ESSENTIALS Veterinary Physiology D. NOEL PATON, M.D., B.Sc, LL.D., F.R.S. PROFESSOR OF PHYSIOLOGY, DNIVKRSITY, GLASGOW LATE LECTURER IN PHYSIOLOGY, ROYAL (DICK) VETERINARY COLLEGE, EDINBURGH AND JOHN BOYD ORR, D.S.O., M.C., M.A., M.D., D.Sc. DIRECTOR, ROWETT INSTITUTE FOR RESEARCH IN ANIMAL NUTRITION, ABERDEEN RESEARCH LECTURER ON PHYSIOLOGY OF NUTRITION, UNIVERSITY, ABERDEEN THIRD EDITION REVISED AND ENLARGED NEW YORK WILLIAM WOOD & COMPANY 1920 'f ' '.' : '. .\ PREFACE TO THE FIRST EDITION Between the Physiology of Man and that of the Domestic Animals there is no fundamental difterence, and most of our knowledge of human physiology has been acquired from experiments upon the lower animals. But while the tissues of a mao, a dog, and a horse act much in the same manner, the mode of nutrition of these tissues is somewhat different, and requires special attention in the case of each. In this volume the attempt is made to give the essentials of general physiology and of the special physiology of the domestic animals in a form suitable to the requirements of Students and Practitioners of Veterinary Medicine. The book is not intended to take the place of the demonstrations and practical work from which alone physiology can be properly learned, but merely to supplement these and to focus the information derived from them. The student must take every opportunity of acquiring a really practical knowledge, and, to facilitate the more direct association of the practical and systematic study of physi- ology, throughout these pages references are made to de- scriptions of the experimental and chemical work which the student should try to do for himself or have demonstrated to him. The histological structure of the tissues and organs which is now studied practically in every school is here described only in so far as it is essential for the proper understanding of their physiology. D. N. P. 461269 PREFACE TO THE THIRD EDITION The Preface to the First Edition sufficiently explains the scope and purpose of the book. The present Edition has been almost entirely rewritten in order to bring it up to date and to give greater prominence to those parts of Physiology which have the most direct bearing upon veterinary practice. Our thanks are due to Dr. Burns for the section on hydrogen ion concentration in Appendix III., and to Mr. William Dunlop of Dunure for valuable suggestions on the section dealing with the limbs of the horse. D. N. P. J. B. O. September 1920. CONTENTS PART I The Growth of Physiology . PART II SECTION I Protoplasm 1. The Nature of Protoplasmic Activity 2. The Structure of Protoplasm 3. The Chemistry of Protoplasm 1. Cell Protoplasm 2. Nucleus 3. Reproduction of Cells SECTION II The Cell SECTION III The Tissues Vegetative Tissues — Epithelium . 32 1. Protective — Squamous Epithelium 32 2. Absorbing— Colu mnar Epithelium 33 3. Secreting Epithelium and Glands 34 4. Motile— Ciliated Epithelium 37 Connective Tissues 37 1. Mucoid Tissue 37 2. Fibrous Tissue 38 i. Fibres . 39 ii. Spaces 40 CONTENTS iii. Cells . Modifications of Cells — a. Endothelium , h. Fat Cells and Fat c. Pigment Cells . Cartilage . i. Hyaline Cartilage ii. Elastic Fibro-Cartilage iii. White Fibro-Cartilage Bone i. Development and Structure ii. Chemistry iii. Metabolism . B. The Master Tissues — Nerve and Muscle — General Arrangement Nerve — 1. Development 2. Structure .... 3. Chemistry .... 4. Physiology of Neurons A. Single Neurons or Neurons in Nerves a. Nerve Fibres — 1. Manifestation of Activity . 2. Excitation . .3. Conduction 4. Classification of 5. The Nature of the Nerve Impulse h. Nerve Cells Degeneration and Regeneration of N Changes in the Cell . B. Action of Neurons in Series . The Neural Arcs A. Arrangement . B. General Action I. The Spinal Arc — Reflex Action . Trophic Action Peripheral Reflexes .... TI. The Cerebral and Cerebellar Arcs . A. The Ingoing Side of the Arcs . I. Body Receptor Mechanisms i. Visceral ii. Cutaneous — Pain Touch Temperature CONTENTS iii. Muscle and Joint .... Connection of Body Receptors with Central Nervous System — 1. Ingoing Nerves .... 2. Upgoing Fibres in Spinal Cord 3. Connections with Brain-Stem and Cerebrum 4. Cerebellar Synapses Labyrintho-Cerebellar Mechanism 1. Labyrinth (1) Structure (2) Connection (3) Physiology 2. The Cerebellum (1) Structure (2) Connections (3) Physiology III. Distance Receptors of the Head — I. For Chemical Stimuli — 1. Buccal Mechanism — Taste 2. Nasal Mechanism — Smell II. For Vibration of Ether — Vision A. General Considerations B. Anatomy of the Eye . C. Physiology .... (I.) Monocular Vision . Formation of Images upon the Retina 1. The Dioptric Mechanism Accommodation . 2. Stimulation of the Retin; 1. Reaction to Varying Illumination 2. Localising the Direction of Illumination 3. Colour Sensation . (II.) Binocular Vision Single Vision with Two Eyes (III.) Connections of the Eyes with the Central Nervous System 1. Optic Nerves and Tracts . 2. Visual Centre III. For Vibration of Air — Hearing L General Considerations. 2. The External Ear 3. The Middle Ear . . . 4. The Internal Ear 5. Connections with the Central Nervous System 6. Auditory Centre in Cortex 105 106 107 112 117 117 117 117 119 121 125 125 126 127 131 133 136 136 139 143 144 144 144 146 151 151 155 155 158 158 162 162 164 166 167 167 170 172 173 CONTENTS IV. The Localisation of Receiving Areas in the Cortex 176 V. The Integration of Sensations in the Cortex . 179 1. Structural Development .... 181 2. Functional Development .... 182 3. Storing and Associating Part of Cortex . .18-5 4. Relationship of Consciousness to Cerebral Action . 185 5. Time of Cerebral Action . . . . .186 6. Fatigue . . . . . . .186 7. Sleep 187 8. Hypnosis. . . . . . 188 VI. The Discharging Side of the Cerebral Arc . . 189 i. The Basal Ganglia . . . . .189 ii. The Cortex Cerebri ..... 189 iii. Fibres from Discharging Area . . . 194 iv. Outgoing Nerves . . . • .195 Cranial Nerves ...... 200 The Effectors— Muscle ...... 202 i. Development and Structure . . . . 2()2 ii. Chemistry . . . . . .207 iii. Physical Characters and Physiology . . . 210 iv. Death of Muscle . . ' . . .214 v. Muscle in Action ..... 215 A. Visceral Muscle ..... 215 B. Skeletal Muscle— 1. Direct Stimulation of Muscle . . 217 2. Methods of Stimulating Muscle . . 218 3. The Changes in Muscle when Stimulated . 219 4. Mode of Action . . . .231 5. Special Mechanism of the Horse . . 233 6. Work Done . . . . .242 7. Heat Produced .... 246 8. Relationship of Work Production to Heat Production . . . .248 9. The Efficiency of the Horse as a Machine . 252 K). Capacity of the Horse for Work . . 252 11. Chemical Changes and Source of Energy . 254 General Metabolism ...... 264 A. Exchange of Energy — I. Basal Metabolism . . . . . .264 II. Factors Modifying Metabolism .... 266 1. Muscular Work ..... 266 2. Rate of Cooling . . . . .267 Loss of Heat . . . . .267 Heat Production . . . . .268 Heat Regulation . . . . .269 CONTENTS 3. Taking of Food . 272 4. Prolonged Fasts . 272 5. Semi-starvation . 274 I Exchange of Material . 275 Water .... . 275 Amino Acids . 275 Salts .... . 279 Accessory Factors . 281 PART III. THE NUTRITION OF THE TISSUES. SECTION I. Food. The Nature of Food .... . 283 A. Food-Stuffs Yielding Energy . 283 1. Nitrogenous Compounds . 283 2. Fats and Allied Bodies . 285 3. Carbohydrates . 285 B. Food-Stuffs not Yielding Energy . 288 4. Ash (Inorganic Elements) . . 288 5. Water .... . 289 6. Accessory Factors . 289 Classification of Feeding Stuffs for Herbivora . . 290 SECTION 11. Digestion. . Structure of the Alimentary Canal . 291 . Physiology ..... . 301 A. Digestion in Carnivora and Omnivora . 302 I. Digestion in the Mouth . . 302 (a) Mastication .... . 302 (6) Insalivation .... . 302 II. Swallowing .... . 306 III. Digestion in the Stomach . 308 A. Stomach during Fasting . 309 CONTENTS IV. B. Stomach atttr Feeding 1. Vascular Changes 2. Secretion (1.) Characters of Secretion . (2.) Source of Constituents (3.) Course of Gastric Digestion (rt) Amylolytic Period . (6) Proteolytic Period . (4.) Digestion of the Wall of the Stomach (5.) Antiseptic Action of the Gastric Juice (6.) Influence of Food on the Gastric Juice (7.) Nervous Mechanism of Secretion (8.) Chemical Stimulation 3. Movements of Stomach 1. Character . 2. Nervous Mechanism C'. Absorption from the Stomach D. Regurgitation of the Gastric Conten 1. Into the Gullet . 2. Vomiting Intestinal Digestion A. Pancreatic Secretion B. Bile .... C. Succus Entericus D. Bacterial Action E. Fate of the Digestive Secretions F. Movements of the Intestine . 1. Small Intestine . 2. Large Intestine . 3. Defsecation B. Digestion in Herbivora 1. Digestion in Ruminants 2. Digestion in the Horse . SECTION III. Absorption op Food. 1. State in which Food is Absorbed 2. Mode of Absorption 3. Channels of Absorption Storage of Surplus Food The Liver as a Regulator of the Supply to the MuscL 1. Regulation of the Supjjly of Sugar 2. Regulation of the Supply of Fats 3. Regulation of the Supply of Proteins . CONTENTS XV PAGE The Fieces ....... 361 Availability of Food .... 363 Digestion Experiments .... 364 Food Reqiiireinents .... 368 1. Method of Determining Requirements 369 2. Rations .... 371 3. Feeding Standards 375 4. Manurial Values 380 SECTION IV. Manner in which Nourishing Fluids are Sent ro THE Tissues. The Circulation. I. General Considerations II. The Heart . A. Structure B. Relations C. Physiology I. The Cardiac Cycle— (A) Frog (B) Mammal . Rate . Sequence of Events Duration of Phases Changes in the Shape The Cardiac Impulse , 6. Changes in Intracardiac Pressure 7. Action of the Valves 8. The Flow of Blood through the Heart 9. Sounds of the Heart . The Work of the Heart of the Chamber; II. III. IV, The Influence of the Central Nervous System The Maintenance and Control of Cardiac Rhythm 1. The Initiation of Contraction 2. The Conduction of Contraction V. The Nature of Cardiac Contraction III. Circulation in the Blood and Lymph Vessels 1. Structure ...... 2. Physiology ...... A. Blood Pressure ..... 1. General Distribution of Pressure . 2. Rhythmic Variations of Pressure . 382 384 384 393 39,3 393 394 394 395 396 397 398 399 402 404 407 410 418 424 424 427 427 431 431 432 432 432 434 CONTENTS PAGE (a) Changes Synchronous with the Heart 1. The Arterial Pulse . . . 434 2. The Capillary Pulse . . .444 3. The Venous Pulse . . . 444 (b) Changes Synchronous with Kespirations — 1. Arterial .... 446 2. Venous .... 447 3. The Mean Blood Pressure .... 447 I. Pressure in the Arteries — (1.) Methods of Determining . . 447 (2.) Normal Pressure . . . 449 (3.) Factors Controlling . . . 450 i. Heart's Action . . . 451 ii. Peripheral Resistance — Condition of the Arteries . . .451 1. Method of Investigating . 452 2. Normal State . . . 453 3. Nervous Control . . 454 Vaso-Constrictor . . 455 Vaso-Dilator . . .458 II. Pressure in the Capillaries . . . 460 III. Pressure in the Veins . . . 463 IV. Pressure in the Lymphatics . . . 464 B. Flow of Blood . . . . . .464 1. Velocity ...... 465 2. Special Characters .... 467 G. Special Characters of Circulation in Certain Situations 468 D. Extra-Cardiac Factors Maintaining the Circulation , 470 1. Movements of Respiration . . . 470 2. Intermittent Muscular Exercise . . . 470 E. Influence of Posture on the Circulation . . 471 F. Fainting ...... 472 (t. Time taken by the Circulation . . . 472 H. Flow of Blood through Different Organs . . 473 SECTION V. Fluids Carrying Nourishment to the Tissues. Blood and Lymph. A. Blood . . . . . . . .474 I. General Characters ...... 474 II. Clotting . . . . . . .475 III. Plasma and Serum ...... 479 CONTENTS xvii PAGE IV. Cells of the Blood .... . 483 Leucocytes ..... . 483 Blood Platelets .... . 484 Erythrocytes .... . 485 V. Gases of the Blood .... . 492 VI. Source of the Blood Constituents . 498 VII. Total Amount of Blood . 501 VIII. Distribution of the Blood . 503 IX. Fate of the Blood Constituent.s . 503 B. Lymph ...... . 507 1. General Character .... . 507 2. Formation of Lymph .... . 508 C. Cerebro-Spinal Fluid .... . 511 SECTION VL Respiration. A. External Respiration . . . . . . .513 I. The Structure of the Respiratory Mechanism . .513 II. Physiology — 1. Physical Considerations . . . . .515 2. Passage of Air into and out of the Lungs . . 516 i. Movements of Respiration .... 516 In.spiration . . . . .516 Expiration ..... 521 Special Respiratory Movements . . . 522 ii. Amount of Air Respired .... 522 iii. Interchange of Air by Diffusion . . . 523 iv. Breath Sounds ..... 524 V. Rhythm of Respiration .... 525 vi. Nervous Control of Respiration . . . 526 1. Chemical Regulation .... 527 2. Reflex Regulation .... 532 3. Interaction of Circulation and Respiration . . 535 A. Influence of Respiration on Circulation . . 535 B. Influence of the Heart on Respiration . . 536 4. Interchange between the Air and the Blood . . 537 i. Effects of Respiration on the Air Breathed . 537 ii. Effects of Respiration on the Blood . . 538 iii. The Causes of the Respiratory Exchange . . 539 1. Partial Pressure of Gases in the Air Vesicles . 539 2. Partial Pressure of Gases in the Blood . 541 B. Intermediate Respiration ...... 545 C. Internal Respiration ...... 547 CONTENTS D. Extent of Respiratory Exchange E. Ventilation . F. Asphyxia PAGE 547 548 548 Voice. A. Structure of the Larynx B. Physiology of Voice . 550 552 SECTION VII. Excretion of Matter from the Body. A. Excretion by the Lungs (see Respiration). B. Excretion by the Intestine {see Intestine). C. Excretion by the Kidneys .... . 554 I. Urine . 554 1. General Consideration . 554 2. Physical Characters . 557 3. Composition .... . 558 II. Formation of LTrine .... . 567 1. Structure of the Kidney , . 571 2. Physiology of Secretion . . 572 (a) Malpighiau Bodies . . 573 (fc) Tubules ... . 575 III. Excretion of Urine .... . 581 D. Excretion by the Skin .... . 582 Sweat Glands ..... . 583 Sebaceous Glands ..... . 585 SECTION VIIL The Regulation of Growth and Function. I. Heredity II. The Nervous System III. Chemical Regulation : The Endoci Developed — (a) From the Nervous System 1. Chromaffin Tissue 2. Hypophysis . {h) From the Buccal Cavity— 3. Thyreoid 4. Pituitary (c) From Intestinal Mucosa — 5. Pancreas 6. Mucosa of Small Inte; . 586 . 587 rinetes . ■ . 588 — . 590 . 594 . 595 . 599 . 601 stine . 601 CONTENTS {(l) From the Branchial Arches — 7. Thymus . . . . .602 8. Parathyreoids . .... 603 (e) From the Mesothelium of the Genital Ridge — 9. Gonads . . . . .605 10. Inter-renals . . . . .609 The Interaction of the Endocriuetes . . . 611 The Mode of Action of the Internal Secretions . .611 Protective Modifications of Metabolism — Immunity . . 612 PART IV. THE ANIMAL AS PART OF THE SPECIES. A. Reproduction. I. Determination of Sex II. The Gonads III. The Secondary Sexual Organs IV. The (Estrous Cycle V. Impregnation B. Development. I. Early Stages of Development II. Attachment of Embryo to Mother III. The Nourishment of the Foetus IV. Growth of the Fcetus V. Metabolism in Pregnancy VI. The Young Animal at Birth VII. Fojtal Circulation VIII. Gestation and Delivery . IX. Lactation . Appendices Index .... 617 618 621 622 623 624 626 628 630 631 631 631 633 634 641 655 PART I. SECTION I. The Growth of Physiology. Physiology formerly embraced the study of all nature ((pua-ig), but it is now restricted to the study of life and the activities of living things. It is really an older science than anatomy, for even before any idea of pulling to pieces, or dissecting plants and animals had suggested itself to our forefathers, speculations in regard to the causes and nature of the various vital phenomena were indulged in, some of which foreshadowed in a truly wonderful way the scientific discoveries of to-day. Thus, about 500 b. c. , Empedocles not only formulated a doctrine of evolution, but indicated that the struggle for existence played a part in the process. About a century later Hippocrates insisted on the importance in the treatment of disease of studying the normal action of the body, and recognised the importance of the vis medicatrix natiircB. His followers adopted the idea of a pneiwia, a subtile agent attracted to the lungs and distributed to the body as the basis of all vital phenomena. The physiology of to-day is the offspring of such speculations. Organ and Function. — The first great and true advance was through anatomy. Galen, about 200 a.d., dissected and made observations on the physiology of animals. He described various organs and endeavoured, more or less successfully, to ascertain their mode of action by experiments on living animals. He may well be called the father of physiology. The Dark Ages fell upon Europe, and little further advance was made till, in the sixteenth century, the group of Italian anatomists showed how the body is built up of 1 1 2 VETERINARY PHYSIOLOGY definite organs which they described in detail, and thus prepared the way for the work of Harvey, which led to such important discoveries, and which established the relationship of function to organ. The connection between organ and function having been demonstrated, the question of why these various functions are connected with the respective organs — why the liver should secrete bile and the biceps muscle contract, next forced itself upon the attention. Tissues and Function. — Again anatomy paved the way to the explanation. The dissecting knife and the early and defective microscope showed that the organs are composed of certain definite structures or tissues, differing widely from one another in their physical characters and appearance, and, as physiologists soon showed, in their functions. By the end of the seventeenth century Leuwenhoek and Malpighi had so advanced the knowledge of the tissues that Haller, in the middle of the eighteenth century, was able to indicate that the function of an organ is really the function of the tissue of which it is composed. Early in the nineteenth century Johannes Miiller, taking a comprehensive survey of a great mass of observations which had accumulated, and adding to them the results of his own investigations, created the modern science of physiology. Cells and Function. — ^Physiologists and anatomists alike devoted their energies to the study of these various tissues, and, as the structure of the microscope improved, greater and greater advances were made in their analysis, till at length Schwann was enabled to make his world-famous generalisa- tion, that all the tissues are composed of certain similar elements more or less modified, which he termed cells, and it became manifest that the functions of the dif event tissues are de/pendent on the activities of their cells. The original conception of the cell was very different from that which we at present hold. By early observers it was described as composed of a central body or nucleus, surrounded by a granular cell substance with, outside all, a cell membrane. As observations in the structure of the cell were extended, it soon became obvious that the cell membrane THE GROWTH OF PHYSIOLOGY 3 was not an essential part ; and later, the discovery of cells without any distinct nucleus rendered it clear that the essential part is the cell substance. This substance von Mohl named protojjlasm, by which name it has been since generally known. Protoplasm and Function. — So far, physiology had followed in the tracks of anatomy, but now another science became her guide. Chemistry, which during the early part of the nineteenth century advanced Avith enormous strides, and which threw such important light upon the nature of organic substances, lent her aid to physiology ; and, morphologists having shown that the vital unit is essentially a mass of protoplasm, the science of life has become the science of the chemistry of irrotoplasm. The prosecution of physiology on these lines has changed the whole face of the science. Physiology is no longer the follower of anatomy. It has become its leader, and at the present time, as we shall afterwards see, not only the various activities, but also the various structural differences of the different tissues, are to be explained in terms of variations in the chemical changes in protoplasm. Already these chemical studies have shown that proto- plasm is not a single substance, but a mixture of many substances in a constant state of flux and change, and that its condition is largely determined by the physical relations of the substances in the mixture. Within recent years the application of molecular physics to physiology has greatly advanced the knowledge of many of the obscure characters of living matter. In the study of physiology the order of its development must be reversed, and from the study of protoplasm the advance must be made along the following lines : — 1. Protoplasm — the physical basis of life ; its activities and nature. 2. Cells. — The manner in which protoplasm forms the vital units of the body. 3. Tissues. — The manner in which these are formed by 4 VETERINARY PHYSIOLOGY cells. Their structure, physical and chemical pro- perties, and vital manifestations. a. The Vegetative Tissues, supporting, binding together, protecting and nourishing the body. h. The Master Tissues — nerve and muscle — through which the external world acts upon the body, and the body reacts upon the surround- ings. 4. Nutrition of Tissues. a. The manner in which substances necessary for the tissues are supplied — Food. Digestion. h. The manner in which the nourishing fluids are brought into relationship with tissues — Circulation, c. The fluids bathing the tissues — Blood and Lymph. cl. The supply of oxygen and the elimination of carbon dioxide. Respiration. e. The manner in which the waste products of tissues are eliminated — ^Excretion, Hepatic, Renal, Pulmonary, Cutaneous. 5. Reproduction and Development. Students who have not the knowledge of Chemistry and Physics necessary for the Study of Physiolog-y are referred to the Appendices. PART II. SECTION I. Protoplasm. I. Nature of Protoplasmic Activity. The first step in the study of physiology must be to acquire as clear and definite a conception as possible of the nature of protoplasmic activity in its most simple and uncomplicated form, for in this way an idea of the essential and non-essential characteristics of life may best be gamed. The common yeast (Saccharomyces Cerevisios) aftbrds such a simple form of living matter. This plant consists of very minute oval or spherical bodies frequently connected to form chains, each composed of a harder outer covering or capsule, and of a softer inner substance which has all the characters of protoplasm. 1. Manifestations of Life. — Its vital manifestations may be studied by placing a few torula? in a solution, containing glucose, CgHi^Og, some nitrogen- containing substances such as urea, CONoH^, or ammonium nitrate, NH^NOg, with traces of disodium phosphate, Na2HP04, and of potassium sulphate, K2SO4 (Practical Physiology). If the vessel be kept all night in a warm place, the clear solution will in the morning be seen to be turbid, and probably covered with froth. An examination of a drop of the fluid shows that the turbidity is due to the presence of myriads of torulse. In a few hours the few torulse placed in the fluid have increased many hundredfold. The whole mass of yeast has grown in amount by the growth and multiplication of the individual units. 6 VETERINARY PHYSIOLOGY This power of growth and reproduction under suitable conditions is an essential characteristic of living matter. 2. Conditions necessary for Manifestations of Life. — (a) If the yeast be mixed with the solid constituents of the solution in a dry state, no growth or reproduction occurs. Water is essential. (b) If the yeast, mixed with the solution, be kept at the freezing point no growth takes place, but this proceeds actively at about 36° C. A certain range of temperature is necessary for the vitality of protoplasm. In the absence of these conditions, protoplasm is only potentially alive, and in this state it may remain for long periods without undergoing any change, as in the seeds of plants and in dried bacteria. 3. Essentials for Growth. — In order that the growth of the yeast may take place, there must be : — {a) A Supply of Material from which it can be formed. The chemical elements in protoplasm are carbon, hydrogen, oxygen, nitrogen, sulphur, and phosphorus. These elements are contained in the ingredients of the solution used. If yeast be sown in distilled water, even if it be kept at a temperature of 36° C, it does not grow. (6) A Supply of Energy to bring about the construc- tion. The source of the energy is indicated by an examina- tion of the fluid in which the yeast has grown. The sugar, CgHioC^e' ^^^ decreased in amount, being converted into alcohol, CgHgO, and carbon dioxide, CO2 — C6Hi206=2COo + 2C2H60. It is this oxidation of the carbon to carbon dioxide which yields the energy, just as the combustion of the coals in the furnace yields the energy for an engine. But in this case the Oo comes from the CgH^.jOe' ^'^^ "^^^ from outside, and the energy evolved in the reaction is only about a tenth of that liberated by the complete oxidation to CO, and HjO which occurs in the animal body. The formation of alcohol from sugar does not lead to the liberation of energy. So far as this is concerned, the alcohol may be considered as a by-product. PROTOPLASM The behaviour of the yeast plant shows that such protoplasm, when placed in suitable conditions, has the power of breaking down certain coviplex substances, and of utilising the energy so liberated for building itself up, and thus increasing and growing. It is this power of using this energy for growth which has enabled living matter to exist and to extend over the earth. 4. Liberation of Energy by Protoplasm. — How is this oxidation and liberation of energy effected ? The answer to this question has been given by the demonstration by Biichner that the expressed juice of the yeast torulce acts on the sugar in the same way as the 1 ~~ — --^^ •••■ .•••'' \ \ '■•A -r ,■■■'-'" •■.\ Fig. 1. — To show the relationship of the rate of enzyme action to tempera- ture. The vertical lines represent different temperatures. The dotted line represents the rate of enzyme action as modified by temperature. The continuous line shows the destruction of the enzyme as the temperature rises. The dash line shows the actual rate of enzyme action as modified by these two factors. living yeast. The yeast therefore manufactures something which splits the sugar. This something belongs to the group of Enzymes or Zymins which play so important a part in physiology generally. (1) Conditions of Enzyme Action. — For the manifestation of their activity these enzymes require the presence of water and a suitable temperature — in the case of the yeast enzyme about 36° C. is the best. At lower temperatures the reaction becomes slower and is finally stopped, and at a higher temperature it is delayed and finally arrested by the destruction of the enzyme (fig. 1). 8 VETERINARY PHYSIOLOGY (2) Nature of Enzyme Action. — (i.) Enzymes act by hastening reactions which go on slowly without their presence, but they do not themselves take any direct part in the reaction ; they modify its rate but not its extent. Hence, a very small quantity may bring about an extensive change in the substance acted upon, (ii.) The reaction does not pass beyond the point of equilibrium. Thus, when the enzyme maltase acts upon malt sugar, it converts it only in part into dextrose, (iii.) With certain enzymes at least, the action may actually be reversed ; the enzyme, which splits esters into their component acid and alcohol, may cause a linking of those components to form esters. (iv.) The rapidity of the reaction is retarded as it proceeds sometimes by the accumulation of H ions, sometimes by the accumulation of the products of the change. When these are removed the action may again be accelerated. The general action of enzymes is catalytic. It may be com- pared to the action of an acid in the inversion of cane sugar — Cx2H220n + H,0 = 2(CeH,A)- Here an acid merely hastens a reaction which would go on slowly in the presence of water alone. (3) Mode of Action of Enzymes. — (a) The precise way in which such catalytic actions are brought about is still not quite clear, but there is evidence that the catalyser acts as a middleman between the reacting substances — in the case of HoO., taking up the and then giving it off and in the case of the decomposition of cane sugar taking up H^O and handing it on. In the same way in the oxidation of glucose which occurs when it is boiled with an alkali, a metallic oxide, such as cuprous oxide, may take oxygen from the air, becoming cupric oxide, and then hand the oxygen on to the glucose, thus making the oxidation more rapid. (b) While such catalysers as the inorganic acids act upon many different substances, the enzymes have generally a specific action upon one substance alone, the substrate of the enzyme. It is as if each enzyme fitted one special substrate as a key fits one special lock. They are generally PROTOPLASM 9 designated by attaching the suffix ase to the name of their substrate, thus malta.se is the enzyme that acts upon malt sugar. Our knowledge of the chemistry of enzymes is not complete, because when attempts are made to isolate them it is frequently found difficult to separate them completely from their substrate. Maltase has been shown not to be of the nature of a protein. (4) Essential Nature of Enzymes. — They are colloids (see p. 12), and their colloidal character helps to explain their activity. The energy liberated by the enzyme of yeast is used by the protoplasm for growth. 5. Metabolism of Protoplasm While ordinary proto- plasm gets its energy by breaking down complex molecules and liberating their stored energy, green plants, by the action of their chlorophyll, are able to store the energy of the sun's rays by building up complex molecules such as sugar and starch. It is through these green plants that the energy of the sun is made available for all living things upon the earth. Protoplasm is not only growing, it is also constantly breaking down, and, if yeast Ido kept at a suitable tempera- ture in water without any supply of material for construction, it gives off carbon dioxide and decreases in bulk on account of these disintegrative changes. These are as essential a part of its life as the building-up changes, and it is only when they are in progress that the latter are possible. Protoplasm {living matter) is living only in virtue of its constant chemical changes {metabolism), and these changes are on the one hand destructive {katabolic), on the other constructive {anabolic). Living matter thus differs from dead matter in this respect, that, side by side with destructive changes, con- structive changes are always going on, luhereby its amount is maintained or increased, so that it has been able to spread all over the surface of the earth. Hence our conception of living matter is not of a definite chemical substance, but of a set of substances constantly 10 VETERINARY PHYSIOLOGY undergoing internal changes. It might be compared to a whirlpool constantly dragging things into its vortex, and constantly throwing them out more or less changed, but itself continuing apparently unchanged throughout. Hoppe- Seyler expresses this by saying : " The life of all organisms depends upon, or, one can almost say, is identical with, a chain of chemical changes." Foster puts the same idea in more fanciful language : " We may speak of protoplasm as a complex substance, but we must strive to realise that what we mean by that is a complex whirl, an intricate dance, of which what we call chemical composition, histological structure, and gross configuration are, so to speak, the Death, — While the continuance of these chemical changes in protoplasm is life, their stoppage is death. For the con- tinuance of life the building-up changes must be in excess of, or equal to, the breaking-down — the evolution of energy must be sufficient for growth or maintenance. It is only the surplus over this which is available for external work. In the young the surplus energy is largely used for growth and develojDment ; in adult life for work. When failure in the sup2)ly or in the utilisation of the energy-yielding material occurs, the protoplasm dwindles and disintegrates. Death is sudden when the chemical changes are abruptly stopped, slow when the anabolic changes are interfered with. The series of changes which occur between the infliction of an incurable injury and complete disintegration of the protoplasm constitute the processes of Necrobiosis, and their study is of importance in pathology. Stimuli. — The rate of the chemical processes in protoplasm may be quickened or slowed by changes in the surroundings, and such changes are called stimuli. If the stimulus increases the rate of change, it is said to excite ; if it diminishes the rate of change, it is said to depress. Thus the activity of the changes in yeast may be accelerated by a slight increase of the temperature of the surrounding medium, or it may be depressed by the addition of such a substance as chloroform. PROTOPLASM 11 II. Structure of Protoplasm. Protoplasm occurs as a semifluid transparent viscous material, usually in small individual particles — Cells — more or less associated. It may, however, occur as larger con- fluent masses — Plasmodia. Protoplasm in its simplest state may be regarded as a fluid, since fine particles in it are seen to move freely in Brownian movement (p. 13 (3)), and if it contains drops of water they assume a spherical form ; certain plasmodial masses of protoplasm among the myxomycetes in which granules exist may creep through cotton wool and emerge without their granules, having actually filtered them off. i^) CJ^^^. '^ . rrt 13 a-^ III ll ^^ '^ .r"^ Sriffi S^ £.-a (^ ^ rt o >^ CJ 1 *j ._ rt rt ^ _a. r ^ o 2 1 PL, Sh o o o o "c ^ ^2; '^ o For a " Classification of Proteins," see Appendix. The tests for the Proteins must he learned practically. B. Synthesis of Proteins. — Emil Fischer and his co-workers have succeeded in building up from the amino acids a series of bodies containing several of the amino acid molecules, linked to one another in series, the hydroxyl, OH, of 1 For a short account of the chemistry of these products of disintegra- tion, see Appendix. PROTOPLASM 19 one being linked on to the amidogen of the other with the giving off of HjO, thus : — :^>- H 1 OH H j H H u 1 H t t 1 1 N— C- 1 H -C— OH Amino-acetic acid. Amino-acetic acid. Glyciu. Glycin. Glycyl-glycin. This he calls glycyl-glycin, — the amino acids which have lost the OH of the acid being designated by the terminal yi- _^ Such compounds he calls peptides, characterising them, according to the number of molecules linked, as di-, tri-, tetra-, and poly-peptides. Some of the higher of these give the biuret test for proteins from the presence of the linked CO.NHo group ; and if an acid with the benzene ring is in the chain, they also give the xantho-proteic test. He has also succeeded in building the pyrrol derivative, pyrrolidine-carboxylic-acid, or prolin, into polypeptides. 2. Fats and Lipoids. In addition to ordinary fats (see p. 41), protoplasm also contains a group of substances which are, like the fats, soluble in alcohol and ether, and which have been called Lipoids. These are generally most abundant in the outer layers of protoplasmic units, where they help to form a covering membrane. One of the most important is Cholesterol, This is a mono- hydric unsaturated alcohol, which, when dissolved in hot alcohol, tends to crystallise out on cooling in flat square plates, generally with a notch out of a corner. Some of the lipoids contain phosphorus, and have been grouped as Phosphatides. The most important of these is Lecithin. This is a fat in which one of the acid radicles is replaced 20 VETEEINARY PHYSIOLOGY by phosphoric acid linked to cholin — hydroxyethyl- trimethyl-ammonium-hydroxide. C Fatty acid. < Fattv aci( Lecithin. Glycerol < Fatty acid. ( Phosphoric acid. I Cholin. Cholin. H H OH 1 1 HO— C— C- 1 /cu. 1 1 \CH3 H H ydroxyethyl trimethyl-ammonium hydroxide. Cholin has some action upon visceral muscle, and some of the symptoms occurring in degenerative changes of the nervous system may be due to its presence. It is closely allied to muscarin, a very powerful jjoison of vegetable origin. In protoplasm, the lipoids are intimately associated with the proteins, and form part of the colloidal complex. By their tendency to adsorb to the surface, and thus to form membranes, they help to differentiate masses of protoplasm from their surroundings and to present a more or less per- meable membrane, through which exchanges between the living matter and its surroundings go on. 3. Carbohydrates. Closely connected with the proteins and fats, and some- times actually built into the molecule of the former, are small quantities of carbohydrates, bodies belonging to the class of starches and sugars (p. 285). C. CRYSTALLOIDS. These may either exist in true solution or be combined with the proteins and lipoids in the colloidal state. Those PROTOPLASM 21 in solution may not be ionised, e.g. glucose, or they may be ionised into an-ions and cat-ions. Among the more important of tlie cat-ions are potassium, calcium, and sodium. The presence of such crystalloids free in true solution chiefly determines the osmotic pressure of the mass of protoplasm, and hence this may vary from time to time according to whether these substances are united to the proteins or are free. The osmotic pressure in the protoplasm of a cell may be ascertained by subjecting it to fluids of different osmotic equivalents and determining whether it swells by the passage of fluid inwards or shrinks by the passage of water outwards, thus ascertaining the molecular concentration of the surrounding fluid and so of the cell itself. This has been called the method of Plasmolysis. The red cells of the blood have a very definite osmotic pressure, and when subjected to a fluid of lower osmotic pressure, they swell, while in a fluid of higher osmotic pressure, they shrink. This is called the method of Hcemolysis. IV, Protoplasmic Activity. This complex of substances called protoplasm is, during life, in a constant state of active chemical change. All its conditions make for great instability : its colloidal nature, its demarcation from its surroundings as the result of surface tension with adsorption, its frequent division into innumerable vesicles separated from one another by very unsubstantial and temporary septa ever changing as the result of internal chemical changes, all of these combine to produce a very labile condition. Thus oxidation may be going on in one part of the mass, drawing oxygen from another, and thus leading to a simultaneous process of reduction. Such a mechanism is pregnant with possibilities as a transformer of energy and as a producer of movement. 22 VETERINARY PHYSIOLOGY That such movements really can be produced, even in dead matter, by the combination of changes brought about by osmosis and by alteration in surface tension, may be demonstrated by the behaviour of mixtures of such substances as camphor and water. SECTION 11. The Cell. Protoplasm occurs in the animal body as small separate masses of Cells. These vary considerably in size, but in the higher animals, on an average, they are from 7 to 20 micro- millimetres^ in diameter. The advantage of this subdivision is obvious. It allows nutrient matter to reach every particle of the protoplasm. In all higher animals each Cell has a perfectly definite structure. It consists of a mass of proto- plasm, in which is situated a more or less defined body, the nucleus. A. Cell Protoplasm. 1. Structure. — The general characters of protoplasm have been already described (p. 11). In some cells condensation at the surface is marked, and a so-called membrane surrounds them. At some point in the protoplasm of many cells, one or two small spherical bodies, the centrosomes (fig. 3), are found, from which rays pass out in ditferent directions. For the detection of these bodies special methods of staining and the use of very high magnifying powers are required. They will be again considered when dealing with the reproduction of cells. The cell protoplasm frequently contains granules, either formed in the protoplasm, or consisting of material ingested by the cells. In the protoplasm, vacuoles are sometimes found, and from a study of these vacuoles in protozoa, it appears that 1 The micro-millimetre is the j oW*-^' ^^ ^ millimetre. 23 24 VETERINARY PHYSIOLOGY they are often formed round material which has been taken into the protoplasm, and that they are filled with a fluid which can digest the nutritious part of the ingested particles. In some cells, vacuoles may appear in the process of disintegration. 2. Activities. — (a). Many cells have the power of ingest- ino" foreign material. This phagocytic action plays an Fia. 3.— Diagram of a Cell to show structure of Protoplasm and Nucleus. In the protoplasm — ^, attraction sphere enclosing two centrosomes ; V, vacuole ; C, included granules ; B, plastids, present in some cells. In the nucleus — B, nucleolus ; F, chromatin network ; G, linin network ; H, karyosome or nodal swelling. (Wilson.) enormously important part both in physiological and in pathological processes in the body. (b) In certain cells, protoplasm undergoes changes in shape (aTtioeboid movement). This may be studied in the white cells in the blood of the frog or newt. Processes (pseudo- podia) are pushed out, and these are again withdrawn, or the whole cell may gradually follow the process, and thus change its position. THE CELL 25 In some unicellular organisms movements take place along some definite line, and fibrils are found arranged more or less parallel to the line of movement. Such contractile processes, from their resemblance to muscles, have been termed myoids. In other protozoa the pseudopodia manifest a to-and-fro rhythmic waving movement, which may cause the cell to be moved along, or may cause the adjacent fluid to move over the cell. Such mobile processes, when permanent, have been called cilia. These movements are the result of chemical changes in the protoplasm, by which alterations in the osmotic pressure and changes in the surface tension of the various parts are produced. The movements are modified by the various Stimuli which alter the activity of the chemical changes (p. 10). The stimulation may be (a) General. — Cooling diminishes and finally stops them. Gentle heat increases them, but when a certain temperature is reached they are stopped. Drying and various drugs, such as chloroform, also arrest the movements. (6) Unilateral. — Changes in the surroundings may cause either contraction or expansion, may repel or attract. When an attracting or a repelling influence, a positive or a negative stimulus, acts at one side of the cell — unilateral stimulation — it may lead to movement of the cell away from it or towards it. If the action is towards the stimulus, it is said to be 'positive ; if away from it, negative. Chemiotaxis is the attraction or repulsion produced by one-sided application of chemical stimuli. This is well seen in the plasmodial masses of cethalium septicum, which grows on tan. Oxygen and water both attract it, exercising a positive chemiotaxis. It is also seen in the streaming of the white cells of the blood to disintegrating tissues, or to various micro-organisms introduced into the tissues which have to be destroyed to prevent their poisoning the organism, and in the attraction exercised by the ovum upon the male element in reprodiiction. Barotaxis is the effect of unilateral pressure or mechanical stimulation. Many protozoa appear quite unable to leave the sohd substance — e.g. the microscope slide — with which 26 VETERINARY PHYSIOLOGY they are in contact, the unilateral pressure seeming to cause a positive attraction in that direction. It is well seen in climbing plants. Phototaxis. — Light, which plays so important a part in directing the movements of the higher plants, also acts posi- tively or negatively on many unicellular organisms. Thus, the swarm spores of certain sdgss are positively attracted by moderate illumination, streaming to the source of light, while they are negatively stimulated by strong light, and stream away from it. Light also plays an important part in directing the movements of certain bacteria. Thermotaxis. — The unilateral influence of temperature is well seen in the plasmodium of cethalium septicum which streams from cold water towards water at a temperature of about 30° C. Galvanotaxis. — A current of electricity has a marked effect in directing the movements of many cells. Certain infusoria, when brought between the poles of a galvanic battery, stream towards the negative pole, while other organisms move to the positive. The etfects of this unilateral stimulation are of great importance in physiology and pathology, since they explain the streaming of leucocytes to the intestine during digestion and to parts of the body infected by micro-organisms and other poisons. They also explain the apparently volitional acts of unicellular organisms. Many of these organisms appear definitely to select certain foods, but in reality tliey are simply impelled towards them by this unilateral stimulation. B. Nucleus. (1) Structure. — The nucleus, seen with a moderate magni- fying power, appears in most cells as a well-defined circular or oval body situated towards the centre of the cell (figs. 2 (c) THE CELL 27 and 3). Sometimes it is obscured by the surrounding proto- plasm. It has a granular appearance, and usually one or more clear refractile bodies — the nucleoli — are seen within it. It stains deeply with many reagents of a basic reaction, such as bjematoxylin, carmine, methylene blue, etc. In some cells the nucleus is irregular in shape, and in some it is broken up into a number of pieces, giving the cell a multi-nucleated character. It is usually composed of (a) fibres arranged in a compli- cated network (fig. 3). These fibres appear to be of two kinds: (1) those forming a fine network — the linin network (G) ; and (2) those forming generally a coarser network, the fibres of which have a special affinity for basic stains — the chromatin network (F). The chromatin fibres vary in their arrangement in dif- ferent cells. Usuall}' they form a network, but occasionall}'- they are disposed as a continuous skein. In nuclei with the former arrangement of fibres, swellings may be observed where the fibres unite with one another — the nodal swellings, or karyosomes, distinct from the nucleolus. The resting nucleus appears to be surrounded by a distinct nuclear membrane, which is either a basket-like interlacement of the fibres at the periphery, or a true membrane produced by adsorption. Between the fibres is (/>) a more fluid material which may be called the nuclear plasma or haryoplasm. Digestion in the stomach removes the nuclear plasma, but leaves the network unacted upon. (2) Chemistry. — The nuclear network is composed of Nucleins. These are combinations of protamines (p. 17) with nucleic acid. Protamines constitute about one-third and nucleic acid about two- thirds of the nucleins. The chief di-amino acid in them is Arginin, which constitutes nearly 90 per cent. The nucleic acid may be broken down into — 1. Purins, such as guanin and adenin (see Appendix). 28 VETERINARY PHYSIOLOGY 2. Pyrimidin Bases, such as thymin, which contain the asymmetric ring — N— C- I I = C C— I II — N— 0— 3. Hexoses (CeHiA)' (P- 285). 4. Metaphosphoric Acid (HPO3). (3) Functions. — The part taken by the nucleus in the general life of the cell is not fully understood. 1st. It exercises an influence on the nutritive processes, since it has been observed in certain of the large cells in lower organisms that a piece of the protoplasm detached from the nucleus ceases to grow, and, after a time, dies. In certain cells, e.g. cells of the nervous S3^stem, it has been found to shrink and to become displaced from its central position as a result of continued activity. Important inter- changes of material go on between the nucleus and the protoplasm. 2nd. It is the great reproductive organ of the cell play- ing an important part in transmitting inherited characters (p. 617). C. Reproduction of Cells. Cells do not go on growing indefinitely. When they reach a certain size they generally either divide to form two new cells, or die and undergo degenerative changes. The reason of this is possibly to be found in the well-known physical fact, that, as a sphere increases in size, the mass increases more rapidly than the superficies. Hence, as a cell becomes larger and larger, the surface for nourishment becomes smaller and smaller in relation to the mass of material to be nourished. Probably the altered metabolism so produced sets up the changes which lead to the division of the cell. These changes have now been very carefully studied in a large number of cells, and it has been shown that the nucleus generally takes a most important part in division. THE CELL 29 A. Mitotic Division. — In a cell about to divide, the first change is a general enlargement of the nucleus. At the same time the centrosome becomes double, and the two portions travel from one another, but remain united by delicate lines to form a spindle-shaped structure (fig. 4 (1)). The spindle passes into the centre of the nucleus, and seems to direct the changes in the reticulum. The nuclear mem- brane disappears, and the nucleus is thus not so sharplj' (3) Fig. 4. — Nucleus in Mitosis. (1) Convoluted stage ; (2) Monaster stage ; (3) Dyaster stage ; (4) Complete division. marked off from the cell protoplasm. The nucleoli and nodal points also disappear, and with them all the finer fibrils of the network, leaving only the stouter fibres, whicli are now arranged either in a skein, or as loops with their closed extremity to one pole of the nucleus and their open extremity to the other. The nucleus no longer seems to contain a network, but appears to be filled with a convoluted mass of coarse fibres, and hence this stage of nuclear division is called the convoluted stage. The spindle continues to grow until it occupies the whole 30 VETERINARY PHYSIOLOGY length of the nucleus. The two centrosomes are now very distinct, and from them a series of radiating lines extends out into the protoplasm of the cell. The nuclear loops of fibres break up into short, thick pieces ; and these become arranged around the equator of the spindle in a radiating manner, so that when the nucleus is viewed from one end it has the appearance of a rosette or a conventional star. This stage of the process is hence often called the single star or monaster stage (fig. 4 (2)). Each loop now splits longitudinally into two, the divisions lying side by side (tig. 4 (2)). The next change consists in the separation ironi one another of the two halves of the split loops — one half of each passing up towards the one polar body, the other half passing towards the other. It is the looped parts which first separate and which lead the way — the open ends of the loops remaining in contact for a longer period, but, finally, also separating. In this way, around each polar body, a series of looped fibres gets arranged in a radiating manner, so that the nucleus now contains two rosettes or stars, and this stage of division is hence called the dy aster stage (fig. 4 (3)). The single nucleus is now practically double. Gradually in each half finer fibres develop and produce the reticular appearance. Nuclear nodes, nucleoh, and the nuclear mem- brane appear, and thus two resting nuclei are formed from a single nucleus. Between these two nuclei a delicate line appears, dividing the cell in two, and the division is com- pleted (fig. 4 (4)). The network of the nucleus of actively dividing cells is rich in nucleic acid, but in cells which have ceased to divide, in which the nucleus has ceased to exercise its great repro- ductive function, the amount of nucleic acid diminishes, and may be actually less than the amount in the cell protoplasm. B. Amitotic Division. — In some cells the nucleus does not appear to take an active part, the cell dividing without the characteristic changes above discussed. SECTION III. The Tissues. All the tissues of the body are formed from a single cell — the ovum. In unicellular organisms the functions of nutrition and of reproduction are performed by the one cell. In the metazoa there is a differentiation into gametic or reproductive cells, and somatic or body cells which form the various tissues of the individual. The latter are primarily developed to nourish and protect the gametic cells which are potentially eternal, going on from generation to generation, while the somatic cells perish with the death of the individual. The mammalian ovum is holoblasdc and undergoes com- plete division. The cells get arranged in three layers, the epiblast, mesoblast, and hypoblast, and from these the tissues are developed. The structure of the tissues nuist be studied practically in the class of Histology. Here all that will be given is a brief summary of their development, and of their structural and chemical characters. (A) THE VEGETATIVE TISSUES. The Vegetative Tissues are those which support, bind together, protect, and nourish the body. They may be divided into the Epithelial Tissues, formed from the epiblast or hypoblast, and consisting of cells placed upon surfaces, and the Connective Tissues developed from the mesoblast, and consisting chiefly of formed-material between cells. VETERINARY PHYSIOLOGY I. EPITHELIUM. 1. Squamous Epithelium— (a) Simple Squamous Epithelium. — This is seen lining the air vesicles of tlie lungs. It consists of a single layer of flat, scale-like cells, each with a central nucleus. The outlines of these cells may be made visible by staining with nitrate of silver, which blackens the cement substance between the cells. (h) Stratified Squamous Epithelium (tig. 5). — The skin and the lining membrane of the mouth and gullet are covered by several layers of cells. The deeper cells divide, and, as the young ones get pushed upwards towards the surface and away from the nourishing fluids of the body, their nutrition is modified, and the protoplasm undergoes a change into keratin, a substance belonging to the group of sclero-proteins (Appendix). It is a hard, horny material. It composes the nails and hair, and the horns and hoofs of certain animals. It first makes its appearance as a number of little masses or gran- ules in the cells, and these run together to fill the cells which „ _ c- -^ ■, c, .. ■ become flattened out into thin J^iG. 0. — btratmed Squamous Epi- thelium from the cornea. SCaiCS. It forms an admirable pro- tective covering to the body, not only on account of its hard- ness and toughness, but because poisons cannot readily pass through it, and also because it is not easily acted on by chemicals. It is characterised by the large proportion of loosely combined sulpluir which it contains. Hence, lead solutions colour keratin black by forming the black sulphide of lead, and are much used as hair dyes (see Chemical Physiology). The sulphur is largely in the form of cystin — EPITHELIUM 33 two thio - amino - propionic acid molecules linked to- gether. H NH., I I H— C— C— CO.OH I I S H I S H I I H—C—C— CO.OH I I H NH, Tyrosin (p, 17) is also relatively abundant. (c) Transitional Epithelium. — A slightly modified stratified squamous epithelium lines the urinary passages. It is char- FiG. 6 -(«) Columnar Epithelium from the small intestine ; (b) Cili Epithelium from the trachea. acterised by the more columnar or pear-like shape of the cells of the deeper layers, and by the cells being very elastic, so that they may be stretched or compressed according to the state of the viscus they line, 2. Columnar Epithelium (fig. 6, a). — The cells lining the stomach and intestine in the embryo elongate at right angles to their plane of attachment, and become columnar in shape. The free border of the cells has an appearance like a hem, due to a series of short rods placed side by side. The great function of this form of epithelium is to absorb the digested matter from the intestine, and to pass it on to the blood. 3 34 VETERINARY PHYSIOLOGY Among these occur some larger, somewhat pear-shaped, cells, attached by their small extremity. Their protoplasm is collected at their point of attachment, while the body of the cell is filled with mucin, a clear, transparent material These chalice cells producing mucin lead to the study of the next type of epithelium. 3. Secreting Epithelium. — This type of epithelium, which has as its function the production of some material which is to be excreted from the cell, is generally arranged as the lining of depressions or pits — the glands. The simplest form of gland is the shnyle tubular — a test- tube-like depression, lined by secreting cells. Instead of being simple, the tube may be branched, when the gland is described Fig. "i.- — A Zymin-secreting Gland, to show an acinus lined by secreting cells containing zymogen granules, and the duct. as racemose. In many glands the secreting epithelium is confined to the deeper part of the tube, acinus (fig. 7), while the more superficial part is lined by cells which do not secrete, forming the duct. In many situations several simple glands are grouped together, their ducts opening into one common duct, and a compound gland results. Secreting epithelium varies according to the material it produces, (A) Mucin-secreting Epithelium. — Many glands have for their function the production of mucus, a slimy substance of use in lubricating the mouth, stomach, intestine, etc. The EPITHELIUM 35 acini containing such cells are usually large. The cells themselves are large, and are placed on a dehcate basement membrane, a condensation of the subjacent tibrous tissue, which bounds the acinus. The nuclei are situated near to the attached margin of the cells. These are somewhat irregular in shape, and are packed close together. Their appearance varies according to whether the gland has been at rest or has been actively secreting. Resting State.— In the former case, in the fresh condition, the cells are large, and pressed closely together. Their protoplasm is filled with large shining granules. After treat- ment with reagents, each cell becomes distended with clear, transparent mucin formed by the swelling and coalescence of the granules, and the cells tend to burst, so that the lumen of the gland becomes filled with the glairy mass. After Activity. — After the gland has been actively secreting, the cells are smaller and the granules are much less numerous, being chiefly situated at the free extremity of the cell, and leaving the nucleus much more apparent. This form of epithelium, during the resting condition of the gland, takes up nourishing matter and forms this mucin- yielding substance. During the active state of the gland the mucin-yielder is changed to mucin, and is extruded from the cells into the lumen of the gland. Mucin is a substance which occurs in many tissues. When precipitated and freed from water it is white and amorphous. On the addition of water it swells up and forms a glairy mass. In the presence of alkalies it forms a more or less viscous emulsoid, and from this it is pre- cipitated by acetic acid. It is a conjugated protein (Appendix) — a protein linked to glucosamiiie — a glucose molecule in which one of the hydroxyls is replaced by amidogen — NH., — /3 It is therefore called a glyco-protein. When boiled 36 VETERINARY PHYSIOLOGY with an acid it yields a sugar (see Chemical Physi- ology). (B) Zymin-secreting Epithelium. — Another kind of secret- ing epithelium forms the various juices which act upon the food to digest it. These juices owe their activity to the presence of enzymes or zymins (p. 7). A zymin-forming gland, after a prolonged period of rest, shows cells closely packed together, so that it is difficult to make out their borders. The protoplasm is loaded with granules which are much smaller than those seen in the mucin- forming cells, and which do not swell up in the same way, under the action of reagents. The nucleus is often obscured by the presence of these granules. When the gland has been actively secreting, the granules become fewer in number, and are confined to the free extremity of the cell ; they are obviously passing out. The cell becomes smaller, and its outline is more distinct and the nucleus more apparent. The granules which fill the cells are not comj^osed of the active enzyme. If extracts of the living cells be made, they are inert, and it is only after the granules have left the cell, or are in the process of leaving, that they become activated. Hence, the granules are said to be composed of zymin-form- iug substance or zymogen. The series of changes are parallel to those described in the mucin-forming cells. During the so-called resting state of the gland, the cells are building up zymogen. When the gland is active, the cells throw off the material they have accumulated, and it undergoes a change to zymin. (C) Excreting Epithelium does not manufacture materials of use in the animal economy, but passes substances out of the body. Such epithelium is seen in the kidneys and sweat glands, and probably in the liver. The cells are composed of a granular protoplasm, in which the presence of the material to be excreted either in its fully elaborated condition, or in process of preparation, may frequently be demonstrated — e.g. iron-containing particles. These cells do not merely take up material from the blood and pass CONNECTIVE TISSUES 37 it out, but tbey may profoundly alter it before getting rid of it. 4. Ciliated Epithelium (fig. (5 (b), p. 83). — The cells are usually more or less columnar, and the free border is pro- vided with a series of hair-like processes, the cilia, which vary in size in different situations. In the living state the cilia are in constant rhythmic motion, each cilium being suddenly whipped or bent down in one direction, and then again assuming the erect posi- tion. All the cilia on a surface work harmoniously in the same direction, and the movement passes from the cilia of one cell to those of the next in regular order, beginning at one end of the surface and passing to the other. As a result of this constant harmonious rhythmic move- ment, any matter lying upon the surface is steadily whipped along it ; and, since the cilia usually work from the inner parts of the body to the outside, this matter is finally expelled from the body. They line the respiratory passages, and their movement plays an important part in getting rid of dust which has been inhaled. The movements of the cilia are dependent on the changes in the protoplasm, and everything which influences the rate of chemical change modifies the rate of ciliary movement, which may thus be taken as an index of the protoplasmic activity. II. CONNECTIVE TISSUES. These are the binding and supporting tissues of the body — fibrous tissue, cartilage, and bone. They are formed from the mesoblast of the embryo, and most of them contain blood-vessels. 1. Mucoid Tissue. — The cells of the mesoblast of the embryo, which at first lie in close apposition with one another, become separated, remaining attached by elongated processes. Between the cells a clear, transparent substance 38 VETERINAEY PHYSIOLOGY makes its appearance, forming a soft, jelly-like tissue. It contains an abundance of mucin (p. 35). This tissue is widely distributed in the embryo as a precursor of the con- nective tissues, and after birth it is still to be seen in the X.-,i / Fig. 8. — Mucoid Tissue from an embiyo rabbit. pulp of a developing- tooth and in the vitreous humour of the eye (fig. 8). 2. Fibrous Tissue. — As development advances, the cells of mucoid tissue elongate and become spindle-shaped, and are Fig. 9. — Fibroblasts from young fibrous tissue. continued at their ends into fibres (fig. 9). These cells are often called fibroblasts. The connective tissues are thus clearly distinguished from the epithelia by having the formed material betiueen and CONNECTIVE TISSUES 39 not in the cells. They are composed of the following parts : — I. Formed material. (a) Fibres. (6) Matrix. II, Spaces (Connective Tissue Spaces). III. Cells. I. FoR.MED Material. — (a) Fibres (fig. 10). — 1st. Non- elastic (White Fibres). These are delicate, transparent fibrils arranged in bundles. They do not branch, and they have a mucin-like matrix between them. They are composed of a non-elastic substance, collagen. This is a sclero-protein (Appendix), and it gives the biuret reaction but not the tests Fig. 10. — Bundles of White Fibres, with Fibroblasts (a) and Elastic Fibres anastomosing with one another (//). for the proteins depending on the presence of the benzene nucleus. It contains neither tryptophan nor tyrosin (p. 17), but it is rich in amino-acetic acid — glycin. It is insoluble in cold water, but swells up and becomes transparent in acetic acid. It has a great aflinity for carmine, and stains a pink colour with it. When boiled, it takes up water to form a hydrate, gelatin, a substance soluble in hot water, and forming a jelly on cooling (see Chemical Physiology). 2nd. Elastic Fibres. These are highly refractile elastic fibres, which branch and anastomose with one another. They are composed of Elastin, a sclero-protein which is very poor in tyrosin, and hence gives the xantho-proteic test very faintly. It is insoluble in both cold and hot water and is not acted on by acetic acid. It stains j'ellow withjpicric acid and it has no affinity for carmine. 40 VETERINARY PHYSIOLOGY (6) Matrix. — This is composed of the miicus-Uke material which is so abundant in the fcetal mucoid tissue. According to the arrangement of the fibres, and to the preponderance of one or other variety, various types of fibrous tissue are produced. When a padding is required, as under the skin and under mucous membranes, the fibres are arranged in a loose felt- work to constitute areolar tissue. In fascia, in tendon sheaths, and in fiat tendons, the fibres are closely packed together to form more or less definite layers. In tendons and ligaments the fibres run parallel and close together. In the tendons of muscles, where elasticity is not required, the fibres are of the white or non- elastic variety. In ligaments, where elasticity is desirable, the elastic fibres preponderate. II. The SPACES of fibrous tissue vary with the arrange- ment of the fibres. In the loose areolar tissue under the skin they are very large and irregular, in fascia they are flattened, while in tendon, where the fibres are in parallel bundles, they are long channels. III. The CELLS of fibrous tissue (Fibroblasts) vary greatly in shape. In the young tissue they are elongated spindles, from the ends of which the fibres extend. In some of the loose fibrous tissues they retain this shape, but in the denser tissues they get squeezed upon, and are apt to be flattened and to develop processes thrust out into the spaces. In certain situations, peculiar modifications of fibroblasts occur. (A) Endothelium. — When these cells line the larger connective tissue spaces they become flattened, and form a covering resembling simple squamous epithelium. Such a layer lines all the serous cavities of the body, and the lymphatics, blood-vessels, and heart, all of which are primarily large connective tissue spaces. To demonstrate the outlines of these cells it is necessary to stain with nitrate of silver, which has a special affinity for the interstitial CONNECTIVE TISSUES 41 substance, and which thus forms a series of black lines between the cells. (B) Fat Cells. — In the areolar tissue of many parts of the body, fat makes its appearance in the cells round the smaller blood-vessels, and when these cells occur in masses Adipose Tissue is produced. Little droplets of oil first appear, and these become larger, run together, and finally form a large single globule, distend- ing the cell, and pushing to the sides the protoplasm and nucleus to form a sort of capsule (fig. 11). Fig. 11. — Fat Cells stained with osmic acid, and lying alongside a small blood-vessel. If the animal be starved, the fat gradually disappears out of the cell, and in its place is left a clear albuminous fluid which also disappears, and the cell resumes its former shape. Fats. — The ordinary fats are esters of the triatomic alcohol, glycerol (see Appendix) — OH C3H5-; OH (oh i formed by the replacement of the hydrogen of the hydroxyls by the radicles of the fatty acids. 42 VETERINARY PHYSIOLOGY The most abundant fatty acids of the body are : — (Palmitic Acid, CisHgiCOOH ; batm-ated— ^g^^^^.^ Acid, C17H35COOH ; Unsaturated — Oleic Acid, C17H33COOH ; The unsaturated acids are more readily oxidised than the saturated. They tend to break at the double link ia the chain thus — H H H H I I 1 I I — C— C=C— C— H I H The three fats are — Palmitin, C,}I,(O.C,Jl,,CO), = Q^HgA' Stearin, C3H,(O.C,,H3,CO)3 = C,,;H,,oOe, Olein, C3H,(O.C\,H33CO)3 = C,,H,o A- It will be observed that the molecules of these fats are very rich in carbon and hydrogen, and very poor in oxygen, containing only about 12 per cent., i.e. they contain a large amount of material capable of being oxidised, and thus capable of affording energy in the process of combustion. The fats resemble one another in being insoluble in water, but soluble in ether and in hot alcohol. As the alcohol cools, they separate out as crystals. They differ from one another in their melting point, palmitin melting at the highest and olein at the lowest temperature. Fat Avhich is rich in palmitin and stearin, as ox fat, is thus hard and solid at the ordinary temperature of the air, while fat rich in olein, as dog fat, is semi-fluid at the same temperature. Olein acts as a solvent for the fats of a higher melting point. (For tests, see Chemical Physiology.) The functions of adipose tissue are twofold ;- — 1st. Mechanical. — The mass of adipose tissue under the skin is of importance in protecting the deeper structures from injury. It is a cushion on which external violence expends itself Further, this layer of subcutaneous fat CONNECTIVE TISSUES 43 prevents the loss of heat from the body, being, in fact, an extra garment. 2nd. Chemical. — Fat, on account of its great quantity of unoxidised carbon and hydrogen, is the great storehouse of energy in the body. (C) Pigment Cells. — In various parts of the eye the connective tissue and other cells contain a black pigment — Melanin. The precise mode of origin of this pigment is not known. It contains carbon, hydrogen, nitrogen, oxygen, and it may also contain iron. Melanin is closely related to a series of dark pigments which are produced by heating protein with mineral acids — the melanoidins — and like them, when heated with potash, it yields indol and skatol (see p. 330;. It is therefore probably connected with tyrosin or Avith tryptophan (see p. 17). It has nothing to do with the blood-pigments. Melanin-like i3igments are widely distributed in nature, occurring not only in the connective tissue pigment-cells of animals, but also in epithelial cells of the epidermis, hair, and eye, and in the tissues of some plants. Its function in the eye is to prevent the passage of light through the tissues in which it is contained. The fibrous-tissue cells containing the pigment are branched, and in many cases they possess the power of move- ment. This is specially well seen in such cells in the skin of the frog, where contraction and expansion may be studied under the microscope. By these movements the skin is made lighter or darker in colour. The movements of these cells are under the control of the central nervous system. 3. Cartilage. — AVhile fibrous tissue is the great binding medium of the body, support is afforded in foetal life and in certain situations in adult life by cartilage. Where cartilage is to be formed, the embryonic cells become more or less oval, and secrete around them a clear pellucid capsule. This may become hard, and persist through life, as in the so-called iiavenchymatous cartilage of the mouse's ear. (1) Hyaline Cartilage. — Development, liowever, usually goes further, and before the capsule has hardened, the cartilage cells again divide, and each half forms a new 44 VETERINARY PHYSIOLOGY capsule which expands the original capsule of the mother cell, and thus increases the amount of the formed material. This formed material has a homogeneous, translucent appearance, and a tough and elastic consistence, and cuts like cheese with the knife (fig. 12). The formed material of cartilage, chondro-onucoid, is not a special substance, but a mixture of chondroitin-sulphuric acid with collagen in combination with proteins. Chondroitin, when decomposed, yields glucosamine, a sugar-like substance containing nitrogen (p. 35) ; glycuronic acid, a sugar with the terminal carbon oxidised to the carboxyl state ; and acetic acid probably derived from the amino-acetic acid of collagen. Cartilage is surrounded by a tibrous membrane, the peri- chondrium, and frequently no hard-and-fast line of demarca- tion can be made out between them. The fibrous tissue gradually becomes less fibrillated, the cells become less elongated and more oval and the interfibrillar substance increases in amount and becomes of the same refractive ^. index as the fibres. During old age, a fibrillation of =^ • "" the homogeneous - looking cartilage is made manifest, ^ ^_. especially in costal cartilage, '^^^^=^'"' --'''. l^y the deposition of lime ;''■?' salts in the matrix, between the fibres. It was long ago shown that in inflammation of cartilage this fibrillation ,,;■. • appears; and by digesting ,/^\ it i'^ baryta water, a similar structure may be brought Fig. 12.-Hyaluie CartUage covered ^^^^_ rpj^^ ^j^^^ connection by perichondnun). of cartilage with fibrous tissue is thus clearly demonstrated. Such homogeneous hyaline cartilage precedes most of the bones in the embryo, and covers the ends of the long bones in the adult (articular cartilage), forms the framework of the larynx and trachea and constitutes the costal cartilages. 9 CONNECTIVE TISSUES 45 (2) Elastic Fibro-Cartilage. — In certain situations — e.g. in the external ear — a specially elastic form of cartilage is developed, elastic fibres appearing in the cartilaginous matrix, and forming a network through it. (o) White Fibro-Cartilage. — In other situations — e.g. the intervertebral discs — a combination of the binding action of fibrous tissue with the padding action of cartilage is required ; and here strands of white fibrous tissue with little islands of hyaline cartil- age are found. It is also found where white fibrous tissue, e.g. tendon, is in- serted into hyaline cartil- age, and it is reall}- a mixture of two tissues — wdiite fibrous tissue and cartilag-e. 4. Bone. — The great supporting tissue of the adult is Bone. (1) Development and Structure. — Bone is formed by a deposition of lime salts in layers or lameUcc of white fibrous tissue. But while some bones, as those of the cranial vault, face, and Fig. 13. — Intra-membranous Bone De- velopment in the lower jaw of a foetal cat. Above, the process of ossification is seen shooting out along the fibres, and on the lower surface the process of absorption is going on. Two osteo- clasts — large multi-nucleated cells — are shown to the left. clavicle, are produced entirely in fibrous tissue, others are preformed in cartilage, which acts as a scaffolding upon which the formation of bone goes on. A. Intra-membranous Bone Development. — This may be studied in any of the bones of the cranial vault where cartilage is absent (fig. 13). At the centre of ossification, the matrix between the fibres becomes impregnated with lime salts, chiefly the phos- phate and carbonate. How this deposition takes place is 46 VETERINARY PHYSIOLOGY not known, and how far it is dependent on the action of cells has not been clearly determined ; but in front of the process, as it shoots outwards from the centre in all direc- tions, accumulations of cells are to be seen, and these cells have been called osteoblasts. The cells get enclosed in definite spaces, lacunce, and become bone cells. Narrow branching channels of communication are left between these lacunee, the canaliculi. The fully formed adult bone, however, is not a solid block, but is composed of a compact tissue outside, and of a spongy bony tissue, cancellous tissue, inside. This cancellous tissue is formed as a secondary process. Into the block of calcareous matter, formed as above described, processes of the surrounding fibrous tissue burrow, carrying in blood- vessels, lymphatics, and numerous cells (fig. 13, lower surface). This burrowing process seems to be carried on by the cells, which eat up the bony matter formed. In doing this they frequently change their appearance, becoming large and multi-nucleated (osteoclasts). Thus the centre of the bone is eaten out into a series of channels, in which the marrow of the bone is lodged, and between which narrow bridges of bone remain. It is by the extension of the calcifying process outwards, and the burrowing out of the central part of the bone, that the dense diploe and spong}^ cancellous tissue are produced. B. Intra-cartilaginous Bone Development. — In the bones preformed in cartilage, the process is somewhat more complex. But all the bone is developed in connection with fibrous tissue, and the cartilage merely plays the part of a scatfblding and is all removed. Where the adult bone is to be produced, a minute model is formed in hyaline cartilage in the embryo, and this is surrounded by a fibrous covering, the 'pevicltondriihtn. In the deepest layers of this perichondrium the process of calcifi- cation takes place as described above, and spreads outwards, thus encasing the cartilage in an ever-thickening layer of bone (fig. 14, a). At the same time, in the centre of the cartilage, at what is called the centre of ossification, the cells begin to divide CONNECTIVE TISSUES 47 actively, and, instead of forming new cartilage, eat away the material, and thus open out spaces (fig. 14, 6). Into these spaces processes of the perichondrium bore their way, carry- ing with them blood-vessels, and thus rendering the cartilage vascular. The vascularisation of the centre of the cartilao-e having been effected, the process of absorption extends towards the two ends of the shaft of cartilage, which con- tinues to elongate. The cartilage cells divide and again divide, and, by absorbing the material between them, form '**"-» -s*. ^^ ..^' Fig. 14. — Intra-cartilaginous Bone Development. A phalanx of a fcetal finger showing the formation of periosteal bone round the shaft (a) ; the opening up of the cartilage at the centre of ossification and the vascularisation of the cartilage by the invasion of fibrous tissue {b) ; and the calcification of the cartilage round the spaces (c). long irregular canals running in the long axis of the bone, with trabeculse of cartilage between them. Into these canals the processes of the periosteum extend, and fill them with its fibrous tissue. A deposition of lime salts takes place upon the trabeculse, enclosing cells of the invading fibrous tissue, and thus forming a crust of bone, while the cartilage also becomes calcified. If this calcification of the cartilage and deposition of bone were to go on unchecked, the block of cartilage would soon be converted to a sohd mass of calcified tissue. But this does not occur. For, as rapidly as the trabeculis become calcified, they are absorbed. 48 VETERINARY PHYSIOLOGY while the active changes extend further and further from the centre to the ends of the shaft. The centre, which was once formed by the embryonic cartilage, is thus changed to a space filled by fibrous tissue which afterwards becomes the bone marrow. The process of absorption does not stop at the original block of cartilage ; but after all of this has been absorbed, the bone formed outside the cartilage in the fibrous tissue is attacked by burrowing processes from inside and outside, Fig. 15.— Cross section through part of the shaft of an adult long bone to show the arrangement in lanielte distributed as Haversian (1), inter- stitial (2), periphei-al (3), and medullary (4). which hollow out long channels running in the long axis of the bone. These are the Haversian spaces (fig. 15). Round the inside of each, calcification occurs, spreading inwards in layers, and enclosing connective tissue cells, until at length only a small canal is left, an Haversian canal, containing some fibrous tissue, blood-vessels, lymphatics, and nerves, with layer upon layer of bone concentrically arranged around it. This constitutes an Haversian system. In this way the characteristic appearance of the shaft of a long bone is produced, with layers of calcified fibrous tissue, the bone CONNECTIVE TISSUES 49 lamelke, arranged as Haversian, interstitial, peripheral, and medullary lamellae (fig. 15). One important function performed by the cartilage is in bringing about the increase in length of the bones. As growth progresses, the cartilage grows in length, and the formation of bone outside the cartilage spreads to each end, and thus the shaft of the bone is formed. But, in addition to the centre of ossification in the shaft — the dicqjhysis, one or more similar centres of ossification form at each end of the bone. These are the epiphyses. Between these and the diaphysis a zone of actively growing cartilage exists until adult life, when the bones stop lengthening. In this zone, the cells arrange themselves in vertical rows, divide at right angles to the long axis of the bone and form cartilage. This cartilage, as it is formed, is attacked by the bone-form- ing changes at the diaphysis and epiphyses. But the amount of new cartilage formed is at first proportionate to this, and thus a zone of growing cartilage continues to exist until early adult life, when epiphyses and diaphysis join and growth in length is stopped. The rate and extent of this growth of the cartilage determines the length of the limbs. It is influenced by many factors, such as the general nutrition of the animal, and also by the influence of the internal secretions of various structures, such as the thyreoid and pituitary body (see pp. 595, 599). (2) Chemistry. — The composition of adult bone is roughly as follows : — Water, 10 per cent. Solids, 90 per cent. Organic, 35 per cent. — chiefly collagen. Inorganic, 65 per cent. Calcium phosphate, 51. carbonate, 11. fluoride, 0-2. Magnesium phosphate, 1. Sodium salts, 1. The most important points are the small amount of water, 4 50 VETERINARY PHYSIOLOGY the large amount of inorganic matter, chiefly calcium phosphate, and the nature of the organic matter — collagen. (3) Metabolism. — Although bone consists so largely of inorganic matter it is permeated by blood-vessels and living cells, and it undergoes metabolic changes not only during development but in the full grown animal. In fasting and in the conditions of acidosis (p. 481) the lime salts may be removed from the bone to the blood and excreted. In rickets the metabolism of growing bone is modified, the lime salts not being properly laid down or being too rapidly removed ; possibly both these changes go on together. The bones are thus softened and undergo deformity. In osteo- malacia there is a softening of the bones due to the removal of lime salts. (5) THE MASTER TISSUES —NERVE AND MUSCLE. By" means of the epithelial and connective tissues the body is protected, supported and nourished. It performs purely vegetative functions, but it is not brought into active relationship with its environments. By the development of Nerve and Muscle the surroundings are able to act upon the body, and the body can react upon its surroundings. These tissues may therefore be called the Master Tissues, and it is as their servants that all the other tissues of the soma functionate. Upon them the very existence of an animal depends. It lives in a world of constant change. The surrounding con- ditions are not always compatible with life ; the temperature may be too high or too low, or it may find itself plunged in a medium in which it cannot breathe and it must escape ; food may be wanting, and it has to be obtained. A thousand changfinw conditions have to be daily, hourly, almost momentarily met by adjustments of the body, and to make these appropriate the various ditferent kinds of change must each produce ditferent effects. Some means by which they can do so is the first essential for the continuance of the animals' existence. Not only must each produce its special effect, but means must exist by which each different effect or combination of effects may produce an appropriate reaction. In unicellular organisms changes in the surroundings act 51 Fig. 16. — Poterio- dendron in its cap- sule, to illustrate the first stage in the evolution of a neuro-niuscular system. 52 VETERINARY PHYSIOLOGY directly on the cell protoplasm, e.g. an amoeba, when touched, draws itself together. But, even in these simplest organisms, certain kinds of external conditions will produce one kind of change, while others will produce a different one, as has been shown in considering unilateral stimulation (p. 25). Even among unicellular organisms— e.(/. among the infusoria — animals are found in which the cell is differ- entiated into a receiving and a reacting part. Poteriodendron, a little infusorian sitting in a cup-like frame, consists of a long process or cilium extending up from a cell, while a contractile myoid attaches the cell to the floor of the cap. When the cilium is touched the myoid contracts, and draws the creature into the protection of its covering (fig. 16). In multicellular organisms the result is secured by the development at the surface of the body of special structures or Receptors, each kind of which is stimulated or made to undergo a change, more especially by some one kind of external change. Thus one kind is specially stimulated by the contact of gross matter, another by the addition of heat, another by its withdrawal ; another kind is specially acted on by the vibration of air called by physicists " sound waves," another by the ethereal " waves of light " ; yet another by the presence of substances suspended in air or in solution in water. But before the reaction of the body upon its surroundings can be appropriate, the effects of these various changes must be brought together and harmonised and integrated, and this is secured by the existence of strands of living matter, nerves, which pass from each receptor and lead to a common or to several common receiving arrangements or stations in the central nervous system. The combined effect of all the different stimuli from without call into play a series of the other stations in the central nervous system which set in action the great re- acting or effector arrangements, the Muscles. It is impossible to study the mode of action of the receptors without also considering the mode of action of the NERVE 53 transmitting nerves and of the receiving stations in the central nervous system. This involves the study of the motor reactions which may follow any given set of stimuli. Before proceeding to study the physiology of the complex set of receptors, nerves, central nervous system, and effectors, it will be well first to consider — 1. How the nervous system is developed. 2. The physiology of single nerve units. I. Development of the Nervous System. To form the nervous mechanism, a part of the epithelial covering of the embryo sinks inwards as a canal, and the cells of this form functional connections with the surface on the one hand, and with the reacting structures on the other. At first the cells composing this tube are undifferenti- ated and alike {neurohlasts), but later some of them throw out processes (a) towards the surface, and others (6) towards the reacting structures. These cells with their outgrowths form the units of which the nervous system is built up — the Neurons. They are separate from one another, but are associated by the close propinquity of their branching twig- like processes or dendrites, such an association being known as a synapse (fig. 17). Fig. 17. — To show a recdring (c) and a reacting Neuron (a), each with den- drites at its extremities, and their connection to one another through a Synapsis {h). 1. Neurons to and from the Body Wall- — The nerve fibres are formed as outgrowths from the nerve cells. This has been demonstrated by the histological investigations of Ramon-y-Cajal, who used a method of impregnating the 54 VETERINARY PHYSIOLOGY fibres with silver, and still more strikingly by the experi- mental investigations of Ross Harrison upon the tadpole. The nerves which come from the central nervous system each consist of two roots, one coming from the back of the neural canal, the other from the antero-lateral aspect. Harrison was able to remove the cells from the back of the neural canal, and he then found that the posterior roots of the nerves did not grow, but that the anterior roots did grow. He also removed the cells from the front part of the neural canal, leaving those at the back, and he then found that processes grew out in the position of the posterior roots only. He also found that from these posterior cells were derived certain covering cells which afterwards formed the «^— ^ f-< 4-^. < 4-< 6 Fig. 18. — To show the formation of a Visceral Nerve, a, the neurons which have travelled out to form the terminal ganglion; b, an emi- grated neuron which has come to rest in a sympathetic ganglion : c, a neuron which has remained in the spinal cord and sent out a process so that it may act upon the emigrated neurons. sheaths of the nerve fibres. Lastly, he excised part of the neural canal before the cells had differentiated, and kept it alive for five weeks in lymph, and he was able to observe the outgrowth of the processes which afterwards form the axons of the nerve fibres. The evidence thus seems to be conclusive, that these somatic nerve fibres are essentially outgrowths from nerve cells. 2. Neurons to the Viscera. — While the nerves to and from the body ivall are formed as described above, those passing to the viscera are developed by a migration outwards of neuroblasts. Some of these come to rest in the sympathetic ganglia in front of the spinal column, others travel on and come to rest in more remote ganglia, while a large number pass right out into the tissues, there to throw out processes NERVE 55 and to form a network which may be called a terminal 2)lexus. These are kept in connection with the central nervous system by the outgrowths of processes from cells which remain in the spinal cord (fig. 18). In certain positions, e.g. in the wall of the gut, these terminal plexuses control the activity of the structure in which they are placed (see fig. 48, p. 109). It is as if the central nervous svstem had devolved Fig. 19.— (a) A Nerve Cell with Nissl's Granules ; (b) a similar cell showing changes on section of its axon. the power of local government upon these emigrated II. Structure. 1. Cells. — The shape and characters of the cells, and their position upon the processes vary greatly, but the}^ have all the following features in common : — They are nucleated protoplasts, the protoplasm of which, after fixing and staining, shows a well-marked network, in the meshes of which a material which stains deeply with basic stains, and which seems to be used up during the activity of the neuron, may accumulate in granules. The granules formed of this material are generally known as Nissl's granules (fig. 19). Mott has failed to find such a structure in living nerve cells, and by the use of the ultra-microscope has observed particles moving freely in the colloidal iluid contents, 56 VETERINARY PHYSIOLOGY which they could not have done had there been such structures. These cells give off at least one process, which continues for some distance, as the axon. Frequently other processes are given off, which form a branching system of dendrites. The axons end in dendrites, so that all the processes are essentially the same. These processes appear to be fibrillated, and in fixed specimens the tibrillse may be traced through the protoplasm of the cells, but this appearance is probably an artefact due to the action of the fixing agents employed. In many cases the dendrites show little buds or gemmules upon their course, and, according to some observers, it is through these that one neuron is brought into definite relationship at one time with one set of neurons, and at another with other adjacent neurons. There is also some evidence that the dendrites as a whole may expand and contract, and thus become connected with those of adjacent neurons. 2. Axon. — The axon process, as it passes away from the cell, becomes a Nerve Fibre, and acquires one or two cover- ings. (1) A thin transparent membrane, the primitive sheath or neurolemma, is present in all peripheral nerves. Between it and the axis cylinder there are a number of nuclei surrounded by a small quantity of protoplasm, the nerve corpuscles. Fibres with this sheath alone have a grey colour, and they may be called grey or non-medullated jihres. They are abundant in the visceral nerves. This sheath is absent from the nerve fibres of the central nervous system. (2) A thick white sheath — the medullary sheath or white sheath of Schwann — which gives the white colour to most of the nerves of the body appears somewhat late in the development of many nerve fibres. It lies between the primitive sheath with its nerve corpuscles and the axon. It is not continuous, but is interrupted at regular intervals by constrictions of the neurolemma at the nodes of Ranvier (fig. 20). It is composed of a sponge-work or felt-work of NERVE 57 a horn-like substance — neuro-keratin — the meshes of which are filled with a peculiar fatty material. The nerve fibres run together in bundles to constitute the nerves of the body, and each bundle is surrounded by a dense fibrous sheath, the 'perineurium. When a bundle divides, each branch has a sheath of perineurium, and in many nerves this sheath is continued, as the sheath of Henle, on to the single fibres which ultimately branch off" from the nerve. Not only do nerves branch and anastomose in the great nerve plexuses, but in the nerves themselves a similar plexus- like rearrangement of the bundles and fibres takes place. Fig. 20. — Pieces of two white Nerve Fibres. Each nerve fibre ends in a series of dendritic expansions, which vary greatly in character according to the structures to which they pass. III. Chemistry of Nerve. The chemistry of neuron cells and their processes has been deduced from a study of the chemistry of the grey matter of the brain where they preponderate, while the chemistry of the white fibres is indicated by the analysis of the white sub- stance of the brain, which consists chiefly of medullated fibres. The grey matter contains over 80 per cent, of water. The solids consist of rather less than 1 per cent, of proteins. Two globulins, one coagulating at a low and the other at a higher temperature, and a nucleo -protein have been isolated. Lecithin and cholesterol each constitute about 3 per cent. The white matter contains only about 70 per. cent of water. The proteins, similar to those in the grey matter, constitute between 7 and 8 per cent. Lecithin occurs in 58 VETERINARY PHYSIOLOGY about the same amount as in the grey matter, but cholesterol and lipoids, other than lecithin, constitute more than 15 or 16 per cent. From the fatty material of the white sheaths various mixtures of lipoid substances have been isolated. These have been named Cerebrosides and have been classified into — 1. Galactosides yielding a sugar — galactose, nitrogen, but no phosphorus. 2. Phosphatides, of which lecithin is the most important (p. 20). 3. Cholesterol, a monohydric alcohol, belonging to the group of terpenes. IV. Physiology of Neurons. The neurons form a most intricate labyrinth throughout all parts of the body, and more especially throughout the central nervous system. Each is brought into relationship with many others by its dendritic terminations, and there is a continued interaction between them, the activity of any one influencing the activity of many others. In this way the constant activity of the nervous system, which goes on from birth to death, during consciousness and in the absence of consciousness, is kept up. It is unnecessary and gratuitous to invoke the conception of automatic action on the part of any portion of the nervous system. Throughout life these neurons are constantly being acted upon from without ; and activity, once started by any stimulus, sets up a stream of action which may be coexistent with life. A. SINGLE NEURONS, OR Neurons lying side by side in Nerves. It has been shown that the great purpose of neurons is to enable external changes to produce appropriate reaction (p. 52). The changes set up in the receptors at the surface must be conducted to the stations in the central nervous system, and again conducted out to the muscles. Conduction is thus the great property of nerve. NERVE 59 1. Manifestations of the Activity of Neurons. When conducting, nerve, like a telegraph wire, manifests no visible change. Its activity is shown chiefly by changes in the structures to which it passes, but also by certain electrical disturbances in the conducting part. (1) Action on other Structures. — The activity of the out- going neurons — neurons conducting impulses from the central nervous system to muscles, glands, etc. — is manifested by changes in the muscles or other structures to which they go : while the activity of ingoing neurons is made evident (a) by their action on outgoing neurons to muscles, etc. (see fig. A B Fig. 21. — To show the union of the vagus A to the anterior end of the sym- pathetic B in the neck. The part of the central nervous s3-steni which normally' acted upon the abdominal viscera becomes trained to act upon the structures in the face and head. 17, p. 5 3), and (6) sometimes by modifications in the state of consciousness which may be of the nature of a simple brief sensation, or, by the implication of a number of other neurons, may develop into a series of changes accompanied by a corresponding series of sensations. Very interesting results follow from this fact, that the activity of neurons is made raanifest by changes in the structure to which they pass. Langley has demonstrated that, if the vagus, which conducts downwards to the abdominal viscera, be cut, and the cervical sympathetic, which conducts upwards to the head, be also cut, and the central end of the vagus united to the peripheral end of tlie sympathetic (fig. 21), fibres grow outwai'ds from the vagus 60 VETERINARY PHYSIOLOGY into the sympathetic, and when the vagus is stimulated, the resuks which naturally follow stimulation of the sympathetic occur. Kennedy has shown that, if the nerves to the flexors and the nerves to the extensors of a dog's forelimb be cut, and the central end of the former united to the peripheral end of the latter, and vice versa, the normal co-ordinate movements of the limb are restored, and that, if that part of the brain which naturally causes extension be stimulated, flexion occurs. He has applied the information thus gained to the treatment of abnormal conditions in the human subject. In a woman who suffered from spasmodic action of the muscles of the face supplied by the seventh cranial nerve, he divided this nerve and connected its peripheral end with the central end of the spinal accessory and thus secured a complete recovery. Such observations are of great interest, since they indicate that the activity of the cells and synapses from which the fibres come may undergo profound alteration in function, that they may in fact be trained or educated to take on activities not natural to them. (2) Electrical Changes. — The part of the neuron in action is electro-positive to the rest of the neuron. This simply means that the parts in action become to the rest of the neuron what the zinc plate (the electro-positive element) in a zinc and copper galvanic cell is to the copper. The flow of current set up along the wire connecting the elements of the cell is made manifest by the deflection of a galvanometer needle. In the same way the zinc-like (electro-positive) action of the acting part of the neuron is made manifest if wires are led off from the nerve round a galvanometer (fig. 22). In order that neurons may produce their effect they must be capable of Excitation and Conduction, and these must now be studied. 2. Excitation of Neurons. Neurons, like all other protoplasm, react to changes in external conditions ; they are capable of stimulation. NERVE 61 A. A neuron is usually stimulated from one or other of its terminal dendritic endings, either by changes set up in the tissues round these, or by changes in other neurons. Thus (fig. 17) one set of neurons may be thrown into action by changes in the tissue at their extremity, and a second set may be stimulated by the activity of the first. B. Neurons may also be stimulated at any part of their course, as may be demonstrated by pinching the ulnar behind the internal condyle of the humerus, when a sensation localised on the ulnar side of the hand is experienced, and by the contraction produced in the gastrocnemius muscle of Fig. 22. — A, To show a galvanic cell with a zinc and copper element and the flow of the electric current passing round a galvanometer. B, A nerve in which the dark part is in action and is acting to the rest of the nerve as the zinc elements in the cell. the frog when the sciatic nerve is {Practical Physiology). stimulated in its middle Means of Stimulation. knj sudden change tends to excite to activity, whether it be mechanical, as in pinching a nerve, or a change in the temjjerature, or in the electric conditions, or in the chemiccd surroundings of the neurons ; agents which withdraw water, like glycerine, stimulating strongly. The electrical method of stimulating nerve is constantly used in medicine, and it must be studied carefully. It is a 62 VETERINARY PHYSIOLOGY matter of no importance how the electricity is procured, but most usually it is obtained either — Isf. Directly from a galvanic battery, accumulator, or electric main ; or 2nd. From an induction coil. list. Galvanic Stimulation. A. Exposed Nerve. The sciatic nerve of the frog passing to the gastrocnemius muscle may be placed upon the wires from a galvanic battery, and the contraction of the muscle may be taken as the index of the stimulation of the nerve. It will be found that — (a) On making the current, and upon breaking the current, a contraction results. While the current is flowing through the nerve, the muscle iisiially remains at rest ; but if the current is suddenly increased in strength, or suddenly diminished in strength, the muscle at once contracts. With strong currents, a sustained contraction — galvanotonus — may persist while the current flows {Practical Physiology). It is the siicldenness in the variation of the strength of the current, rather than its absolute strength, which is the factor in stimulating, as may be shown by inserting some form of rheonome into the circuit by which the current may be either slowly or rapidly varied. This fact is of great importance in applying galvanic currents in the treatment of various diseases in the human subject. Great care is necessary to increase sloivly and to decrease slowly the strength of the current, or painful stimulation may be pro- duced (Practical Physiology). (b) The stimulus on making is stronger than that on breaking, so that, if a current be made weaker and weaker, breaking ceases to cause a contraction, while making still produces it (Practiced Physiology). (c) The two poles do not produce the same effect. The negative pole or cathode stimulates on making ; while the positive pole or anode stimulates at breaking. This may NERVE 63 be stated — the nerve is always stimulated at the ])oint tvhere the current leaves it. On making this is at tlie cathode ; on breaking at the anode (fig. 23) {Practical Physiology). These results may be summarised as follows : — 1. Stimulation on closing (making); stimulation on open- ing (breaking). 2. Closing stimulation stronger than opening stimulation. 3. Stimulation at cathode on closing, at anode on opening. Or, taking the contraction of the muscle as the sign of stimulation, and representing it by C, the law of galvanic stimulation may be expressed thus : — 1. C.C • CO 2. CO CO 3. CCC CAO Explanation of Elec- tric Stimulation. — A study of the influence of the current while it is flowing throws im- portant light on this point. This condition Yig. 23.— To show stimulation at the of the tissue is known cathode on closing and at the anode -,, . . .-rt on opening, at the point where the as EleCtrotonUS {Prac- current lef^es the nerve. tical Physiology). While the current simply flows through a nerve no stimulation is produced, but the excitability is profoundly modified. Round the cathode the nerve becomes more easily stimu- lated, while round the anode or positive pole it becomes less easily stimulated. This may be expressed by saying that the part of the nerve under the influence of the cathode is in a state of catelectrotonus, of increased excitability, while the part of the nerve under the influence of the anode is in a state of anelectrotonus, of decreased excitability or of more stable equilibrium. This is easily demonstrated by passing a galvanic current along a nerve going to a muscle, and 64 VETERINARY PHYSIOLOGY stimulating first in the region of the cathode and then in the region of the anode. A much stronger stimulus will be found necessary to cause contraction of the muscle at the second point, in the region of the anode. It is the sudden production of increased excitability at the cathode on closing which causes an explosion, a stimu- lation. The sudden removal of the increased stabiUty round the anode when the current is broken is sufficient to cause an explosion if the current is strong enough. The study of electrotonus thus explains (1) why any sudden change in the flow of electricity through a muscle stimulates it ; (2) why the stimulation starts from the cathode on closing and from the anode on opening ; and (3) why the closing contraction is stronger than the opening. This law of Polar Excitation, Avhile it applies to normal + Fig. 24. — To show the passage of a galvanic current along a nerve so that distinct polar effects are produced. muscle and nerve, does not apply to all protoplasm. Thus, amoiba shows contraction at the anode and expansion at the cathode when a galvanic current is passed through it. B. Nerve under the Skin. In practice the galvanic current may be used to stimulate nerves and muscles in situ under the skin. To use the current for this purpose an electrode is placed over the nerve or muscle to be investigated and the other over some indifferent part of the body. The very considerable electrical resistance of the skin has to be overcome by using rather large electrodes usually covered with chamois leather well soaked in saturated salt solution. Applied in this way, the current passes from pole to NERVE 65 pole, not along the nerve or muscle (fig. 24), but more or less across it (fig. 25). The nerve, if under the cathode, is thus under the influence of the cathode on the side near the pole, and under the influence of the anode on the side away from the pole, and, vice versa, under the anode (fig. 25). -•^r-**-^"^ i^-^ ,!*■•*- ti t ^^ B S7^ yViiVN^j. ^ Fig. 25. — Electrical Stimulation of human muscle or nerve to show the passage of the current across the structure, and the consequent combination of effects under each pole. Hence there will be a stimulation both at making and at breaking (p. 63) under both cathode and anode. The cathodal closing contraction is the stronger because of its dependence upon the more effective pole, the cathode, as it is a closing contraction, and also because the excitation begins at A, which is near the stimulating pole. The cathodal opening contraction has the less effective pole — the anode as its origin, since it is an opening contraction, and the excitation is at the less effective position B, which is separated from the stimulating pole — the anode by a 5 m VETERINARY PHYSIOLOGY greater distance than is A from the cathode. Similarly, the anodal closing contraction has the better pole, the cathode as the stimalating pole, but in the worst position D, far from the cathode. The anodal opening contraction has the less effective pole — the anode as the origin of excita- tion, but in the better position G, close to the stimulating pole. Position. Strength of Current necessary to stimulate. -c.c. Cathode, Closing A \ Anode, Closing D J Anode, Opening C t . p, Cathode, Opening B j^-^- Better Better Worse Worse Better Worse Better Worse Weakest Medium Medium Strongest The strength of the current required to stimulate is measured in milliamperes. The effective strength varies o-reatly, even in normal individuals of the same species. Changes in Disease and Injury. — In tetany in children, and after the removal of the parathyreoids in man and animals (p. 603), a condition of increased excitability of the nerves to mechanical and galvanic stimulation occurs, and this is used in the diagnosis of these conditions when other symptoms are latent. When the nerve to a muscle is cut it rapidly loses its power of responding to electrical stimulation (p. 76), but the muscle continues to respond, and its response, although at first it may be decreased, is afterwards increased and becomes peculiarly slow. Some neurologists have maintained that there is a qualitative change in the response, that the response to anodal closing — A.C. becomes greater than that to cathodal closing — C.C. With fine electrodes applied to ex- posed muscle this does not occur. It is probably due to the fact that in normal muscle it is the nerve endings which are stimulated, but that in degeneration the response depends upon the number of muscular fibres stimulated rather than upon the pole applied. Hence in anodal closing the worst NERVE 67 position, far from the pole, acts upon more fibres than the cathode acts upon in closing. Fig. 26. — To illustrate the reason for the increase in the anodal closing stimulation in a muscle after degeneration of the nerve and nerve endings. 