including man) both body and neck are solid, with traces of a cavity in the neck. Though developed from the brain, it contains in the adult no nerve cells, but consists mainly of neuroglia. It is surrounded and invaded by the epithelium cells and colloid matter derived from the pars intermedia. It plays the part of a brain gland in virtue of these epithelial cells. What the use of the secretion into the third ventricle may be is far from clear. P. T. Herring, to whom we owe many of the facts already given, suggests that disturbances of the posterior lobe may be responsible for the diabetic condition so frequently seen in cases of acromegaly. Whether this is so or not, injections of aqueous extracts of the gland have pronounced physiological effects, and these may be boiled without losing their activity. Although we do not know the precise nature of the active substance (provisionally called pituitrin.) in the posterior lobe, we can at any rate say, there- fore, that it is not protein. Intravenous injection of such extracts produces : — 1. A temporary rise of arterial blood-pressure ; this is not due to the presence of adrenaline, for a second injection following the first produces no such effect, whereas the rise of pressure produced by adrenaline may be repeated time after time. The second and follow- ing injections of pituitary extract, unless they occur at much pro- longed intervals, produce only a slight fall of pressure, which is the effect produced by most tissue extracts. The rise of pressure which occurs at the first injection is, however, like that of adrenaline, pro- duced mainly by constriction of peripheral arterioles. Slowing of the heart may occasionally also be produced. Pituitrin causes also con- traction of other forms of involuntary muscle, for instance the uterus. 2. The extract has a specific effect on the kidney, and causes en. XXV.] THE PINEAL CL.\ND 345 there not constriction but dilatation of the blood-vessels, which persists for a very long time. Adrenaline, on the other hand, con- stricts the kidney arterioles. This dilatation is accompanied with pronounced diuresis. It can hardly be doubted that this is no mere accident, but that there is some definite relationship between the activity of the posterior lobe of the pituitary and the kidney function. It also stimulates milk secretion (Ott, Sch.ifer). Extracts of the anterior loba produce neither a rise of blood-pressure nor any effect upon the kidney or mammary gland. The pituitary l)ody is essential for life. Paulesco, and later Harvey Gushing and Horsley, found that total removal of the organ is fatal in a few days. The same result follows entire removal of the anterior lobe. On the other hand, removal of the posterior lobe produces no such effect. Partial removal of the anterior lobe produces a condition known as hy popituil arisvi , in which adiposity accompanied by (or secondary to) atrophy of the organs of genera- tion are the most marked signs. If the operation is done tefore adolescence, there is a persistence of sexual infantilism. The trans- plantation of the organ from another animal, or injection of anterior lobe extracts, prolongs the life of animals after total extirpation, or relieves the symptoms after partial extirpation. In many of Hor.sley's experiments no such symptoms occurred, even altliough only minute portions of the anterior lobe were left l)ehind. The Pineal Gland. This gland, which is a small reddish body, is placed beneath the corpus callosum, and rests upon the corpora quadrigemina. It is composed of tubes and saccxiles lined and sometimes filled with epithelial cells, and containing deposits of earthy salts (brain sand). A few small atrophied nerve-cells without axons are also seen. In certain lizards, such as Hatteria, and in certain fishes such as the lamprey, the pineal outgrowth is better developed and may be paired. One divisioa corresponds to the pineal gland ; the other becomes developed into an eye-like structure connected by nerve- fibres to the habenular ganglion ; this third eye is situated centrally on the upper surface of the head, but is covered by skin. The Coccygeal and Carotid Glands. These 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. They are made up of a plexus of small arteries, and are enclosed and supported by 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 suprarenal medulla. CHAPTER XXVr RESPIRATION The respiratory apparatus consists of the lungs and of the air-passages which lead to them. In marine animals the "ills 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, such as 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 in the mammalia 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 Larytvc is the upper part of the passage, and will be described in connection with the voice. en. XXVI. ] THE TK.VCIIEA 347 The Trachea and Bronchi. — Tho trachoa extends from the cricoid cartilawo, which is on a level with the fifth cervical vertebra, to a M"' >u' ^^'- -<^:r W'^^'^Mm Fig. 2S3.A. — Outline showing the general form of the larj'nx, trachea, and bronchi, as seen from the front, h, The great cornu of the hyoid bone : e, epiglottis ; (, superior, and /', inferior cornu of the thyroid carti- lage ; c, middle of the cricoid cartilage ; tr, the trachea, showing sixteen cartila- ginous rings ; h, the right, and fc', the left bronchus. (Allen Thomson.) Fig. 2836. — 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 ; c, epiglottis ; a, points to the back of both the arjtenoid cartilages, which are surmounted by the comicula ; c, the middle ridge on the back of the cricoid cartilage ; tr, the posterior membranous part of the trachea ; h, h', right and left bronchi. (Allen Thomson.) point opposite the third dorsal vertebra, where it divides into the two bronchi, one for each lung (fig. 283). It measures, in man, about four or four and a half inches in length and from three-quarters of 348 RESPIRATION [CH. XXVI. 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- 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. 283b). The inner surface of the trachea is lined with ciliated epithelium ; this, together with the basement mem- ^MMMMearing cilia. X 350. (Kdlllker.) CH. XXVI.] THE LUNGS AND TLKUTIM 349 by successive branchings, are reduced to about /„ 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 relatively more abundant than in the larger ones, and form a distinct circular coat. Most of the structures which have been described are of some clinical importance. The secretion of the mucous glands, for instance, may be greatly increased in the condition known as catarrh of the mucous membrane. The secretion, or phlegm, is worked up to Fig. 2So. — Transverse section of a bronchial tube, about i inch in diameter, c, Epithelium (ciliated), immediately beneath it is the corium of the mucous membrane, of varying thicliness ; rn, muscular layer; s.m, submucous tissue; /, fibrous tissue; c, cartilage enclosed within the layers of fibrous tissue ; g, mucous glands. (P. 15. Schulze.) the larynx by the ciliated epithelium. Its presence irritates the very sensitive surface of that organ, and induces a cough by which the phlegm is expelled from the respiratory passages into the mouth. The whole inner surface of the bronchi may become inflamed and filled with fluid, through which the air has to be forced at each respiration (bronchitis). A disorder of another nature, bronchial asthma, is caused by undue contraction of the circular muscles of the bronchi. The passages are thus rendered too narrow for the necessary volume of air to pass conveniently, and as a result the respiration becomes forced. The bronchial muscles are supplied by the vagus nerve, and relaxation of them may be brought about by drugs which prevent the passage of impulses along the vagus. The Lungs and Pleurce. — The lungs occupy the greater portion of 350 RESPIRATION [CII. XXVI. the thorax. They are of a spongy elastic texture, and are composed of nmnerous 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 by inflammation or pueuiiioTiia) floats in water ; no other tissue (except fat) 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 surface of the chest-wall. The continuity 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. 286. The appearance of a space, however, between the pleura which covers the lung {visceral layer) Fig. 280. — Transverse section of tlie chest. and that which lines the inner surface of the chest (parietal layer) is inserted 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 l)etween them is only just so much fluid as will ensure the hmgs gliding easily, in their expansion and contrac- tion, on the inner surface of the parietal layer, which lines the chest- wall. 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, atmo.spheric pressure bears alike on the inner and CII. XXVI.] THE LUNGS 351 outer surfaces of the lung, and tlieir elastic recoil is no longer prevented. The pleura, like other serous sacs, is frequently the scat of inilain- matory changes (pleurisy; ; the pleural cavity then becomes enlarged by an increase in the amount of fluid lymph which it contains. The increase is accompanied by corresponding collapse of the lungs. A formation of fibrin may take place in the exuded fluid ; this adheres to the pleura and causes its surfaces, originally smooth, to become rough, and painful friction bet^Yeen the two surfaces, or even their adhesion to one another, may supervene. Each lung is partially subdivided into separate portions called lobes ; the right lung into three lobes, and the left into two. Each 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 minia- ture, consisting, as it does, of a branch of the bronchial tube, of air- sacs, blood-vessels, nerves, and lym- phatics, with a sparing amount of areolar tissue. On entering a lobule, the small bronchial tube, the structure of which has just been described (fig. 287) 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, called air-sacs. Such a funnel-shaped terminal branch of the bronchial tube, with its group of pouches or air-sacs, is called an infundibulum, 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 Fio. 287. — Two small iufundibula or groups of air-sacs, a o, with air-sacs, h '<, and the ultimate bronchial tubes, c r, with which the air-sacs communicate. From a new- bom chilli. (Kiilliker.) 352 RESPIRATION [CII. XXVI. walls are nearly in contact, and they vary from -\-,th to ^Vth of aji incli ('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. 288). Outside the air-vesicles a network of pulmonary H "V- Fig. 288.— 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 libres surrounding the alveolar duct. (Klein and Noble Smith.) capillaries is spread out so densely (fig. 289) that the interspaces or meshes are even narrower than the vessels, which are, on an average, awo^h of an inch (8 /m) 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. 205 (p. 223). Area of the Surface of the Lnvr/. — The object of the compli- cated structure of the lung is to provide a very large surface, for the en. XXVI.] BLOOD-SUPPLY OF THE LUNGS 353 interchan<^'G of gases, in a compact organ. The total surface of the inside of the lung has been variously calculated, but it may 1)6 taken to be about 90 square metres in the adult, or about the size of a carpet necessary to cover the floor of a good-sized room (10 yards by 12). 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. Blood-supply. — The lungs receive blood from two sources, (a) the pulmonary artery, (&) the bronchial arteries. The former conveys venous blood to the lungs to be arterialised. The branches of the bronchial arteries convey arterial blood from the aorta for the Fig. 2S9.— Capillary network of the pulmonary blood-vessel-s in the human lung. X 60. (Kolliker.) 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 consist of irregular lacun?e in the walls of the air-sacs, in the walls of the bronchial tubes, and in the pulmonary pleura. The lymphatic vessels from all these irregular sinuses pass in towards the root of the lung to reach the bronchial lymphatic glands. Nerves. — The nerves of the lung contained in the anterior and posterior pulmonary plexuses are formed by branches of the vagus and sympathetic. They follow the course of the vessels and bronchi, and in the walls of the latter many small ganglia are situated. 354 RESPIKATION [OH. XX7L 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 a movement of the side- walls and floor of the chest takes place, so that the capacity of the interior is 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, the opposite movement diminishes the capacity of the chest; the pressure in the interior will be thus 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, there being no other communication with the exterior of the body ; and the lung remains, under all circumstances, closely in contact with the walls and floor of the chest. 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. — This is a muscular act ; the efifect of the action of the inspiratory muscles is an increase in the size of the chest-cavity in the vertical, the lateral, and antero-posterior diameters. 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 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 con- traction of the quadratus lumborum. The diaphragm is supplied by the phrenic nerves. The increase in the lateral and antero-posterior diameters of the chest is effected by the raising of the ribs, the upper ones being fixed CH. XXVI.] MUSCLES OF RESPIRATION 355 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 its lower than at its upper end. The muscles by which the ribs are raised, in ordinary quiet inspira- tion, 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 posticiis superior. In extraordinary or forced inspiration, additional muscles are pressed into service, such as the sternomastoid, the serratus magnus, the pectorales, and the trapezius. Laryngeal 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. 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 respiration. 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). Expiration. — From the enlargement produced in inspiration, the chest and lungs return, in ordinary tranquil expiration, by their elasticity to their previous condition ; the force employed by the inspiratory muscles in distending the chest and overcoming the elastic resistance of the lungs and 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. The chief of these are the abdominal muscles, which, by pressing on che 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 sr.G RESPIRATION [cn. XXVI. 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 intercostals, the triangularis sterni, the serratus posticus inferior, and quadratus luviboruni. When by the efforts of the expiratory muscles, the chest has been squeezed to less than its average size, 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 undue contraction as well as undue dilatation. Graphic Record of Res2nratory Movements. Amoni:^ numerous methods which have been described for record- ing the respiratory movements the simplest in the case of the human Fio. 290.— Stethograph traciii{,'8 from the human subject. Each iipslroke is liue to inspiration ; each dowustroke to expiration. Tlie lowest line is a time-tracing marking lialf-seconds. subject, especially if he be a patient in bed, is to fasten a bandage loosely round the chest. Between the bandage and the chest-wall a flexible hollow rubber ball is placed. This ball communicates by a rubber tube with a recording tambour. All such appliances are en. XXVI. ] Gl{APttIC URCOHt) OP ItRSPIRATlONS 36? called Stcthographs. Tn tracings taken with a stetliograph applied to the chest-wall of man or animals, the large up-and-down strokes duo to respiration have smaller tremors upon them, due to the heart- beats. The tracings in fig. 290 were obtained by applying a stetho- graph to a man's chest. During the tracing shown at the top, he was breathing quietly ; during the tracing shown on the next line, he was breathing deeply. It is also possible to record the diaphragmatic movements by the insertion of an elastic bag connected with a tambour into the Fig. 291. Tracing of the normal cliapliragm re.spirations of rabbit, a, With quick movement of drum ; h, with slow movement. Tlie upstrokes represent inspiration ; the dowiistrokes, expiration. To be read from left to right. The time tracing in each case represents seconds. (Marckwald.) 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 strip serves as a sample of the diaphragm. Fig. 291 shows a tracing obtained in this way. 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. The act of inspiring air, especially in women and children, is a little shorter than that of expelling it, and there is commonly a very 358 RESPIRATION [CH. XX7I. slight pause between the end of expiration and the beginning of the next inspiration. If the ear is placed in contact with the wall of the chest, or is 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 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 host hoard 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. During the action of the muscles which directly draw air into the chest, those which guard the opening through which it enters are not passive. In hurried breathing the instinctive dilatation of the nostrils is well seen, although under ordinary conditions it may not be noticealjle. The ojjening at the upi)er part of the larynx or rima gluttidis 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 ordinary 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 averages about 500 c.c, or rather more than 30 cubic inches, according to the recent measurements made by Haldane. This will be expanded at body temperature to 600 c.c. This amount of air is not sufficient to fill the lungs. Haldane gives the capacity of the upper air-passages and bronchial tubes as 200 c.c, and therefore about a third of the tidal air is required to fill this dead 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 the next inspiration effects a complete mixture of this air with that left in the air-passages; the air in the axial stream of the current will penetrate as far 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 CH. XXVI.] TIDAL AIR 359 the air which leaves the lungs will 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 ordinary inspirations and expirations adequate 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). b. Complemental air is the quantity over and alDove this which can be drawn into the lungs in the deepest inspiration ; its amount averages 100 cubic inches, or about 1600 c.c. c. Reserve or supplemental air. — After an ordinary expiration, such as that which expels the tidal air, a further quantity of air, about 100 cubic inches (1600 c.c.) can be expelled by a forcible deep expiration. This is termed reserve or supplemental air. The last portion of the air thus expelled will consist of air from the alveoli. 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 re.^plratorii capacity, or as John Hutchinson called it, vHdl capacity, i.s 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. Haldane measures the volume of air expired by the reduction which takes place in the volume of the body when placed within a plethysniograph large enough to take a man, with the exception of his head. The number of respirations in a healthy adult person usually ranges from 14 to 18 per minute. It is greater in infancy and childhood. 360 RKSPIRATION [CH. XXVI. It varies also much according to different circumstances, sucli 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 ; l)Ut 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 numter 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 colimin 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 nmscles 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.) 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 jrauge the inspiratory and expiratory power was a mercurial manometer, to whicli 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 b}- 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. During life 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 CH. XXVI.] THE GASES OF THE BLOOD 361 overcome by the musclos 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 Gases of the Blood. Before the student can study either the chemistry of respiration or its regulation, which is in part a chemical process, it is necessary that he should have an adequate conception of the fundamental laws which regulate the retention of oxygen and carbonic acid in the blood ; and as the blood presents many complications, it will be best at the outset to consider the solution of gases in such a simple medium as water. Solution of Gases in Water. If water is shaken up with oxygen, a certain definite amount of oxygen will become dissolved in the water. Under the same condi- tions the same quantity of oxygen would always be dissolved, and in the following argument it is assumed throughout that the tempera- ture remains constant. The amount dissolved depends then upon two circumstances, each of which can be measured. The first is the pressure of the oxygen to which the water is exposed when shaken ; the second is a property of the oxygen itself, namely, its solubility in water. The solubilities of different gases differ very much ; some (for instance, oxygen) are not readily soluble in water, whilst others, such as carbonic acid, are very soluble. If a cubic centimetre of water was introduced into a large air- tight bottle containing pure oxygen at the atmospheric pressure, and another cubic centimetre of water was similarly placed in a bottle containing pure carbonic acid at the same pressure, the former would be found to have dissolved 0-04 c.c. of oxygen, the latter 1 c.c. of carbonic acid. These figures represent the degrees to which the two gases are soluble in water under similar circumstances, and are called their coefficients of solulility. The coefficient of solu- bility of gas in a liquid is therefore the volume of gas which 1 c.c. of the liquid will dissolve at 760 mm. of mercury, that is, atmospheric pressure. S62 RESPIRATION [CH. XXVI. The quantity of gas which a liquid will dissolve depends not only on the solubility of the gas, but upon the pressure of the gas to which the liquid is exposed. Thus, in the instance given above, if the oxygen had been rarefied in the bottle until it only exerted a pressure of one-fifth of an atmosphere, the water would have taken up not 0-04 c.c. of oxygen, but only one-fifth of that amount, 0-008 c.c. To take another example, 1 c.c. of water shaken up with pure nitrogen at 760 mm. pressure will dissolve 0-02 c.c. ; but suppose the pressure to be reduced to four-fifths of the atmospheric pressure the water will dissolve -02 x^ =-016 c.c. If we represent the coefficient of solubility of a gas by K, and the pressure of the gas to which the liquid is exposed by P', and the atmospheric pressure by P ; then the quantity (Q) of the gas dissolved by 1 c.c. of the liquid may be obtained by the following formula — Q = K X ^ Dalton-Henry Law. What has been said above is as true of gases which are mixed together as of pure gases. For instance, we have seen that a cubic centimetre of water shaken up with oxygen at one-fifth of an atmos- phere (153 mm. pressure) will absorb -04 x \ =-008 c.c. ; or if shaken with nitrogen at a pressure of four-fifths of an atmosphere, it will dissolve -02 x 1 =-016 c.c. If now a c.c. of water be shaken with air (a mixture of one part of oxygen to four of nitrogen), it will have absorbed -008 c.c. of oxygen and -016 c.c. of nitrogen. This fact has been stated as the Dalton-Henry Law in the following words: — When two or more gases are mixed together, each of them produces the same pressure as if they separately occupied the entire space and the other gases were absent. The total pressure of the mixture is the sum of \A\(i partial pressures of the individual gases in the mixture. The Tension of Gases in Fluids. In the cases which have been discussed up to this point, a con- dition of equilibrium exists between the gas dissolved in the fluid and the gas in the atmosphere to which the fluid is exposed, so that as many molecules of the gas leave the surface of the fluid as enter it. The gas dissolved in the fluid therefore exercises a pressure which is the same as that of the gas in the atmosphere when equilibrium exists. For the sake of convenience the word T'ension is applied to the pressure of the gas in the fluid. Definition of Tension.— T\\q tension of a gas dissolved in a fluid is equal to the pressure of the same gas in an atmosphere with which the gas in the fluid would be in equilibrium. Above, we have called CFI. XXVI.] TENSION OF GASES 363 the pressure which the gas exerts on the liquid, P'. If we call the tension of the gas in the liquid, T, we find that when equililn'ium exists, P' = T. In the case of all true solutions, therefore, we may / • T replace P in our previous equation by T; therefore, Q = Kx^. We thus arrive at a relation between two separate things, wliich must be most carefully distinguished from one another — the quantity of the gas dis- solved in the liquid and its tension. Measurement of Tension. — Numerous instruments, called tonometers, exist for measuring the tension of gases in fluids. Of these, the instrument which has given the most trustworthy measurements of the oxygen and carbonic acid tensions in circulating blood is that invented by Krogh (fig. 292). A T-shaped cannula (A) is introduced into the blood-vessel, say the carotid artery ; ■^^5 the blood fills the cavity B and leaves it at fk.. 292.— Krogh-s Tonometer. C, so that a constant stream of blood is kept flowing. Into it a small bubble of air (D) is introduced. Exchange of gases takes place between the bubble and the blood, and the former very soon gets into equilibrium with the latter. When it has done so, the bubble is withdrawn up the capillary tube E, taken away, and analysed. As an example, suppose the bubble on analysis proved to consist of 4 per cent, carbonic acid and 12 per cent, oxygen, together with nitrogen and aqueous vapour. The gas in the instrument was compressed by the pressure of the arterial blood (say 120 mm. of mercury) in addition to the atmospheric pressure of 760 mm. of mercury, and therefore the total pressure was 120 + 760 = 880 mm. of mercury. Four per cent, of this would have been due to the carbonic acid ; 4 per cent, of 880 is 35-2. Twelve per cent, would have been due to the oxygen; 12 per cent, of 880 is 105-6. That is, the carbonic acid and oxygen tensions would have been in round figures 35 and 106 mm. of mercury respectively. Measurement of the Quantity of the Gases of the Blood. This may be done by means of an air-pump, or by a chemical method. (1) The extraction of the gases from the blood by means of the mercurial air-pump depends upon the fact that blood gives off all its gases when it is boiled in a vacuum. The total gas obtained is first measured; then the carbon dioxide is removed by caustic 364 RESPniATTON [CH. XXVI. potash, and the gas that remains consists of oxygen and nitrogen ; the oxygon is then removed by pyrogallic acid, and the residual gas is nitrogen. (2) Tlie chemical method * adopted is as follows : — When a solution oi oxyhaemoglobin is shaken with potassium ferricyanide, it yields the same amount of oxygen to the air as it would if boiled in a vacuum. In much the same way urea when treated with sodium hypobromite yields up all its nitrogen, and the apparatus used for determining the oxygen in blood is very similar to a Dupre's urea apparatus (see Chapter XXXIX.). The blood (5 c.c.) is placed in the large bottle (fig. 293, A) under- neath a layer of dilute amiuonia solu- tion (B). The blood is thus protected from the air whilst the apparatus becomes equal in temperature to the bath in which it is placed. The blood is shaken with the ammonia solution, whicli lakes it thoroughly; the ferri- cyanide solution is then spilt into the laked blood from the tube C, and the oxygen is shaken out of the solution. When the oxygen has been determined the bottle is opened and tartaric acid is placed in the small tube C ; this is subsequently spilt into the mixture of blood, ammonia, and ferricyanide ; it liberates the carbonic acid which is also shaken out of the fluid. The carbonic acid does not come completely out, however, and a correction has to be introduced for the quantity which remains in solution. The gas (oxygen or carbonic acid, as the case may be) passes over into the tube D, which was previously filled up to the zero mark with water, and connected to a reservoir (F) ; this would drive water out of F * The apparatus figured is one of the earliest, and many modifications have been invented since wiiich are in use in different laboratories. The differences are, however, in detail only ; the principle throughout is the same. The details of the mercury pump I have considered it best to omit. They are very complicated, and the forms of pump used vary greatly in different laboratories ; the method can only be learnt by actually using the instrument. -Ajiparatus for blooJ-gas analysis. CH. XXVI.] MKASURKMENT OF THE QUANTITY OF THE GASES 365 into the open tube E, and the water will therefore rise in E; but in practice it is convenient to keep the gas always at the same volume ; this may be done by raising the pressure in the open limb (E) of the pressure gauge by squeezing some of the water, with which the gauge is filled, out of a rubber reservoir (G) which forms the base of the ijauge, thus the level of the water in J) is maintained at the zero mark, while that in E rises from H to I. The actual measurement then is the increase of pressure (i.e., the height of the column of water H I) which is necessary to keep the gas at the same volume after the oxygen or carbonic acid has been shaken off as it previously occupied. From this the quantity coming off can be calculated. The chemical method is not quite so accurate as the vacuum pump, but it is much more convenient for the study of many problems, as it requires less blood, and, owing to its simplicity, a great number of observations can be made upon a single animal, or it can be used for the systematic investigation of the blood in man. Relation between Quantity and Tension of Gases in Blood. In the preceding paragraphs the methods of measuring the tension and the quantity of gas in a given sample of blood have been described. It is now necessary to consider the relationship between them. On page 363 we have seen that for gases in solution in water, T Q = K X p^ where Q is the quantity of gas dissolved, T the tension, K the coefficient of solubility, and P the atmospheric pressure. Since K and P are constant, it follows that Q varies directly in proportion to T ; that is to say, if the tension is doubled, the quan- tity of gas dissolved is also doubled ; if the tension is trebled, the quantity of gas is trebled, and so on. These results might be plotted out on a curve in which the quantities are placed on the ordinate and the tension on the abscissa. Such a curve would give the quantity of gas dissolved at any given tension, and in the case of water the curve would turn out to be a straight line. But in the case of both the oxygen and the carbonic acid in blood, the curve is not a straight line. Oxygen in Blood. — From every 100 c.c. of arterial blood, about 20 c.c. of oxygen can be removed by the air-pump. Nearly all of this oxygen is chemically combined with haemoglobin ; the amount in actual solution in the blood is 0-7 c.c. for every 100 c.c. of blood. The quantity of oxygen which 100 c.c. of blood takes up is called the "oxygen capacity," which should not be confounded with the "specific oxygen capacity" defined below. In normal human blood, the figure is 18"5 c c, and this forms the basis of standardisa- tion of haemoglobinometers (p. 445). 366 RESPIRATION [CH. XX7I. Hcemoglobin owes its value as a respiratory pigment to two principal facts. (1) It can unite with a large quantity of oxygen, and therefore blood can carry about thirty times as much oxygen to the tissues as plasma would under the same circinnstances. (2) The interaction l)etween haemoglubin and oxygen is a reversible one ; the two unite in the lungs, where the pressure of oxygen is high ; but when oxygen is absent or at a low pressure, as in the tissues, the hfemoglobin parts with its store of oxygen. The reaction between hcemoglobin and oxygen is a chemical one. At most, one gramme of bfeiiioglobin can unite with 1"34 c.c. of oxygen. This figure is not quite constant, probably on account of slightly different forms of globin (the protein constituent of haemo- globin) united with the haematin (the iron containing constituent) in different animals. The relation between the respiratory oxygen and the iron of the haemoglobin is, however, quite constant, and is called the "specific oxygen ca2Jacity" Each gramme of iron in haemoglobin unites with 400 c.c. of oxygen ; these figures are in the relation of one atom of iron to two atoms of oxygen. The reversible nature of the reaction may therefore be expressed by the equation H6 + 0., ^'T HftO.,. A reversible reaction means that it will go in either direction according to the concentration of the substances present ; thus if the concentration of oxygen in soltUion is increased, Fifi. 294.— Barcroft's Tonometer, suspendtd Ijoii/oiitally in warm balli in whicli it i.s rotated. more of the haemoglobin will become oxyluemoglobin ; and if it is diminished, oxyhaemoglobin will break up into haemoglobin (some- times called reduced haemoglobin) and oxygen. The reader must be clear that when we sjjcak of the concentration of oxygen in solution, we mean in physical solution, that is, not united chemically with the haemoglobin. This quantity varies in the direct ratio of the oxygen pressure to which the haemoglobin solution is exposed ; therefore the problem before us is to determine the relative quantities of oxy- and reduced haemoglobin when a haemoglobin solution is shaken up with oxygen at different pressures. CH. XXVI.] RELATION BETWEEN QUANTITY AND TENSION 367 Suppose that we have six vessels similar to that in fig. 294 (Barcroft's Tonometer), and each contains a few c.c. of a solution of haemoglobin and gases of the following composition : — No. 1. Nitrogen and no oxygen. No. 2. Nitrogen and enough oxygen to give 5 mm. oxygen pressure. No. 3. ,, ,, ,, 10 No. 4. „ ., ,, ^0 No. 5. „ „ ,. 50 No. 6. „ „ ,, 100 Each tonometer is rotated round and round in a bath at bod}- temperature until the hsemoglobin and the oxygen are in equili- Total Haemoglobin 100 Percentage Percentage of reduced ofOxyhsmo himoglobin globm 100% 6 13 28 45 63 100 5 10 20 50 Oxygen Pressure in mm. of Mercury. Fir, 295.— Dissociation curve of liKmoglobin solution at 37° C. Purple, reduced luvmoglobin ; red, oxyha'moglobin. brium; this will take about a quarter of an hour; the solution is then withdrawn and examined in order to ascertain the relative quantities of oxy- and reduced hsemoglobin in the six vessels. 368 RESPIRATION [CH. XXVI. The figures fov a ])nro solution of h8emoglol)iii would lie: — No. 1. No. 2. No. 3. No. 4. No. ."i. No. (!. Percentage of haemoglobin . 100 63 45 28 13 6 Percentage of oxyhaeraoglobin . 37 55 72 87 94 100 100 100 100 100 100 The same answer may be expressed graphically; if the pressures of oxygen are plotted horizontally, and the percentages of oxy- and reduced hemoglobin in the solution are plotted vertically, we get the curve shown in the accompanying diagram (fig. 295), which is called the dissociation, curve of hceynoglobin. In a reversible reaction such as the one under consideration, the molecules are continually forming and breaking up again, and the rate at which this occurs is influenced by various conditions. Among the conditions of importance in the body are (1) tempera- ture ; (2) the presence of salts ; and (3) the presence of acids, especially carbonic acid. These factors tend to make the oxyhsemo- globin molecules break down more rapidly and form more rapidly. J'rom the point of view of the body's needs, it is clearly necessary, not only that hcemoglol)in should acquire oxygen at the pressure of that gas in the lungs, and part with it at the diminished oxygen pressure in the tissues, but that the two processes should occur at about the same rate, that is, within one second, which is about the time occupied by any given portion of blood in travelling along the capillaries (see p. 282). It would be futile to have an oxygen carrier in the blood which took a fraction of a second to acquire its oxygen, and a fraction of an hour to release it. Yet a solution of pure haemoglobin is just such a substance, for its power of acquiring oxygen is very great, and its power of releasing it is very small. Happily, however, a haemoglobin solution and blood are two very different things. In the red corpuscles, the haemoglobin is dissolved in a medium con- taining various salts of which those of potassium are most prominent ; these salts confer on haemoglobin the property of giving up its oxygen much more readily when exposed to low concentrations of oxygen such as are present in the capillaries of the tissues, while at the same time it acquires oxygon more readily at higher oxygen pressures such as blood is exposed to in the lungs. But the mere presence of potassium salts is not in itself capable of rendering the hajnioglobin an efficient oxygen carrier ; two other factors come into play in the body — one is the high temperature, and the second is the presence of carbonic acid. This is illustrated in the curves depicted in fig. 296. "-To obtain the rate of oxidation, oxygen at alveolar pressure, mixed with nitrogen, was passed through reduced blood ; to obtain the rate of reduction, nitrogen, free from oxygen, was passed through CH. XXVI.] RELATION BETWEEN QUANTITY AND TENSION 369 oxygenated blood. The vertical figures represent the percentage saturation of blood with oxygon ; the horizontal figures represent time in minutes. It will be seen that at room temperature (A), the rate of oxidation is rapid, but the rate of reduction is very slow. At ])ody temperature the rate of reduction is enormously increased (B) ; but at body temperature in the presence of carbonic acid the two rates are practically equal (C); the amount of carbonic acid employed was the same as that which pervades the body, viz., at a tension of 40 mm. of mercury. This quantity is also approximately equal to that present A lOOn 90 \ /^ ^ 80. \ O m ^ .3 1 s f ^k 0^ <5 M ^w** 60 M X"^ t; M Vo o X.<=i. ■C: ff N5V5. J 50 f >^ ^ /I ^^^ C? 40 Si /I 5 30 5 1 c. 20- /I c^ 10 j 1 ■ >0 75 20 25 mznuzes. 17° c. Free from CO^ 10 )5 20 37 °c Free from CO, /O /5 20 mjMMtes 37 °c 40 mm CO^ Fio. 296. — Curves showing rate of oxidation and reduction in blood under the conditions described in the text; A, at room temperature (17° C.) ; B, at body temperature (37° C); C, at body tempera- ture when carbon dioxide at 40 mm. pressure was added to the nitrogen. in the alveolar air. The curves show that the rate of reduction is in- creased, but the rate of oxidation is a little lessened. The two curves in C present an extraordinary degree of symmetry, so wonderfully has nature adapted the conditions of life in order that the needs of the body may loe served by a substance htemoglobin which by itself is ill adapted for the purpose of oxygen transport. In order therefore to understand the dissociation of oxygen from haemoglobin in the body, we must study it, not in a pure solution, but under the more complex conditions actually existing in the body. 2 A 370 RESPIRATION [Cll. XXVI. Under these conditions, viz., in the presence of potassium salts, at 37' C, and in the presence of a carl)onic acid pressure of 40 mm. Hg, the dissociation curve is that shown in the next diagram (tig. 279). The two coloured figures (295 and 297) should be carefully compared; they present to the eye graphically the superiority of hemoglobin as an oxygen carrier when it is present in the actual bloi)d,'()ver that wliich it possesses in a pure solution. In the second 10 20 30 40 50 60 70 80 Oxygen Pressure in mm. of Mercury Fkj. 297.— Dis.scjciation curve of liiLiiiOKlobin in Llio actual bluoil. Puri)le, reduced lia;riioglobin ; red, oxyliaimoglobiii. curve, that of the l)lood itself, it will be seen that at an oxygen pressure of over 60 mm. of mercury (the pressure in the lung alveoli is about 100) the blood will nearly saturate itself with oxygen, and that at pressures IjcIow 50 the blood loses its oxygen rapidly, whilst at 10 mm. pressure it is nearly completely reduced. As the rate at which oxygen can diffuse out of the capillaries into the surrounding tissues depends upon the pressure it exerts in the plasma, it is important that the haemoglobin of the blood should be capable of a CH. XXVI.] GASES OF ARTERIAL AND VENOUS BLOOD 37l considerable degree of reduction when it is in contact witli iluid conlainin;_j oxygon at a pressure of 20 to 30 mm. of mercury. Carbonic Acid in Blood. — If blood is divided into plasma and corpuscles, it will bo 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, such as phosphoric or tartaric acid, to displace it. One hundred volumes of venous blood contain about forty-six volumes of carbonic acid. Whether this is in solution or in chemical combination is determined by ascertaining the tension of the gas in the blood. One hundred volumes of blood plasma would dissolve about an equal volume of the gas from an atmosphere of carbonic acid, 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, as we have seen, it proves to be only equal to about 5 per cent, of an atmosphere (that is approximately equal to 40 mm. of mercury). 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. Hence the remainder of the gas, 41 per cent., is in a condition of chemical combination. Of the carbonic acid present in chemical composition, the greater part is present as sodium bicarbonate (NaHCOg). About a third is in loose combination with the proteins of the blood, and a small quantity exists as normal sodium carbonate (NaoCO.3). Differences between Arterial and Venous Blood. — The aver- age quantity of gas that can be extracted from arterial and venous blood respectively is : — Oxygen Nitrogen .... Carbonic acid It will be noticed that the amount of nitrogen which is simply dissolved in the blood from the air is small in amount. It has no physiological significance, and is the same in both varieties of blood. The important distinction between arterial and venous blood is in the other two gases, and as the table shows, on the average every 100 c.c. of blood which pass through the lungs gain 8 c.c. of oxygen and lose 6 c.c, of carbonic acid. We will now study the mechanism by which this gaseous interchange is effected. rial blood. Venous blood. 20 8 to 12 1 to 2 lto2 40 46 to 50 372 RESPIRATION [CH. XXVI. The Mechanism of Gaseous Exchange in the Lung. 1. Oxyfjen. The simplest explanation of the passage of oxygen from the alveolar air into the blood is that the process is one of diffusion. This view (which is generally regarded as adequate in the case of normal respiration) can be maintained if it can be proved that the pressure of oxygen in the alveolar air is as great or greater than the tension of oxygen in the arterial blood, and therefore a fortiori greater than that of oxygen in the venous blood. The conception of respiration based upon this view would be that the pressure of oxygen in the air of the alveoli though less than that in the atmosphere, is 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 oxyhsemoglobiu then undergoes dis- sociation to supply more oxygen to the plasma and lymph, and thus in turn to the tissues once more. This goes on until the oxyhaemo- globin loses on the average about half of its store of oxygen ; 1 c.c. of arterial blood contains 0-2 c.c. oxygen ; 1 c.c. of venous blood contains 0-1 c.c. oxygen. Haldane and Priestley introduced a very simple method of collecting alveolar air which has the advantage of being applicable to man. A piece of rubber tubing is taken about 1 inch in diameter and about 4 feet long. A mouthpiece is fitted into one end. About 2 inches from the mouthpiece a small hole is made into which is inserted the tube of a gas-receiver, or sampling-tube, as in the figure (fig. 298). The gas-receiver is fitted at the upper end with a three-way tap, and the lower end is also closed by a tap. Before it is used, it is filled with mercury. The subject of the experi- ment breathes normally through the tube for a time, and then, at the end of a normal inspiration, he expires quickly and very deeply through the mouthpiece and instantly closes it with his tongue. The lower tap of the receiver is then turned, and as the mercury runs out, a sample of the air takes its place and fills the receiver; this sample is then analysed. A second experi- ment is then done, in which the subject expires deeply at the end of a normal expiration, and another sample obtained. The mean CH. XXVI.] COLLECTION OF ALVEOLAR AIR 373 result of the two analyses represents the mean composition of the alveolar air. Since the gaseous interchange between the blood and the alveolar air is going on continuously, it is evident that at the end of inspiration there will be a maximum percentage of oxygen, and a minimum percentage of carbonic acid; the converse obtains at the end of expiration. These observers proved by other considera- tions which it is unnecessary to go into, that the air obtained was really the alveolar or residual air unmixed with any of the air of the " dead space " of the respiratory passages. From the analysis of this air, they arrived at the conclusion that the normal oxygen pressure in it is 13 per cent, of an atmosphere (that is approximately equal to 100 mm. of mercury). The other important measurement, namely that of the tension of oxygen in the blood, is made by Krogh's tonometer (p. 363), and the experiments show that diffusion is quite sufficient to account MOUTHPIECE SAMPLING TUBE Fig. 298. — Apparatus for obtaining alveolar air. for the passage of oxygen from the alveoli to the blood. The following experiment may be cited as an example, and will be best understood by the next diagram (fig. 299). It shows the relations between the pressures of oxygen and carbonic acid in the air of the lungs and the blood respectively. The pressures of gas are measured vertically, and expressed as percentages of an atmosphere; the horizontal measurements are those of time. It will be seen that the experiment consisted of three periods, separated by the vertical lines A and B. During the first and last periods the animal breathed a mixture consisting of 14-7 per cent, oxygen, and the remainder nitrogen ; in the middle period ordinary air containing nearly 21 per cent, of oxygen was breathed. It will be seen that the oxygen pressure of the alveolar air (dotted line) is always higher than the oxygen ten.sion of the arterial blood (continuous Ijlack line); as the former rises the latter rises, and vice versa. The lower part of the diagram shows the 374 RESPraATION [CH. XXVI. relationships of the carbon dioxide; the alveolar tension of this gas (dotted line) is always lower than that of the arterial blood (continu- ous black line). It will further l>c noticed that the pressure din'orouces are less in the case of carl ionic acid than in that of oxygen ; this coincides with the ease with which carbonic acid passes out through the membrane which separates the blood from the air. A B 19 iij IE „ uj 18 I Q. 1 < 16 u. O u o < 14 \~ z. u o 13 cr LU > O xy q e n in ins l4-7''/o. pi r e d air. - \ \ \ \ \ \ t oxygen V < "lO UJ I ^ A u. o 2 O ^ 2 z UJ zzrz~-^~~~ - car (sonic 1 1 1 1 acid 1 I 1 1 O 10 20 30 40 50 60 70 80 QO minutes. Fia. 299.— Diagram to represnnt the rnlationsliip betwenn the tensions of oxygpn anil carbon diuxide in blood and alveolar air in rabbit (after Krogh). Some authorities consider that in cases of definite oxygen want, such as during violent muscular exercise, or on the tops of high mountains, the lining epithelium of the pulmonary alveoli can, by a process of active secretion, transfer oxygen from the alveolar air to the blood. In the case of exercise the ubservations made liy different workers are at variance, whilst at high altitudes they are so few as to make further work desirable before physiologists generally can accept the possibility of the secretion of oxygen by the lung. That CII. XXVI.] CARBONIC ACID IN THE IJLOOD 375 secretion is not impossible is shown Ly the fact tliat a similar secretion of oxygen is known to occur in the swim-bladder of certain fishes. The swim-bladder corresponds inor})hologically with the lungs of a niamnuil, and the oxygen stored in it is far in excess of anything that can be explained by mere diffusion from the sea-water. This storage of oxygen, moreover, ceases when the vagus nerves which supply the swim-bladder are divided. 2. Carhonic Acid. The tension of carbonic acid in the alveolar air is measured, like that of oxygen, by the method of Haldane and Priestley, whilst the tension in the blood is measured by the tonometer. 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 The following figures (from Fredericq) give the tension of carbonic dioxide in percentages of an atmosphere : — Tissues 5 to 9 "j Venous blood . . . . . . . 3 '8 to 5 "4 in dog. Alveolar air 2*8 J External air ....... 0*04 The arrow indicates the direction in which the gas passes, namely, in the direction of pressure from the tissues to the atmosphere. In view of the above figures and of such experiments as ili it of Krogh, cited on the opposite page, and having regard to the very slight changes in the tension of carbonic acid in the alveolar air, which are capable of affecting the respiratory centre (a subject we shall immediately pass to), we shall adhere to the view that diffusion explains the passage of that gas from the blood to the alveolar air, and that it is unnecessary to call to our assistance the hypothesis that secretory activity of the alveolar epithelium is at work. Cause and Regulation of Respiration. There are three factors, each of which plays a part in maintaining and regulating the rhythmic movements of respiration. They are the respiratory centre, the vagus nerves, and the chemical condition of the blood. 1. The Respiratory Centre. 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 376 RESPIRATION [CH. XXVI. vagus. Tho 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 coincides in position with the sensory centre of the vagus. The existence of subsidiary 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 by such nerves as the vagus, but also by those from the cerebrum; so that we have a limited amount of voluntary control over the respiratory movements. The respiratory centre is probably twofold, consisting of an inspiratory and an expiratory centre. Of these two the inspiratory centre is so much the more active that its importance is a subject of universal agreement ; whereas, the existence of an expiratory centre is doubted by some physiologists, who regard expiration as a mere cessation of the active process of inspiration, and a mechanical falling back of the tissues into their places. 2. The Nervous Factor in Respiration. During normal respiration, as opposed to forced respiration, an impulse passes from the lung to the respiratory centre during each complete respiration. This has been discovered by placing the vagus on non-polarisable electrodes connected to a galvanometer, and observing the current of action which accompanies each impulse. The action-current takes place at the height of each inspiration. The currents that occur in the vagus during respiration can be investigated with the capillary electrometer, as was done by Alcock and Seemann ; they can still be more accurately studied by the iise of Einthoven's string galvanometer (see p. 121). The accompanying figures (fig. 300) are reproduced from Einthoven's work on the sub- ject. They were obtained from a dug. In fig. 300 A, normal respiration was taking place, and the line E is a tracing of the respiratory movements ; the lowermost line (H) is a tracing of the heart-beats. The top tracing (E) is a photographic record of the movement of the quartz fibre in the galvanometer, which was connected by electrodes to the vagus nerve. The vago- eleetrogram, as we may term it, shows large waves, which indicate the changes in the activity of the nerve in reference to respiration ; the en. XXVI.] NERVOUS FACTOR IN RESPIRATION 377 smaller waves upon those are due to its activity in reference to the heart.* In fig. 300 B, a condition of apncea was produced so that the dog did not breathe for a certain time. The vagogram therefore shows no respiratory waves; and the variations due to cardiac action are the only waves seen. During normal respiration, then, it seems that the inspiratory centre alone is active, and that after the inspiration has reached a A H ^t wV—'^^-^^-^' Fig. 300.— a, Upper line (E) is the electro- vagogram ; the middle traciDg R is that of the respiratory movements ; the lowermost line (H) is a tracing of the heart-beats. In B, apncea was produced, and the electro-vagogram shows only the electrical variations in the vagus, which are due to cardiac action. (Einthoven.) certain point, it is checked by an impulse (inhibitory) coming from the lung along the vagus. A theoretical question arises at this point: Supposing no inhibitory impulse came up the vagus, would the inspiration ever cease of itself ? In answer to this question we may say at once that when both vagi are divided, the respirations become much slower and deeper, but they do not entirely cease. If this were the whole case, we should conclude that the respiratory centre had a slow * Einthoven regards these as mainly due to afferent (depressor) impulses ; whether this is so or not is immaterial to the main question discussed above. 378 RESPIRATION [CH. XXTl. inliorent ihytlim, which was quicknnod l)y the vagiis impulses; but it is claimed that when all impulses, both from the brain above and the sensory nerves below, are cut off from the respiratory centre, the respiratory rhythm ceases. The operation is, however, a very severe one, and therefore inconclusive. Leaving the question of normal respiration, we may proceed to consider the impulses passing up the vagus during forced respiration. The presence of impulses in these nerves can again be best detected by their action-currents, and in forced inspiration the same action- current is shown by the galvanometer as we have just mentioned occurs during normal breathing; it can also be induced by artificial inflation of the lung. When the lung is alternately and deeply inflated and deflated, a small electrical variation frequently appears also in the vagus nerve during each deflation. We have, therefore, evidence that a nervous impulse is passing up the vagus during this period, but whether this impulse of the expiratory period is inhibitory to an expiratory centre, or a stimulus to an inspiratory centre, is very difficult to decide. The following experiments of Head, however, suggest the existence of a double centre. His method of recording the movements was by means of that con- venient slip of the diaphragm which is found in rabbits (see p. 357). 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, imtil at last the diaphragm stopped in the position of expiration. Those facts were known previously, but the interpretation of them, in the light of further experiments now to be described, is the following : — There are in the vagus two sets of fibres, one of which produces 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 docs 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 CH. XXVI.] NERVOUS FACTOR IN RESPIRATION 379 inspiratory and expiratory acts. It was sou<^dit and found in the alternate distension and contraction of the air-vesicles of the lungs where the vagus terminations are situated. In one series of experiments positive 'ventilation was performed; that is, air was pumped repeatedly into the lungs, and so increased their normal distension ; 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. 301, A). In a second series of experiments, negative ventilation was per- formed ; 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 contractions of the diaphragm, expiration became less and less, and at last the diaphragm assumed the position of inspiratory standstill (fig. 301, B). Head regards ordinary respiration as 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 re- spiration with a stimulus that leads to expiration. Expiration is a negative ventilation, and so provides the stimulus that leads to inspiration. We must naturally be on our guard against regarding the forcible inflations and deflations produced by a pump as com- pletely analogous to the changes produced in the lungs by or- dinary breathing; nevertheless, the two sets of impulses are undoubtedly called into action if the respiratory processes are sufficiently energetic, and of the two sets of impulses, those which are started by the inspiratory mo^'ement play a more active part in the regulation of respiration than those started by the expira- tory movement, so much so that in unlaboured breathing they alone need be considered. Apnoea. — 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- FiG. 301. — Tracings of diaphragm. The upward move- ments of the tracings represent inspiration ; the do\vnwar• how closely these three centres are connected by association fibres, it is not surprising that the cells of the two latter centres shoidd 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 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. 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- CII. XXVII.] ASPHYXIA 389 sists in making a forcod expiratory effort with the mouth and noso 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 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 ansemia. Asphyxia. Asphyxia may be produced in various ways : for example, by the prevention of the due entry of oxygen into the blood, either by 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. 390 RELATION OF RESPIPwVTION TO OTHER PROCESSES [cn. XXVII. 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 ihe 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 thij'd 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 conjunctivoe 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 foimd 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 empty. The explanation of these appearances may be thus simimar- ised : when oxygenation ceases, venous blood at first passes freely through the lungs to the left heart, and so to the great arteries. 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 passes through the arterioles, and, favoured by the laboured respira- tory movements, arrives at the right side of the heart, wliich 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 tliis way the blood is dammed back in the right heart and veins, and 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 above the normal ; this is due to the constriction of the arterioles which is in part produced by the suprarenal glands pouring out more adrenaline into the circulation, owing to their being stimulated by the excess of carbonic acid in the blood. The fall of pressure in the CII. XXVII.] ASPHYXIA 391 last stago is mainly due to heart failure. If the vagi are not divided previously, the rise of pressure is inuch less, and the heart beats very slowly : this enables the heart to last longer, and is due to excitation •=■2.2 rf I-" (D £ 5 a. 4-3 cj w > of the cardio-inhibitory centre by venous blood. The accompanying photograph of a tracing (fig. 304), which I owe to Dr C. J. Martin, shows these effects; it has been somewhat reduced in size for purposes of reproduction. The lower tracing is that of venous 392 RELATION OF RESPIRATION TO OTHER PROCESSES [CIF. XXVII. pressure taken with a salt solutiun manometer from the jugular vein. It will be noticed that the fall of arterial pressure is accompanied with a great rise of venous pressure due to the venous congestion just described. The Relation of Respiration to Nutrition. The gaseous interchanges in the lungs constitute what is fre- quently termed cxlcrnal respiration. Oxygen obtains an entrance into the blood, and is carried to the tissues in the loose compound known as o.xyhceiuogltjbin. In the tissues, this compound is dis- sociated, and the respiratory oxygen is utilised by the tissue elements for the combustion processes which occur consequent on their activity. Of the ultimate products, carbonic acid and a portion of the water find an outlet by the lungs, to which they are transported by the venous blood. Tlie gaseous interchanges in the tissues con- stitute what is known as internal or tissue respiration. Ins^nrcd and Expired Air. — AVo may conqjare the composition of the inspired or atmospheric air with tliat of the expired air in the followinif table: — The chief change is in the proportion of oxygen and carbonic acid. The loss of oxygen is about 5, the gain in carbonic acid al)Out 4'5. If the inspired and expired airs are carefully measured at the same temperature 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.,) would give rise to a molecule of carbonic acid (CO.,) which would occupy the same volume (Avo- gadro's law). It must, however, Ije romcmljered that carbon is not the only element which is oxidised. Fat and protein 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 taiisc a slight rise in the proportionate volume of nitrof^en per cent. ru. xxvii.] TIIK UESPIRATOKY QUOTIENT 393 ami oLhor carlioliydratos) is takon, and greatest when imicli fat and rr.1 ^- ^ t!0., "iven off . ,, , ,, . , protein are oaten, llie quotient p. " ^ , , is cnhGd tho ^rspiralory 4"5 quotient. Normally it is -:r- = 0"9, but it varies considerably with diet, o as just stated. 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 tulje ; this air has been altered by the respiration of the animal, and in it the car- bonic acid and water are estimated ; it is drawn into bottles containing a known amount of an 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 Regnault and Eeiset's apparatus was potash ; Pettenkofer used baryta water ; Haldane recommends soda-lime. The water is estimated in bottles containing pumice moistened with sulphuric acid. The accompanying drawing (fig. 305) shows the essential part of Fio. 305.— Haldane's apparatus for estimating tlie carbonic acid and aqueous vapour given oft by an animal. 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 contams 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 pure, dry 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, 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- 394 PiELATION OF RESPIRATION TO OTHER PROCESSES [CII. XXVII. croase of wci'j;ht in bottlos 4 and 5 wcitrliod toirotlicr fdvcs tlio amount of carbonic acid produced by the animal in the same time. Itanko skives the following nnml)ors from experiments made on a man, who was taking a mixed diet consisting of 100 grammes of ])rotoin, 100 of fat, and 250 of carbohydrate in the twenty-four hours. The amount of oxygen absorbed in the same time was 606 grammes; of which 560 passed off as carbonic acid, 9 in urea, 19 as water formed from the hydrogen of tlio protein, and 78 from that of the fat. Viorordt from a number of experiments on hnman beings gives the following average numbers: the amount of oxygen absorbed in tlie twenty-four hours is 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 lessoned during sleep. It is especi- ally small in the winter sleep of hibernating animals. During hiber- nation the respiratory quotient sinks to 0'5, so that the animals actually gain weight from retention of oxygen. This aspect of respira- tion is essentially so much a part of " metabolism " that it will be dealt with more in detail in the chapters which deal with that subject. (See especially the respiration calorimeter in ('hap. XLTI.) Tissue Respiration. — As has been already stated, respiration miy be divided into internal or tissue respiration and external or pulmonary respiration. External respiration is much the less obscure, and we have treated of it at considerable length, not only on this account, but also on account of the very frequent impair- ments of the pulmonary mechanism which are met with in disease. It must be borne in mind, however, that pulmonary respiration is but the means, and tissue respiration is the end. Tissue respiration consists in the passage of oxygon from the blood of the capillaries to the cells of the tissues, and the passage of carbonic acid in the reverse direction. This gaseous interchange is no doubt l)rouglit about by a simple process of diffusion. The oxygen passes out of the plasma of the blood through the capillary Hood wall, and then through the lymph ymph until it reaches the cell in which ITllilirt filE" '' i' '''•' f'l^iili''l|!|-MuscieF,bre it is going to he used, which Mimii n i i .iti Utu' i 1' um ■ >- ^yQ ^y^\i suppose IS 'a muscle fibre Fir.. 306. (fig. 306). In order that a con- stant stream of oxygen may pass from the blood to the fibre, there must be a difference of oxygen pressure between the oxygen dissolved in the plasma, and that dissolved in the lymph, and the latter must be at a greater pressure than that dissolved in the muscle fibre. The amount of oxygen which passes will, other things being equal, be directly proportional en. XXVII.] TISSUE RESPIRATION 395 to these pressure differences, and as the aniouut varies greatly at different times, it is obvious that the pressure differences vary greatly also. When the muscle is at rest, the oxygen pressure in the capillaries is very near to that in the muscle libre ; when the muscle is active and using large quantities of oxygen, the intra- capillary oxygen pressure is much greater than the intra-muscular oxygen pressure. Such a change might be brought about by a rise in the intra-capillary oxygen pressure, or a fall in the intra-muscular oxygen pressure, or by both taking place simultaneously. Let us therefore enquire what is known about these quantities. The tension of oxygen in muscle has recently been calculated as being at most equal to 19 mm. of mercury; from this it may vary down to zero. Within these limits the conditions for diffusion cm be increased by a drop in the intra-muscular oxygen pressure. There is, in addition, a mechanism for raising the intra-capillary oxygen pressure. This is the increased quantity of acid (carbonic and sarco-lactic acids) which is thrown into the blood as the result of muscular metabolism. The following diagram (fig. 307) shows the extent, both in degree and time, of this pouring of acid into the blood as the result of a tetanic contraction of a muscle lasting only a few seconds. 10 30 50 70 90 no 130 ;50 170 190 210 230 250 270 290 — > Time In seconds. Fig. 307. — The black area represents the lactic aciil thrown into the blood during the time following a tetanus that lasteil S4 seconds ; the work done by the muscle was 70 gramme-centimetres ; the total quantity of lactic acid formed was 0-103 grammes. The figures on the vertical line represent fract'oiis (jf a gramme of lactic acid per second. In glandular structures the oxygen pressure is higher than in muscle; probably owing to the relatively more copious blood- supply of glands, equilibrium is more readily established between the blood and the gland cells, the oxygen pressure in the cells being almost that present in venous blood. The quantity of oxygen used by different tissues varies not only with the degree of their activity, but also with the nature of the tissues. On the whole it may be said that, weight for weight, glandular tissue uses most oxygen ; next in order come the muscular tissues, and last of all, the connective tissues. There are some important tissues, notably the nervous system, about which little is known in this connection. The amount of oxygen used by 396 KELATION OF RESPIRATION TO OTHER PROCESSES [CU. XXVI^- an organ or tissue per gramme [mv minute is called its cocjiricnl of oxidation. Measuremoii of Coefficient of Oxidation. — The method adopted depends upon whether the observer desires to ascertain the coeflficient at a particular moment of time, or its average value over a considerable jjcriod. If the former is desired, it is necessary: — (1) to estimate the gases in the blood going to and emerging from the organ ; this is performed by the chemical method of expelling the oxygen and carbonic acid from samples of the arterial and venous blood by means of potassium ferricyanide and tartaric acid respec- tively (see p. 364); (2) to determine the amount of blood passing through the organ in a given time, say one minute ; and (3) at the conclusion of the experiment the organ is weighed, so that the gaseous exchange per gramme can be calculated. Fio. 308. — Traciu;,' to illustrate Brodie's methoii of ascertaining the rale of bliMjd-lli)\v through an organ. For exiilanation see text. The rate of the flow of blood through an organ may be ascertained, either by directly measuring the venous blood as it emerges from the organ, or by a very simple method introduced by Brodie; tlie organ is enclosed in an oncometer connected to a bellows recorder ; the issuing vein is compressed for about a second, and the blood flowing into the organ causes it to expand ; the lever of the recorder rises quickly or slowly according to the rate at which the blood is flowing into tlie organ. The recorder is first calibrated by injecting half a cubic centimetre of water into the tubing leading to it, and the position of the lever at rest, and that which it occupies when the oncometer is distended by half a cubic centimetre of water are marked continuously by two fixed writing-points. In the accom- panying figure, obtained from an experiment on a kidney, these two lines are lettered A and B. The surface travels at a (|uick rate, and the time-tracing T shows thirtieths of a second. Tiio line C is traced by the oncometer lever. CII. XXV! l] TISSUE RESPIKATION 397 At the point D the renal vein was compressed, and at the point E the compression ceased. From D to E the inflowing blood caused the kidney to expand and the recording lever to rise. It crosses the two horizontal lines at F and G respectively. During this time (F to G), therefore, half a cubic centimetre of blood entered the kidney, and this time was thirty-three vibrations of the time-marker, that is 1-1 second. Hence the rate of blood-flow would be = 27-3 c.c. of blood per minute. In order to measure the gaseous exchange of an organ over a long period the organ is supplied with blood which alternately traverses the organ and aerates itself in a closed chamber. The amount of oxygen in the chamber is kept constant by the addition of that gas to the air of the chamber at the same rate at which the circulation acquires it. The amount of oxygen so added is measured. The method has recently been applied with conspicuous success to the gaseous exchange of the heart. Relation of Tissue Respiration to Functional Activity. In all organs, so far as is known, increased activity is accom- panied by increased oxidation. j\Iuch interest centres about the question of the order of time in which these events take place. This matter has been investigated 1 1 o X /-M. a ■r \ ^^ d minutes li Iz la 4 Fig. 309.— Tae black-wliite line repre.seiit.s rate of salivary secretion in c.c. per minute. S- line for saliva. Black area = oxygeu used by the glaud. 0— O=oxygen base line. = base in the case of skeletal muscle and the submaxillary gland (fig. 309), both of which organs can be thrown into profound activity for a short space of time ; in each case most of the oxidation follows upon the activity, and not the activity upon the oxidation. The important inference is drawn that the contraction or secretion, as the case may ,be, is not caused by the oxidation in the sense that the machinery of a locomotive is driven by the energy derived from the oxidation of the coal; rather is the mechanism like that of a spring which is liberated at the moment of doing the work, and has to be rewound subsequently ; the process of rewinding involves oxidation. In the case of muscle, the heat-formation which occurs in the period 598 UKLATION OF KESPIRATIUN TO OTHEU I'KOCESSES [CH. XXVII. following acii\ity only lakes jdaco if iho muscle is supplied wilh oxygen. The output of carbonic acid, in ils turn, follows upon the intake of oxygen. The order of events is therefore (1) increase of functional activity, (2) increase of heat formation and oxygen taken in, and (3) increase of carbonic acid put out. The following table .shows the coefficients of oxidation for resting organs, and the extent to which they are increased in activity. Organ. Condition of Rest. Oxygen used Iii;r minute per gramme ! of organ. Condition of Activity. Oxygen used per minute I>er gramme of organ. 1 Voluntary muscle. Nerves cut. 0-003 c.c. Tone absent. Tone existing in rest. Gentle contraction. Active contraction. 006 c.c. 0-020 C.C. 0-080 C.C. Unslriped muscle. Resting ' 0-004 c.c. Contracting. 0-007 c.c. Heart Very .slow and feeble con- tractions. 0-007 c C. Normal contractions. Very active. 0-05 c.c. 0-08 c.c. Submaxillary gland. Nerves cut. Not secreting. 0-03 c.c. i Chorda stimulation. 0-10 c.c. Pancreas. 0-03 c.c. Secretion after injection of secretin. 0-10 c.c. Kidney. Scanty secretion. O'OS c.c. After injection of diuretic. 0-10 c.c. Intestines. Not absorbing. 0-02 c.c. Absorbing peptone. 0-03 c.a Liver. In fasting animal. 0-01 to 0-02 c.c. : In fed animal. 0-03 to 0-C5 c.c. Suprarenal gland. Normal. •045 c.c. In many cases the quantitative relationships have not been worked out. liecent research has shown that in the case of the heart, if N is the number of beats per minute, T, the maximum blood-pressure which is attained at each beat, and 0, the amount of oxygen used ; NxT . then — -- — is a constant quantity, unless the cardiac muscle is itself CII. XXVII.] OXYCEN WANT 399 rendered less efricient, as may be done by tliu use of drugs. This is in agreement with a scries of researches on the heat given out by frogs' muscle, which shows that the heat given out in a single contraction varies directly with the tension in the muscle. The efficiency of the; heart regarded as a machine seems to be low (about 2 per cent.), owing perhaps to the anatomical disposition of the strands of fibres. Intensity of Respiration. — Most of the figures relating to gaseous metabolism given in the preceding paragraphs were obtained from the examination of the tissues and organs of the dog. If all the tissues were examined in turn, and their relative weights known, an average might be struck which would give the gaseous met- al)olism for the body -taken as a whole, and this might be expressed as the amount of oxygen used per minute per gramme of body- weight. An easier and more practicable method, however, is to weigh the animal, and then from the composition of the inspii'ed and expired air and the amount of oxygen taken in and given out, calculate how much is retained and utilised. In the dog, the amount is about 0-016 c.c. of oxygen per minute per gramme of body-weight. This figure, however, is not the same in all animals, and the size of the figure will indicate wdiat we may term the intensity of respiration. Thus in cold-blooded animals, especially fishes with their small supply of oxygen, the figure is very much smaller. Among warm-blooded animals great variations are also seen ; the intensity of respiration, for instance, is much greater in birds than in mammals. Among the mammals, the intensity of respiration varies, roughly, inversely with the size of the animal ; thus, in the mouse, an animal that breathes with extreme rapidity, the intensity is probably ten to fifteen times greater than in the dog, and in the elephant very much less. In man, the average is about half that in the dog, that is, 0-003 c.c. of oxygen per gramme of body-weight per minirte. Oxygen Want. The balance between the demand for oxygen and the supply may be upset either by increasing the demand or decreasing the supply. Oxygen want may therefore take place either as the result of violent exercise or of diminished oxygen pressure. Normally a man takes into his blood about 400 c.c. of oxygen per minute, in sleep about half this, and in such exercise as is afforded by the pushing of a motor bicycle up a steep hill, 3000 c.c. per minute or more are absorbed by the blood. During the violent contraction of a muscle, the blood-flow through it is momentarily retarded, though over a considerible interval of time it is much increased. Nevertheless 400 RELATION OF RESPIRATION TO OTHER PROCESSES [CH. XXVII. the moinontary retardation leads to a certain amount of oxygen want, and this is probably the cause of the lactic acid output, to which we have drawn attention (see pp. 381 and 395). lactic acid production in muscle indicates incomplete oxidation. The acid itself probably increases the blood-supply to the muscle automati- cally by relaxing the arteriole walls. The symptoms produced by exercise and by decreased pressure (as in mountain sickness) are not the same, probably because the former is accompanied by an increase in the production of carbonic acid and of heat. Indeed most of the symptoms which are the ordinary effects of exercise are due probably to these causes, the actual oxygen supply to the brain being adequate during exercise. Mountain Sickness. The symptoms of mountain sickness differ in different persons as do those of other forms of intoxication. In one person vomiting will be the prominent feature, in another, absence of self-restraint, in a third, inability to perform any task, such as arithmetic, involving accurate cerebral processes. There is no doubt that the cause is want of oxygen. This lack of oxygen causes the production of the poisonous materials, which affect the brain and produce the symptoms. These toxic substances are no doubt products of incomplete oxidation ; it is not clear how far these are produced in the brain, and how far they are carried to it in the blood. In considering what is the lowest pressure of oxygen consistent with normal function, it must be borne in mind that with lungs of a given size this limiting pressure varies directly with the number of c.c. of oxygen which must be absorbed (Bohr). The effect of exercise is to increase the amount of oxygen required by the tissues. The amount of oxygen required by the same person under different circumstances varies very much. Thus Zuntz resting and fasting on Monte Rosa required only 259 c.c. of oxygen per minute, whilst in the act of climbing he wanted 1329 c.c. of oxygen per minute. In the former condition he could have remained in comfort at an altitude at which the pressure of oxygen in his alveoli was very low, but as soon as he made any effort he realised that this pressure of oxygen was insufficient to allow him to do muscular work. Now the alveolar pressure depends partly on the barometric pressure, and partly on the nature of the respiration. The deeper the respiration the more nearly does the pressure of oxygen in the alveoli approximate to that in the atmosphere {i.e. the higher is the alveolar pressure of oxygen). Thus it happens that men who take deep respirations can tolerate altitudes which are impossible for CII. XXVri.] MOUNTAIN SICKNESB 401 shallow breathers. This is illustrated by the following figures obtained from observations on three different men : — Subject 1 Mountain sickness therefore attacks different persons at different altitudes. If no form of adaptation took place, the following would be the approximate pressures of oxygen in the pulmonary alveoli at the following altitudes : — i-.c. of air Numter of Height in metres per respirations at which distress inspiration. per minute. was felt. 270 20 3300 440 14 6000 700 8 6500 Sea level . 100 mm. 10,000 feet . 59 mm. 15,000 feet . 38 mm. It is known iliat at alveolar pressures of 60 mm. or thereabouts the symptoms of oxygen want begin in an artificial chamber. Inspec- tion of the dissociation curve of human blood, p. 370, will show that at 59 mm. the arterial blood might be upwards of 85 per cent, saturated with oxygen, but at 38 mm. it would 1)6 only 66 per cent, saturated. This condition of the blood would account for the symptoms. Methods of adaptation to high altitudes. — Apart from the question of "training" which will be dealt with below, adaptation takes place along two lines, each of which tends to bring more oxygen into a given quantity of blood. This is accomplished (1) by raising the alveolar pressure of oxygen higher than the figures given above ; and (2) by increasing the quantity of hsemoglobin in the blood. The rise in alveolar oxygen 'pressure is brought about by more rapid breathing. The more rapid breathing in turn is the result of the respiratory centre being hustled by acid formation if the respira^ tion slows down. There is therefore more oxygen and less carbonic acid in the alveolar air and in the blood than there otherwise would be. Actually, the oxygen pressures in the alveolar air were found to be : — Sea level . .100 mm. 10,000 feet . . 65 mm. 15,000 feet . . 52 mm. The chief difference is naturally at the greatest altitude. Here, instead of the alveolar oxygen pressure being 38 mm. it is 52 mm. ; the blood could therefore become about 80 per cent, instead of 66 per cent., saturated with oxygen — a very material increase. Moreover, since the rate at which the blood becomes oxygenated is directly proportional to the oxygen pressure, the difference between 38 mm. and 52 mm. is most beneficial. The figures for the percentage 2 C 402 RELATION OF KESPIRATION TO OTHER PROCESSES [CII. XXVII. saturation are obtained by employing the dissociation curve for blood at 40 mm. carbonic acid pressure. The legitimacy of this may be questioned, since the carbonic acid pressure in the blood at an eleva- tion of 15,000 feet is only about 25 mm.* The curve is, however, true for the blood at all altitudes since the reaction of the blood remains the same (or may shift a trifling amount to the acid side), some other less volatile acid making up for the deficiency in carbonic acid. Increase of hcemoglohin in the blood. — At high altitudes the number of corpuscles per cubic millimetre in human blood is said to be excessive. Some caution is necessary in attributing physiological significance to such statements, for they may be in part illusory. In balloon ascents, for instance, the number of corpuscles in blood may increase very rapidly. This is not due to fresh formation of blood, but to the excessive secretion of lymph, which leads to concentration of the blood. Nevertheless, in animals kept at high altitudes for some days there is an actual increase in the formation of corpuscles, as shown by the appearance of nucleated corpuscles thrust into the blood by the bone-marrow, and an increase in the amount of iron in the blood at the expense of the quantity of that element in the liver. Training. — We have seen that a factor in the onset of mountain sickness is the amount of oxygen which passes through the lung epithelium. It is a matter of experience that from various causes an individual can do the same amount of muscular work, such as performing the same mountain-climb, with a less degree of metabolism after training. This is in part due to the fact that the trained person has lost unnecessary weight, and in part because he uses his muscles to better advantage. Thus every unit of energy spent in work demanded a total expenditure of energy of 7 units in the case of an untrained town-dweller, 5 units in the case of a partially trained tourist, and 3-3 units in the case of an Alpine porter. Therefore, in the same climb, the Alpine carrier would only suffer half the increase of metabolism that the town-dweller would. He would therefore need correspondingly less oxygen, and he could reach a height at which he would have a correspondingly lower alveolar oxygen tension. Respiration at High Pressures. Prolonged exposure to pressures of oxygen, equal to 1300 to 1400 mm. of mercury, induces pneumonia, and death rapidly follows. It is * The diinimition of carbonic acid tension in alveolar air and blood is termed acapnia, and Thorso attributed mountain sickness to this condition. Although this view is incorrect, it is necessary to remember that carbonic acid is not a mere waste product, but performs certiin duties in the body (stimulatinfj respiration and assistinfT the dissociation of oxyhsemoglobin); in certain conditions, as in shock, acapnia is an important factor. CII. XXVII.] CARBON MONOXIDE POISONING 403 nut possible, thorofore, for men to work in air which is compressed to the extent of producing so great a pressure of oxygen. Caisson disease. — In the boring of tunnels and in carrying out operations in the beds of rivers, it is usual to sink an iron tube in which the men work. This tube or caisson is closed except at the end at which the work is progressing, and the water is prevented from inundating it by pumping air into it at a pressure higher than that of the water. The men enter through a chamber with double doors or "air-lock." In this chamber the pressure can be raised or lowered. The pressure in the caisson rarely exceeds 4 atmospheres, which corresponds to about 600 mm. of oxygen; at this pressure the workers do not suffer whilst they are in the caisson, but grave symptoms may take place shortly after they have come out. Similar symptoms are experienced by divers who come to the surface from great depths. The symptoms may take the form of paralysis, vomiting, severe abdominal pain, vertigo, etc. They are due to the fact that the plasma, and indeed all the fluids which permeate the organs of the body, become saturated with oxygen and nitrogen at the pressure of the caisson, and therefore when the pressure is suddenly removed, minute bubbles form throughout the body and injure such tissues as the spinal cord, or produce blockage of the vessels. Short hours are necessary for caisson workers, for then the body has not time to get saturated with air at the caisson pressure, and in all cases "decompression" must be gradual and slow ; this gradual release from pressure is accomplished in the " air-lock." The dangers we have mentioned then cease to exist. The atmospheric gases are specially soluble in fat; fat people are therefore very susceptible to caisson disease, and should, in fact, be prohibited from labour in caissons. Carbon Monoxide Poisoning. The fatal effects often produced by this gas (as in accidents from burnmg charcoal stoves in small close rooms, or where there is an escape of coal gas), are due to its entering into combination with the haemoglobin of the blood-corpuscles, and thus hindering their oxygen- carrying function. In an atmosphere containing both oxygen and carbon monoxide, the relative quantities of the two gases which the haemoglobin will absorb varies with the partial pressure of the gases. The affinity of haemoglobin for carbon monoxide is, how- ever, much greater than its affinity for oxygen, and the compound formed — carboxyhsemoglobin — is much more stable than oxyhsemo- globin is. If, therefore, any considerable quantity of carbon mon- oxide is present in the air, the haemoglobin will be almost completely charged with carboxyhaemoglobin, and asphyxia would follow. If the patient is given pure oxygen to breathe even at a late stage, 404 RELATION OF KESPIKATION TO OTHER PROCESSES [CII. XXVII. two tilings will happen : — (1) The blood will take up in simple physical solution about seven times as much oxygen as when exposed to air, and this may be sufiicient to carry on life ; (2) as regards the saturation of the haemoglobin, the balance is now in favour of the oxygen, weak as its aflinity for haenioglobin is, and the carbon monoxide gradually works its way out of the body. Cheyne-Stokes Respiration. This is a condition in which the breatliing waxes and wanes to a remarkable degree (fig. 310). It is an exaggeration of the type of respiration which is often seen during sleep in perfectly healthy people. The condition was first observed by the two Dublin physicians whose names it bears. It may be induced in normal persons if they make themselves pant violently for 1-2 minutes. If then respiration is allowed to take its own course, there will first I'll.;, mo. — tJtflliograiih tracing of Oieyne-Slokes ri'Siiiratiuh ijj a Uiaii. Tbc liiiif is marked iu seconds. (Penibrey and Allen.) be a pause (apnoea), then Cheyne-Stokes respiration will be set up. The groups will become less and less distinct, and respiration will ultimately become normal. The explanation of this phenomenon is as follows : — The panting causes an undue amount of carbonic acid to leave the body, with the result that the carbonic acid tension in the blood and ill the tissues sinks to perhaps a quarter or a third of its usual value. Already we have seen that carbonic acid is an active stimulant to the respiratory centre, and its removal causes respiration to cease, hence the apnoea. But during the apnoeic period the arterial blood becomes less and less oxygenated, with the result that lactic acid formation (a constant result of oxi/f/e7i want) takes place in the tissues ; the lactic acid, like carbonic acid, stimulates the respiratory centre, which remains active till the advent of oxygen causes oxidation of the aaid; there is then another pause, and so on. Cheyne Stokes breathing is dependent, then, on oxygen want. CH. XXYIl] DTARETIC COMA 405 " Tf from any causo, sncli as cerebral linemonhage or circulatory failure, the circulation through the respiratory centre is interfered with, or if the absorption of oxygen is interfered with by such causes as diminished barometric pressure or pathological conditions in the lungs, the occurrence of periodic or Cheyne-Stokes breathing becomes easily intelligible." — (Haldane and Douglas). Pathological Cheyne-Stokes respiration may be removed by administration either of oxygen or of carbonic acid. Pembrey and Pitts have also taken tracings of the same condition in the hibernating dormouse, hedgehog, marmot, and bat. In some cases the respiration has the typical Cheyne-Stokes character, with a gradual waxing and waning. In other cases periods of respiratory activity alternate with periods of apnoea, but all the respiratory efforts are about equal in force. This is known as Biot's respiration, Fio. 311. — Biot's respiration in hibernating dormouse. The line marked T gives time in seconds. Line 1 gives the tracing of a respiratory group which occurred once every SO seconds, the tempera- ture of tlie 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 first accompanied by shivering, became continuous. (Pembrey and Pitts.) and is illustrated by the accompanying illustration taken from a hibernating dormouse. Diabetic Coma. En the preceding chapter conditions have been considered which depend upon the stimulus given to the respiratory centre by the con- dition of the gases in the blood. Carbonic acid is, however, not the only body capable of affecting the respiratory centre; lactic acid, as we have just seen, will stimulate it, and probably all other acids in solution will do the same. If, therefore, other acid radicals are thrown into the blood, the respiration will increase till the amount of carbonic acid in the blood is proportionally decreased. It is the total concentration of such radicals, or rather of the hydrogen ions which they carry in their wake, that remains a constant factor. In diabetic coma other acids {e.g., hydroxybutyric) make their appearance, and the respiration is exaggerated till only a small amount of carbonic acid remains. CHAPTER XXVIII THE CHEMICAL COMPOSITION OF THE BODY 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 compounds. The compounds, or, as they are frequently 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 as hydrochloric acid in the gastric juice), ammonia (as in the urine), and 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 — (Proteins — «.//., albumin, myosin, casein, gelatin, etc Nitrogenous Simpler nilroyenous bodies — e.y., lecithin, urea, creatine. (Fdt.s — e.im])ler organic bodies— e.g., cholcsterin, lactic VT .. ] CdrlioJii/dntfis — ^.7., sugar, starch Non-nitrogenous -, x/,„^,/^; „.„.„„> /,;.'/;..._.«. .-hnl, acid. The subdivision of the organic proximate principles into proteins, 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- ever, found in or formed by the animal organism. The most important en. XXVIII.] THE CARBOIIYDKATES 407 of these are glycogen, or animal starch ; dextrose ; and lactose, or milk sugar. The carbohydrates may be conveniently defined as compoimds 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 such as acetic acid, lactic acid, and inosite, which are not carbohydrates. Kesearch 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) and two hydrogen atoms are attached to the same carbon atom ; it, therefore, contains the group CH._,OfI. Thus the formula for common alcohol (primary ethyl alcohol) is CHo.CH.OH. The formula for the next alcohol of the same series (primary propyl alcohol) is CH3.CH,.CH.pH. If a primary alcohol is oxidised, the first oxidation product is called an aldehyde ; thus ethyl alcohol yields acetic aldehyde : — CH3.CH.OH + O = CH3.COH + H,0. [Ethyl alcohol.] [Acetic aldehyde.] The typical group COH of the aldehyde is not stable, but is easily oxidisable to form the group COOH (carboxyl), and the compound so formed is called an acid ; in this way acetic aldehyde forms acetic acid : — CH3.COH + O = CH3.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 and one hydrogen atom are attached to the same carbon atom ; thus secondary propyl alcohol has the formula CH3.CHOH.CH3. Its typical group is therefore CHOH. When this is oxidised, the first oxidation product is called a ketone, thus : — CH3.CHOH.CH3 + o = CH3.C0.CH3 + up. [Secondary propyl alcohol.] [Propyl ketone or acetone.] It therefore contains the group CO. Some of the sugars are ketones of more complex alcohols ; these 408 THE CHEMICAL COMPOSITION OP THE BODY [cn. XXVITI. are called ketoses. Tho only one of those which is of physiological interest is Inevulose. The alcohols of which we have already spoken are called monatomic, because they contain only one OH group. Those which contain two OH groups (such as glycol) are called diatomic ; those which contain three OH groups (such as 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^^IS.^ (OH)^ 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; Itevulose is the ketone of mannite ; and galactose is the aldehyde of dulcite. These sugars all have the empirical formula Cj^Hj.^O^. They furnish an excellent example of what is called stereochemical isomerism ; that is, the position of the atoms or groups of atoms in space within the sugar molecule varies. The constitutional formulae of three important simple sugars are shown below. The six carbon atoms in each case form an open chain, but the way in which the hydrogen and hydroxyl atoms are linked to them differs. CH,OH CH.OH CHpH H- -C— OH H- -C— OH H— C— OH H- -C— OH H _G— OH OH— C— H OH- -C— H 1 OH- -C-H OH— C— H 1 H- -C— OH 1 c=o 1 H— C— OH C— OH [Dextrose.] CH.pH [L.a:VuIose.] C— OH [Galactose.] The aldehyde constitution of dextrose and galactose is at once evident, the typical aldehyde group (COH) being at the end of the chain, whereas the ketone constitution of Irevulose is shown by tlie typical ketone group (CO) not at the end of the chain. By further oxidation, the sugars yield acids with various names. If we take such sugars as typical specimens, we see that their general formula is C„H,„0„ and as a general rule w = m ; that is, the number of oxygen and carbon atoms are equal. This nimiber in the case of the sugars already mentioned is six. Hence they are called hexoses. Sugars are known to chemists, in which tliis number is 3, 4, 5, 7. etc. and these are called trioses, tetroses, jjcntoses, heptoaes. etc. The majority of these en. XXYIII.] THE CARBOHYDRATES 409 have no physiological interest. It should, however, be mentioned that a pentose has been obtained from the cert;iin nucleic acids presently to be described (see p. 431) which are contained in animal orjrans (pancreas, liver, etc.), and in plants (for instance, yeast). If the pentoses which are found in various plants are given to an animal, they are excreted in great measure unchanged in tlie urine. The hexoses are of great physiological importance. The principal ones are dextrose, Isevulose, and galactose. These are called mono- saccharides. Another important group of sugars are called disaccharides ; these are formed by what is called condensation ; that- is, two mole- cules of monosaccharide combine together with the loss of a molecule of water, thus : — C^Hi^O, + C„H,.30, = q.3H,,0„ + H.O. The principal members of the disaccharide group are cane sugar, lactose, and maltose. If more than two molecules of the monosaccharide group undergo a corresponding condensation, we get what are called polysaccharides. «C,H,,0,3 = (C,H,,,0,)„ + «H,0. The principal polysaccharides are starch, glycogen, various dextrins, and cellulose. We may, therefore, arrange the important carbo- hydrates of the hexose family in a tabular form as follows : — 1. Monosaccharides, 1 2. Disaccharides, C«H,„0,. i C.oH„„0,,. 