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6 Absorption spectrum of a dilute solution of reduced haemoglobin, showing the characteristic .-'

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AMERICAN

r-BOOK

PHYSIOLOGY

JOHN G

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W. H. H<

FRE]

,RS- TASKZR 4 TASK*

SB w5ns

L<« Angela cai, *

MBARD, M.D.

, Ph.D., F.R.S. iEdin.) M.D.

ICHERT, M.D. , Ph.D., M.D.

M.D.

Jaltimore, Md.

BLO'

N, DIGESTION vL HEAT;

W. B.

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■

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hi-

AN AMERICAN TEXT-BOOK

OF

PHYSIOLOGY

LM Angeles, CaJ, HENRY P. BOWDITCH, M. D. WARREN P. LOMBARD, M. D.

JOHN G. CURTIS, M.D. GRAHAM LUSK, Ph.D., F.R.S. (EDIN.)

HENRY H. DONALDSON, Ph. D. W. T. PORTER, M.D.

W. H. HOWELL, Ph.D., M.D. EDWARD T. REICHERT, M.D.

FREDERIC S. LEE, Ph.D. HENRY SEW ALL, Ph.D., M.D.

EDITED BY

WILLIAM H. HOWELL, Ph.D., M.D.

Professor of Physiology in the Johns Hopkins University, Baltimore, Md.

SECOND EDITION, REVISED

Vol. I.

BLOOD, LYMPH, AND CIRCULATION; SECRETION, DIGESTION

AND NUTRITION; RESPIRATION AND ANIMAL HEAT;

CHEMISTRY OF THE BODY

PHILADELPHIA AND LONDON

W. B. SAUNDERS & COMPANY

1901

I 4

Copyright, 1900. By W. B. SAUNDERS & COMPANY.

ELECTROTYPED BY PRESS OF

WESTCOTT * THOMSON PHILAOA. W- B- SAUNDERS & COMPA

CONTRIBUTORS TO VOL. L

JOHN G. CURTIS, M.D.,

Professor of Physiology in Columbia University (College of Physicians and Surgeons).

W. H. HOWELL, Ph. D., M. D.,

Professor of Physiology in the Johns Hopkins University.

GRAHAM LUSK, Ph.D., F. R. S. (Edin.),

Professor of Physiology in the University and Belle vue Hospital Medical College, New York.

W. T. PORTER, M.D.,

Associate Professor of Physiology in the Harvard Medical School.

EDWARD T. REICHERT, M. D.,

Professor of Physiology in the University of Pennsylvania.

PREFACE TO THE SECOND EDITION.

Advantage has been taken of the necessity of issuing a second edition of the American Text-Book of Physiology to alter somewhat its general arrangement. The book has proved to be successful, and for the most part has met only with kindly and encouraging criticisms from those who have made use of it. Many teachers, however, have suggested that the size of the book, when issued in a single volume, has constituted to some extent an inconvenience when regarded from the standpoint of a student's text- book that may be needed daily for consultation in the lecture-room or the labora- tory. It has been thought best, therefore, to issue the present edition in two volumes, with the hope that the book may thereby be made more serviceable to those for whose aid it was especially written.

This change in the appearance of the book has necessitated also some alteration in the arrangement of the sections, the part upon the Physiology of Nerve and Muscle being transferred to the second volume, so as to bring it into its natural relations with the Physiology of the Central Nervous System.

The actual amount of material in the book remains substantially the same as in the first edition, although, naturally, very many changes have been made. Even in the short time that has elapsed since the appearance of the first edition there has been much progress in physiology, as the result of the constant activity of experimenters in this and the related sciences in all parts of the world, and an effort has been made by the various contributors to keep pace with this progress. Statements and theories that have been shown to be wrong or improbable have been eliminated, and the new facts discovered and the newer points of view have been incorporated so far as possible. Such changes are found scattered throughout the book.

The only distinctly new matter that can be referred to specifically is found in the section upon the Central Nervous System, and in a short section upon the modern ideas and nomenclature of physical chemistry, with reference especially to the processes of osmosis and diffusion. The section dealing with the < Vntral Nervous System has been recast in large part, with the intention of making it more suitable to the actual needs of medical students ; while a brief presen- tation of some of the elementary conceptions of physical chemistry seems to he necessary at the present time, owing to the large part that these views are taking in current discussions in physiological and medical literature.

The index has been revised thoroughly and considerably amplified, a table of contents has been added to each volume, and numerous new figures have been introduced.

August. 1900.

PREFACE.

The collaboration of several teachers in the preparation of an elementary text-book of physiology is unusual, the almost invariable rule heretofore having been for a single author to write the entire book. It does not seem desirable to attempt a discussion of the relative merits and demerits of the two plans, since the method of collaboration is untried in the teaching of physi- ology, and there is therefore no basis for a satisfactory comparison. It is a fact, however, that many teachers of physiology in this country have not been altogether satisfied with the text-books at their disposal. Some of the more successful older books have not kept pace with the rapid changes in modern physiology, while few, if any, of the newer books have been uniformly satis- factory in their treatment of all parts of this many-sided science. Indeed, the literature of experimental physiology is so great that it would seem to be almost impossible for any one teacher to keep thoroughly informed on all topics. This fact undoubtedly accounts for some of the defects of our present text-books, and it is hoped that one of the advantages derived from the col- laboration method is that, owing to the less voluminous literature to be consulted, each author has been enabled to base his elementary account upon a comprehensive knowledge of the part of the subject assigned to him. Those who are acquainted with the difficulty of making a satisfactory elementary presentation of the complex and oftentimes unsettled questions of physiology must agree that authoritative statements and generalizations, such as are fre- quently necessary in text-books if they are to leave any impression at all upon the student, are usually trustworthy in proportion to the fulness of informa- tion possessed by the writer.

Perhaps the most important advantage which may be expected to follow the use of the collaboration method is that the student gains thereby the point of view of a number of teachers. In a measure he reaps the same benefit as would be obtained by following courses of instruction under different teachers. The different standpoints assumed, and the differences in emphasis laid upon the various lines of procedure, chemical, physical, and anatomical, should give the student a better insight into the methods of the science as it exists

PREFACE.

to-day. A similar advantage may be expected to follow the inevitable over- lapping of the topics assigned to the various contributors, since this has led in many cases to a treatment of the same subject by several writers, who have approached the matter under discussion from slightly varying standpoints, and in a few instances have arrived at slightly different conclusions. In this last respect the book reflects more faithfully perhaps than if written by a single author the legitimate differences of opinion which are held by physi- ologists at present with regard to certain questions, and in so far it fulfils more perfectly its object of presenting in an unprejudiced way the existing state of our knowledge. It is hoped, therefore, that the diversity in method of treatment, which at first sight might seem to be disadvantageous, will prove to be the most attractive feature of the book.

In the preparation of the book it has been assumed that the student has previously obtained some knowledge of gross and microscopic anatomy, or is taking courses in these subjects concurrently with his physiology. For this reason no systematic attempt has been made to present details of histology or anatomy, but each author has been left free to avail himself of material of this kind according as he felt the necessity for it in developing the physiolog- ical side.

In response to a general desire on the part of the contributors, references to literature have been given in the book. Some of the authors have used these freely, even to the point of giving a fairly complete bibliography of the subject, while others have preferred to employ them only occasionally, where the facts cited are recent or are noteworthy because of their importance or historical interest. References of this character are not usually found in ele- mentary text books, so that a brief word of explanation seems desirable. It has not been supposed that the student will necessarily look up the references or commit to memory the names of the authorities quoted, although it is pos- sible, of course, that individual students may be led to refer occasionally to original sources, and thereby acquire a truer knowledge of the subject. The main result hoped for, however, is a healthful pedagogical influence. It is too often the case that the student of medicine, or indeed the graduate in medicine, regards his text-book as a final authority, losing sight of the fad that such books are mainly compilations from the works of various investigators, and that in all matters in dispute in physiology the final decision must be made, so far as possible, upon the evidence furnished by experimental work. To enforce this latter idea and to indicate the character and source of the great literature from which the material of the text-book is obtained have been the main reasons for the adoption of the reference system. It is hoped also that the

PREFACE.

book will be found useful to many practitioners of medicine who may wish to keep themselves in touch with the development of modern physiology. For this class "I readers references to literature are not only valuable, but frequently essential, since the limits of a text-book forbid an exhaustive discussion of mauv points of interesl concerning which fuller information may be desired.

The numerous additions which are constantly being made to the literature of physiology and the closely related sciences make it a matter of difficulty to escape errors of statement in any elementary treatment of the subject. It can- not be hoped that this book will be found entirely free from defects of this character, but an earnest effort has been made to render it a reliable repository of the important facts and principles of physiology, and, moreover, to embody in it, so far as possible, the recent discoveries and tendencies which have so characterized the history of this science within the last few years.

CONTENTS OF VOLUME I.

INTRODUCTION (By W. H. Howell) 17

Definition of physiology and protoplasm, 17 — Animal and plant physiology, 17 — Vital irritability, 18 — Nutrition, assimilation and disassimilation, auabolism, kataholism, metabolism, 19 — Reproduction, 20,28 — Contractility and conductivity, 20 — Physiologi- cal division of labor, 22 — Pfliiger hypothesis of the structure of the living molecule, 23 — Loew's and Latham's hypothesis of the structure of the living molecule, 23 — The chemical structure of proteids, protamine, 24 — Physical structure of living matter, 24 — Vital force, 25 — Secretion and absorption, 27 — Heredity and consciousness, 28 — Gen- eral and special physiology, 29 — Methods of investigation used in the science of physiology, 30.

BLOOD (By W. H. Howell) 33

A. General Properties — Physiology of the Corpuscles 33

Histological structure of blood, 33 — Definition of blood-plasma, blood-serum, and defibrinated blood, 33 — Reaction of blood, 34— Specific gravity of blood, 34 — Histology of red corpuscles, 35 — Condition of the haemoglobin in the red corpuscles, 35 — Laking of blood, 35 — Globulicidal and toxic action of blood-serum, 36 — Isotonic, hypertonic, hypotonic solutions, 36 — Nature and amount of hfemoglobin, 37 — Compounds of haemo- globin with O, CO, NO. and CO2, 38— The iron of the haemoglobin molecule, 39— Haemo- globin crystals, 40 — Absorption spectra of haemoglobin, 40 — Derivative compounds of haemoglobin, 44— Origin and fate of the red corpuscles, 45 — Variations in the number of red corpuscles, 46 — Morphology and physiology of the leucocytes, 47 — Physiology of the blood plates, 49.

B Chemical Composition op the Blood — Coagulation — Total Quantity of

Blood — Regeneration after Hemorrhage 50

Composition of the plasma and corpuscles, 50 — Proteids of the blood plasma, 51 — Serum albumin, 52 — Paraglobulin, 53 — Fibrinogen, 53 — Coagulation of blood, super- ficial appearances, 54 — Time of clottiug, 55 — Theories of coagulation, 55 — Nature and origin of fibrin ferment, 58 — Intravascular clotting, 60 — Means of hastening or retard- ing clotting, 61 — Total quantity of blood in the body, 63 — Regeneration of the blood after hemorrhage, 63 — Transfusion of blood and salines, 64.

C. Diffusion and Osmosis, and Their Importance in the Body 65

Osmotic pressure, 65 — Calculation of, 67 — Electrolysis, 67 — Grammolecular solutions, 67 — Osmotic pressure of proteids, 69 — Diffusion of proteids, 70.

LYMPH (By W. H. Howell) 70

Lymph-vascular system, 70 — Formation of lymph, theories of, 70 — The factors con- trolling the flow of lymph, 75, 145 — Pressure in lymph-vessels, 146 — Effect of thoracic aspiration on lymph-flow, 147— Effect of body movements and valves on lymph-flow, 147.

CIRCULATION 70

PART I. — The Mechanics of the Circulation of the Blood and of the Move- ment of the Lymph (By John G. Curtis) 76

A. General Considerations 76

General course of the blood-flow, 76 — Causes of the blood-flow, 77 — Working of die pumping mechanism, 78 — Pulmonary circuit, 78.

B. Movement of the Blood in the Capillaries, Arteries, \m> Veins .... 79

Anatomical characteristics of the capillaries, 79— The circulation as observed under the microscope, 80 — Behavior of the red corpuscles, 81 Friction, axial stream, and inert layer, 81 — Behavior of the leucocyte-, 82 Emigration of the leucocytes, 83

Velocity of the blood in the small vessels, S3 Capillary blood-pressure. 84

C. The Pressure of the Blood in the Arteries, Capillaries, lnd Veins ... 85

Method of studying bl 1-pressure, manometers, 85— The mercurial manometer and

graphic record of blood-pressure upon a kymograph, 88 — The mean pressure in arteries and veins, 90.

9

10 CONTENTS.

PAGE

D. The Causes of the Pressure in the Arteries, Capillaries, and Veins ... 91 Balance of the factors producing arterial pressure, 92 — The arterial pulse, 93 — The

capillary pressure and its cause, 93- Extinction of tile arterial pulse in the capillaries, 94 — Venous pressure and its causes, 94— Subsidiary forces assisting the blood-flow, 95 — Respiratory pulse in the veins, 96 — The dangerous region, entrance of air into veins, 97.

E. The Velocity of the Blood in Arteries, Capillaries, and Veins 98

Measurement of velocity in large vessels. Stromuhr, 98 — Measurement of rapid

changes in velocity, Kin — Velocity and pressure of blood compared, KM — Relation of velocity to the sectional area of the vascular bed, 102 — Time spent by blood in capillary, 103.

F. The Blood-flow through the Linus 103

(}. The Pulse Volume and the Work Done by the Ventricles 104

The cardiac cycle, 104 — The pulse volume, 105 — The work of the ventricles, 106 — Heart's contraction as a source of heat, 108. II. The Mechanism of the Valves of the Heart 108

I'se of the valves. 108 — The auriculoventricular valves, 108 — Use of the tendinous cords, 109 — The papillary muscles and their uses, 110 — The semilunar valves, 110 — Lunuhe and corpora arantii, 111. I. The Changes in Form and Position of the Beating Heart, and the Cardiac

Impulse 112

General changes in the heart and arteries, 112 — The heart and vessels in the open chest, 113 — Changes of size and form in the beating ventricles, 113 — Changes of posi- tion of the ventricle, 114 — Changes in the auricle, great veins, and great arteries, 115 — Effects of opening the chest, 115 — Probable changes in heart in the unopened chest, 116 — The cardiac impulse or apex beat, 117.

J. The Sounds of the Heart 118

Relations and character of the heart-sounds, 118 — Cause of the second sound, 118 — Causes of the first sound, 119.

K. The Frequency of the Cardiac Cycles 121

L. The Relations in Time of the Main Events of the Cardiac Cycle .... 121 The auricular, ventricular, and cardiac cycles, 122 — The variability of each cycle, 123 — Relative lengths of ventricular systole and diastole, 123 — Lengths of auricular systole and heart pause, 124.

M. The Pressure Within the Ventricles 125

Range of pressure within ventricles, 125 — Methods of recording ventricular press- ures. 126 — General character of curve of intraventricular pressure, 128 — Effect of auricular systole on the curve of ventricular pressure. 130— The opening and closing of the heart valves in relation to the curve of ventricular pressure, 130— Analysis of the curve of ventricular pressure, 133 — Negative pressure within the ventricles, 134.

N. The Functions of the Auricles 135

The auricle as a force pump. 135 — Time relations of auricular systole and diastole, 136 — Statement of functions of auricles, l.;i; Negative pressure within the auricles, 137— Is the auricle emptied by its systole? 138— Question of regurgitation from auri- cles to veins, 138.

O. The Arterial Pulse 139

Nature and importance of the arterial pulse, 139— Rate of transmission of the pulse- wave, 1 1(1 Frequency and regularity of the pulse, 141 — Arterial tension as indicated by the pulse, 141— Size and celerity of pulse. 1 II The pulse-trace, or sphygmogram. 142— Analysis of the sphygmogram, 143— The dicrotic wave, 143— The diagnostic use of i lie sphygmogram. 115.

Part II.— The [nnervation ok the Heart (By W. T. Porter) 148

The cause of the rhythmic heart-heat. IIS The intracardiac ganglion ells and nerves, 148— The nerve theory of the heart-beat, 149— The muscular theory of the heart-beat, 150 The excitation wave and its passage over the heart, 152 The passage of the excitation wave from auricle to ventricle, 154— The refractory period and com- pensatory pause, 156, A. The Cardiac Nerves 159

Anatomical arrangement of the heart nerves, 159 The inhibitory nerves. 161 — Effect of inhibition on the ventricles 162— Effect of inhibition on the auricle and sinus, L64 Effect of inhibition on the bulbus arteriosus, 165 Effect of inhibition on the irritability of the heart. 165 Relation of inhibition to rate and strength of stim- ulus, 165 -Arrest of the heart in systole, 165— Comparative inhibitory power of the two vagi. 166 Effect of the septal nerves on the inhibition, 166— Theories of the nature of vagus inhibition, L66 Relation of age, temperature, and intracardiac press- are to inhibition, 167 — The augmentor or accelerator nerves of the heart, 167 — Effect of stimulating the augmentor nerves, Kill Simultaneous stimulation of the accelerator and inhibitory fibres, 17<» classification of the inhibitory and augmentor fibres, 171 — The centripetal nerves of the heart. 172 Existence of sensory nerves in the heart,

CONTENTS. 11

FAGE

172 — The depressor nerve of the heart, 172 — Analysis of the effect of stimulation of the depressor nerve, 173 — Keflex etTeet of sensory nerves on the heart, 175 — Reflex effects through the sympathetic system on the heart, 175.

B. The Centres of the Heart-nerves 170

The inhibitory centre, 176 — Tonus of the inhibitory centre, 176 — Origin of the car-

dio-inhibitory fibres, 177 — Position of the augmentor centre, 177 — Action of higher parts of the brain on the cardiac centres, 178— The existence of peripheral reflex centres, 178 — Ligatures of Stan n ins, 17."v

Part III.— The Nutrition of the Heart (By W. T. Porter) 179

Spongy structure of frog's heart, 179— The coronary arteries iu the dog, 179 — The terminal nature of coronary arteries, 180— The effect of closure of the coronary arte- ries, 181 — The cause of the arrest of the heart after closure of the coronary arteries, 182— Fibrillary contractions and recovery from, 183— Closure of the coronary veins, 184 — The volume of the coronary circulation, 184— The effect of the heart-eontractious on the coronary circulation, 185 — The vessels of Thebesius and the coronary veins, 186— Blood-supply and heart-beat, 186— Lymphatics of the heart, 186.

C. Solutions which Maintain the Beat of the Heart 187

Methods of nourishing the heart with solutions, 187 — The composition and action of

nutrient solutions, 189— The effect of CO2, organic substances, and physical character- istics of nutrient solutions, 191— Nourishment of the isolated mammalian heart, 191.

Part IV.— The Innervation of the Blood-vessels (By W. T. Porter) 192

Historical account of the discovery of vaso-motor nerves, 192— Methods of demon- strating vaso-motor phenomena, 195— Experimental distinctions between vaso-const ric- tor and vaso-dilator nerve-fibres, 196 — Anatomical course of vaso-motor fibres. 197— Vaso-motor centre in the medulla, 198— Vaso-motor centres in the spinal cord, 199— Sympathetic vaso-motor centres— peripheral tone, 200— Rhythmical changes in vascular tone, 201 — Vaso-motor reflexes, 201, 202— Relation of cerebrum to vaso-motor centres, 202 — Pressor and depressor fibres, 202— Vaso-motor fibres to the brain, 203— Vaso-motor fibres to the head, 204— Vaso-motor fibres to the lungs, 21)5— Vaso-motor fibres to the heart, 206— Vaso-motor fibres to the intestines, 206— Vaso-motor fibres to the liver, 206 — Vaso-motor nerves of the kidney, 207 — Vaso-motor nerves of the spleen, 207 — Vaso- motor nerves of the pancreas, 207 — Vaso-motor nerves of the external generative organs, 207 — Vaso-motor nerves of the internal generative organs, 208 — Vaso-motor nerves of the portal system, 209— Vaso-motor nerves of the limbs, muscles, and tail, 209.

SECRETION (By W. H. Howell) >1\\

A. General Considerations 211

Definition of gland and secretion, 211 — Types of glandular structure, 212— Older

views of secretion and excretion, 213— General proofs that gland cells take an active part in secretion, 214 — Filtration through living and dead tissues, 215.

B. Mucous and Albuminous Glands— Salivary Glands 215

Distinction between mucous and albuminous glands, 215— Goblel cells as unicellular

mucous glands, 216— Anatomical relations of salivary glands, 217 Nerve-sapply to salivary glands, 218 — Histology of salivary glands, 219— Composition id" the saliva, 220 — Significance of the potassium sulphocyanide in saliva, 221 — Discovery of secre tory nerve-fibres to the salivary glands, 221— Distinct ion between "chorda" and "sympathetic" saliva, 222— Effect of varying the strength of the stimulus upon the composition of the saliva, 223 — Theory of trophic and secretory fibres, 224 Vacuoles in gland cells during secretion, 226 —Histological changes in glands as a result of func- tional activity, 226 — Action of atropin, pilocarpin, and nicotin on secretory fibres, 229 — The normal mechanism of salivary secretion, 230— Electrical changes in the salivaVy glands during secretion, 231.

C The Pancreas — Glands of the Stomach and Intestines 231

Anatomical relations of the pancreas, 231 Histological characters of the pancreas, 231 — Composition of the pancreatic secretion, 232 - Secretory nerves of the pancreas, 232 — Histological changes in pancreatic cells during secretion, '.':;:: Distinction between enzymes and zymogens, 235 The normal mechanism of the pancreatic Becre- tion, 235— The histological characteristics of the gastric glands, 237 Composition of the gastric secretion, 238 -Secretory nerves of the gastric plan ds, 239 The normal mechanism of the gastric secretion, 210 Histological changes in the gastric glands during secretion, 242 — The secretion of the intestinal glands, 243.