2. Faradic Stimulation. When nerve is stimulated by induced or faradic electricity Electric Current. Make. Break. Make. Break. Contraction of Muscle. Cathode. Anode. Galvanic. Cathode. Anode. Induced. Fig, 27. — To show separation of make and break stimuli and of anodal and cathodal effects when a galvanic current is used, and their combina- tion when the induction coil is used (faradic). (fig. 28), with each make and break, or with each sudden alteration in the strength of the primary circuit, there is a sudden appearance and equally sudden disappearance of a flow of electricity in the secondary coil. If, therefore, wires from the secondary coil are led ofif to a nerve, each change in the primary circuit causes the sudden and practically simultaneous appearance and disappearance of an electric 68 VETERINARY PHYSIOLOGY current in the nerve, and this, of course, causes a contraction. But here the effects of closing and opening the current are practicall}^ fused, and hence the influence of the anode and cathode, and of closing and opening, need not be considered (fig. 27) {Practical Physiology). It must, of course, be remembered that in an induction coil the opening of the primary circuit produces a more power- ful current in the secondary coil than the closure of the primary circuit, and therefore a more powerful stimulation of the nerve (fig. 28). Relationship of the Excita- tion to the Strength of the Stimulus. — A nerve is made up of a series of axons placed side by side. The ditlerence in the effect of a weak and of a strong stimulus as indicated by the contraction of the muscle supplied may be due either to a graded effect of the stimulus on every fibre or to the number of fibres stimulated by the different strengths of stimulus. The cutaneus dorsi nerve of the frog is composed of only ten fibres, and, as the strength of stimulus is steadily increased, the resulting contractions increase in ten stages. The conclusion is that the result depends upon the number of fibres stimulated, and that, when a stimulus excites a fibre, it does so to call forth its full action — the stimulation of each axon is either all or nothing. Variations in Excitability. — The influence of the galvanic current upon the excitability of nerve has been already considered (Electrotonus, p. 63). Many other factors modify its excitability. It may be increased by a slight cooling, but it is decreased at lower temperatures. It is increased by warming up to a certam point. Drying at first increases excitability, then abolishes Fig. 28.— Course of Elec- tric Current in primary circuit (lower line), and in secondary circuit (upper line) of an induction coil. Observe that in the secondary the make (up- stroke) and break (down- stroke) are combined, and that a stronger current is developed in the secondary circuit upon breaking than upon mak- ing the primary circuit. NERVE 69 it. It is influenced by many chemical substances, some of which increase its excitability in small doses, and diminish it in larger doses ; some again even in the smallest dose depress its activity, e.g. potassium salts, and such drugs as chloroform and ether. Continued activity has no effect on the excitability of axons, and the phenomena of fatigue are not manifested in them. This may be proved by taking two nerve-muscle prepar- ations, A and B, and stimulating both nerves repeatedly with Stimulating Current. \ t f Blocking Current. A B Fig. 29. — Experiment to show that a nerve cannot be fatigued. Two muscle nerve preparations, A and B, are stimulated by the faradic current. B is blocked by a galvanic current or by cooling, till the muscle of A no longer contracts. The block is then removed, and B contracts. the same electric current, but preventing the stimulus from reaching one of the muscles, B, by blocking its passage by passing a galvanic current through the nerve (see p. 71) or by applying ice to it (fig. 29). If, after muscle A no longer contracts, the block is removed, muscle B will contract, showing that the nerve is not fatigued. 3. Conduction in Neurons. When a neuron is stimulated at any point, some time elapses before the result of the stimulation is made manifest, 70 VETERINARY PHYSIOLOGY and the further the point stimulated is from the structure acted upon, the longer is this latent period. This indicates that the change does not develop simultaneously throughout the neuron, but, starting from one point, is conducted along it. (a) The rate of conduction may be determined — 1st By stimulating a nerve going to a muscle at two points at a known distance from one another, and measuring the difference of time which elapses between the contraction Fig. 30. — M, Muscle attached to crank lever marking on revolving drum. The secondary circuit of an induction coil is connected with a commutator, with the crossed wires removed so that the current may be sent either through the wires going to the nerve at A far from the muscle, or at B, a point at a measured distance nearer the muscle. On the drum, A represents the onset of contraction on stimulating at A, and B the onset on stimulating at B. To secure stimulation in each case with the drum in the same position, the make and break of the primary circuit is caused by the point of K touching and quitting the point P. resulting from stimulation at each (fig. 30) (Practical Physiology). 2ncl. By taking advantage of the fact that the conducting part of a neuron is electro-positive, i.e. like the zinc element in a galvanic cell, to the rest (p. 60), and by finding how long after stimulation at one point this electric change reaches another point at a measured distance from it (fig. 8 1 ). The rate of conduction varies considerably; everything stimulating protoplasmic activity accelerating, and everything NERVE 71 depressing protoplasmic activity diminishing it. Under normal conditions in the fresh nerve of the frog, the velocit}' is about 33 metres per second. In man it is about 100 to 150 metres per second, and in the octopus only about 2 metres. (h) Factors modifying Conduction. — Conduction is modified by temperature. Cooling a nerve lowers its power of con- duction ; gently heating it increases it. Various drugs which diminish protoplasmic activity — e.g. chloroform, ether, carbon dioxide, etc. — diminish conduction. But while the excitability of the part of the nerve under the ^-^ R.M. I.R.C. O.R.C. H.C. Fig, 87. — To show the movements of the basilar membrane with the passage of a sound wave, and the manner in which, by the displacement of Cortis' arch I.R.C, O.R.C, the reticular membrane pulls upon the cilia C, which are embedded in the tectorium T., and thus may stimulate the nerve endings N. of enabling the appreciation of the pitch and quality of sound, and of enabling complex sounds to be analysed. How it does so is still somewhat problematical. Helmholtz main- tained that it is by resonance, the fibres of the basilar membrane acting like the strings of a piano, each one of which, or each set of which, is made to vibrate by a particular note and its overtones, and thus to stimulate the nerve endings among the hair cells situated upon these parts of the mem- brane. Some experiments on dogs, in which the apprecia- tion of notes of lower pitch was apparently lost after the upper turns of the cochlea were destroyed, and some few cases of partial destruction of the cochlea in the human NERVE 175 subject with alterations in pitch perception, give support to this theory. But it has recently been pointed out by Wrightson that there is no real proof of this theory, and that it assumes that the air waves are propagated up the scala vestibuli, through the helicotrema, and down the scala tympani. It has further been urged that the small size of the opening at the helicotrema and the large extent of scala media exposed to the perilymph must tend to favour a trans- mission of pressure across this scala from the scala vestibuli to the scala tympani, and so to the round window. Now this would cause a displacement of the basilar membrane — 1st. Downwards. 2nd. Back to the horizontal. 3rd. Upwards. 4th. Back to the horizontal, as in fig. 87. This would result in a lateral displacement of Cortis' arch round the base of the internal rods as a hinge, and this would lead to a pull first in one direction then in the other of the reticular membrane, which would lead to a bending of the cilia embedded in the tectorial membrane, which is firmly attached to the denticulate lamina, and this might stimulate the cells, thus stimulating the nerve endings and so leading to stimulation of the auditory centre. This view of the action of the ear brings hearing into accord with the sense of touch, and it is of interest that the otic vesicle is developed as an invagination of the skin. The mechanism is a most delicate one for "weighing" the small variations of pressure which constitute sound waves. Such a theory serves to explain the possibility of notes of different pitch producing different effects in the short stumpy cochlea of the bird, which is difficult to understand on Helmholtz's theory. 176 VETERINARY PHYSIOLOGY IV. THE METHODS BY WHICH THE RECEIVING AREAS HAVE BEEN LOCALISED. The determination of the exact parts of the cortex cerebri concerned with the reception of the incoming impres- sions from the different peripheral receptors has proved to be by no means easy, but the combination of various methods has overcome these difficulties and has enabled the localisation to be made with exactness. 1st. ExpeTimental Methods. — (a) Sensations are the usual accompaniment of the activity of the receiving mechanism. But, in the lower animals, it is not possible to have a direct expression of whether or not sensations are experienced, and therefore, in determining whether removal of any part of the brain has taken away the power of receiv- ing impressions, we have to depend upon the absence of the usual mode of response to the given stimulus. But the absence of this may mean, not that the receiving mechanism is destroyed, but either that the reacting mechanism is out of action, or that the channels of conduction have been interfered with (see fig. 88). Thus, if light be flashed in the eye of a monkey, it responds by glancing towards the source of illumination ; and if this movement is absent it may be due to (1) loss of the receiving mechanism ; (2) loss of the mechanism causing the movements ; or (3) interruption of the channels be- tween them. Again, it is quite possible that, after removing the receiving mechanism in the cerebrum, external stimuli may lead to the usual response hy acting through lower reflex arcs (fig. 88). If, for instance, we suppose the receiving part of the cerebrum connected with the reception of tactile impressions to be entirely destroyed, scratching the sole of the foot may still cause the leg to be drawn up, just as if a sensation had been experienced. Here, although the upper arc is out of action, the lower arc still acts. (6) In the lower animals, stimulation of a part of the brain, if it be connected with the reception of impres- NERVE 177 sions, may cause the series of movements which naturally follow such an impression. But these movements may also be caused by directly stimulating the reacting mechanism. Wlien, however, removal of a part of the brain causes no loss of power of moveinent, and yet prevents a stimulus frovi causing its natural response, it is justifiahle to conclude that that p)art of the brain is connected with reception. 2nd. Clinical and Patholo- gical Methods. — In man, the ..-- •-._ chief difficulty of obtaining infor- mation is in finding cases where only a limited part of the brain is affected. But such cases have been observed. Tumours of the inner aspect of an occipital lobe, for instance, have been found to be associated with loss of visual sensations without loss of mus- cular power, and thus the con- clusion has been drawn that this part of the occipital lobe is the receiving mechanism for stimuli from the eyes. 3rd Pathological. — As a result of the destruction of certain parts of the nervous system, in the region of the thalamus, either by experiment in the lower animals or by disease in man, a degeneration of nerve fibres may occur to some definite region of the cortex, and this generally shows that the area is a receiving one. 4ith. Anatomical Methods. — When it has been found possible to assign a definite function to any area of the cortex, its extent and limits may be determined by the extent and distribution of the particular character of the arrangement and structure of the nerve cells. 12 Fig. 88. — Diagram to Illustrate Different possible Channels of Cerebral Response to Stimula- tion, and to show how, through reflex action of the lower arcs, the action of the higher arcs may be simulated. 178 VETERINARY PHYSIOLOGY oth. Developmental Methods. — Flechsig has found that bands of fibres going to certain parts of the cortex get their medullary sheaths earlier than others, and that the fibres to each part of the cortex become medullated at a definite date. The areas, the fibres of which get their sheaths first, he calls the primary projection areas, and they correspond very closely with the receiving areas determined by other methods (figs. 51 and 52). Qth. Comparative Anatomy. — The complexity of different BODY SENSE: AUDI TORY - OLFACTORY HiGHFR Associative ""I BODY SENSES AUDITORY ■OLFACTORY ^ Fig. 89. — A purely Schematic Diagram to show the relations of receiving, associating, and discharging parts of the cortex cerebri, and to illus- trate that each of these is in itself receiving, associating, and dis- charging. The mechanism of reaction to visual impressions is given, and the modifying influence of other incoming stimuli is indicated. parts of the cortex is very different in different animals, and this affords some indication of the probable function of the various parts. Thus, the sub-granular layers are first developed and are best marked in the lowest mammals, and it may be concluded that they have specially to do with simple instinctive activities. The granular layer is best developed in what other evidence indicates to be receiving areas. The supra-granular layers are the last to develop and attain their greatest thickness in the higher mammals, especially in the frontal part of the brain, the development NERVE 179 of which is speciall}^ associated with the higher mental activities (fig. 90). Further, in the group of mammals which depend largely on olfactory impressions, the rhinencephalon is markedly developed, while in those in which smell plays a sub- ordinate part this portion of the brain is only slightly developed (fig. 61). It must at once be recognised that if such special parts exist, each must he in nature receiving, reacting, and, to some extent, associative. Thus, if one part of the cortex is specially connected with the reception of impulses from the eye, it must be able to bring about appropriate reactions either by sending impulses directly outwards or by acting upon some part of the brain which has the function of bringing about a reaction. And, in order that the reaction may be appropriate, some associative mechanism, either in these parts of the cortex or elsewhere, must be brought into play (fig. 89). V. THE INTEGRATION OF SENSATIONS IN THE CORTEX. The Cortex Cerebri and Mental Life. We have seen that stimulation of definite parts of the -cortex cerebri may lead not only to modification of move- ment through the spinal arcs, but also to changes of consciousness, which have been described as sensations. But the great object of the development of the cerebral cortex from the basal ganglia is to furnish a means by which these sensations are associated and integrated, so that more complex changes of consciousness may result. A full study of this is beyond the domain of physiology and encroaches on the territory of the psychologist. A pine tree may, through the visual mechanism, produce a sensation of green of a certain extent and from a certain direction ; the odour may act upon our olfactory mechanism ; the wind in the branches may stimulate our hearing, and when we approach and touch the tree our 180 VETERINARY PHYSIOLOGY cutaneous sensations are evoked and our muscle-joint sense is aroused. But, unless these sensations are brought together and integrated, we can have no recognition that some one object, a pine tree, is calling them forth. It is only by an association of the sensations that wo gain the knowledge that all are due to the object which we agree to call a pine tree. If, at a later date, some of these different sensations called forth by this tree are again elicited, they are associated Total . depth' lot*' .^ depth *» 4MontKs Foetxis New bom Child Normal Hu/rvan A.dull Fig. 90. — To show the development of the different layers of the cortex in man, and their condition in one of the lower mammals — the mole. The first column shows the two layers, from the lower of which the infra- granular, granular, and supra-granular layers of the adult cortex are formed. The second column shows the cortex at the time of birth. The third column shows the growth of the supra-granular layers as adult life is reached. In the fourth column the cortex of the adult mole is shown for comparison. (After Bolton.) with the past impressions and again call forth the idea of the pine tree and may lead us to conclude that we are near one. This means that each sensation and each combination of sensations or perceptions of the object producing them must leave an impress on the brain which is the physical basis of memory, and that the repetition of some of them, by NERVE 181 association with these previous impressions, leads to their renewal, leads to our recollecting the past experiences. 1. Structural Development. In the lower vertebrata the ditferentiation of the cortex from the basal ganglia is incomplete, and it is only in the higher mammals — monkeys and man — that the cortex reaches full physiological importance. Fig. 91. — The passage of fibres from the nuclei of the thalamus to the cortex cerebri of a primitive mammal. Th.Op., thalamus ; L.P., lobus pyriformis ; /.r., fissura rhinica ; F///'", auditory area; //'", visual area; ^., hippocampus. (Elliot Smith.) The cerebrum originally developed as a ganglion in connection with the organ of smell, and in the osmatic mammals — those in which smell plays a great part in guiding their actions — a large part of the cerebrum remains specially connected with the nose. This may be called the rhinencephalon (fig. 61, p. 135). The cortex cerebri, or neopallium, is a secondary develop- ment from the thalamus, with which it remains closely associated by outgoing and ingoing neurons (fig. 91). In the human foetus at four months, two layers are visible in the cortex — (1) an outer molecular layer of fibres, and under this (2) layers of unditferentiated cells (fig. 90). By the sixth month this second layer has become divided into two by a well-developed layer of small cells, the 182 VETERINARY PHYSIOLOGY granular layer. The deeper layer becomes differentiated into a layer of ^polymorphic cells, and outside of this a layer of fibres, the layer of Baillarger. Outside the granular layer a layer of 'pyramidal cells appears below the outer layer of fibres. Histology. — At birth, the cortex in the neopallium, from without inwards, consists of (fig. 92) — 1 . Outer layer of fibres. 2. Layer of pyramidal cells, 3. Layer of granules. 4. Inner layer of fibres (Baillarger's layer). 5. Layers of polymorphic cells. It is the supra-granular layers which increase as develop- ment advances. The adult mole has a cortex like that of the six-month human foetus (fig. 90). The cells of the cortex send dendritic processes up towards the surface, Avhere they form a complicated series of synapses, and they also send axon-processes downwards into the white substance of the brain. From these fibres, collaterals come off which connect different parts of the cortex of the same side, and which also connect the cortex of one side with that of the other, and with the basal ganglia (fig. 93). In the rhinencephalon three layers develop in the cortex — (1) the outer layer of fibres; (2) the layer of granules, often curiously broken up into nests ; and (3) the layer of polymorphic cells. 2. Functional Development. An animal at birth is little more than a reflex machine, and the functions of its cortex cerebri are still in abeyance. But the ingoing tracts from the visual, auditory, tactile and other receptors are fully developed, and hence from the first a stream of stimuli pours in upon the cortex. Although these may not at first be properly integrated, they influence and colour one another, giving rise to the pleasurable state of consciousness in the creature signified by NERVE 183 ^^ -^,:^ a condition of rest, and to the unpleasant state associated with restlessness and crying. Only when sensations become more completely integrated in the developing cortex is any real mental life possible. The power of integrating largely de- pends upon : — (1) The previous history of the brain, both phylogenetic and ontogenetic. For, ; just as in the spinal cord channels of action are formed, so in the cerebrum, if a given reaction once follows a given stimulus, it will tend to follow it again. 3 and 4 [r?; ^t.^ ■ a'- Fig. 92. — A, Section of cerebra cortex in the pre-central lobe (a motor area). (For description of zones, see text.) B, Section through cerebral cortex in the region of the calcarine fissure (visual area), stained to show the arrangement of the fibres. (For description of zones, see text.) (Campbell.) 184 VETERINARY PHYSIOLOGY (a) This training or preparation of the brain is in part hereditary. Each member of a species is born with well- estabhshed lines of action in the process of development, and throughout life these inherited channels play an important part in determining the results of stimulation. In young fowls, as soon as they are hatched, the acts of running and of pecking are at once performed, and in many families particular gestures or expressions follow certain modes of stimulation in many different individuals without the Fig. 93. — Diagram of collateral connections of different parts of the cere- bral cortex, a, b, c, pyramidal cells of the cortex, all connected by collateral branches with other parts of the cortex in the same and in the opposite hemisphere, a give off the pyramidal fibres to the cord. {After Ramon y Cajal.) consciousness of the person being involved. They are inherited cerebral reflexes. (6) Paths may also have been developed in the individual as the result of previous activities of the nervous mechanism. For, if a given action has once followed a given stimulus, it always tends to follow it again. This, in fact, is the basis of all training of animals — to open up paths in the nervous system by which the most suitable response may be made to any given stimulus, and to prevent the formation of paths by which inappropriate reaction may be produced. (2) The nutrition of the brain. — Not only will the previous training of the brain thus act as the directive force in the response to stimuli, but the nutrition of the brain also plays an important part. The action of a brain when well nourished and freely supplied with pure blood is often very different from that of the same brain when badly nourished or imperfectly supplied with blood. NERVE 185 3. Storing and Associating Part of the Cortex. The existence of a special part or parts of the brain connected with the storing of impressions, so that they may be associated with present sensations, is indicated by the following considerations : — It is this association of present stimuli with past sensations which is the basis of intellectual life, and in man the frontal and parietal lobes of the brain are much more developed than in the lower animals. So far, stimulation of these has failed to give any indication of resulting sensations, or to produce muscular movements. They may be extensively injured without loss of sensation and without paralysis, and hence it has been concluded that the storing and associating functions must be chiefly located in them. In these regions the nerve fibres acquire their medullary sheath at a very late date. 4. The Relationship of Consciousness to Cerebral Action. Cerebral action frequently goes on without consciousness being implicated ; but, so far as we know, consciousness without accompanying cerebral action is unknown, and there is evidence that it is only when the actions of the various parts of the cerebrum are co-ordinated that consciousness is possible. In cases of Jacksonian epilepsy, as a result of a small centre of irritation on the surface of the brain, a violently excessive action of the cerebral neurons starts at the part irritated and passes to involve more and more of the brain. In such fits, it is found that at first the patient's consciousness is not lost, but that, when a sufficient area of brain is involved in this excessive and inco-ordinated action, consciousness disappears. Unconsciousness may be produced by many conditions which modify the nutrition of the brain. (1) Many drugs, of which chloroform and ether may be taken as types, poison the brain and cause loss of consciousness. (2) Similar poisons may develop in the body as the result of faulty metabolism, as is seen in diabetic coma. (3) A sudden failure of the supply of blood to the higher centres may cause the loss of consciousness which occurs in fainting. 186 VETERINARY PHYSIOLOGY (4) Hsemorrhage into the brain, or a tumour inside the skull may interfere with the blood supply by pressure and also cause loss of consciousness. The study of the action of drugs which abolish conscious- ness — e.g. chloroform and morphine — on the dendrites of brain cells suggests a physical explanation of the condition. It is found that these drugs cause a general extension of the gemmules of all the dendrites ; and, if we imagine that the co-ordinated action of any part of the brain is secured by definite dendrites of one set of neurons coming into relationship with definite dendrites of another set of neurons by their gemmules so as to establish definite paths, the want of co-ordinate relationship estab- lished by the general expansion would explain the dis- appearance of the definite sensations which constitute consciousness. 5. Time of Cerebral Action. The cerebral mechanism takes a very appreciable time to act, and the time varies (1) with the complexity of the action and (2) with the condition of the nervous apparatus. Of the time between the presentation of a flash of light to the eye or a touch to the skin and a signal made by the person acted upon when it is perceived, part is occupied in the passage of the nerve impulses up and down the nerves and in the latent period of muscular contraction, but a varying period of something over one- tenth of a second remains, representing the time occupied in the cerebral action {Practical Physiology). Continued action of the nerve centres may lead first to a shortening of the reaction time as a result of the facilitation of the passage of the impulses over the synapses {practice), but this is soon followed by a prolongation {fatigue). The latter condition is produced by the action of alcohol, chloroform, and other poisons. 6. Fatigue of the Cerebral Mechanism. Fatigue of the cerebral mechanism is manifested {a) by decrease in the power of attention, comparable to the loss NERVE 187 of command of the common path seen in the spinal reflex action (p. 86) ; (b) by prolongation of the reaction time ; and (c) by a more rapid decrease of the force of muscular contraction. The seat of the change is in the cerebral synapses, and, after these have failed to act, the spinal arcs may still be unaffected and spinal reflexes may be produced. The cause of the condition is probably primarily the accumulation of the products of activity and the lack of a free supply of oxygen to the brain, and the condition may often be removed by (a) a short rest, or by (6) the substitu- tion of a change of occupation, or by (c) muscular exercise, which increases the flow of blood through the brain, or (cZ) by sleep. The act of yawning (p. 522) is simply a reflex which increases the flow of blood to the heart and thus on to the brain. It is Nature's effort to overcome cerebral fatigue. As to how the synapses are affected, a consideration of the possible way in which such poisons as chloroform act upon the dendrites and gemmules to abolish definite lines of action suggests that in fatigue the same thing may occur to a lesser degree. Continued action also leads to well-marked changes in the cell protoplasm of the neurons. The Nissl's granules diminish and the nucleus shrivels and becomes poorer in chromatin. 7. Sleep. Fatigue of the cerebral mechanism is closely connected with sleep. As the result of fatigue, external stimuli produce less and less definite effects, and thus the changes, which are the physical basis of consciousness, become less and less marked. At the same time, by artificial means, stimuli are usually so far as possible excluded. Absence of light, of noise, and of tactile and thermal stimuli all conduce to sleep. The purpose of hypnotic drugs is to render the brain less susceptible to external or internal stimuli. As sleep advances (1) consciousness fades away, and, as the cerebral activity diminishes, (2) the arterioles throughout 188 VETERINARY PHYSIOLOGY the body dilate, the arterial blood pressure falls, and thus less blood is sent to the brain, and the organ becomes more bloodless. This may be seen in cases of trephining, where a sinking of the trephine scar occurs during sleep. (3) The eyeUds close, (4) the eyeballs turn upwards, (5) the pupils contract, and (6) the voluntary muscles may relax. In the horse, ox, etc., the tonic contraction of the muscles, with the assistance of the ligaments (p. 237) sustaining the body in the standing position, may persist, and the animal may sleep in that position. The depth of sleep may be measured by the strength of the stimuli required to overcome it. The prejudicial effect of want of sleep has been demon- strated by observations upon young dogs. It was found that they died in five days if prevented from sleeping, while, if allowed to sleep, they withstood even the withdrawal of food for no less than twenty days. More sleep is required by young than by old animals. 8. Hypnosis. This is a condition in some respects allied to sleep. In many of the lower animals it is readily produced, simply by holding the animal firmly and placing it in any unusual position, as on the back, especially if stimuli from without are cut off— e.g. by bandaging the eyes. It may then lie with- out moving for a prolonged period, and may react much in the same way as if decerebrated. The condition may be induced in many people by powerfully arresting the attention, and it is probably due to a removal of the influence of the higher centres over the lower. The respirations and pulse become quickened, the pupils dilate, and the sensitiveness of the neuro - muscular mechanism is so increased that merely stroking a group of muscles may throw them into firm contraction. This suggests an abrogation of the cerebral function and a dominance of the tonic vestibulo-cerebellor- spinal arc. The individual becomes a reflex machine even as regards the cerebral arcs, and each stimulus is followed by an immediate reaction. NERVE 189 VI. THE DISCHARGING SIDE OF THE CEREBRAL ARC. In the previous section the way in which changes in the external world act upon the body and the consciousness has been considered. The reactions of the body through the spinal arcs in reflex action have also been dealt with, and the way in which these reactions are controlled and adjusted by the concomitant action of the proprioceptive mechanisms of the muscles and joints on the one hand, and of the vestibule and semicircular canals on the other, has been explained (p. 121). I. The Basal Ganglia. The way in which all incoming impulses are interrupted and associated in the thalamus has been considered (p. 118). The thalamus is connected not only with the cortex, but also with the different nuclei of the corpus striatum and with the red nucleus from which fibres pass down the cord in front of the crossed pyramidal tract (fig. 97). In man and apes the functions of these connections have been largely handed over to the control of the cortex, but in lower mammals they are of primary importance. Corpus Striatum. — There is some evidence that the corpus striatum plays a part in controlling temperature (p. 269). It was found that stimulation leads to increased heat production, which must be due to increased chemical change in the muscles. More recently it has been found that stimulation by njeans of cold leads to a rise of tem- perature, while stimulation by heat leads to a fall, the first causing a constriction of the blood-vessels of the sl^in, the second causing a dilatation. II. The Discharging Area of the Cortex Cerebri. The way in which movements are originated and dominated by the cortex cerebri, as the result of the integration of the stimuli falliug on the body, and their association with one another and with the impressions of 190 VETERINARY PHYSIOLOGY previous stimulation, so that the resulting action may be appropriate to the surroundings, must now be studied. Ample evidence is forthcoming that in men and apes the part of the cortex round about and chiefly in front of the central fissure performs this function. In the dog, cat and pig it is situated round the cruciate fissure (figs. 52, p. 115, and 94). Fig. 94. — (a) Surface of the left Cerebral Hemisphere of a Monkey to show the situations of some of the Discharging Mechanisms (front to left) ; (b) Mesial Surface of the same Hemisphere (front to right). This area is played upon by all the sensory and associa- tive arrangements in the cortex. Like every other part of the brain it receives and discharges impulses (fig. 89). But unlike the receiving areas, which have been already considered, it discharges outwards from the brain upon the spinal arcs. NERVE 191 The evidence as regards its position is both clinical and experimental. 1. Clinical and Pathological Evidence. — Destructive lesions of this area on one side cause a loss of the so-called voluntary action of groups of muscles on the opposite side of the body, while the muscles themselves and the spinal reflexes connected with them are not interfered with. The spinal reflexes may in fact become more active. Certain lesions may directly stimulate these centres, causing them to act without the previous action of the other cerebral mechanisms and may cause convulsions. This is seen in Jacksonian epilepsy, where, as the result of a spicule of bone or a thickened bit of membrane, one part of the cortex is from time to time excited. This pro- duces movements of certain groups of muscles, which spread outwards to other groups as the stimulation of the cortex extends outwards from its seat of origin, till finally all the muscles of the body are involved in a general convulsion. 2. Experimental Evidence. — Experimental observations have fully confirmed and extended the conclusions arrived at from such pathological evidence. (a) Removal. — If parts of these convolutions be excised in the monkey, the animal loses the power of voluntary movement of certain groups of muscles on the opposite side of the body. Movements requiring the co-operative action of muscles of both sides, e.g. movements of the eyes and trunk, are not abolished by unilateral destruction. In these motor areas the lesion must be extensive to cause coTnplete paralysis of any group of muscles. A limited lesion may simply cause a loss of the finer movements. Thus, a monkey with part of the middle portion of the Eolandic areas removed may be able to move its arm and hand, but may be quite unable to pick up objects from the floor of its cage. Even after removal of a fairly extensive part of these centres, with resulting muscular paralysis, it has been found that after a time more or less complete recovery takes place. Evidently some other part than that removed can take upon 192 VETERINARY PHYSIOLOGY itself the function, is capable of education, just as the lower spinal centres seem capable of adaptation. (b) Stimulation by electricity causes movements of group of muscles of the opposite side of the body and of muscles on both sides when bilateral co-operation is required. These movements are elicited by much weaker currents than are required to produce them on stimulating the typical receiving area already studied. If the cortex is stripped off and the white fibres below Afuaiy^g^- £Ar- / EueLid / citisure Noie Fig. 95. — Left Hemisphere of Brain of Chimpanzee to show the results of stimulating different parts. The Sulcus Centralis is the fissure of Rolando. (From Grunbaum and Sherrington. ) it are directly stimulated, the latent period is shortened and the strength of current required to produce movements is greater. The work of Griinbaum and Sherrington on the brain of anthropoid apes has shown that the discharging mechanism is chiefly in the pre-central convolution (fig. 95), extend- ing forwards into the posterior parts of the superior, middle and inferior frontal convolutions, with a patch far out in the frontal area by stimulation of which movements of the eyes are produced. This is present only in men and apes which use binocular vision. It is associated by a band of NERVE 193 fibres with the visuo-sensory area, and fibres pass from it down the cerebro-pontine tracts to reach the cerebellum (fig. 58). The discharging part of the cortex may be con- sidered as a map of the various muscular combinations throughout the body, the map being mounted so that the lower part represents the face, the middle part the arm, and the upper part the leg, probably corresponding closely to the map of cutaneous and muscle-joint sensibility, although this may lie rather more posteriorly. Each large division is filled in so that all the various combinations of muscular movement are represented (fig. 95). It must be remembered that these centres do not send nerves to single muscles, but that they play upon the spinal centres to produce combined move- ments of sets of muscles. These movements involve inhibition as well as excita- tion, just as the spinal reflexes do. This is very clearly shown as regards the eye movements. In the monkey, the resting position of the eyes is straight forward with the optic axes parallel. If all the nerves to the ocular muscles be cut, this position is assumed, and, if the position of the eye be passively altered, upon removing the displacing force, it springs back to this position. If the III. and IV. nerves of the left side be cut (p. 161), so that the external rectus alone is unparalysed, then, exciting a part of the cortex which causes movements of the two eyes to the right, produces not only a movement of the right eye in that direction, but a movement of the left eye to the right as far as the middle line — the position of rest — showing that the VI. nerve has been inhibited. Stimulation of the cortex causes flexion more readily than extension, apparently because the inhibitory mechanism for the extensors is better developed than that for the flexors. Sherrington finds that this condition is reversed under the influence of strychnine or of tetanus toxin, and that stimuli, which in normal conditions will cause flexion, now cause powerful extension, and hence co-ordinated movement is impossible. 13 194 VETERINARY PHYSIOLOGY up III. Fibres passing outwards from the Discharging Parts of the Cerebrum. The fibres coming from this area of the cortex are mixed with the ingoing fibres from the thalamus ah-eady described. But they are distinguished from them by the fact that they get their medullary sheaths at a late date, so that they may be traced right down into the , cord as the pyramidal tract in the following situations : — 1st. In the corona radiata (figs. 96 and 97). 2nd. In the anterior two- thirds of the posterior limb of the internal capsule, the face fibres lying to the front, the arm fibres behind these, and the leg fibres furthest back (figs. 96 and 97). Srd. In the central part of the crusta of the crus, arranged from within out- wards — face, arm, leg (fig. 97). Uh. In the pons Varolii, between the deep and super- ficial transverse fibres. The face fibres cross here (fig. 97). Hence a unilateral tumour in this situation may cause paralysis of the face on one side and of the limbs on the other — a crossed paralysis. 5th. In the anterior pyramids of the medulla decussate at the junction of Fig. 96. — Diagrammatic horizontal section through base of cerebral hemisphere, showing (1) the out- going fibres for the leg, arm, and face springing from the cortex of the central areas, passing through the internal capsule between the thalamus and the lenticular nucleus. The face fibres cross in the pons, the leg and arm fibres in the medulla. (2) The incoming fibres (fillet, eye, etc.) have cell stations in the thalamus, anfl then pass on to the cortex. oblongata. Most of them the medulla and spinal cord (fig. 97). NERVE 195 6th. In the spinal cord they constitute the crossed pyramidal tract of the opposite side. Those which do not cross run down for some distance in the antero-median tract as the direct pyramidal fibres to cross lower down (fig. 98). 7 th. From the pyramidal fibres collaterals come off and act, through intercalated neurons, on the outgoing neurons from the anterior horn of grey matter to the skeletal muscles (fig. 33). These pyramidal fibres de- generate when the motor cortex is destroyed or when they are severed by a haemorrhage into the internal capsule. Fibres from the Basal Ganglia. — De- generation of the rubro-spinal and of the tecto-spinal fibres does not occur unless this interruption is below the level of the tectum (p. 1 1 3). The course of the various outgoing fibres in the spinal cord in man is shown in fig. 98. In addition to the tracts from the cerebrum, the downgoing fibres forming Fig. 97.— To show the the outgoing part of the vestitalo- ^CIT <:Ttlr c .A A A 1 1 Fig. 114.— Effect of a series of Stimuli onSkeletalMuscle. (See text.) 230 VETERINARY PHYSIOLOCxY and being maintained at this level, till the series of stimuli causing the contraction is removed, or until fatigue causes relaxation of the muscle. This is the condition of " com- plete tetanus" (fig. 114 (3)), (Practical Physiology). The rate at which stimuli must follow one another in order to produce a tetanus depends upon a large number of factors. An37thing which increases the duration of a single contrac- tion decreases the number of stimuli per second sufficient to produce a tetanus, and thus, all the various^ factors modifying a single muscular contraction modify the number of stimuli required (p, 225). The red fibres in tetanus give a more powerful con- traction than do the white fibres. The reason -udiy a very rapid series of stimuli cause a tetanus in skeletal muscle is that the refractory period is so very short (p. 216). Hence, if the stimuli follow one another sufficiently rapidly they fail to produce a tetanus. Every voluntary contraction of any group of the muscles is probably of the nature of a tetanus ; and the question thus arises : — At what rate do the stimuli which cause such a tetanus pass from the spinal cord to the muscles ? Taking advantage of the electrical change which accom- panies each muscular contraction (p. 212), and using the string galvanometer (p. 214), it has been shown that, in sustained voluntary contraction, electric variations occur at a more or less definite rate in different muscles, faster in the shorter, and slower in the longer muscles. Kate per Second. Masseter muscle. . . . . 88 to 100 Arm muscles (flexors) . . . . 47 ,, 50 Quadriceps extensor femoris . . 38 ,, 41 Hence it may safely be concluded that impulses at these various rates pass from the spinal cord to the muscles to produce the sustained contraction of voluntarj' action. Besides change in shape muscle when stimulated undergoes electrical changes (p. 212), changes in elasticity (p. 211), changes in temperature, heat production (p. 246), and chemical changes (p. 254). MUSCLE 231 4. Mode of Action of Muscles. The skeletal muscles act to produce movements of the body from place to place, or movements of one part of the body on another. This they do by pulling on the bony framework to cause definite movements of the various joints. The muscles are arranged in opposing sets in relation to each joint — one causing movement in one direction, another in the opposite direction — and named according to their mode of action, flexors, extensors, adductors, abductors, etc. In the production of any particular movement at one joint — say flexion of the phalanx of a foot — the opposing muscles, the extensors, have their activity suppressed or inhibited (p. 86). Other muscles which give the support needed for the If '- Fig. 115. — The three types of lever illustrated by the movements at tne ankle-joint. movement also come into action. This may be called their Co-operative Antagonism. These muscles, when acting alone, cause a movement in the opposite direction to that being produced, e.g. extension instead of flexion. If the part of the brain which causes flexion of the hand of the monkey be stimulated and the nerve to the flexors divided, the co-operative action of the supporting extensors brings about an extension of the hand. It is very probable that the red muscles act specially in this fixation of joints to enable the pale muscles to bring about different kinds of movements. Thus, with the ankle fixed, the gastrocnemius may flex at the knee ; with the knee fixed, it may extend at the ankle. The muscles act upon the bones, arranged as a series of levers of the three classes at the various joints (fig. 115). These may be illustrated by the foot in man. 232 VETERINARY PHYSIOLOGY 1st Class. — Fulcrum between power and weight. In the ankle this is seen Avhen, by a contraction of the gastroc- nemius, we push upon some object with the toes. 2nd Class. — Weight between fulcrum and power. In M. interosseus M. flexor digitorum _ sublimis Sesamoid bone M. flexor digitorum profundus Tliird metaLarpal bone M. extensor digitorum communis "Ergot' Ligg. sesamoidea obliqua Lig. sesamoideum lectum M. flexor digitorum profundus Lig. plialangosesainoideum Cuneus (" frog' ) Cuneate m»trix Digital torus Solar matrix Fig. 116. — Longitudinal Section of Digit. 1 and 1', 2 and 2', 3 and 3' = Joint capsules. 4 = Synovial sheath of flexor tendons. 5 = Synovial sheath of deep flexor tendon. {From " The Limbs of the Horse." Bradley.) rising on the toes, the base of the metatarsals is the fulcrum, the weight comes at the ankle and the power on the os calcis. MUSCLE 233 3rd Class. — Power between fulcrum and weight. In raising a weight placed on the dorsal aspect of the toes by the contraction of the extensors of the foot, we have the weight at the toes, the power at the tarsus, and the fulcrum at the ankle. In the joints of animals actions involving tbe principle of each of these levers may be found. 5. Special Mechanisms in the Horse. (1) The Limbs of the Horse. The condition of the feet and legs is the chief limiting factors in work production in the horse. An intimate knowledge of the anatomy of the various structures involved must be obtained in the dissecting room. The Foot. — The weight of the horse is transmitted through the second phalanx to the foot (fig. 116). The articular surface of the second phalanx is larger than that of the third, so that its posterior part rests upon the sesamoid bone which is supported by the tendons of the flexor muscles and further held in position by the sesamoid ligaments. This yielding articulation assists in reducing and distributing shock. The tendon of the flexor muscle rests upon the digital torus (the plantar cushion). This is a pyramidal shaped mass of yellow elastic and white fibrous tissue which stretches between the cartilages of the third phalanx to which its edges are attached (fig. 117). The superficial (volar) surface of this structure is arched, but becomes flattened out under pressure. The cartilages to which it is attached are elastic and yield under pressure, being pushed out slightly. The digital torus rests upon the elastic cuneus (the frog), which in the normal unshod hoof is on a level with the wearing edge of the wall. The sole of the foot (fig. 118) is concave. When the weight of the animal is put on it, the arch tends to flatten out, and at the same time there is slight expansion of the heel. This is provided for by the walls at the heel being deflected inward to form the bars instead of being continuous to complete the circle. 234 VETERINARY PHYSIOLOGY The bars, which are also elastic, receive part of the weight of the animal. The posterior part of the foot which first comes to the ground and. receives the impact is thus well adapted for the absorption and dissipation of shock. If the toe of the foot were provided with these elastic yielding structures the propulsive force would be dissipated. Third metacarpal bone First phalanx Second phalanx Cartilage of third phalanx Line of border of hoof Third phalanx Fig. 117. — Lateral Aspect of the Phalanges and the Cartilage of the Third Phalanx. (Br.\dlf.y. ) Rigidity is required to transmit the force from the toe which acts as the fulcrum. In the toe, therefore, the matrix of the hoof is directly adherent to the bone, and the horny part of the hoof is thicker and less elastic than at the heel, so that the force of the thrust with the toe is passed direct from the hoof to the bony column of the leg. MUSCLE 28.= The breadth of the bearing edge of the hoof is greatest at the toe where it is about 10 mm. It becomes less towards the heel, where it is about half that of the toe. The inner surface of the wall of the hoof is marked off from the border of the sole by a line of pale soft horn — " the white line." This line is taken as an indication of the limit of safety in driving shoe nails to avoid the sensitive part of the foot. The histology of the hoof Tnust he studied l^ractically. The Leg. — The conformation of the lesfs is of great Layer of pale horn uniting wall ; Inflected part of - wall (" bar ") Cruro-parietal groove Intercrural groove Base of cuneus (" bulb ") Apex of cuneus Crus of cuneus Fig. 118.— Volar Aspect of the Hoof. (Bradley.) importance, as the resultant forward thrust of the pressure of the toe on the ground is diminished unless the line of action of the force be in the true direction. To obtain this action, in the fore leg viewed from the front a vertical line from the middle of the scapulo-humeral articulation should divide the leg into two equal halves and meet the ground at the middle of the toe. In the hind leg, viewed from behind, a vertical line dropped from the tuberosity of the ischium should divide the leg into two equal halves and reach the ground in the middle of the heel (fig. 119, A). When the legs are as indicated, the line of 236 VETERINARY PHYSIOLOGY 8 O-S Is hi P'-B s n O 1— 1 c« — -- ^nS ^ cS rt 'o o 2 a '5 1^ o 2 .3 tc (U OJ O — 1| o & ,ti o Oi -R^ c6 'C 3 8| o o 'T3 q 1 o .2 > cS -§ = s a i-i -^ ^ 1 ^^ -§ MUSCLE 237 progression of the hoof is a straight line and the full force of the thrust is obtained in moving the mass of the body forward. When the conformation deviates from this standard, as in fig. 119, B, C, D, the line of progression of the foot is in segments of circles. Part of the force is lost and the hoof, or in the shod animal, the shoe, wears unevenly. The shape of the hoof and the slope of the phalanges are of great importance. The slope of the wall of the hoof and of the phalanges should be the same — about 45° to 50° in the front foot, and about 50° to 55'' in the hind foot. When the phalanges are too perpendicular, as in the " upright pastern" or "boxy foot" (fig. 120, A), the concussion absorbing mechanism is less effective, as more of the shock is trans- mitted direct from the third phalanx to the second. When the phalanges are too obliquely placed (fig. 120, C) undue strain is thrown upon the tendons and ligaments supporting the sesamoid bones. These are consequently more liable to injury. A high heel is usually associated with upright phalanges and a low heel with sloping phalanges. The more upright the foot the shorter and lower the stride. Fig. 120 illustrates how the course of the flight of the foot is determined by its shape. (2) Action of the Limbs, (1) In standing the weight of the body is chiefly slung by the serrati magni on the scapulas, which are supported by the bony columns of the fore limbs. The flexor and extensor muscles maintain the condition of partial flexion at the elbow joint. The metacarpo-phalangeal articulation (the fetlock joint) is supported chiefly by the tendons of the flexor muscles and by the interosseus muscle (the suspensory ligament). This is a muscle which has become tendinous in form and function. By it the sesamoid bone is suspended. The tendons of the flexor muscles, which are the chief supports for the fore legs, are connected to the bony column by fibrous bands (the check ligaments). These act as mechanical stays to the limb, relieving the muscles from 238 VETERINARY PHYSIOLOGY & Upright Foot usually associated with short Second Metacarpal and high heel. Stride is short, and foot reaches highest point in second half of flight. Foot of medium slope. Flight of hoof is an arc of circle, with highest point at centre. Acute Angled Foot, usually associated with long Second Metacarpal and low heel. Stride is long, and foot reaches highest point in first half of flight. Fig. 120. — Diagram showing influence of slope of foot (fore) on flight of hoof in walking. (After Lungwitz.) MUSCLE 239 strain when the standing position is long continued. A like arrangement of mechanical braces exists in the hind limbs. The centre of gravity is in a vertical plane passing about 6 inches behind the elbow. In standing, therefore, the greater weight, some 10 to 20 per cent, more, is borne by the fore legs than by the hind. The proportion depends largely on the position of the head. As the head comes down and forward as in sleep, the centre of gravity moves forward, and the proportion of weight carried by the fore legs is increased. In standing for any length of time the hind legs are used alternately to support the weight of the posterior part of the body, the one not in use being partly flexed and resting on the toe. From the fact that the hind legs are less straight than the fore legs, more work is required by the leg muscles in using them as supports. 2. Lying. — Owing to the sharp edge of the sternum the horse cannot lie vertically. It either lies inclined to one side with the four feet tucked under the body, or flat on the side with head and legs extended. 3. Rising. — In rising the head is raised, the fore feet are placed on the ground in front, and the hind legs are placed well below the body and push it up. The raising of the head is the first part of the act of rising, and if it be kept down the animal cannot rise. 4. The movements of the horse at the different paces have been analysed by instantaneous photography. Walk. — The body being balanced on three legs, as shown in fig. 121, one fore leg is advanced, the body moves forward on the corresponding hind leg, and the opposite hind foot leaves the ground before the fore foot reaches it, so that for a moment the horse is balanced on diagonal legs (2). The hind foot which has left the ground is now advanced, and before it is planted the corresponding fore foot is lifted (3), and thus, at this stage, the animal is balanced on the fore and hind leg of the same side (4). As the hind foot comes to the ground, the condition described at the starting is again reached and the process is repeated. Normally in walking the heel comes first to the ground. 240 VETERINARY PHYSIOLOGY but in drawing a heavy load the step is shortened and the toe. reaches the ground first. The speed attained in walking is usually about 4 miles Fio. 121.— The Walk. per hour. Among draught horses the greatest speed is got in the Clydesdale, which has been bred largely for the quality of the feet and legs. Trot. — -The body is driven forward by the alternate pro- pulsive action of the diagonal fore and hind legs. The off Fig. 122.— The Trot. fore and near hind feet leave the ground together, propelling the body upwards and forwards (fig. 122, 1), and are then advanced to again reach the ground, when the near fore and off hind feet repeat the same movements (3). MUSCLE 241 The length and stride of the trot is about 8 or 9 feet. The pace is usually about 7 or 8 miles an hour, but in horses trained for speed in trotting the pace may approach that of the gallop. Amble. — Here the two legs of the same side act together as do the diagonal legs in trotting. Gallop. — At one stage of the pace all the feet are off the ground and well tucked under the body (fig. 123, 1). One Fig. 123.— The Gallop. foot, say the off, first reaches the ground (2), and hind immediately after the opposite hind foot is planted in advance of it (3). The off fore now comes to the ground, and as it does so the off hind is lifted and the horse rests on diagonal fore and hind legs (4). Then the off hind foot leaves the ground and the animal is now on the off fore foot (5). The near fore foot is now planted and the off fore leaves the ground (6), and finally the near fore is also raised and the horse is again in the air. 16 242 VETERINARY PHYSIOLOGY The stride in the gallop is about ]5 to 20 feet. The speed is variable. Race horses attain a speed of 30 to 85 miles an hour on a race course of one to two miles length. Canter. — The canter is a less energetic gallop. At one moment all the feet are off the ground, and they are planted in the same order as in the gallop — near hind, off hind, near fore. But while in the gallop the near hind has left the ground before the near fore is planted, in the canter all these are on the ground at once, and it is only as the off fore comes to the ground that the near hind followed by the near fore is raised. The off hind and then the off fore next follow, and all the feet off the ground. Both the length of the stride and the speed are less in the canter than in the gallop. Jump. — The fore legs propel the body upwards, and the hind legs give a further forward and upward propulsion, and are then fully flexed under the body to clear the obstacle. The animal alights on its fore feet, one reaching the ground before the other. 6. Work of Muscle. As the result of the changes in shape, muscle performs its great function of doing mechanical work ; and the most important question which has to be considered in regard to muscle, as in regard to other machines, is the amount of work it .can do. The work unit generally employed is the kilogram-metre — the work required to raise one kilogram to the height of one metre against the force of gravity. Since the work done depends upon the weight moved and the distance through which it is moved, the work-doing power of muscle is governed by the (a) force of contraction, i.e. the tension developed which determines the weight which can be lifted, and by (6) the amount to which the m^iiscle can shorten, for this governs the distance through which the weight may be moved. It has been already shown that the force of contraction depends upon the sectional area of a muscle. A. thick muscle is stronger than a thinner one. On the other hand, the extent of contraction depends upon the length of the MUSCLE 243 muscle, since each muscle can contract to a fixed proportion of its original length. A glance at the diagram will at once make this plain (fig. 124). The size of the muscle is thus the first great factor which governs its work-doing power. But the tension developed also depends upon the length ■^ m. FiG. 124. — Influence of the length of a Muscle upon the work done. A is a muscle of two inches, and in contracting to half its length it lifts a weight to one inch. B is a muscle of one inch. It lifts the weight to half an inch. of the muscle at the moment of stimulation (p. 224); this and every factor which influences the force of muscular contraction also influences the work which can be done (see p. 245 et seq.). One factor, the eftect of the load, requires special con- sideration. It has already been shown that as this is increased the lift or extent of contraction is diminished. The following experiment, represented in fig. 125, illustrates the influence of increasing the load on the work-doing power ■of a muscle — Fig. 125. — To show the influence of Load on the Work done. Load. Lift. — — — — Work. It will be seen that increasing the load at first increases the amount of work done, but that, after a certain weight is reached, it diminishes it. There is, therefore, for every 244 VETERINARY PHYSIOLOGY muscle, so far as its working power is concerned, an optimum load. In studying the amount of work which a muscle, or set of muscles can do, the element of time must always be considered. Obviously, contracting muscles will do more work in an hour than in a minute. Further, the rate at which the work is done has an important influence, and the amount of work which can be done per unit of time will depend not merely on the condition of the onuscle and the load, but upon the rate at Uf.t Work output 4-7 kgm. per unit of time. Strong stimuli. Lift I I I I I I I I I Work output I I 6 kgm. per unit of time. Weaker stimuli. Fig. 126. — To show the influence of varying the strength of stimulation on the work done per unit of time. which the lifting is performed. This will depend upon (1) the strength of the stimuli and (2) the rate of stimula- tion. (1) Increasing the rate of work by the application of a very strong stimulus at shor-u intervals may rapidly lead to fatigue, and thus to a comparatively low output of work in the time of the experiment, while a smaller stimulus at the same rate may cause a much longer continuance of the response of the muscle and an actually greater output in the total time (fig. 126). (2) On the other hand, a stimulus too rapidly applied may soon lead to fatigue, while if more slowly applied the onset of fatigue may be postponed and the work done in- creased (fig. 127). The same is seen when the work of muscles in bulk is studied. Experiments by Zuntz showed that in the horse, MUSCLE 245 as the speed in walking rose above 78 metres per minute, the rate of expenditure of energy per unit of distance covered was increased. This is confirmed by experiments done on man. It has been found that in marching, the optimum rate — the rate at which the most work can be done on the least expenditure of energy — is something over 3 miles an hour. To force the pace above this leads to a dispro- portionate demand for energy and is less economical. Fig. 128, showing the extent of combustion in muscle measured by the CO2 produced, illustrates this. Lift Rapid succession of stimuli. Lift Work done 4-7 kgm. per unit of time. Work done 6 kgm. per unit of time. Slow succession of stimuli. Fig. 127. — To show the influence of varying the rate of stimulation on the work done per unit of time. The efficiency of a muscle as a machine thus depends upon the — 1. Load lifted. 2. Rate at which work is done. Hence the efficiency of a machine is often expressed in terms of Horse Power — the unit being 76 kgm. per sec. Measurement of work— 1. In the isolated muscle — (a) The work done by the single isolated muscle of the frog in a single twitch is got by multiplying the weight lifted by the extent of shortening of the muscle {Practical Physiology). (b) If the work during a series of contractions is to be measured, some means of adding the effect of each contrac- tion to its predecessor must be employed, as is done by the work-collector of Fick {Practical Physiology). 246 VETERINARY PHYSIOLOGY 2. In groujys of viuscles in the body. — When the work done by groups of muscles within the body has to be studied, some form of work-measurer or ergometer must be devised. A horse may be made to walk upon a platform which moves against a known resistance, or the pull exerted may be measured by means of a dynamometer, a simple form s:^ i i^ / 5 X J ^^ o / •1-0 S / '' / / ^ ^ .--^ S 1 IlLES P ZH Hou \ »-(V- Fig. 128. — Graph to show the effect of increasing the pace of walking upon the expenditure of energy measured by the oxygen consumed and carbon dioxide given off. (Briggs. ) of which would be a spring balance inserted between the horse and the object pulled. By these means the capacity of the horse for work (p. 252) has been determined experimentally. 7. Heat Production in Muscle. In muscle, as in a steam-engine or any other machine, by no means the whole of the energy is used for the production of mechanical work. Much of the energy is lost as heat. But while this is an actual loss in the steam-engine, the pro- MUSCLE 247 Juction of heat is necessary in warm-blooded animals to maintain the temperature of the body at a level at which the chemical changes essential for life are possible. That heat is given off by muscles in contraction is shown by the fact that, after muscular exercise, the temperature of the body rises for a short time. Some delicate method of measuring the temperature must be employed to demonstrate heat production in single isolated muscles. The mercurial thermometer is hardly sufficiently sensitive, and, therefore, the thermo-electrical method is most generally employed. Various forms of thermopile may be used (Appendix). The rise of temperature in a muscle after a single con- traction is extremely small, but after a tetanic contraction, lasting for two or three minutes, it is much greater. By the use of extremely delicate thermopiles it has been Fig. 129. — The continuous line shows the contraction of the heart of the terrapin : the dash line the production of heat, and the dotted line the temperature. shown that in contraction most of the heat is evolved in the relaxation phase. This is more easily demonstrated in the slow contraction of the heart of the terrapin than in skeletal muscle. The above diagram shows the relation of mechanical shortening to heat production (fig. 129). The amount of heat produced by a single isolated muscle may be calculated if (a) the weight of the muscle, (6) its temperature before and after contraction, and (c) the specific heat of muscle, are known. The specific heat of muscle is slightly greater than that of water, but the difference is so slight that it may be disregarded. If, then, a muscle of ten grams had a tempera- ture of 15° C. before it was made to contract, and a tempera- 248 VETERINARY PHYSIOLOGY ture of 15 '05^ C. after a period of contraction, then Oo gram- degrees of heat have been produced ; i.e. heat sufficient to raise the temperature of 0*5 gram of water through 1° C. The amount of energy liberated as heat may be cal- culated by the various methods considered in studying metabolism (p. 259). The heat units employed are the small and large calories — the small calorie, the heat required to raise one gram of water through one degree Centigrade, and the large Calorie — generally written with a large C — the heat required to raise a kilogram of water through one degree Centigrade. 8. The Relationship of Work Production to Heat Production. The Mechanical Eflaciency of Muscle. The proportion of work to heat is not constant in muscle any more than it is in an engine. If an unloaded muscle is made to contract, no work is done and all the energy is given off as heat, and the same thing happens when, in isometric contraction, a muscle is so loaded that it cannot contract when stimulated. Since it is possible to measure the tension exercised upon a spring in isometric contraction and to measure the amount of heat produced, and since in such a contraction all the energy is finally given off as heat, it is possible to calculate the proportion between these. The efficiency in such con- ditions is found to be nearly 100 per cent. ; but this is no measure of the actual efficiency of the muscles. The point of practical importance to decide is — How much of the energy liberated by muscle in normal conditions is available under favourable circumstances for mechanical work, and how much is lost as heat ? To determine this, the way in which muscle develops tension when stimulated must be studied. The Development of Tension by Muscle. It has for long been recognised that muscle like other protoplasm gets its energy from food. But the problem MUSCLE 249 to be considered is whether muscle develops the tension by which it can shorten and do work by a process of direct oxidation, or in some indirect way. Pfliiger long ago deprived a frog of all free oxygen in an air-pump and then kept it in an oxygen-free atmosphere and found that it moved and gave off COo. He concluded that the process of oxidation is not a direct one. Subsequent experiments have confirmed this view. It has been found that — 1. The muscle of a frog may be made to go on contract- ing for some time in nitrogen in the absence of oxygen, but that fatigue is soon manifested and is not removed by Fig. 130.— (To be read from right to left). Contractions of muscle. A, in oxygen ; B, in nitrogen with no oxygen. In both, note onset of fatigue ; in A recovery after brief rest, in B no recovery. (Fletcher. ) rest. Sarcolactic acid is liberated but no carbon dioxide is produced (fig. 180, B). 2. In the presence of oxygen, sarcolactic acid does not accumulate. It is oxidised to COg and HgO. The muscle recovers from fatigue after a short rest (fig. ISO, A), 3. Hence contraction is not due to oxidation, but to the throwing out of sarcolactic acid, i.e. to an increase of H ions which produces changes in surface tension with the develop- ment of " tension." The tension varies with the length of the fibre, which indicates that it is a surface phenomenon (Appendix), When shortening occurs the tension is decreased, and the potential energy becomes kinetic. Muscle, therefore, in contracting does not act as a heat engine by liberating energy by combustion, but as a compression engine which liberates energj^ already stored. 250 VETERINARY PHYSIOLOGY •i. The work of restoring the potential energy is due to the oxidation of sarcolactic acid and of carbohydrates, proteins, and fats. These also yield the materials in which the energy is latent for reconstruction. From these latter " foods " the muscle molecule is regenerated and the energ}-, therefore, ultimately comes from them. This is a process requiring oxidation, and hence CO2 and H2O are liberated and heat is produced (p. 247) in pro- portion to the work done by the muscles. 5. In the contraction phase the efficiency may be nearly 100 per cent., but, when the process of restitu- tion is included, only at most 50 per cent. In considering the efficiency of muscle in liberating the energy stored in the food this point must be taken into consideration. Muscle, like secreting epithelium Fig. 131.— To show the (p. 35)^ thus does its work by storing changes in the effici- r J ■ / 1 / .V ^ / Jl / 7 A' it- f 1-4 t ^ i^ t _j. ency of the muscles as the work done is in- creased. The decrease in efficiency is indi- cated by the divergence the material from which energy may be liberated during its resting phase, and this process dominates the metabolism of muscle. For this, muscle requires between the lines. The jqq^ ^q ^i'v^^ the material and energy ordinates on the left „ *^ . , , , . , lor restoration and the oxygen which is necessary to carry out the recupera- tion. The efficiency of the muscles of the body may be measured by deter- are Calories per minute, those on the right indi- cate work units con- verted to Calories. The abscissae are the num- ber of revolutions of the bicycle at constant work. mining the total energy liberated doing a measured amount of work upon some form of ergometer by direct or indirect calorimetry (p. 259). It has been found that some 30 per cent, of the total energy liberated is about the riiaximum mechanical efficiency. The efficiency of muscle thus compares favourably with that of an ordinary steam-engine which 3'ields some MUSCLE 251 5 to 20 per cent, of the energy of the coal in mechanical work. In the steam-engine, where heat energy is converted to work, the etficiency depends upon the difference of temperature between the cylinder and condenser. The high efficiency of muscle, with an absence of marked temperature variations, shows at once that it is not a heat engine (p. 247). Compared with other energy transformers, muscle does not stand so high. A Diesel engine gives a theoretical efficiency of about 75 per cent, and a practical efficiency of about 50, and an electric battery from 80 to 90 per cent. It must, however, be recognised that the heat produced by muscle is necessary to keep the temperature of the body at such a level that the chemical changes, which are the basis of life, may go on. Probably a return of 30 per cent, is seldom yielded under ordinary working conditions by the whole muscular system. Within certain wide limits of work done, the efficiency of muscle remains constant, that is, the total energy evolved is directly proportionate to the work done. But if excessive work is put upon muscles, or if the work has to be done at a rate greater than the optimum, the mechanical efficiency decreases and the total energy expendi- ture rises out of proportion to the work done, just as, when a steamer is driven above a certain speed, the coal consump- tion is increased out of proportion to the increased speed. This is well illustrated by the increased production of CO2, which occurs when the rate of marching is forced from 3 to 5 miles an hour (fig. 128). Fig. 131 shows the relationship of the work done (effective work performed; to the total output of energy (total heat output). Such a figure indicates very clearly that, while for moderate increments of work the mechanical efficiency of the muscle is fairly constant, with greater increments the efficiency becomes less, i.e. the total expenditure of energy increases out of proportion to the work done. 252 VETERINARY PHYSIOLOGY 9. The Efl&ciency of the Horse as a Machine. The total amount of energy liberated by the horse in performing a measured amount of work lias been estimated by the indirect method of calorimetry (p. 260). By this means the efficiency of the horse as a machine has been determined by Zuntz and others. The total energy expended in work, as in drawing a load, is the sum of three separate items : — (1) The amount for maintenance purposes. This is required whether the animal is working or at rest. (2) The amount spent in moving the body of the animal. (3) The amount spent in moving the load. The proportion which the amount of useful work done bears to the total energy liberated (1 + 2 + 3) is called the gross efficiency. The proportion which the work done bears to the part of the energy expended in moving the load is called the net efficiency. The amount spent solely in moving the load is, of course, the total output (1 + 2 + 3) minus the output when the animal is moving without a load (1 + 2). The net efficiency under the most favourable conditions of load and speed is found to be 30 to 35 per cent., which is about equal to that obtained in man. 10. Capacity of the Horse for Work. Draught. — The amount of work performed by the draught horse has been measured by means of the moving platform (p. 246). Over two million kilogram-metres (about 7000 foot tons) has been registered in an experimental day's work, and the amount of work which the horse is capable of performing daily has been estimated as high as 6000 foot tons (1,854,720 kilogram-metres). F. Smith, however, considers that 5000 foot tons (1,545,600 kilogram-metres) is a severe day's work, and that 3000 foot tons (927,360 kilogram-metres) is a fair average. The capacity of the draught horse for work is doubtless being increased by selective breeding designed to increase the weight of the MUSCLE 253 animal and improve the conformation and qualities of feet and legs. The former has improved in Shires and the latter in Clydesdales. The force that a liorse can extend on a steady pull has been found by F. Smith to be about 75 per cent, of its body weight. The load which can be pulled depends largely on the condition of the road and the nature of the vehicle. On a level road a total weight — vehicle plus load — of 2-5 to 4-5 times the weight of the animal can be pulled at a walking pace. On a rising gradient, in addition to the pull to overcome the inertia of the load on starting and the friction in motion, the load and the animal itself must be raised against gravity. The load that can be drawn up-hill therefore decreases very rapidly as the gradient rises. As the co-ordination of muscle of two or more horses pulHng together is not so perfect as that of a single animal, the amount that can be pulled by more than one horse is always less than the sum of the amounts each can pull separately. Carrying. — The horizontal spine of the horse is not adapted for carrying weights. About one-fifth of the body weight is the maximum load a horse can carry comfortably for any length of time. In this respect it is less efficient than man Avith his vertical spine. An infantry soldier can march carrying more than a third of his weight. The smaller breeds of horse can carry more in proportion to their weights than the larger. Consequently a nuile or pony is a more efficient pack animal than a large horse. Over-work. — -A liorse that is worked beyond its capacity rapidly deteriorates and is liable to injury of the feet and legs caused by excessive strain. When the muscles are tired undue strain is allowed to fall upon the supporting tendons Avhich become injured. Co-ordination of tired muscle is less perfect, and " brushing " and stumbling occur. Severe work, necessitating a propulsive force as in heavy draught, or concussion as in high speed, greater than the elasticity of the structures of the foot can accommodate, is apt to injure the matrix and produce laminitis. Horses 254 VETERINARY PHYSIOLOGY are oftener off work for lameness than for any other ailment, and the chief cause of lameness is work that is excessive either in amount or in rate. The nature of the chemical changes in muscle — the metabolism of muscle — must next be studied. 11. The Chemical Changes in Muscle. Metabolism of Muscle- It has been already pointed out that, on account of (1) its bulk, (2) its constant action, (3) the extent of its chemical changes, the metabolism of muscle dominates the metabolism of the body as a whole. As already stated, it is to supply energy to muscle that food is taken. It is to oxidise this food and to liberate its energy that air is drawn into the lungs, and it is to get rid of the carbon dioxide formed in muscle that air is breathed out. It is to adjust the reaction of the fluid bathing the muscle and to get rid of the products of muscular metabolism that urine is secreted. It is to prepare food for muscle that the digestive organs work. It is to carry food and oxygen to muscle that the flow of blood is maintained, and it is to regulate the supply of food to the muscle that the liver performs its functions. Hence the study of the metabolism of muscle is really the study of the general metabolism of the body. The intake and output of matter and of energy are alike dominated by the requirements of the muscles. One caution, however, must be given. The amount of food taken is not always regulated by the requirements of the body, and hence any surplus over what is required must either be stored for future use (p. 351), or be got rid of from the body, just as the coals thrown into a furnace in excess of the requirements of the engines are burned away. In studying the influence of various factors upon muscular metabolism the influence of food has therefore always to be considered, and should either be eliminated by fasting or be kept constant throughout the observations. (1) The Oxidation in Muscle: Coefacient of Oxidation. — The MUSCLE 255 amount of oxygen used in muscles at rest and in action is ascertained by determining (1) the decrease in the amount of oxygen in the blood leaving the muscles (p. 498) ; (2) the amount of blood flowing through the muscles per unit of time (p. 473): and (3) the weight of the muscle. This allows the coefficient to be stated in terms of c.cm. of oxygen per grm. of muscle per minute. In the skeletal muscles of mammals the following variations have been found according to the condition of activity : oxygen per minute per Nerve cut : Tone absent Tone existing in rest Gentle Contraction , Active Contraction grm of muscle in c.i 0-003 0-006 0-020 0-080 With active contraction the consiimption of oxygen may he increased more than twenty-fold. Similar results are obtained when the influence of muscular work upon the oxygen consumption of the body as a whole is studied (p. 26 6 j. Is this increased oxidation in contraction accompanied by any change in the composition of the muscle ? So long as the blood stream is intact it is probable that any change which may occur is at once made good. But if muscle deprived of its blood supply is investigated it is unsafe to conclude that a change in composition is the result of contraction and is not due to the decreased supply of blood. It has been shown that when muscle contracts without a supply of oxygen, sarcolactic acid accumulates ; but that when it contracts in oxygen, this is oxidised to carbon dioxide (p. 249). In contraction the supply of glycogen in muscle is decreased, and after fasting and strychnine convulsions, it may practically disappear. (2) Material Oxidised by Muscle. — The study of the co- efficient of oxidation of muscle leads to the consideration of what is oxidised to yield the energy. It has been found that only the three great constituents of the body and of the food — the proteins, carbohydrates, and fats — are freely oxidised to yield energy in the body, although some other substances, e.g. alcohol, are capable of a limited oxidation. 256 VETERINARY PHYSIOLOGY (3) The Mode of Oxidation. — Every one knows that, at the temperature of the body, proteins, fats, and carbohydrates do not undergo combustion. To bring this about, the action of something comparable to an enzyme with an activator is necessary. The enzy]ne-like substance appears to be formed, possibly from the lipoids of the protoplasm, by an auto-oxidation by which a peroxide is formed, which has a greater power of oxidising than free oxygen has. But peroxides alone are not sufficient to bring about the combustion of sugars, lactic acid, etc., an activator is necessary, and such an activator has been prepared from various cells, and, since it activates the peroxide, it has been termed a peroxidase. In the oxidation of food- stuffs in muscle and other protoplasm the following steps seem necessary : — First, the formation of a peroxide in which oxygen is stored at a high Dotential ; second, the activating action of a peroxidase. These together may be called an oxydase. (4) Energy Value of Proteins, Fats, and Carbohydrates.— To de-^ termine the amount of energy yielded by the oxidation of each, all that i.-' necessary is to find the amount of heat evolved by its combustion. This is done by burning a known weight in a water calorimeter, an apparatus by which all the heat evolved is used to heat a known volume of water. The Bomb Calorimeter is generally used for this purpose. It consists of a thick metal case in which a weighed quantity of the food to be investigated can be placed in oxygen. By means of wires it can be completely burned by an electric spark. The metal case is placed in a known quantity of water and the heat given off from the food goes to heat this water. By taking the temperature before and after the combustion the amount of energy in heat units, or calories, may be calculated. Suppose that 1 gram of starch was put in the bomb calorimeter and the case then placed in 1 litre, i.e. 1 kilogram of water ; suppose the temperature of the water was raised 4-1'' C, this would mean that 1 gram of starch had liberated 4-1 Calories of energy. It is known that, in the normal individual, fats and MUSCLE 257 carbohydrates are burned completely to COg and HgO, and therefore yield the same amount of energy as in the calorimeter. On the other hand, the proteins are not completely burned in the body, the process of combustion stopping at the form- ation of urea, CONgH^. Something like 3 grm. of protein yield 1 grm. of urea. In the case of fats and carbohydrates where the com- bustion in the body is the same as in the calorimeter, this method is at once applicable to determine the energy which muscle can liberate. The 'physical and 'physiological avail- ability is the same. 1 grm. fat— 93 Calories. 1 grm. carbohydrate— 41 Calories. But in the case of proteins it is necessary to determine — (1) The energy evolved in complete combustion in the calorimeter. (2) The energy evolved by the combustion of the urea formed, and to subtract the latter from the former. Complete combustion of 1 grm. yields about 5-6 Calories — the physical energy equivalent. The combustion of the urea formed from 1 grm. of protein yields about 1-3 Calories. Hence about 4-3 Calories are available in the body — the j^hysiological energy eqidvalent. Variations occur according to the nature of the protein used, and generally it is accepted that — 1 grm. protein yields in tlie body 41 Calories. 5. The Determination of the Amount of Proteins, Fats, and Carbohydrates oxidised in the Body. — To determine the amounts of each of these proximate principles oxidised in the body, it is necessary to investigate — A. Proteins. — The amount of nitrogen excreted gives a measure of the protein used since protein contains 1 6 per cent, of nitrogen. Hence the nitrogen excreted x6"25 = amount of protein used. Proteins contain nearly 3| times as much carbon as nitrogen, so for each grm. of nitrogen from protein, 3*4 grm. of carbon are excreted (iig. 132). B. Fats and Carbohydrates — All carbon excreted, above that derived from proteins, must come from fats and carbo- hydrates (fig. 132). In the fasting animal it comes from 17 258 VETERINARY PHYSIOLOGY fats alone. When food is taken, the determination of the extent to which each of them is being oxidised depends upon the fact that carbohydrates are rich in oxygen, while fats are poor in oxygen. Hence, to oxidise a given weight of fat to CO2 requires more oxygen than to oxidise the same weight of carbohydrates. For this reason the amount of oxygen required to produce say 100 c.c. of CO2 is greater when fats are being Fat 100 :u-5 Protein, 100 5'?' iNJb Fig. 132. — Output of Nitrogen and Carbon in a fasting animal to show how the combustion cf Proteins and Fats is calculated from it. A, the Protein and Fat metabolised. B, the Nitrogen and Carbon excreted, derived from A. consumed than when carbohydrates are being used, and hence, if the CO2 output and the O2 intake are determined and their proportion expressed as — CO., ^. ', the Respiratory Quotient. This is found to be, in the case of Fats, 0-7, and in the case of Carbohydrates, I'O. In the case of proteins, in which the amount of oxygen is intermediate between that in fats and carbohydrates, the respiratory quotient is about O'S. Knowing the amount of carbon coming from proteins we can calculate the O2 necessary for their combustion, and any excess of CO2 and of O2 over this is due to com- MUSCLE 259 bustion of fats and carbohydrates. When this is expressed as a respiratory quotient, the amount of fats and carbo- hydrates respectively used can be determined. Tables giving the significance of different respiratory quotients are prepared and are used in such investigations. The following gives a rough indication of such a table. R.Q. Carbohydrates. Fats I'OO 100 per cent. per cent. 66 „ 34 0-90 0-80 0-70 ^8 100 Owing to the fact that the amount of protein decomposed during the relatively short period of the collection of the sample of expired air is, as a rule, trivial, the calculation may be based solely on the combustion of carbohydrates and fats. Oalorimetry. To determine the extent of these exchanges two different methods have been employed. (1.) Direct Oalorimetry. — By this method the amount of •energy liberated as heat is directly measured by means of a Respiratory Calorimeter. This consists of an air-tight double- walled room, in which an animal may be kept for a day or longer at a time. It is provided (1) with an ar- rangement by which air is supplied and the amount of air measured ; (2) with An arrangement by which the heating of the air and the amount of water vaporised maybe measured; (3) with an air-tight double window, through which the animal can be observed. Fig. 133. — Diagram of a Respiration Chamber to show the method of anah'sis of the expired air and the renewal of the supply of oxygen. With this chamber it is possible to measure — (1.) The heat given off. This is measured by the extent to which water circulating in special coils is heated and by the amount of water vaporised. 260 VETERINARY PHYSIOLOGY (2.) The excretion of matter. This is determined by analysing the air entering and the air leaving the chamber, and thus finding the amount of COg and H2O given off, and by analysing the other excretions for nitrogen and carbon. Methane and hydrogen excreted accumulate in the chamber and connected parts. The amount is determined by analysis at the end of the experiment. (3.) The amount of O2 absorbed. (4.) The composition and energy value of the food. By this means an accurate measurement can be made of the Fig. 1.34. — The Chamber of the Respiratory Calorimeter. E is the double- doored opening fur the supply of food and removal of the excreta. intake of matter and energy in the food and the output of matter and energy from the body, and thus the relationship between them can be determined. When man is used as the experimental animal the chamber is provided with a folding-bed, writing-table and chair, and an ergometer consisting of a fixed bicycle working against a known resistance. The energy expended on the work done on the bicycle can thus be measured in addition to the enel-gy expended as heat. This apparatus has been largely used to determine the energy and material exchange in work in man. (2.) Indirect Calorimetry. — By this method an estimate is made of the O2 consumed and of the CO2 given otf, and from this, conclusions may be drawn, as already indicated, as to the amounts of the proximate principles consumed, and of the energy liberated. The amount of proteins used may be determined by estimating the excretion of nitrogen, MUSCLE 261 Fig. 135. -Douglas bag for collection of expired air. but it has been found that under normal conditions during experiments of short duration, their combustion is so small that it may be neglected. The composition of the air taken in being known, when (1) the quantity of air expired and (2) its composition is ascer- tained, it is possible to determine how much Og has been taken up and how much CO, has been given off in a definite time. In experiments on man this is done by collecting the air in a special rubber bag devised by Douglas, and which can be carried on the back of the subject. A mouthpiece is fitted with two valves, through one of which air is inspired, and through the other of which it is expired into the bag (fig. 135). The amount of air breathed may be measured by passing it through a gas meter, and it may be analysed by means of Haldane's apparatus. In animals the exchange can be determined by usmg a canula inserted into the trachea instead of a mouthpiece This method has been used by Zuntz and his co-workers on experiments on horses at work. The indirect method has been tested against the direct method, and has been found to give very concordant results. Zuntz also used another indirect method. He measured the work done on some form of work-measurer or ergometer, e.g. a wheel turned against a measured resistance. By converting the work units of the work thus done into heat units and subtracting this from the total energy of the food, expressed in heat units, the energy lost as heat may be determined, since ail energy not used for mechanical work is dissipated as heat. Thus the relationship between work VETERINARY PHYSIOLOGY production and heat production may be ascertained, as is shown in the following table for a man : — Food Work Heat Kgm. 212,500 Calories. 3000 500 2500 6. Results of these Investigations. — Investigations by these methods have shown that when there is an abundant supply of carbohydrates and fats, they are used as the chief source of energy, the carbohydrates being the more readily used. Only when the work requires more energy than can be supplied from these sources are the proteins used to any great extent (fig. 13 6). But in a lean animal, i.e. an animal with no 136. — To illustiate the influence of Muscular Work upon the Excretion of Carbon dioxide and of Nitrogen — (1) in a fasting or underfed animal ; (2) in an animal fed on proteins ; (3) in an animal on a normal diet. great store of fats and carbohydrates, fed on proteins the energy for work may be got almost entirely from them. All the three proximate principles of the food are available, but the great use of proteins is in the growth and repair of muscular tissue. It may therefore be concluded that, in a lean fasting animal and in an animal fed on proteins, the muscles get their energy chiefly from proteins, but that, in an animal with an adequate store of fat or upon an ordinary diet, the muscles get it chiefly from the carbohydrates of the food or from the fats of the food and of the body. A study of the ordinary diet of horses doing muscular work corroborates these conclusions. In this country the diet of MUSCLE 263 a draught horse consists of something like the following proportions of food constituents per 1000 kilos, of body weight : — Amount in Grams, Yielding Calories. Actual. Per Cent. Proteins . 2300 9500 14 Fats . 800 7500 11 Carbohydrates . . 12,500 50,000 75 GENERAL METABOLISM OF THE BODY. A. EXCHANGE OF ENERGY. As already indicated (p. 254), the energy exchanges of the body as a whole are determined by the chemical changes in the muscles. Further, the temperature of the body must be maintained at a level at which these chemical changes can go on. For this purpose heat must be produced to compensate for cooling. It will be shown later (p. 272) that the rate of heat production is influenced by the amount and nature of the food taken. Hence the energy requirements depend upon : — (1) Muscular activity ; (2) The rate of cooling, i.e. the amount of heat that must be produced ; (8) The food taken. Before considering the influence of these factors, the lowest rate of metabolism compatible with the maintenance oi life must be investigated. I. The Basal Metabolism. The basal, or, as it might perhaps better be called, the standard metabolism, is the rate of metabolism necessary to maintain life when the three factors mentioned above are reduced to a minimum. The factors of outstanding importance in determining the basal metabolism of an animal are (1) size and (2) age. 1. Size. — The variation in size is in proportion, not to the weight but to the surface, i.e. the rate of cooHng. This is shown by comparing the basic energy expenditure of animals of different size. METABOLIS]\[ 265 Calories per kilo. Calories per square metre of surface. Horse . 11-3 948 Pig . . 191 1078 Goose . 66-7 969 Mouse . 2120 1188 It is seen that this relative uniformity of the ratio of basal metabolism to surface area is present even in animals of difterent species. This relationship may be due to the regulation of the rate of metabohsm by stimuli from the skin. This is doubtless true so far as heat production to compensate for loss of heat is concerned, since the rate of cooling is directly proportional to surface area. It is probable, however, that metabolism is also dependent upon the mass of active tissue, i.e. muscle, and that this accounts for the relatively small variations found in the ratio of metabolism to surface. A comparison of the metabolism in different animals should thus be based on the surface area. In bodies similar in material and shape but diifering in size, the surface is proportional to two-thirds the power of the weight. As animals of the same species are relatively constant in shape and composition, the surface area can be calculated from the weight by the following, known as Meeh's formula : — S = k W* where " S " = unit of surface, W = unit of weight, " k " = constant for each species. The value of " k " for difterent species has been deter- mined by direct measurement of the surface area and calculating the relationship of unit of surface to unit of weight. Some of the values found are : — Horse .... . 90 Pig ... . . 8-7 Bullock, fat . . 7-7 thin . . 9-9 Sheep .... . 12-1 Dog ... . . 10-3-11-2 A direct determination of the extent of body surface of 266 VETERINARY PHYSIOLOGY an animal is a difficult matter. It can be estimated, how- ever, from the weight. Since, for animals of the same species and type, the factor " k " is constant, the basal metabolism is proportional to two-thirds the power of the weight and can be compared on that basis. Thus, for example, if an animal of 1000 lbs. live weight has a basal metaboHsm of 7000 Calories, another of the same species and type, of 1500 lbs. would have a basal metabolism of approximately 7000 X (\fUf, i.e. 9172 Calories. 2. Age. — In the young animal not only is energy required for growth, but the active tissues of the body are in greater proportion than in the full-grown animal. Actual measure- ments in the calorimeter have shown that the basal energy requirements of a boy of ten years of age are about 25 per cent, greater per unit of surface area than those of the adult. A similar relative increase doubtlessly exists in all young animals. The influence of age on metabolism and the energy requirements of growth have not, however, been fully investigated. II. Factors modifying the Metabolism. 1. Muscular Activity. Since the energy for muscular work comes ultimately from the processes of oxidation in muscle, the rate of meta- bolism varies with the amount of work done, and with the rate at which it is done. This is by far the most important factor determining the extent of metabolism and the energy requirements of the individual. Under the influence of muscular work a tenfold increase has been observed in man. In the horse, with its great muscular development, an even greater increase is doubtless sometimes obtained. The close parallelism between muscular activity and energy expenditure is remarkable. Movements which are scarcely noticeable, and even increased tonus of muscle apart from motion, are accompanied by an appreciable rise in the rate of metabolism. Thus a soldier standing rigidly at attention may expend 10 per cent, more energy than METABOLISM 267 when standing at ease, even although in the former case there is no visible movement. The lowest rate of meta- bolism is reached in sleep when the skeletal muscles are relaxed and the action of the other muscles is reduced to a minimum. 2. Rate of Cooling. Since under ordinary conditions the temperature of the surrounding air is lower than that of the body, there must be a constant loss of heat and consequently a constant production of heat to keep the temperature of the body steady. Loss of Heat. 1. Skin. — Heat is lost from the body by the skin in two ways : — (a) by conduction and radiation, and (h) by evaporation of sweat. (rt) Conduction and Radiation. — The extent of this loss depends upon the difference between the temperature of the body and that of the air. Radiation plays the most important part when an animal is at rest in still air ; conduction when the exchange of air over the surface is rapid, as in wind. The influence of variation in the temperature of the air is minimised by the covering of fur or feathers, which retains a stationary layer of air of about 25° to 30° C. over the skin. Cold stimulates the growth of hair. On the other hand, the heavy winter coat tends to be shed when an animal is confined in a warm atmosphere. (6) Evaporation of Siueat. — Heat is rendered latent by the evaporation of sweat, and is taken from the body which is thus cooled, just as the hand may be cooled by allowing ether to evaporate upon it. The extent of loss depends not only on the amount of sweat secreted, but also upon the rapidity with which the evaporation goes on. This is governed by the dryness and temperature of the air, and the rapidity of its exchange by wind and other air currents. The horse sweats easily. Working under ordinary con- ditions of climate, it may lose from 5 to 10 litres of water as sweat per day. 268 VETERINARY PHYSIOLOGY The pig has sweat glands only on the snout ; the dog only on the muzzle and foot pads. The sheep has few sweat glands and perspires very little. Cattle also perspire little, except on the muzzle. Moisture in the air increases the conductivity of the body covering, and consequently the loss of heat by conduction and radiation in a cold atmosphere is greater in proportion to the humidity. On the other hand, moisture in the air hinders the free evaporation of sweat, so that loss of heat by evaporation is less rapid in a hot climate that is moist than in one which is dry. Consequently in climates with temperatures above that of the body the heat is better borne by animals when the air is dry and moving. 2. Respiratory Passages — Evaporation from the respiratory passages and the heating of the respired air may account for 10 to 20 per cent, of the heat lost. In the dog the amount of heat lost in this way may be considerably greater Tp. 269). 3. Urine and Faeces. — A certain amount of heat is lost by raising the ingested food and water to body temperature, at which the urine and fasces are voided. In the dog the amount is small — something less than 2 per cent. Where the food is bulky — as, for example, in ruminants on a heavy root diet — the amount may be as much as 10 per cent. of the total heat lost. Heat Production. A. Muscle. — As already indicated, muscle is the great heat producer on account of its great bulk and constant activity. Not only may it be demonstrated that (1) the temperature of muscle in action rises, but (2) it has been found that the temperature of blood coming from the muscles is slightly higher than that of blood going to them. (3) Muscular exercise raises the temperature of the body. (4) Drugs which interfere Avith muscular contraction, such as curare, diminish the temperature, and (6) young animals, before their muscular tissues become active, have a low temperature unless kept in warm surroundings. B. G-lands. — A certain amount of heat is produced in METABOLISM 269 glands and chiefly, on account of its great size, in the liver. During active digestion the temperature of the blood coming from the liver is distinctly higher than that of the blood going to the organ, and, since the amount of blood passing through the organ is large, an appreciable amount of heat is derived from it. The production in glands, however, is trivial when compared with the production in muscle. Heat Regulation. In spite of wide fluctuations in rate of heat production and heat loss, the body temperature varies within very narrow limits. This constancy is maintained by two means, called respectively the j^hysical regulation, which controls the rate of loss of heat, and the chemical regulation, which controls the rate of production. Physical Regulation. — When heat production exceeds heat loss, the resultant rise in body temperature is accompanied by dilatation of the cutaneous vessels, so that more blood is brought to the surface and the loss of heat increased. Along with this an increased secretion of sweat occurs. Conversely, when heat loss exceeds heat production, constriction of cutaneous vessels and decrease of sweat secretion reduce the loss of heat. These adjustments in the skin to maintain the balance between heat production and heat elimination are reflex effects. In the dog, which has no sweat glands on the part of the body covered by hair, increased elimination of heat is brought about by a panting respiration that increases the loss of heat by the respired air and by evaporation from the respiratory passages. The mouth is held open and the tongue allowed to hang out, so that as large a moist surface as possible may be exposed to the air to allow cooling by evaporation. In cattle increased elimination of heat by sweating is small in amount, and their temperature is therefore especially liable to rise with exercise. Chemical Regulation. — As the temperature of the environ- ment of an animal falls, a point may be reached at which even with loss of heat restricted to the utmost, heat pro- 270 VETERINARY PHYSIOLOGY duction may be insufficient to balance heat loss, and the body temperature begins to fall. When this occurs the rate of metabolism and consequently of heat production is in- creased either by increased muscle tonus or by muscular exercise. This increased muscular activity may consist of Rate of MeUbolism '*■■*•*—, ^^;.. Temperature of the Body ' Radiation and /.. Conduction Physical Physiological ""^•■^•^ \^ r Evaporation "^^ '•^-< Physical x ■ ^^ ''***^ Physiological ^ ,>'' , :--'' Temperature of surroundintr air . *\ in dfegrees centigrade 60 SO Fig. 137. — To show the physical and the chemical regulation of temperature. Note that roughly between 20° and 40° C. the regulation is by changes in the loss of heat, and that below 20° C. increased heat production occurs. Above 40° C. a hyperthermal increase of heat production occurs. voluntary movements, or, if these be prevented, by a shivering fit which is simply a reflex, involuntarily bringing into action a large number of muscles. The voluntary movements for heat production are seen in the " freshness " of a horse brought out of a warm stable into a cold atmosphere. A shivering tit is often seen in the horse after drinkiug a large quantity of cold water, which METABOLISM 271 abstracts heat from the body in being raised to body temperature. The way in which the rate of metaboHsm rises as loss of heat increases, with a fall of temperature, is shown by the following results obtained by Rubner on a fasting dog : — _ ^ Rate of Metabolism in ^e™P- *-• Cal. per kg. body wt. 35 68-5 30 56-2 25 54-2 20 55-9 15 63-0 7 86-4 In this chemical regulation energy-yielding materials, usually carbohydrates and fats, are metabolised solely for the purpose of heat production. Wind has a very marked effect upon the rate of cooling, and consequently upon the rate of metabolism, especially in an animal like the pig where the hair is scanty. Hill has shown that in man exposure to a cold wind may nearly double the energy expenditure. Critical Temperature. — In the case of the fasting dog quoted above, the lowest rate of metabolism is reached in an environment with a temperature of about 25° C. Below this level the rate of metabolism is increased for heat pro- duction by chemical regulation. As the temperature rises above 25° C. not only is loss of heat decreased, but meta- bolism is stimulated by the rise in temperature, so that heat is produced beyond requirements, and its elimination is hastened by physical regulation. The level of the external temperature at which chemical regulation gives place to physical, or vice versa, is known as the critical ter)ipera- ture. It is the temperature of minimum metabolism, and consequently of lowest food requirements. Experimental evidence is lacking to determine the exact critical temperature for domestic animals. It is probably about 20° to 25° C. in the horse and pig, and somewhat lower in ruminants. In the individual it varies with the condition of the coat and the amount of subcutaneous fat. The takinof of food causes an increase in rate of metabolism. 272 VETERINARY PHYSIOLOGY The critical temperature of the fed animal is therefore lower than that of the fastincf animal. 3. Effect of taking Food on Metabolism. The consumption of food by an animal increases the basal metabolism, as is seen in the following results obtained on a horse : — Calories per hour per kg. Fasting 102 3^ hours after feeding . . . 1'13 The increase is influenced by the quantity and character of the food. Each of the proximate principles stimulates chemical changes. Proteins have a special influence in this direction, and, when eaten, metabolism is so increased that something like SO per cent, of the energy they contain may be liberated as heat. This is called their specific dynamic action. Lusk has shown that it is due to the direct action of certain of the amino-acids upon the metabolism. The increased metabolism following feeding was formerly attributed to (1) the muscular work involved in peristalsis, and (2) to the liberation of energy in the disintegration of the molecules of the food in the process of digestion. Hence it was said to be due to the " work of digestion," an unfor- tunate term still widely used. Experiments have shown that the energy expended in the mechanical work done by the intestinal tract is negligible, and that the chemical reactions involved in digestion are isothermic. It is thought that the fermentation that takes place in the digestive tract of the ruminant produces a considerable amount of heat. To what extent this occurs and what increase follows feeding little is known. 4. Metabolism in Prolonged Fasts, When the usual supply of energy in the food is cut oft', the animal gets the energy required by oxidising its own stored material and its tissues. This is shown by the fact that it loses weight and goes on excreting carbon dioxide. METABOLISM 273 urea, and the other waste products of the activity of the tissues. Prolonged fasts have been borne by both men and animals, and, in one or two of these in man, careful observations have been made by physiologists. It has been found that during the first day or two of a fast, the organism draws most lavishly on its store of carbohydrates, and that there is a marked diminution in the protein metabolism. As soon as the carbohydrate depots are exhausted, the protein metabolism suddenly increases, to fall slowly as the fast progresses. Fat metabolism falls slowly throughout the fast. The follow- ing figures obtained by Benedict on a subject who fasted for thirty-one days clearly demonstrates the effect of fasting. Amount of Proteins, Fats, and Carbohydrates in grms. cataholised in tiventy-four hours during a fast. Day. Protein. Fat. Carbohyr! rates. 