3. Polysaccharides (C«H,„0,)a + Dextrose. + Cane sugar. - Lae\Tilose. + Lactose. + Galactose. + Maltose, + Starch. + Glycogen. + Dextrin. Cellulose. The + and — signs in the above list indicate that the substances to which they are prefixed are dextro- and laevo-rotatory respectively as regards polarised light. The formulae given in the table 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, Glucose, or Grape Sugar. — This carbohydrate is found in many 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 410 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXYIII. brown colour. This constitutes Moore's test for sugar. Tn 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 ethyl alcohol and carbonic acid (C,Hi,0, = 2C,H,0 + 2C0,). Dextrose may be estimated by the fermentation test, by the polar- imeter, 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 we shall study it in connection with diabetic urine. Lseviilose or Fructose. — 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 Isevulose. The previously dextro-rotatory solution of cane sugar then becomes Isevo-rotatory, the laevo-rotatory power of the Isevulose being greater than the dextro-rotatory power of the dextrose formed. Hence the term inversion. The same hydrolytic change is produced by certain enzymes, such as the invertase of the intestinal juice and of yeast. Pure Isevulose can be crystallised with difficulty. It gives the same general reactions as dextrose. Galactose is formed by the action of dilute mineral acids or of inverting enzymes 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^HnjO^), which is only slightly soluble in water. J )extrose when treated in this way yields an isomeric acid — i.e., an acid with the same empirical formula, called saccharic 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 enzymes such as that occurring in the CH. XXVIII.] THE CARBOHYDRATES 411 intestinal juice. It then takes up water, and is split into equal parts of dextrose and laivulose. CioH.,,Oji + 11,0 = C,H,,0, + C,,Hj,0,,. [Cane sugar.] [Dextrose.] [L;(vulose.] With yeast, cane sugar is first inverted by means of a special enzyme invertase secreted by the yeast cells, and then there is an alcoholic fermentation of the monosaccharides so formed, which is accomplished by another enzyme called zymase. Lactose, or Milk Sugar, occurs in milk. It is occasionally found in the urine of women in the early days of lactation, or after 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 wuth cane sugar, it takes up water and splits into dextrose and galactose. Ci2Ho.Pii + H,0 = C,Hi.p, + C,HjA- [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 enzymes secreted by certain micro-organisms, which are somewhat similar to yeast cells. Bacteria in the intestine bring about the same result. The two stages of the lactic acid fermentation are represented in the following equations : — (1.) q.,H,.,Oi, + HP = 4C3H,03. [Lactose.] [Lactic acid.] (2.) 4C3H,.03 = 2C,H802 + 400., + 4H._,. [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 enzymes 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 enzymes such as occurs in the intestinal juice, it is converted into dextrose. [Maltose.] [Dextrose.] 412 THE CHEMICAL COMPOSITION OF TOE BODY [cn. XXTIIL Phenyl-hydrazine Test. — The three important reducing sugars witli which we have to deal in physiology are dextrose, lactose, and maltose. They may be distinguished by their relative reducing j)Owers 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 about 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 docs not yield an osazone. 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 or 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 Fig. 312.— Grains of potato an opalcsccnt solutiou in boiliug 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 enzymes, 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(Ci.3HooOio)oo. 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 intermediate products in the hydrolysis of starch or glycogen, and two chief varieties are distin- guished : — erythro-dextrin, which gives a reddish -brown colour with iodine ; and achroo-dextrin, which does not. It is readily soluble in water, but insoluble in alcohol and ether. It is gummy and amorphous. It does not give Trommer's test, nor does it ferment with yeast. It is dextro-rotatory. By hydrolysing agencies it is converted into glucose. Glycogen, or animal starch, is found in liver, muscle, and white blood-corpuscles. It is also abundant in embryonic tissues. Glycoo-en is a white tasteless powder, soluble in water, but it forms, like starch, an opalescent solution. It is insoluble in alcohol CH. XXVni.] TUE CARBOHYDRATES 413 and ether. It is dextro-rotatory. With Trommer's test it gives a bhie sohitiuii, but uo 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. (4) It is precipitated by saturation with ammonium sulphate; erythro-dextrin is only partially precipitable by this means. 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 greater difficulty. The various digestive enzymes 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 outer investment of the Tunicates. Inosite was discovered by Scherer in 1850 as a constituent of muscle, and for a long time was known as muscle sugar. It occurs also in small quantities in other animal organs (liver, kidney, etc.), and in plants it is a fairly constant constituent of roots and leaves, especially growing leaves. It has the same molecular formula as the simple sugars (CgHj.^Oe)' ^^^ i^ ^^s none of the other properties of these substances. Maquenne ascertained that it has the following formula — HOH I HOH— C C— HOH HOH— C C— HOH I HOH which a mere glance at will show is very different from those of the sugars given on p. 408. For the six carbon atoms, instead of forming an open chain, are linked into a ring, as in the benzene derivatives. It is in fact a reduced hexa-oxybenzene. It probably represents a transition stage between the carbohydrates and the benzene compounds. By a closing-up of the open chain of the carbo- 414 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. hydrate molecule its formation from the latter is theoretically possihle. Ou the other hand, the opening of the inosite ring would give rise to an open chain, and it has indeed been found that lactic acid is formed from inosite by the action of certain bacteria. The Fats, Pat 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 solidifies at — 5' C, palmitin at 45 C, and stearin at 53-65" 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. Claemical Constitution of the Fats. — The fats are compounds of fatty acids with glycerin, and may be termed glycerides or glyceric ethers. The fatty acids form a series of acids derived from the monatomic alcohols by oxidation. Thus, to take ordinary ethyl alcohol, CoH^O, the first stage in oxidation is the removal of two atoms of hydrogen to form aldehyde, CH^O ; on further oxidation an atom of oxygen is added to form acetic acid, C.,H40.,. A similar acid can be obtained from all the other alcohols, thus : — From methyl al( ■ohol CH.HO, formic acid H.COOH is obtained. „ ethyl c.,h;ho, acetic „ CH.COOH „ propyl c;h,.ho, propionic- „ CoH-,.COOH „ butyl c;a,Ho, butyric ,. C:h1.C00H ,, amyl C-,H„.HO, valeric „ C\H„.COOH „ hexyl C«Hi,.HO, caproic .. CjHji.COOH and 80 on. The sixteenth term of this series has the formula CiyHsi.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 radical, C„--iHo„_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 en. XXrV'lII.] THE FATS 415 the general formula is Cn-iHi/i-s.COOH. It is the eighteenth term of the series, and its formula is C1VH33.COOH. The first member of the proup of alcohols from which this arryhc series of acids is obtained is called «///// alcohol (CHo: CH.CH,OH) ; the aldehyde of this is (irrolein (Clio : CH.CHO), and the formula for the acid (acrylic acid) is CH., :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 underj^o by uniting with another element a conversion into bodies in wliieh 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. (red coloration) are due. Fat which contains any member of the acrylic series, such as oleic acid, blackens osmic acid, by reducing it to a lower (black) oxide. The fats palmitin and stearin do not give these reactions. Glycerin or Glycerol is a triatomic alcohol, 03115(110)3 — i.e., three atoms of hydroxyl united to a radical glyceryl (O3H5). The hydrogen in the hydroxyl atoms is replaceable by other organic radicals. As an example, take the radical of acetic acid called acetyl (OH3.OO). The following formulae represent the derivatives that can be obtained by replacing one, two, or all three hydroxyl hydrogen atoms in this way : — rOH rOH (OH fO.CH^.CO CHg OH an, OH C..H5J O.CH.CO CsHgJ O.CH.,.CO ioH to.cH,.co " l0.cH3.c0 io.ch;,co [Glycerin.] [Monoacetin.] [Diacetin.] [Triacetin.] Triacetin is a type of a neutral fat; stearin, palmitin, 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 radicals of the fatty acid. This is represented in the following formulae : — Acid. Radical, Fat. Palmitic acid CjjH .i.COOH Palmityl Ci^Hgj.CO Palmitin C.,H5(OCi,H3,.CO)3 Stearic acid C,;H.-,.COOH Stearyl CnH.^.CO Stearin C;H,(OCnH35.CO)3 Oleic acid Ci.Hal.COOH Oleyl C17H33.CO Olein C3H5(OCnH33.CO)3 Decomposition Products of the Pats. — The fats split up into the substances out of which they are built up. Under the influence of superheated steam, mineral acids, and in the body by means of certain enzymes (for instance, the fat-splitting enzyme, lipase, of the pancreatic juice), a fat combines with water and splits into glycerin and the fatty acid. The following equa- tion represents what occurs in a fat, taking tripalmitin as an example : — C3H5(0.q5H3iCO)3 + 3HP = C.UIOH), + 3q5H3,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 416 ■ THE CHEMICAL COMPOSITION OF THE BODY [CII. XXVIII. with the fatty acid which is called a soap. Suppose, for instance, that potassium hydrate is used ; we get — ■ C3H.(O.Ci.H3iCO)3 + 3KH0 = C3H^(OH)3 + SCi^HgiCO.OK. [Tripalmitin— a fat.] [Glycerin.] [Potassium palmitat«— a soap.] Emulsification. — Another change that fats undergo in the body is very different from saponification. It is a physical not a chemical change ; the fat is broken up into very small globules, such as are seen in the natural emulsion — milk. The Proteins. The proteins are the most important substances that occur in animal and vegetable organisms, and protein metabolism is, as already noted (p. 6), the most characteristic sign of life. They are highly complex compounds of carbon, hydrogen, oxygen, nitrogen, and sulphur, occurring in a solid viscous condition or in solution in nearly all parts of the body. The different members of the group present great similarities, for instance, in the heaviness of their molecules, and in giving certain colour tests wo shall be describ- ing presently ; there are, on the other hand, considerable differences between the various proteins. The proteins in the food form the source of the proteins in the body tissues, but the latter are usually different in composition from the former. The food proteins are in the process of digestion broken up into simpler substances, usually called cleavage products, and it is from these that the body cells reconstruct the proteins peculiar to themselves. As a result of katabolic processes in the body, the proteins are finally again broken down, carbonic acid, water, sulphuric acid (combined as sulphates), urea, and creatinine being the principal final products which are discharged in the urine and other excretions. The substances intermediate between the proteins and these final katabolites will be discussed under urine. The following figures will show how different the proteins are even in elementary composition. Hoppe-Seyler many years ago gave the variations in percentage composition as follows : — C H N S O From 51-5 6-9 15-2 O'-i 20-9 To 54-5 7-3 17-0 2-0 23-5 Eecent research has since shown that the variations are even greater than those given hy Hoppe-Seyler. Differences are also seen when the cleavage products are separ- ated and estimated. These differ both in kind and in amount, but nearly all of them are substances which are termed amino-acids. Emil Fischer to whom we owe so much of our knowledge in this CH. XXVIU.] THE PROTEINS 417 direction, cousiders that the proteins are linkages of a greater or lesser number of these aniino-acids, and there is little doubt that in the future this work will result in an actual synthesis of the protein molecule, and with that will come an accurate knowledge of its constitution. When the protein molecule is broken down in laboratory processes, or by the digestive enzymes which occur in the alimen- tary canal, the essential change is due to what is called hydrolysis ; that is, the molecule unites with water and then breaks up into smaller molecules. The early cleavage products, which are called proteoses, retain many of the characters of the original protein, and the same is true, though to a less degree, of the peptones, which come next in order of formation. The peptones, in their turn, are decomposed into short linkages of amino-acids, which are called 'polypeptides, and finally the individual amino-acids are obtained separated from each other. What we have already learnt about the fatty acids will help us in understanding what is meant by an amino-acid. If we take acetic acid, which is one of the simplest of the fatty acids, its formula is CH3 . COOH. If one of the three hydrogen atoms in the CH3 group is replaced by NH.^, we get a substance which has the formula CH, . NH., . COOH. The combination NH.„ which has stepped in, is called the amino- group, and the new substance now formed is called amino-acetic acid ; it is also termed glycine or glycocoll. We may take another example from another fatty acid. Pro- pionic acid is C0H5 . COOH ; if we replace an atom of hydrogen by the amino-group as before, we obtain CoH^ . NH, . COOH, which is amino-propionic acid or alanine. If instead of propionic we take hydroxy-propionic acid, its amino- derivative (amino-hydroxy-propionic acid) is termed serine. A fourth amino-acid is similarly obtained by the introduction of the NH., into valeric acid C4H9 . COOH. Amino-valeric acid C^Hg . NH, . COOH is called Valine. Going to the next fatty acid in the series, caproic acid CgHj^^ . COOH, we obtain from it in an exactly similar way, CjH^o . NH, . COOH, which is amino-caproic acid or leucine. According to the way in which the amino-group is linked, a large number of isomeric aniino-caproic acids, all with the same empirical formula, are theoretically possible. Many of these have been prepared synthetically, and it has been shown that the amino-caproic acid called leucine, formed by hydrolysis from proteins, is the Igevo-rotatory variety, and should be more accurately named a-amino-isobutyl- 2 D 418 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. acetic acid (Cir^XH . CH,(CH . NH,,)COOII. It crystallises in spheroidal clumps of crystals, as shown on the left-hand side of fig. 3ia. Fig. 813.— Crystals of leucine and tyrosine, x 216. All the five aiiiiao-acids meulioued (glycine, alanine, serine, valine, and leucine) are found among the final products of most proteins. A second group of ainino-acids is obtained from fatty acids, which contain two carboxyl (COOH) groups in their molecides. The most important of the amino-dcrivatives obtained from these dicarboxylic acids are : — Amino-succinamic acid (asparagine), Amino-succinic acid (aspartic acid), Amino-pyrotartaric acid (glutamic acid). The third group of amino-acids is a very important one ; these are termed the aromatic amino-acids ; that is, amino-acids united to the benzene ring, and of these we will mention three, namely, phenyl- alanine, tyrosine, and a nearly related substance called tryptophane. Phenyl-alanine is alanine or amino-propionic acid in which an atom of hydrogen is replaced by phenyl (C,;Hr,). Propionic acid has the formula C^Hr, . COOH. Alanine (amino-propionic acid) is CH^NH., . COOH. Phenyl-alanine is C.,H, . C,H, . NH,". COOH. The formula of phenyl-alanine may also be written another way. The grapliic formula of benzene (C^jH^^) is : — H C. H _c^ \c- H H I H C — H OH. XX vm.] AMINO-ACIDS 419 If the H placed lowermost in the above formula is replaced by CH.,CH . NH., . COOH, we obtain the formula of phenyl-alanine : — CH._, . CHNH,COOH the remainder of the benzene ring, which is unaltered, being repre- sented as usual by a simple hexagon. Tyrosine is a little more complicated; it is oxyphenyl-alanine; that is, instead of phenyl (C,;H-) in the formula of phenyl-alanine, we have now oxyphenyl (C(jH^ . OH) ; this gives us C.Hg . (C,;H^ . 0H)NH3 . COOH as the formula for tyrosine written one way, or HO CH, . CHNH^ . COOH when written in the other way. Tyrosine crystallises in collections of very fine needles (see fig. 313). Tryptophane is more complex still ; it is indole amino-propionic acid : that is, amino-propionic acid united to another ringed deriva- tive called indole. Tryptophane is the portion of the protein molecule which is the parent substance of two evil-smelling products of protein decomposition called indole and scatole or methyl indole. Indole is a combination of the benzene and pyrrol rings as shown below : — CH HC HC / CH CH CH is Tryptophane is the radical in the protein molecule which responsible for the colour test called the Adamkiewicz reaction. In all the preceding cases, there is only one replacement of an atom of hydrogen by NH^ ; hence they may be all grouped together as mono-amino-acids. Passing to the next stage in complexity, we come to another group 420 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV HI. of amino-acids which are called diamino-a.cids ; that is, fatty acids in which two hydrogen atoms are replaced by NH^ groups. Of these we may particularly mention lysine, ornithine, arginine, and histidine. Lysine is diamino-caproic acid. Caproic acid is C^H^j . COOH. Mono-aniino-caproic acid or leucine, we have already learnt, is CrHiQ . NH., . COOH. Lysine or diamino-caproic acid is C^Hg . (NH,), . COOH. Ornithine is diamino-valeric acid, and the following formulae will show its relationship to its parent fatty acid — C4H9COOH is valeric acid. C4H-(]SrH2)2COOH is diamino-valeric acid or ornithine. Arginine is a somewhat more complex substance, which contains the ornithine radical. It belongs to the same group of substances as creatine, another important cleavage product of the protein molecule. Creatine is methyl-guauidine acetic acid, and has the formula — N(CH3)CH, .COOH On boiling it with baryta water, it takes up water (H^O) and splits at the dotted line into urea (COCNH.Jo) and sarcosine, as shown below. HoNs H„N' >C_0 1 NH . CH3 . CH. . COOH [Urea.] [Sarcosine or Metliyl-glycine.] Arginine splits in a similar way, urea being split off on the left, and ornithine instead of sarcosine on the right. Arginine is, there- fore, a compound of ornithine with a urea group. Histidine, though not strictly speaking a diamino-acid, is a diazinc derivative (imidazole - amino - propionic acid), and so may be included in the same group. These substances wo have spoken of as acids, but they may also play the part of bases, for the introduction of a second amino-group into the fatty acid molecules confers upon them basic properties. The three substances, Lysine . C,.Hj,N.,0., Arginine . . C^HjjN^O.^ Histidine . . C^jH.jNgO., are in fact often called tlie hexonc bases, because each of them contains 6 atoms of carbon, as the above empii-ical formulae show. CH. XXYIII.] AMINO-ACIDS 421 Cystine is a complex diamino-acid in which sulpliur is present, and in which the greater part of tlie sulphur of the protein molecule is contained. In addition to all these numerous amino-acids there are other cleavage products, of which it will be sufficient to mention proline and ammonia. In the case of the nuclco-proteins the nuclein component yields in addition what are known as purine and pyrimidine bases. (See further under nucleic acid, p. 431, also under uric acid, Chapter XXXIX.) Proline and the purine and pyrimidine bases are all derivatives of rings which remind one of the benzene ring, excejDt that nitrogen is included in the ring formation ; such rings are termed heterocyclic. Thus proline (pyrrolidine-carboxylic acid) is a derivative of the pyrrol ring, and its formula is given below. Cytosine is one of the derivatives of the pyrimidine ring, and hypoxanthine (or oxypurine) is given below as an example of the purine bases. H,C— CH, HN— C.NH., H— N— C=0 'II" II" II H,C CH.COOH OC CH H— C C— NH. \/ I II II II >H N HN— CH N— C N^ I [Cytosine or amino- [Hypoxanthine.] TT oxypyrimidine.] [Proline.] Our list now represents the principal groups of chemical nuclei united together in the protein molecule, and its length makes one realise the complicated nature of that molecule and the difficulties which beset its investigation. "We may put the problem another way. In the simple sugars, with six atoms of carbon, there are as many as thirty-six different ways in which the atomic groups may be linked up ; the formulae on p. 408 give only three of these which represent the structure of dextrose, Icevulose, and galactose ; but the majority of the remainder have also been prepared by chemists. The molecule of albumin has at least 700 carbon atoms, so the possible combinations and permutations must be reckoned by thousands. The workers in Fischer's laboratory are steadily working through the various known proteins, taking them to pieces and identifying and estimating the fragments. 1 do not intend to burden the readers of this book with anything more than a sample of their results, and will, therefore, only give in a brief table (see page 422) the results obtained with some of the cleavage products of a few proteins. The numbers given are percentages. Such numbers, of course, are not to be committed to memory, but they are sufficient to convey to the reader the differences between the proteins. There are several blanks left, on account of no accurate 422 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. estimations having yet been made. Where the sign + occurs, the substance in question has been proved to be present, but not yet determined quantitatively. Among the more striking points brought out are : — 1. The absence of glycine from albumins. 2. The high percentage of glycine in gelatin. 3. The absence of tyrosine and tryptophane in gelatin. 4. The high percentage of the sulphur-containing substance (cystine) in keratin. 5. The high percentage of glutamic acid in vegetable proteins. Glycine . Leucine Glutiimic acid Tyrosine . Arginine . Tryptophane Cystine . 20-0 7-7 2-1 + 2-5 d c E .a o .Q a <1 a to tt> g » s 3-5 6-1 18-7 8-0 8-5 1-1 2-5 + + 0-3 0-7 ^B 10-5 11-0 4-5 4-8 1-5 0-06 16-5 2-1 0-9 7-6 E . o C 4-7 7-1 3-7 3-2 i More than 10 00 S «> O 1-2 15-5 17-2 2-1 11-7 + ! 0-2 18-6 18-3 3-5 1-2 "2? 0-02 5-6 37-3 1-2 3-2 + 0-4 Emil Fischer, Abderhalden, T. B. Osborne, Levene, van Slyke, and others are attempting to make the list complete, and are devising new and more accurate methods of analysis. Fischer has also discovered the way in which the amino-acids are linked together into groups ; and the culmination of his work will be the discovery of the way in which such groups are linked together to form the protein molecule. The last stage has not yet been reached, but it will be interesting to see how the amino-acids are linked together into groups. The groups are termed peptides or polypeptides ; many of these have been made synthetically in his laboratory, and so the synthesis of the protein molecule is foreshadowed. We may take as our examples of the peptides some of the simplest, and may write the formulae of a few amino-acids as follows : — NH, . CH, . COOH Glycine NH; . QH^ . COOH Alanine COOH Leucine NH., . C5H, or in general terms HNH.R.COOH. CH. XXVI II.] PROTEIN CLEAVAGE PRODUCTS 423 Two aiuino-acids arc linked together as shown in the following formula : - HNH . R . CO i OH . H NH . R . COOH What happens is that the hydroxyl (OH) of the carboxyl (COOH) group of one acid unites with one atom of the hydrogen of the next amino (HNH) group, and water is thus formed, as shown within the dotted lines : this is eliminated and the rest of the chain closes up. In this way we get a dipeptide. The names glycyl, alanyl, leucyl, etc., are given by Fischer to the NH^ . R . CO groups which replace the hydrogen of the next NH., group. Thus glycyl-glycine, glycyl- leucine, leucyl-alanine, alanyl-leucine, and numerous other combina- tions are obtained. If the same operation is repeated we obtain tripeptides (leucyl-glycyl-alanine, alanyl-leucyl-tyrosine, etc.); then come the tetrapeptides, and so on. In the end, by coupling the chains sufficiently often and in appropriate order, Fischer has already obtained substances which give some of the reactions of peptone. Hausmann's Method. — This is a short and trustworthy procedure, by which an approximate knowledge of the nitrogen distribution in the protein molecule is ascertained. It is shortly as follows : — The whole nitrogen of the protein is estimated by Kjeldahl's method. A weighed amount is then hydrolysed by means of hydro- chloric acid, and then the cleavage products are separated into three classes and the nitrogen estimated in each, as— 1. Ammonia nitrogen. This comprises the nitrogen of the protein molecule which is easily split off as ammonia, and is determined by distilling off the ammonia with magnesia. 2. Diamino-N. The fluid, free from ammonia, is precipitated by phospho- tungstic acid, and the nitrogen present in the precipitate determined. This represents the nitrogen of the diamino-acids (lysine, arginine, etc.). Z. Mono-amino-N is then estimated in the residual fluid. The method has proved useful for the differentiation of proteins, and interest- ing deductions as to their food value has been drawn from its results. Solubilities. — The proteins 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. All proteins are soluble with the aid of heat in concentrated mineral acids and alkalis. Such treatment, however, decomposes as well as dissolves the protein. Proteins are also soluble in gastric and pancreatic juices ; but here, again, they undergo a change, as we have already seen. Heat Coagulation. — Most native proteins, such as white of egg, * The proteins are not truly soluble in water ; they are in a state of colloidal solution, a condition intermediate between true solution and suspension. Many of their properties are due to this fact. 424 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXV HI. are rendered iusolublo when thoir solutions arc lioatod. The tempera- ture of heat coagulation differs in different proteins ; thus myosinogen and fibrinogen coagulate at 56° C, serum albumin and serum globulin at about 75" C. The proteins which are coagulated by heat come mainly mider two classes : the albumins and the globulins. These differ in solubility ; the albumins are soluble in distilled water, the true globulins require salts to hold them in solution. IndifTusibility. — The proteins (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. Proteins may thus be separated from diffusible (crystalloid) substances such as salts, but the process is a tedious one. If some serum or white of egg is placed in a dialyser (fig. 314) and distilled water out- side, the greater amount of the salts passes into the water through the membrane and is replaced by water ; the two proteins albumin and globulin remain inside ; the globulin is, however, precipitated, as the salts which previously kept it in solution are removed. Crystallisation. — Hsemoglobin, the red pigment of the blood, is a protein substance and is crystallisable (for further details, see The Blood, Chapter XXIX.). Like other proteins it has an enormously large molecule ; though crystalline, it is not crystalloid in Graham's sense of that term. Blood pigment, however, is not the only crystallisable protein. Long ago crystals of protein (globulin or vitollin) 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 recrystallised. Further, egg albumin itself has been crystallised. If a solution of white of egg is diluted with an equal volume of saturated solution 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 concentrated from evaporation, minute spheroidal globules and finally minute needles, either aggregated or separate, make their appearance (Hofmeister). Crystallisation is more rapid if I. 314. — Dialyser made of a tube of parcliment papi-r, suspended in a vessel tlirougli which watex is kept llowiiig. CIT. XXVIII.] PKOPRRTIER OF PROTEINS 425 a little acetic or sulphuric acid is added (Ho])kius). Scrum alliumiu (from some animals) has also been similarly crystallised (Giirber). Action on Polarised Light. — All proteins are laBvo-rotatory, the amount of rotation varying with individual proteins. Several of the conjugated Tproteins, e.g., haemoglobin and nucleo-proteins, are dextro- rotatory, though their protein components are Isevo-rotatory (Gamgee). Colour Reactions. — The principal colour reactions by which proteins are recognised are the following: — (1) The xantlw-proteic reaction; if nitric acid is added to a solution of a protein such as 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 precipitate is not given by certain proteins such as peptones ; but the colours are the same.- The colour is due to the formation of nitro-derivatives from the aromatic portion of the protein molecule. (2) Millon's reaction. Millon's reagent is a mixture of mercuric and mercurous nitrate with excess of nitric acid. This gives a white precipitate which is turned brick-red on boiling. This reaction depends on the presence of the tyrosine radical. (3) Copper sulphate {Rose's or Piotrowski's) test. A trace of copper sulphate and excess of strong caustic potash give with most proteins 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 protein ; but both protein and biuret give the reaction because they possess a common radical, namely, two CONH., groups linked to a carbon or nitrogen atom, or to one another. The native proteins give a violet colour, because the red tint of the copper compound with the biuret group is mixed with another copper compound with a blue colour. Biuret is formed by heating solid urea ; ammonia passes off and leaves biuret, thus : — 2CON2H4 = aOoNgH. + NH3. [Urea.] [Biuret.] [Ammonia.] (4) AdamJciewicz reaction.* When a solution of protein is mixed with a dilute solution of formaldehyde, and then excess of commercial sulphuric acid is added, an intense violet colour is obtained. This is due to the tryptophane radical. Precipitants of Proteins. — Solutions of most proteins are pre- cipitated by: — * In the original test, glacial acetic acid was used, but it is really an impurity in this acid that gives the reaction. Rosenheim was the first to show that this impurity is formaldehyde. The presence of impurities (oxidising agents) in the sulphuric acid is also necessary. 426 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVllI. Strong acids such as nitric acid ; picric acid ; acetic acid and potassium ferrocyanide ; acetic acid and excess of a neutral salt such as sodium sulphate, when these are boiled with the protein solution ; salts of the heavy metals such as copper sulphate, mercuric chloride, lead acetate, silver nitrate, etc. ; tannin ; alcohol ; saturation with certain neutral salts such as ammonium sulphate. It is necessary that the words coagulation and precipitation should in connection with proteins be carefully distinguished. The term coagulation is used when an insoluble protein (coagulated protein) is formed from a soluble one. This may occur : 1. When a protein is heated — heat coagulation ; 2. Under the influence of an enzyme; for instance, when a curd is formed in milk by rennet or a clot in shed blood by the fibrin ferment — enzyme 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 proteins in which the precipitate formed is readily soluble in suitable reagents such as saline solutions, and the protein continues to show its typical reactions. This is not coagulation. Such a precipitate is produced by satura- tion with ammoniimi sulphate. Certain proteins, called globulins, are more readily precipitated by such means than others. Thus, globulins are precipitated by half - saturation with ammonium sulphate. Full saturation with ammoniimi sulphate precipitates all proteins but peptone. The globulins are precipitated by certain salts, such as sodium chloride and magnesium sulphate, which do not precipitate the albumins. This method of precipitation is called "salting out." The precipitation produced by alcohol is peculiar in that after a time it becomes a coagulation. Protein freshly precipitated by alcohol is readily soluble in water or saline media ; but after it has been allowed to stand some time 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 proteins from others. Classification of Proteins. The knowledge of the chemistry of the proteins, which is slowly progressing under Emil Fischer's leadership, will, no doubt, in time enable us to give a classification of these substances on a strictly chemical basis. The following classification must therefore be regarded as a provisional one, which, while it retains the old familiar names as far as possible, yet attempts also to incorporate some of the new ideas. CH. XXVITI.] GLASSIFTOATTON OF PROTEINS 427 The classes of animal pioteins, then, beginning with the simplest, are as follows : — 1. Protamines, 6. Phospho-proteins. 2. Histones. 7. Conjugated proteins. 3. Albumins. i. Chromo-proteins. 4. Globulins. ii. Gluco-proteiiis. 5. Sclero-proteius. iii. Nucleo-proteins. 1. The Protamines. These substances are obtainable from the heads of the spermatozoa of certain fishes, where they occur in combination with nuclein. Kossel's view that they are the simplest proteins in nature has met with general acceptance, and they give such typical protein reactions as the copper sulphate test (Eose's or Piotrowski's reaction). On hydrolytic decomposition they first yield substances of smaller molecular weight analogous to the peptones which are called protones, and then they split up into amino-acids. The number of resulting amino-acids is small as compared with other proteins, hence the hypothesis that they are simple proteins is confirmed. Notable among their decomposition products are the diamino-acids or hexone bases, especially arginine. The protamines differ in their composition according to their source, and yield these products in different proportions. Salmine (from the salmon roe) and clupeine (from the herring roe) appear to be identical, and have the empirical formula C^nH^^Nj-O,; ; its principal decomposi- tion product is arginine, but amino- valeric acid and a small quantity of serine and proline are also found. Sturinc. (from the sturgeon) yields the same products with lysine and histidine in addition. With one exception, the protamines yield no aromatic amino-acids. The exception is ryclopterine (from Ci/clopterus l.umpus) ; this substance is thus an important chemical link between the other protamines and the more complex members of the protein family. 2, The Histones. These are substances which have been separated from blood- corpuscles ; globin, the protein constituent of haemoglobin, is a well- marked instance. They yield a larger number of amino-compounds than do the protamines, but diamino-acids are relatively abundant. They are coagulable by heat, soluble in dilute acids, and precipitable from such solutions by ammonia. The precipitability by ammonia is a property possessed l3y no other protein group. 3. The Albumins. These are typical proteins, and yield the majority of the cleavage products already enumerated. 428 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. Tliey enter into colloiilal solution in water, in dilute saline solu- tions, and in saturated solutions of sodium ehloride and magnesium sulphate. They are, however, precipitated by saturating their solutions with ammonium sulphate. Their solutions are coagulated by heat, usually at 70-73° C. Serum albumin, egg albumin, and lact -albumin are instances. 4. The Globulins. The globulins give the same general tests as the albumins ; they are coagulated by heat, but dififer from the albumins mainly in their solubilities. This difference in solubility may be stated in tabular form as follows : — Reagent. Albumin. Globulin. Water Dilute saline solution .... Saturated solution of magnesium sul- phate or sodium cliloride . Half-saturated solution of ammonium sulphate Saturated solution of ammonium sul- phate soluble soluble soluble soluble insoluble insoluble soluble insoluble insoluble insoluble Globulins are more readily salted out than albumins ; they may therefore be precipitated, and thus separated from the albumins by saturation with such salts as sodium chloride, or better magnesium sulphate, or by half saturation with ammonium sulphate. The typical globulins are also insoluble in water, and so may be precipitated by removing the salt which keeps them in solution. This may be accomplished by dialysis (see p. 424). Their temperature of heat-coagulation varies considerably. The following are the commoner globulins : — fibrinogen and serum globulin in blood, egg globulin in white of egg, paramyosinogen in muscle, and crystallin in the crystalline lens. We must also include under the same heading certain proteins which are the result of enzyme coagulation on globulins, such as fibrin (see blood) and myosin (see muscle). The most striking and real distinction between globulins and albumins is that the former on hydrolysis yield glycine, whereas the albumins do not. 5. The Sclero-proteins. These substances form a heterogeneous group of substances, which are frequently termed albuminoids. The prefix sclero indicates CH. XXVIII.] THE PHOSPHO-PROTEINS 429 the skeletal origin and often insoluble nature of the members of the group. The principal proteins under this head are : — 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. On digestion it is like ordinary proteins converted into peptone-like substances, and is readily absorbed. Though it will replace in diet a certain quantity of such proteins, acting as what is called a " protein-sparing " food, it cannot altogether take their place as a food. Animals whose sole nitrogenous food is gelatin waste rapidly. The reason for this is that gelatin contains neither the tyrosine or the tryptophane groups, and so it gives neither Millon's nor the Adamkiewicz reactions. Animals who receive a mixture of gelatin, tyrosine, and tryptophane in their diet thrive better. Ghondrin is the name given to the mixture of gelatin and mucoid which is obtained by boiling cartilage. 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 most other proteins in its high percentage of sulphur. A similar substance, called neurokeratin, is found in neuroglia and nerve-fibres. In this connection it is interest- ing to note that the epidermis and the nervous system are both formed from the same layer of the embryo — the epiblast. 6. The Phospho -proteins. Vitellin (from egg-yolk), caseinogen, the principal protein of milk, and casein, the result of the action of the rennet-euzyme on caseinogen (see milk), are the chief members of this group. Among their decomposition products is a considerable quantity of phosphoric acid. They have been frequently confused with the nucleo-proteins, and the prefix nucleo — so often applied to them — is entirely misleading, since they do not yield the products (purine bases, etc.) which are characteristic of nucleo-compounds. The phosphorus is contained within the protein molecule, and not in another molecular group united to the protein, as is the case in the nucleo-proteins. The phospho-proteins are specially valuable for the growth of young and embryonic animals. 430 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. 7. The Conjugated Proteins. These are compounds in which the protein molecule is united to other organic materials, which are as a rule also of complex nature. This second constituent of the compound is usually termed a pros- thetic group. They may be divided into the following sub-classes : — i. Cliromo -proteins. — These are compounds of protein with a pigment, which usually contains iron. They are typified by hgemo- globin and its allies, which will be fully considered under Blood. ii. Gluco-proteins. — These are compounds of protein with a carbohydrate group. This class includes the mucins and the mucoids. The mucins are widely distributed and may occur in epithelial cells, or be shed out by these cells (mucus, mucous glands, goblet cells). The mucins obtained from different sources are alike in being viscid and tenacious, soluble in dilute alkalis such as lime water, and precipitable from solution by acetic acid. The mucoids differ from the mucins in minor details. The term is applied to the mucin-like substances which form the chief con- stituent of the ground substance of connective tissues (tendo-mucoid, chondro-mucoid, etc.). Another (ovo-mucoid) is found in w^hite of egg, and others (pseudo-mucin and para-mucin) are occasionally found in dropsical effusions, and in the fluid of ovarian cysts. The differences between the mucins and mucoids are due either to the nature of the carbohydrate group, or more probably to the nature of the protein to which it is united. The carbohydrate substance, however, is not sugar, but a nitrogenous substance which has a similar reducing power to sugar, and which is called glucosamine (C^Hi^O.-NH.,), that is, glucose in which HO is replaced byNH,. Pavy and others have shown that a sviall quantity of the same carbohydrate derivative can be split off from various other proteins which we have already placed among the albumins and globuHns. It is, however, probable that this must not be considered a prosthetic group, but is more intimately united within the protein molecule. iii. Nucleo -proteins. — These are compounds of protein with a complex organic acid called nucleic acid, which contains phosphorus. They are found both in the nuclei and cell-protoplasm of cells. In physical character they often simulate mucin. Niiclein is the name given to the chief constituent of cell-nuclei. It is identical with the chromatin of histologists (see p. 10). On decomposition it yields an organic acid called nucleic acid, together with a variable but usually small amount of protein. It contains a high percentage (10-11) of phosphorus. The nuclein obtained from the nuclei or heads of the spermatozoa consists of nucleic acid without any protein admixture. In fishes' en. XXVIll.] THE CONJUGATED PROTEINS 431 spermatozoa, however, there is an exception to this rule, for there it is, as we have already seen, united to protamine. llic nudco-protcins of cell protoplasm are compounds of nucleic acid with a much larger quantity of protein, so that they usually contain only 1 per cent, or less of phosphorus. Some also contain iron, and the normal supply of iron to the body is contained in the nucleo-proteins or hcematogens (Bunge) of plant or animal cells. Nucleo-proteins maj^ be prepared from cellular structures such as thymus, testis, kidney, etc., by two principal methods : — 1, Woohlrvlfies m'l'fhod. — The organ is minced, and soaked in water for twenty- four hours. Dilute acetic acid added to the aqueous extract precipitates the nucleo- protein. 2. Sodium chloride method.— The minced organ is ground u]) in a mortar with solid sodium chloride ; the resulting viscous mass is poured into excess of water, and tlie nucleo-protein rises in strings to the top of the water. The solvent usually employed for a nucleo-protein, whichever method it is prepared by, is a 1 per cent, solution of sodium carbonate. The relationship of nucleo-proteins to the coagulation of the blood is described imder that heading. Nucleic acid yields, among its decomposition products, phosphoric acid, various bases of the purine group, and bases also of the pyrimidine group. A carbohydrate radical is also obtained. The following diagrammatic way of representing the decomposition of nucleo-protein puts the matter more clearly : — Nucleo-Protein subjected to gastric digestion yields Protein 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 Protein — converted into acid A precipitate consisting of nucleic meta-protein in solution. acid. If this is heated in a sealed tube with hydrochloric acid, it yields I I \ \ I Phosphoric acid. Carbohydrate. Purine bases. Pyrimidine bases. Recent research on the nucleic acids obtained from various mammalian organs indicates that they fall into two main classes : — (1) Nucleic acid proper. — This yields on decomposition — (a) Phosphoric acid. (h) A sugar, which is a hexose, but has not yet been identified further ; Levene has found that in the nucleic acids of vegetable origin (for instance from yeast) the sugar present is a pentose (c^-ribose). (c) Two members of the purine group in the same proportion namely, adenine and guanine. 432 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. (d) Two pyriinidiiie bases, namely, cytosine (see p. 421), and thymine (mcthyl-diuxypyriniidine). The purine bases are specially interesting because of their close relationship to uric acid, and we shall have to deal with them again in our description of that substance. They are all derivatives of an atomic complex, named purine by Fischer, and their relationship to each other is best seen by their formulae : — Purine CjiH.N, THypoxan thine (monoxy-purine) C^H^N^O -p, • 1 Xanthine (dioxy-purine) C.-H.N.O., Purine bases- . , . .^ . -^ ^ . /rt "tr Vt olarised light can be observed and measured. Most of the carbo- hydrates are dextro-rotatory. All the proteins are Ifpvo-rotatory (see i>. 4_'5). There are many varieties of the instrument ; these can only be properly studied in the laboratory, 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 arrows are shot vertically they will pass easily through the gaps between the paUngs, but if they are shot horizontally they will be unable to pass through at all. This rough illustration will helj) us in understanding what is meant by polarised light. Ordinary light is j)roduced by the undulations of the 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 fiat 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 j)asses through it ; it is called the polariser. .\t the other end of the instrument is another called the analyser. Between the two is a tube which can be filleil with fluid. If the analyser is jiarallel 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 Hat 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 jilane of polarised light. But if the water lontains 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 hevo-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 full illumination. This will vary with the length of the tube and the strength of the solution. The Lipoids. This name was first applied by Overton to a heterogeneous group of substances found in the protoplasm of all cells, especially in their outer layer or cell-membrane, which, like the fats, are soluble in such reagents as ether and alcohol. These substances, though present in smaller amount than proteins, appear to be essential constituents of protoplasm, and the labile character of their molecules is a property many of them share in common with the proteins. The lipoids are found inixed with fat in the ether-alcohol extract of tissues and organs, and they are specially abundant in nervous tissues. They can be separated by what is called selective extraction. For instance, cold acetone will dissolve out only choles- terin ; hot acetone then dissolves out a mixture of substances named CH. XXVIII.] CHOLESTERIN 435 protagon ; protagon may be separated into its constituents (phrenosiu and sphingomyelin) by pyridine, and so forth. The lipoids may be classified in the following way : — (1) Those which, like the fats, are free from both nitrogen and phos- phorus. The most important member of this group is cholesterin. (2) Those which are free from phosphorus but contain nitrogen. These yield the reducing sugar called galactose when broken up, and may, therefore, be called galactosides. (3) Those which contain both phosphorus and nitrogen. These are called the phosphatides, and are grouped according to the propor- tion of nitrogen and phosphorus in their molecules, as follows : — (a) Mono - amino - mono - phosphatides, N : P = 1 : 1. JS.g., lecithin and kephalin. (h) Diamino-mono-phosphatides, N : P = 2 : 1. Rg., sphingo- myelin. (c) Mono-amino-diphosphatides, N : P = 1 : 2. One of these, named cuorin, hrs been separated out from the heart by Erlandsen, and a similar substance is found in egg-yolk. (d) Diamino-diphosphatides, IST : P = 2 : 2. One of these was separated from brain by Thudichum, but has not since been examined. (e) Triamino-mono-phosphatides, N : P = 3 : 1. One of these is present in egg-yolk. Cholesterin or cholesterol is found in small quantities in all forms of protoplasm. It is a specially abundant constituent of nervous tissues, particularly in the white substance of Schwann. It is found in small quantities in the bile, but it may occur there in excess and form the concretions known as gall-stones. It can be readily extracted from the brain by the use of cold acetone. In the brain it occurs in the free state. It is a monatomic unsaturated alcohol with the empirical formula C.^-jH.^^ . OH. Ptecent research has shown it to belong to the terpene series, which had hitherto only been found as excretory products of plant life. Windaus has shown that it contains five reduced benzene rings linked together, with a double linkage at the end of an open chain. Cholesterin is now believed to be not merely a waste product of metabolism, but to exert an important protective influence on the body cells against the entrance of certain poisons called toxins. One of the poisons contained in cobra venom dissolves red blood- corpuscles; the presence of cholesterin in the envelope of the blood -corpusck'S to some extent hinders this action, and it has been stated that the administration of cholesterin increases the resistance of the animal. It is certainly the case that with arti- ficial blood-corpuscles, membranous bags containing haemoglobin, 436 THE CHEMICAL COMPOSITION OF THE BODY [CII. XXVllI. Fio. 315.— Cbolesterin crystals. the impregnation of the membrane with cbolesterin, prevents the solvent action of toxins. In order that cbolesterin and its derivatives may act in this way, it is necessary that the double linkage and the bydroxyl atom just referred to should be intact. The latter would not be the case in an ester, and it is probable that the compounds of cboles- terin in the blood previously described as esters by Hiirthle are really mixtures of cbolesterin and fatty acids. From alcohol or ether containing water it crystallises in the form of rhom- bic tables, which contain one molecule of water of crystallisation : these are easily recognised under the microscope (fig. 315). 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 cbolesterin in chloroform, shaken with an equal amount of strong sulphuric acid, turns red, and then purple, the subjacent acid acquiring a green fluorescence. (Salkowski's reaction.) 3. If acetic anhydride is added to a chloroformic solution of cbolesterin, and then sulphuric acid, drop by drop, a red coloration, which changes to bluish green, is produced. (Liebermann's reaction.) A substance called iso-cholcstcrin is found in the fatty secretion of the skin (sebum); it is largely contained in the preparation called lanoUne, made from sheep's wool fat. It differs from cbolesterin in being dextro-rotatory instead of laevo-rotatory in solution, and it docs not give Salkowski's colour reaction. Cholesterins isomeric with animal cbolesterin are also found in many plants ; these are termed phyto-cholesterins, or phytosterins for short. Cbolesterin compounds exhibit the physical phenomenon recently studied by Lehmann, namely, the formation of liquid crystals ; this is also shown by several other lipoids. Virchow in 1855 described what he termed " myelin forms " ; if brain-substance is mixed with water, where the water touches the brain material, threads are observable shooting out and twisting into fantastic shapes ; these are termed " myelin forms," although the word myelin has no definite chemical meaning. It has now been shown that these " myelin forms " are distorted liquid crystals due to the presence of cbolesterin and other lipoids. The fat globules seen in the adrenal cortex, and in the liver and other organs during fatty degeneration, are not wholly composed of fat, for the polarisation microscope shows them to be anisotropic, and further investigation has shown them to CH. XXVIII.] CHOLESTERIN 437 be lipoids in the fluid crystalline condition. Pure cholesterin and pure cholesterin esters do not exhibit the phenomenon; but mixtures of cholesterin and fatty acids do ; it has Ijccii suggested that in such mixtures the acid is incorporated as "acid of crystallisation," analogous to the " water of crystallisation " in many other crystals. The Galactosides. — The substance known as protagon can be separated out from the brain by means of warm alcohol ; on cooling the extract, protagon is deposited as a white precipitate. This, how- ever, also contains cholesterin, which can be dissolved out by ether. Another method of preparing protagon is to take brain and extract the cholesterin first with cold acetone ; then hot acetone is employed to extract the protagon. Protagon is a substance originally described by Couerbe, under the name cerebrote, but named protagon by Liebreich, who regarded it as a definite compound, and the mother substance of all the other phosphorised and non-phosphorised con- stituents of the brain. It has now been definitely proved in confir- mation of what Thudichum stated in 1874, that protagon is not important quantitatively, and is not a definite chemical unit, but a mixture of phosphorised and non-phosphorised substances in such proportions that it usually contains about 1 per cent, of phosphorus. By treatment with appropriate reagents and recrystallisation, pro- tagon can be separated into its constituents, and those which are free from phosphorus and comprise about 70 per cent, of the original protagon are the galactosides. The known galactosides are two in number, namely, phrenosin (or cerebron) and kerasin. The former is a crystalline product, and the latter of somewhat waxy con- sistency. They are probably isomerides. They yield on decomposi- tion three substances: — (1) A reducing sugar, galactose. (2) A base termed sphingosine, about which little chemically is yet known. (3) A fatty acid of high molecular weight, termed neuro-stearic acid by Thudichum, but not definitely identified. It is probably an oxy-acid (Thierfelder). The Phosphatides. — The best known of these is lecithin. This is a very labile substance, but it yields on decomposition four materials, namely — glycerin and phosphoric acid united together as glycero-phosphoric acid, two fatty acid radicals, of which one is usually oleic acid, and an ammonium-like base termed choline. The fatty acid radicals are united to glycerin as in an ordinary fat, the place of the third fatty acid being taken by the radical of phosphoric acid, which in its turn is united in an ester-like manner to the choline. The clinical significance of such substances in cases of degenerative nervous disease has been already alluded to on p. 167. Kephalin resembles lecithin in being a mono-amino-monophos- phatide. It differs from lecithin in being insoluble in alcohol. On decomposition it yields glycero-phosphoric acid, certain fatty acids 438 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. which are less saturated than oleic acid, and probably belong to the linoleic series. It also yields a base, but it is doubtful if this is identical with choline. Kephalin is the most abundant phosphatide in nerve-fibres, and has also been found in egg-yolk. Sphingomyelin is the phosphatide obtained from the mixture called protagon. It is the best known of the diamino-monophos- phatides. If protagon is dissolved in hot pyridine, and the solution allowed to cool, sphingomyelin is precipitated in an impure form as sphsero-crystals, which rotate the plane of polarised light to the left. Choline, fatty acids, and an alcohol have been found among its cleav- age products. It, however, differs from lecithin by containing no glycerin. Enzymes. 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 " fermen- tation." The agent, yeast, which produces this, was called the ferment. Microscopic investigation shows that yeast is composed of minute rapidly-growing unicellular organisms belonging to the fungus group. The souring of milk, the transformation of urea into ammonium carbonate in decomposing urine, and the formation of vinegar from alcohol are brought about by very similar organisms. The complex changes known as putrefaction, which are produced by the various forms of bacteria (see fig. 316), 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 temperature or by antiseptics (carbolic acid, etc). The "germ theory" of disease explains the infectious diseases by oonsidering 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 bacteria appear to be either alkaloidal (ptomaines) or protein in nature. The most virulent poison in existence, namely, snake poison, is a protein of the proteose class. All these micro-organisms require moisture in which to act. They act best at a temperature of about 40' C. Their activity is stopped, but the organisms are not destroyed by cold. The organisms are, liowever, like other living cells, killed by too great heat. Some micro-organisms act without free oxygen ; these are called anaerobic ; those that require oxygen are called acrohic. Another well-known fact concerning micro-organisms is that the substances they produce in time put a stop to their activity ; thus CH. XXVIII.] ENZYMES 439 in the case of yeast, the alcohol produced, and in the case of bacteria acting on proteins, the phenol, cresol, etc., produced, jBrst stop the growth of, and ultimately kill, these organisms. For a Ions time it was uncertain how micro-organisms were able cP c^ Ip lil ^' <^. [<^ ^ ^/ ^ ^^^ Fig. 316. — Types of micro-organisms : o, micrococci arranged singly; in twos, diplococci — if all the micrococci at a were grouped together they would be called staphylococci — and in fours, sarcinse ; fc, micrococci in chains, streptococci ; c and d, bacilli of various kinds (one is represented with a flagellum) ; <■, various forms of spirilla ; /, spores, either free or in bacilli. to effect these chemical transformations. It is now, however, definitely proved that they do so by producing agents of a chemical nature, which are called enzymes. This was first demonstrated in connection with the invertase of yeast cells, and with the enzyme secreted by the micrococcus ureee, which converts urea into ammonium carbonate in putrefying urine. For a long time, however, efforts to obtain from yeast cells an enzyme capable of bringing about the alcoholic fermentation were unsuccessful. This is because the enzyme does not leave the yeast cells, but acts intracellularly. Buchner, by crushing the yeast cells, succeeded in obtaining from them the long-sought enzyme {zymase) ; since then other enzymes have been obtained from other microbes by similar means. Enzymes are also formed by the cells of the higher organisms, both in animal and vegetable life. Familiar instances of these are ptyalin, the starch-splitting enzyme of saliva, and pepsm, the protein-splitting enzyme of gastric juice. The substance upon which the enzyme acts is spoken of as the substrate. We may, therefore, place these essential facts concerning enzyme action in the following tabular way : — The Living Cell. The Enzyme produced. The Substrate. The Products of Action. The yeast cell . The salivary cell The gastric cell Zymase . Ptyalin . Pepsin . Dextrose . . \ Alcohol and carbon dioxide. Cooked starch . Dextrin and mal- tose. Protein . . i Proteoses, peptones, ' and amino-acids. 440 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. Tlie enzymes which bring about the digestion of food in the alimentary canal may be classified as follows: — 1. Amylolytic — those which convert polysaccharides (starch, glycogen) into sugar with intermediate dextrins. Examples : the diastase of vegetable seeds, and the ptyalin of saliva. 2. Inverting — those which convert disaccharides into mono- saccharides. Examples : Invertase of yeast cells ; invertase of intestinal juice ; these convert cane sugar into equal parts of dextrose and leevulose. 3. Lipolytic — those which split fat into fatty acids and glycerin. An example, liimse, is found in pancreatic juice. 4. Proteolytic or proteoclastic — those which split proteins into proteoses, peptones, polypeptides, and finally amino-acids. Examples: the pepsin of gastric, and the trypsin of pancreatic juice. 5. Peptolytic — those which split proteoses and peptones into polypeptides and amino-acids, cjj., the erepsin of intestinal juice. But in addition to the digestive enzymes there are others to be mentioned, for instance : — The enzymes in the foregoing list produce hydrolysis; that is, water is added to the substrate, which then splits into simpler molecules, as for instance in the inversion of cane sugar by invertase. [Caue sugar.] [Water.] [Dextrose.] [Laivulose.) Coagulative enzymes — those which convert soluble into insoluble proteins ; the best example of this class is thrombin or fibrin-ferment, which comes into play in blood-coagulation, convert- ing the soluble protein in blood-plasma called fibrinogen into fibrin. Rennet or rennin, found in the gastric juice, is another; it converts the soluble caseinogenate of milk into casein. Oxidases ; these are not hydrolytic, but are oxygen carriers and produce oxidation : they are mainly found as intracellular enzymes, and are important in tissue respiration. Reductases; these are the counterpart of the oxidases, and produce reduction in the tissues. Deamidases ; these remove the amino-group from amino- compounds. Intracellular or Autolytic Enzymes. — These come into play during cell life, and are important in the metabolic or intracellular chemical changes which occur in protoplasm ; they also may be subdivided into proteolytic, peptolytic, lipolytic, etc., according to the substrate upon which they act. After death their activity continues, and so they i)roduce self-digestion or autolysis of the cells in which they are situated, if the tissue or organ is kept at an appropriate temperature and under aseptic conditions. CH. XXVIir.] CLASSIFICATION OF ENZYMES 441 The foregoing list is not by any means complete, but includes the most important groups. The individual enzymes will be studied in due course, but for the present we will take general considerations only. Zymogens. — These are the parent substances or precursors of the enzymes. The granules seen in many secreting cells consist very largely of zymogen, which in the act of secretion is converted into the active enzyme. Thus, pepsin is formed from pepsinogen, trypsin from trypsinogen, thrombin from thrombogen, and so forth. Activation of Enzymes. Co-enzymes. — Many enzymes contained in secretions are in a condition ready for action. In other cases this is not so, and their action only occurs after they have been rendered energetic by the presence or action of other substances, termed activating agents or co-enzymes. The Specificity of Enzyme Action. — In most cases the action of an enzyme is extraordinarily limited ; thus there are three separate enzymes to hydrolyse the three principal disaccharides, cane sugar, lactose, and maltose, neither of which will act upon either of the other two sugars in the list. Arginase splits arginine into ornithine and urea, but will act upon no other substance. The "lock and key" simile first introduced by Emil Fischer will aid us in under- standing this specificity of action. Each lock must have its special key: so the chemical configuj'ation of an enzyme must be related in some way to the configuration of the substrate to enable it to enter and unlock its parts from one another. The Ojytimum Temperature of Enzyme Action. — As the tempera- ture rises the velocity of the action increases, until a temperature is reached at which the activity is greatest. Most enzymes act best at 40' C, but there are exceptions ; malt diastase, for instance, acts best at 60"' C. Beyond the optimum temperature a further rise inhibits activity, until a temperature is reached when the enzyme is destroyed. The fatal temperature as a rule is in the neighbour- hood of 50° C. The effect of a rise of temperature is thus complex, and is of a two-fold nature. In the first place, and between certain limits, the law of Arrhenius is followed, that is, a rise of 10' doubles or even trebles the velocity of the action of the enzyme, as it does other chemical reactions. But as the temperature rises the velocity of disintegration of the enzyme also rises. The optimum tempera- ture is that at which the enzyme work is best done ; this is a temperature at which the accelerating effect is strong enough to finish the reaction quickly, and the retarding effect due to enzyme destruc- tion is not so great as to neutralise the accelerating effect. The Inexhaustibility of Enzymes. — A small amount of enzyme will act on an unlimited amount of substrate, provided sufficient 442 THE CHEMICAL COMPOSITION OF THE BODY [CH. XXVIII. time is given, and provided also the products of action are removed. The enzyme appears to take a share in intermediate reactions, and there is some evidence that in certain stages it combines with the substrate ; but subsequently when the substrate breaks up into simpler materials, the enzyme is liberated unchanged, and so ready to similarly act on a fresh amount of substrate. Catalytic Action of Enzymes. — The analogy of enzymic action is, in fact, so close to that of inorganic catalysts, that the view at present current regarding it is that the action is a catalytic one. That is to say, the presence of the enzyme induces a chemical reaction to occur rapidly, which in its absence also occurs, but so slowly that any action at all is difficult to discover. To use the technical phrase, its action is to increase the velocity of chemical reactions. It is, for instance, quite conceivable that, if starch and water were mixed together, the starch will in time take up the water and split into its constituent molecules of sugar. But an action of this kind would be so slow, occupying perchance many years, that for practical purposes it does not take place at all. If an inorganic catalyst is added, such as sulphuric acid, and the temperature raised to boiling point, the action takes place in a few minutes ; if an organic catalyst, such as the enzyme ptyalin, is added, the velocity of the change is even greater ; but what is of more importance for the well-being of the animal, a moderate temperature, namely that of the body, amply suffices. The organic catalysts or enzymes are, however, colloidal in nature (possibly pro- tein), and this explains their destructibility by high temperatures. RevcrsihiJity of Enzyme Action. — On page 329 we have considered the general laws of molecular reactions. The majority of enzymatic reactions are unimolecular, or reactions of the first order ; that is to say, one substance only, the substrate, undergoes transformation ; the other substance, the enzyme, does not alter in concentration. The law followed in such reactions is therefore the simple logarithmic law. But in these reactions we meet with the peculiarity that it is not quite completed when the reaction ceases. A certain quantity of the substrate never disappears. Thus a small amount of cane sugar remains unchanged whether the hydrolysis is brought about by the action of an acid or of an enzyme. This phenomenon is due to the fact that two reactions are always taking place in opposite directions. Simultaneously with the splitting up the synthetical reaction begins, and synthesis or building up increases in proportion as the splitting of the compound advances. The velocity of the splitting process decreases at the same rate as the velocity of the synthetic process increases. At a certain point, both have the same velocity, and therefore no further change occurs in the mixture when this condition of equilibrium is reached. This rule is expressed CH. XXVIII.] ACTION OF ENZYMES 443 by writing the chemical equation connected by a double arrow instead of the sign of equation. Two examples follow : — C.Hj; . OH + CH3 . COOH ^J^ C._,H, . COO . CH, + H.,0 [Ethyl alcohol.] [Acetic acid.] ' [Ethyl acetate.] [Water.] c,Hi,o,. + C,,H^ ,0, ^:± Ci2H,.,0,, + H2O [Dextrose.] [L;evulose.] [Cane sugar.] [Water.] This phenomenon is termed " reversihility " and was iBrst demon- strated by Croft Hill in his experiments with cane sugar and invertase. In intracellular action this is a factor of importance, for the same enzyme can in the presence of different proportions of the substrate and its cleavage products both tie (in anabolism) and untie (in katabolism) the knot. It should further be noted that hydrolytic actions are isothermic ; that is, the total energy of the products is equal to that of the substance broken up. The simpler logarithmic law of enzyme action has been demon- strated for the majority of enzymes (invertase, trypsin, erepsin, lipase, etc.). The effect in a given time is directly proportional to the quantity of enzyme present. But there is an exception to this rule in the case of pepsin, as was first pointed out by Schiitz in 1885. He found that peptic activity is proportional to the square root of the amount of pepsin present. Thus if a certain quantity of pepsin produced an amount of digestive action which we will call a, in order to produce a digestive action equal to 2a in the same time, it would be necessary to employ four times the amount of pepsin ; and in order to produce a digestive action equal to 3a, it would be necessary to use nine times the amount of pepsin. This rule (Schiitz's law) has been often confirmed, and a few years ago Arrhenius explained it on mathematical lines into which we need not enter here. Anti-enz)jmes. — Many chemical substances, such as strong acids and alkalis, alcohol, formaldehyde, iodine, potassium cyanide, and salts of the heavy metals, hinder enzyme activity. But the term anti-enzyme is generally limited to substances produced in the metabolism of living organisms. Excess of these organic anti- enzymes can be readily produced by injecting an enzyme into the blood-stream of an animal. This stimulates the production of an anti-enzyme, so that when the blood-serum is mixed with the original enzyme, its power is inhibited. Anti-enzymes are specific, that is, they inhibit the enzyme which was injected into the blood, and no other. CHAPTEE XXIX 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 sangiiinis, in which are suspended numerous blood-corpuscles, the maj(nity of which are coloured, and it is to their presence that the red colour of the blood is due. In addition to the red corpuscles, there are a smaller number of colourless corpiLScles, and some extremely small particles called hlood-platelets. Even when examined in very thin layers, blood is opaque, on account of the dififerent refractive powers possessed by its two constituents, 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 bo of the same specific gravity as that of the standard fluid. The reaction of blood is faintly alkaline to litmus and the taste saltish. Its temperature varies slightly, the average being 37'8' C. (100 R). The blood-stream is warmed by passing through the muscles, 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 an animal is usually estimated in the following manner: — A small quantity * The fiivjiJilu.riis and the leptocephalus. CH. XXIX.] THE BLOOD 445 of blood is taken from an animal by venesection ; it is dcfibrinated 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 saliiie 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 j\ to ^ of the total body-weight. In smaller animals the proportionate blood volume is greater. Haldane and Lorrain Smith have invented another method which has the advantage of being applicable to man. The data required are (1) the percentage of haemoglobin in the blood, and (2) the extent to which the haemoglobin is saturated by a measured amount of carbonic oxide absorbed into the blood. The percentage of hsemoglobin is determined colorimetrically by the Gowers or Gowers-Haldane hsemogiobinometer (see p. 470). 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 hsemoglobin 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 hsemogiobinometer. 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 allowed to breathe 75 c.c. of carbonic oxide, and it is then found that his blood is 15 per cent, saturated with that gas. That is to say, instead of there being 18-5 c.c. of oxygen 446 THE BLOOD [CH. XXIX. per 100 e.c. of blood, 15 per cent, of this 18-5 c.c. is present in the 18-5 X 15 form of carbonic oxide, 15 per cent, of 18-5= -^„ =2-7 c.c. Now if 2-7 c.c. of carbon monoxide per 100 c.c. of blood is the result of breathing 75 c.c. of that gas, the question before us is, How much gas will be necessary to produce the normal figure 18-5 ? 2-7 c.c. per 100 c.c. of blood results from breathing 75 c.c. of CO • 1 ^ 1 lor 75x18-5 and 18-5 c.c. „ „ „ — ^ — „ = 500 c.c. (approximately). In other words, the total oxygen (or CO) capacity of the person's blood is 500 c.c. Since 18-5 c.c. of this total is carried by 100 c.c, of blood, the total volume of the person's blood, that is, the amount V u Ml . • rnA c ■ 500x100 ^_^„ , which will contain 500 c.c. of gas, is — r^-^ — ^ 272 i c.c, or nearly three litres. The total weight of the blood is obtained by multiply- ing the volume by the specific gra\'ity (about 1-055). Some of the results of this method are as follows : — The mass of the blood in man is about 4-9 per cent, (nw.f-) of the body- weight. The corresponding ratio of the blood volume is 462 c.c. per 100 grammes, or -^— « I^ pathological conditions the numbers are different ; thus in anaemia from haemorrhage, the volume ratio is 6'5, in pernicious ansemia 8'6, in chlorosis 10'8. In other words, in various forms of ansemia the actual volume of the blood is increased, but of course the corpuscular and solid constituents are correspond- ingly diminished. Coagulation of the Blood, After the blood is shed it rapidly becomes more viscous and then sets into a firm red jelly. The jelly soon contracts and squeezes out a straw-coloured fluid called the serum. "With the microscope, filaments or fine threads are seen forming a network throughout the fluid (fig. 317), many radiating from small clumps of blood-platelets. These threads entangle the corpuscles, and so the clot is formed. The threads are composed of a protein substance called ^irm, and the formation of fibrin is the essential act of coagulation. Fibrin is formed from the plasma, and may be obtained free from corpuscles when plasma is allowed to clot, the corpuscles having previously been removed by methods we shall immediately study. It may also CH. XXIX.] COAGULATION OF THE BLOOD 447 be 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 subsequent washing with water. Fig. 317. -Reticulum of fibrin, from a drop of human blood, after treatment with rosanilin. The entangled corpuscles are not seen. (Ranvier.) Serum is plasma minus the fibrin which it forms. The relation of plasma, serum, and clot can be seen at a glance in the following scheme of the constituents of the blood : — Plasma f Serum (Fibrin^ Blood Corpuscles rClot 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. 6. Injection of nucleo -protein into the circulation causes intra- vascular clotting. 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. 448 THE BLOOD [CH. XXIX. 2. The addition of a large quantity of neutral salts such as sodium sulphate or magnesium sulpliate. 3. Addition of a soluble oxalate, fluoride, or citrate. 4. Injection of commercial peptone (which consists chiefly of proteoses) into the circulation of the living animal. 5. Addition of leech extract to the blood, or injection of leech extract into the circulation while the animal is alive. 6. Contact with the living vascular walls. 7. Contact with oil. The cause of the coagulation of the blood may be briefly stated as follows : — When blood is within the vessels, one of the constituents of the plasma, a protein of the globulin class, called Jihrinogen, exists in a soluble form. When the blood is shed, the fibrinogen molecule is altered in such a way that it gives rise to the comparatively insoluble material fihrin. The statement has been made that the fibrinogen molecule is split into two parts; one part is a globulin (fibrino-globulin), which remains in solution; the other and larger part is the insoluble substance fibrin. It is, however, doubtful if this really represents what occurs, for recent work seems to show that the fibrino- globulin is not a product of fibrinogen, but exists in the blood-plasma beforehand. At any rate, whether this is so or not, the fact remains that fibrin is the important product and the only one which need concern us. The next question is. What causes the transformation of fibrinogen into fibrin ? and the answer to that is, that the change is due to the activity of an enzyme which is adXled fihrin-ferment or thrombin. This enzyme does not exist in healthy blood contained in healthy blood-vessels, but is formed by the disintegration of the blood- platelets and colourless corpuscles which occurs when the blood leaves the blood-vessels or comes into contact with foreign matter. Hence the blood does not coagulate during life. But it will be said, disintegration of the blood- corpuscles occurs during life, why, then, does the blood not coagulate? The reason is, that although the formed elements do disintegrate in the living blood, such a phenomenon takes place very slowly and gradually, so that there can never, under normal circumstances, be any massive liberation of fibrin-ferment, and further, that there are agencies at work to neutralise the fibrin-ferment as it is formed. The most noteworthy of these neutralising agencies is the presence in the blood of an antiferment called aniithromhin, analogous to the antipepsin and antitrypsin which we shall see are eflficacious in preventing the stomach and intestines from undergoing self-digestion. Nucleo-proteins obtained from most (jf the cellular organs of the body produce intravascular clotting when injected into the circulation of a living animal. In certain diseased conditions intra- vascular clotting or thrombosis sometimes occurs, and this, if it CH. XXIX.] COAGULATION OF THE BLOOD 449 occurs in the heart and main blood-vessels, is fatal. The condition is doubtless due to the entrance of nucleo-protein into the circula- tion from disintegrated cells. The relationship of nucleo-protein and thrombin is an unsettled problem ; the old view that the two are identical is probably incorrect ; it is, however, possible that the nucleo-protein is either identical with thrombokinase, or holds the thrombokinase in loose combination or admixture. Thrombin is believed to originate, chiefly from the blood-platelets and in part from the leucocytes. Birds' blood clots , very slowly, and the absence of blood-platelets in this variety of blood will, in part, account for this. Lymph, which contains colourless cor- puscles, but no platelets, also clots, so in this case the colourless corpuscles must be the source of the ferment. One should, however, be careful in speaking of the disintegration of leucocytes to remember that the word disintegration does not mean complete breakdown leading to disappearance; the colourless corpuscles do not appreciably diminish in number when the blood clots, but what occurs is a shedding out from the surviving leucocytes of certain products, among which fibrin-ferment is one. We have now traced fibrin formation, the essential cause of blood-clotting, to the activity of thrombin ; it is next necessary to allude to what has been discovered in relation to the origin of thrombin. Like other enzymes, it is preceded by a mother-substance or zymogen. This zymogen is called prothrombin or thromhogen, and there appear to be two necessary agents concerned in the conversion of thrombogen into thrombin ; one of these is the action of calcium salts, the other is the presence of an activating agent (analogous to the enter okinase, which activates pancreatic juice) called thrombokinase . The part played by calcium salts is well illustrated by the fact that coagulation is prevented by the decalcification of the blood. This can be accomplished by the addition of a small amount of a soluble oxalate or fluoride to the blood immediately it is shed. The calcium of the blood plasma is then immediately precipitated as insoluble calcium oxalate or fluoride, and is thus not available for the transformation of thrombogen into thrombin. The addition of the oxalate or fluoride must be rapidly performed, otherwise time will be given for the conversion of thrombogen into thrombin, and thrombin, when formed, will act upon fibrinogen whether the calcium has been removed or not. In other words, calcium is only necessary for the formation of fibrin -ferment, and not for the action of fibrin-ferment on fibrinogen. Fibrin is thus not a compound of calcium and fibrinogen. The action of a soluble citrate is also, in a certain sense, a decalcifying action, for although calcium citrate is a soluble salt, it 2 F 450 THE BLOOD [CM. XXIX. does not ionise in solution so as to liberate the free calcium ions which are essential for thrombin formation. Oxalated blood (or oxalated plasma) will clot when the calcium is once more restored by the addition of a small amount of calcium chloride, but such addition to fluoride plasma will not induce clotting ; in this case, thrombin itself must be added as well In some way sodium fluoride interferes with the formation of thrombin, probably by preventing the liberation of thrombokinase from the corpuscular elements of the blood. The latter are certainly very well preserved. The second activating agent, however, thrombokinase, is not only liberated from the blood-corpuscles, but it is also obtained from many other tissues. If a hoemorrhage takes place under ordinary circum- stances the blood as it flows from the wound passes over the muscles and skin that have been cut, and rapidly clots owing to the throm- bokinase supplied by those tissues. If blood is obtained by drawing it off through a perfectly clean cannula into a clean vessel without allowing it to touch the tissues, it remains unclotted for a long time ; in the case of birds' blood this time may extend to many days ; but the addition of a small piece of a tissue such as muscle, or of an extract of such a tissue, produces almost immediate clotting. If a solution of fibrinogen is prepared and calcium added it will not clot; if thrombin, or a fluid such as serum which contains thrombin, is added it will clot. It will not clot if birds' plasma obtained as above is added to it ; nor if tissue extract is added to it ; but if both are added it will. In other words, the thrombogen of the birds' plasma jo^t^s the throm- bokinase of the tissue extract have the same effect as thrombin. The next point to consider is why blood obtained after the previous injection of proteoses (or commercial peptone) into the circulation does not clot. It certainly contains calcium salts, and probably both thrombogen and thrombokinase, for it can be made to clot without the addition of either, for instance by dilution, or the passage of a stream of carbon dioxide through it. There must be something in peptone blood which antagonises the action of thrombin. This something is an excess of antithrombin. Peptone will not hinder blood-coagulation, or only very slightly, if it is added to the blood after it is shed. The antithrombin must therefore have been added to the blood while it was circulating in the body. We can even go further than this, and say what part of the body it is which is concerned in the production of antithrombin. It is the liver; for if the liver is shut o(T from the circulation, peptone is ineffective in its action. The converse experiment confirms tliis conclusion, for if a solution of peptone is artificially perfused through an excised surviving liver, a substance is formed which has the power of hinder- ing or preventing the coagulation of shed blood. Peptone blood is very poor in leucocytes; the cause of their disappearance is not clear. en. XXIX.] COAGULATION OF THE BLOOD 451 We are thus justified in two conclusions: — (1) That the antithrombin (normally present in healthy blood in sufficient quantities to prevent intravascular clotting) is formed in the liver. (2) That commercial peptone, in virtue of the proteoses it contains, stimulates this action to such an extraordinary degree that the accumulation of antithrombin in the blood becomes so great that the blood does not clot even after it is shed. We will conclude by considering only one more of the hindrances to coagulation, and that by no means the least interesting. The leech lives by sucking the blood of other animals ; from the leech's point of view it is therefore necessary that the blood should flow freely and not clot. The glands at the head end of the leech, often spoken of roughly as its salivary glands, secrete something which hinders the blood from coagulating, and everyone knows by experi- ence, who has been treated by leeches, how difficult it is to prevent a leech-bite from bleeding after the leech has been removed ; com- plete cleansing is necessary to wash away the leech's secretion from the wound. Now if an extract of leeches' heads is made with salt solution and filtered, that fluid will prevent coagulation whether it is injected into the blood-stream or added to shed blood. The sub- stance in question is believed to be antithrombin itself. The purified material obtained from leech extract is called hirudin. Blood so obtained can be made to clot by the addition of thrombin, or of such a fluid as serum, that contains thrombin in sufficient amount. We may summarise this viev/ of the causes of coagulation in the following tabular way : — From the platelets, and From the formed ele- to a lesser degree from the merits of the blood, but leucocytes, a material is also from the tissues over shed out, called — which the escaping blood I flows, is shed out an acti- 1 vating agent, called — Thrombogen. Thrombokinase. In the blood plas- In the presence of calcium salts, thrombokinase ma a protein sub- activates thrombogen in such a way that an active stance exists, called— enzyme is produced, which is called — Fibrinogen. Thrombin, Thrombin or fibrin-ferment acts on fibrinogen in such a way that it is trans- formed into the insoluble stringy material which is called — Fibrin. Differing hypotheses are held as to the exact role played by each of the factors in fibrin-formation, and the views enunciated in the preceding paragraphs are in the 452 TIIE BLOOD [cn XXIX. rnaiii those of Mmawitz. Unwell rcf^ards tht- lack of coaf^ulation seen in birds' blood, and peptone blood, as due to ex(!ess of antitliroinl)in, but holds that tlirom- boldnase (or thromboplastin, as he terms it) brings about clotting, not by activating thrombogen, but by neutralising antithrombin. According to liiin, also, thrombo- plastin is probably a lipoid of the phosphatide group. The Plasma and Serum. The liquid in which the corpuscles float may he ohtained hy employing one or other of the methods already descrihcd for pre- venting the blood from coagulating. The corpuscles, being heavy, sink, and the supernatant plasma can then be removed by a pipette or siphon ; the separation can be more rapidly effected by the use of a centrifugal machine. On counteracting the influence which has prevented the blood from coagulating, the plasma then itself coagulates. Thus plasma 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 neutral 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 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 of liquids such as 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 bo 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 Proteins: 1. yield of fibrin 4*05 2. other proteins 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 protein in nature. Fibrinogen, as judged from the yield of fibrin, is the least abundant of the proteins present. Serum contains the same three classes of constituents — proteins, extractives, and salts. The extractives and salts are the same in CH. XXIX.] PLASMA AND SERUM 453 both liquiils. The proteins are difierent, as is sliown in the following table : — Pro/t'ln.i of J'/a.snia. Protithis of Serum. Fibrinoficn. Serum globulin. Serum globulin. Serum albumin. Serum albumin. Fibrin-ferment + nucleo-protein. The gases of plasma and serum are small quantities of oxygen, nitrogen, and carbonic acid. The greater part of the oxygen of the blood is combined in the red corpuscles with ha&moglobin; the carbonic acid is chiefly combined as carbonates. The gases of the blood have already been considered under Kespiration (see pp. 361- 372). We may now study one by one the various constituents of the plasma and serum. A. Proteins, — Fibrinogen, the mother-substance of fibrin, is a globulin. It differs from serum globulin, and may be separated from it by making use of the fact that half-saturation with sodium chloride precipitates it. It coagulates by heat at the low tempera- ture of b^" C. Serum globulin and serum albumin. — These substances exhibit the usual differences already described between albumins and globulins (p. 428). Both are coagulated by heat at a little over 70' C. They may be separated by dialysis or the use of neutral salts.* The readiest way to separate them is to add to the serum an equal volume of saturated solution of ammonium sulphate. This is equivalent to semi-saturation, and it precipitates the globulin. If magnesium sulphate is used as a precipitant of the globulin it must be added in the form of crystals, and the mixture well shaken to ensure complete saturation. Fibrin-ferment or Thi^ombiv. — Schmidt's method of preparing it is to take serum and add excess of alcohol. This precipitates all the proteins and the thrombin. After some weeks the alcohol is poured off; the serum globulin and serum albumin have been by this means rendered insoluble in water ; an aqueous extract is, however, found to contain fibrin-ferment, which is not so easily coagulated by alcohol as the proteins are. B. Extractives, — These are non-nitrogenous and nitrogenous. The non-nitrogenous are fats, soaps, cholesterin, and sugar; the nitrogenous are urea (0'02 to 0'04 per cent.), and still smaller quantities of uric acid, creatine, creatinine, xanthine, and hypo- xanthine and amino-acids. * The globulin of the serum precipitated by " salting out" really consists of two proteins, one of which is precipitated bj' dialysis (euglobulin), and the other is not (pseudo-globulin). 454 ' THE RLOOD [CII. XXIX. C. Salts. — The most abundant salt is sodium chloride ; it con- stitutes botwoon 60 and 90 per cent, of the total mineral matter. Potassium chloride is present in much smaller amount. It consti- tutes about 4 per cent, of the total ash. The other salts are phosphates and sulphates. Schmidt gives the following table : — 1000 parts of plasma yield — Mineral matter . . 8 '550 Chlorine 3-640 SO, 0-115 RA O'lSl Potassium 0-323 Sodium 3-341 Calcium phosphate . . . . . . . . 311 Magnesium phosphate 0-222 The Blood- Corpuscles. Red or Coloured Corpuscles. — Human red blood-corpuscles are circular biconcave discs with rounded edges, ... Jon inch in diameter (7 fi to 8 jj.) and tj^ott inch, or about 2 ix, in thickness. When viewed singly they appear of a pale yellowish tinge ; the deep red colour which they give to the blood is observable in them only when they are seen en masse. According to Rollett they arc composed of a transparent filmy framework infiltrated in all parts by the red pigment hcBmoglobiti. This utroma is elastic, so that as the corpuscles circulate, they admit of change in form, and recover their natural shape as soon as they escape from compression. According to this theory, the consistency of the peripheral part of the stroma is greater than that of the ceniral portions ; the outer layer thus plays the part of a membrane in the processes of osmosis that occur when water or salt solutions are added to the corpuscles. This view of Rollett has been questioned, particularly by Schiifer, who regards the red corpuscles as composed of a colourless envelope enclosing a solution of haemo- globin. The presence of a membrane on the exterior of the corpuscle is undoubted, and can be clearly distinguished by a good microscope in the larger corpuscles of amphibia. It is, however, difficult to explain the elasticity of the corpuscles, and the central position of the nucleus in nucleated red corpuscles, unless we also assume that delicate fibres pass across the interior of the corpuscles. The red corpuscles of other mammals are generally very nearly the size of human red corpuscles. They are smallest in the deer tribe and largest in the elephant. In the camelidre they are biconvex. In all mammals the corpuscles are non-nucleated, and in all other vertebrates (birds, reptiles, amphibia, and fishes) the corpuscles are oval, biconvex, and nucleated (fig. 319), and larger than in mammals. They are largest of all in certain amphibians {amphiuma, proteus). A property of the red corpuscles, which is exaggerated in inflam- matory blood, is a tendency to adhere together in rolls or columns (rouleaux), like piles of coins. These rolls quickly fasten together CII. XXIX.] THE BLOOD-CORPUSCLES 455 by their ends, and cluster ; so that, when the blood is spread out thinly on a glass they form an irregular network (fig. 318). r^f '^ FiQ. 318. — Red corpuscles in rouleaux, white corpuscles are uncoloured. The Fio. 319. — Corpuscles of the frog. The central mass consists of nucleated coloured corpuscles. The other cor- puscles are two varieties of the colourless form. Action of Reagents. — Considerable light has been thrown on the physical and chemical constitution of red blood-cells by studying the eifects produced by mechanical means and by various reagents ; the following is a brief summary of these reactions : — Water. — When water is added gradually to frog's blood, the oval disc-shaped corpuscles become spherical, and gradually discharge their haemoglobin, a pale, transparent envelope being left behind : human red blood-cells swell, change from a discoidal to a spheroidal form, burst and discharge their pigment, becoming quite transparent and all but invisible. This effect is due to osmosis. Phi/tiiolo(;ical saline solution causes no eifect on the red corpuscles beyond pre- venting them running into rouleaux. If a stronger salt solution is used, the cor- puscles shrink and become crenated (fig. 320), owing to osmosis of water outwards. Dilute acetic acid causes the nucleus of the red blood-cells in the frog to become more clearly defined ; if the action is pro- longed, the nucleus becomes strongly granulated, and all the colouring matter seems to be concentrated in it, the surrounding cell-substance and outline of the cell becoming almost invisible ; after a time the cells lose their colour altogether. A similar loss of colour occurs in the red corpuscles of human blood, which, however, from the absence of nuclei, seem to disappear entirely. Dilute alkalis cause the red blood-cells to dissolve slowly, and finally to disappear. Chloroform, ether, and other reagents that dissolve fats dissolve the lipoid substances (lecithin, etc.) of the membrane which surrounds the corpuscles, and so produce laking of the blood. 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 distinct (fig. 321). A somewhat similar effect is produced on the human red blood-corpuscle, the colouring matter being discharged and coagulated as a little knob of hsematin on the surface of the corpuscle. ^ Fig. 320.— Effect of saline solu- tion (crcna- tion). oo in« Fio. 321.— Effect of 456 THK BLOOD [CH. XXIX. The Colourless Corpuscles. — Tho white or colourless corpuscles are masses of nucleated protoplasm ; they are nearly spherical when at rest, but owing to their amoeboid movements (see p. 11) exhibit considerable changes in outline when they are active, as they are at body temperature. In health, the proportion of white to red corpuscles is on the average 1 to 500 or 600, but this varies considerably even in the course of the same day. The number of lymphocytes is greatly increased by a meal. Also, in young persons, after hgemorrhage and during pregnancy, there is a larger proportion of colourless blood- corpuscles ; in old age they are diminished. Several varieties of colourless corpuscles are found in human blood. They are represented in the accompanying coloured plate, stained by different methods ; the column on the left shows their appearances as stained by a mixture of eosin and methylene blue (Jenner's stain). The middle colmnn shows them as stained by Ehrlich's triacid dye (acid fuchsin, methyl-green, and orange G). In the right-hand column, the cells were stained with a mixture of hsematoxylin and eosin. The following are the varieties shown : — (a) Lymphocytes. — These are only a little larger than red corpuscles. The nucleus is relatively large, and usually round ; the protoplasm around it forms quite a narrow zone. The nucleus, as is the case with all nuclei, is basophile, and stains with such basic dyes as methylene blue. The protoplasm presents no distinct granules and is also basophile. The lymphocytes comprise about 25 per cent, of the total colourless corpuscles. (6) Large mononuclear leucocytes. — A relatively small oval nucleus lies near the centre of basophile protoplasm, which again presents no definite granulation. Their diameter is 12-20 /jl, and they form only 1 per cent, of the total colourless corpuscles. (c) Transitional lewocytcs. — The cell-body is somewhat smaller and is mainly basophile. A certain amount of neutrophile granula- tion may be seen. The strongly basophile nucleus may present all gradations between an oval and lobed condition. In normal blood their number is variable, but, as a rule, they only make up about 2 to 4 per cent, of the total colourless corpuscles. They are called transitional on the hypothesis that they represent an intermediate condition between the large mononuclear leucocytes and the poly- nuclear leucocytes described under d. It is, however, doubtful if this hypothesis is correct, and some histologists think the h and c varieties originate from the endothelial wall. {d) Polynvdear leucocytes. — These are 9-12 /x in diameter, and form the main mass of the colourless corpuscles (70 per cent.). They have several nuclei, which are strongly basophile and present many different shapes, and are usually connected by threads of n f m 3 VZ^^. rs7».!" •^l^-f' f f (0^, f stained with Stained with Stained with lethylene Blue Ehrlich's Hiematoxylin and Eosin. Tri-acid Dye. and Eosin. The varieties of colourless corpuscles in normal human blood, stained by different methods. a, Lymphocyte; b, large mono-nuclear hyaline leucocyte; c, transition form ; d, polynuclear leucocyte ; f , eosinophile leucocyte ; /, mast-cell. Magnified about 1000 times. (After Szymonowicz.) {Face page 450. en. XXIX.] THE COLOURLESS CORPUSCLES 457 chromatin. The protoplasm is finely granular, and stains with neutral, and faintly with acid aniline dyes (such as eosin). In certain pathological conditions — for instance, in diabetes — the cell- protoplasm contains excess of glycogen. (c) Eosinophil e leucocytes. — These are usually larger than the preceding (12-15 /x in diameter). They contain either a single irregular-shaped nucleus, or more often two or three nuclei of unequal size. Their protoplasm contains large distinct granules which have an intense affinity for acid dyes such as eosin, and are therefore termed oxyphile, acidophile, or eosinophile. They are stated to be less actively amoeboid than the polynuclear leucocytes. Hfialthy bacillus.