D. Liver and Kidney 244

Histology of liver in relation to the bile-ducts, -J 1 1 Composition of the bile, 215 —

The quantity of bile secreted, 246— Relation of the blood-flow to the secretion of bile, 247 — Secretory nerve-libres to the liver cells, 217 Motor innervation of the bile-ducts and gall-bladder, 248— The normal mechanism of the bile secretion, 248 Effect of occlusion of the bile-ducts, 249— Histological characteristics of the kidney. 249 Com- position of the urine, 250— General theories of the secretion of urine. 251 Secretion of urea and related nitrogenous bodies, 252 Secretion of the water and salts, 253 — The blood-flow through the kidney and its relations to secretion. 255.

12 CONTENTS.

PAGE

E. Cutaneous Glands — Internal Seceetion 257

Sebaceous secretion, 257— The sweat-glands and the quantity of their secretion, 258 — The composition of sweat. 258 Secretory fibres to the sweat-glands, 25!) — The posi- tion of the sweat-centres in the cord and medulla, 26Q— The structure and phylogeny of the mammary glands, 261 — Composition of the milk, 261? Histological changes in the mammary glands during secretion, 262 — Secretory nerve-fibres to the mammary glands, 263 — Normal mcchauism of the secretion of milk, 264 — Internal secretions, general statements, 265 The internal secretions of the liver, 265 The internal secre- tion of the pancreas, 266 -The anatomical and histological relations of the thyroid body, 267 Accessory thyroids, 268 The anatomical relations of the parathyroids, 268 The functions of the thyroids and parathyroids, 268 Effect of removal of the adrenal bodies, 271 — Action of adrenal extracts on the circulation, 271 — Secretory nerves to the adrenals, 272 The isolation of epinephrin, 272— Anatomical relations of the pituitary body, 272— Physiological effects of extracts of the pituitary body, 272 — The internal secretions of the testis and the ovary, 273.

CHEMISTRY OF DIGESTION AND NUTRITION (By W. H. Howell) 275

A. Definition and Composition of Foods Characteristics of Enzymes . . . . 275

General statements regarding foods and food-stuffs, 275 — General nutritive sig- nificance of the food-stuffs, 27<i Analysis of foods, 278 — Definition and classification of enzymes, 279— General reactions of the enzymes, 281

B. Salivary Digestion 283

Properties and composition of the mixed saliva, 283 — Ptyalin and its action on

starch, 2.^4 — Conditions influencing the action of ptyalin, 286 — General functions of saliva, 287.

C. Gastric Digestion 287

General conditions in the stomach during digestion, 287 — Methods of obtaining gas- tric juice, 287 — The properties and composition of the gastric juice, 288 — The nature of the acid of the gastric juice, 289 — The theories as to the origin of the IIC1, 289 — Nature and properties of pepsin, 290 — The preparation of an artificial gastric juice, 291 — The digestive action of pepsin-hydrochloric acid, 292 — Definition of peptone, 294 — The preparation and properties of rennin, 295 — The action of gastric juice on fats and car- bohydrates, 296 — Action of gastric juice on albuminoids, 297 — Why does the stomach not digest itself? 297— General summary of the functions of the stomach, 298.

D. Intestinal Digestion 299

The composition of pancreatic juice, 299 — The properties and methods of preparing

trypsin, 301 — The products of tryptic digestion, 302 — Tryptic digestion of albumin- oids, 304 — Amylopsin, its occurrence and digestive action, 304 — Steapsin, its occur- rence and action on fats, 305 — Emulsification of fats, 306 — The intestinal secretion, 308 — The occurrence and action of the inverting enzymes, 308 — Digestion in the large intestine, 309— Bacterial decompositions in the huge intestine, 309.

E. Absorption — Summary of Digestion and Absorption of Food-stuffs — Feces. 311 General statement of the conditions and products of absorption, 311 — Absorption in

the stomach, 312 -Absorption in the stomach of water, salts, sugars, peptones, and fats, 313— Absorption in the small intestine, 313 — Absorption in the large intestine, 314 — Absorption of proteids, 315 — Absorption of sugars, 317 — Absorption of fats, 317 — Absorption of water and salts, 318 — Composition of the feces, 319.

F. Physiology of the Liver and the Spleen 320

Histological arrangement of the liver lobule, 320 — The composition of bile, 321 —

The bile-pigments, 322 -The bile-acids, 323— Cholesterin, 324 — Lecithin, fats, and nucleo-albumin in bile, 325— General physiological importance of bile, 325 — Glycogen in the liver, 326 — The origin of glycogen with reference to the food-stuffs, 327 — The effect of proteids on glycogen-formation, 328 — The effect of fats on glycogen-formatioa, 329— The function of glycogen, and the glycogenic theory, 329— Glycogen in the mus- cles and other tissues, 330 — Conditions affecting the supply of glycogen in the body, 331 — Formation of urea in the liver, 331— Physiology of the spleen, 332.

<;. The Kidney and Skin \s Excretory Organs 334

Genera] composition of the urine. 334 — The properties and origin of urea, 334 — The physiological history of uric acid and the xanthin bodies, 338 — The physiological his- tory of creatinin, 339- The physiological history of hippuric acid, 339— The conju- gated sulphates in the urine, 340 The physiological history of the water and salts of the urine, 341 — The functions of the skin, :'»11 Sweat as an excretion, 342 — The seba- ceous secretion, ,">I2 The excretion of the COa through the skin, 342,

11. Body-metabolism- Nutritive Value of the Food-stuffs 343

Determination of the total metabolism id" the body, 343 Definition of nitrogen- equilibrium, 344 -Definition of carbon- and general body-equilibrium, 315 — The nutri- tive importance of the proteids, 345 The luxus-consumption idea, 348 The nutritive value of albuminoids, 319 The nutritive value of fats, 350 The formation of fat in the body, 351 — The nutritive value of carbohydrates, 353— The nutritive value of water and salts, 354.

CONTENTS. 13

PAGE

I. Accessory Articles of Diet— Variations of Body-metabolism under Dif- ferent Conditions — Potential Energy of Food — Dietetics 357

Accessory articles of diet, 357 — Stimulants, 357 — Condiments, flavors, and meat extracts, 359 — Conditions influencing body-metabolism, 359 — The effect of muscular work on metabolism, 359 — Metabolism during sleep, 361— The effect of variations in temperature on body-metabolism, 362 — The effect of starvation on body-metabolism, 362 — The potential energy of food, 364 — The principles of dietetics, 366.

MOVEMENTS OF THE ALIMENTARY CANAL, BLADDER, AND

URETER (By W. H. Howell) 369

The physiology of plain muscle tissue, 369 — Mastication, 372 — Deglutition, 372— The Kronecker-Meltzer theory of deglutition, 375 — The nervous control of degluti- tion, 376 — Movements of the stomach, 377 — The extrinsic nerves controlling the move- ments of the stomach, 381 — Movements of the intestines, 3S2 — The peristaltic move- ments, 382 — Mechanism of the peristaltic movement, 384 — Pendular movements of the intestines, 3*4— Extrinsic nerves of the intestines, 384 — Effect of various conditions on the intestinal movements, 385 — The mechanism of defecation, 386 -The act of vomiting, 387 — The nervous mechanism of vomiting, 388 — Micturition, 389 — Move- ments of the ureters, 389 — Movements of the bladder, 390 — Nervous control of the bladder movements, 392.

RESPIRATION (By Edward T. Reichert) 395

General statements, internal and external respiration, 395.

A. The Respiratory Mechanism in Man 395

Physiological anatomy of the lungs and thorax, 395 — Conditions of pressure within

the thorax, 396 — Definition of respiration, inspiration, and expiration, 398— Movements of the diaphragm, 398 — Movements of other muscles assisting the diaphragm, 399— Movements of the ribs, 400 — The function of the intercostal muscles, 402 — Summary of the action of the inspiratory muscles, 405 — Movements of expiration, 406 — Summary of the action of the expiratory muscles, 407 — Associated respiratory movements, 408 — Intrapulmonary and intrathoracic pressure, 408 — Respiratory sounds and nasal breathing, 409.

B. The Gases in the Lungs, Blood, and Tissues 409

Alterations in the gases in the lungs, 409 — Alterations in the gases in the blood. 411 —

The forces concerned in the diffusion of O and CO2 in the lungs, 412 — The interchange of O and CO2 between the alveoli and the blood, 414 — The tension of 0 in the blood and tissues, 415 — The tension of CO2 in the blood and tissues, 416 — The tension of N, 417 — The forces producing the interchange of O and CO2 in the lungs, 417 — The forces producing the interchange of O and CO2 in the tissues, 419 — The extraction of gases from the blood, 420 — Cutaneous respiration, 422 — Internal or tissue respira- tion, 422.

C. The Rhythm, Frequency, and Depth of the Respiratory Movements . . 423 The rhythm of the respiratory movements, 423 — The frequency and depth of the

respiratory movements, 425.

D. The Volumes of Air, Oxygen, and Carbon Dioxide Respired 426

Normal volumes of air respired and capacity of lungs and bronchi. 126 The volumes

of O and CO2 respired, 428— Conditions influencing the volumes of () and COa respired, 429— The respiratory quotient, 436— Conditions influencing the respiratory quotient, 437.

E. Principles of Ventilation 439

F. The Effects of the Respiration of Various Gases tin

G. The Effects of the Gaseous Composition of the Blo< \ the Respi-

ratory Movements I pi

Eupncea, dyspnoea, apncea, and polypncsa, 440 The causes of apnoea, 441- The effect

of muscular activity on the respiratory movements. 442- The conditions producing polypnosa, 443— The conditions producing dyspnoea, 443 -Asphyxia. 145.

H. Artificial Respiration na

I. The Effects of the Respiratory Movements on the Circulation .... 117 The effects of respiration on blood-pressure, 117 The effects of respiration on blood- flow, 450— The effects of respiration on the pulse, 151 The effects of obstruction of the air-passages and of the respiration of rarefied and compressed aii on the circula- tion, 45l.

J. Special Respiratory Movements i;, I

The movements in coughing, hawking, sneezing, laughing, crying, sobbing, sighing, etc., 454.

K. The NERVOUS Mechanism of the RESPIRATORY Movements 455

The respiratory centres, 155 The rhythmic activity of the respiratory centre, 158— The afferent respiratory nerves, 160 Effects of section and stimulation oftbepneumo-

14 CONTENTS.

PAGE

gastric nerves, 460 — Effects of stimulation of the superior laryngeal nerve, 462 — Effects of stimulation of the glossopharyngeal nerve, 462 — Effects of stimulation of the tri- geminal nerve, 463 Effects of stimulation of the cutaneous nerves, 463 — The efferent respiratory nerves, 163.

L. The Condition of the Respiratory Centre in the Fetus 464

The reasons for the absence of respiratory movements in the fetus, 464.

M. The Innervation of the Lings 465

Broncho-constrictor and broncho-dilator fibres, 465 — Vaso-motor fibres to the lungs, 466 Summary of the pulmonary fibres found in the vagus, 466.

ANIMAL HEAT (By Edward T. Reichert) 467

A. Body-temperature 467

Eomothermous and poikilothermous animals. 467 — Temperatures of different spe- cies of animals, 467 — The temperature <>f the different regions of the body, 46s — The conditions affecting body-temperature, 469 — Temperature regulation, 473.

B. Income and Expenditure of Heat 474

The potential energy as furnished by the food-stuffs, 474 — The income of heat and

methods of measuring, 475— The expenditure of heat, 476.

C. Beat-production and Heat-dissipation 477

( alorimetry, 477 — The construction and use of calorimeters, 478 — Conditions affect- ing heat-production, 482 — Conditions affecting heat-dissipation, 485.

D. THE Heat-mkchanism . . 489

The mechanism concerned in thermogenesis, 489 — The thermogenic tissues, 490 —

The thermogenic nerves and centres, 490 — The mechanism concerned in thermolysis, 494 — Therruotaxis, 495 — Abnormal thermotaxis, 496 — Post-mortem rise of tempera- ture, 497.

THE CHEMISTRY OF THE ANIMAL BODY (By Graham Lusk) . 499

A. The Non-metallic Elements 499

The preparation, occurrence, and properties of hydrogen, 499 — The preparation,

occurrence, and properties of oxygen, 500 — Ozone, 502 — Traube's theory of oxidations in the body, 502 — Occurrence, properties, and functions of water, 503 — Peroxide of hydrogen, 505 — The preparation, occurrence, and properties of sulphur, sulphuretted hydrogen, sulphurous and sulphuric acids, 505 — Preparation and properties of chlorine, 508 -Bromine and its compounds in the body, 508 — Iodine and its compounds in the body, 509 — Fluorine and its compounds in the body, 510 — Occurrence and properties of nitrogen and its compounds, 510 — Occurrence of phosphorus, 513 — Phosphorus-pois- oning, 513 — Compounds of phosphorus, 514 — Phosphorus in the body, 515 — Occurrence of carbon, 516 — Compounds of carbon, 517— Metabolism of carbon in the body, 518 — Properties and compounds of silicon, 519 — Occurrence and properties of potassium compounds, 519— Potassium in the body, 520 — Occurrence and properties of sodium and its compounds, 521 — Occurrence of ammonium carbonate and its fate in the body, 523 — Occurrence anil properties of calcium and its compounds, 523 — The history of cal- cium in the body, 525 — Occurrence of strontium in the body, 526 — Occurrence and prop- erties of magnesium compounds, 527 — The compounds of iron and its history in the metabolism of the body, 528.

B. The Compounds of Carbon 531

The derivatives of methane. 531 — General formula and reactions of the monatomic

alcohols, 531 — General formula and reactions of the fatty acids, 532 — The properties and occurrence of methane, 532 -Properties of trichlormethane (chloroform!, 533 — The properties of methyl aldehyde and general properties of aldehydes, 533 — Other methyl compounds and their action in the body, 531 — Properties and occurrence of formic acid, 534 — The properties of ethyl alcohol, 535— The fate of alcohol in the body, 535 -The properties of ethyl ether and chloral hydrate, 535 -The properties of acetic acid. 536— The properties of aceto-acetic acid, 537 — The properties of glycocoll (amido-acetic acid |, 5:;? The properties of Barcosin, 537 — Propyl compounds and their occurrence in the body, 53* Butyl compounds and their occurrence in the body, 539 — Pentyl compounds and their occurrence in the body, 539 Acids containing more than five carbon atoms (leucin, palmitin, etc.), 540 — Amines, their structure and occurrence, 541 — The cyanogen compounds, 541 — The. amines of the olefines [ptomaines, toxines, etc. i, 542 — Occurrence and structure of taurin, 543 — Occurrence and properties of the biliary salts. 513 — The properties and occurrence of lactic acid. 545— -The properties and occurrence of cvstein and cystin, 546— The amido-deri vat i ves of carbonic acid (urea, carbamic acid . 548 The properties and occurrence of urea, 548 — Creatin, creatinin, histidin, arginin, 550 The purin or alloxuric bodies and bases, 552 — Oxalic, succinic, and aspartic acids, 557— The properties and occurrence of glycerin and its compounds, 558 — The properties ami occurrence of lecithin, 559 — The history of fats in the body, 559 — The properties of oleic acid, 560.

CONTENTS. 15

PAGE

Carbohydrates 561

The structure and classification of carbohydrates, 561 — The glycoses, 562 — The di- saccharides, 564 — The cellulose group (starch), 5<ir>.

Benzol Derivatives, or Aromatic Compounds 568

The benzol ring, 568— Phenol, its structure and occurrence, 569— Benzoic acid, its structure and occurrence, 569 — Tyrosiu, its structure and occurrence, 570 — Indol. its structure and occurrence, 571 — Epinephrin, its structure and occurrence, 572 — The history of the aromatic bodies in the urine, 572 — The structure and history of inosit, 573.

Substances of Unknown Composition 573

The properties and occurrence of haemoglobin aud its compounds, 57:5 — The bile-pig- ments aud the melanius, 574 — The properties and occurrence of cholesterin, 575 — The general structure aud reactions of proteids, 575 — The classification of the proteids, 576 — The protamins and remarks upou the theoretical composition of the proteid molecule, 580.

Index 583

CONTENTS OF VOLUME II.

THE GENERAL PHYSIOLOGY OF MUSCLE AND NERVE (By Warren P. Lombard).

THE CENTRAL NERVOUS SYSTEM (By Henry H. Donaldson).

THE SPECIAL SENSES— VISION (By Henry P. Bowditch).

HEARING, CUTANEOUS AND MUSCULAR SENSIBILITY, EQUI- LIBRIUM, SMELL, AND TASTE (By Henry Sewall).

THE PHYSIOLOGY OF SPECIAL MUSCULAR MECHANISMS. THE ACTION OF LOCOMOTOR MECHANISMS (By War- ren P. Lombard).

VOICE AND SPEECH (By Hexry Sewall).

REPRODUCTION (By Frederic S. Lee).

AN AMERICAN

TEXT-BOOK OF PHYSIOLOGY.

I. INTRODUCTION.

The term "physiology" is, in an etymological sense, synonymous with " natural philosophy," and occasionally the word is used with this significance even at the present day.1 By common usage, however, the term is restricted to the liviug side of nature, and is meant to include the sum of our know- ledge concerning the properties of living matter. The active substance of which living things are composed is supposed to be fundamentally alike in structure in all cases, and is commonly designated as protoplasm {-oioroz, first, and nXdofxa, anything formed). It is usually stated that this word was first introduced into biological literature by the botanist Von Mold to designate the granular semi-liquid contents of the plant-cell. It seems, however, that priority in the use of the word belongs to the physiologist Purkinje (1840), who employed it to describe the material from which the young animal embryo is constructed.2 In recent years the term has been applied indif- ferently to the soft material constituting the substance of either animal or plant-cells. The word must not be understood to mean a substance of a definite chemical nature or of an invariable morphological structure ; it is applied to any part of a cell that shows the properties of life, and is therefore only a convenient abbreviation for the phrase " mass of living matter."

Living things fall into two great groups, animals and plant's, and corre- sponding to this there is a natural separation of physiology into two sciences, one dealing with the phenomena of animal life, the other with plant life. In what follows in this introductory section the former of these two divisions is chiefly considered, for although the most fundamental laws of physiology are, without doubt, equally applicable to animal and vegetable protoplasm, nevertheless the Structure as well as the properties of the two forms of matter are in some respects noticeably different, particularly in the higher types of organisms in each group. The most striking contrast, perhaps, is found in the fad that plants exhibit a lesser degree of specialization in form and function and

1 See Mineral Physiology ami Physiography, 'I'. Sterry Hunt, L886.

2 O. Hertwig: Die '/Ale and die (,'ewehe, lS<t.">.

Vol. T.— 2 17

18 I.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a much greater power of assimilation. Owing to this latter property the plant-cell is able, with the aid of solar energy, to construct its protoplasm from very simple forms of inorganic matter, such as water, carbon dioxide, and inorganic salts. In this way energy is stored within the vegetable cell in the substance of complex organic compounds. Animal protoplasm, on the con- trary, has comparatively feeble synthetic properties ; it is characterized chiefly by its destructive power. In the long run, animals obtain their food from the plant kingdom, and the animal cell is able to dissociate or oxidize the complex material of vegetable protoplasm and thus liberate the potential energy con- tained therein, the energy taking the form mainly of heat and muscular work. We must suppose that there is a general resemblance in the ultimate structure of animal and vegetable living matter to which the fundamental similarity in properties is due, but at the same time there must be also some common dif- ference in internal structure between the two, and it is fair to assume that the divergent properties exhibited by the two great groups of living things are a direct outcome of this structural dissimilarity ; to make use of a figure of speech employed by Bichat, plants and animals are cast in different moulds.

It is difficult, if not impossible, to settle upon any one property that absolutely shall distinguish living from dead matter. Nutrition, that is, the power of converting dead food material into living substance, and repro- duction, that is, the power of each organism to perpetuate its kind by the formation of new individuals, are probably the most fundamental charac- teristics of living things; but in some of the specialized tissues of higher animals the power of reproduction, so far as this means mere multiplication li\ cell-division, seems to be lost, as, for example, in the case of the nerve-eel 1- in the central nervous system or of the matured ovum itself before it is fertil- ized by the spermatozoon. Nevertheless these cellular units are indisputably living matter, and continue to exhibit the power of nutrition as well as other properties characteristic of the living state. It is possible also that the power of nutrition may, under certain conditions, be held in abeyance, tempo- rarily at least, although it is certain that a permanent loss of this property is incompatible with the retention of the living condition.

It is frequently said that the most general property of living matter is its irritability. The precise meaning of the term vital irritability is hard to define. The word implies the capability of reacting to a stimulus and usually also the assumption that in the reaction some of the inner potential energy of tin- living materia] is liberated, so that the energy of the response is many time- greater, it may be, than the energy of the stimulus. This la-t idea is

illustrated by the case of a i trading muscle, in which the stimulus acts as a

liberating force causing chemical decompositions of the substance of the muscle with the liberation of a comparatively large amount of energy, chiefly in the form of heat or of heat and work". It may be remarked in passing, however, that we are not justified at present in assuming that a similar liberation of stored energy takes place in all irritable tissues. In the case of nerve-fibres, for instance, we have a typically irritable tissue which responds readily to

INTR OD UCTION. 1 9

external stimuli, but as yet it has not been possible to show that the forma- tion or conduction of a nerve impulse is accompanied by or dependent upon a

liberation of so-called potential chemical energy. The nature of the response of irritable living matter is found to vary with the character of the tissue or organism on the one hand, and, so far as intensity goes at least, with the nature of the stimulus on the other. Response of a definite character to appropriate external stimulation may be observed frequently enough in dead matter, and in some cases the nature of the reaction simulates closely some of those displayed by living things. For instance, a dead catgut string may be made to shorten after the manner of a muscular contraction by the appropriate application of heat, or a mass of gunpowder may be exploded by the action of a small spark and give rise to a great liberation of energy that had previously existed in potential form within its molecules. As regards any piece of matter we can only say that it exhibits vital irritability when the reaction or response it gives upon stimulation is one characteristic of living matter in general or of the particular kind of living matter under observation ; thus, a muscle-fibre contracts, a nerve-fibre conducts, a gland-cell secretes, an entire organism moves or in some way adjusts itself more perfectly to its environment. Considered from this standpoint, "irritability menus only the exhibition of one or more of the peculiar properties of living matter and can- not be used to designate a property in itself distinctive of living structure ; the term, in fact, comprises nothing more specific or characteristic than is implied in the more general phrase vitality. When an amoeba dies it is no longer irritable, that is, its substance no longer assimilates when stimulated by the presence of appropriate food, its conductivity and contractility disappear so that mechanical irritation no longer causes the protrusion or retraction of pseudopodia — no form of stimulation, in fact, is capable of calling forth any of the recognized properties of living matter. To ascertain, therefore, whether or not a given piece of matter possesses vital irritability we must first become acquainted with the fundamental properties of living matter in order to recog- nize the response, if any, to the form of stimulation \\>c(\.