1 42-6 135 68-8 5 62-5 133 151 10 60-3 120 3-9 15 50-8 116 20 46-1 110 25 46-9 109 31 41-6 115 (1) It is from the stored fats that the energy is chiefly derived, and the result of this is that before death the fats of the body are to a great extent used up. (2) The protein- containing tissues waste more slowly and waste at different rates, the less essential being used up more rapidly than the more essential, which, in fact, live upon the former. In cats, deprived of food till death supervened, the heart and central nervous system scarcely lost weight ; the bones, pancreas, lungs, intestines, and skin each lost between 10 and 20 per cent, of their weight, the kidneys, blood, and muscles between 20 and 30, and the liver and spleen between 50 and 70. 18 274 VETERINARY PHYSIOLOGY The rate of waste during a fast depends upon the amount of energy required, and it is therefore increased by muscular work and by exposure to cold (p. 266). The power of withstanding starvation depends chiefly upon the extent of the store of fat in the body. Pigs and have been known to withstand starvation for 60 days WEIGHT fAT PROTEIN Fig, 138. — To show the Effects on the Metabolism of Proteins and Fats of Feeding a Fasting Animal. The continuous hoi-izontal lines indicate the amount of material metabolised, the broken horizontal lines the amount taken. The differences between the levels of these indicate the amount of protein and of fats of the animal body which are metabolised. The first column represents the condition in fasting — the succeeding columns the intake and output each day when food is and dogs for 80 days without permanent injury. In man fasts of 30 days have been borne without injury. Horses and cattle succumb sooner than men. 5. Metabolism in Semi-Starvation. When the food supply of an animal is inadequate to yield the necessary supply of energy, the energy expenditure is reduced by the restriction of all unnecessary movements. Experiments show that, in ruminants at least, the digesti- bility of a ration is increased as its amount is diminished METABOLISM 275 (p. 3G6), so that a greater proportion of the energy of the food is rendered available for metabolism. The stimulus due to taking food is also, of course, decreased as the amount is decreased (p. 272). Hence life is maintained more economically in an under-fed than in a well-fed animal. Short periods of under- feeding cause no damage beyond some loss of weight. From the evidence in man it is most probable, however, that in prolonged periods of under- nutrition the power of resisting disease is diminished. B. EXCHANGE OF MATERIAL. Not only is material necessary as a source of energy, it is also required for the formation of new tissue in growth, and for repair in the full-grown animal. In protoplasmic activity (p. 21) there is a continuous breaking down of complex substances to simpler bodies. Some of these products of katabolism can be re-used to build up the living protoplasm, others, however, are excreted as waste. In some cases, too, essential materials are carried off from the body in combination with excretory products (p. 280). New materials must therefore be supplied to make good the waste to ensure that the destructive phase of metabolism shall be balanced by the constructive. In addition, certain accessory factors (p. 281) are required to secure the harmonious working of the metabolic processes which is necessary to health. Metabolism therefore involves an exchange of material as well as an exchange of energy. The substances that take part in metabolism are : — (1) Water. (2) Amino-acids. (3) Salts. (4) Accessory factors. Water is the chief constituent ; since it is daily given oft" in large quantities by the kidneys, lungs, skin, and bowels, it must be supplied in sufficient amounts, or the chemical change cannot go on, and death supervenes. Amino-acids. — Nitrogenous material is lost to the body in the catabolism of the protein in the tissues and in the 276 VETERINARY PHYSIOLOGY cells shed from the mucous membranes and from the skin and its coverings. Material is used up in the production of enzymes and of internal secretions (p. 588). The new nitrogenous matter required for the replacement of this used-up material and also for formation of new tissue in growth must be supplied to the tissues in the form of amino-acids. The various proteins differ in their amino-acid build-up (p. 16), and hence they are of different value in the growth and repair of the body. Their relative value has chiefly been investigated by feeding young white rats on a basal diet consisting of protein-free dried milk, since this is known to be an adequate diet when suitable proteins, such as the milk proteins, caseinogen and lactalbumin, are added to it. Various proteins or amino-acids may be added to this, and the effect upon the rate of growth and the duration of life determined. In this way it has been shown that some of the amino- acids, certainly glycin, can be formed from others, since caseinogen, which contains no glycin, has proved adequate for normal growth. Other amino-acids cannot be formed in the body, or cannot be formed in sufficient amounts for adequate nutrition. Some proteins contain all the necessary amino- acids, some do not. It has been found that among those which are adequate to maintain normal growth when given in sufficient amount are — Animal Origin. Vegetable Origin. Casein (milk). Edestin (hemp seed). Lactalbumin (milk). Glutelin (maize). Ovalbumin (hen's egg). Glutenin (wheat). Ovovitellin (hen's egg). Glycin (soy bean). While among those which are inadequate are — Legumelin (soy bean). Hordein (barley). Gliadin (wheat). Zein (maize). Legumin (pea). Gelatin. The reason for this failure is the absence of essential amino-acids. Gelatin lacks tyrosin and tryptophan. METABOLISM 277 Zein lacks the tryptophan group and the diamino-acid lysii Ghadin and hordein lack Ivsin. Fig. 139. — Showing typical growth of rats on diets containing a single protein. (1) On casein food (devoid of glj'cin) satisfactory growth is shown ; (2) on gliadin food (deficient in lysin) little more than maintenance of body weight is shown ; (3) after a mixed diet with satisfactory growth, zein food (devoid of glyoin, Ij'sin, and trypto- phan) even maintenance is impossible. (Mendel.) Chart 1 shows the results of feeding rats on an adequate and on an inadequate protein diet. Fig. 140.— To show the eflfect of the addition of tryptophan (A) and of tryptophan and lysin {B) to the food of rats on zein diet. A gives maintenance of weight alone, A and B increase of growth. (Mendel.) Chart 2 shows the etfect of adding the lacking amino- acid. 27i VETERINARY PHYSIOLOGY Some proteins contain only small amounts of certain essential amino-acids, and a larger supply must be given to supply a sufficient quantity. This is well seen in feeding with casein, which is poor in the sulphur-containing cystin. If too small an amount of casein be given the rate of growth is decreased, but it is accelerated when cystin is added (Chart 3). Similarly, if too small amounts of edestin be given, Fig. 141. — To show satisfactory growth of rat upon IS per cent, of casein (A) and defective growth on 9 per cent, without the addition of cystin, but adequate growth when cystin, in which casein is deficient, was added {B). (Mexdel.) the small amount of lysin it contains renders it inadequate, and the addition of lysin is required to restore growth. A most interesting point brought out in these experiments is the fact that, however long the rate of growth has been checked by an insufficient supply of the constituents of the food necessary for growth, when they are again supplied growth begins again, and proceeds till the normal size may be reached. METABOLISM 279 These results explain why a smaller amount of some proteins than of others is sufficient to repair the wear and tear. The more nearl\^ the amino-acid make-up of the protein in the food approaches that of the tissues, and chiefly of the muscular tissue, of the animal consuming it, the smaller is the quantity required. This has been shown by feeding a man on a carbohydrate and fat diet, yielding the energy required and finding the amount of nitrogen excreted, i.e. the amount of protein oxidised, and then adding different proteins. It was found that, while a small quantity of some is capable of making good the loss of nitrogen, nuich larger quantities of others are required. Protein of — ijrms per Da Meat 30 Milk 31 Rice 34 Potato 38 Bean 54 Bread (wheatj . 76 Maize 102 In wheat the defective gliadin forms half the protein content. It has been found that in the dog the loss of nitrogen is covered by the smallest protein intake when dog's flesh is given — a physiological justification of cannibalism. On account of the different values of different proteins, Lusk proposes to classify them into three groups according to their amino-acid build-up and their resultant avail- ability for growth and repair : — 1st Class, e.g. Caseinogen of milk. 2nd Class, e.g. Gluten of wheat flour. 3rd Class, e.g. Gelatin. Salts. — It has been seen (p. 218) that salts as ions play an essential part in regulating the osmotic pressure of the body fluids. 280 VETERINARY PHYSIOLOGY Salts are, however, continually being drained off from the body in the urine and faeces. In the katabolism of proteins the sulphur and phosphorus which they contain are oxidised to sulphuric and phosphoric acids. In herbiv^ra hippuric acid is produced in consider- able amounts. To maintain the neutrality of the body fluids, the acids are neutralised by the bases contained in the carbonates and basic phosphates of the blood, and are then excreted. An equivalent amount of the base need not be excreted, as the kidney is able to separate some of the phosphoric acid, which is then excreted as acid phosphate. Certain amounts of bases are, however, lost to the body in this way. In carnivora these bases are not so necessary, since ammonia is formed from the nitrogen of the proteins in sufficient amounts to neutralise the acids produced in their katabolism. The supply of bases for herbivora is obtained from the sodium and potassium salts of citric, malic, and tartaric acids, which are abundant in green fodder. These are oxidised in the tissues to carbonates which are alkaline salts. Sodium chloride is the salt usually given in largest quantities in the diet. When not supplied in the food, it is retained in the tissues, and hence animals can, when necessary, live on a comparatively small supply. One purpose which it serves is to supply the chlorine required for the gastric secretion. Animals, especially those fed on certain kinds of hay rich in potassium salts, often show a hunger for sodium chloride. Bunge has shown that this is caused by the presence in the food of excessive amounts of potassium, which causes an increase in the osmotic pressure in the body fluids. To readjust this, the kidney eliminates sodium as well as potassium, and consequently a shortage of sodium is produced. Iodine is required for the production of the internal secretion of the thyroid (p. 595). Iron is used for building up the hsemoglobin of the blood. Calcium and phosphorus are especially essential for growing animals for bone formation. METABOLISM 281 Accessory Factors. — By feeding young rats upon diets containing an adequate amount of pure proteins, fats, carbohydrates, and inorganic salts, it has been shown that growth is arrested unless two substances, the chemical nature of which is still unknown, are present. (1) Fat Soluble A. — This usually occurs in close con- nection with animal fats. It is particularly abundant in milk fats and in cod-liver oil. It is also present in green fodder. In rats its absence from the diet not only causes an arrest of growth, but also a peculiar inflammation round the eyes. Rickets is a disease affecting young animals, notably dogs. It is characterised by such constitutional symptoms as muscular weakness, and by changes at the epiphyseal cartilages, and softening of the bones, either due to loss of lime salts or to failure in calcification. An attempt has been made to explain it as a result of a deficient supply of the fat soluble A or of some allied substance, but no sufficient evidence has been adduced in proof of this, and the cause of the disease is still unknown. (2) Water Soluble B. — (a) Anti-neuritic. — This is present abundantly in the germs of plants, but not in the endosperm, in young leaves, and in flesh. Its presence is necessary for growth, and it is at least probable that when the supply is insufficient symptoms of neuritis may develop. A disease known as beri-beri develops in people living too exclusively on polished rice, which is poor in this sub- stance. A polyneuritis which is substantially the same as beri-beri can be similarly produced in animals and especially in fowls. This condition can be cured by adding substances containing water soluble B in the diet. Hence it has been called an anti-neuritic substance. (b) Anti-scorbutic — A closely-allied substance, abundantly present in orange and lemon juice and in many fruits and vegetables, seems to be essential, and in its absence scurvy is apt to develop, either in men or animals. It may be called the anti-scorbutic substance. Practically nothing is known about the relation of these substances to one another. 282 VETERINARY PHYSIOLOGY Accessory substances are destroyed by prolonged heating, so that they are for the most part absent in food stuffs that have been boiled. Animals receiving green stuff's are not likely to suffer from the lack of these accessory factors. The exclusive use of artificially-prepared feeding stuffs which have been heated in the course of their manufacture may, however, produce malnutrition and arrest of development. These accessory factors have been given the name of " vitamines," an unfortunate title, since we do not know if they are amines or what they have to do with life. PART III. THE NUTRITION OF THE TISSUES. SECTION I. The Supply of Energy and Material to the Body. THE FOOD. CONSTITUENTS OF THE FOOD. The nature of the requh^ements of the energy and material have been considered. The supply of these in the food must now be studied. The different constituents of food-stuffs may be classified as : — A. Those supplying energy. (1) Nitrogenous compounds. (2) Fats. (3) Carbohydrates. B. Those supplying no energy. (4) Ash (inorganic elements). (.5) Water. (6) Accessory factors. A. Food-Stuffs yielding Energy. 1. Nitrogenous Compounds. Nitrogenous compounds are divided into two classes, viz. (rt) proteins, and (6) soluble nitrogenous compounds. (a) Proteins. — The chemistry and nature of these have been already discussed (p. 14). Occurrence. — Proteins form the chief and characteristic 284 VETERINARY PHYSIOLOGY constituent of protoplasm. They are present to a much smaller extent in plants than in animals. While carbohydrates form the chief bulk of plant tissues, the greater part of the animal body, apart from bones, visible fat, and water, consists of proteins. Plant Proteins. — The vegetable proteins belong to three groups of native proteins — (a) the glohidins ; (b) the glutelins, requiring a dilute alkali for their solution ; and (c) the gliadins, soluble in 70 to 80 per cent, alcohol. They differ from the animal proteins in the proportion of amino-acids which they contain. Generally they are poorer in leucin, but richer in glutamic acid (C5H9NO4) and in arginin (p. 17). They have a higher percentage of nitrogen than those of animal origin, so that the factors 6 2 5 which is used to multiply the amount of total nitrogen present to obtain the amount of protein is too high in vegetable protein. The true factor varies between 5-5 and 6 for the different substances, (6) Soluble or Non-Protein Nitrogen In addition to proteins, feeding-stuffs contain nitrogenous substances of a simple chemical structure. These are all soluble in water, and the term " soluble nitrogen " is advantageously used to indicate the group. In most cases they are early stages in the building up of proteins from nitrates or ammonium salts (diagram, p, 381). In other cases they are parts of protein that have undergone disintegration to a soluble form, e.g. amino-acids or peptides, for transportation in the fluids of the plant. Amino-acids, therefore, constitute the most abundant group forming usually from 50 to 70 per cent, of the whole. The amides (Appendix), asparagine and glutamine, are usually present to the extent of 10 to 20 per cent. The whole group of soluble nitrogenous substances are sometimes loosely termed " amides," an unfortunate term liable to create confusion. For purposes of analysis this group is differentiated from proteins by the fact that they do not coagulate on heating and are not precipitated by certain reagents which pre- cipitate proteins, e.g. copper hydrate. FOOD 285 Occurrence. — Non- proteins are most abundant in plants where growth is most active, e.g. seedhngs. In young plants the amount of nitrogen in these compounds may exceed that in proteins. As the plant reaches maturity the amount of nitrogen in non-protein form decreases. Soluble nitrogen compounds are especially abundant in roots and tubers. In the potato the greater part of the nitrogen is in the non-protein form. 2. Fats and Allied Bodies. Nature, — The chemistry (p. 41) and energy value (p. 257) of the fats have been already considered. In the food they may be substituted for an amount of carbohydrate of equal energy value, i.e. they are isodynamic with the carbohydrates. Occurrence. — Fats are more abundant in animals than in plants. The amount present in the animal body varies within very wide limits. In fat oxen and sheep nearly 50 per cent, of the weight of the carcase may consist of fat. In plants they occur chiefly in oil seeds where they form a concentrated reserve material. Small quantities are present, however, in all parts of plants. In addition to true fats there exist in plants fatty acids and various bodies related to fats. These, together with resins and waxes which resemble fats in their physical properties rather than in their chemical composition, can all be extracted with ether, which is the conventional method adopted in quantitative analysis. In deahng with the constituents of feeding-stuffs, therefore, it is customary to class all these bodies soluble in ether as " crude fat," or more properly as " ether extract." 3. Carbohydrates. Nature. — Carbohydrates contain carbon, hydrogen, and oxygen, the carbon atoms of the molecule usually number- ing six or some multiple of six, and the hydrogen and oxygen are in the same proportions in which they occur in water. They are aldoses or ketoses (Appendix), and deriva- tives of these, of the hexatomic alcohol, CgHiPg (Appendix). 286 VETERINARY PHYSIOLOGY The simplest carbohydrates are the monosaccharids, of which glucose or dextrose or yrape sugar is the most important. It is the sugar of the animal body. Closely allied to glucose in chemical composition is the fructose or Icevulose, a sugar which, instead of rotating the plane of polarised light to the right as glucose does, rotates it to the left, but which in most other respects behaves like dextrose. The other monosaccharid of importance is galactose, a sugar produced by the splitting of milk sugar, and also found in combination in the nerve tissue (p. 58). It does not occur free in the body. These monosaccharids are easily tested for b}-- boiling their solution with Fehling's solution. A reddish precipitate is formed. Under the influence of yeast they split into ethyl alcohol and carbon dioxide, galactose, however, only very slightly. By the polymerisation of two monosaccharid molecules with the loss of water, disaccharids, or double sugars, are formed. Thus, two glucose molecules polymerise to form one maltose molecule. 0,H,,Os + CeH,,Oe = 2(C«H,,0e) - H,0 = C12H22O11 Maltose is the sugar formed by the action of malt and other vegetable and animal enzymes upon starch. By the action of dilute acids and other agents it can be split into two dextrose molecules. Like the monosaccharids it reduces Fehling's solution, and it ferments with yeast. Lactose, the sugar of milk, is a disaccharid composed of a molecule of dextrose united to a molecule of galactose with dehydration. It readily splits into these two monosaccharids. It reduces Fehling's solution, but it does not ferment with yeast. Cane sugar or succose or saccharose consists of a mole- cule of dextrose united to a molecule of lajvulose with the elimination of a molecule of water. It does not reduce Fehling. Monosaccharids anil disaccharids which are soluble and crystalline substances are usually called sugars. FOOD 287 By further polymerisation of monosaccharids with the further loss of water, molecules of greater size are produced and form the set of substances known as the polysaccharids. ^•(CeHioOe - H„0) or x{C,R,,0,). The polysaccharids are distinguished from the sugars by being precipitated from their solutions by alcohol. They do not reduce Fehling's solution, nor do they ferment with yeast. In cold neutral or acid solution most of them strike a blue or brown colour with iodine. On hydrolysis they split into monosaccharids. Some can be split by dilute mineral acids, or by enzymes. Others can be acted upon by strong acids. Most are insoluble in water, Polysaccharids form a series of bodies of which the following are the most important : — Starch is built up of a large number of dehydrated mono- saccharid molecules. Common starch seems to have a mole- cular weight of 20,000 to 30,000. On hydrolysis it yields glucose. Glycogen occurs mainly in the livers of animals. On hydro- lysis it yields glucose. It gives an opalescent solution, and strikes a brown colour with iodine. Cellulose is the basis of the cell walls of plants. It can be hydrolysed only by strong acids, and is not acted upon by the body ferments. There is in plants, however, a ferment cytase which can act upon it. On hydrolysis it yields glucose. It is attacked and disintegrated by bacteria in the first stomach of the ruminant and in the colon of the horse. On bacterial disintegration it yields lower fatty acids, and the gases methane and carbon dioxide. Pentosans. — In addition to the carbohydrates described above, which all contain either six, or some multiple of six, atoms of carbon in the molecule, there is a group having five carbon atoms, and hence called pentoses. The polysac- charids of this group are called i:)entosa7is. They are represented by gums, pectins, mucilages, and other sub- stances in plant bodies where they occur in great variety. It is supposed that in digestion they are disintegrated by bacteria, yielding the same end products as cellulose. 288 VETERINARY PHYSIOLOGY Occurrence of Carbohydrates. — In animals, except in carnivora, carbohydrates form the chief source of energy in the food, but only small amounts are present in the body. Glucose is present in blood to the extent of 0*1 to 0*15 per cent, usually. Lactose is present in milk ; glycogen in the liver and muscles. In plants, carbohydrates occur in great variety, and form the chief constituents. All the monosaccharids, except galactose, and disaccharids, except lactose, occur in solution in plant juices. Those that are present in greatest amount are glucose, fructose, and cane sugar. Starch is found in large quantities as a reserve food in tubers and seeds, such as the potato and in the common grains, and also in small quantities in all green plants. The cell walls which form the frame- work or skeleton of the plant is formed of cellulose. In the young plant, the cell wall consists mainly of cellulose, but as the plants increase in size, the framework is made stronger by impregnating the cellulose of the cell walls with hard tough substances. The chief of these is lignin, which is a typical constituent of the woody parts of plants. The older and larger the plant, the greater is the amount of this fibrous material present. In the conventional analysis of food stuffs the carbo- hydrates are divided into two groups. (1) " Nitrogen free extract." — This consists of those com- pounds in solution, or which can be brought into solution by the action of dilute acids or alkalies. This group includes all the monosaccharids and disaccharids, and also those polysaccharids like starch that can be hydrolysed to the soluble form by these reagents. (2) "Crude Fibre-" — This includes all the remainder which resist their reagents. Cellulose and lignin are typical, and form the major part of the group. B. Not yielding Energy. 4. Ash (Inorganic Elements). Salts are present in all feeding stuffs, though in different amounts and proportions. An ordinary mixed ration is FOOD 289 likely to contain a sufficiency of all the essential inorganic elements except sodium, which is usually added in the form of sodium chloride. Calcium and phosphorus are of special importance in the feeding of dairy cows and growing animals. In the former there is a loss of these elements in the milk, and in the latter they are required for growth of bone. Calcium is abundant in leguminous hays and in animal products, such as meat meal. It is present only in small quantities in grains. Maize is especially deficient in this element. Phosphorus, as phosphates and phosphohpins, e.g. lecithin (p. 19), is present in relatively large amounts in feeding stutfs that are rich in proteins, such as animal products and leguminous seeds. It is also abundant in bran, middlings, and oil seeds. Roots and straws are deficient. Potassium is abundant in fodders where it is sometimes present in excessive amounts (p. 280;. The total amount of ash of feeding stuffs is determined by incinerating a weighed example, and weighing the residue. 5. Water. The amount of water present in feeding stuffs is very variable, in difi:erent foods, and in the same material at different stages of growth. The following table gives a rough idea of the w^ater content of some common feeding stuffs : — Water per cent Roots and tubers 80-90 Green fodder 65-80 Hay and Straw . 7-15 Grain .... 10-12 Feeding cakes and meals undei 10 As the water yields no energy the percentage present dilutes the nutrition value. Fermentation and the growth of moulds are liable to occur when the water content exceeds 17 or 18 per cent. The percentage of water is estimated by determining the loss of weight on drying a sample at a temperature of 100° C. G. Accessory Factors. These have been dealt with (p. 281). 19 290 VETERINARY PHYSIOLOGY Classification of Feeding Stuffs for Herbivora. Feeding stuffs may be arranged in the following groups : — (1) Green fodder. — Examples — Grasses, silage. These contain a high percentage of water. In the young growing plant the thin cell walls are full of protoplasm. These are therefore rich in protein and easily digested. As the plant gets older and larger the percentage of protoplasm decreases, and the cell walls become impregnated with fibrous matter, difficult to digest. On the other hand, the seeds with their reserve store of food become more valuable as the plant reaches maturity. (2) Dry fodder. — Examples — Hay, straw. These are bulky foods characterised by a high percentage of crude fibre. (3) Roots and Tubers. — Examples — Potatoes, turnips. These contain a high percentage of water and a small amount of crude fibre. (4) Concentrates. — Examples — Grain, oil cakes. A high percentage of digestible material and small amounts of crude fibre and water are the characteristics of this group. (.5) Animal Products. — Examples — Milk, fish meal. With the exception of milk, these are concentrated feeding stuffs rich in proteins. The following table shows the approximate results of analysis of some common feeding stuffs : — Average Perce ntage Composition. Water. Protein. Fat. Fibre. Carbo- hydrate. Ash. Grass 80 4 1 4 10 1 20 to 30 per cent, of nitrogen not in proteins. Hay 15" 10 2 26 40 7 About 10 per cent, of nitrogen not in proteins. Peas . 14 22 " 6 53 3 About 10 percent, of nitrogen not in proteins. Oats 14 12 6 9 57 2 Less than 10 per (crushed) cent, of nitrogen not in protein,?. Potatoes . 76 1 2 1 20 1 Over 40 per cent, of nitrogen not in proteins. SECTION II. DIGESTION. Digestion is the preparation of the food in the ali- mentary canal for absorption and utilisation by the tissues. I. STRUCTURE OF THE ALIMENTARY CANAL. The anatomy and histology of the alimentary tract must be studied practically. A mere outline of the various struc- tures, such as will assist in the comprehension of their physiology, is given here. The alimentary canal (fig. 142) may be divided into the mouth, the o-sophagus or gullet, the stomach, the small and large intestine, and the following sup- plementary structures — the salivary glands, the liver, and the pancreas. The Mouth. — The lips, the tongue, and the teeth are the organs of prehension. The lips of the horse are strong and mobile, and possess acute sensation. Those of the ox are thick and immobile. The upper lip of the sheep is divided into two parts, which can move independently of each other. The horse's tongue has a smooth covering, and is broad at the apex. It is seldom protruded. The tongue of the ox tapers to the apex, which is capable of extensive move- ment, and can be easily protruded. It has a strong, rough covering, which gives it a better grip, and also protects it from injury when used for collecting the grass in ofrazincr. 292 VETERINARY PHYSIOLOGY The inside of the mouth of the ox has papilla3 sloping inwards. These help to prevent the food from falling out. In ruminants the incisor teeth are loosely fixed, and meet the dental pad obliquely. This arrangement prevents injury to the dental pad. The teeth of the horse are peculiar in having an invagina- tion of the enamel covering of the crown. As the crown wears, there comes to be two consecutive rings of hard enamel, enclosing softer cement. This provides an uneven surface, well suited to the grinding of the food. The horse has incisors in both the upper and the lower jaw, and these are used to bite the grass in feeding. The crops closer than horse thus the ox. The incisor teeth of the young horse are vertically placed. With use they gradu- ally come to assume an oblique position and get pushed out of their sockets, so that the fangs are reduced in length and the shape of the teeth altered. The shape and slope of the teeth, and the extent of wear on the crowns, give an indication of the age of the animal. The complex joint of the upper and lower jaws in herbivora allows the movements in mastication to be not only up and down, but also lateral, and to some extent from front to rear. This freedom of movement is more marked in Fig. 142. — Diagram of the Parts of the Alimentary Canal, from Mouth to Anus. T., tonsils; Ph., pharynx ; S.O., salivary glands ; Oe., oesophagus ; C, cardiac, Py., pyloric portion of stomach ; D., duodenum ; Li., Liver ; P., pan- creas ; /., jejunum ; /., ileum ; v., vermiform appendix, present in man and in rabbit ; Col., colon ; R., rectum. DIGESTION 293 the ox than in the horse. In the dog, movements other than vertical are very limited. In herbivora the lower jaw is narrower than the upper (fig. 143), so that when the molar surfaces of the upper and lower teeth meet on one side they do not come into contact on the other. Mastication is therefore always unilateral. In the lateral movement of mastication, the outside of the lower molar teeth and the inside of the upper have the greater amount of wear and tear, and consequently the tables come to be oblique instead of horizontal. In the horse this sometimes produces long, sharp, ragged edges, which prevent the Fig. 143. — Showing relative widths of lower and upper jaw in the horse. proper mastication of the food and consequently lead to malnutrition. Salivary Glands. — Three pairs of salivary glands — parotid, submaxillary, and sublingual — open into the mouth. These are compound tubular glands, and are well developed in herbivora. The acini are lined with mucus and enzyme secreting epithelium (p. 34), The parotid has the most copious secretion, and except in the ox, where the submaxillary is developed to an equal size, it is the largest of the three glands. The CEsophagus is a muscular walled tube, lined by squamous epithelium. The muscles are in two layers — an outer longitudinal and an inner circular. This general 294 VETERINARY PHYSIOLOGY muscular arrangement is present in the whole alimentary canal, from the oesophagus to the anus. In the horse the lumen diminishes, and the muscular wall becomes thicker just outside the stomach. In the ox the lumen is wider and more dilatable than in the horse. In the ruminant there is a series of dilatations near the point where the oesophagus enters the stomach. These are the rumen, the reticulum, and the omasum, which are frequently described as parts of the stomach. The Rumen is a great sac, containing in its walls strong muscular bands that enable it to contract on its content. It Fig. 144. — Stomach of a Ruminant, a, cesophagus ; I, rumen ; c, reticulum with cesophageal groove above ; rf, omasum ; e, abomasum ; /, duodenum. is lined by stratified squamous epithelium. It is a temporary storehouse for the food. The Reticulum — the second reservoir — is very nmch smaller than the rumen, The membrane lining its walls is raised in intersecting ridges, which are arranged to form polyhedral cells resembling a honeycomb. It communicates with the omasum, and also with the rumen, whose overflow it receives. The Omasum — the third compartment — is rather larger than the reticulum. Into its interior are projected folds of its walls, forming leaf-like structures. There are almost a hundred of these of different sizes. They are covered with hard papilla?. The omasum opens into the abomasum, the fourth compartment, which corresponds to tlie stomach in other animals. DIGESTION 295 The oesophageal groove, formed of two longitudinal muscular folds, is a continuation of the lumen of the 03S0f)hagus, which runs along the wall of the first three compartments and ends in the abomasum. By this means fluid food can pass directly from the oesophagus to the abomasum. When the pillars are relaxed the groove communicates with the rumen and the reticulum. The crop of the fowl is a dilatation of the oesophagus that occurs at the root of the neck. It corresponds to the rumen, reticulum, and omasum of the ruminant. The Stomach is a dilatation of the alimentary canal. It bulges out at the oesophageal end — the fundus. Towards the outlet it tapers off to the pyloric canal. A strong circular band of muscle between the stomach and intestine controls the outflow of its contents. In the dog the fundus is separated from the pylorus by a circular band of muscular fibres — the prepyloric sphincter. The mucous membrane is largely composed of tubular glands. Those at the oesophageal end secrete hydrochloric acid and pepsin, those at the pyloric end pepsin only. In the horse (fig. 145) the stratified squamous epithelium of the oesophagus is continued into the stomach, and lines nearly one half of the organ. Only the pyloric part and the fundus are covered with the glandular mucous membrane. The opening of the oesophagus to the stomach is small, and partially occluded by folds of the lining membrane. The Small Intestine is a long convoluted narrow muscular tube suspended in the folds of a membrane slung from the spinal region of the body cavity. The mucous membrane is projected into the lumen of the tube as a series of delicate finger-like processes — the villi — w^hich are covered by columnar epithelium. There are two kinds of glands that secrete the intestinal fluid — the succus entericus. (1) Lieberkilhn's follicles are found throughout the whole small intestine. They are simple test-tube like glands which open between the villi. (2) Brunners glands are found only in the upper part of the small intestine. They are branching glands that pene- 296 VETERINARY PHYSIOLOGY trate the subuiucous layer. The mucous membrane contains masses of lymph tissue scattered throughout it. In some places these are massed together and form Peyers iJatches, which are largest at the lower part of the small intestine. The Large Intestine (fig. 142). — The small intestine enters the proximal end of the large intestine at one side, and the opening is guarded by a fold of mucous membrane and a ring of muscular fibres which form the ileo-csecal valve. jSacc. caec. Fi(}. 145. — Stomach of the Horse to show — R. (cs., the cesophageal part ; Fu., the fundus with true gastric glaiids ; R., jjyl., pyloric part. Above this opening there is a diverticulum — the caecum which is very large in herbivora and only vestigial in carnivora. Below the opening of the small intestine is the colon {col). This ends in the short rectum which opens into the anal canal, and this is surrounded by a strong band of muscle — the internal sphincter ani — by which it is com- pressed. An external sphincter ani composed of striped muscular fibres encircles the anal orifice. The whole large intestine is lined with columnar epithelium, and is studded with Lieberkilhn's follicles, in which the epithe- lium is chiefly mucus-secreting in type. There are no villi. DIGESTION 297 In the horse (fig. 147) the ciecum is an enormous sac with a capacity of 25 to 30 Htres. Both extremities are bhnd, and the two openings are only separated by about two 298 VETERINARY PHYSIOLOGY Small Colon Ventral Taenia Medial Ttenia Left Dorsal Colon Pelvic Flexure Fig. 147. — The Colon and Caecum of the Horse. (From Bradley's Topographical Anatomy of the Abdomen of the Horse.) DIGESTION 299 inches. That leading to the colon is situated above the ileo- csecal opening, so that the contents are passed to the colon against gravity. The large colon is more than double the capacity of the ca3cum. The diameter near the csecum is only two to three inches, but it increases rapidly to nine or ten in the ventral portions. At the pelvic flexure the diameter becomes reduced to three or four inches but rapidly increases, to reach a maximum of as much as twenty inches in the right dorsal colon, which narrows down like a funnel to join the small colon. The small colon has a diameter of three to four inches. The ceecum and the ventral portion of the large colon have four longitudinal bands of muscle — teenia — and four rows of sacculations. The small colon has two bands and two rows of sacculation. These sacculations increase the surface area. According to F. Smith, irregular contractions of the muscular bands produce displacements and distorsions of the colon which are causes of "colic" to which the horse is so liable. Supplementary Structure. — (1) The salivary glands have been described (p. 293). (2) The Liver is a large solid organ, formed originally as a double outgrowth from the alimentary canal. Each of these outgrowths branches repeatedly, and the blood coming from the mother to the foetus flows in a number of capillary channels between the branches. Later, when the alimentary canal has developed, the blood from it is streamed between the liver tubules. The fibrous tissue supporting the liver cuts it up into a number of small divisions, the lobules, each lobule being composed of a series of obliterated tubules arranged radially with blood-vessels coursing between them. The portal vein, which takes blood from the stomach, intestine, pancreas, and spleen, breaks up in the liver, and carries the blood between the lobules. From the interlobular branches capillaries run inward and enter a central vein which carries the blood from each lobule, and pours it into the hepatic veins, which join the inferior vena cava. The supporting tissue of the liver is supplied by the hepatic 300 A^ETERINARY PHYSIOLOGY artery, the terminal branches of which have a very free communication with those of the portal vein. (3) The Pancreas like the liver develops as an outgrowth from the intestine. It is an enzyme secreting gland. In the lobules are certain little masses of epithelium-like cells closely packed together — the islets of Langerhans (fig. 148). fe.. :>:•.•;,: ■-•<■5•^ 5 .^.*- VeC"-. ^\7 '4v..'^ ^^ -;i sr^ * - . • . ^Cs^ Fig. 148. — Section of Pancreas to show Acini of Secreting Cells ; a large duct (a), and in the centre an Island of Langerhans {b). The Nerve Supply of the Alimentary Canal. The muscles round the mouth are supplied by the fifth, seventh, and twelfth cranial nerves. The nerve supply of the saHvary glands will be considered later. The pharynx and the oesophagus are supplied by the ninth and tenth cranial nerves, and by fibres from the sympathetic. The stomach and small intestine get their nerve fibres from the vagus and the abdominal sympathethic (p. 198). The large intestine is supplied by the abdominal sympathetic, the various fibres passing through the abdominal sym- pathetic ganglia. The upper part is also supplied from the vagus and the lower part from the pelvic nerves. In the wall DIGESTION 301 of tlie stomach and intestine these nerves end in an interiacing set of fibres with nerve cells upon them, from which fibres pass to the muscles and glands. One of these plexuses (Auerbach's, or the myenteric plexus) is placed between the muscular coats — the other (Meissner's) is placed in the submucosa. Size and Capacity of Organs. The following tables give some idea of the size and capacity of the parts of the alimentary canal in full-grown animals : — Average Length in Feet of Intestines. Small Inte.stine Large Intestine Ox. Sheep. 130 80 35 21 Capacity. Horse. 70 25 15 Stomach Small Intestine Large Intestine Ox. Sheep. Lit. Gals. Lit. Gals. 182 40 18 4 77 17 11 2-5 36 8 7 1-5 Horse. Lit. Gals. 16 3'5 55 12 159 35 Pig. Lit. Gals. 9 2 11 2-5 13 2-7: In the ox and sheep the figures given as capacity of stomach include the rumen, the reticulum, and the omasum. The relative capacity of these for the ox are: — rumen, 80 per cent. ; reticulum, 5 per cent. ; omasum, 7 per cent. ; and abomasum, 8 per cent. The great capacity of the large intestine of the horse should be noted. In this animal the caecum is also large. Its capacity is 25 to 30 litres ; that of the ox is 8 to 10. II. PHYSIOLOGY. Although the nature of the food is very different in different species of animals, the essential features of the digestive processes are common to all. In herbivora there are adaptations for dealing with bulky food. For the most part, however, these are developed after birth as the animal begins to change its diet from milk — an animal product — , to the bulky vegetable food. They are merely modifications of the simpler system of carnivora, which may be regarded 302 VETERINARY PHYSIOLOGY as the more fundamental type. It is convenient, therefore, to deal first with digestion in carnivora, and thereafter indicate the modifications that exist in herbivora, Omnivora, e.g. man and pig, present such minor differences from carni- vora that they can be included with these. Indeed, the work done to elucidate the physiology of human digestion has been done mainly on the dog — a carnivorous animal. A. DIGESTION IN CARNIVORA AND OMNIVORA. I. DIGESTION IN THE MOUTH. («) Mastication. In the mouth the food is broken up and mixed with saliva in the act of chewing. Mastication is less perfectly performed in carnivora than in herbivora. The dog masticates very imperfectly. After a few rapid chews the food is swallowed. (b) Insalivation. The saliva is formed by the salivary glands — the parotid, submaxillary, sublingual, and various small glands in the mucous membrane of the mouth. 1. Saliva — (1) Characters. — The Saliva is a somewhat turbid fluid which, when allowed to stand, throws down a white deposit consisting of shed epithelial scales from the mouth, leucocytes, amorphous calcic and magnesic phos- phates, and generally numerous bacteria, Its specific gravity is low — generally about 1003. In reaction it is neutral or faintly alkaline. (2) Chemistry. — It is found to contain a very small propor- tion of solids. The saliva from the parotid gland contains only about 0"4< per cent., while that from the sublingual may contain from 2 or 3 per cent. The sublingual and sub- maxillary saliva, in man, is viscous, from the presence of mucin formed in these glands, while the parotid saliva is free from mucin. In addition to mucin, traces of proteins are present, and in certain animals an enzyme — ptyalin — is associated with these proteins. Ptyalin is present in man and in the pig. It is absent in carnivora. DIGESTION 303 (3) The functions of the saliva are twofold : — (1) Mechanical. — Saliva moistens the mouth and gullet, and thus assists in chewing and swallowing. Since the salivary glands are absent from aquatic mammals, and since in carnivorous animals saliva has no chemical action, it would appear that this is the important function. (2) Chemical. — Under the action of the ptyalin of the saliva, starches are broken down into sugar. The starch is first changed into the dextrins, first into erythrodextrins and then into achroodextrins, and lastly into the disaccharid maltose (see p. 286), (Chemical Physiology). Like other enzyme actions, the process requires the presence of water and a suitable temperature, and it is stopped by the presence of strong acids or alkalies, by various chemical substances, and by a temperature of over 60° C, while it is temporarily inhibited by reducing the temperature to near the freezing point. During the short time the saliva acts on the food in the mouth, the conversion is by no means complete. 2. Physiology of Salivary Secretion. — (1) The changes which the secreting cells undergo during the so-called resting state of the gland and during secretion have been already considered (p. 35). (2) The nervous mechanism of secretion. — In order to study the influence of different factors upon salivary secretion, a cannula may be inserted into the duct of one of the glands, and the rate of flow of saliva or the pressure of secretion may be thus measured. In this way, it may be shown that in the dog the taking of food, or simply the act of chewing, or, in some cases, the mere sight of food, causes a flow of saliva. This shows that the process of secretion is presided over by the central nervous system, a fact which is further illustrated in man by the decrease in the secretion of saliva which accompanies some emotional conditions. The submaxillary and sublingual glands are supplied — (1) By branches from the lingual division of the fifth cranial nerve ; and (2) by branches of the perivascular sympathetic fibres coming from the superior cervical ganglion. The 804 VETERINARY PHYSIOLOGY parotid gland is supplied by the auriculo-temporal division of the fifth and by sympathetic fibres (fig. 149). (a) The influence of these nerves has been chiefly studied on the submaxillary and sublingual glands. (1) It has been found that, when the lingual nerve is cut, the reflex secretion of saliva still takes place, but that, when the chorda tympani (Ch.T.), a branch from the seventh nerve, which ioins the linorual, is cut, the reflex secretion does not Fig. 149. — Nervous Supjjly of the Salivai-y Glands. Par., parotid, and S.id. and S.L., the submaxillary and sublingual glands ; T//., the seventh cranial nerve, with Ch.T., the chorda tympani nerve, passing to L., the lingual branch of V., the fifth nerve, to supplj' the glands below the tongue, T. ; IX., the glossopharyngeal giving oft'/.iV., Jacobson's nerve, to 0., the otic ganglion, to supply the parotid gland through Aur.T., the auriculo-temporal nerve. occur. Stimulation of the chorda tympani causes a copious flow of watery saliva, and a dilatation of the blood-vessels of the glands. If atropine has been first administered, the dilatation of the vessels occurs without the flow of saliva. This indicates that the two processes are independent of one another. The secreting fibres all undergo interruption before the glands are reached ; the fibres to the sublingual gland having their cell station in the submaxillary ganglion (S.M.G.), the DIGESTION 305 fibres to the submaxillary gland having theirs in a little ganglion at the hilus of the gland (S.M.). This was demon- strated by painting the two ganglia with nicotine (p. 198). When applied to the submaxillary ganglion, the drug does not interfere with the passage of impulses to the submaxillary gland, but stops those going to the sublingual. If the duct of the gland be connected with a mercurial manometer, it is found that, when the chorda tympani is stimulated, the pressure of secretion may exceed the blood pressure in the carotid, showing that the saUva is not formed by filtration. (2) When the perivascular sympathetics, or when the sympathetic cord of the neck is stimulated, the blood-vessels of the gland constrict, and a flow of very viscous saliva takes place. Some time after section of the chorda tympani nerve an increased flow of saliva has been observed. It may be due to the uncontrolled action of the peripheral nervous mechanism. (b) On the parotid gland (1) the auriculo-temporal nerve (Aur.T.) acts in the same way as the chorda tympani acts on the other salivary glands. But stimulation of the tifth nerve above the otic ganglion, from which the auriculo- temporal takes origin, fails to produce any effect. On the other hand, stimulation of the glossopharyngeal nerve (IX.) as it comes off from the brain, acts upon the parotid gland, Since the glossopharyngeal is united by Jacobsons nerve (/.iV.) to the small superficial petrosal which passes to the otic ganglion, it is obvious that the parotid fibres take this somewhat roundabout course (fig. 149). (2) When the sympathetic fibres to the gland alone are stimulated, constriction of the blood-vessels but no flow of saliva occurs ; but if, when the flow of watery saliva is being produced by stimulating the glossopharyngeal or Jacobson's nerve, the sympathetic fibres are stimulated, the amount of organic soUds in the parotid saliva is very markedly increased. The nerve fibres passing to the salivary glands are pre- sided over by groups of cells, the Salivary Centre, in the medulla oblongata which may be stimulated reflexly or 20 306 VETERINARY PHYSIOLOGY directly by the condition of the blood. Stimulation of the lingual or glossopharyngeal leads to a reflex flow of saliva. Other nerves may also act on this centre. Thus gastric irritation, when it produces vomiting, causes a reflex stimu- lation of salivary secretion. In asphyxia the condition of the blood may directly stimulate the centre. According to the investigations of Pavlov, the salivary glands react appropriately to different kinds of stimuli through their nervous mechanism. When sand or bitter or saline substances are put in a dog's moutb, a profuse secretion of very watery saliva ensues to wash them out. When flesh is given, a saliva rich in mucin is produced. When dry food is given, saliva is produced in greater quantity than when moist food is supplied. Pavlov further states that the sight of different kinds of food produces a flow of the kind of saliva which their presence in the mouth would produce. The flow of saliva has been used by him for the study of cerebral, or "conditioned," reflexes. II. SWALLOWING. 1. Voluntary Stage. — The food, after being masticated, is collected on the surface of the tongue by the voluntary action of the buccinators and other muscles, and then, the point of the tongue is pressed against the hard palate behind the teeth. By a contraction passing backwards the parts of the tongue behind the tip are raised, along with the hyoid and with the larynx, and the bolus of food is thus pushed along the palate and through the pillars of the fauces. 2. Reflex Stage. — Swallowing now becomes a pure reflex. It can be performed only if something is present to excite it, and it is abolished by paralysing the receptors in the pharynx by means of cocaine. (1) The exact position of the receptor spots, stimulation of which thus reflexly causes swallowing, varies in ditferent animals. In man they are chiefly about the base of the tongue and the posterior pliaryugeal wall. Supplementary DIGESTION 307 receptor spots of less importance also exist, from which swallowing may be elicited when food gets lodged upon them. (2) The excito-reflex nerves are the fifth, via the spheno- palatine ganglion, and the vagus. The glossopharyngeal also may contain fibres which act ; but section of this nerve causes a sustained tonic contraction of the gullet, and stimu- lation of its central end inhibits swallowing. It probably acts chiefly to prevent a second act of swallowing occurring while one is already in progress. (3) The centre is situated in the medulla oblongata, and swallowing is readily induced in a decerebrated cat by pressing a bolus of cotton wool through the pillars of the fauces upon the receptor points in the pharynx. (4) The effector mechanism leads to the following changes : — (a) The hyoid and larynx are [)ulled upwards by the muscles which act upon these structures. (h) The upper orifice of the larynx is closed by the action of the lateral crico-arytenoidei,the arytenoidei, and the thyreo- arytenoidei, which pull forward the arytenoids against the posterior surface of the epiglottis. The whole larynx is pulled forwards as well as upwards, and thus the upper part of the oesophagus is opened, and the food slides over the back of the epiglottis and down the posterior aspect of the larynx into the gullet. (c) The passage of food into the naso-pharynx is pre- vented by the contraction of the glossopharyngeus, palato- pharyngeas, and the levator and tensor palati muscles, which approximate the soft palate and the back wall of the pharynx. id) The constrictors of the pharynx contract from above downwards and force the bolus on into the true oesophagus, which may be said to begin at the level of the cricoid cartilage. (5) The outgoing nerves involved are the hypoglossal, the third branch of the fifth, the glossopharyngeal to the stylo- pharyngeus and middle constrictor, and the vagus which supplies both the pharynx and the cesophagus. Section of the vagi nerves paralyses the upper part of the 308 VETERINARY PHYSIOLOGY gullet. In this condition food is forced down entirely by the pressure from the mouth. Fluids are normally shot right down the relaxed gullet by the pressure from the mouth and from the constrictors. Less fluid matter is passed down the oesophagus by a true peri- stalsis — a zone of relaxation passing down in front of a zone of contraction. This peristalsis is stopped for some time if the vagi nerves are cut and as a result food cannot be swallowed. The vagus is the great efferent nerve for the reflex part of the act of swallowing. But it has been found that, after the vagus has been cut for twenty-four hours or more, distension of the oesophagus by food may cause a peristalsis passing on to the stomach. The peripheral nerve plexus in the wall of the gullet must be capable of stimulation by such distension, and it must be able, in these conditions, to initiate and to main- tain peristalsis. Time of Swallowing. — Observations made on the human subject by feeding with food impregnated with bismuth and studying the changes in the oesophagus by X-rays have shown that fluids and solids, well masticated and mixed with saliva, are passed rapidly down the gullet, reaching the orifice of the stomach in about three seconds. Here they are delayed, and do not pass into the stomach for another period of about three seconds. Dry solids take much longer to pass down the ofullet, sometimes as much as fifteen minutes. III. DIGESTION IN THE STOMACH. Most important work on digestion in the stomach has been accomplished by Pavlov on dogs. His method is to make a small gastric pouch opening on the surface, and separated from the rest of the stomach (fig. 150), This is done by cutting out a V-shaped piece along the great curvature, the apex being towards the pylorus and the base being left connected with the stomach wall. By a series of stitches, the opening thus made in the stomach is closed up (top line of XXs in tig. 150), Avhile the cut edges of the V-shaped flap are stitched together to form DIGESTION 309 a tube. The one end of this is made to open u})on the skin surface A, A, and, by folding in the mucous membrane, the deep end is isolated from the stomach. Thus a pouch is formed, still connected with the muscular coat and with the nerves and the vessels of the stomach, the condition of which represents the condition of the whole stomach. Fig. 150. Diagram of Pavlov's Pouch made on the Stomach of a Dog. The condition of the stomach is very different in fasting and after feeding. A. Stomach during Fasting. (i.) The organ is collapsed, and the mucous membrane is thrown into large ridges, (ii.) It is pale in colour because the blood-vessels are not dilated. (iii.) The secretion is scanty, only a little mucus being formed on the surface of the lining membrane, (iv.) Movements may be absent, or rhythmic contractions may occur at regular intervals of from one-half to three or four minutes. These movements are generally associated with the sensation of hunger, and they may be called " hunger contractions:' They are best marked when the muscular tone of the stomach wall is good ; when it is decreased by section of the vagi, they are less marked ; 310 VETERINARY PHYSIOLOGY when it is increased by section of the splanchnic nerves, they are more marked. But the}' persist after section of both nerves, and they must therefore be presided over by the local nervous mechanism in the wall of the stomach. They are inhibited by taking food and even by the sight or smell of food. They do not stop during sleep. B. Stomach after Feeding. When food is taken, (1) the blood-vessels dilate, (2) a secretion is poured out, and (3) movements of the organ become more marked. 1. Vascular Changes. — The arterioles dilate, and the mucous membrane becomes bright red in colour. This is a reflex vaso-dilator effect, impulses passing up the vagus to a vaso-dilator centre in the medulla, and coming down the vagus from that centre. Section of the vagi is said to pre- vent its onset. 2. Secretion. — There is a free flow of gastric juice from all the glands in the mucous membrane. (1) Characters of Gastric Secretion. — The gastric juice from the cardiac end is a clear watery fluid, which is markedly acid from the presence of free hydrochloric acid. In the dog the free acid may amount to over 0-4 per cent., but in the \ng it is less abundant, and, when the gastric juice is mixed with food, the acid rapidly combines with alkalies and with pro- teins and is no longer free. In addition to the HCl, small quantities of inorganic salts are present. Traces of proteins may also be demonstrated, and two enzymes are associated with these — one a proteolytic or protein-digesting enzyme, pepsin, the other a milk-curdling enzyme, rennin. The fact that dilution may abolish the peptic activity while leaving the curdling action intact seems to show that these are not separate bodies but phases in the activity of one body. The secretion from the pyloric portion is alkaline in reaction. (2) Source of the Constituents of the Gastric Juice. — The hydrochloric acid is formed at the cardiac part of the stomach. This may be shown by making a small stomach by the method of Pavlov. Since the parietal or oxyntic cells DIGESTION 311 are confined to this portion of the stomach, it may be con- cluded that they are the producers of the acid. The NaCl of the blood plasma must be the source of the HCl. Pepsin and Rennin are produced in the chief or peptic cells which line the glands both of the cardiac and of the pyloric parts of the stomach. Daring fasting, granules are seen to accumulate in these cells, and when the stomach is active they are discharged. These granules are not pepsin but the forerunner of pepsin — pepsinogen (p. 36). (3) Course of Gastric Digestion. — («) Amylolytic Period. — The action of the gastric juice does not at once become manifest. In the pig for about two hours after the food is swallowed, the ptyalin of the saliva goes on acting, and the various micro-organisms swallowed with the food grow and multiply, and thus there is a continuance of the conversion of starch to sugar which was started in the mouth, and, at the same time, the micro-organisms go on splitting sugar to form lactic acid, which may thus be regarded as a normal constituent of the oesophageal end of the pig's stomach during the first two hours after a meal. (6) Proteolytic Period. — Before the amylolytic period is completed, the gastric juice has begun its special action on Proteins. This may be readily studied by placing some coagulated protein in gastric juice, or in an extract of the mucous membrane of the stomach made with dilute hydro- chloric acid, and keeping it at the temperature of the body. The protein swells, becomes transparent, and dissolves. The solution is coagulated on boiling — a soluble native protein has been formed. Very soon it is found that, if the soluble native protein is filtered off, the filtrate gives a precipitate on neutralising, showing that an acid compound — a meta.- protein — has been produced. If the action is allowed to continue and the meta-protein precipitated and filtered off, it will be found that the filtrate gives a precipitate on half saturation with ammonium sulphate, showing that proto- proteo.^es have been formed. These differ somewhat in their reaction, and apparently differ in the proportion of their constituent amino-acids. On filtering off these proteoses, the filtrate yields a precipitate on saturating with ammonium 312 VETERINARY PHYSIOLOGY sulphate, indicating the formation of deutero-proteoses ; and, if the filtrate after precipitating this be tested, the presence of yet another set of proteins may be demonstrated. These are Peptones (p. 18) {Chemical Physiology). These changes may be represented in the following table : — Coagulated Protein. Soluble Native Protein. I Meta-proteins. I Proto-proteoses. I Deutero-proteoses. I Peptones. The process is one of breaking down a complex molecule into simpler molecules, probably with hydration. It is the first step to the more complete disintegration of the protein to amino-acids which seems necessary before it can be built into the special protoplasm of the body of the particular animal. On certain proteins and their derivatives the gastric juice has a special action. On collagen the HCl acts slightly in converting it to gelatin. The gastric juice acts on gelatin, converting it to a gelatin peptone. On nucleo-jjroteins it acts by digesting the protein part and leaving the nuclein undissolved. Hcemoglobin is broken down into haematin and globin, and the latter is changed into peptone. It is the formation of acid haematin (p. 490) which, after a short time, gives the vomited matter in cases of haemorrhage into the stomach a brown colour. The caseinoge7i calcium compound of milk (p. 636) is first coagulated, and then changed to peptone. The coagulation is brought about by what is generally described as a second enzyme of the gastric juice — rennin. Very probably this action is merely a phase of the action of pepsin. The stomach contains an enzyme, lipase, which splits Fats DIGESTION 313 into fatty acids and glycerol if they are in a very line state of subdivision, as in milk, but it has no action on fats not so subdivided. It is probable that this lipase comes from the duodenum. AVhen fats are contained in the protoplasm of cells, they are set free by the digestion of the protein covering. On Carbohydrates the free mineral acid of the gastric juice has a slight action at the body temperature, splitting the polysaccharids and disaccharids into monosaccharids. (4) Digestion of the Stomach Wall. — Wlien the wall of the stomach dies either in whole, as after the death of the animal, or in part, as when an artery is occluded or ligatured, the dead part is digested by the gastric juice and the wall of the stomach may be perforated. The typical gastric ulcer which so frequently occurs in man in anajmia is of this nature. In the normal condition, a substance may be extracted from the mucous membrane which antagonises the action of pepsin and may be called antipepsin. (5) Antiseptic Action of the Gastric Juice. — In virtue of the presence of free HCl, the gastric juice has a marked action in inhibiting the growth of, or in killing, bacteria. Some organisms, while they do not multiply in the stomach, pass on alive to the intestine, where they may again become active. (6) Influence of Various Diets upon the Gastric Secretion. — This has been chiefly investigated by Pavlov on dogs with a gastric pouch (p. 309). He found that — (1) The amount of secretion depends upon the amount of food taken. (2) The amount and the course of secretion vary with the kind of food taken. Thus, with flesh the secretion reaches its maximum at the end of one hour, persists for an hour and then rapidly falls, while with bread it reaches its maximum at the end of one hour, rapidly falls, but persists for a much longer period than in the case of flesh. (3) The digestive activity of the secretions was tested by allowing them to act upon ca})illary glass tubes filled with egg-white coagulated by heating (Mett's tubes). The extent to which this was digested out of the tube in unit of time gave the activity of the secretion. It varies with the 314 VETERINARY PHYSIOLOGY kind of food and with the course of digestion. It is higher and persists longer after a diet of bread, which is difficult to digest, than after a diet of flesh, which is more easily digested. (4) The percentage of acid does not vary markedly. When more acid is required, more gastric juice is secreted. (5) The work done by the gastric glands, as measured by the amount of secretion multiplied by its AfOSE EYE MOUTH \J STOMACH POUCH Fig. 151. — To show the Nervous Mechanism of Gastric Secretion and how it is reflexly induced through various ingoing channels. activity, is greater in the digestion of bread than in the diofestion of flesh. (7) Nervous Mechanism of Gastric Secretion. — (rt) Intrinsic. — It has been proved that in the dog the secretion of gastric juice can go on after the nerves to the stomach have been divided, and this has been ascribed to a reflex stimulation of the nerve plexus in the submucosa. (6) Extrinsic. — Pavlov found that, when the vagus is cut DIGESTION 81& below the origin of the cardiac nerves so that the heart cannot be inhibited, stimuLation of the lower end of nerve, with a slowly interrupted induced current, causes a flow of gastric juice after a long latent period of a minute or two. This action of the vagus may be called into play, either by the contact of suitable food with the mouth or by the- sight of food. This he demonstrated by making an oesophageal fistula in a dog with a gastric pouch, so tliat food put in the mouth escaped from the gullet and did not pass into the stomach (fig. 151). Mere mechanical or chemical stimulation of the mouth produces no effect, but the administration of meat produces it. In a fasting dog the sight of food produces, after a latent period of five minutes, a copious flow of gastric juice. Pavlov calls thi& " psychic " stimulation. It is an example of how the "distance receptor" in the eye reflexly brings about an appropriate reaction — ^just as the "non-distance receptor" in the wall of the stomach, under other stimuli, brings about an appropriate reaction. (8) Chemical Stimulation. — There is some evidence that the formation of gastric juice is also influenced by the action of a chemical substance produced in the mucous membrane of the pyloric end of the stomach. It has been found that the iojection into the blood-stream of an extract of this membrane, made by boiling with acid or peptone, causes a production of gastric juice. In all probability the initial secretion of gastric juice is dependent on the nervous mechanism, and the secondary secretion, when food is in the stomach, on the action of this substance. The secretion is- also increased by the presence in the stomach of meat extracts and of weak solutions of alcohol. 3. Movements of the Stomach. — These have been studied by feeding an animal or a man with food containing bismuth, and then applying X-rays, which are intercepted by the coating of bismuth, so that a shadow^ picture of the shape of the stomach is given (fig. 152). 1. Character. — It is found that soon after food is taken, a constriction forms about the angular incisure at the 316 VETERINARY PHYSIOLOGY middle of the stomach, due to the contraction of the prepyloric sphincter which separates the cardiac from, the pyloric end. This contraction passes on towards the pylorus. Another contraction forms and follows the first, and thus the pyloric part of the stomach is set into active movement. The fundus acts as a reservoir, and, by a steady con- traction, presses the gastric contents into the more active pylorus, so that, at the end of gastric digestion, it is com- pletely emptied. While the food is well mixed in the p3doric canal, no A ^-N B Fig. 152. — Tracings of the Shadows of the Contents of the Stomach and Intestine of a Cat two hours after feeding (A) with boiled lean beef, and (B) with boiled rice to show the more rapid emptying of the stomach after the carbohydrate food. The waves of contraction in the pyloric part of the stomach are shown. The small divisions of the food in some of the intestinal loops represent the process of rhythmic segmentation. (Cannon.) great mixing takes place in the fundus of the stomach, and, by feeding with different coloured foods, its distribution may clearly be seen (fig. 1 5 3), The pylorus is closed by the strong sphincter pylori muscle, which, however, relaxes from time to time during gastric digestion to allow the escape of the more fluid contents of the stomach into the intestine. These openings are at first slight and transitory, but, as time goes on, they become more marked and more frequent, and, Avhen gastric digestion is complete — after an ordinary meal at the end of four or five hours, the sphincter is completely relaxed and allows the stomach to be emptied. The openings are regu- DIGESTION 317 lated by a local nervous mechanism which is reilexly brought into play by the escape of the acid gastric contents into the duodenum. This leads to an immediate closure of the pylorus, which does not again open till the contents of the duodenum have been neutralised by the alkaline secretions which are poured into it. The rate of passage from the stomach of various kinds of food has been studied by feeding cats with equal amounts of different kinds of food mixed with bismuth, and then, by X-rays, getting the outline of the contents of the small intestine at Prepyloric Sphincter. Pyloric Sphincter. Fig. 153. — Stomach of a Dog fed successively with three different foods to show the absence of mixing at the cardiac end. different periods. Carbohydrates were found to pass on most rapidly and fats most slowly (fig. 15 2). In man after a moderate meal the stomach is usually emptied in about four hours. 2. Nervous Mechanism of Gastric Movements — (a) Intrinsic- — Even after the section of all the gastric nerves, the movements of the stomach may be observed to go on regularly. They are therefore due to a mechanism in the wall of the organ, and, in all probability, judging from the analogy of the small intestine (p. 333), they are controlled by the plexus of neurons in the muscular coat. (/j) Extrinsic. — (i.) The vagus maintains the tone of the muscular coat and augments the movements of the pylorus. It also seems to act upon the cardiac sphincter to relax it. (ii.) The sympathetic fibres decrease the tone and the movements, but seem to maintain the contraction of the pyloric sphincter. Their terminations are stimulated by adrenalin. 318 VETERINARY PHYSIOLOGY C. Absorption from the Stomach. By ligaturing of the pyloric end, it has been found that the stomach plays a very small part in the absorption of food ; water is not absorbed, altliough alcohol and many drugs are raj)idly taken up. There is a slight absorption of peptones and of sugars. While the stomach plays a certain part in digestion, its action is by no means indispensable, for it has been removed in animals and in men without disturbance of the health. It has been shown, however, that tlie splitting of proteins is somewhat different if peptic precedes tryptic digestion. Its main function is to act as a reservoir, and probablj' the .antiseptic action of its secretion is of considerable importance. D. Regurgitation of Gastric Contents. 1. Regurgitation into the Gullet. — Normally, the contents ■of the stomach are prevented from passing back into the gullet by the cardiac sphincter. The tone of this sphincter is easily overcome, and it is relaxed by repeated swallowing, so that no sound is heard as the contents pass into the stomach. Since adrenalin inhibits it, it is probably relaxed by the sympathetic nerves. Stimulation of the vagus first inhibits and then causes it to contract. It tends to undergo rhythmic relaxations, during which the gastric contents pass back into the oesophagus, even up to the mouth, and then, by oesophageal peristalsis, are again passed down. The tone of the muscle is increased by the presence of hydrochloric acid in the stomach, and thus regurgitation does not take place in normal digestion, but is associated witli a neutral reaction of the stomach con- tents which is well marked in some forms of atonic dys2^epsia that occur in man. 2. Vomiting. — Sometimes the stomach is emptied upwards through the gullet instead of downwards through the pylorus. This act of vomiting is generally a reflex one, resulting^ from irritation of the sjastric mucous membrane. DIGESTION 319 and more rarely from stimulation of other nerves. It is a reaction to nocuous stimuli. In some animals, as the dog, it may be voluntarily induced. Usually vomiting is preceded by a free secretion of saliva. The glottis is then closed, and, after a forced inspiratory effort by which air is drawn down into the gullet, a forced and spasmodic expiration presses on the stomach, while at the same time the cardiac sphincter is relaxed, and the con- tents of the stomach are shot upwards. They are prevented from passing into the nares by the contraction of the muscles of the soft palate. The wall of the stomach also acts, the pyloric end being firmly contracted and the cardiac end being also in a state of tonus. But its action is non-essential, since vomiting may be produced in an animal in which a bladder has been inserted in place of the stomach. The centre which presides over the act is in the medulla oblongata, and, while it is usually reflexly called into action, it may be stimulated directly by such drugs as apomorphine. IV. INTESTINAL DIGESTION. After being subjected to gastric digestion the food is o-enerally reduced to a semi-fluid grey pultaceous condition of strongly acid reaction known as chyme, and, in this condition, it enters the duodenum. Here it meets three different secretions : — A. Pancreatic secretion. B. Bile. C Intestinal secretion- A. Pancreatic Secretion. The secretion of the pancreas may be procured by making either a temporary or a permanent fistula. In the former case, the duct is exposed, and a cannula fastened in it ; in the latter, the duct is made to open on the surface of tlie abdomen, a small piece of the intestinal wall, with the mucous membrane round the opening of the duct, being 320 VETERINARY PHYSIOLOGY stitched to the abdominal opening. For experiments on pan- creatic digestion extracts of the pancreas are generally used. 1. Characters and Composition. — When obtained immedi- ately from a temporary fistula, the pancreatic juice is a clear, slimy fluid, with a specific gravity of about 1015 and an alkaline reaction. It contains an abundance of a native protein having the characters of a globulin, and its alkalinity is probably due to sodium carbonate and disodium phosphate. From a permanent fistula a more abundant flow of a more watery secretion may be collected. 2. Action. — Closely associated with the protein, and pre- cipitated along with it by alcohol, are the enzymes, upon which the action of the pancreatic juice depends {Chemical Physiology). 1st. A Proteolytic Enzyme — Trypsin. — This, in a weakly alkaline or neutral fluid, converts native proteins into peptones, and then breaks these peptones into simpler non- protein bodies. The pancreatic juice brings about this breaking down of proteins in stages. It does not cause soHd proteins to swell up, but simply erodes them away. Fibrin and similar bodies first pass into the condition of soluble native proteins and then into dewtevo-proteose. The deutero-proteose is then changed into peptone, and part of that peptone is split into a series of bodies which no longer give the biuret test. These consist chiefly of the component j^oly peptides, amino- acids, and of ammonia compounds (see p. 18). Amino-propionic acid linked to indol — tryptophan — is also spUt off, and, if chlorine water is added to a pancreatic digest which has proceeded for a long time, this gives a rose- red colour. On nucleo- proteins, trypsin acts by digesting the protein and dissolving the nucleic acid so that it may be absorbed. On collagen and elastin trypsin has Httle action ; but on gelatin it acts as upon proteins. 2nd. A Diastase or Amylolytic Enzyme. — This acts in the same way as ptyalin, but more powerfully, converting a DIGESTION 321 certain part of the maltose into dextrose. It acts best in a faintly acid medium. ovd. A Lipase or Fat-splitting Enzyme.— This is the most easily destroyed and the most difficult to separate of the enzymes. It breaks the fats into their component glycerol and fatty acids. The fatty acids link with the alkalies which are present to form soaps, and in this form, or dissolved as free fatty acids in the bile, they are absorbed. But the formation of soaps also assists the digestion of fats by reducing them to a state of finely divided particles, an emulsion, upon which the lipase can act more freely. This process of emulsification is assisted by the presence of proteins in the pancreatic juice and also by the presence of bile. Uh. It is doubtful whether the pancreatic secretion contains rennin apart from trypsin, although it produces a modified clotting of milk, under certain conditions. That these enzymes are independent of one another is shown by the facts that one may be present without the other, e.g. diastase is absent in man in early childhood ; and also that diastase may be in an active state while the trypsin is in its inactive trypsinogen state. As to the mode of production of these enzymes, it is known that trypsin is not formed as such in the cells, for the secretion, direct from the acini, has no tryptic action. A forerunner of trypsin — trypsinogen — is produced, and this changes into trypsin after it is secreted. The intestinal secretion contains a substance of the nature of an enzyme, enterokinase, which has the power of bringing about this change of trypsinogen to trypsin, thus activating it (fig. 154). 3. Physiology of Pancreatic Secretion. — (a) Chemical Control. — The secretion of pancreatic juice is not constant, but is induced when the acid chyme passes into the duo- denum. This occurs, even when all the nerves to the intestine have been cut, and it appears, from the investiga- tions of Bayliss and Starling, to be due to the formation of a material, which has been called secretin, in the epithelium 21 322 VETERINARY PHYSIOLOGY lining the intestine, under the influence of an acid. This is absorbed into the blood in which it is carried round the circulation, and, on reaching the pancreas, stimulates it to secrete (fig. 15-i). It has been shown that the injection into a vein of an extract, made with dilute hydrochloric acid, of the lining membrane of the upper part of the small intestine, leads to a flow of pancreatic juice. Secretin is I TffYPSUI * Fig. 154. — To show the Mode of Action of Secretin and of the vagus nerve on the secretion of the pancreas and the activation of ti'ypsinogen by enterokinase. not destroyed by boiling, and is soluble in strong alcohol. It is therefore not of the nature of an enzyme. (6) Nervous Control. — But, while secretin seems to play so important a role, it has been found that stimulation of the vagus nerve, after a latent period of several minutes, increases pancreatic secretion, so that it must be concluded that the process of secretion is, to a certain extent, under the control of tlie nervous system. The influence of the pancreas in the general metabolism will be considered later (p. 357). DIGESTION 823 B. Bile. 1. Characters and Composition. — The bile is the secretion of the liver, and it may be procured for examination — (a) from the gall bladdei^, or (b) from the bile passages by making a fistula into them. This may be temporary when a tube IS placed in the common bile duct, or permanent when the common bile duct is ligatured, the fundus of the gall bladder stitched to the edges of the abdominal wound and an incision then made into it ; the bile thus flows through the gall bladder to the surface. Bile which has been in the gall bladder is richer in solids than bile taken directly from the ducts, because water is absorbed by the w^alls of the bladder, and the bile thus becomes concentrated. Analyses of gall bladder bile thus give no information as to the composition of the bile when formed. In several cases, where surgeons have produced biliary fistulse, oppor- tunities have occurred of procuring the bile directly from the ducts during life in man. Such bile has a somewhat orange-brown colour, and is more or less viscous, but not nearly so viscous as bile taken from the gall bladder. It has a specific gravity of almost 1005, while bile from this gall bladder has a specific gravity of about 1030. Its reaction is slightly alkaline, and it has a characteristic smell. It contains about 2 per cent, of solids, of which more than half are organic. (1) Bile Salts {Chemical Physiology). — The most abundant solids are the salts of the bile acids. In man the most important is sodium glycocholate. Sodium taurocholate occurs in small amounts. These salts are readily prepared from an alcoholic solution of dried bile by the addition of water-free ether, which makes them separate out as crystals. Glycocholic acid splits into glycin — amino-acetic acid, H0X.CII2.CO.OH— and a body of unknown constitution, cholalic acid, C04H40O5. Taurocholic acid yields amino-ethyl sulphonic acid or 324 VETERINARY PHYSIOLOGY taurin, H2N.CH2CH2.SO2OH, which is amino-acetic acid linked to sulphuric acid. This is joined to cholalic acid. In man there is very little taurocholic acid. Since both are amino-acids, they must be derived from proteins. That they are formed in the liver and not merely excreted by it, is shown by the fact that, while they accumu- late in the blood if the bile duct is ligatured, they do not appear if the liver is excluded from the circulation. The bile salts manifest the following actions : — (i.) They are solvents of lipoids, and they activate the lipase of the pancreatic secretion. For this reason (a) they assist in the digestion and absorption of fats. When bile is excluded from the intestines no less than 30 per cent, of the fats of the food may escape absorption and appear in the fasces. When this is the case, as in jaundice in man from obstruction of the bile duct, the faeces have a characteristic white or grey appearance from the abundance of fat. (6) They keep cholesterol in solution, (c) They act as powerful hsemolytic agents dissolving the lipoid capsules of the erythrocytes and allowing the escape of haemoglobin. (ii.) While the salts have no action on proteins, free taurocholic acid precipitates native proteins and acid meta- proteins. (iii.) They lower the surface tension of solutions, and in this way they may bring the fat and other substances into more intimate contact with the mucous membrane. (2) Bile Pigments. — These amount to only about 0-2 per cent, of the bile. In human bile, the chief pigment is an orange- brown iron-free substance, hiliruhin, C32H36N4O6, while in the bile of herbivora, biliverdin, a green pigment, somewhat more oxidised than bilirubin, CgoHggN^Og, is more abundant. By further oxidation with nitrous acid, other pigments — blue, red, and yellow — are produced, and this is used as a test for the presence of bile pigments (Gmelin's test) (Chemical Physiology). The pigments are iron-free, and they are closely allied to hsematoporphyrin and hasmatoidin (see p. 491). They are derived from hsemoglobin by the splitting of the hasmatin DIGESTION 325 molecule into an iron-containing part, which is retained in the liver, and the iron-free biliary pigment. Their amount is greatly increased when haemoglobin is set free or injected into the blood. Old and breaking down red cells are scavengered from the blood by the endothehal cells of the hepatic capillaries, while free haemoglobin is taken up directly by the liver cells. That the pigments are formed in the liver is shown by the fact that, when the liver is excluded from the circulation, the injection of haemoglobin is not followed by their appearance in the blood. But the formation of haematoidin, which is practically identical with bilirubin, apart from the liver, indicates that other tissues have the power of splitting haematin into its iron-containing and iron-free portions. The liver has the property of excreting not only these pigments formed by itself, but also other pigments. Thus, the liver of the dog can excrete the characteristic pigment of sheep's bile when this is injected into his blood. (3) Cholesterol is a monatomic alcohol — C26H43OH — which occurs free in small amounts in the bile. It is very insoluble, and is kept in solution by the salts of the bile acids. It readily crystallises in rhombic plates, generally with a notch out of the corner. The significance of cholesterol in metabolism and its source in the bile is not definitely known. It is a constituent of all cells, and under various conditions its amount in the blood plasma may be increased, e.g. when the amount in the food is large. It then appears in larger quantities in the bile, and it must therefore be concluded that it is excreted by the liver. Possibly it is derived, at least in part, from the stroma of the erythrocytes. (4) Fats and Lecithin. — The true fats and the phosphorus- containing lecithin are present in small amounts in the bile, and apparently they are derived from the fats of the liver cells. The fats may be increased in amount by the admini- stration of fatty food. (5) Nucleo-protein and Mucin. — The bile ow^s its viscosity to the presence of a muciu-like body, which, however, does 826 VETERINARY PHYSIOLOGY not yield sugar on boiling with an acid and which contains phosphorus. It is precipitated by acetic acid, but the precipitate is soluble in excess. It is therefore a nucleo- protein. In some animals a certain amount of mucin is also present {Chemical Physiology). (6) Inorganic Constituents. — The most abundant salt is calcium phosphate. Phosphate of iron is present in traces. Sodium carbonate, calcium carbonate, and sodium chloride are the other chief salts. 2. Flow of Bile — The bile, when secreted by the liver cells, may accumulate in the bile passages and gall bladder, and later be expelled under the influence of the contraction of the muscles of the ducts or of the pressure of the abdominal muscles upon the liver. The flow of the bile into the intestine thus depends upon — 1st, The secretion of bile ; 2nd, the expulsion of bile from the bile passages. It is exceedingly difficult to separate the action of these two factors. The taking of food increases the flow of bile, and the extent to which it is increased depends largely on the kind of food taken. In the dog, a protein meal has the most marked effect, a fatty meal a less marked effect, and a carbohydrate meal hardly any effect. The increased flow of bile following the taking of food does not reach its maximum till six or nine hours after the food is taken, and some observers have found that the period of maximum flow is even further delayed. Pavlov found in dogs, in which a biliary fistula had been made leaving the opening of the bile duct in the mucous membrane of the intestine, that an expulsion of bile follows the taking of food ; and Starling finds that the flow of bile is increased by the injection of secretin. It thus tends to run parallel with the flow of pancreatic juice. Influence of Nerves upon the Flow of Bile. — (a) Exjoulsion of Bile. — There is good evidence that nerve fibres pass to the muscles of the bile passages and that they mav cause an expulsion of bile by stimulating them to contract. (6) Secretion of Bile. — There is no convincing evidence that nerve fibres act directly upon the secretion of bile. DIGESTION 327 This appears to be governed by the nature of the material brought to the liver by the blood, and by the activity of the liver cells. It is an example of function regulated by chemical substances rather than by a nerve mechanism : although it is quite probable that these chemical substances act through the rich terminal plexus of nerves which runs throughout the liver. o. Mode of Secretion of Bile. — It has been seen that the bile salts are actually formed in the liver-cells, and there is good evidence that the water of the bile is not a mere tran- sudation but is the product of the living activity of these cells. The pressure under which bile is secreted may be determined by fixing a cannula in the bile duct or in a biliary fistula, and connecting it with a water manometer. In man the pressure is as much as 20 to 30 mm. Hg, while the pressure in the portal vein of the dog is only 7 to 1 6 mm. Hg. Hence bile cannot be formed by a process of filtration. 4. Nature and Functions of Bile. — Bile is not a secretion of direct importance in digestion — (1) It has practically no action on proteins or carbohydrates, and its action on fats is merely that of a solvent. Pavlov maintains that it activates the lipase of the pancreatic juice, and others have found that it increases the activity of trypsin and possibly of diastase, while its action on the surface tension of the intestinal contents may favour the absorption of fat. It may thus be considered as an adjuvant to the action of pancreatic juice. (2) Its secretion in relationship to food does not indicate that it plays an active part in digestion. It is formed during intra-uterine life and during fasting, and it is produced many hours after food is taken, when digestive secretions are no longer of use in the alimentary canal. (3) Digestion can go on quite well without the presence of bile in the intestine, except that the fats are not so well absorbed. (4) The composition of bile strongly suggests that it is a waste product. The pigment is the result of the decompo- sition of haemoglobin and the acids are the result of protein disintesrration. 328 VETERINARY PHYSIOLOGY All these facts seem to indicate that bile is the medium by ivhich the waste products of hepatic metabolism are eliminated, just as the waste products of the body generally are eliminated in the urine by the kidneys. (The action of the liver in general metabolism is considered on p. 353.) C Secretion of the Intestinal Wall. (Succus Entericus). 1. Method of Procuring. — This is formed in the Lieber- kiihn's follicles of the intestine, and it may be procured by cutting the intestine across at two points, bringing each end of the intermediate piece to the surface, and connecting together the ends from which this piece has been taken away, so as to restore the continuous tube of the intestine. 2. Characters. — On mechanically irritating the mucous membrane, a pale, yellow, clear fluid is secreted, which contains native proteins and mucin, and is alkaline in re- action from the presence of sodium carbonate. 3. Action. — The succus entericus contains: — (1) An enzyme or enz3^mes which split some disaccharids, as maltose and cane sugar, into monosaccharids, but do not seem to act on lactose. A special lactase seems to be present in the intestine of young animals taking milk. (2) Lipase is also present. (3) Erepsin, an enzyme which seems to act more powerfully than trypsin in splitting peptones into their component non-protein crystalline constituents, the polypeptides and amino-acids. (4) Enterokinase — a zymin which, acting on trypsinogen, converts it into active trypsin (p. 321). 4 Mechanism of Secretion The taking of food leads to a flow of intestinal secretion which reaches its maximum in about three hours ; and this flow is much greater from the upper part of the bowel than from the lower. There is some evidence that the injection of secretin calls forth this secretion, and, according to some observers, the injection of succus entericus into the circulation acts in the same way. DIGESTION 329 Mechanical stimulation undoubtedly causes a ' secretion, probably through a reflex in the nerve plexuses in the wall of the gut. As regards the action of extrinsic nerves very little is known. It has been found that, if the intestine be ligatured in three places so as to form two closed sacs, and the nerves to one of these be divided, that part becomes filled with a clear fluid closely resembling lymph. The dilatation of the blood-vessels may, however, account for this, without secretion being implicated. D. Bacterial Action in the Alimentary Canal. Numerous micro-organisms of very diverse character are swallowed with the food and saliva. It has been susfg'ested that the leucocytes, formed in the lymphoid tissue of the tonsils and pharynx, attack and destroy such organisms, but so far, definite proof of this is not forthcoming. When the food is swallowed, the micro-organisms multiply for some time in the warm, moist stomach, and certain of them form lactic and sometimes acetic acid by splitting sugars. But, when sufficient gastric juice is poured out for the hydrochloric acid to exist free, the growth of micro-organisms is inhibited, and some of them, at least, are killed. Those which are not killed pass on into the intestine, and, as the acid in the chyme becomes neutralised, the acid- forming organisms begin to grow, and, by splitting the sugars, form lactic or acetic acid and render the contents of the small intestine slightly acid. Towards the end of the small intestine, and more especially in the large intestine, the alkaline secretions have neutralised these acids, and, in the alkaline material so produced, the putrefactive organisms begin to flourish and to attack any protein which is not hydrolysed by the digestive enzymes — splitting it up and forming among other substances a series of aromatic bodies, of which the chief are indol, skatol, and phenol. Aromatic Bodies. — This splitting probably occurs through 330 VETERINARY PHYSIOLOGY the liberation of tryptophan — in which amino-propionic acid is linked to a pyrrol-benzene. CH0.CH.NH.-..CO.OH By the breaking down of the amino-propionic acid, skatol- — CH, ! I NH is formed, and, by the removal of the methyl, indol is produced — -H NH Phenol — -0— H C«H.. is a further stage of disintegration. Aonines (Appendix) may also be formed, and some of them have a toxic action. Their absorption from the gut may lead to marked symptoms. Dale has shown that some amines are vaso-constrictors of great strength. Folin has suggested tb.at ammonia is also formed in the bacterial changes, and that this may account for the traces of ammonia which have been found in the portal blood. DIGESTION 331 Bacterial action is not essential to digestion. By taking embryo guinea-pigs at full time from the uterus and keeping them with aseptic precautions, it has been shown that the absence of micro-organisms from the intestine does not inter- fere with their nutrition. E. Fate of the Digestive Secretions. 1. Water. — Although it is impossible to state accurately the average amount of the various digestive secretions MOCTH. >MALL Intestine. Large Intestine. Am LO LYTIC I 1 1 1 Alkaline -^OTEOLYTIC --Lipolytic -Putrefactive Fig. 155. — A Synopsis of the Conditions and Processes in the Different Divisions of the Alimentary Canal in the pig and in man. The nature of the control — nervous or chemical — is indicated in the top line. poured into the alimentary canal each day, it must be very considerable, probably more than one-half of the whole volume of the blood. Only a small amount of this is given off in the faeces, and hence the greater part must be re-absorbed. There is thus a constant circulation between the blood and the alimentary canal, or what may be called an entero-haemal circulation. One portion of this, the entero- hepatic, is particular!}- important. The blood-vessels of the intestine pass to the liver, and many substances, wlien absorbed into the blood-stream, are again excreted in the bile and are thus prevented from reaching the general 332 VETERINARY PHYSIOLOGY circulation. Among these substances are the salts of the bile acids and their derivatives, many alkaloids such as curarine, and in all probability the amines formed by putrefactive decomposition of proteins in the gut. The liver thus forms a protective barrier to the ingress of certain poisons. 2. Enzymes — Ptyalin appears to be destroyed in the stomach by the hydrochloric acid. Pepsin is probably partly destroyed in the intestine, but a proteolytic enzyme acting in an acid medium is present in the urine, and this may be absorbed pepsin. Trypsin appears to be destroyed in the alimentary canal ; but the fate of the other pancreatic enzymes and of the enzymes of the succus entericus is unknown. 3. Bile Constituents. — 1. The bile salts are partly re- absorbed from special parts of the small intestine — sodium glycocholate being taken up in the jejunum and taurocholate in the ileum. The acids of these salts are also partly broken up. The glycocholic acid yields amino-acetic acid, which is absorbed and passes to the liver to be excreted as urea ; while the taurocholic acid yields amino-isethionic acid, which goes to the liver, and yields urea and probably sulphuric acid. The fate of the cholalic acid is not known, but it is supposed to be excreted in the faeces. 2. The pigments undergo a change and lose their power of giving Gmelin's reaction. They appear in the fseces as stercobilin. It is probably formed by reduction of bilirubin in the intestines as the result of the action of micro-organisms. 3. The cholesterol is passed out in the fa3ces in a modified form as coprosterol. F. Movements of the Intestine. 1. The Small Intestine. These are of two kinds — segmental and peristaltic. 1. The segmental movements consist in the formation of local constrictions, which divide the gut up into little segments or compartments. A constriction next forms in the middle of each of these, and the former constriction is DIGESTION 333 relaxed, and its site becomes the centre of another com- partment. This process goes on repeating itself, and thus the contents of the gut are thoroughly mixed and churned. This may be seen by feeding with food mixed with bismuth and employing X-rays. These movements occur when all the nerves have been divided. How far they are dependent upon the action of the myenteric plexus is not definitely established. 2. The peristaltic movements are much more complex and powerful. They consist of a constriction of the muscles, which seems to be excited by the distension caused by the contents, and they may be caused by inserting a bolus of ^^Qyy^l^lu^ ^'^ A i Fig. 156. — Skiagrams to show Segmentation of tlie Small Intestine. (Hertz.) cotton-wool covered with vaseline. Starting at some point of the intestine, the wave passes slowly downwards and gradually dies away. In front of the contraction, the muscular fibres are relaxed, and thus the contracting part drives its contents into the relaxed part below. This move- ment of the contents of the intestine, when they are mixed with gases produced by fermentation, frequently produces gurgling noises. The peristaltic movements go on after the nerves to the gut are cut, but they are stopped when the ganglia in the wall of the intestine are poisoned by nicotine. The myenteric plexus undoubtedly forms a local reflex mechanism which is stimulated by the presence of the residue of the food in the intestine and which brings about the co- 334 VETERINARY PHYSIOLOGY ordinated contraction and relaxation, which together con- stitute a true j^eristalsis. But, while peristalsis is thus independent of the central nervous system, it is nevertheless controlled by it. The splanchnic nerves inhibit, while the vagus, to the small intestine and possibly the first part of the large gut, and the nervi erigenfes or pelvic nerves to the greater part of the large gut are augmentor nerves, increasing the peristalsis. Stimulation of the splanchnic fibres, which inhibit peristalsis, causes contraction of the ileo-Ciecal sphincter. The movements of the intestine may be inhibited either by interference with the local nervous mechanism or by reflex action through the central nervous system. Thus, it has been found that roughly handling the gut will lead to a prolonged inhibition, even after the extrinsic nerves have been cut. Other stimuli — such as crushing the testis under an anaesthetic — lead to a reflex inhibition, which is manifest only if the splanchnic nerves are intact. When a cat, under observation with X-rays, manifests signs of anger, the gastric movements and movements of the small intestine are checked. Under these conditions the movements of the large intestine may be increased and the foeces voided. The Ileo-Caecal Sphincter and Valve.— This sphincter pre- vents the free passage of the contents of the small into the large intestine, and causes a stasis in the ileum — possibly to allow of complete absorption of all the nutrient constituents. It relaxes from time to time, and allows the contents to be forced into the large gut. The valve is formed by a sleeve- like projection of the end of the ileum into the cascum, but it does not completely prevent the backward passage of the contents of the large into the small intestine. Usually the contents of the small intestine travel down at about 1-5 metres per hour. In abnormal conditions the rate of passage may be greatly retarded or accelerated, 2. The Large Intestine. In the large intestine peristaltic waves like those of the small intestine are not prominent, and the segmental move- DIGESTION 335 ments seem to be replaced by rhythmic contraction of the saccules. In the cat peristalsis in a backward direction— an anti-peristalsis — starts in the middle of the colon and passes to the caecum. On several occasions, usually after taking food, a rapid movement of the contents downwards in mass has been observed. This must be due to the rapid passage of a very powerful contraction, and it appears to be originated as a reflex from the stomach — a gastro-colic reflex. The result of the movement of the large intestine is to pass the contents onwards towards the rectum. In this passage the contents become less fluid from the absorption of water. 3. Defaecation. By the peristalsis of the intestine the matter not absorbed from the wall of the gut is forced down and accumulated in the rectum. It is prevented from escaping by two sphincter muscles, viz. the internal sphincter, which is merely a thickening of the circular muscular coat of the colon, and the external sphincter, which is of skeletal muscle. (1) The mechanism of the act of defascation is a local reflex, similar to that controlling the rest of the in- testine. In a dog, with all the lower part of the spinal cord removed, defsecation can, after some time, take place normally. (2) The peripheral mechanism is controlled by a centre in the lumbar enlargement of the spinal cord. When this is destroyed, the sphincters are for a time relaxed, and faeces are passed whenever they are driven down by intestinal contractions. The centre thus seems to exercise a tonic influence on the sphincters. Its action is inhibited by impulses sent up the sacral nerves from the distended rectum. (3) The lumbo-spinal centre is dominated by higher centres in the cerebrum, by the action of which defaecation may be inhibited for a time or the reflex may be liberated. The local centre is stimulated when distension of the rectum is produced by the accumulation of material — 336 VETERINARY PHYSIOLOGY undigested constituents of the food and excretory products. The undigested material usually forms the greater part of the accumulation, especially in herbivora. It has been shown that rabbits on a diet freed from cellulose cease to defecate and die of intestinal obstruction. The higher centres are stimulated by excitement, which, especially in timid animals, may produce diarrhosa. Muscular exercise helps to induce the reflex, probably partly by a sympathetic increased muscular action of the colon, and partly by the contraction of the abdominal muscles forcing material into the lower bowel. The influence of exercise is well seen in dogs, which often defsecate after being released and allowed a run. When defecation takes place, all the various muscles which can increase the pressure in the abdomen are called into play. A deep inspiration is taken, and then, with the glottis closed, expiratory efforts are made. The levator ani which supports the anus is relaxed, and the upper part of the rectum is brought more into line with the lower part of the pelvic colon. Faeces may thus be forced into the rectum, and the reflex act of defa3cation with contraction of the colon and relaxation of the sphincters is eflected. The act is completed by the contraction of the internal sphincter from above downwards and by the contraction of the levator ani and external sphincter. B. DIGESTION IN HERBIVORA. The food of herbivora is characterised by its bulk, and by the fact that the digestive material is for the most part enclosed in cells whose cellulose walls are not dissolved by the enzymes of the digestive tract. The distinctive feature about digestion in herbivora is therefore the provision for detaining a large quantity of food in a specially developed part of the alimentary canal, where, under the influence of bacteria, the cellulose is dissolved and the enclosed digestible material liberated. DIGESTION 337 1. Digestion in Ruminants. Prehension. — In the ox, in grazing, the mobile tongue curls round the grass and pulls it into the mouth, when it is cut off by the incisor teeth against the dental pad. The papillae in the inside of the mouth (p. 292) assist in preventing the food from dropping out. The divided upper lip of the sheep allow the teeth and dental pad to bite closer to the ground than in the case of cattle. In drinking the lips are closed except for a small orifice which is put below the surface of the water. The tongue acts like the piston of a pump and the water is sucked in. Mastication and Insalivation. — Mastication in ruminants is chiefly a side-to-side movement by which the food is ground between the molar teeth. It goes on usually for several minutes in one direction and then changes to the opposite direction. The parotid gland on the side on which the animal is chewing secretes much more actively than that of the opposite side. The sublingual and submaxillary glands secrete equally on both sides. The quantity of saliva poured into the mouth is very large. When dry food is eaten between 50 and 60 litres may be secreted in twenty-four hours. The specific gravity of the saliva is high, nearly 1010. It is doubtful whether the saliva of ruminants contains any ptyalin. If it is present it is in very small amounts. The food is swallowed after a preliminary incomplete chewing. It is returned to the mouth for more complete mastication during rumination which takes place after feed- ing has ceased. Ruminants can therefore eat food about three times as fast as the horse, which completes mastication before swallowing. Rumination. — This complication of the digestive process is peculiar to ruminants. It consists essentially of a re- mastication of the food after a preliminary storage. (1) Mechanism. — The food, when first swallowed, may enter any of the compartments with which the oesophageal groove is connected (p. 294). Liquids for the most part pass on 338 VETERINARY PHYSIOLOGY direct to the abomasum or true stomach. But when solid food is taken the pillars of the oesophageal groove relax, and the oesophagus then communicates with the rumen and reticulum to which the food passes. The fluid part tends to accumulate in the reticulum. After feeding, if the animal be comfortable and undisturbed, rumination or " chewing the cud " begins. By fixation of the diaphragm in the position of inspiration, and the contraction of the muscular walls of the rumen and reticulum and of the abdomen, some of the contents of the rumen accompanied by fluid from the reticulum is passed into the oesophagus. A bolus is cut off by contraction of the cardiac end of the oesophagus, and by a reversed peristalsis, is carried to the mouth. The fluid is immediately squeezed out and reswallowed, passing along the oesophageal groove to the omasum and thence to the true stomach. The mass left in the mouth undergoes a second process of mastication and insalivation. The finely com- minuted pasty material is then reswallowed.. and by a con- traction of the pillars of the oesophageal groove the omasum is drawn towards the oesophagus, and receives the material. In the omasum it is reduced to a still finer state of division by the grinding action of the hard leaves, between which it filters through to the true stomach. Even after remastica- tion the food, if not in a fine enough state of division, may pass again to the rumen instead of to the omasum. A certain degree of distension of the rumen is necessary to make regurgitation possible. This is maintained by the constant activity of the parotid glands, whose secretion constitutes a considerable proportion of the contents of the rumen. The flow of saliva and the process of rumination cease in disease. Under these conditions the food may become dry and caked and set up inflammatory changes. Impaction may occur, especially in the omasum. The moist mouth indicating a flow of saliva, and the commencement of rumination are of great value in prognosis. The ox spends about seven hours out of the twenty-four ruminating. A bolus of about 100 grams is regurgitated, remasticated, and reswallowed in rather less than one minute. DIGESTION 339 Rumination is a reflex act. The centre has not been located with certainty. It is probably situated in the medulla. The two chief nerves involved are the phrenic and the vagus. If the former be cut the diaphragm cannot be contracted, but the food can still be regurgitated by a more powerful contraction of the walls of the cavity and of the abdomen. If the vagus be cut, the walls of the cavities are paralysed and the process ceases. It is a remarkable fact that, though boluses can be returned from the rumen to the mouth, the ox does not vomit, even when distension of the rumen causes distress. Why vomiting does not occur is unknown. It has been suggested that the vomiting centre in the medulla is un- developed. (2) Digestive Changes in the Rumen. — The contents of the rumen are subjected to a churning by the contraction of the powerful muscular bands in the wall of the cavity. Newly added food is therefore mixed with the previous contents. No digestive juice is secreted, the only fluid added to the food being the alkaline saliva from the mouth. In this warm alkaline mass the fibrous substances become softened and prepared for the further digestive processes. It is probable that finely- divided material may pass direct from the rumen to the omasum, though doubtless the greater bulk is remasticated. The conditions in the rumen where the contents are warm and alkaline favour the conversion of starch to maltose by the enzyme ptyalin. Whether ptyalin is present in ruminants, however, is doubtful, and the extent to which the conversion takes place is unknown. Certain enzymes contained in the food may act. Cytase has a feeble action on cellulose. Proteolytic enzymes may act on protein, and amolytic enzymes on starches. These changes due to enzymes contained in the food are, however, of minor importance. Fats are freed by the disintegration of enclosing substances, but in this compartment they undergo no chemical changes. The rumen swarms with bacteria which attack the 340 VETERINARY PHYSIOLOGY cellulose and probably also the pentosans, breaking them down to various organic acids, chiefly acetic and butyric. These combine with the bases of the alkaline saliva. The resulting salts are absorbed from the intestine and are sources of energy. In the upper part of the rumen the contents may be acid from the accumulation of these organic acids. The gases, methane, carbon dioxide, and in small quantities hydrogen, are produced and excreted in the breath. The process is therefore largely a destructive fermentation. It is estimated that about 60 per cent, of the cellulose of the food is disintregated in the rumen. As the cellulose is broken down the cell contents are liberated and rendered accessible to the digestive juices of the following parts of the digestive tract. In addition to cellulose, starch and sugars undergo destructive fermentation. It has been shown that the addition of starch to a fixed diet leads to a corresponding increase in the excretion of methane. Nitrogenous material is also broken down by bacteria, and used to build up the proteins of their own protoplasm. It seems that the soluble non-protein compounds are more readily utilised than the proteins. When a plentiful supply of soluble nitrogen is available, the multiplication and activity of bacteria is increased, and conseqtiently there occurs a more extensive disintegration of cellulose. It has been suggested that the protoplasm of bacteria, which are carried on into the stomach, is digested, and the resulting products absorbed, and that it is by the bacteria consuming the non-protein nitrogenous material and then being themselves digested that non-protein nitrogen is made available. Whether bacterial protein can be hydrolysed by the digestive enzymes is disputed. As the non- protein nitrogenous material consists chiefly of amino-acids and amides — the normal cleavage products of digestion (p. 320) — it seems unnecessary to involve the aid of bacteria for their utilisation. Stomach. — After being triturated between the leaves of the omasum, the food enters the abomasum or true stomach. The course of events in the stomach has been studied by making a Pavlov's pouch in the goat. DIGESTION 341 The stomach contents for some time after being received from the omasum are alkaUne. Micro-organisms flourish and brealc down sugars to form hictic acid. An amoh-tic enzyme converting starch to sugar seems to be produced. Before this amolytic period is completed pepsin and hydrochloric acid are secreted in sufficient amounts to make the contents acid and enable peptic digestion to begin. The concentration of hydrochloric acid, however, is never so great as in carnivora. Intestines. — In the small intestine, so far as is known, the secretions and digestive processes are the same as have been described for carnivora. But a smaller proportion of the food is digested and absorbed so that a bulky residue reaches the ccecum and colon. Here the destructive fermentation of cellulose by bacteria is resumed, and digestive processes are continued by enzymes that have been carried on from the small intestine. The large intestine is therefore a more important structure in herbivora than in carnivora, where its main function is the absorption of water and the storage of food residues and excretory products prior to expulsion in the faeces. In ruminants where important changes go on in the rumen before the food passes through the stomach and small intestine digestion in the caecum and colon are much less important than in the horse (p. 344). Faeces. — The faeces which consist chiefly of undigested residues of the food are more fluid in the ox than in the sheep. The amount varies with the food. In the ox the average weight per diem is about 30 kilos. The composition of the faeces is dealt with later (p. 861). 