-. Heal'liy bacillus Jlealthy bacillus. Partially digested bucillus. ^^ Xucleus. V, ^ /'S^'"v "''''"-"" — Bacillus in leucocyte. Partially digested leucocyte -^ -/-fc .7. ri.. Partially digester! leucocyte. Nuclei vacuolated — \i^i _^p' e*-I ^'-.Foreign matter. Foreign matter - t... \%m] Particles of foreign matter. ^^-^^ Particles of foreign matter. T , (- --iv "f ^', Particles of foreiim matter. Leucocytes . ^^^.g^^' Fio. 322.— MacroiJliages containing bacilli and other stnictures undergoing digestion. (Rufl'er.) They comprise from 2 to 4 per cent, of the total colourless corpuscles. (/) Mast-cells. — These cells we have already seen in the connective tissues (pp. 30-31) and they are very rare in normal blood. Less than 0-5 per cent, is usually present. They measure about 10 /x across; their nucleus is single and irregular in shape. The granules in the protoplasm are much more basophile than the nucleus. (See coloured plate.) Phagocytosis. — The most important outcome of the amoeboid movement of the colourless corpuscles is their power of ingesting foreign particles, such as bacteria, which they engulf and digest. 458 THE BLOOD [CH. XXIX. This is called phagocytosis (see also p. 298). The polynuclear leuco- cytes appear to be the most vigorous phagocytes. The drawings in fig. 322 show some stages in this phenomenon; the cells represented there, however, are not normal leucocytes, but certain large amoeboid cells found in connective tissues, which congregate specially in inflamed parts. 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-protein 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-erformed on one side, the gland of the opposite side also shows a similar condition, and the thin saliva secreted there is called the anfi/i/fir, secretion. The meaning of these phenomena is unknown. Hffect of drugs on the gland. Atropine. — After intravenous injec- tion of this alkaloid stimulation of the chorda tympani no lf)nger produces secretion of saliva. Much larger doses are necessary to abolish the vaso dilator effect of chorda stimu- lation, or the sympathetic flow in those cases where previous stimulation of this nerve evoked a secretion of saliva. Pilocarpine produces a copious flow of saliva, accompanied by vaso- dilatation. Ergotoxine paralyses the effects of sympathetic stimulation, but not those of stimulation of the chorda tympani. Adrenaline produces constriction of the blood-vessels. In some animals it evokes a considerable flow of saliva, and when this occurs the constriction of the vessels is followed by dilatation. This favours a view which has been advanced by some observers, that vaso-dilatation is in part produced by the chemical action of the products of activity (carbonic and lactic acids, etc.). The sublingual gland is innervated by the same nerves as the submaxillary, but the preganglionic fibres of the chorda tympani have their cell-station in the so-called submaxillary ganglion which is situated close to the sublingual gland (see fig. 353). The submaxillary ganglion ought properly to be termed the sublingual ganglion. This has been determined by Langley's nicotine method (see p. 200). The parotid gland also receives two sets of nerve-fibres analogous to those we have studied in connection with the submaxillary gland. The principal secretory nerve-fibres are glosso-pharyngeal in origin ; Fig. 353.— Diagram of secretory nerves of submaxillary and sublingual glands. Two fibres of the chorda tympani (Ch.) are shown, one of which supplies the sublingual gland, of which an acinus is shown ; the cell-station fur this is in S. G., the so-called submaxillary ganglion. The other fibre supplies an acinus of the submaxillary gland ; its cell-station is in Langley's ganglion (L. G.), within the substance of the gland. .Sy. is a fibre of the sympathetic, whicli has its cell- station in the superior cervical ganglion, S. C. G. (Alter Dixon.) 504 SALIVA [en. XXXIT. the 8}Tnpathetic is mainly vaso-constrictor, but in some animals it does contain a few secretory fibres also. 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 tjnnpani, etc.) to the glands. Pawlow has recorded some interesting observations on the salivary glands. 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 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 emphasize the psychical element involved in secretion, and point out also the adaptation of the secretory process to the needs of the animal ; thus the submaxillary saliva, which 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. Tlie Saliva. The saliva is the first digestive juice to come in contact with the food. The secretions from the different salivary glands are mixed in the mouth ; the secretion of the minute mucous glands of the mouth and a certain number, of epithelial scales and the so-called " salivary corpuscles " derived from the tonsils are added to it. The liquid is transparent, slightly opalescent, of slimy consistency, and may con- tain 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 sahva comes next (21 to 25 per cent.). The CH. XXXTI.] COMPOSITION AND ACTION OF SALIVA 505 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 : f a. Mucin : this may be precipitated by acetic acid. ^ . I />. Ptyalin : an amylolytic enzyme. organ c • 1 r. Protein : of the nature of a globulin. l^ (L Potassium sulphocyanide. t ('. Sodium chloride : the most abundant salt. Inorganic . - /. Other salts : sodium carbonate, calcium phosphate and \ carbonate ; magnesium phosphate ; potassium chloride. 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 facihtate swallowing. The chemical action of saliva is due to its active principle, ptyalin. This substance belongs to the class of enzymes which are called amylolytic (starch-splitting) or diastatic (resembling diastase, the similar enzyme 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(CgHjo05)n + 4nH,0 [Starch.] [Water.] = 4nC,3H,,0,, + (C,H,,0,)„ + (qHioOs)^. [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 proteins of the food, but when free acid appears ptyahn is de- stroyed, and so it cannot resume work when the acid is neutralised in the duodenum. Another amylolytic enzyme contained in pan- 506 SALIVA [en. XXXII. creatic juice (to bo considered later) continues the digestion of starch in the intestine. Canaon has 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. These observations were, however, made on animals in a quiescent horizontal position. It is extremely doubtful if they can be applied to man in a vertical position, especially if he is moving about (see more fully Stomach movements in the chapter entitled the Mechanical Processes of Digestion). CHAPTEE XXX I IT THE GASTRIC 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 or proteoclastic enzyme 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.* Gastric 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. Artificial gastric juice is made by mixing weak hydrochloric acid (0"2 per cent.) with the glycerin extract of the stomach of a recently- killed animal. This acts like the normal juice. When examined with a lens, the internal or free surface of the stomach presents a peculiar honeycomb appearance, produced by shallow polygonal depressions. 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. 354), imbedded side by side in the substance of the mucous membrane. The glands of the mucous membrane are of three varieties, (a) Cardiac, (6) Fundus, and (c) Pyloric. (a) Cardiac glands; these are simple tubular glands lined by short columnar granular cells, and are only found quite close to the cardiac orifice. * 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. 508 THE GASTRIC JUICE [CIL XXXIII. (b) Fundus glands are found throughout the remainder of the cardiac half and fundus of tlie stomach. They are arranged in groups of four or five, which are separated by a fine connective tissue. Several tubules 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. The gland-tubules are lined with coarsely granular poly- hedral cells {central cells). Between these cells and the basement mem- brane of the tubes, are large oval or spherical cells, opaque or gran- Fio. 355.— Transverse section through lower part of fundus glands of a cat. a. Parietal cells ; b, central cells ; c, transverse section of capillaries. (Frey.) ular in appearance, with clear oval nuclei, bulging out the base- ment membrane ; these cells are called parietal or oxyntic cells. They do not form a continuous layer. (c) P/jloric Glands. — These glands (fig. 356) have much longer ducts than the fundus glands. Into each duct two or three tubules open by very short and narrow necks, and the body of each tubule is branched, wavy, and convoluted. The lumen is large. The ducts are lined with columnar epithelium, and the tubules with shorter and finely granular cubical cells, which correspond with the central cells of the fundus glands. The pyloric glands have no parietal cells. As they approach the Fio. 354.— From a vertical section through the mucous membrane of the cardiac end of stomach. Two fumhis glands are shown with a duct common to both, a, Uuct with columnar epithelium becoming shorter as the cells are traced downward ; n, neck of gland tubes, with central and parietal cells ; Ij, base witli curved Ciccal extremity — the parietal cells are not so numerous here. (Klein and Noble Smith.) CH. XXXIII.] THE GASTKIC GLANDS 509 duodenum the pyloric glands become larger, more convoluted and more deeply situated. They are directly continuous with Brunner's glands in the duodenum. The central cells of the fundus glands and, to a less degree, the cells of the pyloric glands, are loaded with granules. During secre- tion they discharge their granules, those that remain being chiefly situated near the lumen, leaving in each cell a clear outer zone. These are the cells that secrete the pepsin. Like secreting cells generally, they pump water from the lymph that bathes them into the lumen; tams^^^— : Fig. 356.— Section showing the pyloric glands, s, Free sur- face; d, ducts of pyloric glands ; n, neck of same ; m, the gland tubule.s ; mm, muscularis mu- cosae, (lilein and Noble Smith.) Fig. 357.— 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 ; h, capillaries branching between and around the tubes; c, superlicial 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.) to this certain materials are added which are formed by the proto- plasmic activity of the cells. The most important substance in a digestive secretion is the enzyme. 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 in the cells. The granules are not, how- ever, composed of pepsin, but of a mother-substance which is readily converted into pepsin. We shall find similar enzyme precursors in the cells of the pancreas, and the term zymogen is applied to these enzyme precursors. The zymogen in the gastric cells is called pepsinogen. The rennet-enzyme that causes the curdling of milk is formed by the same cells. 510 THE GASTIIIC JUICK [CII. XXXI II. Tlio parietal cells undergo merely a change of size during secre- tion, being at lirst 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 ad-de-sac of the fundus, in another, of the pyloric region of the stomacli ; the former secreted a juice containing both acid and pepsin ; the latter, parietal cells being absent, secreted a viscid alkaline juice containing pepsin. The formation 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 its actual mode of formation, none is wholly satis- factory. Some theories are chemical, and explain the formation of the acid by an interaction of the chlorides and phosphates. Others call to their assistance the law of "mass action," and we certainly know that by the action of large quantities of carbonic acid on salts of mineral acids, the latter may be liberated in small quantities. We know further that small quantities of acid ions may be continually formed in the organism by ionisation. But in every case we can only make use of these explanations if we assume that the small quantities of acid are carried away as soon as they are formed, and thus give room for the formation of fresh acid. Even then we are unable to explain the whole process. A specific action of the cells is no doubt exerted, for 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. Water Organic substances (chicHy pepsin) HCl CaCl. NaCf KCl NH4Ci Ca,(PO,>, Mg,(I'0,), FePO. Human. 99-44 0-32 0-20 0-006 0-14 0-05 0-01 Dog. ft? -30 1-71 0-40 to 0-60 0-06 0-25 0-11 0-05 0-17 0-02 0-008 en. XXXIII.] NEKVES OF THE GASTRIC GLANDS 511 One seos 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 due 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- position. It is clear, colourless, has a specific gravity of 1003 — 1006, and is feebly dextro-rotatory. It contains 0"4 to 6 per cent, of hydrochloric acid. It is strongly proteolytic, and inverts cane sugar. When cooled to 0' 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 protein, 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. Pepsin stands apart from nearly all other enzymes by requiring an acid medium in order that it may act. 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 hberated. 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. 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 512 THE GASTRIC JUICE [CH. XXXIII. glands are under the control of the nervous system, but the early attempts to discover the secretory nerves of the stomach were unsuccessful. The Eussian physiologist Pavvlow solved the problem by the employment of new methods. He experimented on dogs. In the first place he separated off the diverticulum, which we described on the last page, 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 duodenimi 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 dog, 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 protein in the diet, the more abundant is the juice, and the richer both in pepsin and acid. Indeed, if the animal is hungry and shown the meat and not allowed to swallow it, the effect is almost as great. The following striking experiment also shows the importance of the psychical element. Two dogs were taken, and a weighed amount of protein introduced into the main stomach of each without their knowledge ; one was then sham fed on meat, and one and a half hours later the amount of protein digested by this dog was five times greater than that which was digested by tlie other. In the meat, however, it is not the protein which acts most strongly as the stimulus ; egg-white, for instance, is not a stronger CH, XXXIII.] ACTIONS OF GASTRIC JUICE 513 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 succagog^ies (juice-drivers) such as Liebig's extract, and pcptogcns such as 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. Actions of Gastric Juice. Gastric juice has the following five actions: — 1. It is antiseptic, owing to the hydrochloric acid present ; putrefactive processes do not normally occur in the stomach, and the micro-organisms which produce such processes, many of which are swallowed with the food, are in great measure destroyed, and thus the body is protected from them. 2. It inverts cane sugar into dextrose and laevulose. This also is due to the acid of the juice, and is frequently assisted by inverting enzymes contained in the vegetable food swallowed. The juice has no action on starch. 3. It contains lipase, a fat-splitting enzyme. The protein en- velopes of the fat cells are first dissolved by the pepsin-hydrochloric acid, and the solid fats are melted. They are then split in small measure into theii" constituents, glycerin and fatty acids. This 2 K 514 THE GASTRIC JUICE [CII. XXXIII. action is mainly produced by a regurgitation of tlie contents of the duodenum mixed with pancreatic juice; but even after the pylorus has been ligatured and regurgitation prevented, the gastric juice itself produces a svialL amount of fat-splitting, and therefore con- tains lipase. It is a remarkable fact that the administration of fat in the food increases the regurgitation from the duodenum. 4. It curdles milk. — This is due to the action of the rennet enzyme or rennin. The conditions of this action we have already discussed under milk (see p. 482) ; but it may here be added that Pawlow has advanced the view tliat rennin is not a distinct and separate enzyme, but milk-curdling is only one of the activities of pepsin. This hypothesis has been accepted by numerous physio- logists; but, on the other hand, there is a number of equally eminent observers who still maintain that pepsin and rennin are two separate enzymes. Whichever view is correct, the curd of casein formed from the caseinogen is subsequently digested as other proteins are. 5. It is proteolytic ; this is the most important action of all. The proteins of the food are converted by the pepsin-hydrochloric acid into peptones. This action is a process of hydrolysis; and peptones may be formed by other hydrolysing agencies, such as superheated steam or heating with dilute mineral acids. The first stage in the process of hydrolysis is that of acid meta-protein, formerly called acid-albumin or syntonin ; the next step is the formation of propeptones 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 (elastoscs). Then peptone (probably a mixture of polypeptides) is produced. The products of digestion of protein may be arranged according to the order in which they are formed, as follows : — 1. Acid raeta-protein. 2. Propeptone I \l') Heter^proteose j ^'j^f ^'^'^^ are formed or proteoses | ^^^ peutero or secondary 1^ proteose 3. Peptone. It has been stated that the prolonged action of gastric juice leads to the further splitting of the peptone into amino-acids. But accurate work has shown that pepsin -hydrochloric acid does not split any of the known polypoptidos into their ultimate cleavage i)roducts. 1. Acid meta-protein. — The general properties of the meta- proteins, the first degradation products in the cleavage of the proteins which occurs during digestion are described on p. 433. We shall find later that, in pancreatic digestion, an alkali meta-protein is formed instead of the acid modification. CII, XXXIII.] PROTEOSES AND PEPTONES 515 2. Proteoses. — They are not coagulated by heat ; they are pre- cipitated but not coagulated by alcohol : like peptone, they give the pink biuret reaction. They are precipitated by nitric acid, the jpre,- cipitate being soluble on heating, and reappearing when the liquid cools. This last is a distinctive property of proteoses. They are slightly diffusible. The primary proteoses are precipitated by saturation with magnesium sulphate or sodium chloride. Deutero-proteose is not; it is, however, precipitated by saturation with ammonium sulphate. Proto- and deutero-proteose aire soluble in water ; hetero-proteose is not ; it requires salt to hold it in solution. 3. 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 proteins. 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 annexed table will give us at a glance the chief characters of peptones and proteoses in contrast with those of the native proteins. albumins, and globulins. Variety of protcid. Action of lieat. Action of alcohol. Action of nitric acid. Action of ammonium sulphate. Action of copper sulphate and caustic potash. Dillusi- bility. Albuniiu Coagulated Precipitated, then coagu- lated Precipitated in the cold ; not reailily soluble on heating Precipitated by complete saturation Violet colour Nil Globulin Ditto Ditto Ditto Precipitated by half satu- ration ; also precipitated by MgSO, Ditto Ditto Proteoses Not coagulated Precipitated, but not co- agulated Precipitated in the cold ; readily sol- u b 1 e on heating ; the precipitate reappears on cooling* Precipitated by satura- tion Rose-red colour (biuret reaction) Slight Peptones Not coagulated Precipitated, but not co- agulated Not precipi-' tated Not precipi- tated Rose-red colour (biuret reaction Great In the case of deutero-albumose this reaction only occurs in the presence of pxoess rif salt. 516 THK GASTRIC JUICE [CH. XXX III. The question has been often raised why the stomach does not digest itself during life. The mere fact that the tissues are alkaUne and pepsin requires an acid medium in wliich to act is not an explanation, but only opens up a fresh difficulty as to why the j)ancreatic juice which is alkaline dois not difrest 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. 474) have furnished us with the key to the problem ; just as poisons introduced from without stimulate the tells to produce antitoxins, so harmful substances produced within the body are provided witli anti-substances capable of neutralising their effects ; for this reason the blood does not normally clot within the blood-vessels, and W einland has shown that the gastric epithelium forms an antipepsin, the intestinal epithelium an antitrypsin, and so on. The bodies of parasitic worms that live in the intestine are particularly rich in these anti-bodies. Mett's Tubes. 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 3t) C, and the coagulated egg-white is digested. After a given time the tubes are removed ; and if the digestive jirocess has not gone too far, only a part of the little colunm of coagulated protein 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 tiuid. Hamburger has used the same method in investigating tlie digestive action of juices on gelatin. The tubes are filled witli 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 (S'i — tO 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. Colour Tests for Gastric Acids. Hydrochloric acid is absent in some diseases of the stomach, notably in cancer ; many colour tests for hydrochloric acid have been introduced from time to time, but by far the most characteristic and delicate is the following : — 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 tliis 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 fiquor ferri perchloridi of tlie British Pharmacopoeia. On mixing a solution containing a mere trace (up to 1 part in 10,000) of lactic acid with this violet solution, it is instantly turned yellow. Larger percentages of other acids (for instance, more than 0-2 per cent of hydrochloric acid) are necessary to decolorise the test solution, but they do not turn the solution yellow. Another colour test, that of Hopkins, is performed as follows :— 5 c.c. of sulphuric acid and 3 drops of a saturated solution of copper sulphate are added to a few drops of lactic acid dissolved in alcohol. The mixture is placed in boiHng water for five minutes, and then cooled ; 2 drops of 0-2 per cent, alcoholic solution of thiophene are then added ; on replacing the tube in boiling water, a eherry-red colour develops. CHAPTER XXXIV 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 cells (islets of Langerhans) which are supplied by a close network of capillaries (fig. 359). 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 filled in the inner two-thirds with small granules ; but the outer third is left clear, and stains readily with protoplasmic dyes (fig. 358). Durincr 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 or more probably of a mixture of zymogens, the precursors of the enzymes in the juice. In the centre of the acini, spindle-shaped cells (ceyitro -acinar cells) are often seen ; their function and origin are unknown. ; 35S. — Section of the pancreas of a dog during digestion, a, Alveoli lined with ceUs, the clear outer zone of which is well stained with haematoxylin ; d, duct lined with short cubical cells, x 350. (Klein and Xoble Smith.) 518 DIGESTION EN THE INTESTINES [cn. XXXIV. Composition and Action of Pancreatic Juice. The pancreatic juice may bo obtained by a fistula in animals, a cannula being inserted into the main pancreatic duct ; but as in the case of gastric juice, experiments on the pancreatic secretion are freiiuently performed with an artificial juice made by mixing a weak alkaline solution (1 per cent, sodium carbonate) with an extract cf pancreas which is usually made with glycerin. Fio. 359.— Section of the pancreas of armadillo, showing alveoli and an islet of Langerlians in the connective tissue. (V. D. Harris.) Quantitative analysis of human pancreatic juice gives the follow- ing results : — Water 97 -6 per cent Organic solids . . . 1*8 ,, Inorganic salts . . . .0*6 „ In the dog the amount of solids is much greater. The organic substances in pancreatic juice are — (a) Enzymes. These are the most important both quantitatively ami functionally. They are four in number : — i. Trypsin, a proteolytic or proteoclastic enzyme. In the fresh juice, how^ever, this is present in the form of trypsinogen. ii. Amylopsin, an amylolytic (amyloclastic) enzyme, iii. Lipase, a fat-splitting or lipolytic (lipoclastic) enzyme, iv. A milk-curdling enzyme. (b) A small amount of protein matter, coagulable by heat. (c) Traces of leucine, tyrosine, xanthine, and soaps. The inorganic substances in pancreatic juice are — Sodium chloride, which is the most abundant, and smaller quan- tities of potassium chloride, and phosphates of sodium, calcium, and CII. XXXIV.] COMPOSITION OF PANCREATIC JUICE 519 magnosiuin. Tlio alkalinity oi Llio jiiico is duo to phosphates and car- bonates, especially of sodium. 1. Action of Trypsin. — Tiypsin acts like pepsin, but with certain differences, which are as follows : — (a) It acts in an alkaline, pepsin in an acid medium. (b) It acts more rapidly than pepsin ; deutero-proteoses can be detected as intermediate products in the formation of peptone ; the primary proteoses have not been detected. (c) Alkali-meta-protein is formed in place of the acid-meta- protein of gastric digestion. (d) It acts more powerfully on certain proteins (such as elastin) which are difficult of digestion in gastric juice. It does not, however, digest collagen. (e) Acting on solid proteins such as fibrin, it eats them away from the surface to the interior ; there is no preliminary swelling as in gastric digestion. (/) Trypsin acts further than pepsin, and rapidly splits up the proteose and peptone which have left the stomach into simpler sub- stances, the polypeptides. The polypeptides in their turn are resolved into their constituent amino-acids, such as leucine, tyrosine, alanine, aspartic acid, glutamic acid, arginine, tryptophane, and many others. The constitution and properties of these cleavage products are described on pp. 417 to 422. In addition to these there is a certain amount of ammonia. The red colour which a tryptic digest strikes with chlorine or bromine water is due to the presence of trypto})hane (indole-amino-propionic acid). When once the peptone stage is passed, the products of further cleavage no longer give the biuret reaction ; hence they are frequently termed aMuretic. A variable fraction of the protein molecule is broken off with comparative ease, so that certain free amino-acids appear in the mixture, at a time when the remainder are still linked together as polypeptides. But ultimately the whole molecule is resolved into amino-acids, either entirely separated or in very short polypeptide linkages. It will thus be seen that there are two important differences between pepsin and trypsin ; one is a diflerence of degree, trypsin being by far the more powerful and rapid catalyst; the second is a difference of kind, pepsin not being able to cleave polypeptides into amino-acids in the way trypsin can. The preliminary action of pepsin, however, is beneficial, for trypsin cleavage occurs more readily after pepsin has acted on a protein. 2. Action of Amylopsin. — The conversion of starch into maltose is the most rapid of all the actions of the pancreatic juice. Its power in this direction is much greater than that of saliva, and it will act 520 DIGESTION IN THIJ INTE8TINBS [CH. XXXIV. even on unboiled starch. The absence of this enzyme in the pancreatic juice of infants is an indication that milk, and not starch, is their natural diet. 3. Action on Fats. — These are split by pancreatic lipase into glycerin and fatty acids. The fatty acids unite with the alkaline bases present to form soaps (saponijicatioii, see p. 415). If a glycerin extract of pancreas is filtered, the filtrate has no lipoclastic action ; the material deposited on the filter is also inactive, but on mixing it with the inactive filtrate once more, a strongly lipoclastic material is obtained. In this way lipase is separable into two fractions: the material on the filter is inactive lipase ; the material in the filtrate is its co-enzyme; the latter is not destroyed by boiling. Bile salts also activate the inactive lipase, and this explains the fact that bile favours fat-splitting. Pancreatic juice also assists in the emulsification of fats ; this it is able to do because it is alkaline, and it is capable of liberat- ing fatty acids, which form soaps with the alkali present; the soap forming a film on the outer surface of each fat globule prevents them running together. Emulsions are much more permanent in the presence of such colloids as gum or protein. The presence of protein in the pancreatic juice renders it therefore specially suitable for the purpose of emulsification. 4. Milk-curdling Enzyme. — The addition of pancreatic extracts or pancreatic juice to milk causes clotting; but this action (which differs in some particulars from the clotting caused by rennet) can hardly ever be called into play, as the milk upon which the juice has to act has been already curdled by the rennin of the stomach. The so-called Peripheral Reflex Secretion of the Pancreas. One of the most efifective ways of producing a flow of pancreatic juice is to introduce acid into the duodenum. Popielski and Wertheimer and Le Page showed that this flow still occurs when the nerves supplying the duodenum and pancreas have been cut through. Wertheimer also mentions that the flow can be excited by injection of acid into the jejunum, but not when it is injected into the lower part of the ileum. These authors concluded that the secretion is a local reflex, the centres being situated in the scattered ganglia of the pancreas, or, in the case of the jejunum, in the ganglia of the solar plexus. This subject has been reinvestigated by Starling and Bayliss, and the results they have obtained are most noteworthy. They consider that the secretion cannot be reflex, since it occurs after extirpation of the solar plexus, and destruction of all nerves passing to an isolated loop of intestine. Moreover, atropine does not paralyse the secretory CH. XXXIV.] SECRETION OF THE PANCREAS 521 action. It must therefore be due to direct excitation of the pancreatic cells, by a sul)stance or substances conveyed to the gland from the bowel by the blood-stream. So many of the connections between organs are made by nerves (the telegraphic service of the body), that we are apt to forget the other messenger, the blood, whom we may compare to the postman. The exciting substance is not acid; injection of 04 per cent, of hydrochloric acid into the blood-stream has no influence on the pancreas. The substance in question must be produced in the intestinal mucous membrane under the influence of the acid. This conclusion was confirmed by experiment. If the mucous membrane of the jejunum or duodenum is exposed to the action of 0"4 per cent, hydrochloric acid, a substance is produced which, when injected into the blood-stream in minimal doses, produces a copious secretion of pancreatic juice, and also, but to a less extent, of bile. This substance is termed secretin. It is associated with another substance which lowers arterial blood-pressure. The two substances are not identical, since acid extracts of the lower end of the ileum produce a lowering of blood-pressure, but have no excitatory influence on the pancreas. Secretin is split off from a precursor, 'prosecretin, which is present in relatively large amounts in the duodenal mucous membrane, and gradually diminishes as we descend the intestine. Pro-secretin can be dissolved out of the mucous membrane by normal saline solution. It has no influence on the pancreatic secretion. Secretin can be split o£f from it by boiling or by treatment with acid. "What secretin is chemically we do not yet know. It is soluble in alcohol and ether. It is not a protein, but probably is an organic substance of low molecular weight. It is, moreover, the same sub- stance in all animals, and not specific to different kinds of animals. Pawlow by experiments of a similar nature to those which led him to the discovery of the secretory nerves of the gastric mucous membrane, thought he had also discovered the secretory nerves of the pancreas in the vagus, and to a less extent in the splanchnic nerves. His failure to produce this result in some experiments he explained by the concomitant stimulation of secreto-inhibiting fibres. It is quite possible that nerves of this nature exist ; but Pawlow's experiments do not prove their existence, because the passage of acid chyme into the duodenum was not excluded, and so he may only have been dealing with a production of secretin, the chemical stimulus to pancreatic activity. Starling's work on secretin naturally led him and others to seek for other chemical messengers employed in the regulation of the activities of the body, and it has already been established that secretin is by no means a solitary instance of such. The general name given to these agents is that of hormone. The chemical 52i DIGESTION IN THE INTESTINES [cil. XXXIV. substances secreted liy such glands as the thyroid ami suprarenal must be included under this term, and the part played by carbonic acid in the regulation of breathing (see p. o80) also conies into the same category. In our study of gastric digestion, we have seen the powerful peptogenic action of dextrin, a substance formed during the salivary digestion of starch ; Edkins has given the name gastrin to the special hormone which is the result of the action of the salivary products on the gastric mucous membrane. Another example of a hormone is furnished by the material formed in the ovary, and which, passing into the maternal blood-stream, stimulates the mammary gland to action. Adapfalioii of Ihi' Pancreas. — To a certain degree it cannot be doubted that the pancreas adapts its secretion to the work it has to do. Thus, whereas jrastric juice has a maximal How soon after the ingestion of food, the pancreatic How does not attain its full force until some time later, that is, when it is wanted. The view that this is due to the hormone named secretin, which is not formed until the gastric contents enter the intestine, fully explains the reason for the delay. But Pawlow went further than this, and stated that the proportion of the various enzymes of the juice was adapted to the proportions of proteins, carbo- hj'drates, and fats in the food taken. Considerable doubt has been cast on these results, because of the failure to confirm one of the most remarkable instances of such adaptation ; this is the power of the pancreas to secrete lactase (an enzyme capable of hydrolysing lactose into glucoses). Normal pancreatic juice contains no lactase, but certain observers stated that by feeding an animal on milk, the pancreas could be educated to secrete it. Careful exjjeriments by I'limmer have recently shown this is not really so, and so much more stringent experimental conditions will have to be imposed before the other cases of adaptation can be considered proven. Internal Secretion of the Pancreas— See Diabetes, next chapter. The Succus Entericus. Succus entericus has been obtained free from other secretions by means of a fistula. Thiry's method is to cut the intestine across in two places; the loop so cut out is still supplied with blood and nerves, as its mesentery is intact; this loop is emptied, one end is sewn up, and the other stitched to the abdominal wound, and so a cul-de-sac from which the secretion can be collected is made. The continuity of the remainder of the intestine is restored by fastening together the upper and lower portions of the bowel from which the loop has been removed. Vella's method resembles Thiry's, except that both ends of the loop are sutured to the wound in the abdomen. Fig. 360 illustrates the two methods. The succus entericus possesses the power of converting disaccha- rides into monosacclmridcs. This power it owes to three enzymes. Inveriase or sucrase is the enzyme which inverts cane sugar — that is, it converts cane sugar into dextrose and Irevulose. The original use of the term " inversion " has been explained on p. 410. Ii may be extended to include the similar hydrolysis of other disaccharides, although there en. XXXIV.] THE SUCCUS ENTERICUS 523 may be no formation of l?evo-rotatory substances. The enzyme in the juice which converts maltose into dextrose is called maltasc ; and that which acts upon lactose is called lactase. Up till a few years ago little or nothing was known regarding the action of the intestinal juice beyond this, but investigations published since that time have altered this state of things, and in the light of these the succus entericus is seen to be a juice of the highest importance. Pawlow was the first to show that one of its main actions is to reinforce and intensify the action of the pancreatic juice, especially in reference to its proteolytic power. Fresh pancreatic juice has practically no digestive power on proteins. Claude Bernard, the earliest to study the pancreatic secretion, entirely missed its tryptic action. On standing, the juice very slowly acquires proteolytic activity. Vernon has shown that much the same is true for extracts of the pancreas. There is no doubt that what the fresh juice con- Fio. 300— Diagram of intestinal fistula. I., Thiry's method ; II., Vella's method. A, Abdominal wall ; B, intestine, with mesentery; 0, separated loop of intestine, with attached mesentery. tains is trypsinogen, and this is slowly transformed into the active enzyme trypsin. If fresh pancreatic and intestinal juices are mixed together, the result is a powerful proteolytic mixture, though neither juice by itself has any proteolytic activity. Pawlow speaks of the substance in the intestinal juice which has this action as an "enzyme of enzymes," and has named it entero- kinase. Starling, like Pawlow, worked with dogs, and has confirmed his main results. A valuable contribution to the same subject has also been made by Hamburger. He has had the unusual opportunity of examining human succus entericus. It became necessary in a patient for surgical reasons to isolate a loop of the small intestine, and this loop continued to discharge intestinal juice to the exterior for some 524: DIGESTION IN THE INTESTINES [CH. XXXI V. time after the operation. He found that this juice, like that of the dog, contains a substance which renders pancreatic juice active. He could not find that it exercised any activating influence on the fat-splitting and araylolytic enzymes of the pancreas, but its action on the tryptic enzyme was most marked. His quantitative experi- ments do not bear out Pawlow's view that the active substance in the intestinal juice is an enzyme, for it is unable, like an enzyme, to act on an unlimited amount of pancreatic juice. Starling, however, supports Pawlow's view ; provided sufficient time is allowed to elapse, it will activate any amount of pancreatic juice. Delezenne has advanced a hypotliesis on the linos of Ehrlich's explanation of the action of hsemolysins (see p. 475). He regards trypsinogen as the amboceptor which enables the enterokinase to become effective. Starling's subsequent work did not support this view. We may therefore best explain the action of enterokinase as an activating agent, by the fact that it is capable of transforming the zymogen trypsinogen into the effective enzyme trypsin. How it does this is explained by J. Mellanby and Woolley in the following way: — Trypsinogen is a complex consisting of trypsin united by a protein moiety, and so long as the enzyme is combined in this way it is inactive ; enterokinase is a proteolytic enzyme which adsorbs and then digests this protein moiety, and thus liberates the trypsin. The mixture of pancreatic and intestinal juice is extraordinarily powerful. If secretin is administered to a fasting animal, the juice secreted, having no food to act upon, will produce erosion and inflammation of the intestinal wall. (Starling.) Dixon and Hamill's recent work has made clearer the mechanism of pancreatic secretion. There are in the pancreas three precursors of enzymes, namely, pro trypsinogen, proamylopsin, and prolipase. Secretin combines chemically, or at any rate acts chemically, on all three ; it liberates amylopsin and lipase from their precursors, and these two active enzymes pass into the pancreatic juice. It liberates trypsinogen from protrypsinogen, and trypsinogen passes into the juice; finally trypsinogen is converted into the active enzyme trypsin by the enterokinase of the succus entericus. Another discovery in connection with succus entericus has been made by Otto Cohnheim. The juice has no action on native proteins such as fibrin and egg-white, but it acts on proteoses and peptone. It rapidly breaks them up into simpler substances, of which amn)onia, leucine, tyrosine, and the hcxone bases have been identified. Cohn- heim has named the enzyme to which this is due erepsin. Ham- burger found that erepsin is also present in the human juice ; it is not identical with enterokinase, because erepsin is destroyed by heat- ing the juice to 59^ C. for three hours ; enterokinase is not destroyed CH. XXXIV.] BACTERIAL ACTION 525 until tho temperature is raised to 67° C. Otlier observers have con- tinued the discovery of erepsin, but have found that it or a similar enzyme is present in most tissues; it is most abundant in the kidney (Vernon). Cohuheim has investigated the action of erepsin on a large number of proteins; it acts energetically on proteoses, peptone, and protamines : on histone, which occupies an intermediate place between protamines and the other proteins, it has a slight action. On the other native proteins it has no action, with the single excep- tion of caseinogen, which is speedily broken up into simple sub- stances ; this opens up the interesting physiological possibility that the suckling infant is able to digest its protein nutriment even if pepsin and trypsin are absent. The bile, as we shall find, has little or no digestive action by itself, but combined with pancreatic juice it assists the latter in all its actions. This is true for the digestion of starch and of protein, but most markedly so for the digestion of fat. Occlusion of the bile- duct by a gall-stone or by inflammation prevents bile entering the duodenum. Under these circumstances the faeces contain a large amount of undigested fat. The importance of the work of Pawlow, and the other physi- ologists whose names have been mentioned, arises from the entirely new light thrown upon the digestion process as a whole. We have been too apt to think of the occurrences in the alimentary canal as a series of isolated phenomena. We now see that each step follows in an orderly manner as the result of the previous steps. For example, the acid gastric juice reaches the small intestine, and there produces secretin from its forerunner ; the secretin is taken by the blood -stream to the pancreas, where it excites a flow of pancreatic juice ; this juice arrives in the duodenum ready to act on starchy substances and on fat. With the assistance of the bile, fatty acid is liberated which in its turn forms more secretin, and so more pancreatic juice. The pancreatic juice, however, cannot act on proteins without enterokinase, which is supplied by the succus entericus ; this sets free the trypsin ; and trypsin with the assistance of erepsin effectively carries out digestive proteolysis. Bacterial Action. The gastric juice is an antiseptic; the pancreatic juice is not. An alkaline fluid like pancreatic juice is just the most suitable medium for bacteria to flourish in. Even in an artificial digestion the fluid is very soon putrid, unless special precautions to exclude or kill bacteria are taken. It is often difficult to say where pancreatic action ends and bacterial action begins, as many of the bacteria that grow in the intestinal contents (having reached that situation in 526 DIGESTION IX THE INTESTINES [CH. XXXIV. Spite of the gasLiic juice) produce enzymes which act in the same way as the pancreatic juice. Some form sugar from starch, others peptone, and araino-acids from proteins, while others, again, break up fats. There are, however, certain actions that are entirely due to these putrefactive organisms. i. On carbohydrates. The most frequent fermentation they set up is the lactic acid fermentation : this may go further and result in the formation of carbonic acid, hydrogen, and butyric acid (see p. 411). Cellulose is broken up into carbonic acid and methane. This is the chief cause of the gases in the intestine, the amount of which is increased by vegetable food. ii. On fats. In addition to acting like lipase, they produce lower acids (valeric, butyric, etc.). The formation of acid products from fats and carbohydrates gives to the intestinal contents an acid reaction. Eecent researches show that the contents of the intestine become acid much higher np than was formerly supposed. Organic acids do not, however, hinder pancreatic digestion. iii. On proteins. Peptones, amino-acids, and ammonia are pro- duced; but the enzymes of these putrefactive organisms have a specially powerful action in liberating substances having an evil odour, such as indole (C^H;N), skatole (C^HgN), and phenol (CgHgO). Indole and skatole originate from the trytophane radical of proteins. There are also gaseous products in some cases. Ammonia-producing organisms flourish best in the lower regions of the small intestine; the ammonia neutralises the organic acids produced higher up, and in the large intestine the contents have in consequence an alkaline reaction. If excessive, putrefactive processes are harmful ; if within normal limits, they are useful, helping the pancreatic juice, and, further, prev^nting"^ the entrance into the body of poisonous products. It is possible that, in digestion, poisonous alkaloids are formed. Certainly this is so in one well-known case. Lecithin, a material contained in small quantities in many foods, and in large quantities in egg-yolk and brain, is broken up by the pancreatic juice into glycero- phosphoric acid, fatty acids, and an alkaloid called choline. We are, however, protected from the poisonous action of chohne by the bacterial enzymes, which break it up into carbonic acid, methane, and ammonia. Sour milk has been recently extolled not only as a useful food, Ijut as a cure for many dyspeptic disorders. Although its efficacy in this direction has been much exaggerated, its usefulness in certain cases is explicable on the ground that the lactic acid bacillus, which is a harmless one in itself, possesses the power, when it is actively growing, of destroying other micro-organisms of a more harmful kind. CHAPTER XXXV THE LIVEU The Liver, the largest gland in the body, is an extremely vascular organ, and receives its supply of blood from two sources, viz., from the portal vein and from the hepatic artery, while the blood is returned from it into the vena cava inferior l)y the hepatie veins. Fig. 301.— The under surface of the liver, g. b., Gall-bladder ; n. d., common bile-duct ; h. a., hepatic artery ; v. p., portal vein ; l. q., lobulus quadratus ; l. s. , lobulus spigelii ; l. c, lobulus caudatus ; D. v., ductus venosus ; u. v., umbilical vein. (Xoble Smith.) Its secretion, the bile, is conveyed from it by the hepatic duct, either directly into the intestine, or, when digestion is not going on, into the cystic duct, and thence into the gall-bladder, where it accumu- lates until required. The liver is in origin a tubular gland, but as development pro- gresses it soon loses all resemblance to the tubular glands found elsewhere. It is made up of small roundish or oval portions called iohules, each of which is about ^V of an inch (about 1 mm.) in diameter, and composed of the liver cells, between which the blood- vessels and bile-vessels ramify. The hepatic cells (fig. 364), which form the glandular or secreting part of the liver, are of a spheroidal 528 THE LITER [CH XXXV. form, but somewhat polygonal from mutual pressure. Each possesses a nucleus, sometimes two. The cell protoplasm contains numerous fatty particles, as well as a varial)le amount of glycogen. The portal vein, hepatic artery, and hepatic duct, run in company, and their appear- ance on longitudinal section is shown in tig. 362. Eunning together through the substance of the liver, they are contained in small channels called portal canals, their immediate invest- ment being a sheath of areolar tissue continuous with Glis- son's capsule. In its course through the liver the portal vein gives off small branches which divide and subdivide between the lobules surrounding them and limiting them, and from this circumstance called inter- lobular veins. From these vessels a dense capillary net- work is prolonged into the substance of the lobule, and this network converges to a single small vein, occupying the centre of the lobule, and hence called m/!ra-lobular. This arrangement is well seen in fig. 363, which represents a section of a small piece of an injected liver. The m^ra-lobular veins discharge their contents into veins called sw&-lobular; these by their union, form the main branches of the hepatic veins, which leave the posterior border of the liver to end by two or three principal trunks in the inferior vena cava, just before its passage through the diaphragm. The so-called capillaries of the liver are really sinusoids (see p. 222); they are in direct contact with the liver-cells, and are not surrounded with lymph spaces as in other secreting glands; their endothelial covering is in many places incomplete, and its cells are irregularly branched and more or less isolated from their neighbours. They are called the stellate cells of Kupffer. The result is that the blood comes into direct contact with the liver-cells. The hepatic artery, the chief function of which is to distribute blood for nutrition to Glisson's capsule, the walls of the ducts and blood-vessels, and other parts of the liver, is distributed in a very Fio. 362. — Longitudinal .section of a portal canal, con- taining a portal vein, hepatic artery and hepatic duct, from the pig. p, Branch of vena porta, situated in a portal canal amongst the lobules of the liver; I, I, and giving otV interlobular veins; there are also seen within the, large portal vein numerous orifices of interlot)uIar veins arising directly from it; '», hepatic artery ; il, bile duct. X 5. (Kiernan.) CH. XXXV.] THE LIVER 529 similar manner to the portal vein, its blood being returned by small Fig. 363.— Capillary network of the lobules of the rabbit's liver. The figure is taken from a very successful injection of the liver veins, made by Harting : it shows nearly the whole of two lobules, and parts of three others ; ;>, interlobular (portal) branches running In the interlobular spaces ; h, Intralobular (hepatic) veins occupying the centre of the lobules. The interlobular and intralobular vessels are connected by radiating capillaries, x 4.5. (Kolliker.) branches which pass into the capillary plexus of the lobules which connects the inter- and m^ra-lobular veins. The hepatic duct divides and subdivides in a manner very like that of the portal vein and hepatic artery, the larger branches being lined by columnar, and the smaller by small polygonal epi- thelium. The bile capillaries commence between the hepatic cells, and are always bounded by hepatic cells on all sides, and are thus separated from the nearest blood capillary by at least the breadth of one cell (fig. 364). To demonstrate the iwi'cr-cellular net- work of bile capillaries, Chrzonszezewsky employed a method of natural injection. A saturated aqueous solution of sulph- indigotate of soda is introduced into the circulation of dogs and pigs by the jugular vein. The animals are killed an hour and a half afterwards, and the blood-vessels washed free from blood, or injected with gelatin stained with carmine. The bile- ducts are then seen filled with blue, and the blood-vessels with red material. If the animals are killed sooner than this, the indigo pigment is found within the hepatic cells, thus demonstrating it was through their agency that the canals were filled. 2 L Vie. 304.— Fortiun of a lobule of liver, a, Bile capillaries be- tween liver-cells; b, blood capillaries, x 350. (Klein and Noble Smith.) 530 THE LIVER [CII. XXXV. Pliiigor and Kupffor lalor discovGred that the relation between the hepatic cells and the bile canaliculi is even more intimate, for they demonstrated the existence of vacuoles in the cells com- municating by minute mtra-eQ\\\\]a,v channels with the adjoining bile canaliculi (lig. 365). //i^ra-cellular canaliculi in the liver-cells are not unique. Recent research by Golgi's method has shown that in the salivary and gastric glands, and in the pancreas, there is a similar condition. Flo. 365. — Sketches illustrating the mode of commencement of the bile canaliculi within the liver- cells (Heiilenhain, after Kupll'er). A, rabbit's liver, injected from hepatic duct with Berlin blue. The tfticr-cellular canaliculi give oil' minute twigs which penetrate into the liver-cells, and there terminate in vacuole-like enlargements. B, frog's liver naturally injected with sulph-indigotate of soda. A similar appearance is obtained, but the i7i«ra-cellular canaliculi are ramified. Schiifer has further demonstrated that the liver-cells contain not only the intracellular bile canaliculi, but also intracellular blood canali- culi passing into the cells from the capillaries between them. These are too minute to admit blood-corpuscles. The liver-cells take certain materials from the plasma and elaborate the constituents of the bile, the bile-salts, and the bile pigments. There can be no doubt that these substances are formed by the hepatic cells, for they are not found in the blood nor in any other organ or tissue ; and after extirpa- tion of the liver they do not accumulate in the blood. AVe thus see that in the liver, lymph does not act as a middleman, as it does in the formation of other secretions. The fvinctions of the liver are connected with the general metab- olism of the body, especially in connection with the metabolism of carbohydrates (glycogenic function) and of fats; its relationship to the metabolism of nitrogenous material (formation of urea, uric acid, etc.), we shall discuss with the urine. Another function is the formation of bile, which it will be convenient to take first. CH. XXXV.] BILE 531 Bile. Bile is the secretion of the liver which is poured into the duo- denum : it has been collected in living animals by means of a biliary fistula ; the same operation has occasionally been performed in human beings. After death the gall-bladder yields a good supply of bile which is more concentrated than that obtained from a fistula. Bile is being continuously poured into the intestine, but there is an increased discharge soon after the arrival of food in the duodenum. Though the chief blood supply of the liver is by a vein (the portal vein), the amount of blood in the liver varies with its needs, being increased during the periods of digestion. This is due to the fact that in the area from which the portal vein collects blood — stomach, intestine, spleen, and pancreas — the arterioles are all dilated, and the capillaries are thus gorged with blood. The peristalsis of the intestine and the pumping action of the spleen are additional factors in driving the blood onwards to the liver. The bile is secreted from the portal blood at much lower pressure than one finds in glands such as the salivary glands, the blood supply of which is arterial. Herring and Simpson, in experiments performed upon numerous animals, found that the bile pressure averages 30 ram. of mercury, which is about three times the pressure in the portal vein. This fact illustrates the general truth that secretory cells exercise pressure. Nothing is known of any nervous agency which regulates the flow of bile ; the stimulus appears to be of a chemical nature, and the increased flow which occurs soon after the arrival of the chyme in the intestine is chiefly due to the action of secretin, for this material stimulates the liver as well as the pancreas. The chemical process by which the constituents of the bile are formed is obscure. We, however, know that the biliary pigment is produced by the decomposition of haemoglobin. Bilirubin is, in fact, identical with the iron-free derivative of haemoglobin called hsema- toidin, which is found in the form of crystals in old blood-clots such as occur in the brain after cerebral haemorrhage (see p. 464). An injection of haemoglobin into the portal vein or of substances such as water which liberate haemoglobin from the red blood-corpuscles produces an increase of bile pigment. If the spleen takes any part in the elaboration of bile pigment, it does not proceed so far as to liberate haemoglobin from the corpuscles. No free haemoglobin is discoverable in the blood plasma in the splenic vein. The amount of bile secreted is differently estimated by different observers ; the amount secreted daily in man varies from 500 c.c. to a litre (1000 c.c). 532 THE LIVER [CH. XXXV. The constituents of the bile are the bile salts proper (tauro- cholate and glycocholate of soda), the bile pigments (bilirubin, biliverdin), a niucinoid substance, small quantities of fats, soaps, cholesterin, lecithin, urea, and mineral salts, of which sodium chloride and phosphates of calcium and iron are the most important. Bile is a yellowish, reddish-brown, or green fluid, according to the relative preponderance of its two chief pigments. It has a musk-lik© odour, a bitter-sweet taste, and an alkaline reaction. The specific gravity of human bile from the gall-bladder is 1026 to 1032; that from a fistula, 1010 to 1011. The greater concentra- tion of gall-bladder bile is partly explained by the addition to it from the walls of that cavity of the mucinoid material it secretes. The amount of solids in gall-bladder bile is from 9 to 14 per cent., in fistula bile from 1'5 to 3 per cent. The following table shows that this low percentage of solids is almost entirely duo to want of bile salts. This can be accounted for in the way first suggested by SchifiF — that there is normally a bile circulation going on in the body, a large quantity of the bile salts that pass into the intestine being first split up, then reabsorbed and again secreted. Such a circulation would obviously be impossible in cases where all the bile is dis- charged to the exterior. The following table gives some analyses of human bile : — Constituents. Fistula bile (healthy woman. Copeman and Winston). Hstula bile (case Normal bile creancer. \eo (WreTichar and Herroun). (trenchs). Sodium f^dycocholate Sodium taurocholate Cholesterin, lecithin, fat . Mucinoid material . Pigment .... Inorganic salts 1 0-6280 1 0-0990 0-1725 0-0725 0-4510 0-165 0-055 0-038 1 0-148 0-878 J iV14 1-18 2-98 0-78 Total solids . Water (by difference) 1-4230 98-5570 1-284 98-716 14-08 85-92 Bile Mucin. — Tlicre has been considerable diversity of opinion as to whether Ijile mucin is really mucin. The most recent work in Hammarsten's laboratory shows that differences occur in different animals. Thus in the ox there is very little true mucin, but a great amount of nucleo-protein ; in human bile, on the other hand, there is very little if any nucleo-protein ; the mucinoid material present there is really mucin. The Bile Salts. — The bile contains the sodium salts of complex CH. XXXV.] BILE SALTS AND PIGMENTS 533 amino-acids called the bile acids. The two acids most frequently found are glycocholic and taurocholic acids. Tho former is the more abundant in the bile of man and horbivora ; tho latter in carnivorous animals, such as tho dog. An important difference between tho two is that taurocholic acid contains sulphur, and glycocliolic acid does not. Glycocholic acid (CoH^^NOj is by the action of dilute acids and alkalis, and also in the intestine, hydrolysed and split into glycine or amino-acetic acid and cholalic acid. a.H.gNO, + H,0 = CH^.NH^.COOH + a,H,,0,. [Glycocholic acid.] [Glycine.] [Cholalii: acid.) The glycocholate of soda has the formula C.,,3H4.2]SraNOg. Taiirocliolic acid (C.^i^HjgNO^S) similarly splits into taurine or amino-isethionic acid and cholalic acid. C,,.H4.N07S + H.,0 = (CH,),.NH,,.SO,.OH + C.^H^qOs [Taurocholic acid.] [Taurine.] [Cholalic acid.] The taurocholate of soda has the formula C.jeH^^NaNO^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 this is by no means always so. The bile pigments show no absorption bands with the spectroscope. Bilirubin has the formula Cg.jHyjjN^O,. : it is thus an iron-free derivative of haemoglobin. 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. Biliverdin has the formula (CieHi8N204),; the value of x is uncertain : it may occur as such in bile ; it may be formed by simply exposing red bile to the oxidising action of the atmosphere ; or it may be formed as in GmeUn'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 clioletelin, C^.^H-jgN^Ojo. Hydrobilirubin. — If a solution of bilirubin or biliverdin in dilute 534 THE LITffR [CIL XXXV. alkali is treated with sodium amalgam or allowed to putrefy, a brownish pigment, which is a reduction product, is formed called hydrobilirubin, C3oH4i3'N'^07. It shows a dark absorption band between h and F, and a fainter band in tlio region of the D line. This substance is interesting because a similar substance is formed from the bile pigment by reduction processes 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 lias been frequently disputed, but the recent work of Garrod and Hopkins has confirmed the old statement that they are the same substance with different names. Hydrobilirubin differs from urobilin in containing more nitrogen (9'2 instead of 41 per cent.). Cholesterin, — Small quantities of this substance are found in normal bile. It may occur in excess, and form the concretions known as gall-stones, which are usually more or less tinged with bilirubin. Its properties and reactions are described on p. 435. The Uses of Bile. — Bile is doubtless, to a certain extent, excretory. Some state that it has a slight action on fats and carbo- hydrates, 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 protein. 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 stimulates peristalsis in the large intestine. Bile is alkaline; it therefore assists the pancreatic juice in neutralising the chyme that leaves the stomach. It assists the absorption of fats (see p. 548). 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 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 en. XXXV.] THE BILE CIKCULATION 535 at onco raisod. 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 fajcos ; they are only represented to a slight extent in the urine : hence it is calculated that seven-eighths of them are reabsorbed from the intestine. Small quantities of cholalic acid, taurine, and glycine are found in the faeces; the greater part of these products of the decomposition 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. The pigment is changed into stercobilin and leaves the body partly in the faeces, but some is absorbed and is finally excreted as urobilin in the urine. The cholesterin in the faeces was formerly supposed to be a bile-residue; but in some animals, especially those which feed on grass, the source of the faecal cholesterin is the phytosterin (vegetable cholesterin) in the food. In some cases it is reduced and forms a derivative termed coprosterin (Austin Flint's stercorin). 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 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 cholagogues (bile-drivers), such as 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 processes, will often be sufficient, as the bile is secreted at comparatively low pressure. Under these circumstances, the faeces 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. 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. Some 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. 536 THE LR'ER [CH. XXXV. 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 lyinph even when there is no obstruction. The Glycogenic Fiinction 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 sngar 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 carbohydrates 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 l)een 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 starcn. 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 protein 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 colour) with iodine, and moreover, when the hardened sections are soaked in water to dissolve out the fdycogen, the protoplasm of the cell may be so vacuolated as to appear little more than a framework. In the liver of a hibernating fro" the amount of glycogen stored up in the liver cells is very considerable. CH. XXXV.] GLYCOGENIC FUNCTION 537 Average Amount of Glycogen in the Liver of Dogs under rnrions 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 Rahhits 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 protein. It is also possible that fats may form a source of glycogen, in virtue of the glycerin they contain. Destination of Glycogen. — There are two chief theories as to the destination of the hepatic glycogen. (1) That the glycogen is con- verted into sugar during life by the agency of an enzyme {liver diastase or qlycogrnase) found in the liver; and that the sugar is conveyed away by the blood of the hepatic veins, to undergo com- bustion in the tissues. (2) That the conversion into sugar only occurs after death, and that during life glycogen is transformed into fat. 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 accurate estimation of sugar in a fluid rich in proteins 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 once a minute, so that a very small increase each time would mount up to a large total. Pavy f urthei 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 an enzyme which is only formed after death. During life, he regards the glycogen as a source of other sub- stances, such as fat and protein. It is certainly a fact that increase 538 THE LIVER [CII. XXXV. 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 proteins, lie has shown that many proteins contain a carbohydrate radical. The prevalent opinion is that the liver-cells may be able to con- vert part of the store of glycogen into fat ; part also of the sugar formed from glycogen may unite with protein to form a gluco- protein ; but 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 metabolism, excess of sugar occurs in the blood, and leaves the body by the urine {glycosuria). Under normal circumstances, the transformation of the hepatic o-lycogen into sugar is a sufficiently slow process to keep the sugar in the blood at such a low percentage that glycosuria does not occur. Glycosuria takes place when the transformation of glycogen into sugar is excessive, as in puncture diabetes, described below. "Alimentary glycosuria" is usually a temporary condition, in which either the diet contains too much carbohydrate for the liver to store as glycogen, or else the liver is comparatively inactive and incapable of dealing with the usual carbohydrate supply. This state of things may be remedied by reducing the amount of carbohydrate ingested, or by improving the condition of the liver. The normal "assimilation limit" for dextrose in man given in one dose by the mouth is about 200 grammes. We must, however, remember that sugar is not poured into the blood to accumulate there, but is removed by the muscular and other tissues which the blood traverses, and is there burnt to serve as a source of energy ; if the tissues are unable to utilise the sugar in this way, it accumulates in the blood and overflows into the urine ; this is the usual condition in the disease called diabetes mellitus in man; and a similar condition may be produced in animals by removal of the pancreas. Many cases of diabetes mellitus in man are due to disease of the pancreas. In many cases the diabetic condition may be removed by rigid abstention from starchy and saccharine food. In other cases diet makes little or no difference; in this condition the sugar must come from the metabolism of the protein constituents of protoplasm ; 40 per cent, or more of the kata- bolised protein may leave the body as sugar, certain of its cleavage products (for instance, alanine, see p. 615) acting as intermediate substances in sugar formation. This serious condition is analogous to what can be produced artificially by the poison known as phloridzin, and is possibly produced in man by some poison acting in a similar way. The principal ways in which diabetes may be produced are: — (1) By diabetic puncture. — Claude Bernaid was the first to show CH. XXXV.] DIABETES 539 that injury to the floor of the fourth ventricle in the region of the vaso- motor centre leads to glycosuria. In man, also, disease of the bulb is frequently associated with glycosuria. These observations led to the erroneous conclusion that diabetes is always of nervous origin. The diabetes produced in this way cannot be the result of vaso-motor disturbances, but is due to an influence on the glycogenolytic nervous mechanism (see p. 541), and the glycosuria only occurs when the liver has within it a store of glycogen. (2) By extirpation of the pancreas. — Minkowski and v. Mering in 1889 showed, that complete extirpation of the pancreas produces in animals a diabetic condition, even if no carbohydrate food is contained in the diet. The disease terminates fatally within a few weeks. If the removal is not complete, the intensity of the glyco- suria depends upon the amount of pancreatic tissue left behind. One-fourth to a fifth of the gland is usually sufficient to prevent the occurrence of the diabetic state. It does not depend on the connec- tion of the pancreas with the intestine, and this proves that the suppression of pancreatic juice is not the cause of the diabetes. The same conclusion was reached in other experiments in which the gland ducts were occluded by paraffin wax ; no glycosuria resulted. Moreover, the effect of pancreatic extirpation, so far as diabetes is concerned, can be prevented by grafting a portion of the pancreas into the abdominal wall, or even under the skin. It is therefore believed that the pancreas forms an internal secretion, in addition to its external secretion or pancreatic juice. The former passes into the blood and plays an essential part in carbohydrate metabolism. The islets of Langerhans have by many been held responsible for this portion of the duties of the pancreas. The evidence in favour of this view is that in human diabetes the islets are frequently degenerated, atrophied, or even absent ; in animals, ligature of the pancreatic ducts leads to atrophy of the pancreatic acini, but not of the islets, and under those conditions no glycosuria occurs. This view may be accepted with considerable confidence, for the observations of certain investigators that the islets merely represent a stage in the development of the ordinary acini, have been disproved or at any rate discredited. We have seen that in diabetes, the power of the tissue cells to burn sugar is lessened ; nevertheless, other diseases in which diminished oxidation occurs are not necessarily accompanied with glycosuria. The difficulty in diabetes probably lies in an impair- ment of the capacity of the cells of the body to prepare the sugar for oxidation. In this process the sugar or its derivative glycuronic acid is split into smaller molecules, and ultimately into water and carbon dioxide. If two hydrogen atoms in the CH.^OH group of dextrose are replaced_by one of oxygen, we obtain glycuronic acid. 540 THE LIVER [CII. XXXV. 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. Possibly it is here that the internal secretion of the pancreas comes in. Gohnheira discovered that muscle by itself and that an extract of pancreas by itself have very little effect in destroying sugar at body temperature; but if a mixture is made of surviving muscle, pan- creatic extract, and sugar, the last-naiued substance rapidly dis- appears. Several observers have confirmed this observation, but others attribute it to bacterial action; aecordincr to this view, the pancreas forms a substance which activates the glycolytic (sugar- destroying) enzyme of muscular tissue. The activating substance is not an enzyme, because the pancreatic extract does not lose this property when it is boiled. Levene, like others, finds that sugar disappears when mixed with muscle and pancreatic extract, but he does not regard this as glycolysis in the usual accepta- tion of tlie word, namely, conil)nstion into carbonic acid and water. He considers that the su<>ar disappears because its molecules are condensed into a heavier carbohydrate, and states that the sugar can once more be recovered from the mixture after hydrolysis with acid. If this is confirmed the view above advanced will need revision, and the action of the pancreatic hormone is best explained, as suggested on tlie next page, as antagonistic to that of adrenaline. Of all the tissue ceils examined by Levene, the leucocytes alone were found to possess real glycolytic power, lactic acid being an intermediate stage before the final products (carbonic acid and water) are reached. (3) By administration of phloridzin. — Many drugs produce temporary glycosuria; some, such as morphine, may act on the diabetic nerve-centre ; others, such as anaesthetics and carbon monoxide, may upset the l)alance between the bluod-gases, and thus affect tissue respiration and lead to an accumulation of sugar in the blood. The most potent poison in producing a diabetic state is, however, phloridzin, which is a glucoside, but the sugar passed in the urine is far 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 protein metabolism. The increase in protein metabolism is signalised liy the rise in the output of nitrogen ; in these cases the ratio of dextrose to nitrogen in the urine is 36 : 1. If such a ratio occurs in inan on a diet free from carbohydrates, a serious condition is revealed ; Clraham Lusk calls it the " fatal ratio." A puzzling feature is the absence of an increase of free sugar in CFI. XXXV.] THE LIVER AND FAT METABOLISM 541 the blood ; if the phloridzin is directly injected into one renal artery, sugar rapidly appears in the secretion of that kidney ; sonic explain this by supposing that the sugar is formed within the kidney cells from some substance in the blood, possibly protein ; whereas others consider tliat the kidney is rendered so permeable to sugar, that the percentage in the blood is kept at a low figure. This view is sup- ported by Underhill's recent work : he has shown that in dogs and rabbits, if the renal structures are ligatured, or the kidney injured by sodium tartrate, the secretion of urine ceases, and after the administration of phloridzin, the sugar in the blood rises consider- ably over the normal. (4) By administration of adrenaline. — This drug also produces a diabetic condition, but in this case there is excess of sugar in the blood also. Recent research indicates that adrenaline produces an increased discharge of sugar from the liver, and that under normal conditions this is regulated by an antagonistic hormone present in the internal secretion of the pancreas. Glycogenolytic Nerves. — The disappearance of glycogen from the liver cells after the stimulation of the splanchnic nerves can be seen histologically. This is due to a direct influence of the nerves on the liver cells, for the effect is obtained after the circulation is stopped by ligature of the aorta and portal vein. The most complete work on this subject is that by J. J. E. Macleod, who finds that the glycogenolytic fibres (the action of which is to increase the sugar in the blood at the expense of the hepatic glycogen) are demonstrable with certainty only in the case of the greater splanchnic nerves. If it occurs as the result of vagus stimulation (as Bernard stated), it is due to the asphyxia which is produced ; if precautions are taken to prevent asphyxia, no increase of the blood sugar is found. In asphyxia it is increase of carbonic acid, and not loss of oxygen, which produces the glycosuric condition, and the former gas probably acts directly on the liver cells themselves. The Liver and Pat Metabolism: The work of Loathes, Hartley, and others has shown that the liver has an important use in the preparation of fats for their final disintegration into carbonic acid and water. The fat stored in adipose tissue must first be transported into the blood- stream ; the lipase found in connective tissue liberates the glycerin and fatty acids, and thus renders such transportation possible. It is first taken to the liver, where it can be easily detected, but not in other organs, and the rupture of the long carbon chains of the fatty acid begins: it is first desaturated and then broken up into lower fatty acids such as caproic and butyric. The unsaturated products 542 THK LIVKR [CH. XXXV. which ave next found in the cells of other organs throughout tlie body disintegrate, probably whore the unsaturated links have been introduced, and the lower acids so formed by successive oxidations break down to molecules of the size of acetic acid, and are lastly completely burnt to carbonic acid and water. Acidosis. — This condition is seen in diabetes; poisonous acids in the blood produce a state of coma, or deep unconsciousness, which may finally cause death. For a diabetic is not only unable to burn and so utilise carbohydrate, but he fails in a similar way in hi? utilisation of fat. Butyric acid and /3-hydroxybutyric acid are prob- ably normal intermediate products in fat katabolism, but a healthy man on a normal diet is able still further to oxidise them into carbonic acid and water. But on an abnormal diet, for instance, when carbohydrate food is absent, fat-cleavage largely stops short at the hydroxybutyric acid stage; consequently this and possibly other related fatty acids accumulate and cause acidosis ; this condi- tion is increased the more fat is given in ihe food, and the acidosis of diabetes is similarly increased by fatty food. These poisonous acids were once believed to originate from proteins; if that weie so there ought to be an increase of other protein katabolites in the urine, which there is not. The acids decrease the alkalinity and carbonic acid of the blood, and the ammonia of the urine is increased ; this indicates an attempt of the body to neutralise the acids. The hydroxybutyric acid does not pass entirely unchanged into the urine. /3-Hydroxybutyric acid is CH... ChOH. CH,. COOH. By oxidation, the two hydrogen atoms in thick type are removed to form water, and this leaves CHy . CO . CHo . COOH, which is aceto- acetic acid : when the COO in thick type is removed we get acetone (CH3. CO . CH.j), which gives the breath and urine of such patients an apple-like smell. In these changes the liver plays an important part by means of certain enzymes which Dakin has proved to exist. One enzyme, called (i-hydroxyhutyrase, is an oxidase; it oxidises the ;8-hydroxy- butyric into aceto-acetic acid, and its action is increased by the addition of blood or oxyhoemoglobin, which furnishes the necessary oxygen. It probably is active in health as well as in disease, the aceto-acetic acid being finally burnt into carbonic acid and water. The other enzyme which forms acetone is not an oxidative one, and acetone formation probably never occurs in the healthy state. Pat Synthesis. — So much for the relationship of the liver to fat katabolism ; but it appears that the liver is also important in the building up of fats, especially of those complex fats called phospha- tides. It is, however, possible that this is not exclusively the property of liver cells : when once the desaturated acids are supplied by the liver, each organ can make its own phosphatides for itself. CHAPTEK XXXVI 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 indigestible 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 very slightly in the stomach. The most recent observations show that water is not absorbed in the stomach, but alcohol is absorbed to some extent. Salts also do not seem to be absorbed unless present in great concentra- tions, such as do not occur in normal diets ; sugar is absorbed with difficulty. The small intestine, with its folds and villi to increase its surface, is the great place for absorption.* Absorption begins in the duodenum, and the products of digestion have largely disappeared by the time the intestinal contents reach the ileo-csecal valve at the commencement of the large intestine ; in the large intestine, absorp- tion (mainly of water) occurs 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 such as starch and protein being converted respectively into the diffusible materials sugar and amino-acids. There are two channels of absorption, the blood-vessels (portal tributaries) and the lymphatic vessels or lacteals. In general terms, the proteins and carbohydrates are absorbed by the blood-vessels, and the fats by the lacteals. Diffusion and osmosis do occur in the intestine, for if a strong solution of salt is introduced into a loop of intestine, there is a flow of water into the loop, owing to the high osmotic pressure of the salt ; at the same time some of the salt diffuses into the blood in accordance with the laws of diffusion. But if some of the animal's own serum is introduced into the loop, it also is absorbed, although it has the * The superficial area of the small intestine, if it was flat, is about I'd square metres. This by the presence of the villi is increased to about 42 square metres. 643 5-4-4 THE ABSORPTION OF POOD [CII. XXXVI. same osmotic pressure and concentration as the animal's blood. This e.vperiraent alone shows us that known physical laws will not com- pletely explain absorption. In fact, absorption is a subject upon which we can speak with little certainty ; the energy that controls it is doubtless some form of imbibition, and resides in the living epithelium ; for if the epithelium is injured or destroyed by the action of such a poison as sodium fluoride, absorption almost ceases, and what does occur follows the laws of osmosis and diffusion. A marked feature during absorption is the increased activity of the lymphocytes which lie beneath the epithelium ; the number of these cells in the blood increases markedly ; it may be even doubled. It has, therefore, been surmised that these cells share in the work of transporting absorbed materials. Absorption of Carbohydrates. — Though the sugar formed from starch by ptyaliu 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 passes. Cane sugar and milk sugar are also converted into mono- saccharides 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 food. It must, then, be formed by the protoplasmic activity of the liver cells from their protein constituents (see preceding chapter). Monosaccharides(;ind especially glutjose) are the only sugars from which the liver is capable of forming glycogen. If other carbohydrates such as 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 Proteins. — It is possible for the alimentary canal to absorb soluble })rutein in an unchanged condition. Thus, after taking a large number of eggs, egg-albumin is found in the urine. Patients fed per rectum derive some nourishment from protein food, although proteolytic enzymes are absent from that part of the intestine. But such occurrences are exceptional ; they are merely illustrations of the fact that under unusual conditions certain parts of the body can rise to the occasion and perform unusual feata The normal course of events is that the food proteins are broken up into their constituent amino-acids, and it is in this form that they are absorbed. If an animal receives, instead of protein the final cleavage products of pancreatic digestion, it continues to maintain its nitrogenous equilibrium ; that is to say, the cells of the body are able to synthesise tissue-proteins from the fragments of the food proteins. ClI. XXXVI.] ABSORPl'ION 545 It is somewhat difficult to find the amino-acids in the blood during absorption, for several reasons: (1) the absorption during any given time is slow, and tlie products are diluted with the whole volume of the blood ; (2) the presence of coagulable proteins in the blood in large quantity renders a search for the amino-acids difficult ; and (3) when the amino-acids get into the blood they do not accumulate there, but are rapidly removed by the cells of the tissues. In spite of these difficulties, Leathes, Howell, and, later, Folin have succeeded in demonstrating that during absorption the non-protein (that is, the amino-acid) nitrogen of the blood increases. The hypothesis that proteins are synthesised during absorption in the intestinal wall from amino-acids was for long held by Abder- halden, but in view of these researches, he has finally aban- doned it. We have now a rational explanation of why it is that the organism can construct the proteins peculiar to itself and maintain its chemical individuality, although the food taken varies so widely in composition. If a man wants to build a house from the bricks of another previously built house, he naturally takes the latter to pieces first, and uses the bricks most suitable for his purpose, and arranges them in a different way to their previous arrangement. The Germans have recently coined the expression Bausteine (or building stones) for the final products of proteolysis with the same underlying idea ; these fragments are rearranged by the tissue cells into tissue- protein, which is different architecturally from the food-protein. Abderhalden has published a very striking experiment in confirmation of this view. He collected the blood of a horse, separated out the various proteins of the plasma, and estimated in each the yield of certain cleavage products (f^lutamic acid and tyrosine) whicli resulted from hydrolysis. He then fed the horse so that it formed new blood, but the only protein given was gUadin, a vegetable protein, which is remarkable for its high percentage yield (-ST-S) of glutamic acid. But in the regenerated blood proteins the percentage yield of glutamic acid was not increased at all ; they exactly resembled the proteins previously present. It is a far cry from the highly specialised organism of the horse to the proto- plasm of the simple mould known as Aspergillus niger ; nevertheless, the same general rule holds ; the protein matter present yields on hydrolysis, glycine, alanine, leucine, glutamic and aspartic acids, but aromatic products, such as tyrosine and phenylalanine, were not discovered. The mould was then cultivated on media of widely varying composition, but the protein formed in the living protoplasm remained constant in composition, and is thus independent of the composition of the nutritive medium. What, then, if this is the case, would be the fate of food proteins introduced directly into the blood-stream without the intervention of the alimentary digestive processes ? If the preliminary cleavage in the gastro-intestinal tract is absol- utely necessary, one would anticipate that a foreign food protein (such as edestin from hemp seed, or excelsin from Brazil nuts) administered by intravenous or intraperitoneal injection would not be assimilated, but would be cast out of the body in one or more of the excretions. But Mendel and Rockwood found that they were not eliminated in either urine or bile. In some cases, a proteose 2 M 546 TUE ABSOUITION OK FOOD [CU. XXXYI. wa3 foiniil in small (jiJuntities in the urine, but the f^realer part of llu- protein Hclniinibtered was retained in the body, especially if the injection was slowly performed. Tiie fact that proteins are retained after this method of administration and api).irently used in the body does not really militate against the theory that proteins under normal conditions are more or less completely broken down in the alimentiiry tract. It is more than probable that cleavage is absolutely necessary for assimilation, and here the enzymes present in the lissue-cells step in ; they are capal)le of taking the place of the pancreatic trypsin and intestinal erepsin and doing their work. The presence of a proteose in urine in some of Mendel and Rockwood's cxi)eriments points in this direction, and this view is supported also by Vernon's discovery that every tissue of the body has an ercptic action, and that in some tissues this power is even greater than in the intestinal mucous membrane. It must not, however, be supposed that all the building stones of the food-protein are utilised in this way. The body is remarkable for its economical use of the tissue-proteins, and quite a small quantity relatively is used up in our daily activities, and so repair is only necessary to the same small extent. We may again get some assistance from our example of the man building a house. When he takes the first house to pieces, there will be a lot of useless bricks and other rubbish, and if the house he wants to build is a smaller one than the one he has destroyed, he will have to dis- card also many bricks which are not rubbish. So it is with the fragments of the food-protein, which, on usual diets, are mure abun- dint than is necessary for the building of tissue-protein. The excess is carried to the liv^er, where the amino-group is removed ; this is termed dea niidation : the nitrogenous moiety of the amino-acid is then converted into urea, which is finally discharged from the body by the kidneys. It should be further noted that the nitrogen of the jn-otein is split off from it by hydrolysis, not by oxidation, so that the products of breakdown retain almost intact the previous energy of the protein, and the non-nitrogenous residue is then available for calorific processes in the same way that the non-nitrogenous foods (carbo- hydrates and fat) are. To continue our analogy of the house-builder, it is generally found that in addition to the building stones provided from the destruction of the previous house, he may want some new bricks altogether. Is this a possibility in the body ? Again recent research answers this question in the affirmative, and has shown that the body-cells possess a previously unsuspected power of synthesising amino-acids for themselves. Wo shall return to this in the chapter on metabolism. 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 CH. XXXVl ] A.BSORPTION OF FATS 547 for fat absorption, and their name lacteals is derived from the milk- like appoarauco 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 micro- scopic preparations of the villi. Figs. 366 and 367 illustrate the appearances observed. 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 ultunately penetrate into the central lacteal, where they either disintegrate or discharge their cargo into the lymph-stroam. 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 abun- dant fatty meal the blood-plasma is quite milky ; the fat droplets are so small that they circulate without hind- rance through the capillaries. The fat in the blood after a meal is eventu- ally 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 origin- ate from carbohydrate, and according to some observers from protein also. The great difficulty in fat absorption was to explain how the fat first gets into the columnar epithelium : these cells will not take up , '^'^^^^--gv '>» atf Fio. 306. — Section of the villus of a rat killed during fat absorption, e-p, Epitlielium ; sir, striated border; c, lymph-cells; c, lymph-cells in the epitheliara ; I, Central lacteal containing disintegrating lymph- corpuscles. (E. A. Schafer.) r;> Fig. 3(57. — Mucous membrane of frog's intes- tine during fat absorption, cp, Epithe- lium ; stT, striated border; C, lymph corpuscles ; I, lacteal. (E. A. Schafer.) 548 THE ABSORPTION OF FOOD [CH. XXXVI. other particles, and it is certain that the epithelial cells do not protrude pseudopodia from their borders (this, however, does occur in the endoderm of some of the lower invertebrates) ; moreover, fat particles have never been seen in the striated border of the cells. The difficulty has now been solved. Munk and, later, Moore and Rockwood, showed quite conclusively that in the intestine fat is completely broken down into glycerin and fatty acids ; preliminary emulsification is advantageous for the formation of these substances, but is not essential. Fat, therefore, is entirely absorbed as glycerin and fatty acids ; the latter, however, in great measure are first converted into soaps, that is, compounds of the fatty acids and alkalis. These soluble cleavage products pass readily through the striated borders of the intestinal epithelial cells; and these cells perform the synthetic act of building them into fat once more, the fat so formed appearing in the form of small globules, surromiding or becoming mixed with the protoplasmic granules that are ordi- narily present. Another remarkable fact which Munk 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. Bile aids the digestion of fat, the bile salts acting in the same way as the co-enzyme of pancreatic lipase; bile also is a solvent of fatty acids, and it probably assists fat absorption by reducing the surface tension of the intestinal contents; membranes moistened 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 fteces. The faeces on an ordinary mixed diet contain comparatively little food residues, and a small quantity is excreted even during starvation. Voit and Hermann showed independently that an intestinal loop which had been emptied and separated from the rest of the bowel contained a few days later, material identical with faeces, and consisting of intestinal juice, desquamated epithelium cells, and bacteria. The increase in the amount of faeces which occurs when food is taken, even when the food is free from cellulose, is due to the mechanical and chemical stimulation which leads to an increase in the succus entericus, and in the shedding of epithelial cells. The faeces contain about 1 per cent, of nitrogen, but this is chiefly contained in the bodies of bacteria, and the dismtegrated epithelial cells. Addition of protein to the diet makes practically no difference to the nitrogen in the faeces under normal conditions. The addition of cellulose to the diet increases the bulk of the faeces, partly because much of the cellulose is excreted unchanged, partly because it stimulates the mucous membrane to secrete more en. XXXYI.] THE FiECES 549 succus entericus, and finally because the larger food residue favours the development of bacteria. On an average, from one-third to one-fifth (varying with the diet) of the weight of dried faeces consists of bacteria. The average weight of dried bacteria excreted daily is 8 grammes; this contains 0-8 gramme of nitrogen, or about lialf the iiitrogen of the faeces. Strasburger estimated that about 128,000,000,000,000 bacteria are evacuated in the faeces of a man every day. The vast majority of these are dead. When cellulose is absent from the diet, the faeces contain from ■ 65-75 per cent, of water; the dry residue contains about 7 per cent, of nitrogen, and the non-nitroc^enous material consists of about equal quantities of ash and substances soluble in ether, with small quantities of stercobilin and other bile residues. The ash contains mainly calcium phosphate, with small amounts of iron and magnesium. The ethereal extract contains cholesterin, lecithin, fatty acids, soaps, and a very small amount of neutral fat. The proteins are chiefly mucin and nucleo-protein, and are derived not from the food, but from the intestinal wall, or are contained in the bacteria ; no doubt a large part of the ethereal extract is also supplied by the bacteria. Cellulose is thus the only important constituent of the food which is unaffected by the digestive juices, although a variable amount, which is largest in herbivorous animals, undergoes bacterial decomposition. The presence of cellulose also interferes with the absorption of proteins, for the digestive juices have difficulty in penetrating the cellulose membranes of vegetable cells. Thus Voit found that 42 per cent, of the nitrogen in the food were lost in the faeces of a vegetarian. This is due solely to the cellulose and not to any difference in the digestibility of animal and vegetable proteins, for if vegetable food is finely subdivided, and then thoroughly cooked and softened, this loss is lessened, and if vegetable protein is entirely freed from cellulose, it is as thoroughly absorbed as animal protein. Fifteen per cent, of the dry substance of green vegetables and brown bread, 20 per cent, of carrots and turnips, and a still larger amount of beans are lost in the faecal residue. The intestinal contents travel more rapidly when vegetables are present, for the indigestible cellulose stimulates peristalsis, and there- fore a large quantity of water escapes absorption in the colon. Thus on an ordinary mixed diet 35 grammes of dry substance and 100 grammes of water are daily excreted in the faeces, whereas on a vegetable diet the quantities are 75 and 260 grammes respectively. CHAPTER XXXVI [ THE MECHANICAL PROCESSES OF DIGESTION Under this head we shall study the neuro-muscular 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 Ititing 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 "chewing the cud"; the food is then once more swallowed, and passes on to the digestive regions of the stomach. 