Nutrition or assimilation, in a wide sense of the word, has already been referred to as probably the most universal and characteristic of these prop- erties. By this term we designate that scries of changes through which dead matter is received into the structure of living substance. The term in its broadest sense may be used to cover the subsidiary processes of digestion. respiration, absorption, and excretion through which {'<><><{ material and oxygen are prepared for the activity of the living molecules, and the waste products of activity are removed from the organism, as well as the actual conversion of dead material into living protoplasm. This last act, which is presumably a synthetic process effected under the influence of living matter, is especially designated as anabolisni or as assimilation in a narrower sense of the word as opposed to disassimilat ion. By disassimilation or katabolism we mean those changes leading to the destruction of the complex substance of the living molecules, or of the food material in contact with these molecules.

20 AN AMERICAN TEXT-HOOK OF PHYSIOLOGY.

As was said before, animal protoplasm is pre-eminently katabolic, and the evidence of its katabolism is found in the waste products, sucb as C02, II.O, and area, which arc given off from animal organisms. Assimilation and disassimilation, or anabolism and katabolism, go hand in hand, and together constitute an ever-recurring cycle of activity that persists as long as the material retains its living structure, and is designated under the name metabolism. In most forms of living matter metabolism is in some way self-limited, so that gradually it becomes less perfect, old age comes on, and finally death ensues. It has been asserted that originally the metabolic activity of protoplasm was self-perpetuating — that, barring accident, the cycle of changes would go on forever. Resting upon this assumption it has been suggested by Weissmann that the protoplasm of the reproductive elements still retains this primitive and perfect metabolism and thus provides for the continuity of life. The speculations bearing upon this point will be discussed in more detail in the section on Reproduction.

Reproduction in some form is also practically a universal property of living matter. The unit of structure among living organisms is the cell. Under proper conditions of nourishment the cell may undergo separation into two daughter cells. In some cases the separation takes place by a simple act of fission, in other cases the division is indirect and involves a number of interesting changes in the structure of the nucleus and the protoplasm of the body of the cell. In the latter case the process is spoken of as karyokinesis or mitosis. This act of division was supposed formerly to be under the con- trol of the nucleus of the cell, hut modern histology has shown that in kary- okinetic division the process, in many cases at least, is initiated by a special structure to which the name centrosome has been given. The many-celled animals arise by successive divisions of a primitive cell, the ovum, and in the higher forms of life the ovum requires to be fertilized by union with a sper- matozoon before cell-division becomes possible. The sperm-cell acts as a stimulus to the egg-cell (see section on Reproduction), and rapid cell-division is the result of their union. It must be noted also that the term reproduc- tion includes the power of hereditary transmission. The daughter-cells are

similar in form to the parent-cell, and tl rganism produced from a fertilized

ovum is substantially a facsimile of the parent forms. Living matter, there- fore, not only exhibits the power of separating off other units of living matter, but of transmitting to its progeny its own peculiar internal structure and properties.

Contractility and conductivity are properties exhibited in one form or another in all animal organisms, and we must concede that they are to be counted among the primitive properties of protoplasm. The power of con- tracting or shortening is, in fact, one of the commonly recognized features of a living thing. It is generally present in the simplest forms of animal as well as vegetable life, although in the more specialized forms it is found most highly developed in animal organisms. The opinion seems to be general among physiologists that wherever this property is exhibited, whether in the

INTlt OD UCTIO N. 2 1

formation of the pseudopodia of an amoeba or white blood-corpuscle, or in the vibratile movements of ciliary structures, or in the powerful contractions of voluntary muscle, the underlying mechanism by which the shortening is produced is essentially the same throughout. However general the property may be, it cannot be considered as absolutely characteristic of living struc- ture. As was mentioned before, Engelmann ' has been able to show that a dead catgut string when surrounded by water of a certain temperature and exposed to a sudden additional rise of temperature will contract or shorten in a man- ner closely analogous to the contraction of ordinary muscular tissue, and it is not at all impossible that the molecular processes involved in the shortening of the catgut string and the muscle-fibre may be esseutiallv the same.

That conductivity is also a fundamental property of primitive protoplasmic structure seems to be assured by the reactions which the simple motile forms of life exhibit when exposed to external stimulation. An irritation applied to one point of a protoplasmic mass may produce a reaction involving other parts, or indeed the whole extent of the organism. The phenomenon is most clearly exhibited in the more specialized animals possessing a distinct nervous system. In these forms a stimulus applied to one organ, as for instance light acting upon the eve, may be followed by a reaction involving quite distant organs, such as the muscles of the extremities, and we know that in these cases the irritation has been conducted from one organ to the other by means of the nervous tissues. But here also we have a property that is widely exhibited in inanimate nature. The conduction of heat, electricity, and other forms of energy is familiar to every one. While it is quite possible that con- duction through the substance of living protoplasm is something mi generis, and does not find a strict parallel in dead structures, yet it must be admitted that it is conceivable that the molecular processes involved in nerve conduction may be essentially the same as prevail in the conduction of heat through a solid body, or in the conduction of a wave of pressure through a liquid mass. At present we know nothing definite as to the exact nature of vital conduction, and can therefore affirm nothing.

The four great properties enumerated, namely, nutrition or assimilation (including digestion, secretion, absorption, excretion, anabolism, and katabolism), reproduction, conduction, and contractility, form the important features which we may recognize in all living things and which we make use of in distin- guishing between dead and living matter. A fifth property perhaps should be added, that of sensibility or sensation, but concerning this property as a general accompaniment of living structure our knowledge is extremely im- perfect; something more as to the difficulties connected with this subject will •be said presently. The four fundamental properties mentioned are all ex- hibited in some degree in the simplest forms of life, sueli as the protozoa. In the more highly organized animals, however, we find thai specialization of function prevails. Hand in hand with the differentiation in form that is

displayed in the structure of tin istituent tissues there goes a specialization

1 Ueber dt'n Uraprung der Muskelkraft, Leipzig, 1893.

22 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

in certain properties with a concomitant suppression of other properties, the outcome of which is that muscular tissue exhibits pre-eminently the power of contractility, the nerve tissues are characterized by a highly developed power of conductivity, and so on. While in the simple unicellular forms of animal life the fundamental properties are all somewhat equally exhibited within the compass of a single unit or cell, in the higher animals we have to deal with

a vast < linunity of cells segregated into tissues each of which possesses some

distinctive property. This specialization of function is known technically as the physiological division of labor. The beginning of this process may be recognized in the cell itself. The typical cell is already an organism of some complexity as compared with a simple mass of undifferentiated protoplasm. The protoplasm of the nucleus, particularly of that material iu the nucleus which i- designated as chromatin, is differentiated, both histologically aud physiologically, from the protoplasm of the rest of the cell, the so-called cyto- plasm. The chromatin material iu the resting cell is arranged usually in a network, but during the act of division (karyokinesis) it is segmented into a number of rods or filaments known as chromosomes. Iu the ovum there are good reasons for believing that the power of transmitting hereditary charac- teristics is dependent upon the structure of these chromosomes. The nucleus, moreover, controls in some way the metabolism of the entire cell, for it has been shown, iu some cells at least, that a non-nucleated piece of the cytoplasm is not only deprived of the power of reproduction, but has also such limited powers of nutrition that it quickly undergoes disintegration. On the other hand contractility and conductivity, and some of the functions connected with nutrition, such as digestion and excretion, seem often to be specialized iu the cytoplasm. As a further example of differentiation in the cell itself the ex- istence of the centrosome may be referred to. The centrosome is a body of very minute size that has been discovered in numerous kinds of cells. It is considered by many observers to be a permanent structure of the cell, lying either in the cytoplasm, or possibly in some discs within the boundaries of the nucleus. When present it seems to have some special function in connection with the movements of the chromosomes during the act of cell-division. In the many-celled animals the primitive properties of protoplasm become highly developed, in consequence of this subdivision of function among the various tissues, and in many ways the most complex animals are, from a physiological standpoint, the simplest for purposes of study, since in them the various prop-' erties of living matter are not only exhibited more distinctly, but each is, as it were, isolated from the others and can therefore be investigated more directly. We are at liberty to suppose that the various properties so clearly recognizable in the differentiated tissues of higher animals are all actually or potentially contained in the comparatively undifferentiated protoplasm of the simplest uni- cellular forms. That the lilies of variation, or in other words the direction of specialization in form and function, are not infinite, but on the contrary comparatively limited, seems evident when we reflect that in spite of the numerous branches of the phylogenetic stem the properties as well as the

poss

INTR OD UCTION. 21 1

forms of the differentiated tissues throughout the animal kingdom are strikingly alike. Striated muscle, with the characteristic property of sharp and powerful contraction, is everywhere found; the central nervous system in the inver- tebrates is built upon the same type as in the highest mammals, and the variations met with in different animals are probably but varying degrees of perfection in the development of the innate possibility contained in primitive protoplasm. It is not too much to say, perhaps, that were we acquainted with the structure and chemistry of the ultimate units of living substance, the key to the possibilities of the evolution of form and function would be in our ossession.

Most interesting suggestions have been made in recent years as to the essentia] molecular structure of living matter. These views are necessarily very incomplete and of a highly speculative character, and their correctness or incorrectness is at present beyond the range of experimental proof; never- theless they are sufficiently interesting to warrant a brief statement of some of them, as they seem to show at least the trend of physiological thought.

Pfliiger,1 in a highly interesting paper upon the nature of the vital pro- cesses, calls attention to the great instability of living matter. He supposes that living substance consists of very complex and very unstable molecules of a proteid nature which, because of the active intra-molecular movement pre- sent, are continually dissociating or falling to pieces with the formation of simpler and more stable bodies such as water, carbon dioxide and urea, the act of dissociation giving rise to a liberation of energy. " The intra-molecular heat (movement) of the cell is its life." He suggests that in this living mole- cule the nitrogen is contained in the form of a cyanogen compound, and that the instability of the molecule depends chiefly upon this particular grouping. Moreover the power of the molecule to assimilate dead proteid and convert it to living proteid like itself he attributes to the existence of the cyanogen group. It is known that cyanogen compounds possess the property of polymerization, that is, of combining with similar molecules to form more complex mole- cules, and we may suppose that the molecules of dead proteid when brought into contact with the living molecules are combined with the latter by a pro- cess analogous to polymerization or condensation. By this means the stable structure of dead proteid is converted to the labile structure of living proteid, and the molecules of the latter increase in size and instability. When living substance dies its molecules undergo alteration and become incapable of ex- hibiting the usual properties of life. Pfliiger suggests that the change may consist essentially in an absorption of water whereby the cyanogen grouping passes over into an ammonia grouping. Loew2 assumes also that the dif- ference between dead and living or active proteid lies chiefly in the fact thai in the latter we have a very unstable or labile molecule in which the atoms are in active motion. The instability of the molecules he likewise attributes to

1 Archiv fur die gesammte Physiologie, 1ST"), I'd. lo. S. 251.

2 Ibid., 1880, Bd. 22; Loew and Bokorny: Die chemische Kraftquelh in lebenden Protoplasma, Miinchen, 1882; Imperial Institute of Tokyo (College of Agriculture), 1894.

24 AN AMERICA X TEXT-BOOK OF PHYSIOLOGY.

the existence of certain groupings of the atoms. Influenced in part by the power of living material to reduce alkaline silver solutions, he supposes that the specially important labile group in the molecule is the aldehyde radical

— C ~ it • The nitrogen exists also in a labile amido- combination, — NH2,

and the active or living form of these two groups may be expressed by the

-CH-NH2 formula Q. 11 this grouping by chemical change became con-

= c -c j,

f 1TT VII

verted to the grouping __ ^ — PHOH' li wou^ ^orm a comparatively inert

compound such as we have in dead proteid. Latham1 proposes a theory which combines the ideas of Pfliiger and of Loew. He suggests that the living molecule may be composed of a chain of cyan-alcohols united to a ben- zene nucleus. The cyan-alcohols are obtained by the union of an aldehyde with hydrocyanic acid ; they contain, therefore, the labile-aldehyde grouping as well as the cyanogen nucleus to which Pfliiger attributes such importance.

Actual investigation of the chemical structure of living matter can hardly be said to have made a beginning. The first step in this direction has been made in the study of the chemical structure of the group of proteids which have usually been considered as forming the most characteristic constituent of protoplasm. Proteids as we obtain them from the dead tissues and liquids of the body have proved to be very varied in properties and structure, so much so in fact that it is impossible to give a satisfactory definition of the group. Man) of them can be obtained in a pure, even in a crystalline form, and their percentage composition can therefore be determined with ease. But the fundamental chemical structure that may be supposed to characterize the proteid group, and the changes in this structure producing the different varieties of proteids are matters as yet undetermined. Several promising efforts have been made to construct proteids synthetically, but the results obtained are at present incomplete. On the other hand, Kossel 2 has isolated from the spermatozoa of certain fishes a comparatively simple nitrogenous body of basic properties (protamine), which he regards as the simplest form of pndeid and the essential cure or nucleus characterizing the structure of the whole group. It is an interesting thought that in the heads of the sperma- tozoa with their complex possibilities of development and hereditary trans- mission, dependent as these properties must be upon the chemical structure of the germ protoplasm, there may be found the simplest form of proteid. Kossel's work, it may be noted, has not gone so far as to indicate the possible molecular structure of the protamines.

It has been assumed by many observers that the properties of living matter, as we recognize them, are not solely an outcome of the inner structure of the hypothetical living molecules. They believe that these latter units are

1 British Medical Journal, 1886, p. 629. Zeitschrift fur physiol. Chem., 1898; xxv. L899, xxvi.

INTR OD UCTION. 2 5

fashioned into larger secondary units each of which is a definite aggregate of chemical molecules and possesses certain properties or reactions that depend upon the mode of arrangement. The idea is similar to that advanced by mineralogists to explain the structure of crystals. They suppose that the chemical molecules are arranged in larger or smaller groups to which the name "physical molecules" has been given. So in living protoplasm it may be that the smallest particles capable of exhibiting the essential properties of life are groups of ultimate molecules, in the chemical sense, having a definite arrangement and definite physical properties. These secondary units of structure have been designated by various names such as " physiological molecules,"1 "somacules,"2 micellae,3 etc. Many facts, especially from the side of plant physiology, teach us that the physical constitution of protoplasm is probably of great importance in understanding its reaction to its environ- ment. Microscopic analysis is insufficient to reveal the existence or character of these " physiological molecules," but it has abundantly shown that proto- plasm has always a certain physical construction and is not merely a struc- tureless fluid or semi-fluid mass.

What has been said above may serve at least to indicate the prevalent physiological belief that the phenomena shown by living matter are in the 11 i;i in the result of the action of the known forms of energy through a substance of a complex and unstable structure which possesses, moreover, a physical organization responsible for some of the peculiarities exhibited. In other words, the phenomena of life are referred to the physical and chemical struc- ture of protoplasm and maybe explained under the general physical and chemical laws which control the processes of inanimate nature. Just as in the case of dead organic or inorganic substances we attempt to explain the differences in properties between two substances by reference to the difference in chemical and physical structure between the two, so with regard to living matter the peculiar differences in properties that separate them from dead matter, or for that matter the differences that distinguish one form of living- matter from another, must eventually depend upon the nature of the under- lying physical and chemical structure.

In the early part of this century many prominent physiologists were still so overwhelmed with the lnvsteriousness of life that they took refuge in the hypothesis of a vital force or principle of life. By this term was meant a something of an unknown nature that controlled all the phenomena ex- hibited by living things. Even ordinary chemical compounds of a so-called organic nature were supposed to be formed under the influence of this force, and it was thought could not be produced otherwise. The error of this latter view has been demonstrated conclusively within recent years : many of the substances formed by the processes of plant and animal life are now easily produced within the laboratory by comparatively simple synthetic methods.

1 Meltzer : " Ueber die fundamentale Bedeutung der Erechiitterung fur die lebende Ma- terie," Zeitschrift fur Biologie, Bd. xxx., 1894.

-Foster: Physiology (Introduction). sNSgeli: Theorieder Oahrung, Miinchen, 1879.

26 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

By the distinguished labors of Kinil Fischer1 even the structure of carbohy- drate bodies lias been determined, and bodies belonging to this group have been synthetically constructed in the laboratory. Moreover, the work of Schiitzenberger, Grimaux, and Pickering gives promise that before long pro- teid bodies may be produced by similar methods. Physiologists have shown, furthermore, that the digestion that takes place in the stomach or intestine may be effected also in test-tubes, and at the present day probably no one doubts that in the act of digestion we have to deal only with a series of chemical reactions which in time will be understood as clearly as it is possible to comprehend any form of chemical activity. Indeed, the whole history of food in the body follows strictly the great physical law- of the conservation of matter and of energy which prevail outside the body. No one disputes the proposition that the material of growth and of excretion comes entirely from the food. It has been demonstrated that the measureable energy given off from the body is all contained potentially within the food that is eaten.2 Living things, so far as can be determined, can only transform matter and en- ergy ; they cannot create or destroy them, and in this respect they are like inan- imate objects. But, in spite of the triumphs that have followed the use of the experimental method in physiology, every one recognizes that our knowledge is as yet very incomplete. Many important manifestations of life cannot be explained by reference to any of the known facts or laws of physics and chemistry, and in some cases these phenomena are seemingly removed from the field of experimental investigations. As long as there is this residuum of mystery connected with any of the processes of life, it is but natural that there should be two points of view. Most physiologists believe that as our knowledge and skill increase these mysteries will be explained, or rather will be referred to the same great final mysteries of the action of matter and energy under definite laws, under which we now classify the phenomena of lifeless matter. Others, however, find the difficulties too great, — they perceive that the laws of physics and chemistry are not completely adequate at present to explain all the phenomena of life, and assume that they never will be. They suppose that there is something in activity in living matter which is not present in dead matter, and which for want of a better term may be desig- nated as vital force or vital energy. However this may be, it seems evident that a doctrine of this kind stifles inquiry. Nothing is more certain than the fact that the great advances made in physiology during the last four decades are mainly owing to the abandonment of this idea of an unknown vital force and the determination on the part of experimenters to make the greatest pos- sible use of the known laws of nature in explaining the phenomena of life. There is n<> reason to-day to suppose that we have exhausted the results to be obtained by the application of the methods of physics and chemistry to the study of' living things, and as a matter of fact the great bulk of physiological research is proceeding along these lines. It is interesting, however, to stop

1 Die Chemieder Kohlenhydrale, Berlin, 1S94. 2Kubner : Tkitschrift fur Biologic, Bd. xxx. 8. 73, 1894.

INTRODUCTION. 27

for a moment to examine briefly some of the problems which as yet have escaped satisfactory solution by these methods.

The phenomena of secretion and absorption form important parts of the digestive processes in higher animals, and without doubt are exhibited in a minor degree in the unicellular types. In the higher animals the secretions may be collected and analyzed, and their composition may be compared with that of the lymph or blood from which they are derived. It has been found that secretions may contain entirely new substances not found at all in the blood, as for example the mucin of saliva or the ferments and HC1 of gastric juice; or, on the other hand, that they may contain substances which, although pres- ent in the blood, are found in much greater percentage amounts in the secre- tion— as, for instance, is the case with the urea eliminated in the urine. In the latter case we have an instance of the peculiar, almost purposeful, elective action of gland-cells of which many other examples might be given. With regard to the new material present in the secretions, it finds a sufficient general explanation in the theory that it arises from a metabolism of the protoplasmic material of the gland-cell. It offers, therefore, a purely chemical problem which may and probably will be worked out satisfactorily for each secretion. The selective power of gland-cells for particular constituents of the blood is a more difficult question. We find no exact parallel for this kind of action in chemical literature, but there can be no reasonable doubt that the phe- nomenon is essentially a chemical or physical reaction involving the activity of some of the forms of energy with which the study of inanimate objects has already made us partially familiar. We may indulge the hope that the details of the reaction will be discovered by more complete chemical and micro- scopical study of the structure of these cells. If in the meantime the act of selection is spoken of as a vital phenomenon, it is not meant thereby that it is referred to the action of an unknown vital force, but only that it is a kind of action dependent upon the living structure of the cell-substance.

The act of absorption of digested products from the alimentary canal was for a time supposed to be explained completely by the laws of imbibition, diffusion, and osmosis. The epithelial lining and its basement membrane form a septum dividing the blood and lymph on the one side from the contents of the alimentary canal on the other. Inasmuch as the two liquids in question ;irc of unequal composition with regard to certain constituents, a diffusion stream should be set up whereby the peptones, sugar, salts, etc. would pass from the liquid in the alimentary canal, where they exist in greater concen- tration, into the blood, where the concentration is less. Careful work of recent years has shown that the laws of diffusion and osmosis are not adequate to explain fully the absorption that actually occurs; a more detailed account of the difficulties met with may be found in the section on Digestion and Nutrition. It has become customary to speak of absorption as caused in part by the physical laws of diffusion and osmosis, and in pari by the vital activity of the epithelial cells. It will be noticed that the vital property in this case is again an elective affinity for certain constituents similar to that which has been

28 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

referred to in discussing the act of secretion. The mere fact that the physical theory has proved so far to be insufficient is in itself no reason for abandoning all hope of a satisfactory explanation. Most physiologists probably believe that further experimental work will bring this phenomenon out of its obscurity and show that it is explicable in terms of known physical and chemical forces exerted through the peculiar substance of the absorptive cell.