2. Digestion in the Horse. Prehension. — In grazing, the Hps of the horse are drawn back to allow the teeth free access to the grass. If the nerves supplying the lips cut, it becomes impossible for the horse to graze. In manger-feeding the lips are used to gather the food. In drinking, as in the ruminant (p. 3 3 7;, the tongue acts like 342 VETERINARY PHYSIOLOGY the piston of a pump sucking in the water. If an opening be made in the cheek above the level of the water so that air gets in water cannot be sucked up. When drinking, the head is extended, and there is a forward movement of the ears as each gulp is swallowed. The reason for this peculiar backward and forward movement of the ears in the horse when drinking is unknown. Mastication and Insalivation. — The process of mastication is very completely performed, the animal taking about five to ten minutes to eat a pound of corn and about fifteen to twenty minutes to eat the same amount of hay. As in the ruminant, mastication is chiefly a side-to-side movement and is unilateral, the parotid gland on the chewing side being the more active. The parotid gland is relatively large in the horse, being about twice as large as that of the ox. Unlike the ruminant where the parotid secretion never ceases in health the gland is only active during mastication. The saliva probably con- tains ptyalin. The quantity of saliva secreted has been measured by making an oesophageal fistula and collecting the boluses of food which are swallowed, and so flnding the amount of fluid which has been secreted in the mouth. About 40 to 50 litres may be produced in a day. The amount is determined by the dryness of the food. Dry fodder absorbs about four times its weight of saliva ; green fodder about half its weight. In abdominal pain there is complete cessation of all the salivary glands, and the mouth and tongue become dry. Stomach. — In the horse the process of gastric digestion differs from that of carnivora in the following particulars. In the first place, the horse has to eat a very large quantity of food in proportion to the size of its stomach, and it is found that part of the food begins to pass very rapidly through the stomach into the intestine. Colin found, when he killed a horse which in two hours had eaten 2500 grms. of hay, that the stomach contained only 1000 grms. But while this is the case, a small residue of the meal remains for a very long time in the stomach, and passes out only when the next meal is taken. DIGESTION 343 The churning action of the stomach is less complete in the horse than in the dog, and hence when the animal has received hay, followed by oats, these are found lying more or less separate. Even when the animal has taken water the contents are not much disturbed (p. 367). In the horse, the amyolytic period is well marked, and the percentage of hydrochloric acid is never so high as in the dog. Lactic acid is always formed from the carbohydrate Fig. 157.— Stomach of Horse fed successively on four dififerently coloured foods to show the distribution of the various foods in the viscus. of the food, and on a diet of hay it may exceed the hydro- chloric acid. The proteolytic action of the gastric juice of the horse is slower than that of carnivora, but it is very marked, and peptones are found abundantly in the stomach at the end of digestion. In the stomach of the horse the cellulose of the food is partly decomposed, probably by the action of an enzyme in the grain. Intestines. — In the small intestine the processes that go on are much the same as in carnivora. 344 VETERINARY PHYSIOLOGY In the large intestine the caecum and double colon perform much the same function as the oesophageal diverticula of the ruminant (p. 389). The Caecum acts as a reservoir. The contents of the small intestine pass through it to reach the colon. Water drunk passes very rapidly to the caecum. The contents are always fluid, varying from a pea-soup-iike consistency to a quite watery liquid, with particles of undissolved food floating throughout it. Some of the food may remain for as long as twenty-four hours in the caecum. On the other hand, some may pass rapidly through to the colon. Food has been found in the colon four hours after being eaten. The outlet to the colon is above the level of the inlet — the ileo-caecal valve. The contents therefore are emptied against gravity by the contraction of the four longitudinal muscular bands in the walls of the organ. The contents of the large colon and of the first foot or so of the small colon resemble those of the caecum. There- after by the absorption of water the contents rapidly become inspissated, and by the sacculation of the colon, formed into balls of faeces, ready for expulsion. The digestive change that takes place in the ca3cum and large colon are much the same as those that occur in the rumen of the ox. The contents are alkaline in reaction and swarm with bacteria. Fibrous material that has resisted the action of the stomach and small intestine becomes macerated. Cellulose is attacked by bacteria and broken down, yielding the same products as the disintegration of cellulose in the rumen (p. 340). The gases appear as little bubbles scattered throughout the fermenting mass. As the cellulose envelope is broken down, the contents that were protected from the action of the digestive secretion of the stomach and small intestine are hydrolysed by the enzymes that have been carried into the large intestine. Proteins that have not been hydrolysed by the digestive enzymes are disintegrated by putrefactive organisms giving rise to a series of aromatic bodies (p. 329), which are absorbed. Some of these are toxic and affect the health of the animal. Absorption of the products of digestion takes place in the DIGESTION 345 cfficum and colon. So rapid is absorption in the lower bowel that the animal may be easily anaesthetised by giving ether per rectum. The rapid absorption allows of life being maintained by nutrient enemata. Some of the movements of the alimentary tract are of special interest in the horse. In neither the small nor the large intestine have segmental movements been observed, but an anti-peristaltic movement has been described. As the contents of the intestine are Kquid Fig. 158. — Mesial Section through the Head of a Horse, to show the long soft palate,/, lying against the front of the epiglottis, i ; c, the tongue ; I, the arytenoids. (Ellenberger.) seo-mentation is unnecessary. Anti-peristaltic movements serve by mixing the contents to bring the food into more intimate contact with the intestinal secretions, and also prevent the too rapid emptying of the small intestine into the csecum. In defsecation the contraction of the rectum is so powerful that the act can be performed without fixation of the dia- phragm or closing of the glottis, though these usually occur when the animal is at rest. The crouching attitude common to nearly all animals is not adapted. The horse can there- fore defsecate when trotting. 346 VETERINARY PHYSIOLOGY Vomiting in the horse seldom occurs. The oesophagus joins the stomach very obliquely and folds of mucous mem- brane of the stomach tend to prevent the passage of stomach contents back into the oesophagus. Further, the lumen of the oesophagus is diminished at the cardiac end, and there the circular coat is thicker and firmer. On the few occasions when vomiting does occur the vomited material, which is prevented from entering the mouth by the long soft palate, escapes from the nostrils (fig. 158). SECTION III. ABSORPTION OF FOOD 1. State in which Food leaves the Alimentary Canal- (1) The carbohydrates generally leave the alimentary canal as inonosaccharids ; but some resist the action of digestion more than others. Lactose seems to be broken down in the intestine only when the special enzyme, lactase, is present in the succus entericus, but in all cases it is broken down before it reaches the liver. Cane sugar, when taken in large excess, may also be absorbed unchanged, and it is then excreted by the kidneys, (2) The proteins are absorbed as amino-acids, formed by the action of trypsin and erepsin (pp. 320 and 328). Native pro- teins may be absorbed to a small extent unchanged, as is shown by the fact that the administration of very large amounts of egg albumin may cause its appearance in the urine. Egg- white, when injected into the pelvic colon isolated from the rest of the intestine, and hence free of proteolytic enzymes, may disappear, probably as the result of bacterial action ; but in carnivora the amount absorbed, as indicated by the increased excretion of nitrogen, is trivial. In the horse absorption in the colon is more complete (p. 344). (3) Non-protein nitrogenous material may be absorbed as amino-acids, the form in which it is largely present in the food, or may be acted upon by bacteria prior to absorption (p. 340). (4) The fats are chiefly absorbed as soaps and as fatty acids. (5) The results of the digestion of cellulose are absorbed as salts of organic acids (p. 340). 348 VETERINARY PHYSIOLOGY 2. Mode of Absorption of Food. — That absorption is not due merely to a process of ordinary diffusion is clearly indicated by many facts. (1) Heidenbain has shown that absorption of water from the intestine takes place much more rapidly than diffusion through a dead membrane. (2) The relative rate of absorption of different substances does not follow the laws of diffusion. Griibler's peptone passes more easily through the intestine than the more diffusible glucose, while sodium sulphate, which is more diffusible than glucose, is absorbed much less readily. Again, an animal can absorb its own serum under conditions in which filtration into blood capillaries or lacteals is excluded. (8) Absorption is stopped or diminished when the epithelium is removed or injured, or poisoned with fluoride of sodium, in spite of the fact that this must increase the facilities for diffusion. (4) During absorption, the oxygen consumption by the wall of the gut is increased. 8. Channels of Absorption. — There are two channels of absorption from the ahnientary canal (see fig. 162, p. 388) — (1) the veins, which run together to form the portal vein of the liver, and (2) the lymphatics, which run in the mesentery and, after passing through some lymph glands, enter the receptaculum chyli in front of the vertebral column. From this, the great lymph vessel, the thoracic duct, leads up to the junction of the subclavian and innominate veins, and pours its contents into the blood stream. The lymph formed in the liver also passes into the thoracic duct. (1) Proteins. — (1) During the digestion of proteins the number of leucocytes in the blood is enormously increased, sometimes to more than twice their previous number. This is due to an emigration from the red marrow of bone. The digestion leucocytosis passes off in a few hours, but what becomes of the leucocytes is not known. Possibly they are- I ABSORPTION 349 the carriers of the amino-acids which are formed in digestion ; but, since it has been found possible to dialyse these from the blood, the leucocytes must either break down in the blood stream or give up the amino-acids before the tissues are reached. (2) The amount of amino-acids is increased in the blood. That they are absorbed by the blood-vessels and not by the lymphatics is indicated by the fact that ligature of the thoracic duct does not interfere with the absorption of the nitrogen of the proteins. (8) The amino-acids are rapidly removed from the blood by the tissues, and chiefly by the liver. Their concentration 'NON;.^TOGEN0US Liver Intestine Fig. 159. — To show the Splitting of the Amino-aeid Part of Proteins into a nitrogenous part, which is changed to urea in the liver and excreted by the kidneys, and into a non-nitrogenous part yielding sugar, which is sent into the muscles. in this organ may be three or four times that of the blood. Apparently, any surplus over that immediately required by the tissues, accumulates in the liver and is so prevented from exercising a toxic action on the heart. In the liver the stored amino-acids are rapidly split up and the amidogen portion converted to urea and excreted by the kidneys, while the non-nitrogenous part is converted into carbo- hydrates to a greater or less extent (fig. 159). The muscles and other tissues accumulate these amino-acids to a much smaller extent and hold them longer, probably for the 350 VETERINARY PHYSIOLOGY synthesis of their proteins, and possibly in order to use their non-nitrogenous part as a source of energy. (2) Carbohydrates. — These are absorbed as monosaccharids in solution, and are carried away in the blood of the portal vein. Any surplus, over that required by the body, may be stored in the liver and subsequently sent to the tissues (p. 3 5 4). (3) Fats. — After being split up into their component acids and glycerol, fats pass, as soluble soaps or as fatty acids soluble in the bile, through the borders of the intestinal epithelium. Here they ap])ear to be again converted into fats by a synthesis of the acid with glycerol. Fine fatty particles are found to make their appearance in the cells at some distance from the free margin and to increase in size. A similar synthesis occurs even when free fatty acids alone are given, so the cells must be capable of producing the necessary glycerol to combine with the acids. The fats are sent on from the cells, through the lymph tissue of the villi, into the central lymph vessels, and thus on, through the thoracic duct, to the blood stream. Unlike the proteins and carbohydrates, they are not carried directly to the liver. In some animals they are stored in the fatty tissues, in others to a certain extent in the liver. Since neither the character nor the amount of food consumed are determined by the actual requirements of the muscular and other tissues, it is of importance that there should be some regulator which will control the amount and cliaracter of the nourishment sent to the muscles. Such a regulator is found in the liver. When more food is taken than is at once required by the tissues, one of three things may happen — 1. It may be oxidised with the evolution of heat. This is specially the case with proteins, the high specific dynamic action of whicli markedly increase heat production (p. 272). 2. It may be excreted, unchanged in the urine as in the case of sugar. 3. It may be stored and sent to the muscles as it is required, and thus the supply of energy-yielding material may be regulated. ABSORPTION 351 A. Storage of Surplus Food. 1. Fat. — Since, bulk for bulk, fat has more than twice the energy value of proteins or carbohydrates (p. 257), it is an advantage to store surplus food as Fat. In fat oxen or sheep the fat may constitute nearly 50 per cent, of the weight of the carcase. This stored fat is not immediately available. It may be regarded as invested capital which has to be placed at current account before it can be used. This storage takes place chiefly in three situations : (1) Fatty tissue ; (2) Muscle ; (3) Liver. (1) In Fatty Tissue- — In most mammals the chief storage of surplus food is in the fatty tissues. (a) That the fat of the food can be stored in them is shown by the fact that the administration of large amounts of fats, different from those of the body, leads to their appearance in those tissues. The administration of erucic acid to dogs leads to its appearance in the fat, and cows fed on maize oil yield butter of a low melting-point. Fats stained with Sudan III. carry the stain into the fatty tissue in which they are deposited. (b) That fat is formed from carbohydrates was proved by Laws and Gilbert in the feeding of young pigs. Two of a litter were taken and one was killed and analysed. The other was fed for weeks upon maize, the amount eaten being weighed, and the excretion of nitrogen by the pig being determined. The animal was then killed and analysed, and it was found that the fat gained was more than could be accounted for by the fat and protein of the food eaten. In this process of fat formation the respiratory quotient may rise above I'O. It is probably carried out as follows: — 6 CeHiA + 13 O, = 20 CO, + CieHaA + 20 H,0 Glucose. Fatty Acid. The greater energy of the fatty acid molecule as compared with that of the sugar is got by the oxidation of some of the sugar along with a reduction of the rest. (c) The evidence that fats may be formed from the proteins of the food is conflicting. (1) In the ripening of 352 VETERINARY PHYSIOLOGY cheese it is undoubted that, under the influence of micro- organisms, proteins are changed to fats. (2) In all proba- bility the same thing occurs in the formation of the fatty adipocere in the muscles of the dead body during putrefaction. (3) At one time it was supposed that, under the influence of such poisons as phosphorus, the proteins of the cells of the mammalian tissues are changed to fat. But careful chemical examination has shown that the so-called fatty degeneration is due to accumulation of already existing fats in the affected organs. (4) If a dog be fasted till all the fat of the body is used up, and then fed on lean beef, it will lay on fat. But analysis of such beef shows that it contains enough fat and glycogen to yield all the fat laid on. At present we have no direct evidence that the fats of the body are formed from proteins, although the facts (1) that carbohydrates are formed from proteins (p. 354), and (2) that fats are formed from carbohydrates, make it possible that proteins may be a source of fat, but that their specific dynamic action prevents the fat from accumu- lating. (2) In the Liver. — In some animals, e.g. the cod and the cat, fats are largely stored in the liver. (3) In Muscle. — The salmon stores fats within its muscle fibres ; but in mammals such a storage is very limited in amount, although large amounts may be deposited between the bundles of fibres (p, 374). 2. Proteins may, to a small extent, be stored in muscle, especially after a fast or a prolonged illness, and during rapid growth a suckling animal ma}^ store more than 40 per cent, of the protein of the mother's milk. But in the normal mammal it is difficult to induce such a storage, except in athletic training, where the muscles may be enormously increased by the building up of the protein-derivatives of the food into their protoplasm. 3. Carbohydrates are stored to a small extent in the liver and in muscle (p. 354). Probably, at most about 10 per cent, of glycogen occurs in the liver and 1 per cent, in ABSOEPTION 353 muscle. The amount varies with the diet, and in a dog which is not fasting, it may be anything from 5 to 30 grms. per kilo of body weight. This small store is rapidly used up in fasting and is drawn upon in muscular exercise. Glycogen may be compared to money at current account ; glucose, like money in the pocket, may be used at once. B. The Liver as a Regulator of the Supply to Muscles. The liver develops as two diverticula from the embry- onic gat, and is thus primarily a digestive gland. In invertebrates it remains as a part of the intestine both structurally and functionally. But in mammals, early in foetal life, it comes to have important relationships with the blood going to nourish the body from the placenta (see p. 623). The vein, bringing the blood from the mother, breaks up into a series of capillaries in the young liver. (1) Blood Formation. — The development of the cells of the blood goes on for a considerable time in these capillaries. (2) Bile Secretion. — Soon the liver begins to secrete bile. (3) Glycogenic Function. — Animal starch and fat begin to accumulate in its cells. Gradually, the formation of blood cells stops, and the mass of liver cells becomes larger in proportion to the capillaries. As the foetal intestine develops, the vein bringing blood from it — the portal vein — opens into the capillary network of the hver, so that, when at birth the supply of nourishment from the placenta is stopped, the liver is still associated with the blood which brings nutrient material to the body, and it performs an important function in regulating the supply of nourishment to the tissues, and more especially to the great energy-liberating tissue, muscle. 1 . Regulation of the Supply of Sugar. — It has been already shown that sugar is an essential source of energy in muscle. (1) Production of Sugar. — The relationship of the liver to the metabolism of sugar was discovered by Claude Bernard in the middle of last century. Even in the most prolonged fast, the liver continues to supply to the blood enough dextrose to maintain the normal proportion of about 23 354 VETERINARY PHYSIOLOGY 15 per cent. In fasting the only possible sources of this sugar are the proteins and the fats of the body, (a) That proteins are a source of sugar is shown by the fact that, in diabetic patients and in dogs rendered diabetic by removal of the pancreas, i.e. in animals which are excreting and not using the sugar (p. 357), the output of sugar is increased by giving proteins. It has further been found that most of the amino-acids which build up the proteins, undergo the same change, the non-nitrogenous part being to a greater or less extent converted to sugar, the nitrogenous part being excreted as urea. Claude Bernard had discovered that, after feeding a dog, which had fasted till all the stored carbohydrates of the liver had disappeared, on lean beef, glycogen, the precursor of sugar, appeared in the liver. (6) The question of whether the liver can form sugar from the fats of the body is more difficult to answer. The argument in favour of such a conversion is that in many cases of pancreatic diabetes the amount of sugar formed is more than could be derived from the proteins decomposed, as indicated by the nitrogen excreted. Hence, it would seem that it must be derived from the fats. (2) Storing Sugar as Glycogen. — The liver not only manufactures sugar for the muscles when the supply from outside is cut off, but it also has the power of storing sugar derived from an excess of carbohydrates in the food, or from an excess of proteins. This it does by converting the monosaccharid into a polysaccharid — animal starch, or glycogen. This substance accumulates in the protoplasm of the cells, and its presence may be demonstrated by staining with iodine. Since the same glycogen is derived from all the single sugars, Isevulose (a ketose) as well as dextrose (an aldose), the liver protoplasm must perform a chemical change in the process of synthesising them into glycogen, from which dextrose alone is formed. The storage of glycogen may be very great, amounting in certain conditions to as much as 10 per cent, of the weight of the liver. (3) Conversion of Glycogen to Dextrose. — When sugar is required by the muscles, it is again converted to glucose, and passes off in the blood. This subsequent conversion of ABSORPTION 355 glycogen to glucose is generally ascribed to the action of an hepatic diastase. This conclusion is supported by the fact that the liver tissue, after prolonged treatment with alcohol, has an active diastatic action. But (i) fresh liver has no greater diastatic power than any other tissue. (ii) While the conversion of glycogen to glucose in the liver removed from the animal immediately after death, is at a maximum during the first few minutes and gradually decreases, the conversion of glycogen to glucose, under the influence of liver tissue treated with alcohol, gradually reaches a maximum in an hour and gradually wanes, (iii) It has Also been shown that the injection of methylene blue, which poisons protoplasm, but does not interfere with the action of enzymes, checks the conversion, and (iv) that stimulating the splanchnic nerves going to the liver increases the conversion of glycogen, without increasing the amylolytic enzyme in the liver and blood. It is therefore possible that the conversion results from chemical changes in the proto- plasm which are controlled by the nerves of the liver. These nerves are derived from the true sympathetic system. Carbohydrate Tolerance. — If more sugar is taken than the liver can deal with, it passes on into the general circulation, and is excreted in the urine. Every animal has a certain power of oxidising or of storing sugar. If the carbohydrates are taken as starch instead of sugar, the process of digestion iind the slower absorption enables the liver to deal with much larger quantities. The carbohydrate tolerance varies greatly, and even in the same animal it is different under different conditions. Glycosuria. — If the limit of carbohydrate tolerance is overstepped, sugar increases in amount in the blood (glycsemia) and appears in the urine. Glycosuria is produced. Glycosuria may be caused in several different ways. 1. By decreased carbohydrate tolerance — alimentary glycosuria (fig. 160). 2. ^Yhen the glycogen stored in the liver is changed to glucose more quickly than is required by the tissues, the glucose may, to a small extent, be again stored in the 356 VETERINARY PHYSIOLOGY muscles as glycogen (p. 352), or it may accumulate in the blood and be excreted in the urine. This latter condition is seen when large doses of adrenalin, the active principle of the medullary part of the suprarenal bodies (p. 598), is injected subcutaneously. This substance has a specific action on the termination of the true sympathetics, and, in all probability, it acts upon the termination of the splanchnic nerves in the liver to increase the conversion of glycogen to Fig. 160. — To show the various waj's in which glycosuria may be produced (see text). glucose. Ergotoxin, which checks its action elsewhere (p. 592), also hmits its power of causing glycosuria (fig. 160). 3. The condition is also caused, if the liver is rich in glycogen, by puncturing the posterior part of the floor of the fourth ventricle of the brain. Since this effect is not produced after the suprarenals have been removed, it has been concluded that it is due to a stimulation of these structures through the splanchnic nerves by Avhich an increased outpouring of adrenalin is induced. This might ABSORPTION 357 act in the same wa}' as the administration of large doses of adrenalin. It is probable that two elements are involved — (a) the stimulation of the suprarenals, and (6) the stimulation of the branches of the splanchnic nerves to the liver and that the latter action is merely facilitated or activated by the former, since the accumulation of adrenalin in the blood found in puncture diabetes is not sufficient in itself to cause the glycosuria, and since M'Leod found that section of the hepatic nerves generally prevents its onset (fig. 160). 4. The injection of phloridzin and some other substances such as chrome salts, or even solutions of neutral sodium salts, also causes sugar to appear in the urine. Under the influence of these, the sugar in the blood is not increased. It must be concluded that they act by causing the kidneys to excrete glucose too rapidly, so that it is not available for the tissues. But, even when carbohydrates are withheld or cleared out of the body, phloridzin causes glycosuria. Hence, a formation of glucose from the proteins of the blood plasma must occur (fig, 160). 5. Removal of the pancreas also causes glyctemia and glycosuria. This may be prevented by transplanting a piece of the pancreas under the skin if the graft grows (p. 601). The pancreas forms something which (i) checks the conversion of glycogen to glucose in the liver, so that, when it is removed, this process goes on too rapidly. (ii) At the same time the utilisation of sugar by the muscles seems to be interfered with. This failure to use sugars is indicated by the fact that the respiratory quotient (p. 258) is low in diabetes, indicating that proteins and fats are being used and not carbohydrates, and that it is not raised when sugar is administered. The carbohydrates of the food are no longer available as a source of energy, and the animal has to use proteins and fats alone. (i) But the part of the jjroteins which is normally used as a source of energy is the non-nitrogenous, and this is not available and is simply excreted as sugar. Hence, although the animal decomposes its proteins, the non-nitrogenous part is lost as sugar, and energy is not got from them. 858 VETERINARY PHYSIOLOGY (ii) Nor are the fats fully available, because the metabolism of carbohydrates is necessary for their combus- tion, and this is in abeyance. As a result of this incomplete metabolism of fats, /S-oxybutyric acid is produced, which leads to a decrease in the alkalinity of the blood and tissues, to a condition of acidosis. The /S-oxybutyric acid is not oxidised to CO., and HoO as it normally is, but is converted to diactic acid, and this in turn to acetone, and these bodies may be detected in the urine (Chemical Physiology). /3-Oxybutyric Acid . CHg.ClH.OHiCH.CO.OH Diacetic Acid . . CHgCO.CH^j CQ.OHl Acetone . . . CH3CO.CH3. Hence, in fully-developed pancreatic diabetes, none of the proximate principles of the food yield the energy required, and the animal or man rapidl}^ becomes weak, emaciates and dies. 2. Regulation of the Supply of Fats — (1) Storage The fats leave the intestine not by the blood of the portal veins which goes straight to the liver, but through the lymphatics which enter the blood stream, just where it returns to the heart, through the thoracic duct. They thus reach the liver by the arterial blood. Nevertheless, when taken in excess of the immediate requirements, they are stored in large amounts in the liver of some animals — e.g. the cod among fish and the cat among mammals. Animals which have little power of storing fat in the muscles and other tissues seem to have a marked capacity for accumulating it in the liver. Even in starvation, the fats do not disappear from the liver, and throughout all conditions of life a fairly constant amount of lecithin (p. 20) is present in the liver cells. Lecithin, in the yolk of the egg, is an intermediate stage in the formation of the more complex nucleins of living cells ; and the formation of lecithin in the liver by the synthesis of glycerol, fatty acids, phosphoric acid, and cholin is probably a first step in the construction of these ABSORPTION 359 nucleins. The fat of the liver thus plays an important part in retaining and fixing phosphorus in the body. (2) Change in Liver. — The fats of the liver have a higher iodine value than the fats of adipose tissue, i.e. they are less saturated, and the theory has been advanced that this indicates that in the liver the first stage in the breaking- down of fats takes place, in preparation for their use in the muscles. When the fatty acid chain has two hydrogens removed at any point so that a double link between carbon atoms is formed, this becomes a weak point in the chain at which the higher acids are apt to break across with the production of lower acids. Lower fatty acids, liberated by the de-aminisation of certain amino-acids from proteins, e.g. leucin, tyrosin, phenyl-alanin are not changed to glucose (p. 354) but to /3-oxy butyric acid, which is oxidised. 3. Regulation of the Supply of Proteins. — The part played by the liver in the storage of the surplus amino-acids formed from proteins and in their de-aminisation, and the conversion of the amidogen to urea, has already been indicated (p. 349). When the supply of amino-acids is too large, or when the liver is not acting properly in grave hepatic disease, this conversion takes place imperfectly and amino-acids appear in the urine. Urea is the bi-amide of carbonic acid. II H— 0— C--0— H H^ 11 /H J\N— C— N< H \h Carbonic Acid. Urea. It contains 4 6 '6 per cent, of nitrogen. It is a white sub- stance crystallising in long prisms. It is very soluble in water and alcohol — insoluble in ether. With nitric and oxalic acids it forms insoluble crystalline salts. It is readily decomposed into nitrogen, carbon dioxide and water by nitrous acid and by sodium hypobromite in excess of sodium hydrate (Chemical Physiology). 360 VETERINARY PHYSIOLOGY Urea is chiefly formed in the Liver. — This is indicated — (1) By the fact tliat when an ammonium salt, such as the carbonate, dissolved in blood, is streamed through the organ, it is changed to urea ; (2) by the evidence that the liver stores the surplus amino -acids, and that, as they again disappear from the liver, urea increases in the blood ; (3) by the observation that, when the liver is cut out of the circulation, the urea in the urine rapidly diminishes, and ammonia and lactic acid take its place. The exclusion of the liver from the circulation in mammals is difficult, because, when the portal vein is ligatured, the blood returning to the heart tends to accumu- late in the great veins of the abdomen. But this difficulty has been overcome by Eck, who devised a method of connect- ing the portal vein with the inferior vena cava, and afterwards occluding the portal vein, and of thus allowing the blood to return from the abdomen to the heart without passing through the liver. That it is not produced in the kidneys was first shown by the French chemist Dumas. He found that when these organs are excised, urea accumulates in the blood. Later investigators found that when ammonium carbonate is added to blood artificially circulated through the kidney of an animal just killed, no urea is formed. That it is not formed to any marked extent in the muscles is shown — (1) By the absence of a definite increase in urea formation during muscular activity ; (2) by the fact that when the blood, containing ammonium carbonate, is streamed through the muscles, urea is not produced. The Sources of Urea. — (1) The source of urea from the amino-acids formed in the digestion of proteins in the food has already been discussed (p. 349). (2) But urea is also formed during starvation, and it must therefore be derived from the proteins of the tissues. It has been found that in starvation there is an increase of the amino-acids in such tissues as muscle, and it would thus seem that they are pro- ducts of the disintegration of the muscle proteins, and that they are carried to the liver to be converted to urea. The fate of haemoglobin tends to show that the whole ABSORPTION 361 process of protein catabolism ma}' be conducted in the liver cells. When haemoglobin is set free from the corpuscles in moderate amounts, the nitrogen of its protein part is changed to urea, while the pigment part is deprived of its iron and excreted as bilirubin. The process of urea formation from proteins may be divided into four stages — (I) The liberation of the amino- acids. (2) The de-aminisation of the amino-acids. This is probably effected by de-aminising enzymes. (3) The ammonia set free is probably linked to carbonic acid ; and (4) the carbonate of ammonia is then dehydrated by other enzymes and so changed into urea (p. 5 59). The nitrogen excreted is not all in the form of urea. The other nitrogen-containing waste products are dealt with on p. 559 et seq. Summary of the Functions of Liver. — The functions of the liver may be briefly summarised as follows : — (1) It regulates the supply of glucose to the muscles (a) by manu- facturing it from proteins when the supply of carbohydrates is insufficient, and (6) by storing it as glycogen when the supply of carbohydrates is in excess, and giving it off after- wards as required. (2) Along with the intestinal wall, it regulates the supply of proteins to the body by de-aminising any excess, conserving the non-nitrogenous part by convert- ing it into glucose for use by the muscles, and giving off" the nitrogen as urea, etc. (3) It regulates, in many animals at least, the supply of fat to the body by storing any excess ; and it probably plays an important part in de-saturating the fatty acids, and thus making them more available for combus- tion in the tissues. (4) It breaks down the haemoglobin of old erythrocytes, and retains tlie iron for further use (see p. 491). (5) From the part it plays in the enterohepatic circulation, it protects the body against certain poisons by excreting them in the bile (see p. 831). The Faeces. The unabsorbed contents of the alimentary tract, whether originally derived from the food or from the tract itself, are 362 VETERINARY PHYSIOLOGY constantly being passed onward to the lower part of the large intestine. Here absorption of water leaves a more or less inspissated mass which collects and is periodically voided as the faeces. (1) Carnivora. — (a) In fasting animals, fseces are passed at long intervals, and consist of mucin, shed epithelium, the various products of the bile constituents, inorganic salts, and enormous numbers of bacteria. (b) In feeding animals the amount and character of the faeces depend largely (1) upon the amount and character of the food ; and (2) upon the bacteria which are growing in the large intestine. If digestion and absorption of food are com- plete, the fasces are the same on different diets, and consist of the intestinal products, which are increased in amount by the stimulating action of the food in the alimentary canal. The solids of the fa?ces of a feeding animal consist of the same constituents as the fasces in a fasting animal, with the addition of the undigested constituents of the food — elastic and white fibrous tissue, remains of muscle fibres, fat, and the earthy soaps of the fatty acids, the fat forming about one-third of the weight of dry fteces. When a vegetable diet is taken, the cellulose of the vegetable cells, and some- times starch, are present. The cellulose, by stimulating the intestine, is a valuable natural purgative. Phosphates, as well as calcium, magnesium, and iron, de- rived from the metabolism of the tissues, are largely excreted into the large intestine, and are passed out in the feces. Probably in an ordinary mixed diet some 80 to 40 per cent, of the phosphorus, about 90 per cent, of the calcium, some 70 per cent, of the magnesium are excreted in the faeces. The odour is due to the presence of many different sub- stances, and it varies with the character of the bacterial flora of the large intestine. (2) Herbivora. — In these the residual products of digestion are very bulky and evacuation is more frequent than in car- nivora. The horse usually defascates about ten times a day. The amount passed in twenty-four hours varies with the nature of the food. On an ordinary diet about 15 kilos per diem are passed by the horse, and about 20 by the ox. ABSORPTION 363 An idea of the average amount of water present is shown in the following table given by Gamgee : — Approximate percentage Composition of the Fceces. Horse. Cow. Sheep. Pig- Water . 76 84 58 80 Organic Matter . 21 13-6 36 17 Mineral Matter . 3 2-4 6 3 100 100 100 100 When first passed fa3ces usually float in water owing to the amount of gas contained in them. They are nearly always acid in reaction from the presence of organic acids. As in carnivora fseces consist of material derived from two sources — (1) food residues ; and (2) excretions by w\ay of the intestines. Food Residues. — These consist of indigestible material such as lignin and waxes, which pass through the gut unchanged, and also of material that has escaped digestion either because as in the case of cellulose digestion is difiicult, and only part is dealt with, or because it is protected by an envelope that is not dissolved by the digestive juices. This part consists chiefly of the constituents of the crude fibre of the diet. Excretions. — These consist of the same material as in the case of carnivora. Inorganic matter, e.g. calcium, magnesium, iron, and phosphates are, however, excreted by the bowel to a much greater extent than in carnivora. Meconium is the name given to the first fasces passed by the young after birth. It is greenish-black in colour, and consists of inspissated bile and shed epithelium from the intestine. Availability of Food-Stuffs. Only that part of the food which is digested and absorbed is available as a source of either energy or material to the animal. In carnivora the indigestible residue is very small. In herbivora, however, a very large proportion of the food is not digested. In comparing the value of different food- stufts, therefore, it is necessary to know what proportion is available. 364 VETERINARY PHYSIOLOGY In the literature of aniinul nutrition the term "digesti- bility " is used in a specific sense. It denotes the percentage of the food or of any constituent of the food that is absorbed from the aUmentary tract. Thus in a digestion experiment on a horse, 57 per cent, of the protein of hay was apparently digested and absorbeil as that proportion was not recovered in the fteces. The "digestibility" of the protein of hay for the horse in this case is said to be 57 per cent. The per- centage of digestibility is often termed the " coefficient of digestibility." Digestion Experiments. The availability of food-stuffs is determined by digestion experiments. In these the animal is fed on a weighed quantity of the food to be tested for a preliminary period of about ten days to make sure that the previous food has com- pletely passed out of the intestinal tract. The feeding is then continued for another period of not less than ten days, during which time twenty-four hourly collections of fa3ces are made. The difference between the amount of each constituent of the food eaten and that found by analysis in the fceces is regarded as the digested portion. Concentrates cannot be fed alone to ruminants. Their availability is determined by superimposing a weighed quantity upon a roughage diet, whose availability has been previously determined. The increased amount of the various constituents found in the f^ces is retjarded as the undig'ested matter of the concentrate tested. Accuracy of the Method. — Digestion experiments, though of great use, indicate only apparent digestibility. The issue is confused by (1) excietory products ; and (2) loss through fermentation. (1) Nitrogenous substances, ether soluble substances, and inorganic salts are present in the faeces even if absent in the food (p. 362). The smaller the amount of these present in the food the greater is the percentage error due to excretory products ; with fats and salts the error may be so great as to make the results of little value as a means of determining the real amount di^^ested. ABSORPTION 865 In the case of protein an attempt has been made to diderentiate between excretory nitrogen and undigested nitrogen, by regarding nitrogenous material which can be rendered soluble by pe[)sin and hydrochloric acid as excretory, and that which remains insoluble as undigested nitrogen. It has also been suggested that for every 100 grams of dry matter in the food, 4 grams of nitrogen of the faeces should be regarded as excretory nitrogen. Even if precautions such as those indicated be taken, the results of digestion experiments on food-stuffs with small amount of nitrogenous constituents should be received with caution. It is probable that in the adult animal at least, a more accurate determination of the percentage digestibility of nitrogenous material would be obtained by regarding the urinary nitrogen as an index of the amount digested and absorbed, instead of taking the fsecal nitrogen as an index of the amount not digested (see p. 558 ei seq.). (2) The part of the crude fibre and soluble carbohydrate that disappears in transit through the alimentary canal is not all digested. Part is lost through destructive fermentation (p. 340). In estimating the availability of the food, this must be taken into account. The excretion of methane and hydrogen gives an indication of the extent of the fermentation. According to Armsby, the following deduc- tions should be made for fermentation Factors for computing Fermentation Losses. Per 100 grams digested carbohydrates — Weight. Equivalent Energy. Grams. Cals. Ruminants— Methane . 4-5 60-1 Swine — Methane . 0-65 8-7 Hydrogen . 0-07 2-4 Total . 0-72 IM Per 100 grams digested crude fibre- Horse — Methane . 4-7 62-7 Hv VffiTmCLEL 3ULBU5 Fig. 169.— Scheme of the Cardiac Cycle in the Frog. S.S. , sinus systole ; A.S., auricular systole; V.S., ventricular systole; B.S., bulbus systole; P., rest of all chambers. The upstrokes represent systole, the downstrokes diastole. B. Mammal. 1. Rate of Recurrence. — The rate of recurrence of the cardiac cycle varies with the animal examined. In man it is, in adult life, about 72 per minute. In the adult horse it is about 36 to 40 per minute. HEART f heart per minute in different animals :- Horse . 36 to 40 Ox . 45 to 50 Sheep . 70 to 80 Dog . 90 to 100 Rabbit . 120 to 150 395 Many factors modify the rate of the heart, among the most important of which are — (1) The Period of Life. — The following table shows the average rate of the heart at different aofes : — Horse New born Under 1 year 4 years 92 to 132 per minute 50 to 68 50 to 56 (2) The Period of the Bay. — The rate is generally lowest in the early morning, and quickest in the evening. (3) Temperature of the Body. — The rate varies with the body temperature, in man being increased about ten beats with each degree Fahr. of elevation of temperature. (4) The condition of the central nervous system may modify the rate of the heart, any disturbance accompanied by emotional changes either accelerating or retarding it. (5) Muscular exercise markedly accelerates the heart (Practical Physiology). 2. Sequence of Events. — The sequence of events making up the cardiac cycle is simpler in the mammal than in the frog- (1) The contraction starts in the neighbourhood of the sino-auricular node. This is indicated by the fact that Lewis has found that this region is the first to become electro- positive, or " zincy," to the rest of the auricles (p. 212). The contraction spreads out rapidly in all directions, over the auricles and up the mouths of the great veins, as the circle of waves produced by throwing in a stone pass over the surface of the pond. It next seems to pass to the strip 396 VETERINARY PHYSIOLOGY of primitive tissue along the back of the auricular septum, and then to the mouths of the great veins partially occluding them, then over the rest of the auricles, which become smaller in all directions and seem to be pulled down towards the ventricles. The contraction of the auricles in mammals is not accompanied by so marked a dilatation of the ventricles as in the frog. (2) The wave of contraction in the auricles is propagated to the ventricles through the auriculo-ventricular band, and when this is diseased the passage of the wave of contraction is interfered with. (3) As the ventricles contract, the auricles relax. The ventricular contraction develops suddenly, lasts for some time, and then suddenly passes off. The wave of contraction is chiefly conducted by the primitive tissue which runs on the interior aspect of the ventricles. Lewis has shown AVRICU6 ^/LtiTRICLE^ Fig. 170. — Scheme of the Cardiac Cycle in the Human Heart. A.&., auri- cular sj'stole ; V.S., ventricular systole ; P., pause. that, if this layer is divided, conduction is markedly delayed, while, if the outer fibres of the ventricles are cut, no marked delay occurs. (4) The contraction of the ventricles is followed by a period during which both auricles and ventricles remain relaxed. This is called the pause of the cardiac cycle. The cardiac cycle in mammals may be represented as in fig. 170. iA r 1 1 / |a51 \i.5. \ / \ P 3. Duration of the Phases. — Ventricular systole lasts three times as long as auricular systole. The duration of these two phases in relationship to the pause varies very greatly. Whatever may be the rate of HEART 397 the heart, the auricular and ventricular systoles do not vary, but in a rapidly acting heart the pause is short, in a slowly acting heart it is long. Taking the ordinary human heart rate of 72 per minute, the auricular systole lasts for one-eighth of the whole cardiac cycle, the ventricular for three-eighths, and the pause for four-eighths. 4. Changes in the Shape of the Chambers. 1. Auricles. — These simply become smaller in all directions during systole. 2. Ventricles. — The changes in the diameters of the ventricles may be studied by iixing them in the various phases of contraction and measuring the alterations in the various diameters. The shape in diastole when the muscular fibres are relaxed is determined by the fibrous pericardium which surrounds the heart, and by the position of the body, the force of gravity leading to the expansion of the ventricles at their dependent part. The condition at the end of systole may be studied by rapidly excising the heart while it is still beating, and plunging it in some hot solution to fix its contraction. The condition iii the early stage of systole, before the blood has left the ventricles, may be studied by applying a ligature round the great vessels, and then plunging the heart in a hot solution to cause it to contract round the contained blood which cannot escape. Measurements of hearts so fixed show that, at the beginning of contraction, the antero-posterior diameter is increased, while the lateral diameter is diminished. In contracting, the lateral walls appear to be pulled towards the septum — the increase in the antero-posterior diameter being largely due to the blood in the right ventricle pressing on and pushing forward the thin wall of the infundibulum below the pulmonary artery. As the ventricles drive out their blood, both antero- posterior and lateral diameters are diminished — but the diminution in the lateral direction is the more marked, and thus the section of the heart tends to become more circular. 398 VETERINARY PHYSIOLOGY There is no great shortening in the long axis of the ventricles ; but the auriculo-ventricular grooves are drawn somewhat downwards towards the apex, which does not alter its position. This was demonstrated by Leonardo da Yinci in the living pig by inserting long pins through the chest wall into the wall of the ventricle and observing the movements. In systole the ventricles have the form of a truncated cone. 5. The Cardiac Impulse. (1) Cause. — During contraction the heart undergoes, or attempts to undergo, a change in position. In the relaxed Fig, 171. — Cardiograph consisting of a Receiving Tambour, with a button on the membrane which is placed upon the cardiac impulse, and a Recording Tambour connected with a lever. condition it hangs downwards from its plane of attachment, but when it becomes rigid in ventricular contraction, it tends to take a position at right angles to its base — Cor sese erigere, as Harvey describes the movement. Since the apex and front wall are in contact with the chest, the result of this HEART 399 movement is to press the heart more forcibly against the chest wall. This gives rise to the cardiac impulse with each ventricular systole (fig. 168), but this is not easily felt in the horse unless the action of the heart is exaggerated. If the chest is opened and the animal placed on its back this elevation of the apex is readily seen. (2) Position. — The position of the impulse is determined by the relationship of the heart to the anterior chest wall and to the lungs. (3) Character. — It is felt as a forward impulse of the tissues, which develops suddenly, persists for a short period, and then suddenly disappears. In many forms of heart disease its character is markedly altered. The cardiac impulse may be recorded graphically by means of any of the various forms of cardiograph (fig, 173). One of the simplest consists of a receiving and a recording tambour connected by means of a tube (fig. 171) (Practical Physiology). 6. Changes in the Intracardiac Pressure. — These have been studied in the horse and dog. (1) Methods. — The most common way of determining the pressure in a cavity is to connect it to a vertical tube and to see to what height the fluid in the tube is raised. If such a method be applied to the ventricles of the heart, the blood in the tube undergoes such sudden and enormous changes m level that it is impossible to get accurate results. The same objection applies to the method of connecting the heart with a manometer, a U tube filled with mercury. When this is done, the changes in pressure are so sudden and so extensive that the mercury cannot respond to them on account of its inertia. Various means of obviating these difficulties have been devised. (1) One of the best is to allow the changes of pressure to act upon a small elastic membrane tested against known pressures. A tube is thrust through the wall of the heart and connected with a tambour covered by a membrane to which a lever is attached. (2) Probably the most delicate method is by the use of Piper's stilette manometer (fig. 172), 400 VETERINARY PHYSIOLOGY which consists of a tube or cannula with a sharp pointed trocar, which can be thrust out of the end of the tube to perforate the chest and ventricular wall, and then retracted through a tap, which can be closed. On the tube is a membrane carrying a small mirror, from which a beam of light may be reflected on to a sensitive paper covering a moving surface so that the variations of pressure are photographed. (2) Results. — A. Pressure in the Great Veins (small dotted line in fig. 173). — The pressure in these is so low and undergoes such small variations that it may be investigated by a water manometer. When the auricles contract, the flow of blood from the great veins into these chambers is arrested, and, as a result, the pressure in the veins rises. As the auricles relax the D Fig. 172. — Piper's Stilette Manometer. A., trocar for puncturing (with- drawn) ; C, tap to close cannula; E., rubber membrane with mirror, F. pressure falls, but, as the auricles fill up, it again rises. When the ventricles relax blood again flows in from the great veins and the pressure falls, again to rise, as the auricles and veins are both filled up, towards the end of the pause. B. Pressure in the Auricles (dash line in fig. 173). — At the moment of auricular contraction there is a marked rise in the intra-auricular pressure. When the auricular systole stops, the pressure falls rapidly, but the fall is interrupted by a rise due to the upward pressure from the closed auriculo-ventricular valves. It reaches its lowest level early in ventricular systole. From this point the pressure in the auricles rises until the moment when the ventricles relax, when another fall in the pressure is observed. The pressure again rises slightly and remains HEART 401 p. A3 ii mmm m TLOW of BLOOD from I CrcM Veins to Auricjes 8. Auricles to Ventricles a Ventricles to Arteries CLOSURE of I Auriculo-Ventncular Valve 2 Semilunar Valves SOUNDS of HEART CARDIAC IMPULSE / ELECTRO CARDIOGRAM Fig. 173. — Diagram to show the Relationship of the Events in the Cardiac Cycle to one another. A.S., auricular systole; V.S., ventricular systole ; P., pause. 26 402 VETERINARY PHYSIOLOGY about constant from this point until the next auricular contraction. C. Pressure in the Ventricles (continuous line in fig. 173). — The intra-ventricular pressure rises slightly during auricular systole. It rises suddenly at the moment of ventricular systole to reach its maximum, but on the trace there is sometimes a shoulder due to the opening of the semi- lunar valves. It then falls, but the fall is gradual, and is interrupted by a more or less well-marked period during which the pressure remains constant. When the ventricles relax, the pressure suddenly falls to zero, then rises a little, and is maintained until the next ventricular systole. The diastolic expansion of the ventricle is due chiefly to the inflow of blood from the auricles and veins, possibly in part to the elasticity of the muscular wall, and to the filling of the coronary arteries which takes place in diastole. D. Pressure in the Arteries (dot-dash line in fig. 173). — This, since it is always high and undergoes no great and sudden variations, may be measured by means of a mercury manometer. The aortic pressure is high throughout. There is a sudden rise soon after the beginning of ventricular systole, as the blood rushes out of the ventricles. The pressure then falls, but the fall is not steady. Often it is interrupted by a more or less marked increase corresponding to the later part of the ventricular contraction. At the moment of ventricular diastole the fall is very sharp and is interrupted by a well-marked and sharp rise. Following this, the fall is continuous till the next systohc eleva- tion. These changes in the pressure in the different chambers are due to— \st The alternate systole and diastole of the chambers, the first raising, the second lowering,, the pressure in the chambers. Ind. The action of the valves. 7. Action of the Valves of the Heart. A. Auriculo-ventricular (tig. 174). — These valves have already been described as funnel-like prolongations of the HEART 403 auricles into the ventricles. They are firmly held down in the ventricular cavity by the chordae tendinete. When the ventricles contract, the papillary muscles pull the cusps of the valves together and thus occlude the opening between auricles and ventricles. The cusps are further pressed face to face by the increasing pressure in the ventricles, and they may become convex towards the auricles. They thus form a central core around and upon which the ventricles contract. On the left side of the heart, the strong anterior cusp of the mitral valve does not materially shift its position. It may be somewhat pulled backwards and to the left. The posterior cusp is pulled forwards against the anterior. On the right side, the infundibular cusp of the tricuspid 1. 2. .3. 4. 5. Fk;. 174. — State of the various parts of the Heart throughout the Cardiac- Cycle. 1, auricular s3-stole ; 2, beginning of ventricular systole (latent period) ; 3, period of outflow from the ventricle ; 4, period of residual contraction ; 5, beginning of ventricular diastole. valve is stretched between the superior and inferior papillary muscles, and is tluis pulled towards the bulging septum, against which it is pressed by the increasing pressure inside the ventricles. The posterior cusp has its anterior margin pulled forward and its posterior margin backwards, and is thus also pulled toward the septum. The septal cusp remains against the septum. The greater the pressure in the ventricle, the more firmly are the two outer cusps pressed against the septum, and the more completely is the orifice between the auricle and the ventricle closed. On the right side of the heart other factors play an important part in occluding the orifice ; the muscular fibres which surround the auriculo-ventricular opening contract, and the papillary muscles pull the auriculo-ventricular ring downwards and inwards by means of the chordae which are inserted into it. 404 VETERINARY PHYSIOLOGY Nevertheless, the occlusion of this orifice is apt to be in- complete when the right side of the heart becomes in the least over-distended, and this gives rise to what may be called a safety-valve action from the right ventricle, which prevents over-distension. The auriculo-ventricular valves are open duHng the whole of the cardiac cycle, except during the ventricular systole (fig. 173). B. Semilunar Valves. — Before the ventricles contract these valves are closed and the various segments pressed together by the high pressure of blood in the arteries. As the ventricles contract the pressure rises, until the intra- ventricular pressure becomes greater than the pressure in the arteries. This is the lyresphygmic period. Then the cusps of the valves are thrown back and remain open until the blood is expelled. When the outflow of blood is com- pleted, the cusps are again approximated by the pressure of blood in the arteries. As relaxation of the ventricles occurs, the intra-ventricular pressure becomes suddenly very low, and the high pressure of the blood in the arteries at once falls upon the upper surfaces of the cusps, which are thus forced together and downwards, and completely prevent any back-flow of blood. The prejudicial effect of too great pressure upon these cusps is obviated by the lower cusp of each being mounted on the top of the muscular septum upon which the pressure falls — the other cusps shutting down upon this one (fig. 167). The semilunar valves are open only during the flow of blood from the ventricles to the arteries in the second and third periods of ventricular systole (fig. 173). 8. The Flow of Blood through the Heart. — The circula- tion of blood through the heart depends upon the difterences of pressure in the difterent chambers and upon the action ot the valves. A. From Great Veins into Auricles. — This occurs when the pressure in the great veins is greater than the pressure in the auricles (fig. 173). HEART 405 The pressure in the auricles is lowest at the moment of their diastole. At this time there is therefore a great flow of blood into them, but gradually this becomes less and less, until, when the ventricles dilate, another fall in the auricular pressure takes place and another rush of blood from the great veins occurs. Gradually this diminishes, and, by the time that the auricles contract, the flow from the great veins has stopped. The contraction of the mouths of the great veins in auricular systole drives blood from the veins into the auricles, and prevents any back-flow from the auricles. B. From Auricles to Ventricles. — As the ventricles dilate, a very low pressure develops in them, and hence a great rush of blood occurs from the auricles. During the later stage of ventricular diastole, the intra-ventricular pressure becomes nearly the same as the intra-auricular, and the flow diminishes or may stop. When the auricles contract, a higher pressure is developed causing a fresh flow of blood into the ventricles. When the ventricles contract the auriculo- ventricular valves are closed, and all flow of blood from the auricles is stopped (fig. 178). G. From Ventricles to Arteries. — When the ventricles begin to contract, the intra-ventricular pressure is low, while the pressure in the arteries is high, which keeps the semi- lunar valves shut. This is the Latent or Presphygmic Period. As ventricular systole goes on, the intra-ventricular pressure rises, until, after about 0"03 of a second, it becomes higher than the arterial pressure. Immediately the semi- lunar valves are forced open and a rush of blood occurs from the ventricles. This is the Period of Outfioiv, which usually lasts less than 0'2 second. (rt) If the ventricles are contracting actively, and if the pressure in the arteries does not offer a great resistance to the entrance of the blood, the ventricles rapidly empty themselves into the arteries, and the intra-ventricular pressure varies as shown in fig. 175, b. (6) If the heart, however, is not contracting actively, or if the arterial pressure offers a great resistance to the entrance of blood, then the outjlow is slow and more continued, and in 406 VETERINARY PHYSIOLOGY this case, the trace of the intra-ventricular pressure is as in fig. 175, a, with a well-marked Period of Residual Con- traction. It is not the absolute force of the cardiac contraction or the absolute intra-arterial pressure which governs this, but the relationship of the one to the other. The heart may not be acting very forcibly, but still, if the pressure in the arteries is low, its action may be relatively Fig. 175. — Diagram to show the Relationship of the Pulse Wave to the Cardiac Cycle and the effect of altering the relationship between the activity of the heart and the arterial blood pressure. h is the curve of intra-ventricular pressure, and h^ is a pulse curve with an active heart and a relatively low arterial pressure. — a and a^ are the same with a sluggish heart and a relatively high arterial pressure. The period of outflow under each condition is also shown. The Coronary Arteries, unlike all the other arteries, are filled during ventricular diastole. During systole they are compressed by the contracting muscle of the heart, and it is only when the compression is removed in diastole that blood rushes into them. This helps to dilate the ventricles. The interpretation of the various details of the Cardiogram (fig. 173) is now rendered more easy. The ventricles, still full of blood, are suddenly pressed against the chest wall in systole. As the blood escapes into the arteries they press with less force, and hence the sudden slight downstroke. But, so long as the ventricles are contracted, the apex is kept tilted forward, and hence the horizontal plateau is HEART 407 maintained. The pressure of the heart disappears as the ventricles relax. 9. Sounds of the Heart. — On listening over the region of the heart, a pair of sounds may be heard with each cardiac cycle, followed by a somewhat prolonged silence. These are known respectively as the First and Second Sounds of the Heart (fig. 173) {Practical Physiology). By placing a finger on the cardiac impulse, while listen- ing to these sounds, it is easy to determine that the first sound occurs synchronously with the cardiac impulse — I.e. synchron- ously with the ventricular contraction. It develops suddenly, and dies away more slowly. In character it is dull and rumbling, and may be imitated by pronouncing the syllable lub. In pitch it is lower than the second sound. The second sound is heard at the moment of ventricular diastole. Its exact time in the cardiac cycle has been deter- mined by recording it on a cardiac tracing by means of a microphone. It develops suddenly and dies away suddenly. It is a clearer, sharper, and higher-pitched sound than the first. It may be imitated by pronouncing the syllable dupp. According to the part of the chest upon which the ear is placed, these sounds vary in intensity. Over the apical region the first sound is louder and more accentuated ; over the base the second sound is more distinctly heard. A. The Cause of the Second Sound is simple. At the moment of ventricular diastole, when this sound develops, the only occurrence which is capable of producing a sound is the sudden stretching of the semilunar valves by the high arterial pressure above them and the low intra-ventricular pressure below them. The high arterial pressure comes on them suddenly like the blow of a drum-stick on a drum-head, and, by setting the valves in vibration, produces the sound. Aortic and Pulmonary Areo.s. — The second sound has thus a dual origin — from the aortic valve and from the pulmonary valve ; and it is possible, by listening in suitable positions, to distinguish the character of each of these. B. The Cause of the First Sound is twofold. When it is 408 VETERINARY PHYSIOLOGY heard, two changes are taking phace in the heart, either of which would produce a sound. 1st The muscular wall of the ventricles is contracting. 2nd. The auriculo-ventricular valves are being stretched. 1 st. That the first factor plays a part in the production of the first sound is proved by rapidly cutting out the heart of an animal and listening to the organ with a stethoscope while it is still beating — but without any blood passing through it to stretch the valves. With each beat the lub sound is distinctly heard. Apparently the wave of contraction, passing along the muscular fibres of the heart, sets up vibrations, and, when these are conducted to the ear, the external meatus picks out the vibration corresponding to its fundamental note, and thus produces the characters of the sound. 2nd. The auriculo-ventricular valves are being subjected on the one side to the high ventricular pressure, and on the other to the low auricular pressure. If the valves are destroyed or diseased, the characters of the first sound are materially altered, or the sound may be entirely masked by a continuous musical sound — a murmur. It has been main- tained that a trained ear can pick out in the first sound the note corresponding to the valvular vibrations. The idea that the impulse of the heart against the chest wall plays a part in the production of this sound is based upon the fallacious idea that the heart " hits " the chest wall. All that it does is to press more firmly against it. Mitral and Tricuspid Areas. — On account of the part played by the valves in the production of the first sound, it may be considered to be double in nature — due partly to the mitral valve, partly to the tricuspid. The mitral valve element may best be heard not over the area of the mitral valve — which lies very deep in the thorax — but over the apex of the heart, as at this situation the left ventricle, in which the valve lies, comes nearest to the thoracic wall and conducts the sound thither. A tJdrd sound has been described by Gibson. It is heard during the diastole of the ventricles, and it has been ascribed to the rebound of the semilunar valves. HEART 409 By means of the microphone apphed over the heart, two faint sounds have been recorded during auricular systole, but so far they cannot be considered as of clinical importance. Cardiac Murmurs- — When the valves are diseased and fail to act properly, certain continuous sounds called cardiac murmurs are heard. These owe their origin to the fact that, while a current of ^Jim's AS. v.s. V.D. -rimM m Ill lllllli hnm !!!'! rmi. i P ii i k^ ^Il kmi-J EK'CE.l Fig. 176. — To show the Periods in the Cardiac Cycle at which the various Murmurs of Stenosis and Incompetence occur. fluid passing along a tube of fairly uniform calibre is not thrown into vibrations and therefore produces no sound, when any marked alterations in the kimen of the tube occurs — either a sudden narrowing or a sudden expansion — the flow of fluid becomes vibratory, and, setting up vibrations in the solid tissues, produces a musical sound. 410 VETERINARY PHYSIOLOGY Such changes in the calibre of the heart are produced in two ways : — 1st. By a narrowing, either absolute or relative, of the orifices between the cavities — stenosis. 2nd. By a non-closure of the valves — incompetence. \st. Stenosis. — If one of the auriculo-ventricular orifices is narrowed, a murmur is heard during the period at which blood normally flows through this opening (p. 405). A reference to fig. 176 at once shows that this occurs during the whole of ventricular diastole, and that the flow is most powerful during the first period of ventricular diastole and during auricular systole. If the aortic or the pulmonary valve is narrowed the murmur will be heard (fig. 176) during ventricular systole. The narrowing need not be absolute. A dilatation of the artery will make the orifice relatively narrow, and will pro- duce the same result. 2nd. Incompetence. — If the auriculo-ventricular valves fail to close properly, then, during ventricular systole, blood will be driven back into the auricles, and a murmur will be heard during this period (fig. 176). If the aortic or the pulmonary valve fails to close, the blood will regurgitate into the ventricle from the arteries during ventricular diastole, and a murmur will be heard during this period (fig. 176). By the position at which these murmurs are best heard the pathological condition producing them may be deter- mined. II. The Work of the Heart. The enormous variations in metabolism which the muscles undergo between rest and activity have already been considered (p. 266). The oxygen intake and output of carbon dioxide may increase tenfold during muscular work. To supply this oxygen the flow of blood through the muscles must be proportionately increased, and this increase is secured by (1) a dilatation of the blood-vessels going to the muscles with, at the same time (2), a constriction of the blood-vessels of the abdomen. HEART 411 But the flow of blood is determined by the difference of pressure between the arteries and veins, and hence the arterial pressure must be maintained when the dilatation of the small arteries is allowing the increased outflow of blood. This must be met by an increased action of the heart to maintain the pressure. The heart must be capable of great variations in its action, so that at one time it may pump out only a small amount of blood, at another an enormously greater quantity. The heart must be able to perform very varying amounts of work. To determine the variations in the work done, it is necessary to measure the amount of blood expelled and the resistance against which it is expelled. A certain amount of work is done in giving velocity to the blood, but this is small when compared with the work of overcoming resist- ance. (1) The resistance in the aorta may be measured by a mercury manometer (p. 447). (2) The determination of the amount of blood expelled from the heart has proved a very difficult problem. It has been attempted both by direct and by indirect methods. A. Direct Methods. So far it has not proved possible to measure the output of the heart by a direct method with the heart acting normally in situ. (1) Cardiometer Method.— The output of blood at each beat of the heart of the dog may be measured by a cardio- meter, a rigid walled air-tight case, which is placed round the heart and connected with a piston-recorder, so that the decrease in the volume of the enclosed heart, due to the blood leaving it, may be directly recorded by means of a lever attached to the piston. (2) The Isolated Heart-Lung Preparation.— We shall presently consider the way in which Starling was able to remove the heart and lungs from a dog and to allow blood to circulate through them. Fig. 178 shows how, by means of the side tube, the blood driven from the heart may be collected and its amount measured. 412 VETEEINARY PHYSIOLOGY These methods, of course, give no measurement of the normal output of the heart. B. Indirect Methods. 1. The Oxygen Method. — (1) By finding the amount of oxygen which the blood gains per unit of time iu passing through the lungs, and (2) the amount of oxygen which is taken from the lungs per unit of time, the amount of blood passing through the lungs, i.e. leaving the right ventricle may be calculated. Since the right and left ventricles must discharge equal amounts of blood, the output of the left ventricle is thus ascertained. CC.O2 100 100 100 100 100 100 Cc. Blood. Fig. 177. — To illustrate the method of determining the amount of blood leaving the right ventricle. The inverted funnel represents the lungs from which 30 cc. of O2 have been taken up by tlie blood. The blood has gained 5 cc. of Oo per 100 cc Therefore 600 cc. of blood must have passed through the lungs, i.e. left the right ventricle. (1) The amount of oxygen in the blood is determined as described on p. 497 (Practical Physiology). To ascertain the amount of oxygen in the blood going to the lungs, blood from a vein is taken ; for the amount of oxygen in the blood leaving the heart the blood from an artery is taken. If lower animals, e.g. goats, are used, the method may be made even more accurate by taking blood by means of trocars simultaneously from the right (venous blood) and left ventricle (arterial blood). (2) The amount of oxygen taken from the lungs is determined by means of the Douglas bag (p. 261). Suppose the blood gains 5 per cent, of oxygen, and suppose that in HEART 413 unit of time, 30 c.c. of oxygen are taken up by the lungs, then this 30 c.c. must be distributed in the blood to the extent of 5 c.c. for each 100 c.c. of blood (fig. 177), and hence 600 c.c. of blood must have passed through the lung in unit of time. 2. The Nitrous Oxide Method. — Instead of estimating the increase in the oxygen of the blood, a measured quantity of nitrous oxide, N2O, the solubility of which in the blood at the pressure and temperature at which it is present in the lungs is known, may be inhaled into the lungs and estimate may be made of — (1) The amount of NgO in the arterial blood. (2) The amount of N.3O which has been taken from the lungs by the blood per unit of time. From this the amount of blood passing through the lungs, i.e. from the right ventricle, may be calculated as it is by the oxygen method. Krogh has shown that the left ventricle in man pumps blood into the arteries at the following rates according to the condition of muscular activity : — 1. At rest about 3 litres per minute. 2. With moderate exercise ,, 12 ,, 3. With hard „ „ 21 In the horse the quantities are probably greater. The Average Work. — It is thus impossible to attempt to form an estimate of the average work of the heart since these variations are so great. The Adaptation of the Work. — A more interesting question is — How is the heart able to adapt itself to perform the very different amounts of work required ? This has been elucidated by Starling by the use of the isolated heart-lung preparation (fig. 178). (i.) The heart and lungs are carefully removed from a dog, all the vessels being clamped or ligatured, (ii.) The 414 VETERINARY PHYSIOLOGY trachea is connected with a pump and the lungs are thus supplied with air so that the blood is oxygenated, (iii.) A tube or cannula is tied into a carotid artery, CA., and it has a side attachment to a mercury manometer to measure the arterial pressure, i¥;. (iv.) The tube passes on to a very thin piece of tubing, jK., enclosed in a rigid walled glass tube, T., in which the pressure can be raised to any extent which may be desired, and may be measured by a manometer, Mg. (v.) The tube Yic. 178.— The isolated heart-lung preparation (the lungs are not shown). For description see text. (Starling.) passes on and is provided with a by-pass, X., from which the blood may be allowed to escape if the amount passed through the heart is to be measured, (vi.) The blood passes through an arrangement by which the blood is kept at body temperature, (vii.) It returns to the superior vena cava, SVC, and right auricle by a tube provided with a clamp so that the amount entering the heart may be controlled, (viii.) The blood then passes to the right ventricle, and so through the lungs m which artificial respiration is kept up, back to HEART 415 the left side of the heart, (ix.) Variations in the size of the heart may be recorded by enclosing the ventricles in some form of cardiometer (p. 411). (1) It has thus been shown that the adaptation is largely independent of the central nervous system, although this too, as will laier be shown, plays an important part. Fia. 179. --To show the effect of a sudden rise in arterial pressure upon the cardiac contractions recorded by enclosing the heart in a cardiometer. The upstrokes are systolic. Note the increased diastole with the increase in the systole, i?./*., the arterial blood-pressure ; F.P., the venous blood pressure. (Starling.) (2) By such an apparatus it is found that the output of blood is not dependent on the arterial pressure, but that within wide limits of pressure the heart continues to pump out the same amount of blood at each systole, thus doing a greater and greater amount of work as tlie arterial pressure rises. With a sudden rise of pressure it may fail to do so 416 VETERINARY PHYSIOLOGY for the first few beats, and the ventricles may thus become distended (fig. 17 9), but with this distension and the resulting elongation of the muscular fibres of the heart the force of contraction is increased (p. 224), and the heart performs the increased work. In the healthy animal this dilatation Fig. 180. — To show the effect of increasing the venous filling of the heart recorded as in fig. ITS. The upstrokes are systolic. Note the enormous increase of the diastolic filling with the very marked increase in the sj-stolic contraction leading to an increased output of blood. (Stakling.) is temporary, but, in conditions of debiUty, over-distension beyond the physiological limit may be produced, and permanent distension may result. Next time a strain is put upon the heart the distension may be still further increased, and heart-failure may occur. The muscle of the heart thus acts as we have seen skeletal muscle to act within physiological limits, HEART 417 the force of contraction varies with the length of the fibres. For increased work the heart muscle requires more oxygen, and the increased supply is secured by the increased arterial pressure driving more blood into the coronary arteries. This has been demonstrated by actual experiment. The output of the heart is thus not controlled by the arterial pressure. (3) It is controlled by the inflow from the veins, as may be shown by loosening the clamp on the venous tube, and allowing more blood to enter the heart (fig. 180). The in- creased inflow leads to a distension of the ventricles, and so to an increased force of contraction. This depends upon the lengthening of the ventricular fibres. The normal heart drives out just as much blood as it receives from the veins. The way in which the heart adjusts itself may be seen in a man or animal starting to run. (1) The muscular movements pump more blood into the heart from the veins. (2) The heart is distended, and pumps more blood into the arteries. (8) The pressure in these is further raised, in spite of the dilatation of the arterioles to the muscles, by the con- traction of the abdominal vessels. In discussing the rapid adaptation of the heart to the varied requirements, the possibility of the production of a chronic dilatation has been discussed. When, as the result of some obstruction to the flow of blood, the heart is called upon to perform continuously an increased amount of work, it is found that the muscle of the ventricular walls increases or hypertrophies. In this way the prejudicial effects of grave valvular disease of the heart may be compensated for. But this compensation is apt to be disturbed and heart-failure to be induced by any interference with the flow of blood through the coronary arteries. The self-regulation of the heart is itself insufiicient to maintain the necessary distribution of pressure throughout 418 VETERINARY PHYSIOLOGY the vessels. Some means must be provided of preventing a too great rise of arterial pressure and of preventing an over- distension of the heart when the venous return is too great. This is effected by the action of the central nervous system. III. The Influence of the Central Nervous System on the Heart. In the frog, a branch from the vagus connects the central nervous system with the heart. When the branch is cut no effect is produced, showing that it is not constantly in action ; but, when the lower end is stimulated, the heart is generally slowed or brought to a standstill. Sometimes the effect is not produced. The reason for this is that the cardiac branch of the vagus in the frog is really a double nerve, derived in part from the spinal accessory, and in part from fibres which reach the vagus from the superior thoracic sympathetic ganglion. If the spinal accessory nerve, or the medulla oblongata from which it springs be stimulated, the heart is always slowed ; and if the sympathetic fibres are stimulated, it is quickened. Generally, stimulation of the cardiac branch containing these two sets of fibres simply gives the result of stimulating the former, but sometimes the stimulation of the latter masks this effect {Practical Physiology). In the mammal three sets of nerve fibres pass to the heart : — Ist. The superior cardiac branch of the vagus starts from near the origin of the superior laryngeal nerve, and passes to the heart to end in the endocardium (fig. ISl, S.C). 27id. The inferior cardiac branch of the vagus leaves the main nerve near the recurrent laryngeal, and passes to join the superficial cardiac plexus in the heart (fig. 181, I.G.). ^rd. The symijathetic nerve fibres come from the superior thoracic and inferior cervical ganglia, and also end in the superficial cardiac plexus (fig. 181, S.). \st. The Superior Cardiac Branch of the Vagus is an ingoing nerve. Section produces no effect ; stimulation of the lower HEART 419 end causes no effect ; stimulation of the upper end causes (1) slowing of the heart and (2) a marked fall in the Fig. 181. — Connections of the Heart with the Central Nervous System. Au., auricle; V., ventricle; V.D.C., abdominal vaso-dilator centre; C./.C., cardiac inhibitory centre; C.A.G., cardio-augmentor centre; S.C, superior cardiac branch of the vagus; I.C., inferior cardiac branch of the vagus with cell station in the heart; S., cardio- sympathetic fibres with cell station in the stellate ganglion ; V.D.A6., vaso-dilator fibres to abdominal vessels. The continuous lines are outgoing, the broken lines are ingoing nerves. pressure of blood in the arteries, and it may cause pain. The slowing^ of the heart is a reflex effect through the 420 VETERINARY PHYSIOLOGY inferior cardiac branch ; and the fall of blood pressure, which is the most manifest effect, is due to a reflex dilata- tion of the vessels of the abdomen, causing the blood to accumulate there, and thus to lessen the pressure in the arteries generally. On account of its effect on the blood pressure, this nerve is called the depressoo' nerve. ^nd. Inferior Cardiac Branch of Vagus. — Section of the vagus or of this branch causes acceleration of the action of the heart. The nerve is therefore constantly in action. Stimu- lation of its central end has no effect ; stimulation of its peripheral end causes a slowing or stoppage of the heart. Less blood is pumped into the arteries, and the pressure in them falls (fig. 188). It is therefore the checking or in- hibitory nerve of the heart. The right vagus is chiefly connected with the sino-auricular node, and its stimulation slows the rate of the heart. The left vagus is specially connected with the auriculo-ventricular node, and its stimu- lation tends to slow or prevent conduction of contraction from the auricles to the ventricles. But these two actions are not always clearly differentiated. 1. Course of the Fibres. — These fibres leave the central nervous system by the spinal accessory, and pass to the heart to form connections with the cells of the cardiac plexuses. 2. Centre. — The fibres arise from cells in the medulla oblongata, which can be stimulated to increased activity either directly or reflexly. (1) Direct stimulation is brought about by (a) sudden anaemia of the brain, as when the arteries to the head are clamped or occluded ; (6) increased venosity of the blood, as when respiration is interfered with ; (c) the concurrent action of the respiratory centre (see p. 585). (2) Reflex stimulation is produced through many nerves, e.g. those of the abdomen — a point of great importance in abdominal surgery. The superior cardiac branch of the vagus from the ventricles and wall of the aorta is stimulated Avhen the arterial pressures rises and leads to a reflex slowing of the heart, which, along with the dilatation of the abdominal vessels, reduces the pressure. HEART 421 The reflex stimulation of the centre may be used to determine its position. It can be induced after removal of the brain above the medulla, but destruction of the medulla entirely prevents it, (3) The action of this centre may be checked or inhibited. This happens when the diastolic filHng is markedly increased as a result of increased venous inflow, and since it does not occur after section of the vagi it is a central effect. 3. Mode of Action. — These inhibitory fibres appear to act by stimulating the intra-cardiac nervous mechanism. When these peripheral neurons have been poisoned by atropine, the vagus cannot act {Practical Physiology). Nicotine, which poisons the synapses between the vagus nerve and the terminal neurons, also prevents stimulation of the vagus from slowing the heart, but, as is shown by experiments on the heart of the frog, direct stimulation of the terminal neurons does act. Gaskell found that stimulating the inhibitory fibres causes a positive variation of the current of injury, indicating that the difference between the living part of the heart and the injured part is increased (p. 213), and he concluded that they excite anabolic changes in the heart. 4. Result of Action. (a) The rate of botli auricles and ventricles is slowed, but the effect on the auricles is more marked than upon the ventricles. The rigljt vagus has usually the most marked effect upon the rate of the heart (fig. 182, A.). (6) The /o?-ce of contraction of the auricles is decreased. In the ventricles the systole becomes less complete and the cavities become more and more distended, partly as a result of decrease in the force of contraction, partly as a mechanical result of over-distension due to the decreased output. (c) Conduction, especially from auricles to ventricles, is decreased so that the ventricles may not contract with each auricular contraction, and a condition of heart-block may be established. This is usually best marked upon stimulation of the left vagus. C Sympathetic Fibres.— The outgoing fibres are the aug- 422 VETERINARY PHYSIOLOGY mentors and accelerators of the heart's action. ^Vhen they are cut the heart beats slower, therefore they are constantly in action. When the peripheral end is stimulated, the rate and force of the heart are increased. 1. Course of the Fibres.- — These are small medullated fibres, which leave the spinal cord by the anterior roots of Fig. 182. — Simultaneous Tracing from Auricles and Ventricles. A., during stimulation of the vagus ; B., during stimulation of the sympathetic. Each downstroke marks a systole, each upstroke a diastole. (From Roy and Adami. ) the 2nd, 3rd, and 4th dorsal nerves, and in most animals pass to the stellate ganglion where they have their cell stations (fig. 181). From the cells in this ganglion, non-medullated fibres run on in the annulus of Vieussens, and from this and from the inferior cervical ganglion, they pass out apparently directly to the muscular fibres of the heart. HEART 423 2. The Centre is in the medulla, and it may be reflexly stimulated through various ingoing nerves, such as the sciatic ; or it may be set in action from the higher nerve centres in various emotional conditions. It is also called into play, along with inhibition of the action of the vagus, when increased venous inflow in diastole leads to over-distension. 3. Mode of Action. — The fibres seem to act (a) upon the muscular fibres, by increasing their excitability and conduc- tivity ; (6) upon the inhibitory mechanism, by throwing it out of action. 4. Results of Action (fig. 182, B). (a) The rate of the rhythmic movements of auricles and ventricles is increased. (6) The force of contraction of auricles and ventricles is increased. Thus, the output of blood from the heart is increased, and the pressure of blood in the arteries is raised. It is probable that the cardiac sympathetic also carries ingoing fibres which enter the cord in the lower cervical region. The pain experienced down the inside of the arm in heart disease in man is generally thought to be due to the implication of these fibres leading to sensations which are referred to the corresponding somatic nerves. The vagus is thus the protecting nerve of the heart, reducing its work and diminishing the pressure in the arteries, and it is called into action when the systolic pressure rises too high, while it is inhibited when the venous inflow is too much increased. The sympathetic is the whip which forces the heart to increased action in order to keep up the pressure m the arteries, and it is brought into action by increase in the venous inflow, so that the intrinsic response is supplemented by this extrinsic eflect. 424 VETERINARY PHYSIOLOGY IV. The Maintenance and Control of the Cardiac Rhythm. That there is an intrinsic mechanism in the heart for the maintenance and control of its action is shown by the fact that the excised heart continues to beat in cold-blooded animals for a considerable time without any supply of blood and in warm-blooded animals if oxygenated blood is supplied at a suitable temperature. In considering the nature of this mechanism, it must be borne in mind : first, that two distinct questions have to be investigated : — \st. How the rhythmic contractions are initiated and maintained ; Ind. How they are propagated over the heart ; and second, that nerve structures as well as muscular fibres exist in the heart, so that either one or other or both of these may be involved in the starting and conduction of con- tractions. 1 . The Initiation and Maintenance of Rhythmic Contraction. — (1) In the embryo, the heart begins to beat before any nervous structures can be shown to have migrated into it. (2) Hooker finds that, after removal at a very early stage of development of the anterior part of the neural canal from which the neurons to the heart come, the formation of the heart still goes on while it beats in a normal manner. (3) A little piece of the heart of an embryo kept under aseptic precautions in the animal's blood plasma will grow, and will manifest typical rhythmic contractions. (4) Even in the adult amphibian it is possible to start rhythmic contractions in the apex of the ventricle — a part in which nerve cells have not been observed — either by repeated rhythmic stimulation or by distending it with Ringer's solution perfused through a tube. The conclusion thus seems inevitable that rhythmic contraction is primarily a function of the muscle. But there is evidence that, when nerve structures have HEART 425 grown out to reach the heart, they play a not unimportant part in initiating contraction. (1) There is the negative evidence that, if during Hfe the apex of the frog's ventricle has been separated from the rest by crushing, it remains passive. (2) Chloral, apparently by poisoning the nervous struc- tures, may stop the rhythmic action of the heart, but leave the muscle capable of responding to stimulation (3) Carlson has shown that the heart of the king crab stops if the nervous structures are dissected off it. But the muscle of this heart is of the type of skeletal muscle, and it is perhaps unsafe to apply these results to ordinary heart muscle. (4) The contractions normally start in the sinus region, a part of the heart richly supplied with nerve cells and fibres (p. 388), The importance of this part of the heart in originating the movements of the rest of the organ is shown by experiments on the heart of the frog (Practical Physiology). If a ligature be applied between the sinus and auricles, the sinus goes on beating while the rest of the heart stops (Stannius' Exjyeriment). This shows the dominant influence of the sinus. But, if now a ligature be applied between the auricles and ventricles, these latter generally begin to beat with a slower rhythm than the sinus (Practical Physiology). The second part of this experiment seems to indicate that each part of the heart has the property of rhythmic contractility. It has also been shown that if the ventricle be made to beat faster than the sinus, the contraction wave may travel in the reverse direction, from ventricle to sinus. It, and not the sinus, becomes the " pace-maker." The whole question of the relative parts played by nerve and muscle in starting contraction is still unsettled. The evidence seems to indicate that the rhythmicity is a function of the primitive cardiac tissue which is at first purely muscular, but which later contains nervous elements, and in connection with which, in the mammal, the chief masses of nerve cells occur. The maintenance of this rhythmic contraction and relaxa- 426 VETERINARY PHYSIOLOGY tion deiDends upon the presence of certain electrolytes in the circulating blood. A due admixture of salts of sodium, potassium, and calcium is essential. For the frog's heart Ringer found that the proportions which give the best results are — NaCl .... 0-70 per cent. KCl .... 0-08 CaCl .... 0025 The mammalian heart may be kept contracting for a long time after removal from the body by perfusing the coronary arteries through a tube fixed in the aorta with a suitable saline solution well oxygenated and kept at the temperature of the animal. Sodium salts when supplied alone to the heart in con- siderable amounts cause relaxation. Potassium salts in much smaller amounts have the same effect. Calcium salts when in excess cause a sustained contraction. The amount of carbon dioxide in the blood circulating in the coronary system affects the action of the heart. A decrease in the amount accelerates the heart, an increase leads to increased diastolic relaxation ; but at first the con- tractions are also so increased that the output of blood remains unaltered. Later the contractions decrease in force and the heart may stop in diastole. The intra-cardiac nervous mechanism seems to exercise a controlling influence on cardiac contraction. (1 ) If the region between the sinus and auricles in the frog's heart is stimu- lated by the interrupted current from the induction coil, the heart is slowed or stopped, even after the synapses with the nerves coming from the central nervous system have been poisoned by nicotine. If atropine, which poisons the terminal plexus, be first applied, electric stimulation is without result (Practical Physiology). (2) Further, if the intra- ventricular pressure in the heart of the frog is raised by clamping the aorta, a slowing of the rhythm occurs even after section of the vagi, but not after the intra-cardiac neurons have been poisoned by atropine. HEART 427 2. Conduction of Contraction. — There is little evidence that nerve structures play a part in the conduction of the impulse when once started. The syncytial structure of heart muscle is specially well fitted to secure the propagation of the contraction, and poisoning the nerve structures with chloral does not abolish this. While conduction is a function of the muscular tissue of the heart, it is undoubtedly modified through the action of nerves (p. 418). The propagation of the wave of contraction over the auricles and ventricles and the part played by the primitive tissue have been already considered (p. 395). V. The Nature of Cardiac Contraction. The contraction of the ventricle lasts for a considerable fraction of a second. Is it of the nature of a single contrac- tion, or of a tetanus ? (i.) A single stimulus applied to heart muscle produces a single prolonged contraction (Practical Physiology). (ii.) It is impossible to tetanise the heart by rapidly repeated induction shocks. This is due to the long refractory period after contraction has occurred. The resistance to further stimulation gradually wanes, till, just before the onset of the next contraction, a very small stimulus is effective. By a slower sequence of stimuli it is therefore possible to produce an incotnplete fusion of contractions. (iii.) The steady passage of the contraction wave along the heart is against the idea that the normal action of the heart is a tetanus. (iv.) That it is really a single contraction is demonstrated by taking advantage of the fact that the contracting part of a muscle is electro-positive (" zincy ") to the rest. By the use of the string galvanometer, it is possible to show that the region of the sino-auricular node first becomes " zincy," and that this variation then travels over the auricle and onward to the ventricle. In man, by leading off from the right hand and left foot 428 VETERINARY PHYSIOLOGY to the galvanometer, it is possible to get an electrocardiogram, the left foot being the pole connected with the apex, the right hand that connected with the base. Such tracings not only throw important light upon the nature and course of contraction, but have proved of considerable im- portance in the diagnosis of abnormal conditions of the heart. The string galvanometer is generally used for this purpose (p. 214). The base of the heart shows first (a) an electro-positive phase (fig. 173) due to auricular contraction. This may be followed by (6) an electro-negative variation just at the beginning of ventricular contraction, which has been ascribed to the early contraction of the papillary muscles at the apex, making that part of the heart electro-positive to the base, (c) This is immediately followed by the most marked electro- positive variation, due to the contraction of the ventricle starting at the base, (d) At the very end of ventricular contraction another small electro-positive variation occurs, and this has been ascribed to the contraction ending in the infundibulum of the right ventricle. Heart muscle resembles visceral muscle in that the minimum stimulus is also a maximum stimulus — i.e. the smallest stimulus which will make the muscle contract makes it contract to the utmost. This seems to be due to the fact that, while in skeletal muscle a small stimulus calls into play a few fibres a more powerful stimulus calls into play a greater number, whereas in heart muscle all are stimulated at once by the minimum effective stimulus, because of the continuity of the fibres in the syncytial network. The general law of the " all or nothing" in contraction applies to heart muscle. But while this is the case, the strength of stimulus necessary to call forth a contraction varies at different periods of the cardiac cycle as indicated above. In cardiac muscle, perhaps more than in any other, a staircase increase in the extent of contraction with a series of stimuli is manifested. Tone of Heart Muscle. — As already indicated, tonus is a HEART 429 marked feature of visceral muscle (p. 215), and it is also manifest in skeletal muscle (p. 211), It would, therefore, be curious if it were absent in cardiac muscle. The rapid rhythmic contraction makes it more difficult to investigate, and some physiologists actually deny its existence and maintain that tone of the heart muscle, which should prevent over-distension, is rendered unnecessary by the action of the fibrous pericardium. But there is considerable evidence that it does exist, and that it plays a not unimportant part. Gaskell found in the heart of cold-blooded animals that perfusing a fluid con- taining a weak alkali gradually decreased the diastolic filling and finally stopped the heart in systole, while perfusing a weak solution of lactic acid increased the diastole and reduced the systole, and, finally, brought the heart to a standstill in full diastole. Strophanthus acts like an alkali. Clinically a condition of over-distension of the heart is frequently observed and the administration of strophanthus is found to decrease the distension. Physicians generally regard this as due to loss of tone. Some investigators maintain that it is simply due to too great diastolic filling, with too great lengthening of the muscle fibres. Pathological Disturbances of Contraction and Conduction. (1) Heart-block. — Since, in the mammalian heart, muscular continuity between auricles and ventricles through the band of His is of small extent, the wave of contraction is delayed at this point, and in the dying heart and in various pathological conditions, the contraction frequently fails altogether to pass this block, and the ventricles do not contract after each auricular systole, and may either stop, or contract only after two or three auricular contractions have occurred. In such cases the pulse rate is reduced to a half or even less of its normal rate. A condition of bradycardia through "heart-block" is produced. This condition is revealed by a study of the pulse in the veins of the neck or by the electrocardiogram. (2) Auricular Flutter- — Another condition in which the 430 VETERINARY PHYSIOLOGY contraction wave is not regularly propagated from auricles to ventricles is seen in the condition of auricular flutter when, as the result of increased excitability of the sino- auricular node, the normal " pacemaker," the rate of contraction of the auricles is enormously increased, some- times to two or three hundred per minute. In such cases the contraction reaches the auriculo-ventricular band while the ventricular fibres have not completed their contraction while they are still in the refractory phase. Hence, only one ventricular contraction for every two or three auricular contractions may occur. In these cases there is practically a heart-block, but the rate of the ventricles is not decreased as in true heart-block. The condition is fairly common, and it may be detected by the study of the venous pulse, or still better, by the electro- cardiogram. (3) Fibrillation. — While under normal conditions the contractions are conducted in an orderly manner over auricles and ventricles, interference with the coronary circulation with the consequent decreased supply of oxygen to the wall of the heart is apt to lead to marked inco-ordination of the contractions, so that some bundles of fibres are contracting while others are relaxing. Thus a peculiar fluttering and ineffective fibrillar contraction ov fibrillation is seen in the myocardium. This may affect either the auricles or the ventricles. Since the auricles are practically the cisterns of the heart, the con- dition does not so seriously interfere with the circulation when it affects them as when it affects the ventricles which are the pumps. Ventricular fibrillation prevents the proper expulsion of blood and soon leads to a fatal result. It may be produced by powerful electrical stimulation of the ventricles and is one factor in causing death in electrocution. BLOOD VESSELS 431 III. CIRCULATION IN THE BLOOD AND LYMPH VESSELS. The general distribution of the various vessels — arteries, capillaries, veins, and lymphatics — has been already con- sidered (fig. 162, p. 383). 