650 CII. XXXYIl] DKGLUTITION 551 In iimn, mastication is also an important process, and in people 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- foi'ined 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 opening of the larynx without entering them. When it has been 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 tliis 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. If we suppose the bolus to te at one particular place in the tube, it acts 552 THE MECHANICAL PROCESSES OF DIGESTION [CH. XXX7II. 8timulatins;ly on the circular muscular fibres l)ohind it, and inhil)it- ingly on those in front ; the contraction therefore squeezes it into the dilated portion of the tube in front, where the same process 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 those 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 l)olus as (juickly as possible past the opening of the respiratory tract. 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 uphill, and the same feat can be performed by jugglers. 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 corro- sive substances, such as 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. Kroneckor's view has also been confirmed in man by the X-ray method. 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. 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 ; glosso-pharyngeal, 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 liulbar 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 en. XXXVII.] MOVEMENTS OF THE STOMACH 553 branch ; and the liypo-glossal, the muscles of the tongue. The nerve-centres by which the muscles are harmonised in their action, are situated in the medulla oblongata. Stimulation of the vagi gives rise to peristalsis of the CESophagus. The cell-stations of these fibres are in the ganglion trunci vagi. Division of both pneumogastric nerves produces 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 accumulates in the gullet and never reaches the stomach. In discussing peristalsis on a previous occasion (p. 141), 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. 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 stomach 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 by 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 later 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 554 THE MECnANICAL rUOCKSSF.S OK DICKSTION [cil. XXXTII. portions are gradually moved towards the pylorus, also ensures thorough admixture with the gastric juice. 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. In certain patho- logical conditions, 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. A few years ago the subject was taken up by Cannon. He gave an animal food mixed with bismuth subnitrate, and obtained by the Ermtgen rays shadow photographs of the stomach, because the bismuth salt renders its contents opaque. His results confirm those of the earlier investigators; the principal peristalsis occurs in the pyloric portion of the stomach. The cardiac portion (including the fundus) 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. After an ordinary mixed meal it is usually stated that the pylorus usually opens for the first time about half an hour after tligestion begins, and some of the acid chyme passes into the duodenum. This, however, is incorrect, as food can be seen by the X-ray method in the duodenum within a few minutes after a meal. The action of this muscular ring is intermittent, and the explanation of its alternate openings and closings may be briefly summed up in the phrase used by Cannon : " the acid control of the pylorus." It is necessary that the food should be retained in the stomach until it is acid; otherwise it would not, on reaching the duodenum, give rise to the formation of secretin, the chemical stimulus for the flow of pancreatic juice, and bile. He has found that acid on the gastric side of the pyloric sphincter opens it, and acid in the duodenum closes it. As soon therefore as the chyme is neutralised by the alkaline juices of the duodenum, there is no longer any hindrance to the action of the acid chyme in the pyloric end of the stomach in opening the door which was temporarily closed by acid on its duodenal side. This action does not occur if a ring is cut through the muscular coat immediately beyond the pylorus, and so the effect from the duodenum is a local reflex action mediated like the movements of the small intestine by the plexus of Auerbach. The time taken for the complete emptying of the stomach is CM. XXXVlI.] MOVEMENTS OF THE STOMACH 55: vaiiable; the size of the meal, its digestibility, the general stale of the body and mind of the individual, are all factors that influence the rate of the act. The average time, however, is probal^ly somewhere about three hours. Dr Hertz and his colleagues at Guy's Hospital have recently applied tlie Ei'mtgen ray method to man with very instructive results. Large doses of bismuth oxychloride (or barium sulphate) can be given to human beings without harm, and by the X-rays the shadow of the opaque food can then be followed, from swallowing onwards to defipcation. The old ideas of the shape and pcsition of the stomach during life, which were derived from examining it in the post-mortem room, are wholly incorrect. In the upright position the pyloric portion is lowermost, and when food is taken it sinks into this lower portion ; and above the ordinary semi-fluid contents there is a horizontal upper limit above which is air. In the erect position the stomach, however, is not quite vertical, but is usually slightly inclined towards the right; and in the recumbent position this obliquity is increased. The following three figures illustrate the shape and position of the stomach when the man is erect: — (a) when the organ is empty; (h) when it is partly tilled; and (c) when it is full. Fig. 36S. — (, -iSlWEK.iiiC" ••-■•' "•''^ » ~»~ ^"' "--»'•'» »■ rS^T Fio. 373.— 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 Malpigliian corpuscle, which arearranged in lobules ; n, neck of capsule ; c, convoluted tubes cut in various directions ; li, zigzag tubule ; d, e, and /, are straight lubes in a medullary ray : d, collecting lube ; c , spiral tube ; /, narrow section of ascending limb. X 380. (Klein and Noble Smith. ) The extent of the zone of clear cells in the loop of Henle varies a good deal in dififerent animals ; a diminution of this part of the tubule lessens the length of the total loop; in most animals there is an admixture of long and short loops, though the proportion of the two varies greatly in different parts of the animal kingdom. ' CH. XXXVTII.] THE KIDSiOY TUBULKS 569 Blood-vessels of Kidney.— Tho roiial artery enters the kidney at tho hihis, and divides into hraiudies that pass towards the cortex, then turn over and form in- complete arches in the region hetween cortex and medulla. From these arches vessels pass to the surface which arc called the interlobular arteries ; they give off vessels at right angles, Fro. 375.— Diagram showing the relation of the Malpighiau body to the urin- iferous ducts and blood - vessels. n, One of the interlobular arteries; a', atterent artery passing into the glomerulus; c, capsule of llie Mal- pighian body, forming the com- mencement of and continuous with the uriniferous tube; t', e', etl'erent vessels which subdivide and f(jrm a plexus, p, surrounding the tube, and finally terminate in the branch of the renal vein e. (After Bowman.) which are the afferent vessels of the glomeruli; a glomerulus is made up of capillaries as pre- viously 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 convoluted tubules. These unite to form veins (interlobular veins) which accompany the interlobular arteries ; they pass to venous arches, parallel to, but more complete than, the corresponding 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 stellulce). Fio. 374.— Vascular supply of kidney, o. Part of arterial arch ; b, interlobular artery ; c, glo- merulus ; d, efferent vessel passing to the medulla as false arteria recta ; <■, capillaries of cortex ; /, capillaries of medulla ; g, venous arch ; h, straight veins of medulla ; i, inter- lobular vein ; j, vena steUula. (Cadiat.l 570 THE URINARY APPARATUS [CH. XXXVIII. Tho medulla is supplied by pencils of lino straight arterioles which arise from the arterial arches. They are called artericB rectce. The efferent vessels of the glomeruli nearest the medulla may also break up into similar vessels which are called false arterice rectce. The veins {vence rectce) take a similar course and empty them- selves into the venous arches. In the boundary zone groups of vcLsa recta alternate with groups of tubules, and give it a striated appearance. 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 length, which, continuous above with the pelvis, ends below by perforating obliquely the walls of the bladder, and opening on its internal surface. It is constructed of three coats : (a) an outer fibrous coat ; (b) a middle muscular coat; and (c) a mucous membrane continuous with that of the pelvis above, and of the urinary bladder below ; it is composed of areolar tissue lined by transitional epithelium. The Urinary Bladder is pyriform; its widest part, which is situate above and behind, is termed the fundus ; and the narrow constricted portion, by which it becomes continuous with the urethra, is called its cervix or ueck. It is constructed of four coats, — serous, muscular, areolar or submucous, and mucous. The circular muscular tibres are especially developed around the cervix of the organ and form the sphincter vesicce. 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 hypogastric 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 the epithelium is stratified like the epidermis, with which it becomes continuous. The female urethra has stratified epithelium throughout. The epithelium rests on a vascular cerium, and this is severed by submucous tissue containing an inner longitudinal and an outer circular muscular layer. Outside this a plexus of veins passes insensibly into the surrounding erectile tissue. Into the urethra open a number of oblique recesses or lacunce, a number of small mucous glands (glands of Littn'), 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 CH. XXXVIII.] THE KIDNEY ONCOMETER 571 are tubular and lined by columnar epithelium ; tlieii' secretion dilutes the semen. Very little is known of the function of the prostate; it often enlarges and becomes calcareous in old age, and gives rise to discomfort and difficulty in micturition. Its removal under these circumstances is a most beneficial operation. The Nerves of the Kidney. These are derived from the renal plexus of each side. The renal plexus consists of both medullated and non-medullated nerve-fibres, with collections of ganglion cells. Fibres from the anterior roots of the eleventh, twelfth, and thirteenth dorsal nerves (in the dog) pass into this plexus. They are both vaso-constrictor and vaso-dilator in function. The nerve-cells on the course of the constrictor fibres are situated in the cceliac, mesenteric, and renal ganglia ; the nerve-cells on the course of the dilator fibres are placed in the solar plexus and renal ganglia. We have, at present, no knowledge of true secretory nerves to the kidney, and the amount of urine is influenced, to a certain extent at any rate, by the blood-pressure in its capillaries. We shall, a few pages hence, however, see that the amount of urine does not depend wholly on the height of the blood-pressure ; and one very striking fact in this relation may be mentioned now, — namely, that if the blood-pressure is increased without allowing the blood to flow, the amount of urine formed is not increased; 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 Kidney Oncometer, This is an instrument constructed on plethysmographic principles, by means of which the volume of the kidney is registered. The general characters of this instrument are described in the diagrams on p. 310. The special form introduced by Eoy for the kidney is shown in fig. 376. Eoy's instrument, however, is but seldom used at the present day. An air oncometer, connected with a Marey's tambour or a bellows recorder (like that figured for the spleen on p. 311), is much less complicated, and gives better results. It is found that the effect on the voliune of the organ of dividing or stimulating nerves corresponds to blood-pressure. If a rise of 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. 377) shows that in a normal oncometric curve from the kidney there is a rise of volume, due to 572 THE URINARY APPARATUS [CH. XXXVIIL each lieart-l)cat, and larger waves, which accompany respiration. In some cases lander sweeping waves (Mayer curves) are S(!en as well, Fio. 370. — Ononmetei s f^ ■ but they are absent in the tracing reproduced : if, in such a tracing, the kidney curve is compared with the tracing of arterial Fin. 377.- -Curvij taken by rfiial DiicuiiiBter conipareU wiUi iliat of oniiiiary biuoii-iiressure. a, Blood- pressure curve ; 6, kidney curve. (Roy.) pressure, it will be seen that the rise of pressure is simultaneous with the fall in kidney volume due to constriction of the renal vessels. The Functions of the Kidney. The function of the kidneys is to separate the urinary con- stituents from the blood, and by this means the blood is maintained of constant composition. The kidney cells are remarkably sensitive, so that alterations in the composition of the blood which are too slight to be detected by chemical analysis (such as an increase of water or of chlorides after a meal) are felt by the kidney, and increased secretion (diuresis) occurs. In the case of some urinary constituents, they are practically entirely removed by the kidney ; urea is an example of this class. In other cases excess beyond a CH. XXXVIII.] FUNCTIONS OF THE KIDNEY 573 certain percentage is removed from the blood ; sodium chloride is an instance of these. Although the glandular epithelium of the convoluted tubes is pai' excellence the secreting mechanism of the kidney, much difference of opinion exists as to the part played by each of the several units in the histological complex we have already described, and this is especially the case in relation to that unique structure, the glomerulus. We have seen that the efferent vessel of each glomerulus has a smaller calibre than the afferent vessel, and this produces high pressure in the glomerular capillaries. The efferent vessel, more- over, resembles an arteriole in its abundance of muscular tissue, and this maintains the high intra -glomerular blood -pressure. This arrangement led Ludvvig to the conception that the glomerulus is a filter, and the filter theory has formed the basis of much subsequent work, and numerous theories. It is impossible in a question upon which physiologists are so divided, to make a complete statement of the case which will meet with universal acceptance, and still more difficult is it to build any sure system of medical treatment upon so insecure a foundation ; and before we attempt to consider the function of this or that type of cell in the kidney, let us see what can be laid down in relation to the physiology of the kidney as a whole. We may sum up the process of urinary secretion as follows : — One fluid, the arterial blood, enters the kidney ; two fluids, the venous blood and the urine, leave it. Both of these fluids are different in composition from the arterial blood. The following table gives the approximate values of the principal constituents in the plasma of the arterial blood, and in the urine : — Total solids . Proteins . Sodium chloride Urea Sup^ar Uric acid . Hippuric acid . We know that it is not possible to convert any fluid into two others, each of different composition from itself, without an ex- penditure of energy which must come from somewhere outside the fluids themselves. In the case of the kidney, as in other secreting glands, this energy comes from the cells of the organ. The secretion of urine is therefore the result of worJc done by the kidney. The quantity of this work may be measured within certain limits, and the energy transformed by the kidney may be estimated in more than one way. The urine is much more concentrated, as regards Arterial Blood-plasma. Urine. 10 per cent. 4 per cent •5 to 8 ,, ,, ,, ,, 0-8 „ ,, 1"2 „ 0-03 „ ,, 2-0 ,, „ 0-15 ,, ,, ,, „ traces 0-05 „ ,, 0-07 „ ,, 574 THE URINARY APPARATUS [CH. XXXVni. crystalline constituents, than the plasma from which it was produced. Thus, urine contains about 2 per cent, of urea on an average, plasma 0'03 per cent., and the same is true in different degrees for other sub- stances. It follows that if urine were placed inside an osmometer and an unlimited su[)ply of plasma outside, water would be sucked into the osmometer until a column of fluid of great height had been established and much work had been performed in raising it. In a specific instance, the blood-plasma had an osmotic pressure equivalent to a 0"92 per cent, solution, and the urine to a 4 per cent, solution, of sodium chloride. From these data, and from the amount of urine secreted, it is possible to make a calculation of the work performed by the kidney. In other words, the energy used by the kidney in secreting the urine cannot be less than what is given by this purely physical consideration. The maximum energy used up by the kidney may be calculated in quite another way. Estimations have been made of the amount of oxygen used by the kidney in secreting urines of known concen- tration ; this oxygen may be taken as a measure of the amount of kidney material used up. If the amount of metabolism be thus determined, we can arrive at the amount of energy used up by a knowledge of the heat produced by the decomposition of this amount of kidney material. The kidney cannot be doing more work than its metabohsm actounts for. If we suppose the kidney living on protein (and the figures would not differ greatly if we siij)posed it to be living on carbohydrate), we may start with the following constants : 1 c.c. of oxygen oxidises 1 milligramme of protein, and forms water, carbon dioxide, urea, etc. In doing so, it gives out 4000 small calories (see Chapter XLII.), and this is equivalent to 170,000 gramme-centimetres of work. In a typical experiment during diuresis, the kidney used 1 c.c. of oxygen per minute; this was, therefore, equivalent to 680,000 gramme-centimetres of work, and the energy transformed from potential to kinetic energy by the kidney cannot have been less than this. Let us consider what evidence there is of nuchanical work which the organ does as an offset against this ; one way in which the work manifests itself is in the concentration of the urine; this lluid is many times more concentrated than the blood-plasma. Tlie degree of concentration can be calcu- lated from a knowledge of the freezing-points of the blood and urine; the greater the concentration of a solution of a crystalline substance, the lower is its freezing- point (see p. 32(!). In this way, it was calculated that 14,700 gramme-centimetres of work was done in the case just referred to. If the calculation is made for each salt separately, a much higher figure than this would, however, be obtained. The practical importance of these considerations to the physician lies in the fact that the expenditure of energy involves combustion, and combustion demands oxygen. For this reason, if for no other, an efficient supply of oxygen, that is, an efficient circulation of blood, is the first condition necessary to a healthy kidney. Eenal trouble is often secondary to cardiac trouble, and may be the result of accumulation of blood in the great veins ; in such cases it is obvious that the renal trouble cannot be overcome by treating the kidney, CIT. XXXVIIl.] URINAKY SECRETION AND BLOOD-PRESSURE 575 but the cardiac difificulty must be dealt with. Again, the physician may endeavour, with a certain measure of success, to decrease the work which falls upon the kidney, by transferring the excretory functi(in as far as possible to the skin. This may be accomplished by stimulating the skin to action by hot air baths, or even more successfully by ordering the patient to a hot dry climate. The importance of changes in the circulation is still further accentuated by the fact that the arterial pressure appears to exercise a direct effect upon the volume of urine secreted by the kidney. In a general sense, those forms of experimental procedure which increase the volume of the kidney, as measured by the oncometer, increase also the flow of urine. This is illustrated by the data given in the following table : — Procerlnrc. General blood- pressure. Renal vessels. Kidney volume. Urinary flow. Division of spinal cord in neck Falls to 40 mm. Relaxed Shrinks Ceases Stimulation of cord . Rises Constricted Shrinks Diminished Stimulation of cord after section of renal nerves Rises Passively dilated .Swells Increased Stimulation of renal Unaffected Constricted Shrinks Diminished nerves Stimulation of splanchnic Rises Constricted Shrinks Diminished nerve Plethora .... Rises Dilated Swells Increased Haemorrhage . Falls Constricted Shrinks Diminished liesults obtained by the oncometer are less easy to interpret in the kidney than in other organs, because of the complexity of its vascular mechanism. For example, constriction of the efferent vessels of the glomeruli might raise the pressure in the glomerular capillaries, and simultaneously lower the pressure in other parts of the kidney, and the net result would be no material alteration in the volume of the whole kidney. The oncometric record is also com- plicated by the consideration that when diuresis is established an increase in the volume of the kidney may not be wholly of vascular origin, but may be partly due to accumulation of urine. In spite of these difficulties, we are nevertheless justified in concluding that pronounced changes in the size of the kidney are of 576 THE URINARY APPARATUS [CH. XXXVIH. vascular origin, and they furnish the best index we have of the pressure of tlie blood iti the capillaries. They give no indication of the rate of blood-flow through the organ, which is an altogether different thing. Finally, from the medical point of view, the activity of the kidney may be invoked by the administration of drugs. Such drugs are called diuretics. They act in different ways, some locally on the kidney, such as caffeine, and certain saline diuretics ; others, such as digitalis, act upon the general blood-pressure. It is important, in prescribing these drugs, not to lose sight of the fact that whilst the greatest benefit may attend their action, it is doubtful whether any of those commonly administered through the alimentary canal (the digitalis group excepted) can be regarded as doing their work without throwing a greater or less strain upon some portion of the renal epithelium. Having in this way considered the kidney as a whole, we must next consider the function of the different types of cell found in the kidney tubule, including the capsule of Bowman in that expression. A complete statement of the case would involve for each type a description of (1) which of the urinary constituents traverses its protoplasm ; (2) the mechanism, whether secretory or physical diffusion or filtration, by which the constituent is propelled ; and (3) the direction in which it goes, whether from the blood to the urine, or from the urine to the blood. Fortunately, however, it is not necessary to discuss the matter quite so exhaustively, for certain possibilities have never been advanced, and so can be put upon one side. For instance, no one has ever suggested that the thick glandular cells of the tubules allow materials to pass through them by physical diffusion ; here, undoubtedly, we have to deal with secretory action alone. Again, the direction of flow through the capsule of Bowman is undoubtedly from the blood to the urine, and the passage of water in the opposite direction, if it does occur at all, is limited to certain regions of the tubule itself. Our problem, therefore, is simplified, and the questions remaining are (1) whether the flow in the glomeruli is due to physical or to physiological (secretory) processes; (2) the evidence of secretory action in the tubules ; and (3) the question whether reabsorption of fluid occurs in the tubules. In relation to the first of these points we may ask the preliminary question. Is there any evidence of physical diffusion or filtration in the kidney ? or, to put it another way, is there any evidence of a urinary flow without the performance of work on the part of the kidney cells ? The answer to this is as follows : such a flow cannot take place as the result of any agency which alters the composition of the fluid ; nevertheless, the appropriate injection into the circulation of CH. XXXVIII.] ludwig's theory 577 Ringer's fluid causes a copious flow of urine which is in its composi- tion" virtually Riuger's fluid. On physico-chemical grounds such a flow would not necessarily demand work on the part of the kidney cells, and as a matter of fact, estimation of the oxygen used during such excretion reveals no measurable rise in the amount of work performed. The general relationship shown in the table on p. 575, between the pressure of blood in the kidney capillaries and the volume of urine secreted, points also to the possibility that under normal conditions filtration is a factor in urine formation. The cells of Bowman's capsule, thin though they are, can, however, exercise selective action. The simplest phase of this is that massive molecules (protein) do not pass through them in health ; this, however, is also true for films of gelatin. In addition to this, these living cells may exercise a more active selection, as is seen in the type of urine excreted by kidneys in which the tubules have undergone necrosis as the result of injection of uranium salts. We may take next the point mentioned last, namely, that of reabsorption. Carl Ludwig imagined that the urine filtered off" at the glomerulus becomes more concentrated as it descends the tubule, and that the work of the cells in the tubule is to reabsorb the water and pass it back into the blood. There is in our opinion no satisfactory evidence that this occurs ; still it is not possible to categorically deny its existence ; if it does occur it does not take place on the massive scale * which Ludwig's views involve, and is limited to the clear epithelium of the descending limb of Henle's loop. The majority of physiologists do not admit even this, and one piece of evidence which we owe to Brodie appears to me to be quite conclusive ; it is this : if the pressure of urine in the ureter is artificially raised by partially blocking it, absorption of water back into the blood ought to be increased ; but as a matter of fact this does not take place, but the exact contrary, for the flow of urine provoked by the injection of sodium sulphate is more abundant from the kidney with the partially blocked ureter, than in the other kidney which serves as a control. Tins brings us then to our main conclusion concerning the function of the epithelium of the tubular part of the apparatus. Here undoubtedly the main function is secretion, and the obviously secreting nature of the cells is revealed by microscopic examination. The following experiments, among others, support this view : — (a) In frogs the glomeruli can be cut out of action by ligaturing the renal artery ; the kidney is then supplied only by the renal portal vein, a vessel which goes to the tubules only. If urea is then injected under the skin, a secretion of urine occurs, which though * Ludwig's theory would involve the reabsorption of nearly 70 litres of water In the day ! 2 O 578 THE URINARY APPARATUS [CII. XXXvni. scanty in amount, is peculiarly rich in urea. Urea, therefore, in the frog is secreted l)y the epithelium of the tuhules. In order to ol)tain this result, the kidney must receive also sufticiont oxygen for the maintenance of the functional activity of its cells ; as the arterial su])ply is cut off by ligature of the renal artery, this must be accomplished in some other way, for instance, by keeping the frog during the experiment in an atmosphere of pure oxygen, (b) The same result is reached in the frog in another way. The renal portal system of the frog's kidney may be artificially perfused with oxygenated liinger's solution, the renal arteries as before being ligatured ; if certain diuretics are added to the solution (caffeine, urea, phloridzin, sodium sulphate, etc.), these induce secretion which is accompanied by a marked increase in the oxygen consumption of the kidney. (c) In mammals the arrangement of the blood-vessels is different, and it is not possible to isolate the tubules as in the frog. 'Nevertheless, the same diuretics cause a copious flow of urine, which is accompanied in all cases by the evidence of increased work on the part of the kidney cells, namely, a large rise in the amount of oxygen used up. In all tliese cases the urine secreted is unlike the plasma in composition, and varies somewhat with the diuretic employed ; for instance, injection of sodium sulphate prcduccsa urine almost devoid of chlorides. (d) In mammals also it is possible to trace certain substances with the eye. A research of great importance was performed along this line by Heidenhain. By cutting the spinal cord he removed the arterial tone from the whole visceral area, and consequently produced a blood-pressure so low that no fluid came down the tubules. Sulphindigotate of soda is a nitrogenous substance, and it can easily be recognised by its blue colour. If it is injected into the blood-stream it is excreted by the liver and kidney, and on post-mortem examination of the kidney, it is found in those cells of the tubules which bear the impress of secreting cells, whereas it is absent from the colls of Bowman's capsule. Numerous hypotheses have been put forward to explain all these results, and the two great historic theories are those of Ludv^ig and of Ijowman, The gist of Ludwig's views will have been gathered from what has just been said; he supposed that the urine filtered through at the glomeruli is a fluid of the same general composition as the blood -])lasma, so far as its crystalline constituents are concerned, and that this fluid is gradu- ally turned into urine as it travels along the tubules by the absorption from it into the blood of water and certain salts. That fluid isotomic with blood-plasma can or does filter through the flat epithelium cells of P.owman's capsule appears to be true, but CH. XXXVIII.] EXTIRPATION OF THE KIDNEYS 579 the part of the theory which deals with reabsorption we have seen reasons for not accepting. The general appearance of the capsular epithelium resembles that lining a lymph space, and some morphologists hold the view that each capsule is in development part of the peritoneum, whilst others regard it as part of the kidney tubule. It is possible that the glomerulus has other functions besides that of a fdter. r)rodie, for instance, has suggested that its main, if not its only use is that of a driving force to propel the secreted urine along the tubule, the resistance of which is very great; he has invented models which demonstrate that pulsations of the kind alleged to occur in the glomeruli will drive fluid along a tube ; he further supports his theory by the observation that the maximum pressure in the ureter as measured by a manometer is usually at least 30 to 44 mm. of mercury less than the arterial blood-pressure, and is probably equal to the pressure in the glomerular capillaries. But these views have not at present been fully accepted by the majority of physiologists. Plowman's classical theory was formulated more than seventy years ago, that is, long before many of the experiments just described were performed. It accords much more nearly with modern views than that of Ludwig, and was founded mainly as a deduction from anatomical structure, namely, the histological appearances of the epithelial cells whicli line the tul)ules, and the double vascular supply which in the frog indicates that the work of the tubule is distinct from that of the glomerulus. He considered that the cells lining the capsule have much the same function as those lining a lymph space, and that it is the glandular epithelium of the tubules which secretes the nitrogenous constituents of the urine. We may accept the last part of the theory as now definitely proven. But whether the glomerular flow is conditioned by physical or by physiological factors is the main point at issue between investigators at present. In the minds of both Ludwig and Bowman the physical factor was uppermost. Heidenhain, and more recently Brodie, regard the flat glomerular cells as true secreting cells. Our own view is that although active secretion on the part of these cells has not been proved to exist, the possibility cannot be altogether denied, and as will be gatheied from what has preceded this, our bias is distinctly in favour of the physical or filtration hypothesis. 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. 680 . THE URINARY APPARATUS [CII. XXXVIII. Extirpation of both kidneys is fatal ; the urea, etc., accumulate in the blood, and the animal dies in a few days ; uraemic convulsions do not usually occur in such experiments. Ligature of both renal arteries amounts to the same thing as extirpation of the kidneys, and leads to the same result. If the ligature is released the kidney after a time again 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 ])lood supply. The Passage of Urine into the Bladder. As each portion of urine is secreted it propels that which is 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 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. Its flow is aided by the peristaltic contractions of the ureters, and is increased in deep inspira- tion, 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 desire to void the urine arises from a sense of fullness of the bladder, and the increase of pressure in this viscus, which results from its distension, is probably the most important factor in the causation of the reflex. Mosso states that in the dog's bladder a pressure of 20 cms. of water sets the reflex in action. The afferent impulse so produced finds its way to the sacral region of the cord chiefly through the second and third sacral nerves, and stimulates the so-called vesical centre, which is situated in the grey matter there ; the reflex takes place perfectly well in an animal whose spinal cord has been cut across as low as the lower part of the lumbar region. It has therefore been proved that the reflex centre CH. XXXVIII.] MICTURITION 581 must be situated below this point. In such animals there is no consciousness of the afferent impulse, and the same is true for the human subject with corresponiling injuries to the spinal cord. Such animals or men have also no voluntary control over the act; it occurs in them purely reflexly. The efferent nerves to the bladder fall into two sets :— (1) The nervus crvjens ; this is undoubtedly the more important of the two. Stimulation of this nerve causes contraction of the bladder, and relaxation of its sphincter, the two necessary acts by which the urine is expelled. (2) The hypoijastric nerves; pre-ganglionic fibres leave the cord in the lumbar region, pass thence to the inferior mesenteric ganglion, from the cells of which the post-ganglionic fibres ultimately reach the bladder by the hypogastric nerves. Much difference of opinion has been expressed regarding the action of these nerves, but in most animals they cause constriction of the sphincter, and in some cases relaxation of the bladder walls also. The hypo- gastric nerves would therefore appear to be the functional anta- gonists of the nervi erigentes. In many animals the bladder constantly exhibits rhythmic contractions. In theory, therefore, micturition is a reflex action ; but in practice it is a voluntary act, and the voluntary muscles of the abdomen press upon the bladder and assist its emptying. It is only in the cases of cord injury or disease already alluded to that the voluntary factor is absent. The simplest view to take of voluntary micturition is the follow- ing: — The will causes the abdominal muscles to contract, and the increased pressure on the bladder so produced is the signal for the reflex to occur. It is further probable that the mere thought of micturition may influence the sacral vesical centre, and heighten its sensitiveness. This certainly is the case in the neighbouring centre for the erection of the penis; erection can be evoked as a reflex act, yet it is a matter of experience that it also takes place as a result of the emotions. If urine is voided too frequently, the cause may be (1) peripheral, as in inflammation of the bladder ; here the organ is unduly sensitive to the pressure of fluid; and (2) central, as in cases of fear and excitement ; here the sensibility of the vesical centre is heightened. In children where control of the vesical centre is often not fully established while they are young, frequent and involuntary micturi- tion may occur. Deficiency of power to expel the urine may be due to actual obstruction, from an enlarged prostate or a stricture in the urethra. It may also be due to weakness of the bladder, as in cases where the organ is much distended and its musculature attenuated ; this condition is often secondary to obstruction produced by stricture, or other causes. CHAPTER XXXIX THE URINE Quantity. — A man of average weight and height passes from 1400 to 1600 C.C., or al)Out 50 fluid oz. daily. This contains about 60 grammes (Ih oz.) of solids. Colour. — This is some shade of yellow which varies considerably with the concentration of the urine. It is due to a mixture of pig- ments; of these the most abundant is a yellow one, originally named urochromc by Thudichuni, whose investigations have in the main been confirmed and supplemented by the recent work of Dombrowski. It shows no absorption bands, and does not fluoresce with zinc salts as urobilin does. It yields a pyrrol derivative which is not hsemopyrrol, and so urochrome is proba])ly not related to urobilin. It contains 11-1 per cent, of nitrogen and 5 per cent, of sulphur, most of which is easily split off as sulphide by cold alkali. It is probably derived from protein. Urobilin, which is normally present in small quantities only, has a reddish tint, and like bile pigment is an iron-free substance. It has an absorption band near the F line. The bile pigment in the intestines is converted into stercobilin, most of which leaves the liody with the fseces ; some, however, is reabsorbed and is excreted into the urine, and is then called uroldlin (see p. 534). A chromogen or mother-substance called urobilinogen, which by oxidation — for instance, standing exposed to the air — isconverted into the pigment proper, is more aljundant than urobilin itself. In certain diseased conditions the amount of urobilin is considerably increased. Uroerythrin, the colouring matter of pink urate sediments, appear to be a small but constant constituent of urine, but its orio-in is unknown. Normal urine contains also a trace of hocmato- porphyrin, and the amount is increased in certain diseased states. Reaction. — The reaction of normal urine is acid ; this is not due to free acid, but to acid salts, of which acid sodium phosi)hate is the most important. The uric and hippuric acids of the urine are combined as urates and hippurates respectively. Under certain circumstances the urine becomes less acid and even alkaline; the most important of these are as follows : — 562 CII. xxxix] COMPOSITION OF URINE )83 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 such as tartaric, citric, malic, etc. These acids are oxidised into carbonates, which, passing into the urine, give it an alkaline reaction. Specific Gravity. — 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, iirina 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 taking an ordinary diet containing about 100 grammes of protein in the twenty-four hours: — Total quantity of urine Water . *. . 1500*00 grammes . 1440-00 Solids . 60-00 Urea 35-00 Uric acid 0-75 Hippuric acid . Sodium chloride 1-05 16-5 Phosphoric acid Sulphuric acid Ammonia 3-5 2-0 0-65 Creatinine 0-9 Chlorine . n-o Potassium 2-5 Sodmm . 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 are combined to form salts, such as urates, chlorides, sulphates, phosphates, etc. Urea, Urea, or Carbamide, CO(N'H.2).2, is isomeric (that is, has the same empirical, but not the same structural formula) with ammonium cyanate (NH4)CN0, from which it was first prepared synthetically by Wuhler in 1828. Since then it has been prepared synthetically in other ways. Wohler's observation derives interest from the fact 58-t THE URINE [CH. XXXIX. tliat tliis 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 l)oth in water and alcohol : it has a saltish taste, and is neutral to litmus paper. The form of its crystals is shown in fig. 378. When treated with nitric acid, nitrate of urea (C0N._,H4 . HNO3) is formed ; this crystallises in octahedra, lozenge-shaped tablets or hexagons (fig. 379). When treated with oxalic acid, flat or prismatic crystals of urea oxa- late (C0NoH,.H,C,04 + H.,0) are formed (fig. 380)." 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, a micro-organism, the micrococcus in stale urine, urea takes up water, and is converted into ammonium carbonate [CON0H4 -f- 2HoO = (NHi).^C03]. Hence the ammouiacal odour of putrid urine. By means of nitrous acid, urea is broken up into carbonic acid, water, and nitrogen, CON.,H. + 2HNO., = CO, + 3H.,0 + 2K,. The Fio. 378. — Crj-stals of urea. Under the influence of ureae, which grows readily Fio. 379.— Crystals of urea nitrate. Fio. 3S0. — Crj'stals 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._,H4 + 3NaBrO = CO., + N._, + 2H,0 + 3NaBr. [Urea.] [Sodium [Carbonic [Nitrogen.] [Water.] [Sodium hypobromite.) acid.] bromide.] This reaction is important, for on it one of the readiest methods for estimating urea depends. There have been various pieces of * Meldola has pointed out that the EngUsh chemi.st Henry HennelJ prepared alcohol from olefiant gas simultaneously with Wiihler's synthesis of urea. The honour of founding the science of organic chemistry must, therefore, be shared between the two men. CH. XXXIX.] ESTIMATION OF UREA 585 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. 381) consists of a bottle (A) united to a measuring tube by india-rubber 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 hypobroraite (made by mixing 2 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-piece. The third limb ©f the T-piece is closed by a piece of india-rubber 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 imtil the surfaces of the water inside and out- side it are at the same leveL Read off the amount of gas (nitrogen) evolved. 3.") "4 c.c. of nitrogen are yielded by O'l gramme of urea. From this the quantity of urea in the 5 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 taken from the total for analysis ; and then, by a simple sum in proportion, the total amount of urea is ascertained. Folin's method is the best for accurate work ; it depends on the fact that urea is decomposed into ammonia and carbonic acid by boiling with magnesium chloride in the presence of hydrochloric acid. The ammonia is estimated by distilling it into standard acid and subsequent titration. Kjeldahl's method of estimating nitrogen consists in boiling 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 amoimt of ammonia, and thence the amount of nitrogen. This is the best method for the estimation of the total nitrogen in the urine. Fig. 3S1.— Dupre's Urea Apparatus. The quantity of urea is variable, the chief cause of variation being the amount of protein food ingested. In a man in a state of 586 TMK UUINB [CH. XXXIX. nitrogenous equilibrium, taking daily 100 to 120 grammes of protein in his food, the quantity of urea secrotorl daily is about 33 to 35 grammes (500 grains). The percentage in human urine would then Ite 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 proteins. If, therefore, people adopt the Chittenden diet, which contains about half the quantity of protein which is present in the more usual Voit dietary, their urine will naturally show a nitrogenous output of half of that which is now regarded as normal. In those who adopt such a reduced diet, Folin has shown that the decrease in urinary nitrogen falls mainly on the urea fraction, and in some cases the urea excreted accounted for only 66 per cent, of the total nitrogen. The other nitrogenous katabolites of the urine alter comparatively little under such circumstances, and the creatinine in particular remains remarkably constant in amount. In our study of protein absorption (p. 545), we have already indicated that the amino-acid fragments of the food-protein are utilised in two ways. A small part is used by the tissue cells for the reconstruction of their protein which has undergone katabolism. In time this will in turn be katabolised, and the waste products discharged as ammonia, creatinine, and a certain amount of urea. This form of metabolism may be termed tissiie or endof/enous metabolism, and its amount is constant and independent to a great extent of the food. The other and larger part of the cleavage pro- ducts of the food protein are not made use of thus, but are d«amidised, and the nitrogenous portion is converted into urea by the liver, and discharged by the kidney. This part of metabolism may be termed exogenous ; it is variable in amount, and depends on the quantity of ingested protein. That the liver is the organ where urea is made is shown by the following considerations : — 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 oocur 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 amino-acids such as leucine and tyrosine are also found CH. XXXIX.] ORIGIN OF UKEA 587 in the urine; they arise from the disintegration of the proteins of the liver cells, but they may in part originate in tlio intestine, and, escaping further decomposition in the degenerated liver, pass as such into the urine. That the amino-acids are the substances from which the liver forms urea is shown by the fact that if such amino-acids as glycine, leucine, arginine, etc., are administered by the mouth, or injected into the blood-stream, the excretion of urea is correspondingly raised. The transformation of arginine into urea is a subject on which we have more accurate information than in the case of any other amino- acids, for there is no doubt that the chano-e, which can be brought about in a test-tube, is also accomplished in the organism. If the account of arginine given on p. 420 is referred to, it will be seen to consist of a urea radical and a substance called ornithine. On hydrolysis we therefore get urea and ornithine (diamino-valeric acid), and this in the body is accomplished by a special enzyme called arginase (Kossel and Dakin), which is more abundant in the liver than in any other tissue. The actual yield of urea is, however, greater than one would anticipate, and so it must be supposed that the ornithine in its turn is broken up and urea is the result. If we glance at the formula of ornithine, and compare it with that of certain other amino-acids which are also undoubted urea forerunners, we have the following : — Glycine CoHgNOo Leucine CJiHj.NC)., Ornithine CgHjXo; In all cases, the atoms of carbon are more numerous than those of nitrogen. In urea (COISr^H^) 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. These simpler compounds are ammonium salts. 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 : — (NHJ^.COg = CON,H^ + 2H2O. [Ammonium [Urea, f 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 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 588 THE URINE [CH. XXXIX. in urea formation. Similar results were obtained by Noncki with ammonium carbamate. The importance of ammonia is accentuated when we remember that ammonia is one of the products of pancreatic digestion, and probably also of endogenous protein metabolism. The ammonia, whether it is formed directly or through the intermediate stage of amino-acid, will combine with the carbonic acid of the blood to form ammonium carbonate or carbamate, and the following structural formulae exhibit the close relationship between these substances 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, /NH, /NH, O = C\^O.NH, ^ = *-\O.NH, ^ = ^\NH, [Ammonium carbonate.] [Ammonium carbamate.] (Urea orcarbamiproxiinately so, and suppression of urine occurs from the simultaneous blocking of both renal arteries by dot, or of both ureters by stones, again uraemia does not follow. On the other hand, uraemia may occur even while a 5)atient 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. Aiuinonia. A small quantity of ammonia always slips through into the urine, because a portion of the ammonia-containing blood passes through the kidney before reaching the organs that are capable of converting it into urea. In man the daily amount of ammonia excreted varies between CH. XXXIX.] AMMONIA 589 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, such as ammonium chloride, is given, it appears as such in the urine. Under normal conditions the amount of ammonia depends on the adjustment between the production of acid substances in met- abolism 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, 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 such as 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. Creatine and Creatinine. Creatine is ap. abundant constituent of muscle ; its chemical structure is very like that of arginine; it contains a urea radical, and by boiling it with baryta it splits into urea and sarcosine (methyl-glycine), as shown in the following equation : — C.H^NgO, + H,0 = CON,H^ + CgH.NO^. [Creatine.] " [Water.] [Urea.] [Sarcosine.] The same decomposition is shown graphically on p. 420. Creatine is absent from normal urine, but it is present in the urine during starvation, in acute fevers, in women during involution of the uterus, and in certain other conditions in which there is rapid loss of muscular material. Its normal fate in the body is unknown ; it may be converted into urea as in the foregoing equation, but injection of creatine into 590 THE URINE [Cn. XXXI X. the blood-stream does not cause any increase in urea formation ; the creatine injected is almost wholly excreted unchanged. It also is not converted into creatinine, although it has been generally assumed that this conversion does occur. The transforma- tion of creatine into creatinine is shown in the following equation : — [Creatine.] [Water.] [Creatinine] Eecent researches have entirely failed to substantiate the view that the urinary creatinine originates from the muscular creatine. If creatine (an innocuous neutral substance) were converted Ity the loss of water in the muscles into creatinine (a strongly basic substance), it would be contrary to all that is known of the chemical changes that occur in the body. Creatinine is present in the urine; it is, in fact, next to urea the most abundant nitrogenous substance found there. Amid all the inconstancies of urinary composition, it appears to be the substance most constant in amount, diet and exercise having no effect on it. Folin's view, that its amount is a criterion of the extent of endogenous nitrogenous metabolism, has steadily gained ground, and the work of the past few years has shown that the liver and not the muscles is the seat of its formation. Some observers have supposed that certain tissue enzymes, termed creatase and creatinase, are agents in its formation and destruction ; others have failed to discover the presence of these enzymes in the liver. On this and on other points there are differences of opinion, but without discussing the pros and cons of minor details, the following view of Mellanby may be taken as a working hypothesis of the metabolic history of the substances in question. Mellanby took as his starting-point an investigation of the contradictory data relating to the proportion of creatine and creatinine in muscle, and by improved methods showed that creatinine is never present in muscle at all, even after prolonged muscular work. He then studied in the developing bird the amount of creatine at different stages, and found that it is entirely absent in the chick's musculature up to the twelfth day of incubation; after this date the liver and the muscular creatine develop pari passu. After hatching, the liver still continues to grow rapidly, and the creatine percentage in the muscles increases also, although the development in the size of the muscles occurs very slowly. This and other experiments on the injection of creatine and creatinine into the blood-stream finally led Mellanby to the following hypo- thesis : — Certain products of protein kataliolism, the nature of which is uncertain, are carried by the blood to the liver, and from these the liver forms creatinine ; this is transported to tlic muscles and there stored as creatine; when the muscles are saturated with creatine, CII. XXXIX.] URIC ACID 591 oxcess of creatinine is then excreted by tlie kidneys. The small amount of creatinine excreted in diseases of the liver also supports the view that that organ is responsible for creatinine formation. These views will no doubt be subjected to the usual tests of criticism and renewed research ; they certainly appear to explain some of our previous difficulties, though the ultimate fate of the muscular creatine is still unsolved. Uric Acid. Uric Acid (C5N4H4O3) is, in mammals, the medium by which a very small (piantity of nitrogen is excreted from the body. It is, however, in birds and some reptiles the principal nitrogenous con- stituent of their uriae. 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 liy 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 con- sists 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 colour- less rectangular plates or prisms. In striking contrast to urea it is a most in- soluble substance, requiring for its solu- tion 1900 parts of hot and 15,000 parts of cold water. The forms which uric acid assumes when precipitated from himian urine, either by the addition of 1 1 1 1 . ^^ . , . .-, Fig. 3S2. — A arions forms of uric acid hydrochloric acid or m certain patho- crystals. logical 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. 382). The murexide test is the principal test for uric acid. The test 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 Murcx. 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 due to the 592 THE URINE [CH. XXXIX. formation of purpurate of ammonia. On the addition of potash the colour becomes bluer. Another reaction that uric acid undergoes (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^H.,]S[.,04) or allantoin (C^H^jN^Oo) are intermediate products. It is, however, doubtful whether a similar oxidation occurs in the normal 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 such as sodium ; an acid urate is one in which only one atom of hydrogen is thus replaced. The formulae would be — CsH^NiOg = uric acid. C^HgNaN^Og = acid sodium ui-ate. CyHoNa^N^Oa = 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.X', the normal urates may be represented by M.,U, and the acid urates by MHU. Bente Jones, and later Sir W, Roberts, considered that the urates actuallj' occurring in urine are what are termed quadri- urates MHU. HoU. There is no doubt that such compounds do not really exist; they are merely mixtures of acid urate, MHU, and free uric acid, H.^U. The quantity of uric acid excreted by an adult varies from 7 to 10 grains (Oo to 075 gramme) daily. The best method for estimating uric acid in urine is that of Hopkins (Folin's modification). The urine is made alkaline with ammonia and saturated with ammonium sulphate. This precipitates all the uric acid as ammonium urate ; the precipitate is collected on a filter, and washed free from chlorides with a 10 per cent, solution of ammonium sulphate; it is then rinsed into a flask with hot water; when cold, sulphuric acid is added. It is then titrated at 60' C. with a standard solution of potassium permanganate until a perma- nent rose colour is obtained. From the amount of the permanganate solution used to obtain the end point, the quantity of uric acid present is calculated. Uric acid may also be determined colori- metrically by the blue colour it strikes with phospho-tungstic acid (Folin and A. B. Macallum, jun.). Origin of Uric Acid. — Uric acid is not made by the kidneys ; when these organs are removed, uric acid continues to be formed, and accumulates in the organs, especially in the liver and the spleen. After extirpation of the liver in birds (in which animals uric acid is such an important katabolite), the formation of uric acid practically ceases, and its place is taken by ammonia and lactic acid, and the CII. XXXIX.] URIC ACID 593 conclusion is Lherefore drawn that in these animals, ammonia and lactic acid arc normally synthesised in the liver to form uric acid. But in mammals, this is not the history of uric acid formation ; in those animals, including man, uric acid is the end-product of the metabolism of nuclein, from the bases of which it arises by oxidation. Nuclein, the main constituent of the nuclei of cells (see p. 431), yields, on decomposition, certain products called purine substances, and their close relationship to uric acid is shown by their f ormulce : — Purine ..... Hypoxanthine (monoxypurine) Purine bases Xanthine (dioxypurine) I Adenine (amino-punne) V Guanine (amino-oxypurine) Uric acid (trioxypurine) C,H,Nj c;h4n,o CHjN^O., C^H.Nj.NH. c^h'nanh^ C^H.Np.. Just as the ordinary protein metabolism is both exogenous and endogenous, so is it the case with nuclein metabolism. There are certain kinds of food (such as liver and sweetbread) which are rich in nuclei, and others, such as meat, which are rich in purine bases (especially hypoxanthine). The increase in uric acid excretion after partaking of such food is exogenous, and those liable to uric acid disorders should avoid such articles of diet. Other forms of diet lead to an increase in uric acid formation by increasing the number of leucocytes in the blood, and there is a conseqvient increase in the metabolism of their nuclei. Increase in leucocytes may, however, be present independently of diet, and in. the disease known as leiucocy- thcemia, this occurs to a marked degree; in such cases uric acid formation increases. Although special attention has been directed to the nuclei of leucocytes because these can readily be examined during life, it must be remembered that the nuclein metabolism of all cells may contribute to uric acid formation. Uric acid, which originates by metabolism, is spoken of as endogenous. We must next consider the mechanism by which the tissue cells form uric acid from nuclein. This question is not only of interest in itself, but also because it illustrates a general truth concerning the importance of the tissue enzymes. The enzyme of the liver which turns glycogen into sugar is the oldest known example of these; in more recent times, the importance of autolytic enzymes (see pp. 136 and 440) of tissue erepsins (see p. 546) and arginase (see p. 587) has been recognised. In uric acid formation we have the very striking example of the action of a succession of enzymes. These are present to an almost negligible extent in the juices of the alimentary canal, and have been studied in the extracts of different organs; their distribution varies a good deal in different animals, and in the different organs of the same animal; speaking generally, they are must abundant in liver and spleen. The general term 2 P 594 TnK URINE [CH. XXXIX. nuclease is given to the whole group, and a dozen or more have been isolated which deal with different stops in the cleavage of the nucleic acid complex. They are classified into nucleinases which resolve the molecule into mononucleotidases, i.e., compounds of carbo- hydrate, phosphoric acid, and one base; nucleotidases which liberate phosphoric acid, leaving the carbohydrate still united to the base ; iimleosidascs which hydrolytically cleave the base and carbohydrate apart; deamidases which remove the amino-group from the purine bases so set free ; one of these, called adenase, converts adenine into hypoxanthine, and another, called guanase, converts guanine into xanthine. Finally, oxidases step in, which convert hypoxanthine into xanthine, and xanthine into uric acid. But even that does not bring the list to a conclusion, for in some organs (especially the liver) there is a capacity to destroy uric acid after it is formed, and so we are protected from a too great accumulation of this substance. What exactly happens to the uric acid is not certain, although it is clear that the products of its breakdown (probably allantoin and urea) are not so harmful as uric acid itself. The enzyme responsible for uric acid destruction is called the uricolytic enzyme. The uric acid which ultimately escapes as urates (normally) in the urine is the undestroyed residue. In gout and allied disorders there may be increased formation of uric acid, or a smaller amount of that formed may be destroyed; the excess may pass into the urine, partly as free uric acid or excess of urates, and so there is a liability to concretions (calculi, gravel, etc.), forming in the kidney or bladder. There is also a tendency to the deposition of urates in certain parts, and the joint cartilages in particular are liable to these concretions. The uric acid diathesis is, however, much too large a subject to treat in a physiological text- book, and medical students, when they come to the study of pathology, will discover that many views are held in relation to it. Hippuxic Acid. Hippviric Acid (CyHyNOa), 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 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 — CHg.NH,, CH.NH.CO.CgHg C,H,.COOH +1 = I ' + H.O COOH COOH [Benzoic acid.] [Glycine.] [Uippuric acid.] [Water.] This is a well-marked instance of synthesis carried out in the CH. XXXIX.] SALTS OF URINE 595 animal body, and experimental investigation shows that it is accom- plished by the living cells of the kidney 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. In the conversion of benzoic into hippuric acid which occurs in herbivora, the necessary glycine comes from the kidney itself. Fig. 3S3. — Crj-stals of hippuric acid. The Inorganic Constituents of Urine, The inorganic or mineral constitu- ents of urine are chiefly chlorides, phosphates, sulphates, and carbonates ; the metals with which these are in combination are sodium, potassium, ammonium, calcium, and mag- nesium. 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 substances are derived from two sources — first from the food, and secondly as the result of metabohc 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. 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 decom- posed to form the hydrochloric acid of the gastric juice. The salt in the body fulfils tlie useful office of stimulating metabolism and secretion. Sulphates. — The sulphates in the urine are principally those of potassium and sodium. 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. They are derived from the metabolism of proteins, and the excretion of sulphates, though it occurs earlier than that of urea, runs parallel with it. The sulphates are, therefore, like urea, the result of exogenous protein metabolism. The sulphur of the protein, which is endogenously katabolised, is not converted into ordinary sulphates to any great extent, but reappears in the urine partly as ethereal sulphates, and partly as certain obscure but not fully oxidised sulphur compounds, and is usually spoken of as neutral sul;pliur. 696 THE URINB [CH. XXXIX. The ethereal sulphates just mentioned form about a tenth of the total sulphates. They are combinations of sulphuric acid with organic radicals, and the greater part of them originate from putre- factive changes 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. The indican of urine, however, 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 tlie formation of potassium phenyl-sulphate is as follows : — C.H^OH + SO,<^gg - SO / g-^«"^ + H,0. [Phenol.] [Potassium [Potassium [Water.] hydrogen phenyl-sulphate.] sulphate.] Indole (CjjHyN) on absorption is converted into indoxyl : — P„ /C.OH :CH The equation representing the formation of pota.ssiura indoxyl-sulphate is as follows : — CsH.NO + SO.,<^g^ - SO./^gjp«"«^ + H.,0. [Indoxyl.] [Potassium [Potassium [Water.] hydrogen indoxyl-sulphate.] sulphate.] 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 calciiun (abundant) and magnesium (scanty). The composition of the })hosphates in urine is liable to variation. In acid urine the acidity is due to the acid salts. The chief are: — Sodium dihydrogen phosphate, NaHoP04, and calcium dihydrogen phosphate, Ca(H.J^04)o. CH. XXXIX.] SALTS OF URINE 597 In neutral urine, in addition, disodium hydrogen phosphate, Na.,HP04, calcium hydrogen phosphate, CaHPO^, and magnesium hydrogen phosphate, MgHP04, are found. In alkaline urine there may be instead of, or in addition to, the above, the normal phosphates of sodium, calcium, and magnesium [ISra3P04, Cay(P04).„ Mg3(P04).,]. 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 (NH4MgP04 + 6H,0). This crystallises in " coffin-lid " crystals (see fig. 384) 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 some- times 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 protein 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 P0O5 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.). The urine also contains minute quantities of organic phosphates, for instance, glycero-phosphates. Fig. .384.— Urinary sediment of triple phosphates (large prismatic crj'stals) and urate of ammonium, from urine which had undergone alkaline fer- mentation. 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. Suljihatfs. — 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 earthj- (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. 598 THE URINE [CH. XXXIX. QiKDi/ifd/ivf pstimal'inn of the salts is accnnn|)lishe(l by the use of solutions of standard strengtli, which are run into thi' urine till the formation (jf a precipitate ceases. The sbmdards are made of silver nitrate, barium chloride, and uranium nitrate or acetate for chlorides, suljihates, and |)iiosphates res|)ectively. 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 cystine. We shall, however, here only consider the commoner deposits, and for their identification the microscope and chemical tests must both be employed. Deposit of Uric Acid. — This is a sandy reddish deposit resembling cayenne pepper. It may be recognised by its crystalline form (fig. 382, p. 591) and by 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 sodium urate, the formation of which from the normal sodium urate of the urine may be represented liy the equation : — 2C,H,Na,N,0, + H,0 + CO, = 2C,H3NaN,0, + Na^COg. [Normal sodium [Water.] [Carbonic [Acid soilium urate.] [Sodium urate.] acid.] carbonate.] This deposit may be recognised as follows : — (1) It has a pinkish colour ; the pigment called wo-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. 384 may occur. Crystals of calcium oxalate may be mixed with this deposit (see fig. 385). Deposit of Calcium Oxalate. — This occurs in envelope crystals (octahedra) or dumb-bells. It is insolul)lc in ammonia, and in acetic CH. XXXIX.J URINARY DEPOSITS 599 acid. It is soluble with difficulty in hydrochloric acid. Calcium oxalate calculi are the commonest kind of stones in the kidne}^ Fig. 335. — Crystals of calcium oxalate. Fio. 380.— Crystals of cy.stiii. Deposit of Cystine. — Cystine (C(;Hi2N.2S.p4) is recognised by its colourless six-sided crystals (fig. 386). These are rare: they occur only in acid urine, and they may form concretions or calculi. Cystinuria (cystine 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.,H^ + 2H2O = (NHJ.COg. [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, Ca3(P04).2; amorphous. (2) Triple or ammonio-magnesium phosphate, MgNH^POi 5 coffin- lids and feathery stars (fig. 384). (3) Crystalline phosphate of calcium, CaHPO^, in rosettes of prisms, in spherules, or in dumb-bells. (4) Magnesium phosphate, Mg3(POJ.2-|-22H.,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 (CaHPO^ + 2H.30) may occasionally be GOO TRK URINE [CH. XXXIX. 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, CaCO^, appears but rarely as wliitish 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 IX URINE. In Acid Urine. i In Alkaline Urink. Uric Acid. — Whetstone, dumb-bell, | Phosphates. — Calcium phosphate, or sheaf-like aggregations of crystals Ca;(P04)j. Amorphous, deeply tinged by pigment. Triple phosphate, rrates. — Generally amorphous. The MgNH4P04 - 6H0O. Coffm-lids or acid urate of sodium and of ammonium feathery stars, may sometimes occur in star-shaped Calcium hydrogen phosphate, clusters of needles or sjiheroidal clumps CaHPO^. Rosettes, spherules, or dumb- with projecting spines. Tinged brick- bells, red. Soluble on warming. I Magnesium phosphate. Calcium 0.mlaffi. — Octahedra, so- ! Mg^iCPO^).. + 22HoO. Long plates, called envelope crystals. Insoluble in All the preceding are soluble in acetic acetic acid. acid without eifervescence. Cj/stim. — Hexagonal plates. Rare. Calriam Carhunatf, CaCO:-. — Biscuit- Leucine and TijTosine. — Rare. [ shaped crystals. Soluble in acetic acid Calcium Phosphafu, . \ with effervescence. CaHPOj + 2H.,0.— Rare. Ammonium Urate, C,H,(NH,),.N,0,. — "Thorn-apple" I spherules. I Leucine and Ti/rosine. — Very rare. Pathological Urine. Under this head we shall briefly consider only those abnormal constituents which are most frequently met with. Proteins. — There is no protein 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 especially euglobulins, 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 protein are the following : — (rt) 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 * This absolute statement is true for all practical purposes. Morner, however, has stated that a trace of protein (serum albumin pbiii the protein 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. XXXIX.] ALBUMIN AND SUGAR IN URINE 601 in a few drops of acetic acid, and so may be distinguished from pliosphates. If the urine is ;dlii Esh Fic.389. — Vertical section of skin. A. Sebaceous glan; Double Window. iiiiiiiiiiiiiiiiiiiiiiiiiiiiniiiniiiiiii^ kC Calorimeter Chamber. r I Air + Water + CO^; deficient in Oxygen Water Water removed by HpSO.. C02 removed by Soda-Lime Air minus COg and V\/ater; deficient in Oxygen, Oxygen enters/ Fig. 304. — The Atwater-Benedict Calorimeter. The above drawing contains one mistake ; the position of the soda-lime and sulphuric acid should be transposed. the carbon dioxide and the water are absorbed, and subsequently estimated. As the oxygen is used up by the individual, fresh oxygen is admitted in known quantities. The urine and fseces are analysed as well as the air, at the beginning and end of the experi- ment. The following additional data are therefore forthcoming : (1) the carbon, hydrogen, and nitrogen given out by the body ; (2) the oxygen taken in, and from these the amounts of protein, fat, and carbohydrate metabolised in the body, can be calculated and compared with the food ingested (see p. 613). In the calorimeter is a bicycle, the hind-wheel of which is replaced by a copper disc. The disc may be rotated in the field of G34 THE CONSERVATION OF ENERGY [CH. XLII. an electro-magnet by the turning of the pedals, which thus enables the rider to perform a measurable quantity of mechaiiical work. The calorimeter is also supplied with a bed, a table, a chair, and a double window, through which food of known weight and com- position can be supplied, so that an experiment may continue over two or three days, and the effect of work, sleep, various diets, etc., can be studied. 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 organisni 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 Voit's diet (see p. 480) :— Production of heal. Metabolism of Protein (T20 gr.) . 120 x 4000- Fat(100gr.) . 100x9400 = Carbohydrates Calories. 480,000 940,000 ( = 333 gr. starch)) I 333x4160 = 1,385,280 2,805,280 Ditfcharffi' of heat. Warming water in food, 2-6 kilos X 25 C.= 65,000 Warming air in respiration, 16 kilos x25 x0-24= 96,000 Evaporation in lungs, 630gr. x582r= 366,660 Radiation, evaporation, etc., at surface, jilms the thermal equivalent of mechanical work done accounts for the remainder .... 2,277,620 2,805,280 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. Hdnce the weight of water multiplied by 25 gives the number of calories expended in heating it. The weight of air is taken as * The calorie we are taking is sometimes called the small caloric ; by some the word calorie is used to denote the amount of heat necessary to raise 1 kilogramme of water 1° C, This is called the large calorie. CH. XLII.] HEAT-VALUE OF FOODS 635 weighing 16 kilos ; this also has to bo 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. If the man does external work the amount of energy dissipated is increased, and he would, in consequence, require more to be supplied in the form of food. Very few men in active work get on well with a smaller supply than 3000 large calories ( = 3,000,000 small calories) in their diet. A man, however, at rest is always doing what is called internal work, that is, maintaining the circulation, respiration, etc. From experiments of this nature, it has been found that the principle of the conservation of energy holds in the living body. The results may be stated as follows: — 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. CHAPTER XLIII TEMPERATURE Since departures from the normal body-temperature are among th9 fundamental physical signs of disease, and since observations of the temperature of the patient are only less frequent in medical practice than those of the pulse or of the tongue, it is necessary to have as complete an understanding as possible of the principles that regulate the fluctuations of the clinical thermometer. Animals may be divided into two great classes : — (1) Warm-blooded or homoiothermal animals, or those which have an almost constant temperature. (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 all invertebrates. The temperature of a man in health varies but slightly, being between 36'5° and ST'S'' C. (98' to 99" F.). Most mammals have approximately the same temperature : horse, donkey, ox, 3 7 '5 to 38° ; dog, cat, 385' to 39'; sheep, rabbit, 38' to 39'5" ; mouse, 37"5''; rat, 37"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 inaximum 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 tiinos of the maximum and minimum temperatures are also inverted. Inanition causes the 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. 630 CH. XLIII.] HEAT PRODUCTION 637 Heat Production. (1) IJffect of Chanycs of External Temperature. — In theory there is a fundamental difference between cold- and warm-blooded animals in their reactions to external temperature. A cold environment, since it lowers the temperature of the poikilothermic creature, reduces the metabolism of all its tissues, and thus reduces its heat production. The warm-blooded individual reacts in precisely the opposite way. Since his temperature remains constant, his heat production increases, in order to neutralise the effect of his cold surroundings. This has been demonstrated in the case of fasting dogs. An example may be given. Temperature of Air. IS-S" c. 14-7° C. 17-3° C. 18' C. Heat production in calories per kilo per diem . 78-7 74-7 69-8 67-1 In practice it is doubtful whether any such exact relation can be discerned in man, as it may be masked by other factors. We have already insisted upon the equality between the respective energy values of the food eaten and of the heat produced, and upon the advantage of an ample diet. In practice it is the amount of food taken which controls the heat production, rather than the reverse. The majority of well-to-do people, whose appetite is stimulated by their palate, maintain a constant body-temperature by regulating the loss rather than the production of heat. In this connection the following figures, derived from observations made upon a dog who was fed upon considerable quantities of meat, may be compared with those obtained when the same animal was fasting. Temperature of Air. re. 15° C. 20' G. 25° C. 30' C. Calories per kilo per diem — dog \ fasting J 86-4 63-0 55-5 54'2 56-2 Calories per kilo per diem— dog 1 given 320 g. meat -81 calories per / kilo \ 87-9 86-6 76-2 ... 83-0 In the fasting dog a lowering of the surrounding temperature, increases heat production in the animal ; in the well-fed dog this is hardly noticeable. On the other hand, it is instructive to note the types of food eaten by the natives of different climates. The Indian, who eats rice gets 638 TEMPERATURE [CH. XLIII. his carbon with less than half the heat production of the Esquimaux, who makes blubber his staple article of diet. (2) The Seat of Heat Production. — So far as our present knowledge goes, the amount of metabolism in the bones, cartilages, and connec- tive tissues is so small as to form but a* trifling part of the whole metabolism of the body. The same is probably true of unstriped muscle. Of the coetficient of oxidation (i.e. the amount of oxygen used up per gramme of tissue per minute) of the central nervous system we have no accurate knowledge. Any discussion, therefore, of the principal seats of chemical action in the body resolves itself into a comparison batween the glandular and muscular (skeletal) structures. These present a remarkable contrast. The very vascular nature of the secreting glands (the liver is said to contain one-quarter of all the blood in the body), as well as actual measurements of the oxygen used up by many of them, indicate that they are the seat of very active chemical changes, which, relatively to muscle, is maintained with a considerable degree of constancy. The very function which the digestive glands serve implies at least a certain constancy of rhythm. Be the climate what it may, the daily food must be digested. Quite otherwise is it with the muscles. When they are active they are the seat of metabolism as great as that of the glands, but their metabolism is capable of much more complete suspension during rest. When the muscles are inactive the glandular structures, in spite of their smaller bulk, account for a very appreciable quantity of the whole metabolism of the body — perhaps as much as half. But when the muscles are exercised to any considerable extent, the con- tribution of the glands becomes an insignificant item in the met- abolism of the body. The muscles, then, by reason of their large mass, and of the great variations of which their metabolism is capable, are essentially the regulators of heat production. Apart from active contraction, the muscles differ at different times in tonus. This difference finds its metabolic expression. Zuntz, by cutting the nerves of the already resting leg of a dog, abolished the muscular tonus and greatly lessened the metabolism. Alterations in tonus probably play a very important part in the production of heat. Our muscles are "braced" in cold and "slack" in warm climates. The latter effect is very strikingly shown by the extreme muscular flabbiness which evinces itself in such a climate as that of the Ked Sea. Where the cold is such that increased tonus proves inadequate to meet the demand for heat, a greater degree of muscular activity (shivering) supervenes unless actual exercise is taken. Heat Loss. The two channels of loss susceptil^le of any amount of variation are the lungs and the skin. The more air that passes in and out CH. XMII.] HEAT LOSS 639 of the lungs, the greater will be the loss in warming the expired air and in evaporating the water of respiration. 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 evaporation that occurs from its surface. The great regulator, however, is un- doubtedly 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. The production of perspiration has a cooling effect, since the latent heat necessary for the evaporation of the sweat is derived chiefly from the body. The relative importance of radiation and evaporation depends very much upon the humidity of the atmosphere. Here it is necessary to distinguish between "relative" and "absolute" humidity. The important point is the amount of water which the air can absorb. Now, cold air, even though it is almost dry, is capable of taking up very little aqueous vapour. Warm air may contain a good deal {i.e. the absolute humidity may be greater than that of the cold) and yet may be far from saturated (i.e. its relative humidity may be low). The loss of heat by evaporation is therefore relatively small in cold weather, even though it be dry. The burden of heat regulation then falls upon radiation, and it, to be efficient, demands a warm skin ; hence the glow of heat we experience when we take exercise in still, cold weather. In hot climates radiation becomes less important, and the possibility of heat loss from the skin therefore depends upon evaporation. Evaporation in its turn depends upon the "relative" humidity of the air and upon the existence of winds. The loss of heat by evaporation is at its maximum in dry hot climates, and is greatly promoted by the wearing of clothes which are relatively porous. In such climates physical "fitness" is pro- moted by the taking of a considerable amount of out-of-door exercise. 640 TEMPERATURE [Cn. XLIII. Quite otherwise is it in climates like that of the coast-line of British East Africa, where the tropical sun is combined with the moisture-laden wind. There the possibilities of heat loss both by radiation and by evaporation are small, and the English official per- force reduces his heat production to a minimum. He lives indoors, takes as little exercise as possible, and the pallor of his countenance contrasts strongly with the high colour which his colleague in India or Egypt exhibits. Certain Factors -which govern the Relation bet^veen Heat Production and Heat Loss. (1) Size. — The heat production of the body, other things being equal, depends upon the mass of the body; the heat loss, on the surface. The production therefore varies with the cube of the linear dimensions, whilst the loss of heat only varies with the square. The smaller the animal the greater must be its heat production relatively to its heat loss. The loss of heat is diminished both by the occurrence of fur and by the absence of sweat in the skins of most small animals, and the smaller the animal the greater is its metabolism per gramme (see also p. 399), The same is, no doubt, true of individuals ; but in this, as in other cases, the natural conditions may be much modified by artificial ones, such as clothing. (2) ^//e.— Inasmuch as the young are small, active, and growing, their heat production is relatively large; and further, since the extreme constancy of temperature which an adult man has attained is an evolved characteristic, very young children, in common with animals, are subject to changes of body-temperature which would be of much graver import in older people. Warm-blooded animals in the embryonic stage are practically cold-blooded, the regulatory mechanism which keeps the bod3'-temperature constant not being fully developed at this stage. (3) Constitution. — Different individuals differ greatly in their power of heat loss. Apart from differences in size and in the faculty of perspiration, there remains such differences as those of compactness of shape, and especially in the amount of adipose tissue with which the viscera are protected. The Influence of the Central Nervous System on Heat Regulation. — The central nervous system controls the loss of heat directly through the vaso-motor and secretory nerves supplying the skin. That the control of heat production is important, is shown by the effect on the body-temperature of cutting the spinal cord, or of the drug curare. Curare cuts off the muscles from the stimuli which would naturally reach them through the motor nerves. Not only CH. XLITI.] FEVER 641 does the temperature at once fall, but the animal becomes poikilo- thermic. The seat of the heat-regulating mechanism in the brain is a matter of much uncertainty. It is possibly in the basal ganglia of the cerebrum, or in this neighbourhood. Fever. — Diseases may cause the temperature to vary considerably, especially those which we term febrile. A mere increase in the production of heat does not necessarily cause fever. The administration of food causes increased combustion in the body ; but there is no rise of temperature in health, because pari passu with the increased production there is increased loss of heat. Similarly, diminution in the loss of heat, such as 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. A febrile condition may, however, occur if tight-fitting and otherwise unsuitable clothing which interferes with the proper action of the skin is worn in hot weather ; this is the frequent cause of " heat- stroke " among soldiers in the tropics. In fever there is increased production of heat, as is shown by metabolic balance-sheets; the intake of food is usually small, and the discharge of carbon, nitrogen, etc., results mainly from tissue disintegration ; this is even greater than in ordinary inanition ; the tissues are said to be in a " labile " condition, that is, they are easily broken down. Usually the skin is dry, the sweat-glands, like most of the secretory glands, being comparatively inactive, and so the discharge of heat is lessened. The skin, however, may sometimes be bathed in perspiration and yet high fever be present. The essential cause of the high temperature in fever is neither increased formation nor diminished discharge of heat, but an interference with the mechanism which in health operates so as to equalise the two. The Action of Drugs. — From what has been said, it will be evident that drugs may reduce fever in more than one way : for instance, they may reduce the metabolism of the muscles, e.g. quinine ; they may cause increased heat loss by promoting perspiration and vascular dilatation in the skin, e.g. pilocarpine ; or they may act on the central heat-regulating mechanism (corpus striatum ?), e.g. phen- acetin. 2 S CHAPTER XLIV THE CENTRAL NERVOUS SYSTEM The central nervous system is contained within the cranio-spinal cavity, and consists of brain and spinal cord. These two parts are Fig. 395.— Base of the brain. 1, Superior lonpituiiinal fissure ; 2, •!', 2", anterior cerebral lobe ; 3, fissure of Sylvius, between anterior anTamidal bundles; po., transverse fibres passing po, behind, and po„, in front of py; r., niphe ; o.s., superior olive ; a. v., bundles of motor root of V. nen-e enclosed in a prolongation of the substance of Rolando ; t, trapezium ; Vf., the sixth nerve, n.Vf., its nucleus ; I'//., facial nerve; Vll.a., intermediate por- tion, n.VII., its nucleus; VIIL, auditory nerve; n.VIII., J)eiters' nucleus, formerly called the lateral nucleus of the auditory. (After Quain.) fibres, most of which are passing to the cerebellar hemispheres and form the middle cerebellar peduncles. Intermingled with these is a considerable amount of grey matter {nuclei pontis). From the cells of the nuclei pontis, the fibres of the middle peduncle take origin, and many fibres and collaterals of the pyramidal tract arborise around them. The continuation of the pyramids {py) is imbedded between these transverse bundles. The pyramidal fibres which terminate in the pons are situated postero-laterally, and are spoken of as cortico-jwntine in contradistinction with those of the pyramidal tract proper (corticospinal) which pass down through the bull) to the cord. The pyramidal bundles are separated from the reticular formation en. XLVI.] SECTIONS OF PONS AND MID-BRAIN 671 by deopor transvorso fil^res, which constitute what is known as the trapezium {t). These fi])res holong to a different system, and form part of the central auditory path ; some of them connect the auditory nuclei of the two sides together. The larger olivary nucleus is no longer seen, but one or two small collections of grey matter {o.s.) repre- sent it and constitute the superior olivary nucleus. These as well as a collection of nerve-cells in the trapezium {nucleus of the trapezium) are connected with fibres of the trapezium, while some of their axons pass into the adjacent lateral part of the fillet. The nucleus of Deiters (n. VIII., fig. 413) begins to appear in the upper part of the bulb, and extends into the pons ; it lies near the floor of the ventricle, a little mesial to the restiform body. The nerve-fibres connected with its cells pass towards the middle line, and enter the posterior longitudinal hundle, which is more clearly seen in the two next sections (fig. 414). This bundle of fibres connects Deiter's nucleus, the nucleus of the third and sixth nerves, and the anterior horn cells of the spinal cord. The fibres which pass into it from Deiters' nucleus bifurcate, one branch passing upwards to arborise around the cells mainly of the oculo-motor nucleus of the opposite side ; the other extends downwards through the bulb into the cord, where they are found in the antero-lateral descending tract of each side. They end by synapses around the anterior horn cells. This bundle receives in addition to the fibres from Deiters' nucleus, other fibres from the sensory nucleus of the fifth nerve, and from large cells in the reticular for- mation of mid-brain, pons, and bulb. The nerves which are connected with the grey matter of this region of the pons are the sixth, seventh, and eighth, as shown in the diagram. The nuclei in connection with the fifth nerve are higher up, where the floor of the ventricle is again narrowing. At last, in the region of the mid-brain, wo once more get a canal (Sylvian aqueduct) which corresponds to the central canal of the spinal cord. Fifth and Sixth sections are taken through the mid-brain, and are drawn on a smaller scale than the others we have been examin- ing ; they represent the actual size of the sections obtained from the human subject. Near the middle is the Sylvian aqueduct, with its lining of ciliated epithelium. In the grey matter which surrounds it are large nerve- cells from which the fourth nerve, and higher up the thii'd nerve, originate ; the fibres of the third nerve are seen issuing from these in fig. 414, B., III. The reticular formation of the pons is continued up into the mid-brain, and is called the tegmentum. It is composed of both longitudinal and transverse bundles of fibres intermingled with grey matter. Its transverse fibres include those of the superior peduncles of the cerebellum which decussate in the middle line (fig. 414, A., S.C.P.). 672 STRUCTURE OF THE BULB, PONS, AND MID-BRAIN [CH. XLVI Another important longitudinal bundle in the tegmentum is the fillet. This, we have seen, is the longitudinal continuation of the internal arcuate libres, which, starting from the colls of the posterior column nuclei of the opposite side, form the second relay on the sensory path; to those libres others are added which originate from Fig. 414. — Outline of two .sections across tlie mid-brain: A, through the middle of the inferior; B, through the middle of the superior corpora quadrigemina, C.Q. Cr., crusta; S.N., substantia nigra — shown only on one side ; T, tegmentum; S, Sylvian aqueduct, with its surrounding grey matter; L.G., lateral groove; ji.l., i)ost«rior longitudinal bundle; d.V., descending root of tlie fifth nerve; S.C.P., su[)erior cerebellar peduncle; P, fillet ; HI., third nerve. The dotted circle in 1! represents the situation of the tegmental nucleus. In 15 the three divisions of the cnista are indicated on one side. The pyramidal tilires (Pi/) are in the middle, and the fronto-cerebellar (F.C.) and temporo- occipital cerebellar (T.O.C.) at the sides. (After Sch^ifer.) other masses of grey matter in bulb and pons. In the mid-brain the fillet splits into three bundles, termed the lateral, the upper, and the mesial fillet. (1) The lateral fillet is chiefly formed by fibres derived from the accessory audi- tory, the inferior olivary, and trapezoid nuclei of the opposite side. Some of its fibres terminate by synapses around a new collection of cells (tiie lateral fillet nucleus) ; their axons pass inwards towards the raphe. The rest of its fibres can be traced to the grey matter of the inferior corpora quadrigemina. (2) The upper fillet consists of fibres which go to the superior corpora quadri- gemina and partly to the tegmental region of the mid-brain and optic thalamus. (3) The mesial fillet goes on through tlie tegmentum of tlie crus cerebri, and its fibres terminate around the cells of the optic thalamus, and the subthalamic region. From here fresh axons forming a new relay continue the afferent impulses to the cortex of the cerebrum. The mesial fillet is the important link in this region between the sensory spinal nerves and the part of the brain which is the seat of those processes we call sensations. But most of the fibres which continue the sensory path of the cranial nerves form another less well-defined tract {the central tract of the sensory cranial nerves) which Ues dorsal to the fillet, but terminates like it in the subthalamic region and optic thalamus, whence a new relay carries on the impulses to the cortex. Ventral to the tegmentum is a layer of grey matter, of which the cells are deeply pigmented ; hence it is called the substantia nigra (S.N.). This receives many collaterals from the pyramidal bundles. The white matter on the ventral side of this is known as the ClI. XLVI.] ORIGINS AND FUNCTIONS OF CRANIAL NERVES 673 criLsta (Or) or pes. It is here that the pyramidal bundles are situated ; these occupy its middle three-fifths (Py). The mesial fifth is occupied by fibres passing from the frontal region of the cerebrum to the pons, and thence to the cerebellum ; hence they are called fronto-cerebellar fibres. The fibres occupying the lateral fifth are usually spoken of as temporo-occipital cerehdlar fibres, but there is no certainty as yet regarding their origin or functions. The corpora quadrigemina are formed mainly of grey matter ; from each superior corpus a bundle of white fibres passes upwards and forwards to the geniculate bodies, eventually joining the optic tract of the same side. The white layer on the surface of the grey matter of the C. quadrigemina is derived from the optic tract ; these fibres come from the retina, and terminate by arborising around the cells of the grey matter of the C. quadrigemina. The cells of the grey matter of the corpora quadrigemina differ greatly in form and size ; the destination of their axons is not pre- cisely known, but some pass ventralwards, cross at the raphe, and constitute the fountain decussation of Meynert ; after decussation they form the main mass of the ventral longi- tudinal bundle ; this gives off collaterals to the x X ^v^' nuclei of the three nerves that supply the eye muscles, and then runs ventro-laterally to the posterior longitudinal bundle, with which its fibres ultimately mix in the antero-lateral descending tract of the spinal cord. ^^^_ 4i5.