The facts of heredity and consciousness offer difficulties of a much graver character. The function of reproduction is two-sided. In the first place there is an active multiplication of cells, beginning with the segmentation of the ovum into two blastomeres, and continuing in the larger animals to the formation of an innumerable multitude of cellular units. In the second place there is present in the ovum a form-building power of such a character that the great complex of eel Is arising from it produces not a heterogeneous mass, but a definite organism of the same structure, organ for organ and tissue for tissue, as the parent form. The ovum of a starfish develops into a starfish, the ovum of a dog into a dog, and the ovum of man into a human being. Herein lies the great problem of heredity. The mere multiplication of cells by direct or indirect division is not beyond the range of a conceivable me- chanical explanation. Given the properties of assimilation and contractility it is possible that the act of cell-division may be traced to purely physical and chemical causes, and already cytological work is opening the way to credible hypotheses of this character. But the phenomena of heredity, on the other hand, are too complex and mysterious to justify any immediate expectation that they can be explained in terms of the known properties of matter. The crude theories of earlier times have not stood the test of investigation by modern methods, the microscopic anatomy of both ovum and sperm showing that they are to all appearances simple cells that exhibit no visible signs of the wonderful potentialities contained within them. Histological and experi- mental investigation has, however, cleared away some of the difficulties for- merlv surrounding the subject, for it has shown with a high degree of prob- ability that the power of hereditary transmission resides in a particular sub- stance in the nucleus, namely in the so-called chromatin materal that forms the chromosomes. The fascinating observations J that have led to this con- clusion promise to open up a new field of experimentation and speculation. It seems to be possible to study heredity by accepted scientific methods, and we may therefore hope that in time more light will be thrown upon the con- ditions of its existence and possibly upon the nature of the forces concerned in it> production.

In the facts of consciousness, lastly, we are confronted with a problem seemingly more difficult than heredity. In ourselves we recognize different states of consciousness following upon the physiological activity of certain parts of the central nervous system. We know, or think we know, that these so-called psychical state- are correlated with changes in the protoplasmic material of the cortical cells of the cerebral hemispheres. When these cells 'Wilson: Tht Cell in Development and Inheritance, 1896.

INTRODUCTION. 29

are stimulated, psychical states result; when they are injured or removed, psychical activity is depressed or destroyed altogether according to the extent of the injury. From the physiological standpoint it would seem to be as justifiable to assert that consciousness is a property of the cortical nerve-cells as it is to define contractility as a property of muscle-tissue. But the short- ening of a muscle is a physical phenomenon that can be observed with the senses — be measured and theoretically explained in terms of the known prop- erties of matter. Psychical states are, however, removed from such methods of study ; they are subjective, and cannot be measured or weighed or otherwise esti- mated with sufficient accuracy and completeness in terms of our units of energy or matter. There must be a causative connection between the objective changes in the brain-cells and the corresponding states of consciousness, but the nature of this connection remains hidden from us ; and so hopeless does the problem seem that some of our profouudest thinkers have not hesitated to assert that it can never be solved. Whether or not consciousness is possessed by all animals it is impossible to say. In ourselves we know that it exists, and we have convincing evidence, from their actions, that it is possessed by many of the higher animals. But as we descend in the scale of animal forms the evidence becomes less impressive. It is true that even the simplest forms of animal life exhibit reactions of an apparently purposeful character which some have explained upon the simple assumption that these animals are endowed with consciousness or a psychical power of some sort. All such reactions, however, may be explained, as in the case of reflex actions from the spinal cord, upon purely mechanical principles, as the necessary response of a definite physical or chemical mechanism to a definite stimulus. To assume that in all cases of this kind conscious processes are involved amounts to making psychical activity one of the universal and primitive properties of protoplasm whether animal or vegetable, and indeed by the same kind of reasoning there would seem to be no logical objection to extending the property to all matter whether living or dead. All such views are of course purely speculative. As a matter of fact we have no means of proving or disproving, in a scientific sense, the exist- ence of consciousness in lower forms of life. To quote an appropriate remark of Huxley's made in discussing this same point with reference to the crayfish, " Nothing short of being a crayfish would give1 us positive assurance that such an animal possesses consciousness." The study of psychical states in our- selves, for reasons which have been suggested above, does not usually form a part of the science of physiology. The matter has been referred to lure simply because consciousness is a fact that our science cannot :is yet explain.

So far, some of the broad principles of physiology have been considered — principles which are applicable with more or less modification to all forms of animal life and which make the basis of what is known as general physiology. It must be borne in mind, however, that each particular organism possesses a special physiology of its own, which consists in part in a study of the properties exhibited by the particular kinds or variations of protoplasm in each individual, and in large part also in a study of the various median-

30 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

isms existing in each animal. In the higher animals, particularly, the com- binations of various tissues and organs into complex mechanisms such as those ol* respiration, circulation, digestion, or vision, differ more or less in each group and to a minor extent in each individual of any one species. It follows, therefore, that each animal has a special physiology of its own, and in this sense we may speak of a special human physiology. It need scarcely be -aid that the special physiology of man is very imperfectly known. Books like the present one, which profess to neat of human physiology, con- tain in reality a large amount of general and special physiology that has been derived from the study of lower animal forms upon which exact experi- mentation is possible. Most of our fundamental knowledge of the physiology of the heart and of muscles and nerves has been derived from experiments upon frogs and similar animals, and much of our information concerning the mechanisms of circulation, digestion, etc. has been obtained from a study of other mammalian forms. We transfer this knowledge to the human being, and in general without serious error, since the connection between man and related mammalia is as close on the physiological as it is on the morphological side, and the fundamental or general physiology of the tissues seems to be every- where the same. Gradually, however, the material for a genuine special human physiology is being acquired. In many directions special investigation upon man is possible; for instance, in the study of the localization of function in the cerebral cortex, or the details of body metabolism as obtained by exam- ination of the excreta, or the peculiarities of vaso-motor regulation as revealed by the use of plethysmography methods, or the physiological optics of the human eye. This special information, as rapidly as it is obtained, is incorpo- rated into the text-books of human physiology, but the fact remains that the greater part of our so-called human physiology is founded upon experiments upon the lower aninals.

Physiology as a science is confessedly very imperfect; it cannot compare in exactness with the sciences of physics and chemistry. This condition of affairs need excite no surprise when we remember the very wide field that physiology attempts to cover,a held co-ordinate in extent with the physics as well as the chemistry of dead matter, and the enormous complexity and instability of the form of matter that it seeks to investigate. The progress of physiology is therefore comparatively slow. The present era seems to be one mainly of accumulation of reliable data derived from laborious experiments and observa- tions. The synthesis of these facts into great laws or generalizations is a task l.ir i lie future. Corresponding with the diversity of the problems to be solved we find that the methods employed in physiological research are mani- fold in character. Inasmuch as animal organisms are composed either of single cells or aggregates of cells, it follows that every anatomical detail with regard to the organization of the cell itself or the connection between dif- fered cells, and every advance in our knowledge of the arrangement of the tissues and organs that form the re complicated mechanisms, is of imme- diate value to phvsiology. The microscopic anatomy of the cell (a branch of

I ST HO DICTION. 31

histology that is frequently designated by the specific name of cytology),

general histology, and gross anatomical dissection arc therefore frequently employed in physiological investigations, and form what may be called the observational side of the science. On the other hand, we have the experimental methods, that seek to discover the properties and functional relationships of the tissues and organs by the use of direct experiments. These experiments may be of a surgical character, involving the extirpation or destruction or alteration of known parts by operations upon the living animal, or they may consist in the application of the accepted methods of physics and chemistry to the living organism. The physical methods include the study of the physical properties of living matter and the interpretation of its activity in terms of known physical laws, and also the use of various kinds of physical apparatus such as manometers, galvanometers, etc. for recording with accuracy the phenomena exhibited by living tissues. The chemical methods imply the application of the synthetic and analytic operations of chemistry to the study of the composition and structure of living matter aud the products of its activity. The study of the subjective phenomena of conscious life — in fact, the whole question of the psychic aspects or properties of living matter — for reasons that have been mentioned is not usually included in the science of physiol- ogy, although strictly speaking it forms an integral part of the subject. This province of physiology has, however, been organized into a separate science, p-ychology, although the boundary line between psychology as it exists at present and the scientific physiology of the nervous system cannot always be sharply drawn.

It follows clearly enough from what has been said of the methods used in animal physiology that even an elementary acquaintance with the subject as a science requires some knowledge of general histology and anatomy, human as well as comparative, of physics, and of chemistry. When this preliminary training is. lacking, physiology cannot be taught as a science; it becomes simply a heterogeneous mass of facts, and fails to accomplish its function as a preparation for the scientific study of medicine. The mere facts of physiology arc valuable, indeed indispensable, as a basis for the study of the succeed im.: branches of the medical curriculum, but in addition the subject, properly taught, should impart a scientific discipline and an acquaintance with the possible methods of experimental medicine ; for among the so-called experi- mental branches of medicine physiology is the most developed and the ino.-t exact, and serves as a type, so far as methods are concerned, to which the others must conform.

II. BLOOD AND LYMPH.

BLOOD.

A. General Properties : Physiology op the Corpuscles.

The blood of the body is contained in a practically closed system of tubes, the blood-vessels, within which it is kept circulating by the force of the heart- beat. The blood is usually spoken of as the nutritive liquid of the body, but its functions may be stated more explicitly, although still in quite general terms, by saying that it carries to the tissues food-stuffs after they have been properly prepared by the digestive organs; that it transports to the tissues oxygen absorbed from the air in the lungs ; that it carries off from the tissues various waste products formed in the processes of disassimilatioD ; that it i> the medium for the transmission of the internal secretion of certain glands ; and that it aids in equalizing the temperature and water contents of the body. It is quite obvious, from these statements, that a complete consideration of the physiological relations of the blood would involve substantially a treat- ment of the whole subject of physiology. It is proposed, therefore, in this section to treat the blood in a restricted way — to consider it, in fact, as a tissue in itself, and to study its composition and properties without special reference to its nutritive relationship to other parts of the body.

Histological Structure. — The blood is composed of a liquid part, the plasma, in which float a vast number of microscopic bodies, the blood-corpus- cles. There are at least three different kinds of corpuscles, known respectively as the red corpuscles; the white corpuscles or leucocytes, of which in turn there are a number of different kinds; and the blood-plate*. As the details of structure, size, and number of these corpuscles belong properly to text- books on histology, they will be mentioned only incidentally in this section when treating of the physiological properties of the corpuscles. Blood-plasma, when obtained free from corpuscles, is perfectly colorless in thin layers — for example, in microscopic preparations; when seen in large quantities it shows a slightly yellowish tint, the depth of color varying with dillerent animals. This color is due to the presence in small quantities of a special pigment, the nature of which is not definitely known. The ml color of blood is not due, there- fore, to coloration of the blood-plasma, but is caused by the mass of red cor- puscles held in suspension in this liquid. The proportion by bulk of plasma to corpuscles is usually given, roughly, as two to one.

Illood-xcrum and I )<jlbrinafed Blood. — In connection with the explanation

of the term " blood-plasma" just given, it will be convenient to define briefly

the terms " blood-serum " and "defibrinated blood." Blood, after it escapes

from the vessels, usually clots or coagulates; the nature of this process is

Vol. I.— 3 :v.\

34 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

discussed in detail on p. 54. The clot, as it forms, gradually shrinks and squeezes out a clear liquid to which the name blood-serum is given. Serum resembles the plasma of normal blood in general appearance, but differs from it in composition, as will be explained later. At present we may say, by way <>f a preliminary definition, that blood-serum is the liquid part of blood after coagulation has taken place, as blood-plasma is the liquid part of blood before coagulation has taken place. If shed blood is whipped vigorously with a rod or some similar object while it is clotting, the essential part of the clot — namely, the fibrin — forms differently from what it docs when the blood i- allowed to coagulate quietly; it is deposited in shreds on the whipper. Blood thai has been treated in this way is known as defibrinated blood. It consists of blood-serum plus the red and white corpuscles, and as far as appearance- go it resembles exactly normal blood ; it has lost, however, the power of clot- ting. A more complete definition of these terms will be given after the sub- ject of coagulation has been treated.

Reaction. — The reaction of blood is alkaline, owing mainly to the alka- line salts, especially the carbonates of soda, dissolved in the plasma. The degree of alkalinity varies with different animals: reckoned as Xa,C03, the alkalinity of dog's blood corresponds to 0.2 per cent, of this salt; of human blood, 0.35 per cent. The alkaline reaction of blood is very easily demon- sl rated upon clear plasma free from corpuscles, but with normal blood the red color prevents the direct application of the litmus test. \ number of simple devices have been suggested to overcome this difficulty. For example, the method employed by Zuutz is to soak a strip of litmus-paper in a concentrated solution of NaCl, to place on this paper a drop of blood, and, after a few seconds, to remove the drop with a stream of water or with a piece of filter- paper. The alkaline reaction becomes rapidly less marked after the blood has been shed; it varies also slightly under different conditions of normal life and in certain pathological conditions. After meals, for instance, during the act of digestion, it is said to be increased, while, on the contrary, exercise causes a diminution. In no case, however, does the reaction become acid. For details of the methods used for quantitative determinations of the alka- linitv of human blood, reference must be made to original sources.1

Specific Gravity. — The specific gravity of human blood in the adult male may vary from 1041 to 1067, the average being about 1055. Jones2 made a careful study of the variations in specific gravity of human blood under different conditions of health and disease, making use of a simple method which requires only a few drops of blood for each determination. He found that the specific gravity varies with age and sex, that it is diminished after eating and is increased by exercise, that it falls slowly during the day and rises gradually during the night, and that it varies greatly in individuals, "so much so that a specific gravity which is normal for one may be a sign of dis- ease in another." The specific gravity of the corpuscles is slightly greater

1 Wright: The Lancet, 1897, p. 8; Winternitz: Zeitschrifl furphysiol. Chemie, 1891, Bd. 15, s. 505.

2 Journal o) PhysiiAofjy, 1891, vol. xii., p. 299.

BLOOD. 35

than that of the plasma. For this reason the corpuscles in shed blood, when its coagulation is prevented or retarded, tend to settle to the bottom of the containing utensil, leaving a more or less clear layer of supernatant plasma. Among themselves, also, the corpuscles differ slightly in specific gravity, the red corpuscles being heaviest and the blood-plates being lightest.

Red Corpuscles. — The red corpuscles in man and in all the mammalia, with the exception of the camel and other members of the group Camelidae, are biconcave circular disks without nuclei; in the Camelidae they have an elliptical form. Their average diameter in man is given as 7.7 ft (1// = 0.001 of a mm.); their number, which is usually reckoned as so many in a cubic millimeter, varies greatly under different conditions of health and disease. The average number is given as 5,000,000 per cubic mm. for males and 4,500,000 for females. The red color of the corpuscles is due to the presence in them of a pigment known as " haemoglobin." Owing to the minute size of the corpuscles, their color when seen singly under the microscope is a faint yellowish-red, but when seen in mass they exhibit the well-known blood-red color, which varies from scarlet in arterial blood to purplish-red in venous blood, this variation in color being dependent upon the amount of oxygen contained in the blood in combination with the haemoglobin. Speaking generally, the function of the red corpuscles is to carry oxygen from the lungs to the tissues. This function is entirely dependent upon the presence of haemoglobin, which has the power of combining easily with oxygen gas. The physiology of the red corpuscles, therefore, is largely contained in a description of the properties of haemoglobin.

Condition of the Haemoglobin in the Corpuscle. — The finer structure of the red corpuscle is not completely known. It is commonly believed that the corpuscle consists of two substances — a delicate, extensible, colorless pro- toplasmic material, which gives to the corpuscle its shape and which is known as the stroma, and the haemoglobin. The latter constitutes the bulk of the cor- puscle, forming as much as 95 per cent, of the solid matter. It was formerly thought that haemoglobin is disseminated as such in the interstices of the porous spongy stroma, but there seem to be reasons now for believing that it is present in the corpuscles in some combination the nature of which is not fully known. This belief is based upon the fact that Hoppe-Seyler ' has shown that haemoglobin while in the corpuscles exhibits certain minor differ- ences in properties as compared with haemoglobin outside the corpuscles. In various ways the compound of haemoglobin in the corpuscles may be destroyed, the haemoglobin being set iri'v and passing into solution in the plasma. Blood in which this change has occurred is altered in color and is known as " laky blood." In thin layers it is transparent, whereas normal blood with the haemoglobin still in the corpuscles is quite opaque even in very thin strata. Blood may be made laky by the addition of ether, of chloroform, of bile or the bile acids, of the serum of other animals, by an excess of water, by alternately freezing and thawing, and by a number of other methods. In connection with two of these methods of discharging haemoglobin from the 1 ZeUschrifi fur physiologische Chemie, Bd, xiii., 1889, S. 177.

3b' AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

corpuscles there have come into use in current medical and physiological literature two technical terms which it may be well to attempt to define.

Globulicidal Action of Serum. — It was shown first by Landois that the serum of one animal may have the property of destroying the red corpuscles in the blood of another animal, thus making the blood laky. This fact, which ha- since been investigated more fully, is now designated under the term of " globulicidal " action of the serum. Jt has been found that different kinds of serum show different degrees of globulicidal activity, and that white as well as red corpuscles may be destroyed. Dog's serum or human serum is strongly globulicidal to rabbit's blood. Tt would seem that this action is not due to mere variations in the amounts of inorganic salts in the different kinds of serum, since the remarkable tact has been discovered that heating serum to 55° or 60° C. for a few minutes destroys its globulicidal action, although such treatment causes no coagulation of the proteids nor any visible change in the liquid. Moreover, it is known that foreign scrum injected into the veins of a living animal may exert a marked toxic effect that cannot be explained solely by its globulicidal action — for instance, 7 to 14 c.c. of fresh dog's serum will suffice to kill a rabbit — and lastly, serum is known to exert a similar destructive effect on bacteria, its so-called bactericidal action. These three effects of serum, globulicidal, bactericidal and toxic, seem all to be destroyed I >y heating to 50°-60° C, and it is possible that they arc all traceable to the existence in the blood of some proteid substance, an alexine, which is present in -mall quantity and is different for each species of animal, the material in the blood of one species being more or less globulicidal and toxic, as a rule, to the tissues of another species.1

Tsoto i iii- Solutions. — When blood or defibrinated blood is diluted with water, a point is soon reached at which haemoglobin begins to pass out of the corpuscles into the plasma or the serum, and the blood begins to appear laky. It appears that the liquid surrounding the corpuscles must have a certain concentration as regards salts or other soluble substances, such as sugar, in order to prevent the entrance of water into the substance of the corpuscle. Normally the substance of the red corpuscle possesses a certain osmotic pressure which may be supposed to be equal to that of the plasma by which it is surrounded, so that the interchange of water between them is at an equilibrium. If the concentration of the outside Liquid is diminished, this equilibrium is destroyed and water passes into the corpuscle ; if the dilution has been sufficient, enough water passes into the corpuscle to make it swell and eventually to force out the haemoglobin. Liquids containing inorganic salt-, or other soluble substances that possess an osmotic pressure sufficient to pre- vent the imbibition of water by the corpuscles, are -aid to be "isotonic to the corpuscles." Red corpuscles suspended in such liquids do not change in shape nor lose their haemoglobin. When solutions of different substances are com- pared from this standpoint, it is found that the concentration necessary varies with the substance used. Tim-, a solution ofNaClofO.64 per cent, is isotonic

1 For :i recenl paper .-mil the literature see Friedenthal and Lewandowsky, Arehiv fiir Phys~ - 531.

BLOOD. 37

with a solution of sugar of 5.5 per cent, or a solution of KX03 of 1.09 per cent. When placed in any of these three solutions red corpuscles <1<» not take up water — at least not in quantities sufficient to discharge the haemo- globin. For a more complete account of these relations the reader is referred to original sources (Hamburger1). A solution whose osmotic pressure is lower than that of blood-plasma is said to be hypo-isotonic <>r hypotonic to blood. Such solutions may cause the blood to lake. Solutions of a higher osmotic pressure than that of the plasma are spoken of as hvper-isotonic or hypertonic. Whenever it is necessary to dilute shed blood or to inject any quantity of a neutral liquid into the circulation care must be taken to have the solution isotonic with the blood. (See p. 65 for an explanation of the term osmotic pressure.)

Nature and Amount of Haemoglobin. — Haemoglobin is a very complex substance belonging to the group of combined proteids. (For the definition and classification of proteids, as well as for the purely chemical properties of haemoglobin and its derivatives, reference must be made to the section on "The Chemistry of the Body.") When decomposed in various ways haemoglobin breaks up into a proteid (globin, 86 to 96 per cent.), a simpler pigment (haemal- tin, 4 per cent.), and an unknown residue.2 When the decomposition takes place in the absence of oxygen, the products formed are globin and haemo- chromogen, instead of globin and luematin. Haemochromogen in the presence of oxygen quickly undergoes oxidation to the more stable luematin. Hoppe- Seyler has shown that haemochromogen possesses the chemical grouping which gives to haemoglobin its power of combining readily with oxygen and its distinctive absorption spectrum. On the basis of facts such as these, haemo- globin may be defined as a compound of a proteid body with haemochromogen. It seems, then, that although the haemochromogen portion is the essential tiling, giving to the molecule of haemoglobin its valuable physiological prop- erties as a respiratory pigment, yet in the blood-corpuscles this substance is incorporated into the much larger and more unstable molecule of haemoglobin, whose behavior toward oxygen is different from that of the haemochromogen itself, the difference being mainly in the fact that the haemoglobin as it exists in the corpuscles forms with oxygen a comparatively feeble combination that may be broken up readily with liberation of the gas.

Haemoglobin is widely distributed throughout the animal kingdom, being

found in the blood-corpuscles of mammalia, birds, reptiles, amphibia, and

fishes, and in the; blood or blood-corpuscles of many of the invertebrates.