1. STRUCTURE. {The structure of the walls of each kind of Vessel must he studied practically.) The capillaries are minute tubes of about 1 2 micromilli- metres in diameter, forming an anastomosing network throughout the tissues. Their walls appear to be composed of a single layer of endothelium. On passing from the capillaries to arteries on the one side, and to veins and lymphatics on the other, non-striped muscle fibres make their appearance encircling the tube. Between these fibres and the endothelium, a fine elastic membrane next appears, while, outside the muscles, a sheath of fibrous tissue develops. Thus the three essential coats of these vessels are produced : — Tunica intima, consisting of endothelium set on the internal elastic membrane. Tunica media, consisting chiefly of circularly arrano-ed visceral muscular fibres. Tunica adventitia, consisting of loose fibrous tissue. A. Arteries. — The coats of the arteries are thick. In the large arteries, the muscular fibres of the media are largely replaced by elastic fibres, so that the vessels may better stand the strain of the charge of blood which is shot from the heart at each contraction. The great characteristic of the walls of the laiye arteries is the toughness and elasticity given by the abundance of elastic fibrous tissue, and of the small arteries, the con- tractility due to the preponderance of muscular fibres. 432 VETERINARY PHYSIOLOGY B. Veins. — In the veins, double flaps of the tunica intima form valves which prevent any back -flow of blood. The walls of the veins are thin. 2. PHYSIOLOGY. The circulation of blood in the vessels is that of a fluid in a closed system of elastic-walled tubes, at one end of which (the great arteries) a high pressure, and at the other (the great veins) a low pressure, is kept up. As a result of this distribution of pressure, there is a constant flow of blood from arteries to veins. Many points in connection with the circulation may be conveniently studied on a model, or schema, made of india-rubber tubes and a Higginson's syringe (Practical Physiology). A. Blood Pressure. The distribution of pressure is the cause of the flow of blood, and must first be considered. 1. General Distribution of Pressure. That the pressure throughout the greater part of the blood-vessels is positive — greater than the pressure of the atmosphere — is indicated by the fact that if a vessel is opened, the blood flows out of it. The force with which blood escapes is a measure of the pressure in that i^articular vessel. If an artery be cut, the blood escapes with great force ; if a vein be cut, with much less force. 1. Arteries. — If the pressure in the aorta, in the radial, in the dorsalis pedis, and in one of the smallest arteries is measured, it is found that there is no marked change till the very smallest arteries are reached, when the pressure rapidly falls. In the aorta the pressure may be over 150 mm. Hg, while in the capillaries it may be only about 20 mm. Hg. This distribution of arterial pressure may be plotted as in fig. 183, Ar. 2. Veins, — If the pressure in any of the small veins, in BLOOD VESSELS 433 a medium vein, and in a large vein near the heart be measured, it will be found — 1st. That the venous pressure is less than the lowest arterial pressure. 271(1. That it is highest in the small veins, and becomes lower in the larger veins. In the great veins entering the heart during inspiration it is lower than the atmospheric pressure. 3. Capillaries. — The pressure in the capillaries must C. Fig. 183. — Diagram of the Distribution of Mean Blood Pressure throughout the Blood Vessels. Ar., the arteries ; C, the capillaries ; V., the veins. obviously be intermediate between that in the arteries and in the veins. The pressure in any part of a system of tubes depends upon two factors : — 1st. The force propelling fluid into that part of the system. 2nd. The resistance to the outflow of fluid from that part of the system. The pressure in the arteries is high, (1) because with each beat of the heart the contents of the ventricle are thrown with the whole contractile force of the heart into the corre- sponding artery ; and (2) because the resistance offered to the outflow of blood from the arteries into the capillaries and veins is enormous, since the blood, as it passes into 28 434 VETERINARY PHYSIOLOGY innumerable small vessels, is subjected to greater and greater friction — just as a river, in flowing from a deep narrow channel on to a broad shallow bed, is subjected to greater friction. Thus, in the arteries the powerful propulsive force of the heart and the great resistance to outflow keep the pressure high. When the capillaries are reached, much of the force of the heart has been lost in dilating the elastic coats of the arteries, and thus the inflow into the capillaries is much weaker than the inflow into the arteries. At the same time, the resistance to outflow is small, for, in passing from capillaries to veins, the channel of the blood is becoming less broken up and thus offers less friction to the flow of the blood. When the veins are reached, the propelling force of the heart is still further weakened, and hence the force of inflow is very small. But there is no resistance to outflow from the veins into the heart during diastole. Further, the great veins, before they reach the heart, pass into the thorax, an air-tight box in which, during each inspiration, a low pressure is developed. What has been said of the pressure in the veins applies equally to that in the lymphatics. 2. Rhythmic Variations in Blood Pressure. Before considering the methods of investigating the pressure in these different vessels, and the changes which they undergo, certain rhythmic variations in pressure may first be considered. A. Changes in Pressure Synchronous with the Heart Beats. 1. The Arterial Pulse. With each ventricular systole, the contents of each ventricle are thrown into the already full arteries, and the pressure in these vessels is suddenly raised. BLOOD VESSELS 435 If the finger be pressed upon an artery, a distinct expansion, due to this rise of pressure, will be felt following each systole. This is the arterial pulse. It is simply a rise of pressure, and it has nothing to do with the flow of blood. The pulse wave may be compared to a wave at sea, which is also a Avave of increased pressure, the only difference being that, while the wave at sea travels freely over the surface, the pulse wave is confined in the column of blood, and manifests itself by expanding the walls of the arteries. If a vein be investigated in the same way, it will be found that no such pulse can be detected. In the capillaries, also, this pulse does not exist. It is best marked in the great arteries, and becomes less and less distinct as the small terminal arteries are reached. 1. Causes of the Pulse. — The arterial pulse is due to — 1st. The intermittent inflow of blood. The arteries expand from the sudden increase of pressure due to each sudden rush of blood from the heart into the arterial system. 'Unci. The resistance to outflow from the arteries into the capillaries. If blood could flow freely from the arteries into the capillaries, then the inrush of blood from the heart would simply displace the same amount of blood into the capillaries and the arteries would not be expanded. As already indicated, the friction between the walls of the innumerable small arterioles and the blood is so great that the flow out of the arteries is not sufficiently free to allow the blood to pass into the capillaries as rapidly as it is shot into the arteries. Hence, with each beat of the heart, an excess of blood must accumulate in the arteries to be passed on into the capillaries and veins between the beats. 3rcZ. The elasticity of the walls. To allow of their expanding to accommodate this excess of blood the walls of the arteries must be elastic. It is upon these three factors that the arterial pulse depends. Do away with any of them, and the pulse at once disappears. 436 VETERINARY PHYSIOLOGY 2. Why is there no Pulse in the Veins? — Their walls have a certain amount of elasticity, but, instead of there being a resistance to the outflow of blood from the veins into the heart, this is favoured by the suction action of the thorax in inspiration. Hence, even if an intermittent inflow were well marked, the absence of resistance to outflow would in itself prevent the development of a venous pulse. But the inflow is not intermittent. The arteries are so overfilled that just as much blood passes into the veins between the beats as during the beats of the heart. Hence the most important factor in causing a pulse, an intermittent inflow, is absent. With no intermittent inflow, and with no resistance to outflow, the development of a pulse is impossible. In certain abnormal conditions, where, from the extreme dilatation of the arterioles, the inflow into the veins is very free, and where the outflow from the part of the body is not so free, a local venous pulse may develop. A special pulse in the great veins near the heart is considered on p. 444. 3. Characters of the Pulse Wave. — If a finger be placed on the carotid artery and another upon the radial artery, it will be felt that the artery near the heart expands (pulses) before that further from the heart {Practical Physiology). The pulse develops first in the arteries near the heart and passes outwards towards the periphery. The reason for this is obvious. The arteries are always overfilled with blood. The ventricle drives its contents into the overfilled aorta, and, to accommodate this, the aortic wall expands. But, since the aorta communicates with the other arteries, this increased pressure passes outwards along them, expanding their wall as it goes. It greatly simplifies the study of the pulse to regard it in this light, and to study it just as we should study a wave at sea. 1. Velocity. — To determine how fast a wave is travelling, the time may be ascertained which it takes to pass from one point to another at a known distance from the first. So with the pulse wave : two points on an artery at a known BL0{3D VESSELS 437 distance from one another may be taken, and the time which the wave takes to pass between them may be measured. In this way it is found that the pulse Avave travels at about 9 or 10 metres per second — about thirty times as fast as the blood flows in the arteries (p. 465). 2. Length of the Wave. — To determine this in a wave at sea is easy, if we know its velocity and know how long it takes to pass any one point. The same method may be appHed to the pulse wave. We know its velocity, and, by placing the finger on an artery, we may determine that one wave follows another in rapid succession, so that there is no A. B. Fig. 184.— Two Pulse Tracings — A. with a relatively sluggish heart and relatively high arterial pressure ; B. with a relatively active heart and relatively low arterial pressure. Both show the primary crest exaggerated by the inertia of the sphygmograph. pause between them. Each wave lasts the length of a cardiac cycle. There are about 40 cycles per minute — i.e. per 60 seconds; hence, each must last 1'5 second. The pulse wave takes I'o second to pass any place, and it travels at 10 metres per second ; its length then is 15 metres, or about five times the length of the body. It is then an enormously long wave, and it has disappeared at the periphery long before it has hnished leaving the aorta. 3. The Height of the Wave. — The height of the pulse wave, as of a wave at sea, depends primarily on the pressure causing it. It is really the difference between the maximum systolic pressure (fig. 190) and the minimum diastolic pressure. It may be most accurately measured by determin- 438 VETERINARY PHYSIOLOGY ing these by means of the Riva Rocci apparatus (p. 448). The character of the arterial wall modifies it very largely and the true height of the pulse wave in the great arteries near the heart is masked by the thickness of the arterial wall. The pulse wave is highest near the heart, and becomes lower and lower as it passes out to the periphery, where it finally disappears altogether (fig. 190). This disappearance is due to its force becoming expended in expanding the arterial wall. 4. The Form of the Wave. — Waves at sea vary greatly in Fig. 185. — Diagram of Dudgeon's Sphygniograph. CI., clockwork driving the smoked paper, Tr., under the writing point of the liver, L., 8p., is a steel spring, with a button, B., which is applied over the radial artery. With each expansion of the artery the button is moved upwards, and causes a movement of the system of levers indicated by the arrows. form, and the form of the wave might be graphically recorded on some moving surface, such as the side of a ship, by some floating body. If the ship were stationary, a simple vertical line would be produced as the wave passed, but, if she were moving, a curve would be recorded, more or less abrupt according to her speed. From this curve the shape of the wave might be deduced, if the speed of the vessel were known. The same method may be applied to the arterial pulse. By recording the changes produced by the pulse wave as it BLOOD VESSELS 439 passes any point in an artery the shape of the wave may be deduced from the tracing. This may be done by any of the various forms of sphygmograph (fig. 185), {Practical Physiology). Such a tracing is not a true picture of the wave, but simply of the eifect of the wave on one point of the arterial wall. Its apparent length depends upon the rate at which the recording surface is travelling, and not upon the length of the wave. Its apparent height depends (i.) upon the length of the i^WVKf4x]^^ fJ^NsKKNKKN^vKKKf^ Fig. 186. — Three Sphygmographic Tracings made from the Radial Artery of a healthy man in the course of one hour without removing the sphygmograph. 1 was made immediately after muscular exercise ; 2 was made after sitting still for half an hour ; and 3, after an hour. recording lever, (ii.) upon the resistance offered by the instru- ment, (iii.) upon the degree of pressure with which the instru- ment is applied to the artery, and (iv.) on the thickness of the arterial wall. Such a trace (figs. 184 and 186) shows — 1st. That the pulse waves generally follow one another without any interval. Ind. That the rise of the wave is much more abrupt than the fall. 3rd That there are one or more secondary waves upon the descent of the primary wave. 440 VETERINARY PHYSIOLOGY One of these is constant and is very often well marked. It forms a second crest, and is hence called the dicrotic wave (fig. 184, c). Between the chief crest and this secondary crest, a smaller crest is often manifest (fig. 184, A., b). From its position, it may be called the predicrotic wave. If the wave has only one crest the pulse is called a one- crested or monocrotic wave. If the dicrotic crest is well marked it is called dicrotic. That the wave actually has the characters disclosed by a sphygmographic tracing may be demonstrated by letting the blood from a cut artery play upon a moving surface when a Hcemautograph showing the waves is produced. To understand the various parts of the pulse wave, it is necessary to compare it with the changes in the intra- ventricular pressure throughout the cardiac cycle. This may be done by taking synchronously tracings of the intra- ventricular pressure and of the aortic pressure (fig. 173, p. 401). Such a tracing shows that, at the moment of ventricular systole, the pressure in the aorta is higher than that in the left ventricle. As ventricular systole advances, the intra-ventricular pressure rises and becomes higher than the aortic. At that moment, the aortic valves are thrown open and a rush of blood takes place into the aorta, raising the pressure and expanding the artery, and causing the upstroke and crest of the pulse curve. In a sphygmographic tracing this crest is exaggerated by the inertia of the instrument (fig. 184). After the ventricle has emptied itself, the intra-ventricular pressure tends somewhat to fall, and, at the same time, a fall in the intra-aortic pressure begins, and goes on till ventricular diastole, while the elastic wall of the artery recovers and reduces the size of the vessel. With diastole, the intra-ventricular pressure suddenly becomes less than the intra-aortic, and the semilunar valves are forced downwards towards the ventricles, and thus the capacity of the aorta is slightly increased and the pressure falls sharply. This fall BLOOD VESSELS 441 in pressure is indicated by the dicrotic notch. But the elasticity of the semilunar valves at once makes them spring up, thus increasing the pressure in the aorta and causing the second crest, the dicrotic wave (fig, 184, c). After this the pressure in the arteries steadily diminishes till the minimum is reached, to be again increased by the next ventricular systole. If all the blood does not leave the ventricle in the first gush, e.g. when the intra-aortic pressure is high as compared with the force of the heart (fig. 175, continuous line), there is a residual outflow which, by catching the lever of the sphygmograph on its back-spring from the initial crest, may again raise it, causing the predicrotic wave. It is thus manifest that the form of the pulse ivave varies according to the relationship between the arterial pressure and the activity of the heart. It is not the actual activity of the heart or the actual arterial pressure, but their relation- ship to one another which is of importance. Thus, a heart actually weak may, with a low arterial pressure, be relatively active. (A) If the heart is active and strong m relation to the arterial pressure, the main mass of the blood is expelled in the first sudden outflow, and the residual flow is absent or slight (fig. 175, dotted line). In this case there is a sudden and marked rise of the arterial pressure, followed by a steady fall till the moment of ventricular diastole. The rebound of the semilunar valves is marked and causes a very prominent dicrotic wave, while the predicrotic wave is small or absent (fig. 184, B.). Such a condition is well seen after violent nmscular exertion, and in certain fevers. In these con- ditions the dicrotic wave may be so well marked that it can be felt with the finger. (B) On the other hand, if the ventricles are acting slowly or feebly in relationship to the arterial pressure, the initial outflow of blood does not take place so rapidly and com- pletely (fig. 175, continuous line), and the initial rise in the pulse is thus not so rapid. The residual outflow of blood is more marked and causes the well-marked secondary rise in the pulse curve — the predicrotic wave. In certain cases, 442 VETERINARY PHYSIOLOGY this may be higher than the primary crest, producing the condition known as the anacrotic pulse. The relatively high intra-arteriai pressure in such a case prevents the development of a well-marked dicrotic wave. In extreme cases of this kind, when the arterial walls are very tense, they may recover in an irregular jerky manner, and may give rise to a series of katacrotic crests producing a polycrotic pulse (fig. 186, s). From what has been said, it will be seen that a study of the pulse wave gives most valuable information as regards the state of the circulation, and the physician constantly makes use of the pulse in diagnosis. Palpation of the Pulse. — On placing the finger on the artery the points to determine are — 1st. The rate of the pulse — i.e. the rate of the heart's action. Ind. The rhythm of the pulse — i.e. of the heart's action, as regards — (1) Strength of the various heats. — Normally the beats differ little from one another in force — since the various heart-beats have much the same strength. Respira- tion has a slight effect which will afterwards be considered (see p. 535). In pathological conditions great differences in the force of succeeding pulse waves may occur. (2) Time relationship of the beats. — Normally the beats follow one another at regular intervals — somewhat shorter during inspiration — somewhat longer during expiration. In patho- logical conditions great irregularities in this respect may occur. Srd. The volume of the pulse wave. Sometimes the wave is high and greatly expands the artery — sometimes it is less high and expands the artery less. This is a measure of the difference between systolic and diastolic pressure. The former condition is called a full pulse {pulsus pleniis), the latter a small pulse (pulsus parvus). The fulness of the pulse depends upon two factors : — 1st. The average tension in the arteries between the pulse-beats — the diastolic pressure. If this is high, the walls of the artery are already somewhat stretched, and therefore the pulse wave may expand BLOOD VESSELS 443 them further only slightly. On the other hand, if the diastolic pressure is low, the arterial wall is lax, and is readily stretched to a greater extent. '2.nd. The force of the heart which de- termines the systolic pressure. To stretch the arterial wall to a large extent requires an actively contracting heart throwing a large wave of blood into the arterial system at each systole. The full pulse is well seen after violent exertion, when the heart is active and the peripheral vessels moderately dilated. It is also seen in a slow pulse, on account of the greater diastolic filling of the ventricles, Mh. Tension of the pulse. This is really a measure of the maximum systolic blood pressure, which may be more accurately measured by the Riva Rocci apparatus (p. 448). To test it, two fingers must be placed upon the artery, and the one nearer the heart pressed more and more firmly on the vessel until the pulse wave is no longer felt under the other finger. The tension of the pulse varies directly with the force of the heart and with the peripheral resistance. The first state- ment is so obvious as to require no amplification. It is also clear that, if the peripheral resistance is low, so that blood can easily be forced out of the arteries into the capillaries, the arterial wall will not be so forcibly expanded as when the resistance to outflow is great. Hence a high-tension pulse is indicative of a strongly acting heart with constric- tion of the peripheral vessels. It is well seen during the shivering fit which so frequently precedes a febrile attack, since at that time the peripheral vessels are constricted and the heart's action excited. oth. The form of the pulse wave may be investigated by means of the finger alone, or by means of the sphygmo- graph. The points to be observed are : — (1) Does the wave come up suddenly under the finger ? In the pulsus celer (or active pulse) it does so ; in the pulsus tardus, on the other hand, it comes up slowly. The former condition is indicative of an actively contracting heart with no great peripheral resistance — the latter indicates that the heart's action is weak in relationship to the arterial blood pressure. 444 VETERINARY PHYSIOLOGY (2) Does the wave fall slowly or rapidly ? Normally the fall should not be so sudden as the ascent. When the aortic valves are incompetent the descent becomes very rapid (p. 410) in the so-called " water-hammer " pulse. (3) Are there any secondary waves to be observed ? The only one of these which can be detected by the finger is the dicrotic wave, and this only when it is well marked. When it can be felt, the pulse is said to be dicrotic, and, as before stated, this indicates an actively contracting heart with an arterial pressure low relatively to the strength of the ventricles (p. 441). 2. The Capillary Pulse. For the reasons already given, there is normally no pulse in the capillaries (p. 434). If, however, the arterioles to a district are freely dilated, so that little resistance is offered to the escape of blood from the arteries, and if, at the same time, the outflow from the capillaries is not proportionately increased, intermittent inflow and resistance to outflow are developed, and a pulse is produced. Such a condition is seen in certain glands during activity. 3. The Venous Pulse. 1. The absence of a general venous pulse has been already explained. But just as in the capillaries, so in the veins, a local pulse may develop. 2. In the veins entering the auricles and in the veins at the root of the neck a pulse occurs. This may be recorded by means of M'Kenzie's polygraph which consists of a small metal cup connected with a recording tambour. The cup is applied closely to the skin over the vein. This pulse has no resemblance to the arterial pulse, although depending on the same three factors. Its form is indicated in fig. 187. Its features are to be explained as follows : — (a) Normal. — Blood is constantly flowing into the great veins, pressed on from behind, (i.) When the auricles con- tract, the outflow from these veins into the heart is suddenly BLOOD VESSELS 445 checked, and consequently the veins distend, causing a crest (^.*S^.)- -^t the moment of auricular diastole the outflow is again free, a rush of blood takes place into the distending auricles, and thus the pressure in the veins falls, (ii.) But, as this is occurring, two things happen — (a) blood is shot from the ventricles into the arteries, and the carotid, lying behind the jugular vein, transmits its pulse through the vein ; (b) the auriculo-ventricular valves are closed and pressed upon from the ventricular side, and thus a wave of pressure is sent back through the auricles. These two together cause a second wave early in ventricular systole, (iii.) While the ventricle is Fig. 187.— Tracings of the Pulse in the Great Veins in Relationship to the Cardiac Cycle. normal venous pulse, on which is shown the fourth crest which is often absent. a and b, venous pulse in tricuspid incompetence. contracted, blood cannot pass on from the auricles, and hence it accumulates in the great veins and makes a third crest at the end of ventricular systole. At the moment when the ventricles dilate, a sudden rush of blood takes place from the veins and auricles into the ventricles, and thus a sudden fall in the pressure is produced, (iv.) This may be interrupted by the rebound of the auriculo-ventricular ring, which was pulled downwards during ventricular systole, and this may cause a fourth crest on the pulse. Gradually, as the ventricles fill, the pressure in the auricles and veins increases till the next auricular systole. 446 VETERINARY PHYSIOLOGY (6) Pathological. — If the auriculo-ventricular valves are incompetent (p. 410) blood is forced back into the auricles and veins when the ventricles contract, and the crest during ventricular S3^stole becomes more and more marked (fig, 187,6). The height of this crest is a good index of the amount of regurgitation. B. Changes in Pressure Synchronous with the Respiration. 1. Arterial. — Not only do rhythmic changes in the arterial pressure occur with each beat of the heart, but Fig. 188. — Tracing of the Arterial Blood Pressure to show large respiratory- variations, and small variations due to heart beats upon these, and the sudden fall in the pressure produced by stimulating the inferior cardiac branch of the vagus nerve. larger changes are caused by the respirations — the rise in pressure in great measure corresponding to the phase of inspiration, the fall in pressure to the phase of expiration. This statement is not quite accurate, as will be seen when considering the influence of respiration on circulation (see p. 535). These variations are easily seen in a tracing of the arterial pressure taken with the mercurial manometer (fig. 188). BLOOD VESSELS 447 2. Venous. — A pulse, synchronous with the respirations, may also be observed in the great veins at the root of the neck and in the venous sinuses of the cranium when it is opened. With each inspiration they tend to collapse ; wath each expiration they again expand. The reason for this is that during inspiration the pressure inside the thorax becomes low, and hence blood is sucked from the veins into the heart. Hence the danger that in operating on the neck a vein may be opened and air sucked into the circulation to block the vessels in the lungs. During expiration, the intra- thoracic pressure becomes higher and thus the entrance of blood into the heart is opposed. 3. Mean Blood Pressure. L Pressure in the Arteries. (1) Methods. A. In Lower Animals. — 1. The first investigation of the pressure in the blood-vessels was made by the Rev. Stephen Hales in 1733. He fixed a long glass tube in the femoral artery of a horse laid on its back, and found that the pressure supported a column of blood of 8 feet 3 inches, while, when the tube Avas placed in a vein, only 1 foot was supported. The capillary pressure is, of course, intermediate between these two. 2. At the present time, instead of letting the blood pressure act directly against the force of gravity, it is found more convenient, in studying the pressure in an artery, to let it act through a column of mercury placed in a U tube (fig. 189, A.). (1) To record the changes in pressure a float is placed upon the mercury in the distal limb of the tube, and this carries a writing style which records the changes upon a moving surface. (2) The tube and the proximal end of the manometer are filled with a strong solution of sodium sulphate to prevent clotting and to transmit the pressure to the mercury, (3) Before the artery is undamped, the pressure is raised in the proximal 448 VETERINARY PHYSIOLOGY end of the manometer so that it nearly equals that in the artery, and thus prevents the animal from bleeding into the tube. With such an apparatus a record such as is shown in fig. 188 is given. The actual pressure is measured by taking the difference between the level of the mercury in the two limbs of the tube. To make the measurement, it is customary to describe an abscissa when the mercury is at the same level in the two sides of the tube. The heigrht of ¥Z> Pig. 189. — A., The Mercurial Manometer with Recording Float, used in taking records of the arterial blood pressure of lower animals. The clamped tube is to allow of the pressure being raised. The long tube is connected with the cannula placed in the artery. B., The Riva Rocci Sphygmometer, for measuring the arterial pressure in man. M., manometer ; P., pump ; V., valve. the style above the abscissa must be multiplied by two to give the pressure, on account of the depression in the proximal limb which accompanies the rise in the distal limb. On the record made with such an instrument, the rhythmic variations in the arterial blood pressure already considered on p. 434 et seq. are clearly visible (Practical Physiology). BLOOD VESSELS 449 B. In the intact Animal. — 1. To measure the systolic pressure it is necessary to find the pressure which must be appHed to an artery in order to prevent the pulse from passing. This may be done with Riva Rocci's apparatus (fig. 189, {B.) by applying a bag round the limb so that it rests upon the brachial artery. The bag is firmly strapped on by means of a broad supporting belt, and it is connected with a pump, by which the pressure within it may be raised, and with a mercurial manometer by which the pressure applied may be measured in mm. of mercury. The pressure is then raised either (a) till the pulse beyond the band is no longer felt, or (6) till no sound is heard with each pulse wave through a stethoscope applied to the artery beyond the band. The pressure is then gradually relaxed till (a) the pulse is again Fig. 190. — To show the Difference between Systolic, Diastolic, and Mean Blood Pressure throughout the Arterial System. S., systolic pressure ; D., diastolic pressure ; J/., mean pressure. felt or (6) the sound with each pulse wave heard through the stethoscope reappears. The column of mercury, at this moment, indicates the systolic pressure in the artery {Practical Physiology). 2. The diastolic pressure may be measured by further relaxing the pressure and noting the point at which the pulse sound again disappears. (2) Normal Arterial Pressure. By these methods it has been found that the systolic pressure in the brachial artery of man is about 120 mm. of 29 450 VETERINARY PHYSIOLOGY mercury, while the diastohc pressure is only about 70 mm. The difference between these, of course, gives the pulse pressure. (3) Factors controlling Arterial Pressure. (1) The/o7^ce of the heart and (2) the degree of 'peripheral resistance both modify the arterial pressure, and normally these so act together that any disturbance of one is com- pensated for by changes in the other. Thus, if the heart's action becomes increased and tends to raise the arterial pressure, the peripheral resistance falls and prevents any marked rise. Similarly, if the peripheral resistance is increased, the heart's action is diminished, and the rise in the pressure is checked. Under certain conditions, however, this compensatory action is not complete, and changes in the arterial pressure are thus brought about. (3) The volume of blood has a comparatively small influence on the arterial pressure (1) because by changes in the degree of contraction of the peripheral vessels, the volume of the vascular system may be adapted to the volume of blood contained, and (2) because there is a very free exchange of water between the blood and the tissues through the walls of the capillaries. Hence, after a hemorrhage, the volume of the blood is rapidly restored, and hence, after transfusion of salt solution, the fluid rapidly passes out of the vessels. But if an excessive loss of blood occurs, or if a large quantity of blood stagnates in any region and is thus put out of effective circulation, the vessels may not be able to adapt themselves, and the arterial pressure may fall. From observations made during the Great War it appears that in man a loss of 40 per cent, of the blood is generally accompanied by a fall of the systolic pressure to about 80 mm. Hg. When the pressure falls in this way it may be restored by injecting into a vein a sufficient amount of some fluid which has no prejudicial action on the blood and which does not too readily transude out of the capillaries. In man, gum arable in 6 per cent, solution has been used. BLOOD VESSELS 451 L Heart's Action.— The influence of this may be readily demonstrated by stimulating the vagus nerve while taking a tracing of the arterial pressure. The heart is inhibited, less blood is forced into the arteries, and the pressure falls (tig. 188). If, on the other hand, the augnientor nerve is stimulated, the increased heart's action drives more blood into the arteries, and the pressure rises. II. Peripheral Resistance.— The resistance to outflow from the arteries to the capillaries and veins depends upon (1) the resistance offered in the small arteries, the walls of which are surrounded by visceral muscle fibres. When these fibres are contracted, the vessels are small and the resistance is great. When they are relaxed, the vessels dilate, and the resistance to outflow is diminished. This muscular tissue of the arterioles acts as a stop-cock to the flow of blood from the arteries to the capillaries. It is of great importance — 1st, in maintaining the uniform pressure in the arteries ; 2nd, in regulating the flow of blood into the capillaries. (2) The condition of the capillaries. — Krogh has shown that in resting muscle most of the capillaries are closed, while in contracting muscle they are dilated and filled with blood even when the arterial pressure has not been allowed to rise. The capillaries thus seem able to contract and expand. Recently Dale has shown that the administration of histamine to dogs and monkeys causes such a dilatation with, at the same time, a contraction of the arterioles. Krogh also finds that a dilatation of capillaries may be produced by stimulating directly. He considers that the state of the arterioles regulates the pressure of blood in the arteries, while the state of the capillaries regulates the rate of jioiv. A slow current through dilated capillaries means arteriole con- striction. Dilatation of the arterioles and of the capillaries is gener- ally local, and its effects upon the general arterial pressure is 452 VETERINARY PHYSIOLOGY generally compensated for by contraction in other parts of the body (p. 460). (3) The viscosity of the blood. — The friction between the walls of the blood-vessels and the blood is modified by the viscosity of the latter (p. 475). After severe haemorrhage this is markedly decreased, and the resistance to the flow in the small vessels is correspondingly decreased, and hence the arterial pressure tends to fall. Q) Methods of Studying the Condition of the Arterioles and Capillaries. 1st. By direct observation. — 1. With the naked eye. A red engorged appearance of any part of the body may be due to dilatation of the arterioles leading to it. But the capillaries may be more particularly dilated, when, as a result of partial stagnation and the more complete removal of oxygen from the blood, the part may have a bluish colour. The engorgement may, however, be due to some obstruction to the outjioiv of blood from the part. 2. With the micro- scope. In certain transparent structures, such as the web of the frog's foot, or the wing of the bat, or the mesentery, it is possible to measure the diameter of the arterioles and the capillaries by means of an eye-piece micrometer, and to study their dilatation and contraction. 2nd. Engorgement of the capillaries brought about either by dilatation of the arterioles, of the capillaries, or of both, or simply by increased force of the heart raising the arterial pressure, manifests itself also in an increased size of the jxirt. Every one knows how, on a hot day, when the arterioles of the skin are dilated, it is difficult to pull on a glove which, on a cold day, when the cutaneous vessels are contracted, feels loose. By enclosing a part of the body in a case with rigid walls, filled with fluid or with air, and is connected with some form of recording tambour, an increase or decrease in the size of the part, due to the state of its vessels, may be registered. Such an instrument is called a bulk-measurer (plethysmograph or oncograph). SrcZ. When the arterioles in a part are dilated and the blood is flowing freely into the capillaries, the part becomes warmer, and, by fixing a thermometer to the surface, BLOOD VESSELS 453 conclusions as to the condition of the arterioles may be drawn. The temperature of the surface of the body is also modified by the activity of the heart ; if the heart begins to fail the temperature tends to fall. Uh. By streaming blood through the vessels, gener- ally of a frog, and observing the rate at which it escapes, the changes in the state of the small vessels may be made out. This perfusion method is much used in studying the action of drugs (Practical Physiology). 5th. Since the state of the arterioles influences the arterial pressure (p. 450), if the heart's action is kept uniform, changes in the arterial blood pressure indicate changes in the arterioles — a fall of pressure indicating dilatation, a rise of pressure, constriction. (•2j Normal Condition of the Arterioles. — Normally the arterioles are in a state of semi-contraction ; but if the arterioles in some transparent tissue be examined, they will be found to undergo periodic slow changes in calibre. The ear of a white rabbit shows such slow changes ; it seems at one time pale and bloodless, at another time red and engorged. During this latter phase numerous vessels appear which in the former condition were invisible. These slow changes are independent of the heart's action and of the rate of respira- tion. They appear to be due to the periodic rhythmic contraction of the walls of the vessels. During the functional activity of a part, a free supply of blood to its capillaries is required. This is brought about by a relaxation of the muscular coats of the arterioles leading to the part, and probably by an active as well as a passive dilatation of the capillaries. When the part returns to rest, the free flow of blood is checked by the contraction of the muscular walls of the arterioles, and probably of the walls of the capillaries. The action of the arterioles is well seen under the influence of certain drugs (vaso- dilators and vaso- constrictors). If nitrite of aniyl is inhaled by the animal, it will be seen that the skin and mucous membranes become red and engorged with blood, while at the same time the arterial pressure falls. Nitrites cause the muscular 454 VETERINARY PHYSIOLOGY coat of the arterioles to relax, and thus, by diminishing peripheral resistance, permit blood to flow freely from the arteries into the capillaries. Salts of barium have precisely the opposite effect, causing the skin to become pale from imperfect filling of the capillaries, and producing a marked rise in the arterial pressure. Contraction of the muscles of the arterioles is produced, and the flow of blood from arteries to capillaries is retarded. Histamine seems to have the peculiar action of constrict- ing the arterioles, and in some animals at least of dilating the capillaries. (3) Nervous Mechanism Controlling the Arterioles- — If the sciatic nerve is cut, the small vessels in the foot at once dilate. If the nerve is stimulated, they contract. The same results follow if the anterior roots of the lower spinal nerves, from which the sciatic takes origin, are first cut and then stimulated. TJie Ci^ntral nervous system, therefore, exerts a constant tonic influence ui^on the arterioles, keeping them in a state of semi-contraction, and this action may be increased, and thus a constriction of the arterioles produced. In this way, if the effect is a general one, the flow of blood from arteries to capillaries is obstructed and the arterial pressure may be raised. This influence may also be diminished, so that the arterioles dilate and allow an increased flow into the capillaries from the arteries. Thus the arterial pressure may be lowered if the action is not too local, and is not compensated for by constriction elsewhere. These mobile arterioles, under the control of the central nervous system, constitute a vaso-motor mechanism, which plays a part in nearly every vital process in the body. By it the pressure in the arteries is governed, the supply of blood to the capillaries and tissues is controlled, and the loss of heat from the skin is largely regulated (p. 269). This vaso-motor mechanism consists of two parts : — Is^. Peripheral. — This consists of the muscular fibres in the walls of the arterioles with the nerve structures among them. BLOOD VESSELS 455 2i}d. Central. — The portions of the central nervous system presiding over these and the nerves which pass from them. 1st. Peripheral Mechanism. — The muscular fibres are maintained in a state of tonic semi-contraction by nerves passing to them, and when these nerves are divided, the muscular fibres relax. But if, after these nerves have been cut, the animal be allowed to live, in a few daj's the arterioles ar/ain pass into a state of tonic semi-contraction, although no union of the divided nerve has taken place. Certain drugs, e.g. digitalis and the salts of barium, act as direct stimulants to these nuiscle fibres, while nitrites inhibit their activity. The precise part played by the nerve plexus in the walls of the arterioles has not been definitely established, but certain drugs appear to act specially upon it. Thus, apocodeine, while it does not prevent barium salts from constricting the vessels, prevents the constricting action of adrenalin, even when the nerves are cut. Hence, it must be concluded that apocodeine paralyses a nervous mechanism in the arteriole wall which is stimulated by adrenalin. On the other hand, nicotine seems to block the action of barium, but not that of adrenalin. Deductions from the antagonistic action of drugs are by no means satisfactory, as their action varies so much with dosage and with the functional condition of the tissues at the time when they are administered. '2nd. Central Mechanism. — When a nerve, going to any part of the body, is cut, the arterioles of the part generally dilate ; when it is stimulated, the arterioles usually contract ; sometimes, however, they dilate. In no case does section of a nerve cause constriction of the arterioles. These facts prove that the central vaso-motor nervous mechanism may be divided into two parts : — A. Vaso-constrictor mechanism. B. Vaso-dilator mechanism. A. Vaso-constrictor Mechanism- — The fact that section of most nerves at once causes a dilatation of the arterioles 456 VETERINARY PHYSIOLOGY proves that they are constantly transmitting vaso- constrictor impulses from centres in the nervous system. (1) Course of the Nerves. — The course of these fibres has been investigated by section and by stimulation (lig. 191). They leave the spinal cord, chiefly in the dorsal region, by the anterior roots of the spinal nerves, pass into the sympathetic ganglia, where they have their cell stations, and then, as non- medullated fibres, pass, either («) along the various sym- pathetic nerves to the vis- cera, or (h) back through the grey ramus (see fig. 46, p. 106) into the spinal nerve, in which they run to their terminations. (2) Mode of Action of the Mechanism. — This mechanism is constantly in action, maintaining the tonic contraction of the arterioles. (a) Reflex Stimulation. — If any afferent nerve be stimulated the effect is to cause a general constriction of arterioles, and thus to raise the general arterial pressure. A central mech- anism therefore exists cap- able of reflex excitation. In ordinary conditions, so many afferent nerves are constantly being stimulated, that it is not easy to say how far the tonic action of this centre is reflex and dependent on the stream of afferent impulses. (6) Direct Stimulation. — The centre may undoubtedly Fig. 191. — Diagram of the Distribu- tion of Vaso-niotor Xerves. The continuous line shows the vaso- constrictors, the dotted line the vaso-dilators. C.iV., cranial nerves; Vag., vagus; T.S., thoracic sym- pathetic; A.S., abdominal sym- pathetic ; N.L., nerves to the leg. BLOOD VESSELS 4-57 be directly acted upon by the condition of the blood and lymph circulating through it. When the blood becomes charged with carbon dioxide, as in asphyxia, this centre is stimulated and a general constriction of arterioles with high blood pressure results (p. 548). The same thing happens as a result of a marked decrease in the amount of oxygen in the blood. This leads to an imperfect oxidation of such products as lactic acid, and to their accumulation in the blood, and this concentration of H ions stimulates the vaso- motor mechanism. (3) Position of the Centres. — (a) Primary Centre. — In investigating the position of the centre advantage may be taken of — 1st. Its constant tonic influence. Removal of the centre at once causes dilatation of the arterioles. 2nd. The fact that it may be reflexly stimulated. If the vaso-constrictor centre be removed, stimulation of an afferent nerve no longer causes constriction of the arterioles. Removal of the whole brain above the pons Varolii leaves the action of the centre intact. Separation of the pons Varolii and medulla oblongata from the spinal cord at once causes a dilatation of the arterioles of the body with a marked fall in arterial pressure, and prevents the production of reflex constriction by stimulation of an afferent nerve. The main part, at least, of the vaso-constrictor mechanism therefore is situated in the pons Varolii and medulla oblongata. The extent of this centre has been determined by slicing away this part of the brain from above downwards, and studving the influence of reflex stimulation after the removal of each slice. It is found that, at a short distance below the tectum, the removal of each succeeding part is followed by a diminution in the reflex constriction, until, at a point close to and just above the calamus scriptorius, all reflex response to stimula- tion stops. The centre is therefore one of very considerable longi- tudinal extent. (6) Secondary Centres. — It has been found that if, after 458 VETERINARY PHYSIOLOGY section of the spinal cord high up, the animal be kept alive for some days, the dilated arterioles again contract. If the spinal cord below the point of section be now destroyed, another marked fall of blood pressure occurs. This shows that secondary vaso-constrictor centres exist all down the grey matter of the spinal cord. Normally these are under the control of the dominant centre, but when this is out of action they then come into play. B. Vaso-dilator Mechanism. — A good example of a vaso- dilator nerve is to be found in the chorda tympani branch of the facial nerve, which sends fibres to the submaxillary and sublingual salivary glands. If this nerve be cut, no change takes place in the vessels of the glands, but, when it is stimulated, the arterioles dilate and allow an increased flow of blood through the capillaries. These fibres, therefore, instead of increasing the activity of muscular contraction, inhibit it. The gastric branches of the vagus carrying vaso- dilator fibres to the mucous membrane of the stomach, and the nervi erigentes carrying vaso-dilator fibres to the external genitals, are further examples of vaso-dilator nerves. 1. Course of the Fibres. — The vaso-dilator nerves of most parts of the body run side by side with the vaso-constrictor nerves, and hence curious results are often obtained. If the sciatic nerve of a dog be cut, the arterioles of the foot dilate. If the peripheral end of the cut nerve be stimulated, the vessels contract. But after a few days, if the nerve be pre- vented from uniting, the arterioles of the foot recover their tonic contraction. If the sciatic nerve be now stimulated, a dilatation, and not a constriction, is brought about. The vaso-constrictor fibres seem to die more rapidly than the vaso-dilator fibres which run alongside of them. Under certain conditions, the activity of the vaso-dilator fibres seems to be increased. Thus, if the sciatic nerve be stimu- lated when the limb is warm, dilatation rather than con- striction may occur. Again, while rapidly repeated and strong induction shocks are apt to cause constriction, slower and weaker stimuli tend to produce dilatation. The vaso-dilator nerves pass out chiefly by the anterior BLOOD VESSELS 459 roots of the various spinal nerves, and do not pass through the sympathetic gangha, but run as medullated fibres to their terminal ganglia (fig. 191). Bayliss has shown that the vaso-dilator fibres for the hind limb of the dog leave the cord by the posterior roots. Evidence has been adduced that dilatation can be brought about by irritation of the skin even after the posterior root is cut above the ganglion, but not when it is cut below it (p. 98). The possible action of this secondary vaso-dilator mechanism in the production of inflam- mation and of such trophic disturbances as shingles or herpes zoster is worthy of attention. The probable existence of &, 'peripheral vaso-dilator rtiech- anism indicated by the action of nitrites and of weak acids may be of importance in ex- plaining local dilatation of vessels during the functional activity of a part (p. 455). 2. Mode of Action. — {a) Reflex Stimulation. — This mechanism is not constantly in action, since section of a vaso-dilator nerve does not cause constriction. It may, however, be excited reflexly. Stir>iulatio7i of an afferent nerve causes a dilatation of the arterioles in the part from which it comes, and a con- striction of the arterioles throughout the rest of the body. If a sapid substance such as pepper be put in the mouth, the buccal mucous membrane and the salivary glands become engorged, while there is a constriction of the arterioles throughout the body. The vaso-dilator mechanism is not general in its action like the vaso-constrictor, but is specially related to the difterent parts of the body. Again, it has been shown that stimulation of the central end of the depressor nerve (superior cardiac branch of the vagus) causes a dilatation of the arterioles, chiefly in the Fig. 192. — To show Local Vaso- dilatation with General Vaso- constriction. S., skin; V.D., local vaso-dilator centre; V.C., vaso-constrictor centre. 460 VETERINARY PHYSIOLOGY abdominal cavity, but also throughout the body generally. This is the most generalised vaso-dilator reflex known (see p. 418). (6) Stimulation from the Cerebrum. — Not onlydoes peripheral stimulation thus act reflexly, but various states of the brain, accompanied by emotions, may stimulate part of the vaso- dilator mechanism, as in the act of blushing. The vaso-constrictors and vaso-dilators have a reciprocal action, and this is of the greatest importance in ph3'si- ology and pathology. It explains the increased vascularity of a part when active growth is going on. The changes in the part, or the products of these, stimulate the afferent nerve. This reflexh' stimulates the vaso-dilator mechanism of the part, and thus causes a free flow of blood into the capillaries, and, at the same time, maintains or actually raises the arterial pressure by causing a general constriction of the arterioles, and thus forces more blood to the situation in which it is required. It also explains the vascular changes in inflammation (fig. 192). This reciprocal action may be disturbed just as the reciprocal action of motor and inhibitory nerves in reflex action may be disturbed. The administration of strychnine, which in reflex action converts inhibitory into motor responses, also converts vaso-dilator into vaso-constrictor responses, while chloroform tends to convert vaso-constrictor into vaso-dilator actions. (3) Position of the Centres.— While the dominant vaso- constrictor centre is in the medulla, the vaso-dilator centres seem to be distributed in the medulla and spinal cord. The vagus is the great outgoing vaso-dilator nerve from the centres in the medulla, and the nervi erigentes, or pelvic nerves, from the sacral part of the cord. II. Pressure in the Capillaries. This may be determined (a) by finding the pressure required to blanch the skin or to occlude the capillaries of some transparent membrane, or (6) by inserting a hypodermic BLOOD VESSELS 461 needle connected with a reservoir of water and a manometer, and estimating the capillary pressure by the pressure required to drive the water into the subcutaneous tissue. The assumption is made that the pressure in the tissues is about equal to that in the capillaries. The movement of the water may be determined by watching the movement of a bubble of air in the tube (fig. 193). At the level of the heart the capillaries may be com- pressed by a pressure of some 10 to 20 mm. Hg, but in the leg about 90 mm. is required. It has already been shown that the pressure is less than in the arteries and greater than in the veins. Fig. 193.— Method of Estimating Capillary Blood Pressure (see text). Like the pressure in the arteries, the pressure in the capillaries depends upon the two factors — 1st. Force of inflow. 2nd. Resistance to outflow. It must be remembered that all the blood does not flow through capillaries, but that in many situations arterioles open directly into venules. Thus, in obstruction of the capillaries, the blood may find its way through to the veins. 1st. Variations in the Force of Inflow. — The capillary pressure may undergo marked local cnanges through the vaso-motor inechanism. Wherever the function of a part is active, dilatation of the arterioles and an increased capillary pressure exist, and, as has been already seen, the condition of the capillaries plays a part. But the capillary pressure may also be modified by the 462 VETERINARY PHYSIOLOGY A--. c V \ '; I ? Il !„;_. ^' ., c heart's action, inasmuch as the arterial pressure, by which blood is driven into the capillaries, depends upon this. In cardiac inhibition not only is arterial pressure lowered, but capillary pressure may also fall. In augmented heart action both arterial and capillary pressure are raised (fig. 194, B.). 2nd. Variations in Resistance to Outflow. — Normally the flow from capillaries to veins is free and unobstructed ; but, if the veins get blocked, or if the flow in them is retarded by gravity, the capillaries get engorged with blood. This in- creased pressure in the capillaries is very differ- ent from that caused by increased inflow. The flow through the vessels is slowed or may be stopped instead of being accelerated, and the blooil gets deprived of its oxygen and of its nourishing constituents, loaded with wast6 products, and tends to exude into the lymph spaces, causing dropsy (fig. 194, C). A very simihir condition results if the arterioles are contracted and the capillaries dilated ; the same stagna- tion of blood may occur. It is therefore most important to distinguish between high capillary pressure from dilated arterioles or an active heart, and high pressure due to venous obstruction. A condition very similar to that described, but producing a capillary pressure high relatively to the pressure in the arteries — though not absolutely high — is seen in cases of failure of the heart, when that organ is not acting sufficiently strongly to pass the blood on from the venous into the arterial system. Here the arterial pressure becomes lower and lower, the venous pressure higher and higher, and, along with this, the capillary pressure becomes high in relationship to Fig. 194. —The Changes in Blood Pressure in the Capillaries produced by increasing the arterial pressure , and by obstructing the venous flow . A., arteries ; G. , capillaries ; V. , veins. BLOOD VESSELS 463 the arterial pressure. The blood is not -driven through these channels, and congestion of the capillaries and dropsy may result. 3rd The influence of gravity plays a very important part on the capillary pressure, since it has so marked an influence on the flow of blood in the veins. At the level of the heart the pressure is about 20 mm. Hg. In the feet it is much higher. When, through heart failure or want of exercise, the blood is not properly returned from the legs, this increased pressure becomes very marked, stagnation of blood occurs, and swelling of the legs is apt to occur. ■ith. Volume of the Blood. — The pressure in the capillaries may also, to a certain extent, be varied by the ivithdrawal of ivater from the hotly, as in purgation or in diuresis, or by the addition of large quantities of fluid to the blood. In both cases there is a rapid readjustment by the passage of water from the tissues to the blood, or vice versa. The venous system is so capacious that very great changes in the amount of blood in the vessels may take place without materially modifying the arterial or capillary pressure. III. Pressure in the Veins. The pressure in the veins is so low that it may best be determined in the lower animals by a water manometer. In man it may be estimated in a prominent superficial vein by stroking the vein downwards from the peripheral side of a valve, applying the band of a Riva Rocci apparatus (p. 448), and then relaxing the pressure and allowing the blood to flow up into the emptied vein, and reading the pressure at which this occurs. It may also be estimated in the veins of the hand by finding at what level above the heart they collapse. In the veins the force of inflow is small ; the resistance to outflow is nil. Hence the pressure is low, and steadily diminishes from the small veins to the large veins entering the heart (fig. 183). The venous pressure may be modified by variations in these two factors. Constriction of the arterioles tends to lower the 464 VETERINARY PHYSIOLOGY venous pressure, dilatation to raise it. In the legs the veins are abundantly supplied with valves which support the long column of blood. When the veins of the legs become over- distended and the valves incompetent, the veins become large and tortuous and are known as varicose veins. The condi- tion is temporarily relieved by elevating the legs. Gorripression of the thorax retards the flow of blood from the great veins into the heart, and thus tends to raise the venous and to lower the arterial pressure. Venous pressure may be temporarily modified by the loss or gain of water, but the venous system is so capacious that it can accommodate a considerably increased volume of fluid without any marked rise of pressure. Further, there is a very rapid adjustment between the fluid in the vessels and in the tissues. IV. Pressure in the Lymphatics. No exact determination of the lymph pressure in the tissue spaces has been made, but, since there is a constant flow from these spaces through the lymphatic vessels and through the thoracic duct into the veins at the root of the neck, the pressure in the tissue spaces must be higher than the pressure in the great veins. This pressure is kept up by the formation of lymph from the blood, and from the cells of the tissues (see p. 508). B. FLOW OF BLOOD. The flow of blood, as already indicated, depends upon the distribution of pressure, a fluid always tending to flow from the point of higher pressure to the point of lower pressure. Since a high pressure is maintained in the aorta and a low pressure in the veins entering the heart and in the cavities of the heart during its diastole, the blood must flow through the vessels from arteries to veins {Practical Physiology). If for any reason the difference of pressure is decreased, the BLOOD VESSELS 465 rate of flow must be decreased. This occurs in various forms of heart failure, and when the heart has an insufficient supply of blood to contract upon. 1. Velocity. The velocity of the flow of a fluid depends upon the width of the channel. Since in unit of time unit of volume must pass each point in a stream, if the fluid is not to accumulate at one point, the velocity must vary with the sectional area of the channel. In other words, the velocity (V) of the stream is equal to the amount of blood passing any point per second (v) divided by the sectional area of the stream (S) — V Avhere S is the radius squared multiplied by the constant 3-14. In the vascular system the sectional area of the aorta is small when compared with the sectional area of the smaller arteries ; while the sectional area of the capillary system may be no less than 700 times greater than that of the aorta. In the venous system the sectional area steadily diminishes, although it never becomes so small as in the corresponding arteries, and, where the great veins enter the heart, it is about twice the sectional area of the aorta (fig. 195). This arrangement of the sectional area of the vascular system gives rise to a rapid flow in the arteries, a somewhat slower flow in the veins, and a very slow flow in the capillaries. The suddenness of the change of pressure has a certain influence on the rapidity of flow, as is well seen in a river. If from any cause the pressure is raised at one point, the flow will tend to be more rapid from that point onwards till the normal distribution of pressure is re- established. When the difference between the pressure at the arterial end and at the venous end of a set of capillaries is increased, a more rapid flow of blood takes place through the tissues. 30 466 VETERINARY PHYSIOLOGY Friction has also a certain etfect. A river runs much faster in mid -stream than along the margins, because near the banks the flow is delayed by friction, and, the more broken up and subdivided is the channel, the greater is the friction and the more is the stream slowed. In the capillary system considerable resistance is offered by friction in the innumerable small channels, and this is markedly influenced by the viscosity of the blood (p. 475). Measurement of Velocity. — The velocity of flow in the arteries and veins may be measured by various methods, of A R / --:-r"' \ \ \ c V Fig. 195. — Diagram of the Sectional Area of the Vascular System, upon which the velocity of the flow depends. A.R., arteries; C, capillaries ; V. , veins. which one of the best is that by means of the strovuchr, an instrument by which the volume of blood passing a given point in an artery or vein in a given time may be deter- mined (Practical Physiology). The velocity of the flow in the capillaries may be measured in transparent structures by means of a microscope with an eye-piece micrometer. The velocity of the blood varies greatly but is roughly as follows : — Carotid of the dog about . . 300 mm. per sec. Capillaries about . . . O'S to 1 m. ,, Veiu (jugular) about . .150 mm. BLOOD VESSELS 467 Definite figures for the velocity of the lymph stream cannot be given. Disturbance of any of the factors which govern the rate of fiow will bring about alterations in the velocity of the blood in arteries, capillaries, and veins. 2. Special Characters of Blood Flow. (a) Arteries. — This may be investigated by a hcemodromo- graph, which consists of a paddle suspended in a box. By means of a tube at each end the box is inserted into the course of an artery, and with each acceleration of the flow the paddle is pressed forward. The movements of the other end of the paddle are recorded through a tambour on a cylinder. The flow of blood in an artery is rhythmically accelerated with each ventricular systole. This is due to the pulse wave. As the wave of high pressure passes along the vessels, the blood tends to flow first forwards and then backwards from it — so that in front of the wave there is an acceleration of the stream and behind it a retardation, just as occurs in a wave at sea. (b) Capillaries. — In the capillaries the flow is uniform, unless when in excessive dilatation of the arterioles the pulse wave is propagated to them. (c) Veins. — In most veins the flow is uniform, but in the great veins near the heart it undergoes acceleration — l.?;", with each diastole of auricle and of ventricle (p. 444) ; 2nd, with each inspiration (p. 447). In all vessels, the blood in the centre of the stream moves more rapidly than that at the periphery on account of the friction between the blood and the vessels. This rapid " axial " and slow " peripheral " stream is well seen in a small vessel placed under the microscope. The erythrocytes are chiefly carried in the axial stream, while the leucocytes are more confined to the peripheral stream, where they may 468 VETERINARY PHYSIOLOGY be observed to roll along the vessel wall with a tendency to adhere to it. When, from any cause, the flow through the capillaries is brought to a standstill, the leucocytes creep out through the vessel walls and invade the tissue spaces. This is the process of diapedesis, which plays an important part in inflammation. C. SPECIAL CHARACTERS OF THE CIRCULATION IN CERTAIN SITUATIONS. 1. Circulation Inside the Cranium (tig. 196). — Here the blood circulates in a closed cavity with rigid walls, and there- fore its amount can vary only at the expense of the cerebro- spinal fluid (p. 511). This is small in amount, some 150 c.cm., and permits of only small variations in the volume of blood. Increased arterial pressure in the body does not therefore markedly increase the amount of blood in the brain, but simply drives the blood more rapidly through it. There seems to be no regulating nervous mechanism connected with the arterioles of the brain, and the cerebral pressure simply follows the changes in the general arterial pressure. The splanchnic area is the great regulator of the supply of blood to the brain. Since the cerebral arteries are supported and prevented from distending by the solid wall of the skull, the arterial pulse tends to be propagated into the veins. In these veins the respiratory pulse also is very well marked. The condition of the intra-cranial circulation is indicated by the circulation in the fundus of the eye which communicates with it, and this may be observed by means of an ophthalmoscope (p. 143). 2. Circulation in the Lungs — The action of the vaso-con- strictor nerves is feeble, and adrenalin fails to cause a constriction of the arterioles. The amount of blood in the lungs is regulated by the blood pressure in the systemic vessels, and hence the intravenous administration of adrenalin, BLOOD VESSELS 469 by increasing the arterial pressure, drives more blood to them. The circulation through the lungs is impeded in many cases of heart disease, and especially in mitral stenosis INTRACRANIAL CIRCULATION PULMONARV CIRCULATION ABDOMINAL CIRCULATION Fig. 196. — Scheme of the Circulation, modified from Hill, to illustrate the influence of the various extra-cardiac factors which maintain the flow of Vjlood. (p. 410), and a condition of 'passive congestion is set up, which may lead to h;eraorrhage from the lungs. 3. Circulation in the Heart Wall. — The sympathetic fibres are vaso- dilator not vaso-constrictor to the arterioles of the coronary vessels and the administration of adrenalin dilates these arterioles. 4. Circulation in the Spleen. — Here the blood has to flow through a labyrinth of large sinusoid capillaries in the 470 VETERINARY PHYSIOLOGY pulp, and it is driven on by the alternate contraction and relaxation of the non-striped muscle in the capsule and trabeculse (see p. 215). 5. Bone-Marrow. — The tissue is surrounded by rigid bony walls, and the amount of blood can vary only slightly. The circulation is through sinusoid capillaries. D. EXTRA-CARDIAC FACTORS MAINTAINING CIRCULATION. The central pump, the heart, is not the only factor main- taining the flow of blood through the vessels (flg. 196). 1. Movements of Respiration. — (i.) The thorax, in the movements of respiration, is a suction pump of considerable power, which draws blood into the heart during inspiration. The auricles may be regarded as the cisterns of the heart, the abdominal ;blood-vessels as the great blood reservoir, and the diaphragm, contracting in inspiration, presses the blood from this reservoir up into the thorax and heart. (ii.) Expiration also helps, for the blood, which has filled the vessels of the lungs in inspiration, is driven on into the left side of the heart in expiration. The blood is thus forced on into the arteries. The respiratory movements apparently play a great j)art in maintaining the circulation when the heart has undergone extensive calcareous degeneration. 2, Intermittent Muscular Exercise. — This acts in three ways: (1) by increasing the respiratory movements; (2) by augmenting the action of the heart ; (3) by the contract- ing and relaxing muscles pressing on the blood-vessels, and so forcing the blood onwards into the veins and to the heart, back-flow in the veins being prevented by the valves ; (4) by the increased venous filling of the heart leading to stronger contractions fp. 417), and reflexly to acceleration (p. 421). The arterial blood pressure is thus raised and the intra- cranial circulation accelerated, so that more blood is sent to the brain. Too marked a rise of pressure during such exercise is prevented by dilatation of the arterioles throughout the body. BLOOD VESSELS 471 In sustained muscular strain the thorax is fixed, and hence, (a) at first (1) the pressure on the heart and thoracic organs is raised, and the increased pressure in the thorax helps to support the heart and to prevent over-distension. (2) The rigid thorax prevents the blood being sucked into the heart by the respiratory movements. (3) The abdominal vessels are pressed upon by the contraction of the abdominal muscles, and the blood is pressed on to the heart, while the sustained contraction of the limb muscles tends to prevent the free flow of blood through the capillaries. Arterial pressure is thus raised, and the blood is forced to the central nervous system in which the pressure rises, and, if a weak spot in the vessels is present, rupture is apt to occur. (b) Later, if the strain is still further sustained, the high intra-thoracic pressure tends to prevent proper diastolic filling of the heart, and the pumping action of respiration is in abeyance. The abdominal vessels being pressed upon prevents the free flow of blood through them to the heart, and the venous inflow fails and the force of contraction of the heart decreases. Thus, less blood is sent to the arteries and the arterial pressure falls, less blood goes to the brain, and fainting may result (see below). E. INFLUENCE OF POSTURE ON CIRCULATION. In the "head down" position, as in the horse in drinking, the accumulation of blood in the head is prevented by the vessels being packed inside the skull, and in the right side of the heart by the supporting pericardium. In man, in the erect posture, the position of the abdominal reservoir of blood at a lower level than the heart increases the work of that organ. Especially is this the case with animals, in which the abdominal wall is lax, so that the blood can accumulate in the abdominal vessels, e.g. rabbits bred in confinement. In these, failure of the heart or fainting may occur when they are placed in the " head up " position. In the normal position of quadrupeds the work is much easier, for the reservoir is on the same level as the pump. 472 VETERINARY PHYSIOLOGY F. FAINTING. This is a sudden loss of consciousness produced by failure in the supply of blood to the brain. It is accompanied by loss of control over the muscles. It may be induced by any sudden lowering of the arterial blood pressure, whether due to decreased inflow of blood or to decreased peripheral resistance. 1. Decreased inflow may be caused by — (1) Cardiac inhibition brought about reflexly (a) by strong stimulation of ingoing nerves, and more especially of the nerves of the abdomen ; (b) by strong stimulation of the upper brain neurons accompanied by changes in the consciousness of the nature of emotions — (2) Failure of the heart to pump blood from veins to arteries against the force of gravity, as when a hutch rabbit is held in the " head up " position for some time. 2. Decreased resistance to outflow through sudden dilatation of arterioles may result from changes in the upper brain neurons, sometimes as a result of digestive dis- turbances. However induced, the anaemic state of the brain leads to a stimulation of the cardio-inhibitory centre and the condition is thus accentuated. In man the cerebral anaemia is accompanied by pallor of the face. The treatment consists in depressing the head to allow the force of gravity to act in filling the cerebral vessels and in giving diffusible stimulants to increase the action of the heart. G. THE TIME TAKEN BY THE CIRCULATION. This has been determined by injecting ferrocyanide of potassium into the proximal end of a cut vein, and finding how long it took to appear in the blood flowing from the distal end. From observation in the horse, dog, and rabbit, it appears that the time corresponds to about twenty-seven beats of the heart, so that in man it should amount to about twenty-three seconds. BLOOD VESSELS 473 H. FLOW OF BLOOD THROUGH DIFFERENT ORGANS. This may be studied — (-4) In lower animals in the following ways : — (1) By use of the Stromuhr (p. 466) ; (2) by the plethysmo- graph method. This consists in enclosing the organ in a plethysmograph, and, while the blood is flowing, clamping the vein for a very brief period. The organ expands according to the amount of blood which flows in, and the increased volume gives a measure of the blood flow. The vein is again undamped, and the observation may be repeated. In lower animals it has been found that the flow of blood through different organs when measured per 100 grm. of organ per minute is very different, in the stomach only about 21 c.c, in the kidney, 150 c.c, and in the thyreoid no less than 5 60 c.c. (8) The time taken by the blood to pass through an organ may be determined by injecting some electrolyte, e.g. NaCl solution, into the artery, and measurmg the electrical conductivity of the blood in the vein by means of a Wheatstone's bridge. When the salt solution reaches the vein this is increased. SECTION V. The Fluids carrying Nourishment to the Tissues. BLOOD AND LYMPH. The blood carries the necessary nourishment to the tissues, and receives their waste products. But it is enclosed in a closed system of vessels, and does not come into direct relationship with the cells. Outside the blood-vessels, and bathing the cells, is the lymph which plays the part of middleman between the blood and the tissues, receiving nourishment from the former for the latter, and passing the waste from the latter into the former. A. BLOOD. TJie physical, chemical and histological characters of blood must he investigated practically. I. General Characters. Colour. — Blood, when it has stood for some time, is dark purple, but when shaken with air it assumes a bright cinnabar red colour. Elements of Blood. — Microscopic examination shows that blood is composed of a clear fluid (Liquor Sanguinis or Plasma) in which float myriads of small disc-like yellowish-red cells (Erythrocytes), a smaller number of greyish cells (Leucocytes), and certain very minute grey particles (Blood Platelets). The Opacity of Blood is due to the erythrocytes, and, when the pigment is dissolved out of them by water and they are rendered transparent, the blood as a whole becomes transparent and is said to be "laked" (p. 485). The Specific Gravity is about 1055. It BLOOD 475 may be estimated by finding the specific gravity of a solution of sodium sulphate or of chloroform and benzene in which a drop of blood remains where it is placed, neither sinking nor floating. The lowering of the freezing-point of blood or A is 0-o6 C. This is equivalent to the osmotic pressure of a solution of about 9 per cent, of NaCl and is the same as that of the cells of the tissues. Viscosity— The viscosity of blood, or the intermolecular and intermolar friction, may be measured by the time taken to pass through a given length of capillary tube compared by the time taken by water. It depends partly on the viscosity of the plasma, which, being of the nature of an emulsoid colloid, manifests viscosity, but chiefly upon the blood cells. Hence when these are diminished in number the viscosity of the blood is decreased. The Taste and Smell are characteristic, and must be experienced. Reaction. — Blood, so far as the balance of H and OH ions is concerned, is slightly alkaline, its hydrogen ion concentration, Cjj, being lower than that of pure water (see Appendix ni.). The cells of the blood constitute about 33 per cent., one- third of its weight, and the total sohds of the blood are about 20 per cent. II. Clotting or Coagulation. Blood, when shed, becomes a firm jelly in the course of three or four minutes. The primary object of the process is to seal wounds in the blood-vessels, and so to prevent haemorrhage. When the blood is collected in a beaker or other dish, the process starts from the sides, and spreads throughout the blood until, when clotting is complete, the dish may be inverted without the blood falling out. In a short time, drops of clear fluid appear upon the surface of the clot, and, in a few hours, these have accumulated and run together, while the clot has contracted and drawn away from the sides of the vessel, until it finally floats in the clear fluid — the Serum. If clotting occurs slowly, e.g. when the shed blood is cooled, the erythrocytes subside, leaving a layer of clear plasma above, which, when coagulation takes place, forms a " bufty coat " in the upper part of the clot. 476 VETERINARY PHYSIOLOGY Clotting is due to changes in the plas'ina, since this fluid will coagulate in the absence of corpuscles. The change may be represented thus : — Blood I Plasma I 1 I Serum Clot Corpuscles The change consists in the formation of a series of fine elastic threads of fibrin throughout the plasma, and, if red corpuscles are present, they are entangled in the meshes of the network and give the clot its red colour. These threads may be readily collected in mass upon a stick with which the blood is whipped as it is shed. The red fluid blood which is left, consisting of blood cells and serum, is said to be dejibrinated. Blood Plasma I .1. I Fibrin Serum Corpuscles Defibrinated Blood A study of clotting blood by means of the ultra- microscope shows that the fibrin first separates as small acicular particles which run together to form threads. Fibrin is a protein substance. It is slowly dissolved in solutions of neutral salts. It is coagulated by heat, and is precipitated when an excess of a neutral salt is added. It therefore belongs to the group of globulins. The plasma, before clotting, and the serum, squeezed out from the clot, both contain in the same proportions an albumin (serum albumin) and a globulin, or series of globulins, which may be classed together as serum globulin. But the BLOOD 477 plasma contains a small quantity — about 0'4 per cent. — of another globulin (fibrinogen) which coagulates at a low- temperature, and which is absent from serum. It is this which undergoes the change from the soluble form to the insoluble form in coagulation. If, by taking advantage of the fact that it is more easily precipitated by sodium chloride than the other proteins, it is separated from them, it may still be made to clot. The source of this substance seems to be the intestine and liver, and when these are removed it is not formed. The essential points in coagulation were discovered by Andrew Buchanan in 184.5. He showed that something which he called "soluble fibrin" exists in the plasma and that this changes to insoluble fibrin. He further showed that the addition of the white cells of the blood brings about the change. The process of clotting is due to the action of a substance, thrombin, Avhich does' not exist as such in the blood, but which is formed by the union of a precursor with calcium ions. This is proved by the fact that if blood is directly collected in alcohol, it is found to yield no thrombin, although when treated with alcohol after clotting it is rich in this substance. Its precursor may be called prothrombin. If calcium salts are precipitated by the addition of oxalates to the blood, clotting does not take place. The mere conversion of the calcium from an ionised state to a non-ionised state, such as that in which it exists in the citrate, prevents clotting. Hence, when unclotted blood is wanted, it may be collected in a vessel containing some potassium oxalate or a solution of sodium citrate {Chemical Physiology). Although prothrombin and calcium ions exist together in the blood, they do not form the thrombin necessary to produce clotting, apparently because an anti-prothrombin is also present. This may be separated from fibrinogen and from prothrombin by heating the plasma to 60° C, which pre- cipitates the fibrinogen and destroys the prothrombin, but leaves the antithrombin unaltered. Before clotting can occur, antithrombin must be thrown 478 VETERINARY PHYSIOLOGY out of action by the development of some substance which neutralises it. Such a substance is yielded by the breaking down of tissue cells or the cells of the blood, especially the platelets. It is perhaps best called thromboplastin. It is a lipoid compound, probably identical with cephalin. The steps in the process might thus be represented as follows : — {From Cells) {In Plasma) Prothrombin .S Calcium Ions Thromboplastin^ Many circumstances influence the rapidity of clotting. Tem- perature has a marked effect, a low temperature retarding it, a shght rise of temperature above the normal of the particular animal accelerating it. If a trace of a neutral salt be added to blood, coagulation is accelerated ; but if blood be mixed with strong solutions of a salt, coagulation is prevented because the formation of thrombin is checked. Calcium salts have a marked and important action, and if they are precipitated by the addition of potassium oxalate, blood will not clot, apparently because thrombin cannot be formed. The injection into the blood-vessels of a living animal of commercial 'peptones, which consist chiefly of proteoses, generally prevents the blood from clotting when shed. This appears to be due to the formation, probably in the liver, of an excess of anti-thrombin. Hirudin, an extract of the head of the medicinal leech, also retards clotting, both when injected into the blood-vessels and when added to the blood BLOOD 479 when shed. It appears to be of the nature of an anti- thrombin. The blood does not coagulate in the vessels under normal conditions because of the absence of thromboplastin in any quantity and the presence of anti-thrombin. Under certain conditions clotting does take place. (1) If inflammation is induced in the course of a vessel, coagulation occurs rapidly. (2) If the inner coat of a vessel be torn, as by a ligature, or if any roughness occurs on the inner wall of a vessel, coagulation is apt to be set up. (3) Various substances injected into the blood stream may cause the blood to coagulate, and thus rapidly kill the animal. Among such substances are extracts of various organs — thymus, testis, and lymph glands, which yield thromboplastin — and snake venom, which seems to contain active thrombin. The injection of pure thrombin does not usually cause clotting, apparently because an anti-thrombin is developed to neutral- ise it. The blood usually clots wlien shed, because the damaged tissues yield thromboplastin, and thus thrombin is formed. This acts upon the fibrinogen before it can be antagonised by the anti-thrombin. If blood is received into oil, or into a vessel anointed with vaseline and filled with paraflSn oil, it will remain fluid for a considerable time. Any roughness in the wall of the blood-vessel or of the vessel in which the blood is received probably serves to catch the blood platelets (p. 484), so that thromboplastin is liberated freely as they disintegrate. III. Plasma and Serum. These may be considered together, since serum is merely plasma minus fibrinogen. As serum is so much easier to procure, it is generally employed for examination, but plasma may be readily obtained by centrifuging blood which has been prevented from clotting by the addition of an oxalate or a citrate (p. 477). Both are straw-coloured fluids, the colour being due to a yellow lipochrome. Sometimes they are clear and trans- 480 VETERINARY PHYSIOLOGY parent, but, after a fatty diet, they become milky. They have a specific gravity of about 1025, and contain about 90 per cent, of water and 10 per cent, of solids. The chief solids are the native proteins — serum albumin and serum globulin (with, in the plasma, the addition of fibrinogen). The proportion of the two former proteins to each other varies considerably in different animals, but the variations are small in the same animal at diiTerent times. The globulin probably consists of at least two bodies— euglobulin precipitated by weak acid, and pseudoglobulin not so pre- cipitated. The amount of albumin is generally greater when the body is well nourished. In man they together form about 7 per cent, of the serum. In virtue of the presence of these proteins the plasma is colloidal, and it has little tendency to transude through the walls of the vessels. These proteins further seem to have a small osmotic pressure (p. 574). The other constituents of the serum are in much smaller amounts, and may be divided into — 1 . Substances to be used by the tissues. Glucose is the most important of these. It occurs only in small amounts — about O'l to O'lo per cent. Part of it is free, but part is probably in combination. It is present in larger amount in blood going to muscles than in blood coming from them, and this difference seems to be more marked when the muscles are active. Fats occur in very varying amounts, depending upon the amount taken in the food, but in addition to these true fats there is also a small amount of other lipoids. 2. Substances given off by the tissues. The chief of these is urea, which occurs constantly in very small amounts in the serum — about '05 per cent. It will afterwards be shown that it is derived from the liver, and that it is excreted in the urine by the kidneys (p. 559). Creatin and uric acid, and some allied bodies, appear to be normally present in traces, and their amount may be increased in diseased conditions, especially of the kidneys. 3. Inorganic constituents. — The most abundant is chloride of BLOOD 481 sodium, to which the osmotic pressure of the plasma is partly due, and which is present in the proper proportion of sodium with the other cations, potassium, calcium, and magnesium, to maintain the activity of the tissues (p. 218). Perhaps the most important salt is sodium bicarbonate, which maintains the reaction, the Cg (see Appendix III.) of the blood, and of the body fluids, at the level at which their chemical activity can best be carried on. Sodium pbos- pbate is also present in very small quantities. Calcium, potassium, and magnesium occur in very small amounts. Sodium bicarbonate is an ideal salt for maintaining the balance of H and OH ions in the blood. When stronger acids, such as sarcolactic acid, are liberated from the tissues, they combine with some of the sodium, and the weak, slightly dissociated COo is set free, and is at once got rid of by the lungs (p. 5 27). When, on the other hand, alkalies are absorbed and added to the blood, there is available in the tissues an abundant supply of CO,, with which they will combine as bicarbonates. The maintenance of the propor- tion of NaHCOg in the blood is of the utmost importance. It may be termed its alkaline reserve. Only when this alkaline reserve is drawn upon can anything like a real condition of acidosis, a real increase in the C^, occur. This has been termed an uncompensated acidosis, to distinguish it from the condition in which an increased production of acids has been met by the alkaline reserve {compensated acidosis). In venous blood there are something like 60 parts of CO., per 100 parts of blood. Of this, at the temperature of the body and the pressure of CO, in the lungs to which the blood is subjected (p. 539), some 3 parts are dissolved; the remainder is in combination with sodium as NaHCOg, so that the balance is H.COg _ 3 _ J^ NaHCOg ~ 60 ~ 20' If the amount of CO., is increased, then it must either be got rid of from the lungs, or the proportion of Na in the denominator must be increased, while if the Na is combined 31 482 VETERINARY PHYSIOLOGY with other acids, such as /3-oxybutyric, then the amount of CO2 must be decreased. The proteins of the blood are amphoteric, and it has been suggested that they too may combine with COg. The protein of the pigment of the red cells does seem to form such a combination. This will be considered later. Behind the regulation of the Cjj of the blood by the NaHCOg and the lungs are two further lines of defence. 1. The dissociated HCl of the NaCl of the plasma can, Avhen the Cjj of the blood increases, pass into the cells and, seizing upon some of the sodium of the NajHPO^ turn out NaH2P04 into the plasma to be excreted by the kidneys. Thus some of tlie excess H ions is got rid of. Plasma H2CO3 + NaCll^NaHCOs + HCl Cell Wall Cell HCl + Na„HP04^NaHoP0, + NaCl I Plasma In fact, the kidneys play a part only second to the lungs in regulating the Ch of the blood by getting rid of any excess of H ions in acidosis and of OH ions in alkalosis. 2. With any increase of the H ions and the development of acidosis, the ammonia, which is in the liver normally converted into urea, is passed into the blood to unite with and neutralise the acids (p. 360). BLOOD 488 IV. Cells of Blood. 1. Leucocytes— White Cells. These are much less numerous than the red cells, and their number varies enormously in normal conditions. On an average there are about 7500 per cubic millimetre. {The method of counting must be studied 'practically.) They are soft, extensile, elastic, and sticky, and each contains a nucleus and a well-developed double centrosonie. In size they vary considerably, most being larger than the red cells, some slightly smaller. The character of the Fio. 197.— Cells of the Blood, a, erythrocytes ; b, large, and c, small lym- phocyte ; d, polymorpho-nuclear leucocyte ; e, eosinophil leucocyte. nucleus varies greatly, and from this and from variations in the protoplasm, they may be divided into three classes. (1) Lymphocytes. — Cells with a clear protoplasm and a more or less circular nucleus. Some are very small, while others are larger. They constitute about 20 to 25 per cent, of the leucocytes (fig. 197, 6 and c). (2) Polymorpho-nuclear leucocytes have a much-distorted and lobated irregular nucleus and a finely granular proto- plasm whose granules stain with acid and neutral stains. These constitute about 70 to 7 5 per cent, of the leucocytes (fig. 197, cZ). ,.1 (3) Eosinophil or oxyphil leucocytes have a lobated nucleus 484 VETERINARY PHYSIOLOGY like the last, but large granules in the protoplasm which stain deeply with acid stains. From 1 to 4 per cent, of the leucocytes are of this variety (fig. 197, e). Basophil leucocytes are practically absent from normal blood. They have a lobated nucleus and granules in the protoplasm staining Avith basic stains. Myelocytes are large leucocytes with a large circular or oval nucleus and a finely granular protoplasm. They are not normal constituents of the blood, but appear when the activity of the bone-marrow is increased in certain patho- logical conditions. The leucocytes show — (a) Amoeboid movement. — Under suitable conditions they undergo changes in shajie, as may be readily seen in the blood of the frog or other cold-blooded animal. The motion may consist simply of the pushing out and withdrawal of one or more processes (pseudopodia), or, after a process is extended, the whole corpuscle may follow it and thus change its place, or the corpuscle may simply retract itself into a spherical mass. As a result of these movements the corpuscles, in certain conditions, creep out of the capillary blood-vessels between the endothelial cells and wander into the tissues {diapedesis). The amoeboid movement is best marked in the polymorpho-nuclear leucocytes. (b) Phagocyte Action. — The linely granular leucocytes and the lymphocytes have further the power of taking foreign matter into their interior, and of digesting it. By this devouring action useless and effete tissues are removed and dead micro-organisms in the body are taken up and got rid of. This scavenger action of the leucocytes is of vast importance in pathology. 2. Blood Platelets. These are small circular or oval discoid bodies about one-third the diameter of a red blood corpuscle. Some observers have stated that they contain a central nucleus. They are very sticky and mass together when blood is shed and adhere to a thread passed through the blood or to any rough point in the lining of the heart or vessels. They BLOOD 485 there form clumps, and in these they disintegrate, probably liberating thromboplastin, and so start clotting. They are present in the blood of mammals only. Their source is not definitely known, but it has been suggested that they are the extruded nuclei of developing erythrocytes, or that they are derived from the giant cells of the bone-marrow (p. 500). 3. Erythrocytes— Red Cells. 1. Characters. — All mammals, except the camels, have circular, biconcave, discoid erythrocytes, which, when the blood is shed, tend to run together like piles of coins. The camels have elliptical biconvex corpuscles. The fully developed mammalian erythrocytes are without a nucleus. In birds, reptiles, amphibia and fishes, the corpuscles are elliptical biconvex bodies, with a well-marked central nucleus. 2. Size. — The size of the human erythrocytes is fairly constant — on an average 5-5 micro-millimetres in diameter. 3. Number. — The number of red cells in health is about 7,000,000 in the horse, but in disease it is often decreased. The number of corpuscles per cubic millimetre is estimated by the Haemocytometer. This consists of (1) a pipette by which the blood may be diluted to a definite extent with a salt solution of the same osmotic equivalent as the plasma, and (2) a cell of definite depth ruled in squares,' each containing above it a definite small volume of blood, so that the number of corpuscles in that volume may be counted under the microscope (Practical Physiology). The pale yellow colour of the individual corpuscles is due to a pigment held in a fine sponge-like stroma which seems also to form a capsule round the cell. 4. Haemolysis. — This pigment may be dissolved out by various agents, and the action is termed haemolysis. It may be brouglit about in different ways — 1st. By placing the erythrocytes in a fluid of lower osmotic equivalent, i.e. of lower molecular concentration, than the blood plasma and corpuscles. A solution of 0'9 per cent, of sodium chloride has the same osmotic equivalent as the plasma and preserves the corpuscles unaltered ; in more dilute fluid the corpuscles tend to swell up by 486 VETERINARY PHYSIOLOGY endosmosis, the capsule bursts, and the pigment escapes. Erythrocytes may therefore be used as a means of determin- ing the osmotic equivalent — the molecular concentration — of a fluid. 2nd. By the action of substances which dissolve the lipoids of the stroma, e.g. salts of the bile acids (see p. 324), chloroform, ether, etc. ord. By Hsemolysins. («) The serum of each species of animal contains a substance, destroyed by heating to 5 5' C, which is hsemolytic to the blood of animals of other species, e.g. the serum of eels' blood contains a powerful ha3molysin for rabbits' erythrocytes, and the serum of the dog a less powerful one. (6) Further, by injecting the blood or the erythrocytes of one species of animal into another species, a hsemolysin is developed which has a specific action on the erythrocytes of the first species (p. 614), Mh. By killing the erythrocytes in the body by inject- ing substances which poison them, such as phenylhydrazin. They are subsequently disintegrated and their pigment removed. This, of course, is not a true hiemolvsis. 5. Chemistry. — (1) The stroma of the erythrocytes which is left after the pigment is washed out is a sponge work made up of a globulin-like substance, in which lipoids, such as cholesterol and lecithin, occur in considerable quantities, and seem to form a capsule or cell membrane. Potassium is the base most abundantly present in man. (2) Haemoglobin. — The pigment is HaBmoglobin. It con- stitutes no less than 90 per cent, of the solids of the erythrocytes. In many animals, e.g. the rat, when dissolved from the corpuscles, it crystallises very readily {Chemical Physiology). The crystals prepared from human blood are rhombic plates. When exposed to air they are of a bright red colour, but if placed in the receiver of an air- pump at the ordinary temperature they become of a purplish tint. The same thing occurs if the haemoglobin is in solution, or if it is still in the corpuscles. The addition of any reducing agent such as ammonium sulphide or a ferrous BLOOD 487 salt causes a similar change. This is due to the fact that hannoglohin has an acuity for oxygen, which it takes up from the air, forming a definite compound of a bright red colour in which one molecule of haemoglobin links with a molecule of oxygen, HbO,. This is known as oxy haemoglobin. Haemoglobin is closely allied to the proteins, but differs from them in containing 0-42 per cent, of iron in organic combination. When light from the sun is allowed to pass through solutions of blood pigments, certain parts of the solar spectrum are absorbed, and when the spectrum is examined, dark bands — the absorp- tion bands — are seen. In a weak solution of oxy- haemoglobin in a thin layer, a dark band is seen in the green and another in the yellow part of the spectrum between Frauenhofer's lines D and E, while the violet end of the spectrum is absorbed (fig. 199). These bands may be broadened or narrowed by strengthening or weakening the solution, or varying the thickness of the layer. In stronger solutions they become broader and finally run together, while more and more of the violet end of the spectrum is absorbed, until, with a solution of sufhcient strength, only the red end of the spectrum is visible (fig. 198). When the oxygen is taken away and the dark reduced hsemoglobin is formed, a single broad band between D and E takes the place of the two bands (fig. 199). If the solution is again shaken up with air, oxygen is taken up and the bands of oxyhsemoglobin reappear {Chemical Physiology). The property of taking oxygen from the air and of again giving it up at a moderate temperature and under a low aCB D Eb F Oh Fic. 198. — The parts of the specirum absorbed by solutions of oxyhfemo- globin of different percentage strengths in a layer of 1 cm. thick. 488 VETERINARY PHYSIOLOGY pressure of oxygen is the great function of the blood pigment in the body. The hcemoglobin plays the part of a middle- man betiueen the air and the tissues, taking oxygen from the one and handing it on to the other (Chemical Physi- ology). Amount- — Haemoglobin constitutes about 13 or 14 cent, of the blood, but in various decreased. or i 4 per its amount is Carbon-monoxide ~| Hsemoglobiu . V Osyhaemoglobin . J Haemoglobin. Methasmoglobin . Acid Hsematin . Carbon - dioxide Hasmodobin . Reduced Alkali Haematin . Yellow. D Gkekn. Blue. m il ;i^ Pi^ Fig. 199. —Spectra of the more important Blood Pigments and their more important derivatives. (The spectra of oxyhaemoglobin and carbon monoxide haemoglobin and those of acid hiematin and methrerno- globin are not identical.) The arrows indicate that oxyhemoglobin and meth:iimoglobin are changed to htemoglobin by reducing agents. The best method of estimatmg its amount is by Haldane's Hsemoglobinometer. This consists of two tubes of uniform calibre, one filled with a 1 per cent, solution of normal blood saturated with carbon monoxide, and another containing water in which 20 c.mm. of the blood to be examined, measured in a pipette, are placed, mixed with coal gas to saturate with CO, and then diluted till it has the same tint as the standard tube. The percentage of haemoglobin, in terms of the normal, is indicated by the mark on the tube at which the fluid stands {Chemical Physiology). BLOOD 489 Derivatives of Haemoglobin. — The following pigments are derived from luemoglobin : — (1) Methsemoglobin. — Haemoglobin forms another com- pound with oxygen — methtemoglobin ; a substance which must be acted on by strong reducing agents before it will part with its oxygen. When, therefore, this pigment is formed in the body, the tissues die from want of oxygen. It may be produced by the action of various substances on oxyhemoglobin. Among these are ferricyanides, nitrites, and permanganates. It crystallises in the same form as oxyhasmoglobin, but it has a chocolate brown colour. Its spectrum is also different from haemoglobin and oxyhaemo- globin, showing a narrow sharp band in the red part of the spectrum, with two or more bands in other parts according to the reaction of the solution in which it is dissolved (fig. 199). It is of importance, since it occurs in the urine in such pathological conditions as 'paroxysmal methcemo- glohinuria. (2) Carboxyhaemoglobin. — Hemoglobin also combines with some other gases. Among these is Carbon monoxide, CO. Haemoglobin has a greater affinity for this gas than it has for oxygen, so that, when carbon monoxide haemoglobin is once formed in the body, the blood has little power of taking up oxygen, and the animal dies. Carbon monoxide is evolved freely in the fumes from burning charcoal, is present in coal gas, and is found in the air of coal mines after explosions. Carbon monoxide hemoglobin forms crystals like oxyhemoglobin, and has a bright pinkish red colour, without the yellow tinge of oxyhemoglobin. Since, after death it does not give up its carbon monoxide and become changed to purple hemoglobin, the bodies of those poisoned with the gas maintain the florid colour of life. Its spectrum is very like that of oxyhemoglobin, the bands being slightly more to the blue end of the spectrum (fig. 199). It maybe at once distinguished by the fact that when gently warmed with ammonium sulphide it does not yield reduced hemo- globin {Chemical Physiology). (3) Nitric oxide, NO, has even a greater affinity for Hb than has CO. The compound is very similar in all its 490 VETERINARY PHYSIOLOGY characters to the last. Some of it is generally found, along with methgemoglobin, after poisoning with uitrites. (4) Carbon dioxide Hsemoglobin. — By bubbling CO2 through a solution of hsemoglobin, in the absence of oxygen, a two- banded spectrum resembling methsemoglobin has been produced, and on evacuating the gas in an air-pump the single band of haemoglobin has been found to appear. This, again, gives place to the two bands when COo is passed through the solution. It appears from this that haemoglobin can carry CO2 as a definite compound. Probably it is the globin part of the molecule which acts in this way, while the htematin part carries the oxygen. Decomposition of Hsemoglobin. — Haemoglobin is a somewhat unstable body, and, in the presence of acids and alkalies, it splits up into about 96 per cent, of a colourless protein — globin, belonging to the group of histones (Appendix II.), and about 4 per cent, of a substance of a brownish colour called hsematin {Chemical Physiology). (1) Haematin, — The spectrum and properties of haematin are different in acid and alkaline media, (a) In acid media it has a spectrum closely resembling methjemoglobin, but it can at once be distinguished by the fact that it is not changed by such reducing agents as ferrous salts. It is sometimes important to distinguish between these pigments, since both may appear in the urine, methaemoglobin occurring in paroxysmal methsemoglobinuria and acid htematin as the result of the action of the acid salts of the urine upon hfemoglobin present as the result of kidney disease. (6) Haematin, in alkaline solution, can take up and give off oxygen in the same way as hfemoglobin does. Reduced alkaline haematin has a very definite spectrum (fig. 198), and its preparation affords a ready means of detecting old blood stains (Chemical Physiology). Haematin contains the iron of the hemoglobin, and it is this pigmented iron-containing part of the molecule which has the affinity for oxygen. It is the presence of iron which gives it this property, 1 grm. of iron being able to carry 400 c.cm. of oxygen. BLOOD 491 (2) Haematoporphyrin. — If hsemoglobin is broken down and the iron removed from the htematin by means of sulphuric acid, a purple-coloured substance, iron-free hcematin, hsematoporphyrin, is formed, which has no affinity for oxygen. This pigment occurs in the urine in some pathological conditions (Chemical Physiology). One point of great interest in the chemistry of hieniatin and its derivatives is that they, like the green chlorophyll of plants, yield upon decomposition very similar bodies belong- ing to the pyrrol group (see Appendix). (oj Bilirubin and Haematoidin. — In the liver, hEemoglobin IS broken down to form bilirubin and the other bile pigments (p. 324). These are iron-free, and, like haematoporphyrin, do not take up and give off oxygen. But not only are these iron-free pigments formed from haemoglobin in the liver, but they are produced in the cells of other parts of the body, and thus in blood-extravasations a yellow pigment hiematoidin is formed which is really the same as bilirubin. (4) Haemin — the hydrochloride of hcematin — is formed when blood is heated with sodium chloride and glacial acetic acid. It crystallises in small steel-black rhombic crystals, and its formation is sometimes used as a test for blood stains (Chemical Physiology). The following table shows the relationship of these pig- ents to one another : — Relationship of Hb and its Derivatives. Methffimogiobin HbO., HI .CO \ I Hh Hsemati I Acid Haematin Alkaline Haematin I I Oxidised Iron-free Haematin ^ HcBmatoporphy rin) Reduced / I Haematoidin Bilirubin Globin , Contain Iron Iron-free 492 VETERINARY PHYSIOLOGY V. Gases of the Blood. A. The Oxygen of the Blood. The study of the pigments of the blood has shown that the function of h;emoglobin is to carry oxygen from the lungs and to give it off to the tissues. It has been shown that it is the coloured iron-containing hsematin, constituting only about 4 per cent, of the molecule which acts as the carrier. Haemoglobin carries oxj^gen in virtue of the fact that, when it is exposed to a high partial pressure of the gas in the lungs it takes it up, while it gives it off when exposed to a low pressure in the tissues. The partial pressure of a gas in an atmosphere is got by multiplying its percentage amount by the atmospheric pressure and dividing by 100. Thus, taking the oxygen at 20 per cent, of atmospheric air, at normal pressure at sea- level of 7 GO mm. Hg the partial pressure of the oxygen is — 20x760 _^ ^ = 1 o 2 mm. Hg. 100 "^ The tension of a gas in a fluid, i.e. its tendency to escape, may be measured by finding the partial pressure of the gas in the atmosphere to which the fluid is exposed at which the gas is neither given otf nor taken up. Thus, if three vessels containing oxygen in blood had over the fluid 2, 5, 10 per cent, of 0,, i-e. Oo at partial pressures of 15'2, 38"0, and 76"0 mm. Hg, and it were found that Oo came otY in the first and was taken up in the third, but remained constant in the second, we should say that the tension of the gas was 38 mm. Hg. 0, Beginning in Air 2% 15 -2 mm. Hg. t 5% 38-0 mm. Hg. ^0% 76-0 mm. Hg. J.' End_ in Air 5% 3S-0 mm. Hg. 5% 38-0 mm. Hg. 5% 38-0 mm. Hg. BLOOD 493 The amount of oxygen taken up and given off is not proportionate to the partial pressure of the gas to which the Hb is exposed. This has been ascertained by exposing solutions of Hb to atmospheres with different percentages of oxygen, i.e. to oxygen at different pressures. Starting from an atmosphere containing no oxygen — with 28 45 63 100 ^ Dissociation Curve in '20 30 4 or aCMOGLOBlN AT 37° C. n f)0 (^0 70 80 9 94 87 72. 55 2.7 . . --^ ^ / / / / ; ^ 1 \/ / 1 / 1 1 1 y /; OXY _— — GEN ft E5SUR :iNTn m.op Hg. 80 . H o 70 i o 50 1 40 % 30 20 ( 10 Dissociation Curve ofH/EMOglobin inthe3lood. Fig. 200. — The Dissociation Curve of Haemoglobin in pure solution (continu- ous line) and in blood (broken line). The oxj-gen pressure in mm. is indicated by the ordinates, and the percentage saturation is indicated by the abscissas. Note the more rapid dissociation under 50 mm. Hg in blood than in pure solution of Hb. no partial pressure of oxygen — it is found that the Hb is entirely reduced — carries no oxygen. When exposed to atmospheres containing higher and higher percentages of oxygen it is found that the amount taken up rapidly increases till at 30 mm. Hg, equivalent to about 6 per cent, of oxygen in the atmosphere at sea-level, the Hb is saturated to about 80 per cent. 494 VETERINARY PHYSIOLOGY Further increasing the proportion and pressure of oxygen in the air brings about only a slightly increased taking up. Conversely, if Hb saturated with oxygen is exposed to lower and lower pressures of the gas, it gives up its oxN^gen slowly till a pressure of 30 mm. Hg is reached and then more rapidly. This is shown in fig. 200. In blood the curve given is different because of the 'r -^ :::= ■ — // / ^ ^ __^ / / X ^ ^..