-section through Seventh section. — This is through the crus of cerebrum, cr, T. • 1 i> j/i'ia_- crusta ; S.N., substantia crus. it IS made up OI crusta (which contains nigra; T, tegmentum. the motor fibres), tegmentum (which contains the sensory fibres, especially the bundle called the mesial fillet), and the substantia nigra, the grey matter which separates them. Origins and Functions of the Cranial Nerves, Having now studied the internal construction of these parts, we can take up more fully the origins and functions of the cranial nerves which originate there. The olfactory nerve is connected to the cerebrum, and will be considered with the sense of smell. The optic nerve will be studied with vision, though it is, as we have seen, immediately connected with the mid-brain. The third, fourth, and sixth nerves supply the muscles of the eye. Gaskell discovered among the rootlets of the third and fourth nerves the vestiges of a degenerated and functionless ganglion, which indicates the previous existence of a separate sensory root. Sherrington has shown that in these three nerves sensory fibres are present which are connected to the sensorial nerve endings (muscle-spindles). The third nerve (motor octdi) arises in a group of nerve-cells in 2 u 674 STRUCTURE: Otr THE BULB, PONS, AND MtD-BRAIN [cn. XLVt, the 'Trey matter on tlio side of the Sylvian aqueduct underneath the superior corpus quadrigeminum, and close to the middle line. The anterior part of this nucleus is composed of small cells from which small nerve-fibres originate for the ciliary muscle and sphincter of the iris (intrinsic muscles of the eyeball). These fibres correspond to the visceral libres of a spinal nerve, and, like them, have a cell station, namely, in the ciliary ganglion. The posterior part of the nucleus is composed of larger cells, and these give rise to larger fibres which supply the following extrinsic eye-muscles: — superior rectus, inferior rectus, internal rectus, inferior oblique and levator palpebrse. The fourth nerve (trochlear) takes origin from the grey matter immediately below the centre of the third, but slightly more lateral in position. It is underneath the inferior corpus quadrigeminum. It supplies the superior oblique muscle of the opposite eyeball. The sixth nerve (ahducens) arises from a centre beneath the eminentia teres in the upper part of the floor of the fourth ventricle near the middle line. It supplies the external rectus. It is obviously necessary that the eye-muscles should work tor^ethor harmoniously, that the two eyeballs should also be moved simultaneously and in corresponding directions, and that such move- ments should take place in accordance with the necessities of vision. This is provided for in the shape of association fibres which link the centres of the eye-muscles together. The principal association tracts are the posterior longitudinal bundle, which connects the nuclei of the third and sixth nerves, and the ventral longitudinal bundle which unites the optic nerves through the intermediation of the cells of the C. quadrigemina, with the nuclei of all these nerves. It should also be remembered tliat all the fibres of the fourth, and some of those of the third nerve, decussate in the middle line. The fifth nerve (trigeminal) is a mixed nerve ; it leaves the side of the pons in a smaller motor, and a larger sensory division. The former supplies the muscles of mastication, the tensors of the palate and tympanum, the mylo-hyoid, and the anterior belly of the digastric; the sensory division has upon it a ganglion called the Gasserian ganglion; it is the groat sensory nerve of the face and head. The motor fibres arise from the motor nucleus (V^n, fig. 408), which lies at the lateral edge of the upper part of the floor of the fourth ventricle, but a certain number of its filjres arise from cells in the lower part of the mid-brain and upper part of the pons; this long stretch of nerve-cells, indicated by the long blue tail in the diagram, is called the accessory or siqjerior motor nucleus of the fifth. The sensory fibres arise from the cells of the Gasserian ganghon, which resemble in structure those of a spinal ganghon ; one branch of each passes to the periphery in the skin of the head and face, and CH. XLVI.] THE SEVENTH NERVE 675 the other grows centralwards ; or reaching the pons these bifurcate, the ascending branches arborise around the 2^'^'''ncipal sensory nucleus of the fifth (Vd, fig. 408), which lies just lateral to the motor nucleus, while the descending branches pass down into the bulb, where they form the descending root of the fifth, and some reach as far down in the spinal cord as the second cervical nerve. Mingled with these descending fibres are numerous nerve-cells, many of which are grouped in clusters (islands of Calleja), and the descending fibres form synapses around them. The new axons arising from the cells of the sensory nuclei pass upwards in three principal tracts: — (1) The greater number cross the raphe and join the mesial fillet ; (2) some ascend the fillet of the same side ; and (3) others pass into a special ascending bundle which lies near the ventricular floor (the central tract of the cranial sensory nerves). The seventh nerve (facial) is the great motor nerve of the face muscles. It also supphes the platysma, the stapedius, stylo-hyoid, and posterior belly of the digastric. When it is paralysed, the muscles of the face being all powerless, the countenance acquires on the paralysed side a characteristic, vacant look, from the absence of all expression : the angle of the mouth is lower, and the paralysed half of the mouth looks longer than that on the other side ; the eye has an unmeaning stare, owing to the paralysis of the orbicularis palpe- brarum. All these peculiarities are exaggerated when at any time the muscles of the opposite side of the face are made active in any expression, or in any of their ordinary functions. In an attempt to blow or whistle, one side of the mouth and cheeks acts properly, but the other side is motionless, or flaps loosely at the impulse of the expired air ; in trying to suck, one side only of the mouth acts ; in feeding, on account of paralysis of the buccinator muscle, food lodges between the cheek and gums. The motor fibres originate from a nucleus in the ventricular floor below that of the fifth and to the outer side of that of the sixth nerve. As they curve over the nucleus of the sixth, they give ofi" a bundle of fine fibres which cross the raphe, but their destination is unknown. The facial nucleus receives collaterals from the sensory tracts in the reticular formation. The seventh nerve, however, is not wholly motor. The geniculate ganghon on it is of spinal type ; the fibres which arise from it pass centrally into the pars intermedia of Wrisberg, which enters the pons between the seventh and eighth nerves ; these, like other sensory fibres, divide into ascending and descending branches ; the latter have been traced down to the sensory nucleus of the glosso-pharyngeal nerve. The peripheral branches of the geniculate ganglion cells pass into the large superficial petrosal and chorda tympani, the gustatory fibres of which they probably furnish. The secretory fibres of the chorda 676 STRUCTURE OF THE BULB, PONS, AND MID-BRAIN [CH. XLVI. tympani are effereat fibres which reach it from the facial nucleus via the pars intermedia. The eighth nerve (auditory) runs into the hinder margin of the pons by two roots. One winds round the restiform body dorsal to it, and is known as the dorsal or cochlear division ; the other passes ventro-mesially on the other side of the restiform body, and is known as the ventral or vestibular division. We will take these two parts separately. The fibres of the cochlear nerve take origin from the bipolar nerve-cells of the spiral gangUon of the cochlea ; the peripheral axons ramify among the hair cells of the organ of Corti, and the central axons pass towards the pons ; as they enter they bifurcate, and some pass to and arborise NUCL LEMNISCI JAORiGEMINA NERVE-ENDINGS IN ORGAN OF CORTi Fig. 41tj. — Cochlear division of tlie auditory nerve, r, Restiform body ; V, descending root of the fifth nerve; tub.ac, acoustic tubercle; n.acc, accessory nucleus; .1.0., superior olive; n.tr., trapezoid nucleus; 71. 1'/., nucleus of the sixth nerve ; I'/., issuing fibre of sixth nen-e. (Schafer.) around a collection of nerve-cells situated between the two roots and the restiform body, called the accessory auditory nucleus ; the remain- ing fibres terminate similarly in a collection of cells in the grey matter overlying the restiform body, and extending into the ventricular floor in its widest part. This is called the ganglion of the root, and the mass of grey matter is termed the acoustic tubercle. The auditory path is continued by new axons that arise from these cells. Those from the accessory nucleus enter the trapezium, and pass in it partly to the superior olive and trapezoid nucleus of the same side, but mainly to the corresponding nuclei of the opposite side ; some fibres end here, others traverse the nuclei, and merely give off collaterals to them ; they then turn upwards in the lateral fillet, and so reach the inferior C. quadrigemina. The fibres which arise in the acoustic CH. XLVI.] THE Eir.HTH NEKVE 677 tubercle pass superficially over the floor of the ventricle, forming the strice acousticcc; having crossed the raphe, they join the fibres from the accessory nucleus in their course to the superior olive and fillet. Here again, however, a few fibres pass to the fillet of the same side. The vestibular nerve arises from the bipolar cells of the gan(jlion of Scarpa, which is situated in the internal auditory meatus. The peripheral axons ramify among the hair cells of the epithelium in the utricle, saccule, and semi-circular canals. The central axons enter a collection of small nerve-cells between the restiform body and the descending root of the fifth ; this is termed the principal nucleus ; here TO VERMI FIBRES O VESTIBULA ROOT NERVE ENDINGS IN MACUL/E & AMPULL/E Fig. 417. — Vestibular division of the auditory nerve, r, Bestiform body ; V, descending root of the fifth nerve ; d, fibres of descending vestibular root ; n.d., cell of descending vestibular nucleus ; D, nucleus of Deiters ; B, nucleus of Becbterew; n.t., nucleus tecti of cerebellum : p.l.h., posterior longitudinal bundle. (Schafer.) they bifurcate ; the descending branches run towards the lower part of the bulb, and arborise around the cells of the neighbouring grey matter (descending vestibular nucleus). The ascending branches pass upwards in the restiform body to the cerebellum, in their course giving off many collaterals which form synapses with the large cells of two nuclei near the outer angle of the ventricular floor, and known as the nucleus of Deiters and nucleus of Bechterew respectively. The fibres which arise from Deiters' nucleus pass into the posterior longitudinal bundles of both sides (see p. 674) ; those which start in Bechterew' s nuclenis become longitudinal, but their destination is uncertain. The accompanying diagrams (figs. 416 and 417) will serve to render these complex relationships clearer. 678 STRUCTURE OF THE nULB, PONS, AND MID-BRAIN [CII. XLVI. The ninth nerve (glosso-pharyngeal) gives filaments through its ' tympanic branch (Jacoljson's nerve) to parts of the middle ear; also, to the carotid plexus, and through the great superficial petrosal nerve to the sphono-palatine (Meckel's) ganglion. After communi- cating, either within or without the cranium, with the vagus, it leaves the cranium, divides into the two principal divisions indicated by its name, and supplies the mucous membrane of the posterior and lateral walls of the upper part of the pharynx, the Eustachian tube, the arches of the palate, the tonsils and their mucous membrane, and the tongue as far forwards as the foramen caecum in the middle line, and to near the tip at the sides and inferior part. It contains motor fibres to the stylo-pharyngeus, the constrictors of the pharynx, and probably to the levator palati and other muscles of the palate, except the tensor, which is supplied by the fifth nerve. The nerve also contains fibres concerned in common sensation, and the sense of taste, and secretory fibres for the parotid gland. The cells from which the motor fibres originate are situated in a special nucleus, which is a continuation upwards of the nucleus ambiguus (the chief motor nucleus of the tenth or vagus nerve). The sensory fibres arise in the jugular and petrosal ganglia from cells of the spinal ganglion type. When the central axons reach the bulb they bifurcate as usual; the descending branches pass down the funiculus solitarius and terminate in synapses around the cells scattered among its fibres. The ascending branches pass almost horizontally to arborise around the cells of the principal nucleus (IX. in fig. 408). The arrangement, in fact, is very like that of the tenth nerve now to be described. The tenth nerve {vagus or pneumo-gastric) has so many and important functions that I shall not attempt to describe them here ; it would mean rewriting a great deal of what we have already learnt in connection with heart, respiration, digestion, etc. It is sufficient to say that it contains both efferent and afferent fibres. The efferent fibres arise partly from the upper part of the combined nucleus, which lower down gives origin to the spinal accessory nerve (fig. 408, X.) but mainly from the nucleus ambiguus, the position of which is shown in fig. 408, coloured blue, and also in transverse section in figs. 412 and 418. The afferent fibres originate from the cells of the ganglion of the trunk and of the root ; they enter the bulb and bifurcate ; the ascending branches are short and arborise around the cells of the principal nucleus (X. in fig. 408) ; the descending fibres, together with similar ones derived from the glosso-pharyngeal nerve, and pars intermedia, pass down in the descending root of vagus and glosso- pharyngeal, which is also known as the funiculus solitarius. These fibres terminate by arborising around the cells of the grey matter that lies along its mesial border (descending nucleus of vagv^ and Cir. XLVI.] TIIK KLEVKNTII AND TWELFTH NKRVKS 679 glosso-pharyiKjeal). This approaches tho middle lino as it descends, and finally joins that of the opposite side over the central canal {commissural nucleus). The eleventh nerve {spinal accessory) is wholly efferent : it arises by two distinct origins — one from a centre in tho floor of the fourth ventricle, and connected with the glosso-pharyngeal-vagus-nuclous ; the other, from the outer side of the anterior cornu of the spinal cord as low down as the fourth cervical nerve. The fibres from the two origins come together at the jugular foramen, but separate again into two branches, outer and inner. The outer, consisting of large medullated fibres from the spinal origin, supplies the trapezius and FiQ. 418. — The tenth and twelfth nerves, pyr, Pyramid ; n.XlI., nucleus of hypoglossal ; XH., fibre of hypoglossal; d.n.X.Xl., combined nucleus of vagus and spinal accessory; n.amli., nucleus ambiguus; f.s., fasciculus solitarius, descending fibre.s of vagus and glosso-pharyngeal; f.s.n., its nucleus; A'., motor fi bre of vagus ; g, ganglion cell in vagus trunk giving rise to a sensory fibre; d.y., descending root of the fifth nerve ; r, restifoim body. (Schafer.) sterno-mastoid muscles. The inner branch, consisting of small medullated fibres from the medulla, supplies chiefly viscoro-motor and cardio-inhibitory filaments to the vagus. The muscles of tho larynx, all of which are supplied by branches of the vagus, derive their motor nerves from the accessory; Vrolik states that in the ■ chimpanzee the internal branch of the accessory does not join the vagus at all, but goes direct to the larynx. The crico-thyroid, how- over, receives fibres which leave the bulb by glosso-pharyngeal rootlets. The twelfth nerve {hypoglossal) is also entirely efferent. It sup- plies the muscles of the tongue. It arises from a large celled and long nucleus in the bulb, close to the middle line (see figs 408 and 418). CHAPTER XLVri STRUCTURE OF THE CEREBELLUM The cerebellum is composed of an elongated central portion or lobe, called the vermis or vermiform process, and two hemispheres. Each hemisphere is connected with its fellow by means of the vermiform process. The cerebellum is composed of white and grey matter, the latter Fio. 419. — Cerebellum in section .iti'l fourth ventricle, with the nei;,'hbourin^' parts. 1, median Lrroove of fourth ventricle, emling below iu the cidntims scriptorins, with the loii;_'ituiiinal eminences formed by the fasciculi rcriYc,--', one on each side; '2, the same i;roove, at the place where the white streaks of the auditorj' nerve emerge from it to cnjss the floor of the ventricle ; 3, inferior peduncle of the cerebellum, formed by the restiform body; 4, funiculus gracilis; above this is the calamus scrip- tonus ; 5, superior i)eiluncle of cerebellum ; G, (>, fillet to the side of the crura cerebri ; 7, 7, lateral grooves of the crura cerebri ; 8, corpora (luadrigeniina. (From Sappey, after llirschfeld and Leveille.) being external, like that of the cerebrum, and like it, infolded, so that a larger area may be contained in a given space. The convolu- tions of the grey matter, however, are arranged after a different pattern, as shown in fig. 419. The tree-like arrangement of the white 680 CH. XLVII.] THE CEREBELLUM 681 matter on section has given rise to the name arbor vita. Besides the grey substance on the surface, there are, in the centre of the white substance of each hemisphere, small masses of grey matter, the largest of which, called the corpus dentatum (fig. 420, cd), resembles very closely the corpus dentatum of the olivary body in appearance. Fig. 420. — Outline sketch of a section of the cerebellum, showing the corpus dentatum. The section has been carried through the left lateral part of the pons, so as to divide the superior peduncle and pass nearly through the miildle of the left cerebellar hemisphere. The olivary body has also been divided longitudinally so as to expjose in section its corpus chntatma. cr, (,'rus cerebri ; /, fillet ; q, corpora quadrigemina ; sp, superior peduncle of the cerebellum divided ; mp, middle peduncle or lateral part of the pons Varolii, with fibres passing from it into the white stem ; ay, continuation of the white stem radiating towards the arbor vitaj of the folia ; cd, corpus dentatum ; o, olivary body with its corpus dentatum ; p, pyramid. (Allen Thomson.) §. In a section through the cerebellar cortex the following layers can be seen. Underneath the pia mater is the external layer of grey matter; it is formed chiefly of fine nerve-fibres with small nerve-cells scattered through it. Into its outer part, processes of pia mater pass verti- cally; these convey blood-vessels. There are also here numerous long tapering neuroglia-cells. The internal or granular layer of grey matter is made up of a large number of small nerve-cells mixed with a few larger ones, and some neuroglia-cells. Between the two layers is an incomplete stratum of large flask-shaped cells, called the cells of Purkinje. Each of these gives oS" from its base a process which becomes the axon of one of the medullated fibres of the w^hite matter ; the neck of the flask passing in the opposite direction breaks up into dendrites which pass into the external layer of grey matter. By Golgi's method (fig. 421) these dendrons have been shown to spread out in planes transverse to the direction of the lamellae of the organ. Each ceU of Purkinje is further invested by arborisations of two sets of nerve-fibres. One of these (originating from the fibres of the white matter which are not continuous as axis-cylinders from the cells of Purkinje) forms a basket-work round the dendrons ; the other (originating as axis-cylinder processes from the nerve-cells of the external layer) forms a felt-work of fibrils round the body of the cell. The ceUs of the internal layer of grey matter are small ; their 682 STRUCTURE OF THE CEREHELLCM [CH. XLYIl. dendrites intermingle with those of neighbouring cells ; their axons penetrate into the external layer, but their final destination is uncertain. Eamifying among these cells are fibres characterised by possessing bunches of short branches at intervals (moss-fibres of Cajal). The jioduncles of the cerebellum are three in number — superior, nuddle, and inferior ; we have already had occasion to mention them in our study of the bulb, pons, and mid-brain. The course of the fibres has been chiefly studied by the degeneration method. The inferior peduncle, or restiform body, is composed of ascending fibres which pass into it — (1) from the cerebellar tracts of the Km. 421.— Section of cerebellar cortex, stained by Golgi's method ; I. taken across the lamiua ; II. in the direction of the lamina; a, outer or molecular layer; h, inner or granular layer ; i^ white matter, n, Cell of I'urkinje; !>, small cells of inner layer; c, dendrons of these cells; t/, axis- cylinder process of one of these cells becominK lont,'iluilinal in the outer layer ; f , bifurcation of one of these ; jr, a similar cell lying in the white matter. (Ramon y Cajal.) same side, and (2) from the olivary nucleus of the opposite side; (3) possibly a few fibres from the nucleus gracilis and nucleus cuneatus also join it; and lastly, (4) it rcccivi^s numerous fibres from the vestibular nerve, or from the nuclei in which it terminates in the pons. The inferior peduncle is thus inainly a spino-cere- bellar path, serving by the cerebellar tracts to unite the same side of the cord with the vermis, and the opposite side of the cord with the cereliellar hemisphere via the opposite olivary nucleus and reticular formation of the bulb. The middle peduncle is wholly formed of fibres which originate from the cells of the nuclei pontis : they pass from one side of the pons to the opposite cerebellar hemisphere. This peduncle is the last relay of the cerebro-cerebellar path. CH. XLVII.] CONNECTIONS OF THE CEREBELLUM 683 The awperior peduncle : the axons of the cells of Piirkinjo mainly terminate in the nucleus dentatus, and the other subsidiary masses of ^rey matter situated in the interior of the cere])ollum ; from the cells of these nuclei a fresh relay of fd)res issues, conveying impulses from the cerebellum to other parts, but mainly to the opposite cerebral hemisphere ; these fibres constitute the superior cerebellar peduncle. They cross the middle line, give off numerous collaterals to the red nucleus of the opposite side, and also to the nucleus of the opposite third nerve. The majority terminate in the optic thalamus, whence a fresh relay continues the impulse to the cerebral cortex. This therefore is the cerebello-cerebral path. After the fibres of the superior peduncle have crossed the middle line, they give off descending branches which run towards the bulb and cord, though whether they reach as far down as the spinal cord is doubtful. There is, however, a cerebello -spinal path via the red nucleus with which the fibres that issue from the cerebellum com- municate after crossing, for it is from the red nucleus that the bundle of Monakow arises which crosses the middle line and is seen in the cord as the rubro-spinal or prepyramidal tract ; it terminates in the anterior horn of the spinal grey matter. The cerebello -spinal path therefore exhibits a double crossing ; the first is that of the superior peduncle to reach the opposite red nucleus, and the second is that of the bundle of Monakow ; in this way the cerebellar hemi- sphere is linked to the same side of the spinal cord. In addition to all these fibres, the superior peduncle also contains some fibres of the spino - cerebellar tracts, which after ascending the spinal cord, bulb and pjons turns round and course back along the superior peduncle into the cerebellum; these fibres are distributed mainly to the lower part of the vermis. The next figure (fig. 422) shows the principal connections of the cerebellum in a diagrammatic way. Beginning at the bottom, we see one of the cells of a spinal ganglion (s.G.) sending its peripheral axon to the skin (s.) ; its central axon enters the spinal cord and ascends its posterior column, to terminate in the posterior column nuclei of the bulb. This is marked " to Bulb." This is the first segment of the sensory path to the cerebrum, but its further course is not shown. The entering fibre of the posterior root gives off collaterals to the spinal grey matter ; some of these pass to cells in the posterior horn (p.H.c), from which a fresh relay carries on the impulse to anterior horn cells, one of which (a.h.c.) is seen sending its axon via the anterior root, to end in the muscular fibre M. Other collaterals terminate by synapses around the cells of Clarke's column (c.c). Two of these cells are shown; this is the 684 STRUCTURE OF THE CEREBELLUM [CH, XLVII. Optic Thalamus Fio. 422.— The main connections of the cerebellum. CH. XLVII.] CONNECTIONS OF THE CEREBELLUM 685 first cell-station on the cerebellar path. One of these is represented as giving origin to a fibre of tho direct cerebellar tract (d.c.t.), which enters the cerebellum by its inferior peduncle. The other cell of Clarke's column is shown giving origin to a fibre of Gowers' tract (g.t.) ; it is represented as making a sharp turn after having readied its highest point, and enters the cerebellum by its superior peduncle ; both of these spino-cerebellar tracts (coloured blue in the diagram) terminate in the cortex of the vermis ; but only a small proportion of their fibres take the roundabout path by the superior peduncle (see p. 658). Coming next to the middle peduncle, we see one of its fibres (m.p.) arising from a cell of the nucleus pontis, and crossing the middle line to terminate in the cortex of the opposite cerebellar hemisphere ; entering the nucleus pontis, we see one of the cortico- pontine fibres from the cerebrum The arrows indicate that this is the path (coloured red in diagram) by which impulses reach the cerebellum from the cortex of the cerebrum. The fibres from the cerebrum to the nucleus pontis come in large measure from the frontal lobe (see next chapter). The superior peduncle is more complicated. P is one of tho cells of Purkinje in the cortex cerebelli ; its axon passes to the nucleus dentatus of the cerebellum ; from the cells of the nucleus dentatus fresh axons carry on the impulse to the optic thalamus of the opposite side ; one of these fibres (s.P.) is shown. From the optic thalamus a fresh relay continues the impulse to the cortex cerebri. Each fibre of the superior peduncle, after it has crossed the middle line (oo), gives off a descending branch (d.), the destination of which is uncertain; it also gives off branches to the red nucleus ; from the cells of the red nucleus the fibres of Monakow's bundle (m.b.) continues the impulse down to the anterior horn-cells of the opposite side ; owing to the double crossing the cerebellar hemisphere is thus brought into connec- tion with the same side of the spinal cord. OHAPTEK XLVlll STKUCTUKE OF THE CEREBRUM The cerebrum cousists of two halves, called cerebral hemispheres, separated by a deep longitudinal fissure and connected by a large I- !(.. •) J3.-\ lew of the Corpus Callosmn from above. L-The upper surface of the corpus callo'^um has been fully expose.l by sei^aratiu- the cerebral hemispheres and throwing tlieni to tl>e si.ie u'o CTrnl fornicatus has been rletache.l, ami the transverse libres of the corpus callosun, trace.! for some distance mto the cerebral medullary substance. 1, the upper surface of the corpus c-losum^o" median furrow or raphe; :;, lon-itudiual .striic bounding llie furrow; I, swelliir' formed bv the transverse bands as ihey pass into the cerebrum; i>, anterior extremity or kneo <7f the corpus cai osu.n; 0, posterior extremity ; 7, anterior, and ., posfrior part of the mas.s of bres proceeding from the corpus callosum ; !., marsin of the swelling; 10, anterior j.art of the convolution of the corpus caUosum; 11, hem or band of union of this convolution ; l', internal convolutions of the parietal lobe ; 13, upper surface of the cerebeUum. (Sappey, aaor Fo\-ille.) ^""^"'""O"* <" tne band of transverse commissural fibres known as the corpus caUosum (fig. 423). The interior of each hemisphere contains a cavity of com- en. xLviii.] STRUCTURE OF THE CEREBRUM 687 plicated shape, called the lateral ventricle; the lateral ventricles open into the third ventricle. Fig. 424 represents a dissected brain in which the greater part of the corpus callosum has been removed ; the ventricles are thus exposed. Each hemisphere is covered with grey matter, which passes down Fio. 4'i4. — Dissection of brain, from above, exposing the lateral, fourtli, and fifth ventricles with the surrounding parts. %. — a, anterior part, or genu of corpus callosum ; h, corpus striatum ; h', the corpus striatum of left side, dissected so as to expose its grey substance ; c, points by a line to the taenia semicircularis ; d, optic thalamus; c, anterior pillars of fornix divided ; below they are seen descending in front of the third ventricle, and between them is seen part of the anterior commis- sure ; in front of the letter c is seen the slit-like fiftli ventricle, between the two laminie of the septum lucidum ; /, soft or middle cdiiimissure ; (j is placed in the posterior part of the third ventricle ; immediately behind the latter are the posterior commissure (.just visible) and the pineal gland, the two crura of which extend forwards alon^,' the inner and iijiper margins of the optic thalanii ; h and i, the corpora quadrigemina ; ];, superior cms of cerebellum ; close to k is the valve of Vieussens, which has been divided so as to expose the fourth ventricle ; I, hippocampus maior and corpus limbriatum, or twnia hi[)poeampi ; m, hippocampus minor; 71, eminentia collateralis ; 0, fourth ventricle ; p, posteiior surface of medulla oblongata ; r, section of cerebellum ; s, upper part of left hemispliere of cerebellum exposed by the removal of part of the jiosterior cerebral lobe. (Hirschfeld and Levpille.) into the fissures. This surface grey matter is called the cerebral cortex. The amount of this grey matter varies directly with the amount of convolution of the surface. Under it white matter is situated ; and at the base there are masses of grey matter ; part of these basal ganglia are seen forming part of the wall of the ventricles. The anterior basal ganglion is called the corpus striatum ; it is 688 STRUCTURE OF THE CEREBRUM [CH. XLVIM. divided into two parts, callod the lenticular or extra-ventricular nucleus, and the caudate or intra-ventricular nucleus. It has received the latter name because it is seen in the interior of the ventricle. The posterior basal ganghon is called the optic thalamus. Passing up between the basal ganglia are the white fibres which enter or leave the cerebral hemisphere by the crus ; these constitute the internal capsule. This passes in front between the two subdivi- sions of the corpus striatum, and behind between the optic thalamus and the lenticular nucleus of the corpus striatum. The relationship of these parts is best seen in a vertical section ; such as is represented in the next diagram (fig. 425). r—VBL via Fig. 425.— Vertical section through the cerebrum and basal ganglia to show the relations of ilie latter. CO., Cerebral convolutions; c.c, corpus callosum ; v.l., lateral ventricle; /, fornix; vlll. third ventricle; n.c, caudate nucleus; (/i, optic thalamus ; Ji.Z. .lenticular nucleus ; c.i., internal capsule; el., claustrum ; c.c, external cajisule ; m, corjius maniniillare; t.o., optic tract ; s.t.t., stria termin- alis ; n.a.., nucleus amygdahu ; cm, soft commissure ; co.i., Island of Keil. (Schwal'be!) One hemisphere is seen, with portions of the other. The surface darkly shaded indicates the grey matter of the cortex, which passes down into the fissures ; one very extensive set of convolutions {co.i.), passes deeply into the substance of the hemisphere; this is called the Island of Eeil ; the lowest stratum of grey matter is separated from this to form a narrow isolated strip of grey matter called the claustrum (cl.). In the middle line the great longitudinal fissure is seen extending as far as (c.c.) the corpus callosum, the band of white matter that forms the great commissure between the two hemispheres ; beneath this are the lateral ventricles which com- municate by the foramen of Munro with the third ventricle : the fornix is indicated by the letter /. Contributing to the floor of the lateral ventricle, one next sees the optic thalamus {th.), and the tail CH. XLVIII.] STRUCTURE OF THE CEREBRUM 6^0 end of the nucleus caudatus (n.c.) ; the section being taken somewhat posteriorly. The nucleus lenticularis is marked nl. ; and the band of white fibres passing up between it and the thalamus is called the internal capsule (c.i.) ; the narrow piece of white matter between the claustrum and the lenticular nucleus is called the external capsule (c.e.). For the student of medicine the internal capsule is one of the most important parts of the brain. In it are the continuations of the fibres which we have previously traced as far as the crus cerebri ; the motor-fibres of the crusta are continued into the anterior two- thirds of its posterior limb {i.e. behind the genu * in fig. 426) ; the sensory fibres of the tegmentum into the posterior third of this limb. When these fibres get beyond the narrow pass between the basal ganglia, they spread out in a fan-like manner and are distributed to the grey cortex ; the motor-fibres come down from the motor area in front of the fissure of Eolando ; the sensory fibres go to certain con- volutions behind this fissure. The name corona radiata is applied to the fan-like spreading of the fibres; the fibres as they pass through the handle of the fan, or internal capsule, communicate with the nerve-cells of the grey matter of the basal ganglia; the pyramidal fibres on their way down to the medulla and cord from the motor area of the brain send off collaterals or side branches which arborise around the cells of the corpus striatum, and to a less degree around those of the optic thalamus ; the axis-cylinder processes of these cells pass out to join the pyramidal tract on its downward course. The sensory fibres on their way up terminate by arborising round the cells of the optic thalamus, and in the subthalamic area. This, in fact, is another cell-station or position of relay : the fibres passing out from the cells of the thalamus continue the impulse up to the cortex. The importance of the internal capsule is rendered evident when one considers the blood supply of these parts ; at the anterior and posterior perforated spots, numerous small blood-vessels enter for the supply of the basal ganglia, and these are liable to become diseased, and if they rupture, a condition called apoplexy is the result ; if the haemorrhage is excessive, death may occur almost immediately ; but if the patient recovers, a condition of more or less permanent paralysis remains behind ; and a very large amount of paralysis results from a comparatively limited lesion, because so many fibres are congregated together in this narrow isthmus of white matter. If the haemorrhage is in the anterior part of the posterior limb, motor paralysis of the opposite side of the body (hemiplegia) will be the most marked symptom. If the haemorrhage occurs in the posterior part, sensory paralysis of the opposite side of the body will be the most marked symptom. If the motor-fibres are affected, degeneration will occur 2 X 690 STRUCTURE OF TIIK CEHEBRUM [CH. XLVIII. in the pyramidal tract, and can be traced through the pes of the crus and mid -brain to the pyramid of tho pons and bulb, and then in the crossed pyramidal tract of the opposite side and in the direct pyra- midal tract of the same side of the cord. Fig. 426 represents a horizontal view through the hemisphere. The internal capsule (c) at the point* makes a bend called the genu .45^IP «■■ Fig. 426 — Diagram to show tlie connection of the Frontal and Occipital Lobes with the Cerebellum, etc. The dotted lines passing in the crusta (t.oc), outside the motor fibres, indicate the connection between the temporo-occipital lobe and the cerebellum, k.c, The fronto-cerebellar fibres, which pass anteriorly to the motor tract in the crusta ; i.f., fibres from the caudate nucleus to the pons. Fr., frontal lobe ; Oc, occipital lobe; a.f., ascending frontal ; ap., ascending parietal convolutions ; PCF., precentral fissure in front of the ascending frontal convolution; fr, fissure of Rolando; ipf. , intraparietal fissure. A section of the crus is lettered on the left side. s..n., Substantia nigra; pv., pyramidal motor fibres, which on the right are shown as continuous lines converging to pass through the posterior limb of i.e., internal cajisule (the knee or elbow of which is shown thus *) upwards into the hemisphere and downwards through the pons to cross at the medviUa in the pyramidal decussa- tion. Ipf, Crossed pyramidal tract; aj)f, direct pyramidal tract. (Gowers.) or knee, behind which the motor-fibres, and more posteriorly still the sensory-fibres, pass. Some of the connections between cerebrum and the cerebellum are also indicated. The Convolutions of the Cerebrum. The surface of the brain is marked by a great number of depres- sions which are caWedJissurcs or sulci, and it is this folding of the surface that enables a very large amount of the precious material called the grey matter of the corte.x 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. CH. XLVIII.] THE CONVOLUTIONS OF THE CEREBRUM 691 In an early embryonic stage of tho linnian foetus the lirain is also smooth, but as development procuresses tho sulci appear, until the climax is reached in the brain of the adult. Tlie sulci, which make their appearance first, both in the animal Vm. 427. A. Cerebral Hemisphere of ariult Macacque monkey. 13. Cerebral Hemisphere" of child shortly before birth. Tho two brains are very much alike, but the t^rowth forwards of tho frontal lobes even at this early stage of doveloi)nient of the human brain is quite well seen. S, fissure of Sylvius ; K, fissure of Rolando. 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 vrimary fissures or sulci, and they divide the brain into Fig. 428. — Brain of the Orang, 3 natura' size, showing the arrangement of the convolutions. S//, (issure of Sylvius; ;j, fissure of Rolando ; BP, external parieto-occipital fissure; Olf, olfactory lobt; ; Ch, cerebellum ; PV, pons Varolii ; MO, medulla oblongata. As contrasted with the human brain, the frontal lobe is short and small relatively, the tissure of Sylvius is oblique, the temporo-sphenoldal iobe very prominent, and the external parieto-occipital lissure very well marked. Note also the bend or genu in the Rolandic tissure. This is found in all anthropoid apes lohes ; 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 692 STRUCTURE OF THE CEREBRUM [CH. XLVIII. studies the brain in different stages of development, or compares the 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 (fig. 427), 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. 428 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. 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 Reil. 2. The fissure of Rolando (the central fissure) runs from about p B ON_TA I. ^ LOBE 'EMPORal LOBf- Fio. 429.— Right cerebral hemisphere, outer surface. the middle of the top of the diagram (fig. 429), downwards and forwards. 3. The external parieto-occipital fissure (par. OC. f.) is parallel to the fissure of Eolando, but more posterior and much shorter ; in monkeys it is longer (see fig. 428), as it is not interrupted by annectent gyri. These three fissures divide the brain into five lobes : — 1. The frontal lohe ; in front of the fissure of Eolando. 2. The parietal lohe; between the fissure of Rolando and the external parieto-occipital fissure. 3. The occipital lohe ; behind the external parieto-occipital fissure. 4. The temporo-sphenoidal lohe ; below the fissure of Sylvius. 5. The Island of Reil. It will be noticed that the names of Ihe lobes correspond to those of the bones of the cranial vault which cover them. There is no CH. XLVIII.] THE CEREBRAL CONVOLUTIONS 693 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 lo 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 ot precentral sulcus, which runs upwards parallel to the fissure of Eolando, and two 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 outwards 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, and the superior parietal convolution, or parietal lohule, in front of the external parieto-occipital fissure. lo B r FiG. 430. — Right cerebral liemispliere, mesial surface. 3. The occipital lobe is divided into upper, middle, and lower occipital convohUions by two secondary fissures running across it. 4. The temporal or temporo-sphenoidal lobe is similarly divided into upper, middle, and lower temporal coiivohttions by two fissures running parallel to the fissure of Sylvius ; the upper of these fissures is called the parallel fissure. 694 STRUCTURE OF THE CEUEBRUM [CH. XLVIII. 5. The Island of Reil is divided into convolutions by the break- ing up of the anterior limb of the Sylvian fissure. Coming now to the mesial surface of the hemisphere (fig. 430), 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 Rolando. The convolution above this is called the marginal convolution, and the one below it the callosal convolution or gyrus fornicatus. 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 ; the hippocampal convolution, 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 ia the inferior temporal convolution wliich we have previously seen on the external surface of the hemisphere (see fig. 429). In the occipital region the internal parieto- occipital fissure, which is a continuation of the external parieto-occipital fissure, passes downwards and forwards till it meets the calcarine fissure, which is a primary fissure ; these two enclose between them a wedge-shaped piece of brain called the cuneus or cuneate lobule; the square piece above it is called the precuneus or quadrilateral 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. 395, 2 2' 2" (p. 642), and may be seen diagrammatically in fig. 431, the end of the temporal lobe being cut off to expose the convolu- tions of the central lobe or Island of Reil. 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. O.S Orbital surface of fronlal lolie. JI, niar^'iiial convolution. 0, olfactory sulcus. O.S., orl)ital sulcus. 1, Island of Keil. S.a., anterior limb of Sylvian fissure. .S.;)., posterior limb of Sylvian lissure. A.P.8., anterior perforated spot. CII XLVUI.] STRUCTUKE OF THE COllTEX 695 Histological Structiire of the Cerebral Cortex. The possibility of differentiating the cerebral cortex in relation to its functions took origin in the work of Bevan Lewis and Henry Clarke in 1878, and the subject has in recent years received attention *'# ft MM, Fu:. 432.— The layers of the conical grey matter of the cerebrum. (Meynert.) Fio. 433. — Principal types of cells in the cerebral cortex. A, medium-sized pyramidal cell of the second layer. B, large pyramidal cell. C, polymorphic cell. D, cell of which the axis-cylinder process is ascending. E, neuroglia cell. F, cell of the first layer, forming an inter- mediate cell-station between sensory fibres and motor cells. Notice the tangential direction of the nerve- fibres. G, sensory fibre from the white matter. II, white matter. 1, collateral of the white matter. (Ramon y Cajal.) at the hands of A. AV. Campbell, Brodmann, J. S. Bolton, and others. Certain main features have been established, although unanimity on the interpretation of all the facts has not yet been reached. 696 STRUCTURE OF THE CEREBRUM [CH. XLVIII. The cortex may be divided into five primary laminae : — 1. The outer fibre layer or superficial lamina. — The fibres are largely derived from the dendrons of the cells of the next layer. The nerve-cells (F in fig. 433) intermingled with these are branched, and have several processes which lie horizontally beneath the surface (tangential fibres). There are doubtless association units linking the incoming afferent neurons to those which are motor. Neuroglia cells are also present. 2. Tkii outer cell lamina or layer of small pyramids. — There are several deep, and the largest cells are situated most deeply. Each of these has an apical process running to the surface, where the branches run tangentially. The lateral processes are also branched Fig. 431.— Human cerebral cortex : Golgi's method. Low power. (Mott.) dendrons. The axon originates from the base. The layer of small pyramids increases in depth as we ascend the animal scale. They are believed to be association units subserving the higher mental processes. 3. The middle cell lamina (numbered 4 in figure 432). — This consists of small cells called granules. This layer is a distinguishing mark of sensory areas, and is practically absent in the pre-Rolandic or motor convolutions. 4. The inner fibre layer. — In certain regions of the cortex this contains the giant pyramids or Betz cells, which are characteristic of the motor areas. In the visual cortex the so-called solitary cells of Meynert are present here. CH. XLVIII.] STRUCTURE OF THE CORTEX 697 5. The inner cell lamina or polymorphic layer. — These are small scattered cells, many of a fusiform shape. In the Island of Eeil this layer is hypertropbied, and is separated from the rest of the grey matter by a stratum of white fibres ; it is known then as the claustrum. The Golgi method of staining has proved conspicuously useful for studying the shapes and dispositions of the cells (figs. 433, 434, 435). Nerve-fibres pass in vertical streaks through the deeper layers of the grey matter ; some of these are axons conveying impulses down- wards, others are sensory in function and carry impulses upwards. Some strands lie parallel to the surface of the cortex; this is specially noticeable in the layers we have numbered 1 and 4. In Fig 435.— II ;man cerebral cortex, showing a Betz cell or giant pyramid : Golgi's method. High power. (Mott.) the portion of the occipital lobe which is the visual sphere, the granule layer (No. 3), which is so specially characteristic of sensory function, is of great depth and is divided into two by optic radiations running horizontally, which constitute the white line of Gennari. Bolton regards the fifth lamina as the fundamental cell layer, the others being formed from it from within outwards, both in embryonic and historical development. Defect of development of the outer layers leads to various forms of amentia (inborn lack of mental develop- ment, or idiocy); in dementia (degenerative mental change coming on later in life) there are retrograde changes in the upper layers of cells. The fifth or inner cell layer is probably concerned with the performance of organic and instinctive activities, and there is but 698 STRUCTURE OF THE CEREBRUM [CH. XLVllI. little difference seen here between man^ monkey, and do*,'. The second layer, on the other hand, is concerned with the psychic or associational functions, and attains its niaximiini dcptli in man. The archipalliuni (p. 646) is tlie portion of the cortex which makes it appearance earliest in vertebrates, and is associated with the rhinencephalon or olfactory lobe of the pala-encephalon. In mammals it is reduced to small proportions in comparison with the rest of the cortex, which is termed, on account of its later appearance in historical development, the neopallium. In man, the archipalliuni is duu))led in to form the liippocampus major, which projects into the lateral ventricle; this is continuous externally around the dentate sulcus with the syi"us hippocampi. This part of the corLex is easily distinguishable from the neopallium, being much simpler in structure — the pyramids, for instance, are reduced to a single layer, and the smaller cells nearer the surface are grouped in a characteristic nest- like way. The White Matter of the Cerebr\im. The white matter of the cerebrum, like white matter elsewhere, is made up of medullated nerve fibres. According to the direction of the fibres, they may be divided into three principal groups : — 1. Association fibres. — These pass from convolution to convolution, and the principal bundles of these are shown semi-diagrammatically in fig. 436. 2. Commissural fibres. — These pass by the commissures of the brain, of which the most important is the corpus callorum, so as to link the convolutions of one hemisphere with the corresponding convolutions in the opposite hemisphere, where they terminate in arborisations (synapses) around the cells of the grey cortex. 3. Projection fibres. — These are the fibres which run more or less vertically and link the cerebrum to the lower portions of the central nervous system. They may be subdivided into the efferent projection fibres, which convey impulses downwards, and the afferent projection fibres, which convey impulses upwards. They are shown semi-diagrammatically in fig. 437. The term projection fibre almost explains itself. By means of the efferent projection system the cerebrum is able to project its impulses to the cord, and thence to the muscles at the periphery. By means of the afferent projection system the surface of the body, provided as it is with sense organs, is able to project its impulses to the seat of sensation. The efferent projedion system. — The most important portion of this is the cerebro-spinal motor tract. The cells of the cortex which give rise to these fibres are par excellence the ]-]etz cells, which are found in the fourth layer in the region of the brain, known as the CH. XLVIII.] TIIK PltOJECTION FIBRES 609 . 430. — Lateral view of a human hemisphere, showing the main bundles of association fibres (Starr). A, A, bet\\een adjacent convolutions ; B, between frontal and occipital areas ; C, between frontal and temporal areas (cinguluni) ; D, between frontal ami temporal areas (fasciculus uiiciiiatus) ; E, between occipital and temporal areas (fasciculus longitudinalis inferior) ; C.N., caudate nucleus; O.T., optic thalamus. Kio. 437.— Schema of the projection fibres within the brain (Starr). A, tract from the frontal gyri to the pons nuclei and so to the cerebellum; B, motor pyramidal tract; C, sensory tract for touch ; D, visual tract; E, auditory tract; F, G, 11, superior, middle, and inferior cerebellar peduncles ;_ J, fibres between the auditory nucleus and the inferior corpus quailrigeminum ; K, motor decussation in the bulb ; F.V., fourth ventricle. The numerals refer to the cranial nerves. The sensory radia- tions are seen to be massed towards the occipital end of the hemisphere. 700 STRUCTURE OF THE CEREBRUM [CH. XLYTII. motor area (the convolutions immodiately in front of the Kolandic fissure). The axon of each of these giant pyramids originates from its base, and fig. 438 (next page) shows in outUne the destination of tlie fibres. 1 is a cell of the motor or Kolandic area of the cerebral cortex ; its axon (Ax) passes down in the pyramidal tract, and crosses the middle line (oo) at the pyramidal decussation. It gives off collaterals, one of which (assoc.) is an association fibre passing to terminate in the cortex of a neighbouring convolution ; another, labelled commis, is a commissural fibre passing in the corpus callosum to the opposite hemisphere ; others pass into basal ganglia. In the cord, collaterals pass off to end in synapses around cells at the base of the posterior horn, and the main fibre has a similar termination ; from each of these posterior horn cells, a short axon passes to end in an arborisation around an anterior cornual cell ; only one of these is shown ; the motor nerve-fibre passes from this to muscular fibres, to terminate in end-plates there. The pyramidal cell numbered 2 is taken to illustrate the similar relationships between the cortex and muscles supplied by cranial nerves ; its axon is represented as ending in the motor nucleus of the seventh nerve, and the new axon arising there passes to face- muscles. In order to prevent confusion in the diagram, cell 2 is placed in one of the upper convolutions ; the face area of the cortex is really below those for the limbs. The cell numbered 3 illustrates the fact that certain axons never reach the spinal cord, but terminate in the grey matter of the mid- brain and pons ; such fibres may therefore be called cortico-pontine, in contradistinction to the pyramidal fibres, which are cortico-spinal. From these subsidiary masses of grey matter in the pons and mid- brain, new tracts, such as the bundle of Monakow or prepyramidal tract, arise (ponto-spinal fibres), which continue on the impulse to the anterior cornual cells. No attempt has been made in this diagram to insert autonomic fibres with their accessory cell-stations in ganglia outside the central nervous systems. For these the reader is referred back to Chap. XVIL The afferent projection system. — This is also indicated in outline in the same diagram (fig. 438). A is a cell of one of the spinal ganglia on the posterior nerve-roots; its peripheral axon terminates in muscular tendons or in skin, and the impulse it conducts is afferent, as shown by the arrow. The central axon passes into the spinal cord, and its impulse ultimately arrives at the cortex of the opposite side through several intermediate cell-stations. The last relay on the sensory path passes from O.T., the optic thalamus, to the cortex, and is linked up to the motor cell (1) by the associa- CH. XLVIII.] AFFERENT TRACTS TO THE CORTEX 701 tion unit (4) in the superficial layer of the grey matter. Its intervening course from spinal ganglion to optic thalamus is, to save confusion in the diagram, represented by a dotted line. The diagram on the next page (fig. 439) fills in the details of the sensory path. Beginning at the lower part of the diagram (fig. 439) on the right- FACE MUSCLE Fio. 488,— Diagram of the principal efferent channels. hand side, we see one of the cells of a spinal ganglion. Its central axon enters the cord, runs up the posterior column, and terminates in one or other of the dorsal column nuclei (gracilis or cuneatus) ; the new axons arising there, called arcuate fibres, cross the middle line and ascend as fibres of the main fillet to the optic thalamus ; from which, as we have seen, a new relay carries on the impulse to the cortex. 702 STRUCTURE OF THE fEREHKUM [CH. XLVIII. 'Dialamivs Fihn:fm7/h s^evisory nncietts qf ce7vbraZ~ ucrve(Vth.)to thahunus- Upper or main fillet FiM-c of Unvi /■ or laleral j'iU4it to corjx (jiiad?: pc)5t: Fibre of Tn^vn, fillet to tJuilaytius Fibre. fro7Ji cord to thalaynios Qa/iigli on- cell of cerebral nerve ( VUt ) \~ Se?isory nucleus of I cerebral nerve (Vth.) Ganglhon-c.cll of c6chLca,r nerve Qrcy m^ttir of (lorscil horn Fio. 430.— Diagram of i.iineii)al sensory cliauiiels. (K. A. Scliiifer.) CH. XLVIII.] AFFERENT TRACTS TO THE CORTEX 703 In the cord, however, it gives ofif many collaterals, some of which arborise around anterior horn cells of the same or the opposite side, to form the basis of spinal reflex action. Others are shown crossing the middle line, and they ultimately reach the thalamus by the ascending tracts of the opposite side of the spinal cord and bulb. The arrangement of the sensory cranial nerves is very similar ; a cell of the Gasserian ganglion is seen sending its peripheral axon to the face region in the fifth nerve, and its central axon to arborise around the cells of the sensory nucleus of the fifth nerve in the bulb. From these cells the second relay carries on the impulse to the thalamus. The arrangement of the cochlear nerve is very similar ; the second relay, via trapezium and lateral fillet, carries the impulse, however, to the posterior corpus quadrigeminum instead of to the optic thalamus ; a third relay, not shown in the diagram, completes the journey from this mass of grey matter to the cortex. The connections of the cord and cerebrum to the cerebellum we have previously studied (see fig. 422, p. 684), and so they are not shown in the present diagrams. Particular attention should be paid to the following point: when an afferent fibre enters the spinal cord, it divides into three main sets of branches. The first set, the shortest, forms synapses with the motor cells of the anterior horn ; here we have the anatomical basis of spinal reflex action. The second set passes through an intermediate cell-station in Clarke's column to the cerebellum, the emerging fibres from which also influence the motor discharge of the cortical and anterior horn cells. The third set, the longest, passes through three intermediate cell-stations (the first in the nucleus gracilis or cuneatus, the second in the optic thalamus, the third in the association units in the cortex), and ultimately reaches the pyramidal nerve-cells of the cerebral cortex, the efferent fibres (pyramidal fibres) of which pass to the motor cells of the anterior cornu and influence their discharge. The motor nerve-cells of the anterior horn may thus be influenced by the afferent impulses via three paths or nervous circles. In health, all these nervous circles are in action to produce coordinated muscular impulses. In locomotor ataxy, which is a degeneration of the cells of the ganglia on the posterior roots and their branches, all these nervous circles are deranged, and the result is loss of reflex action, and incoordina- tion of muscular movements. CHAPTEE XLIX FUNCTIONS OF THE SPINAL COIID The functions of the spinal cord fall into two categories : functions of the grey matter, which consist in the conversion of afferent into efferent impulses {reflex action) ; and functions of the white matter, which are those of conduction. The Cord as an Organ of Conduction. The fibres of the spinal cord consist of three main groups ; these are — (1) the association tracts, which connect together different segments of the cord and thus bring about coordination of the impulses, which leave it at various levels, in relationship to the impulses which enter the cord either below or above any particular region ; (2) the efferent projection fibres, which connect the cord with the different parts of the brain above it. The main motor path, the pyramidal tract, comes into this category ; and after our full descrip- tion of its course, we need not do more here than remind the reader that it originates from the giant pyramids of the motor area of the cortex, and that its fibres cross to the opposite side of the spinal cord, the principal decussation occurring at the lowest level of the bulb ; from the grey matter in which it terminates in the cord, the impulse is continued onwards, until in the end it reaches the muscles via the fibres which leave the cord in the anterior nerve-roots ; (3) the afferent projection system of fibres ; these primarily enter the cord by the posterior spinal nerve-roots. The impulses which these convey enter {a) the spinal grey matter, (h) the cerebellum, and (c) the cerebrum, the seat of consciousness. It is these sensory tracts which are the most complex, not only on account of the cell-stations in their course, but also on account of the difficulty of determining in animals the different kinds of sensa- tions which are present in health, or which may be absent after injury to various tracts. It is, however, certain that ultimately, so far as the cerebrum is concerned, crossing occurs somewhere, so that CH. XLIX.] CONDUCTION IN THE CORD 705 each hemisphere is related to the opposite half of the body, not only in regard to motion but in regard to sensation also. The main difficulty of investigators has been to determine exactly where the crossing occurs ; in man especially, many of the impulses cross shortly after their entry into the cord, and then travel up to the higher centres by paths on the opposite side of the cord to that by which they enter. In such investigations on man, various injuries to the cord have to be carefully studied, and it is such careful study that has led to this conclusion. For fifty years, physiologists, stimulated by the work of Brown- Sequard, have attempted to trace the upward paths of afferent impulses through the spinal cord. By experiments on animals, the secondary ascending degenerations which follow injury can be fol- lowed with exactitude, and traced into bulb, cerebrum, cerebellum, or other parts. But even though such animals may be long under observation, they cannot tell us, and we can only with difficulty and ill-success guess, how their sensations are affected by the lesion. On the other hand, the clinical observer may expend much time and trouble in determining the nature of the loss of sensation, but it is usually impossible to verify the anatomical position and nature of the lesion. In many cases where a microscopical examina- tion has been made, the disease has been of a progressive nature, or the patient has died from complications, which detract from his suitability for an examination of this kind. Nevertheless, by a combination of the experimental and clinical methods, we have now arrived at some accuracy on these points, and it is impossible to overestimate in this direction the value of the psycho-physical examination of patients which has within the last few years been made by Head, Eivers, and Sherren. In order, however, to examine the sensations of a patient, it is necessary to know first how to classify the sensations which are the result of cutaneous stimulation. To do this, we must somewhat anticipate what we shall go into more fully in the chapter on the Cutaneous Senses. It has been proved that, scattered over the external surface of the body, are a number of spots, some which are more susceptible to one form of stimulus than others. The spots are of four kinds, known as touch spots, pain spots, heat spots, and cold spots, and these correspond to the four kinds of sensations which we experience as the result of cutaneous excitation. They correspond to different kinds of end-organs in the skin, and the impulses are carried to the central nervous system by different groups of fibres. Dr Head found, from an experiment he made by cutting a sensory cutaneous nerve in his own arm, that although the patch of skin supplied by the nerve was entirely destitute of sensation, the under- lying parts were still sensitive to pressure and to pain. These deep 2 Y t06 FUNCTIONS OF THE SPINAL CORD [CH. XLIX. sensations are subserved by norve-fibres which are di.-^tributed with the muscular nerves. It is by means of the sensory nerves of muscles, tendons, and joints that we are aware of the position of our limbs, and the extent of muscular contraction. After a time true cutaneous sensation returned when the severed nerve regenerated, but it was not until many months elapsed that sensation was as sharp and as accurately localised as it was before the nerve had been cut. The first sensations that returned enabled Head to feel pain, to distinguish large differences of temperature, and to localise the position of a touch somewhat inaccurately. Head terms such imperfect sensations j^rofopafhi'-. The ability to localise accurately, to distinguish small differences of temperature and the finer distinctions generally of cutaneous sensations, returned later, and are spoken of as epicritk. We may thus divide the main sensa- tions coming from the periphery of the body into deep and cutaneous ; and the cutaneous sensations into protopathic and epi- critic. The other classification into sensations of touch, heat, cold, and pain, cuts across the first ; thus we may have pain that is of deep or of cutaneous origin ; we may have temperature sensations which are both rough or protopathic, and accurate or epicritic ; and we may feel pressure and localise it by means of the cutaneous sense proper, or by the stimulation of the sensory nerves in the deeper structures. Whether different nerve-fibres are concerned in the transmission of protopatliic and epicritic impulses is a matter of doubt. It is quite possible that the same fibres may be concerned in the transmission of both. Diseases of the spinal cord in man usually are widespread and affect many tracts; the disorders of muscular paralysis and of sensa- tion thus produced will therefore be complex. The more limited the lesion, the fewer tracts will be affected, and such conditions are therefore more on all fours with these localised lesions or sections of tracts which can be performed on animals. The operation of hemisection in an animal produces paralysis of the same side of the body below the injury. So it is in a man in whom disease has pro- duced an interruption of the pathways on one side only of the cord. But such an animal or man (and the observation is more accurate in man) will not have lost all sensation on the same side ; tactile discrimination, and the motorial sense will have largely disappeared, but sensations of pain, of heat, and of cold will still remain, because the tracts which convey such impulses cross over in the cord at varying levels after entering it, and therefore any loss in such sensa- tions will occur on the opposite side to that which is injured. It was no doubt absence of correct knowledge on this question that led Schiff to imagine that impulses translated by the brain, as sensations of temperature and pain, travelled up by the grey matter, CH. XLIX.] CONDUCTION IN THE CORD 707 and not by the posterior columns. It certainly is the case that in the condition called syrirKjomyelia (a disease of the grey matter of the cord), sensations of heat, cold, and pain are lost, Ijut this is due to the disease cutting through the crossing fibres whicli convoy the impulses in question. Head has pointed out that disease strictly limited to the grey matter does not produce loss of any kind of sensation, except by interfering with those paths which pass through its substance. We have seen that afferent impulses pass into the cord by peripheral nerves (the primary or peripheral level) in certain com- binations from the protopathic, epicritic, and deep systems. In the spinal cord these are sorted out and travel up in new combinations, and it is possible that before they finally reach the cortex a fresh sorting may take place in higher cell-stations before they ultimately arrive at the seat of consciousness. The first rearrangement occurs at the secondary level, that is on entrance into the cord, and a further sorting at the third level, but of this but comparatively little is known at present. We shall here only deal with the rearrangement at the second level, as derived from a study of spinal cord disease. We may make a rough comparison of what occurs, to what takes place in the correspondence which flows in from all quarters to a busy man, such as a Secretary of State. The letters will come from all quarters, and deal with numerous topics ; some will be private letters, some will be advertisements, some will be official, some begging letters, and so forth. This mass of correspondence will be sorted out by minor officials, the advertisements and the begging letters will probably never reach the busy officer of State, and he will therefore not be conscious of their existence unless he examines the waste-paper basket. But the private letters and the official letters will be sorted out into separate bags, whether they come from England or from outlying parts of the Empire, and these ultimately reach his eye. In the same way, the impulses that give rise to pain, whether from cutaneous or deep structures, will all be combined and travel up one path. Those due to heat or to cold, whether protopathic or epicritic, in other paths ; those which are tactile or motorial, in another. And so a localised spinal lesion may interrupt all the fibres subserving the sensation of heat without interfering with those which underlie sensations of cold, and so forth. Tactile, painful, and thermal impulses, and those associated with tactile localisation, cross in their passage through the spinal cord at varying levels soon after entrance. But the sensory impulses which underlie the recognition of passive position and movement, and finer tactile discrimination, do not cross within the limits of the spinal cord ; they pass up the posterior column on the side of entrance, and 708 FUNCTIONS OF THK SPINAL CORD [CH. XLIX. SO reach the gracile and cuiieate nuclei of the bulb, and it is the fibres which arise from the cells of these nuclei which cross in the decussation of the fillet. The ra|)i(lity with which the sensory impulses cross to the opposite side varies greatly. Some, such as those associated with pain, heat, and cold, cross over in the space of five or six spinal segments. With tactile imijulses the crossing is evidently less rapid ; but until the crossing is completed there will obviously be two channels, one on each side of the cord, open for tactile impulses ; and such a double patli will be shorter for the impulses which cross more rapidly; and finally, as just stated, the impulses associated with position, movement, and tactile discrimination have only one path in the cord, as the decussation does not take place until the bulb is reached ; hence a hemisection of the cord, or of one posterior column, will abolish these forms of sensibility from the parts below the lesion, on the same side of the body as the lesion. Painful impulses from the skin arriving in the cord from proto- pathic fibres pass into the second level at the point of entry, and rapidly cross over to the other side. Fibres of the deep system running with the muscular nerves and carrying impulses also of a painful kind from the same part of the body do not necessarily enter the cord by the same posterior roots as those carrying cutaneous painful stimuli. Thus more than one segment of the cord is required before all painful impulses from any one part of the body can be gathered together and recombined. This is the reason why, in a local lesion in the cord, there may be a want of correspond- ence between the extent of the cutaneous and deep analgesia (loss of sensation to pain). Up to this point we liave only considered the sorting out of those impulses which reach the cerebrum and thus rise into consciousness. In addition to this there is another group of impulses which never rise into consciousness at all, and although these are afferent they are therefore not sensory. Our previous illustration of the correspondence of a busy man may help us again in understanding this. His clerks sort his letters, and those of a certain kind (circulars and the like) will probably never reach him at all. So it is with afferent impulses; the primary sorting is into sensory and non-sensory ; the sensory impulses are again sorted into those of touch, pain, and temperature; the non- sensory impulses are those mainly destined for the cerebellum, and reach it by the cerebellar tracts. These travel up the cord on the side of entry, and reach the same side of the cerebellum. This explains the delay in the crossing of the sensory impulses which subserve the sense of position and movement and tactile discrimina- tion, a crossing which, as we have seen, does not occur until the bulb en. XLIX.] REFLEX ACTION OF THE CORD 709 is reached. It is impulses from the joints and muscles which are specially important for the cerebellum to enable it to carry out its functions of equilibration and coordination of muscular movements. These impulses are non-sensory, but they are carried by fibres which originate as collaterals from those which carry the true sensory impulses of the same nature to the cereljrum. This group of fibres therefore remains in the cord on the side of entry, in order to be in the neighbourhood of the cerebellar tracts ; the impulses reach the cerebellar tracts with the intermediation of a cell-station in Clarke's column. AVhen the tract conveying what we may term the motorial sensations to the cerebrum has ministered in this way to the needs of the cerebellum, there is nothing to prevent it following the example of the other tracts, so when the spinal cord is passed and the bulb reached, crossing of these fibres occurs in due course. To sum up — the spinal cord is the seat of the transmutation of most of the impulses of the first or peripheral level into those of the secondary level of the afferent projection system. This recom- bination takes place on the same side as that by which the impulses enter the cord. The secondary paths for sensory impulses then cross with greater or less rapidity, so that ultimately all except those subserving the sense of position and movement and tactile dis- crimination have passed to the opposite side within the limit of the spinal cord ; and those which do not cross in the cord do so after reaching the nuclei of the posterior columns. At the same time, within the spinal cord afferent impulses become separated into sensory and non-sensory, and the latter are exemplified by those which reach the same side of the cerebellum by the cerebellar tracts. Reflex Action of the Spinal Cord. The reflex actions of the spinal cord may first be studied in the brainless frog. In such a low type of animal, the interdependence of cord and brain is not such a marked feature as it is in the higher animals, and the spinal cord possesses within itself a great power of controlling and coiJrdinating very complex reflex actions. A study of the reactions of the frog's spinal cord, moreover, illustrates most of the fundamental facts in relation to reflex action generally. After destruction of the brain the shock of the operation renders the animal for a variable time motionless and irresponsive to stimuli, but later on it gradually assumes a position which differs but little from that of a living conscious frog. If thrown into water it will swim ; if placed on a slanting board it will crawl up it (Goltz) ; if stroked on the flanks it will croak (Goltz) ; if it is laid on its back, and a small piece of blotting-paper moistened with acid be placed on the skin, it will generally succeed in kicking it off; if a 710 FUNCTIONS OF THE SPINAL CORD [CH. XLIX. foot is pinched it will draw the foot away ; if left perfectly quiet it remains motionless. The muscular response that follows an excitation of the surface is purposive and constant, the path along wliich the impulse is pro- pagated being delinite. Under certain abnormal conditions, however, the propagation of the impulse in the cord is widespread, the normal paths being, as it were, broken down. This is seen in the convulsions that occur on slight excitation in animals or men who have suffered from profuse haemorrhage, or in the disease called lockjaw or tetanus. Such a condition is easily demonstrable in a brainless frog under the influence of strychnine: after the injection of a few drops of a 1 per cent, solution under the skin, cutaneous excitation no longer produces co- ordinated responses, but paroxysms of convulsions, in which the frog assumes a characteristic attitude, with arms flexed and legs extended. Spreading of reflexes. — If one lower limb is excited, it is that limb which responds : if the excitation is a strong one it will spread to the limb of the opposite side, and if stronger still, to the upper limbs also. Pfliiger taught that the direction of irradiation within the spinal cord was always upwards. Sherrington has shown that this is not so, and has discovered many descending paths (see p. 659). Cumulation of reflexes. — This is well illustrated by Turck's method. If a number of beakers of water are prepared, acidulated with 1, 2, 4, etc., parts of sulphuric acid per 1000, and the tips of the frog's toes are immersed in the weakest, the frog at first takes no notice of the fact, but in time the cumulation or summation of the sensory impulses causes the animal to withdraw its feet. If this is repeated with the stronger liquids in succession, the time that intervenes before the muscles respond becomes less and less. This method also serves to test reflex irritability when the frog is under the influence of various drugs. Inhibition of reflexes.— If, instead of the whole brain, the cerebrum only is destroyed, and tlio optic lobes are left intact, response to excitation is much slower, the influence of the remaining part of the brain inhibiting the reflex action of the cord. Or if in doing the experiment with acid just described the toes of the other foot are being simultaneously pinched, the response to the acid is delayed. This influence of the brain on the cord is also illustrated in man, by the fact that a strong effort of the will can control many reflex actions. It is, for instance, possible to subdue the tendency to sneeze ; if one accidentally puts one's hand in a flame, the natural reflex is to withdraw it : yet it is well known that Cranmer, when being burnt at the stake, held his hand in the flames till it was consumed. After the spinal cord has been divided by injury or disease in the thoracic region, the brain can no longer exert this controlling action ; CH. XLIX.] REFLEX ACTION IN MAN 711 hence the part of the cord below the injury having it, as it were, all its own way, has its reflex irritability increased.* The increase of reflex irritability is also seen in the disease called lateral sclerosis ; here the lateral columns, including the pyramidal tract, become degenerated, and so the path from the brain to the cells of the cord is in great measure destroyed. In these patients the increase of reflex irritability may become a very distressing symptom, slight excitations, like a movement of the bed-clothes, arousing powerful convulsive spasms of the legs. Reflex Action in Man. The reflexes obtainable in man form a most important factor in diagnosis of diseases of the nervous system ; each action is effected through an afferent sensory nerve, a system of nerve-cells in the cord termed the reflex centre, and an efferent motor nerve; the whole constitutes what is called the rejlex arc. The absence of certain reflexes may determine the position in the spinal cord which is the seat of disease. Two forms of reflex action must be distinguished : — 1. Superficial reflexes. These are coordinated reflex actions, and are excited by stimulation of the skin. 2. Deep reflexes or tendon reflexes. Superficial Reflexes. — These are obtained by a gentle stimula- tion, such as a touch on the skin ; the muscles beneath are usually affected, but muscles at a distance may be affected also. Thus a prick near the knee will cause a reflex flexion of the hip. The most important of these reflexes are : a. Plantar reflex: withdrawal of the feet when the soles are tickled. b. Gluteal reflex : a contraction in the gluteus when the skin over it is stimulated. c. Cremasteric reflex : a retraction of the testicle when the skin on the inner side of the thigh is stimulated. d. Abdominal reflex: a contraction of the muscles of the abdominal wall when the skin over the side of the abdomen is stroked ; the upper part of this reflex is a very definite contraction at the epigastrium, and has been termed the epigastric reflex. e. A series of similar reflex actions may be obtained in the muscles of the back, the highest being in the muscles of the scapula. f. In the region of the cranial nerves the most important reflexes are those of the eye — (i) the conjunctival reflex, the movement of the * In some injuries to the cord produced by crushing, there is a loss of reflexes below the injury! These, however, are not simple transverse lesions ; the loss of reflex action is due partly to shock, and partly to extensive injury of the grey matter. 712 FUNCTIONS OF THE SPINAL CORD [CII. XLIX. Fio. 4t0.— The Knee-jerk. (Gowera.) eyelids when the front of the eyeball is touched ; and (ii) the con- traction of the pupil on exposure of the eye to light, and its dilatation on stimulation of the skin of the neck. Tendon Reflexes. — When the muscles are in a state of slight tension, a tap on their tendons will cause them to contract. The tendon reflexes which are generally examined are the patella tendon reflex or knee- jerk, the tendo Acliillis reflex or ankle-jerk, and phenomenon known as ankle-clonus. The knee-jerk. — The quad- riceps muscle is slightly stretched by putting one knee over the other; a slight blow on the patella tendon causes a movement of the foot for- wards, as indicated in the dotted line of fig. 440. The phenomenon is present in health. The ankle-jerk is one of great importance, for in such diseases as locomotor ataxy, in which the tendon reflexes are lost, it usually disappears before the knee-jerk. It is best elicited if the patient kneels with one knee upon a cushioned chair, whilst standing on the other leg by the side of the chair. The calf muscles of the kneeling leg are thus relaxed, and a sharp tap upon the tendo Achillis elicits the jerk. Ankle-clonus. — This is eli- cited as depicted in the next figure: the hand is pressed against the sole of the foot, the calf muscles are thus put on the stretch and they contract, and if the pressure is kept up a quick succession or clonic series of contractions is obtained. This, however, is not readily obtained in health. The phenomena depend for their occurrence on the integrity of the reflex arc. Disease or injury to the afferent nerve, efferent Fig. 441. — Ankle-clonus. (Cowers.) CTT. XLTX.] REFLEX ACTION IN MAN 713 nerve, or spinal grey matter, abolishes them. Thus they cannot be obtained in locomotor ataxy (damage to the posterior nerve-roots), or in infantile paralysis (damage to the anterior horns of grey matter). They are excessive in those conditions which increase reflex irritability, such as severance of brain from cord, and in lateral sclerosis, that is, a degenerative condition of the pyramidal tract. In order that the muscle may respond, it is necessary that it be in an irritable condition; this is accomplished by putting it slightly on the stretch, and so calling forth the condition called tonus, and thus a readiness to contract on slight provocation. Until the last few years, considerable doubt existed as to whether the tendon- reflexes were true reflex actions, because it was asserted that the time intervening between the stimulus and the muscular response was too short. Now that we know that nerve-impulses are in man propagated at the rate of 120 metres per second (and not at the rate of 30 metres per second as was formerly supposed), this difficulty has disappeared. Jolly has made careful time measurements, and demonstrated that in the knee-jerk there is sufficient time for the nerve impulse to travel to the spinal cord and back again, but that the time occupied in the cord itself is only about half that which is necessary in the case of ordinary coordinated reflex actions. This is explicable on the assumption that the tendon reflexes are subserved by the collaterals of the entering afferent fibres which go direct to the anterior horn cells, whereas ordinary reflexes are worked through intermediate neurons, and therefore have to pass through additional synapses. The increased rapidity of a tendon reflex is useful, for a sudden strain on a ligament would rupture some of its fibres or lead to injury of the joint surfaces if too great a time intervened before the muscles could contract and so save the joint. The exact course of the reflex arc concerned in the knee-jerk has been worked out by Sherrington in the monkey. The nerve-fibres are mainly those which pass (1) to and from the crureus by the anterior crural nerve, and (2) to and from the hamstrings by the sciatic nerve. The fibres which supply the crureus arise from the spinal nerve-roots which in man correspond to the 3rd and 4th lumbar; the hamstring supply is from the 5th lumbar and 1st and 2nd sacral roots. Lombard's experiments upon the knee-jerk indicate that it is sometimes more readily obtained even in the same person than at other times. It varies with changes in mental activity, and during sleep may be entirely absent. It is increased and diminished by whatever increases or diminishes the relative state of irritability of the nervous system as a whole. 714 ' FUNCTIONS OF THE SPINAL CORD [CIL XXIX. Closely related to this is the phenomenon known as reinforcement of the knee-jerk, which was first described by Jendrassik in 1883, and has since been studied by numerous observers. The extent of the jerk may be increased if at the time the patella tendon is struck, a strong voluntary contraction, such as clenching the fists or the jaw, is made by the individual. In many normal persons the knee-jerk is difficult to elicit, but in these it may usually be obtained by the reinforcing action just described. After the reinforcing action has occurred it is followed by an interval in which the knee-jerk is lessened (inhibition or negative reinforcement). Many explanations have been offered of the phenomenon ; one is the " overflow " theory, that is, motor impulses from the brain which produce a contraction of hands or jaw will not only affect the lower centres concerned in such movements, but will also overflow to other regions, for instance, those which come into play in the knee-jerk and influence motor irritability there. The " drainage " theory of M'Dougall to be described a few paragraphs ahead may possibly explain reinforcement; the drainage of nervous potential to one part will lessen the resistance of the synaptic junctions and cause a drainage of nervous energy from other parts, and so allow reflex actions to be more readily elicited there. We have devoted most space to the knee-jerk because this tendon reflex is the one which has been longest known and most worked at. The recent investiga- tions of Babinski have, however, shown that other tendon phenomena may be quite as easily investigated, and in some cases are more valuable aids to diagnosis than the knee-jerk. Amongst these we have already referred to the ankle-jerk. Another phenomenon allied to these is usually called Ji(i/>inxkl\s {■■iraina{fe" theory. — This theory is an attempt to explain the reciprocal action of antagonistic muscles. The accompanying diagram represents two antagonistic muscles (fig. 442) with FLEXOR EXTENSOR Fio. 442.— Diagram to illustrate M'Doagall's "Drainage" tlieory. their nerve supplies. Each is in connection with a reflex arc shown in a simple schematic way, as consisting of three neurons, Ai, A.,, A^, and Bj, B., and B.; respectively. Aj and Bj are the afferent neurons ; A, and B., are the association or internuncial neurons within the central nervous system. A.; and B^ are the efferent or motor neurons. When a stimulus is applied to A; it generates nervous ener^ry, and discharges across the synapse to A._„ and finally to A ;, and the muscle contracts. The problem then is to imagine such a mode of connection between arc A and arc B as will cause arc A during activity to drain off from arc B the smaller amount of nerve energy in it which normally keeps the muscle suppUed by B . in a state of tonus ; if this is done, the muscle of arc B will lose its tonicity and become relaxed. -It is probable that this connection is by means of a collateral of the internuncial neuron B., crossing, as shown in the figure and taking part with the axon of A^ in the formation of the synapse with .\;. The normal resistance of this synapse is lowered by the stimulation applied to the arc A, and this lowering of resistance is participated in by the part of the synapse to which the crossing collateral from B.j contributes ; owing to this lowering of resistance, nervous energy therefore drains over from the arc B, and so the muscle it suppHes is relaxed. The theory may also be applied to explain (1) alternating reflexes, as described under our description of the scratch reflex (p. 712); (2) the reinforcement of the knee-jerk and other phenomena in which reflex arcs are concerned (p. 708) ; and (.3) cerfciin psychological phenomena such as attention. The Principle of the Common Path (Sherrington). — When an afferent nerve is stimulated, the impulse enters that complex network CH. XLIX.J THE COMMON PATH 717 of conducting paths, which is called the central nervous system. So numerous are the potential connections in this labyrinth that the impulse may, under such abnormal conditions as strychnine poison- ing, radiate in all directions, and be discharged so as to throw all the muscles of the body into action. But under normal circumstances the irradiation is limited to certain lines, which increase in number with the strength of the entering impulse. The general pattern of the nervous web remains fairly constant, but its details are subject to great variations, and a new stimulus may act like a tap on a kaleidoscope, and throw a new pattern into being. At the commencement of every reflex arc is a receptive neuron extending from a sensory surface to the brain or cord, and this is a private path exclusively occupied by impulses from its own receptive points on the surface of the body. These impulses pass along certain association tracts or internuncial paths in the central nervous system, and at the termination of the arc we have a final neuron which acts as the conducting link between the central nervous system and the muscle or gland which it supplies. This final neuron does not subserve exclusively impulses generated at one receptive source, but can be used in the conduction of impulses generated at many points of the body's surface. The arm muscles, for instance, can be thrown into play in response to visual, auditory, tactile, and other sensations. The final neuron thus differs from the initial neuron in being public, not private, and may be spoken of as the final comvion path. Of course, in every reflex action we are not really concerned with individual neurons, but with thousands of them acting in harmony ; still, for descriptive purposes, it is well to speak of one set of neurons only as a sample of the rest. An ordinary motor nerve is thus a collection of many final common paths. Now let us suppose that two stimuli are acting on different parts of the body's surface, each of which would produce impulses that ultimately reach the same final common path together, though they may throw the motor organ into action in rather a different way. Under such circumstances, it is found that the occupation of the public path by one impulse prevents it being simultaneously used by the other ; one reflex or the other takes place, but not both of them. For the investigation of such a problem, the " scratch reflex " of the dog is one that lends itself admirably. This can best be studied in the " spinal " dog, that is in a dog in which cerebral influence is shut off by division of the spinal cord in the lower cervical region. If the skin over a large saddle-shaped area covering the shoulders and back is gently irritated on one side, the hind leg of the same side executes scratching movements, which involve flexor muscles princi- pally ; the rate of scratching is about 4 per second, and each move- ment is presumably a short tetanus. The best " artificial flea " to 718 FUNCTIONS OF THE SPINAL CORD [on. XLIX. employ is a weak faradic current, and it is the nerves at the roots of the hair follicles which are specially susceptible when eliciting Fio. 443. -The Soratcli reflex. Tracing of the flexors of left liip evokeii by stimulation of the skin of the shoulder. The depression in the signal line S indicates the cominencoment of the stimulation, and its rise the termination. While this was going on, the left foot was stimulated, and the depression of the signal line L indicates the duration of this stimulation; during the stimulation of the foot, and for a short time afterwards, the scratch reflex is inhibited, but the scratch reflex returns so'jn afterwards. The time is registered in Bfths of seconds. To be read from left to right. (Sherrington.) the reflex. The internuncial paths in the cord are in the lateral part of the lateral column, and division of that region of the cord abolishes the reflex. CH. XLIX.] THE SCRATCH REFLEX 719 But there is another form of stimulation which also throws the same flexor muscles into action, although in rather a different way, and that is stimulation of the sole of the foot. The foot and leg are withdrawn, and the action is a steady one, and not a succession of rhythmic discharges as in scratching. Both reflexes, however, end in the same final common path ; and if while scratch- ing is being elicited by stimulation of the shoulder, the foot is then stimulated simultaneously, scratching immediately ceases; one set of impulses has displaced the other from the final common path. If then one ceases to stimulate the foot, the scratch reflex returns if the irritation of the shoulder is kept up. This is well illustrated by the tracing (fig. 443). But there is also another way in which the inhibition of reflexes may be produced. The contraction of one set of muscles is usually accompanied by relaxation of its antagonists, and the contraction of the flexors in the scratch reflex may therefore be inhibited by making the antagonistic muscles (the extensors) contract. Further, the scratch reflex is unilateral, but this does not mean that the muscles supplying the other legs are inactive, for they must act in such a way as to support the dog on three legs, while it scratches with the fourth. So if the right shoulder is stimulated, the right hind leg scratches ; if the left shoulder is stimulated, the left hind leg scratches ; but if both shoulders are stimulated together, only one or the other leg scratches, not the two at once; parts of the final paths are common to both sides, and there is a struggle for their occupa- tion. Some instances of reinforcing action were found ; for example, if two points of the skin of one shoulder are stimulated with a very feeble current, neither stimulus alone may be sufficient to evoke the scratch reflex, but the two together may elicit it; in order to attain this result the two points of skin must be fairly close together. The afferent neurons (private paths) of the body are about five times more numerous than the efferent (final common paths), and in the struggle for the occupation of these public paths by the impulses that enter the central nervous system by the more numerous private paths, three factors are specially concerned : — (1) Strength of stimulus ; the stronger the stimulus the better chance the resulting impulse has of getting round to the motor organ. (2) Character of impulse ; sensations of painful nature and sexual feelings win the final path easily; it is a matter of common experience that such sensations dominate and even exclude other sensations ; a man with bad toothache is not likely to take much notice of anyone who pulls his coat tails. (3) Fatigue; at the end of a long stimulation, a stimulus applied to a fresh reflex arc has a better chance of capturing the common path. 720 FUNCTIONS OF THE SPINAL CORD [CH. XLIX. Reaction Time in Man. — The term rfaclion time is applied to the time occu- pied ill tiie CLMitiJil nervous system in tiiat complex response to a pre-arranged stimulus in which the brain as well as the cord comes into play. It is sometimes called the prrsonat /(jiia/ion. It may be most readily measured by the electrical method, and the accompanyinjij diagram (fig. 414) will illustrate one of the numerous arrangemi-nts which have been projjosed lor the purpose. In the i)rimary circuit two keys {A and B) are included, and a chronograph (1), arranged to write on a revolving cylinder (fast rate). Another chronograph (2), Fni. 444. — Reaction time. marking 1-lOOths of a second, is placed below this. The experiment is performed by two persons C and D. The key vi, under the control of C, is opened. The key B, under the control of D, is closed. The electrodes E are applied to some part of D's body. C closes ^/. The primary circuit is made, and the chronograph moves. As soon as D feels the shock he opens B, the current is thus broken, and the chronograph lever returns to rest. The time between the two movements of the chronograph (1) is measured by means of the time-tracing written by chronograph (2). From this, the time occupied by transmission along the nerves has to be deducted, and the remainder is the renction time. It usually varies from 015 to 0*2 second, but is increased in : — The Dilemmd. — The primary circuit is arranged as before. The wires from the secondary coil lead to the middle screws of a reverscr without cross wires. To each pair of end sc-rews, a pair of electrodes E and E' pass ; these are applied to different parts of D's body (fig. 44;")). It is arranged previously that D is to open B, when one part is stimulated, but not the other, C adjusting the reverser unknown to D. Under these circumstances the reaction time is longer. The reaction time in response to various kinds of stimuli, sound, light, pain, etc., varies a good deal; the condition of the subject of the experiment is also an Fi(?. 445. — The Dilemma. important factor. This, however, is really a practical branch of psychology, and has recently been much worked at by students of that science (see also p. lyl). CH. XLIX.] VISCEIIAL REFLEXES 721 Spinal Visceral Reflexes. The spinal grey matter contains centres which regulate the operation of many involuntary muscles. Some of these centres are : — The cilio-spinal centre controls the dilatation of the pupil ; it is situated in the lower cervical region, reaching as far down as the origin of the first to the third thoracic nerve. Subsidiary vaso-motor centres. The principal vaso-motor centre is situated in the bulb, and subsidiary centres are scattered through the spinal grey matter (see p. 302). The same is probably true for all the muscular viscera, but particular study has been directed to those in the pelvis, and centres for micturition, defcecation, erection, and parturition are contained in the lumbo-sacral region of the cord. If the spinal cord is cut through above the situation of these centres, the result is in general terms that any influence of the higher (voluntary) centres over these actions is no longer possible. The actions in question are then simply reflex ones occurring unconsciously at certain intervals, and set in movement by the peripheral stimulus (fulness of bladder, or of rectum, etc.). If the portion of the cord where these centres are placed is entirely destroyed, the result is paralysis of the muscles concerned, though in certain cases, even after such a severe injury, some amount of recovery has been noticed, which must be attributed to the peripheral ganglia being able to play the part of reflex centres. The phenomena of micturition (p. 580), and defsecation (p. 562) have, however, already been described at length, and it only remains to add a few words concerning two other reflexes in which the generative organs are concerned. uterine Reflexes. — Uterine contractions can be induced by rectal injections, the passage of a foreign body into the uterus, the application of the child to the breast, and by other means. In animals faradisation of the central end of the first sacral nerve produces the same result. The contractions of the uterus are therefore reflex. Several cases have been recorded in which parturition has occurred normally in women who have had the cord divided across completely in the thoracic region ; it is thus evident the centre must be a lumbar one. In such cases the uterine con- tractions technically called "pains" are strong, but pain is, of course, absent. The communication with the lumbar region appears to be principally by the first three lumbar nerves. Similar observations have been made experimentally in animals, and in one of Goltz and Ewald's dogs in which the cord had been removed from the lower thoracic region downwards, pregnancy followed coitus, and terminated with success- ful parturition. The mammary glands enlarge as usual in such cases, even when, as in Rouths well-known case (where the cord was completely destroyed at the seventh thoracic segment), there can be no nervous communication between the pelvis and the breast. Erection. — This can be excited in man even immediately after a transverse lesion of the cord ; so also can ejaculation, but not so commonly. The evidence in favour of such acts being spinal reflexes is very complete in the case of animals. 