The compositi >f its molecule is found to vary somewhat in different animals,

so that, strictly speaking, there are probably a number of different (onus

of haemoglobin — all, however, closely related in chemical and physiological

properties. Elementary analysis of dog's haemoglobin shows the following

percentage composition (Jaquet) : C 53.91, H 6.62, N 15.98, S 0.542,

Fe 0.333, O 22.62. Its molecular formula is given as < \J I ,..,,, N,,,S,Fe< ),ls,

which would make the molecular weight 16. <>(!!». Other estimates are given of

1 Du Bois-Keyniond's Arehivfur Physiologic, L886, 8. 176; 1887, 8. 31.

1 See Scbnlz, Zeitschrift fur physiol. Chemie, Bd. 24; also Lauraw, ibid., Bd. 26.

38 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the molecular formula, but they agree at least iu showing that the molecule is of enormous size. The molecular formula for haemochromogen is much sim- pler; one estimate makes it C31H.j6X4Fe05. The exact amount of heemoglobin

in human blood varies naturally with the individual and with different condi- tions of life. According to Preyer,1 the average amount for the adult male is 14 grams of haemoglobin to each 100 grams of blood. It is estimated that in the blood of a man weighing 68 kilos, there are contained about 750 grams of haemoglobin, which is distributed among some twenty-five trillions of corpuscles, giving a total superficial area of about 3200 square meters. Practically all of t 1 1 i — large surface of haemoglobin is available for the absorption of oxygen from the air in the lungs, for, owing to the great number and the minute size of the capillaries, the blood, in passing through a capillary area, becomes subdivided to such an extent that the red corpuscles stream through the capil- laries, one may say, in single file. In circulating through the lungs, therefore, each corpuscle becomes exposed more or less completely to the action of the air, and the utilization of the entire quantity of haemoglobin must be nearly perfect. It may be worth while to call attention to the fact that the biconcave form of the red corpuscle increases the superficies of the corpuscle and tends to make the surface exposure of the haemoglobin more complete.

Compounds with Oxygen and other Gases. — Haemoglobin has the property of uniting with oxygen gas in certain definite proportions, forming a true chemical compound. This compound is known as oxyhoemoglobin ; it is formed whenever blood or haemoglobin solutions are exposed to air or otherwise brought into contact with oxygen. Each molecule of haemoglobin is supposed to combine with one molecule of oxygen, and it is usually estimated that 1 gram of dried haemoglobin (dog) can take up 1.59 c.c. of oxygen measured at 0° C. and TOO mm. of barometric pressure, although according to a later determination by Hufneiy the ()-capacity of the lib of ox's blood is only 1.34 c.c. () to each gram of III). Oxyhemoglobin is not a very firm compound. If placed iu an atmosphere containing no oxvgen, it will be dissociated, giving off free oxygen and leaving behind haemoglobin, or, :is it is often called by way of distinction, "reduced haemoglobin." This power of combining with oxygen to form a loose chemical compound, which in turn can be dissociated easily wdien the oxygen-pressure is lowered, makes possible the function of haemoglobin in the blood as the carrier of oxygen from the lungs to the tissues. The details of this process are described in the section on Respiration. Haemoglobin forms with carbon- monoxide gas (CO) a compound, similar to oxyhemoglobin, which is known as carbon-monoxide heemoglobin. In this compound also the union takes place in tin' proportion of one molecule of haemoglobin to one molecule of the gas. The compound formed differs, however, from oxy- haemoglobin in being much more stable, and it is for this reason that the breathing of carbon monoxide gas is liable to prove fatal. The CO unites with the haemoglobin, forming a firm compound; the tissues of the bod v are

1 Die Blutkrystalle, Jena, 1871.

2 Archir Oh- Physiologie, 1894, 8. 130.

BLOOD. 39

thereby prevented from obtaining their necessary oxygen, and death results from suffocation or asphyxia. Carbon monoxide forms one of the constituents of coal-gas. The well-known fatal effect of breathing coal-gas for some time, as in the case of individuals sleeping in a room where gas is escaping, is trace- able directly to the carbon monoxide. Nitric oxide (NO) forms also with haemoglobin a definite compound that is even more stable than the CO- haemoglobin ; if, therefore, this gas were brought into contact with the blood, it would cause death in the same way as the CO.

Oxyhemoglobin, carbon-monoxide haemoglobin, and nitric-oxide haemoglo- bin are similar compounds. Each is formed, apparently, by a definite combina- tion of the gas with the haemochromogen portion of the haemoglobin molecule. and a given weight of haemoglobin unites presumably with an equal volume of each gas. In marked contrast tothese facts, Bohr x has shown that haemoglobin forms a compound with carbon-dioxide gas, carbo-hcemoglobin, in which the quantitative relationship of the gas to the haemoglobin differs from that shown by oxygen. In a mixture of O and C02 each gas is absorbed by haemoglobin solutions independently of the other, so that a solution of haemoglobin nearly saturated with oxygen can unite with as much C02 as though it held no oxygen in combination. Bohr suggests, therefore, that the O and the COL> must unite with different portions of the haemoglobin — the oxygen with the pigment portion, the haemochromogen, and the C02 possibly with the proteid portion. It seems probable that haemoglobin plays a part in the transportion of the earl ion dioxide as well as the oxygen of the blood, but its exact value in this respect as compared with the blood-plasma, which also acts as a carrier of COa, has not been definitely determined (see Respiration).

Presence of Iron in the Molecule. — It is probable that iron is quite generally present in the animal tissues in connection with nuclein compounds, but its existence in haemoglobin is noteworthy because it has long been known and because the important property of combining with oxygen seems to be connected with the presence of this element. According to the analyses made, the proportion of iron in haemoglobin varies somewhat in different animals: the figures given arc from 0.335 to 0.47 per cent. The amount of haemoglobin in blood may he determined, therefore, by making a quantitative determination of the iron. The amount of oxygen with which haemoglobin will combine may he expressed by saying that one molecule of oxygen will be fixed for each atom of iron in the haemoglobin molecule. In the decom- position of haemoglobin into globulin and haematin, which has been spoken of above, the iron is retained in the haematin.

Crystals. — Haemoglobin maybe obtained readily in the form of crystals (Fig. 1). As usually prepared, these crystals are really oxyhaemoglobin, but it has been shown that reduced haemoglobin also crystallizes, although with more difficulty. Haemoglobin from the blood of different animals varies to a marked degree in resped to the power of crystallization. From the blood of the rat, do^, cat, guinea-pig, and horse, crystals arc readily obtained, while haemoglobin from the blood of man and of most of the vertebrates crystallizes

1 Skandivavisches Archivf&r Physiologie, 1892, Bd. '■'<. S. -17.

40

AN AMERICAN 7 1: XT-BOOK OF PHYSIOLOGY.

much less easily. Methods tor preparing and purifying these crystals will be found in works on Physiological Chemistry. To obtain specimens quickly for examination under the microscope, one of the most certain methods is to take some blood from one of the animals whose haemoglobin ervstallizes

easily, plaee it in a test-tube, add to it a few- drops of ether, shake the tube thoroughly until the blood becomes laky — that is, until the haemoglobin is discharged into the plasma — and then place the tube on ice until the crystals are deposited. Small portions of the crystalline sedi-

Cment may then be removed to a glass I slide for examination. Haemoglobin

from different animals varies not only as to the ease with which it crystal- lizes, but in some cases also as to the form that the crystals take. In man and in most of the mammalia haemoglo- bin is deposited in the form of rhom- bic prisms; in the guinea-pig it crys- tallizes in tetrahedra (d, Fig. 1), and in the squirrel in hexagonal plates. The crystals are readily soluble in water, and by repeated crystallizations the haemo- globin may be obtained perfectly pure.

Fig. 1. -Crystallized hemoglobin fafter Frey): ^s j„ tne case of Other Soluble proteid- a, b, crystals from venous blood of man ; r, from t . ,

the blood of a cat; d, from the blood of a like bodies, solutions of haemoglobin are

gninea-pig; .from the blood of a hamster; /, precipitated by alcohol, by mineral acids, from the blood of a squirrel. l L J » J

by salts of the heavy metals, by boiling,

etc. Notwithstanding the fact that haemoglobin crystallizes so readily, it is not easily dialyzable, behaving in this respect like proteids and other colloidal bodies. The compounds which haemoglobin forms with carbon monoxide (CO) and nitric oxide (XO) are also crystallizable, the crystals being isomor- phous with those of oxyhemoglobin.

Absorption Spectra. — Solutions of haemoglobin and its derivative com- pounds, when examined with a spectroscope, give distinctive absorption bands. A brief account of the principle and arrangement of the spectroscope, although 1 1 n necessary for those familiar with the elements of Physics, is given by way of introduction to the description of these absorption bands.

Light, when made to pass through a glass prism, is broken up into its constituent rays, giving the play of rainbow colors known as the spectrum. A spectroscope is an apparatus for producing and observing a spectrum. A simple form, which illus- trates sufficiently well the construction of the apparatus, is shown in Figure 2, P being the glass prism giving the spectrum. Light falls upon this prism through the tube (a) to the left, known as the "collimator tube." A slit at the end of this tube (s) admits a narrow slice of light — lamplight or sunlight — which then, by means of a convex lens at the other end of the tube, is made to fall upon the prism

BLOOD.

41

(p) with its rays parallel. In passing through the prism the rays are dispersed by unequal refraction, giving a spectrum. The spectrum thus produced is examined by the observer with the aid of the telescope (b). When the telescope is properly focussed for the rays entering it from the prism (p), a clear picture of the spectrum is seen. The length of the spectrum will depend upon the nature and the number of prisms through which the light is made to pass. For ordinary purposes a short spectrum is preferable for hemoglobin bands, and a spectroscope with one prism is generally used. If the source of light is a lamp-flame of some kind, the spectrum is continuous, the colors gradually merging one into another from red to violet. If sunlight is used, the spectrum will be crossed by a number of narrow dark lines known as the " Frauuhofer lines"

pIG o — Spectroscope : p, the glass prism ; a, the collimator tube, showing the slit (s) through which the light is admitted ; b, the telescope for observing the spectrum.

(see PL I. , Frontispiece, for an illustration in colors of the solar spectrum). The position of these lines in the solar spectrum is fixed, and the more distinct ones are designated by letters of the alphabet, A, b, c, d, e, etc., as shown in the charts below. If while using solar light or an artificial light a solution of any substance which gives absorption bands is so placed in front of the slit that the light is obliged to traverse it, the spectrum as observed through the telescope will show one or more narrow or broad black bands, that are characteristic of the substance used and constitute its absorption spectrum. The positions of these bands may be designated by describing their relations to the Frauu- hofer lines, or more directly by stating the wave-lengths of the portions of the spectrum between which absorption takes place. Some spectroscopes are provided with a scale of wave-lengths superposed on the spectrum, and when properly adjusted this scale enables one to read off directly the wave-lengths of any part of the spectrum.

When very dilute solutions of oxyhemoglobin are examined with the spectroscope, two absorption hands appear, both occurring in the portion of the spectrum included between the Frauuhofer lines i> and E. The band nearer the red end of the spectrum is known as the "a-band ;" it is narrower, darker, and more clearly defined than the other, the "/3-band " (Ki^-. 3, and also PI. I. spectrum 4). With a solution containing 0.0!' per cent, of oxy- hemoglobin, and examined in layers one centimeter thick, the a-band extends over the part of the spectrum included between the wave-lengths I oS.'i

42

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

(583 millionths of a millimeter) and / 571, and the ,9-band between X 550 and / 532 (Gamgee). The width and distinctness of the bands vary naturally with the concentration of the solution used (see PI. I. spectra 2, .'>, 4, and 5),

70 65

55

B C

It

E b

F

G

Fig. 3.— Diagrammatic representation of the absorption spectrum of oxyhemoglobin (after Rollett). The numerals give the wave-lengths in hundred-thousandths of a millimeter; the letters Bhow the positions of the more prominent Fraunhofer lines of the solar spectrum. The red end of the spectrum is to the left. The a-band is to the right of d, the /3-band to the left of e.

or, if the concentration remains the same, with the width of the stratum of liquid through which the light passes. With a certain minimal percentage of

oxyhemoglobin (less than 0.01 per cent.) the /3-band is lost and the a- band is very faint in layers one cen- timeter thick. With stronger solu- tions the bands become darker and wider and finally fuse, while some of the extreme red end and a great deal of the violet end of the spec- trum is also absorbed. The varia- tions in theabsorption spectrum with differences in concentration are clear- ly shown in the accompanying illus- tration from Rollett1 (Fig. 4) ; the thickness of the layer of liquid is supposed to be one centimeter. The numbers on the right indicate the percentage strength of the oxy- hemoglobin solutions. It \vill be noticed that the absorption which takes place as the concentration of the solution increases affects the fed- orange end of the spectrum last of all. Solutions of reduced haemo- globin examined with the spectro- scope show only one absorption band, known sometimes as the "y-band." This band lies also in the portion of the spectrum included between the lines i> and K; its relations to these lines and the bands of oxyhemoglobin are shown in Figure 5 and in PI. I. spectrum 6. The 1 Hermann's Handbuchder Pkysiologie, Bd. iv., 1880.

Fig. 4. — Diagram to show the variations in the ab- sorption spectrum of oxyhemoglobin with varying concentrations of the solution (after Rollett). The numbers to the right give the strength "f the oxy- globin solution in percentages; the lettersgive th<> positions of the Fraunhofer lines. To ascertain tin- amounl of absorption for any given concentration up to l per cent., draw a horizontal line across tin' diagram at the level corresponding to the concentra- tion. Where this line passes through the shaded part of the diagram absorption takes place, and the width of the absorption bands i- seen al once. The diagram .-how- clearly that the amount of absorption increases

a- the solutions become m<>rc ncentrated, especially

the absorption of the blue end of the spectrum. It will he noticed that with concentrations between or, and 0.7 per cent, the two bands between Dandi fuse into '

BLOOD.

IS

y-band is much more diffuse than the oxyhemoglobin bands, and its limits therefore, especially in weak solutions, are not well defined; in solutions of blood diluted 100 times with water, which would give a haemoglobin solution of about 0.14 per cent., the absorption band lies in the part of the spectrum included between the wave-lengths X 572 and X 542. The width

70 65

B C

E b

Fig. 5.— Diagrammatic representation of the absorption spectrum of haemoglobin (reduced haemoglo- bin) (after Rollett). The numerals give the wave-lengths in hundred-thousandths of a millimeter ; the letters show the positions of the more prominent Fraunhofer lines of the solar spectrum. The red end of the spectrum is to the left. The single diffuse absorption band lies between d and e.

and distinctness of this band vary also with the concentration of the solution. This variation is sufficiently well shown in the accompanying illustration (Fig. 6), which is a companion figure to the one just given for oxyhemoglobin (Fig. 4). It will be noticed that the last light to be absorbed in this case is partly in the red end and partly in the blue, thus explaining the purplish color of hemoglobin solutions and of venous blood. Oxyhemoglobin so- lutions can be converted to hemo- globin solutions, with a correspond- ing change in the spectrum bands, by placing the former in a vacuum or, more conveniently, by adding reducing solutions. The solutions most commonly used for this pur- pose are ammonium sulphide and Stokes's reagent.1 If a solution of reduced hemoglobin is shaken with air, it quickly changes to oxyhemo- globin and gives two bands instead of one when examined through the spectroscope. Any given solution may be changed in this way from oxyhemoglobin to hemoglobin, and the reverse, a great number of times, thus demonstrating the facility with which haemoglobin takes up and surrenders oxygen.

1 Stokes's reagent is an ammoniacal solution of a ferrous salt. It is made by dissolving 2 parts i by weighl ) of ferrous sulphate, adding ."> parts of tartaric acid, and then ammonia to dis- tinct alkaline reaction. A permanent precipitate should not be obtained.

Fig. (i.— Diagram to show the variations In the ab- sorption spectrum of reduced haemoglobin with vary- ing concentrations of the solution (after Rollett). The numbers to the right give the strength <>t' the haemo- globin solution in percentages ; the Letters give the posi- tions of the Fraunhofer Lines. For further directions as in the use of the diagram, see the description of Figure 1.

44 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Solutions of carbon-monoxide haemoglobin also give a spectrum with two absorption bands closely resembling in position and appearance those of oxy- hemoglobin (see PI. I. spectrum 7). They are distinguished from the oxy- hemoglobin bands by being slightly nearer the blue end of the spectrum, as may be demonstrated by observing the wave-lengths or, more conveniently, by superposing the two spectra. Moreover, solutions of carbon-monoxide haemoglobin are not reduced to haemoglobin by adding Stokes's liquid, two bands being still seen after such treatment. A solution of carbon-monoxide haemoglobin suitable for spectroscopic examination may be prepared easily by passing ordinary coal-gas through a dilute oxyhemoglobin solution for a few minutes and then filtering.

Derivative Compounds of Haemoglobin. — A number of compounds directly related to haemoglobin have been described, some of them being found normally in the body. Brief mention is made of the best known of these substances, but for the details of their preparation and chemical proper- ties reference must be made to the section on " The Chemistry of the Body."

Methcemoglobin is a compound obtained by the action of oxidizing agents on haemoglobin ; it is frequently found, therefore, in blood stains or patho- logical liquids containing blood that have been exposed to the air for some time. It is now supposed to be identical in composition with oxyhemoglobin, with the exception that the oxygen is held in more stable combination. Methemoglobin crystallizes in the same form as oxyhemoglobin, and has a characteristic spectrum (PI. I. spectrum 8).

//" mochromogen is the substance obtained when haemoglobin is decomposed by acids or by alkalies in the absence of oxygen. It crystallizes and has a characteristic spectrum.

Hit matin (C32H30N4FeO3) is obtained when oxyhemoglobin is decomposed by acids or by alkalies in the presence of oxygen. It is amorphous and has a characteristic spectrum (PI. I. spectra 9 and 10).

lln mill ((\32II;,„X1Fe03HCl) is a compound of haematin and HC1, and is readily obtained in crystalline form. It is much used in the detection of blood in medico-legal cases, as the crystals are very characteristic and are easily obtained from blood-clots or blood-stains, no matter how old these may be.

Hcematoporphyrin (C16HI8N203) is a compound characterized by the absence of iron. It is frequently spoken of as "iron-free haematin." It is obtained by the action of strong sulphuric acid on haematin.

Hcematoidin (C16H18N203) is the name given to a crystalline substance found in old blood-clots, and formed undoubtedly from the haemoglobin of the clotted blood. It has been shown to be identical with one of the bile- pigments, bilirubin. Its occurrence is interesting in that it demonstrates the relationship between haemoglobin and the bile-pigments.

Histohcematins are a group of pigments .-aid to be present in many of the tissues — for example, the muscles. They are supposed to be respiratory pig- ment-, and are related physiologically, and possibly chemically, to hemoglobin. They have not been isolated, but their spectra have been described.

BLOOD. 45

] HI c-pigments and Urinary Pigments — Haemoglobin is regarded as the parent-substance of the bile-pigments and the urinary pigments.

Origin and Fate of the Red Corpuscles. — The mammalian red corpuscle is a cell that has lost its nucleus. It is not probable, therefore, that any given corpuscle lives for a great while in the circulation. This is made more certain by the fact that hemoglobin is the mother-substance from which the bile- pigments are made, and, as these pigments are being excreted continually, it is fair to suppose that red corpuscles are as steadily undergoing disintegration in the blood-stream. Just how long the average life of the corpuscles is has not been determined, nor is it certain where and how they go to pieces. It has been suggested that their destruction takes place in the spleen, but the observa- tions advanced in support of this hypothesis are not very numerous or con- clusive. Among the reasons given for assuming that the spleen is especially concerned in the destruction of red corpuscles, the most weighty is the histo- logical fact that one can sometimes find in teased preparations of spleen-tissue certain large cells which contain red corpuscles in their cell-substance in various stages of disintegration. It has been supposed that the large cells actually ingest the red corpuscles, selecting those, presumably, that are in a state of physiological decline. Against this idea a number of objections may be raised. Large leucocytes with red corpuscles in their interior are not found so frequently nor so constantly in the spleen as we would expect should be the case if the act of ingestion were constantly going on. There is some reason for believing, indeed, that the whole act of ingestion may be a post- mortem phenomenon ; that is, after the cessation of the blood-stream the amoeboid movements of the large leucocytes continue, while the red corpuscles lie at rest — conditions that are favorable to the act of ingestion. It may be added also that the blood of the splenic vein contains no haemoglobin in solu- tion, indicating that no considerable dissolution of red corpuscles is taking place in the spleen. Moreover, complete extirpation of the spleen does not seem to lessen materially the normal destruction of red corpuscles, if we may measure the extent of that normal destruction by the quantity of bile-pigment formed in the liver, remembering that haemoglobin is the mother-substance from which the bile-pigments are derived. It is more probable that there is no special organ or tissue charged with the function of destroying red corpus- cles, and that they undergo disintegration and dissolution while in the blood- stream and in anv part of the circulation, the liberated haemoglobin being carried to the liver and excreted in part as bile-pigment. The continual destruction of red corpuscles implies, of course, a continual formation of new- ones. It has been shown satisfactorily that in the adult the organ for the reproduction of red corpuscles is the red marrow of bones. In this tissue /in inatopoiesis, as the process of formation of red corpuscles is termed, goes on continually, the process being much increased after hemorrhages and in certain pathological conditions. The details of the histological changes will be found in the text-books of histology. It is sufficient here to state simply that a group of nucleated colorless cells, erythroblasts, i> found in the red marrow.