^^ / / / / /^ ■■■/■ 1 / i / f 1/ \l I Fig. 201. Dissociation curves of oxyhivmoglobin to show the influence of temperature i., at 16' ; ii., at 25' ; in., at 32' ; iv., at 3S' ; and v., at 49' C. Oxygen pressure along abscissa percentage of reduced h;emoglobin on vertical line. presence of CO., and of electrolytes. The taking up of oxygen rises rapidly to 50 mm. Hg, equivalent to 10 per cent, of oxygen in the air, when the hremoglobin is saturated to about 80 per cent. The giving olT takes place in the same ratio (fig. 200). This association of Hb and O2 and the dissociation are modified by — 1st. Temperature. — Fig. 201 gives the results at iv. about the temperature of the body. If the temperature BLOOD 495 is raised the dissociation curve is lowered v., and if the temperature is lowered the curve is raised i., ii., m. '2nd. The H ion concentration of the blood. — This, as already shown (p. 481), is controlled by the sodium bicar- bonate of the plasma, and is chiefly determined by the amount of dissociated HgCOg in the blood. Any increase of the Ch alters the form of the curve, tending to bring about dissociation of HbOo at higher pressures, as is shown infis. 202. 20 30 50 60 Fig. 202. — To show the effect of the tension of COo in the blood upon the giving off of oxygen. The pressures of oxygen are given as the abscissa; in mm. Hg, and the saturation of the htenioglobin as the ordinates. Note the marked difference at 20 mm. Hg of oxygen with 5 and with 40 ram. Hg pressure of COo- In fact, the CO.. of the blood plays a most important part in setting free the 0., for the tissues, since it raises the C^ of the blood. Zrd. The presence of electrolytes also lowers the curve. B. The Carbon Dioxide in the Blood. The carriage of CO.2 in the blood has already been dealt with. It has been shown that it exists to a large extent as NaHCOg and to a small extent in solution (p. 481). By subjecting blood to different pressures of CO2, it is found that the amount carried practically varies directly 496 VETERINARY PHYSIOLOGY with the partial pressure in the air to which the blood is exposed. As already indicated, the proteins of the blood plasma and of the red cells, notably the globin, which is the chief constituent of ha?moglobin, may combine with CO.,. Attempts have been made to determine the amounts of CO2 in the various combinations, but at present our knowledge is too defective to allow of definite figures being given. It has been maintained that, since NaHCOg is not dis- sociated at the temperature of the body with a partial pressure of COg such as occurs in the lungs, therefore the bicarbonate does not play the part of carrying the CO.2 from the tissues to the lungs, and that the main carrier is the ha^mo- globin, the HbCOo being more unstable in the presence of 0,. This theory seems to ignore the significance of the . , H,COo 1 , . \. , proportion between „ unr) = ^ ^^^ ^^^ adjustment under various conditions. It is certain that the amount of CO., which leaves the blood in the lungs is a very small part of the amount held in the blood (p. 498). The actual quantities of oxygen and of carbon dioxide in the blood are of much less importance than their tension. Method of Determining. (i.) They may be extracted by subjecting the blood to the Torricellian vacuum over the barometric colunm of mercury. Many forms of mercury gas pumps have been devised. One is shown in fig. 203. By raising the mercury ball M.B., air may be driven out of the blood bulbs a-h by filling them with mercury. On clamping at a and lowering M.B., a TorricelHan vacuum is produced. The bulbs are then detached and weighed, and blood is collected in them from a vessel. The blood bulbs are then connected with the apparatus and a vacuum produced in G.B., where the gases are collected. By turning the two-way tap T., they can be passed into the eudiometer tube E., and then analysed, the carbon dioxide being absorbed by caustic soda and the oxygen by alkaline sodium pyrogallate. BLOOD 497 The fact that the CO2 can be completely removed from blood containing the red cells but not from the plasma without the addition of a weak acid seems to show that the haemoglobin acts as an acid. (ii.) Haldane and Barcroft have devised a convenient method, which depends upon the fact that the oxygen can Fig. 203. — Diagram of one Form of Mercury Pump for Collecting the Gases of the Blood. M.B., the mercury bulb which can be raised so as to fill G.B. and a-h with mercury, and lowered so as to produce a Torri- cellian vacuum in them, a and h, clamps by which the blood bulbs may be shut off, to be weighed and to receive the blood. G.B., the bulb in which the gases are collected. T., the three-waj- tap by which the gas bulb G.B. is connected, either with the blood bulb, or with the eudiometer tube, E. B. is the bath of mercury in which the tube filled with mercury is set. be driven otF from blood treated with dilute ammonia, by the addition of potassium ferricyanide, and that the carbon dioxide is liberated by adding an acid. The amount of gas may be (a) directly measured in a Duprd's apparatus, or (6) determined by measuring the increased pressure in the tube in which the gas has been given otf, by means of Barcroft's apparatus {Chemical Physiology). 32 498 VETERINARY PHYSIOLOGY (iii.) Van Slyke has devised an apparatus for the liberation of the CO2 of the blood by weak sulphuric acid and of the Oo by potassium ferricyanide. The gases are then collected in a Torricellian vacuum and measured at atmospheric pressure. The method may be carried out in a few minutes and is of use in clinical work. Amounts of Gases. — The amount of gases which may be extracted varies considerably. About 60 c.c. of gas, measured at 0° C. and 760 mm. pressure, from 100 c.c. of blood may be taken as a rough average. The proportion of the sases varies in arterial and venous blood. Average Amount of Gases per Hundred Volumes OF Blood. Arterial Blood. Venous Blood. Oxygen _ _. 20 8-12 Carbon dioxide 40 46-60 Recently a series of analyses of the arterial and venous blood in normal men has been made, and it has been found that the average content is about Arterial Blood. Venous Blood. Oxygen 21 14 Carbon dioxide . 50 55 In the lungs the blood gains about 5 per cent, of oxygen and loses about 5 per cent, of carbon dioxide. While there is an exchange of something like 36 per cent, of the oxygen, the exchange of carbon dioxide amounts to only between 8 and 9 per cent, of the total amount in the blood. In the tissues there is, of course, a reversal of the changes that go on in the lungs. VI. Source of the Blood Constituents. A. Plasma. — The water of the blood is derived from the water ingested. But there is a free interchange of water between the blood and the tissues so that after bleeding water rapidly passes into the blood to make up the original BLOOD 499 volume, and after the injection of hyjjotonic saline and other non-colloidal fluids into the blood-vessels, water passes out into the tissues. The volume of the blood is thus regulated. The origin of the proteins is unknown, although ultimately they must come from the food ; very probably they are in part derived from the tissues. But the signifi- cance of the two proteins, albumin and globulin, and of their variations has not yet been elucidated. The glucose is derived from the carbohydrates and from the proteins of the food, and during starvation it is constantly produced in the liver and poured into the blood (p. 354). The fats are derived from the fats and carbohydrates of the food and tissues (p. 351). The urea and other waste constituents are derived from the various tissues. A transference of sodium phosphate from the tissues to the blood occurs when acidosis is threatened, probably by the dissociated HCl of the NaCl of the blood passing into the cells and turning out the phosphate as NaHoPO^ to be excreted (p. 482). B. Cells- — I. Leucocytes. — 1. In the embryo these are lirst developed from the mesoderm cells generally. In extra- uterine life they are formed in the lymph tissue and in the red marrow of bone. 2, Lymph Tissue is very widely distributed in the body, occurring either in patches of varying shape and size, or as regular organs, the lymphatic glands (fig. 205). These are placed on the course of lymphatic vessels, and consist of a sponge-work of fibrous tissue, in the interstices of which are set patches of lymph tissue, in which multiplying lymphocj^tes are closely packed together. Each mass of lymphatic tissue is surrounded by a more open network, the sinus, through which the lymph flows, carrying away the lymphocytes from the germ centres. In the sinuses are foimd many cells with a marked phagocytic action, and, when erythrocytes are destroyed by htemolytic agents, the pigment and the iron derived from the haemoglobin are often found abundantly in the cells in the sinuses of lymph glands. Round some of the lymphatic glands of certain animals large blood spaces or sinuses are seen, and these glands are 500 VETERINARY PHYSIOLOGY called hsemolymph glands (fig. 205). They are intermediate between lymphatic glands and the spleen. 3. Bone Marrow (fig. 204). — Young leucocytes or leuco- blasts, in the condition of mitosis, are abundant in this tissue, often in patches, the leucoblastic areas, and they pass away in the blood stream. They are of all varieties. In digestion leucocytosis and in certain pathological conditions the for- mation of these cells is increased and a leucocytosis results. . ^ *' I 'i ^ < ■ Fig. 20-4. — Section of Red Mairuw of Bone, u, lymphocyte; h, fat cell; c, erythroblast ; (/, giant cell ; e, erythrocyte ; /, erythroblast in mitosis ; g, neutrophil myelocyte; h, eosinophil myelocyte; k, eosinophil leucocyte ; I, polymorpho-nuclear leucocyte. II. Erythrocytes. — In the embryo, these cells seem to be formed by a process of budding from the mesoderm cells, which become vacuolated to form the primitive blood-vessels. The primitive red cells are larger than those of later life, and they have a very distinct nucleus. In extra-uterine life they occur in the blood as megalohlasU in some blood diseases. A new set of nucleated red cells next develops in the liver, and later in the spleen and bone marrow. They are smaller than the megaloblasts, and they are known as normoblasts when they appear in the blood in extra-uterine life, as they BLOOD 501 do in certain pathological conditions. After birth, erythro- cytes are formed in the red marrow of bone (fig. 204). Marrow consists of a fine fibrous tissue with large blood capillaries or sinusoids running in it. In the fibrous tissues are numerous fat cells (clear spaces h in fig. 204) and generally a considerable number of multi-nucleated giant cells (d) and myelocytes (g). In addition t,o these are the young leucocytes, leucoblasts (a.g.h.), and lastly, young nucleated red cells, the erythrohlasts (c./.). After hemorrhage, the formation of these becomes unusually active, and may implicate parts of the marrow not generally concerned in the process, and hence, the red marrow may spread from the ends of the long bones, where it is usually situated, towards the middle of the shaft. After haemorrhage, when the process of regeneration is very active, red cells with nuclei, normoblasts, escape into the blood. Young erythrocytes, even after they have lost their nucleus, may be distinguished by a peculiar reticulated appearance when they are stained with brilliant cresyl blue. The nuclei of the erythrohlasts atrophy, and the cells escape into the blood stream. The red marrow has the power of retaining the iron of disintegrated erythrocytes, which, in different stages of disintegration, are found enclosed in large modified leucocytes or phagocytes. The iron is often very abundant after a destruction of erythrocytes. VII. Total Amount of Blood in the Body. 1. Welcker's method consists in (1) bleeding an animal, measuring the amount of blood shed, and determining the amount of haemoglobin contained in it; (2) then washing out the blood-vessels, and, after measuring the amount of fluid used, determining the amount of haemoglobin in it to ascertain the amount of blood it represents. By this method the amount of blood was found to be about xV — 7 7 per cent, of the body weight. 2. Haldane and Lorrain Smith have devised a method which can be applied to the living animal. It depends upon 502 VETERINARY PHYSIOLOGY the fact that, after an animal or person has inhaled carbon monoxide, it is possible to determine to what proportion the gas has replaced ox3'gen in the oxyhsemoglobin. If, then, an individual breathes a given volume of carbon monoxide, and if a measured specimen of blood is found to contain a definite percentage of the gas, the rest of the gas must be equally distributed through the blood, and thus the amount of blood may be deduced. If, for instance, 50 c.c. have been taken up, and there is 1 per cent, in the blood, the whole blood holding the 50 c.c. must be 5000 c.c. They conclude that the blood is about ^tt' ^ P®^' cent., of the weight of the body in the human subject. This method has been adversely criticised on the ground that the CO may be taken up by the tissues of the body as well as by the blood. 3. Dreyer has devised another method for the living animal. After bleeding, the volume of blood is restored in a a few minutes by the passage of fluid from the tissues (p. 450). The number of red cells per c.mm. is determined. A definite amount of blood is drawn ; and after a few minutes the number of corpuscles is again counted. The reduction indicates the dilution of the blood. Thus, suppose the first count gave 5,000,000 per c.mm., and that 400 c.c. of blood were taken, and that the second count gave 4,500,000 — a fall of 500,000 or 10 per cent. — the 400 c.c. must be 10 per cent, of the whole blood which is thus 4000 c.c. 4. The vital red method. Vital red is a non-toxic pigment, which forms a colloidal solution in the blood, and does not readily transude from the vessels. By injecting a measured quantity into a vein and determining its dilution in the blood plasma, the total amount of plasma may be calculated, and if the volume of cells is determined by centrifuging in an ha^uiatocrit, the total volume of blood may be calculated. These last two methods give results corresponding to Welcker's (Practical Physiology). As has been shown in the study of circulation (p. 4 50), the total amount of blood in the body does not always correspond with the amount in effective circulation. In such conditions as wound or operation shock considerable amounts of blood may stagnate in the capillaries, and thus ' BLOOD 503 reduce the volume in circulation to such an extent that the supply of oxygen to the tissues is seriously interfered with. VIII. Distribution of the Blood. y Roughly speaking, the blood is distributed somewhat as follows : — Heart, lungs, large vessels ■ . . ^ Muscles ...... ^ Liver ^ Other organs i- IX. Fate of the Blood Constituents. A. Of the Plasma. — The water of the blood is got rid of by the kidneys, skin, lungs, and bowels. About the fate of the proteins we know nothing. The glucose and fat are undoubtedly used up in the tissues. The urea and waste products are excreted by the kidneys. As already indicated, the salts of the blood play the triple part (1) of supplying the tissues with the necessary cations; (2) of maintaining the osmotic pressure of the blood; (3) of regulating the C^ of the blood. Their due proportion is maintained chiefly by the action of the kidneys, which respond at once to any change in the C^ of the blood by eliminating the excess of anions or of cations. B. Of the Cells. — (1) The leucocytes break down in the body — but when and how is not known. They are greatly increased in number after a meal of proteins (digestion leucocytosis, p. 348), and, since the increase lasts only for a few hours, they are probably rapidly broken down, possibly to liberate amino-acids. But it is also possible that they may return to the bone-marrow and lymph tissue, from which they emerged during digestion. (2) The erythrocytes also break down. How long they live is not known. It is found that, after injecting blood from another animal of the same species, the original number of corpuscles is not reached for about a fortnight ; and hence it has been concluded that the corpuscles live for that 504 VETERINARY PHYSIOLOGY period. Advantage has been taken of the fact that the blood of different individuals belongs to one of four groups as regards power of agglutinating cells of other groups. If a man be transfused with a blood which does not belong to his group, specimens of his blood treated with a serum which agglutinates his corpuscles leaves the transfused corpuscles unagglutinated. It has been found that this condition may last for over a month, indicating that the corpuscles have continued in the blood for this period of time. The methods are unsatisfactory, and the results must be accepted with reservation. The method of disposal of old and effete erythrocytes in the body has been studied by poisoning them with various reagents such as phenylhydrazin. It is then found that they are removed from the circulation more especially by two organs. 1. The Liver. In the endothelial cells lining the capillaries, erythrocytes in all stages of disintegration may be seen, and the iron of the haemoglobin in a compound, or series of compounds, generally called haemosiderin, may be demonstrated by the green colour developed by treating with hydrochloric acid and potassium ferrocyanide. When haemoglobin is set free in the plasma, it is chiefly taken up by the true liver cells. That the pigment is split up and the iron-free part excreted is shown by the presence of the bile pigments in the bile. 2. The Spleen. 1. Structure. — This organ is composed of a fibrous capsule containing visceral muscle, and of a sponge-work of fibrous and muscular trabecular, in the interstices of which is the spleen pulp. The branches of the splenic artery run in the trabeculse, and twigs pass out from these trabecule, and are covered with masses of lymph tissue forming the Malpighian corpuscles. Beyond these, the vessels open into a series of complex sinusoids, lined by large prominent endothelial cells. From these capillary sinuses the blood is collected into channels, the venous sinuses, which carry it BLOOD 505 back to branches of the splenic vein in the trabeculae. The pulp may thus be compared with the blood sinuses of the hffimolymph glands, and the spleen may be considered as being a still further development of the hsemolymph gland from the lymph gland (fig. 205). 2. Functions — A. Blood Formation. — (1) Lymphocytes are undoubtedly formed in the Malpighian corpuscles. But their formation is probably unimportant. Their number is not greater in the blood of the splenic vein than in that of the artery, and H.EMOLYMPH Fig. 205.— To show the Relationship of the Spleen to Lymph Glands and Hremolymph Glands. The black indicates lymphoid tissue ; the coarsely spotted part, lymph sinuses, and the finely dotted part, blood sinuses. (Lewis. ) removal of the spleen causes no change in the number in the blood. f2) Erythrocytes. — That the spleen is not a seat of the formation of erythrocytes in normal extra-uterine life is indicated — (i) by there being no greater number in the blood of the splenic vein than in that of the splenic artery ; (ii) by the fact that removal of the spleen causes no decrease in the total number of erythrocytes ; and (iii) by the equally rapid regeneration of erythrocytes in animals from which the spleen has been removed and in normal animals. B. Blood Destruction. — 1. That it takes no active part in 506 VETERINARY PHYSIOLOGY the destruction of erythrocytes is shown by the facts (i) that injections of extracts of the spleen cause no change in the number of corpuscles ; (ii) that removal causes no increase in the number of erythrocytes ; (iii) that, when blood is injected, the added corpuscles are not removed more quickly in the normal than in the spleenless animal. 2. The spleen is rather to be regarded as a scavenger, which removes dead erythrocytes from the blood. This is indicated by the facts (i) that, after injecting h^emolytics, such as phenylhydrazin, there is less marked anaemia in the spleenless animals on the fourth day, because the dead corpuscles are not removed from the blood ; (ii) that the remains of the corpuscles may be seen in the cells of the spleen, and chiefly in the endothelial cells of the sinuses ; (iii) that iron compounds from the hemoglobin accumulate in the spleen after haemolysis. A result of this is that if rabbits are fed on a food poor in iron such as rice they become anaemic more rapidly if the spleen has been removed, because they have a smaller store of iron to draw upon. C. Digestion. — It has been suggested that the spleen manufactures a kinase which activates the pancreatic juice, but the evidence is against this theory. The spleen probably acts as a blood reservoir regulating the supply of blood to the digestive organs. On the purin metabolism it may have an effect (see p. 556) ; on the general metabolism it has no action. D. Movements. — The visceral muscle in the framework of the spleen undergoes rhythmic contraction and relax- ation, and the organ thus contracts and expands at regular intervals of about a minute. In the dog the movements are very marked. These movements may be recorded by enclosing the organ in an oncometer, a closed capsule connected with some form of recording apparatus. They are controlled by nerve fibres, from the true sympathetic system, leaving tlie spinal cord chiefly in the 6 th, 7th, and 8th dorsal nerves of both sides. Strong stimulation of these causes contraction, which is also caused by the intravenous injection of adrenalin. LYMPH 507 B. LYMPH. Lymph is the fluid which plays the part of middleman between the blood and the tissues. It fills all the spaces in the tissues and bathes the individual cell elements. Those who maintain that the lymphatics are shut off from the tissue spaces prefer to call the fluid filling these spaces tissue fluid. They consider that it is separated from the lymph in the lymphatics by a layer of endothelium. These spaces in the tissues open into vessels — the lymph vessels — in which the lymph flows away and is conducted through lymph glands and back to the blood through the thoracic duct (see fig. 162, p. 383). 1. Characters of Lymph. — Lymph varies in character according to the situation from which it is taken and accord- ing to the condition of the animal. (1) Lymph taken from the lymph spaces — e.g. the peri- cardium, pleura, or peritoneum — is a clear straw-coloured fluid. It has little or no tendency to coagulate. Microscopic examination shows that it contains few or no cells — any cells which may exist being lymphocytes. It has the same Cjj as the blood plasma. The specific gravity varies according to its source, being lowest when from the limbs and highest when from the liver. Apparently the cause of the non-coagulation of such lymph is the absence of cells from which thromboplastin may be set free. If blood or leucocytes be added to it, a loose coagulum forms. (2) Lymph, taken from lymphatic vessels after it has passed through lymphatic glands, is found to contain a number of lymphocytes and to coagulate readily. Chemically, lymph resembles blood plasma, but the proteins are generally in smaller amount, while the inorganic salts are in the same proportion as in the blood. The amount of proteins varies in lymph from difterent organs. Lymph of Proteins. Limbs .... About 2-3 per cent. Intestines ... ,, 4-6 ,, Liver .... ,, 6-8 ,, 508 VETERINARY PHYSIOLOGY In the lymphatics, coming from the alimentary canal, after a meal containing fat, the lymph has a milky appear- ance and is called chyle. This appearance is due to the presence of fats in a very fine state of division, forming what is called the molecular basis of the chyle. Lymph, in various diseases, tends to accumulate as serous eflfusions in the large lymph spaces — e.g. the pleura, peri- toneum, pericardium — and these effusions behave differently as regards coagulation. The following table helps to explain this (S.A. is Serum Albumin, S.G. Serum Globulin) : — CoAGULABlLlTy 01 Lymph, Sef.um, AND Effusions. Plasma and Lymph. Serous Effusion. Serum. Coag. Coag. with Thrombin. Uncoag. Uncoag. S.A. S.A. S.A. S.A. S.A. S.G. .S.G. S.G. S.G. S.G. Fibrinogen. Fibrinogen. Fibrinogen. .. Prothrombin Prothrombin Thrombin. and Throm- and ThroTii- boplastin. boplastin. Ca Ca Ca Ca Ca 2. Formation of Lymph. — The amount of lymph formed is measured by opening the thoracic duct in the neck and collecting the lymph which flows from it. Lymph is derived partly from the blood and partly from the tissues. Two processes may be involved — (1) Filtration, the forcing of fluid and of substances dissolved in it through the pores of a membrane under pressure. (2) Osmosis, the passage of water through semi-permeable membranes — membranes allowing the passage of water, but not of substances in solution — to a point of higher molecular con- centration. Diffusion, or the passage of dissolved substances through a membrane from a point of high to a point of low concentration, can play only a small part. If the formation of lymph cannot be explained in terms of these purely physical processes, then some unknown action of the cells of the capillaries must be invoked to LYMPH 509 explain it. The most careful study seems to show that these physical factors are adequate and that filtration plays the most prominent part. (1) The formation of lymph from the blood depends largely upon the permeability of the walls of the capillaries and the pressure of blood in the blood-vessels. Thus, although the pressure in the blood-vessels of the limbs is much higher than the pressure in the vessels of the liver, hardly any lymph is usually produced in the former, while very large quantities containing a high percentage of proteins are produced in the latter — apparently because of the slight permeability of the limb capillaries and the great permeability of the hepatic capillaries. The permeability may be increased bv the injection of hot water or of proteoses, probably because these injure the capillary walls, but possibly because they increase the activity of the organ. While the permeability of the vessel wall is the most important factor controlling lymph formation, any increase of the intravascvda.r 'pressure of a region may increase the flow of lymph, and for this reason any obstruction to the free flow of blood from a part leads to increased lymph production from that area. Asher has pointed out that the flow of lymph from the salivary glands and from the liver is increased with the increased activity of the organ irrespective of changes in blood pressure. Even after death, the flow of lymph may go on. He explains this by supposing that the activity of a gland leads to the breaking down of larger into smaller molecules, which increases the osmotic j^ressure of the fluid in the lymph spaces and thus causes an osmosis of water and an increased lymph formation. After death the disintegra- tive changes may produce these smaller molecules and have the same effect. A method of washing out wounds by causing a flow of lymph has been based upon this action of osmosis. The application to the w^ound of a hypertonic saline brings it about. (2) That lymph is also formed from the tissues is indicated by the fact that the injection of substances of high osmotic ilO VETERINARY PHYSIOLOGY equivalent into the blood — such as sugar or sodium sulphate — leads to a flow of fluid into the blood by a process of osmosis so that it becomes diluted, and also, to an increased formation and flow of lymph. This increase of water in both blood and lymph can be explained only by its with- drawal from the tissues (fig. 206). (3) The amount of lymph formed is not great. In man probably only about 100 c.cm. of lymph pass into the blood per hour. Hardly any of this comes from the muscles, although these hold about 70 per cent. of the water in the body ; nearly all comes from the abdominal organs, chiefly from the liver, although these hold only about 7 per cent, of the water of the body. LYMPH VESSEL mam exchange of is directly between TISSUE FLUID 206. — Diagram to illustrate the formation of lymph and the inter- change between tlie blood and the issue fluids. CAPILLARIES The water the blood and the tissues through the fluid in the tissue spaces and not by Fig. 206.— Diagram to illustrate the the lymphatic vessels. Fluid injected into the blood-vessels very rapidly transudes to the tissues, and, when blood is withdrawn from the vessels, the water of the tissues very rapidly passes into the vessels to make up the original volume. It is by way of the blood-vessels that serous effusions into the pleura, peritoneum and other serous cavities are removed, as is indicated by the fact that methylene blue, injected into the pleural cavity, appears in the urine in about 10 minutes, but is not found in the lymph for from 20 to 120 minutes. Such facts as these rather favour the view that the true lymph is separated from the tissue spaces by a layer of endothelium (fig. 206). CEREBRO-SPINAL FLUID 511 C. THE CEREBRO-SPINAL FLUID. 1. Distribution. — This fluid fills the pericellular spaces so that the nerve cells lie bathed in it, the perivascular spaces, the subarachnoid space, the ventricles of the brain and the central canal of the spinal cord. At the base of the brain the subarachnoid spaces filled with fluid are large and they protect this important part of the nervous system against injury by acting as a water cushion. 2. Characters. — The cerebro-spinal fluid is clear and transparent, with a specific gravity of 1006 to 1008. It is devoid of cells and contains only traces of proteins. Its Ch is practically the same as that of the blood plasma. Its principal constituent is sodium chloride with sodium bicarbonate and traces of phosphates, urea and dextrose. It has much the composition of Locke's modification of Ringer's solution, and it contains oxygen in considerable amounts. 8. Source- — It was formerly supposed to be formed like lymph by filtration from the blood. The amount formed may be measured by inserting a cannula into the sub- cerebellar space, (i) In this way it is found that, while the amount produced does vary with the blood pressure, it is not proportional to it, (ii) On the other hand, any increase of CO., in the blood, the administration of such anesthetics as chloroform, and, above all, the injection of extracts of the choroid plexus increase its production. While diftusible substances pass readily into the lymph they do not all pass from the blood to the cerebro-spinal fluid. Some, like urethane and alcohol, do pass, but salvarsan is held back and is thus of little use in the treatment of syphilitic affections of the nervous system in man. The fluid thus seems to be a secretion from the choroid plexus. This is covered by cubical vacuolated cells, and is, in fact, an inverted gland, which passes on from the blood the inorganic constituents and oxygen, but which holds back the proteins and many toxic substances. On the other hand, diftusible substances pass out readily 512 VETERINARY PHYSIOLOGY from the cerebro-spinal fluid of the brain to the blood ; but in the lower part of the spinal cord they do not pass out freely, and therefore anaesthetics like cocaine may be injected into the subarachnoid space in this region to anaesthetise the cord. This outward passage into the blood seems to show that the fluid secreted by the choroid plexus is carried away in the blood stream. It may escape along certain of the cranial nerves, more especially along the olfactory nerve. This channel is of importance in allowing the entrance of certain micro-organisms such as those of infective poliomyelitis and of cerebro-spinal meningitis in man. It is also probably passed into the blood of the dural sinuses by the arachnoidal villi which project into these, and which are covered by curious collections of cells, and from the perivascular spaces into the capillaries which they surround. Excessive secretion or blocking of the lateral ventricles may cause an increase in the fluid, a rise of pressure and cerebral symptoms. The fluid naturally escapes from the fourth ventricle by the foramen of Magendie and the foramen of Luschka into the subarachnoid space. 4. Quantity. — The quantity of fluid contained is small, in man about 130 c.cms. 5, Functions. — (i) The cerebro-spinal fluid, filling all the spaces in the brain, equalises pressure throughout the cerebro-spinal system and acts as a water cushion, especially at the base of the brain, protecting the medulla against shock, (ii) In the perivascular lymphatics it acts as a support to the thin- walled blood-vessels. (iii) It also acts as an adjusting mechanism in variations of blood supply to the central nervous system, (iv) It plays the part of a middle- man between the blood and the nerve cells. SECTION VI. RESPIRATION. The study of the metabolism of muscle has taught that a process of oxidation is constantly going on in the living tissues for which oxygen is constantly required, and by which carbon dioxide is constantly being produced. In the lowliest animals a direct exchange of gases takes place between the cells and the surrounding medium. In the higher and more complex animals a special mechanism has been evolved for carrying the oxygen from outside to the tissues, and of transporting the carbon dioxide from the tissues to the exterior. This is the Respiratory Mechanism. In mammals it consists of arrangements by which — 1. Air is brought into relationship with the blood. 2. The exchange of gases between air and blood takes place. 3. The blood carries the oxygen to the tissues, and the carbon dioxide from the tissues. 4. The oxygen is passed from the blood to the tissues, and the carbon dioxide from the tissues to the blood. 5. The oxygen brings about combustion in the tissues. The first two constitute the process of External Respira- tion, the third and fourth that of Intermediate Respiration, and the last that of Internal Respiration. This last has been already dealt with in the study of muscle (p. 255) and of meta- bolism, and it dominates the other parts of the process. A. EXTERNAL RESPIRATION. I. STRUCTURE OF THE RESPIRATORY MECHANISM. In aquatic animals the mechanism by which this process is carried on is a gill or gills. Each consists of a process 33 513 514 VETERINARY PHYSIOLOGY from the surface covered by a very thin layer of integument, just below which is a tuft of capillary blood-vessels. The oxygen passes from the water to the blood ; the carbon dioxide from the blood to the water. A lung is simply a gill or mass of gills, turned outside in, with air, instead of water, outside the integument. While in aquatic gill-bearing animals there is constantly a fresh supply of water passing over the gills, in lung-bearing animals the air in the lung sacs must be exchanged by some mechanical contrivance. {The structure of the various parts of the respiratory tract must be studied practically.) The lungs consist of myriads of small thin-walled air sacs attached round the funnel-like expansions (infundibular passages) in which the air passages terminate. These infundibula are the most ex- pansile structures in the lung, and they are largest where the expansion of the lung is greatest (fig. 207). Each air sac is lined by a Fig. 207.— Scheme of the Distribu- layer of simple squamous S:;:r„7Attcs'o°/rLut" ep'theUum. with smaller, more granular cells between them. The cells are readily stimulated to proliferate by the action of irritant substances, and the cells so produced take upon them- selves a phagocytic action. The epithelium is placed upon a framework of elastic fibrous tissue richly supplied with blood- vessels. It has been calculated that, if all the air vesicles in the lungs of a man were spread out in one continuous sheet, a surface of about 100 square metres would be pro- duced and that the blood capillaries would occupy about 75 square metres of this. Through these vessels about 5000 litres of blood pass in twenty-four hours, and during muscular exercise the flow may be increased some sevenfold (p. 413). The larger air passages are supported by pieces of hyaline cartilage in their walls, but the smaller terminal passages, RESPIRATION 515 the bronchioles, are without this support, and are surrounded by a specially well-developed circular band of non-striped muscle — the bronchial muscle — which governs the admission of air to the infundibula and air sacs. II. PHYSIOLOGY. I. Physical Considerations. The lungs are packed in the thorax round the heart, completely filling the cavity. They may be regarded as two compound elastic-iualled, sacs, which completely fill an air-tight box with movable walls — the thorax — and which communicate with the exterior by the windpipe or trachea. No space exists between the lungs and the sides and base of the thorax, so that the so-called pleural cavity is simply a potential space. The lungs are kept in the distended condition in the thoracic cavity by the atmospheric pressure within them. Their elasticity varies according to whether they are stretched or not. As they collapse, their elastic force naturally become less and less, as they are expanded, greater and greater. Taken in the average condition of expansion in which they exist in the chest, the elasticity of the excised lungs of a man is capable of supporting a column of mercury of about 30 mm. in height, so that they are constantly tending to collapse with this force. But the inside of the lungs freely communicates with the atmosphere, and this, at the sea-level, has a pressure of about 760 mm. Hg. During one part of respiration, this pressure becomes a few mm. less, during another part a few mm. more ; but the mean pressure of 760 mm. of mercury is constantly expanding the lung, and acting against a pressure of only 30 mm. of mercury, tending to collapse the lung (fig. 208> Obviously, therefore, the lungs must be kept expanded and in contact with the chest wall. When a pleural cavity is opened, the distribution of 516 VETERINARY PHYSIOLOGY forces is altered, for now the atmospheric pressure tells also on the outside as well as on the inside of the lung and acts along with the elasticity of the organ ; so that now a force of 760 mm. + 80 mm. = 790 mm. acts against 760 mm., causing a collapse of the lung, which comes to occupy a small space posteriorly round the bronchus and pulmonary vessels (fig. 208). In the surgery of the thorax, as well as in the physiology of respiration, these points are of great importance. It is possible that a small opening may not immediately lead to collapse, because the surface tension between the 1^^ Fig. 208. — Shows the Distribution of Pressure in the Thorax with the Chest Wall Intact, and with an Opening into the Pleural Cavity, (j) indicates the atmospheric pressure of 760 mm. of mercury ; 30 is the elasticitj' of the lungs, also in mm. of mercury. parietal and pulmonary pleura may be sufficient to overcome the atmospheric pressure. II. The Passage of Air into and out of the Lungs. This is brought about — \st. By the movements of respiration — breathing. Ind. By diffusion of gases. The air is made to pass into and out of the lungs by alternate insjnratlon and expiration. 1. Movements of Respiration. 1. Inspiration. — During this act, the thoracic cavity is increased in all directions — lateral, vertical, and antero- RESPIRATION 517 posterior. As the thorax expands, the air pressure inside the lungs keeps them pressed against the chest wall, and the lungs expand with the chest. As a result of this expansion of the lungs, the pressure inside becomes less than the atmospheric pressure, and air rushes m until the pressures inside and outside again become equal. This can be shown by placing a tube connected with a water manometer in the mouth, closing the nostrils, and breathing (Practical Physiology). This expansion of the lungs can readily be determined in the antero-posterior direction by percussion, and in the trans- verse planes by measurement. By tapping the chest with the finger over the lung in the intercostal spaces, a resonant note is produced, while if the percussion is per- formed below the level of the lung, a dull note is heard. If the lower edge of this resonance be determined before an inspiration, and again during it, the lung will be found to have expanded backwards (Practical Physiology). The change from before backwards cannot be seen directly, but it is indicated by a downward movement of the wall of the abdomen. It will be further described when considering the mechanism by which it is brought about. The expansion of the chest in inspiration is a muscular act and is carried out against the following forces : — 1st. The Elasticity of the Lungs.— To expand the lungs their elastic force has to be overcome, and the more they are expanded the greater is their elasticity. This factor therefore plays a smaller part at the beginning than towards the end of inspiration. 2nd. The Elasticity of the Chest Tr«^^.— The resting position of the chest is that of expiration. To expand the chest the costal cartilages have to be twisted. Srd. The Elasticity of the Abdominal Wall— As the cavity of the thorax increases downwards, the abdominal viscera are pushed against the muscular abdominal wall, which, in virtue of its elasticity, resists the stretching force. The changes in inspiration are brought about by — 1st. An Increase in the Thorax from before backwards. This is due to the contraction of the diaphragm (fig. 209) ; see also fig. 168, p. 392. 518 VETERINARY PHYSIOLOGY In expiration this dome-like muscle, rising (a) from the vertebral column, and (6) from the lower costal margin, arches forwards, lying for some distance along the inner surface of the ribs, and then curving inwards to be inserted into the flattened central tendon, to which is attached the pericardium containing the heart. In inspiration the muscular fibres contract. But the central tendon being fixed by the pericardium does not undergo extensive movement. The result of the muscular Fig. 209. — Vertical- tangential, Transverse, and Vertical Mesial Sections of the Thorax in Inspiration and Expiration in man. Similar changes occur in quadrupeds. contraction is thus to flatten out the more marginal part of the muscle and to withdraw it more or less from the chest wall — thus opening up a space, the complemental pleura, into which the lungs expand (fig. 209). The vertebral part of the diaphragm pulls downwards, the costal part pulls backwards, and together they act like a piston extending the vertical diameter of the thorax (fig. 168). ^nd. An Increase in the Thorax in the transverse and vertical diameters. This is brought about by the pulling forwards of the ribs which rotate round the axes of their attachments to the vertebral column. To understand this, the mode of connection of the ribs RESPIRATION il9 to the vertebral column must be borne in mind. The head of the rib is attached to the bodies of two adjacent vertebrae. The tubercle of the rib is attached to the transverse process of the hinder of these vertebrae. From this, the shaft of the rib projects outwards, downwards, and backwards, to be attached in front to the sternum by the costal cartilage running for- wards. If the rib is made to rotate round its two points of attachment, its lateral margin is elevated and carried outwards, while its sternal end is carried downwards and forwards. The first pair of ribs does not undergo this movement ; the motion of the second pair of ribs is slight, but the range of movement becomes greater and greater as we pass down- wards. This greater movement is simply due to the greater length of the muscles moving the ribs. The muscles are the external intercostal muscles, and they may be considered as acting from the fixed first rib. Now, if the fibres of the first inter- costal muscle are one inch in length, the second rib can be pulled forwards, say, half an inch. The first and second intercostals acting on the third rib will together be two inches in length, and, in contract- ing, they can move the third rib through, say, half of two inches — i.e. one inch. The first, second, and third intercostals, acting on three inches in length, and can rib half of three, or one and a half inches. The floating ribs are fixed by the abdominal muscles, and limit the move- ment of the ribs next above them. Fig. 210.— Rib and vertebral column, A., in an anterior rib segment, and B., in a posterior rib segment to show the difference in the obliquity of articulation and the resulting differ- ence in the expansion of the chest, which is greater from side to side in the more posterior part of the chest. the fourth rib, therefore move are this 520 VETERINARY PHYSIOLOGY The expansion of the lungs is very unequal, being most marked at the anterior and lower margins and much less marked posteriorly, especially round the roots. The ventilation of the air vesicles is thus much greater in the former than in the latter parts, where, if the breathing be shallow, the exchange of gases comes to depend more largely upon diffusion from the air of the dead space (p. 523). In these parts the proportion of carbon dioxide in the vesicles will be greater and the proportion of oxygen less than in the other parts of the lungs. When the diaphragm takes the chief part in inspiration the breathing is said to be abdominal in type — when the intercostal s take the chief part it is said to be thoracic. The diaphragm and the external intercostals are the essential muscles of inspiration, but other muscles also participate in the act. The nostrils dilate with each inspira- tion. The nostrils expand due to the action of the dilatores narium, which contract synchronously with the other muscles of inspiration. Again, if the larynx be examined, it will be found that the vocal cords slightly diverge from one another during inspiration. This is brought about by the action of the posterior crico-arytenoid muscles (p. 551), and this movement is interfered with in " roarers " (p. 553). Forced Inspiration — This comparatively small group of muscles is sufficient to carry out the ordinary act of inspira- tion. But, in certain conditions, inspiration becomes forced. A forced inspiration may be made voluntarily ; often it is pro- duced involuntarily. Every muscle which can act upon the thorax to expand it is brought into play. The body and spinal column are fixed. The head is thrown back and fixed by the posterior spinal muscles. The forelimbs and shoulders are fixed, and every muscle which can act from the fixed spine, head and shoulder girdle upon the thorax is brought into play. Normally, these act from the thorax upon the parts into which they are inserted ; now they act from their insertions upon their points of origin. The sterno-mastoids, sterno-thyroids, and sterno-hyoids assist in expansion of the thorax. The serratus RESPIRATION 521 magnus, pectoralis minor, and posterior fibres of the pectoralis major, and the part of the latissinius dorsi which passes from the humerus to the posterior ribs, also pull these structures forwards. The facial and laryngeal movements also become exaggerated. 2. Expiration is a return of the thorax to the position of rest. The various muscles of inspiration cease to act, and the forces against which they contended contract the thorax in its three diameters — The elasticity of the lungs is no longer overcome by the muscles of inspiration, and the external atmospheric pressure acting along with it drives the chest wall in- wards. The elasticity of the costal cartilages tends to bring the chest back to the position of rest; the elasticity of the abclomninal wall drives the abdominal viscera against the relaxed diaphragm and again arches it towards the thorax, bringing its marginal portion in contact with the ribs and occluding the complemental pleura. By this constriction of the thorax, the air in the lungs is compressed and the pressure is raised above the atmospheric pressure outside, and so the air is driven out. Experimental evidence shows that the internal intercostals contract with each expiration, and help to draw the ribs backwards. Ordinary expiration is thus normally mainly a passive act, being simply a return of the thorax to the position of rest. But voluntarily, and, in certain conditions, involuntarily, expiration may be forced. Forced expiration is due to the action ot muscles. Every muscle which can, in any way, diminish the size of the thorax comes into play. Chief of these are the abdominal muscles, which, by compressing the viscera, push them upwards and press the diaphragm further up into the thorax. At the same time, by acting from the pelvis to pull back the ribs, they decrease the thorax from side to side and from below upwards. The serratus posticus inferior and part of the sacro-lumbalis pull downwards the lower ribs, and the triangularis sterni also assists in this. 522 VETERINARY PHYSIOLOGY 3. Special Respiratory Movements. — There are several peculiar and special reflex actions of the respiratory muscles, each caused by the stimulation of a special region, and each having a special purpose. They are generally protective reflexes in response to nocuous stimuli. Coughing. — This consists of an inspiration followed by a strong expiratory effort during which the glottis is constricted but is forced open repeatedly by the current of expired air. It is generally due to irritation of the respiratory tract, and its object is to expel products of inflammation or foreign matter. Sneezing. — This is generally produced by irritation of the nasal mucous membrane, and its object is to expel irritating matter. It consists in an inspiratory act followed by a forced expiration during which, (a) by contraction of the pillars of the fauces and descent of the soft palate, and (b) by the tip of the tongue being pressed against the hard palate, the air is compressed and finally forced through the nose and mouth. Hiccough consists in a sudden reflex contraction of the diaphragm causing a sudden inspiration which is interrupted by a spasmodic contraction of the glottis. It is allied to vomiting. Abdominal irritation is its chief cause. Sighing and Yawning are deep involuntary inspirations which serve to accelerate the circulation of the blood in the brain when, from any cause, it becomes less active. They are probably due to cerebral anemia, which they help to correct by increasing the general arterial pressure, and they are the result of direct chemical stimulation of the respiratory centre rather than reflex actions (p. 527). II. Amount of Air Respired. The amount of air respired is difl"erent in ordinary and in forced respiration (fig. 211). In an ordinary respiration in the horse about 3000 ccms. of air enter and leave the chest. That is called the tidal air- Its amount varies with the size and muscular development of the chest. RESPIRATION 523 Vihcl Cooac.h '0/ By a forced inspiration a much larger quantity of air may be made to pass into the lungs— a quantity varying with the size and strength of the individual — but on an average about 14,000 c.cms. This is called the complemental air. By forced expiration, an amount of air much larger than the tidal can be expelled, an amount usually about the same as the complemental air, and called the reserve air. The total amount of air which an individual can draw into and drive out of his lungs is a fair measure of the size and muscular development of the thorax, and it has been called the vital capacity of the thorax, and in the horse it amounts to something like 25,000 to 30,000 c.cms. Even after the whole of the reserve air has been driven out of the chest, a considerable quantity still remains in the air vesicles, its amount depending upon the size of the chest, but averaging about 10,000 c.cms. This is called the residual air. This very important point must always be remembered, that the air taken into the chest never fills the air vesicles, and that air is never driven completely out of them. The air in them is thus not changed by the movements of respiration, hut by the process of diffusion. A fairly reliable conclusion as to the vital capacity may be arrived at by measuring the circumference of the chest in expiration and inspiration {Practical Physiology). Fig. 211. — The Amount of Air Respired in Ordinary Respira- tion, and in Forced Inspiration and Expiration. III. Interchange of Air in the Lungs by Diffusion of Gases. Since, in ordinary breathing in the horse, a residue of almost 24,000 c.cms. of air remains in the lungs while only 3000 c.cms. pass into and out of them, the question whether any of this gets to the air vesicles must be considered. The trachea and bronchi have a capacity of probably about 1400 c.cms. and they constitute a " dead space," so that, after filling these, about 1600 c.cms. are available to reach the vesicles. But, so large is the capacity of 524 VETERINARY PHYSIOLOGY these vesicles, that, if this air were uniformly distributed, it would add only about -fth to the volume of each. The exchange of gases depends, in fact, largely upon the process of diffusion (fig. 212). Oxygen is constantly being removed by the blood from the air in the air vesicles, and carbon dioxide is constantly being added to it. Hence, the pressure of oxygen is lower and the pressure of carbon dioxide higher than in the air breathed, and hence, a diffusion of oxygen to the air in the vesicles and a diffusion of carbon dioxide from it are constantly going on. In the less expansile parts of the lung the exchange of gases will Fig. 212. — To show the exchanges of gases by diffusion between the tidal air and the reserve and residual air. depend more largely upon diffusion than in the more expansile parts. IV. Breath Sounds- The air, as it passes into and out of the lungs, produces sounds that may be heard on listening over the thorax. The character of the breath sounds is of the utmost importance in the diagnosis of diseases of the lungs, and must be studied practically (Practical Physiology). On listening over the trachea or over the bifurcation of the bronchi behind (between the 4th and 5th dorsal vertebrae), a harsh sound, something like the guttural oh (German ich), may be heard with inspiration and expiration. This is called the bronchial sound. If the ear be applied over a spot under which a mass of air vesicles lies, a soft sound, somewhat resembling the sound of RESPIRATION 525 centle wind among leaves, may be heard throughout inspira- tion, and for a third or less of expiration. This is called the vesicular sound. When the air vesicles become consolidated by disease, the vesicular sound is lost, and the bronchial sound takes its place. The cause of the vesicular character is therefore to be sought in the vesicles, infundibula, or small bronchi. The cause of the bronchial sound has been determined by experiments on horses. In the study of the cardiac circulation, it was shown that a column of fluid moving along a tube of uniform calibre, or with the calibre only slowly changing, pro- duces no sound. The same is true of a column of air. Any sudden alteration in calibre produces vibration and a musical sound, as explained on p. 409. The first sharp constriction of the respiratory tract is at the glottis, and it is here that the bronchial sound is produced. If the trachea be cut below the larynx and drawn freely outwards, the bronchial sound at once stops and the vesicular sound becomes lower and less distinct. The cause of the vesicular sound is not so satisfactorily explained. It is in part due to propagation of the bronchial sound, altered by passing through vesicular tissue ; but it is also probably due to the expansion and contraction of the infundibula drawing in and expelling air. The reason why the sound is best heard during inspiration may be that the sound is best conducted in the direction of the air stream. V. Rhythm of Respiration. The movements of respiration are carried on in a regular rhythmic manner. They may be recorded — 1. By recording the movement of the chest wall by some form of stethograph. 2. By recording the movements of the column of air by placing a glass tube in one nostril and connecting it with a recording tambour {Practical Physiology). 3. In lower animals, by connecting a strip of the diaphragm to a lever. Their rate varies with many factors; but the average number of respirations per minute in the adult horse is about 526 VETERINAKY PHYSIOLOGY ten to twelve, or about one to every four or five beats of the heart. Deep breathers are slow breathers, and shallow breathers are quick breathers, and in the latter a smaller part of the lung is ventilated. The most important factor modifying the rate of respiration is muscular exercise. After galloping the respirations may be over 60 per minute. The other modifications in the rate of breathing will be better understood after studying the nervous mechanism of respiration. Inspiration is more rapid than expiration (see fig. 216). As soon as it is completed, a reverse movement occurs, which is at first rapid, but gradually becomes slower, and may be followed by a pause, during which the chest remains in the collapsed condition. The existence and duration of this pause varies much, and it may really be regarded as the terminal period of expiration. Considering it in this light, we may say that inspiration is to expiration as 6 is to 7. VI. The Nervous Control of Respiration. The rhythmic movements of respiration require the har- monious action of a number of muscles, and this is directed by the nervous system. The Respiratory Centre. If the spinal cord be cut above the third cervical nerves the movements of respiration at once stop. Obviously there is some nervous mechanism above this level presiding over these muscles. A. Position. — Removal of the brain above the medulla oblongata does not stop the respiratory rhythm. The mechan- ism must therefore be situated in the medulla oblongata. If the medulla be split into two by an incision down the middle line, respiration continues, but the two sides do not always act at tlie same rate. The mechanism, then, is bi- lateral. Normally the two parts are connected, and thus act together. Destruction of the part of the medulla lying near the root RESPIRATION 527 of the vagus arrests respiration, and it may therefore be con- cluded that the nervous mechanism presiding over this act is situated there. This centre sends fibres down the lateral column of the cord to act upon the outgoing neurons to the muscles of respiration, and it is by influencing the activity of these that the respiratory centre controls the act of respiration. Outgoing Nerves. — The diaphragm is supplied by the phrenic nerves arising from the third and fourth, and partly from the fifth cervical nerves. The intercostals are supplied by branches from their corresponding dorsal nerves. If the spinal cord be cut or the neck broken below the fifth cervical nerves, the intercostal muscles cease to act. If the section be made above the third cervical nerves, the diaphragm, too, is paralysed, and the animal dies of suffocation. B. Mode of Action. — The respiratory centre is under the control of higher nerve centres, and, through these, it may be thrown into action at any time, or prevented from acting for the space of over a minute and, under certain conditions, for two or three minutes. But, sooner or later, the respiratory mechanism acts in spite of the most powerful attempts to prevent it. Pearl divers rarely are able to stay under water for more than 85 seconds ; the record period of submergence is 4 minutes 45 seconds. 1. Chemical Regulation. A. Carbon dioxide. The activity of the centre is chiefly regulated by the tension of CO2 in the blood going to it (p. 495), and everything which leads to an increase in the COg increases the activity of respiration, while everything which decreases it decreases the activity of breathing. The tension of C0„ in the blood is directly proportional to the partial pressure of COj in the medium to which the blood is exposed (p. 496). The amount and tension of COo in the blood and therefore its action upon the respiratory centre, depend upon its production in the muscles on the one hand, and on its tension in the alveolar air on the other. The latter may be raised by breathing air with an increased amount of C0„, e.g. 5 per cent. 528 VETERINARY PHYSIOLOGY With any increase in the amount, the respiratory centre is stimulated and the respirations increased Qiyperpncea), till the tension of COo in the blood becomes normal. The power of ad- justment is extraordinarily efficient, so efficient that the tension of C0„ in the alveolar air is maintained at a constant level of about 40 mm. Hg under wide variations of atmospheric pressure. It has been found that an increase of 0*2 per cent, in the COo of the alveolar air, i.e. a rise of tension from 40 to 41 6 mm. Hg is sufficient to double the ventilation of the lungs. By forced breathing the tension of COo in the alveolar air may be so lowered that the tension in the blood is markedly reduced, and the stimulus to the respiratory centre so decreased, that a long period without breathing, an ajjnoea, may occur. In fact, in some cases in man, the face may become livid from want of oxygen before breathing is re-established. Alveolar Air COo tension 40 mm. Hg. \ 45 40 \ 35 Hy Ten aerpnoea sion of COo in Bl in mm. Hg. Normal Breathing ood Apnoea B. Oxygen. The influence of the oxygen content of the blood upon the respiratory centre is not so manifest. The amount and tension of Oo in the blood, and its transit to the tissues and the respiratory centre, are in some respects more complex than in the case of CO^. As already explained (p. 498)— (1) the amount in the blood is not directly proportional to the partial pressure of the gas to which it is exposed. As the latter rises from zero the amount in the blood rapidly increases, till at 50 mm. Hg the hemoglobin RESPIRATION 529 is saturated to the extent of about 80 per cent., and a further rise causes only a slight increase in the saturation. (2) The giving off of O., from the haemoglobin depends upon the hydrogen ion concentration of the blood which is mainly determined by the tension of COo. With a pressure of 80 mm. Hg of COo 75 per cent, of the oxygen is given off at an oxygen pressure of 20 mm. ; with 5 mm. Hg pressure only about 30 per cent, is given at the same pressure (fig. 202). With a low C0„ tension the blood may pass through the tissues and the respiratory centre and remain of a bright red colour because it has not parted with its oxygen, and the tissues and the centre may thus have an inadequate supply. A due proportion of CO 2 in the blood is therefore of importance in securing an adequate transference of Oo to the centre. When oxygen deficiency is sufficiently marked, the re- spiratory centre not only becomes more sensitive to the stimu- lating action of CO.., but may be stimulated quite apart from any action of COo. This is seen in the oxygen- want experienced in high aviation and in re-breathing air from which the COo is removed by passing over soda lime. The rate rather than the depth of breathing is increased. This increase may lead to an increased intake of oxygen although, on account of the rapid shallow breathing, it does not necessarily do so (p. 526). It may thus fail to relieve the condition, because at the same time the CO. is driven out of the blood and thus the giving off of oxygen to the respiratory centre may be decreased. The result is that, under the continued want of oxygen, the respiratory centre may fail, the breathing stop, and death supervene, as is seen in death from asphyxia (p. 548). Fortunately, the decreased supply of O2 to the muscles leads to a failure to oxidise the sarcolactic acid, which may accumulate in the blood and by causing an acidosis — an increase in the Ch of the blood — may stimulate the respiratory centre, and at the same time facilitate the giving off of Oo to the tissues. The primary increase of breathing with oxygen-want appears to be due to a direct action on the centre, and not as was formerly supposed to the development of an acidosis. It 34 530 VETERINARY PHYSIOLOGY occurs under conditions when such an acidosis could hardly develop. While an increase of free CO., increases the depth, and also generally the rate of breathing, and thus secures a more thorough ventilation of all parts of the lung, oxygen deficiency seems chiefly to cause an acceleration of rate. In consequence of this quicker, more shallow breathing only the more expansile parts of the lung are ventilated (p. 523). The result is that a greater proportion of the blood passes through parts of lung imperfectly ventilated, from the alveoli of Giving off of COj in hyper- ventilated part of lung. Giving off of COj normal and actual. • ^ Taking up of O2 by the blood in hyper- ventilated part of lung. Taking up of O2 normal. .^ Taking up of Oj actual. Giving off of CO, in non- ventilated part of lung. Taking up of O3 in same. Fig. 2lo. — To show effects of shallow breathing and imperfect ventilation uf the lungs upon the taking up of Og and giving oft' of COo. The shaded part of the square represents the badly ventilated part. which the oxygen gets used up and reduced to a low partial pressure. If the pressure falls below 50 mm. Hg the blood will be imperfectly oxygenated. The rest of the blood passing through the well-ventilated expansile part of the lung cannot take up much more oxygen than it does at a pressure of a little over 50 mm. Hg (p. 493), so that any rise in the partial pressure as the result of better ventilation produces only a small effect. Thus imperfectly oxygenated blood is mixed with a smaller quantity of normally oxygenated blood, and thus the total blood leaving the lungs carries less oxygen than normally (fig. 213). On the other hand, since the C0„ tension varies directly with the partial pressure, the decreased giving off of C0„ in the badly ventilated parts of the lung may be compensated for RESPIRATION 531 by the increased giving off in the well-ventilated parts, and thus the amount of COo in the blood may not be raised, and so the normal stimulus to the respiratory centre may not come into play (fig. 213). It has been suggested that in these conditions the addition of COo to the air breathed may have an even more beneficial effect than the addition of ox3'gen. Possibly a combination would be more efficacious. There is some evidence that a sufficient clearing out of COo from the blood by forced breathing may so decrease the Ch of the blood, may produce so marked an alkalosis, that the HbOo is not dissociated, and the central nervous system may be so imperfectly supplied with oxygen that consciousness may be lost, the arterioles may contract and the heart fail as in Fig. 214.— To show the Characters of Cheyne-Stokes Breathing and the factors producing it (see text). asjjJiyxia. This has been termed by Yandell Henderson acajynia. In some people and under some conditions a deficient supply of oxygen to the respiratory centre leads to a periodic type of breathing. The patient stops breathing for a time (ajmcBa), then begins to breathe, first quietly, then more forcibly Qiyperpnoea), and, after several respirations, again with decreasing depth till the respirations stop. In these cases, the respiratory centre is less excitable than usual, and it is called into action only when CO 2 has accumulated in the blood. After this accumulation has been got rid of by the forcible respirations, the activity of the centre again wanes. Since the forced breathing tends to produce excessive clearing out of COo, it may lead to a decreased dissociation of HbOo and to a 532 VETERINARY PHYSIOLOGY limitation of the free supply to the tissues of the oxygen which has been taken up by the blood. This has been called Cheyne- Stokes breathing (fig. 214). 2. Reflex Regulation- The i'espiratory centre is also acted upon by various ingoing nerves. (1) The Vagus. — Since the vagus is the ingoing nerve of the respiratory tract, we should expect it to have an important influence on the centre (fig. 215). Section of one vagus generally causes the respirations to become slower and deeper ; but, after a time, the effect wears Dyaph Fig. 215. — Nervous Mechanism of Respiration. B.C., respiratory centre; Citt., cutaneous nerves ; Ph., phrenics ; In.C, intercostal nerves ; P., pulmonarj- branches of vagus ; S.L., superior laryngeal branch of vagus; La., the larynx; G.Ph., glossopharyngeal nerve; Diaph., diaphragm. off and the previous rate and depth of respiration are regained (fig. 216). Section of both vagi causes a very marked slowing and deepening of the respiration, which persists for some time, and passes ofi" slowly and incompletely. But if, after the vagi have been cut, the connection of the respiratory centre with the wpjper brain tracts is severed, the mode of action of the centre changes. Instead of discharging rhythmically, it may discharge irregularly (fig. 216, c). To investigate further this influence of the vagus it is neces- sary to study the effect of stimulating the nerve. Strong stimulation of the pulmonary branches of one RESPIRATION 533 vagus, below the origiu of the superior laryngeal, generally causes the respirations to become more rapid, the inspiratory phase being chiefly accentuated. Weak stimuli, on the other hand, may cause inhibition of the respirations. Such experiments prove that impulses are constantly travel- ling from the lungs to the centre to regulate its rhythmic activity. Positive and Negative Ventilation, i.e. passively inflating and deflating the lungs, shows that two sets of fibres come into play in normal respiration. If the lungs be forcibly inflated, the inspirations become feebler and finally stop. The nature of the gas, if non-irritant, a ■V L d d' Fif4. 216.— Tracings of the Respiratiou— Downstroke is inspiration ; Upstroke is expiration. At a one vagus nerve was cut ; at h the second was divided ; at c the upper brain tracts also were cut off; d and d' show the effect of stimulating the glossopharyngeal nerve. with which this inflation is carried out, is of no consequence. If, on the other hand, air is sucked out of the lungs, inspira- tions become more dominant, and may end in a spasm of the inspiratory muscles. Inspiration is thus checked by one set of fibres and expira- tion by another, and tlie vagus thus regulates the action of the respiratory nervous mechanism, much as the pendulum regu- lates the action of a clock. Under some conditions, e.g. after gassing, the activity of this reflex may be increased so that inspiration and expiration are checked too soon, and the breath- ing may thus be made shallow and quick. (2) Other Ingoing Nerves. — (a) Section of the superior laryn- 534 VETERINARY PHYSIOLOGY geal branch of the vagus, the sensoiy nerve of the larynx, does not alter the rhythm of respiration. Stimulation of the upper end of the cut nerve causes first an inhibition of inspiration, and, if stronger, produces forced expiratory acts. This is well illustrated by the very common experience of the effect of a foreign body, such as a crumb, in the larynx. The fit of cough- ing that ensues is a series of expiratory acts reflexly produced through this nerve. (b) When the splanchnics in the abdomen are stimulated, inspiration is inhibited. Every one has experienced the " loss of wind " as the result of a blow on the abdomen. (c) The glossopharyngeal, which supplies the back of the tongue, when stimulated, as by the passage of food in the act of swallowing, causes an instant arrest of the respiratory move- ments either in inspiration or expiration. The advantage of this in preventing the food, as it is swallowed, from passing into the trachea is obvious (fig. 216, d and d'). (d) Stimulation of the cutaneous nerves stimulates the in- spiratory centre and causes a deep inspiration. This is seen when cold water is dashed upon the skin. Stimulation of the skin by slapping is sometimes used to establish breathing in the newly born infant. The reaction is most clearly demonstrated in animals with the vagi cut when an inspiratory movement may often be liberated by merely touching the skin. 3. Influence of Temperature- — The temperature of an animal also acts on the respiratory centre. Increase in temperature accelerates the rate of the heart and it also accelerates the rate of the respirations in about the same proportion. This is seen in feverish attacks, where pulse and respirations are proportion- ately quickened so that their ratio remains unaltered. When the respiratory rate rises out of proportion to the rate of the pulse it is usualh' an indication that some pulmonary irritation is present. 4. Postural Control. — In diving birds the respirations are controlled by a postural reflex from the labyrinths and neck. When the head is put in the diving position respirations are stopped. The respiratory centre in these birds does not respond to the Ch of the blood, but rather to the want of oxygen. RESPIRATION 535 III. Interaction of Circulation and Respiration. The lungs aud heart, being packed tightly together in the air-tight thorax, and both undergoing periodic changes, neces- sarily influence one another. At the same time, the close proximity of the respiratory and cardiac centres in the medulla seems to lead to the activity of one influencing the other. A. Influence of Respiration on Circulation. — The circulation is modified in two ways by respiration. First, the pulse, and second, the arterial blood pressure undergo alterations. l.sf. Pulse. — (a) Rate. — If a sphygmographic trace, giving the pulse waves during the course of tw^o or three respirations, be examined, it Avill be found that during inspiration the heart is acting more rapidly, while during expiration its action is slower. If the vagus be cut, these changes are not seen, showing that the inspiratory acceleration is not the result simply of the larger amount of blood which enters the heart during inspiration, but is really due to changes in the cardio-motor centre — the accelerating part of which has its activity in- creased during inspiration, while the inhibitory part is more active during expiration. This is therefore partly a reflex effect from the lung through the vagus, although it may be in part due to the proximity of the centres in the medulla. (b) Volume. — Not only is the rate of the pulse altered by respiration, but the waves are smaller during inspiration and larger during expiration. This is simply due to there being more time for diastolic filling when the heart is beating more slowly. •2rtd. Blood Pressure.— J.. If, in an anaesthetised animal tracings of the arterial pressure and of the respiratory movements are taken at the same time, it is found that there is a general rise of pressure during inspiration and a general fall during expiration, but that at the beginning of inspiration the pressure is still falling, and at the beginning of expiration it is still ri.sing. This influence of respiration on arterial pressure is chiefly a mechanical one, depending on the variations in the pressure in the pericardium, which is decreased during inspiration, allowing )36 VETERINARY PHYSIOLOGY greater diastolic filling. By allowing access of air into the pericardial sac the differences are abolished. B. In man, and this is probably also the case in the unansesthetised animal, in thoracic breathing the arterial pressure falls during inspiration and rises during expiration, on account of the retention of blood in the distended thorax in inspiration and its expulsion in expiration, and that, in abdominal breathing, the reverse is the case ; inspiration, by pressing on the abdominal vessels and sending more blood on into the arteries, increasing the pressure. B. Influence of the Action of the Heart on Respiration. — The heart lies in the thorax sur- rounded by the elastic lungs. As it contracts and dilates it must alternately pull upon and compress the lungs, and thus tend to cause an inrush and an outrush of air — the cardio-pneu- matic movements. If a simultaneous tracing of the heart-beat and of the movements of the air column be taken, it will be seen that (1) at the beginning of ventricular systole there is a slight outrush of air from the lungs, probably caused by the blow given to the lungs by the suddenness of the systolic movement. (2) This is followed by a marked inrush of air corresponding to the out- flow of blood from the ventricles, and caused by the fact that the contracting ventricles draw on and expand the lungs. (3) Succeeding this is a slower outrush of air corresponding to the active filling of the ventricles during the beginning of ventricular diastole. (4) Lastly, during the period of passive diastole, the cardio-pneumatic movements of air are in abeyance (fig. 217). These cardio-pneumatic movements are of importance in two ways. (1) In animals during hibernation, the ordinary Fig. 217. — To show Relations of Cardio-pneumatic Movements, A., to the Cardiac Cycle, B. In A. the upstrokes are expira- tory, the downstrokes inspira- tory. RESPIRATION >37 respirations almost stop, but a sufficient gaseous interchange is kept up by these cardio-pneumatic movements. (2) If, as is often the case in bronchitis, there is a plug of mucus in a small bronchus near the heart, the rush of air past it may give rise to a murmuring sound, in character very like a cardiac murmur and synchronous with the heart's action. IV. Interchange between the Air breathed and the Blood in the Lung Capillaries. I. Effects of Respiration upon the Air breathed. — 1. Method Air PerCe NTT PerCent OF Gases Inspired Expired Hi N19 0^21 Venous N19 ai6 Arterial 0.22 0.3E N1-2 co,u N1-2 CO. 6(9 4 F iG. 218. — .4. Shows the Composition of Inspired and Expired Air. B. Shows the Difference in the percentage Composition of the Gas of Venous and Arterial Blood. of Investigation. — A measured quantity of air is collected in a graduated burette. It is then forced into a chamber contain- ing caustic potash, by which the COg is absorbed, and the volume of air is again measured. It is next forced into a chamber containing sodium pyrogallate in caustic soda, which absorbs the 0„, and is again measured. The residue is nitrogen. In this way the amount of the gases present is determined {Practical Physiology). 538 VETERINARY PHYSIOLOGY 2. Results. — (1) Gases — The following table shows the average percentage composition of the air inspired and the air expired (fig. 218):- Percent, of N. o„. CO, [nspired air 79 21 Expired air SO 16 4 i.e. about 5 per cent, of oxygen is taken from the air, and about 4 per cent, of carbon dioxide is added to it. In man the amount of carbon dioxide given off is smaller than the amount of oxygen taken up, and hence, as already explained (p. 258), the Respiratory Quotient^^^^^^^ is generally less than unity — usually about 0'8 to 0'9 — and the percentage of nitrogen in expired air is increased. (2) Expired air is saturated with watery vapour, and there- fore it usually contains more water than inspired air. (3) Expired air also contains small amounts of organic riiatter, which may give it an offensive odour. These are not derived from the lungs, but are produced by putrefactive changes in the mouth and nose. The injurious effects of the "foul air" in overcrowded spaces are chiefly due to bad ventilation with imperfect movements of the air, which result in an increased humidity and a decreased elimination of heat, and at the same time to the accumulation of the volatile products from dirty skins. (4) Expired air is usually warmer than inspired air, because usually the body is warmer than the surrounding atmosphere. When, however, the temperature of the air is higher than that of the body, the expired air is cooler than the inspired. II. Effects of Respiration on the Blood- — To understand these changes in the air, we must refer to the changes in the gases of the blood in passing through the lungs. These have already been partly considered when dealing with the gases of the blood (p. 492). Analyses show that the blood going to the lungs is poorer in oxygen and richer in carbon dioxide than the blood coming from the lungs (fig. 218). The following table gives not the percentage composition of RESPIRATION 539 the gas extracted from blood, but the amount of each gas per 100 parts of blood : — Amount in 100 /lajV*' of Blood {Human). CO,. 0,. Venous . . 55 15 Arterial . . 50 20 Oxygen is taken by the blood from the air, carbon dioxide is given by the blood to tJte air. III. The Causes of the Respiratory Exchange- — How is this effected ? The extensive capillary network in the walls of the air vesicles in man, if spread out in a continuous sheet, would present a surface of about 75 square metres. Between the blood in the capillaries and the air in the air vesicles are two layers of living cells — 1st. The endothelium lining the capillaries. 2nd. The flattened cells lining the air vesicles. Through these cells the interchange of gases must take place. The interchange might take place in either or both of two ways — 1st. By simple diffusion. 2nd. By some special action of the cells. If the process follows strictly the laws of diffusion, it is unnecessary to invoke the activity of the cells as playing a part. But, if the gaseous interchange does not strictly follow these laws, we must conclude that the cells do play a part. Diffusion tal:es place from the point of higher partial pressure to the point of lower pressure till equilibrium is established. To determine if the process can be accounted for by diffusion, it is therefore necessary to know — 1. The partial pressure of the gases in the air in the vesicles of the lungs. 2. The partial pressure or tension of the gases in the blood going to and coming from the lungs. 1. Partial Pressure of Gases in the Air Vesicles.— The method 540 VETERINARY PHYSIOLOGY of determining the partial pressure or tension of a gas in the atmosphere has been described on p. 492, and it has been shown that at sea-level, with an atmospheric pressure of 760 mm. Hg, the tension of oxygen is about 152 mm. Hg. The air in the vesicles or alveoli is renewed partly by direct ventilation from without, and partly by a process of diffusion (p. 492). For this reason the amount of oxygen in the vesicles must be smaller, the amount of carbon dioxide larger, than in the air respired. Haldane has devised a method of procuring samples of the alveolar air for analysis. A wide tube is fitted with a measured glass bulb near one end, and this bulb is made a vacuum. The Mouthpiece SsLmpling Tube Fig. 219. — Haldane's Apparatus for Determining the Composition of Alveolar Air. end of the tube near the bulb is put in the mouth or fitted to a mask, and the person under observation breathes through it. At the end of an ordinary inspiration he expires deeply through the tube, closes the mouthpiece with his tongue, and by opening the upper stop-cock collects a sample of the expired air. A second sample is taken in the same way at the end of a normal expiration. The mean of these samples represents the average composition of the alveolar air (fig. 219). By the use of this method, it has been found that the partial pressure of the 0„ varies within wide limits, while tlie partial pressure of the CO 3 remains very constant. Thus, at the top of Ben Nevis the tension of oxygen in the air vesicles was 76 mm. Hg, at the bottom of a mine it was 111 mm.; while in both jolaces the tension of carbon RESPIRATION 541 dioxide was about 42 mm., the amount varying from about 4 to 5'5 per ceut. At sea-level the partial pressure or tension in the alveoli may be taken as about — O, = 100 mxn. Hg. 00^=42 mm. Hg. From the great inequality in the expansion of the lungs in different parts of the thorax and the resulting differences in the ventilation of the air vesicles, the samples of alveolar air taken by Haldane's method will tend to give too low a carbon dioxide and too high an oxygen figure, since the sample is chiefly derived from the better ventilated part of the lung. This means that in the less expanding parts of the lung the blood is subjected to a higher partial pressure of CO.-,, and a lower partial pressure of 0„. 2, The Partial Pressure or Tension of the Gases in the Blood. — The tension of Oo and C0„ in the blood has been already considered (p. 492). Whether a gas is simply dissolved, or whether it be held in loose chemical combination, its amount will depend upon the temperature of the fluid and upon the 'pressure of the gas over the fluid. If the temperature is raised, the fluid will hoM less of the gas. If the pressure of a gas over a fluid is increased, some will be taken up by the fluid ; if it be decreased, the gas will tend to come off from the fluid, as occurs when a bottle of soda water is opened. Thus, for every temperature, there is a certain pressure of the gas in the atmosphere at which the solution or chemical combination exposed to it will neither give off nor take up more of the gas, and this gives the measure of the tension of the gas in the fluid. Theoretically, the determination of the tension of a gas in a fluid is simple (p. 492). But when it has to be carried out in circulating blood it becomes extremely difficult. It must be carried out without marked disturbance of the circulation, and a thorough exposure of the air to the blood must be secured. The trouble of clotting has also to be faced. The best results have been obtained by the aerotonometer of Krogh, in which a bubble of air is exposed to the blood. 542 VETERINARY PHYSIOLOGY and, after equilibrium has been established, is withdrawn and analysed. Its volume is measured in a line graduated tube. It is then forced through caustic soda solution till all the CO2 is absorbed, again drawn into the tube and measured, the decrease in volume giv- ing the amount of CO2. Xext, it is passed through a solution of sodium pyrogallate in caustic soda to absorb the Og ____> and is again measured. ^, The residual gas is nitro- :20.-Kroglvs Microtonometer. B., g^U, a _ small amount of chamber attached to blood-vessel whicll is always dissolved with bubble of air ; -1 fine graduated J^ the blood. From the tube in water jacket tor analysis of gases. " percentage of these gases in the bubble their ten- sion in the circulating blood in which the bubble of air lay is calculated. The apparatus is shown in fig. 220. It has been found that the tension of 00^ in arterial blood is identical with that in the air in the vesicles of the lungs. When the amount in the air is altered, the tension in the blood follows the variation. The Og tension in venous blood is in all cases lower (by 1 to 4 per cent.) than that in the air of the lung vesicles, and it also follows any alteration in the latter. Krogh has also shown that, by modifying the air breathed, 0„ may be made to come off from the blood, and COo to be taken up by the blood. The difference in the pressure of these gases in the alveolar air and in the blood may be represented as follows in mm. Hg : — Oxygen. Carbon Dioxide. Alveolar Air . Blood from Lungs 100 96 RESPIRATION 543 The exchange of gases between the air of the lungs and the blood may therefore be explained by simple diffusion. So perfect is the exchange that the tension of a gas in the air of the alveoli may be taken as a measure of the tension in the blood flowing through the lungs. Brodie has suggested that a dead lung, through the vessels of which the blood is allowed to flow, might be used a tonometer. Haldane maintains that at low partial pressures of oxygen, the passage of the gas from the alveoli to the blood cannot be explained by diffusion and that it must be due to some as yet unknown factor. Certainly the accumulation of gas in the swim bladder of fishes cannot be explained by the laws of diffusion of gases, and it seems to be dependent on the activity of the cells lining tlie bladder. It may be arrested by section of the nerves supplying the bladder. A. The Effects of Decreased Almosplieric Pressure. — The fact that the hEemoglobin in the blood is so nearly fully oxygenated at a pressure of only 50 mm. Hg (p. 493), explains why the pressure of this gas in the atmosphere may fall to about one-half of its normal 152 mm. Hg without interfering with the supply of oxygen to the blood, why men and animals can live at high altitudes, and why aviation to such enormous heights is possible. The record height is probably 30,500 feet, or about 10,000 metres. The following table shows the relationship of the height, partial pressure of oxygen in the alveolar air, and the per- centage saturation of the haemoglobin with oxygen, and it shows that at about 5000 metres (16,000 feet) the marked decrease in the oxygen carrying capacity of the blood begins (consult p. 545). When an animal is suddenly subjected to a very marked decrease of pressure, especially if it has to do muscular work, as in climbing, the decreased supply of oxygen leads to shortness of breath, palpitation, and even to sickness (mountain sickness). These symptoms generally pass off, increased pulmonary venti- lation and increased heart's action augmenting the intake of oxygen. Hence, residence in high altitudes tends to increase the power of the respiratory muscles and the strength of the heart. It also increases the richness of the blood in erythro- cytes and in haemoglobin. 544 VETERINARY PHYSIOLOGY If a markedly deficient supply of oxygen is long continued, permanent damage may be done to many important structures, such as the heart and the central nervous system, and the respiratory centre may be so seriously modified that it may fail to act. The early implication of the higher centres in the brain may prevent the level 1 2 3 4 6 7 800 "•^.^ / "x " 62 / 85 54 ^0 48 76 41 i / N / V / ^^ / ^ Fig. 221.— To show the effects of altitudes from sea-level to SLKJO metres upon the pressure of oxygen in the alveoli of the lungs — — — and the saturation of the blood with oxygen individual from noticing the onset of the symptoms till consciousness is lost. It is therefore most important to administer oxygen as early as possible in such cases. B. The Effects of Increased Atmospheric Pressure- — On the other hand, the atmospheric pressure may be enormously increased without any change in the respirations being produced. The haemoglobin will not take up more than a definite amount of oxygen, and any increase is due to the gas dissolved in the plasma. RESPIRATION 545 In a diving bell, 200 feet under water, a pressure of seven atmospheres — 5120 mm. Hg — is sustained. As a result of the high pressure of the gases of such an atmosphere, they are dissolved in large quantities in the blood and tissues, and there is great danger in a too sudden relief of pressure, since this may cause bubbles of gas to be given off in the vessels, and these may lead to air embolism and a plugging of the smaller vessels (Caisson disease)- B. INTERMEDIATE RESPIRATION. 1. The Carriage of Gases in the Blood has been already considered (p. 492). 2. The Passage of Gases between Blood and Tissues- 1. Oxygen. — In studying the metabolism of muscle (p. 254), which may be taken as a type of all the active tissues, it was seen that oxygen is constantly being used by the muscle. The living tissues have such an affinity for oxygen that they can split it off from such pigments as alizarin blue. The tension of oxygen in muscle is therefore always very low. We have seen that the tension of oxygen in arterial blood is nearly 100 mm. Hg, and that, below a pressure of 50 mm., the oxygen is rapidly given off, till at 10 or 20 mm. Hg the oxyhsemoglobin is largely reduced. The influence of the €„ of the blood and of temperature upon the process has already been considered (p. 495). Hence, when the blood is exposed to a low tension of oxygen in the capillaries, the oxygen comes off from the blood and passes into the tissues by the ordinary laws of diffusion. The process takes place in three stages. The " head of oxygen," as it may be called in arterial blood, i.e. the difference of tension between that of the HbOj and that of the tissues is, in normal conditions, far in excess of the requirements. The haemoglobin is generally saturated to about 95 per cent., but in various pathological conditions of the lungs, e.g. pneu- monia, it may fall to as low as 50 per cent, saturation and still the same amount of oxygen per unit of volume of blood may be given off to the tissues, the saturation of the venous blood falling proportionately, i.e. the difference between them remain- ing at about 5 per cent. (fig. 222). 35 546 VETERINARY PHYSIOLOGY The tissues must be able to take up the oxygen they require from a wide range of pressure in the blood. CYAN 05 15 +H- + 4> ^ ^ nX^ -- 4 y J < f A' f / / PER CENT 10 20 20 40 50 60 JO 60 9 Fig. 222. — To show the relationship between the .saturation or unsaturation with oxygen of arterial and venous blood, with variations in the unsaturation of arterial blood from 5 to 50 per cent., in cases of pneumonia, with different degrees of cyanosis. (Stadie.) Such results cannot fail to raise the question of the beneficial effects of administering oxygen in pneumonia in order to increase the supply to the tissues. When a stagnation of blood in the capillaries occurs, it is very probable that the removal of oxygen is so complete that a true oxygen starvation of the tissues exists. (1) The tissue elements are always taking up oxygen from the tissue fluids, because of the very low tension of oxygen in the protoplasm. (2) As a result of this, the oxygen pressure in the fluids falls and becomes lower than the oxygen pressure of the blood plasma, and thus the gas passes from the blood, through the capillary walls, to the fluids. (3) As a result of the withdrawal of oxygen from the plasma, the partial pressure round the erythrocytes is diminished, a dissociation of oxyhsemoglobin takes place, and the oxygen passes out into the plasma, leaving some of the ha?moglobin in the erythrocytes in a reduced condition. 2. Carbon Dioxide. — The tissues are constantly producing carbon dioxide, so that it is at a high tension in them — about 60 mm. Hg. In the blood, as already indicated, it is partly dissolved and partly combined with sodium as the bicarbonate. Possibly it is partly combined with the proteins of the plasma, and probably in part with the globin of haemoglobin (p. 496). It RESPIRATION 547 is at a tension of a little over 40 mm. Hg in venous blood. Hence there is a constant passage of carbon dioxide from the tissues to the blood. The amount of C0„ Avhich the blood carries from the tissues to the lungs to be eliminated is a very small proportion of the total amount carried — only between 8 and 9 per cent, of the whole. Possibly this amount may be carried by the hasmoglobin (p. 496). C. INTERNAL RESPIRATION. This has been already considered under muscle (p. 254 et seq.). The rate of internal respiration depends upon the activity of the tissues, and not upon the amount of oxygen in the blood. It has been shown that, when a tissue is stimulated, the increased activity precedes the increased taking up of oxygen and giving off of carbon dioxide, thus confirming the view that the evolution of energy is not due to a direct oxidation (p. 249 et seq.). When the oxidation processes in the tissues are decreased as in poisoning with cyanides, the oxygen tension in the tissues is not lowered and COo is not evolved. Under these conditions the sarcolactic acid liberated passes into the blood and increases the 0^. But without the low tension in the tissues the partial pressure of the oxygen in the blood plasma remains so high that dissociation of HbOg does not take place and bright red blood passes on to the veins. D. EXTENT OF RESPIRATORY EXCHANGE. This has been studied under metabolism of muscle (p. 254 et seq.). The extent of the respiratory interchange in the lungs is governed by the extent of the internal respiratory changes, i.e. by the activity of the tissues and chiefly of muscle. Merely increasing the number or depth of the respirations has only a transient influence on the amount of the respiratory interchanges. Every factor which increases the activity of the metabolic changes in the tissues increases the intake of oxygen and the output of carbon dioxide by the lungs. 548 VETERINARY PHYSIOLOGY E. VENTILATION. The rate of gaseous exchange governs the necessary supply of fresh air. The subject is considered under Stable Manage- ment. In byres, some 800 cubic feet are generally allowed per cow. The bad effects of breathing in a crowded, close, badly- ventilated space is dealt with on p. 538. F. ASPHYXIA. This is the condition caused by any interference with the supply of oxygen to the blood and to the tissues, (a) It may be induced rapidly and in an acute form by preventing the entrance of air to the lungs, as in drowning or suflfocation, or by causing the animal to breathe air deprived of oxygen, or by interfering with the flow of blood through the lungs, or with the oxygen- carrying capacity of the blood, as in CO poisoning, or with the processes of oxidation in the tissues, as in poisoning with cyanides. (6) It is slowly induced, in a less acute form, when the muscles of respiration fail as death approaches. In acute asphyxia there is (1) an initial stage of increased respiratory effort due to the accumulation of C0„, the breath- ing becoming panting, and the expirations more and more forced. The pupils are contracted, and the heart beats more slowly and more forcibly, while the arterioles are strongly contracted, and a rise in the arterial pressure is generally produced. In some animals this is very transitory. When the vagi are cut, the slowing of the heart does not occur, and the rise of blood pressure may be more marked. (2) Usually within a couple of minutes, a general convulsion, involving chiefly the muscles of expiration, occurs. The intestinal muscles and the muscles of the bladder may be stimulated, and faeces and urine may be passed involuntarily. (3) Then, as the result of oxygen want, the respirations stop, deep gasping inspirations occurring at longer and longer intervals. The pupils are dilated, and consciousness is abolished. The heart fails, and thus, although the arterioles RESPmATION 549 are still contracted, the pressure in the arteries falls. (4) Finally, the movements of the heart cease and death supervenes. Before the heart has stopped, recovery may be brought about by artificial respiration, which may be performed by slow rhythmic compressions of the thorax and abdomen at a rate not exceeding the normal rate of breathing in the animal or by connecting the trachea to a respiration pump. VOICE. In connection with the respiratory mechanism of many animals, an arrangement for the production of sound or voice is developed. This is constructed on the principle of a wind instrumeat, and it consists of (1) a bellows, (2) a windpipe, (3) a vibrating reed, and (4) resonating chambers. In man and other mammals the bellows is formed by the lungs and thorax ; the windpipe is the trachea ; the vocal cords in the larynx are the vibrating reeds; and the resonating chambers are the pharynx, nose, and mouth. the structure of A. Structure of the Larynx. The points of physiological importance in the larynx are the following : — 1. Cartilages (figs. 223, 224).— The ring-like cricoid (Cr.), at the top of the trachea, is thickened from below upwards at its posterior part and carries on its upper border two pyramidal cartilages, triangular in section— the arytenoids (Ar.). These articulate with the cricoid by their inner angle. At the outer angle, the posterior and lateral crico-arytenoid muscles are attached. The vocal cords arise from their anterior angles and run forward to the thyreoid.^ The thyreoid cartilage (Th.) forms a large shield, which articulates by its posterio-iaferior processes with the sides of the cricoid, so that it moves round a horizontal axis. The epiglottis, or cartilaginous lid of the larynx, is fixed to its upper and anterior part. 2. Ligaments. — The articular ligaments require no special attention. The true vocal cords are fibrous ligamentous structures which run from the anterior angle of the arytenoids forward to the posterior aspect of the middle of the thyreoid. They contain many elastic fibres and are covered by a stratified squamous epithelium, and they appear white and shining. The vocal cords increase in length as the larynx grows ; in adult life, they are generally longer in the male than in the 1 The name thyroid, instead of thyreoid, is based upon a mistake ; Ovpeoi is a shield, while dupos is a door or aperture. 550 VOICE 551 female and the whole larynx is larger. The cleft between them is the rima glottidis, 3. Muscles. — The crico-tJtyreoidei take origin from the antero-lateral aspects of the cricoid, and are inserted into the inferior part of the lateral aspect of the thyreoid. In contract- ing they approximate the two cartilages anteriorly, and render tense the vocal cords (fig. 223). The crico-arytenoidei postici arise from the back of the cricoid and pass outwards to be inserted into the external or muscular process of tlie arytenoids. In contracting, they pull these pro- cesses inwards, and thus diverge the anterior processes and open the glottis (fig. 224). The crico-arytenoidei later- ales take origin from the lateral aspects of the cricoid, and pass backwards to be inserted into the muscular processes of the arytenoids. They pull these forwards, and so swing inwards their anterior processes and approximate the vocal cords (fig. 224). A set. of muscular fibres runs between the arytenoids— the arytenoideus transversus — while other fibres run from the arytenoids up to the side of the epiglottis. These help to close the upper orifice of the larynx. The thyreo-arytenoidei bands are of muscular fibres lying in the vocal cords, and running from the thyreoid to the arytenoids. Their mode of action is not fully understood. 4. Mucous Membrane.— The mucous membrane of the larynx is raised on each side into a well-marked fold above each true vocal cord— the false vocal cord. Between this and the true cord on each side is a cavity— the ventricle of the larynx. The other folds of mucous membrane, although of importance in medicine, have no special physiological significance. Fig. 22.3.— Side View of the Carti- lages of the Human Larynx. CV., cricoid cartilage; Ar., left ary- tenoid cartilage; Th., thyreoid cartilage. The dotted line shows the change in the position of the thyreoid by the action of the crico-thyreoid muscle, and the stretching of the vocal cords which results. 552 VETERINARY PHYSIOLOGY The interior of the larynx may be examined during life by the laryngoscope {Practical Physiology). 5. Nerves. — The muscles of the larynx are supplied chiefly by the recurrent laryngeal branch of the vagus, which comes oflF in the thorax, and arches upwards to the larynx. On the left side, where it curves round the aorta, it is apt to be pressed upon in aneurismal swellings. Paralysis of this nerve causes the vocal cord on that side to assume the cadaveric position, midway between adduction and ab- duction, and makes the voice hoarse or abolishes it altogether. The superior laryngeal is the great ingoing nerve, but it also supplies motor fibres to the crico - thyreoid muscle. Paralysis prevents the stretching of the vocal cords, makes the voice hoarse, and renders it im- possible to produce a high note. Centre. — These nerves are presided over by (a) a centre in the medulla. When this is stimulated abduction of the vocal cords is brought about. (6) This centre is controlled by a cortical centre situated in the inferior frontal convolution. Stimulation of this causes adduction of the cords as in phonation, while destruction leads to no marked change. Fig. 224. — Cross Section of the Larynx, to show the cricoid, Cr. ; thyreoid, Th. ; arytenoid cartilages, Ar. The continuous line shows the parts at rest, the dotted line under the action of the lateral crico-arytenoid muscle, and the dot-dash line under the action of the posterior crico-arytenoid. B. Physiology of the Voice. When a blast of air is forced between the vocal cords when they are approximated by the lateral crico-arytenoids, they are set in vibration both wholly and in segments like other vibrating VOICE 553 reeds aud sounds are thus produced. These sounds may be varied in loudness, pitch, and quality. The loudness, or amplitude of vibration, depends upon the size of tiie larynx and of the resonating chambers — the pharynx, uaso-pharynx, and mouth — and upon the force of the blast of air acting upon the cords. The pitch, or number of vibrations per second, depends upon the length and tension of the vocal cords. The greater length of the vocal cords in the male, as compared with the female, makes the voice deeper. The tension of the cords is varied by the action of the crico-thyreoid muscle. The power of varying the pitch of the voice differs greatly in different animals. The average difference between the lowest and the highest note which the ordinary human individual can produce is about two octaves. The quality of the voice, upon which the characteristic sound produced by each species of animal is largely due, depends upon the overtones which are made prominent by resonance in the pharynx, nose, and mouth. By varying the shape and size of these cavities, and more especially of the mouth, the quality of sound may be considerably altered. Roaring is the peculiar sound made by some horses when exercised. It is due to paralysis of the posterior crico-arytenoid muscle on the left side. This when in action abducts the vocal cord of that side, but when not in action it allows it to be drawn inward. This partially occludes the rima glottidis, and thus not only causes the characteristic sound, but also limits the entrance of air and oxygen to the lungs. The con- dition appears to be due to disease of the recurrent laryngeal nerve. It is more common in stallions than in mares, and most frequent in thoroughbreds. By some it is considered to be hereditary. Tracheotomy with the insertion of a tube into the trachea relieves the evil effects of the condition. SECTION VII. EXCRETION OF MATTER FROM THE BODY. I. EXCRETION BY THE LUNGS (see Respiration, p. olSet seq.). II. EXCRETION BY THE BOWEL (see p. 361). Ill EXCRETION BY THE KIDNEYS. I. URINE. I. General Consideration. The urine is a fluid formed in the kidneys, and in it are excreted from the body — 1. The nitrogen, sulphur, and phosphorus containing pro- ducts of the catabolism of proteins and of nucleo-proteins of the body and of the blood. 2. Any excess of H or OH ions in the blood. 3. Any excess of certain substances taken with food or produced in the body, e.g. sugar and sodium chloride. 4. Various drugs. Its composition should be studied in the light of the ■ catabolism of proteins and nucleo-proteins. (In reading this part, the Table on pj). 568 and 569 should be constantly referred to.) 1. Catabolism of Proteins. — As already indicated, the pro- tein molecule breaks down into its constituent amino-acids (p. 16), and these are de-aminised chiefly in the liver (p. 359). The ammonia liberated, probably as ammonium carbonate, is dehydrated chiefly in the liver (p. 359) to form urea — 554 URINE 555 II II H,— N C N— H., ^H.,N— C— NH. "I H„ O i i H. + 2H.0 When a condition of acidosis (p. 482) develops, a certain proportion of the ammonia is not dehydrated, but is used to neutralise the acid and to decrease the Ch of the blood (p. 482), and the proportion of NH3 to CO(NH,), is thus raised. When alkalies are given the proportion of ammonia is decreased. In the diamino acids, such as lysin, arginin, histidin (p. 17), the amidogen is dealt with as in the mon-amino acids. But in the case of arginin, where the guanidin nucleus — NH II H.,N-C-NH., is present, this may in part, at least, escape complete oxidation to urea, may be methylated and then linked to acetic acid to form creatin (p. 209), from which creatinin may be formed by dehydration. The amino acids linked to the benzene ring, e.g. tyrosin, are deaminised and the amidogen changed to urea, while the propionic acid chain is oxidised from its free end with the formation of homogentisic acid (alkapton) then hydroquinone, which is finally oxidised to CO., and H.O, the former of which is largely excreted by the lungs. In one abnormality of metabolism the oxidation stops at alkapton, and this is excreted in the urine. It oxidises to a black pigment. In tryptophan not only is the propionic acid chain oxidised, but the pyrrol ring is split off and the molecule then undergoes the same changes as tyrosin. When, as a result of bacterial putrefaction in the intestine (p. 329), the tryptophan molecule has had the propionic acid oxidised without the removal of the pyrrol ring, skatol and indol are formed. These are hydrated to skatoxyl or indoxyl. 556 VETERINARY PHYSIOLOGY and, in the liver, linked to sulphuric acid or potassium sulphate derived from the sulphur of the protein molecule, and thus excreted as ethereal sulphates, the amount of which in the urine is a fair measure of the putrefaction changes in the intestine. The remaining sulphur of the protein is chiefly oxidised to sulphuric acid, linked to bases and excreted as the inorganic sulphates. A small part of the sulphur which in the protein exists as cystin may escape oxidation and appear in the urine. In some people this excretion of cystin is large, and cystin crystals appear in the urine (neutral sulphur). The sulphates and the neutral sulphur are derived from the sulphur of the proteins, and the amount excreted in the urine is a measure of the amount of protein catabolised. Tbe nucleo-proteins are first split into the protein moiety, which is broken down as described above, and the nucleic acid moiety, which is broken down, possibly by an enzyme, a nuclease, and the phosphorus and purin parts then undergo ciianges and are excreted in the urine. (a) The purins of nucleic acid, e.g. adenin, are amino-purins i.e. they have an amidogen molecule attached. This is split off, possibly by the action of an enzyme, and excreted as urea. The deaminised purins, such as hypoxanthin, are then oxidised to uric acid and partly excreted in this form. In this process an enzyme may play a part. About one-half of the uric acid is split into two molecules of urea, probably by the action of another enzyme (uricoclastase) in the liver, while the connecting chain is oxidised to C0„. (6) The phosphorus is oxidised to P.^Og and linked with monobasic sodium and potassium and dibasic calcium and magnesium. 