2 Z CHAPTER L FUNCTIONS OF THE CEREBRUM The cerebriiin is the seat of those psychical or mental processes which are called volition and feeling; volition is the starting-point in motor activity; feeling or consciousness is the final phase of sensory impressions ; the correlation of sensations with one another, and with volitional impulses so generated is what constitutes thought. That the brain is the organ (or anatomical correlate) of mind is to-day a matter of such common knowledge that it is almost superfluous to mention it in a physiological text-book. Yet its functions were entirely unknown or only dimly conjectured by ancient philosophers, and the overwhelming importance of the grey matter on its surface in mental phenomena is a discovery of com- paratively recent date. Effects of Removal of the Cerebrum. The functions of any organ may be discovered (in part, at any rate) by removing it ; and the brainless frog which we have studied in relation to the functions of the spinal cord is also a useful object- lesson to teach us the uses of the part removed, by observing in what manner the animal differs from one which has its brain intact. If, instead of taking a frog, we take an animal lower in the scale, where the brain is not so fully developed, the effect of removing that organ will be less marked ; or if we remove the brain in a more highly developed animal, the simultaneous removal of the brain functions will be naturally more noticeable. "We have already seen (Chapter XLIV.) that the development of the cerebral hemispheres increases in importance as we rise in the animal scale. If the cerebral hemispheres are removed in a teleostean or bony fish (and in such animals there is only a rudimentary 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 CH. L.] REMOVAT, OF THE CEREBRUM 723 damage the primary centres of vision (the optic lobes, which corre- spond to the corpora quadrigemina of the mammal), 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 cerebrum. In either case the path between the olfactory bulbs and the centres that control the cord are interrupted. Going higher in the animal scale to the frog, we find that re- moval 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. 709. If the brain and the anterior end of the bulb are removed the lower centres of the cord are set free, and the result is incessant movement provoked by slight stimuli. A bird treated in the same way remains perfectly motionless, sleepy, and unconscious, unless it is disturbed (see fig. 446). When Fio. 446. — Pigeon after removal of the hemispheres. (Dalton.) disturbed in any way it will move ; for instance, when thrown into the air it will fly ; but these movements are, as in the frog, purely reflex in character ; when the animal is made to fly its movements are directed by the sense of sight, the optic lobes being still intact, and it w^ill select a perch to settle on in preference to the floor, It wiU start at a noise ; it will not eat voluntarily ; it exhibits no emotions such as fear, sexual feeling, or maternal instincts. In mammals the operation of extirpation of the brain is attended with such severe haemorrhage that the animal dies very rapidly, but in some few cases where the animals have been kept alive, the 724 ' FUNCTIONS OF THE CKREBRUM [CII. L. phenomena they exhibit are similar to those shown by a frog or pigeon. The difficulty of the operation was overcome by Goltz of Strassburg, in dogs, by removing the cerebrum piecemeal. One dog treated in this way lived in good health for eigliteen 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 coordinated move- ments, its reactions were entirely reflex, and memory, emotions, feelings, or the capacity to learn were absent. 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. 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. 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 I '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. There are 80,000 fibres in each pyramidal tract of the human cord. They are, moreover, not the only tracts which connect the cerebrum to the spinal cord, and section of these other tracts (see p. 656) may i)roduce quite as marked paralysis. In man, it appears that when the pyramidal tracts are diseased, it is the finer and more delicate movements which are permanently lost (Schiifer.). CH. L.] CEREBRAL LOCALISATION 725 Localisation of Cerebral Functions. The different parts of the brain and of its cortex are related to different parts of the body. The right hemisphere, for instance, con- trols the voluntary movements on the left side of the body, and receives sensory impulses from the left side, and vice versa. Then in each hemis})here there are certain areas, termed motor areas, which are the starting-points of those volitional impulses which give rise to movements; and other areas primarily concerned in the reception of sensory impulses ; these are termed sensory areas. These various areas have been mapped out by means of experiments on animals, and by the observation of disease in man. Before these facts were ascertained it was usual for physiologists to say that " the brain acts as a whole," and although we do not now attach the same meaning to that phrase as did the physiologists of the past, it still has an underlying substratum of truth. Let us take an example, and imagine the smell of an orange ; such an abstract idea of an isolated sensation is impossible ; we cannot think of the smell of the orange apart from the other characteristics of the fruit, the smell recalls the taste, the shape, the colour, the act of peeling it, fingering it, cutting it, eating it, and so forth. One sensation due to the activity of one area, such as the olfactory area, calls into play the activity of other sensory areas, and of the motor areas, and of the links between the sensory and motor areas. The brain is acting as a whole because its various parts are called into play simultaneously, though the whole brain is not concerned in each of the component sensations and volitions associated with any particular mental state. Moreover, the doctrine of cerebral localisation is not accurately expressed by the statement .that a cortical centre is one, the stimula- tion of which produces a definite response, and the extirpation of which abolishes the response. We shall, for instance, immediately see that the stimulation of certain areas in the dog's brain produces certain movements, but Goltz showed that in his dogs, the removal of an entire hemisphere did not cause permanent 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 or from them. 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 hmited 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 726 FUNCTIONS OF THE CEREBRUM [CH. L. 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. The earliest to work in the direction of localisation were Hitzig and Fritsch. The subject was then taken up by Terrier and Yeo, and later by Schiifer, Horsley, etc., in this country, and by Munk and many others in Germany. The main point which these researches have brought out is what we have just termed the overwhelming importance of the cortex ; it contains the highest cerebral centres. Before Hitzig bec^an liis work, the corpus striatum was regarded as the great motor centre, and the optic thalamus as the chief centre of sensation ; and the idea that the basal ganglia were so important arose from the examination of the brains of people who had died from, or at least suffered from, cerebral haemorrhage. The most common situation for cerebral haemorrhage is either in the region of the corpus striatum or optic thalamus ; it was noticed that motor paralysis was the most marked symptom if the corpus striatum was injured, and sensory paralysis if the optic thalamus was injured. The paralysis, however, is due, not to injury of the basal ganglia, but of the neighbouring internal capsule. The internal capsule consists in front of the motor fibres passing down from the cortex to the cord, and behind of the sensory fibres passing up from the cord to the cortex (see p. 689). Hence, if these fibres are ploughed up by the escaping blood, paralysis naturally is the result. If a haemorrhage or injury is so limited as to affect the basal ganglia only, and not the fibres that pass between them, the resulting paralysis is slight or absent. The question will next be asked : What, then, is the function of the basal ganglia ? They are what we may term subsidiary centres : the corpus striatum, principally in connection with movement, and the optic thalamus, in connection with sensation, including the sense of vision, as its name indicates. A subsidiary centre may be compared to a subordinate ofiBcial in an army. The principal centre may be compared to the commander- in-chief. Tliis highest officer gives a general order for the movement of a body of troops in a certain direction ; we may compare this to the principal motor-centre of the cortex sending out an impulse for CH. L.] MOTOR AND SKNSOKY AltEAS 727 a certain movement in a limb. But the general does not give the order himself to each individual soldier, any more than the cereljral cortex does to each individual muscle ; but the order is first given to subordinate officers, who arrange exactly how the movement shall be executed, and their orders are in the end distributed to the individual men, who must move in harmony with their fellows with regard to both time and space. So the subsidiary nerve-centres or positions of relay enable the impulse to be widely distributed by collaterals to numerous muscles which contract in a similar orderly, harmonious, and coordinate manner. There is just the same sort of thing in the reverse direction in the matter of sensory impulses. Just as a private in the army, when he wishes to communicate with the general, does so through one or several subordinate officers, so the sensory impulse passes through many cell-stations or subsidiary centres on the way to the highest centre, where the mental process called sensation, that is, the appreciation of the impulse, takes place. There are two great experimental methods used for determining the function of any part of the cerebrum. The first is stimulation ; the second is extirpation. These words almost explain themselves ; in stimulation a weak interrupted induction current is applied by means of electrodes to the convolution under investigation, and the resulting movement of the muscles of the body, if any occurs, is noticed. In extirpation the piece of brain is removed, and the result- ing paralysis, if any, is observed. It is essential, when the experiment of stimulating the cortex of the brain is being performed, that the animal should be anaesthetised and absolutely uncon- scious, otherwise voluntary or reflex actions will occur which mask those produced by stimulation. If, however, the animal is too deeply under the influence of a narcotic the brain is inexcitable. In an anaesthetised animal the brain is inactive, and if methylene blue is injected into the blood, the brain is seen to be of a blue colour. If, however, a spot of the cerebral surface is stimulated, that part of the brain is thrown into action, oxygen is used up, and the methylene blue is reduced, and in consequence that area of the brain loses its blue tint. If the animal is so deeply narcotised that the brain does not discharge an impulse, the part stimulated remains blue. By such means the cortex has been mapped out into what we may term motor areas and sensory areas. Motor area. — The name Rolandic area which this part of the brain has also received is derived from its anatomical position. Stimulation of the motor area produces movement of some part of the opposite side of the body ; excitation of the same spot is always followed by the same movement in the same animal. In different animals excitation of anatomically corresponding spots produces similar or corresponding results. It is this which has enabled one to apply the results of stimulating areas of the monkey's 728 FUNCTIONS OF THE CEREBRUM [CH. L. brain to the elucidation of the function of the similar brain of man. If the stimulation used is too powerful the movement spreads to other parts, and a considerable portion of the body may be thrown into convulsive movements similar to those seen in epilepsy. Extirpation, or removal, of these areas produces paralysis of the same groups of muscles which are thrown into action by stimulation. The degeneration tracts after destruction of the motor area are shown in fig. 447. The shaded area in each case represents the injured or degenerated material; A in the cortex, B in the anterior part of the posterior liml) of the internal capsule, c in the middle INTERNAL CAPSULE , Fillet MID. BRAIN Fio. 447.— Degeneration after destruction of the Rolandic area of the right hemisphere. (After Gowers.) of the crusta of the mid - brain, d in the pyramidal bundles of the pons, E in the pyramid of the bulb, and f in the crossed and direct pjTamidal tracts of the cord. Sensory areas. — Stimulation of these produces no direct move- ments, but doubtless sets up a sensation called a subjective sensation ; that is, one produced in the animal's own brain, and this indirectly leads to movements which are reflex ; thus on stimulating the auditory area there is a pricking up of the ears ; on stimulating the visual area there is a turning of the head and eyes in the direction of the supposed visual impulse. That such movements are reflex and not direct, is shown by the long period of delay intervening between the stimulation and the movement. J^xtirpation of a sensory area leads to loss of the sense in question. en. L.] HEMIPLEGIA AND MONOPLEGIA 729 The rougher experiments performed by nature in the shape of diseases of the brain produce corresponding results. Some diseases are of the nature of extirpation. An instance of this is cerebral hemorrhage. If the haemorrhage is in the region of the internal capsule, it cuts through fibres to the muscles of the whole of the opposite side of the body, as they are all collected together in a narrow compass, and the condition obtained is called hemiplegia. The varieties of hemiplegia are Fig. 448. — Brain of dog, viewed from above. F, frontal fissure, sometimes termed crucial sulcus, corresponding to the fissure of Rolando in man. S, fissure of Sylvius, around which the four longitudinal convolutions are concentrically arranged; 1, flexion of head on the neck, in the median line; 2, flexion of head on the neck, with rotation towards the side of the stimulus; 3, 4, flexion and extension of anterior limb; 5, 6, flexion and extension of posterior limb; 7, 8, 9, contraction of orbicularis oculi, and the facial muscles in general. The unshaded part is that exposed by opening the skull. (Dalton.) numerous, according as motor or sensory fibres are most affected, and in one variety of hemiplegia, called crossed hemiplegia, the face is paralysed on one side of the body, the limbs on the other ; this is due to injury of the tracts in the bulb, above the crossing of the pyramids. If now the haemorrhage occurs on the surface of the brain, a much more limited paralysis, called monoplegia, is the result ; if the arm area is affected, there will be paralysis of the opposite arm ; if the leg area, of the opposite leg ; if a sensory area, there will be loss of the corresponding sense. 730 FUNCTIONS OF THE CEREBRUM [CH. L. Some diseases, on the other hand, act as the induction currents do in artificial stimulation ; they irritate the surface of the brain ; such a disease is a tumour growing in the membranes of the brain ; if the tumour irritates a piece of the motor area, there will be involuntary movements in the corresponding region of the body ; these movements may culminate in the production of epileptiform convulsions commencing in the arm, leg, or other part of the body which corresponds to the brain area irritated. It is these cases of " Jacksonian Epilepsy" which have given the best results in surgery; the movement produced is an indication of the area of the brain which is being irritated, and the surgeon after trephining is able to remove the source of the mischief. If the area of the brain which is irritated is a sensory area, the result produced is a subjective sensation, similar to what we imagine is produced in animals with an electric current. AVe may now proceed from these general considerations to particular points, and give maps of the brain to show the areas we have been speaking of. Fig. 448 is a view of the dog's brain. It is convenient to take this first because it was the starting-point of the experimental work on the subject in the hands of Hitzig and Fritsch. If the text beneath the figure is consulted, it will be seen that the motor areas, mapped out by the method of stimulation, are situated in the neighbourhood of the crucial sulcus, which probably corresponds to the fissure of Rolando in man. Coming next to the brain of the monkey, figure 449 is repro- duced from Ferrier's book. He marked out the surface into a number of circles, stimu- lation of each of which produced movements of various sets of muscles, face, arm, and leg, from below upwards ; extirpa- tion of these same areas produced the correspond- ing paralysis. It will be further noticed that these areas are all grouped around the fissure of Eolando, particularly in the ascending frontal con- ^'*^" **^' volution. Much of our knowledge concerning the localisation of the motor area in the human brain has been deduced from experiments on the lower monkeys. Valuable as such knowledge is, infinitely more CH. L.] THK f'lTTMrANZEE'S BKAIN 731 useful knowledge, from the standpoint of the human brain, would be obtained by examining the brains of those monkeys nearest to man, which are known as the anthropoid apes. The difficulty and expense of obtaining such animals has largely deterred investigators from performing such experiments. Horsley and Beevor examined Toes Ankle "\ Knee Anus iKvaL^ina. ,:' SiilciLS ,■" . cenwaJis Abdomen Chest ringers 6r thum ' Opening of jav^ Vocal cords Sulcus centraJis Mastication Fir.. 450.— Brain of Chimpanzee. Left hpmisphere viewed from side and above so as to obtain the configuration of the Rolandic area. The figure Involves some foreshortening about both ends of the sulcus centralis or fissure of Rolando. The extent of the so-called motor area on the free surface of the hemisphere is indicated by black stippling which extends back to the central sulcus. Much of the " motor " area is hidden in sulci ; for instance, it extends into both the central and precentral sulci. The names printed in capitals on the stippled area indicate the main subdivisions of the "motor" area; the names printed small outside the brain indicate by their pointing lines some of the chief subdivisions of the main areas. But there is much overlapping of the areas which it is not possible to indicate in a diagram of this kind. The shaded regions marked " eyes " in the frontal and occipital regions indicate the areas which under faradisation yield conjugate movements of the eyeballs. S.F.=superior frontal sulcus. S.Pr. = superior precentral sulcus. I.Pr. =iuferior precentral 3ulcu3.i£(After Sherrington and Gninbaum.) the brain of an orang-outang some years ago, and now Sherrington and Griinbaum have made a number of experiments ; several speci- mens of two species of chimpanzee, the orang and the gorilla, have been examined. Their conclusions are of great importance. The above figure (fig. 450) of the chimpanzee's brain shows what has been found; the orang and the gorilla gave practically the same 732 FUNCTIONS OF THE CEREBRUM [CH. L. results, and no doubt the human brain would give identical results also if it could be examined. The method used is to expose the brain in an anaesthetised animal, and thoroughly explore it with a weak faradic current, one electrode being placed on the brain, and the other attached to an indifferent part of the animal's body. This allows of finer localisation than is possible with the ordinary double-point electrodes. The motor area includes continuously the whole length of the ascending frontal, or as it is sometimes called, the precentral convolution. It never extends behind the central sulcus, or, as it is sometimes called, the fissure of Eolando. On the mesial surface it extends but a short distance, and never as far as the calloso-marginal fissure. The motor area extends also into the depth of the Eolandic and other fissures ; the part of the excitable area thus hidden equals or may even exceed that on the free surface of the hemisphere. The arrangement of the various regions of the musculature follow the segmental sequence of the cranio-spinal series to a remarkable extent ; in fact, the excitable area may be compared to the spinal cord upside down. The accompanying figure indicates this better than any verbal description. It cannot fail to strike even a superficial observer how large the cortical area is that deals with movements of the head and arm regions when compared with that of the lower limb, and still more with that of the trunk. The trunk itself has a larger mass of muscular tissue, but it is in the head region (which includes the complex movements of the tongue and such structures as the vocal cords) and in the arm and hand that the movements are most varied and most delicate. No doubt this is the explanation of the greater size of their cortical representation. It is these finer movements 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. In experiments on unilateral extirpation in animals, and in destructive lesions of one side of the brain in man, it is the muscles which act normally unilaterally which are most paralysed. The muscles which normally move bilaterally, e.g., the chest muscles in breathing, the trunk muscles in maintaining an erect position, are comparatively little affected ; the spinal centres of such muscles are no doubt connected by commissural fibres, and therefore can be affected from both sides of the brain. The raarginal convolution on the mesial surface of the hemisphere was first investigated by Schafer and Horsley, in the lower monkeys. They found in these animals that it contained a considerable extension of the "motor" area, including the cortical centres for the trunk muscles. This, at any rate, is not the case for the higher apes, and therefore probably is not true for man. CII. l] THE SPEECH AND TACTILE AllEAS 733 It will be noticed in the diagram (fig. 450) that there are two regions of the brain from which eye movements can be elicited ; one is in the frontal lobe, the other at the occipital pole. The frontal eye area is the motor centre for conjugate movements of the two eyeballs, and in the lower monkeys is continuous with the rest of the motor area, but in the higher monkeys and man is separated from the Rolandic area by a field of inexcitable cortex. The occipital region from which eye movements can be obtained is the visuo-sensory sphere (see p. 736). The next illustration is an outline map of the left cerebral hemi- sphere in man. In it are indicated the various motor and sensory areas, which are largely deduced from experiments on the higher monkeys. VISUO-PSYCMIC SPHERE VISUO-SENSORY SPHERE TASTE AND SMELL Flu. 451. — Left cerebral hemisphere, outer surface. The lobes and the principal sulci are indicated by their initial letters ; A.E.M., anterior centre for eye movements ; B.C., Broca's convolution. One part of the motor area is peculiar to man, and that is : — The Speech Centre. — This is surrounded in the diagram by a dotted circle and marked B.C. There are other centres concerned in speech, as we shall see when considering the question of association fibres ; but this is the centre for the muscular actions concerned in speech. The discovery of this centre was the earliest feat in the direc- tion of cerebral localisation. It was discovered by a French physician named Broca ; he noticed that patients who died after haemorrhage in the brain, but who previous to death exhibited a curious disorder of speech called aphasia, were found, after death, to have the seat of the haemorrhage in this convolution. The convolution is generally called Broca's convolution. Experiments on animals are useless in discovering the centre for speech, Sherrington found in the higher apes that faradisation of the Broca area does not evoke vocalisation. The most curious fact about the speech-centre is that it is uni- lateral ; it is situated only on the left side of the brain, except in left-handed people, where it is on the right. We are thus left- brained so far as the finer movements of the hand-muscles are con- 734 FUNCTIONS OF THE CEREBRUM [CH. L. cerned, as in writing, and we are also left-brained in regard to speech, an action intimately associated with writing. There is but little doubt that spoken language originated from gesture language; in fact, one sees this in children learning to speak. In gestures the right hand (and left brain) will take a prominent part; hence the unilateral position of the speech centre receives a rational develop- mental explanation. That Broca's area is the chief speech centre has for long been a matter of doubt among physiologists and pathologists. The recent researches of Marie have thrown further doubt upon the hypothesis ; for he has shown that in many cases of aphasia Broca's area is uninjured, and that in cases where Broca's area is injured, aphasia is not always present. His main conclusion is that injury to Broca's convolution is only one factor in the causation of aphasia ; the other areas related to the speech mechanism are situated more posteriorly, and arc called the visual word area and the auditory word area (see further, p. 741), and injury to these alone will produce aphasia, whereas injury to Broca's area alone will not do so; he argues that the cases described in which aphasia followed an injury, apparently limited to Broca's area, had not i3een thoroughly investigated, and if the other areas had been properly examined injuries would have been found there also. These conclusions will naturally be tested in the future by others who have the opportunity of examining such cases. The Tactile Area, — Volition and the tactile and muscular senses are associated together so closely physiologically, that anatomically we should expect to find the commencement of the volitional fibres not far removed from the terminations of the sensory fibres, and as a matter of fact, this is actually the case. Some of the sensory fibres possibly pass direct into the ascending frontal convolution, but the vast majority terminate in its neighbour the ascending parietal convolution, which is on the other side of the central or Kolandic fissure. In the early days of brain map-making, the ascending parietal convolution was believed to be a part of the motor area, and this found expression in such diagrams as those of Terrier (see fig. 449). A cortical injury in man seldom involves the ascending frontal without also involving the ascending parietal, and so loss of sensation and motion usually go together. The more exact methods introduced by Sherrington and Griinbaum have, however, shown that stimulation of the ascending parietal produces no direct move- ments; secondary movements may be elicited, just as stimulation of the visuo-sensory area provokes secondary movements of the eyes. Extirpation of the ascending parietal, however, leads to no motor paralysis, and no degeneration of the pyramidal tracts. Histological examination of the ascending parietal grey matter shows it, moreover, to possess the structure of a sensory rather than of a motor area. Before this distinction was recognised, the term scnsori-motor was used as a comprehensive expression to include the functions of the two convolutions one on each side of the Kolandic fissure. The ascending parietal convolution is the cortical seat of those sensations CH. L.] THE VISUAL AREA 735 vvhicli are tactile discriminatory, and related to position and move- ment of the muscles. AVe still await exact information regarding the cortical representation of sensations of pain and temperature. This conclusion regarding the sensory function of the ascending parietal convolution has received support from a number of carefully observed clinical cases, for Sherrington and Griinbaum's delimitation to a relatively narrow strip of what had previously been considered a widespread motor territory, left for some time uncertain the function of the remainder of the original motor area — Munk's sensori-motor field — lying posterior to the central fissure. The most remarkable confirmatory evidence regarding the sensory functions of what we may call the post-central convolution has been recently afforded by two patients, who voluntarily allowed Dr Gushing of Baltimore the opportunity of experimentally testing the point after operations in which this part of the brain was exposed, and during a time they were in a conscious state. In both of them characteristic motor responses were obtained from the precentral gyrus (ascending frontal convolution) without any conscious sensation, except that which accompanies forced change of position in the parts moved. On the other hand, stimulation of the post-central gyrus (ascending parietal convolution) produced no movements, but gave definite sensory impressions which were likened by one patient to a sensation of numbness, and by the other to definite tactual impressions. There is, of course, a close connection between the two convolu- tions in question, by short association fibres passing from one to the other; and the necessity for sensation in normally provoking the corresponding motor outflow is also illustrated by the following experi- ment : — If the posterior roots of the spinal nerves are divided there is a loss of sensation, and so the sense of movement cannot reach the brain from the muscles, and consequently the muscles are not called into action ; when all the posterior roots coming from a limb in a monkey are cut, the muscles, so far as voluntary movements are concerned, are as effectually paralysed as if the anterior roots of the spinal nerves had been cut. The muscles, however, do not degenerate as they would if the anterior roots had been cut. They merely undergo a small amount of wasting, due to want of use. The Visual Area. — 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 in the optic lobes 736 FUNCTIONS OF THE CEREBRUM [CH. L. 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 sub- divisions of the visual cortical area, which correspond to different regions of the retinae. We may in fact speak of the visuo-sensory field in the cortex as the cortical retina upon which the impulses from the actual retina in the eye are projected, in a manner analogous to the way in which the field of vision is projected upon the actual retina. In the fishes which have no cortex cerebri, the optic lobes, analogous to the C. tiuadrigeinina, 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 distinct occipital lobe by the parieto-occipital fissure, which is frequently called the Afienspalte (ape's split). In the lower monkeys this lobe is smooth (fig. 427, A, p. 691), but as the great parietal association centres get larger with increase of intelligence, the visuo-sensory area is pushed back, and the lobe 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. This calcarine area is also named the striate area, because it is characterised by the white stripe called the line of Gennari. 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 hemi- sphere. 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-limbs, 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 retince, 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 versd. The appearance of the macula lutea (with cortical representation in both hemispheres) in the primates is the culminating point in visual development among the mammals. CH. L.] THE VISUAL AREA 737 A man or an animal who loses both eyes is blind, but in time manages to tind 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 sensory memories and motor impulses is then impossible. Kemoval of one occipital lobe will be followed by different results in the two classes of animals just referred to. In those with pano- ramic vision, the result will be blindness of the opposite eye, because the decussation of the optic nerve is complete at the chiasma. But in animals such as monkeys with stereoscopic vision (in which the only decussating fibres are those which come from the inner halves of the two retinae) removal of one occipital lobe, or disease of that lobe in man, produces blindness of the same side of each retina, or inability to see the opposite half of the visual field. This is called hemianopsia ; the head and eyes are turned to one side, namely, the side of injury {conjugate deviation to the side of the injury). Such an operation does not destroy vision in the central portion {macula lutea) of either retina, because each macula sends impulses to both sides of the brain. Stimulation of one visual area leads to a subjective sensation apparently coming from the same halves of both retinae, and also excites the solitary cells of Meynert; this produces conjugate deviation of head and eyes towards the opposite side to that stimulated. These solitary cells are so called because they are few and far between ; they are large cells not at all unlike the Betz cells of the motor cortex. Their axons, no doubt, pass in long association tracts to the motor eye centre of the frontal region and to the corpora quadrigemina. The optic radiations consist of (1) sensory fibres from the optic tracts via the external geniculate bodies; (2) efferent fibres to the centres for eye-movements ; and (3) association fibres, which are last developed. The last named link one convolution to others, and the two hemispheres together, and bring about association of ideas of vision in both hemispheres, and with other sensations. A large collection of such fibres runs horizontally through the grey matter. This white stripe is often visible to the naked eye ; it is the anatomical mark of the visuo-sensory cortex, and is called the line of Gennari. The visuo-psychic region (fig. 451) has no line of Gennari, but possesses many small and medium-sized pyramidal cells in its outer layers, which play the part of association units, where memory pictures are stored and visual sensations correlated with those from other sense-organs; the higher one ascends the animal scale, the greater becomes the depth of this layer. The eye centre in the frontal lobe is separated, in the higher apes and man, by inexcitable grey matter from the rest of the 3 A 738 FUNCTIONS OF THE CEIIEBKUM [CII. L. motor area. No cortical centre is purely motor or ])iirely sensory, and this one, though usually called motor, has its sensory complement probably from the eyeballs and eyelids (5th nerve). The newly developed grey matter between it and the Pujlandic region is an area probably concerned in the association of eye movements with equilibration and the maintenance of the erect position ; we know, moreover, that the fibres from the frontal lobe to the cerebellum (the centre for equilibration) are very numerous (see fig. 437, A, p. 699). The Auditory Area is in the posterior part of the upper temporal convolution. This has been definitely proved by clinical observation in man, and supported by experiments on animals, though it is by no means easy to ascertain whether or not an animal is deaf. It is doubtless surrounded, as are the visuo-sensory area and other sense areas, by a psychic or association sphere, and is connected to surrounding parts, and especially to the visual area, by annectent gyri. A good deal of the auditory area is situated in the depth of the Sylvian fissure where the gyri tranversales which cross it are found. Taste and Smell are closely connected ; their cerebral area is the uncinate and hijtpocampal gyrus, and the tip of the temporal lobe. These parts are relatively more important in animals who rely upon smell and the oral sense for their guidance. This part of the cortex is of simpler structure than the rest, and on account of its early appearance in the animal scale is known as the archipallium (see p. 698). The Silent Areas, — On referring once more to the maps of the brain, it will be seen that there are many blanks; one of these is in the anterior part of the frontal region. Extirpation or stimulation of this part of the brain in animals produces but little result. The large size of this portion of the brain is very distinctive of the human brain, and it has therefore been sup- posed that here is the seat of the higher intellectual faculties. Such a question is obviously very difficult to answer by experi- ments on animals. Both experimental physiology and pathology have localised the sensory areas (and sensations are the materials for intellect) behind the Eolandic fissure, but this does not necessarily mean that the frontal convolutions have nothing to do with intellectual functions. The celebrated American crowbar accident is generally quoted as a proof to the contrary; owing to the premature explosion of a charge of dynamite in one of the American mines a crowbar was sent through the frontal region of the foreman's head, removing the anterior part of his brain. He is usually stated to have subsequently returned to his work, without any noteworthy symptoms. Kecent examination of the records of the case has shown that this is not correct ; when he returned to work he was practically useless, having lost just those higher CH. L.] FUNCTION AND MYELIN ATION 739 fauctious which are so importaut in the superintendence of other people. Mott's observations on lunatics show that this region is important for intellectual operations, though not so important as the parietal association area behind the Eolandic area; the greater the intellectual development, the larger and more convoluted does this parietal region become. The association fibres have been the subject of special study by Flechsig, who has shown that in the development of the brain these are the last to become myelinated ; white fibres do not become fully functional until they receive their medullary sheath. This coincides with the well-known fact that association of ideas is the last phase in the psychical development of the child. It has been shown that the frontal convolutions are connected by important association tracts with the more posterior regions of the brain (see fig. 436, p. 699), and there is therefore no difficulty in understanding that the frontal coavolutioQS play the pxrt of a centre for the association of ideas, or in other words for intellectual operations. Function and Myelination. Flechsig's embryological method has ^ven us most valuable knowledge of the structure and functions of the human brain. The method depends on the fact that various tracts of fibres become myelinated, i.e., acquire their medullary sheath at successive periods of time in development. The myehn sheath appears three or four months after the axis cyUnder is formed. The Weigert method of staining renders Fig. 452.— Diagram of vertical secliuii through braiu of new-bom child, drawn from one of Flechsig's I>holographs. The section was treated by Weigert's method, by which myelinated fibres are deeply stained. Attention is drawn to the deep shading indicating myelination around the central fissure, which corresponds to the sensori-motor area, and also around the calcarine fissure in the visual sphere. The association fibres are not myelinated. The fibres of the pyramidal efferent system have also no myelin. M.O., medulla oblongata; P.V., pons Varolii; O.M.N., oculo-motor nerve; CO., optic commissure; F.A.C., frontal association centre; C.C., corpus callosum ; C.F., central fissure, or fissure of Rolando; P.A.C., posterior association centre; V.S., visual sphere; C, cere- bellum ; S.C, spinal cord. the detection of a medullary sheath an easy task. Flechsig's method is in short the complement of the Wallerian method. In the former method the tracts are isolated by the differences in the origin of the myelin sheath ; in the latter method, the same object is obtained by observing the degeneration which is most noticeable in the same sheath. In the central nervous system, the afferent projection fibres are myelinated first ; 740 FUNCTIONS OF THE CEREBRUM [CH. L. tlie efTerenl projection fibres and the association fibres are myelinated later. Tlius in the human fn'tus the peripheral nerves and nerve-roots become myelinated in the fifth month of intra-uterine life ; of the tracts in the cord, those of Burdach and GoU {exufienoiis fibres springing from the cells of the spinal ganglia) are the first to be myelinated ; next come the tracts of Flechsig (dorsal cerebellar) and of Gowers (ventral cerebellar) : these are oidiniinints fibres springing from cells within the cord. All these tracts are afTerent. The pyramidal tracts, the great efferent or motor channels, are not myelinated until after birth. The whole afferent tract is myelinated at birth ; these fibres have in ntcro been exercised in conveying impressions to the afferent reception centres, the stimuli arising from contact of the foetal integuments with the maternal tissues. There is also early myelination around the calcarine fissure in the visual sphere, and in connection with the areas related to other special senses. This is shown in figs. 452 and 453, where the condition at birth and that some months later are compared. Ambronn and Held confirm Flechsig in finding that the afferent fibres are myelinated before the efferent, in the central nervous system, but in the case of the nerve-roots this is reversed, the anterior root-fibres being myelinated before the posterior. Held has also demonstrated the important influence of stimulus on myehnation. His experiments were made on cats, dogs, and rabbits, which are born bhnd. If C.F. < s '^^-^^"'■'^^ 'A \ RA.C Fio. 453.— Diagram of vertical section of the brain of a child 5 months of age. The greater part of the white matter now shows myelination, thus iniiicating development of the association centres. The letters have the same meaning as in Fig. 452. (After Flechsig ; Weigert method of staining.) light is admitted to one eye by opening the lid, more obvious myelination is subse- quently found in the corresponding optic nerve than in that of the opposite side. This is not due to the irritation caused by forcibly opening the lid, for if the lid be opened and the animal kept in the dark, no difference in the myelination of the two optic nerves is observable. Flechsig also showed that a child born at 8 months had more marked myehnation of its optic nerves, a month later, than a child born in the usual way at the ninth month. The richness of the brain in myelinated fibres increases for many years after birth with the progress of intellectual development. Kaes states this continues up to forty years of age, and that in old age the number diminishes. Myelin appears to be necessary for the functional activity of nerve tracts, and its development progresses pari passu with development of function ; the reverse change (atrophy and degeneration) correspondingly accompanies marked disturb- ances of function. Association Fibres and Association Centres. We know by common experience that any group of muscles can be voluntarily contracted in reply to any form of stimulus, cutaneous, visual, auditory, eta If, for instance, the wrist is flexed in response to an auditory stimulus, the nerve CH. L.] MYELOGENETIG FIELDS 741 impulses pass first to the auditory area, then by certain fibres to the cerebral cells which control the muscles of the arm. The fibres which connect the two areas are termed ossoriafion fihrts. A diagrammatic view of the principal bundles of association fibres is given in fig. {3(), p. 699. The term ''■ ci((fi<»i. centres'''' is given by Flechsig to those portions of the cortex that lie between the sensory centres. The function of these centres is first to furnish pathways between the several centres, and secondly to retain as memories previous sense impressions, so that in action they may modify the impulses sent into them, and by these modifications adjust to an almost infinite degree the form of the final response. The association centres comprise a very large area of the cortex, and are divided into three:— (1) The great anterior association centre in the frontal lobe ; (2) the posterior association centre in the parieto-temporal region ; (3) the Fig. 454. — Lateral view of the left cerebral hemisphere of man (after Donaldson). V is the cortical area damage to which produces "word blindness " ; it is situated in the angular gyrus, and is called the visual word centre. H is the area in the superior temi)oral convolution, called the auditory word centre, damage to which produces " word deafness." S is Broca's convolution, damage to which produces loss of audible speech (motor aphasia); this is the motor area for the movements of the tongue, vocal cords, etc., concerned in speaking; Bastian terms it the glosso-kimesthetic area. The area W, called by Bastian the cheiro-kincesthetic area, is the corresponding region concerned in hand movements, damage to which abolishes the power of writing (agraphia). middle association centre ; this is smaller and coincides with the island of Reil. These regions are in fact those in which no evident response follows excitation ; they are sometimes called the " latent or silent or inexcitable cortex." The human brain is characterised by the high development of these parts, and as already explained they are doubtless, as Flechsig terms them, the organs of thought. The importance of the association of ideas, which has for its anatomical basis the association of cortical centres, will be at once grasped when one considers such complex actions as speaking, reading aloud, or writing from dictation. The accompanying diagram (fig. 4.54) shows the position of the main centres involved, particulars of which will be found in the small text beneath the figure. In reading aloud, the impressions of the words enter by the eyes, reach that portion of the visual sphere known as the risnal loord centre, travel across to the auditor}/ word centre by association fibres, where the memory of their sounds is revived ; another tract of association fibres connects this to the sensori-motor area in Broca's convolution called by Bastian the (/losso-kincesthetic area, whence motor impulses originate which finally reach the muscles concerned in pronouncing the words originally seen. Writing from dictation is just as complex; the course of the impulses is by the auditory channels to the auditor}/ word centre, then by association tracts to the visual word centre, where the shapes of the letters composing the words are revived ; another association tract carries the impulse thence to the sensori-motor 742 FUNCTIONS OF THE CEREBRUM [cn. L. area connected with the movements of the liand (Bastian's clinro-kinasfh/tic arfu) near the middle region of the Roiandic cortex, and finally the movement of writing is accomplished. The diverse symptoms exhibited l)y patients suffering from various forms of aphasia can be all explained l)y more or less extensive damage Fio. 455.— Outer surface of human brain, showing Flechsig's developmental zones; primarj- (1—10) darkly shaded ; intermediate (1 1 — 31), less deeply shaded ; terminal (3:;— 3i'i), not shaded. (Flechsig.) either to the centres themselves or to the association tracts which connect them. In the cerebral convolutions the fibres become myelinated in a strictly regular sequence ; some convolutions have their fibres medullated three months before birth, while in others complete myelination has not occurred six months later. Fia. 456. — Inner surface of same. (Flpchsi Fibres of equally great importance become medullated at the same time; those of primary importance first, and so on. In this way, myelogenetic cortical fields can be mapped out, which retain their contours for some time. Thirty-six of such fields were made out by Flechsig, and can be divided chronologically mto three groups, primary, in/nrmeduthu and iermiri^ 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. Electrical Variation in Central Nervous System. Du Bois Eeymond 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 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. 744 FUNCTIONS OF TUE CEREBRUM [CH. L. Sleep and Narcosis. 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 control, as, for instance, in closing the eyes, or retiring to a quiet 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 profoimd ; 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. Sensations of sound appear to be the last to disappear as sleep comes on, and the first to be realised on awakening. 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. 313); 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. Howell among others believes it to be the cause, and attributes the sleepiness that follows a heavy meal to the mechanical effect of a dilatation of the abdominal vessels in producing a diminished blood- flow through the brain ; but the sleep that normally comes on at the end of the day, he believes to be produced by cerebral anoemia follow- ing dilatation of the blood-vessels of the skin, such dilatation being due to vaso-motor fatigue. 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 acid in nature, and others regard them as alkaloidal. These theories CH. L.] SLEEP AND NARCOSIS 745 all rest upon the flimsiest 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 such as opium and chloroform, which is different from that which obtains in the waking state. Demoor and others found in animals in which deep anaesthesia has occurred, that the dendrites exhibit moniliform swellings, that is, a series of minute thickenings or varicosities. On the strength of this observation, what we may call a biophysical theory of sleep has been formulated ; in the waking state, the neighbouring 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 an outline of a few of the cells and their branches. A more satisfactory histological 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 Golgi 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. 457). 746 FUNCTIONS OF THK CERRBKUM [CII. L. 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 biochemical rather than biophysical, and he has been led to this conclusion by the employment of other histological 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 cells consequently present what Wright calls a rarefied appearance ; A B Fio. 457.— Jlohiliform eiilargemenls on deii'Jriles of Leive-cells, rei.dcreiJ evident by Cox's modification of Golgi's nietliod. A, in a cortical cell of a rabbit ; C, in a corresijonding cell of a dog's biain, after six hours' ansesthetisalion with ether in each case, (llamillon Wright.) 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 tlie anaesthetic no doubt interferes with the normal metabolic activity of the cell-body, and this produces efTects on the cell-branches. In CII. L.] SLEKP AND NARCOSIS 747 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 raoniliform enlargements seen during the temporary pseudo-degenera- tive effects produced by anaesthetics are comparable to this. These 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. Moore and Roaf believe that the substance in the nerve-cells (as well as the other cells of the body) which is affected by chloroform is the protein. They have shown that unstable compounds of protein and chloroform are obtainable ; hence the greater solubility of chloro- form in blood than in water. They compare the chloroform-protein compound to oxyhoemoglobin, for it undergoes dissociation in the same sort of way. Just as oxyhfemoglobin parts with its oxygen to the tissue-cells, so the chloroform parts company from the blood- protein, and enters into combination with the cell-protein, limiting its activity and producing quiescence or anaesthesia. When the administration of the chloroform ceases, the tension of chloroform in the blood is no longer maintained, so the combination between the cell-protein and chloroform dissociates, and anaesthesia passes off. The theory which has met with most favour in relation to anaes- thetics, however, is that known as the Meyer- Overton hypothesis; this theory, which has received abundant confirmation by numerous observers, points out that the cells are easily permeable to the vola- tile anaesthetics owing to the presence of fat and lipoid material in their plasmatic membrane (see p. 330). It can hardly now be doubted that the solubility of the volatile anaesthetics in the lipoids of the membrane (or, what comes to the same thing, the solubility of the lipoids in the anaesthetic) is an important factor in anaesthesia ; the anaesthetic thus enters the cell easily, and throws the lipoid con- stituents of the protoplasm (and perhaps secondarily the protein constituents also) out of gear, the net result being a lessening of the oxidative changes which are essential in active vital processes. The volatile anaesthetics, and especially chloroform, are dangerous drugs, and although their discovery is one of the greatest blessings to suffering humanity, and in experiments on animals, means should be adopted for preventing the fatalities which are even now too frequent. It is specially needful that anaesthetists should not administer the drug in a haphazard way, but take care that the amount 748 FUNCTIONS OF THE CEREBRUM [CH. L. of chloroform in the inspired air should never rise over 2 per cent. ; smaller percentages may be employed when once tlie patient is under the influence of the drug. There have been several instruments invented (by AYaller and otliers) by means of which the concentration of the chlorcjform given can be easily measured. But the artificial sleep of a deeply-narcotised animal is no criterion of what occurs during normal sleep. The sleep of anaesthesia is a pathological 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 culmi- nate in death. Natural sleep, on the other hand, 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. This is true for many other organs in addition to the central nervous system ; sleep is a time of repose for them also, but the amount of rest varies ; the voluntary muscles, except those concerned iji breath- ing, will rest most, but the heart continues to beat, the urine is still being secreted, the processes of digestion go on, so that for such organs activity is only diminished. It should be recognised by the public that sleep is the period of anabolism, repair and growth, and a large allowance is therefore necessary in growing children. The mistaken Spartan discipline of certain parents and schoolmasters in insisting upon a short period of repose often does incalculable harm both mental and physical to those under their charge. When in the children of the poorer classes, early rising for the purpose of earning a miserable pittance is com- bined with late hours of retiring to rest, and with the discomforts of crowded bedrooms, and crowded beds which render real rest impos- sible, the damage done is greater still, and is one cause of physical deterioration. Many children judged to be "defective" are really only suffering from want of sleep. Loss of sleep is more damafring than starvation. Dofrs will recover after being starved for three weeks, but they die from loss of sleep in five days. The body temperature fails, refiexi-s disappear, and jios/-t»ortem the brain is found to contam capiJlary hsemorrhages, the cord is dry and anjpmic, 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 temi>erature 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, excej)t 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, includiiitr the increase of weight, disappeared. The slcej) produced by hypnotic- suggestion differs from ordinary sleep. But exact knowledge of the phenomena of this kind of sleep is at present lacking. CHAPTER LI 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 famihar fact that in displacements of equihbrium 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 cerebeUum does receive certain impulses from the viscera. 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 cerebeUum. 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 cerebeUum was first pointed out by Flourens, who showed that the cerebellum is the great centre for the coordination of muscular movement, and especiaUy for that variety of coordination which is called equiUbration — that is, the harmonious adjustment of the working of the muscles which maintain the body in a position of equiUbrium. It must not be supposed from this that the cerebeUum is the sole centre for coordination. We have already seen that all the machinery necessary for carrying out very comphcated 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 cerebeUum. An instance of a complex coordinated movement is seen in what we learnt to call in the last chapter conjugate deviation of head and eyes. The higher cortical centre gives the general word of conmiand to turn the head 750 FUNCTIONS OF THE CKREBELLUM [Cll. LI. 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 suppHed 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 suppUed by numerous nerves. The relaxation of the antagonistic muscles has also to be provided for. We thus see how the complicated intercrossing of fibres and connec- tions 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) which are employed in similar researches on the cerebrum. The anatomical connections of the cerebellum with other parts of the cerebro-spinal axis by its three peduncles have been already considered on p. 684. Fig. 458. — Pigeon after removal of ihe cerebellum. (DalU)n.1 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 coordination of the bodily movements. The cerebellar hemispheres are especi- ally connected with the opposite cerebral hemispheres ; and just as the different regions of the body have corresponding areas in the cerebrum, so also they are similarly represented in the cerebellum ; but it does not appear necessary from the practical standpoint to go here into the scanty and disputed details of cerebellar localisation already discovered. If the cerebellum is removed in an animal, or if it is the seat of disease in man, the result is a condition of shght muscular weak- ness ; but the principal symptoms observed are lo.ss of muscular tonus and a condition of incoordination, 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 (fig. 458); the CII. I.l] FUNCTIONS OF THK CERKBKLLUM 751 disturbed condition of the animal contrasts very torcihly with the sleepy state produced by removal of the cerebrum (see fig. 4-46, p. 723). 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. Impulses also pass out to the cord (see p. 685), but the exact course of some of the descending tracts 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. 459). In order that the cerebellum may send out impulses in this way, it is necessary that it receive impulses which guide it by keeping it informed of the position of the body in space. These impulses, we have already insisted, though afferent are non- sensory; they travel by paths which at the start, however, are offshoots from those which carry the real sensory impulses to the cerebrum. These afferent impulses originate from or are associated with the impulses which in the cerebrum produce sensations of the four following kinds : — Fio. 459. — This is a rpproduction of a photograph of a lunatic's brain lent me by Dr Fricke. One cerebral and the opposite cerebellar hemisphere are atrophied. 1. Tactile. 2. Motorial. 3. Visual 4. Labyrinthine. 1. Tactile impressions. — The importance of the tactile sense is obvious ; and in diseases of the afferent tracts, loss of that sense in the lower limbs leads to disturbances of equilibrium ; in such cases a man has difficulty in balancing himself wdiile standing with his eyes shut. Sherrington, however, has shown how comparatively unimportant is the loss of tactile sensibility from the feet. A cat, in which the feet have been completely desensitised by division of all their nerves, can stand and walk without obvious inconvenience. It is not until the sensitiveness of the joints, especially in the upper segments of the limb, is interfered with that marked disturbances of balance are noticeable. 2. Motorial impressions. — Another important sense is that which 752 FUNCTIONS OF TTIE CEREBELLUM [CH. LL enables us to know what we are doing with our muscles. Sensory fibres 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 ascending parietal convolution. Their offshoots, which carry the non-sensory impulses to the cere- bellum, reach it via Clarke's column and the cerebellar tracts. In many cases of locomotor ataxy there is but little loss of tactile sensibility, and the condition of incoordination is then chiefly due to the loss of impressions from motorial organs (muscles and joints). 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. Under more ordinary cir- cumstances, the nou-sensory visual offshoots which enter the cere- bellum are sufficient to maintain equilibrium. In speaking of visual impressions it should be understood that these in themselves are not the actual guide. It is the projection of what is seen in relation to the position of the body (ascertained by the innervation of the head muscles and ocular muscles) that is the chief guide. 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, and in this case the sensory element is subordinate to the non-sensory. Here, however, we must pause to consider some anatomical facts in connection with the semicircular canals that make up the labyrinth. Fig. 460 is an external view of the internal ear ; it is enclosed within Fi(.. 4(30. — Right 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; *, ampulla; of the semicircular canals ; 6, first turn of the cochlea ; 7, second turn ; S, apex ; 9, fenestra rotunda. The smaller figure in outline below shows the natural size. (Summering.) CH LI.] LABYRINTHINE IMPRESSIONS 753 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 remainder of the internal ear is concerned not in hearing, but in the reception of the impressions we are now studying; it is sup- plied by the vestibular division of the eighth nerve. 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 endolymph, 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. 461 shows in transverse section the way in which the membranous is contained within the bony canal ; the membranous 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 papillae except just where the attachment of the membranous to 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. 462) ; the cells of the epithelium become columnar in shape, and to some of them fibres of the eighth 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- FiG. 461.— Section of human semicircular canal. (After Riidinger.) 1, Bone; 2, periosteum ; 3, 3, tibrous bands connecting tlie periosteum to 4, the outer fibrous coat of the membranous canal ; 5, tunica propria ; 6, epithelium. 754 FUNCTIONS OF THE CEREBELLUM [CH. LL cells which act as supports (fig. 463). When tlie endolymph in the interior of the canals is thrown into vibration, the hairs of the hair- Fio. 462. — Section llirougli the wall of the amimlla of a semicircular canal, passint; through the crista acoustica. 1, Epithelium ; 2, tunica jiropria ; 3, librous layer of canal ; N, bumiles of nerve-fibres ; C, cupula, into which the hairs of the hair-cells project. (After Scliafer.) cells are affected, and a nervous impulse 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 of the vestibular nerve are distributed. 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 vestibular nerve; these impressions are set up by the varying pressure of the endolymph in the ampuUse. Thus a sudden turning of the head from right to left will cause movement of the endolymph towards, and therefore increased pressure on, the hair-cells connected to the am- pullary nerve-endings of the left horizontal canal, and diminished pressure on the corresponding apparatus 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. It may Fid. 463.— 1, Uair-cell; 3, hair-cell, showinj; the hair broken, and the base of the hair split into its constituent librils ; 2, libre- cell ; N, bundle of nerve-libres which have lost their medullary sheath, and terminate by arborising round the base of the hair-cells ; A 13, surface of tunica l)roi)ria. (After Retzius.) CM. LI.] THE SEMICIRCULAR CANALS 755 even be that increased pressure on one side of a crista is accompanied by diminished pressure on the opposite face of the same crista. " 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 ampullar turned opposite ways. Each pair would thus Ite 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. 464). Fio. 464. — Diagram of semicircular canals, t/O sbuw their posilion.s in three i)lanes at ri<,'lit angles to each other. It will be seen that the two liorizontal 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. (The student will understaml that though in the diagram the canals are entirely separated from one another, that they are really connected, as shown in fig. 460.) (After Ewald.) When these canals are diseased in man as in Meniere's disease, there are disturbances of equilibrium : a feeling of giddiness, which may lead to the patient's falling 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. Goltz describes a pigeon so treated which always kept its head with 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 manner. Gyon says it is almost impossible to give an idea of the perpetual 756 FUNCTIONS OF THE CEREBELLUM [CH. LI. 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 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, probably 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 sensa- tions 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. 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 conHicting ideas of the position of the body relatively to external objects. A cerbiin 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 is a})proximately the frequency in which abnormal conditions of the canals have been found post-morlem in deaf mutes. Section and stimulation of the inferior cerebellar peduncles (the path by which the vestibular fibres reach the cerebellum, see p. tiS2) cause incoordination, chiefly evidenced by rotatary and circus movements similar to those that occur when the nerve-endings in the semicircular canals are destroyed or stimulated. Stimulation of the cerebellum itself — and this has been done through the skull in man — causes giddiness, and consequent iimscular efforts to correct it. The results of stinmlation, 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 secondary changes in the brain. CHAPTEE LI I THE PHYSIOLOGY OF CONSCIOUS STATES There are certain considerations, relating to the physiology of con- scious states in general, to which it will be well to pay attention, before we pass to a detailed study of the special senses. It is sometimes argued that states of consciousness are the product of the activity of nerve-cells, just as bile is the product of the activity of the liver-cell, or as contraction results from the activity of the muscle fibre. But this analogy will not bear close investigation. It is, however, true : — (1) That the different senses are dependent for their manifesta- tion on the integrity of different definitely localisable areas of the cerebral cortex. (2) That such drugs as alcohol, caffein, and chloroform, which have a known action on living substance, also affect the course of conscious processes. (3) That disease or malformation of the brain is accompanied by impairment or absence of intelligence. But because nervous substance is essential for the manifestation of conscious states, one cannot legitimately infer that this substance 'produces those states. Indeed, by a vast number of philosophers a very different position has been upheld. So far from believing that mind results from the activity of living matter, they have insisted that all matter, living and lifeless, results from the activity of mind. They maintain that, were it not for mental activity, there would be no conception, nay not even existence, of those qualities {e.g., sound, colour, force, weight, hardness) of which our non-mental world of matter is composed. There is no difficulty in accepting the statement that bile is secreted by the liver ; in this case the product is physical, and it is produced by physiological {i.e., presumably, by chemical and physical) conditions. On the other hand, if we state that consciousness is secreted by the brain, we are linking together two sets of phenomena, the psychical and the physiological, between which a connection is inconceivable. 757 758 THE PHYSIOLOGY OF CONSCIOUS STATES [CH. LII. Consequently, instead of stating that physiological activity is the cause of mental (or psychical) activity, it is more satisfactory to assume that the two activities run parallel with one another, and to recognise that the nature of their relation is unknown. This con- ception of psycho-physical parallelism affords the physiologist by far the best working hypothesis. It leaves unanswered the great question whether brain ever acts on mind, or mind on the brain — which of the two is the master or the servant of the other. It merely implies that a change in nerve substance underlies every psychical change ; and it bids the physio- logist investigate the functions of the nervous system, and determine what structures are called into activity in the development of various conscious states. We must recognise that, however completely we may one day have mapped out the functions of the various parts of the brain, we shall nevertheless not have approached a step nearer towards under- standing the relation between the data of physiological and psychical activity. If we knew the function of every nerve cell of the body, the gap between the material and the mental would not be a bit less wide. Just as a ray of light cannot see itself, so we cannot expect to understand states of consciousness from a mere study of cerebral function. It is therefore imperative to avoid confusion between the two aspects involved in this psycho-physical parallelism. The psychical is one language, the physical (i.e. the physiological) is another; and the two vocabularies must be kept distinct from one another. Psychology and physiology stand in the relation of an object and its mirrored reflection. To confound object and image — to speak, for instance, of a sensation (instead of an impulse) being transmitted along a nerve-fibre, is to blur and to confuse two distinct sciences. The psychologist distinguishes three modes in which conscious- ness is manifested. These are (1) the cognitive, (2) the affective, and (3) the conative modes. Through the cognitive mode we become aware of the object thought of. Owing to the affective mode, our state of consciousness is toned with pleasure, indifference, or dis- pleasure. The conative mode manifests itself as a striving or " felt tendency" towards an end. In every state of consciousness these three modes are present, but their relative prominence is always different. For example, in perception, in memory, or imagination, the cognitive element is to the fure; in love, sorrow, or doubt, the affective element predominates ; while in intense desire, the conative element is most easily recognisable. Into the physiology of affection and conation we shall not enter here. They receive adequate atten- tion in books devoted to physiological and experimental psychology. But a conscious state implies also a contrast between what is CII. LII.] THE PHYSIOLOGY OF CONSCIOUS STATES 759 outside of ourselves (the object) and our feelings and strivings in connection with it, which are spoken of as subjective. The existence of this " subject-object relation " implies the activity of an E ( »' \ A 9 I 5 i » , < > » ^ 'f L f ^ l' V 1 i >, J t ' 'l ' ► 1 ' ^ l' < > 1 1 ► ) 1 f ' ' ' ' 1 7 1 ^ ) •r 1 - 1 1 )i 1 -\ c )' A ; *■ i ( ,< ) ( ) (J H. JL Fio, 477.— Heat and cold spots. (Somewhat enlarged ; after Donaldson.) represent cold spots, their size indicating the strength of the reaction. The open circles represent heat spots. All these facts clearly indicate that different varieties of sensation are the result of the stimulation of different end-organs, and that the impulses are conveyed to the central nervous system by different groups of nerve-fibres; they moreover form the clearest piece of evidence we have that pain is a distinct kind of sensation. The question is more difficult to answer, which particular end- organ is concerned with each variety of sensation. There is, how- ever, little doubt that the nerve-fibrils around the hair follicles of the short hairs are the terminations most affected by changes of pressure, and also that Meissner's corpuscles are purely tactual, taking the place of hairs in hairless parts. In the palmar surface of the last phalanx of the index finger, there are 21 Meissner's corpuscles per square centimetre; in other parts of the palm and sole the number varies from 2 to 8. End-bulbs are believed to 774 CUTANEOUS SENSATIONS [CH. LIIL be the organs for cold ; they are most numerous in the conjunctiva and glans penis, where " cold spots " are almost exclusively present. The end-organs in "heat spots" have not been identified with certainty, but they are probably larger organs, and placed more deeply in the skin. We have spoken of the pressure sense as the true tactile sense ; but Meissner pointed out many years ago that the hand immersed in a fluid such as mercury at body-temperature, does not feel the contact of the fluid, although the fluid pressure may be far above the limen ; it is, however, equal in all directions ; it is therefore clear that the adequate stimulus for touch organs consists in a deformation of the skin surface. As compared with the sensation obtained from pain spots, touch is quicker both in development and subsidence. Thus vibrations of strings are recognisable as such by the finger, even at a frequency of 1500 vibrations per second. A revolving wheel with toothed edge does not give a sensation of smoothness till the teeth meet the skin at the rate of from 480 to 640 per second. Head, in his recent study of nerve-regeneration, cut one of the nerves in his own arm, and, in conjunction with Rivers, noted accurately the date and other particulars of return of function. The first sensations return about the eightieth day after the operation ; they are termed by him protopathic. Protopathic sensibility depends on definite specific end-organs distributed over the skin as sensory " spots," viz., heat, cold, and pain spots. When this sensibility is alone present, the spaces between these spots are insensitive to cutaneous stimuli ; the heat spots only react to temperatures above 37 ' C, the cold only to temperature below 26 C. ; the sensation radiates widely, and is often wrongly localised. The tactile sensa- tions of the skin, the intermediate temperature sensations, the power to localise them accurately, the sensibility of the spaces between the spots, and a more refined sensibility to pain, return much later, and this epicritic sensibility was not perfect until many months after the regeneration started. As previously stated (p. 706), it is not known whether protopathic and epicritic impulses are sub- served by the same or by different nerve-fibres. Quite apart from these two forms of cutaneous sensation is the deep sensibility of subjacent structures, and the fibres subserving this run mainly with the motor nerves ; this form of sensation is not destroyed by division of all the nerves to the skin (see also p. 705). Adaptation plays a part as important in cutaneous as in other sensations. The same room feels warm to a man who enters it from the street, and cold to another who has been in a conservatory. Hering calls the point of adaptation to temperature " the physiological zero." Thus the temperature of the mouth and the hps may actually differ by several degrees, yet neither of them will feel hot or cold because each is at the physiological zero temperature. Sensations of warmth or cold arise when the CH. LIII.] PROTOPATHIC AND EPICRITIC SENSATIONS 775 physiological zero is altered : they persist until a new zero is formed, i.e. until adapta- tion is complete; according to Rivers and Head, adaptation to temperature is impossible when epicritic sensibility is absent. So, too, heavy weights feel unduly heavy after light weights, and ricf versa. When eyeglasses or false teeth are first worn, their contact is well-nigh unbearable; yet later, tlirough adaptation, the dis- comfort vanishes. It is very difiicult to draw any hard-and-fast line between the cutaneous sensa- tions we have just described, and those which are grouped under the name " common or general sensibility (coeiicifsthesia)." Sensations which are difficult to describe but which are perfectly familiar, such as those accompanying tickling, shivering, shudder- ing, and the like, are regarded as varieties of "common sensation." Pain may be looked upon as an excessive form of "common sensation, " but cutaneous pain is so distinct a sensation that most psychologists agree to place it under a " special" rather than a "common" heading. The term "common sensation "is most frequently employed in reference to sensations from the interior of the bod}'. Dnit/s. — Cocaine applied locally depresses all forms of cutaneous sensibility, but especially the true tactile sense ; carbolic acid acts similarly but less strongly. Chloroform produces a temporary burning sensation, and then blunts sensibility, especially to temperature changes. Menthol produces a feeling of local cold because it first causes hypersesthesia of the end-organs for cold ; this is followed by a depres- sion of the activity of these organs, together with that subserving other forms of cutaneous sensation. CHAPTER LIY MOTOPJAL AND VISCERAL SENSATIONS We shall in the present chapter deal with the motorial or muscular sense, and with sensations from the viscera. Tlie Motorial or Kin aesthetic Sense, By this sense we become aware that movement is taking place in some part of the body. "We are especially conscious of willed muscular action, and the sense has thus been confused and identified with the ■' feeling of innervation," or " sense of effort," which accompanies voli- tional movements. By some this feeling has been attributed to a direct discharge from the motor to the sensory cells of the cerebral cortex occurring at the very birth of the efferent impulse. No doubt part of the effect involved in movement is of central origin, and this part is the effect inherent in all conative (p. 758) processes, and characterises all forms of mental activity, for instance, reasoning or imagination ; but its physiological basis is quite unknown. Most, however, of the sense of effort is unquestionably due to afferent impulses peripherally generated by the accompan}4ng respiratory and other strains. It is in the estimation of weights that the value of these peripheral sensations can be most clearly seen. When a weight is first handled, the amoimt of force necessary to lift it is estimated in the light of past experience. As it is being lifted, sensations from the mo\'ing limb guide the expenditure of force: a weight which flies up too fast or does not move at once, calls for less or more muscular force. Similarly, the motorial sense is invoked when we estimate the extent to which we have moved our Limbs, or to which they have been passively moved by others. These guiding sensations are not merely of cutaneous origin. Persons whose skin has been rendered insensitive by cocaine, or by certain diseases, yet retain the power of estimating weights and the extent of their movements. In locomotor ataxy the motorial sense may be destroyed while the skin retaLois its usual sensitiveness to touch. On the other hand, we must remember that it is not at all certain that the muscles are solely or even predominantly the seat of these peripheral sensations ; the term " motorial " or " kinsesthetic " ia therefore preferable to that of " muscular " sense, by which name 776 CH. LIV.] VISCERAL SENSATIONS 777 it is still often called. It is true that sensory end-organs and nerve-fibres occur in muscles and tendons, which presumably transmit impulses upon change of muscular form or of tendinous strain. But we have experimental evidence that the pressure and movement of joint- surfaces are most important factors in the development of kinesthetic sensations. The " motorial sense " is thus of very complex origin. Visceral Sensations. Epicritic sensibility is a special characteristic of the cutaneous area. Protopathic sensibility is found in other parts also, but in most internal structures of the body it is limited to pain. The oesophagus and anal canal alone seem to be endowed with the tempera- ture sense ; the feelings of warmth and cold on swallowing liquids of different temperatures are entirely referable to the upper portion of the alimentary canal. Hertz's recent experiments place this beyond question; immediately the food has passed into the stomach we are unaware of its temperature except by the warming or cooling of the neighbouring portion of the gullet, or the skin overlying the viscera. Pain is the most widely distributed sense in the body, but in internal organs is not localised accurately, and it is here that the "referred pains" in corresponding skin areas (see p. 205) are useful for diagnostic purposes. Pain, however, is not produced in the viscera by handling or even by cutting or burning : it appears to be associated with excessive action, stretching, and with inflammatory conditions which involve the sensitive parietal layer of the peri- toneum. Inflammation of the serous membranes is an exceedingly painful condition — for instance, in pleurisy and peritonitis — but this condition, 'per se, does not apparently cause any referred pain or tenderness in cutaneous areas. In connection with the question of referred pain, we must mention the pathological condition known as allochiria. When the sktn sensations in any given area are depressed, stimulation of that area may give rise to sensations which are referred to the corresponding area on the other side of the body ; it appears to be a general rule, as Head first pointed out, that the mind projects sensations arising from an area of low sensibility to that area of higher sensibility which is related to it most closely by connections within the central nervous system, and this underlies the causation of referred visceral pains. There are, however, special kinds of sensation arising from internal viscera which have no counterpart in the sensations of the cutaneous surface. Of these, hunger and thirst are the most familiar. Hunger when slight is termed appetite, and there is some differ- ence of opinion whether the two are separate sensations, or only differ in degree. Appetite is referred to the stomach, and is a normal sensation, which arises at an interval after a meal, and as is 778 MOTORIAL AND VISCERAL SENSATIONS [CH. LIV. well known it is intensified by muscular exertion, especially if the air is cool. It has been suggested that the oxidation processes which occur in the muscles produce some substance or substances which excite the sensory nerve-terminals in the stomach. In diabetes, where oxidation runs an unusual course, carbohydrates escaping oxidation to a large extent, intense appetite may be present in spite of abundant feedinrr. Hunger is due to pronounced motor activity of the stomach ; this excites the sensory norve-terminals there (Hertz) ; these movements, and therefore the sensation of hunger, can be appeased by filling the stomach even with indigestible or non-nutritious material. Carlson has recently shown that the movements are reflexly inhibited when food enters the mouth and is masticated ; the nerves of taste act as the afferent channel for the reflex ; hence the feeling of hunger passes off long before absorption of food begins. These observations confirm the view that its origin is a local condition set up in the stomach by its condition of emptiness, and that it is not immediately due to any general change in the nutrition of the body as a whole. We must, however, recognise that the gastric sense is a complex one, as is illustrated by the aversion for food felt during monotonous diets or after over-feeding, or in the case of certain articles of diet, but the explanation of these and similar phenomena we do not know. Thirst is a sensation referred to the pharyngeal region rather than to the stomach, and apfjears, like hunger, to be a protective signal, locally excited to warn the living organism of the necessity for regularity in the intake of nutriment. Although its intensity increases with the loss of water from the body, it occurs normally long before there is any serious upset of the normal relationship of the water percentage of the organs and tissues, and may be artifici- ally produced by drying of the throat ; it is appeased immediately by the administration of fluid, and although fluids reach the absorbing surface of the duodenum sooner than was formerly supposed to be the case (see p. 555), it is unquestionable that the relief of thirst is mainly the result of moistening the local surface, the impulses from which excite the sensation. Very frequently thirst can be relieved by letting the water touch the pharyngeal mucous membrane without its being swallowed. Thirst which is due to prolonged deprivation of water is not a mere local sensation, but is no doubt produced by loss of water in the tissues, generally, exciting widespread sensory terminations therein ; the bodily and mental anguish experienced are then of an intense character. The independence of the two sensations hunger and thirst is well illustrated in many diseases, where a loss of appetite occurs without any corresponding loss of desire for fluid. CHAPTER LV TASTE AND SMELL Taste. Certain anatomical facts must be studied first in connection with the tongue, the upper surface of which is concerned in the reception of taste stimuli. TJie tongue is a muscular organ covered by mucous membrane. The muscles, which form the greater part of the substance of the tongue {intrinsic muscles) are termed linguales ; and by these, which are attached to the mucous membrane, its smaller and more delicate movements are performed. By other muscles {extrinsic muscles), such as the genio-hyoglossus, the styloglossus, etc., the tongue is fixed to the surrounding parts ; and by these its larger movements are performed. Its mucous membrane resembles other mucous membranes in essential points, but contains papillce, peculiar to itself. The tongue is also beset with mucous glands and lymphoid nodules. The lingual papillce are thickly set over the anterior two-thirds of its upper surface, or dorsum (fig. 478), and give to it its character- istic roughness. Three principal varieties may be distinguished, namely, the (1) circumvallate, the (2) fungiform, and the (3) conical and filiform papillae. They are all formed by a projection of the corium of the mucous membrane, covered by stratified epithelium ; they contain special branches of blood-vessels and nerves. The corium in each kind is studded by microscopic papillae. (1.) Circumvallate. — These papillae (fig. 479), eight or ten in number, are situate in a V-shaped line at the base of the tongue (1, 1, fig. 478). They are circular elevations, from T^Vth to y\;th of an inch wide (1 to 2 mm.), each with a slight central depression, and surrounded by a circular moat, at the outside of which again is a slightly elevated ring or rampart; their walls contain taste-buds. Into the moat that surrounds the central tower, a few little glands {glands of Ehner) open. These glands form a thin, watery secretion. 779 780 TASTE [CH. LV. (2.) Fungiform. — The fungiform papillae (3, fig. 478) are scattered chiefly over the sides and tip, and sparingly over the middle of the 7/ ^'i-'-'^ ' ^#|^#il' Fio. 478.— Papillar surface of the tongue, with the fauces and ton.sils. 1, 1, Circumvallate papillw in front of ■_', the foramen ca;cum ; 3, funKiform pajnllip ; 4, liliforin and conical papillae ; 5, transverse and oblii|ue nig* ; ('>, mucous glands at the base of the tongue and in the fauces ; 7, tonsils ; S, part of the epiglottis ; '.>, median glosso-epiglottidean fold (fnenum epiglottidis). (From Sappey.) dorsum, of the tongue ; their name is derived from their being shaped like a pufif-ball fungus. (See fig. 480.) (3.) Conical and Filiform. — These, which are the most abundant papillae, are scattered over the whole upper surface of the tongue, but especially over the middle of the dorsum. They vary in shape, some being conical (simple or compound) and others filiform ; they are covered by a thick layer of epithelium, which is either arranged CH. LV.] THE LINGUAL PAPILLA 781 over them, in an imbricated manner, or is prolonged from their sur- face in the form of line stiff projections (fig. 481). In carnivora they are developed into horny spines. From their structure, it is likely that these papillte have a mechanical and tactile function, rather than that of taste; the latter sense is seated especially in the other two varieties of papillae, the drcumvallate and the fungi- form. In the circumvallate papillae of the tongue of man peculiar structures known as taste-hids are found. They are of an oval shape, and consist of a number of closely packed, very narrow and fusiform, cells (gustatory cells). This central core of gustatory cells is enclosed in a single layer of broader fusiform cells (encasing cells). The gustatory cells terminate in fine stiff spikes which project on the free surface (fig. 482, a). Taste - buds are also scattered over the posterior third of the tongue, the palate and the pharynx, as low as the posterior (laryngeal) Fig. 479. — Vertical section of a circumvallate papilla of the calf. 1 and 3, Epithelial layers covering it ; 2, taste-buds ; 4 and 4', duct of serous gland open- ing out into the pit in which papilla is situated ; E 5 and 0, nerves ramifying within the papilla. (Engelmann.) Fio. 480. — Surface and section of the fungiform papilla;. A. The surface of a fungiform papilla, partially denuded of its epithelium ; p, secondary papillse; c, epithelium. B. Section of a fungiform papilla with the blood-vessels injected ; a, artery ; v, vein ; c, capillary loops of similar papillse in the neighbouring structure of the tongue ; d, capillary loops of tlie secondary papillaj ; c, epithelium. (From KuUiker, after Todd and Bowman.) surface of the epiglottis. The gustatory cells in the interior of the taste-buds are surrounded by arborisations of nerve-fibres. The arrangement of papillae, taste-buds, etc., varies a good deal in different animals. The papilla foliata of the rabbit's tongue consists of a number of closely packed papillae, similar to the circumvallate papillae of man ; this forms a con- venient source for the histological demonstration of taste-buds. 782 TASTE [CH. LV. The middle of the dorsum of the tongue is but feebly endowed with the sense of taste ; the tip and margins, and especially the posterior third of the dorsum (i.e., in the region of the taste- buds), possess this faculty. The anterior part of the tongue is supplied by the lingual branch of the fifth Kki. 4S2. — Taste-bud from dog's eijif;lott.i3 (larj-ngeal surface near the base), precisely similar in structure to those found in the tonj^ue. a, Depression in eiiitlieliuin over bud; bolow the letter are seen the line hair-like processes in wliich the cells terminate; c, two nuclei of the axial (j;ustatory) cells. The more superlicial nuclei belong; to the suiierficial (encasing) cells ; the conver^^ing lines indicate the fusiform shape of the encasing cells, x 400. (8choliel, The substance of the papilla', dividing at their upper extremities Into seconilary papilla; ; c, artery, and v, vein, dividing into capillarj' loops ; i , epithelial covering, lamin- ated between the papilla-, but extended into hair- like jjrocesses, /, from the extremities of the secondarj- papilla;. (From KiUliker, after Todd and Bowman.) nerve and the chorda tym- pani, and the posterior third by the glosso - pharyngeal nerve. Considerable discus- sion has arisen whether there is more than one nerve of taste. The view generally held is that the glosso-pharyngeal nerve is the nerve of taste, and the lingual the nerve of tactile sensa- tion. Nevertheless, the lingual and the chorda tympani do con- tain taste-fibres, which probably take origin from the cells of the geniculate ganglion; the central axons of these cells pass by the pars intermedia to the sensory nucleus of the glosso-pharyngeal nerve. Gowers holds that the fifth nerve is the only nerve of taste, and has recorded a case of loss of taste where the fifth nerve alone was the seat of disease ; other cases, however, do not support this view. en. LV.] THE NKRVE OF SMELL 783 Tastes may be classified into — 1. Sweet. 2. Bitter. 3. Acid or Sour. 4. Salt. Whether alkaline and metallic tastes are elementary, is as yet undecided. All the above affect to a varying extent the nerves of tactile sense as well of those of touch proper, sweet having the least, acids the most marked action upon the latter. Sweet tastes are best appreciated by the tip, acid at the side, and bitter tastes at the back of the tongue. The substance to be tasted must be dissolved; here there is a striking contrast to the sense of smell ; flavours are really odours. In testing the sense of taste in a patient, the tongue should be protruded, and drops of the substance to be tasted applied with a camel's hair brush to the different parts ; the subject of the experiment must signify his sensations by signs, for if he with- draws the tongue to speak, the material gets widely spread. The more concentrated the solution, and the larger the surface acted on, the more intense is the taste; some tastes are perceived more rapidly than others, saline tastes the most rapidly of all. The best temperature of the substance to be tasted is from 10° to 35 C. Very high or very low temperatures deaden the sense. Individual papillae, when thus treated with various solutions, show great diversity: from some only one or two tastes can be evoked, from others all four. The papillae may also be stimulated electrically. Cocaine and gymnemic acid, prepared from the leaves of the plant Gymnema sylvestre, act deleteriously, chiefly on the bitter and sweet tastes ; cocaine abolishes especially the bitter, gymnemic acid especially the sweet, leaving the salt and acid tastes almost untouched. It will thus be seen that there are many facts pointing to the conclusion, that the varieties of gustatory like those of cutaneous sensation are due to the stimulation of different end-organs. When diluted sweet and salt solutions are simultaneously appHed to the tongue, they tend to neutralise one another, but a true indifferent point is difficult or impossible to reach. Sweet and bitter, sweet and acid liquids are antagonistic to a similar but less perfect extent. Contrast-effects of one taste upon another are matters of common observation, but can only be experimentally investigated with difficulty. SmeU. The entrance to the nasal cavity is lined with a mucous membrane closely resemblmg the skin. The greater part of the rest of the cavity is lined with ciliated epithelium; the corium is thick and 784 SMELL [CH. LV. Fic. 483. — Cells from the olfactury rej,'iuu of the rabbit. st, Supporting cells ; r, r', olfactorial cells ; /, ciliateil cells ; s, cilia- like processes ; h, cells from Bowman's glands. (Stiihr.) contains numerous mucous glands. The olfactory region in man is limited to a portion of the membrane covering the upper turbinal bone, and tlie adjacent portion of the nasal septum ; it is only 245 square millimetres in area. The cells of the epithelium here are of several kinds : — first, columnar cells not ciliated (fig. 483, st), with the broad end at the surface, and belovir tapering into an irregular branched process or processes, the termina- tions of which pass into the next layer: the second kind of cell (fig. 483, r) consists of a small cell body with large spherical nucleus, situ- ated between the ends of the first kind of cell, and sending upwards a process to the surface between the cells of the first kind, and from the other pole of the nucleus a pro- cess towards the corium. The latter process is very delicate, and may be varicose. The upper process is prolonged beyond the surface, where it becomes stifif, and in some animals, such as the frog, is provided with tiairs. These cells, which are called olfactorial cells, are numerous, and the nuclei of the cells not being on the same level, a compara- tively thick nuclear layer is the result. They are in reality bipolar nerve-cells. In the corium are a number of serous glands called Bowman's glands. They open upon the surface by fine ducts passing up between the epithelium cells. The distribution of the olfactory nerves which penetrate the cribriform plate of the ethmoid bone and pass from this region to the olfactory bulb is shown in fig. 484. The nerve-fibres are the central axons of the bipolar nerve-cells we have termed olfac- torial ; the columnar cells between these act as supports to them. The olfactory tract is an outgrowth of the brain, which is originally hollow, and remains so in many animals ; in man the cavity is obliterated, and the centre is occupied by neuroglia : outside this the white fibres lie, and a thin superficial layer of neuroglia covers these. The three "roots" of the olfactory tract have been traced to the uncinate gyrus and hippocampal regions of the same side of the brain, which is the portion experimentally found to be associated with the reception of olfactory impulses (see pp. G98 and 738). From the cells of the grey matter here fibres pass by a complex path to the corresponding regions of the opposite side. There is also a communication via the corpora mammillaria with the optic thalamus and tegmentum of the mid-brain. CH. LV.] THE OLFACTORY APPARATUS 78J The olfactory hulh has a more complicated structure ; above there is first a continuation of the olfactory tract (white fibres enclosing „vn ivvviXli M i -^\jK,JJU Fig. 484.