46 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

These cells multiply by karyokinesis, and the daughter-cells eventually pro- duce haemoglobin in their cytoplasm, thus forming nucleated red corpuscles. The nuclei arc subsequently lost, either by disintegration or, more likely, by extrusion, and the newly-formed non-nucleated red corpuscles are forced into the blood-stream, owing to a gradual change in their position during develop- ment caused by the growing haematopoietic tissue. When the process has been greatly accelerated, as after severe hemorrhages or in certain pathological conditions, red corpuscles still retaining their nuclei may be found in the circu- lating blood, having been forced out prematurely as it were. Such corpuscles may subsequently lose their nuclei while in the blood-stream. In the em- bryo, haematopoietic tissue is found in parts of the body other than the mar- row, notably in the liver and spleen, which at that time serve as organs for the production of new red corpuscles. In the blood of the young embryo nucleated red corpuscles are at first abundant, but they become less numerous as the fetus grows older.1

Variations in the Number of Red. Corpuscles. — The average number of red corpuscles for the adult male, as has been stated already, is usually given as 5,000,000 per cubic mm. The number is found to vary greatly, however. Outside of pathological conditions, in which the diminution in number may be extreme, differences have been observed in human beings under such conditions as the following: The number is less in females (4,500,000); it varies in individuals with the constitution, nutrition, and manner of life; it varies with age, being greatest in the fetus and in the new- born child ; it varies with the time of the day, showing a distinct diminution after meals; in the female it varies somewhat in menstruation and in preg- nancv, being slightly increased in the former and diminished in the latter condition. Perhaps the most interesting example of variation in the number of red corpuscles is that which occurs with changes in altitude. Residence in high altitudes is quickly followed by a marked increase in the number of red corpuscles. Viault 2 has shown that living in the mountains for two weeks at an altitude of 4.°>!)2 meters caused an increase in the corpuscles from 5,000,000 to over 7,000,000 per cubic mm., and in the third week the number reached 8,000,000. The accuracy of this observation has been demonstrated since by many investigators. Some very careful work done under the direction of Miescher3 has shown that a comparatively small increase in altitude, 700 meters, causes a marked increase in the number of red corpuscles and in the amount of haemoglobin, while return to a lower altitude quickly brings the blood back to its normal condition. From these observations it would seem that a diminished pressure of oxygen in the atmosphere stimulates the hema- topoietic organs to greater activity, and it is interesting to compare this result with the effect of an actual loss of blood. In the latter case the production of red corpuscles in the red marrow is increased, because, apparently, the anaemic condition causes a diminution in the oxygen-supply to the haematopoietic tissue,

1 Howell : "Life History of the Blood-corpuscles," etc., Journal of Morphology, 1890, vol. iv.

2 La s, maine m&dicale, 1890, p. 4G4.

s Archiv fib- erp. Pathol, u. Pharmakol., 1897, Bd. 39, S. 426-464.

BLOOD. 47

and thereby stimulates the erythroblastic cells to more rapid multiplication. Iu the case of a diminution in oxygen-pressure, as happens when the altitude is markedly increased, we may suppose that one result is again a slight dimi- nution in the oxygen-supply to the tissues, including the red marrow, and in consequence the erythroblasts are again stimulated to greater activity. This variation in haemoglobin with the altitude is an interesting adaptation which ensures always a normal oxygen-capacity for the blood.

Physiolog-y of the Blood-leucocytes. — The function of the blood-leuco- cytes has been the subject of numerous investigations, particularly in connection with the pathology of blood diseases. Although many hypotheses have been made as the result of this work, it cannot be said that we possess any positive information as to the normal function of these cells in the body. It must be borne in mind in the first place that the blood-leucocytes are not all the same histologically, and it may be that their functions are as diverse as is their mor- phology. Various classifications have been made, based upon one or another difference in microscopic structure and reaction. Thus, Ehrlich groups the leuco-

b

Fig. 7.— Blood stained with Ehrlich's "triple stain" of acid-fuchsin, methyl-green, and orange G. (drawn with the camera lucida from normal blood) (after Osier): a, red corpuscles; b, lymphocytes; c, large mononuclear leucocytes; <l, transitional forms; >, neutrophilic leucocytes with polymorphous nuclei (polynuclear neutrophiles) ; /, eosinophilic leucocytes.

cytes according to the size, the solubility, and the staining of the granules (contained in the cytoplasm, making in the latter respect three main groups; oxyphiles or eo&inophiles, those whose granules stain only with acid aniline dyes — that is, with dyes in which the acid part of the dye acts as the stain ; basophiles, those which stain only with basic- dyes; and neutrophiles, those which stain only with neutral dyes1 (Fig. 7). This classification is fre- quently used, especially in pathological literature, but it is not altogether satisfactory, since no definite functional relationship of the granules has been established ; and, moreover, it is undecided whether or not the granules arc permanent or temporary structures in the cells. A simpler classification

1 Ehrlich : Die Ancemie, Vienna, 1S98; Kanthack and Hardy, Journal of Physiology, vol., xvii., 1894, p. 81.

48 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

based on morphological characteristics is the following: 1. Lymphocytes, which arc small corpuscles with a round vesicular nucleus and very scanty cytoplasm ; they are not capable of amoeboid movements. These corpuscles are so called because they resemble the leucocytes found in the lymph-glands, and are supposed in fact to be brought into the blood through the lymph. According to Ehrlich, they form from 22 to 25 per cent, of the total number of leucocytes. 2. Mononuclear leucocytes, which are large corpuscles with a vesicular nucleus and abundant cytoplasm : they have the power of making amoeboid movements and arc present in only small numbers, 1 per cent. 3. Polymorphous or polynucleated leucocytes, which are large corpuscles with the nucleus divided into lobes that are either entirely separated or are con- nected by line protoplasmic threads. This form shows active amoeboid move- ments and constitutes the largest proportion of the blood leucocytes, 70 to 72 per cent. 4. The eosinophile cells, similar in general to the last, except that the cytoplasm contains numerous coarse granules that take acid stains (eosin) readily. They are present in small numbers, 2 to 4 per cent.

It is impossible to say whether these varieties of blood-leucocytes are distinct histological units that have independent origins and more or less dissimilar functions, or whether, as seems more probable to the writer, they represent different stages in the development of a single type of cell, the lymphocytes forming the youngest and the polymorphic or polynucleated leucocytes the oldest stage. Perhaps the most striking property of the leuco- cytes as a class is their powrer of making amoeboid movements — a charac- teristic which has gained for them the sobriquet of " wandering " cells. By virtue of this property some of them are able to migrate through the walls of blood-capillaries into the surrounding tissues. This process of migration takes place normally, but is vastly accelerated under pathological conditions. As to the function or functions fulfilled by the leucocytes, numerous sugges- tions have been made, some of which may be stated in brief form as follows: (1) They protect the body from pathogenic bacteria. In explanation of this action it has been suggested that they may either ingest the bacteria, and thus destroy them directly, or they may form certain substances, defensive proteids, that destroy the bacteria. Leucocytes that act by ingesting the bacteria are spoken of as "phagocytes" {ipaystv, to eat; xvrot;, cell). This theory of their function is usually designated as the "phagocytosis theory of Metschni- kotf ;" it is founded upon the fact that the amoeboid leucocytes are known to ingest foreign particles with which they come in contact. The theory of the protective action of leucocytes has been used largely in pathology to explain immunity from infectious diseases, and for details of experiments in support of it reference must be made to pathological text-books. (2) They aid in the absorption of fats from the intestine. (3) They aid in the absorption of peptones from the inte-tine. It maybe noticed here that these theories apply to the leucocytes found SO abundantly in the lymphoid tissue of the aliment- ary canal, rather than to those contained in the blood itself. (4) They take pari in the process of blood-coagulation. A complete statement with refer- ence to this function must be reserved until the phenomenon of coagulation is

BLOOD. 49

described. (5) They help to maintain the normal composition of the blood- plasma as to its proteids. It may be said for this view that there is considerable evidence to show that the leucocytes normally undergo disintegration and dis- solution in the circulating blood, to some extent at least. The blood-proteids are peculiar, and they are not formed directly from the digested food. It is possible that the leucocytes, which are the only typical cells in the blood, aid in keeping up the normal supply of proteids. From this standpoint they might be regarded in fact as unicellular glands, the products of their metab- olism serving to maintain the normal composition of the blood-plasma. The formation of granules within the substance of the eosinophiles offers a suggestive analogy to the accumulation of zymogen granules in glandular cells. As to the origin of the leucocytes, it is known that they increase in number while in the circulation, undergoing multiplication by karyokinesis ; but the greater number are probably produced in the lymph-glands and in the lymphoid tissue of the body, whence they get into the lymph-stream and eventually are brought into the blood.

Physiology of the Blood-plates. — The blood-plates are small circular or elliptical bodies, nearly homogeneous in structure and variable in size (0.5 to 5.5//), but they are always smaller than the red corpuscles (see Histology). Less is known of their origin, fate, and functions than in the case of the leucocytes. It is certain that they are not independent cells, and it is altogether probable, therefore, that they soon disintegrate and dissolve in the plasma. When removed from the circulating blood they are known to disintegrate very rapidly. This peculiarity, in fact, prevented them from being discovered for a long time after the blood had been studied microscopically. Recent work has shown that they are formed elements, and not simply precipitates from the plasma, as was suggested at one time. The theory of Hayem, their real discoverer, that they develop into red corpuscles may also be considered as erroneous. There is considerable evidence to show that in shed blood they take part in the process of coagulation. The nature of this evidence will be described later.

Lilienfeld1 has claimed that chemically the blood-plates contain a nucleo- albumin (see section on Chemistry of the Body), to which he gives the specific name of "nucleohiston." The same substance is contained in the nuclei of leucocytes. This latter fact may be taken as additional evidence for a view which has already been supported on morphological grounds — that the blood- plates are derived from the nuclei of the leucocytes. According to this theory when the polynuclear leucocytes go to pieces in the blood the frag- ments of nuclei contained in them persist for a longer or shorter time as blood-plates, that in time eventually dissolve in the plasma. If this last statement is correct, then it follows that the substance contained in the blood- plates either goes to form one of the normal constituents of the plasma, useful in nutrition or otherwise, or that it forms a waste product that is eliminated from the body.

1 Da Bois-lleymond's Archiv fiir Physiologic, 1893, S. 5G0. Vol. I.— 4

oO

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

B. Chemical Composition of the Blood ; Coagulation; Total Quantity of Blood ; Regeneration after Hemorrhage.

Composition of the Plasma and Corpuscles. — Blood (plasma and cor- puscle-) contains a great variety of substances, as may be inferred from its double relation- to tin4 tissues as a source of food-supply and as a means of removing the waste products of their functional activity. The constituents existing in quantities sufficiently large for recognition by chemical means are as follows: (lj Water j (2) proteids, of which three varieties at least are known to exist in the plasma — namely, fibrinogen, paraglobulin (serum- globulin), and serum-albumin; (3) combined proteids (haemoglobin, nucleo- albumins) j (I) extractives, including such substances as fats, sugar, urea, lecithin, cholesterin, etc.; and (5) inorganic salts. The proportions of these substances found in the blood of various mammals differ somewhat, although the qualitative composition is practically the same in all.

'I lie following tables, taken from different sources, summarize the general result- of the quantitative analyses made by several observer-:

Analysis of the Whole Blood, Human (C. Schmidt).

Water

Solids

Proteids and extractives

Fibrin (derived from the fibrinogen)

I lamatin (and iron)

Salts

Man	Woman
(25 years).	(30 years.)
788.71	824.55
211.29	175.45
191.78	157.93
3.93	1.91
7.7(1	6.99
7.88	8.62

Inorganic Sails of Human Blood, 1000 parts (C. Schmidt).

Blood-corpnscles. CI 1.75

i< i > 3.091

Na20 0.470

S03 0.061

P265 1.355

CaO

MgO

Blood-plasma.

CI 3.536

K20 0.314

Na20 3.410

so 0.129

I '.<>., 0.145

CaO

MgO ■ .

These acids and bases exist, of course, in the plasma and the corpuscles as salts. It is not possible to determine exactly how they are combined as salts, but Schmidt suggests the following probable combinations:

Probable Salts in the Corpuscles.

Potassium sulphate 0.132

Potassium chloride 3.679

Potassium phosphate 'J..".!:;

Sodium phosphate 0.633

ira carbonate 0.3 tl

< 'alcium phosphate 0.09 I

Magnesium phosphate .... 0.060

Probable salt- in the Plasma.

Potassium sulphate 0.281

Potassium chloride 0.359

Sodium chloride 5.5 16

Sodium phosphate 0.271

Sodium carbonate 1.532

< alcium phosphate 0.298

Magnesium phosphate .... 0.218

BLOOD.

51

One interesting fact brought out in the above table is the peculiarity in

distribution of the potassium and sodium salts between the plasma and the corpuscles. The plasma contains an excess of the total sodium salts, and the corpuscles contain an excess of the potassium salts.

Composition of Blood-plasma (1000 parts).

Water

Solids .

Total proteids

Fibrin (derived from the fibrinogen

Paraglobidin

Serum-albumin

Extractives and salts

Horse.

917.6 82.4 69.5 6.5 38.4 24.6 12.9

Composition of Blood-serum (1000 parts).1

Horse.

85.97 72.57

45.65 26.92 13.40

Man.

92.07 76.20

31.04 45.16

15.88

Ox.

89.65 74.99

41.69 33.30 14.66

Bed Corpuscles, Human Blood (Hoppe-Seyler).

I. II.

Oxyhemoglobin 86.8 94.3 per cent.

Proteid (and nuclein ?) 12.2 5.1

Lecithin 0.7 0.4 "

Cbolesterin 0.3 0.3 "

Leucocytes, Thymus of Calf (Lilienfeld). In the 'total dry substance of the corpuscles, which was equal to 11.49 per cent., there were contained —

Proteid 1.76 per cent.

Leuco-nuclein 68.78 "

Histon 8.67

Lecithin 7.51 "

Fat 4.02 "

Cholesterin 4.40 "

Glycogen 0.S0 "

The extractives present in the blood vary in amount under different conditions. Average estimates of some of them, given in percentages of the entire blood, have been reported as follows :

Dextrose (grape-sugar) 0.117 percent.

Urea 0.016

Lecithin 0.0844 "

Cholesterin 0.041 "

Proteids of the Blood-plasma. — The properties and reactions of proteids and the related compounds, as well as a classification of those occurring in t lie animal body, are described in the section on the Chemistry of the Body. This description should be read before attempting to study the proteids of the plasma and the part they take in coagulation. Three proteids are usually described as existing in the plasma of circulating blood — namely, fibrinogen, paraglobulih, or, as it is sometimes called, "serum-globulin," and serum-albu- min. The first two of these proteids, fibrinogen and paraglobidin, belong to the group of globulins, and hence have many properties in common. Serum- albumin belongs to the group of so-called ''native albumins" of which egg- albumin constitutes another member.

1 Haramarsten : .1 Text-book of Physiological Chemistry, 1898 [translated by Mandel).

52 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Serum-albumin. — This substance is a typical proteid. It can be obtained readily in crystalline form. Its percentage composition, according to Hara- marsten, is as follows : C 53.06, H 6.85, N 16.04, S 1.80, O 22.26.

Its molecular composition, according to Schmiedeberg,1 may be represented by C'.J 1 ,.,,\ ,,,S( ),( or some multiple of this formula. Serum-albumin shows the general reactions of the native albumins. One of its most useful reactions is its behavior toward magnesium sulphate. Serum-albumin usually occurs in liquids together with the globulins, as is the case in blood. If such a liquid is thoroughly saturated with solid MgS04, the globulins are precipitated com- pletely, while the albumin is not affected. So far as the blood and similar liquids are concerned, a definition of serum-albumin might be given by saying that it comprises all the proteids not precipitated by MgS04. When its solutions have a neutral or an acid reaction, serum-albumin is precipitated in an insoluble form by heating the solution above a certain degree. Precipi- tates produced in this way by heating solutions of proteids are spoken of as coagulations — heat coagulations — and the exact temperature at which coagulation occurs is to a certain extent characteristic for each proteid. The temperature of coagulation of serum-albumin is usually given at from 70° to 75° C, but it varies . greatly with the conditions. It has been asserted, in fact, that careful heating under proper conditions gives separate coagula- tions at three different temperatures — namely, 73°, 77°, and 84° C. — indi- cating the possibility that what is called " serum-albumin " may be a mixture of three proteids. Serum-albumin occurs in blood-plasma and blood-serum, in lymph, and in the different normal and pathological exudations found in the body, such as pericardial liquid, hydrocele fluid, etc. The amount of serum- albumin in the blood varies in different animals, ranging among the mam- malia from 2.67 per cent, in the horse to 4.52 per cent, in man. In some of the cold-blooded animals it occurs in surprisingly small quantities — 0.36 to 0.69 per cent. As to the source or origin of serum-albumin, it is frequently stated that it comes from the digested proteids of the food. It is known that proteid material in the food is not changed at once to serum- albumin during the act of digestion ; indeed, it is known that the final product of digestion is a proteid or group of proteids of an entirely different character — namely, peptones and proteoses ; but during the act of absorption into the blood these latter bodies are supposed to undergo transformation into serum- albumin. From a physiological standpoint serum-albumin is considered to be the main source of proteid nourishment for the tissues generally. As will be explained in the section on Nutrition, one of the most important requisites in the nutrition of the cells of the body is an adequate supply of proteid material to replace that used up in the chemical changes, the metabolism, of the tissues. Serum-albumin is supposed to furnish a part, at least, of this supply, although as a matter of fact there is no substantial proof that this view is correct. As long as the serum-albumin is in the blood-vessels it is, of course, cut off from the tissues. The cells, however, are bathed directly in lymph, 1 Archivjur exper. Pathol, u. PhannakoL, 1897, Bd. 39, S. 1.

BLOOD. 53

and this in turn is formed from the plasma of the blood which is transuded, or, according to some physiologists, secreted, through the vessel-walls.

Paraglobulin, which belongs to the group of globulins, exhibits the general reactions characteristic of the group. As stated above, it is completely pre- cipitated from its solutions by saturation with MgS04. It is incompletely pre- cipitated by saturation with common salt (NaCl). In neutral or feebly acid solutions it coagulates upon heating to 75° C. Hammarsten gives its percentage composition as— C 52.71, H7.01, N 15.85, S 1.11, O 23.24. Schmiedeberg gives it a molecular composition corresponding to the formula 0,^11, ^N^SO^ + ^H20. According to Faust,1 the precipitate of paraglobulin usually obtained with MgS04 contains a certain amount of an albuminoid body, glutolin, which he believes to be a constant constituent of blood-plasma. Paraglobulin occurs in blood, in lymph, and in the normal and pathological exudations. The amount of paraglobulin present in blood varies in different animals. Among the mam- malia the amount ranges from 1.78 per cent, in rabbits to 4.56 per cent, in the horse. In human blood it is given at 3.10 per cent., being less in amount, therefore, than the serum-albumin. It will be seen, upon examining the tables of composition of the blood-plasma and blood-serum of the horse (p. 51), that more of this proteid is" found in the serum than in the plasma. This result, which is usually considered as being true, is explained by supposing that during coagulation some of the leucocytes disintegrate and part of their substance passes into solution as a globulin identical with or closely resembling paraglobulin. The figures given above show that a considerable amount of paraglobulin is normally present in blood. It is reasonable to suppose that, like serum-albumin, this proteid is valuable as a source of nitrogenous food to the tissues. It is uncertain, however, whether it is used by the tissues directly as paraglobulin or is first converted into some other form of proteid. It is entirely unknown, also, whether its value as a proteid supply is in any way different from that of serum-albumin. The origin of paraglobulin remains undetermined. It may arise from the digested proteids absorbed from the alimentary canal, but there is no evidence to support such a view. Another suggestion is that it comes from the disintegration of the leucocytes (and other formed elements) of the blood. These bodies are known to contain a small quantity of a globulin resembling paraglobulin, and it is possible that this globulin may be liberated after the dissolution of the leucocytes in the plasma, and thus go to make up the normal supply <>i* paraglobulin. The fact remains, however, that at present the origin and the special use of the paraglobulin are entirely unknown.

Fibrinogen is a proteid belonging to the globulin class and exhibiting all the general reactions of this group. It is distinguished from paraglobulin by a number of special reactions; for example, its temperature of heat coagula- tion is much lower (50° to 60° C), and it is completely thrown down from its solutions by saturation with NaCl as well as with MgS04. It- most impor- tant and distinctive reaction is, however, that under proper conditions it gives 'Faust, Inaugural Dissertation, Leipzig, L898,

54 AN AMERICAN TEXT-HOOK OE PHYSIOLOGY.

rise to an insoluble proteid, fibrin, whose formation is the essential phenom- enon in the coagulation of blood. Fibrinogen has a percentage composition, according to Eammarsten, of— C 52.93, H 6.90, N 16.66, S 1.25, () 22.26; while its molecular composition, according to Schmiedeberg, is indicated by the formula C^gH^gN^SO^.

Fibrinogen is found in blood-plasma, lymph, and in some cases, though not always, in the normal and pathological exudations. It is absent from blood- serum, being used up during the process of clotting. It occurs in very small quantities in blood, compared with the other proteids. There is no good method of determining quantitatively the amount of fibrinogen, but estimates of the amount of fibrin, which cannot differ very much from the fibrinogen, show that in human blood it varies from 0.22 to 0.4 per cent. In horse's blood it may be more abundant — 0.65 per cent. As to the origin and the special physiological value of this proteid we are, if possible, more in the dark than in the case of paraglobulin, with the exception that fibrinogen is known to be the source of the fibrin of the blood. But clotting is an occasional phe- nomenon only. What nutritive function, if any, is possessed by fibrinogen under normal conditions is unknown. No satisfactory account has been given of its origin. It has been suggested by different investigators that it may come from the nuclei of disintegrating leucocytes (and blood-plates) or from the dissolution of the extruded nuclei of newly-made red corpuscles, but here again we have only speculations, that cannot be accepted until some experi- mental proof is advanced to support them.