2. Regulation of the H— OH ions of the Blood. — The phos- phates play an important part in regulating the Ch of the tissues and in determining the reaction of the urine (Appendix III.). If the Ch of the blood is increased in acidosis (p. 481), the Na„HPO, of the cells is changed to (NaH.PO J (p. 482) and is turned out into the plasma to be excreted in the urine and thus to carry off H ions. URINE 557 If, on the other hand, a condition of alkalosis (p. 531) is produced, Na.^HPO^ is excreted — OH ions being elimin- ated. Under normal conditions the reaction of the urine varies between Na„HPO^ and NaH,PO,. The administration of acids does not materially increase the hydrogen ion concentration. They combine with the sodium of the bicarbonate of the plasma, turn out the CO2, increase the amount of dissolved COo, and thus stimulate the respiratory centre to increase the ventilation of the lungs and then to eliminate the COo and adjust the proportion of — HXO3 ^ 2 NaHCOg 20" But when alkalies are given, or the citrates, malates, and tartrates of sodium or potassium which are oxidised to carbonates in the body, the kidneys then act in eliminating the increased OH ions and thus readjusting the balance of ions in the blood plasma. II. Physical Characters. The characters of the urine depend largely on the relative proportion of water and of solids which are excreted in it : at one time it may be very concentrated, while at another time it may be very dilute indeed. For this reason its specific gravity, which depends upon the percentage of solids in solution, varies within wide limits. But the average specific gravity in the horse is about 1036. It is possible from the specific gravity to form a rough idea of the amount of solids present, for by multiplying the last two figures by 2'22 the amount of solids per 1000 parts is given. Since the percentage of pigments in the urine varies like that of the other constituents, the colour of the urine shows wide divergence in the normal condition. A concentrated urine has a dark amber colour, while a dilute urine may in some animals be almost colourless. Under average conditions the urine has a straw-yellow colour. The reaction of urine is normally acid in dog and other carnivora. 558 VETERINARY PHYSIOLOGY In herbivora, when suckling or when fasting, the urine is acid, but when on their normal diet it is alkaline. The alkalinity is due to the presence of alkaline carbonates formed from the citrates, malates, and tartrates of the vegetable foods, and also from the acetates, etc., produced by the decom- position of cellulose in the rumen and intestine. Urine in carnivora is normally transparent; but when it has stood for a few hours, a cloud of a mucin-like substance is seen floating in it. In herbivora, as the urine cools, it rapidly becomes turbid and throws down a white precipitate composed chieriy of carbonate of lime. The smell of urine is characteristic, and it may be modified by the ingestion of many different substances. III. Composition. The tests for the various constituents of the urine must he studied ijractically {Chemical Physiology). Since the relative amounts of water and solids vary within such wide limits, the percentage amount of the later is of little moment. Under average conditions, the water constitutes about 96 per cent., and the solids about 4 per cent. Of these solids, rather more than half is organic, rather less than half is inorganic. Since water and solids are derived from the water and solids taken by the animal, the amounts excreted depend upon the amounts taken, and must be considered in connection with them. Thus, if a horse takes little fluid, it will pass little water in the urine. If it takes little food, a small quantity of solids will be excreted by the kidneys. Since excretion and ingestion must be studied in relation- ship to one another, it is convenient to compare them during a definite period of time, and the natural division into days of twenty-four hours is generally adopted. Under ordinary conditions, the amount of solid food taken per day does not vary very greatly, but the amount of fluid imbibed varies within much wider limits. For this reason, Avhile the amount of water excreted in the urine per diem varies enormously, the amount of solids is more fixed. In the horse, on an averagfe diet, about 5 to 8 litres' of water URINE 559 are daily eliminated, while in the ox as much as 20 litres may be passed. 1. Nitrogenous Constituents. The waste nitrogen of the body occurs in the urine in different substances, the origin of each of which has been considered. A. Urea. — Urea is the most abundant constituent of the urine. Its chemistry and mode of formation have been discussed on p. 359. The amount excreted depends upon the amount of iwotein taken in the food, and for this reason, in man during fasting, the excretion may fall as low as 10 grms. per diem, while on a diet containing an average amount of proteins, about 86 grms. of urea — 16 "7 grms. of nitrogen — are excreted. On a normal diet about 90 per cent, in the dog and 80 per cent, in the horse of the waste nitrogen is excreted as urea, but, when the protein intake is decreased and non-nitrogenous food is substituted, the proportion of urea-nitrogen may fall as low as 60 per cent, of the whole (p. 562). When urine is allowed to stand, micro-organisms are apt to gain access, and to cause a hydration of the urea, whereby it is changed into ammonium carbonate — O II il H,N— C— NH,-F2H,0 = H,N— O— C— 0— NH, The urine is thus made alkaline, and the earthy jDhos- phates are precipitated. The magnesium phosphate combines with the ammonia to form ammonium-magnesium-phosphate, XH^MgPO^ +6H^0 (triple phosphate), which crystallises in characteristic prism-like crystals (fig. 225). B. Non-Urea Nitrogen. — Some 20 per cent, of nitrogen which, on an ordinary diet, is not excreted as urea is distributed in — 1. Ammonium Salts. — In herbivora a very small proportion of nitrogen is normally excreted as ammonium salts. But, under certain conditions, the proportion is increased (p. 554). Anything which tends to raise the Ch of the blood, e.g. the formation of /3-oxybutyric acid (p. 358), causes an in- creased excretion of ammonia — the ammonia being formed 560 VETERINARY PHYSIOLOGY from the proteins to neutralise the acids. In carnivorous and omnivorous animals the production of ammonia is a protective mechanism against acid intoxication, Herbivora have not the same power of forming ammonia to neutralise acids. 2. Creatinin. — Creatinin, like the creatin in muscle (p. 209), is characterised by containing the guanidin nucleus. It may be readily formed from creatin by treatment with acids which remove a molecule of water. NH II C /^N— H CH.,— N \ I NH ^\C— C— iO— H; But, when creatin is administered by the mouth or injected subcutaneously, the creatinin of the urine is not proportionately increased ; some of the creatin may appear in the urine, but much of it may not be recoverable, especially on a protein- free diet with abundance of carbohydrates. It seems to be retained or changed in the body, possibly being used in the resynthesis of the protein molecule. On the other hand, there is evidence that the creatinin in the urine may be taken as a rough measure of the muscular development and tone of the individual, and it is difficult to avoid the conclusion that it is derived either from the creatin of the muscle, or from some guanidin-containing precursor common to both. It is possible that every animal has a limited power of changing creatin to creatinin, and that this limit is readily overstepped — as the limit of sugar tolerance may be overstepped — and that under these conditions creatin is not converted to creatinin, but is excreted as creatin or changed in the body to some other substance not yet identified. In young children creatin is a normal constituent of the urine. In the wasting of muscles which occurs in fasting, creatin appears in the urine along with creatinin. In birds it takes the place of creatinin in the urine and the excretion is increased when the muscles waste. URINE 561 3. Purin Bodies. — A very small proportion of the nitrogen is found in these bodies. They consist of two unmodified or modified urea molecules, linked together by a nucleus of an acid radicle. In birds and reptiles the most important have as the linking part an oxy-acid with three carbons in series — Uric Acid— Tri-oxy-purin — an exceedingly insoluble substance which tends to crystallise in large polymorphic crystals. O II H— X— C I I = C C— N— H I II >c=o H— N— C— N— H Uric Acid. In these animals uric acid largely replaces urea as the sub- stances in which nitrogen is eliminated, and they are formed in the liver from the various products of the decomposition of protein molecules. But in mammals the purins appear to be very largely derived from the decomposition of nucleic acid (p. 556). Even when all supplies of nucleins and purin bodies from without are cut off, a certain amount of these purins is daily eliminated. These have been called the " endo- genous " purins, while those derived from the constituents of the food are termed the " exogenous " purins. A small amount is undoubtedly formed from the purins of muscle (p. 210). In most mammals the chief purin is Allantoin. In this two urea molecules are linked by the radicle of glyoxylic acid. H I H— N— C— N— H I C = I o = c I H— N C— N— H I II H 36 562 VETERINARY PHYSIOLOGY 4. Hippuric Acid. — This is benzoyl-amino-acetic acid — O II -C— CeHJ H H O i I II .N—C-C— O— H I H It is fornied from benzoic acid taken in the food by linking it to g'lycin — amino-acetic acid. This synthesis appears to take place in the kidneys, for it has been found that hippuric acid is not formed when these organs are excised, and that, when blood containing benzoates is circulated through them, hippuric acid is produced. Its chief interest is in the fact that it is one of the first organic compounds which were demonstrated to be formed synthetically in the animal body. Normally it is present in human urine in very small quantities, but in the urine of herbivora the amount is considerable, from the presence of benzoic acid in the fodder, and is most abundant on a diet of grass or hay, less so upon one of oats. The acid itself is insoluble, and it occurs as the soluble sodium salt. 5. Mon-amino Acids are always present in traces in the urine, and any interference with the activity of the liver, the organ chiefly concerned in changing them to urea, leads to their appearance in increased amounts (p. 860). 6. Undetermined Nitrogen. — A small quantity of the nitrogen in the urine exists in substances the chemical nature of which has not been determined. The amount of these varies con- siderably. The proportions of the total nitrogen of the urine in these various compounds varies with the kind of food taken. Folin gives the following table for the human subject, which shows this very clearly : — Per cent, of Total Nitrogen. Protein-rich Diet. Protein-poor Diet. Total Nitrogen Urea , , NH3 Creatinin Nitrogen Uric Acid Nitrogen Undetermined Nitrogen 14-8 to 18-2 grms. 86-3 ,, 89-2 per cent. 3-3 ,, 5-1 3'2 „ 4-5 ,, 0-5 „ 10 2-7 ,, 5-3 „ 4-8 to 8-0 grni.'?. 62-0 ,, 80-4 per cent. 4-2 ,, 11-7 5-5 „ 111 1-2 „ 2-4 4-8 „ 14-6 URINE 563 From these results he draws the conclusion that urea is largely the result of the metabolism of the proteins of the food, of " exogenous " protein metabolism, and that the creatinin and uric acid nitrogen and neutral sulphur (p. 564) are chiefly the result of " endogenous " protein metabolism. 2. Sulphur-containing Bodies. The sulphur excreted in the urine is derived from the sulphur of the protein molecule, and the amount of sulphur excreted may be taken as a measure of the amount of protein decomposed. A. Acid Sulphur. — The greater part of the sulphur is fully oxidised to sulphuric acid. (a) Preformed Sulphates. — The greater part of this is linked with bases to form ordinary inorganic sulphates. (h) Ethereal Sulphates. — Nearly all of the remaining sulphur is in organic combination, linked to benzene compounds, formed by oxidation of the indol, skatol, and phenol (see p. 330), which in carnivora are produced by the putrefaction of proteins in the bowel, and in herbivora from the aromatic compounds which occur chiefly in the roughage of the food. Indol is oxidised into indoxyl thus — f^ \ ,0-H NH This, when linked to potassium sulphate, forms potassium indoxyl-sulphate or indican. ,O.SO.,OK NH From skatol, which is methyl-indol, potassium skatoxyl- sulphate is formed in the same way. These bodies are colourless, but when oxidised they yield pigments — indican yielding indigo blue, skatoxyl-sulphate of potassium yielding a rose colour. 564 VETERINARY PHYSIOLOGY Phenol- IC.H J -''-'' kHl-°-'° = °^ is also linked with potassium sulphate, and excreted in the unne. The amount of these ethereal sulphates depends upon the activity of putrefaction in the intestine, and is a good index of its extent. Dioxybenzene or Pyrocatechin — — 0-H l^eH,, _o_H is also linked to potassium sulphate and excreted. This com- pound is always present in the urine of the horse. When oxidised it yields a greenish-brown pigment when urine containing it is allowed to stand. B. Neutral Sulphur. — A small quantity of sulphur is excreted in a less oxidised state, in the form of neutral suljjJiur. The most important compound of this kind is cystin, the disulphide of amino-propionic acid — two molecules of amino-propionic acid linked by sulphur — Amino-propionic acid. I Sulphur. I Sulphur. Amino-propionic acid. H H I I H_C-S — S-C-H I I H— C— NH.. H..NC— H I " ■ I C_OH HO— C II li o o URINE 565 The condition of cystinuria has been already explained (p. 556), as has also the occurrence of alkaptonuria (p. 555). 3. Phosphorus-containing Bodies. In herbivorous animals phosphates are practically absent from the urine. They are excreted from the mucous membrane of the bowel. Hence, in the horse, crystals of triple phosphates are found in the faeces, not in the urine. In carnivores the phosphorus in the urine is derived partly from phosphates taken in the food, and partly from the nucleins of the food and tissues and from the bones. (a) Normally the phosphorus is fully oxidised to PoO,, which is linked to alkalies and earths, and excreted in the urine. The most important phosphate is the phosphate of soda, NaH.PO^, which is the chief factor in causing the acidity of the urine. When the urine becomes ammoniacal, triple phosphate is formed (p. 559). (b) It is probable that a small quantity of the phosphorus is excreted in organic compounds, such as glycero-phosphates ; but so far these have not been fully investigated. 4. Chlorine Compounds. Sodium chloride is the chief salt of the urine. It is entirely derived from the salt taken in the food, and its amount varies with the amount ingested. From 10 to 15 grms. are usually excreted per diem in a person on a normal diet. In starvation, to a certain extent, and very markedly in fever, the tissues of the body have a great power of holding on to the chlorine, and the chlorides may almost disappear from the urine. 5. Inorganic Bases of the Urine. Sodium, potassium, calcium, and magnesium occur in the urine in amounts varying with the amounts taken in the food. On a flesh diet and in starvation potassium is in excess of the others. Calcium and magnesium are present in much smaller quantities. In herbivora potassium is the chief salt, and in the horse calcium is also abundant. 566 VETERINARY PHYSIOLOGY 6. Pigments. A brown hygroscopic substance, Avhich gives no bands in the spectrum, may be extracted from urine. This has been termed urochrome. By reducing it, another pigment, urobilin, is produced, which gives definite bands, and which is frequently present in the urine. It is probably identical with the hydro- bilirubin which has been prepared from the bile pigments, and it contains C, H, 0, and N. The pigment that gives the pink colour to urates has been called uroerythyrin, and its chemical nature is unknown. Hsematoporphyrin (see p. 491) is normally present in traces in the urine, but in certain pathological states it is increased in amount and gives a brown colour to the urine. 7. Nucleo-Protein. A mucin-like nucleo-protein, derived from the urinary passages, is always present in small amounts, and forms a cloud when the urine stands. 8. Carbonic Acids. 1. Carbonic Acid. — Small amounts of this are present in urine of carnivora. In herbivora it is present in large amounts, combined with Fig. 225. — The Three most Common Urinary Crystals : 1, Triple phosphate; 2, uric acid ; 3, calcium oxalate. potassium, lime, and magnesia, and also free. The carbonate of lime readily crystallises out in large dumb-bell-like crystals which may be confused with crystals of oxalate of lime, but which are quickly soluble, with effervescence, on the addition of an acid. FORMATION OF URINE 567 9. Oxalic Acid O O II II H_0— C— C-0— H is a substance in a stage of oxidation just above that of carbonic acid. It is frequently present in the urine linked with lime, and the lime salt tends to crystallise out in characteristic octohedra, looking like small square envelopes under the micro- scope. Under certain conditions these crystals assume other shapes. The oxalic acid of the urine is chiefly derived from oxalates in vegetable foods, but it has been detected in the urine of animals on a purely flesh diet. The differences between the urines of different herbivora are not important. The urine of the ox and cow is more abundant and more dilute than the urine of the horse, while the urine of the sheep is considerably more concentrated and contains a very high proportion of hippuric acid. II. FORMATION OF URINE. No problem of physiology has proved more difficult than that of the mode of formation of urine in the kidneys. This is largely due to the fact that theories were made by famous physiologists upon imperfect data, and that subsequent workers have tended to view their results in the light of one or other of these theories. The purpose of the formation of urine, as already explained, is twofold — 1 . To get rid of waste matter from the body. 2. To help to maintain the Oh of the blood plasma (p. 554). The problem of how it is produced may best be approached by considering — 1st. The differences between the urine formed and the blood from which it is formed. 2nd. The apparatus which has to bring about these changes — the kidney. RELATIONS OF THE DECOMPOSITION PRODUCfS NUCLEO-PROTEIXS Xiicleases I NL^CLEIC ACID P,05 PURIXS e.g. Adenin PCRINS OF Flesh Mox-Amixo Acids N=C H I i I -C C— N. II II \C-H N— C— N — Deamidase e.g. I Hypoxanthine O -N— C H I I I -C C-N X— c- -n/ C— H Oxydase I Uric Acid H i :i N — C I : I =C ; C I N I H H -C— C- l H -OH Deamidase a.mmonium Carbonate Di-Amino Acid3 e.g. Argiiiin I . \ ? NHo H H H i H N i i I M I II HO-C-C— C-C-C-N-C-^] 1 li I I I ' : ! I H H H H I I I Ornitliin Guanija I I H,N-0-C-0— NH, Dehydrating Enzymes H„N-C- Creatiii XHCH3H I! i I , N— C— C— OH I H I Creatiniii NH HX'- C A -N N-H Trea U H^C Phos- phates Uricodastase 7- H.X — C — XH, Uric Acid Urea 'or Ammoxia) The NH2 groups marked with ♦ are chaii^ C Creatini>- to urea. )F PROTEINS TO THE CONSTITUENTS OF URINE V PROTEINS 'OLYPEPTIDES ' 1 1 jiiDES Benzene Compodnds, e.g. Tryptophan 1 Sulphur, Organic Compounds, e.g. Cystin II ♦ t-C-NH, /\ H 1 -C- H 1 II -C— C— OH H,N- H H 1 1 1 \/\/ NH 1 H 1 NH, Jc fo -C— H H-C— NH. 1 1 (a) Digestion and Tissue Enzymes Tyrosin /x^OH 1 1 H H (6) Bacteria Skatol /^ CH3 1 ' H- -C-S- 1 H _ S-C-H 1 H \/_(^_C-C- 1 1 ♦ H NHj Homogentisic Acid -0- -h\/\/^ NH Indol (Alkapton) \ ' ' ,A0H NH \^ _C-C-0- 1 H Hydroquinone -H Indoxyl /\ 1 1 r NH " Indican " r HOI^ /\ -0 II — S- 11 0-K III NH Ethereal Sulphates K,& iNORGi Sulph O4 vNic Neui ATES SuLP e.g.C ^RAL hur, ystin 570 VETERINARY PHYSIOLOGY 1st. The chief differences between the urine and the blood plasma. 1. The blood plasma contains some 7 to 8 per cent, of native proteins ; in normal urine these are absent. 2. The blood plasma is almost neutral, i.e. it has a Ch of 10"'^ or pH 7'4. The urine is generally markedly acid with a pH of about 6 (Appendix III.). 3. The molecular concentration of the plasma, as determined bv the reduction of the freezing-point, corresponds to about A 0-56'' C, corresponding with about 0-9 per cent, of NaCl. The urine has a molecular concentration of from Al to 2-5 or even higher. 4-. The urea in the plasma amounts to about O'OS per cent. In the urine it is about 2 per cent., i.e. it is concentrated 60 times. 5. Uric acid is concentrated 25 times. Ammonia „ 40 ,, PO, „ 30 „ SO, „ 60 „ 2nd. The apparatus which brings about these changes. — The kidnev, the apparatus which has to effect this change, is a structure evolved from the nephridium of the annelid. This nephridium consists of a tube, opening by a funnel- shaped end into the coelomic cavity and by a narrower orifice on the surface. The tube is lined by a syncytial secreting epithelium, in which may be seen the waste particles which occur in the coelomic fluid, or which have been injected into the ccelome, e.g. Indian ink. It thus allows an escape of fluid from the cffilome and passes out waste particles through the epithelium. In the vertebrate the coelomic orifice of each tubule is invaded by a tuft of capillary vessels, forming the glomerular tuft round which the remains of the funnel-shaped opening persists as the capsule of Bowman. The whole structure is often called a Malpighian body. The tubule in the vertebrate becomes enormously lengthened and differentiated into distinct segments. Myriads of these Malpighian bodies and tubules are massed together to form the kidney. This may be briefly described as follows : — FORMATION OF URINE 571 I. Structure of the Kidney. {TJiis must he studied practically.) Each kidney presents a depression or hilus on its inner aspect from which the ureter, the duct of the kidney passes, and by which the renal artery enters and the renal vein emerges. The nerves and lymphatics of the organ pass along with these. The whole organ is enclosed in a fibrous capsule, from which processes of fibrous tissue carrying small blood-vessels enter the organ. Fk;. 226. —Diagram of the Structure of the Kidney. M.P., Malpighian pyramid of the medulla ; M.R., medullary ray extending into cortex ; L., labyrinth of cortex; M.B., a Malpighian body consisting of the glomerular tufi and Bowman's capsule; P.C.T., a proximal convoluted tubule; H.L., Henle's loop on the tubule; D.C.T., distal convoluted tubule; C.T., collecting tubule; R.A., branch of renal artery, giving off I. LA, interlobular artery, to supply the glomeruli and the con- voluted tubule; ZL.Z?., interlobular artery bringing blood back from the cortex. The ureter opens from the basin of the kidney, and into this the renal tissue projects as pyramidal processes. This renal tissue is clearly divided into a thin outer cortex and an internal medulla. This latter is again subdivided into a paler pyramidal part, and a redder part between this and the cortex— the boundary zone. The medulla extends out into the cortex in a series of long medullary rays (fig. 226), so that the 572 V^ETERINARY PHYSIOLOGY cortex may be subdivided into these rays and the parts between the rays — the labyrinth of the cortex. It is in this that the Malpighian bodies already described are situated. Extending away from each of them is a proximal convoluted tubule, also in the labyrinth {P.C.T.), lined by pyramidal and granular epithelial cells. This dives into the boundary zone of the medulla, becomes constricted and lined by a transparent flattened epithelium, and is known as the descending limb of the looped tubule of Henle. Turning suddenly upwards and becoming lined by a cubical granular epithelium, it forms the ascending limb, and, reaching the labyrinth of the cortex, it ex- pands into the distal convoluted tubule (D.C.T.), which resembles the proximal. It opens into a collecting tubule, running in a medullary ray, and {G.T.), lined by a low transparent epi- thelium, which conducts the urine to the pelvis of the kidney. The renal artery breaks up and gives off a series of straight branches — the interlobular arteries (IL.A.) — which, as they run towards the surface, give off short side branches which terminate in the glomeruli. The efferent vein passing from each glomerulus breaks up again into a series of capillaries between the con- voluted tubules, and these pour their blood into the interlobular veins (IL.V.). This arrangement helps to maintain a high pressure in the capillary loops of the glomerular tuft. Nerves to the kidney in the dog pass in the splanchnic nerves from the anterior roots of the sixth to the thirteenth dorsal nerves, and from the vagus, chiefly through the semilunar ganglion, and the renal plexus upon the renal blood-vessels. The terminal fibres not only supply the arterioles, but may be traced into the secreting cells of the tubules. Apparently the old differentiation of the nephridium with the arrangement for allowing the escape of coelomic fluid and for the excretion of waste material is preserved in the vertebrate kidney, but now the coelomic fluid is confined to blood-vessels which are related to both the coelomic expansions and the tubules. II. Physiology of the Formation of Urine. Bowman, from his investigations of the structure of the kidney, but without giving consideration to its phylogenetic FORMATION OF URINE 573 development, pointed out that two distinct mechanisms exist — 1st. In the Malpighian bodies, an arrangement manifestly- suited to allow of filtration from the blood. 2nd. In the tubules, a series of secreting structures. A. Malpighian Bodies. 1. It has been shown by injecting acid fuchsin, which is colourless in alkaline solution and red in acid solution, into the blood-vessels that the urine formed in these bodies is alkaline in reaction. It becomes acid as it passes down the convoluted tubules. 2. It is also known that these bodies are thrown out of action by lowering the pressure in the renal arterioles and by decreasing the flow of blood through the kidney. The amount of blood in the kidneys may be measured by enclosing the organ in a closed vessel with rigid walls connected with a piston recorder — an oncometer — so that changes in the volume of the organ may be recorded, while the rate of flow may be estimated by measuring the amount of blood coming from the renal vein (p. 473). These two methods are frequently used in combination. (a) Section of the splanchnic nerves to the kidney causes a dilatation of the renal arterioles, an expansion of the kidney, and an increased flow of urine. (6) Stimulation of these nerves has the opposite eff"ect. Sometimes stimulation with slow induction shocks may cause a dilatation, but the action of these dilator fibres is generally masked by that of the constrictors, (c) A fall in the general arterial pressure, to about 50 mm. Hg in the dog, causes a decreased flow of blood through the kidney and practically stops the flow of urine, although the tubules, as will presently be shown, still act. (d) Conversely, a stoppage of the formation of urine may be brought about by raising the pressure in the ureter to about 50 mm. Hg. 3. In the frog the renal arteries supply the Malpighian bodies, while portal veins, from the posterior end of the animal, supply the convoluted tubules. Ligature of the renal arteries stops the flow of urine ; but the flow may be again induced by injecting urea and other substances. 4. Even when this flow is induced dextrose, egg albumin 574 VETERINARY PHYSIOLOGY or peptone when injected into the blood are not excreted, although in the frog with the vessels unligatured they appear in the urine. These observations seem to show that the Malpighian bodies have to do chiefly with the filtering off from the blood plasma of water and of solids held in true solution, and that their activity depends upon the rate of blood-flow through them, and upon the pressure in the glomerular capillaries. That such a purely physical process is involved seems to be indicated by the fact that a free flow of urine (diiwesis) can be induced, without increasing the chemical changes in the kidneys, as indicated by Fk;. 227.— To show the reUitionship between the i^roduction of urine and the consumption of oxygen by the kidney under the influence of Ringer- Solution and of Sodium Sulphate. The black area indicates the amount of urine secreted, the thin line the consumption of oxygen. (Barcroft.) the oxygen consumption, by injecting into the blood hypertonic solutions of various salines, such as NaCl, which dilute the blood and increase its volume (fig. 227). The reason why the formation of urine stops when the arterial pressure falls to about 50 mm. Hg seems to be due to the fact that the filtration pressure must be well above the osmotic pressure of the colloids of the blood which are not filtered off. By determining the difference between the osmotic pressure of blood serum and of the filtrate from it through a semi-perme- able membrane Starling concluded that the osmotic pressure of the blood proteins is about 30 mm. Hg, and that therefore the- filtration pressure must be above this. When this osmotic FORMATION OF URINE 575 pressure, due to the colloids, is decreased formation of urine goes on at a lower pressure than 50 mm. Hg. He showed that the formation of urine is increased by injecting hypertonic solutions of glucose which caused a hydrsemic plethora by producing an endosmosis from the tissues to the blood (p. 450), and he further proved that this is not simply the result of an increased pressure due to the increased volume of the blood by demonstrating that the injection of fluids of high colloidal content did not increase the flow of urine. It is thus clear that filtration is the main factor in the formation of urine in the Malpighian bodies, and the membrane of cells through which this occurs must form a semi-permeable membrane which prevents the passage of the colloidal proteins of the blood. On the other hand, that a selective action of the epithelium is involved seems to be suggested by the passage into the urine in Bowman's capsule of such large molecules as those of egg albumin and haemoglobin and of various pigments such as carmine. The point of practical importance is that the secretion of water takes place cliiejiy through the Malpighian bodies, and that this is reduced or stopped by a fall in the general arterial pressure, such as occurs in failure of the heart. The decreased excretion of water may lead to the development of dropsy. B. The Tubules. In the filtrate, the percentage of the various substances in solution cannot be higher than it is in the blood plasma. But, as already stated, the concentration of most of the con- stituents of the plasma is generally enormously increased in the urine while the reaction is acid. These changes must be effected in the tubules. There are manifestly two ways in which they might be brought about. 1. By the secretion of solids by the epithelium from the blood to the urine (Bowman and Heidenhain). 2. By the absorption of some of the water filtered through the crlomeruli back into the blood (Ludwig). Since the degree 576 VETERINARY PHYSIOLOGY of concentration of the various urinary constituents, compared with their amount in the blood, varies very greatly (p. 570), some of these substances would also have to be absorbed along with the water. It is of course possible that both these processes are in operation. In carrying out either process the epithelium has to do an equal amount of ivork. This may be rendered clearer by the figure 228 — URINE IN TUBULE CELLS BLOOD ■^l||H,.0 |,|li'i reabsorbed. Ions secreted. Fig. 228. — To illustrate the two views of the mode of action of the renal tubules. The figures 16-2 and 6"7 give the osmotic pressures of the urine and of the blood plasma respectively. On the secretion theory, electrolytes have to be piled up from the point of low concentration in the blood to the point of high concentration in the urine ; while on the reabsorption theory water has to be taken from a point of high osmotic pressure and passed to a point of low osmotic pressure. It is well to understand what the reabsorption theory implies. To produce the average 30 grms. of urea excreted per diem by a man from the plasma containing 0'03 per cent, would mean the filtration through the glomeruli of some 30,000 cc. But since only 1500 cc. of urine are generally secreted, this would mean the reabsorption of no less than 28,500 cc. — about 95 per cent, of what was filtered off! The work of filtering off some 30,000 cm. has superimposed upon it the work of reabsorb- FORMATION OF URINE 577 ing 28,500 cc. ! The process, on the face of it, seems somewhat wasteful. But such evidence as has been procured must be examined on its merits, and the reabsorption theory cannot be rejected simply because it seems improbable. 1. Uric acid crystals are frequently found in the cells of the convoluted tubules of the kidney of birds. Further, uric acid is very soluble in piperazine, and when injected in solution of this substance into the veins of a mammal, the uric acid appears in the tubules and in the cells of the convoluted tubules, but not in the glomeruli or in the medulla. 2. Heideuhain, by injecting into the circulation of the rabbit a blue pigment — sulph-indigotate of soda — found that the cells of the convoluted tubules take it up and seem to pass it into the urine. In the normal rabbit the whole of the kidney and the urine became blue. But, if the formation of urine in the Malpighian bodies be stopped by cutting the spinal cord in the neck so as to lower the blood pressure, then the blue pigment is found in the cells of the convoluted tubules and of the ascending limb of Henle's tubule, since it is not washed out of these. The fact that later investigators have found after injection of aniline blue and Congo red, that these pigments appear first in the part of the cells next the lumen of the tubules seems of small significance. They might well accumulate there before being excreted. The subcutaneous injection into rats of pyrrol blue leads to the appearance of the pigment in the cells of the convoluted tubules but not in the Malpighian bodies nor in the collecting tubules. 3. When the Malpighian bodies of the frog have been thrown out of action by ligaturing the renal arteries, the injection of urea still causes a flow of urine and the excretion of urea by the tubules. When the portal veins, which supply the tubules, are ligatured on one side, it is found that less urine is formed on the ligatured than on the uniigatured side. 4. If the formation of urine in the Malpighian bodies of a dog be stopped by cutting the spinal cord in the neck, the administration of certain substances such as of caffeine, or Na„SO^, causes an increased flow of urine, although the blood pressure in the kidneys is not raised. In this diuresis the 37 578 VETERINARY PHYSIOLOGY consumption of oxygen by the kidney is increased, indicating an increased metabolism (fig. 227). The renal cells are in fact doing work. These last experiments seem to indicate that the cells of the convoluted tubules are capable of secreting water as well as solids. Large doses of caffeine poison the cells, and in this condition a flow of urine without increased consumption of oxygen is produced. This supports the view that filtration from the glomeruli plays a part. The stimulating action of such drugs as caffeine is taken advantage of in cases of heart-disease when the secretion of urine is almost arrested from low arterial pressure and when dropsy is rapidly advancing. The kidneys may be stimulated to get rid of water by means of such diuretics until compensa- tion of the heart is established. 5. The fact that after drinking copious amounts of water a urine of a lower osmotic pressure than the plasma may be produced, can be equally well explained by an increased secretion of water by the tubules as by the reabsorption of solids by them. 6. The action of extracts of the hypophysis cerebri in increas- ing the flow of urine while actually lowering the arterial pressure (p. 594) seems to indicate a direct stimulation of the cells of the tubules. 7. When a mixture of NaCl and of Na.SO^ are injected, the proportion of the latter in the urine increases after some time, and the conclusion has been drawn that the NaCl is being reabsorbed to be returned to the blood. If this were the case the cells would do work and the 0„ consumption should be increased. But the injection of NaCl leads to a diuresis, as explained above, which is not accompanied by increased consumption of 0„, while, on the other hand, the diuresis caused by Na„S0^ is accompanied by an increased metabolism of the kidney (fig. 227). An increased secretion of Na^SO^ seems to explain the facts of the case just as well as a supposed increased absorption of NaCl. Similarly, the fact that when NaCl is withheld, it practically disappears from the urine, although it persists in the blood may just as well be explained on the theory of a FORMATION OF URINE 579 decreased elimination, possibly as the result of its more intimate association with the blood proteins retarding its filtration, as on the theory of an increased absorption. At present it seems that no conclusive evidence of the theory that the concentration of the urine depends upon reabsorption has been adduced. Much of the evidence points to an active secretion, and the facts which do not directly point to this may be explained as well on the theory of secretion as on that of reabsorption. A verdict of not proven must be given, but since in the nephridial tubules of the annelid the epithelium is secretory, the onus of proving that the changes in the con- centration and reaction of the urine are due to absorption lies upon the supporters of this theory. The secretion theory does not raise the difficulty of explaining why a mechanism involving the filtration under pressure of such an enormous quantity of water with the sole purpose of having it again reabsorbed has been evolved, or of attempting to say at v/hat stage of evolution the epithelium of the nephridial tubules reversed their function. It has been suggested that, when animals became terrestrial, the need of conserving water arose and the tubules took upon themselves this function. But the tubules of aquatic animals are as well developed as those of terrestrial animals. Those who accept the reabsorption hypothesis claim that while such substances as urea are eliminated as fully as possible, other substances which are noi'mally present in the blood in appreciable amounts are reabsorbed to the extent of maintain- ing that amount. The first set of substances they call " non- threshold substances," the second " threshold substances." But the differentiation between these is just as readily explained on a theory of secretion as on a theory of reab- sorption. While the evidence at present forthcoming does not directly point to the changes in the urine as it passes down the tubules being due to reabsorption, it by no means excludes the possibility that some reabsorption may take place. The extraordinary differences in the structure of the epithelium in the convoluted tubules on the one hand, and of the looped tubules of Henle on the other, suggests the possibility that different processes may be carried on in these parts, that 580 VETERINARY PHYSIOLOGY possibly secretion may occur in the former and absorption in the latter. The kidney responds readily to very small changes in the concentration or composition of the blood. Dilution, even to an amount insufficient to disturb the blood pressure, may lead to increased secretion of water, and the increase of various salts in the blood, and especially of anions, may bring about an increase of secretion. Thus an arrangement is secured by which the composition of the blood plasma is kept constant, and its carry- ing capacity for carbon dioxide is regulated. Hence renal disease mav induce disturbance in the respirations (p. 527). The Influence of the Nervous System on the Kidneys. That renal secretion is fundamentally independent of the control of the central nervous system is shown by the facts (1) that it goes on after the nerves to the kidneys have been cut; (2) that it proceeds normally in a kidney which has been excised and transplanted. As already indicated (p. 573), stimulation of the splanchnic nerves causes a constriction of the renal vessels and a stoppage of the formation of urine. Stimulation of the vagus by inhibiting the heart and lowering the arterial pressure causes a fall in the secretion of urine. Stimulation below the cardiac branch, or after its cardiac endings have been poisoned with atropine, seems to produce no definite result. The action of the nervous system is therefore probably entirely through the vaso-motor mechanism. Vaso-constriction may be brought about — 1st. By direct stimulation of the vaso-constrictor centre as in asphyxia. 2ncl. Reflexly by stimulation of many ingoing nerves, e.g. (a) by the application of cold to the skin ; (6) by irritation of the bladder or urethra after the use of the catheter. Vaso-dilator effects on the kidney are produced by stimu- lating the posterior roots of the lower dorsal nerves, which may explain the beneficial action of warm applications over the EXCRETION OF URINE 581 loins in suppression of urine. There is some evidence that slight obstruction of a ureter may also cause a reflex vaso- dilatation with increased secretion of urine. III. EXCRETION OF URINE. 1. Passage from Kidney to Bladder. — The pressure under which the urine is secreted is sufficient to drive it along the ureters to the bladder. If these are obstructed, the pressure behind the obstruction rises, and may distend the ureters and the pelvis of the kidney, and when it reaches about 50 mm. Hg in the dog, the secretion of urine is stopped. The muscular walls of the ureters show a rhythmic peristaltic contraction, which must also help the onward passage of the urine to the bladder. 2. Micturition — As the urine accumulates in the urinary bladder, the viscus expands to accommodate it, the tone of the visceral muscular fibres being adapted to the degree of distension. The backward passage of the urine into the ureters is prevented by the way in which these tubes pass obliquely through the muscular coat of the bladder. When a certain distension is reached, rhythmic contractions are produced, which become more and more powerful. These are primarily dependent on the muscular fibres ; but the wall of the bladder is richly supplied with peripherally placed neurons, and the possible action of these in controlling the contractions has not been excluded. Even after section of the nerves to the bladder, this peripheral mechanism is capable of controlling the act of micturition. This involves not merely the contraction of the wall of the bladder, but also the relaxation of the visceral muscular fibres (the sphincter trigonalis) which surround the neck of the bladder, and of the striped fibres which surround the upper part of the urethra. It is therefore an act requiring the co-ordinated contraction and relaxation of muscles, and it is presumably presided over by the nervous mechanism in the wall of the bladder. 582 VETERINARY PHYSIOLOGY Normally this is controlled by the central nervous system. The bladder is supplied hy the ijelvic nerve, in which white fibres run to the peripheral plexus, and by si/mpathetic fibres which have their cell stations in the inferior mesenteric ganglion, from which post-ganglionic fibres run to the bladder. In most animals the former are chiefly augmentor, and the latter inhibitory, but in some animals, e.g. the ferret, the reverse is the case. Adrenalin causes relaxation or contraction, according to whether the inhibitory or augmentor fibres run in the sympathetics. The nerves are derived from a centre in the lumbar region of the spinal cord which normally controls the peripheral mechanism, and which may be reflexly excited by the passage of some urine from the bladder into the urethra or in other wa3'S, e.g. in the dog by sponging the anus with warm water. In some cases of inflammation of the spinal cord (myelitis), the increased activity of the centre may prevent the expulsion of urine, while later in the disease, when the nerve structures have been destroyed, the urine is not retained and dribbles away on account of the absence of the tonic contraction of the sphincter arrangement. The expulsion of the last drops of urine is carried out by the rhythmic contraction of the bulbo-cavernous muscle ; while the peristaltic contraction of the bladder wall is assisted by the various muscles which press upon the contents of the abdomen and the bladder. The horse micturates standing, but the ox can do so while walking. In the young, micturition is a purely reflex act, and in the dog it is perfectly performed when the spinal cord is cut in the back. As age advances, the reflex mechanism comes to be more under the control of the higher centres, and the activity of the sphincters may be increased or abolished as circumstances indicate. IV. Excretion by the Skin. The skin is really a group of organs, and some of these have been already studied. (The structure of the skin and its appendages must be studied practically.) (1) The Protective functions of the horny layer of epidermis, SKIN 583 with its development in hair, and of the layer of sub- cutaneous fat, are manifest. Hair. — The hairy coat of animals maintains a layer of air next the skin at a more equable temperature than that of the surrounding air, and so plays an important part in the regula- tion of temperature (p. 269). The strong hairs developed about the muzzle and in the eyelashes are tactile organs (p. 102). Attached to each hair follicle is a band of non-striped muscle, the arrector pili, which can erect the hair by contracting. These muscles are under the control of the central nervous system, and the nerve fibres have been demonstrated in the cat to take much the same course as the vaso-constrictor fibres of somatic nerves. They belong to the true sympathetic set of nerves. A hair after a time ceases to grow, and the lower part in the follicle is absorbed and the hair is readily detached. From the cells in the upper part of the follicle, a new down-growth occurs, a papilla forms and the hair is regenerated. In the horse this process occurs twice a year, and the thickness of the coat grown depends upon the degree of exposure to cold. The hair of the mane and tail and the tactile hairs are not shed with the rest of the coat. (2) The Sensory functions have been studied under the Receptors (p. 99 et seq.). (3) The Respiratory action of the skin in mammals is of little importance. (4) The Excretory Function of the Skin. Two sets of glands develop in the skin — sweat glands and sebaceous glands. A. Sweat Glands. 1. Structure. — The sweat glands are simple tubular glands coiled up in the subcutaneous tissue with ducts opening on the surface of the skin. The secreting epithelium somewhat resembles that of the convoluted tubules of the kidney. Sweat glands are Avidely distributed over the skin of the horse. In oxen and sheep they are less abundant, being most developed on the muzzle. In the dog and cat they are found in the nose and in pads of the feet. 584 VETERINARY PHYSIOLOGY 2. Functions. — From these glands, a considerable amount of sweat is poured out ; but to form any estimate of the daily amount is no easy matter, since it varies so greatly under different conditions (p. 269). When poured out, sweat evapor- ates, and in doing so causes loss of heat. When large quantities are formed, or when, from coldness of the surface, or of the air, or from the large quantity of watery vapour already in the air, evaporation is prevented, it accumulates, and when it evaporates causes loss of heat. Hence the importance of grooming after exercise. In the horse the salts of evaporated sweat may accumulate on the coat if evaporation is allowed. A free secretion of sweat is usually accompanied by a dilatation of the blood-vessels of the skin, but this may be absent, and it may occur without any sweat secretion, e.g. under the influence of atropine. The secretion of sweat and the condition of the blood vessels play an important part in regulating the temperature of the body (p. 269). 3. Nervous Mechanism of Sweat Secretion. — That the sweat glands are under the control of the central nervous system may be demonstrated in the cat. The sweat glands are chiefly in the pads of the feet, and, if a cat be put in a hot chamber, it sweats on the pads of all its feet. But if one sciatic nerve be cut the foot supplied remains dry. If the cat be placed in a warm place and the lower end of the cut sciatic stimu- lated, a secretion of sweat is produced. The secreting fibres for the sweat glands run in the true sympathetic system. They leave the cord by the anterior roots in the thoracico-abdominal region, pass to the sympathetic ganglia, where they have their cell stations. From these, nou-medullated fibres pass back by the grey ramus into the somatic branch of the nerve and so onwards to plexuses round the sweat glands. The centres presiding over these nerves are distributed down the medulla and cord. They are capable (a) of reflex stimulation, as when pepper is taken into the mouth ; and (6) of direct stimulation (i.) by a venous condition of the blood, as in the impaired oxygenation of the blood which so fre- quently precedes death as the respirations fail, and (ii.) by a rise in the temperature of the blood supplied to them. Even after the nerves of the sweat glands are cut, the glands may be stimulated by certain drugs, e.g. pilocarpine. SKIN 585 Adrenaliu causes so powerful a contraction of the cutaneous vessels that any stimulating action it may have upon the sweat glands is masked. The action of heat seems also to be chiefly peripheral, setting up an unstable condition of the gland cells so that they respond more readily to stimulation. 4 Chemistry of Sweat. — Sweat from the horse is a sherry- coloured fluid, which, when pure, has a neutral or faintly alkaline reaction. Its specific gravity is about 1020 in the horse, and it contains about 5'5 per cent, of solids, of which 5 per cent, are inorganic and about 0"5 organic. When the sweat dries on the coat a white deposit is left. Potassium is the most abundant base. Chlorides are present in small amounts. The chief organic substances present are proteins — some globulin and some albumin. Fat is also present, probably derived from the sebaceous secretions, and it combines with the potassium to form a soap. B, Sebaceous Glands. The sebaceous glands are simple racemose glands which open into the hair follicles, and their function is to supply an oily material to lubricate the hairs. This secretion is pro- duced by the shedding and breaking down of the cells formed in the follicles of the glands. Those lining the basement mem- brane are in a condition of active division, but the cells thrown off into the lumen of the follicle disintegrate and become con- verted into a semi-solid oily mass, which consists of free fatty acids and of neutral glycerol and cholesterol fats. These cholesterol fats are the lanolins, which differ from ordinary fats in being partly soluble in water. Free cholesterol is also present in the sebum. Grooming.— This is of great importance in the horse. It removes salts of the sweat, shed epithelium, and loose hairs and dirt. It prevents the development of mange and of lice, and it acts as a form of massage to the skin and subjacent muscles. SECTION VIII. THE REGULATION OF GROWTH AND FUNCTION. In all the members of a species the course of the chemical changes in the various tissues and organs are fairly constant and depart but little from a normal course. Upon these changes depend not only the development and growth of each tissue and organ and of the animal as a whole, what might be called the static adaptation to surrounding conditions, but also the various responses to changes in external conditions, the functional adaptation. The development and the activities of each organ are co-related and co-ordinated with those of all the other organs, and in this co-relation three main factors play a part. I. Heredity. This is primarily the result of the chemical changes inherited from the parents. The principle of Inertia, that — " Every particle of matter in the universe remains in a state of rest or of uniform motion in a straight line, unless it is acted upon by external force," is applicable to living as w.ell as to dead matter. Generation after generation a similar piece of protoplasm the ovum, undergoing the same molecular movements, is placed in the same external conditions, and hence must undergo the same course of development, under the influence of what may be called Hereditary Inertia. A proof of it is afforded by the development, both structural and functional, of embryonic tissues removed from the body and kept in the plasma of the animal blood. A fragment of the cell mass from which the heart develops undergoes the change into the muscular fibres of REGULATORS 587 the heart, and these manifest their characteristic regular rhythmic pulsation. Scraps of some organs when removed and transplanted in other parts of the body may grow, and the cells may multiply and develop into those characteristic of the organ from which they were taken. Hereditary inertia seems to be all-powerful in early embry- onic life, and its influence extends on into the adult condition. Hooker found that, even after all that part of the central nervous system from which the nerves to the heart arise has been destroyed in the tadpole, the heart develops and beats in the usual way. Its influence is dominant both in structural develop- ment and in the development of functional activity, not only in such simple actions as cardiac contraction, but in the most complex responses of the central nervous system upon which the conduct of the individual depends. II. The Nervous System. As development advances, the nervous system comes to play a part in the regulation of metabolism, and thus in the development of the static adaptations. Its effect is seen in the failure of regeneration after removal of structures in some invertebrates and in many amphibia if the nerves to the part are destroyed. It is also seen in infantile paralysis, a disease which follows destruction of the cells of the anterior horn of grey matter. The growth of the limb connected with that part of the spinal cord becomes arrested. The condition of herpes zoster, or shingles, a painful eruption of vesicles on the skin over a nerve, has already been considered (p. 91) as an example of the trophic influence of the nervous system. The part played by the nervous system in regulating and co-ordinating the functional adaptations, i.e. the activities of one structure with those of others has been repeatedly indicated in the previous pages. The effect of a heightened arterial pressure in inhibiting the heart through the inferior cardiac branch of the vagus may be taken as an example; and that this 588 VETERINARY PHYSIOLOGY is fundamentally an alteration in the course of metabolism is indicated by Gaskell's observation that the vagus is an anabolic nerve (p. 421). III. Chemical Regulation. Yet another factor plays an important part. The products of the metabolism of one structure have an effect upon other structures, and so co-relate and regulate their reciprocal activity. It has already been shown that the carbon dioxide pro- duced in muscle stimulates the respiratory centre (p. 527). The slightest increase in the Ch of the blood increases the activity of the kidneys (p. 580). A product of the activity of the duodenum — secretin — has been shown to cause secretion by the pancreas (p. 822). Chemical regulation plays a very important part in verte- brate animals, and special organs have been evolved which have as their function the elaboration of products which are passed into the blood, each to produce definite and specific actions in the body. Such structures may be called glands with internal secre- tions, or endocrinetes. The name of hormones, from op/xaco " I excite," has been suggested for the internal secretions, but, since they do not always increase functional activity, but may check it, the name is unsuitable. Before deciding that any structure is a true endocrinete, it is necessary to prove that it produces a specific product or products with definite and specific actions. The evidence required is of various kinds. 1. The effects of removal may be studied, and if these are definite — 2. The effects of transplanting a part of the structure in preventing the onset of the changes may be tried. If this is successful — 3. The effects of removing the graft may be observed. 4. The effects of administering extracts of the structure REGULATORS 5S9 either with or without its previous removal may be investi- gated. This method has been largely used, but it must be employed with great care for the following reasons : — i. The method of extraction may fail to remove the active product from the structure. ii. The method of extraction may remove all sorts of con- stituents of the structure, and any result produced may be due to the combined action of many substances. iii. Products of decomposition may be removed either alone or along with the active substance, and when administered may produce symptoms which may be ascribed to an active con- stituent which may not exist. The demonstration of the rapid development in decomposition of amines having a powerful physiological action shows that this is a real danger. iv. When massive doses of the extracts produce an effect, there is a danger in concluding that a similar action is produced by the amount normally poured into the blood, but it has been shown that a massive dose may produce a totally different effect from a small dose. V. It has been found that the action of these extracts may be materially altered by the functional condition of the structure to which they are applied; e.g. the uterus of the virgin guinea-pig may respond quite differently from that of the recently pregnant animal. vi. The method of administration may modify the action. Thus, while the intravenous injection of the product of the medulla suprarenalis causes very marked symptoms, these may be entirely absent when it is injected under the skin or given by the mouth. vii. Lastly, the danger of expectancy on the part of the observer must not be overlooked. This is of no small import- ance in the therapeutic administration of such extracts. Classification of the Endocrinetes — These endocrinetes are derived from different parts of the embryo, and they may be arranged according to their embryological source. Such a classification is more satisfactory than one based upon their anatomical position, for, in several cases, two of these organs, entirely separate in origin, structure, and function, have come 590 VETERINARY PHYSIOLOGY to lie in close juxtaposition and so to constitute a sini organ according to anatomical nomenclature. I. From the Nervous System. 1. Chromaffin Tissue (Medulla suprai'enalis).< — 2. Hypophysis Cerebri. II. From the Buccal Cavity. 3. Thyreoid.< 4. Pituitaiv.^ III. IV. From the Intestine. 5. Pancreas. 6. Mucosa of Small Intestine. From the Branchial Arches. 7. Parathyreoids.< 8. Thymus. V. From the Mesothelium of the Genital Ridge. 9. Gonads. 10. Inter-renal Bodies (Cortex suprarenalis). ■? The pairs which occur in anatomical juxtaposition are indicated by joining lines. I. From the Nervous System. 1. Chromaffin Tissue. This in mammals is chiefly disposed as the medullary part of the suprarenal bodies. But smaller masses are found along the aorta and some of the large arteries. In fishes it lies entirely separate from the equivalent of the cortex suprarenalis — the inter-renal tissue. 1. Development. — It is developed from the emigrating cells which form the true sympathetic or visceral system of nerves (p. 54). 2. Structure. — It consists of rather large irregular cells containing granules which stain of a brown colour with chrome salts — hence the names of the tissue. These cells occupy spaces between large sinusoid capillary vessels. 3. Physiology. — (I) It is impossible to remove the chromaffin tissue in mammals without removing the inter-renal tissue of REGULATORS 591 the cortex with it. But recently Vincent has attempted com- pletely to destroy the medulla in dogs by thermocautery, and he has found that the animals remain apparently normal. (2) The discovery that the injection of extracts of the medulla suprarenalis gives rise to marked symptoms was the first step to the explanation of its functions. The demonstra- tion that the active constituent is a definite chemical substance, Adrenalin, has enabled physiologists to carry out investigation with great precision. Adrenalin is — HO- HO- Ortho-dioxy-phenyl. H H I I — C — C- I I OH H ethanol. H H I I _N— C— H I H methyl-amine. It has been prepared synthetically. It may be recognised by its reaction with chrome salts, and by the ease with which it is oxidised, especially in alkaline solutions. On account of this it strikes a green colour with ferric chloride. With phosphotungstates along with phosphoric acid it gives a blue colour, and by this test 1 part in 3 million may be detected. That it is a product of the chromaffin tissue is shown by the fact that the staining of the medulla is proportionate to its physiological activity, and by the great amount of adrenalin in the blood coming from the suprarenals. By pressing on the suprarenals its amount in the blood may be increased. Section of the branches of the splanchnic nerve going to the suprarenals checks its liberation, while stimulation increases it. It acts — (1) On the Blood-vessels. When injected into a vein or perfused in Ringer's Solution through the vessels, it causes constriction of the peripheral arterioles, and thus raises the arterial blood pressure (Practical Physiology). Its action is most powerful on the abdominal vessels, and hence blood is forced to the muscles of the limbs. The vessels of the skin, however, are contracted. On the pulmonary vessels, and on the intracranial vessels its action is slioht. while it causes 592 VETERINARY PHYSIOLOGY dilatation of the coronary arteries. Hoskins finds that in very small doses it causes dilatation of all the arterioles. That it does not act directly on the muscle fibres is shown by the fact that, after the administration of apocodeine which poisons the endings of the abdomino-thoracic or true sympathetics, it no longer acts, although barium salts still cause a contraction, because theyact directly on the muscle (p. 455). Ergotoxin poisons the endings of the augmentor fibres of the true sympathetic, and, after it has been administered, adrenalin may cause a dilatation of vessels because its action on the endings of the inhibitory fibres is thus unmasked. In fact, the action of adrenalin is absolutely specific, and consists in a stimulation of the endings of the true sympathetic nerves. It thus produces on any organ the effect which is produced by stimulating these nerves. (2) On the Heart. If the vagi are intact, it produces a slowing which is due to the raised arterial pressure (p. 420). When the vagi are cut it causes an acceleration and generally an increased amplitude of contraction by stimulating of the augmentor endings. (3) On the Alimentary Canal it acts, as does stimulation of the splanchnic nerves, by inhibiting peristalsis and stimulating the sphincters (p. 333). (4) On the Bladder its action varies in different animals according to whether motor or inhibitory fibres pass to the organs through the splanchnics by way of the inferior mesenteric ganglion and hypogastric nerves (p. 582). In the former case it causes contraction (ferret) ; in the latter case relaxation (cat). (5) On the Uterus it generally causes contraction, but, in the virgin uterus, it may cause relaxation, showing that its action may be modified by the functional condition of the tissue. (6) On the Iris, when applied to the excised eye of the frog, it has the same action as stimulation of the cervical sympathetic — it dilates the pupil. But in mammals this occurs only when (a) the superior cervical ganglion has been excised — a procedure which is supposed to make the nerve terminations more sensitive ; and (h) in some cases of de-pancreatic diabetes (p. 357). Hence it has been concluded that an internal secretion REGULATORS 593 of the pancreas may inhibit the action of adrenalin on these terminations. (7) It acts on the sweat glands, which are supplied by the true sympathetic nerves, but its action is masked by the constriction of the vessels which supply these glands. (8) On the kidney its constricting action on the arterioles leads to a decreased production of urine. (9) As already indicated (p. 356), injections of extracts of the suprarenal bodies profoundly modify the metabolism, leading to an increase of sugar in the blood and to its excretion in the urine. This is best marked when the animal is well fed and has a store of glycogen in its liver ; but, since it occurs in fasting animals, after the stored carbohydrates have been markedly reduced by the administration of phloridzin (p. 357), it would appear to be due in part to an increased production of sugar from proteins. It has been suggested that the supra- renal secretion acts through the pancreas by preventing the formation of the internal secretion which checks carbohydrate metabolism in the liver (see p. 356). But the fact that it produces glycosuria in the bird after the pancreas has been excised negatives this view. The universality of the law that adrenalin acts on the terminations of true sympathetic nerves, and the fact that stimulation of these nerves to the liver causes a glycosuria, indicates that it probably acts on these nerve endings. This is supported by the fact that it does not cause glycosuria after the administration of ergotoxin. 4. Nervous Control of the Chromaffin Tissue. — The supply of adrenalin to the body from the chromaffin tissue is influenced by the nervous system through the splanchnic nerves, pregan- glionic medullated fibres of which go to the gland. Various injuries to the central nervous system may stimulate these nerves, and a glycosuria may be thus produced, as in Bernard's diabetic puncture (p. 356). Since this does not occur when the suprarenals are removed, it has been supposed that it is caused by the excessive supply of adrenalin to the blood. But the amount in the blood after Bernard's puncture is insufficient to cause a glycosuria. The adrenalin probably acts merely as an adjuvant to nerves. 5. Significance of Adrenalin. — The amount of adrenalin normally present in the blood is quite insufficient to exercise 38 594 VETERINARY PHYSIOLOGY any marked physiological effect or to account for the tone of the arterioles. An amount sufficient to act upon them causes marked paralysis of the gut. It is to be regarded as a reserve stimulant which is called upon when the true sympathetic system is powerfully stimulated, as it is in various disturbances of the central nervous system which are accompanied by such emotional conditions as fright or anger. The stimulation of the true sympathetics leads to the increased action of the heart and the contraction of the abdominal vessels with the increased flow of blood to the muscles, and to the other physical accompaniments of the emotions which are preparations for meeting the conditions producing them. If the stimulus is sufficiently powerful, the effect is augmented and sustained by an outpouring of adrenalin. 5. Detection of Adrenalin in the Blood. — The most delicate method for testing the amount of adrenalin is the inhibitory action upon a strip of intestine in oxygenated Ringer's solution at the body temperature. This action is manifested by as little as 1 in 400 million. 6. Toxic Action. — The administration of large doses of adrenalin may cause death from pulmonary congestion. Re- peated doses result in degenerative changes in the liver, and in a thickening of the inner coat of the arteries. 2. Hypophysis Cerebri. 1. Development. — Tliis is formed as a hollow downgrowth from the base of the third ventricle of the brain. In some animals the stalk remains open, but in man it is closed (fig. 230). 2. Structure. — It forms what is anatomically the posterior lobe of the pituitary body lying in the sella turcica. It is com- posed of neuroglia cells, but in it are frequently found little masses of colloid and cells resembling those of the inter- mediate part of the pituitary (p. 599) a structure which closely embraces the hypophysis. 3. Physiology. — (a) Removal produces no marked symptoms. (h) Extracts, when injected into a vein cause — (1) A rise of blood pressure from constriction of the arterioles. If the dose be repeated within half an hour, this REGULATORS 595 may be replaced by a dilatation and fall of pressure. In birds the first dose produces this dilator effect. In the renal arterioles it causes a dilatation, and in the coronary arteries a constriction, thus differing from adrenalin. (2) On the heart it acts to increase the force of contraction, whether the vagus is intact or is cut. After section of the vagus it does not accelerate the heart as does adrenalin. (3) Upon the iris it acts like adrenalin. (4) On the intestine, uterus, and bladder it acts as an excitant, and it also increases the effect of stimulating the hypogastric nerves on the last two organs. (5) It causes a great outpouring of milk from the mammary glands, probably by its action on the walls of the ducts, but it has no influence on milk secretion. (6) It has a marked diuretic action, and, since this occurs even after a second dose when the arterial blood pressure falls, it has been ascribed to a specific stimulating action on the secreting cells of the kidney. (7) Its action on metabolism requires further investigation. According to some investigators, it causes glycosuria. So far the chemical nature of the active principles, which may be called Hypophysin, has not been ascertained, although active crystalline proilucts have been prepared Like adrenalin, it is not destroyed by heating. Whether it is a normal product, and whether it has any physiological significance, has yet to be proved. Herring's results seem to show that the passage of a colloidal material may be traced into the ;erebro-spinal fluid. It is entirely formed in the hypophysis or lu the pars intermedia of the pituitary. Some observations by Herring tend to show that the action on milk flow and on the uterus is more particu- larly due to a product of the latter. II. From the Buccal Cavity. 3. Thyreoid Gland. 1. Development. — This structure is formed as a hollow out- growth from the anterior part of the alimentary canal, which breaks up into numerous branches. -' The gland was named after the shield-like cartilage of the larynx. Since dvpeos is a shield, and dvpos a door, it should be called thyreoid. The name thyroid given by British anatomists is manifestly erroneous. 596 VETERINARY PHYSIOLOGY 2. Structure. — It early loses its connection with the ali- mentary canal, and becomes cut up by fibrous tissue into a number of small more or less rounded cysts or follicles, each lined with cubical epithelium and filled with a mucus-like colloid substance, with a marked affinity for acid stains (fig. 229). It is enormously vascular and has a rich supply of lymphatics. 3, Chemistry — The colloid substance is characterised by containing- iodine, but the amount varies in different animals and in the same animal according to the mode of feeding. Fig. 229.— Section through Part of the Thyreoid (TA.) and a Parathyreoid (P.) of a Mammal. A very stable organic compound of iodine, known as iodothyrin, may be prepared, but this is actually combined in a globulin- compound which is the active constituent of the organ, and is known as iodothyreoglobulin. Kendall has described a crystal- line product of definite composition containing the indol nucleus (p. 330) with iodine attached to the benzene ring — a thyreo- oxyindol. 4. Physiology. — In 1873 Gull described a peculiar disease chiefly affecting women which has received the name of myx- cedema (p. 597), and in 1877 Ord was able to show that it is associated with atrophy of the thyreoid. Kocher and the I I REGULATORS 597 Reverdins in 1882 described a somewhat similar condition after removal of the thyreoids in operations for goitre. In the last decade of the nineteenth century the experimental investiga- tion of the effects of removal was taken up. (1) Removal. — A diflSculty is experienced in studying the effects of removal, inasmuch as the parathyreoids lie embedded in the thyreoid of most animals, and in close juxta-position to it in others, and care is required to leave a sufficient amount of these to carry on their functions. When proper precautions are taken, it is found that the effect of removal of the thyreoid in young animals is to check the growth, and especially to check the growth of cartilage in developing bone (p. 46). This leads to marked shortening of the long bones, causing stunted growth. The basis cranii is also aflFected, and, since the intra-membranous bones continue to grow, the frontal bones tend to arch forward. The gonads do not develop, but remain infantile. The animal is generally dull — lethargic. In adults the changes are less prominent. Muscular weak- ness and apathy are marked. The hair falls out, and the tem- perature is low. There is often a peculiar swelling of the skin, which does not pit on pressure. The rate of metabolism is markedly decreased. The mobilisation of carbohydrates is lowered and the carbohydrate tolerance is raised. Removal of the thyreoid decreases the glycosuria produced by removal of the pancreas, and in this respect the influence of the thyreoid co-operates with that of the chromaffin tissue in facilitating the mobilisation of carbohydrates, which is held in check by the pancreas. The functions of the sexual organs are disturbed. The condition is sometimes known as cachexia strumipriva. (2) Hypothyreoidism (Decreased Functional Activity). — (a) Iji the IToung. — The thyreoid may be congenitally imperfectly developed in man and animals, and all the conditions described under the eff"ects of removal of the gland are in a very marked degree, (b) In the adult human subject. — When the thyreoid atrophies, the disease myxcedema is produced. The sufferer manifests the symptoms described above as cachexia strumi- priva. (3) Transplantation. — If, when the symptoms following re- 598 VETERINARY PHYSIOLOGY moval have developed, a small piece of the tissue of the thyreoid is grafted in a suitable part of the body, blood-vessels may grow in, the tissue may survive and increase, and this may bring about a disappearance of symptoms. On removing the graft the symptoms recur. (4) Extracts. — The administration of extracts of the thyreoid subcutaneously, or by the mouth as was shown by Murray, frequently leads to the disappearance of the symptoms of removal or deficiency, and this line of treatment is now uni- versally used in cases of cretinism and myxoedema in man. lodothyreo-globulin or thyreo-oxyindol appears to be the active principle. The Avay in which the thyreoid acts upon the metabolism is demonstrated by the study of the effects of its administra- tion to normal animals. When given in large doses over loug periods, all the symptoms of hyperthyreoidism may be produced. Tadpoles fed on thyreoid tissue undergo a very rapid develop- ment, and Hoskins and Herring have shown that in young white rats the continued administration of thyreoid causes an extra- ordinary increase in the suprarenals, heart, kidneys, and pancreas with a decrease in the size of the pituitary in the female. The main effect is to increase metabolism. A further effect is to activate the terminations of the true sympathetics and of the para-sympathetics of all the visceral nerve fibres. Hence both the augmentor and the inhibitory terminations in the heart are activated, and the heart responds more readily to stimulation of the vagus or of the augmentor. The same seems to be the case with the nerve terminations in the blood-vessels, e.g. the reflex response to the depressor nerve (p. 418). Since these thyreoid preparations act upon the true sympathetic termination, they facilitate the action of adrenalin. Further, the suprarenals are supplied by the splanchnic nerves, and apparently the active principle of the thyreoid facilitates the action of these, and so increases the output of adrenalin. (5) Hyperthyreoidism. — {Increased Functional Activity). — This condition in man is known as Graves Disease or exoph- thalmic goitre. It is characterised by a condition of hyper- excitability and sleeplessness, rapid action of the heart, a I I KEGULATORS 599 tendency to flushing from increased vaso- motor activity, sweating, increased secretion of urine, often prominence of the eyeballs and enlargement of the thyreoid forming a soft goitre. The rate of metabolism is markedly accelerated, proteins are more rapidly broken down, and carbohydrates are too rapidly mobilised and hence sugar may appear in the urine. The symptoms may all be explained in terms of the action of thyreoid extracts. The prominence of the eyeballs in man is probably due to stimulation of visceral muscular fibres in the eyelids by which they are unduly opened and the bulging of the eyeball allowed to take place. It may occur in lower animals. In simple goitre the thyreoid tissue undergoes a slow hyper- trophy and no general symptoms are manifest. (6) Nervous Control. — Taking as indices (a) the sensitising action of the internal secretion of the thyreoid on the abdominal sympathetic nerve ; and (6) the decrease in the amount of iodine in a lobe, it has been found that stimulation of the nerves supplying the gland leads to an increased output of the internal secretion. The thyreoid thus seems to produce an internal secretion rich in iodine which exercises a stimulating effect upon the metabolism. Whether it does so by a direct action, or whether through the autonomic nervous system, upon which it undoubtedly acts, cannot at present be decided. 4. Pituitary. The true pituitary is the anterior part of the pituitary of anatomists. 1. Development.— It is formed by a hollow outgrowth from the roof of the buccal cavity, and it lies in front of and embraces the hypophysis. 2. Structure. — It consists of (1) an anterior j^art, composed of dense columns of cells of two kinds— (a) the chief cells, which are large and do not stain readily; (b) the chromophil cells which contain granules, some staining with acid, some with basic stains. It is very vascular. (2) A 2^^'^^^ intermedia, separated from the former by a cleft and applied closely to 600 VETERINARY PHYSIOLOGY the hypophysis, and consisting of cells with colloid material between them. 3. Physiology. — (a) Removal of the true pituitary is generally rapidly fatal; muscular tremors, slow pulse and respiration, and a fall of temperature preceding death. Partial removal in young animals is followed by decreased growth, persistence of the infantile characters, and arrested growth of the gonads. Often there is an accumulation of fat. The thyreoid is generally hypertrophied. (h) Acromegaly, a disease in man characterised by greatly increased growth of the bones, and more especially of the intra-membranous bones, and with increased growth of the fars inlermed \^ i>»Of 'mi Pars tuU . ^•'Y')j Fig. 230. — Longitudinal section through the Hypophysis and Pituitary. (Edinger.) subcutaneous fibrous tissue, has been associated with disease of the pituitary. According to Gushing, it shows two phases : — First, the irritative phase, in which there is an increased growth of bone and a premature development of the testis, and, second, the destructive stage, in which the testes atrophy and the sexual functions are in abeyance. Very probably the development of giantism is associated with increased activity of the pituitary, for, in most cases, an enlargement of the sella turcica has been described. The fatal effects of removal may apparently be delayed for a time by the transplantation of a part of the gland, but the grafts do not persist. Administration of extracts of the pituitary has not given conclusive results. It has ' been claimed that a substance of definite composition which has been called tethelin may be prepared from it, which first decreases then increases the growth of young mice and causes a persistence of the soft coat of the young animal. REGULATORS 601 A physiological hypertrophy occurs in pregnancy, during which the ovarian functions are in abeyance, the chief cells being increased. In the male, removal of the testes leads to hypertrophy of the pituitary. While the pituitary thus exercises a stimulating action on the growth of the connective tissues and of the gonads, the latter appear to have a checking action on the pituitary. More work upon this is required. III. From the Intestine. 0. Pancreas. The development and structure of the pancreas have been described (p. 300). The effects of removal in producing the condition of diabetes have been considered (p. 357), and it has been shown that the organ produces an internal secretion which checks the mobilisa- tion of sugar in the liver, and possibly facilitates its utilisation by the muscles. The transplantation of a piece of pancreas prevents the onset of these symptoms, but the administration of pancreas or of extracts of the pancreas does not do so. The internal secretion of the pancreas acts in the opposite direction to that of the chromaffin tissue and the thyreoid. The fact that, after removal of the pancreas, adrenalin causes dilatation of the pupil seems to indicate that its internal secretion inhibits the action of the termination of the true sympathetic in the iris, and therefore probably also in the liver. It is probably the islets of Langerhans which yield the active principle. The true islets are developed early in foetal life from the epithelium of the ducts. A case has been described in which excision of a piece of pancreas, which had been left after partial removal of the organ, led to glycosuria, and in which the fragment was found to have degenerated and to be composed entirely of islet tissue. 6. The Mucous Membrane of the Small Intestine. The production of secretin and its action on the pancreas have been dealt with on p. 321. ■f 602 VETERINARY PHYSIOLOGY IV. From the Branchial Arches. 7. Thymus. 1. Development. — The thymus is formed as epithelial out- growths from the branchial arches — in mammals from the ventral side chiefly of the third and, to a lesser extent, from the fourth cleft. 2. Position. — In man and in most mammals it lies in the thorax just in front of the heart. Islets of thymus tissue are ' T< Fig. 231. -Section of the Lobules of the Thymus to show the Lobules, with Hassall's Corpuscles in the Central Part. frequently found in and around the thyreoid. In the guinea- pig it is entirely in the neck. 3. Structure — It is composed of two lobes, each made up of a series of separate lobules surrounded by a fibrous capsule and showing a denser cortical and a less dense medullary part. It consists essentially of a network of epithelial cells, which, in the medullary part, are here and there massed together to form concentric agglomerations of cells, some in a state of degenera- tion — the Hassall's Corpuscles. In the meshes of the network are lymphocyte-like cells which are probably derived from outside the gland, but which, according to some observers, are formed from the epithelial cells (fig. 231). REGULATORS 603 4. Life History. — The thymus reaches its greatest size, in relationship to the weight of the body, about the time of birth ; it continues to grow till puberty, when it begins to atrophy, being replaced by fatty tissue. In adult life, it is reduced to a mass of adipose tissue with only some islands of thymus substance. Conditions of malnutrition lead to a tem- porary atrophy of the gland. 5. Physiology. — (1) Removal. — In young guinea-pigs this produces no marked symptoms. In young dogs very different results have been recorded by different investigators ; but the most recent series of experiments shows no observable differ- ence between normal pups and those deprived of their thymus. Some investigators describe a peculiar sluggish condition with manifestations of muscular fatigue ; others state that a condi- tion of decreased calcification of the bones and the peculiar enlargement of their ends, characteristic of rickets, are produced ; but rickets develops very readily in puppies, and just as readily in those with, as in those without, the thymus. A thymusless pup may escape rickets while other members of the litter may develop it. (2) Feeding tadpoles with thymus leads to continued growth and absence of development, while feeding with thyreoid leads to more rapid development, (3) After castration of male animals, the thymus persists in adult life. If thymus and testes are both removed, the growth of the animal is delayed. It would thus seem as if the thymus and testes co-operate in stimulating growth, and that, if one of these structures is removed, a compensatory hypertrophy of the other occurs. As the testes increase in size, the thymus begins to atrophy and to play a less important part. Similar relations Avith the ovaries have not been established. 8. Parathyreoids. 1. Development. — These are formed as epithelial outgrowths from the dorsal aspect of the third and fourth branchial clefts on each side, there being thus two on each side. 2. Position. — The parathyreoids formed from the third clefts, in most animals, lie close to the thyreoid lobes, but outside of them. Those from the fourth clefts are generally embedded in them. In man, both sets lie outside of the 60-i VETERINARY PHYSIOLOGY thyreoid. Supplementary parathyreoids are frequent, and in some animals, e.g. cats, they are embedded in the thymus. It is therefore impossible to be sure that, after removing the usual four parathyreoid bodies, a considerable amount of parathyreoid tissue is not left. This explains the negative results got by some experimenters. 3. Structure. — Each consists of columns of cells (a) the chief cells, large and not staining readily, (6) oxyphil cells, smaller than the last, and with granules staining with eosin. Masses of colloid material may occur, giving the structure somewhat the appearance of the thyreoid gland (fig. 229). 4. Physiology. — (1) Removal. — Since 1882 it has been known that, after removal of the thyreoid gland for goitre in the human subject, a peculiar condition of spasm of the muscles, and even of convulsions leading to death, may occur. This was first ascribed to removal of the thyreoid, but in 1896 Vassal e and Generali definitely showed by experiments upon animals that it is due to removal of the parathyreoids, and that, if a sufficient amount of their tissue is left, the symptoms do not develop. The symptoms are (i) depression and emaciation ; (ii) tonic contraction of various muscles, chiefly the extensors ; (iii) tremors and jerkings of the muscles, which may go on to a general convulsion. Sometimes these disturbances of the neuro-muscular system are accompanied by disturbances of balancing. (iv) A peculiar increase in the excitability of the peripheral motor neurons, so that if a motor nerve is compressed or tapped a violent convulsive movement of the muscles supplied by it may be produced, while the response to galvanic stimulation is enormously heightened, (v) In the dog increased rate of the heart and of the respirations. The symptoms vary greatly from time to time, and may remain latent except for the increased excitability of the nerves which persists. The spasticity and tremors are due to the implication of the motor neurons of the spinal cord and are arrested by cutting the nerve to the muscles. The increase in the response to the stimulation of peripheral nerves is due to an increased excitability of the nerve endings in the muscles. These two conditions are not necessarily proportional to one another. All the symptoms are due to a poison developed in the \ REGULATORS 605 body and present in the blood. They are all temporarily removed by bleeding and transfusing with a 0*9 per cent. NaCl solution. NH II The evidence points to guanidin, NH^ — C — NHo NH CH3 II I or to methyl guanidin, NHo — C — N — H, as the toxic sub- stance. The administration of the salts of these reproduces all the symptoms following removal of the parathyreoids, while the amount in the blood and in the urine is increased after parathyreoidectomy. The parathyreoids thus seem to regulate the guanidin metabolism of the body and to prevent such an increase as will lead to symptoms. There is evidence that guanidin or methyl guanidin liberated in the body is linked to acetic acid to form the non-toxic creatin (p. 209). In rats which have survived removal of the parathyreoids lying beside the thyreoid, but which presumably have some parathyreoid tissue left, defective calcification of the teeth has been observed. This is probably associated with a decrease in the calcium of the blood. A decrease in the growth of the bones and changes resembling those of rickets have also been described. (2) Transplantation of parathyreoid tissue has been found to abolish the symptoms, and they recur when the graft is excised, (3) Extracts. — Beebe has isolated a nucleo-protein which, according to some observers, suppresses or mitigates the symptoms of tetany. V. From the Mesotheliuin of the Genital Ridges. 9. The Gonads, or Sex Glands. 1. Development. — These are formed by ingrowths of meso- thelial cells over the genital ridge of the embryo. A. Testes. — In the male, these cells, for the most part 606 VETERINARY PHYSIOLOGY become arranged in tubules, forming (a) the spermatogonia, from which the spermatozoa are produced (p. 620), and (6) certain larger cells, the supporting cells of Sertoli, (c) Some of the mesothelial cells remain outside and between the tubules, and form the interstitial cells of Ley dig. These are large cells, and they contain a large amount of lipoids. Some observers maintain that they are really connective tissue cells. B. Ovaries. — In the ovaries the ingrowing mesothelial cells form separate masses, the Graafian follicles, (a) One of the cells enlarges and becomes the ovum, the female gamete (p. 619) ; while (6) the others remain smaller and form the cells of the zona granulosa, (c) In many animals between the Graafian follicles a considerable number of the mesothelial cells remain as the interstitial cells of the ovary. The interstitial cells of the testis and ovary I'esemble one another very closely and are both very similar to the cells of the inter-renal organ which forms the cortex suprarenalis. They are very rich in lipoids and especially in cholesterol compounds. 2. Physiology. — The part played by the gonads in the process of reproduction will be considered later (p. 618). At jjresent their action as endocrinetes has to be dealt with. A. Testes. (1) Removal- — Removal of the testes in young boys and in young animals leads to a persistence of the infantile type of body, and to the absence of development of the secondary sexual structures, such as the prostate gland, the hair of the body and face in men, the horns of sheep and cattle, and the antlers of deer. The temperament is generally phlegmatic, and hence a gelded horse is more easily managed. Castrated animals fatten more readily. The cartilaginous growth of bone tends to persist, and hence the bones tend to be longer and more slender than in the entire animal. (2) Precocious Development. — In man this is accompanied by premature development of the secondary sexual orgaa.s, by abnormal growth of hair, prematui'e union of the epiphyses of the long bones, and increased growth of the bones in thickness. These conditions have been observed in connection with tumour REGULATORS 607 growths of one testis, and removal of the tumour has been followed by their disappearance. A similar condition is associated with hypertrophic changes in the cortex suprarenalis (p. 610), and with irritative changes in the pituitary (p. 600). Whether these act through the testes or directly is not known, (3) Transplantation — The first demonstration of the action the endocrinetes was afforded by Berthold, who showed that transplanting the testis into a capon leads to the develop- ment of the typical sexual characters of the cock. This has been fully confirmed by other observers in different species of animals. (4) Extracts. — There is some evidence that in frogs the development of sexual character may be produced by the adminis- tration of testicular substance, but it is not quite satisfactory. The testis thus exercises an important influence on the growth and development of the animal, and it does this by yielding an internal secretion. That the source of this is the interstitial cells is shown by the fact that ligature of the vas deferens causes atrophy of the spermatogonia, and also in course of time, of the cells of Sertoli, leaving only the inter- stitial cells, and yet there is no arrest of the development of the sexual characters. In the mole, these interstitial cells reach their greatest development before the beginning of the breeding season. In man they are well developed at birth, but disappear in the course of the early weeks of life to reappear again at puberty and to persist throughout life. B. Ovaries. (1) Removal of the ovaries has the same effect on the female as removal of the testes has on the male. The development of the secondar}'^ sexual organs, the uterus, mammee, etc., is arrested. But, after removal of the ovaries, there is frequently a tendency to develop the characters of the male. Thus, hinds with diseased ovaries may develop horns and hen pheasants and ducks may develop male plumage. The ovaries thus seem to check the development of male characters. (2) Transplantation acts in the same way in the female as in the male in preventing the effects of removal. In most animals 608 VETERINARY PHYSIOLOGY it is the interstitial cells which are the active part ; for, after complete degeneration of all the cells of the Graafian follicles, the graft of ovarian tissue still produces the development of the sexual characters. The transplantation of ovaries into young castrated male rats and guinea-pigs has led to the development of female characters, such as excessive growth of the nipples, to the secretion of milk, and in rats to characteristic sexual reflexes. The evidence is thus quite clear that the gonads exercise a direct influence upon the soma! cells through an internal secretion. But certain peculiar modifications in the development of the sexual characters have been recorded which appear inexplicable on any theory of the action of an internal secretion. Bond has described a pheasant with male plumage on one side and female plumage on the other, and a similar condition has been recorded in a bullfinch. In the pheasant an atrophic ovo-testis was present. It is, of course, inconceiv- able that an internal secretion could have had this bilateral action. In insects there is also evidence that the sexual characters develop after castration of the caterpillar. In the feinale the ovaries not only act in the young in determining the development of the sexual characters, but in adult life they have an important influence on — (1) The Course of Pregnancy. — In the bitch if the ovaries are removed early in pregnancy the ovum does not become embedded in the mucous membrane of the uterus. The cells of the corpus luteum exercise an influence on the uterus which brings this about. This structure is formed when the Graafian follicle ruptures and discharges its ovum. It is produced essen- tially by an enormously increased growth of the cells of the zona granulosa, which become loaded with lipoids. If the ovum is fertilised the corpus luteum grows to a large size ; if the ovum is not fertilised it grows to a less extent. When the corpus luteum is formed, any irritation of the uterine mucosa may cause the development of the typical tissue for the emiaedding of the ovum. REGULATORS 609 Removal of the ovaries late in pregnancy produces no disturbances. (2) The Mammary Gland. — When the ovaries are removed in early life the mammary gland does not grow. The growth of the gland in pregnancy seems to be associated with the develop- ment of the corpus luteum. It has been found that, in the rabbit, the injection of extracts of the foetus leads to a rapid growth and to a functional activity of the gland, and it has been deduced that a secretion from the foetus is the specific stimulus to the development of the gland and to milk formation. But milk secretion occurs after the expulsion of the foetus, and it is more probable that the retention in the mother of the material which was formerly passed to the foetus, and which is virtually foetal material, is the stimulus to milk secretion, rather than that this is caused by a reabsorption from the foetus. That an internal secretion from the foetus does not play an essential part is shown by the fact (i.) that milk secretion may occur in the young of both sexes; and (ii.) that it may be caused by stimulation through the nervous system, since it has been induced, even in the virgin animal, by continued stimulation of the nipple by sucking; (iii.) that milk may be produced in bitches some weeks after oestrus without impregnation. In such bitches development of the corpus luteum and of the uterus and mammary glands occurs and retrogressive changes do not appear till after thirty days. This may explain the secre- tion of milk which in these cases seems to follow atrophy of the corpus luteum, while increase of the mammarv gland is associated with its growth. 10. Inter-renal Tissue. In mammals, this is chiefly massed as the cortex supra- renalis, but separate masses occur along the course of the aorta, in the epididymis testis and near the ovaries. In some animals, e.g. the rat, they are more abundant than in others. In fishes the inter-renals lie quite separately from the chromaffin tissue. (1) Development. — The tissue is developed from ingrowths of the mesothelium of the genital ridge. (2) Structure. — The cells are large, and the protoplasm con- tains an abundance of lipoids, with a high proportion of cholesterol. They closely resemble the interstitial cells of the 39 610 VETERINARY PHYSIOLOGY testes and ovaries and the cells of the corpus luteum. Brown granules are also often present in them. The cortex suprarenalis is covered by a fibrous capsule which sends trabeculge inwards. Under the capsule, the cells are arranged in somewhat fan-like groups to form the zona glomerulosa. Deeper, they run in parallel rows at right angles to the surface, and constitute the zona fasciculata. In the deepest layer, the zona reticularis, their arrangement is in looser and less regular columns. (3) Physiology. — (1) Removal. — Biedl has succeeded in removing the inter-renals in selachian fishes, and he finds that the animals die. In mammals it is impossible to remove this tissue without also removing the chromaffin tissue of the medulla suprarenalis (see p. 590). (2) Extracts of this tissue are without the action of extracts of the medulla. Some experiments on continuous feeding in young rats indicate that the growth of the testis may be stimulated. (3) Relation to Gonads.— The physiological significance of the inter-renals is obscure, but that they are probably of the same nature as the interstitial and other ancillary cells of the gonads is indicated by (i.) their common origin with the cells of the gonads ; (ii.) their close resemblance to the interstitial cells ; (iii.) the fact that pieces of inter-renal tissue are frequently found in close relationship to the gonads ; (iv.) the fact that abnormalities of this tissue are frequently counected with abnormalities of the gonads. Hypertrophy seems to be associated with premature sexual development in the male and with the assumption of male characters by the female, such as the typical growth of hair and muscular development ; and (v.) the observation that the cells of the cortex suprarenalis of the guinea-pig undergo marked changes in pregnancy. It has been found that in infants born with the brain un- developed, the cortex suprarenalis is also defective. Addison's Disease. — Addison described in man a condition of great muscular weakness and emaciation with a curious bronzing of the skin which ends fatally, and he was able to associate this with destructive lesions of the suprarenals. The evidence at present forthcoming as to whether this condition is due to an implication of the inter-renal tissue of the cortex is inferential REGULATORS 611 and is based upon Biedl's experiments upon fish (p. 610), and Vincent's experiments on mammals (p. 591). The Interaction of the Endocrinetes. The endocrinetes, with their internal secretions, exercise a balanced injiuence on the metabolism. This is very clearly shown by the reciprocal action on the mobilisation of sugar of the chromaffin tissue and thyreoid on the one hand, and of the pancreas on the other, the two former stimulating it, the latter checking it. There is also evidence that they act upon one another. Thus, while thyreoidectomy has not been shown to have any influence upon the adrenalin content of the chromaffin tissue, feeding with thyreoid does increase it. The true pituitary and the thyreoid exercise an influence on the growth and on the functional activity of the gonads, and they in turn are acted upon by the gonads. In some cases these structures seem to supplement one another. The thymus, testis, and anterior lobe of the pituitary all seem to combine in maintaining growth in the young. Mode of Action of Internal Secretions. The study of the action of these internal secretions involves the question of how far they act independently of or through the nervous system. The evidence that adrenalin acts through the nerve structures appears to be conclusive, and in all proba- bility the products of the hypophysis, the thyreoid, and the pancreas act in the same way. On the other hand, in domin- ating the growth and development of the body in early life, it is very possible that the thymus and gonads, possibly the thyreoid and pituitary, act directly upon the tissues. If this be so, the internal secretions may act (1) as primary chemical regulators and (2) as neiiro-cheinical regulators. The influence of the various factors dominating metabolism, growth, and development, might be represented in fig. 2.32, where the influence of hereditary inertia is shown as dominant in embryonic life ; where the influence of the nervous system 612 VETERINARY PHYSIOLOGY is shown as gradually increasing in importance; where the primary chemical regulators are indicated as playing an im- portant part towards the end of foetal and the beginning of extra-uterine life; and where the part played by the neuro- EmbryonLc Life . Post-embryonic Life d Fig. 232. — To show the Relative Parts played during Embryonic and Post- embryonic Life in the Regulation of Metabolism by (a) hereditary inertia, (h) the primary chemical regulators, (c) the nervous system, and id) the neuro-ohemical regulators. chemical regulators is shown as advancing with the increased importance of the nervous system. Modifications of Metabolism for Protection against Toxic Agents. The study of the production and modes of action of these internal secretions leads to the consideration of the protection of the organism against the action of various poisons of animal or bacterial origin. This will be dealt with very briefly, since it viust be studied fully in connection luith Pathology. The question may be most simply approached by consider- ing first the probable mode of action of the toxin or poison of snake venom and of that produced by the diphtheria bacillus, and the way in which protection against these is established by the development oi antitoxins. 1. Snake Venom and Diphtheria Toxin. — By injecting, under the skin of the horse, increasing doses of such toxins the animal is made quite resistant to the poison. A certain quantity of its serum can then neutralise a definite quantity of the toxin, so that, when the mixture of serum and toxin is injected into another animal, the latter is uninjured. Something has been REGULATORS 613 formed in the horse which seizes on the molecules of the toxin and makes them harmless, just as when soda is added to sul- phuric acid a neutral salt is formed. The two molecules have a definite chemical affinity for one another, so that the toxin or antigen is no longer free to seize upon the protoplasm of the animal's body. To explaiu this, Ehrlich has suggested that the protoplasm molecule (fig. 233) is made up of a central core with a number of side-chains or rece'ptors, which play an important part in taking up nourish- ment of different kinds, special receptors being developed for each kind of material. He supposes that some of these side- chains fit the toxin molecule, and are thus capable of anchoring it to the cell and allowing it to exercise its toxic action. The production of antitoxin he explains by supposing that, as these side-chains get linked to the toxin and are thus, as it were, thrown out ot action, others are produced to take their place, since they are necessary for the nourishment of the protoplasm. If the toxin is continually administered in small doses this production of side-chains may be so increased that they get thrown off into the blood, and in it they are capable of linking to the toxin and so preventing it from fixing itself to the cells. If, therefore, some of the blood be injected into an animal which afterwards receives a dose of the toxin, that toxin will not act, and the animal will be immune. 2, Enteric Toxin. — But immunity may also be established not merely against toxins separate from organisms, but against organisms which hold their toxin, as in the case of the bacillus of enteric fever. Here, repeated injections of increasing doses of the dead bacilli cause the production of a serum which has the power of destroying the organism when added to it even outside the body. This is not a simple combination; because, if the serum be heated to 55° C, it loses its power, but, if a few drops of the fresh serum even of an unimraunised animal be added, the power is restored. Obviously the anti-body which destroys the organ- ism^ — the bactericidal or bacteriolytic body, oiten called the ambo- ceptor — requires the co-operation of another body to enable it to act, and this body has been called the complement or alexine. This is readily destroyed at a comparatively low temperature. Ehrlich supposes that the immune body does link to the proto- plasm of the organism, but that it must, in its turn, be linked 614 VETERINAEY PHYSIOLOGY to the complement before it can act. The figure may help to explain this (fig. 234). 3. Cytotoxins. — Similar anti-bodies, acting upon the cells of the animal body, may be produced by injecting the particular kind of cell into an animal of another species. Thus, if human blood be repeatedly injected into a rabbit, the serum of the rabbit's blood becomes hcemolytie — i.e. acquires the power of dissolving the erythrocytes in human blood. In this case too, the immune body requires the presence of a complement, readily destroyed at a comparatively low temperature, to enable it to act (see p. 486). If such hgemolytic serum be injected into another animal an anti-hceniolysin may be developed — a body which will sc Fig. 233.— To illustrate the For- mation of Side-chains or Recep- tors, sc, bywhich the toxin mole- cules, T, are either anchored to the cell or neutralised. When the side-chains are set free an anti-toxin is formed. Fig 234.— To illustrate the Anchoring of the Anti- body or Amboceptor, a, to the cell by a side-chain or receptor, sc, and the action upon it of comple- ment, com. antagonise the action of the hsemolysin. Possibly this is a body which links with the amboceptor to prevent its linking to the complement. 4. Precipitins. — By the injection of the proteins of the blood of any particular animal into an animal of another species, a serum is developed which, in association with the proteins of the blood of the first species, forms a precipitate. This action is specific, unless in the case of closely allied species when it may occur to a slight extent. 