— Nerves of the septum nasi, seen from the right side, s- — 1> tbe olfactory bulb ; 1 , the olfactory nen'es passing through the foramina of the cribriform plate, and descending to be distri- buted on the septum ; 2, the internal or septal twig of the nasal branch of the ophthalmic nerve ; 3, naso-palatine nerves. (From Sappey, after Hirschfeld and Leveillc?.) neuroglia); below this four layers are distinguishable; they are shown in the accompanying diagram from Eamon y Cajal's work, the histological method used being Golgi's. Fig. 485. — Nervous mechanism of the olfactory apparatus. A, bipolar cells of the olfactory apparatus (Max Schultze's olfactorlal cells) ; B, olfactory glomeruli ; C, mitral cells ; D, granule of white layer ; E, external root of the olfactory tract; P, grey matter of the sphenoidal region of the cortex ; a, small cell of the mitral layer; h, basket of a glomerulus ; c, spiny basket of a granule e, collateral of the axis-cylinder process of a mitral cell ; /, collaterals terminating in the molecular layer of the frontal and sphenoidal convolutions ; g, superficial triangular cells of the cortex ; ft., supporting epithelium cells of the olfactory mucous membrane. (Ramon y Cajal.) (1) A layer of white fibres containing numerous small cells, or "granules" (d). 3D 786 SMELL [CH. LV. (2) A layer of large nerve-cells called "mitral cells" (c), with smaller cells (a) mixed with them. The axis-cylinder processes of these cells pass up into the layer above and eventually become fibres of the olfactory tract E, which passes to the grey matter of the base of the brain f. They give off numerous collaterals on the way {e,f). (3) The layer of olfactory glomeruli (b). Each glomerulus is a basket-work of fibrils derived on the one hand from the terminal arborisations of the mitral cells, and on the other from similar arborisations of the non-medullated fibres which form the next layer. (4) Hie layer of olfactory nerve-fibres. — These are non-medullated ; they continue upwards the bipolar olfactory cells, which are placed among the epithelial cells of the mucous membrane. Animals may be divided into three classes : — those wliich, like the porpoise, have no sense of smell (anosmatic) ; those which possess it in comparatively feeble degree (man, most primates, monotremes, and some cetacea) ; these are called microsmatic. In man the thickness of the olfactory membrane is only 0"06 mm. Most mammals are in contradistinction macrosmatic, the thickness of the membrane being 0"1 mm. or more, and its area larger. The mucous membrane must be neither too dry nor too moist ; if we have a cold we are unable to smell odours or appreciate flavours (which are really odours). When liquids are poured into the nose, their smell is imperceptible, as they damage the olfactory epithelium, owing to the difference of osmotic pressure. But even if a " normal " saline solution of an odorous substance be substituted, the sense of smell is still lost so long as air-bubbles are carefully excluded from the nasal cavity. It is therefore necessary that odorous substances should be in a gaseous state in order to act upon the olfactory nerve-endings ; they are normally conveyed to the olfactory surface by the air currents passing through the nose. Generally, the odours of homologous series of compounds increase in intensity with increase of molecular weight, but bodies of very low molecular weight are odourless, while vapours of very high molecular weight, which escape and diffuse slowly, have little or no smell. A slight change in chemical constitution may produce marked alteration in the character of the odour of a substance ; certain modes of atomic grouping within the molecule appear to be more odoriferous than others. Attempts have been made to discover the elementary sensa- tions of smell, but hitherto with scant success. Many odours have unquestionably a complex physiological effect. For example, when nitrobenzol is held before the nose, it yields first the smell of heliotrope, next the smell of bitter almonds, and finally the smell of benzene ; just as if different end - organs became successively fatigued. Some substances have a very different smell according CII. LV.] OLFACTORY SENSATIONS 787 to their concentration. Chemical dissociation, too, unquestionably plays a prominent part. Nevertheless, there are certain observations which indicate the existence of primary sensations of smell. First, some persons are congenitally insensible to one or more odours, but yet smell others quite normally. Hydrocyanic acid, mignonette, violet, vanilla, benzoin, are substances which appear to certain people to have no smell. Secondly, some odorous bodies, when simultaneously given, antagonise one another; others produce a mixed smell. Thirdly, fatigue of the epithelium with one odour will modify or abolish the effect of some smells, but will leave that of others untouched. The delicacy of the sense of smell is most remarkable even in man. Valentin calculates that even loo.ooo.ooo °^ ^ grain of musk can be dis- tinctly smelled. Solutions of camphor afford a good means of testing olfactory acuity. Two tubes of camphor solution are presented to the subject along with two tubes of water, and the former pair is replaced with weaker and weaker solutions until it is indistinguishable from the tubes containing water. Pungent substances, such as ammonia, are unsuited for olfactometrical experiment. They stimulate the endings of the fifth as well as those of the olfactory nerve. CHAPTEE LYI HEARING Anatomy of the Ear, The Organ of Hearing (tig. 486) is divided into three parts, (1) the external, (2) the middle, and (3) the internal ear. External Ear. — The external ear consists of the pinna and the external auditory meatus. The central hollow of the former is named the concha. The auditory canal, with a slight arch directed upwards, passes inwards and a little forwards to the membrana tympani, to which it thus serves to convey the vibrating air. Middle Ear or Tympanum. — The middle ear, or tympanum or drum (3, fig. 486), is separated by the membrana tympani from the external auditory meatus. It is a cavity which communi- cates posteriorly with the mastoid cells in the mastoid pro- cess of the temporal bone ; but its only opening to the external air is through the Eustachian tube (4, fig. 486). The walls of the tympanum are osseous, except where apertures in them are closed with membrane, as at the fenestra rotunda, and fenestra oralis, and at the outer part where the bone is replaced by the membrana tympanL Its cavity is lined with mucous membrane, which is continuous through the Eustachian tube with that of the pharynx. A chain of small bones extends from the membrana tympani to the fenestra ovalis. The membrana tympani is placed in a slanting direction at the bottom of the external auditory canal, and consists of fibres, some running radially, some circularly ; its margin is set in a bony groove ; its outer surface is covered with a continuation of the cutaneous lining of the auditory canal, its inner surface with the mucous membrane of the tympanum. The ossicles are three in number ; named malleus, incus, and stapes. The malleus, or hammer-bone, has a long slightly-curved process, called its handle, which is inserted vertically between the CH. LVI.] ANATOMY OF THE EAR 789 Fig. 486. — Diagrammatic \iew from before of the parts composing the organ of hearing of the left side. The temporal bone of the left side, with the accompanying soft parts, has been detached from the head, and a section has been carried through it transversely, so as to remove the front of the meatus extemus, half the tympanic membrane, the upper and anterior wall of the tympanum and Eustachian tube. The meatus intemus has also been opened, and the bony labyrinth exposed by the removal of the surrounding parts of the petrous bone. 1 , The pinna and lobe ; 2, meatus extemus ; 2', membrana tympani ; 3, cavity of the tympanum ; 3', its openiii.i; backwards into the mastoid cells ; between 3 and 8', the chain of small bones ; 4, Eustachian tube ; 5, meatus intemus, containing the facial (uppermost) and the auditor^' nen-es ; 6, placed on the vestibule of the laby- rinth above the fenestra ovalis ; a, apex of the petrous bone ; h, internal carotid artery : c, styloid process ; d, facial nerve issuing from the stylo-mastoid foramen ; c, mastoid process ; /, squamous part of the bone covered by integument, etc. ( Amold.) Fio. 487.— The hammer- bone or malleus, seen from the front. l.The head ; 2, neck ; 3, short ijrocess ; 4, handle. (Schwalbe.) Fig. 488. — The incus, or anvil-bone. 1, Body; 2, ridged articulation for the malleus ; 4, fjrocessus brevis, with 5, rough articular surface for ligament of incus ; 6, processus magnus, with articu- lating surface for stapes ; 7, nu- trient foramen. (Schwalbe.) 2--1 Fig. 489.— The stapes, or stirmp-bone. 1, Base; 2 and 3, arch ; 4, head of bone, which articu- lates with orbicular process of the incus ; 5, constricted part of neck; 6, one of the crura. (Schwalbe.) 790 HEARING [CH. LTI. layers of the membrana tympani. The head of the malleus is irregularly rounded ; its ueck, or the line of boundary between the head and the handle, supports two processes: a short conical one, and a slender one, processus gracilis, which extends forwards, and is attached to the wall of the cavity at the Glaserian fissure. The incus, or anvil-bone, shaped like a bicuspid molar tooth, is articulated by its broader part, corresponding with the surface of the crown of the tooth, to the malleus. Of its two fang-like processes, one, directed backwards, has a free end attached by ligament to a depres- sion in the mastoid bone ; the other, curved downwards, longer and more pointed, articulates by means of a roundish tubercle, formerly called OS orhiculare, with the stapes, a little bone shaped like a stirrup, of which the base fits into the membrane of the fenestra ovalis. The muscles of the tympanum, are two in number. The tensor tympani arises from the cartila- ginous end of the Eustachian tube and the adjoining surface of the sphenoid, and from the sides of the canal in which the muscle lies ; the tendon of the muscle bends at nearly a right angle over the end of the processus cochleariformis, and is inserted into the inner part of the handle of the malleus. The stapedius is concealed within a canal in the bone in front of the aqueductus Fallopii. Its tendon is inserted into the neck of the stapes posteriorly. The Internal Ear. — The proper organ of hearing is formed by the distribution of the auditory nerve, within the internal ear, or laby- rinth, a set of cavities within the petrous portion of the temporal bone. The bone which forms the walls of these cavities is denser than that around it, and forms the osseous labyrinth ; the membrane within the cavities forms the membranoiLS labyrinth. The mem- branous labvrinth contains a fluid called endolymph ; while outside it, between it and the osseous labyrinth, is a fluid called perilymph. This fluid is not pure lymph, as it contains mucin. The Osseous Labyrinth consists of three principal parts, namely, the vestibule, the cochlea, and the semicircular canals. The vestibule is the middle cavity of the lab}Tinth, and the central chamber of the auditory apparatus. It presents, in its inner wall, several openings for the entrance of the divisions of the auditory nerve ; in its outer wall, the fenestra ovalis (2, fig. 491a), Fio. 490.— Interior view of the tjTnpanum, with membrana tympani and bones in natural posi- tion. 1, Membrana tympani ; 2, Eustachian tube ; 3, tensor tympani muscle ; 4, lig. mallei exter. ; 0, lig. mallei super. ; 6, chorda-tympani nerve ; a, b, and e, sinuses about ossicles. (Schwalbe.) CH. LVI.] THE COCHLEA 791 an opening filled by membrane, in which is inserted the base of the stapes ; in its posterior and superior walls, five openings by which the semicircular canals communicate with it: in its anterior wall, Fio. 491a. — Right bony labyrinth, viewed from the outer side. The specimen here represented is prepared by sepa- rating piecemeal the looser substance of the petrous bone from the dense walls which immediately enclose the labyrinth. 1, The vestibule; 2, fen- estra ovalis ; 3, superior semicircular canal ; 4, horizontal or external canal ; 5, posterior canal ; *, ampullae of the semicticular canals ; 5, first turn of the cochlea ; 7, second turn ; 8, apex ; 9, fenestra rotunda. The smaller figure in outline below shows the natural size. Y • (Summering.) Fi<;. 491 ?j.— View of the interior of the left labyrinth. The bony wall of the laby- rinth is removed superiorly and exter- nally. 1, Fovea hemielliptica ; 2, fovea hemispherica; 3, common opening of the superior and posterior semicircular canals ; 4, opening of the aqueduct of the vestibule; 5, the superior; 6, the posterior, and 7, the external semicir- cular canals; 8, spiral tube of the cochlea (scala tympani); 9, opening of the aqueduct of the cochlea; 10, placed on the lamina spiralis in the scala ves- tibuli. Y ■ (Sommering.) an opening leading into the cochlea. The semicircular canals are described in Chapter LT. The Membranous Labyrinth corresponds in general form with the osseous labyrinth. The vestibule contains two membranous sacs, named the utricle and the saccule (fig, 492); the utricle com- municates with the three membranous semicircular canals; the saccule communicates with the utricle and with the canal of the cochlea. The vestibular division of the auditory nerve is distributed to the five spots shown in the diagram, namely, the macules of utricle and saccule, and the cristas of the semicircular canals. The cochlear division of the auditory nerve is distributed to the whole length of the canal of the cochlea. The Cochlea. — This is shaped like a snail's shell. It is traversed by a central column or modiolus, around which a spiral canal winds with two and a half turns from base to apex. It is seen in vertical section (fig. 493) that this canal is divided partly by bone (the sjtiral lamina), partly by membrane (the basilar membrane), 792 HEARING [CH. LVI. into two spiral staircases or scalae, the scala tympani and scala vestibuli (fig. 493). The scala vestibuli is separated from the tympanum by the membrane of the fenestra oval is, and the scali tympani is similarly separated from the tympanum by the membrane of the fenestra rotunda. Fio. 492. — Diagram of the rii,'ht mem- branous labyrinth. U, utricle, into which the three semicircular canals open ; S, saccule, communicating with the cochlea (C) by C.l{., the canalis reuniens, and with the utricle by a canal having on it an enlar^^e- ment, the saccus endolymphaticua (S.E.). The black shading repre- sents the places of termination of the auditory nerve, namely, in the macula- of the utricle and saccule; the cristae in the ampullary ends of the three semicircular canals ; and in the whole length of the canal of the cocMea. (After Schufer.) Fio. 403. — View of the osseous cochlea divided through the middle. 1, Central canal of the modiolus ; 2, lamina spiralis ossea ; 3, scala tympani; 4, scala vesti- buli ; 5, porous substance of the modiolus near one of the sections of the canalis spiralis modioli. }. (Arnold.) Both scalae are filled with perilymph. The basilar membrane increases in breadth from the base towards the apex of the cochlea. It contains fibres (about 24,000 in all) imbedded in a homogeneous matrix, and running radially, from the spiral lamina to the spiral ligament, where its other end is again attached to the bone. At the apex of the cochlea, the lamina ends in a small hamu- lus, the inner and concave part of which being detached from the summit of the modiolus, leaves a small aper- ture named the helicotrcma, by which the two scalae, sepa- rated in all the rest of their length, communicate. Besides the scala vestibuli and scala tympani, there is a third space between them, called scala media or canal of the cochlea {GO, fig. 494). In section it is triangular, its external wall being formed by the wall of the cochlea, the scala vestibuli) by the Fio. 494. — Section through one of the coils of the cochlea (diagrammatic). ST, scala tympani; SK, scala vesti- buli ; CC, canalis cochlea or canalis membranaceus ; 7i, membrane of Reissner ; Iso, lamina spiralis ossea ; Us, limbus laminae spiralis ; ss, sulcus spiralis ; nc, cochlear nerve; qs, ganglion sjiirale ; (, membrana tectoria (below the membrana tectoria is the lamina reticularis) ; h, membrana basilaris ; Cu, rods of Corti ; Up, ligamentum spirale. (Quain.) its upper wall (separating it from CH. LVI.] THE ORGAN OF CORTI 793 membrane of Reissner, and its lower wall (separating it from the scala tympani) by the basilar membrane, these two meeting at the outer edge of the bony lamina spiralis. Following the turns of the cochlea to its apex, the scala media there terminates blindly; at the base of the cochlea a narrow passage (canalis reuniens) unites it with the saccule. The scala media (like the rest of the membranous labyrinth) contains endolymph. Organ of Corti. — Upon the basilar membrane are arranged cells of various shapes. About midway between the outer edge of the lamina spiralis and the outer wall of the cochlea are situated the rods of Corti. Viewed sideways, they are seen to consist of an external and internal pillar, each rising from an expanded foot or hose attached to the basilar membrane (o, n, fig. 495). They slant '^^g>D0O^pp60 '~^' Fig. 495. — 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 jieriosteum of lamina spiralis ossea ; c, thickened commencement of the membrana basilaris near the point of perforation of the nerves h ; (7, blood-vessel (vas spirale) ; e, blood-vessel ; /, nerves ; g, the epithelium of the sulcus spiralis intemus; t, internal hair-cell, with basal process k, surrounded with nuclei and ijrotoplasm (of the yranular layer), into which the nerve-libres radiate ; I, hairs of the internal hair-cell ; n, base or foot of inner pillar of organ of Corti ; TO, 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; ii', nerva-tibre arborising round the first of the external bair-cells ; { 2 to 2, lamina reticularis. X 800. (Waldeyer.) inwards towards each other, and each ends in a swelling termed the head ; the head of the inner pillar overlies that of the outer. Each pair of pillars forms a pointed roof arching over a space, and by a succession of them a tunnel is formed. There are about 3000 of these pairs of pillars, in proceeding from the base of the cochlea towards its apex. They are found pro- gressively to increase in length, and become more oblique ; in other words, the tunnel becomes wider, but diminishes in height as we approach the apex of the cochlea. Leaning against the rods of Corti are certain other cells called hair-cells, which terminate in small 794 HEARING [CH. LVI. hair-like processes. There are several rows of these on the outer and one row on the inner side. Between them are certain sup- porting cells called cells of Deiters (fig. 495, x). This structure rests upon the basilar membrane ; it is roofed in by a fenestrated mem- brane or lamina reticularis into the fenestrae of which the tops of the various rods and cells are received. When viewed from above, the organ of Corti shows a remarkable resemblance to the key- board of a piano. The top of the organ is roofed by the membrana tedoria (fig. 494, t) which extends from the end of the limbua {Us, fig. 494), 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. 676). 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 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 LI. The external and 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 whirh the vibrations pass, but the endolyniph may be affected in other ways, for instiince through the otlier bones of the herocess : 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 Cart. Santorini Cart, aryten Proc. muscul Lig. crico-aryten. Lig. cerato-crico. post. sup. Comu infer. Lig. cerato-crico. post. inf. Cart, tracheae, Pars menibran. Fig. 500. — The larynx as seen from behind after removal of the muscles. only remain. (Stoerk.) The cartilages and ligaments the arytenoids ; the cuneiform cartilages, or cartilages of Wrisbcrg, are in a fold of mucous membrane ; the epiglottis looks like a lid to the whole (fig. TiOO). The thyroid cartilage is connected with the cricoid, by the crico-thyroid mem- brane, and also by joints with synovial membranes ; the lower cornna of the thyroid clasp the cricoid between them, yet not so tightly but that the thyroid can revolve, within a certain range, around an axis passing transversely through the two joints CH. LYII.] THK LARYNX 801 at which the cricoid is clasped. The vocal cords are attached beliind to the front portion of the base (vocal j)rocess) of the arytenoid cartilages, and in front to the re-entering angle at the back of tlie thyroid ; it is evident, therefore, tliat all move- ments of either of these cartilages must produce an elFect 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 nmst 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 (jlottiilis (see fig. 501). 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, such as 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. Arj'tenoid. 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. 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-ari/tenoid. — This arises from the broad depression on the corresponding half of the posterior surface of the cricoid cartilage ; its fibres con- 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. These muscles draw the outer angles of the arytenoid cartilages backwards and 3E 501.— Vertical section through the larynx, passing from side to side. 11, hyoid bone ; T., thyroid carti- lage; T.C.M., thyro-crlcoid 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.) 802 VOICE A\P SPEECH [CH. LVll. inwards, and thus rotate the anterior or vocal processes outwards, and widen the riraa 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 dyspmra is produced. 3. Lafcnil rric(j-en(>iil. 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. 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. Tlii/ro - (iri/tenoid. — This consists of two portions, inner and outer. The innti/ro- epi(/lolti(lean) ; it resembles the crico-arytenoid in that some of its fibres arc lon- 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 etRct 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- brane 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 arj'tenoid cartilage will tend to draw the arytenoid cartilage forwards and rotate it inwards ; finally, the fibres which pass into the aryteno-ei)iglottidean 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. r>. An/ffiioul. — When the mucous membrane is removed from the back of the arytenoid cartilages, a band of transverse fibres is exj)osed, on the dorsal surface of which are two slender decus.sating oblique bundles. These are often described as Lig. ary-epiglott. Cart. Wrisbergil Cart. Saiitorini mm Arj'ten. obliqu. Crico-arytenoid. post. Comu inferior Lig. cerato-cric. Pars post. inf. membrani Pars cartilag Fio. 502. — Ttie larynx as seen from beliind. To sliow the intrinsic muscles posteriorly. (Stoerk.) CH. LVII.] THE LARYNGOSCOPE 803 Separate inuscles (arytenoid and arytt-no-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 nuiscles. The arytenoid muscle draws the arytenoid cartilages together. If it is paralysed, the intcrcartilaginous part of the glottis remains open, although the membranous hps can still be approximated during vocaUsation. 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 j)rojects 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 remarked that " the muscles which lie in the space enclosed by the laminae of the thyroid cartilage and above the cricoid may be regarded in their totaUty 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 hiryncfeal is the sensory nerve ; by its external branch, it supphes one muscle, namely, the crico-thyroid. These fibres, however, probably arise from glosso-pharyngeal root- lets. The rest of the muscles are supphed by the inferior lari/ngeal 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 r-o Fia 503 —To show the position of the operator and patient when using the Laryngoscope 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 Uttle 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 hghts up the cavity of the mouth, and by a 804 VOICE ANT) SPEECH [CH. LYIL little alteration of the distance between the operator and the patient the point at which the greatest amount of Hght is reHected by tlie 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 puttinfr 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 preliniiiiaries 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 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. The structures seen will vary somewhat according to the condition of the parts as to inspiration, expiration, phonation, etc. ; they are (fig. o04) first, and apparently at the posterior part, the base of the tomiue, immediately below which is the arcuate outline of the epi'. We may give a ft-w examples of the shape of the resonatinj; cavities in pronouncinjj vowel sounds, and producing tiuir characteristic timbre : when sounding a (in father) the moutli lias the shape of a funnel wide in front ; the tongue lies on the floor of the mouth ; the lips are wide open : the soft palate is moderately and tlie larynx slightly raised. In pronouncing ii (oo), the cavity of the moutli is shaped like a capacious flask with a sliort narrow neck, 'i'he whole resonating cavity is then longest, the lips being protruded as far as possible ; the larynx is depressed and the root of the tongue approaches the fauces. In pronouncing o, the neck of the flask is shorter and wider, the lips being nearer the teeth ; the larynx is slightly higher than in sounding oo. In pronouncing i', the flask is a small one with a long narrow neck. The resonating chamlier is then shortest as the larynx is raised as much as possible, and the mouth is bounded by the teeth, the lips being retracted ; the approach of the tongue near the hard palate makes the long neck of the flask. The Consonants are produced by a more or less complete closure of certain doors on the course of the outgoing blast. If the closure is complete, and the blast suddenly opens the door, the result is an explosive ; if the door is partly closed, and the air rushes with a hiss through it, the result is an aspi)-afe .• if the door is nearly closed and its margins are thrown into vibration, the result is a ril>ra(ire .- if the mouth is closed, and the sound has to find its way out througli the nose, the result is a rt'sonanf. These doors arc four in number ; Briicke called them the artimlation positions. They are — 1. Between the lips. 2. Between the tongue and hard palate. 3. Between the tongue and soft palate. 4. Between the vocal cords. The following table classifies the principal consonants according to this plan : — Articulation ])Ositioii. 1 2 3 4 The introduction of the phonograph has furnished us with an instrument which it is hoped in the future will enable us to state more accurately than has hitherto been possible, the meaning of the changes in nature and intensity of the complex vibrations which constitute speech. The microscopic- study of the tracing on the recording phonographic cyfinder, and various methods of obtaining a high magnifi- cation of the movements of the recording style have been carried out by M'Kendrick and others. The subject is, however, not yet sufficiently ripe for definite statements to be made. Defects of Speech. Speech may be absent in certain forms of lunacy, and temj)orariIy in that defect of will called ln/s/eria. It may be absent owing to congenital defects. Children born deaf are dumb also. This is because we think with remembered sounds, and in a person born deaf the auditory centres are never set into activity. By educating the child by the visual inlet, it can be taught to think with the remembered shapes of the mouth and expressions of the face produced in the act of speaking, and so can itself speak in time. If a child becomes deaf before it is six or seven years old, there is a liability it will forget the speech it has learnt, and so become dumb. In congenital hemiplegia there may be speechlessness, especially if the injury is Explosives. Aspirates. Vibratives. R«soDants. B, P. F, V, W. M. T, D. S, Z, L, Sch, Th. R. N. K, G. J, Ch. Palatal R. Ng. H. R of lower Saxon CH. LVII.] DEFECTS OF SPEECH 809 due to ineiiinfreal h.Temorrhage affecting the fj^rey cortex of the left hemisphere. These children generally talk late, the riglit side of the brain taking on the function of the left. Disorders of speech and voice occur from affections of the larynx, and of the nerves which supply the larynx. Stammering is a want of cocirdination between the various muscles employed in the act of speaking. Perhaps the most interesting of the disorders of speech, however, are those associated with brain disease in adults, and to which the general term ^}ih((sia is given. There may be an entire loss of the power to articulate words, or there may be a mere blurring of the speech. In other cases there is a loss of memory for words, the words spoken being well pronounced, but are not those wliich the patient wishes to utter. This is often associated with At/raphia, a similar condition in respect to writing. Some writers distinguish between motor aphasia, which is associated with disorganisation of the motor word-centre (Broca's convolution), and sensory apliasia, in which the defect is in the association of ideas of things and the ideas of their names. This is due to injury of the visual word-centre, or the auditory %coril^centre (see p. 741), or to a severance of the tracts which unite them to one another and to the motor word-centre. It will readily be understood that the actual symptoms will vary greatly according to the position of the lesion. It is generally admitted that injuries to the sensory word-centres are more potent in the production of aphasia than injuries to Broca's convolution. Marie, as already noted on p, 734, has gone so far as to assert that a lesion limited to Broca's convolution will not produce aphasia, but this view has not yet been fully verified. With regard to the auditory word-centre, impressions for the sounds of words are revived in one of three ways : — a. Spontaneous or volitional ; owing to accumulated traces which constitute memory, a man when he wants to express his thoughts in words remembers the sounds it is necessary to use ; impulses pass to the motor-centre (Broca's convolu- tion), thence to the nerve-centres, nerves, and muscles of the larynx, mouth, chest, etc. , and the man speaks. />. 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. (f() Spontaneous or normal. (6) 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. Some operations, such as reading aloud and writing from dictation, require the combined activity of several centres. This, however, we have previously considered in connection with the subject of association in the brain (see p. 741). C H A P T E K L V I 1 1 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 palpebrce 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, imder ordinary circumstances just sufiBces to keep the conjunctiva moist. It passes out through two small openings (puncta lacrimaKa) near the inner angle of the eye, CH. LVTII.] THE EYEBALL 811 one in each lower 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. 507) consists of the following structures Ciliaiy muscle - Ciliary jiroccss- Canal of Fotit- Comea- Aiiterior cliamber- Lens- Iris- Ciliary process- Ciliary inuscle- — Sclerotic coat. — Choroid coat. — Retina. — Vitreous humour. Fio. 507.— Section of the anterior four-fifths of the eyeball. The sclerotic, or outermost coat, is made of connective tissue and envelops about five-sixths of the eyeball : continuous with it, in front, and occupying the remaining sixth, is the transparent cornea (fig. 508). Immediately within the sclerotic is the choroid coat, and within the choroid is the retina. The interior of the 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 cur- tain, — the iris, which is continuous with the choroid ; it regulates the admission of light; at the junction of the sclerotic and cornea is the ciliary muscle, the function of which is to adapt the eye for seeing objects at various distances. The Choroid Coat is the vascular coat of the eyeball, and its connective tissue contains abundance of branched pigment cells. It is separated from the retina by a fine elastic membrane (memhrane of Bruch). 812 THE EYE AND VISION [CH. LVIII. The choroid coat ends in front in what are called the ciliary processes (figs. 509, 510). These consist of from 70 to 80 meridion- ally arranged radiating plaits, which consist of blood-vessels, fibrous connective tissue, and pigment corpuscles. They are lined by a continuation of the membrane of Bruch. The ciliary processes terminate at the margin of the lens. The ciliary muscle (13, 14, and 15, fig. 509), 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 direc- tions, (a) Meridional fibres near the sclerotic and passing to the choroid ; (b) radial fibres inserted into the choroid behind the ciliary processes ; and (c) cir- cular fibres (muscle of Miiller), more internal ; they constitute a sphincter. Tlie Iris is a continuation of the choroid inwards beyond the ciliary pro- cesses. It is a fibro-muscular membrane perforated by a central aperture, the pupil. Posteriorly is a layer of pigment cells (uvea), which is a continuation forwards of the pigment layer of the retina. 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. Sur- rounding 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 pupillce. The iris is covered an- teriorly by a layer of epithelium con- tinued 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. Fio. 508. — Vertical section of rabbit's cornea, stained with gold chloride. e, Stratified anterior epithelium. Immediately beneath this is the anterior homogeneous lamina of IJowman. n, Nerves forming a delicate sub-epithelial plexus, anrl sending up fine twigs between the epithelial cells to end in a second plexus on the free surface; ^t^= - — / r t / f ' < / \ Ap IN/' — T^X 1 1 , N /r Fk;. 521.— If P P' is a line which separates two media, tlie lower one being the cleuser, and A O is a ray of light falling on it, it is Ijent at O towards the normal or perx>endicular line N N'. A O is called the incident ray, and O B the refracted ray ; A O N is called the angle of incidence {i), N' O 13 the angle of refraction (r). If any distance O X is measured off along O A, and an equal distance O X. along O B, and perpendiculars drawn to N N'; then^j7Y>= index of refraction. 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. 522) is included between the lines Fio. 022.— Diagram of the optical angle. CII. LVIII.] FORMATION OF IMAGES 823 drawn from the borders of any object to the nodal point; if the lines are prolonp;ed backwards they include an equal angle. It has been shown by Helmholtz that the smallest angular distance between two points which can be appreciated as two distinct points = 50 seconds, the size of the retinal image being 3'65 ix ; this is a little more than the diameter of a cone at the fovea centralis which = 3 /x, the distance between the centres of two adjacent cones being = 4 /x. 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. 523), 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 C represents the curvature of the schematic or reduced eye ; the ray which passes through the centre of the circle Fio. 523. —Diagram of the course of the rays of light, to show how an Image is formed upon the retina. The surface G C should be supposed to represent the ideal curvature. of which C C is part is not refracted ; this point is represented as an asterisk in fig. 523 ; it is near the posterior surface of the crystal- line lens ; the ray A 0, 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 points have corresponding focusses. It will thus be seen that an inverted image of external objects is 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 cannot be satisfactorily answered without entering into matters which require a previous psychological train- ing. Suffice it to say here that the localisation of objects in space depends not only on the retina, but also on tactile and general 824 THE EYE AND VISION [Cn. LVIIL experience; that the mind localises objects with reference to its own body, and that from the first it knows nothing of the inversion of the retinal image, as its powers of localisation only appear with developing general experience. 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 efifect required. The posterior surface, which during rest is more convex than the anterior, is thus ren- dered the less convex of the two during accommodation. The following simple ex- periment illustrates this point : If a lighted 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. 524). The first and brightest is (1) a small erect image formed by the an- terior convex surface of the cornea ; the second (2) is also erect, but larger and less distinct than the pre- ceding, 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 Fio. 524. — Diagram showing three reflections of a candle. 1 , From the anterior surface of cornea ; •?., from the anterior surface of lens ; 3, from the posterior sur- face of lens. Fio 5''5 — Dia<^am of Sanson's images. A, Wlien 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. the eye is now adjusted for a far point, the second image enlarges atrain. becomes less distinct, and recedes from the first. In both CH. LVIII.] ACCOMMODATION 825 cases the first and third images remain unaltered in size, distinct- ness, and position. This proves that during accommodation for near objects the curvature 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. 525) are used ; the two images from the front surface of the lens during accommodation not only approach those from the cornea, but also approach one another, and become somewhat smaller. (Sanson's Images.) Helmholtz's Phakoscope Fig. 526 Phakoscope of Helmlioltz, At B B' are two prisms, by which the light of a candle is con- centrated on the 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 flg. 525, reflected from the eye under examination when the eye is lixed upon a distant object ; the position of the images having been noticed, the eye is made to focus a near 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. (fig. 526) is a 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 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 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 the tension of this ligament, diminishes to a proportional degree the flattening of which it is the 826 THE EYE AND VISION [CH. LVllI. cause. On diminution or cessation of the action of the ciliary muscle, the lens returns to its former shape, by virtue of its elas- ticity (fig. 527). From this it will appear that the eye is usually Fio. 527. -Diagram represeuliiig by dotted lines the alteration in the shape of the lens on accomino- dation for near objects. (E. Landolt.i 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 (r) of curvature of a convex reflecting surface is given by the formula r= — ; a is the distance of c the object from the surface, h the diameter of the image, and r that of the object. (I and r are easily measured ; l> is measured by Helmholtz's oiilitltalmometer, 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 or left ; if the glass plate is then placed obUquely 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 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, CH. LVIII.] ACCOMMODATION 827 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. 528) 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. AVhen the needle is at a moderate distance, the two pencils of light coming through 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 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. 528. — 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) Hie eyes converge owing to the action of the internal rectus muscle of each eyeball. (2) The pupils contract. The contraction of all of the muscles which have to do with accommodation, \iz., 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 as 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 828 THE EYE AND VISION [CH. LVIII. the retractor Untia. In cephalo])ods 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 objicts ; 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 tew 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, and (6) Presbyopia. The normal {emmetropic) eye is so adjusted that at rest parallel rays are brought exactly to a focus on the retina (1, fig. 529), Hence all objects except near ones (practically ail 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. 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. 529). 1. Myopia (short-sight), (4, fig. 529). — This defect is due to an 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. Eays 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. Hypermetropia (3, fig. 529). — 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, CH. LVIII.1 ERRORS OF REFRACTION 829 I' etc. They rest the eye by relieving the ciliary muscle from excessive work. Fi,. 50M -Diagram showing-l, 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 shmN^ 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 arXcussed behind the retina; i, viyopic eye ; in this case the axis of the eye is abnormally Ion' parallel ravs are focussed in front of the retina. The figure incorrectly represents the refraction as occurring only in the crj^stalline lens; the principal refraction really occurs at the anterior surface of the cornea. 3. Astigmatism.— This defect, which was first discovered by Airy, is due 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 crossmg 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 aU eyes, is generally seated m the cornea, but occasionaUy in the lens as weU; it may be 830 THE EYE AND VISION [cn. LVm. 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 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 aberrcition, 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 l)e 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 CH. LVIII.] SKIASCOPY 831 a white square on a black ground appears larger than a black sijuare of the same size on a white ground. The phenomenon is naturally more marked when the white object is a little out of focus. G. 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 Skiascope or Retinoscope. The refractive power of a lens is expressed in terms of its principal focal distance ; if this is 1 metre, it is said to have the refractive power of 1 diopter (1 D.) ; a lens 2 D. has a focal length of ^ a metre, and a lens ^ 1). has a focal length of 2 metres, and so on. The lenses necessary for correcting errors of refraction in an eye are best determined by a simple instrument called a retinoscope ; this is a small circular plane mirror, perforated by a hole in the centre through which the observer looks. If one reflects a spot of light from this on to a flat surface, any movement of the mirror produces a movement of the spot of light in the same direction ; if the surface selected, however, is the eye of another person, the direction of movement of the illuminated spot on the retina may or may not be the same as that in which the mirror is moved, according as whether the observed eye is normal, hypermetropic, or myopic. If the observed eye is just a metre away from the observer, and is emmetropic, then as the mirror is tilted from side to side the spot moves in the same direction. If a convex lens is placed in a spectacle frame in front of the observed eye, the parallel rays which emerge from the retina are brought to a focus and cross before reaching the eye of the observer. Then the spot will move in the opposite direction to the mirror. A lens of less than 1 D. will not, however, accomplish this reversal ; a lens of more than 1 D. will. So that a lens of 1 D. marks the exact point of reversal. If the observed eye is hypermetropic, the movement of the spot of light is also with the mirror, but stronger lenses than 1 D. must be intro- duced to get the point of reversal. If the lens in any particular case necessary for this purpose is 5 D., then spectacles of 4 D. must be ordered for the patient ; for one always has to subtract 1 D., since that is required to get reversal with the normal eye. 832 THE EYE AND VISION [CH. LVIIL When the spot of light moves against tlie mirror's movements from the first, then the observed eye is myopic, and the myopia is greater than 1 D. The " point of reversal " is determined by intro- ducing concave lenses of increasing strength into the spectacle frame, until the spot moves in the same direction as the mirror, and the spectacles ordered must have the value of the lens v^^hich accomplishes the reversal flus 1 D. to allow as before for the normal eye. Many people have differences in the refractive error of their two eyes ; so each should be tested separately. If the observed eye is astigmatic, the observations are more complicated, and must be made in the different meridians of the eye, and the point of reversal determined in each meridian by means of suitable cylindrical lenses. Functions of the Iris The iris has the following two uses : — 1. To act as a diaphragm in order to lessen spherical aberration in the manner just described. This is specially necessary when one wishes to obtain a clearly defined image of an object; the pupil therefore contracts when accommodation for a near object takes place. 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. 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 due 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 ciliary ganglion and short ciliary nerves supplies the circular fibres (fig. 530). (&) The cervical sympathetic supplies the radiating fibres. The cilio-spinal centre which governs them is in the cervical region of the cord (see p. 721). The fibres leave the cord by the anterior root of the second thoracic nerve, pass into the cervical sympathetic, CII. LVIII.] NERVES OP THI-: IRIS 833 and reach the eyeball via the ophthalmic branch of the fifth, and long ciliary nerves (fig. 530). (c) Fibres of the fifth nerve which are sensory. ; MID-BRAIN C.G. Fig. 530.— Diagram uf Llie motor uerves of the iris. Around the upper lialf of the pupil tlie circular fibres (C) only are indicateri. These are sup- plie l/^ /<5 <$^ >^0 ^°r~-/- Jrl& ^ ^ vW u 9 80 7 60 j 5 4 sp' ~2;o~^^;^ ■,'-i',o ^te' 3J0 40 50 6 7 ao 9 lI-— Vn' ,L-;^ ■' t' ~' :" -4__ I looV — r i^^ ^ ^ 6Ss Q 120^ \^^ ^ >y ^/>^ ^20 140\^ y^ / 7/^ ■■■-^ $\ >^o 160^ ^^^X- ■"^leo 80 100 180 Fio. "535.— Perimeter chart for the right eye. CH. LVIII.] VISUAL SENSATIONS 841 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 for different colours; thus a blue or yellow object is seen to be blue or yellow over a wider field than a red or green object. In disease of the optic nerve, contraction of the field of .vision for white and coloured objects is found. This often occurs 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. Visual Sensations. Visual sensations are of two kinds, colour sensations and colour- less sensations. Colour sensations 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, for instance, a weak sensation or a strong sensation. These differences are in part dependent respectively on the length, the purity, and the amplitude of the light-wave ; but they are also dependent on the local or general condition of the cerebro-retinal apparatus at the time of stimulation. Colours also differ (4) in brightness or luminosity; this is a purely psychological 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 equiv^alent. Even the most saturated colours (for instance, yellow and blue) have different degrees of brightness. Colourless sensations include the grey series from the deepest black to the most blinding wliite. 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 other rays which are invisible but which have definite properties ; those to the 842 THE EYE AND VISION [CH. LVIII. 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 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 compounding successive colour stimuli is by means of a rapidly revolving disc to which two or more coloured sectors are fixed. Each colour is viewed in rapid succession, but owing to the per- sistence of retinal impressions, the constituent colour stimuli give a single sensation of colour. A colourless sensation can be produced by the mixture of three 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 comiAementary. Thus blue and orange, when rotated on the colour-wheel, produce a colourless sensation ; but it is well known that a mixture of blue and orange paint gives green. This is explained on the supposition that the colours used are not pure and that each contains green ; the true blue and orange present neutralise each other to produce white, and thus green is the only colour sensation obtained. Three properly chosen colours will not only produce a colourless sensation, but when combined in appropriate amounts they can be made to yield any other colour sensation. It is on this principle that Thomas Young based his trichromatic theory of colour vision, which was subsequently elaborated by Helmholtz and Clerk-Maxwell. It is known as the Young-Helmholtz theory. The theory selects red, green, and violet as the three primary colour-sensations. These three particular colours are chosen, partly because of their position within the spectrum, partly on account of the phenomena of colour- blindness, and for other reasons. The Young-Helmholtz theory teaches that there are in the retina certain elements (? within the cones) which answer to each of these primary colours, whereas the innumerable 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 spec- trum, 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 considerably, the green rather more, and the violet slightly, the resulting sensation being that of orange, and so on (fig. 536). Another theory of colour vision (Hering's) supposes that there are six primary colour-sensations, viz. : three antagonistic (complemen- CH. LVIII.] COLOUR VISION 843 Fio. 536. — 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. tary) pairs, 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, which (the theory supposes) exist in the cerebro-retinal apparatus. Each of the substances corresponding to a pair of colours is capable of undergoing two changes, one of disintegration, and the other of construction, with the result of producing one or other colour. For instance, in the white-black substance, when disintegration is in excess of construction or as- similation, 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 colour-sensation occurs. The rays of the spectrum to the red end produce changes in the red-green substance, with a resulting sensation of red, whilst the (orange) rays further to the right affect both the red-green and the yellow-blue substances ; blue rays cause constructive changes in the yellow-blue substances, but none in the red-green, and so on. All colours act on the white-black substance as well as on the red-green or yellow-blue substance. Neither theory satisfactorily accounts for all the numerous com- plicated 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 (see further p. 848), 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 or green are absent, or very imperfectly developed, and Hering's would be that the red-green substance is absent from the cerebro-retinal apparatus. Other varieties of colour-blindness, in which the other colour-perceiv- ing elements are absent, have been shown to exist occasionally. Hering's theory appears to meet the difficulty best, for if the red 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. These two theories have been for a long time 844 TnE EYE AND VISION [CH. LVIII. before the scientific world. As facts have accumulated, it has beeu 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. C. J. Hurch found that by exposing the eye to bright sunhght in the focus of a burning-glass behind transparent coloured screens, it is possible to produce temporary colour blindness. After red hght, the observer is for some minutes red- blind, scarlet geraniums look black, yellow Howers 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 produced. If one eye is made purple-blind, and the other green-blind, all objects are seen in their natural colours, but in exaggerated perspective, 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 bhnd 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 iniportant 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. Testing for Golour-Uindness. — The test formerly adopted by the Board of Trade consists in matching skeins of wool from a heap of skeins of different colours (Holmgren's worsteds). It has, however, been shown that the test is not trustworthy, and it has been supple- mented by one in which the subject is required to name the colours of lights in a lantern. The Edridge-Green lantern is one of the best to employ ; in it the intensity and colour of the light and the order in which the colours are shown can be easily varied. If the colour- blind person is made to examine and report on the colours of a spectrum, or in portions of the spectrum exposed to view, the results obtained are more accurate, but this is not so simple as the lantern test. 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 distribution of brightness and colour. In negative after-images bright i:)arts appear dark, dark parts bright, and coloured parts in the complementary 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 II. III. IV. Plate to illustrate simultaneous and successive contrast. For explanation see text. CH. LVIII.] SIMULTANEOUS AND SUCCKSSIVE CONTRAST 845 the Young-Helmholtz theory, this is explained on tlio hypothesis that the excitation does not decHne with equal rapidity in the three colour terminals. A positive after-imago is readily obtained by momentarily looking at a bright object, e.g. a window, after waking from sleep. Negative after-images 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 l)y the. Young-Hclmholtz theory, on 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. Simultaneous and Successive Contrast. — Negative after-images are frequently spoken of as phenomena of successive contrast. The phenomena of simultaneous contrast are well illustrated by the four figures of the accompanying Plate. In all these figures the oblong grey strip is actually of the same brightness. This can easily be proved by screening from view the surrounding parts of the figures, which cause the greys to appear different. The grey in I. appears darker than that in II., while the grey in III. appears yellowish and in IV. reddish. If these effects are not sufficiently obvious, they immediately become so when the entire surface is covered over with a sheet of thin tissue paper. Figs. I. and II. are examples of brightness contrast ; Figs. III. and IV. of colour contrast. The effects of these two varieties of simultaneous contrast may be stated thus : a given grey object looks darker when viewed against a bright background than when viewed against a dark background ; when the background is coloured, it is tinged with the complementary colour of the former. Helmholtz attributed the effects of simultaneous contrast to errors of judgment, and not to altered conditions of the retinal apparatus.* But there can be no doubt that simultaneous contrast has as simple a sensory origin as successive contrast (negative after- images). For if either of the two lower figures of the plate is care- fully fixated for about a minute (fixation of the central dot will help to prevent involuntary movements of the eyes), and if the gaze be then transferred to a spot on a sheet of white or grey paper, not only will the outer squares appear in their complementary colour, but also the grey strips will appear tinged, now likewise in 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. 846 THE EYE AND VISION [CII. LVHL complementary colour. So, too, if a point midway between Figs. I. and II. is fixated, and the plate held at a sufficient distance for both figures to be simultaneously visible, the after-image of the grey strip of II. will appear darker than that of I. Seeing that simultaneous contrast persists in after-images, and seeing how generally recognised are its effects (for instance, by the painter, who depicts in hlue the shadows cast by an object on the yellow sand), it seems far more probable that the part played by the higher mental processes consists, not, as Helmholtz supposed, in causing the illusion, but in reducing or overcoming it. According to this view, experience educates us in seeing objects in what we know to be their real colour, instead of in the colour which would result from the operation of simultaneous contrast. Some support is lent to this view by the fact that contrast is much enhanced when all irregu- larities are, as far as possible, eliminated from the surface of the object (here, the grey oblong) in which the contrast colour is induced, or when that object is made to appear, e.g. by covering the whole with tissue paper to combine with the object (the coloured square) which induces the contrast colour, so as to form an apparently single object. On the other hand, colour contrast is very markedly reduced, if the grey object is outhned in pencil on the tissue paper through which it is viewed. Thus, whatever tends to the apparent independence of the object in which the contrasting colour is induced tends to the reduction of the contrast effect. Insisting on the sensory nature of simultaneous contrast, Hering explained it in the following way. He supposed that excitation of an area of the retina by a stimulus of given colour or brightness simultaneously induces an opposite metabolic process in the same colour apparatus in neighbouiing areas of the retina. When, for example, a part of the retina is being stimulated by blue, the anabolic change thus evoked in the yellow-blue apparatus simultane- ously is supposed to induce a katabolic change in the same apparatus in the neighbouring retinal area which is being excited by a grey stimulus. Consequently, the grey acquires a yellowish tinge. Binocular colour-mixture. — 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 other 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 "riv^alry of the fields of vision " occurs, first one then the other disc rising into consciousness. A stereoscopic combination of black and white produces the appear- ance 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 CH. LVIII.] RETINAL CHANGES DURING ACTIVITY 847 as indicating a polished surface, because a polished surface reflects rays irregularly, so that the two eyes receive 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 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 physico-chemical alteration in the protoplasm, and that this change stimulates the optic nerve-end- ings. The discovery of a certain temporary reddish-purple pigmenta- tion 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 chromophanes, and are found in the retinae 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 ox 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). Eed light has no action on visual purple ; the maximum bleach- ing effect takes place in greenish-yellow light. Now, when the living eye is brought into a condition of " dark adaptation," that is, when 848 THE EYE AND VISION [CH- LVIII. 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, known as Purkinge's phenomenon, 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. in the " dark-adapted " eye), while the cones are affected under more ordinary conditions 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 sensa- tion ; then it produces 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 " pJioto-chromalic interval." lied 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, arc 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 brightest 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 colourless 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 hcn\ 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 CH. LVIIl.] MOVliMENTS OF THE EYKBALLS 849 is the same as in extra-foveal vision of the normal eye ; in many of these cases there is a central scotoma (bUnd spot), that is, the rodless fovea is blind ; there is reduced acuity of vision as in the " dark-adapted " eye, and phu/opliohia (fear of strong light); nj/stu(jnim (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 adai)lation," and a pathological change known as re/inUin piijmentoita 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 were discovered by M'Kendrick and Uewar, and have been recently reinvestigated by Waller. The excised eyeball of a frog is led off by non-polarisable electrodes to a galvanometer. ( )ne 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, ^^'hen 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 stimidation 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. AVhen this has subsided, the true current of rest is from cornea to fundus, /.^., it is like that of the skin, 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 eye, especially the crystalline lens, participate in their causation. The response of the eye to non-luminous stimuli lasts some time, 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 M'aller, draws attention to the long latent period and sustained character of the response. The photo-electric changes are all monophasic effects, whether produced by illummation, 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, i.f., 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 %aew that the photo-chemical changes are of opposite characters, for the photo-electric change is always in the same direction, differing onlj^ 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 850 THE EYE AND VISION [CH. LVIII. 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. The muscles of the two eyes act simultaneously, so that images of the objects looked at may fall on corresponding points of the two retinae. 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 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 subject 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 wUl 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 palpebrae 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 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 109 mm. behind the front of the cornea. CII. LVIII.] POSITIONS OF thp: eyeballs 851 The three axes around which the movements occur are : — 1. The visual or antero-posterior axis. (A P, fig. 537.) 2. The transverse axis, which connects the points of rotation of the two eyes. (Tr, fig. 537.) 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 Fig. 537.— Diagram of the axes of rotation to the eye. The thin lines indicate axes of rotation, the thick the position of muscular attachment. 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 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 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). 852 TIIK EYE AND VISION [CII. LVIII. 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 disregarded by the brain, which pays particular attention to those images which fall on corresponding points. The accompanying diagrams will assist us in understanding what is meant by corresponding or identical points of the two retinae. If R and L (fig. 538) represent the right and left retinae respectively, O and 0' the two yellow spots are identical ; so are A Fui. ."iSS. — Identical points of tlie retina^. 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. 539 shows the same thing in rather a different way ; A and B represent horizontal sections through the two retinae ; the points a a', b b', and c c', being identical. In the lower part of the diagram is shown the way in which the brain combines the images in the two retinae, one overlapping so as to coincide with the other. The Horopter is the name given to the surface in the outer world which Fio. 539.-Diagram to^ijow ^^^^^^^ coutaius all the poiuts which fall on the identical points of the retinae. The shape of the horopter will vary with the position of the eye- balls. In the primary position, and in the lirst variety of the en. Lvni.] THE OPTIC NEPiVES 853 Fig. 540. — The Horopter, wlien the eyes are convergent. secondary position, the visual lines are parallel ; hence the horopter will be a plane at an infinite distance. Tn 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. 540) which passes through the nodal points of the two eyes, and througli the fixed point (I) in the outer world at which the eyes are looking, and which will consequently fall on the two yellow spots (0 and 0'). All other points in this circle (II, III) will fall on identical points of the retinae. The image of II will fall on A and A'; of III on B and B'; it is a simple mathematical problem to prove that OA = 0'A', and OB = 0'B'. 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. 736). Nervous Paths in the Optic Nerves. The correspondence of the two retinae and of 4;he 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. 541) 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 retinae that cross ; and that those represented by con- tinuous lines from the right side of the two retinae ultimately reach the right hemisphere, and those represented by interrupted lines from the left side of the two retinae ultimately reach the left hemisphere. The two halves of the retinae are not, however, separated by a hard-and-fast line from one another; this is represented by the two halves being de- picted as slightly overlapping, and this comes to the same thing as saying that the central region of each retina is represented in each hemisphere. The part of the hemisphere concerned in vision is the occipital lobe, and the reader should turn back to our previous consideration Left Retina Right Retina Left Hemisphere Right Hemisphere 541. — Course of fibres at optic chiasma. 854 THE EYE AND VISION [CH. LVIII. of this subject in connection with cerebral localisation, the pheno- mena of hemianopsia and the conjugate deviation of head and eyes (pp. 736, 737). Fig. 542, 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 from the retina to the external geniculate body end there by arborising around its cells, and a fresh relay of fibres from Fio. 542 —Relations of iier\'e cells and libres of visual apijaralus. (Schafet) these cells passes in the posterior part of the internal capsule to the cortex of the occipital lobe. Those to the anterior corpus quadrige- minum 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, whence a fresh relay continues the impulse to the oculo-motor nucleus. Sherrinfrton's observations on binocular flicker have shown that there are difficulties in accepting fig. r.42 as a complete anatomical basis for the psychological processes involved in binocular vision, although it is probably correct so far as the motor mechanisms involved are concerned. 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. en. LVIII.] VISUAL JUDGMENTS 855 We have already seen that in spite of the reversion of the image in the retina, the mind sees objects in their proper position ; this is explained on p. 823. 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. 835. Our estimate of the size of various objects is based partly on the visual angle (p. 822) 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 estimate of distance is, however, 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 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 mind, into which the sensations of vision are incorporated, invests the images of objects, together with the whole field of vision in the retina, with very vary- ing 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 such as 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- 856 THE EYE AND VISION [Cn. LVIII. 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. 543) 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 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. 543), be presented to corresponding parts of the two retinae, as may be readily done by means of the stereoscope, the mind will perceive not merely a single representa- Fio. 543. — Diagrams to illustrate how a judgment of a figure of three dimensions is obtained. 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 versd. An instrument contrived with this purpose is termed a pseudoscope. 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 are 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. Further, if we want carefully to examine any object, we always direct the eyes straight to it, so that 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. 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 CH. LVIII.] VISUAL JUDGMENTS 857 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. In fig. 544, 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- A B C D Fig. 544.— Diagrams to illustrale visual illusions. division of a space or line increases its apparent size or length. In fig. 544 D, ab is equal to he. Vertical distances also are usually over-estimated. In fig. 545 the long lines are parallel, thougli FiQ. 545.— Zullner's lines they do not appear so, owing to the influence of the intercrossing lines. CHAPTEE LIX REPIIODUCTION, DKVELOPMENTj GROWTH AND DEATH The history of the fully formed animal from the ovum, and a description of the origin and formation of its tissues and organs, constitutes the portion of biological science known as embryology. The scientific discussion of embryology must not be limited to man, however important he may be, but must embrace a wide survey of the whole animal kingdom, because the changes which occur in the embryological history of the highest animals forms a compressed, though in many cases a modified picture of the changes which have taken place in their historical development from lower types, during the long and misty ages of the past. To attempt an adequate discussion of this large subject would mean the writing of a book as long as the present volume. It would lead us far into biological fields, and also into discussions of a philosophical and hypothetical nature which would be quite out of place in a physiological text book. All we can do is to put down the important facts, and specially to dwell on those which have a physiological bearing. Evolution has in the past been specially studied from the anatomical point of view; but it has its physio- logical counterpart ; for as structures increase in complexity, so also does function become correspondingly differentiated and varied. The great problem of evolution is associated with the immortal name of Darwin. He showed that although the offspring resembles the parents there are always certain slight variations which may be transmitted to future generations, and in their turn these are magnified or admixed with other variations in each succeeding generation. In the struggle for existence those will survive in which the variations are beneficial and helpful, so that in the end the fittest will live on. The piling up of variations which in themselves ■ may be trivial thus leads to the development of new types and species, and this, prolonged over immense periods of time, has led to the evolution of complex from simple forms of life. The explanation of heredity is a subject on which much difference 86S CH. LIX.] HEREDITY 859 of opinion prevails. It does, however, appear to l)e pretty well accepted that the material of the nucleus of the male and female reproductive elements is of special importance in the transmission of hereditary characters. That the chromosomes of the nucleus are of vital importance is clearly shown by several facts. For instance, they are constant in number not only in the cells of the body but in all individuals of any particular species of animal or plant, though differiug in number in different species. The equal halving of each chromosome, which occurs during mitosis, maintains this numerical constancy, except in a certain period of the life history of each individual, and this period occurs in the formation of the reproductive cells (often called gametes). During one step in the karyokinetic cell-division, half of the normal number of chromo- somes are thrown out, and the act of fertilisation consists in the fusion of the male and female gametes; each parental nucleus provides half the normal number of chromosomes, and thus the fertilised egg-cell starts with the full complement once more. A large number of biologists regard the chromosomes as the actual bearers of the characters which an organism inherits from its parents, or, at any rate, adopt this view as a working hypothesis. This places the transmission of characters from parent to offspring upon a material foundation, Weismann's view that characters acquired after birth are not transmissible rests mainly upon negative evidence, and so cannot be considered as fully proved. The development of the two sexes took place fairly early in the history of the animal world, but there are many animals of the simplest kind in which no differentiation of sex occurs. The determination of sex, that is, why a mother should bear at one time a male, at another time a female infant, is a question of great importance, and numerous theories have been advanced to explain it. In certain invertebrate animals there is some evidence that sex is preformed either in the ovum or the spermatozoon, or in both ; that is to say, there are male and female ova, and male and female spermatozoa which exhibit slight differences of structure; the question of sex of the offspring will then depend upon which element predominates after union. Others hold that potentialities of producing either sex are present in all ova and all spermatozoa, and that the ultimate sex is determined by some relationship which is at present unknown, but which in all probability operates at the time of fertilisation. The original Darwinian doctrine, just stated in outline, has since been modified in several directions as research has progressed. The work of Weismann just alluded to is important, liut of all the theories which have been grafted upon the original theory, that of Mendel is perhaps of the greatest interest ; it certainly appeals to 860 REPBODUCTION, DEVELOPMENT, GROWTH AND DEATIF [CIT. LIX. the scientific mind, for it is one which is susceptible of proof and demonstration. It may be best iUustrated by a concrete example. If two kinds of ])lant, such as dwarf and tall peas, are crossed, the seeds obtained all produce tall plants; but if the plants of this generation are crossed, the third generation contains 25 per cent, dwarf and 75 per cent, of tall plants. If the dwarfs are crossed, they breed true, that is, they produce dwarf plants only ; but if the tall plants are inter-crossed, again one-quarter of the next generation are dwarfs and the remainder tall. Of the 75 tall plants, 25 breed true, and of the remaining 50, one-quarter produce dwarfs which breed true, and the remaining three-quarters are tall plants. In successive generations the same holds : the dwarfs, when self-crossed, always produce dwarfs, and tall plants always produce a progeny in which 25 per cent, are dwarfs and 75 per cent, tall, some of which breed true and the remainder breed a mixture in the same pro- portions as before. This is explained by calling certain characters chminant and others recessive ; thus, in the example taken, tallness is dominant and dwarfness is recessive. So in the first generation the progeny all exhibit the dominant character, but in the second only 25 per cent, will be pure dominants (that is, will produce only dominants in successive generations), 25 per cent, will be pure recessives, and 50 per cent, are mixed; and the mixed type will again produce 25 per cent, dominants, 25 per cent, recessives, and 50 per cent, mixed, as before. This discovery has been found important for breeders and horticulturists, but the law appears to fail sometimes ; for instance, when the black and white races intermarry, the result is brown children, and not a definite proportion of blacks and whites. Looked at from the evolutionary point of view, the whole of the complex animal body is but the temporary dwelling-place of the reproductive cells, and nature provides lavishly, both in animals and plants, for the continuance of the species. These temporary homes, which we call the father and the mother, pass away, but they live on and on in their descendants. In the future we cannot doubt that upward progress will still continue as in the past, and man in time should be in very truth " but little lower than the angels." Some hold that civilisation in some ways places a slight obstacle on the path of progress of the race; numerous works of charity militate against the inexorable law of the survival of the fittest, so that many live to propagate their species who may be weaklings both in body and mind. There are no doubt extreme cases where it is desirable that deteriorated characters should be debarred from introducing into the world a continuance of beings destined for misery and crime. But I myself believe that the present development ClI. LIX.] THE CYCLE OF LIFE 861 of charitable endeavours is in itself a sign of progress ; it indicates a growth of the feelings of compassion and nnselfishness which con- stitute a great asset in the possessions of a race. The laws of evolu- tion operate in spite of artificial hindrances; this is exemplified in what is termed the law of anticipation ; by this is meant that in a heritable disease its effects develop at an earlier and earlier age in successive generations, until at last it causes death at a period before the sexual organs attain maturity, and thus automatically its continued propagation is put a stop to. In a simple unicellular organism such as the amoeba, there is not only no differentiation of sex, but there is also no differentiation between the reproductive element (Weismann's germ jjlasm) and the remainder of the body (Weismann's somatoplasm). When the amoeba propagates itself by dividing into two new amoebaj, the whole animal is concerned in the act of reproduction, and, barring accidents, the new amoeb?e may behave in this way indefinitely, and so may be spoken of as immortal. In this sense the only part of the body which is immortal (in the material as opposed to the theo- logical use of the word) in the higher animals is the germ plasm, which lives beyond us to repeat the process an infinite number of times in our descendants. If now we deal in a more matter-of-fact way with the present instead of the past or the future, the faculty which living organisms have of reproducing themselves furnishes us with a new conception of the life process. The common lot of all is to die, and life in the individual is then extinct; but each individual is only a link in a long chain of lives, and life is thus not something which begins and ends like a straight line ; it is rather to be compared to a circle, in which a series of events is repeated over and over again. If we start with the ovum we are led to the foetus, and then to the child, and the adult who produces or fertilises an ovum once more ; and so history goes on repeating itself. I propose, however, in the following account of some of the details of the long story, to start at a different point in the cycle. We will take first the new-born child, and rapidly run through what occurs after its birth until the state of sexual maturity is reached, Next it will be our duty to consider the structure and physiology of the reproductive organs, and how the ova in one sex, and the spermatozoa in the other sex, originate. Next will follow an account of the union of these reproductive cells, and the production of a fertilised ovum. This will be followed by a brief account of the development and life of the foetus, until we reach the mechanism by which the new-born child is expelled from the uterus into the world, which will bring us back to the point from which we started. 862 ueproduction, development, growth and death [ch lix. The Neav-born Child and the Changes it Undergoes AFTER Birth. The new-born child, which in the uterus was obtaining its nutriment and oxygen from its mother's blood, is severed from the organ called the placenta, by means of which this was accomplished, by cutting through the umbilical cord. The want of oxygen is met by the child beginning to breathe, and its nutriment is supplied by its mother's milk, which later on is supplemented and replaced by other articles of diet. Immediately after birth certain changes occur in the circulatory system ; the foramen ovale, the opening between the two auricles, begins to close, and so do the ductus arteriosus and the ductus venosus. The now functionless umbihcal vessels close also until they are reduced to mere fibrous cords. These changes are completed in a few days, and the circulation then takes the course it traverses for the rest of life. In addition to this there are changes of a more general kind, the most obvious of which is growth; this is accompanied with the completion in the formation of certain organs and tissues which are in a comparatively immature condition when the child is born. Thus medullation of the fibres in the central nervous system is taking place, and the process of ossification continues until the bony skeleton is perfected. The generative organs reach maturity at the period of life known as puberty. The rate of growth after birth is not so rapid as it is in utero ; and every year the relative increase in size gets less and less. On the average, girls in the earlier years grow more than boys, but at the onset of puberty this relationship is usually reversed. At puberty there is generally an acceleration of the rate of growth in both sexes, but this gradually declines, and finally growth ceases. Puberty then is the period at which the sexual organs become matured and functional. In girls this occurs on the average at about fourteen or fifteen years of age, and is marked by the onset of menstruation. Menstruation, or the monthly flow, continues until the age of forty-five to fifty, when it ceases either gradually or suddenly, and after this period (the menopause or climacteric) further production of offspring is not possible. The menopause is usually accompanied with great depression and other disturbances of a physical and mental nature. In boys, puberty is usually a little later developed than in girls, but there is no limit at the other end of life corresponding to the menopause. In both sexes the onset of puberty is accompanied by the secondary sexual characters becoming pronounced, such as the increase in fullness of the mammary glands in the female, and the CH. LIX.] THE MA1,E KKPIiODUCTlVK ORGANS 863 growth of liair on llio face and tlie increase in size of tlic larynx wliicli leads to the eleepening of the pitch of the voice in the male. The Male Reproducj'ive Organs These consist of the two testes which produce spermatozoa, and the ducts which lead from them. The testis is enclosed in a serous membrane called the tunica vaginalis, originally a part of the peritoneum, which descends into the Fig. 546. — 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, o a, Tubuli semi- niferi coiled up in the separate lobes ; h, tubuli recti ; c, rete testis ; d, vasa efferentia ending in the coni vasculosi ; I, e, g, convo- luted canal of the epidi- dymis ; h, vas deferens; /, body of Highmore ; i i, fibrous processes running between the lobes. Fig. 547. — 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.) 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 alhuginea. Passing from its inner surface are a number of septa or trabeculge, 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 of High- 864 REPRODUCTION, DEVELOPMENT, GROWTH AND DEATH [CH. LIX. more) or mediastinum testis. Attached to this is a much convoluted tube, which forms a mass called the epididymis. 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 tuhule, 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 efferentia) arise, which become convoluted to form the coni vasculosi, and then pass into the tube of the epididymis. The convoluted or seminiferous tubes (fig. 548) have the following Fio. 54S. — l)ia;.;ram of a purLloii of a seminal tubule sbowliiK developnieut of spermatozoa. 1, Primi- tive germ cell; i, spermat Oogonia Heterotype mitosis ] and reduction of the | chromosomes to half/ the usual number Secondary oocyte Mature ovum 4 Period of growth — Primary oocyte First polar body Division of the First Polar body -Second polar body Fig. 5<53. — Diagram to illustrate oogenesis. within the Graafian follicle. Its maturation, which occurs outside the ovary, is represented in the lower part of the diagram, which is a repetition of what is also seen in fig. 562. Each primary spermatocyte gives rise to four spermatozoa of equal value. Each primary oocyte gives rise to four cells, which are of unequal value ; one of these is the mature ovum, the other three are the minute polar bodies which may be regarded as abortive ova. The mitosis which results in the halving of the normal number of chromosomes occurs in each sex at the same stage, namely, in the formation of the secondary spermatocyte, and of the secondary oocyte respectively. 878 REPRODUCTION, DEVELOPMENT, GROWTH AND DEATH [CH. LIX. Tlu' meaning of tin- polar bodies has been tlie subject of imicli speculation; it is svipposed that the female cell casts out certain constituents in order to make room for the addition to it of material from another individual, namely, the male. Some animals multiply without the intervention of the male sex, or the intervention occurs at lon^- intiTVals with many intermediate generations ; this is known as ■j)ar/lieno(/enexis. One must therefore suppose that the female cell has within it a male component which can be transmitted to future generations. The ovum of these animals only extrudes one polar globule. It may therefore be that the second polar body contains the hereditary male element which is retained in parthenogenesis, but in animals which nmltiply sexually this is got rid of prior to the inee])tion of the new male element. This brings us to the stage in our story when both male and female elements are ripe and ready for union. Logically we should next study how tlie union is accomplished. But first wo must step into a bye-path, and before leaving the ovary and testis enquire whether these organs have any other functions than those we have already discussed. This may best be done under the following new heading. Internal Secretions of Ovary and Testis The operation of castration, that is, the removal of the essential generative organs, naturally leads to a loss of reproductive power, but it has other effects of a more general kind on the organism, which mainly influence what are known as the secondary sexual characters. This effect is believed to be due to the lack of certain internal secretions formed by testis and ovary respectively. Testis. — Some years ago Brown-Sequard, then an old man of seventy-two, stated that the subcutaneous injection of testicular extracts into himself produced marked rejuvenating effects. More recently Poehl has described the beneficial stimulating effects of a substance prepared from the testis, wliich he terms spermine. He has assigned to it the formula C^Hj^No, but Dixon has shown that it is a mixture of proteins with other organic and inorganic materials. The supposed tonic effects of such injections are regarded with great suspicion, and temporary benefit, if it does occur, is mainly attributable to suggestion. The principal evidence upon which the assumption rests that the testis forms an internal secretion, is derived from the effects of castration, or from cases in which the testes do not descend into the scrotum. If the operation of castration is performed before puberty, the reproductive apparatus which is left (vesiculse seminales and prostate, but not the penis) atrophy ; the secondary sexual characters (growth of hair on the face, deepening of the voice, etc.) do not develop ; the body remains infantile, but never assumes female characters. The body, however, grows, and in some cases there is overgrowth of the skeletal and adipose tissues. In animals there is corroborative evidence of the same nature. CIl. LIX.] SECONDARY SEXUAL CIIAliACTEHS 879 Thus in the cock castratiun arrests the development of the comb and spurs ; in the stag of the antlers. In the eland and in horned cattle where both sexes have horns, their growth is not inhibited by castration, though their shape may be affected (Marshall). In Herdwick sheep, where the males are horned and the females horn- less, it has been shown that the presence of the testes is essential, not merely for the initiation but also for the continuance of horn growth. Castration stops further horn growth forthwith, and at every stage of development. Ligature of the vas deferens leads to atrophy of the seminiferous tubules, whilst the interstitial cells are not affected, and the secondary sexual characters develop as usual. It is on this ground that most investigators agree that the interstitial cells of the testis are the source of the internal secretion. These cells have all the appearances of secreting cells, and their full development coincides with the first appearance of spermatogenesis. Transplantation of a testis in an abnormal position in the body cavity is followed by development of the secondary sexual characters, and the view is generally held that the internal secretion acts chemically on the parts concerned, rather than through the intermediation of the nervous system. The Prostate. — As already stated, the removal of the testis leads to atrophy of the prostate, but the converse has been stated to be also true, and that in dogs prostatectomy causes the testes to lose their functional activity. Attempts to repeat these effects, by other observers, have, however, failed, and as Marshall points out, it is unlikely, on phylogenetic grounds, that the functions of the essential reproductive organ should depend upon the presence of an accessory gland of comparatively late appearance in the history of evolution. Tke Ovary. — Extirpation of the ovaries prevents the onset of puberty and the occurrence of menstruation, but produces no noticeable effects on the general form and appearance of a woman. Ovariotomy after puberty brings menstruation to an end, and there may be slight atrophy of the breasts, uterus, and external genital organs ; this, however, does not always occur. In animals the same operation prevents the occurrence of the cestral cycle, but the " periods" continue to recur if one of the ovaries is grafted into the abdomen. The ovary does not appear to have such far-reaching effects on general metabolism as the testis possesses; its internal secretion seems to act especially upon the uterus. Marshall's observations on dogs, and Heape's on monkeys, favour the view that the interstitial cells of the ovary are responsible for the production of a hormone which initiates the oestrous cycle, and if this is the case the occurrence of menstruation in the human female is attributable to the action of the same cells. 880 REPRODUCTION, DEVELOPMENT, GROWTH AND DEATII [CH. LIX. The Corpus Lutcnm. — Special interest attaches to the function of the corpus luteuni which is formed in the Graafian follicle after the exit of the ovum. We have already seen that this structure attains a great size if pregnancy ensues. The luteal cells are formed from the lining cells of the follicle and not from the interstitial cells just alluded to. It has been generally assumed that the corpus luteum forms a hormone or hormones, and the functions which have been assigned to these chemical messengers are four in number. 1. To affect the uterus and bring about there the oestrous or menstrual cycle. This view may be dismissed at once ; the hypothesis is negatived, first, because it does not explain the occurrence of the first oestrous cycle in the young animal, and secondly, because injection of luteal extracts does not induce uterine changes. The cells concerned in that function are, as already stated, the interstitial ovarian cells. 2. To inhil)it the ripening of Graafian follicles during pregnancy (Loeb). This may bo an effect, but it is hardly a function. 3. To assist in some way the fixation ancl early development of the impregnated ovum in the uterus. This view is mvich favoured by most authorities, and the principal evidence in its favour is that removal of the ovaries, or even destruction of the corpus luteum shortly after pregnancy has begun, brings that process to an end ; the same operation later in pregnancy has no effect upon the development of the foetus or the subsequent act of parturition. 4. To stimulate the growth of the mammary glands during the early months of pregnancy. Prolonged search for the secretory nerves of the milk glands have failed to reveal their presence. Cases have occurred in which severe injuries to the nervous system preclude any possible nervous connection between the generative organs and the mammary glands; nevertheless, the latter grow and ultimately produce milk. Such considerations point to the conclusion that the correlation must be chemical rather than nervous. A few years ago Starling and Miss Lane Claypon thought that the hormone in question must be secreted by the foetus, because the injection of foetal extracts in rabbits led to a hypertrophy of the mammary tissue. The hyper- trophy, however, is imperfect, and doubt was felt in many quarters whether this could be the whole explanation, because mammary evolution occurs in many virgin animals in which ovulation is not followed by pregnancy ; moreover, in many cases enlargement of the breasts occurs at each menstrual epoch. The view is now advanced that a hormone is secreted by the corpus luteum, which is an inciting cause of the early growth of mammary tissue. The close corre- spondence between the stages in the development of the corpus luteum and of the mammary glands has been clearly brought out CH. LIX.] FERTILISATION 881 by the recent work of O'Donoghue. One must, however, point out that as a rule there is no corpus luteum in the ovaries during menstruation, or during the pre-cestral period in sows, when the mammary glands show signs of growth and congestion. The therapeutii- use of ovarian extracts appears, from the evidence available, to stand in the same uncertain position as that of testicular extracts. If the reader refers back to the chapter on the ductless glands he will find that some of these (thymus, pituitary, etc.) influence the formation of the genera- tive organs. The structure of the mammary glands and the composition of milk have already been treated at length in our chapter on Foods (see pp. 481-48G). Fertilisation We are now in a postion to resume the thread of the history of the further development of a new individual. The next step is the union of the male and female gametes, that is to say, of the spermatozoon and the mature ovum. The act of coitus or copulation is associated in both sexes with much psychical excitement, and with the phenomenon of erection (see p. 313). The spermatozoa are thus deposited at the entrance of the uterus, and by means of the flagellar movement of their tails they make their way against the stream of ciliary movement into the Fallopian tubes, where they are found in a living condition for many days. It is here that they meet the mature ovum; but fertilisation or impregnation only requires the entrance of one spermatozoon into the ovum. By means of its sharp head cap the spermatozoon pierces the zona pellucida, and the head, neck, and possibly part of the body, enter the substance of the ovum, where they undergo trans- formation, and are converted into a male pronucleus with an attendant attraction sphere and its centrosome. The male pro- nucleus contains the same number of chromosomes as the female pronucleus, for the mitosis which occurs when the primary sper- matocyte divides to form two secondary spermatocytes, is a heterotype mitosis, in which only half the usual number of chromosomes appear ; and consequently the secondary spermatocytes, and their descendants the spermatids, also contain only half the typical number of chromosomes. These are retained in the spermatozoa, which are produced by modifica- tion of the spermatids, and they reappear in the male pronucleus. 3 I- ZONA PELLUCIOA Fig. 5G4. — The fertilised ova or blastosphere, showing its new nucleus and attraction spheres ; the yolk granules have been omitted. 