Coagulation of Blood. — One of the most striking properties of blood is its power of clotting or coagulating shortly after it escapes from the blood- vessels. The general changes in the blood during this process are easily fol- lowed. At first shed blood is perfectly fluid, but in a few minutes it becomes viscous and then sets into a soft jelly which quickly becomes firmer, so that the vessel containing it can be inverted without spilling the blood. The clot continues to grow more compact and gradually shrinks in volume, pressing out a smaller or larger quantity of a clear, faintly yellow liquid to which the name blood-serum has been given. The essential part of the clot is the fibrin. Fibrin is an insoluble proteid that is absent from normal blood. In shed blood, and under certain conditions in blood while still in the blood-vessels, this fibrin is formed from the soluble fibrinogen. The deposition of the fibrin is peculiar. It i- precipitated, if the word maybe used, in the form of an exceedingly fine network of delicate threads that permeate the whole mass of the blood and give the clot its jelly-like character. The shrinking of the threads causes the subsequent contraction of the clot. If the blood has not been shaken during the act of clotting, almost all the red corpuscles are caught in the line fibrin meshwork, and as the clot shrinks these corpuscles are held more firmly, only the clear liquid of the blood being squeezed out, so that it is possible to get specimens of serum containing few or no red corpuscles. The leucocytes, on the contrary, although they arc also caught at first in .the forming mesh- work of fibrin, may readily pass out into the serum in the later stages of clot-

BLOOD. 55

ting, on account of their power of making amoeboid movements. It' the blood has been agitated during the process of clotting, the delicate network will be broken in places and the scrum will be more or less bloody — that is, it will contain numerous red corpuscles. If during the time of clotting the blood is vigorously whipped with a bundle of fine rods, all the fibrin will be deposited as a stringy mass upon the whip, and the remaining liquid part will consist of serum plus the blood-corpuseles. Blood that has been whipped in this way is known as " defibrinated blood." It resembles normal blood in appearance, but is different in its composition: it cannot clot again. The way in which the fibrin is normally deposited may be demonstrated most beautifully under the microscope by placing a good-sized drop of blood on a slide, covering it with a cover-slip, and allowing it to stand for several minutes until coagu- lation is completed. If the drop is now examined, it is possible by careful focussing to discover in the spaces between the masses of corpuscles many examples of the delicate fibrin network. The physiological value of clotting is that it stops hemorrhages by closing the openings of the wounded blood- vessels.

Time of Clotting. — The time necessary for the clot to form varies slightly in different individuals, or in the blood of the same individual varies with the conditions. It may.be said in general that under normal conditions the blood passes into the jelly stage in from three to ten minutes. The separation of clot and serum takes [dace gradually, but is usually completed in from ten to forty-eight hours. The time of clotting shows marked variations in different animals; the process is especially slow in the horse and the terrapin, so that coagulation of shed blood is more easily prevented in these animals. In the human being also the time of clotting may be much prolonged under certain conditions — in fevers, for example. This fact was noticed in the days when bloodletting was a common practice. The slow clotting of the blood permitted the red corpuscles to sink somewhat, so that the upper part of the clot in such cases was of a lighter color, forming what was called the " buffy coat." The time of clotting may be shortened or be prolonged, or the clotting may be pre- vented altogether, in various ways, and much use has been made of this fact in studying the composition and the coagulation of blood as well as in con- trolling hemorrhages. It will be advantageous to postpone an account of these methods for hastening or retarding coagulation until the theories of coagulation have been considered.

Theories of Coagulation. — The clotting of blood is such a prominent phe- nomenon that it has attracted attention at all times, and as a result numerous theories to account for it have been advanced. Most of these theories possess simply an historical interest, and need not be discussed in a work of this charac- ter, but some reference to older views is unavoidable for a proper presentation of the subject. To prevent misunderstanding it may he stated explicitly in the beginning that there is at present no perfectly satisfactory theory. Indeed, the subject is a difficult one, as it is intimately connected with the chemistry of the proteids of the blood, and it may lie said that a complete understanding

56 AN AMERICAN TENT-BOOK OF PHYSIOLOGY.

of clotting waits upon a better knowledge of the nature of these proteids. It is possible that at any moment new facts may be discovered that will alter present ideas of the nature of the process. In considering the different theories that have been proposed there are two general facts that should always be kept in mind : first, that the main phenomenon that a theory of coagulation has to explain is the formation of fibrin ; second, that all theories unite in the common belief that the fibrin is derived, in part, at least, from the fibrinogen of the plasma.

Schmidt's Older Theory of < 'oagulation. — The first theory that gained general acceptance in recent times was that of Alexander Schmidt. It was proposed in 1861, and it has served as the basis for all subsequent theories. Schmidt held that the fibrin of the clot is formed by a reaction between para- globulin (he called it " fibrinoplastin ") and fibrinogen, and that this reaction is brought about by a third body, to which he gave the name of fibrin ferment. Fibrin ferment was believed to be absent from normal blood, but to be formed after the blood was shed. Further reference will presently be made to the nature of this substance. Schmidt was not able to determine its nature — whether it was a proteid or not — but he discovered a method of preparing it from blood-serum, and demonstrated that it cannot be obtained from blood immediately after it leaves the blood-vessels, and that consequently it does not exist in circulating blood, in any appreciable quantity at least. Finally, Schmidt believed that a certain quantity of soluble salts is necessary as a fourth " fibrin factor."

Uammarsten's Theory of Coagulation. — Hammarsten, who repeated Schmidt's experiments, demonstrated that paraglobulin is unnecessary for the formation of fibrin. He showed that if a solution of pure fibrinogen is prepared, and if there is added to it a solution of fibrin ferment entirely free from paraglobulin, a typical clot is formed. This experiment has since been confirmed by others, so that at present it is generally accepted that paraglob- ulin takes no direct part in the formation of fibrin. Hammarsten's theory was that there are two fibrin factors, fibrin ferment and fibrinogen, and that fibrin results from a reaction between these two bodies. The nature of this reaction could not be determined, but Hammarsten showed that the entire fibrinogen molecule is not changed to fibrin. In place of the fibrinogen there is present after clotting, on the one hand, fibrin representing most of the weight of fibrinogen (60-90 per cent.), and, on the other hand, a newly- formed globulin-like proteid retained in solution in the serum, to which pro- teid the name fibrin-globulin has been given. Hammarsten supposed that although paraglobulin took no direct part in the process, it acted as a favor- ing condition, a greater quantity of fibrin being formed when it was present. Later experiments1 indicated that this supposition was incorrect, and that paraglobulin may be eliminated entirely trom the theory. The theory of Hammarsten, which is perhaps generally accepted at the present time, is incomplete, however, in that it have.- undetermined the nature of the ferment 1 Frederikse: Zeitschrift fur physioloyische Chemie, lid. 19, 1814, S. 143.

BLOOD. 57

and of the reaction between it and fibrinogen. The aim of the newer theories has been to supply this deficiency.

Schmidt's Theory of Coagulation. — In a volume1 containing the re- sults of a lifetime of work devoted to the study of blood-coagulation, Schmidt has modified his well-known theory. His present ideas of the direct and indirect connection of the proteids of the plasma with the formation of fibrin are too complex to be stated clearly in brief compass. He classifies the conditions necessary for coagulation as follows : (1) Certain soluble proteids — namely, the two globulins of the blood — as the material from which fibrin is made. Schmidt does not believe, however, that paraglobulin and fibrinogen react to make fibrin, but believes that fibrinogen is formed from paraglobulin, and that fibrinogen in turn is changed to fibrin. (2) A specific ferment, fibrin ferment, to eifect the changes in the proteids just stated. He proposes for fibrin ferment the distinctive name of thrombin. (3) A certain quantity of neutral salts is necessary for the precipitation of the fibrin in an insoluble form.

The Relation of Calcium Salts to Coagulation. — It has been shown by a number of observers that calcium salts take an important part in the pro- cess of clotting. This fact was first clearly demonstrated by Arthus and Pages, who found that if oxalate of potash or soda is added to freshly-drawn blood in quantities sufficient to precipitate the calcium salts, clotting will be prevented. If, however, a soluble calcium salt is again added, clotting occurs promptly. This fact has been demonstrated not only for the blood, but also for pure solutions of fibrinogen, and we are justified in saying that without the presence of calcium salts fibrin cannot be formed from fibrinogen. This is one of the most significant facts recently brought out in connection with coagulation. We know that fibrinogen when acted upon by fibrin ferment produces fibrin, but we now know also that calcium salts must be present. What is the relation of these salts to the so-called "ferment"? The most explicit theory proposed in answer to this question we owe to Pekelharing.

Pekelha ring's Theory of Coagulation. — Pekelharing- succeeded in sepa- rating from blood-plasma a proteid body that has the properties of a nucleo- albumin. He finds that if this substance is brought into solution together with fibrinogen and calcium salts, a typical clot will form, while nueleo- albumin alone, or calcium salts alone, added to fibrinogen solutions, cause no clotting. His theory of coagulation is that what has been called "fibrin ferment" is a compound of nucleo-albumin and calcium, and that when this compound is brought into contact with fibrinogen a reaction occurs, the calcium passing over to the fibrinogen and forming an insoluble calcium compound, fibrin. According to this theory, fibrin is a calcium compound with fibrinogen or with a part of the fibrinogen molecule. This idea is strengthened by the unusually large percentage of calcium found in fibrin ash. The theory supposes also that the fibrin ferment is not present in blood- plasma — that is, in sufficient quantity to set up coagulation — but that it is formed

1 Zwr Blutlehre, Leipzig 1893.

2 lTnttrsiirliu)it/rn iibcr (lax Fibriiifcnnrnt, Amsterdam, 1S<)'J.

58 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

after the blood is shed. The nucleo-albumio part is derived faom the cor- puscles of the blood (leucocytes, blood-plates), which break down and go into solution. This nucleo-albumin then unites with the calcium salts present in the blood to form fibrin ferment, an organic compound of calcium capable of reacting with fibrinogen. The theory is a simple one ; it accounts tor the importance of calcium salts in coagulation, and reduces the interchange be- tween fibrinogen and fibrin ferment to the nature of an ordinary chemical reaction; but it cannot be accepted without reservation at present, since the experimental evidence is not entirely in its favor. Hammarsten, for instance, in some careful experiments seems to have obtained facts that are at variance with a part at least of this theory. Hammarsten1 states that blood-plasma or fibrinogen solutions to which an excess of potsssium oxalate had been added, and which therefore was free presumably from precipitable calcium salts, underwent typical coagulation when mixed with blood-serum to which an excess of oxalate had also been added. In other words, a solution of fibrinogen free from calcium reacted with a solution of fibrin ferment (blood-serum) also apparently free from calcium. It might be urged against this experiment, however, that in the blood-serum used the combination of calcium and nucleo- proteid to form ferment had already taken place, and that in this combination the calcium is not acted upon by the oxalate. Hammarsten indeed admits that something of this kind may occur, for he is convinced, like others, that calcium in some way is essential to coagulation, his suggestion being that it plays an un- known part in the formation of the ferment. He supposes that in the plasma of shed blood a material is present which he designates as prothrombin, and the calcium in some way converts this into the active ferment, the thrombin. According to the more explicit hypothesis of Pekelharing, the prothrombin is a form of nucleo-proteid and the thrombin a calcium compound of this pro- teid. The second part of IVkelharing's theory, namely, that the reaction between the ferment and the fibrinogen consists in a transfer of the calcium from the former to the latter, is directly contradicted by Ilammarsten's experi- ments. Quantitative analysis of fibrinogen and fibrin showed that the latter docs not contain any larger amount of calcium than the former. This author is inclined to consider the ( a contained in fibrin of the nature of an impurity, and not as an essential constituent of the fibrin molecule. By the use of special methods he has succeeded in obtaining typical fibrin containing as little as 0.005 per cent, of ('a. We must be content to say that in the clot- ting of blood three factors are necessary — namely, the fibrinogen and the calcium salts of plasma, which are present in the circulating blood, and the fibrin ferment, which is formed after the blood is shed.

Nature and Origin of Fibrin Ferment (Thrombin). — Recent views as to the nature of fibrin ferment have been referred to incidentally in the description of the theories of coagulation just given. The relation of these newei' views to the older idea- can be presented most easily by giving a brief description of the development of our know ledge concerning this body. 1 Zeitschriftfiir physiologische Chemie, Bd. -:-2. S. 333, and 1899, Bd. 28, S. 98.'

BLOOD. 59

Schmidt prepared solutions of fibrin ferment originally by adding a large excess of alcohol to blood-serum and allowing the proteids thus precipitated to stand under strong alcohol for a long time until they were thoroughly coagu- lated and rendered nearly insoluble in water. At the end of the proper period the coagulated proteids were extracted with water, and there was obtained a solution which contained only small quantities of protcid. It was found that solutions prepared in this way had a marked effect in inducing coagulation when added to liquids, such as hydrocele liquid, that contained fibrinogen, but did not clot spontaneously or else clotted very slowly. It was after- ward shown that similar solutions of fibrin ferment are capable of setting up coagulation very readily in so-called salted plasma — that is, in blood-plasma prevented from clotting by the addition of a certain quantity of neutral salts. It was not possible to say whether the coagulating power of these solutions was due to the small traces of proteid contained in them, or whether the pro- teid was merely an impurity. The general belief for a time, however, was that the proteids present were not the active agent, and that there was in solu- tion something of an unknown chemical nature which acted upon the fibrinogen after the manner of unorganized ferments. This belief was founded mainly upon three facts : first, that the substance seemed to be able to act powerfully upon fibrinogen, although present in such minute quantities that it could not be isolated satisfactorily ; second, it was destroyed by heating its solutions for a few minutes at 60° C. ; and, third, it did not seem to be destroyed in the reaction of coagulation which it set up, since it was always present in the serum squeezed out of the clot. Schmidt proved that fibrin ferment could not be obtained from blood by the method described above if the blood was made to flow im- mediately from the cut artery into the alcohol. On the other hand, if the shed blood was allowed to stand, the quantity of fibrin ferment increased up to the time of coagulation, and was present in quantity in the serum. Schmidt believed that the ferment was formed in shed blood from the disintegration of the leucocytes, and this belief was corroborated by subsequent histological work. It was shown in microscopic preparations of coagulated blond that the fibrin threads often radiated from broken-down leucocytes — an appearance that seemed to indicate that the leucocytes served as points of origin for the deposition of the fibrin. When the blood-plates were discovered a great deal of microscopic work was done tending to show that these bodies also are con- nected with coagulation in the same way as the leucocytes, and serve probably as sources of fibrin ferment. In microscopic preparations the fibrin threads were found to radiate from masses of partially disintegrated plates ; and, more- over, it was discovered that conditions which retard or prevent coagulation of blood often serve to preserve the delicate plate- from disintegration. At the present time it is generally believed that there is derived from the disintegra- tion of the leucocytes and blood-plates something that is necessary to the coagulation of blood, but there is sonic difference of opinion as to the nature of this substance and whether it is identical with Schmidt's fibrin ferment. Pekelharing thinks that the substance sel free from the corpuscles and plates

60 AN AMERICA* Til XT-BOOK OF PHYSIOLOGY.

is a nucleo-proteid, but that this nucleo-proteid is not capable of acting upon fibrinogen until it has combined with the calcium salts of the blood. According to his view, therefore, fibrin ferment, in Schmidt's sense, is a compound of cal- cium and nucleo-proteid. Lilienfeld has shown by chemical reactions that blood-plates and nuclei of leucocytes contain nucleo-proteid material which in all probability is liberated in the blood-plasma by the disintegration of these elements after the blood is shed. Lilienfeld contends, however, that solu- tions of fibrin ferment prepared by Schmidt's method do not contain any nucleo-proteid material, and that, although the liberation of nucleo-proteid material is what starts normal coagulation of blood, nevertheless so-called fibrin ferment is something entirely different from nucleo-proteid. In this point, however, his results are contradicted by the experiments of Pekelhar- ing and of Halliburton, who both find that solutions of fibrin ferment pre- pared by Schmidt's method give distinct evidence of containing nucleo-pro- teid material. We may conclude, therefore, that the essential element of Schmidt's fibrin ferment is a nucleo-proteid compound. The nature of the action of the ferment on fibrinogen is quite undetermined. As was mentioned before, only a portion, and apparently a variable portion, of this fibrinogen appears as fibrin after clotting is completed. Along with the fibrin a new proteid fibrin globulin makes its appearance in the serum. This fact has suggested the view that perhaps the fibrin ferment acts after the manner of the digestive ferments by causing hydrolytic cleavage of the fibrinogen, that is, causes the fibrinogen molecule to take up water and then dissociate into two parts, fibrin and fibrin globulin. Hammarsten, however, is inclined to believe that the reaction is of a different nature, resembling more the change that occurs in the heat coagulation of proteids. According to this suggestion, the ferment causes a molecular rearrangement of the fibrinogen, resulting in the formation of fibrin, most of which is deposited in an insoluble form, while a smaller part, after suffering a still further alteration, appears as fibrin globulin.

Intravascular Clotting-. — Clotting may be induced within the blood- vessels by the introduction of foreign particles, either solid or gaseous — for example, air — or by injuring the inner coat of the blood-vessels, as in ligat- ing. In the latter case the area injured by the ligature acts as a foreign surface and probably causes the disintegration of a number of corpuscles. The clot in this case is confined at first to the injured area, and is known a- a " thrombus." Intravascular clotting more or less general in occurrence may be produced by injecting into the circulation such substances as leucocytes obtained by macerating lymph-glands, extracts of fibrin ferment, solutions of nucleo-albumins of different kinds, etc. According to the theory of coagu- lation adopted above, injections of these latter substances ought to cause coagu- lation very readily, since the blood already contains fibrinogen, and needs only the presence of ferment to set up coagulation. As a matter of fact, however, intravascular clotting is produced with some difficulty by these methods, show- ing that the body can protect itself within certain limits from an excess of

BLOOD. 61

ferment in the circulating blood. Just how this is done is not positively known, but there is evidence that it may be due mainly to a defensive action of the liver. Delezenne1 states that when blood-serum is circulated through a liver it loses its power of inducing coagulation in a coagulablc liquid, that is, probably its contained fibrin ferment is altered or destroyed. It seems prob- able that this action of the liver may be of importance in the normal circula- tion in maintaining the non-coagulability of the blood in the living animal. Moreover, injection of leucocytes sometimes diminishes instead of increasing the coagulability of blood, making the so-called " negative phase " of the injection. To explain this latter fact, it may be said that leucocytes give rise on disintegration to a complex nucleo-proteid known as nucleo-histon. Nucleo-histon in turn is said to be broken up in the circulation, with the formation of a second nucleo-proteid, leuconuclein, that favors coagulation, and a proteid body, histon, that has a retarding influence on coagulation. The predominance of the latter substance may account for the " negative phase " under the conditions described.

Why Blood does not Clot within the Blood-vessels. — The reason that blood remains fluid while in the living blood-vessels, but clots quickly after being shed or after being brought into contact with a foreign substance in any way, has already been stated in describing the theories of coagulation, but will be restated here in more categorical form. Briefly, then, blood does not clot within the blood-vessels because fibrin-ferment is not present in sufficient quantities at any one time. Leucocytes and blood-plates probably disintegrate here and there within the circulation, but the small amount of ferment thus formed is insufficient to act upon the blood, and the ferment is quickly destroyed or changed, probably by an action of the liver as stated above. When blood is shed, however, the formed elements break down in mass, as it were, liberating a relatively large amount of nucleo-proteids, which, together with the calcium salts, produce fibrin from the fibrinogen.

Means of Hastening" or of Retarding- Coagulation. — Blood coagulates normally within a few minutes, but the process may be hastened by increasing the extent of foreign surface with which it comes in contact. Tims, moving the liquid when in quantity, or the application of a sponge or a handkerchief to a wound, will hasten the onset of clotting. This is easily understood when it is remembered that nucleo-proteids arise from the breaking down of leucocytes and blood-plates, and that these corpuscles go to pieces more rapidly when in contact with a dead surface. It has been proposed also to hasten clotting in case of hemorrhage by the use of ferment solutions. Plot sponges or cloths applied to a wound will hasten clotting, probably by accelerating the formation of ferment and the chemical changes of clotting. Coagulation may be retarded or be prevented altogether by a variety of means, of which the following are the most important :

1. By Cooling. — This method succeeds well only in blood that clots slowly — for example, the blood of the horse or the terrapin. Blood from 1 Travaux <lr Physiologie, I'niversiK? do Montpellier, 1898.

62 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

these animals received into narrow vessels surrounded by crushed ice may be kepi fluid for an indefinite time. The blood-corpuscles soon sink, so that this met In id is an excellent oue for obtaining pure blood-plasma. The cooling probably prevents clotting by keeping the corpuscles intact.

2. By the Action of Neutral Salts. — Blood received at once from the blood- vessels into a solution of such neutral salts as sodium sulphate or magnesium sulphate, and well mixed, will not clot. Jn this case also the corpuscles settle slowly, or they may be centrifugalized, and specimens of plasma can be obtained. For this purpose horse's or rat's blood is to be preferred. Such plasma is known as "salted plasma ;" it is frequently used in experiments in coagulation — lor example, in testing the efficacy of a given ferment solution. The besl -alt to use is MgS04 in solutions of 27 per cent.: 1 part by volume of this solution is usually mixed with 4 parts of blood ; if cat's blood is used a smaller amount may be taken — 1 part of the solution to 9 of blood. Salted plasma or salted Mood again clots when diluted sufficiently with water or when ferment solutions are added to it. How the salts prevent coagulatiou is not definitely known — possibly by preventing the disintegration of corpuscles and the formation of ferment, possibly by altering the chemical properties of the proteids.

.1. By the Action of Albumose Solutions. — Certain of the products of proteid digestion, peptones and albumoses, when injected into the circulation retard clotting for a long time. For injection into dogs one uses 0.3 gram to each kilogram of animal. If the blood is withdrawn shortly after the injection, it will remain fluid for a long time. The peptone solutions, on the contrary, have no effect on the clotting of blood if added to it in a glass out- side the body. This curious action of peptone has been much discussed. In an interesting paper by Delezenne, referred to on the previous page, two important facts are brought out that furnish the author a basis for a credible theory of the anticoagulating effect of the injections. It has been shown, in the first place, thai the peptone injections cause a marked and rapid destruc- tion of blood leucocytes. Secondly, that if blood and peptone are circulated together through a living liver the mixture not only docs not clot itself, lmt will prevent clotting when added to freshly drawn blood. The hypothesis to explain these facts and also the action of peptone on coagulation is that the peptone by destroying the leucocyte- sets \'v<-c nucleo-proteid and histon (see p. 61 ): the former of these by forming fibrin ferment would promote coagu- lation, lmt in passing through the liver it is destroyed or neutralized in some way. and the histon left in the blood isthe substance that retards the clot- ting. It would be desirable, in connection with this hypothesis, if chem- ical proof were furnished that histon is present in the blood after pepton< injections.