5. Agglutinins. — These constitute another group of anti- substances. They may be developed towards bacteria, erythro- REGULATORS 615 cytes, etc., by repeated injections of these substances into an aaimal. Their action, is shown by their causing clumping or agglutination when added to a suspension of the corresponding antigen. Agglutinins may appear in the blood during an attack of certain diseases, e.g. enteric fever, and the reaction may be used for diagnosis. In these various cases, the active body is produced by the throwing off of side-chains from the protoplasm, and, since these products are carried away in the blood, the process is analogous to the formation of internal secretions. Opsonins. — Many bacteria, after treatment with the serum of the animal, are taken up by the leucocytes, but if not treated with serum are not taken up. Apparently the serum contains something, which has been called an oi)sonin, which prepares the bacteria to be devoured. The action of opsonins is destroyed by temperatures between 55° and 65° C. The opsonic power of the serum for a particular bacterium is often increased by the injection of small quantities of that organism in the dead condition (Vaccines). PART IV. THE ANIMAL AS PART OF THE SPECIES. A. Repeoduction. So far the animal has been studied simply as an individual. But it has also to be regarded as part of a species, as an entity which has not only to lead its own life, but to transmit that life to offspring from generation to generation and thus to secure the survival of the species. When a unicellular organism reaches such a size that the proportion of mass to surface begins to interfere with nutrition, the metabolism undergoes alterations which lead to the division of the cell (p. 28). In certain cases conjugation between two cells may occur and this appears to precipitate the process of division. In multicellular organisms the gametic cell or cells early throw off the somal cell or cells from which all the tissues of the body are developed. In Ascaris this occurs at the very first division. The purpose of somal development, of the development of the body as a whole in all its marvellous complexity, is simply for the nutrition and protection of the gametic cells. These latter are eternal, going on from one generation to another and in each building up a body. The body is mortal, perishing with the death of the individual. In all higher forms of animals conjugation of two gametic cells precedes division and development. In many inverte- brates this is not always necessary and reproduction without conjugation — i^arthenogenesis — may occur. In vertebrates and in a large number of invertebrates two sets of gametes are formed — one the ovum which is generally EEPRODUCTION 617 large and which manifestly undergoes division, multiplication, and development to form the new individual, and one the sperm or spermatozoon, which is generally smaller and which con- jugates with the former. In vertebrates these are produced in separate individuals of the species which have the distinctive anatomical and physio- logical characters of the female and male. The dependence upon the gonads of the development of these distinctive characters has been considered on p. 606 et seq. I. Determination of Sex. The problem of what determines in any ovum its develop- ment either into ova associated with the female type of body or into spermatozoa associated with the male type is a most difficult one. A consideration of importance is that, under normal con- ditions of sexual reproduction, the number of males and of females produced is approximately equal. (1) In some animals the sex is determined before the ovum is impregnated. Among vertebrates this seems to be the case in birds. A hen with barred pattern of feathers transmits this character to male chicks only, unless the father is also barred. Hence it seems clear that there must be two kinds of ova — one to produce males and one to produce females. (2) In other animals, and almost certainly in mammals, the sex seems probably to be determined by there being two types of spermatozoa. It is probable that certain special chromosomes, often called the X chromosomes, are the determining factors. When two of these are present, a female develops, when one is present, a male ; and the gametic cells developed in each sex will be characterised by the possession of these numbers. When these cells undergo their reduction division (pp. 619 and 620), before forming ova and spermatozoa, each female cell is left with one X chromosome, while half the male cells contain an X chromosome and half do not contain one. When one of the former impregnates an ovum, that ovum has two X chromo- somes and develops into a female; when one of the latter per- forms the impregnation, the ovum has only one X chromosome and develops into a male. The existence of these two kinds of spermatozoa and the 618 VETERINARY PHYSIOLOGY fact that only those ova which have the paternal X chromosome will develop into females explains the transmission of certain paternal characters through the daughters. In the human sub- ject this is seen in colour blindness and in haemophilia, a disease characterised by excessive bleeding from slight wounds. These conditions are common in the male but very rare in the female. But since the female gamete alone contains the paternal chromo- some, the abnormal conditions can pass only through the females to become manifest in the male progeny. Such observations suggest that the determination of sex may be co-related with the Mendelian hypothesis. (3) In some animals, e.g. the frog, the nutritional condition of the ovum may determine its sex. By varying the condition of the eggs before fertilisation the proportion of males to females may be modified. It would appear that in some animals the course of development of the gamete is firmly established from the first, that in others it may be determined by the X chromosome in impregnation, while in a third group it may be modified by the nutrition of the cell either before impregnation or at the time of impregnation. How far this last factor acts in the case of mammals we do not at present know. There is some evidence in invertebrates that the number of X chromosomes in a cell may be reduced under certain con- ditions, and thus a potential female cell changed into a male cell. The problems of Heredity are fully dealt with in all text- books of Biology, and therefore they need not be considered here. II. The Gonads. {The structure of the organs ofreproductionmust he studied practically.) The development of the true gametic cells of the gonads and of their ancillary cells has been already considered on p. 605. While the individual is actively growing, the reproductive organs are quiescent ; but, when puberty is reached, they begin to perform their functions — the testes to produce spermatozoa. REPRODUCTION 619 the ovaries to produce ova, and, as they become functionally active, the secondary sexual characters develop (p. 606). A. Ovary. — The ovaries are oval structures lying in a fold of peritoneum — the broad ligament. The cells covering the genital ridge grow downwards as the oogonia. These become disposed (1) as a covering layer of columnar cells ; (2) as interstitial cells (p. 608) ; (3) as clumps of cells forming the Graafian follicles. The central cell of each of these undergoes further growth, becomes larger than the surrounding cells and forms the primary oocyte. This cell throws out the first polar body and becomes a secondary oocyte. A second polar body is Proliferation Fig. 235.— Scheme of Spermatogenesis and Oogenesis. then thrown out, and half the chromosomes are thus elimi- nated and the mature ovum is formed (fig. 235). This becomes surrounded by a capsule, the zona j^ellucida. The surround- ing cells forming the zona granulosa multiply, and a fluid, the liquor folliculi, appears among them, dividing them into a set attached to the capsule of the follicle and a set surrounding the ovum. When the follicle is ripe, it projects on the surface of the ovary, and finally bursts, setting free the ovum, which escapes into the peritoneal cavity and passes into the trumpet-shaped fimbriated upper end of the Fallojnan tube through which it reaches the uterus. The ruptured Graafian follicle generally becomes filled with blood, and later with the 620 VETERINARY PHYSIOLOGY proliferated cells of the zona granulosa and forms the corpus luteum. If the ovum is fertilised and pregnancy occurs the corpus luteum goes on growing, attains a considerable size, and plays an important part in the course of gestation (p. 608). B. Testis. — The testis is enclosed in a dense fibrous capsule — the tunica albuginea. Posteriorly this is thickened, and forms the corpus Highmori. Processes extend from this Fig. 236. — I, To show this development of spermatozoa from spermatogonia ; II and III, heads of spermatozoa dipping into cells of Sertoli ; IV, mature spermatozoa. Two inter- stitial cells shown below. (Mott.) and form a supporting framework. In the spaces are situated the seminiferous tubules, which open into irregular spaces in the corpus Highmori — the 7'ete estis. From these the efferent ducts, vasa eferentia, pass away and join together to form the vas deferens, which, after receiving the duct from a diverticulum of the seminal vesicle, opens into the urethra. In the seminiferous tubules, the spermatozoa are produced. Some of the lining cells divide into two, forming a supporting cell next the membrane and a spermatogonium. The latter divides and subdivides till a group of cells, the primary spermatocytes, are formed. Each of these undergoes a division, in which the number of chromosomes in each cell formed is REPRODUCTION 621 reduced to one half, and thus secondary sjjermatocytes are pro- duced. These again divide to form the spermatids (fig. 235). In each spermatid the nucleus elongates and passes to the attached extremity, the protoplasm decreases in amount, and a long cilium develops from the free end, and the spermatozoon is thus pro'lnced. As they develop they seem to bore into the cells ol Sertoli (fig. 236), the lipoids of which probably act as nutr'ont material. The interstitial cells of Leydig have been already described (p. 606). They are very rich in phospholipins. III. The Secondary Sexual Organs. A. In the Male. 1. The Prostate consists of a dense framework of fibrous tissue with visceral muscular fibres enclosing dense branching glands which secrete a fluid which undergoes coagulation. In some animals, e.g. the guinea-pig, it is ejaculated after the rest of the seminal emission and forms a plug in the vagina. Semen. — When the testes have become active, the glands of the prostate increase and produce a fluid which, with the spermatozoa, forms the semen. 2. The Penis. — Thisconsistsof erectile tissue — a dense fibrous tissue filled with irregular blood spaces, into which arteries open. The penis of the bull is pointed, while that of the ram terminates in a filiform process. In these animals the semen is passed into the mouth of the uterus. B. In the Female. 1. The Fallopian Tubes. — A tube, with a trumpet-like fimbriated upper end, lying close to the ovary on each side, leads to the uterus. It is lined by a mucous mem- brane raised into complex ridges and covered by a ciliated epithelium. 2. The Uterus is a hollow organ with a wall composed of visceral muscle fibres. In the sheep and cow and bitch it con- sists of two distinct cornua — in the mare of a central part. It is lined by a mucous membrane, which is covered by a ciliated epithelium, and in which are tubular glands that extend down 622 VETERINARY PHYSIOLOGY to the muscular coat. The nature of their secretion requires investigation. The nerve supply is considered on p. 633. IV. The (Estrous Cycle. The female of all species of mammals, and the male of some, pass through a cycle of sexual activity and sexual rest. This has been called the osstrous cycle. In the anoestriim the ovaries, uterus, and other sexual organs are quiescent, and their blood-vessels more or less contracted. In the procestrum one or more ova ripen, the blood-vessels dilate, haemorrhages occur into the mucous membrane of the uterus, and blood may escape by the vagina. In the (esiriim these conditions reach their maximum, and in the lower animals coitus is allowed. In the mare, cow, pig, and sheep the cestrum may recur at short intervals at some special season of the year, while in carnivora, e.g. the dog, it occurs only once at a given sexual season. In the mare the usual sexual season is early summer. Each cestrum may last 4 or 5 days. In the cow the season varies, and in it cestruon may recur at intervals of about 20 days. In the sheep the season is in autumn, and oestrum may recur repeatedly at intervals of about 12 days, lasting each time for only about a day or less. In the sow oestrum may recur at intervals of about 20 days, and the whole cycle is generally repeated twice a year. In the bitch an oestrum cycle recurs generally twice a year. CEstrum usually lasts for about a week. Even if not impreg- nated, the ovary, uterus, and mammary gland show the same chano-es as occur in pregnancy and which may be secreted. In the postc£strum the organs return to their normal condi- tion, and the corpus luteum or corpora lutea grow in the ovaries. In some animals, e.g. the rabbit, rupture of the follicle occurs only if copulation takes place. If this does not occur the follicle atrophies. REPRODUCTION 623 V. Impregnation. Impregnation is effected by the transmission of spermatozoa into the genital tract of" the female. For this purpose erection of the penis is brought about reflexly through a centre in the Fig. 237. — Ovum, after Segmentation, showing the Formation of the Ectoderm (.4.) and Endoderm (B.). From the cells of the latter the Blastoderm is formed. (Ellenberger.) lumbar enlargement of the cord, the outgoing nerves being the nervi erigentes, or pelvic nerves which dilate the arterioles, and the internal pudics supplying the transversus perinei and bulbo- cavernous muscles by which the veins of the penis are constricted. The semen is ejected by a rhythmic contraction of the bulbo- A. B. C. Fig. 238. — To show A., the Spreading out of the Endoderm Cells to Form the Blastoderm ; B., the Formation of Epiblast and Hypoblast ; and C, of Mesoblast. In B. and G. the ectoderm is not shown. (Ellexberger.) cavernous and other perineal muscles, an action which is also presided over by a centre in the lumbar region of the cord (p. 89). The spermatozoon meets the ovum in the Fallopian tube or upper part of the uterus. 624 VETERINARY PHYSIOLOGY B. Development. I. Early Stages. As the ovum passes down the Fallopian tube it is surrounded by cells of the zona granulosa, and these probably serve as a source of nourishment and may prevent the ovum from becom- ing attached till it reaches the uterus and absorption of the cells is completed. Sometimes implantation occurs in the tube and a tubal pregnancy may ensue. It is unnecessary here to describe the changes in the ovum before or immediately after its conjugation with the spermato- FiG. 239. — Transverse Section of more advanced Blastoderm, to show Epiblast, Mesoblast, and Hypoblast, formation of Neural Groove and splitting of the Mesoblast. Fig. 240. — Longitudinal Section through Embryo to show it Sinking Down into Ovum and the Formation of the Amnion, am. In the Meso- blast round, all., the allantois, the blood-vessels grow out to form the placenta. zoon, since they are so fully dealt with in all works on Biology (p. 29). The mammalian ovum is holoblastic, that is, undergoes com- plete segmentation, and forms a mulberry-like mass of cells (fig. 237, A.). The cells then get disposed in two sets, a layer of small surrounding cells and a set of large central cells (fig. 237, jB.). The former constitute the Ectoderm and take part in forming the processes or 'primitive villi by which the ovum becomes attached to the maternal mucous membrane. The latter spread out at one pole to form the blastoderm (fig. 238, A.) and dispose themselves in three layers — the epiblast, meso- blast, and hypoblast (fig. 238, B. and C). From these layers the various parts of the body are derived as follows : — I. Epiblast. — Nervous system ; epidermis and appendages ; epithelium of the mouth, nose, naso-pharynx, and all cavities and glands opening into them, and the enamel of teeth. DEVELOPMENT 625 II. Hypoblast. — Epithelia of (a) the alimentary canal from the back of the mouth to the anus and of all its glands ; (h) of the Eustachian tube and tympanum ; (c) of the trachea and lungs ; (d) of the thyreoid and thymus ; and (e) of the urinary bladder and urethra. III. Mesoblast. — All other structures. By the formation of a vertical groove down the back of the blastoderm, a tube of epiblast cells (the neural canal) is enclosed, from which the nervous system develops by the conversion of Fig. 241. — Longitudinal Section through the Human Uterus and Ovum at the Fifth Week of Pregnancy. D.S., deoidua serotina, which will become the placenta ; D.R., decidua reflexa ; D. V., the uterine mucous mem- brane called the decidua vera. some of the cells into neurons, and others into neuroglia cells (fig. -239). The mesoblast on each side of this splits, and the outer part, with the epiblast, goes to form the body-wall (Somatopleur), while the inner part with the hypoblast gets tucked in to produce the alimentary canal (Splanclinopleur) (fig. 239). The developing embryo sinks into the blastocyst, and, as a result of this, the somatopleur folds over it and, uniting above, en- closes it in a sac — the amniotic sac (fig. 240, am.), which becomes distended with fluid — the amniotic fluid, in which the embryo 40 626 VETERINARY PHYSIOLOGY floats during the latter stages of its development, and which acts as a most efficient protection against external violence. The source of this fluid has been much debated. In birds it is certainly of foetal origin. In mammals it has been contended that it is derived from the maternal circulation. But, since in herbivora it resembles urine more than a blood transudate and since the urethra of the foetus opens into the amniotic sac, it is probably chiefly derived from the foetal kidneys. In rabbits, when the foetus is killed in utero, no fluid is formed in the sac, although the maternal part of the placenta persists. A very significant fact is that in herivora it contains a sugar, Isevulose, which is present in the fcetal blood but not in the maternal blood. 11. Attachment to the Mother. (1) By the action of its ectoderm cells the ovum burrows its way into the mucous membrane of the uterus which is hypertrophied and very vascular. These ectoderm cells grow outwards as syncytial masses of protoplasm forming the trophoblast layer. The burrowing action may be due to the development of some powerful proteolytic enzyme, although definite proof of its existence is not forthcoming. Certainly, in some way the maternal tissues are killed and digested. When a maternal blood-vessel is opened into, the blood is hsemolysed, thus probably rendering the iron of the heemoglobin available for absorption by the embryo. At this stage of development the embryo is a parasite upon the mother living upon her substance. The important part played by the corpus luteum in de- termining the implantation of the ovum has been discussed on p. 608. (2) Later, the mesoblast of the embryo extends out in a number of finger-like processes into the trophoblast layer, and soon afterwards blood - vessels shoot into these, and the chorionic villi are formed. These are at first covered by a definite layer of cubical cells, the layer of Langhans with outside it a syncytial trophoblast layer of protoplasm. Later the layer of Langhans disappears and the syncytium becomes extremely thin (fig. 242). DEVELOPMENT 627 The origin of the first blood-vessels in the villi is not known, but ultimately they are derived from the allantoic arteries which pass out from near the posterior end of the hind gut. As the villi grow, the blood-vessels of the maternal mucosa in the decidua serotina (fig. 241, B.S.) dilate, and the capillaries form large sinuses or blood spaces. Into these the chorionic villi pass, and thus the loops of foetal vessels hang free in the maternal blood, and an exchange of material is possible between the mother and foetus. The distribution of these villi is different in different animals. In the horse they are diffusely scattered ; in the cow and sheep they are arranged in circular patches, the cotyledons ; in carnivora they are generally in a zone. Fig. 242. — Longitudinal Section through the Tip of a Villus of the Placenta, covered by its trophoblast layer, and containing a loop of blood-vessels, and projecting into a large blood sinus, J. V.S., in the maternal mucosa. In the pig, horse, and in ruminants, the connection of the foetal blood-vessels with the maternal structures is not very intimate, and when the young are born the foetal part of the placenta separates from the maternal part, which is thus not shed. Hence such animals are called non-deciduata. In rodents, insectivora, apes, man, and carnivora, the associa- tion is so intimate that at birth the maternal part of the placenta is shed along with the foetal. Hence these are called deciduata. In the mesoblast, through which the allantoic arteries pass 628 VETERINARY PHYSIOLOGY out, a vesicle, filled with fluid, and at first communicating with the posterior gut, is developed (fig. 240, all.). This is the allantois. In man it never attains any size, but in most of the Fig. 243. — Schematic section through the pregnant uterus of the Mare to show the large allantoic sac, All., filled with fluid surrounding the amniotic sac ; Am., the fluid in which the fa?tus floats. lower animals it spreads all around and encloses the amnion, and is distended with a large quantity of fluid. This fluid has all the characters of urine, and when fluorescin is injected into c A Fig. 244. — Schematic section of one cornu of the uterus of a ruminant at an early stage of gestation to show the elongated umbilical vesicle. A, and allantois, B, and the embryo in the amniotic sac, G. the maternal circulation, it appears in the foetus before it shows in the allantoic fluid. It is almost certainly produced from the first by the foetal kidney. III. The Nourishment of the Foetus. The Placenta is formed on the foetal side by these processes; on the maternal side by the increased growth and increased vascularity of the maternal mucosa. DEVELOPMENT 629 In the deep layer of the mucosa under the placenta the connective tissue cells enlarge and form a thick mass of decidual cells. Possibly these are protective, preventing the enzymes or other products of foetal metabolism from invading the mother, A new stage in the physiological relationship of the foetus to the mother is now established. It is no longer a parasite but rather a guest which shares with the mother the supply of nourishment in the maternal food. The placenta becomes (1) the foetal lung, giving the embryo the necessary oxygen and getting rid of the waste carbon dioxide, (2) The foetal alimentary canal supplying the necessary material for growth and development ; and (3) the foetal kidney through which the waste nitrogenous constituents are thrown off. When this stage of gestation is reached, it is generally found that the maternal body shows the same increased power of storing the constituents of the food as is seen during the period of growth. The pregnant animal stores material like the growing young, generally taking just what is required to satisfy the normal growth of the foetus, but frequently retaining more and storing it in its body. Hence the practice of having cows rendered pregnant in feeding them for market. Carbohydrates are early stored as glycogen in the cells of the maternal placenta, and, since no glycogen is found in the foetus till much later, it must be taken up by the chorionic villi as sugar. Whether the diastase for this conversion is formed by the mother or by the foetus is not known. Fats appear earlier in the chorionic villi than in the maternal placenta, and there is no evidence that fats stained with Sudan III. are passed to the foetus. Probably the foetal fats are formed from carbohydrates. Iron also appears earlier in the foetal j)lacenta than in the maternal, and it is probably taken up from the hasmolysed maternal blood (p. 626). As regards the passage of proteins nothing is known with any certainty. It may be that the proteins of the maternal blood are passed to the fostus unchanged. Since amino-acids are found in the fcetal blood it has been argued that the pro- teins may be digested to this condition before passing to the foetus. But it must be recognised that possibly these 630 VETERINARY PHYSIOLOGY amino-acids are the results of the protein metabolism of the fcBtus. Chemical examination of the allantoicfluid of ungulates,which is foetal urine (p. 626), shows, in the early stage of development, a high proportion of nitrogen in amino-acids,peptides and allantoin. This seems to indicate a less complete catabolism of protein and a more active nuclear metabolism than in extra-uterine life. The placenta manifests little power of regulating the materials which are passed to the foetus, and most drugs and toxic substances reach it. Even the micro-organisms which are the cause of various diseases may pass through the placenta. In this respect it seems to differ from the cells of the choroid plexus, which manifest a selective action on the materials which it passes to the cerebro-spinal fluid (p. 511). IV. Growth of the Foetus. The growth of the foetus is steady and slow, and the daily demands on the mother are comparatively small. At birth the human foetus is less than 8 per cent, of the weight of the mother, while in some animals, e.g. the dog, the litter may weigh 20 or 25 per cent, of the maternal weight. Considering the fact that the power of fixing material in the body is increased during pregnancy, the amount of the food consumed which has to be transmitted to the foetus is com- paratively trivial. Only in the later period of intra-uterine life is the demand for proteins, and, more especially, for fats in any way considerable. It may thus be said that under all conditions of normal nutrition it is the surplus of nourishment which is passed from the mother to the foetus, and, if in the later months of pregnancy her nourishment is limited, the size of the young may be reduced. The maternal tissues part more readily with some sub- stances than with others. Thus the demands of the foetus for calcium, when the supply to the mother is inadequate, may be met by removal of calcium from her bones, which may thus be softened. On the other hand, the maternal tissues do not become depleted of iron in the same way to meet the require- •ments of the young. I DEVELOPMENT 631 V. Metabolism in Pregnancy. During pregnancy the increase in the metabolism is pro- portionate to the increase in the weight of the mother. This increase is due not only to the growth of the foetus, but also to the growth of the uterus and mammary glands and to the formation of the amniotic and allantoic fluids which are inert. Hence probably the metabolism of the foetal tissues is more active than that of the maternal. Experiments upon guinea-pigs support this conclusion. It has been found by means ot the respiratory calorimeter (p. 259) that the total metabolism of the mother just before delivery is practically the same as that of the mother and young after delivery. VI. The Young Animal at Birth. At birth the young animal is suddenly precipitated from its prolonged bath in the warm amniotic fluid Avhere its temperature has been maintained, and where it has received a steady supply of oxygen and of food without any exertion on its part into the chill air of the outer world where it has to secure its oxygen by the efforts of breathing, to get its food by sucking and digesting and to maintain its temperature by its own meta- bolism. No wonder that this sudden change proves too much for the less robust, and that the mortality during the first week of life is high. The power of heat regulation is not at once developed, and the young animal at first tends to react to the temperature of its surroundings in the manner of a cold-blooded animal. In a day or two its power of adaptation improves and the rate of its chemical changes increases so that from this time onwards throughout the period of active growth they are in excess of those of the adult (p. 266). VII. Fcetal Circulation. The performance of its functions by the placenta is associated with a course of circulation of the blood somewhat different to that in the post-natal state (fig. 245). The blood coming from the placenta to the foetus is collected into a single umbilical vein, u.v., which passes to the liver, I. This divides into the ductus venosus, d.v., passing straight 632 VETERINARY PHYSIOLOGY through the organ, and into a series of capillaries among the cells. From these the blood flows away in the hepatic vein to the inferior vena cava, 'p.v.c, and mixed blood passes to the right auricle. In this it is directed by a fold of endocardium, A.y. Fig. 245. — Scheme of Circulation in the Foetus, u.v., umbilical vein ; d.v., ductus venosus ; p.v.c, inferior vena cava pouring blood through the right auricle and through the foramen ovale, f.o., into the left heart ; a.v.c, superior vena cava bringing blood from the head to pass through the right side of the heart, and through the ductus arteriosus, d.a. ; Jit. v., portal vein. The degree of impurity of the blood is indicated by the depth of shading. through the foramen ovale, f.o., a hole in the septum between the auricles, and it thus passes to the left auricle, and thence to the left ventricle, l.v., which drives it into the aorta, a.a., and chiefly up to the head, ant.a. From the head the blood returns to the superior vena cava, a.v.c, and, passing through the right DEVELOPMENT 683 auricle, enters the right ventricle, r.v., which drives it into the pulmonary artery, p.a. Before birth this artery opens into the aorta by the ductus arteriosus, d.a., while the branches to the lungs are still very small and unexpanded. In the aorta, this impure blood from the head mixes with the purer blood from the left ventricle, and the mixture is sent to the lower part of the body through the descending aorta, yo.a. From each iliac artery, i.a., an umbilical artery, u.a., passes off, and these two vessels carry the blood in the umbilical cord, u.c, to the placenta. When the animal is born, the flow of blood between it and the mother is arrested. As a result of this, the respiratory centre is no longer supplied with pure blood, and is stimulated to action. The lungs are thus expanded and the blood flows through them. In the ductus venosus a clot forms and the vessel becomes obliterated. The ductus arteriosus also closes up, and the foramen ovale is occluded. The circulation now takes the normal course in post-natal life. VIII. Gestation and Delivery. The length of gestation is different in different animals — Mare . Cow . . 11 months (330 to 340 days) . 9 „ (270 to 290 „ ) Sheep Sow . . 5 „ (145 to 155 „ ) . 4 „ (115 to 120 „ ) Dog . Cat . . 62 days . 63 „ At the end of this period labour occurs, and the foetus and its membranes are expelled. The mechanics of labour must be studied with obstetrics. Nervous Control. — The uterus is supplied by fibres leaving the spinal cord by true sympathetic fibres from the splanchnics. These fibres pass to the inferior mesenteric ganglion and on in the hypogastric nerves to end in two large plexuses or ganglia, containing numerous nerve cells, one on each side of the cervix. From these, fibres pass to the uterus and to the vagina. There is evidence that, in lower animals at least, the contents of the uterus may be expelled after complete separa- 634 VETERINARY PHYSIOLOGY tion of the organ from the central nervous system. The peri- pheral mechanism, like that of the intestine and bladder, is capable of independent action. But normally a centre in the lumbar enlargement of the spinal cord appears to be excited reflexly. This centre is further acted upon by the brain, and various disturbances, accompanied by emotional changes, may, for a time, arrest uterine contraction. IX. Lactation. 1. The Mammary Gland. — The mammary glands consist essentially of a collection of specially developed sebaceous glands, the function of which has been modified to yield a nutritive secretion for the young. In some of the lower mammals (Monotremes) the secretion is provided by the enlarged skin glands which open direct on to the surface of the abdominal wall, and the young are nourished by licking the wall where aggregations of these occur. In the higher mammals the glands are more highly developed and more definitely collected into groups forming the mammar}^ glands, with sinuses to act as reservoirs for the secreted fluid, and a teat for convenience of the young in sucking. The number of glands present is roughly in proportion to the usual number of young born at a time. The mare, the sheep, and the goat have two glands. The pig has ten to fourteen, the dog eight to twelve. The udder of the cow is usually spoken of as having four "quarters." A fibrous septum in the median line divides the udder into two halves. There is no dividing line between the two quarters of the same side, though the sinuses of the same side do not communicate. 2. Physiology — (1) Development. — Rudimentary glands are present in both male and female animals. In the male, normally they remain undeveloped. In the female, as sexual maturity is reached, the gland increases in size, the increase consisting chiefly of fibrous tissue with a large amount of fat. In pregnancy, proliferation of the glandular tissue occurs. The tubules, which were solid blocks of cells, grow outward and alveoli develop. As the cells of the tubules and the alveoli divide, some remain attached to the DEVELOPMENT 635 basement membrane, and some come to lie in the lumen of the tubules and the cavities of the alveoli. These latter undergo fatty degeneration and are shed with the first milk — colostrum. It is the cells left on the basement of the membrane of the alveoli that elaborate the constituents of the milk. (2) Regulation of Activity — ((() Chemical Stimulation. — This subject is dealt with on page 609. (6) Nerve Stimulation. — The extent to which the secretion of milk is influenced by the nervous system has not been determined with certainty. After secretion of all the nerves passing to the gland, if the animal be lactating, secretion continues, though the amount may be diminished ; if the animal be pregnant, glandular development proceeds, and at parturition normal secretion of milk occurs. On the other hand, pain or excitement reduces the quantity of milk. Whatever influence the nervous system does exert is probably produced through vasomotor nerves and intrinsic nerves of the gland. On the whole, it seems certain that control through the nerves is subsidiary to chemical control through the blood. The flow of the milk can be influenced by the central nervous system. The walls of the ducts contain muscle fibres which can act by constricting the lumen and stopping the flow. In this way the cow is able to "hold up" its milk, as often occurs when milking is attempted by a person to whom the animal is unaccustomed, or when a cow that has been sucked by its calf is milked by hand. (c) Mechanical Stimulation. — The distension of the ducts with milk inhibits further secretion. The periodical emptying of the udder, therefore, by sucking or milking is necessary to maintain functional activity. The influence of the sucking is not entirely due to the relief of the distension. The mechanical stimulation probably induces secretion through a nervous reflex, as by this means a flow of milk may be produced in a virgin animal (p. 609). 3. Composition of Milk — (1) Adaptation for Needs of Young Animal. — Milk is produced to supply material and energy to a rapidly growing animal. The materials present, there- fore, are in proportion to the requirements for growth. It 636 VETERINARY PHYSIOLOGY has already been shown (p. 372) that the percentage of proteins present varies with the rate of formation of new tissue. The relationship between the salts of the milk and those con- tained in the tissues of the growing animal is shown by the following table given by Bunge. The percentage composi- tion of the chief inorganic constituents of the tissues of a young rabbit, of the milk it was receiving, and of the serum of the mother's blood are compared :— Potash . Kabbit 14 days old. 10-8 Kabbit's Milk. 10-1 Mother's Blood Serum 3-2 Soda 6-0 7-9 54-7 Lime Magnesia 35-0 2-2 35-7 2-2 1-4 0-6 Iron Oxide 0-23 0-08 0- Phosphoric Acid Chlorine 41-9 4-9 39-9 5-4 3-0 47-8 This close adaptation of the composition of the milk to the needs of growth affords an explanation for the difference in percentage composition of the milk of different species. It also accounts for the well-recognised fact that, after wean- ing, especially if this takes place too early, the rate of gain of weight per day suffers a marked decrease, since, in practice, no combination of food-stuffs can yield the perfect proportion of the necessary materials which is present in milk, (2) Constituents — (i.) Protein. — The chief protein of milk is casein, a phospho-protein. It exists in milk in the form of a calcium salt. Casein contains all the amino-acids, except one, necessary for building up the various proteins of the young animal. The one absent — glycine — can be easily formed in the body from other amino-acids. The other proteins present are an albumin and a globulin, which closely resemble those found in the blood. (ii.) Fat. — Milk fat consists of olein, palmitin, and stearin to the extent of nearly 90 per cent. The remaining 10 per cent, consists of fats of lower molecular weight. It is the latter that gives the characteristic flavour to butter. Lecithin and cholesterin are also present. The phospho- DEVELOPMENT G37 lipins of the milk are much more abundant than those in the blood serum. The fat occurs in the form of minute globules. Coal- escence is prevented by the surface tension of the spheres, and by the adsorption of protein on the surface. It cannot be separated from milk by ether till the globules are broken down by an acid or an alkali. The specific gravity of the fat is "93, while that of the milk free from fat is about I'OSo. The globules of fat, therefore, tend to rise to the surface to form cream. The mechanical agitation in churning causes the globules to coalesce with the formation of butter. (iii.) Carbohydrates. — The carbohydrate of the milk is lactose (p. 286). It only occurs in milk. (4) Ash. — The ash of milk contains the same inorganic substances as are found in the tissues (p. 636). The substance present in greatest amounts are calcium and phosphorus. Iron is present only in traces. 3. The proportion in which constituents are present in the milk of some species is shown in the following table : — (8) Percentage Composition. Cow. Goat. Mare. Sow. Bitch. Water . 86-3 85-7 91-6 84-0 75 Protein 3-0 4-3 10 7-3 10 Fats . 3"5 4-8 1-3 4-5 11 Carbohydrates 45 4-4 5-7 3-1 3 Ash . 0-7 0-8 0-4 1-1 1 The cells of the mammary gland transfer to the milk many substances administered Avith the food, hence the taste of the milk may be altered and certain drugs given by mouth may appear in the milk. (4) Colostrum. — The fluid drawn from the gland for the first two or three days after parturition difl^ers from true milk. It is characterised by^ (1) A large proportion of solids — 25 to 30 per cent. (2) A high percentage of albumin and globulin. (3) The presence of multinuclear bodies, probably leuco- cytes and desquamated glandular cells. 638 VETERINARY PHYSIOLOGY The percentage of fat and carbohydrates are not markedly different from those of milk. Colostrum is valuable to the newly born animal. Its food value is high, and it stimulates evacuation of the bowels. (5) Factors affecting Milk Production in Cows — (1) Breed- — The amount and composition of the milk produced is partly dependent upon the breed of cows. Thus the milk of the Jersey is especially rich in fat, frequently containing over 5 per cent., while that of the Friesian Holstein and the Holderness has a comparatively low fat content. In general, the breeds noted for a large yield give milk with a low percentage of fat. The differences due to breeds are, how- ever, comparatively small — less than what is often found between individuals of the same breed. (2) Milking. — It has been definitely proved that in a cow with a large yield the cavities of the udder have not the capacity to contain all the milk that can be obtained at a milking. There must be rapid secretion during the time of milking. In the interval between the milkings secretion is most active when the udder is empty. As the cavities get filled the distension appears to inhibit secretion. The more frequent the emptying of the udder therefore up to the point where the prejudicial influence of over-action of the gland cells appears, the greater the quantity of milk obtained. It is estimated that three milkings per day may yield nearly 5 to 20 per cent, more milk than two, and two may yield nearly 50 per cent, more than one. When the intervals between the milkings are of an unequal length, milk with a higher fat content is got after the shorter period. It has been suggested that this is due to the distension of the ducts, which occurs in the longer interval, preventing the extrusion of the fat globules from the secreting cells and consequently slowing the synthesis of far. Marked differences occur in the fat content of the milk drawn at different stages of milking. The first portion may contain less than 1 per cent., the last portion drawn, " the strippings," may contain over 10 per cent. The fat only is involved, the other constituents remain uniform throughout the period of milking. DEVELOPMENT 639 The complete emptying of the udder at milking is necessary, not only to obtain the valuable fat in the last portion, but to maintain the full activity of the gland. In incomplete milking the amount secreted diminishes. (3) Food. — (1) The percentage composition of tlie milk of any individual animal is within wide limits independent of the relative proportions of the constituents of the food. Only small deviations from the normal standard can be obtained by feeding excessive amounts of one constituent. So great is the tendency to secrete milk of normal composition that when one of the constituents is deficient in the food, the animal draws upon its own body for material, salts being supplied by the skeleton and protein and fat by the tissues. The amount secreted is however diminished. This prevents undue depletion of the body. The body possesses only a small reserve store of carbohydrate (p. 353). In an experiment in ■which the carbohydrate of the food was reduced, and the reserve store depleted by drawing off sugar through the kidneys by means of phloridzin, it was found that instead of milk deficient in sugar being secreted the quantity decreased. ilk CO. Lactose per cent. 230 3-9 238 4-0 238 3-9 ) Sugar drawn off 3-8 j bv phloridzin. 218 170 3-8 (2) Nature of Fat. — The composition of fat can be modified by the food. Abnormal fats fed may appear in the milk. Feeding stuffs rich in oils, such as linseed cake, produce butter which is deficient in the higher fatty acids and consequently soft at a low temperature. (3) Yield. — So long as food is given to supply (1) the maintenance requirement of the animal and (2) sufficient material for milk formation, the yield depends upon the capacity of the animal as a milk producer much more than on the food. When, however, cows are put to graze on young pasture-grass increased flow almost invariably occurs, and in certain experiments, increasing the proportion of 640 VETERINARY PHYSIOLOGY protein in the diet increased the yield. Excess of carbo- hydrate or fat tends to fat formation and deposit in the animal's body. The food requirements for milk cows are given on page 375. (4) Housing. — It was formerly a custom to restrict ventilation for the purpose of maintaining heat in byres, the idea being that in warm byres the milk flow Avas increased. Spier and Hendrick have shown that cool byres and free ventilation do not reduce milk production. The following are results obtained at different temperatures : — Aver. temp. Milk lbs. Fat of byre. per cow. per cent. Cool byres, free ventilation 41-2° F. 29-0 3-51 Warm byres, restricted ventilation . . . 61 "T" F. 28-9 3-48 m The animals in the cool byres had better coats and were better condition at the end of the winter. It has been found however that a marked decrease in the temperature reduces milk secretion, and that animals exposed in winter eat more food than those comfortably housed. The temperature below which more food is required, or at which the milk secretion begins to diminish, depends upon the critical temperature (p. 2 7 1 ) of the animal. Unfortunately comparatively little work has been done to determine the critical temperature of dairy cows. Owing to the stimulus to metabolism caused by the large amount of food eaten it is probably comparatively low. From the evidence available it would appear to be not higher than 7° to S'' C. To have animals housed in an atmosphere above the critical temperature should lead neither to a saving in food nor to an increased production of milk. APPENDICES I. SOME ELEMENTARY FACTS OF ORGANIC CHEMISTRY The following elementary facts may help the student who has neglected the study of the outlines of Organic Chemistry in understanding the chemical jJi'oblems of physiology. Organic compounds are built round the four-handed carbon atom ! — c— I When each hand links to the one-handed hydrogen atom, Methane— H i H— C— H is formed. I H By taking away a hydrogen atom from two Methane molecules and linking the two molecules together Ethane— H H I ! H — C— C— H is produced. I I H H By further linking more and more of those molecules together, similar molecules containing three, four, five or more carbon atoms are jsroduced. When the carbons are arranged in a straight line the normal series is produced — I I I I — C— C-C-C— I I I I Where the line is branched the series is known as iso — I 'C— I I When each carbon has its due proportion of hydrogen atoms it is 41 6U 642 APPENDICES saturated, but if two hydrogen atoms are let go, the unocsupied hands of the carbon may join and form an unsaturated molecule, thus : — Ethane becomes Ethylene H H ! I H— C = C— H When one hydrogen atom is taken away, and the molecule has a hand ready to link with some other substance, a radicle is constituted, and these are known as Methyl, Ethyl, etc. Alcohols- — If one of the hydrogen atoms of Methane is oxidised to hydroxyl ( -OH), an alcohol is formed — The hydroxyl group ( — OH) is characteristic of alcohols. H H— 0— OH Methvl Alcohol. I H Similarly Ethane gives H H i I .C-C— OH Ethvl Alcohol, I I H H and so on for compounds having a longer carbon chain. If only one — H is oxidised to — OH, the alcohol formed is termed Monohydric. If tAvo — H atoms are oxidised, the alcohol is Dihydric. If more than two — OH groups are present, the alcohol is Polyhydric, e.g. H H H I I I HO— C— C— C— OH Glycerol (Glycerine). 1 I I H OH H Propane C^H^, and compounds having more than three carbon atoms, may form more than one monohydric alcohol, according to the C atom on which the — OH is placed. Thus, there are two propyl, four butyl, and eight amyl alcohols. Primary Alcohols are those in which a terminal carbon is oxidised. Secondary Alcohols have one or more of the middle carbons oxidised. Polyhydric alcohols may contain primary or secondary groups or both. Aldehydes — When, from a Primary Alcohol, two hydrogens are APPENDICES 6VS removed, the vacant hand of the oxygen links to the vacant hand of the terminal carbon to form an Aldehyde — H I H— C— C = Ethyl Aldehyde. I I H H Ketones- — These are formed in the same way from the Secondary Alcohols, a carbon atom, which is not the terminal one, being involved, thus :— H O H TT J, '1 I rr Acetone, the Ketone of Secondary I I Propyl Alcohol. H H Acids. — If the hydrogen of the terminal carbon atom of the Aldehyde is replaced by hydroxyl —OH an acid is produced — H : I i II H— C--C— 0— H Acetic Acid. I H The carhoxyl group (to the right of the dotted line) is characteristic of the acids. The oxidation may be carried on at each end of the line ; divalent acids being thus produced — H— 0— C— C— 0— H Oxalic Acid. If, in the radicle of one of these acids, a hydrogen is replaced by hydroxyl — OH, an oxy-acid is formed, thus : — H H I I II H— C— C— C— 0— H Propionic Acid. I I H H Tins may be converted to the two Lactic acids called respectively a and 3 hydroxy-propionic acid, according to the carbon whif^li is oxidised. H OH I I II a H-C-C— C— 0-H and I i H H OH H O ! I II H-C— C— C-O-H H H Similarly oxy-acids are formed from the divalent acids. 644 APPENDICES Ethers. — These are formed by the union of two alcohol molecules, with dehydration. CH. . CHo CH., . CH. OH CHo . CH.3 CH., . CH. Esters. — These are formed by linking an alcohol and an acid mole- cule with dehydration. CH3 . CHo OH CH., .CO OH CH.J . CH. CH., . CO ^0 Anhydrides.— These are formed by the union of two acid molecules with dehydration. CH3 . CO . ; OH CH. . CO . oIh CH, . CO CH., . CO Cyclic Compounds. (1) An important series of carbon compounds contains a ring of six carbons, each with an unsatisfied affinity, thus : — 1 C c I When each hand holds a hydrogen, Benzene is formed. These hydrogens may be replaced by yarious molecules giving rise to a large series of different compounds. (2) If a ring contains atoms of other elements besides carbon, it is called heterocyclic. One of the most important of these is Pyrrol — H— C— C— H H-C C— H N which occurs, linked to a benzene ring, in certain important constituents of the protein molecule. APPENDICES 645 Nitrogen-containing Compounds. Ammonia. — The three-handed Nitrogen by linking with three hydro- gens forms Ammonia, H i H— N— H If one of these hydrogens is removed, Amidogen, — NH„, which can link with other molecules, is produced. Amino Acids- — If one of the hydrogen atoms directly joined to carbon in the radicle of an acid is replaced by amidogen, a mon-amino acid is formed, thus : — H O /N — C — C — — H Amino acetic acid. H i H When two hydrogen atoms are thus replaced, a di^amino acid is produced — NH„NH„ r r ii H — C — C — C — — H or, «, 3^ di-amino propionic acid. i I H H Amines. — In these, NHa takes the place of OH of an alcohol ; or, looked at in another way, they are formed from NH3, by replacement of hydrogen atoms by alkyl groups. H H H H I 1 I H— C— |0-H H -N =H— C— N Methvl-amine. I ! I H H H H Methyl alcohol. Ammonia. Di- and tri-amines may be formed thus — CH3 CH3 \^^ ]]i:r=NH Di-methvl amine. CH3 J>N Tri-methvl amine. CH3 ' ^^^^ CH3 1 The carbon atoms are named a, ,3, and 7 from their position in relation- ship to the carboxyl group. 646 APPENDICES Amides.— If the amidogen molecule takes the place of the hydroxyl : the carboxyl of an acid, an amide results, thus : — HO H H-iJ_ 1 0_H— H 1 H H Acetic acid. H H 1 11 1 H— C-C-N 1 1 H H Acetamide. Compare 'Methylanmie, CHgNH., with Acetamide, CH3 — CO — NH.,. From the divalent carbonic acid — H-0— C-O-H H\ ii H >N-U-Nv H/ -H the important substance Urea or Carbonic Diamide. Urea molecules may link together — (a) By dropping NH3 when Biuret is produced- H Hx II I II /H \N— C— N— C— N( H' ^H (6) By holding on to an intermediate radicle of an acid, e.g. an unsatu- rated three carbon acid. These are Diureides, or Purins, of which the most important is Uric Acid — H— N- I o=c I H— N- -N— H ^C=0 -N--H APPENDICES 647 II. CLASSIFICATION OF THE PROTEINS. I. Native Proteins. A. Uncombined. 1. Poor in Di-amino Acidi. (i.) Albumins.— Coagulated on heating; soluble in water ; not precipitated by half saturation with (NHJ.^SO^. (ii.) Globulins.— Coagulated on heating; insoluble in water ; precipitated by half saturation with (NHJ.SO,. 2. Rich in Di-amino Acids. (i.) Protamines from the heads of spermatozoa, (ii.) Histones from blood corpuscles, e.g. globin of haemo- L'lobin. B. Combined. 1. Phospho-proteins.— Yield phosphoric acid on decom- position, but not purin bases, e.g. vitellin of yolk of egg and carcinogen of milk. 2. Nucleo-proteins.— Compounds of protein with nucleic acid. The nucleo-proteins with the largest amount of nucleic acid are called nucleins. Nucleic acid may be broken down into phosphoric acid, a carbohydrate, purin bases and pyrimidin bases. 3. Gluco-proteins, e.g. mucin (p. 35). 4. Cbromo-proteins, e.g. haemoglobin (p. 486). II. Modified Proteins. The Sclero-proteins. 1. Collagen with its hydrate gelatin (p. 39 j. 2. Elastin (p. 39). 3. Keratin fp. 32). III. Products of Digestion of the Proteins. 1. Proteoses (p. 16 et seq.). 2. Peptones (p. 16 et seq.). 3. Polypeptides (p. 19). 648 APPENDICES III. SOME ELEMENTARY FACTS OF PHYSICS. Diffusion. The molecules of a gas are in continual movement, and if two different gases be brought into contact the molecules of the two gases freely intermingle till a homogeneous mixture results. The molecules of a liquid are also in continual motion, the only difference from the gaseous state being that, owing to the greater concentration of the molecules, the paths are more restricted. When two miscible fluids, e.g. alcohol and water, are brought into contact, intermingling of molecules occurs as in the case of the gases with a resulting homogeneous mixture. This phenomenon whereby two gases or two miscible fluids in contact become uniformly mixed is known as diffusion. It may occur through a membrane permeable to the molecules. In solids, molecules are also in motion, but the paths are so restricted and the mutual attraction of the molecules so great owing to their proximity to each other, that difi'usion between solids in contact is extremely difficult, and only proceeds at a very slow rate. That it can occur, however, has been shown by the fact that if gold and lead be kept in contact for several years some gold is found to be deposited on the lead. Kinetic Energy of Molecules. As molecules have a definite mass, their movement endows them with kinetic energy which is in proportion to their velocity. When the temperature of a substance is raised the velocity of the molecules is increased, and as a result their kinetic energy is increased. Consequently when a gas is heated the molecules impinge on the containing vessel with gi eater force, tending to distend it. In other words, the pressure of the gas is increased. When liquids are heated the kinetic energy of the molecules is increased so that they may break loose from the surface of the fluid and" become free, forming gas, as occurs when water reaches 100° C. at ordinary atmospheric pressure. In the same way, under the influence of heat, the molecules of a solid may increase their movement and the solid become a liquid. Conversely, reducing the temperature decreases the kinetic energy and the velocity of the molecules, and consequently a gas may become a liquid, and, on still further cooling, a solid. The heat of a substance is thus identical with its molecular energy. As heat is added the velocity and consequently the energy of the mole- cules are increased ; as heat is withdrawn the velocity is decreased. Solutions. If a piece of solid cane sugar be put in water some of the molecules of the sugar break loose from the surface of the solid and move among the APPENDICES 649 molecules of the water. As in the case of two miscible fluids in contact a uniform mixture is produced. The sugar is said to go into solution in the water. The sugar is termed the solute and the water the solvent. The solvent is usually a licjuid. The solute may be a solid, e.g. sugar in water, a liquid, e.g. alcohol in water, or a gas, e.g. CO, in water. In their erratic flight some of the molecules of the sugar in solution impinge upon the solid sugar. When the free molecules of the solute have reached such a degree of concentration in the solvent that as many molecules are striking the solid as are leaving it, no higher concentration is possible, and the result is termed a saturated solution. If the solution be heated the kinetic energy of the molecules of the sugar both in solution and in the solid mass is increased and more break free from the solid, and consequently the degree of concentration is increased. This explains why, under the influence of heat, a substance dissolves more rapidly and a higher degree of concentration is obtained. According to the foregoing description a solution can be regarded as a homogeneous mixture of two substances, the molecules of which are in free movement throughout the whole of the mixture. Colloids (see p. 12). The essential character of the colloidal state consists, in the existence together in a physical combination, of two substances, one of which is in the form of ultra-microscopic particles dispersed in the other. The dispersed particles are separated from each other by the containing sub- stance which forms a continuous film or medium surrounding the particles. Each particle has thus a surface of contact with the substance forming the continuous medium. At that surface the dispersed particle is internal and the continuous substance external. In this colloid state, therefore, matter is in two forms or "phases" — (1) dispersed or internal, and (2) continuoxis or external. When the two substances are immiscible fluids the colloid complex forms an emulsion. In protoplasm, however, the condition is not simply a dispersion of one fluid in another immiscible fluid, since in it matter may exist in all degrees between the liquid and the solid condition. Protoplasm is termed an Emulsoid. The main points of difference between a solution and a colloid may be noted : — Solution. Colloid. Molecules small. Molecules very large or molecules aggregated into particles. Free movement of molecules of Dispersed particles separated by con- solute which possess kinetic tinuous phase. Little or no energy. movement, therefore little or no kinetic energy of particles. No surface phenomena. Large size of molecules introduces phenomena of surface tension and adsoi-ption between the dispersed and continuous phases. 650 APPENDICES While tliere is sucli a marked difference between a true solution and the colloid state, there is no clear line of demarcation between the two conditions. As the size of the molecules or agj]>regates of molecules of the dispersed phase of a colloid becomes smaller, the colloid comes to take on the character of a solution, so that the particles or molecules of the colloid show movement, and therefore kinetic energy. Substances that go into a true solution and pass through an animal membrane {see Osmosis) have been called crystalloids to distinguish them from colloids. There is, however, no fixed dividing line between crystalloids and colloids. Some colloids, e.g. htemoglobin, can be obtained in the crystalloid form. Ions. When salts are dissolved in water they become ''dissociated." Thus NaCl in a dilute solution becomes Na, carrying a positive charge of electricity usually indicated by the sign + or by a dot, e.g. Na+ or Na-, and CI carrying a negative charge usually indicated by a dash, e.g. Cl~ or Cr. Na does not exist as an atom of sodium nor CI as an atom of chlorine. Each is combined with a definite quantity of electricity. A monovalent atom or group of atoms carries one unit charge, a divalent two and so on. Thus, if a phosjihate be dissociated, the PO4 part, being trivalent, carries three unit charges and is written PO4'". In an ammonium salt the NH^ is monovalent. It carries one unit charge and is written NH4-. The atom or group of atoms thus dissociated and carrying a quantity of electricity is termed an Ion. It is the presence of ions that enables a salt solute to conduct electricity. Substances that become dissociated into ions when in solution are called Electrolytes, to distinguish them from substances such as sugar that are not dissociated when dissolved. Nearly all salts, acids, and bases are electrolytes. The Reaction of Watery Fluids. The Hydrogen Ion Concentration. Water between 22' and 23° C. is, to a slight extent, ionised. That is, some of the water molecules are dissociated into hydrogen and hydroxyl ions. According to the law of mass action, the ratio of the product ot the ions to the undissociated water is a constant. This may be written — IHWOHi^ ,,,„,^,,^, This constant has been found experimentally for the temperature of 23° C. to 1)6 — 100,000,000,000,0(10 or 10" APPENDICES 651 It has also been found that in pure water at this temperature there is an equal number of H an.i OH ions, i.e. [H] = [OH]. Therefore the concentration of hydrogen ions or Ch = J^10~'^* = 10~'^ and Coh = Ch =10~^ For short, the H ion concentration is often denoted by the logarithmic exponent, i.e. Ch of 10-'= pH of 7. It has been found that all substances which make a solution acid do so by mcreasiiig the number of H ions, e.g. HCi \ H,oJ n.o j H+ + ci- H+ + OH H + + HCO; H- \- OH NaH.PO^ ^ HoO J H+ + Na+ + HP04 H+ 1 + 0H~ and as [H] x [OHj is a constant, [OH] -.uust be correspondingly decreased. Similarly, alkalies and alkaline salts cause an increase in the number of free OH and a decrease in the free H ions. Any increase in the concentration of the H ions will be denoted by a decrease in the denominator of the fraction e.xpressing concentration. At the neutral point Therefore, if the pH is denoted by a figure less than 7 the solution is acid, if by a figure greater than 7 the solution is alkaline. A value lying between two whole numbers may be written in either of two ways. For example, water just slightly alkaline may have a concen- 0'5 tration of hydrogen ions of 1 in 20 million = ^^ ^^^ q^^ - This may be written as Ch = 0-5x10-7 or the fraction may all be put as a power of 10 = 10-7-3 or pH = 7-3. 652 APPENDICES To convert one system of notation to the other is a simple matter of logarithms. For example, to convert pH 7-6 to other notation— pH 7-6 =-10-7-6= 10-7x10-0-6 (the antilogarithm of -0-6 is 0-25) . •, =0-25 x 10-7. Conversely, Ch 5x 10-6 = log 5 + log 10-6. = 0-6990 + (-6-0000). = 5-3, cr 5 X 10-6 = 10-699 X 10-6 = 10-5-3 = pH 5-3. (The student will remember that in dealing with logs, multiplication is done by addition division by subtraction, and squaring by multiplication by 2, etc.) Se.mipkrmeable Membrane. A membrane is simply a thin film of substance. It may be composed of almost any material, and therefore may have all degrees of permeability. When a membrane allows water to pass through, but prevents the passage of a substance in solution in the water, it is said to be semipermeable to the solution. Thus water passes through a membrane of copper-ferro- cyanide, but cane sugar in solution is kept back, Copper-ferrocyanide is therefore said to be semipermeable to a solution of cane sugar in water. Osmosis and Dialysis, The passage of water through a semipermeable membrane is termed Osmosis. The passage of substance in solution through such a membrane is termed Dialysis. Osmotic Pressure. If a solution of a substance in water be placed in a bag which is semi- permeable to the solution, and the bag with its contents be immersed in pure water, the molecules of water will have free passage through the walls of the bag, but the molecules of the solute will be held back. No pressure will be exercised by the water, since it has free passage. The molecules of the solute, however, will impinge on the inside surface of the bag with a certain amount of force, which is not balanced by molecules of solute impinging on the outside. There will thus be a force exerted tending to distend the bag. This force is called Osmotic Pressure, It has been found that the osmotic pressure of a solution is the same as the pressure exerted by a gas having the same number of molecules per unit of volume as the solute. The solute thus behaves as if it were a gas and the solvent absent. As in the case of a gas, the pressure is proportional to the temperature and to the concentration. This is easily understood, APPENDICES 653 since the greater the concentration the more molecules hit the containing membrane, and the higher the temperature the greater the velocity, and consequently the greater the force -with wliich they impinge on the membrane. The osmotic pressure may be very high. A 10 per cent, solution of cane sugar has an osmotic pressure of over ten atmospheres. If a solution be separated by a semipermeable membrane from pure water or a less concentrated solution, water passes from the pure water to the solution or from the dilute to the more concentrated solution. Osmosis, there- fore, always occurs towards the more concentrated solution. On the other hand, if the molecules of the solute are free to pass through the membrane the passage is from the concentrated to the dilute solution, the tendency being to establish a uniform mixture (see Diffusion). Dialysis, therefore, always occurs towards the more dilute solution. Surface Tension. In the body of a fluid the molecules are equally attracted on all sides by other molecules, and the resultant is zero. At the surface, however, the attraction is one-sided — towards the liquid. The molecules are there- fore subjected to unbalanced forces, and the surface is consequently in a state of tension. It is this tension that makes a drop spherical. The same state of tension exists at the interface of two Huids. If the fluids are miscible a solution occurs and there is no interface. If, however, the fluids are immiscible an interface exists (see Colloids) and surface tension is present. In a colloidal state formed by two immiscible fluids, there is an enormous extent of surface (p. 13). Surface tension plays an extremely important jjart in many physiological processes. The surface tension at the interface between immiscible fluids or between a solid and a fluid is lowered by the presence of substances in solution. Adsorption. According to the second law of thermo-dynamic, any process that diminishes free energy always tends to take place. Surface tension is diminished by substances in solution. These, therefore, tend to concentrate at the interfaces where the tension exists. This depositing of a solute at a surface of contact is termed Adsorption. In the colloidal state where there is a great extent of .surface, adsorption is of great physiological importance. It facilitates chemical reaction between the substance composing the dispersed phase and those in solution in the continuous phase. Thermopile. In a circuit composed of two difterent metals, if one of the junctions of the metals be at a different temperature from the other junction, a current 654 APPENDICES of electricity is produced in the .circuit. The strength of the current is in proportion to the difference of temperature of the junctions, and it can be measured by means of a galvanometer. By increasing the number of junctions the strength of the current produced by changes of temperature is proportionally increased. In the figure, if the junctions B B be warmer tlian A A A, a current flows in the direction in- dicated and the needle is deflected, the degree of deflection being in proportion to the strength of the current. The thermopile thus converts a heat change which is difficult to measure directly by a thermo- meter, into an electrical change which can be detected and measured with great accuracy by means of a sensitive galvanometer. When the strength of the current is known, the amount of heat can be calculated, since for each thermopile there is a direct relationship between the degree of diff"erence of the tempera- ture uf the junctions and strength of the resulting current. Fio. o-ie. Diagram of Thermopile. ^■ = Iron. [131= German Silver. A, B = Junctions. G = Galvanometer. N = Needleof G. INDEX Abdomen, nerves of, 198 Abdominal breathing, 520 muscles of respiration, 520 Abducens nerve, 201 Aberration, spherical, 147 chromatic, 157 Abomasum, 294 Absorption, channels of, 348 from the stomach, 318 mode of, 348 of carbohydrates, 347 et seq. of fats, 347 of food, 347 of proteins, 347 Accessory factors, 281 Accommodation, far point, 147 near point, 146 positive, 146 range of, 149 Acetone, 358 Achroridextriii, 303 Acid sulphur in urine, 563 Acidosis, 481 Acids, divalent (see Appendix I.) organic (see Appendix) Acinus of gland, 34 Acromet,'aly, 600 Action of limbs of horse, 237 Addison's disease, 610 Adenin, 556 Adipose tissue, 42, 351 Adrenalin, 591 as vaso-constrictor, 591 action of, 591 Adsorption, 14 (see Appendix III.) ^rotonometer, 541 After-discharge in reflex arcs, 84 After-image, negative, 154 positive, 154 Agglutinins, 614 Air breathed, influence of respira- tion on, 537 complemental, 523 interchange by diffusion, 523 passages, structure of, 514 Air, residual, 523 reserve, 523 respired, amount of, 522 tidal, 522 vesicles in the lungs, 514 Alanin, 17 Albumin (see Apjjendix II.) „ nucleo (see Appendix II.) Alcapton, 555 Alcohols, chemistry of (see Appen- dix I.) Aldehydes (see Appendix I.) Aldoses (see Appendix I.) Alexine, 613 Alimentary canal, 291 et seq. bacterial acticm in, 329 nerve supply of, 300 structure, 291 Alkaline reserve, 481 Alkalosis, 531 Allantoic arteries, 627 Allantoin, 561 Allantois, 628 Amble, 241 Amboceptor. 613 Amides, 17 (see Appendix I.) Amines, 330 (see Appendix 1.) Amino-acetic acid (see Appendix I.) Amitotic division, 30 Ammonio-magnesium phospha te, 559 Ammonium carbonate, 554 Ammonium salts in urine, 559 Amniotic fluid, 625 sac, 625 Amoeboid movement, 24, 484 Amount of respired air, 522 Amylolytic period of gastric diges- tion, 311 Anabolism, 9 Anacrotic pulse, 442 Anal canal, 296 Analysis of alveolar air, 540 Anelectrotonus, 63 Anhydrides (see Appendix I.) 656 INDEX Animal products as food, 290 Antipepsiii, 313 Antiperistalsis, 335, 345 Antithi'Oinbin, 477 Antitoxin, 612 Aortic area, 407 valve, 392 ApncBa, 531 Apocodeine and suprarenal extract, 592 Aqueous humour, 140 Arc, cerebellar, 95 cerebral, 95 spinal, 82 Areolar tissue, 40 Arginin, 17, 555 Armsby's standard, 378 Arterial pressure, 449 pulse, cause of, 435 Arteries, 431 factors controlling pressure, 435 pressure in, 434 Arterioles, nervous mechanism, 454 normal state of, 453 Artificial respiration, 549 Arytenoid cartilages, 550 Ash of food, 288 Asparagine, 284 Asphyxia, 548 Astigmatism, 151 Atmospheric pressure on respira- tion, 543 Auditory centre, 173 Auerbach's plexus, 30 1 Augmentor nerve of heart, 421 Auricle, 386 Auricular flutter, 429 Auriculo-ventricular rings, 385 nodes, 385 valves, 390 Availability of food-stuffs, 363 Axon, 56 reflex, 93 Bacterial action in the alimentarv canal, 329 Balance sheet experiments, 369 Barotaxis, 25 Basal ganglion, 189 metabolism, 264 Bases of the urine, 565 Basilar membrane, 170 Basophil leucocytes, 484 Bell's paralysis, 201 Benzene compounds (see Appendix) Benzoates, 562 Bi-amide of carbonic acid {see Urea) Bidder's ganglion, 389 Bile, 323 et seq. flow of, 326 flow, influence of nerves on, 326 functions of, 327 mode of secretion, 327 pigments, 324 salts of, 323 Bilirubin, 324. 491 Biliverdin, 324 Binocular vision, 158 Birth, young at, 631 Biuret (see Appendix I.) Bladder, reflex, 93 urinary, 581 Blastoderni, 624 Blind spot, 151 Blood, 474 et seq. amount of, 501 carbon dioxide, 495 cells, 483 changes in respiration, 538 clotting, 475 constituents, fate of, 503 source of, 498 corpuscles, 483 deftbrinated, 476 distribution, 503 erythrocytes, 485 flow of, 464 velocity of, 465 flow through heart, 404, 411 flow through different organs, 473 gases of, 492 general characters, 474 influence of respiration on, 538 inorganic constituents, 480 laked, 474 leucocytes, 483 mean pressure, 447 methods of recording, 447 opacity of, 474 plasma, 479 platelets, 484 pressure, 432 diastolic (see Diastolic pressure) general distribution, 432 rhythmic variations, 434 serum, 479 sodium bicarbonate, 481 specific gravity, 474 Bodv, connections with brain stem, 112 INDEX 657 Body receptors, 97 Bone, 45 et seq. chemistry of, 49 development, 45 et seq. diaphysif? of, 49 epiphysis of, 49 Haversian system of, 48 marrow, 500 metabolism of, 50 ossification, centre of, 45 osteoblasts, 46 osteoclasts, 46 Bowman's capsule, 571 Bradycardia, 429 Brain (see Cerebrum, etc.) Breath sounds, 524 Breathing shallow, 530 Bronchial muscle, 515 sound, 524 Bronchioles, 515 Brunner's glands, 295 Bundle of His, 385 Cachexia strumipriva, 597 Ctecum, 296, 344 Caffeine, 578 Calcium in clotting, 477 in food, 289 Calories, definition of, 248 Calorimeter, 256 bomb, 256 respiratory, 259 Calorimetry, direct, 259 indirect, 260 Canaliculi, 46 Canals, semi-circular, 117 Cancellous tissue, 46 Cane sugar, 286 Canter, 242 Capillaries, 431 pulse in, 444 pressure in, 460 Carbohydrates, 20, 285 absorption of, 347, 350 determination of amount oxi- dised, 258 in foods, 288 storage of, 352 tolerance, 355 Carbon dioxide in blood, 481, 495 haemoglobin, 490 in the urine, 566 passage from tissues to blood, 546 Carboxyhsemoglobin, 489 Cardiac contraction, nature of, 427 42 Cardiac nerves, function of, 418 propagation of, wave, 427 starting mechanism, 424 cycle, 393, 401 impulse, 398 muscle, 205 branches of the vagus, 418 Cardiac rhythm, control, 424 Cardiogram, 398 Cardiograph, 398 Cardio-pneumatic movements, 536 Cartilage, 43 elastic fibro-, 45 hyaline, 43 white fibro-, 45 Cartilages of the larnyx, 550 Casein, 636 Castration, effect of, on thymus, 603 effect of, on body, 606 Catalytic action, 8 Catelectrotonus, 63 Cathode, 63 Cells, 23 et seq. activity of, 24 chalice, 34 nucleus, 26 oxyntic, 310 peptic, 311 reproduction of, 28 Cellulose in food, 287 Centre, auditory, 173 for dilator pupillas, 148 for smell, 136 for sphincter pupillse, 148 oculo-motor, 161 of ossification, 45 respiratory, 526 taste, 132 ' thermal sense, 116 touch, 116 vaso-constrictor, 457 vaso-dilator, 460 visual, 164 Centrosome, 23 Cerebellar arc, 95 synapses, 117 Cerebellum, structure, 125 celk of Purkinje, 125 connections of, 126 functions of, 127 removal, 128 stimulation, 129 Cerebral action, time of, 186 Cerebral arc, 95 cortex {see Cortex cerebri) 658 INDEX Cerebral arc, discharging side, 189 mechanism, fatigue of, 186 time of action, 186 Cerebrosides, 58 Cerebro-spinal fluid, 511 Cerebrum development, 181 discharging mechanism of, 189 evolution, 181 fatigue, 186 localisation of functions, 1 76 removal of, 127 storing mechanism, 185 Chalice cells, 34 Check ligaments, 237 Chemical regulation of growth and function, 588 et seq. Cheniiotaxis, 25 Cheyne-Stokes respiration, 531 Chlorine-containing bodies in urine, 565 Cholalic acid, 323 Cholesterol, 19, 58, 325 Cholin, 20 Chondro-mucoid, 44 Chondroitin, 44 Chondroitin-sulphuric acid, 44 Chordae tendinese, 388 Chorda tympani nerve, 304 Chorionic villi, 626 Choroid, 139 Choroid plexus, 511 Chromaffin tissue, 590 Chromatic aberration, 157 Chromatin, 27 Chromo-proteins {see Appendix II.) Chromosomes, 617 Chyle, 508 Chyme, 319 Cilia, 37 Ciliary muscle, f39, 147 processes, 139 Ciliated epithelium, 37 Circulation, tlie, 382 et seq. factors, extra-cardiac, in, 470 fcetal, 631 " head down and up position," 471 in bone-marrow, 470 in cranium, 468 influence on respiration, 536 in heart wall, 469 in kidney, f)72 in lungs, 468 in spleen, 469 in vessels, 431 schema of, 383 Circulation, time taken by, 472 Classification of food-sturt's for herbivora, 290 Coagulation of the blood, 475 Cochlea, 170 connections with central ner- vous Hvstem, 172 Coefficient of oxidation, 254 Cold spots, 104 Collagen, 39 Collecting tubules of kidney, 572 Colloids, 12 Colon, 296 Colostrum, 637 Colour-blindness, 157 Columnse carnese, 387 Columnar epithelium, 33 Common path, 86 Complemental air, 523 pleura,' 518 Concentrates, 290 " Conditioned '■' reflexes, 131 Conducting paths {see Spinal cord, etc.) Conduction of nerve impulse, 69 Cones of I'etina {see Retina) Connective tissues, 37 Consciousness, 185 relations to cerebral action, 185 Contraction of muscle, changes during, 219 Convoluted tubules of the kidney, 572 Cooking, effects of, on food, 366 Co-operative antagonism of groups of muscles, 231 Coprosterol, 332 Cord, spinal {see Spinal cord) Cornea, 139 Corona radiata {see Cerebrum) Coronary arteries, 406 Corpus Arantii {see Valves of heart) Highmori, 620 luteum, 608 striatum, 189 trapezoideum, 172 Corpuscles, blood, 483 et seq. of Hassall, 602 tactile, 102 Cortex cerebri, synapses, 115 discharging area, 189 receiving areas (how localised), 176 fibres, 194 functional development, 182 storing and associating part, 185 INDEX 659 Cortex cerebri, structural develop- ment, 181 Corti, organ of, 171 Coughing, 522 Cranial nerves, 200 nuclei of, 200 Creatin, 209, 560 Creatinin, 560 Cricoid cartilage, 550 Critical temperature, 271 Crossed pyramidal tract, 194 Crude fat, 285 fibre, 288 Crystalline lens, 141 Crystalloids, 20 Curare experiment, 217 Current of action, 213 injury, 212 Cutaneous nerves, influence on re- spiration, 534 receptors, 99 Cystin, 32, 564 Cytase, 339 Cytotoxins, 614 Dairy cows, food requirement, 375 Death, 10 of muscle, 214 Decerebration rigidity, 113 Decidua reflexa, 625 Deftecation, 335 Degeneration, Nissl's, 77 Deiters' nucleus, 126 Delivery, 633 Dendrites, 53, 56 axon of, 56 Dentate nucleus of the cerebellum, 125 )r nerve {see Cardiac branches of vagus) Deutero-proteose, 312 {see Appendix II.) Development, 624 Dextrose, 286 Diabetes {see Glycosuria), 357 Diacetic acid, 358 Di-amino acids, 17 Diapedesis, 468 Diaphragm, 517 Diaphysis, 49 Diastase, 320 Diastole of heart, 394 Diastolic pressure, 449 Dicrotic notch, 441 wave, 440 Diets, influence of various, on gastric secretion, 313 Diffusion of gases in lungs, 523 Digestibility of food, 364 apparent, 364 Digestion, 291 et seq. experiments, 364 fate of the secretions of, 331 gastric, 308 in carnivora, 302 in herbivora, 336 in horse, 341 in mouth, 302 in ruminants, 337 intestinal, 319 of stomach wall, 313 Digital torus, 233 Dilator, pupillje, 140 Dioptric mechanism, 144 imperfections, 149 Diphtheria bacillus, 612 toxin, 612 Diploe of bone {see Bone) Diplopia, 162 Disaccharids, 286 Disc, optic, 141 Dissociation of oxy-hiiemoglobin, 494 Diureides {see Appendix I.) Divalent acids {see Appendix I.) Dobie's line, 204 Douglas bag, 261 Dropsy, 462 Ductus arteriosus, 633 venosus, 631 Dynamometer, 225 Ear, anatomy of, 167 annular ligament, 168 cochlea, connections with central nervous system, 173 external, 167 internal, 170 middle, 167 osseous labyrinth, 170 ossicles of, 167 Eck's fistula, 360 Effectors (see Muscle), 202 Efferent nerves, 195 Elastic-fibro cartilage, 45 Elastin, 39 Electrical changes in muscle, 212 Electricity induced, action on muscle, 219 Electrocardiogram, 428 Electrotonus, 63 660 INDEX Eleventh nerve (see Spinal accessory) Embryo, attachment to mother, 626 Emmetropic eye, 146 Empedocles, 1 Emulsion, 13 (Appendix III.) Endocardium, 390 Endocrinetes, 588 et seq. classification, 589 interaction, 611 Endogenous purins, 561 Endolymph (see Ear) Endothelium, 40 Energy requirements, 264 et seq. factors modifying, 266 Energy value of carbohydrates, 257 determination of, 356 fats, 257 proteins, 257 Enteric fever, toxin of, 613 Entero-hEsemal circulation, 331 Entero-hepatic circulation, 331 Enterokinase, 321 Enzymes, 7 Eosinophils, 483 Epiblast, 624 parts developed from, 624 Epiglottis, 307, 550 Epiphysis, 49 Epithelium, ciliated, 37 columnar, 33 excreting, 36 glandular, 34 mucin-secreting, 34 secreting, 34 simple squamous, 32 stratified squamous, 32 transitional, 33 zymin-secreting, 36 Equilibrium of body, 130 Erection, 623 Erepsin, 328 Erythroblasts, 501 Erythrocytes, 500, 505 Erythro-dextrin, 303 Esters {see Appendix I.) Ethane (see Appendix I.) Ethereal sulphates in urine, 563 Ether extract, 285 Ethers (see Appendix I.) Ethylene (see Appendix I.) Euglobulin (see Blood serum), 480 Eustachian tube, 167, 169 Excito-motor nerves, 74 reflex nerves, 74 secretory nerves. 74 Excreting epithelium, 36 Excretion, by the lungs (see Respira- tion) by the skin, 583 by the intestine, 363 Exogenous purins, 561 Exophthalmic goitre, 598 Expiration, 521' Expiration, forced, 521 Expired air, 537 Extensor thrust, crossed, 85 Exteroceptive receptors, 96 Eye, 139 et seq. anatomy of, 139 astigmatic, 151 blind spot, 151 connection with central nerv- ous system, 162 dark adapted, 153 emmetropic, 146 fluids of, 140, 143 hyaloid membrane of, 140 hypermetropic, 149 myopic, 150 physiology, 143 presbyopic, 149 Eyeballs, glance movements of, 160 movements of, 159 muscles of, 159 nervous mechanism of, 161 Facial nerve, 201 Faeces, 361 composition of, 363 Fainting, 472 Fallopian tube, 621 Faraday-Tyndall phenomenon, 13 Faradic stimulation, 67 Far point of accommodation, 147 Fascia, 40 dentata, 135 Fasting, metabolism during, 272 rate of waste during, 273 Fat cells, 41 in foods, 285 storage of surplus, 351 soluble A, 281 Fat-splitting enzyme of pancreas (see Lipase) Fate of food absorbed, 350 Fatigue of cerebral mechanism, 186 nerve, 69 of muscle, 225 Fats, 19, 41, 285 absorption of, 347, 350 determination of amount oxi- dised, 258 INDEX 661 Fats, energy value of, 257 regulation of supply, 358 Fattening, 373 Fatty acids, 29 lower, 359 tissue, 351 Feeding, standards, 375 Fenestra ovalis, 167 rotunda, 167 Fermentation in rumen, 340 losses, 365 Fetlock joint, 237 Fibres, elastic, 39 nerve, 56 non-medullated nerve, 56 splanchnic, 54 somatic, 54 white, 39 Fibrillar twitching, 220 Fibrillation of heart, 430 Fibrin, 476 Fibrinogen, 477, 480 Fibroblasts, 38 Fibro-cartilage, elastic, 45 white, 45 Fibrous tissue, 38 Field of vision, 152, 158 Fifth cranial nerve, 201 Filiform papillae {see Tongue) Flocculus of cerebellum, 125 Flow of blood, 464 to heart, 404 Fluids, swallowing of, 308 Fodder, green, 290 dry, 290 Fcetal circulation, 631 Fcetus, growth of, 630 nourishment of, 628 Food, 283 et seq. absorption of, 347 absorbed, fate of, 350 availability of, 363 effect of, on metabolism, 272 not yielding energy, 288 requirements, 368 et seq. methods of determining 369 for fattening, 373 for growth, 371 for maintenance, 371 for milk production, 374 for meat production, 374 for work, 375 residues, 363 storage of surplus, 351 yielding energy, 283 Food stuffs, classification of, for herbivora, 290 Foot, horse's, 233 ft seq. Foramen ovale, 632 occlusion of, 633 Formamide {see Apj^endix I.) Formic acid {see Appendix I.) Fourth cranial nerve, 201 Fovea centralis {see Retina) Frauenhofer's lines, 487 Frog of horse's foot, 233 Frog's heart, 393 Galactose, 286 Galactosides, 58 Galen, 1 Gall-bladder, 323 Gallop, 241 Galvanic current, stimulation by, 62 Galvanometer, 212 string, 214 Galvanotaxis, 26 Ganglia, nicotine on, 198 terminal, 55 Gas pump, 496 Gases of the blood, 492 Gastero-colic reflex, 335 Gastric digestion, amylolvtic period, 311 proteolytic period, 311 Gastric glands, 295 Gastric juice, 310 action on gelatin, 312 action on proteins, 311 antiseptic action, 313 influence of diet on, 313 nervous mechanism of, 314 source of constituents, 310 Gastric movement, nervous mechan- ism of, 317 Gelatin, 39 action of trypsin on, 320 value as a food, 276 Gels, 13 Gemmules, 56 Generative organs {see Gonads) Gennari, layer of, 164 Gestation, 633 Giant cells, 501 Giantism, 600 Gills of aquatic animals, 513 Glance movements of eyeballs. 160 Glands, 34 Glaucoma, 143 Gliadins, 284 Globin, 490 662 INDEX Globulin (see Appendix II.) Glomerulus of kidney, 572 Glossopharyngeal nerve, 201, 305 Glucosamine, 35 Glucose, 288 Glutamine, 281 Glutelins, 284 Glycaemia, 355 Glycerol, 41 (Appendix I.) Glycero-phosphates in urine, 565 Glycin, 16 Glycocholate of soda, 323 Glycocholic acid, 323 Glycogen, 287 Glyocogenic function of the liver, 354 Glyco-proteins (see Appendix II.) Glycosuria, 355 alimentary, 355 experimental, 356, 357 Glycuronic acid, 44 Glycyl-glycin, 19 Gmelin's test, 324 Goitre, exophthalmic, 598 Goitre, simple, 599 Golgi, organs of, 105 Gonads, 605 Graafian follicle, 619 Granules, in cells, 23 Nissl's, 86 Grass, 290 Graves' disease, 598 Gravity, influence on capillary pres- "'sure, 463 Grey matter (see Cerebrum, etc.) Grooming, 585 Growth, essentials for, 6 rations for, 371 regulation of, 586 Guanidin, 209, 555 methyl guanidin, 605 HyEMATIN, 490 Hsematoidin, 491 Hivmatoporphyrin, 491, 566 Hsemautograph, 44(t Hfemin, 491 Hasmocytometer, 485 Haemoglobin, 486 decomposition of, 589 derivatives, 489 Htemoglobinometer, Haldane's, 488 Hteinolymph glands, 500 Hemolysin, 486 Hceniolysis, 21, 486 organs connected with, 504 Hemosiderin, 504 Hair, 583 Haller, 2 Harvey, 2 Hassall, corpuscles of (see Thymus) Haversian canals, spaces, etc., 48 Hay, 290 " Head down position,'' effect on blood pressure, 471 Hearing, 166 Heart action, influence on blood pressure, 451 attachments and relations, 393 auriculo-ventricular node, 385 band of His, 385 block, 429 changes in shape, 397 in i^osition, 399 in pressure, 399 chordae tendineje, 388 columnaj carnese, 387 compensation, 417 connection with central nerv- ous system, 418 endocardium, 390 failure, 462 fibrillation, 430 fibrous rings of, 385 hypertrophj', 417 influence of nerves upon, 418 intra-cardiac nervous mechan- ism, 388 intra-cardiac pressure, 399 muscle, 205 nerves of, 388, 418 neurons, 388 impillary muscle, 387 pericardium, 389 physiology of. 393 et seq. pulmonic, 383 relations of, 393 sino-auricular node, 385 sounds of, 407 structure, 384 sympathetic fibres to, 421 tone, 428 valves (see Valves) work of, 410 Heat elimination, 267, 271 elimination from respiratory passages, 268 elimination in urine and faeces, 268 production, 268 INDEX Heat production in glands, 268 in muscle, 268 regulation of, 269 chemical, 269 physical, 269 units (see Calories) Hemispheres, cereljral (see Cere- brum) Henle's loop, 572 sheath, 57 Hepatic vein, 299 Herbivora, digestion in, 336 Hereditary inertia, 586 Herpes zoster, 91 Hexoses, 28 Hiccough, 522 High tension pulse, 443 Highmori, corpus (see Corpus High- mori) Hippocampus, 135 Hippocrates, 1 Hippuric acid, 562 Hirudin, action on blood, 478 His, bundle of (see Bundle of His) Histamine, 451 Histidin, 17, 555 Histones (see Appendix II.) Holoblastic segmentation, 624 Homogentisic acid, 555 Hoof, horse's, 234 et seq. Hormones, 588 Horse, action of limbs, 237 et seq. amble, 241 caecum, 297, 344 canter, 242 capacity for work, 252 colon, 298, 344 diet, maintenance, 371 for work, 375 digestion, 341 efficiency as machine, 252 foot, 237 gallop, 241 grooming, 585 jump, 242 legs, conformation of, 235 lying, 239 mastication, 293 overwork, 253 rising, 239 standing, 237 stomach, 295 sweat, 585 sweating, 267 teeth, 292 trot, 240 Horse, vomiting, 346 walk, 239 watering, 367 work, 375 Hot spots, 104 Humour, aqueous, 140 vitreous, 140 Hunger, 99 contraction, 309 Hyaline cartilage, 43 Hyaloid membrane, 140 Hydrocarbons, unsaturated (-see Appendix I.) saturated (see Appendix I.) Hydrogen ion concentration (see Appendix III.) Hydroquinon, 555 Hydrosols, 15 Hydroxyl molecule (-^ee Appen- dix III.) Hypermetropia, 149 Hyperpncea, 528, 531 Hyperthyreoidism, 598 Hypnosis, 188 Hypnotic drugs, 187 Hypoblast, 625 parts developed from, 625 Hypoglossal nerve, 200 Hypophysin, 595 Hypophysis cerebri, 594 Hypothyreoidism, 597 Hypoxanthin, 556 Ileo-c^cal valve, 296, 334 Impregnation, 623 Impulse, nature of nervous, 74 Incompetence (cardiac), 410 Incus, 167 Indican, 563 Indol, 329 Indoxy], 563 Induced electricity, stimulation, 62 Inferior oblique muscle, 159 Infundibula, pulmonary, 514 Infundibular passages, 514 Inhibitory action of vagus, 420 Inorganic salts in food, 288 Inosite, 209 Insalivation, 302 Inspiration, 516 forced, 520 Interchange of air in lungs, 537 Intercostal muscles in respiration, 519 external intercostals, 519 internal intercostals, 521 664 INDEX Intermittent muscular exercise, 470 Internal respiration, 547 secretions, mode of action, 611 Interoceptive receptors, 96 Interrenal tissue, 609 Intestinal wall, enzymes of, 328 mechanism of secretion, 328 Intestine, 295 absorption from, 348 capacity, 301 digestion in, 319 ef seq. large, 296 length, 301 movements of, 332 secretion, 328 Intracardiac pressure, 399 Inverted image rectified, 166 lodothyreoglobulin, 596 lodothvrin, 596 Iris, 140 Islets of Langerhans, 300, 601 Isometric contraction, 225 Isotonic contraction, 225 Jacksonian epilepsy, 191 Jacobson's nerve, 305 Karyoplasm, 27 Karyosomes, 27 Kellner's standards, 376 Keratin, 32 Ketones (see Appendix I.) Kidney, 571 et seq. influence of nervous system, 580 nerves of, 572 regulation of ions, 556 structure, 571 Kilogram-metre, 242 Kinsesthetic sense {see Muscle-joint sense) Knee-jerks, 89 Labyrinth, osseous, 117, 170 connections with central nerv- ous system, 119 physiology, 121 Labyrintho-cerebellar mechanism, 117 physiology, 121 Lactase, 328 Lactation. 634 Lactose, 286 Lacuna, 46 Lsevulose, 286 Lamellae (see Bone) Laminitis, 253 Langerhans, islets of, 300, 601 Lanolins, 585 Large intestine, 296, 334 Laryngoscope, 552 Larynx, cartilages of, 550 centre, 552 ligaments of, 550 mucous membrane of, 551 muscles of, 551 nervous mechanism of, 552 position in deglutition, 307 structure of, 550 Latent period of muscle, 216 time of reflex action, 83 Lateral fillet, 172 Lecithin, 19 Leg, horse's conformation of, 235 Lens, capsule, 141 crystalline, 141 physiological, 145 Lenticular nucleus (see Cerebrum) Leucin, 17 Leucoblasts, 500 Leucocytes, 483 fate of, 503 phagocytic action, 484 source of, 499 Leucocytosis digestion, 348 Leuwenhoek, 2 Levers, 231 Leydig's cells, 606 Lieberkiihn's follicles, 295 Life, 5 Ligaments, 40 Linin network, 27 Lipase, 321, 328 Lipoids, 19 Liquor folliculi, 619 sanguinis, 474 Live weight test, 369 Liver, 299 circulation in, 353 development of, 353 formation of urea in, 359 glycogenic function, 353 regulator of sujjply to muscles, 353 relation to fats, 358 relation to general metabolism, 353 et seq. relation to proteins, 359 storage of carbohydrates, 354 Living matter, essentials of, 5 Lobus pyriformis (see Smell) Loudness of sounds, 553 INDEX 665 Lungs, 514 circulation in, 468 interchange between air and blood in, 537 physiology of, 515 et seq. Lymph, 507 formation of, 508 in disease, 508 Lymphatic glands, 499 Lymphatics, pressure in, 464 Lymphocytes, 483 Lysin, 17, 278 Macula lutea {see Retina) Maize as food, 276 Malleus, 167 Malpighi, 2 Malpighian bodies of kidney, 573 corpuscles of spleen, 504 Maltose, 286 Mammary glands, 609 Manometer, papers, 400 Manurial values, 380 Marchi's method of nerve-staining, 76 Marey's muscle forceps, 225 Mariotte's experiment, 151 Mastication, 302, 337 in horse, 293, 342 in ruminant, 337 Maternal attachment of ovum {see Placenta) Meat production, 374 Meconium, 363 Medulla of kidney {see Kidney) Medullary sheath {see Nerve) Meeh's formula, 265 Megaloblasts, 500 Meissner's plexus {see Intestine) Melanin, 43 Melanoidins, 43 Membrana nictitans, 140 reticularis, 172 tectoiia, 172 tympani, 167, 169 Membranous labyrinth, 118, 171 Memory, 180 Mesoblast, 625 parts developed from, 625 Metabolism, basal, 264 during fasting, 272 effect of food on, 272 factors modifying, 266 general, 264 method of investigating, 257 of fats and carbohydrates, 257 Metabolism of protoplasm, 9 protein, 257 regulation of, 586 semi-starvation in, 274 Metaphosphoric acid, 28 Meth^emoglobin, 489 Methane (see Appendix L) Methyl-guanidin, 209, 605 Micro-organisms in rumen, 339 in intestine, 329 Micturition, 581 Milk, 635 composition of, 637 enzyme causing curdling, 310 fats, 636 proteins of, 636 production, 374 secretion of, 635 sugar of, 637 Mitotic division, 29 Mitral area, 408 valve, 390 Molecular layers of retina (see Retina) Mon-amino acids {see Appendix I.) Monaster stage of cell division, 30 Monocular vision, 144 Monosaccharids, 286 Motor areas, 191 nerves {see Nerves) Mountain sickness, 543 Mouth, 291 Mucin, 35 secreting epithelium, 34 Mucoid tissue, 37 Mucus, 35 Midler, 2 Murmurs, cardiac, 409 simulation of, by breath sounds, 537 Muscarin, 20 Muscle, 202 et seq. absolute force of, 224 action, mode of, 231 carbohydrates of, 208 cardiac, 205 changes in shape, 219 chemical changes in, 254 chemistry of, 207 ciliary, 147 colour of, 210 contraction, 222 contracture, 226 corpuscles, 204 course of contraction, 222 death of, 214 666 INDEX Muscle, deaeneration of, 66 development, 202 direct stimulation, 217 Dobie's line, 204 efficiency, 248, 250 elasticity, 210 electrical changes in, 212 electrical condition of, 212 electrotonus, 63 extent of contraction, 223 factors modifying contraction, 225 fatigue, 226 force of contraction, 223 forceps, Marey's, 225 galvanotonus, 62 heart, 205 heat production in, 212, 246 in action, 215 isometric tracings, 225 isotonic tracings, 225 latent period of contraction, 223 lever arrangement of, 231 metabolism. 254 mode of action, 231 optimum load, 244 oxidation, 254 material oxidised, 255 mode of, 256 paradoxical contraction, 72 physical characters of, 210 physiology of, 210 pofar exciWion of, 62, 67, 219 proteins of, 207 red, 205 sarcolemma of, 204 sarcous substance, 204 skeletal, 217 spindles, 105 stapedius, 167, 169 stimulation bv galvanic current, 219 stimulation by induced elec- tricity, 219 " stimulation, direct, 217 stimulation, methods of, 218 stimulation temperature, 219 storage of food in, 352 structure of, 202 successive stimuli, 228 tension developed, 224, 242, 248 tensor tympani, 167, 169 tetanus of, 229, 230 tonus of, 211 visceral, 203, 215 Muscle, voluntary contraction, 230 white, 205 work, 242 work measurement, 245 work production, relationship to heat production, 246, 248 Muscles, and joint sense, 105 co-operative antagonism of, 231 of eyeball, 159 of larynx, 551 Muscular sense, 105 work, effect on metabolism, 266 work, effect on respiratory in- terchange, 258 et seq. Myelocytes, 484, 501 Myenteric plexus, 94 Myocardium, 384 Myoglobulin, 208 Myohsematin, 210 Myoids, 202 Myopia, 150 Myosin, 207 Myosinogen, 207 Myostromin, 208 Myxcedema, 596, 597 Native proteins (see Appendix II.) Near point of accommodation, 1 46 Necrobiosis, 10, 214 Neopallium, 181 Nephridium, 570 Nerve, 58 automatic action of, 75 cells, 75 centres {see Centres) changes in disease and injury in, 66 chemistry of, 57 conduction, 76 corpuscles, 56 degeneration of, 67 development, 53 electrical changes in, 60 excitability, variations in. 68 exposed, stimulation of, 62 fibres, 56 fibres, medullary sheaths of, 56 fibres, non-medullated, 56 grey, 56 impulse, nature of, 74 stimulous, relationshijj of, 68 structure of, 55 under skin, stimulation of, 64 Nerves, afferent, 74 anterior roots, 107 auditory, 172 INDEX 667 Nerves, augmentor, 73 cranial, 200 degeneration of, 76 etterent, 73, 195 excite- motor, 74 excito-reflex, 74 excito-secretory, 74 excito-vaso dilator, 74 factors modifying conduction in, 71 ingoing, 106 inhibitory, 73 mixed, 74 motor, 73 nature of impulse in, 74 optic, 162 posterior root, 107 rate of conduction in, 70 regeneration of, 76 secretory, 73 sensory, 74 somatic, 54 splanchnic, 54, 196 thoracico-abdominal, 197 vagus, 200 vaso-constrictor, 456 vaso-dilator, 458 visceral, 195 Nervous mechanism, intra-cardiac, 388 extra-cardiac, 418 gastric movement, 318 regulation of metabolism, 587 system, 53 development of, 53 structure of, 55 Neural arcs, 78 et seq. cerebellar, 81 cerebral, 80 general action of, 80 spinal, 78 Neurilemma, 56 Neuroblast, 53 Neuro-keratin, 57 Neuromyal junction, 205 Neurons"^ of heart, 388 Neurons, 53 axon of, 56 cell of, 55 cell, Nissl granules in, 55 classification of, 73 conduction in, 69 degeneration of, 77 dendrites of, 56 excitation of, 60 function of cell, 76 Neurons, gemmules of, 56 in series, 77 manifestations of activity, 59 means of stimulating, 61 nature of impulse, 74 neuro-myal junction, 205 nutrition of, 76 physiology, 58 regeneration of, 77 stimulation of, 61 et seq. structure, 55 synapsis, 54 Neutral sulphur in urine, 564 Nicotine, effect of painting ganglia, 198 Ninth nerve, 201 Nissl's degeneration, 77 granules, 55 Nitric oxide, 489 Nitrogen in the urine, 559 free extract, 288 non-protein, 284 Noci-ceptive receptors {see Pain) Nocuous stimuli, 100 Nodes of Eanvier, 57 Non-medullated nerve fibres, 56 Non-polarisable electrodes (see Elec- trodes) Normoblasts, 501 Nuclei of the cranial nerves, 200 _ Nucleic acid {see Appendix I.), 27 Nucleins (see Appendix I.), 27 Nucleolus, 27 Nucleo-proteins {see Appendix II.), 556 action of gastric juice on, 312 action of trypsin on, 320 of urine, 566 Nucleus, 26 et seq. accessorius, 172 chemistry of, 27 division of, 28 functions of, 28 membrane of, 28 of Deiters', 126 structure of, 26 Nutritive ratio, 368 Oats, 366 Oblique muscles of eye, 1 59 Oculomotor nerve, 161, 201 Esophageal groove, 295 CEsophagus, 293 peristaltic action of, 308 (Estrous cycle, 622 Oleic acid, 42 668 INDEX Olein, 42 Olfactory area, 134 bulb and tracts, 134 tubercle, 134 Omasum, 294 Oncometer, 452, 573 Oocytes, 619 Ophthalmoscope, 142 Opsonins, 615 Optic axis, 159 chiasma, 162 disc, 141 fibres, decussation of, 162 nerve, 162 thalamus, 112, 162 tracts, 162 Optimum stimulus, 227 Ora serrata, 142 Organ of Corti, 171 Organic acids as salts in food, 340 Organs of Golgi, 105 Osmosis, 21 (see Appendix III.) Osseous labyrinth, 170 Ossicles of ear, 167 Ossification, process of, 45 centre of, 45 Osteoblasts, 46 Osteoclasts, 46 Osteomalacia, 50 Otoliths, 118 Ovary, 607, 619 Ovum, 616, 618 Oxalates on blood, 477 Oxalic acid in urine, 566 Oxidation coefficient, 254 Oxy-acids (see Appendix I.) Oxybutyric acid, 358 Oxygen, head of, 545 in blood, 492 Oxyhsemoglobin, 487 Oxyntic cells, 310 Oxyphil leucocytes, 483 Pacemaker of heart, 430 Pacinian corpuscle, 97 Pain, 100 referred, 98 sensation of, 100 spots, 100 Palmitic acid, 42 Palmitin, 42 Palpation of pulse, 442 Pancreas, 300, 601 islets of Langerhans {see Lan- gerhans) removal of, 357, 601 Pancreatic secretion, 319 action of, 320 character of, 320 enzymes of, 320 nervous, control of, 322 physiology of, 321 Papillary muscles, 387 Paradoxical contraction, 72 Paralysis, 191 crossed, 194 Paramyosinogen, 208 Parathyreoid, 603 Parotid gland, 305 Parthenogenesis, 616 Partial pressure of oxygen and car- bon dioxide in blood, 541 pressure of gases in air vesicle, 539 Passage of carbon dioxide from tissues to blood, 546 of oxygen from blood to tissues, 545 Peas as food, 290 Pectinate muscle, 386 Peduncles of cerebrum (see Cerebrum) Pelvis, nerves of, 198 Penis, 621 erection, 623 Pentosans, 287 Pepsin, 310 source of, 310 Pepsinogen, 311 Peptides, di-, tri-, 19 Peptone (see Appendix II.) Perfusion method of studying action of drugs, 453 Pericardium, 389 Perichondrium, 46 Perilymph, 170 Perineurium, 57 Peripheral resistance, 451 Peristalsis, 333 nervous mechanism of, 333 of bladder wall, 581 of intestine, 333 et seq. of wall of ureter, 581 Peyer's jaatches, 296 Pfliiger's law, 72 Phacoscope, 147 Phagocyte action, 484 Pharvnx, 307 Phenol, 330, 563 Phloridzin, injection of, 357 Phosphatides, 19, 58 Phospho-protein (see Appendix II.) Phosphorus in food, 289 INDEX 669 PhosphoriTs-containing bodies in the urine, 565 Phototaxis, 26 Phrenic nerves, 527 Physiology, growth of, 1 study of, 3 Pigment, blood {see Hsemoglobiii) cells, 43 Pigments of the bile, 324 of the urine, 566 Pitch of sounds, 174, 553 Pituitary, 599 Placenta, 628 Plantar cushion, 233 Plasma, 479 Plasmodia, 11 Plasmolysis, 21 Platelets, blood, 484 Plethysmograph, 452 Pleura, complemental, 518 Pleural cavity, 515 Plexus, Auerbach's (see Auerbach) Meissner's {see Meissner) terminal, 55 Pneuma, 1 Polar excitation, law of, 64 Polycrotic pulse {see Pulse) Polymorph o-nuclear leucocytes, 483 Polypeptides, 19 Polysaccharids, 287 Portal circulation, 353 Positive accommodation, 147 et seq. accommodation, varying power of, 149 Posterior columns of spinal cord (see Spinal cord) ganglion reflex, 93 grey commissure (.s«e Spinalcord) roots, ganglia of, 107 Posture on circulation, 471 Potassiiim in food-stuffs, 289 Potatoes, composition, 290 Precipitins, 614 Predicrotic wave, 441 Preformed sulphate in urine, 563 Pregnancy, course of, 608 metabolism, 631 Prepyloric sphincter, 295 Presbyopia, 149 Presphygmic period, 404 Pressure, arterial, 447 et seq. arterial, factors controlling, 450 blood, 432 in capillaries, 460 in lymphatics, 464 intracardiac, 399 Pressure, variations in, due to respiration, 446 venous, 463 Primitive nerve sheath, 56 Private path, 87 Production of heat (in muscle), 268 Propionic acid {see Appendix 1.) Proprioceptive receptors, 96 Prostate gland, 621 Protamine, 17 Proteates {see Appendix II.) Protein, absorption of, 347 chemistry of, 15 classification of {see Appendix II.) conversion into fat, 352 determination of amount oxi- dised, 257 disintegration of, 16 energv value of, 257 in food, 283 metabolism of, 257 et seq., 554 native {see Appendix II.) physical characters, 14 products of, 15 regulation of supply 359 Protein, requirements, 370 storage of, 352 synthesis of, 18 vegetable, 284 Proteins, 15 {see Appendix II.) Proteolytic period of gastric diges- tion, 311 Proteoses, 311 Prothrombin, 477 Protoplasm, 5 chemistry of, 12 liberation of energy by, 7 metabolism of, 9 structure, 11 Protoplasmic activity, 5, 21 Proto-proteoses, 312 Pseudoglobulin, 480 Pseudopodia, 24 Ptvalin, 302 Puberty, 618 Pulmonarv area, 407 valve^ 392 Pulmonic heart {see Heart, pul- monic), 383 Pulse, anacrotic, 442 arterial, 434 capillary, 444 characters of wave, 436 dicrotic, 440 form of wave, 438 670 INDEX Pulse, height of wave, 437 high tension, 443 length of wave, 437 palpation of, 442 polycrotic, 442 rate of, 442 rhythm, 442 tension, 443 velocity of wave, 436 venous, 444 volume of, 442 Pulsus celer, 443 parvus, 442 plenus, 442 tardus, 443 Pupil, 140 dilatation, 148 dilator of, 140 drugs, action, 149 sphincter of, 140, 147 Purin bodies, 556, 561 Purkinje's cells, 125 images, 152 Pyloric end of the stomach, 295 sphincter, 316 Pyramidal tracts (see Spinal cord), 194 Pyriform lobe, 134 Pyrimidin bases, 28 Pyrocatechin, 564 Pyrrol derivatives {see Appendix I.) Quality of sounds, 553 Racemose glands, 34 Radiation of heat from skin, 267 Radicles, organic (see Appendix I.) Ranvier, nodes of, 57 Reaction time, cerebral, 186 of degeneration, 66 Receptor spots, 306 Receptors, 96 connection with central nervous system, 106 distance, 130 Recti muscles (see Eye) Rectum, 296 Recurrent laryngeal nerve (see Nerves of larynx) Red cells of blood (see Erythrocytes) marrow of bone, 501 nuclei (see Cerebrum) Reduced alkaline hteniatin, 490 Referred pain, 98 Reflex action, 82 et seq. bladder, 93 I Reflex action, fatigue, 89 jjosture, 88 Reiiexes, peripheral, 92 visceral, 89 Refraction of light, 144 Refractive indices of media of eye, 144 Refractory period of muscle, 216 Regeneration of nerve, 77 Regulation of growth and function, 586 Rennet (see Rennin) Renuin, 312, 321 Reproduction, 616 et seq. Requirements, food, 368 et seq. proteins, 370 Reserve air, 523 Residual air, 523 Respiration, 513 et seq. artificial, 549 at high altitudes, 543 chemical regulation, 527 Cheyne-Stokes, 531 eifect of, on air breathed, 537 effect on the blood, 538 external, 513 influence of heart's action on, 536 influence on circulation, 535 intermediate, 545 internal, 547 mechanism of, 513 et seq. movement of ribs in, 519 et seq. movements in, 516 nervous mechanism of, 523 number per minute. 525 physiology of, 515 reflex control of breathing, 532 rhythm of, 525 vagus, influence on, 532 Respiratory calorimeter, 259 centre, 526 reflex regulation, 532 Respiratory interchange, extent of, 647 ; causes of, 539 movements, special, 522 passages, elimination of heat by, 268 quotient, 258 Rete testis (see Testis) Reticulum, 294 Retina, 140 central spot, 153 corresponding areas on the two sides, 158 fatigue of, 154 INDEX 671 Retina, layers of, 141 modes of stimulation, 153 nature of changes in, 154 rods and cones of, 142 stimulation of, 153 et seq. Rhinencephalou, 135, 181 Rhodopsin, 154 Ribs, movements of, in respiration {see Respiration) Rickets, 50, 281 Rigor mortis, 214 Riva Rocci blood pressure apparatus, 438 Roaring, 553 Rolandic area (see Motor areas) Roof nucleus of the cerebellum {see Cerebellum), 125 Roots as food, 290 Roots of the spinal nerves, 107 Rubro-spinal fibres, 195 Rumen, 294 digestion in, 339 Rumination, 337 Saccharomyces cerevisfe, 5 Saccule, 118 Saliva, 302 et seq. character of, 302 chemistry of, 302 functions of, 303 influence of chorda tympani in secretion of, 304 physiology of, 303 reflex stimulation of secretion, 304 stimulation of sympathetic effect on, 305 Salivarv centre, 305 glands, 293 glands, nerve supply, 303 secretion, physiology of, 303 Salts of the bile acids, 323 Sanson's images, 147 Sarcolactic acid, 209, 250 Sarcolemma, 204 Sarcostyle, 204 Sarcous substance, 204 Scala media, 171 tympani, 170 vestibula, 170 Scheiner's experiment, 146 Schwann, 2 white sheath of {see Nerve) Sclero-proteins (see Appendix II.) Sclerotic, 139 Scratch reflex, 87 Sebaceous glands, 585 Secretin, 321, 601 Secreting epithelium, 34 Secretions, internal, 588 et stq. Sectional area of circulatory system, 383 Semen, 621 Semicircular canals, 117 Semilunar valves, 391 Semi-starvation, metabolism of, 274 Seminiferous tubules, 620 Sensation, colour, 155 integration, 179 of hunger (see Hunger) of pain {see Pain) of smell (see Smell) of taste (see Taste) of thirst (.see Thirst) physiology of colour, 155 Sensation, production of colour, 156 Sense of acceleration and retarda- tion of motion (see Labyrinth) of hearing, 166 et seq. joint and muscle, U)5 tactile, 101 thermal, 103 Sensibility, common, 98 Sertolis cells, 606 Serum, 479 albumin, 476, 480 globulin, 476, 480 Sesamoid ligaments, 233 Seventh cranial nerve, 199 Sex, determination of, 617 Sexual organs, 618 organs, effect of removal of, 606 Sheath of Schwann, white, 56 Shingles, 91 Side-chain theory, 614 Sight, 136 et seq. Sino-auricular node, 385 Sinus of Valsalva, 392 Sixth nerve (see Abducens), 201 Skatol, 330 Skatoxyl-sulphate of potassium, 563 Skin, elimination of heat by, 267 excretion by, 582 receptors, 99 Slaughter test, 369 Sleep, 187 Small intestine, 295, 332 Smell, 133 centre for, 134 mechanism of, 133 672 INDEX Smell, physiology of, 136 Snake toxin, 612 Sneezing, 522 Sols, 13 Soluble nitrogen in feeding stuffs, 284 Somatic fibres, 54, 195 Somatopleur, 625 Sounds of the heart, 407 Specific dynamic action of foods, 272 nerve energy, 97, 138 Spermatids, 621 Spermatocytes, 621 Spermatogonia, 620 Spermatozoa, 618 Spherical aberration, 147 Sphincter ani, 296 centre, 148 ileo-caecal, 334 of stomach, 316 pupillee, 140, 147 Sphygmograph, 439 Sphygmomanometer(see Riva Rocci) Spinal accessory nerve, 200 Spinal cord, 106 et seq. anterior columns. 111 arc, 78, 82 ascending degenerations, 108 conducting paths in, 108, 194 hemisection, 108 lateral columns. 111 nerves, 106 posterior columns of, 111 reflexes, 82 et seq. tracts of, 107, 194 upgoing fibres, 107 " Spinal dog," 82 Spino-tectal synapsis, 1 1 3 Spino-thalamic synapsis, 113 Splanchnopleur, 625 Spleen, 504 circulation in, 469 movements, 506 Spot, blind (see Blind spot) cold {see Cold spot) hot (see Hot spot) Squamous epithelium, 32 Squint, 162 Stannius' experiment, 425 Stapedius muscle, 167, 169 Stapes, 167 Starch, 287 equivalent, 377 value, 377 Stearic acid, 42 Stearin, 42 Stenosis, valvular, 410 Stercobilin, 332 Stereoscopic vision, 158 Stethograph, 525 Stimulation, unilateral, 25 nocuous, 85, 100 of muscle direct, 217 Stimuli, 10 successive, on muscle, 228 Stomach, 295 absorption from, 318 after feeding, 310 digestion in, 308 in horse, 342 in ruminant, 34(i during fasting, 309 movements of, 315, 318 nervous mechanism of, 317 rate of passage of food from, 317 regurgitation, 318 secretion of, 310 structure of, 295 Storage of surplus food, 351 Storing mechanism (cerebral), 185 Strain, muscular, 253, 471 Stroma of red cells of blood (see Erythrocytes) Strom uhr, 466 Sublingual gland, 293 gland, nerve supply, 304 Submaxillary gland, 293 gland, nerve supply, 304 Subminimal stimulus, 84 Substrate, 8 Succus entericus, 328 Sulcus centralis, 190 Sulphates, ethereal, 563 inorganic, 556, 563 preformed (see Inorganic sul- phates) Sulphur-containing bodies in the urine, 563 Sulphur, neutral, 556, 564 Superior cardiac branch of vagus, 418 oblique muscle, 159 Suprarenal bodies, 590 cortex, 609 medulla, 590 metabolism after injection of, 593 Surface tension, 13 (Appendix III.) Suspensory ligament of eye, 141 Swallowing, 306 time of, 308 INDEX 073 Sweat, chemistry of, 585 evaporation, 267 glands, 583 secretion of, 584 Sympathetic nerves, true, 198 nerves, para, 199 Synapsis, 53 Systemic heart {see Heart), 382 Systole of heart, 394 Systolic blood-pressure, 449 Tactile sense, 101 corpuscles, 102 Tapetum nigrum, 142 Taste, 131 Taurocholate of soda, 323 Taurocholic acid, 323 Tecto-spinal fibres, 195 Tectum, 112, 127 Teeth of horse, 292 of ruminant, 292 Temperature, 264 et scq. chemical regulation, 269 physical regulation, 269 Tendon sheaths, 40 Tendons, 40 Tensor tympani muscle, 167, 169 Tenth nerve (see Vagus) Terminal ganglia, 55 Testis, 606, 618 interstitial cells, 606 Tetanus, complete, 230 incomplete, 229 Tetany, 65 Thermal sense, 103 Thermo-electric method, 247 Thermopiles, 247 (Appendix III.) Thermotaxis, 26 Third nerve, 199 Thirst, 99 Thoracic breathing, 520 Thoracico-abdominal sympathetic, 198 Thorax, in respiration, 518 Thrombin, 477 Thromboplastin, 478 Thymus, 602 effect of castration on, 603 removal of, 603 Thyreoid, 595 gland, administration of extracts of, 598 gland removal of (thyroidec- tomy), 597 Thyreo-oxy-indol, 596 Tidal air, 522 43 Tissues, 31 adipose, 41 areolar, 40 cancellous, 46 connective, 37 fibrous, 38 lymph, 499 master, 51 mucoid, 37 vegetative, 31 Tone, plastic, 212 Tongue, 291 Tonometer, 541 Tonus, muscle, 211 Touch, centre for, 115, 116 spots, 100 Tract, crossed jayramidal, 195 direct cerebellar, 112 Tracts of cord, 112, 194 Transitional epithelium, 33 Tricuspid valve, 390 Trigeminal nerve, 201 Triple-phosphate, 559 Trochlearis nerve, 201 Trophoblast, 626 Trypsin, 320 Trypsinogen, 321 Trytophan, 17, 320, 555 Tuberculum acusticum, 172 Tubers as food, 290 Tubules, secretion in kidney, 575 Tunica albuginea, 620 Turnips as food, 290 Twelfth nerve, 220 Tympanic cavity, 167 Tyrosin, 17, 33, 555 Umbilical veins, 631 Unconsciousness, 185 Unilateral stimulation, 25 Urates, 561 Urea, 359, 559 sources of, 360 Ureter, 581 Urethra, 582 Uric acid, 556, 561 Uricoclastase, 556 Urinary bladder, 581 Urine, 554 composition, 558 excretion of, 581 formation of, 567 method of estimating solids in, 557 micro-organisms in, 559 nitrogenous substances of, 559 674 INDEX Urine, non-urea nitrogen in, 559 pigments of, 566 reaction, 557 Urobilin, 566 Urochrome, 566 Uroerythrin, 566 Uterus, 621 nervous control, 633 Utricle, 118 Vaccines, 615 Vagus, 200 Valsalva sinus ct' {see Sinus of Val- salva) Valve action m reflexes, 84 ileo-csecal, 334 Valves of the heart, 390, 402 action of, 402 Valvular incompetence, 410 Vas deferens, 620 Vasa efferentia, 620 Vaso-constrictor centre, 457 mechanism, 454 Vaso-dilator centres, 460 mechanism, 458 Vegetable proteins, 284 Veins, 432 pressure in, 463 umbilical, 631 Velocity of blood, 465 Vena cava, inferior (foetal), 632 cava, superior (foetal), 632 Venous pulse, 444 Ventilation, 548 positive and negative, 533 Ventricles of the heart, 386 left, 386 muscular structure of, 387 pressure in, 402 right, 388 Vermis, superior, of cerebellum, 125 Vesicular sound, 525 Vestibular root of the eighth nerve, 119 Vestibule of the ear, 117, 170 Villi, chorionic, 626 of intestine, 295 primitive, 624 Visceral muscle, 203, 215 receptor mechanism, 97 Vision, 136 binocular, 158 colour, 155 distant, 144 double, 159 Vision, field of, 152, 158 glance, 160 monocular, 144 Visual centre, 164 sensation, duration of, 165 strength of, 165 purple, 154 Vital capacity of the thorax, 523 Vitamines, 2S2 Vitreous humour, 140 Vocal cords, 550 Voice, 552 physiology, 552 Volar aspect of hoof, 233 Voluntary contraction, nature of, 230 Vomiting, 318 in horse, 346 von Mohl, 3 Wallerian degeneration, 76 Waste, rate of (during fasting), 274 Water in feeding stuffs, 289 soluble B, 281 Watering, 367 Wave, characters of pulse (see Pulse) Weigert's method of nerve-staining, 76 Weight estimation, 106 White cells of blood, 483 fate of, 503 source of, 499 White fibro-cartilage, 45 line (hoof), 235 Wolff-Lehmann standards, 376 Work collector, 245 done by muscle, 242 muscular, effect on excreta, 262 X-CHROMOSOMES, 617 X-rays in the examination of the stomach, 315 of the intestine, 333 Yawning, 522 Yeast, 5 Zein, 277 Zona granulosa, 619 pellucida, 619 Zymin, 7 (see also Enzymes) secreting epithelium, 36 Zymogen, 36 Lorimer & Chalmers, Printers, Edinburgh. THIS BOOK IS DUE ON THE LAST DATE STAMPED BELOW AN INITIAL FINE OF 25 CENTS WILL BE ASSESSED FOR FAILURE TO RETURN THIS BOOK ON THE DATE DUE. THE PENALTY WILL INCREASE TO SO CENTS ON THE FOURTH DAY AND TO $1.00 ON THE SEVENTH DAY OVERDUE. f^f)^f7 fr^( ^^,f fl [|[p^ffT)/ji^rpi^'.^ LD 21-100m-8,'34 • (^, s 461269 BlOLOG^ UNIVERSITY OF CALIFORNIA LIBRARY '-^%