882 IlEPRODUCTION, DEVELOPMENT, GUOWTH AND DEATH [ciI. LIX, 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 l)y two attrac- tion spheres with their centrosomes (see fig. 564) ; one of these spheres is introduced with the male pronucleus, and tlie other probably originates from it by division, since the centrosomc of the ovum is lost during maturation. Loeb has suggested that the action of the spermatozoon is essentially chemical, because in certain invertebrate animals (for instance, sea urchins) he has been able to produce artificial partheno- genesis by purely chemical methods. In his latest work, he placed the ova in dilute acetic or formic acid; by this means, a membrane is formed upon the surface of the egg-cell as it is in normal fertilisation ; if the ova are then transferred to concentrated sea water for a short time and then placed in ordinary sea water, they segment and produce normal larvae. He considers that the sperma- tozoon brings with it enzymes or other chemical substances which excite the ovum in the same way as the chemical reagents mentioned. The changes by which the fertilised 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 the yolk is a whitish speck, the cicatricula, which is a small mass of protoplasm, about I of an inch in diameter. In the cicatricula lies the nucleus or germinal vesicle, and it is this small mass of protoplasmic substance which divides and grows to produce the chick ; the yolk and the surrounding white being used as food. Ova such as the hen's, in which only a small part, the cicatricula, divides and grows, are called meroblastic. 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 further development of the individual systems of organs by CH. LIX.] SEGMENTATION 883 which the oiiibrycniic rudiments are converted into the uwyg fully developed condition in which they are found at birth is a subject fully treated in works on anatomy, embryology, and obstetrics, and we shall not go into those matters here. The nutrition of the embryo and the circulation of its blood are, however, matters of physiological moment, so that it will be necessary to refer to the origin of the foetal membranes, as it is by their means that nutrition is carried on. Let us, however, first briefly take up the early stages in development. 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 many 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 (see figs. 566, 567). 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, the outer layer being called epiblast and the inner hypoblast. A little later the mesoUast or third layer of the blastoderm grows 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 protovertebr?e or meso- blastic somites (see also fig. 570). The more laterally situated part of the mesoblast constitutes the lateral plates, and the narrow strand of meso- blastic cells which connects the lateral plate on each side with the Fio. 565. — Diagrams of the early stages of cleavage of the ovum. (Dalton.) 884 REPRODUCTION, DKVELOPMENT, GROWTH AND DEATH [CH. LIX. protovertebral somites is the intermediate cell mass. Soon after its formation the lateral mosoblast is cleft into two layers, and the space which appears between the two layers is called the coeloni (figs. 568, 569). The outer or somatic layer of the mesoblast adheres to the epiblast; the two together form the somatopleur. The inner or splanchnic layer fuses with the hypoblast to form the splanchnopleur. Fig. 503. — Diaf^ram of a surface view of a youiit; mammalian blastula. 1, Goniiinal area. A, line of section represented in tig. 567. Fio. 567. — Diagram of a section of the mammalian l)lastula shown in lig. 50(5 alon;; the line A. 1, Ger- minal area; 'J, epiblast; 3, inner cell mass. Whilst the mesoblast is extending and cleaving, the neural ridges, which are longitudinal epiblastic upgrowths on each side of the middle line, 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 com- pleted the neural groove is converted into a closed tube, the neural Fm. 568. — Diagram of a transverse section through a mammalian blastoderm after the formation of the three jjriniary layers. 1, Primitive groove ; '2, primitive streak ; 8, epiblast; 4, mesoblast; 5, hypoblast; 6, cculom ; 7, archenteron. Via. 569. — Diagram of a transverse section through a mammalian blastoderm, show- ing the neural ridges. 1, Neural groove ; •J, neural ridge ; 8, epiblast ; 4, somatic mesoblast ; 5, splanchnic mesoblast ; 6, hypoblast ; 7, somatopleur ; 8, splanch- nopleur ; 9, notochord ; 10, coelom ; 11, archenteron. canal, which is the central canal of the nervous system. In the embryo at this period there are, therefore, three cavities : (1) The neural canal lined by epiblast ; (2) The coelom or space in the meso- blast; (3) The archenteron within the hypoblast. While these changes are in progress the embryonic area begins to fold off from the rest of the embryo. A sulcus appears all round the margins of the area, and over this sulcus the area bends forwards, backwards. CH. LIX.] EARLY FCETAL STRUCTURES 885 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 this way, the embryo is clearly separated into two parts, an upper, the fcetus, and a lower, which becomes the appendages of the foetus.* 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. The portion of the archenteron en- closed in the foetus forms the primitive gut. The part contained in the head fold is the fore-gut, that in the tail fold is the hind-gut, and the remainder is the mid- gut (fig. 572). _ The constriction where the body of the foetus becomes continuous with the re- maining structures, is known ultimately as the umbilicus. It remains pervious till birth, 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. 571, The portion of the mesoblastic cavity enclosed in the foetus is called the body cavity. It gradually differentiates into the pericardial, pleural and peritoneal cavities, which are eventually entirely separated from one another. 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. 569). This ridge is the notochord or Fio. 570.— Embryo chick (36 hours), viewed from beneath as a trans- parent object (magnified), pi, Out- line of pellucid area ; Fjy, 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 ba, the bulbus arte- riosus ; , primitive blood- vessel of embryo ; (J, amnion cavity (outer surface of amnion is fused with inner surface of chorion) ; 7, um- bilical cord ; 8, fuital villus in placenta. Cir. LIX.] TflK FfETAL CIRCULATION 891 occur in muscles, glands, tendons, and especially in serous membranes. On account of their affinity for pyrrliol-bluc they were originally termed pyrrhol cells, and it seems probable that they originate in the bone marrow. By means of such intra-vitam stains one can further differentiate the Kupffer-cell of the liver, the reticulum cell of lymph glands and spleen, the interotitial cell of the testis, the follicular cell in the maturing follicles of the ovary, the cortical cell of the suprarenal, the epithelial covering of the choroid plexuses, and the cells which line the convoluted tubules of the kidney. When pregnancy occurs in the stained animal, the appearance and behaviour of the placenta are most striking; the blue colour disappears from the skin and is concentrated in the uterus, and in time the latter, forming a centre of attraction for the dye, ultimately dispossesses all the remaining tissues of their blue. In the uterus it is the free cells of the decidua basalis where the stain is mainly found. In quite early stages the stained cells penetrate into the primitive placenta and cast off their stained granules, which are snatched up by fcetal cells in the way nutritive material is. But when once the placenta has attained maturity, the dye is found only in the fcetal cells which form the layer which separates the maternal and fcetal tissues. The foetus itself remains per- fectly colourless, the stain not being able to penetrate this protective barrier. Further research has shown another important point, for the same cells which vigorously absorb the vital stain store also glycogen, fat, and haemoglobin temporarily before these suljstances pass into the foetal circulation. The avidity of such cells for the dye is thus connected with their functional activity in relation to really nutritive material; the importance of vital staining in embryological research is therefore apparent. Equally important are its applications to pathological research, but into this aspect of the question it will be beyond our purpose to pass. The Fcetal Circulation We shall not enter into the complex manner in which the heart and blood-vessels of the foetus develop from the embryonic rudiments ; but when these are fully formed the circulation of the blood is found to differ considerably from that which occurs after birth. It will be convenient to begin its description by tracing the course of the blood, which, after being carried to the placenta by the two umbihcal arteries, has returned, oxygenated and replenished, to the foetus by the umbilical vein. It is at first conveyed to the under surface of the liver, and there the stream is di\dded, — a part of the blood passing straight on to the 892 REPRODUCTION, DEVELOPMENT, GROWTH AND DEATH [CH. LIX. inferior vena cava, through a venous canal called the dudtcs venostcs, 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 L.Com Caroho/. t. $ubelat> Su/ur-ioT Vena Cat. ^..A-DuclAyt l,ii,er--f,-\ Ri^he Lobt '■'■\---Ty^Srir!: X»fenoi-Vena Cam. ,aU,.r\ Wm Fio. 677.- Diagram of tlie Fuital Circulatiou. from the placenta by the umbilical vein reaches the inferior vena cava at last, and is carried by it (together with the blood from the lower part of the body and lower limbs) 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 CH. UX.] PAETURITION 893 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 auric ulo-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 from there 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 imibilical vein to the under surface of the liver, from which the description started. Paktueition During pregnancy the uterus and its contents increase in size, and we have already alluded to the changes in its mucous membrane or decidua, and the formation of the placenta ; the principal factor in the distension of the uterus is the accumulation of the amniotic fluid. The muscular wall of the uterus also hypertrophies ; this is in part due to the formation of new muscular fibres, and in part of the increase in size of the pre-existing muscular fibres. The muscular wall is one of immense strength. The foetus " comes to term " in the human subject on the tenth menstrual epoch after conception; this averages about 280 days after the last menstruation. Delivery is the result of uterine contractions or " labour pains " ; the liquor amnii is thus forced downward and presses the membrane formed by the fused amnion and chorion through the cervix of the uterus which is gradually distended. When the distension is sufficient the membrane ruptures, and the amniotic fluid escapes. The os is then fully distended, and the foetal head enters the pelvis ; the pains become more frequent and energetic, and the voluntary muscles of the abdomen are brought into play, so that ultimately the new-born child is expelled to the 894 REPRODUCTION, DEVELOPMENT, GROWTH AND DEATH [CH. LIX. exterior. The process usually lasts some hours, but the time is much prolonged (ten, twenty, or even more hours) in the birth of a first child. The child is still connected with the placenta by the umbilical cord, which is about 20 inches long, and this connection should not 1)0 severed for a few minutes in order that as much lilood as possible may be aspirated from the foetal part of the placenta into the child as breathing commences. After the child is expelled, the contractions of the uterine walls recommence after a lapse of twenty to thirty minutes, and the placenta is separated and forced out. The separation extends through the decidua alon^ 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 umbiHcal cord is tied and separated, the umbilical arteries inside the child become filled with blood-clot, and ultimately they are converted into fibrous cords, tlie 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. The haemorrhage from the uterus which acconi})anies and follows the after-birth may be profuse at first, but under normal circum- stances is soon checked by the firm contraction of the uterine walls. Although it has been shown that dehvery may occur when all nerves connect- ing the uterus with the central nervous systena are cut through (see p. 721), the contractions of the organ are normally influenced reflexly through the nervous system. Stimulation of various sensory nerves will produce contractions of the pregnant uterus, and premature delivery may occur as the result of mental and physical disturbances. The determining factor which produces the labour pains at a particular date has been much discussed; some suppose it may be maternal in origin, such as a degenerative condition set up in the placmta or decidua, whereas otliers consider the initial impulse may come from the foetus, which secretes certain products that stimulate uterine contraction. After delivery, the uterus undergoes reduction in size at a fairly rapid rate. This has been attributed to fatty degeneration, but of this there is but little evidence. The theory at present most in vogue to explain "involution of the uterus" is that the process is one of autolysis due to tlie action of intracellular digestive en/ymes. Whilst it is occurring, the urine of the mother contains a good deal of creatine, a substance which is normally absent from that secretion. It has been supposed that this substance originates from the rapid destruction of the uterine mupcle. It has, however, been shown that creatine occurs after delivery even if the uterus is amputated, so that the muscular creatine cannot then be the source of the urinary CII. UK.] DEATH 895 (.•reatine ; there is some evidence that the creatine is associated in some way with the metabolism of the mammary gland. The atrophy or involution of the uterus which occurs at the menopause appears also to be produced in the same way, and it has been suggested, with some reason, that the symptoms exhibited at tliat period of life may be in part explained as due to the absorption of the products of the autolysis of the uterine tissue. Death We have now completed the task we set ourselves, and having arrived at the new-born child have reached the point in the life cycle from which we set out. The bearers and transmitters of the germ plasm, its hosts, the parents, pass away in due course, making room for their successors who live, repeat the process, and likewise die in their turn. It is not altogether inappropriate to conclude a book which deals with life, by a few sentences on Death, wliich forms the final chapter for each individual. As the prime of life is past, signs of old age begin to appear, the eyes become feeble, the hair becomes grey, the cartilages calcify, the muscles become weaker, digestion gets feebler, and metabolism in every way more and more imperfect. If this continues, life is ultimately terminated by natural death, in which the functions get weaker and weaker and finally cease. Death from old age is, however, comparatively rare ; the common cause of death is accident, in which term we include disease. In the activity of youth many a disease is vanquished, but as the powers of resistance duninish with increasing years, some ailment usually upsetting more particularly some important organ will ultimately find the body unable to repel its attack. "That ends this strange, eventful history." INDEX Abderhalden's feeding experiments, 545 Abdominal muscles, action in respiration, 357 Abdominal reflex, 711 Abducens nerve, 603, 674 centre, 674 Aberration, chromatic, 830 spherical, ib. Abiuretic products, 519 Abrin, 475 Absorption of carbohydrates, 544 fats, 546, 547 food, 543 et seq. proteins, 544 by the skin, 60S Acapnia, 402 Accelerator nerves, 144 urinse, 580 Accessory auditory nucleus, 676 Accommodation of eye, 820, 824 et seq. defects of, 828, 831 mechanism of, 825 Acetonsemia, 542 Acetyl, 415 Achromatic sjjindle, 16, 876 Achromatin, 10 Achromatopsia, 848 Achroo-dextrin, 412, 505 Acidemia, 542, 619 Acids in gastric juice, 511 Acid-albumin, 433 Acidosis, 542, 619 Acini of secreting glands, 496, 498 Acoustic tubercle, 676 Acrolein, 415 Acromegaly, 343 Acrylic series, 414 Adamantoblasts, 58, 59 Adamkiewicz reaction, 425, 429 Adam's apple, 800 Adaptation in sensations, 774 Addison's disease, 341, 342 Adenase, 594 Adenine, 432, 593 Adenoid or lymphoid tissue, 35 Adipose tissue, 28, 33-35. See Fat. cells, 34, 35 development, 33 situations of, ib. structure, ib. uses, 34 vessels and nerves, 34, 35 Adrenaline, 342 administration of, 541 effect of, on salivary gland, 503 897 Alimestarv Canal. Adsorption, 328 n. Aerobic, 438 j Aerotonometer, 303 J^sthesiometers, 772 Affective mode in consciousness, 758 tone, 763 Affenspalte, 736 Afferent fibres when entering the spinal cord, 703 Afferent nerves, 73, 144 et seq. projection system, 700 root-cells, 194 After-birth, 894 After-images, 844 After-sensations, 764 Agglutinin, 476 Agraphia, 809 Air, atmospheric, composition of, 392 breathing, 358 changes by breathing, 392 complemental, 359 quantity breathed, ib. reserve, ib. residual, ib. tidal, ib. transmission of sonorous vibrations through, 794 undulations of, conducted by external ear, 795 Air-calorimeters, 631, 633 Air-sacs, 351, 352 Air-tubes. See Bronchi. Airy's discovery of astigmatism, 829 Alanine, 417, 422 Albumin, 424, 427, 433, 601 absence of glycine from, 422 acid, 433 alkali, 433 character of, 515 egg, 433 of blood, 454 Albuminates, 433 Albuminoids, 428, 429 Albuminonieter, Esbach's, 601 Albuminous alveoli, 499 Albuminous substances. See Proteins. action of gastric fluid on, 519 Albumins, 424, 427 Alcapton, 602 Alcaptonuria, 602 Alcohol as an accessory to food, 490 Alcohols, monatomic, 408 Aldehyde, 407 Aldoses, 407 AUmentap/ canal, 492 et seq. glycosuria, 538 nerves of, 563 3 L 898 INDEX Al.KALI-ALHUMIN. Alkali-albumlii, -133 properties of, ili. AUantoin, b'.>2 AUantois, development of, SbG Allodiiria, 777 Alloxan, 5!>2 AUyl alcohol, 415 Alveolar air apparatus, 373-375 Alveoli, 4'J8-500 Amacriiie cells, 816 Amino-acids, 410, 433, 045, G03 Aniino-('ai)roic acid, 417 Amiiio-oxy[)yriiiii(liiu!, 421 Ammonia", 4'il, 5S8, 589 cyaiiate of, isomeric with urea, 583 Amnion, 886, 8SS, 890 Amniotic cavity, 888 fluid, 888, 890 Amoibai, 5, 11, SC7 Ama-boid movements, 11 ft si'.q., 80 calls, 5, 13 colourless corpuscles, 14, 455 cornea-cells, 813 protoplasm, 11 Tradescantia, 12, 13 Amyloids or starches, 412 action of pancreas and intestinal glands, 519 of saliva on, 513 Amylolytic enzymes, 440 Amylopsin, action of, 519 Anabolic nerve groups, 203 Anabolic phenomena, 612 Anacrotic pulse, 293 Anai lobic, 438 Anapliylaxis, 478 Anderson on the auto-nenetic theory, 150, 151 Anelectrotonus, 171, 173 Angina pectoris, 312 Angio-neuroses, 311 Angular convolution, 693 Angulus opticus seu visorius, 823 Animal cell, structure of, 7 ft seq. Animal heat. See Heat and Temperature. Anions, 322 Ankle-clonus, 712 Annulus of Vieussens, 196, 251, 302 Anosniatic animals, 780 Antagonistic muscles, reciprocal action of, 714 Antero-lateral ascending tract, 658 Antero-latoral descending tract, 656 Antidromic, 303 Anti-enzymes, 443 Antilytic secretion, 503 Antithrombin, 448, 450, 451 Antitoxin, 474, 475 Anvil bone, 789 Aphasia, 733, 809 Apnrua, origin of, 379 Apoplexy, 089 A(iueduct of Hylvius, 614, 645, 663, 671 A(iueductus Fallopii, 790 A(iueou3 humour, 811 Arbor vitfe, 681 Archcnteron, 884 ct srij. Arohipallium, 646, 047, 698 Arcuate fibres, COS Area cheiro-lRo's Law. Avogailro's law, 32(), 39J Axipeial comluction, law of, 191 Axia-cylinder of nerve-libre, 74, 185 Axons. !Sc( Nurvo.s. B. Uabiiiski's sign, 711 Bacilli, types ol", 43S Bacterial action in intestinal digestion, 'jiiS Uacterio-lysin, 473, 475 13acterinm lactis, 414 Baicroft's tonometer, 306 Barnard's cardiometer, 248 Basal ganglia, (587, 720 Basilar membrane of ear, 7'J2, 793 BasopliUe cells, 457 Batteries and keys, S7 ct $eq. Danlell cell, 87, 88 Bausteine, 545, (527 Bayliss, mammalian heart, 245 observations on vaso-dilator nerves of dogs, 303 on adsorption, 328 n. on pancreatic secretion, 520 Bechterew, nucleus of, 677 Beckmann's differential thermometer, 326 Beef-tea, the making of, 489 Beer's experiments on accommodation of the eye, 827 Bellini's ducts, 567, 568 Bell's experiments on spinal nerve roots, 156 Bence-Jones' protein, 601 Beri-beri, 491 Bernard's discovery in the liver, 331, 536-539 experiment on independent muscular irrita- bUity, 83 on pancreatic secretion, 523 Bert's experiments on crossing of nerves, 161 Bethe's autogenetic theory, 150 Betz cells, 697 Bezold's ganglion, 255 Bicuspid valve, 213 Bidder's ganglion, 255 Biedermann's fluid, 83 n. Bilaminar blastoderm, 8S3 Bile, 525, 527, 531 tt seq., 602 absorption by lymph, 536 analyses of human, 532 canaliculi, 530 capillaries, ib. characters of, 531 constituents of, 532 digestive properties, 525 doubtful antiseptic power, 533 expelling mechanism, 535 human, analyses of, 532 influence of, on fat absorption, o-l8 mixture with chyme, 534 mucia, 532 pigments, 533 process of secretion, 531 quantity secreted, ib. salts, 532 secretion and flow, 531 , 532 specific gravity, 532 uses, 533 BUlrubln, 465, 533 BUiverdln, 533 Bimolecular reactions, 329 Binocular colour-mixture, 846 Binocular vision, 856, 857 Biot's respiration, 405 Bipolar nerve-ceUs, 155, 182 et seq., 786 Bl.OOD-CORPUSCLES, RKD. Birth, changes after, 894 Biuret reaction, 425 "Black-wator fever," 603 Bladder, epithelium of, 22 Bladder, urinary. Sec Urinary bladder. Blastocyst, blastoderm, blastula, bilaminar, 883 et seq. Blastosphere, 881 " Blaze current," 849 Blind spot, 834, 849 Blocking, 257 Blood, 28, 29, 60, 61, 444 et seq. agglutinatint; action of, 476 amino-acids in, 545 arterial and venous, dill'erence between, 215, 371 bactericidal power of, 473 bufl'y coat, 447 carbonic acid in, 371, 375 circulation of, 227 et seq. in the fcetus, 891 local peculiarities, 312 schema of, 229 coagulation, 61, 137, 446 et seq. colour, 61, 444 colouring matter, 444 relation to that of bUe, 465 corpuscles or cells of, 6, 7, 00, 444. See Blood- corpuscles, red, 454 white or colourless, 456 crystals, 462 et seq. extractive matters, 454 fatty matters, 454 fibrin, 61, 137, 447 separation of, 448 flow, velocity of, 281 gases of, 361 et seq., 396 et seq. globulicidal power of, 473 haemoglobin. See Ilajmoglobin. lymph, relation to, 321 nitrogen in, 362, 363, 371 odour or halitus of, 444 oxalated, 450 oxygen in, 362, 305, 372 oxyhaemoglobin. See Oxyhccmoglobin. photographic spectrum of, 402, 463 plasma, 371, 444, 452 proteins of, 452 quantity, 444 Haldane's and Lorratn Smith's experiments, 445 reaction, 444, 455 salts, 454 serum of, 446, 452 specific gravity, 444 splenic, 334, 335 structural composition, 454 taste, 444 temperature, ib. tests for, 472 transfusion of, 319 in the urine, 603 venous, 01 Blood-corpuscles, red, 61, 297, 454 action of reagents on. 455 et seq chemistry of, 461 composition of, 461 development of, 459 et srq. disintegration and removal, 334 emigration of, 298 formation in the spleen, 460 methods of counting, 458 origin of, 459 rouleaux, 464 specific gravity, 457 900 INDEX Blood-corpuscles, Red. Ulooii-corpuscles, red — continued stroma, 45t teiiu(i(Z stimulation, 750, 7&6 structure, CSO Cerebral cortex, ISO, 044, 096, 697, 725 grey uuitter of, 0S7 histolo^'ical structure, 695 et seq. liyrainiilal cells, 095 Cerebral hemispheres. See Cerebrum. Cerebral nerves, orifjin of, 663 ct seq. See under names of nerves. Cerebral vesicles, primary, 045 Cerebro-spinal axis, 181 Cerebro-spinal fluid, 108, 644 Cerebro-sjilnal nervous system, ISl See lirain, Spinal cord, etc. Cercbrote, 437 Cerebrum, 680 et seq. convolutions of, 690 et seq. crura of, 644 defeneration tracts after injury of Rolandic ' area, 728 effects of in.jury, ih. removal, 721 external capsule, 689 extirpation, 727, 72s functions of, 721 et seq. early notions, 721 ^rey matter, 687, 090 hemispheres, 6S6, 691-093, 704, 731, 733, 730, 741, 742 internal capsule, 088, 689 localisation of functions, 726 motor areas, ib. relation to speech, 808 sensory areas, 728 extirpation, ib. stimulation, 727 structure, OSO et seq. white matter, 698 Ceruminous glands of ear, 60S Cervix of urinary bladder, 570 Chambers of the eye, 819 Chauveau's dromograph, 287 Chauveau's apparatus for intracardiac pressure, 241 Cheiro-klnaesthetic area, 742 Chemical composition of the human body, 406 et seq. Chest, expansion In inspiration, 354 vertical diameter of, ib. vital capacity of, 359 Chest-voice, 800 " Chewing the cud," 550 Chejme-Stokes' respiration, 404, 405 Child, new-born, and changes after birth, 802 et seq. Chimpanzee's brain, 731 Chittenden dift, 480, 481, 023 important character uf his work, 623 Chlorides in urine, 595 Chloroform, action on cardiac mechanism, 253 Cholagogues, 535 Cholallc acid, 533 Cholesterln or cholesterol, 9, 75, 166, 435, 430, 534 Choline, 166 Chondrln, 38, 429 Chorda secretion, 502 Chorda tympanl, 602, 504 Chordae tendineae. See Heart. Chorion, 887 ct seq. Chorionic epiblast, 883, 884 Chorionic villi, 888, 889 Choroid coat of eye, 811 Choroid gland, 108 Chromatic aberration, 830 Cohniieim's Experimknt. Chromatin, 10 Chromatolysis, 193 Chromatoplasm, 192 Chromogen, 341 Chromophanes, 847 Cliroiiiujihilic material, 192 ChromoiJlasm, 10, 11 Chronio-proleins, 427, 430 Chromosomes, 16 el sc'i, 870 Chrzonszezewski's meiliod of natural injection, 529 Chyle, 220, 316, 547 molecular basis of, 310 Chyme, 554 Cilia, 23, 24 Ciliary epithelium, 24 function of, ib. Ciliary motion, 25, 82 nature of, 25 Ciliary muscles, 812, 813 action of, in adaptation to distances, 825 Ciliary processes, 812, 813 Cilio-spinal centre, 721 Circular layer of heart, 212 "Circulating protein," 622 Circulation of blood, 00, 227 ct seq action of heart, 213 in bloo(l-\essels, 203 et seq. in brain, 312 capillaries, 297 course of, 214 et seq. ellect of gravity on, 279 etlVct of respiration on, 385 erectile structures, 313 in foetus, 891, 892 influence of respiration on, 385 of gravity, 279 peculiarities of, in different parts, 312 portal, 215 pulmonary, ib. renal, ib. systemic, 3 in veins, 61 velocity of, 281 Circulatory system, 208 et seq. Circumvallate papillae of the tongue, 779 Clarke's column, 050, 061 Clasmatocyti's, 31 Claustrum, OSS Cleavage products, 18, 410, 417 Clerk-Maxwell's experiment, 841 Clitoris, 313 Clot or coagulum of blood. See Coagulation. Clupeine, 427 Coagulation of blood, 60, 137, 446 et seq. conditions affecting, 447 theories of, 448 of milk, 482 Coagulative enzymes, 420, 439 Cocaine, 490 Coccygeal gland, 345 Cochlea of the ear, 753, 791 et seq. theories in connection with, 767, 768 Cochlear division of auditory nerve, diagram of, 676 Cochlear nerve, 003 Coeflicient of oxidation, 395, 397, 898 Coelom, 884 Co-enzymes, 441 Cognitive mode in consciousness, 758 Cohnheim, areas of, 06 Cohniieim's experiment on passage of blood- corpuscles, 298 on diabetes, 640 on erei)sin, 525 with succus entericus, 524 INDEX 903 Coitus. Coitus, 881 Collagen, 29, 40, 429 CoUiiloral tissure, (394 Colloidal solution, 828, 423 n. Colloids, 323, 424 Colon, the, 601 Colostrum, 4St'i corpuscles, ih. Colour-blindness, 843 testing' for, S44 Colour-perception, 841 Colour reactions of proteins, 425 Colour sensations, 841 Hurch's experiments, 844 theories of, 842 Colours, optical phenomena, 841 et seq. Coluiuua' carncic, 211 Columnar epithelium, 21, 22, 529 Coma, diabetic, 405 Combination-tones, 797 Comma tract, 054, 056 Commissural fibres, 648, 60S nucleus, 679 Common path, principle of, 717 Common sensations, 775 Complement, the, 475 Complemental air, 359 Complementary colours, 842 Compound tubular glands, 490, 497 racemose glands, 497 Conative modes in consciousness, 758 Concha, 788 Condiments as accessories to food, 490 Conducting paths in cord, 704 et seq. Conduction, law of axipetal, 191 Conductivity, 172 Cones and rods, 817 movement of, 847 Conical and filiform papilloe of tongue, 780 Conl vasculosi, 864, 865 Conjugate deviation of head and eyes, 737 Conjugated proteins, 430 Conjunctiva, 810 Conjunctival reflex, 711 Connective tissues, 28 et seq. classification, ib. corpuscles, 30 elastic, 32 fibrous, ib. general structure of, 28 jelly-like, 86 retiform, 35 varieties, 30, 31 Conscious states, physiology of, 757 et srr/. Conservation of energy, law of, 630 Consonants, SOS Contractile substance, 63 Contractility of muscle, 81 et seq. Contraction, heat, 165 Contraction of heart, 128, 282 Contraction of pupil, 827 Contraction, Pfluger's law of, 174, 175 Contrast of colour, 845 Conus medullaris, 648 Convergence of eyes, 827 Convoluted tubes, 864 Convolutions, cerebral, 690 et seq. Cooking, efifect of, 489 Coordination of muscular movements, 107 Copper sulphate, or Piotrowski's test, 425 Copulation, S81 Cord, spinal. See Spinal cord. Cornea, 811, 813 corpuscles, 812 Comeo-scleral junction, 813, 814 CvsTic Duct. Coronary arteries, 237 Corona radiata, 689 Corpora cavernosa, 313, 866 ([uadrigemina, 663, 673, 681 Corpus Arautii, 214 callosum, 080 dentatum of cerebellum, 681 of olivary body, ib. Ilighmorianum, 803 luteum, 870, 880 of human female, ib. spongiosum, 313, 866 striatum, 687 Corpuscles of blood, 444. See Blood-corpuscles Corpuscles, Malpighian, 334 Corpuscles, of Grandry, 768, 769 of Uassall, 330, 337 of Herbst, 766 of Meissner, 767, 774, 775 of Pacini, 700, 707 Cortex, 181, 342, 044, 6S2, 695 Corti on rotation of cell sap, 13 Corti, organ of, 793 Cortical retina, 736 Cortico-pontine fibres, 070, 700 Cortico-spinal fibres, 670, 700 Corti 'b rods, 793 Cotyledons, 889 Coughing, mechanism of, 3S1 Cowper's glands. 570 Cranial nerves, 004 ct seq. nuclei of, 664, 005, 067, 670 origin and functions of, 073 et seq. Creatine, 166, 420, 589-591, 894 Creatinine, 590 Cremasteric reflex, 711 Crescents of Gianuzzi, 499 Cretinism, cause of, 338 Crico-arytenoid muscles, 800-803 Cricoid cartilage, 799 Crico-thyrold muscle, 800 Crista acoustica, 753 Crossed hemiplegia, 729 Crossed pyramidal tract, 655 Crosses of Ranvier, 75 Crowbar accident, 738 Crucial sulcus, 730 Crura cerebelll, 664 cerebri, 644, 673, 689 grey matter of, 645 Crusta, 673 petrosa, 56, 59 Crypts of Lieberkuhn, 493 Crystallin, 814 Crystalline lens, 811, 813 Cry stall Isable proteins, 424 Crystalloids, 424 Cubical epithelium, 21 Cuneus or cuneate lobule, 694 Cuorin, 435 Cupula, 753 Curative inoculation, 473 Curdling ferments, 482 Currents of action, 121 constant, 88 demarcation, 123 Induced, 89 of rest, 121 Cutaneous sensations, 706 et seq. varieties of, 772 Cuticle. See Epidermis, Epithelium. Cutis vera, 604 Cybulski's haematacbometer, 280 Cyclopterine, 427 Cystic duct, 527 904 INDEX CVSTIKB IN UnrNK. CysttDC in urine, 598 Cystine, 421, 422, 599 Cytosiiie, 421 D. Dalton-Henry law on gases iu the blooJ, 302 Daniell's battery, 88 Dark-adaptation of eye, 848 Darwin, 858 Deaf-mutes and equilibrium, 756 Deaniidases, 440 Di-amidation, 546 Death, 895 Decidua, 887 basalts, or serotina, S87-8S9 capsularls or retlexa, 887 development of, 888 menstrualis, 873, 874 reflexa, or capsularis, SS7-889 vera, 887, 888 Decussation of fibres in medulla oblonirata, C68, 669 of optic nerves, 853 Deep sensibility, 774 DefiEcation, mechanism of, 562, 721 centre, 721 influence of spinal cord on, 563 Deficiency diseases, 491 Degeneration method, 148, 156, 178, 307 tracts of descending, 655 ascending, 657 Deglutition. See Swallowing. Deiters, ceUs of, 794 nucleus, 670, 671, 677 Delezenne on trypsinogen, 524 Demarcation current, 123 Demilunes of Gianuzzi, 499 Demoor's sleep theory, 746 Dental germ, 56 papilla, 56, 58 periosteum, 59 Dentate fissure, 694 Dentate nucleus, 669 Dentine, 28, 54 formation of, 57 structure, 54 Depressor nerve, 249, 305 Dermis, 604 Descemet's membrane, 812, 813 Descending tubule of lienle, 567 Development, 858 ct seq adipose tissue, 34 blood-corpuscles, 459 blood-vessels, 459 bone, 40 et scq. cartilage, 39 decidua, 887 embryo, diagrams of, 885, 887, 8SS fertilisation, 881 fietal circulation, 891 foetal membranes, 887 impregnation, SSI nerve-fibres, 83 ovary, 879 ovum, 875 segmentation, 883 teeth, 58 Dextrin, 409, 412 Dextrose, 407, 409, 411, 439, 440 in urine, 601 tests for determining, 409, 410, 601, 602 Diabetes, 409, 538, 539, 542, 77S artificial production in animals, 538, 539 Diabetic coma, 405 Diabetic puncture, 538 Kar. Dialyser, a, 424 Dialysis, 324, 453 Diamino-aciils, 421 Diainmo-dipliospliatides, 435 Diamino-monopliospliatidi's, ;/). Diapedesis of blood-corpuscles, 298 Diaphragm. See Inspiration, etc. Diastase of liver, 537 Diastole of heart, 238 Diastolic pressure, 296 Diastolic sound, 236 Dicrotic pulse, 294 Diet, 613 et seq. a healthy, 480 Chittenden's, 480, 481 nutritive value, 479 ct seq. Ranke's, 480 tables, 480, 482, 613 et seq. Voit's, 480 Difference-tones, 797 Diffusion and osmosis distinguished, 323 Digestion, in the intestines, 517 et seq. mechanical processes, 550 et seq. See Gastric fluid, Food, Stomach Dilator pvpillip, 812 Dilemma, 720 Dipeptides, 423 Diphasic variation, 123, 124 Diphtheria toxin, 474 Diplococci, 439 Diplopia, 850 Direct cerebellar tract, 658 pyramidal tract, ib. Disaccharides, 409 Discus proligerus, 809 Disease, " germ theory " of, 438 Distributing nerve-cells, 194, 195 Disuse atrophy, 148, 194 Diuretics, 576 Dixon on spermine, 878 Dobie's line, 65 Dog, " scratch " reflex of, 719 Dog's brain, 729 nerves, 162, 303 spleen, 335 submaxillary gland, 499 Dorsal cord, 165 Double vision, 850 " Drainage " theory, M'Dougall's, 716, 717 Dromograph, Chaiiveau's, 287 Drugs, action of, 775 on the eye, 833 on the heart, 253 on perspiration, 611 Ductless glands, 331 ct seq. theories of secretion, 331 Ducts of BeUmi, 566, 567 Ductus arteriosus, 893 closure of, 894 venosus, 892 closure of, 894 Dudgeon's sphygmograph, 292 Duprd's urea apparatus, 585 Dynamometer, 114 Dyne, 267 Dyspnoea, 389 E. Ear, 788 et scq. bones or ossicles of, function of, 796 development, 78 external, 788 function of,* ^95 INDEX 905 Eak. EiT—continuid Intenial or labyrintb, 790, 791 function of, 796 middle, 7SS function of, 795 Ectopia vesica', 580 E lriiige-Gr,en lantern, S44 Elterent channels, diagram of, 701 Eil'erent nerves, 73, 143 ner\'e-cells, 194 projection system, 69S Et;gs as food, 4S6 EhrlicU's side-chain theory, 475 Einthoveu's string galvanometer, 121, '245 nervous factor in respiration, 376, 377 third heart sound, 246 Elastic cartilage, 37, 39 fibres, 87 tissue, 32 Elastin, 30, 429 Electrical currents of retina, S49 nerves, 144 phenomena of muscle, 116 et seq., 170 variation m central nervous system, 743 in glands, 497 Electricity, in muscle, 116 et seq., 176 nerve, 170 Electrocardiogram, 243 et seq. Electrodes, non-polarisable, 118, 119 Electrometer, Lippmann's capillary, 120, 121, 124 record, 124-126 Electrotonus, 169 et seq. Eleidin, 604 Elementary substances in the human body, 406 Embryo, 858 et seq., SS5 n. See Development. Embryo chick, diagram of, 885 Embryological method, 651 Embryonic area, 883 Emetics, 557 Eminentia teres, 663 Emmetropic eye, S2S Emulsitication, 416, 520 Enamel of teeth, 55 formation of, 5S Enamel organ, ib. Enchylema, 7 End-bulbs, 767 Endocardium, 209 Endogenous fibres, 740 Endogenous protein metabolism, 022 End-plates, motorial, 70, 78 Endolymph, 753, 793 Endoneurium, SO, 81 Endothelial colls, 226, 321 layer, 218 membrane, 222 Endothelium, 21, 208, 222 Energy, law of conservation of, 030 et seq. Enterokinase, 523, 524 Enzyme action, coagulation, 420 inexhaustibility of, 441 law of, 441 optimum temperature of, 441 reversibility of, 442 specihcity of, 441 Enzymes, 426, 43S et seq., 448 activation of, 441 catalytic action of, 442 inexhaustibility of, 441 Eosinophile cells, 457 Epiblast, 19, 883 et seq. organs formed from, 886 Epicardium, 208 EVEIIALL. Epicritic sensibility, 707, 774, 777 Epidermis, 22, 604,886 Epididymis, 864, 865 Epigastric reflex, 711 Epiglottis, 551, 800, 801 Epineurium, 76, 77 Epithelium, 20 ctscq., 570, 604, 886, 887 cells of, 784 chemistry of, 27 ciliated, 21, 23, 24, 81, 348 columnar, 21, 22, 23 compound, 21 cubical, ib. goblet-shaped, 21, 22 nutrition of, 26 pavement, 21 renal, 574 simple, 21 spheroidal, 23 stratified, 22, 23, 26 transitional, 21, 22 Erectile structures, circulation in, 313 tissue of penis, 865 Erection, 313, 314, 721 cause of, 314 influence of muscular tissue in, 314 Erepsin, 440, 524 Erg, 267 Ergograph, Mosso's, 132 Ergotoxin, eflect of on salivary glands, 503 Erythroblasts,41, 460 Erythro-dextrin, 412, 505 Esbach's albuminometer, 001 Euglobulins, 600 Eustachian tube, 078, 789, 790, 795 function of, 795 valve, 209, 893 Ewald's induction coil, 92 Ewald, " sound picture " theories of, 798 Excitability of nerves, 172 of tissues, 81 Exhaustion in asphyxia, 389 Exogenous fibres, 741 Exogenous protein metabolism, 622 Exostosis, 60 Expiration, 355 et seq. force of expiratory act, 360 influence on circulation, 355, 360 mechanism of, 355 muscles concerned in, 356 relative duration of, 357 External auditory meatus, 789 External capsule, 689 External respiration, 392 Extractives, 166, 453 Extraventricular nucleus, 088 Eye, 810 et seq. accommodation, 820, 824, 827, 831 action of drugs on pupil, 833 adaptation of vision at different distances, 824 et seq. blood-vessels, 820 causes of dilatation and contraction of pupil, 834 chambers of, 820 focus, 820, 821 optical apparatus of, 820, 821 defects m, 828 principal point, 821 refractive media of, 820 resemblance to camera, ib. Eyeball, 811 blood-vessels of, 820 electrical currents of, 845 muscles influencing movement, 849 point of rotation, 850 906 INDEX Eyeball. Eyeball— co«(/«i(fd transverse and visual axis, 851 various positions of, 850 Eyeliiis, development of, 810 Eyes, simultaneous action In vision, S50 Facial nerve, 668, 675 efl'ects of paralysis of, 675 origin, ib. relation of, to expression, ib. F;eces, composition of, 548 quantity passed, 549 Fallopian tubes, i;4, 25, S71 False vocal cords, 801, 805 Falsetto voice, 806 Farailisatlon, 101, 104 Far-point, 828 Fat. See Adipose tissue. action of bile on, 535 of pancreatic secretion, 523 metabolism of, 541, 610 situations, where found, 33, 34 synthesis, 542 uses of, 34 Fatigue, 744 in nerves, 132 Fats, absorption of, 546 acids of, 414 action of pancreatic juice on, 520 chemical constitution, 414 decomposition products, 415 emulsiticatlon, 416 metabolism of, 616 of milk, 483 saponification, 415 Fatty acids, 414 Fehling's solution, 601, 602 Female generative organs, 867 pronucleus, 876 Fenestrated membrane of Henle, 217 Fenestra ovalls, 788, 791 rotunda, 788, 791 action of, 797 Fermentation , 438 Ferments, 440. See also Enzymes Blood, Milk, Digestive juices. Fertilisation, 881 Fibres of MUller, 815, 816 of R«mak, 77 of Sharpey, 44 Fibrils of muscle, 65 of nerve, 74 Fibrin, 60, 61, 446 ferment, 440, 449, 453 formation, 447, 451 reticulum of, 447 Fibrinogen, 60, 315, 448, 451, 453 Fibroblasts, 80 Fibro-cartilage, 37 classification, ih. development, 39 white, 37, 38, 40 yellow, 37, 39, 40, 41 Fibrous tissue, 28 et seq. white, 29 yellow, SO Fick on work of muscles, 115 Pick's spring kymograph, 275, 276 Fifth cranial nerve, 663, 674 Filiform pajjillse of tongue, 779 et seq. Fillet, 668, 672 Filtration, 319, 320, 324 FUum terminale, 648 Galactosides. Fischer's laboratory, the work in. 410, 421 theory of drojisy, 821 Fishes, circulatory system In, 230 Fistula, intestinal, 523 Flechsig's oinbryologiral method, 740 I'"leischl'8 hamoglobinonieter, 471 Fleming's chromatin, 10 Flesh of animals, 479 Flicker, 836, 854 Flour as food, 488 Flourens' experiment, 749 Fluids, swallowing, 552 Fluids, tension of gases in, 362 et seq. Fluoride of calcium, 40 Focal distance, 824 Foetal circulation, 891-893 Ftetal membranes, 887 development of, ib. Fcetus, 885 m., 886, 893 circulation in, 891 communication with mother, 890 Folin's method of estimating urea, 585 Follicles, Graafian. See Graafian follicles. Follicles, Meibomian, 496, 810 Fontana, spaces of, 814 Food, 479 et seq. absorption of, 543 et seq. accessories to, 490 chemical compounds of, 479 constituents, unknown but essential, 491 cooking, 489 digestibility of articles of, 479 value dependent on, ib. fluidity of, 555 heat- value of, 635 of man, 479 proximate principles in, ih. vegetable, ib., 489 Foramen ovale, 893 of Magendie, 64 4 of Mnnro, 688 Fore-gut, 886 Formaldehyde, 425 Formatio reticularis, 667 Formic acid, 414 Fornix, 688 Fossa ovalls, 209 Fovea centralis, 814, 818, 841 Fovea hemielliptica et hemispherica, 791 Franck's cannula, 273 Frogs, circulatory system in, 230, 281 corpuscles of, 454 gracilis of, 160 heart, 230, 231, '251, 259 mucous membrane, 547 nen'es, 251 reflexes in, 709 Fromann's lines, 75 Frontal lobe, 690, 692 Fundus glands, 508 Fundus of eye, 836 of urinary bladder, 570 Fungiform pai)illae of the tongue, 779, 780 Funiculus cuneatus, 662, 665 Funiculus ^acilis, 662, 665 Funiculus solitarius, 670, 678 Furfuraldehyde, 538 Furth, on muscle proteins, 138, 139 Fuscin granules, 847 Galactose, 410 Galactosides, 166, 437 INDEX 907 GALL-llLADfiKR. Gall-bladder, 532 structure, I';. Galvanism, 122 Galvanometer, 117 f/ seg., 24.'> the string, 121, 245 Gameti's, 859 Gamgee, photographic spectrum of haemoglobin and its derivatives, 408, 409 Ganglia, ISO, 190 et sfy. See Nerve-centres. sympathetic, functions of, 500, 502 Ganglion cells, layer of, 815 Ganglion of Scarpa, 677 Ganglion spirale, 794 trunci vagi, 249 Gases, extraction from blood, 364 of the blood, 301 ct W7. in the lungs, 372 of plasma and serum, 453 tension, 302 Gaskell's heart- block, 257 Gastric fistula, 507 Gastric glands, 493 Gastric .juice, 507 et seq. acids in, 510 test for, 510, 516 action on bacteria, 525 action on food, 513 artificial, 507 composition of, 510, 511 pepsin of, 511 secretion of, 509 Gastrin, 522 Gay-Lussac's law for gases, 325 Gehuchten, van, law of axipetal conduction, 191 Gelatin, 29, 40, 54, 429 Generative organs of the female, 807 of the male, 803 Gennari, line of, 097, 736, 737 Genu of internal capsule, 690 Gerlach's network, 050 Germ plasm, Weismanns', 801 Germ theory, 438 Germinal area, 883 epithelium, 868, 871 spot, 18, 19, 871 vesicle, ib. Giant cells, 41 Giaiiuzzi's crescents or demilunes, 499 Gibson, third heart sound, 240 Gilbert's experiments, 748 Gland cells, function of, 496 Glands. See names of different. Gliadin, 434 Glisson's capsule, 528 Globln, 427, 403 Globulins, 138, 165, 424, 427, 483, 600 character of, 515 distinctions from albumin, 428 Glomeruli, 567, 569, 573 olfactory, 786 Glosso-kinaesthetic area, 741 Glosso-pharyngeal nerve, 663, 678 communications of, 678 functions, ib. motor filaments, ib. a nerve of common sensation and of taste, ib. Glottis, movements of, 551, 805 Gluco-proteins, 427, 430 Glucosamine, 430 Glucose. .Si c Dextrose. In liver, 537 test for, 412 Glutamic acid, 422 Gluteal reflex, 711 Glutelins, 433 n.EMODVNAMOMKTKR. Gluten, 488 Glutenin, ib. Glycerides, 414 Glycerin or Glycerol, 415 origin of, 619 Glycine, 417, 422 Glycocholic acid, 533 Glycogen, 8, 407, 412, 413, 537, 53.S characters, 412 destination of, 537 preparation, ib. quantity formed, ib. source of, 530 variation with diet, 537 Glycogenolytic nerves, 541 Glycolysis, 540 Glycosuria, 538, 540 Glycuronlc acid and sugar, 540 Gmelln's test, 533, 002 Goblet ceUs, 21, 22 Goldman's intra-vitam staining, 890 Golgi's method, 180, 097, 746 Goll's column, 651, 054, 057, 600, 662 Goltz, experiments on the cerebrum, V25 "Goose skin," 607 Gotch, experiments on heart, 248 on nerves, 159, 176 Gowers' haemoglobinometer, 470, 471 tract, 657 Gowers-Haldane haemoglobinometer, 470 Graafian follicles, 800 et seq. formation and development of, ib. et seq. relation of ovum to, 870 rupture of, changes following, 870 et seq. Gradient, pressure, 285, 386 Gramme-molecular solutions, 323 Grandry, corpuscles of, 708, 709 Granular layers of retina, 816 Grape-sugar. See Dextrose. Graphic method, 87 Gravity, influence of, on circulation, 279 Grey matter of cerebellum, 180, 644, 680 of cerebrum, 181, 186, 088 of crura cerebri, 045 of medulla oblongata, 180, 067, 668 of spinal cord, 181, 650 Grossmann, on the course of the inhibitory fibres in mammals, 249, 252 Ground substance of connective tissue, 31 Growth of bone, 50 Guanase, 594 Guanine, 432 Guanylic acid, ib. Gullet. See CEsophagus. Gustatory cells, 781 Gyrus fornicatus, 694 H. Haemacytometers, 458 Haemadromometer, Volkmann's, 282 Haematachometer, Cybulski's, 286 Vlerordt's, 287 Hsematin, 463 Haematoblasts, 334 Hiematogens of cells, 431 Hsematoidin, 404 Haematoporphyrin, 464, 582 Haematoscope, Herrmann's, 466 Haematoxylin, 10 Haemautograph, 295 Haemin, 463, 464 Haemochromogen, 403 Haemodromometer, 282 Haemodynamometer, 272 908 INDEX H.y.MOOLOBIN. Haemoglobin, 61, 370, 424, 454 analysis of, 461 and carbon monoxide, 403 compounds of, 405 crysialllsable, 424 crystals of, and how to obtain them, 402 dissociation curve of, 30", 370 distribution, 401 estimation of, 470 increase in the blood at high altitudes, 402 photographic spectrum of, 40S, 469 reaclion with oxygen, 307 solution of, 307, 308 Hsemoglobinometers, 470, 471 Haemoglobinuria, 003 Haemolymph glands, 336 Haemolysins, 475 Haemopyrrol, 4t".4 Hair-cells, 754, 794 Hair-follicles, 605, 606 Hairs, 605 structure of, ib. Haldane's apparatus for estimating the carbonic acid and aqueous vapour given off by an animal, 393 carbonic oxide method of estimating oxygen tension of arterial blood, 374, 375 Haldane and Priestley's method in dealing with respiration, 375 Haldane's measurement of air breathed, 358 Haldane's modification of Gowers' haemoglobin- ometer, 445 Hales' investigations on blood-pressure, 271 Hallucination, 764 Hamburger's experiments with Succus entericus, 523 Hammer bone, 788, 789 Hamulus, 792 Hannover's stratum intermedium, 58 Haptophor groups, 475 Hardy, microscopic structure of cells, 8 Harvey on circulation of the blood, 227, 234 Hassall, concentric corpuscles of, 330, 337 Hausmann's method of analysing proteins, 423 Haversian canals, 42, 43 lamella-. 44 Head's experiments, 378, 379, 705 Hearing, anatomy of organ of, 7S8 et seq. influence of external ear on, 794 of middle ear, ib. physiology of, ih. range of, 797 See Sound, Vibrations, etc. Heart, 208 et seq. action of, accelerated, 253 forc« of, 247 frequency, ib. inhibited, 253 isolated, 260 self-steering, 23S auricles of, 209-212 block. 240, 257 chambers, 209 capacity of, 212 chordae tendineie of, 213, 234, 230 columnae cameae of, 212 conduction In the, 254 course of blood in, 214 cycle, 232 endocardium, 209 excised mammalian, 201 force, 245 frog's, 230,231, 259 nerves of, 251 Hertz on thr Procf.!1s of Dioestioh. Heart — continued ganglia of, 255 gaseous exchanges during inhibition, 254 Influence of drugs, 253 of sympathetic nerve, 251 innervation, 249 intracardiac pressure, 240 Investing sac, 20s muscular fibres of, OS musculi papillares, 214, 234 nervous system, influence on, 249 output of, 247 pericardium, 208 physiology, 232 et seq plethysmograjih, 260 reflex Inhibition, 253 situation, 20S size and weight, 212 sounds of, 235, 245, 246 causes, 236 structure of, 212 valves, 210, 213 aurlculo- ventricular, 210-212, 234, 230 function of, 234 semilunar, 210, 212, 214, 235 function of, 235 structure, 209 et seq. ventricles, their action, 209-212 work of, 247 Heat, .inimal. See Temperature, influence of nervous system, 040 of various circumstances on, 637 losses by radiation, etc., 638-041 ■ regulation of, 640 value of foods, 634 variations of, 036 Heat and cold spots, 773 Heat coagulation, 423, 424, 426 Heat contraction, 164 Heat production, 637, 638, 640 Heat-rigor of muscle, 139 Heat- value of food, 634 Heidenhain's researches, 320, 578, 579 Held, experiments on myelination, 740 Helicine arteries, 866 Ilelicotrema, 792 Heller's nitric-acid test, 601 Helmholtz's induction coil. 91, 92 myograph, 87, 92, 104, 108 phakoscope, 825 resonance theory, 798 Helweg's bundle, 656, 657 Hemianopsia, 737 Hemiplegia, 729 Hemisection of spinal cord, 659 Hemispheres, cerebral. See Cerebrum. Henle, fenestrated membrane of, 219 layer of, 606 on muscles of the larynx, 803 sheath of, 77 tubule of, 567 Henry-Dalton law for gases. 326 Hensen's line or disc, 05, 07 Hepatic artery, 527 Hepatic cells, 527 colic, 535 duct, 527 glycogen, 615 veins, 527, 529 Herbst, corpuscles of, 766 Bering's experiments on blood circulation, 289 290 Hering's theory of colour, 842, 843 Herrmann's current of rest, 122, 128 hsmatoscope, 466 Hertz on the process of digestion, 555 INDEX 909 Hkuzkn on Succaoooues. Iler/.en on siiccagoj^ues, 513 Helorocyclic riiij;s, 421 Helerotype mitosis, 870 llexatoniic alcohols, 408 Hexone bases, 4li0 llexoseg, 408 Hill (Croft) on inverting; tinzynies, 443 Hill (Leonard) on the circulation of blood In th^ brain, 313 et seq. Hllus, the, 317, 318, 332, 565 Ilippocamiial convulutioii, 689 lli[ipocarai)U3 major, 694 Ui[)purlc acid, 594 Hirudin, 451 His, bundlo of, 257 Uis on ^,'rowtli of nerve-fibres, 14S Uistidine, 420 Histone, 427 llonioiotliermal animals, 636 Ilomotype mitosis, 87(3 Hope's experiments on heart sounds, 237 Hopkins' test for lactic acid, 510 for uric acid, 592 on foods, 491, 627 Hoppe-Seyler on proteins, 410 Hormone, 521, 880 Horopter, 852 llunjier, 778 Hurst, " sound-picture" theories of, 798 Hurthle's manometer, 242, 270 Huxley's layer, 600 Hyaline cartilage, 88, 40, 45 Hyaloplasm, 7, 14, 68, 83 Hydrobilirubin, 534 Hydro-kinetic force, 284 -static force, 284 Hydrolysis, 417, 514 Hypermetropia, 828 Hyperpnoea, 389 Hypertonic solutions, 327 Hypoblast, 19, 883 Hypogastric nerves, 581 Hypoglossal nerve, 664, 679 distribution, 679 origin, ib. Hypopituitarism, 345 Hypotonic solutions, 327 Hypoxanthine, 166, 421, 432 Hysteria, 808 I. Idiosome, 865 Hlusion, 765 Image, formation on retina, 824 Immunity, 472 ct scq. Impregnation of ovum, 881 Inanition or starvation, 628 Incoordination, 750, 756 Incus, or anvil-bone, 789 Indican, 596 Inditlusibility of proteins, 424 Indigo, ib. Induction coil, 89 et seq. current, 89 Infantile paralysis, 770 softness of head, 46 Infundibulum, 351 Inhibition, vagus, 253 Inhibitory nerves, 144 Inoculation, curative, 473 protective, ib. Inogen, 138 Inorganic compounds in body, 400 salts in nerve, 166 salts in protoplasm, 9 IsoMETBic Contraction. Inosito, 166, 413 Insalivatlon, 550 Inspiration, 354, 378 elastic resistance overcome by, ib, expansion of chest In, ib. extraordinary, ib. force cmiiloyed In, 251, 258 mechanism of, 354 ct scq. tracings of liiaphragm, 379 Instruments for demonstrating muscular action, 87 et sr:q. Intercellular material, 4, 29 jjassage, 351 Intercentral nerves, 145 Intercostal muscles, action in inspiration, 355 ct scq. action in expiration, 355 Intercrossing libres of Sharpey, 44, 45 Interglobular layer, 55 Interglobular spaces, 57 Interlobular arteries, 569 veins, ib. Intermediary nerve-cells, 194, 195 Intermediate areas, 742, 743 Interiuittent pulse, 290 Internal capsule, 088 Importance of, ib. respiration, 392 Internal ear, 7i)0 Internal secretion theory of the ductless glands, 331, 332 Interstitial cells, 44, 865 Intestinal fistula, diagram of, 523 Intestinal juice, 518 et scq. Intestines, 492, 557 et seq. digestion in, 517 ct scq. duration of, 563 large, 560 coats of, 493 glands, 494 structure, ib. view of, 561 movements, 560 mucous membrane of, 494 nervous mechanism. 558, 563 small, coats of, 493 glands, 493, 494 movements of, 557 structure, 493, 494 Intracardiac nerves, 252 pressure, 240 Intracellular enzyme.s, 440 Intraventricular nucleus, 688 lutra-vitani staining, 890 Inversion, 410, 522 Invertase, 522 Inverting enzymes, 440 Involuntary muscles, 62 (_sec 140 et seq.) structure of, 62 lodo-thyrin, 339 Ionic reactions, 328 Irla, 812, 813 angle of, 814 functions, 832 motor nerves, diagram of, 833 reilex actions, ib. Irradiation, 830 Irritability of tissues. 81 et seq. Island of Reil, 688, 692 Islands of Calleja, 675 Islets of Lanccerhans, 517, 539 Iso-cholesterin, 436 Isolated heart, 260 Iso-maltose, 411 Isometric contraction, 115 910 INDEX Isotonic Comtbaction. Isotonic contraction, 115 solutions, 326 Ivory, 54 J. Jacksouian epilepsy, 730 Jacobsen's nerve, 678 Jaundice, 535 Jecorin, 341 Jelly-like connective tissue, 2S, 30 Jugular ganglia, 249 Juice, gastric, 607 K. Kaiser's views on muscular contraction, 115 Karyuklnesis, 16 et seq. phases of, 17 KataboUc nerve groups, 203 Katabollc phenomena, 012 KatabDlism, 618, 619 Katelectrotonus, 171, 173 Rations , 322 Kennedy, experiment on nerve crossing, 101 Kent's bridge. 257 Kephalin, 166, 435, 438 Kerasin, 43S Keratin, 23, 27, 429, 436, 604 Ketone, 407 Ketoses, 408 Key, Du Bois Reymond's, 88 Kidney oncometer, the, 571 Kidneys, 561 et stq. blood-vessels of, how distributed, 569 calyces, 565 capillaries of, 568 diseases of, effect on the akin, 611 extirpation of, 579 function, 572. See Urine. hilus of, 565 Malpighlan corpuscles of , 566, 567 nerves, 571 oncometer, ib. pelvis of, 565 plan of, ib. structure, ih. tubules of, 566 et seq., 569 vascular supply of, 569 weight, 565 Kiii.-f-sthetif sense, 776 Kinetoplasm, 192 Kjeldahl's method of estimating nitrogen, 585, 586 Knee-jerk, 712 K'inig's apparatus for obtaining flame-pictures of musical notes, 807 Kossel on protamines, 428 Krause's membrane, 65, 67 Kro2h'3 tonometer, 363, 373 Kiihne's gracilis exjieriment, IGO muscle plasma experiment, 138 Kupller's stellate cells, 528 Kyes on lecithin, 477 Kymograph, Flck's spring, 275, 276 diagrams of mercurial, 272, 274 Lud wig's, 272, 273 tracings, 275, 277 Kymoscope, Anderson Stuart's, 271 Labyrinth of the ear. See Ear. Labyrinthine impressions, 752 Lacrimal gland, 810 Lact-albumtn, 482 LiVKR. Lacteals, 225, 316, 547 lactic aci'i, 160 fermentation, 411 tests for, M6 I..actiferous ducts, 485 Lactose, 407, 411, 483, 601 LacunuE, 43, 670 Laevulose, 408-410 LamellsK of compact bone, 44 Lamellar cells, 30 Lamina of cortex, 090, 697 cribrosa, 815 spiralis, 792 terminalis, 646 Langerhans, islets of, 517, 539 Langley on the autogenetic theory, 150, 151 Langleys experiment on vagus and cervical sympathetic nerve, 161 ganglion, 502, 504 nicotine method, 200 Lanoline, 436 Large Intestine. See Intestines. Laryngoscope, 803 Larynx, 346, 347, 799 et seq. anatomy of, 799 cartilages of, ib. diagrams of, 805 mucous membrane, 801 mu.scles of, 801 et seq. nerves of, 803 ventricle of, 801, 805 vocal cords, SOI movements of, 804 Lateral sclerosis, '711 Lateral ventricle, 687 Lateritious deposit, 592 Lawes' and Gilberts' experiments, 618 Layer, papillary, 212 circular, ib. spiral, 213 Lecithin, 9, 166, 435, 437, 477, 520 Lee's experiment.'!, 755 Lens, crystalline, 812-814 Lenticular nucleus, 688 Le Page's investigations into pancreatic secre- tion, 520 Leucine, 417, 418, 422 Leucocytes. See Blood -corpuscles (white). Leucocythsmia, 334, 593 Leucosin, 433 Levene on nucleic acid of yeast, 432 Lewis on hoemolymph glands, 336 Leydig's theorv of protoplasmic structure, 7 Lleberkuhn'a gUnds, 493, 494, 496, 497 Liebermann's reaction, 436 Ligamentum pectinatiim iridis, 813, 814 Limbic lobe, 694 Line of Gennari, 697, 736, 737 Lipase, 440, 513, 618, 617 Lipoids, 9, 165, 166, 43 J Lipolytic ferments, 440 Lippmann's capillary electrometer, 120, 121 Liquor sanguinis, or plasma, 60, 444 Lissauer, tract of, 657 Listing's reduced eye, 821 Litmus, 165 Littre, glands of, 570 Liver, 527 et seq. bUe, 528 blood-vessels, 528, 529 capillaries, 629 cells of, 628 cirrhosis of, 586 circulation in, 628 diastase, 637 extirpation in mammals, 539 INDEX 911 LlVKR. Liver - continued fat metnl>olisin, 541 el seq. ^Ivcogenlc function of, 536 lobules of, 527-52H secretion of. See Uile. structure, 5'2S sugar formed by, 537, 538 supply of blooii to, 627 under-surface of, ib. " Living test-tube " experlmenl, 452 Local sitnii "02 Localisation of tactile sensations, 770 Locke's solution, 202 Locomotor ataxy, 715 Loeb on classilication of ions, 323 on spermatozoon, 882 Loewcntlial's tract, 656 Loop of Henle, 567 Lorlet on the carotid flow, 289 Loudness of voice, 806 Ludwig's graphic method, 87 Ludwdg's kymograph, 272, 273 Ludwig on the lymph tlow, 319 on function of kidneys, 573, 577 on swaying movements of small intestine, 557 Stronmhr, 282 Lugaro's sleep theory, 745 Lunatic's brain, 751 Lungs, 346 et seq. air-sacs of, 351 et sc/. area of surface of, 352 blood-supply, 353 capillaries of, 352 changes of air in, 372 circulation in, 352 coverings of, 350 diffusion of gases within, 372 lobes of, 351 lobules of, ib. lymphatics, 353 muscular tissue, 352 nerves, 353 nutrition of, 352 position of, 346 structure, 349 Lunula, 605 Lymph, 26, 32, 61, 70, 224, 315 cl seq. composition of, 315 current of, 318 filtration theory, 319, 320 formation of, 26, 319 path, 317 relation to blood, 319 Lymph capillaries, 224 origin of, 226 structure, t'l. Lymph-hearts, structure and action of, 318 relation to spinal cord, ih. Lymphagogues, 320 Lymphatic glands, 36, 316 et seq. Lymphatic vessels, 208, 223 et seq. of arteries and veins, 221 communication with blood-vessels, 224 structure of, 221 Lymphocytes, 315, 456 Lymphoid or retiform tissue, 28, 35 See Adenoid tissue. Lysine, 420 M. Macallum's reagent, 27, 106 Macdonald on nerves, 164, 166 M'DougaU's " drainage " theory, 715, 710 MacEwen on bone regeneration, 50 Macleod on the nerves of the liver, 541 Memxrana. MacMunn, use of the term myo-hicmatln, 188 Macropliagos, 457 Macrosmatic annuals, 786 Macula, 764 lutea, 737, 814, 815, 818 Magendie, experiments on spinal nerve-roots, 150 foramen of, 644 Magnesium phosphate, 40, 54 Male organs of generation, 803 pronucleus, 881 sexual functions, 803 Malleus or hammer bone, 789, 790 Malpighian bodies or corpuscles of kidney, 566, 667, 569. See Kidney. corpuscles of spleen, 36, 334 Malpighian discovery of capillaries, 228 Malpighian layer, 604 Maltase, 441 Maltose, 411 , 439, 441 Mammal, nerves of, 248 Mammalian heart, excised, 201 Mammalian ovum, 884, 886, 887 Mammary glands, 485 evolution, 486 involution, ib. lactation, ib. structure, 485 Mannite, 408 Mannose, ih. Manometer, Hiirthle's, 242, 276 Martin's, 391 Marchi reaction, 168, 169 Marchi's method, 651 Marey'ssphygmograph, 291 tambour, 105, 107, 240 Marrow, 41 Martin's sphygmometer, 295, 296 Mast cells, 30 Mastication, 550 Mastoid cells, 788 Maturation of the ovum, 875 Maximal pulsation, 290 Maxwell's experiments on nerve impulse, 163 Jlay, Page, reaction of degeneration, 179 Mayer's waves, 305 Mayo's experiments on cranial nerves, 166 Meat as food, 487 Meatus of ear, 789 Meckel's ganglion, 678 Mediastinum testis, 864 Medulla oblongata, 180, 643 et seq. decussation of fibres, 666-668 diagrams of, 068, 669 dorsal aspect, 606 fibres of, how distributed, 201, 662 pyramids, anterior, 661 posterior, ib. structure of, 002 Medullary cavity, 41 segments, 75 sheath, 75 et seq. substance, 340 Meibomian follicles, 496, 810 Melssner's corpuscles, 708, 774, 775 plexus, 493 Melanin granules, 847 Mellanby on creatine, 690 Membrana, decldua, 8S7 granulosa, 869 development into corpus luteum, 870 hyaloidea, 819 limitans externa, 817-819 interna, 815 propria or basement membrane. See Basement- membrane. 912 INDEX Memukana. Mi'inbraiia — conttnu«(i tectoria, 792, 794 action of, 797 tymi)ani, 78^, 789, 792, 79') .Membrane, vitelline, 871 Membranes of the brain and spinal cord, IbO Membranes, mucous. See Mucous membranes. semipermeable, 325 Membranous labyrinth, 792, 793. Sec Ear. Memory ima;.;e, 761 Meniiel and liuckwood's experiments, 546 Meiiii re's disease, 755 Meningeal streak, 812 Mfiioipausf, 802, 874 Menstruation, 802, 873, 874 colnclUent with discharge of ova, 862 corpus luteum and, ib. Mercurial air-pumps, 364 Mercurial kymograph, 272, 274 Mesencephalon, 045 Mesial lillel, 072 Mesoblast, 10, 29, 41, 75, 883 e« scq. organs formed from, 887 Mesoblastic somites, 883 Metabolic balance-sheets, 613 et scq Metabolism, 6, 541 general, 612 et seq. uf fat, 616 et scq. of prot<;iii, 021 et scq. Metakinesls, 17, 18 Meta-protelns, 433 Metencephalon, 045 Methiemoglobin, 465 photographic spectrum of, 409 Metschnlkoiron inflammation, 298 on phagocytosis, 476 Mett's tubes, 516 Meyer, atucstlietics, 167 Meyer, "souml-picture" theories of, 798 Meyer-Overtoil on narcotic etl'ect on cells. 330 Meynerf 8 fountain decussation, 673 Micrococci, 439 Micrococcus urese, 599 Micro-organisms, types of, 439 Microsmatic animals, 786 Micro-spectroscope, 407 Micturition, 580 centre, 580, 721 Mid-brain, 644 anterior aspect, 661 posterior aspect, ib. structure of, 601 et seq. Middle ear. See Tympanum. Mid-gut, 886 MUk, as food, 481,482 alcoholic fermentation of, 483 chemical composition, 472 coagulation of, ih. fats of, 483 chemical composition, ib. globules of cow's milk, 481 proteins of, 482 reaction and specific gravity, ib. salts of, 483 secretion of, 481 souring of, 483 Milk-curdling ferment, 520 Milk-sugar, 411, 483 properties of, 411 Milk-teeth, 50 et scq. Mlllon's reagent and test, 425 Mitochondrial sheath, 860 Mitosis, 15, 876 Mitral cells, 785 Mitral valve, 211,214 Modiolus, 791 M t'SCLK. Molars. See Teeth. Molecular layers, 816, 817 reactions, 329 Momentum, 267 Monakow's bundle, 657, 083, 085 Monaster stage of karyokineaU, 16, 18 Monatomic alcohols, 408 Monkey's brain, 730 spinal cord, COO Mono-amiuo dii)liosphatides, 435 Mono-amino-mono pliospliatidos, 435 Monophasic variation, 125 Monoplegia, 729 Monosaccharides, 409 Monro-Kellie doctrine, 313 Moore and Kockwood's experiments on fat absorji- tion, 548 Moore's test for sugar, 410 Morula, 883 Mosso's ergograph, 132 experiments on the effects of fatigue, 133 expfriraents on micturition, 580 Motor areas of cerebrum, 728 impulses, transmission In cord, 709 nerve-tibres, 73 Motor nerves, 70 of tlie iris, 833 Motor ocull nerve, 663, 673 origin of, 063 Motorial impressions, 751 sense, 776 Mountain sickness, 400 Movements of protoplasm, 11, 12, 82 peristaltic, of involuntary muscle, 140 of stomach, 555 Muclc acid, 410 Mucigen or Mucinogen, 21, 27, 499 Mucin, 21, 27, 430,505 Mucoids, 30, 430 Mucous membrane, 493 gland-cells of, ih. of Intestines, ib. of larynx, 801 of stomach, 493 Midler's fibres, 815, 810 Midler's fluid, 168 Miiller's law of .specific nerve energy, 762 MuUer's muscle, £12, 813 Multipolar nerve-cells, 183 ct seq. Munk's experiments on fat absorption, 548 Munro, foramen of, 645, 688 Murexlde test, 591 Muscarine, action of, on the heart, 253 Muscle, 02 et seq. blood-vessels of, 70 cardiac, 71, 255 changes in form, when It contracts, 86 ft seq. chemical changes In, 131 composition of, 136 clot, 137 columns, 65 contractility, 08 curves, 93, 90, 99, 101, 114 development, 72 dynamometer, 114 elasticity, 108 et seq. electrical phenomena of, 116 ct seq , 176 extensibility of, 116 ct seq. fatigue, effect of, 97, 98, 182 curves, 96 Hensen's line, 05, 67 Involuntary, 62, T9 (see 140 et seq.) irritability, 83 evidence of, ib. lever system of, 100 INDEX 9i; MUHCLK. Musfle — continiteU nervea of, 70 plain, 71 plasma, 137, 138 proteins, 139 reciiirooal action of antagonistic, 714 red, 70 response to stimuli, 84 et scq. rigor, 130, 13'J sarcolenima, 03, 64 sensory nerve-endings in, 709 serum, 138 shape, changes In, 104 skeletal, 03 sound, dpveloped In contraction of, 104 spindle, 70. 6V« Neuro-muscular spindle. stimuli, 85, 101 8tiiat«d, structure of, 66 ct scq. tetanus, 103 et seq. negative vanation of, 123 thermal changes in, 129 tonus, 113, 142 twitch, 101 (see 123) voluntary, 62, 140 et seq. wave, loO, 123 work of, 113 Muscular action, condition.s of, 114 Mu.scular coat of alimentary canal, 492 Muscular contraction, 84, 94, 'J6 et seq. effect of two succe.ssive stimuli, 101 of more than two stimuli, ib. voluntary- tetanus, 104 Muscular fibres, development, 72 plain, 02 et seq. transversely striated, ih. voluntary, 72 Muscular force. 111 irritability, 81 tissue, 62 et seq. composition of, 137 Muscular .sound, 236 Muscularis mucosae, 348 Musculi papillares, 213, 214, 234 Musical sounds, 806 Mydriatics, 833 Myelencephaloii, 645 Myelination, ~'S'J Myelocytes, 401 Myeloplaxes, 41 Myogen-fibrin, 139 Myogenic, 560 Myoglobulin, 138 Myobaematin, ih. Myograph, 87, 92 Helmholtz's, 92 pendulum, 94 spring, ib. transmission, 105 Myopia, or short-sight, 828 Myorectes, 05 Myoprotein, 139 Myosin, 136 et seq. Myosinogen, 137 et seq. Myotics, 833 Myxcedema, 338 N. Nails, 605 Xarcosis, 744 et seq. Nasal cavities In relation to smell, 783 et seq, Nasmyth's membrane, 59 Near point, 826 Nkrves. Negative variation, 121 Neoenceplialon, 046, 647 Neoiialliiini, 047 Nerve-cells, classification of, 194 structure of, 182 et seq. Nerve-centres, 180 et seq. See CerebeUum, Cere- brum, etc. ano-spinal, 664 cUlo-splnal, 721 defaecatlon, 562 deglutition, 551 erection, 721 micturition, 580, 721 parturition, 721 secretion of saliva, 500 speech, 733 vaso-motor, 300, 716 Nerve-corpuscles, 176 bipolar, 183 unipolar, ib. Nerve-fibres, cardio-inhlbltory, 249 in spinal cord, 653 intercentral, 145 Nerve-Impulse, nature of, 163 velocity of, 159 Nerves, 73 et seq. accelerator, 144 action of stimuli on, 81 afl'erent, 73, 144, 204, 557 analyses of, 160 axis-cylinder of, 74 axons, 152, 188, 198 cells, 79, 181 centrifugal, 143 centripetal, 144 cerebro-spinal, 181 changes in, during activity, 158 classification, 143 conductivity of, 159 cranial, 180, 181, 663 et seq. crosses of Ranvier, 75 crossing of, 161 degeneration, 146, 178, 307 chemistry of, 16.!) n-action of, 178 direction of a nervp impulse, 100 efferent, 73, 143, 557 electrical, 144 stimulation of, 176 excitability of, 169 fibres, 74 et seq., 143 et seq. development of, 79 functions of, 146 funiculi of, 76 grey matter, 73 hypogastric, 581 inhibitory, 144 irritability of, 81 laws of conduction, 144 et seq., 159 medullary sheath, 74 medullated, 74 motor, 143 termination of, 78 nodes of Ranvier, 76 non-medullated, 77 olfactory, 180, 663, 786 physiology of, 143 et seq. I)Uo-motor, 607 plexuses of, 79 reflex actions, 145, 188 secretory, 144 section of, 146, 500 shocks, method of slow interrupted, 307 size of, 77 spinal. See Spinal nerves. stimulation of cut, 146 3 M uu INDEX Nerves. 'Serves— continw'l structure, 74 symijatbetic, Influence on heart, 24'J taste, TSl temperature, influence of, 308 terminations of, in corpuscles of Golgi, "69 In corpuscles of Graniiry, 768 In corpuscles of Herbst, 760 in end-bulbs, 7C7 in motorial end-pjiates, 78 in networks or plexuses, 770 In Pacinian corpuscles, 766 In touch-corpuscles, 767 trophic, 144 Nervous circles, 715 Nervous system, autonomic, 196 et seq. central, 640, 642 et scq. cerebro-splnal, ISl electrical variation in central, 743 Influence on the heart, 3S9 >iympathetic, 249 vaso-motor, 300 et seq. N<-rvous tissues, chemistry of, 165 et scq. chemical changes during activity, 167 chemical changes in degenerative condi- tions, 167 potassium salts in, 166 Nervus erigens, 581 Neurilemma, 74, 153, 181 Neuroglia, 181,649 Neurolceratln, 75, 165, 182, 429 Neuro-mnscular spindles, 70, 769, 770 Neuron, 189 Neutral sulphur, 595 New-bom child and changes after birth, 862 et seq, Nicol's prism, 68, 434 Nicotine, action of, 200 Nipple, tha, 485 Niasl's granules, 165, 184, 192, 194 significance of, 192 Nitric oxide hsemoglobln, 465, 470 Nitrogen in the blood, 362 eliminated in the form of urea, 479 Nodal point, S20 Nodes of Kanvier, 75 Noll, nerve degeneration, 167 Normoblasts, 400 Nose. See .Smell. Notochord, 884, 885, 886 Nuclear layers, 816, 817 Nuclear membrane, 9 sap or matrix, 9, 10 Nuclease, 432, 594 Nucleic acid, 431, 432 Nucleln, 8, 10, 430 Nuclei pontis, 664 Nucleoli, 9, 10, 12, IS Nucleo-protelns, 8, 105, 427, 430, 431 Nucleotidf-s, 422 Nucleus of animal cell, 5, 7, 9 ft tcq. chemical composition, 10 division, 15 of cranial nerves, diagram of, 665 staining of, 10 structure, ih. Nucleus ambiguns, 669, 670, 678 Nucleus cuneatus, 667, 669 gracilis, ih. Nucleus of Bechterew, 677 of Deiters, 670, 671, 677 Nutrition, effect on respiration, 392 Nyctalopia, 849 Nystagmus, (6. Ovo-iincoiD o. Occipital convolutions, 693 OccipiUl lobe, 690, 692, 603 O'Uonogliue on corpus luteum, 881 OdontoDlatlH, 53, 55, 57 Odontogen, 57 Odours, 786. See Smell. tKrsted's electro-magnetism, 117 Q:.sophagus, 492, 493 Oistrus, 874 Oleaginous principles, 414 Oleic acid, ih. Olein, 35, 414 Olfactory bulb, 784 cells, ('/. glomeruli, 7S6 nerves, 663, 785, 786 tract, 7S4 " roots" of, ih. Olivarj- bcly, 661, 668, 671, 681 Oliver's method of e.sti mating haemoglobin, 472 Oncograph, Roy's, 310 Oncometer, 309, 571 Roy's, 310, 571, 572 0'>cytes, 86S et seq. ©..genesis, S73, 877 0.igonia, 871 Ophthalmometer, Helmholtz's, 826 Ophthalmoscope, 836 et seq. Opsonins, 476 Optic disc, 814 Optic ner\e, 663, 815 decussation of fibres In, 853 fibres, 815 nervous paths in, 853 Optic radiations, 737 Optic thalamus, CS9 Optical angle, 822, 823 apparatus of eye, 820 defects in, 828 axis, 822 defects In, 828 Optogram, 847 Ora serrata of retma, 814, 815, 819 Orang's brain, 691 Orbicularis muscle, 810 Orbital sulcus, 091 Organ of Corti, 794 Organic compounds in bo'iy, 406 et seq. Ornithine, 417, 583 Osazone, 412 Osmosis, 323, 324-6 distinguished from diffusion, 424 Osmotic pressure, method of estimating, 322 et seq. calculation of, 326 determination of, 326 of proteins, 327 phenomena, 322 et $eq, physiological applications, 326 Os orbiculare, 790 Osseous labjTlnth, 790. Sre Ear. Ossicles of the ear, 788, 795 action of, 796 Ossification, stages of, 45 et seq. Osteoblasts, 45 ft scq. Osteoclasts, 49, 50 Osteogen, 45 Ovarian ovum, 870 Ovariotomy, 879 Ovary, 867 W ^c/., 878, 879 Graafian follicles in, 860, 870 interrjal secretions of, 878 Oviduct, or Fallopian tube, 867 Ovo-mucold, 480 INDEX 915 Ovulation. Ovulation, soy, S74 Ovum, IS, lU, 870, 885 ;i. action of seminal llulii on, 875 et sci] I'han^jes In ovary, 876 l)revious to fecundation, 875 cleaving of yolk, 883 development, 88'J diagrams of, S6S, 870 tt scq. fertilised, 881 formation of, 870 germinal vesicle and spot of, 18, I'J, 87U, 871 Impregnation of, 881 maturation, 875 d scq. segmentation, 883 structure of, 870 in mammals, 871 subsequent to cleavage, 883 ct icq Oxidases, 440, 594 Oxidation, measurement of coefUcient of, 306, 307 Oxygen In the blood, 305 ct scq., 309 tt seq. pressure of, where fatal, 400 want, 399 Oxyhaimoglobin, 61, 210, 372, 402, 401, 402, 405, 409 crystals of, 402 spectrum of, 408, 409 Oxyntic ceUs, 608, 510 P Pacinian corpuscles, 700, 707 I'am, 777 Tain spots, 772, 774 Pala-encephalon, 640, 047 Palmitic acid, 414 Palmitm, 34, 414 Pancreas, 517 adaptatiou of, 522 extirpation of, 539 diabetic condition produced m animals by, 539 so-called peripheral reflex, secretion of, 520 structure, 517 Pancreatic juice, 518 action on fats, 520 composition and action, 618 ferments in, ib. PupiUai, of the kidney, 505 of skin, distribution of, 004 of tongue, 770 et seq. Papillary layer uf lieart, 212 Paradoxical contraction, 172 Paralytic secretion, 503 Paramyosinogen, 138, 142, 105 Paraplasm, 8 Parathyroids, 339 Parietal cells, 508, 510 Parietal layer of pericardium, 208 Parietal lobe, 092, 693 Parieto-occipital Assure, 692, 694 Parotid gland, 503 alveoli of, 500 Pars ciliaris retinae, 819 Pars intermedia, 343 of Wrisberg, 075 Parthenogenesis, 878 Parturition, 893-895 Par vagum. See Pneumogastric nerve. Pathological conditions of nervous .system, 311 Pathological urine, 000 Pathogenic organism, 476 Patrick's experiments, 748 Pavy's views as to the liver being a sugar- forming organ, 537 Pinna. Pawlow'g method for obtaiuing pure gastric juice, 511, 512, 522 his observations on the salivary glands, 504 on the .secretory nerves of the pancreas, 521 on the succus entericus, 523, 525 Peduncles of the cerebellum, 043 Peduncles, stijicrior ciTcbellar, 058 Pelvis of the kidney, 505 Pendulum myograph, 94, 95 Penis, structure, 800 Pentosuria, ()02 Pepsin, 439, 440, 510 Pepsinogen, 509 Pepsin-hydrochloric acid, 511 Peptides, 422 Peptogens, 613 Peptolytic enzymes. 440 Peptones, 417, 433, 450, 001 characters of, 515 Peptonuria, 001 Perforated spots, 089 Perforating fibres of bhariiey, 44 Pericardium, 208 Perichondrium of cartilage, 47 Peiilymph, or fluid of labyrinth of ear, 753, 790 Perimeter, 839 Perineurium, 70, 77 Periosteum, 42, 45, 60, 59, 00 Peripheral resistance, 204 el tf/., 297 Peristalsis, 83, 140, 5.06, 659, 5i;i Peristaltic movements of intestines, 83, 557 of involuntary muscle, 14U (see 553) of stomach, 653 et scq. Peritoneum, 209 Permanent teeth. Sec Teeth. Personal equation, 720 Perspiration, cutaneous, 009 insensible and sensible, ih. ordinary constituents of, 010 Pes, 673 Petit 's canal, 820 Petteiikofer's reaction, 533 Peyer's patches, 36 Pfluger's law of contraction, 174, 178 on hepatic ceUs, 530 on menstruation, 876 on proteins, 022 Phagocytes, 457, 473, 470 Phakoscope, Helmholtz's, 825 Pharynx, 492, 805 Phenyl alanine, 418 Phenyl-hydrazine test, 412, 602 Phloridzin-diabetes, 540 Phosphates in urine, 596, 5G9, 000 Phosphatides, 100,' 167, 438 Phospho-proteins, 427, 429 Photo-chromatic interval, 848 Photo-hajmatochometer, 286 Photophobia, 849 Phrenograph, 357 Physical chemistry, 322 ct seq. Physiological applications of physical chemistry, 327 methods, 1 it seq. pit, 838 rheoscope, 127 zero, 774 Pia mater, 1S2, 644 Picric acid test, 602 Pigment cells, 30 of retina, 82, 818 movement of, 847 Pilocarpine, ellect of, on salivary gland, 503 Pilo-motor nerves, 607 Pineal gland, 345, 665 Pinna, 789 916 INDEX I'lOTIiOWSKl's Kkac TION. Piotrowskl's reaction, 425 ripor's oxperiiiu'iits on inusclo coiilraclioii, lOU Pilch of voice, 7'Ji, 800, 807 ritot's tube, 280 ritultary body, 343 et seq. etlects of removal, 345 Viaceiita, maternal, 889 fcEtal, ill. Plantar rellex, 711 Plasma cell, 211 Plasma of blooii, 00, 444, 449, 452 et snq. gasea of, 453 Plasmatic membrane, 330 Plethysmograph, 308 Schiifer's, 200 Pleura, 209, 349 Plexus, terminal, 770 of Auei'bach, 79 of Meissnor, 493 Pneumogastric nerve, 249 et scq., 004, 078 distribution of, C7S functions, 004, 678 influence on deglutition, 553 gastric secretion, 512 heart, 249 muscles of stomach, 656 pancreatic secretion, 520 vomiting, 650 mixed function of, 678 origin, ib. Poehl on testis, 878 Poggendorf's rheochord, 170 Pohl's commutator, 169 Poikilothermal animals, 630 Poiseuille's haemodynamometer, 272 Polarimeter, 434 Polygonal epithelium, 529 Polymorphic layer, 697 Polynuclear leucocytes, 456 Polypeptides, 417, 422, 433 Polysaccharides, 409 Pons Varolii, 042, 043, 646, 662 grey matter in, 644 Popielski's investigations into pancreatic secre- tion, 520 Portal canals, 528 circulation, 215 vein, 527, 528. Sec Liver. Postero-lateral column, 658 Post-ganglioiiic libres, 198 ct stq., 249, 303 Potato starch, grains of, 412 Precipitants of proteins, 426 Precipitin, 477 Precuneus or quadrilateral lobule, 094 Preganglionic libres, 198 et seq., 302 Pregnancy, corpus luteum of, 870 Prepyramidal tract, 067 Presbyopia, 831 Pressor nerves, 305 Pressure gradient, 285, 380 Pressure head, 286 Pressure-measurers, 207 I'ressure, positive and negative, 271 Primary areas, 742 Primary areoUe, 48 Primary responses of eye, 848 Primitive nerve-sheath, or Schwann's sheath, 78 Primitive gut, 880 Projection libres, 098, 740 Projection systems, 698, 700 Proline, 421 Pronucleus, female, 876, 882 male, 876, 881, 882 Propeptone, 514 Pus IN rilK UlIlNK. Prose<'rBtin, .')21 I'roseiiceplialon, 045 Prostate gland, 570, 879 Prosthetic group, 430 I'rotagon, 437 Protamines, 427 Protective inoculation, 473 Protein-hydrolysis, 432 Protein metabolism, 6, 416, 621 Proteins, 0, 8, 10, 105, 410 H seq.,Ab3 absorption of, 544 action on jiolarised light, 425 of blood, 453 IJenci'., Jones', 601 classification, 420 ct seq. cleavage products, 410 coagulated, 42t) colloidal solution, 424 colour reactions, 425 composition, 410 conjugated, 427, 430 crystallisation, 424 enzyme coagulation, 440 heat coagulation, 426 in food, 479 ct seq. indiflusibllity of, 425 metabolism of, 6, 621 et seq. osmotic pressure of, 327 of plasma, 453 precipitants of, 417, 425, 426 of serum, 453 simple, 410 solubilities, 423, 424 in urine, 000 Protensity, 703 Proteoclastic enzymes, 440 Proteolytic enzymes, 440, 514 Proteoses, 417, 433, 001 characters of, 515 Prothrombin, 449 Protones, 427 Protopathic sensations, 700, 774, 777 Protoplasm, 5, 7, 10 chemical structure, 8 irritability, 13 movements, 8, 11 ct seq. Proto-vertebra;, 884 Protrusion of eyeball, 849 Przibram, Hans, theory of classiticatlon by muscle proteins, 139 Pscudopodia, 11, 14 Pseudoscope, 856 Pseudo-stoniata, 222 Psycho-physical parallelism, 758 Ptosis, 850 Ptyalin, 439, 499, 505 Ptyalinogen, 499 Puberty, 802 Pulmonary artery, 215 Pulmonary circulation, pressure in, 281 Pulsation, maximal, 290 Pulse, anacrotic, 293 arterial, 290 et seq. dicrotic, 293, 294 intermittent, 290 velocity, ib. venous, 299 volume, 809 water hammer, 291 wave, 295 Pupil of the eye, 838, 834 Purine bases, 421, 432, 593 Purklnje'8 cells, 187, 081 libres, 71, 72,213, 256, 267 figures, 836 Pus in the urine, 003 INDEX 017 Pylouic Glaniis. Pyloric glamU, 507, 508 orilice, SfiS, 654 ryramWal tracts, 655 Pyramlils of medulla oblon^'ata, 001 of kidney. So' Kidney, ryrimidino bases, 4"il Pyrrhol blue, 890 Pyrrolidine derivativi^s, 421 R. Racemose ^'laiids, 490 Hanii coininunicantes, 190 Hanke'8 diet, 304, 028 Ranvier's idasniatocytes, 31 Ranvier's crosses, 75 Ranvier's nodes, ib. liaynaud's disease, 312 Reaction time in man, 720 velocity, 328 Reactions of inoteins, colour, 425 Receptive groups, 475 substances, 104 Recurrent sensibility, 150 Rectum, the, 502 Red marrow, 41 Reduced eye, 821 Reductases, 440 Reflex arc, 711 actions, 145, 188, 709 ct seq. inhibition of, 253, 719 in frog, 709 in man, 145, 711 superficial, 711 tendon, 712 of dog, 719 of nerves, 145 of spinal cord, 709 et scq. " scratch," 719 Reflex secretion, 504 Reflexes, cumulation of, 710 inhibition of, ib. spinal visceral, 721 spreading of, 710 uterine, 722 Refraction, laws of, S21 Refractive media of eye, ib. Reid, osmotic pressure, 828 Reil, island of, 088, 092, 094 Reissner's fibre, 044 Reissner's membrane, 792, 794 Relaxation of heart, 232 Remak, fibres of, 77 ganglion of, 255 Renal circulation, 215, 580 epithelium, 577 oncometer, 572 plexus, 571 Rennet or renuiii, 440, 483, 514 Reproductive organs, 0, 858 et seq. ilevelopment of, 858 vt sciy. female, 807 et seq. male, 803 et seq. physiology of, 872 et seq. Requisites of diet, 618 Reserve air, 359 " Reserve force," 025 Residual air, 359 Resistance, peripheral, 204 Resonance theory, 798 Respiration, 340 et seic frot;, 127 Khodopsin or visual purple, 847 Uliytlim in cardiac muscle, 25.'> liliytlimical contraclioii and dilatation, 299 Hhythmicallty of movement, US, MO Uicin, 475 Rigor mortis, ISO et srq. alTecta all classes of muscles, 136 phenomena and causes of, ib. physical basis of, 131 Rima plottldis, 801, 805 Ringer's investigations on drug action, 200 fluid, 677 solution, 260 Ritter's tetanus, 176 Rocci, Riva, his sphygmometer, 295 Rods and cones, 817 Rolandic area, 087, 089, 722, 723, 727, 733 injury of, 723 Rolando, tissuie of, 692-094, 729, 732 substantia gtdatiiiosa of, 067, 668 tubercle of, 667 Rollett's view of the red corpuscles, 454 Rose's test, 425 Riisel on protoplasmic movement, 13 Rotation, 13 method for estimating specific 'gravity of blood, 444 Roy's cardiometer, 248 oncograph, 310 oncometer, ih, Rubner, on action of food stuffs, 625 law of conservation of energy, 630 Rumination, 550 Itul, S!I4 Rutherford's " sound-picturn " theories, 798 s. Saccharic acid, 410 Saccharosf'S, 409 St Martin, Alexis, case of, 507, 554 Saccule, 791 Salathc, effect of gravity on the circulation, 279 Saliva, 409, 504 et Sf/. action of, 505 composition, 504 jirocess of secretion, ib. rellex secretion, ib. secretion following stimulation of nervi^s, 500 et seq. Salivary glands, 498 el .'nq. digestion, 506 extirpation of, 504 influence of nervous system, 502, 503 effect of drugs on, 603 secretory nerves of, 502 structure, 498 Salkowski's reaction, 430 Salmine, 427 Salts In the blood, 454 Sanderson's cardiograph, 239 on electrical change in muscles, 125 Sanson's images, 824, 825 Santorinl's cartilages, 800, 802 Saponification, 416, 520 Sarcina;, 439 Sarcolemma, 03, 64, 137 Sarcomeres, 07, 68 Sarcoplasm, 65, 67, 72 Sarcostyles, 65 rl sei/. Sknsorv Impke.ssions. Sarcous elements, 67 el srq. Sartorius, record of injureil, 130 Scala media, 792 Seal a typani, 791, 797 Scala vestlbuli, 791, 797 Scarpa, g;inglion of, 077 Schufer, heart plethysmograph, 200 observations on liver cells, 530 method of artificial respiration, 3S3, 384 protoplasmic structure, 7, 14 researches on the structure of a sarcostyle, 67 views regarding the function of the Rolandic area, 731 white blood ccjrjmscles, 8 Scheiner's exjieriment, 826 Schematic eye, 821 Schenk on muscular contraction, 115 Schlenini, canal of, 813, 814 Schmidts method of preparing fibrin ferment, 453 Schrijder's experiment, 587 Schwann, white substance of, 74 Sclero-proteins, 427-429 Sclerotic, 807, 808, 809, 811-813 Scotoma, 849 Scratch reflex, 717, 718 Sebaceous glands, 60S Sebum, 608 Secondary contraction, 128 Secretin, 521 Secreting glands, 81, 492 et seq. classification of, 496 diagram of, 497 Secreting membranes. See Mucous aiul Serous membranes. Secretion, internal, 331 of kidney, 671 pancreas, 520 paliva, 500 paralytic. r>03 reflex, 504, 520 suprarenal, 340 thyroid, 337 Secretory nerves, 144 diagram of, 503 of pancreas, 521 of salivary glands, 502 effect of section of, 503 of sweat glands, 610 Segmentation of cells, 883 in chick, 885 nucleus, 876 ovum, 883 Semen, S(i6, 867 spermatozoa, ib. Semicircular canals of ear, 794 diagrams of, 754, 756 structure, 753 et seq. Semilunar valves. See Heart valves. Semiijermeable membranes, 324 Sensation, 760, 704 cutaneous, 766 et seq. difference in quality, 762 extensity, ib. hallucination, 764 memory image, ib. nerves of, 144 tactile, 751 thresholds, 763 Weber's law, ib. Sensibility, recurrent, 156 Sensory areas in cerebral cortex, 728 Sensory channels, diagram of, 702 Sensory impresoions, conduction of, by !»p1niC Sensory nerves TO Septum nasi, nerves of, 785 Serine, 417 Serous coat, 493 Serous membranes, 208 Sertoli, cells of, 804 Serum, albumin, SI 5. 453 of blooil, 60, 452 ei seq. globulin, 315, 453 Seventh cerebral nerve, 063, 073 Sex, iletermination of, 859 Sexual organs in the female, 8G7 (/ seq. in the male, 803 it seq. Sliarpey on bone formation, 50 tibres of, 44 Sherrington, experiments on motor area, 731 on course of reflex in knee Jerk, 712 observations on binocular flicker, 854 principal of the common path, 710, 717 reciprocal action of antagonistic muscles, 714, 715 Short sight, 828 Side-chain theory, 475 Sight. See Vision. Silent areas, 738 Silver nitrate reaction of cementing substance, 27 Simple tubular glands, 496 Sino-auricular node, 218, 250 Sinus, coronary, 209 Sinuses of Valsalva, 214, 237 Sinusoids, 222, 528 Sixth cerebral nerve, 603, 671 Skein, 15, 10, 18 Skeletal muscles, 03 Skiascope, 831 Skin, 004 absorption by, 008 dermis, 604 diseases, 611 epidermis of, 604 functions of, 608 nerve-endings m, 760 papillK of, 604 respiration, 603 rete mucosum of, 004 sebaceous glands of, 008 secretions, ib. sections of, 605 et seq. sweat, 009 tt seq. sweat-glands, 496, 008 vaniishing the, 611 Sleep, 744 et seq. Smell, sense of, 738, 782 H seq. anatomy of regions, 784 connection with taste, 738 delicacy of sense of, 787 testa for, varies in different animals, 780 Smith, Lorrain, experiments on quantity of the blood, 445 Smith's perimeter. Priestly, 840 Sneezing, mechanism of, 382 Snoring, mechanism of, ib. Soap, 416 Sobbing, 382 Sodium chloride method, 431 Solitary glands. See Peyer's patches. Solubilities, 423 Solutions, gramme-molecular, 323 Somatic mesoblast, 872, 884, SS7 Somatoplasm, A eismaiin's, 801 Somatopleur, 884 Somites, mesoblastic, 884 Spirilla, Variois Forms ok. Sonorous vibrations, how communicated in ear, 794 et seq. in air and in water, 795. See Sound. Sound, conduction by ear, 701 heart, 235, 246 jjroduction of, 800 Soup, value as food, 490 Sour milk as cure for dys|)eptic disorder.s, 527 Spaces of Fontana, 814 Speaking, mechanism of, 807 Special senses, 700 et seq. Specific nerve energy, law of 702 Spectroscope, 405 et seq. Speech, 807 • t seq. centre, 733 defects of, 808 Spermatids, 804, 805, 873 Spermatocytes, ib. Spermatogonia, ib. Spermatozoa, 19, 800, 807, S81 form and structure of, 800, 867 Spheno-palatine ganglion, 678 Spherical aberration, 830 correction of, ib. Sphincter ani. See Defaication. pupiDaj, 812 vesicae, 570 Sphingomyelin, 166, 435, 488 Sphygmographs, 291, 292 tracings, 291 et seq. Sphygmometers, 295 Spinal accessory nerve, 6C4 functions of, 079 origin, ib. Spinal cord, 648 ct seq. association fibres in, 058 canal of, 048 columns of, 049 commissures of, 648 conduction of impressions by, 704 et seq. course of fibres in, 053 diagrams of, 049, 650, 060 fissures and furrow i of, 048 functions of, 704 et seq. of columns, 654 grey matter, 181,650 cells in, 050 hemlsection, 059 injiiries of, 704, 709 membranes of, 643 nerves of, 053 reflex action of, 709 et seq. inhibition of, 710 in frog, 709 in man, 711 superficial, ib. reflex irritability of, 712 regions of, 059 section of, ib. special centres in, 720 structure of, 048 et seq. tracts, 051, 055, 703 transverse section of, 659 white matter, 107, 649 tracts in, 651 Spinal nerves, 155 functions of roots of, 155, 049 origin of, 155 et seq. Spinal visceral reflexes, 721 ■ Spiral canal of the ear, 791 Spiral ganglion, 794 Spiral layer, 21 3 Spiral ligament of ear, 792 Spirem, 15, 18 Spirilla, various forms of, 439 920 INDEX Spirometer. Spirometer, 359 Splanchnic mesoblast, S84, 887 Splanclinii- nerves, 342 Splanchnopleur, SS4 Spleen, 332 apparatus for splenic cun-es, 134, 313 functions, 334 Influence of nervous system upon, 335 Mali)it.'hian corpuscles of, 334 pulp, 333 structure of, 382 trabecula of, ib. Spongioblasts, 810 Spongioplasm, 7, 8, 14, 68, 83 Spot, germinal, 871 Spring myograph, 94 Staircase phenomenon, 97, 141, 259 Stannius' experiment, 258 Stapedius muscle, 790, 796 Stapes or stirrup bone, 789, 790 Staphylococci, 439 Starch, 412, 537 Starling mammalian heart, 245 on pancreatic secretion, 520-525 Starvation, 621, 62S effects of, ib. Stearic acid, 414 Stearin, 84, 414 Stellate cells of Kupffer, 528 StercobUln, 534 Stethographs, 357 Stewart's experiments on the circulation of the blood, 289, 290 on muscle proteins, 142 on the output of the heart, 247 Stimulants as accessories to food, 490 Stimulation fatigue, 134 Stimuli, varieties of, 13, 14, 81, 84, 85 Stirrup bone, 780, T90 Stokes' reagent, 465 Stolnikow, measurement of the heart's output, 247 Stomach, blood-vessels, 509 digestion in, 525, 563 glands, 508 movements, 553 Influence of nervous system on, 55C mucous membrane, 507 nervous mechanism of, 556, 557, 563 secretion of. See Gastric juice. time taken to empty, 554 view of empty, 555 StomaU, 226 Stratum granulosum, 604 intermedium of Hannover, 58 lucldum, 604 Streptococci, 439 Strlic acousticje, 663, 677 Striated muscle, 66 et seq. Sec Muscle. Striate area, 736 Stroma, 454, SOS Stromuhr, Ludwig's, 282 Tigeratedfs, 2S4 Structure of cells, S et seq. Stnart's kymoscope, 271 Sturine, 427 Stylo-pharj-ngeos, 678 Subendothelial layer, 218 Sublingual glami.'oOS Submaxillar}' gland of dog, 499 Submaxillary and sublingual glands, 499, 500 Submaxillary ganglion, 502 Submucous coat, 493 Substantia gelatinosa of Rolando, 650, 667, 668 nigra, 672, 673 TKMPERATrRK. Substrate, 439 Subthalamic area, 689 Succagogues, 513 Succus entericus, 522 el seq. functions of, ib. Sucroaes, 409 Sugar. See Dextrose, Lactose, etc. Sulci, 690 et seq., 730, 731 Sulphates in urine, 595 Summation-tones, 797 Supnrlicial reflexe.s, 711 Superior larj-ngeal nerve, effects of stimulation of cut, 378 olivary nucleus, 671 parietal convolution, 693 Supra-renal capsules, 340 cortex, 342 function, 341 structure, 340 Surface tension, 330 Sustentacular libres of Mailer, 815, 816 Swallowing, 551 centre, ib. fluids, 552 nerves engaged, ib. Sweat, 609 et seq. Sweat-glands. See Skin. Sylvius, aqueduct of, 644, 645, 663, 671 Sylvius, flssnre of, 642, 643, 692-694 Sympathetic nerve, 251 Sympathetic secretion, 502 Syntonln, 434 Syringomyelia, 707 Systemic circulation, 215. Sfc Circulation. Systole of heart, 232 Systolic pressure, 296 Systolic sound, 235 T. Tabes dorsalis, 715 Tache cerebrale, 311 Tactile area, 734 discs, 770 end-organs, 766 cl seq. impressions, 751 sensIbUlty, 734, 770, 771 variations in, 772 Talbot's law, 836 Tapetum lucidum, 837 n. Tarsus, 810 Taste, sense of, 73S, 779 et seq. classification of, 783 connection with smell, 738 delicacy of, 783 nerves of, 781 Taste-buds, 781 , 782 Taurine, 533 Taurocholic acid, ib. Taxis, positive and negative, 14 n. Tchistovitch's discovery of distinguishing hnman and other blood, 477 Teeth, 50 H seq. development, 56 eruption, times of, 51 incisor, 51 structure, 62 et seq. temporarj- and jtermanent, 50 et seq. Tegmental nucleus, 071 Tegmentum, ib. Tfli'iiceplialon, 645 Temperature, 368, 686 et seq. avera;,'e of body, 636 changes of, effects, 036 et seq. INDEX 921 TkMI'KKATUUK. 'l'em\toTainri^—conti lived ellect on muscular contraction, d\) exti'nsibility, intlucnce on, ll'J of cold-blooded and warm-blooded animals, C30 In disease, 041 loss of, 638-0-11 maintenance of, 080 of Mammalia, birds, etc., ih. sensation of variation of, 772. Hcc Heat. Tomporo-occipital cerebellar fibres, 073 Temporo-sphenoidal lobe, 092, 693 Tendon-rellexes, 711, 712 Tension of .^ases in fluids, 365 Tensor jialati muscle, 795 tympanl muscle, 790, 796 action of, 795 Terminal areas, 743 Terminal ganglia, 249 Testicle, S03, 804 structure, ib. Testis, SOS, S7S internal secretions of, 878 Tetanus, composition of, 103 injured sartorius during, 126 Hitter's, 176 voluntary, 104, 142 Tetany, 340 Thalamencephalon, 045 Thalami optici, OSS Theine, 490 Theobromine, ib. Thermopile, 130 Thirst, 778 Thoma-Zeiss lia;macytometer, 458 Thomson's galvanometer, 118 Thoracic duct, 01, 224 innervation of, 319 Thresholds of the stimulus, 703 Throat deafness, 795 ventricle, SOI Thrombin, 440, 448, 449, 453 Thrombogen, 449-451 Thrombokinase, ib. Thudjchum on protagon, 437 Thymus gland, 336 effects of removal, 337 function, ib. structure, 330 Thyro-arj'tenoid muscle, 801, 802 Thyro-epiglottidean muscle, 802 Thyroid cartilage, 799 Thyroid gland, 337 function, 342 structure, 337 Thyro-iodin, 339 ettect of Intravenous injection of, on blood- pressure, 339 Tigerstedt, measurement of the heart's output, 247, 290 Stromuhr, 284 Timbre of voice, 794, 806 Tissue-erepsin, 546, 593 Tissue-respiration, 394 et acq. Tongue, 779 action in deglutition, 548 epithelium of, 780 muscles of, 779 papillae of, t5. parts most sensitive to taste, 781 structure of, 779 Tonometer, Barcroft's, 366 Krogh's, 366, 373 Tonus, 113, 142, 713 Tripfer's test, 516 Touch, 766 et seq. muscular sense, 776 Ukktkks. Touch — cnnlinued sense of locality, 770 of pressure, 771 of temjierature, t'f. tactile end-organs, 706 Touch-corpuscles, 707 Toxin, 474 Trabecule, 317, 332 Trachea, 347 Tract of Flechsig, 658 of Gowers, 057, 658 of I^issauer, ib. of Loewenthal, 056 Tracts in the spinal cord, 651, 055 tl secj. Tradescaiitla, cells of, 12, 13 Transfusion of blood, 319 Transmission myograiili, 105, 159 Transverse axis of eyeball, 851 Trapezium, the, 071 Traube-Hering curves, 304, 305 Triacetin, 415 Triamino-mono phosphatides, 4i5 Tricuspid valve, 210, 213 Trigeminal nerve, 063, 674 function, 674 origin of, ib. Trimethylamine, 106 Trochlear nerve, 003, 074 origin of, 674 Trommer's test, 412 Trophic nerves, 144 Trypsin, action of, 51S, 519 Trypsinogen, 523, 524 Tryptophane, 419, 422 Tubercle of Rolando, 667 Tubular glands, 490, 497 Tubuli seminiferi, 804, 865 uriniferi, 506 et scq., 509 Tubulo - racemose or tubulo - acinous glands, 496 Tunica adventitia, 217 Tunica albuginea of testicle, 863 dartos, 72 propria, 753 vaginalis, 863 Tiirck's column, 655 method of cumulation of reflexes, 710 Tympanum or middle ear, 788 diagram of, 780 membrane of, 788, 790 muscles of, 790 structure, 788 Tyrosine, 418, 419, 422 u. Umbilical arteries, 890 cord, 888, 890 vesicle, 8S7 Uncinate convolution, 094 Unicellular organisms, 5 Unilaminar blastoderm, 883 Unimolecular reactions, 329 Uraemia, 588, 611 Urate of sodium, 598 Urates, deposit of, 598, 600 Urea, 166, 583 apparatus for estimatmg quantity, 585 chemical composition of, 583 formation of, by liver, 528, 586 isomeric with ammonium cyanate, 583 quantity, 586 Ureters, 565, 570 922 INDEX Ukktiiha. Uretbra, 665, &70 Uric acid, 100, 432, 51)1 couditioii in which il exists in uriuo, 5C'3 crystals, various forms of, 5U1 lieposit of, 5'JS forms m which It is ilepositeil, 591 origin of, 5S3, 593 presence in tlie spleen, 335 presence in the urine, 000 proportionate quantity of, 592 tests, 592 Uricolytic enzyme, 594 Urina i>otus, 5S3 Urinary apparatus, 505 cl seq. . Urinary bladder, 570 nerves, ii/. structure, ib. Urinary deposits, 5'JS et seq. Urme, 5S2 et seq. analysis of, 5S3 bile in, 002 blood in, 003 chemical sediments in, 000 colour, 5S2 composition, 683 cystine in, 599 expulsion, 5S0 How into bladder, 679 hippuric acid in, 694 inorganic constituents, 595 mineral salts in, ib. pathological, 600 phosphates in, 597, 599 physical characters, 5S2 pigments, ib. proteins, COO pus in, 001, 003 quantity, 5S2 vanes with blood-pressure, 672 reaction of, 5S2 in difl'erent animals, 5S3 made alkaline by diet, ib. saline matter, 5S3, 5SS solids, 5b2 specific gravity of, 5S3 variations of, ib. sugar in, 601, 002 tests for estimating, 602 tests for inorganic salts of, 597 urates, 698 urea, 583 uric acid in, 591 Uriniferous tubes, diagram of, 500 Urobilin, 534, 582 Urochrome, 682 Uro-erythrin, 582, 594 Uterine muscle, 890 rellexes, 721 Uterus, 807, 871 atrophy or involution of, 895 development in i)regnancy, 893 diagram of, 867, 887-890 structure, 871 Utricle, 791 Uvea, 812 V. Vaccination, 478 Vagina, 867 Vago-sympathetic of frog, 251 Vagus, electrical variations in, 377, S7S escape, 251 nerve. See Pneumogastric. VlSCKKAl, LaVKK ok I'KKICAKDIUM. Valentine's experiments on velocity of blojd (low, 281 Valine, 417 Valsalva's experiment, 388 Valves of heart, 213. i'lv lli'ari. Vas deferens, 804, 805, 879 Vasa ellerentia of testicle, 864, 865 Vasa vasorum, 218 Vascular system, in asphyxia, 389 Vaso-conslrictor nerves, 300, 302 Vaso-dilator nerves, 300, 303 Vaso-motor nerves, 204, 300 distribution of, 302 ellect of section, 307 et seq. experiments on, 300, 307 lutluence upon blood-pressure, 306 stimulation fati^^ue, 135 Vaso-motor nerve-centres, 301, 303, 305, 721 nervous system, 300 et sty. retlex action, 306 Vegetables as food, 479, 490 Vegetable cells, 6 protoplasmic movement in, 12, 13 Veins, 20S, 214, 218 et seij circulation hi, 299 et seq. velocity of, 281 distribution, 218 interlobular, 509 pressure in, 278 jmlmonary, 219 rhythmical action in, 299 structure of, 219 valves of, 219 el seq. Velocity head, 280 pulse, 284, 300 Velocity of blood in arteries, 281 in capillaries, ib. in vems, ib. of circulation, ib. of eiizyuie action, 510, 520 of nervous impulse, 159 Vena cava, 210 Venae rectae, 570 Venae stellulic, 569 Venous flow, 299 Ventilation, 379, 384 Ventral cerebellar tract, 658 Ventricles of the brain, 044 Ventricles of heart. See Heart. Ventricular diastole, 233, 23 1 systole, ib. Veratriue, effect of, on muscular contraction, 99 Vernon, heat rigor experiment, 139 on tissue-erepsin, 540 pancreatic secretion, 523 Vertical axis of eyeball, 851 Verwom, Max, strychnine and fatigue, 135 Vesical centre, 580 Vesicle, germinal, IS Vesiculu; semlnales, 805 Vestibular nerve, 063 Vestibule of osseous internal ear, 753, 790 Vibrations, conveyance of, to auditory nerve, 796 et seq. Vierordt'3 experiments on blood-circulatiou, 289 Vierordt's ha;matachometer, 287 Vieussen's aunulus, 190, 251, 302 Villi in chorion, function of, 888 of intestines, 494, 495 Vincent, Hwale, muscle proteins, 142 Visceral layer of pericardium, 208 mesoblast, 884 pain, 777 sensations, 777 INDEX 923 Vision. Vision, 810 an^le of, S'.'2 at different distances, aiiai>tatloii of eye to, 824 et srq. correction of aberration, 830 ct scq. defects of, 8-28 el .■.'(/. distinctness, liow seoirod, SM ct seq. duration of sensation in, 836 estimation of tlie size and form of objects, 854- 850 focal distance of, 824 range, 827 relation of nerve-cells and fibres, 854 single, wltli two eyes, SCO et seq. Visnal area, 735 apparatus, relations of nerve-cells and libres, 854 axis, 822, 851 Impressions, 752 judgments, 854 et scq. plane, 851 purple, 817, 847 sensations, 83(5, 841 et scq. word-centre, 741, 809 Visno-psychic region, 737 Visuo-sensory cortex, ib. Vital action, 327 force, 2 Vitamlne, 491 Vitellin, 429, 487 membrane, 871 Vitello-intestinal duct, 88G Vitreous humour, 811, 819 Vocal cords, 801 action in respiratory actions, 804 approximation of, etfect on height of note, 805 vibrations of, cause voice, 800 Voice, 799 et scq., 806 range of, 806 Voit's diet, 480, 618, 629 on "circulating protein," 622 Volkmann's hasmadromometer, 282 experiment on lymph hearts, 318, 319 Volta on galvanism, 116 Voluntary muscle, 63 et scq., 140 ct seq. nerves of, 70 Voluntary tetanus, 104 Vomiting, 556, 557 action of stomach in, ib. centre, ib. nerve actions in, ib. voluntary and acquired, ib. VorticelUe, 82 Vowels and consonants, 808 Vulpian's experiments on nervo regeneration, 149, 151 w. Wagner's hammer, 90 Wallerian degeneration method, 146, 149, 151, 156, 651, 652 Waller, dynaraograph, 132 electrocardiogram, 245 fatigue theory, 133 on the electrical currents of the eyeball, 849 on the passage of blood-corpuscles, 297, 298 ZvMOLvsia. Waller— continued on work of heart, 247 " sound-picture " theories of, 798 variation In nerve action, 159 Wander cells, 31 Water-hammer pulse, 291 Wave of blood causing the pulse, ib. velocity of, ih. Weber-Fechner law, 763 Weber's experiment on velocity of blood-How, 281 on heart-beats, 249 Weber's paradox, 112, 114 Weigert's method, 051, 739 Waisniann's gin'in jjlasm, 859, 861 somatoplasm, 861 Wertheimer's investigations into pancreatic secre- tion, 520 Wharton's jolly, 36 Whey protein, 4S2 White corpuscles. See Blood-corpuscles, white ; and Lymph-corpuscles. emigration of, 298 White fibro-cartilage, 37, 38 fibrous tissue, 29, 30 spot. 814 Widal's reaction, 476 Wooldridge's method of preparing tissue-fibrino- gen, 431 Word-centres, 809 Worms, circulatory system in, 230 Wright, Hamilton, sleep theory, 746 Wright's opsonins, 476 Wrisberg, cartilages of, 800, 805 pars intermedia of, 675 Xanthine, 166, 482 Xantho-proteic reaction, 425 Y. Yawning, mechanism of, 382 Yeast plant, cells of, in process of budding, 5, 439 Y'ellow elastic fibre, 29, 30 fibro-cartilage, 37,40 marrow, 41 spot of Siimmering, 814 Y^eo's experiment on gaseous exchanges in the heart, 254 Yolk-sacs, 888 et scq. Y'olk-spherules, 870 Y'oung-Helmholtz theory, 842 et seq. Zona fasciculata, 340 Zona pellucida, or striata, 19, 870, 881 Zonule of Zinn, 820 Zuntz, on mountain sickness, 400 Zymase, 439 Zymogen, 441, 449, 499, 509 Zymolysis, reversible, 614 PRINTKD BY OLIVER AND BOYD EDINmiROn Jt.