I. .Many other organic substances have an effect similar to peptone when injected into the circulation or in some cases when mixed with shed blood. For example, extracts of leech'- head, extract- of the muscle of the crayfish, the serum of the eel, a number of bacterial toxins, and many of the soluble

BLOOD. 63

enzymes such as pepsin, trypsin, diastase, etc. The hypothesis u>rd to ex- plain the action of peptone may possibly apply also to these cases.

5. By the Action of Oxalate Solutions. — If blood as it flows from the vessels is mixed with solutions of potassium or sodium oxalate in proportion sufficient to make a total strength of 0.1 per cent, or more of these salts, coagulation will be prevented entirely. Addition of an excess of water will not produce clotting in this case, but solutions of some soluble calcium salt will quickly start the process. The explanation of the action of the oxalate solutions is simple : they are supposed to precipitate the calcium as insoluble calcium oxalate.

Total Quantity of Blood in the Body. — The total quantity of blood in the body has been determined approximately for man and a number of the lower animals. The method used in such determinations consists essentially in first bleeding the animal as thoroughly as possible and weighing the quan- tity of blood thus obtained, and afterward washing out the blood-vessels with water aud estimating the amount of haemoglobin in the washings. The results are as follows: Man, 7.7 per ceut. (y1^) of the body-weight; that is, a man weighing 68 kilos, has about 5236 grams, or 4965 c.c, of blood in his body; dog, 7.7 per cent.; rabbit and cat, 5 percent.; new-born human being, 5.26 per cent. ; and birds, 10 per cent. Moreover, the distribution of this blood in the tissues of the body at any one time has been estimated by Ranke,1 from experiments on freshly-killed rabbits, as follows :

Spleen 0.23 per cent.

Brain and cord 1.24 " "

Kidneys 1.63 u

Skin 2.10 " "

Intestines 6.30 '

Bones 8.24 " "

Heart, lungs, and great blood-vessels 22.76 " "

Resting muscles ' 29.20 " "

Liver 29.30 " «

It will be seen from inspection of this table that in the rabbit the blood of the body is distributed at any one time about as follows: one-fourth to the heart, lungs, and great blood-vessels; one-fourth to the liver; one-fourth to the resting muscles; and one-fourth to the remaining organs.

Regeneration of the Blood after Hemorrhage. — A large portion of the entire quantity of blood in the body may be lost suddenly by hemorrhage without producing a fatal result. The extent of hemorrhage thai can be recovered from safely has been investigated upon a number of animals. Although the results show more or less individual variation, it can be said thai in dogs a hemorrhage of from 2 to 3 per cent, of the body-weight8 is recovered from easily, while a loss of 1.5 per cent., more than half the entire bl 1, will probably prove fatal. In eats a hemorrhage of from 'J i<> •"» per

'Taken from Vieronlt's Anatoimsche, physiologische >ni<l physikaltsche Daten "»'/ Tabellen,Jen&, 1893.

2 Kredericq : Iravavx du LaftorotoiVe l University de LiSge), L885, t. i. p L89.

64 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cent, of the body-weight is not usually followed by a fatal result. Just what percentage of loss can be borne by the human being has not been deter- mined, but it is probable that a healthy individual may recover without serious difficulty from the lo.-s of a quantity of blood amounting to as much as 3 per cent, of the body-weight. It is known that if liquids that are iso- tonic to the blood, such as a 0.9 per cent, solution of NaCl, are injected into the veins immediately after a severe hemorrhage, recovery will be more certain ; in fact, it is possible by this means to restore persons after a hemorrhage that would otherwise have been fatal. In addition to the mechanical effects on blood pressure such an infusion tends to put into circulation all the red cor- puscles. Ordinarily the number of red corpuscles is greater than that neces- sary for a barely sufficient supply of oxygen, and increasing the bulk of liquid in the vessels after a severe hemorrhage makes more effective as oxygen-carriers the remaining red corpuscles, inasmuch as it insures a more rapid circulation. If a hemorrhage has not been fatal, experiments on lower animals show that the plasma of the blood is regenerated with great rapidity, the blood regaining its normal volume within a few hours in slight hemorrhages, and in from twenty-four to forty-eight hours if the loss of blood has been severe ; but the number of red corpuscles and the hemoglobin are regenerated more slowly, getting back to normal only after a number of days or after several weeks.

Blood-transfusion. — Shortly after the discovery of the circulation of the blood (Harvey, 1628), the operation was introduced of transfusing blood from one individual to another or from some of the lower animals to man. Ex- travagant hopes were held as to the value of such transfusion not only as a means of replacing the blood lost by hemorrhage, but also as a cure for various infirmities and diseases. Then and subsequently, fatal as well as successful results followed the operation. It is now known to be a dangerous under- taking, mainly for two reasons: first, the strange blood, whether transfused directly or after defibrination, is liable to contain a quantity of fibrin ferment sufficient to cause intravascular clotting; secondly, the serum of one animal may be toxic to another or cause a destruction of its blood-corpuscles. Owing to this globulicidal and toxic action, which has previously been referred to (p. 36), the injection of foreign blood is likely to be directly injurious instead of beneficial. In cases of loss of blood from severe hemorrhage, therefore, it is far safer to inject a neutral liquid, such as the so-called " physiological salt- solution " — a solution of NaCl of such a strength (0.9 per cent.) as to be iso- tonic with the blood-serum. The volume of the circulating liquid is thereby augmented, and all the red corpuscles are made more efficient as oxygen- carriers, partly owing to the fact that the bulk and velocity of the circulation are increased, and partly because the corpuscles are kept from stagnation in the capillary areas.

DIFFUSION AND OSMOSIS. 65

Some Preliminary Considerations upon the Processes of Diffusion and Osmosis, and their Importance in the Nutritive Exchanges of the Body.

In recent years the physical conceptions of the nature of the processes of diffusion and osmosis have changed considerably. As these newer conceptions are entering largely into current medical literature, it seems advisable to give a brief description of them for the use of those students of physiology who may be unacquainted with the modern nomenclature. The very limited space that can be devoted to the subject forbids any- thing more than a condensed elementary presentation. For fuller information reference must be made to special treatises.1

Diffusion, Dialysis, and Osmosis. — When two gases are brought into contact a homo- geneous mixture of the two is soon obtained. This interpenetration of the gases is spoken of as diffusion, and it is due to the continual movements of the gaseous molecules to and fro within the limits of the confining space. So also when two mis- cible liquids or solutions are brought into contact a diffusion occurs for the same reason, the movements of the molecules finally effecting a homogeneous mixture. If the two liquids happen to be separated by a membrane, diffusion will still occur, provided the membrane is permeable to the liquid molecules, and in time the liquids on the two sides will be mixtures having a uniform composition. Not only water molecules, but the mole- cules of many substances in solution, such as sugar, may pass to and fro through mem- branes, so that two liquids separated from each other by an intervening membrane and originally unlike in composition may finally, by the act of diffusion, come to have the same composition. Diffusion of this kind through a membrane is frequently spoken of as dialysis or osmosis. In the body we deal with aqueous solutions of various substances that are separated from each other by living membranes, such as the walls of the blood- capillaries or of the alimentary canal, and the laws of diffusion through membranes are of immediate importance in explaining the passage of water and dissolved substances through these living septa. In aqueous solutions such as we have in the body we must take into account the movements of the molecules of the solvent, water, as well as of the substances dissolved. These latter may have different degrees of diffusibility as compared with one another or with the water molecules, and it frequently happens that a membrane that is permeable to water molecules is less permeable or even impermeable to the mole- cules of the substances in solution. F'or this reason the diffusion stream of water and of the dissolved substances may be differentiated, as it were, to a greater or less extent. In recent years it seems to have become customary to limit the term osmosis to the stream of water molecules passing through a membrane, while the term dialysis, or diffusion, is applied to the passage of the molecules of the substances in solution. The osmotic stream of water under varying conditions is especially important, and in connection with this process it is necessary to define the term osmotic pressure as applied to solutions.

Osmotic Pressure. — If we imagine two masses of water separated by a permeable membrane, we can readily understand that as many water molecules will pass through from one side as from the other; the two streams in fact will neutralize each other, and the volumes of the two masses of water will remain unchanged. The movement of the water molecules in this case is not actually observed, but it is assumed to take place on the theory that the liquid molecules are continually in motion and thai the membrane, being permeable, offers no obstacle to their movements. If, now. on one side of the membrane we place a solution of some crystalloid substance, such as common salt, and on the other side pure water, then it will he found that an excess of water will pass from

1 Consult: II. C. Jones, The Theory of Electrolytic Dissociation, 1900; " Diffusion, Osmosis, and

Filtration," by E. W. Reid, in Schlifer's Test-book of Physiology, 1898; Solution and Electrolysis, by W. C I). Whetham, Cambridge Natural Science Manuals. 1895. Vol. I.— 5

66 l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the water side to the Bide containing the solution. In the older terminology it was said thai the sail attracted this water, but in the newer theories the same fact is expressed by saying that the salt in solution exerts a certain osmotic pressure, in eonse- quence of which more water flows from the water side to the side of the solution than in the reverse direction. A- a matter of experiment it is found that the osmotic pressure varies with the amount of the substance in solution. If in experiments of this kind a semi-permeable membrane is chosen — that is, a membrane that is permeable to the water molecules, hut not to the molecules of the substance in solution— the stream of water to i lie Bide of the crystalloid will continue until the hydrostatic pressure on this side reaches a certain point, and the hydrostatic pressure thus caused may he taken as a measure of the osmotic pressure exerted by the substance in solution. Under these con- dition- it can he shown that the osmotic pressure is proportional to the concentration of the solution, or, in other words, to the Dumber of molecules and ions of the crystalloid in solution. As a matter of fact it is difficult, if not impossible, to construct membranes that are truly semi-permeable; most of the membranes that we have to use in practice are only approximately semi-permeable— that is, while they are readily permeable to water molecule-, they arc also permeable, although with more or less difficulty, to the substances in solution. In such cases we get an osmotic stream of water to the side of the dissolved crystalloid, but at the same time the molecules of the latter pass to some extent through the membrane, by diffusion, to the water side. In course of time, therefore, the dissolved crystalloid will he equally distributed on the two sides of the membrane, the osmotic pressure on both sides will become equal, and osmosis of the water will cease to be apparent, since it will be equal in the two directions. All substances iu solution are capable of exerting osmotic pressure, and the important discovery has been made that the osmotic pressure, measured in terms of atmospheres or the pressure of a column of water or mercury, is equal to the gas pressure that would be exerted by a number of molecules of gas equal to that of the crystalloid in solution, if confined within the same -pace ami kept at the same temperature. A perfectly satisfactory explanation of the nature of osmotic pressure has not been furnished. We must be content to use the term to express the fact described. A comparatively simple explanation, however, has been suggested, which has the great merit of referring the whole phenomenon to the molec- ular movements of the solvent and of the substance dissolved — that is, to the same ultimate cause that brings about the entire process of diffusion in liquids. The nature of this explanation may he understood from a simple illustration. Suppose that we have a solution of cane-sugar separated from a mass of water by a semi-permeable mem- brant — that is, in this case a membrane permeable to the water molecules but not to the sugar molecules. Under these conditions the stream of water from the two sides will lie unequal, because on the one side we have water molecules moving against the membrane in what we may call normal numbers, while on the other side both water and BUgar molecules may be considered as striking against the membrane. On this side the sugar molecules screen the membrane, as it were, from contact with a certain num- ber of water molecules, and the result follows that in a given unit of time fewer mole- cule- of water will penetrate the membrane from this side than from the other; or, to put it in another way, the osmotic stream of water from the unscreened water side to the sugar side will be greater than in the reverse direction. Upon this hypothesis one can readily see why the osmotic pressure should be proportional to the number of mole- cules of the crystalloid in the solution — that is, to the concentration of the solution. It i- a matter of great importance to measure the osmotic pressures of various solutions. A- was -tated above, this mea-uremeiit could lie made easily for any solution provided a really -emi-permeable membrane could be constructed. As a matter of experience, however, it is possible to make stub membranes in only a few cases, and in these cases perhaps the semi-permeability is only approximately complete. In actual experiments

other methods must 1 mployed, and a brief statement of a theoretical and a practical

method of arriving at the value of osmotic pressures may be of service in further illus-

DIFFUSION AND OSMOSIS. 67

trating the meaning of the term. Before stating these met Ik ids it hecomes necessary to define two terms, namely, electrolytes and gram-molecular solutions, that are much used in this connection.

Electrolysis. — The molecules of many substances when brought into a state of solution are believed to be dissociated into two or more parts, known as ions. The complete- ness of the dissociation varies with the substance used, and for any one substance with the degree of dilution. Roughly speaking, the greater the dilution the more nearly complete is the dissociation. The ions liberated by this act of dissociation are charged with electricity, ar.d when an electrical current is led into such a solution it is conducted through the solution by the movements of the ions. The molecules of per- fectly pure water undergo practically no dissociation, and water therefore does not appre- ciably conduct the electrical current. If some NaCl is dissolved in water, a certain num- ber of its molecules become dissociated into a Na ion charged positively with electricity and a CI ion charged negatively, and the solution becomes a conductor of the electrical current. Substances that exhibit this property of dissociation are known as electrolytes, to distinguish them from other soluble substances, such as sugar, that do not dissociate in solution and therefore do not conduct the electrical current. Speaking generally, it may be said that all salts, bases, and acids belong to the group of electrolytes. The con- ception of electrolytes is very important for the reason that the act of dissociation obviously increases the number of particles moving in the solution and thereby increases the osmotic pressure, since it has been found experimentally that, so far as osmotic pressures are concerned, an ion plays the same part as a molecule. It follows, there- fore, that the osmotic pressure of any given electrolyte in solution will be increased in proportion to the degree to which it is dissociated. As the liquids of the body contain electrolytes in solution it becomes necessary in estimating their osmotic pressure to take this fact into consideration.

Gram-molecular Solutions. — The concentration of a given substance in solution may be stated by the usual method of percentages, but from the standpoint of osmotic press- ure a more convenient method is the use of the unit known as a gram-molecular solution. A gram-molecule of any substance is a quantity in grams of the substance equal to its molecular weight, while a gram-molecular solution is one containing a gram- molecule of the substance to a liter of the solution. Thus a gram-molecular solution of sodium chloride is one containing 58.5 grams (Na 23, CI 35.5) of the salt to a liter, while a gram-molecular solution of cane-sugar contains 342.1 grains (C12H22On) to a liter. Sim- ilarly a gram-molecule of H is 2 grains by weight of this gas, and if this weight of II were compressed to the volume of a liter it would be comparable to a gram-molecular solution. Since the weight of a molecule of II is to the weight of a molecule of cane-sugar as 2 is to 342.1, it follows that a liter containing 2 grams of II contains the same number of molecules of H in it as a liter of solution containing 342.1 grains of sugar has of sugar molecules. Since it is known that a molecule in solution exerts an osmotic pressure that is exactly equal to the gas-pressure exerted by a gas molecule moving in the same space and at the same temperature, we are justified in saying that the osmotic pressure of a ^ram-molecular solution of cane-sugar, or of any other substance that is not an electrolyte, is equal to the gas-pressure of 2 grams of II when compressed to the volume of 1 liter. This fact gives a means of calculating the osmotic pressure of solutions in certain cases according to the following method :

Calculation of flu' Osmotic I'rcssurr of Solution.-!. -To illustrate this method we may take a simple problem such as the determination of the osmotic pressure of a 1 per cent. solution of cane-sugar. One gram of II at atmospheric pressure occupies a volume of 11.16 liters ; 2 grains of II, therefore, under the same conditions will occupy a volume of 22.32 liters. A gram-molecule of H— that is, 2 grams of II — when broughl to the volume ofl liter will exert a gas-pressure equal to that of 22.32 liters compressed to I liter — that is, a pressure of 22.32 atmospheres. A gram-molecular solution of cane-sugar, since it con- tains the same number of molecules in a liter, must therefore exert an osmotic pressure

68 AN AMERICAN TEXT-HOOK OF PHYSIOLOGY.

equal to -~2.'-','2 atmospheres. A 1 per cent, solution of cane sugar contains, however, only 10 grams of sugar to a liter, hence the osmotic pressure of the sugar in such a solu- tion will be ■ - of 22.32 atmospheres, or 0.G5 of an atmosphere, which in terms of a 342.J

column of mercury would give 760 X 0.65 = 494 mm. This figure expresses the osmotic pressure of a 1 per cent, solution of cam-sugar when dialyzed against pure water through a membrane impermeable to the sugar molecules. In such an experi- ment water would pass to the sugar side until the hydrostatic pressure on this side was increased by an amount equal to the pressure of a column of mercury 494 mm. high. Certain additional calculations that it is necessary to make for the temperature of the solution need not be specified in this connection. If, however, we wished to apply this method to the calculation of the osmotic pressure of a given solution of an electrolyte, it would be necessary first to ascertain the degree of dissociation of the electrolyte into its ions, since, as was said above, dissociation increases the number of parts in solu- tion and to the same extent increases osmotic pressure. In the body the liquids that concern us contain a variety of substances in solution, electrolytes as well as non- electrolytes. In order, therefore, to calculate the osmotic pressure of such complex solu- tions it would be necessary to ascertain the amount of each substance present, and, in the case of electrolytes, the degree of dissociation. Under experimental conditions such a calculation is practically impossible, and recourse must be had to other methods. One of the simplest and most easily applied of these methods is the determination of the freezing-point of the solution.

Determination of Os?notic Pressure by Means of the Freezing-point. — This method depends upon the fact that the freezing-point of water is lowered by substances in solu- tion, and it has been discovered that the amount of lowering is proportional to the number of parts (molecules and ions) present in the solution. Since the osmotic pressure is also proportional to the number of parts in solution, it is convenient to take the lowering of the freezing-point of a solution as an index or measure of its osmotic pressure. In practice a simple apparatus (Beckmann's apparatus) is used, consisting essentially of a very delicate and adjustable differential thermometer. By means of this instrument the freezing-point of pure water is first ascertained upon the empirical scale of the thermometer. The freezing-point of the solution under examination is then determined, and the number of degrees or fractions of a degree by which its freezing-point is lower than that of pure water is noted. The lowering of the freezing-point in degrees centi- grade is expressed usually by the symbol A. For example, mammalian blood-serum gives A = 0.56° C. A 0.95 per cent, solution of XaCl gives the same A ; hence the two solutions exert the same osmotic pressure, or, to put it in another way, a 0.95 per cent. solution of NaCl is isotonic or isosmotic with mammalian serum. The A of any given solution may be exprc-sed in terms of a gram-molecular solution by dividing it by the constant 1.87, since a gram-molecular solution of a non-electrolyte is known to lower the freezing point 1.87° C. Thus if blood-serum gives A = 0.56° C, its concentration in

0.56 terms of a gram-molecular solution will be T~o-, or 0.3. In other words, blood-serum

has 0.3 of the osmotic pressure exerted by a gram-molecular solution of a non-electro- lyte—that is, 22.32 x 0.3, or 6.696 atmospheres.

Remarks upon tin Application of the Foregoing Fact* in Physiology. — In the body water and substances in solution are continually passing through membranes, for example, in the production of lymph, in the absorption of water and digested food-stuff's from the alimentary canal, in the nutritive exchanges between the tissue-elements and the blood or lymph, in the production of the various secretion-;, and so on. In these cases it is a matter of the greatest difficulty to give a satisfactory explanation of the forces control- ling the flow to and fro of the water and dissolved substances; but there can be little doubt that in all of them the physical forces of filtration, diffusion, and osmosis take an important part. Whatever can be learned therefore concerning these processes must iu

DIFFUSION AND OSMOSIS. 69

the end have an important bearing upon the explanation of the nutritive exchanges between the blood and tissues. Some additional facts may be mentioned to indicate the applications that are made of these processes in explaining physiological phenomena.

Osmotic Pressure of Proteids. — The osmotic pressure exerted by crystalloids, such as the ordinary soluble salts, is, as we have seen, very considerable, but the ready diffusi- bility of most of these salts through animal membranes limits very materially their influ- ence upon the flow of water in the body. Thus if we should inject a strong solution of common salt directly into the blood-vessels, the first effect would be the setting up of an osmotic stream from the tissues to the blood and the production of a condition of hydremic plethora within the blood-vessels. The salt, however, would soon diffuse out into the tis- sues, and to the degree that this occurred its effect in diluting the blood would tend to dimin- ish because the part of the salt that got into the extra-vascular lymph-spaces would now exert an osmotic pressure in the opposite direction, drawing water from the blood. This fact, together with the further fact that an excess of salts in the body is soon removed by the excreting organs, gives to such substances a smaller influence in directing the water stream than would at first be supposed when the intensity of their osmotic action is con- sidered. In addition to the crystalloids the liquids of our bodies contain also a certaiu amount of proteid, the blood, especially, containing over 6 per cent, of this substance. It has been generally assumed that proteids in solution exert little or no osmotic pressure, but Starling 1 and others have claimed, on the contrary, that proteids in solution exert a distinct although small osmotic pressure, and it is probable that this fact is of special importance in absorption because the proteids do not diffuse or diffuse with great difficulty, and their effect remains therefore, so to speak, as a permanent factor. Accord- ing to Starling, the osmotic pressure exerted by the proteids of serum is equal to about 30 mm. of mercury. That the osmotic pressure of the serum proteids is so small is not surprising if we remember the very high molecular weight of this substance. In serum the proteids are present in a concentration of about 7 per cent., but owing to their large molecular weight comparatively few proteid molecules are present in a solution of this concentration ; and assuming that the dissolved proteid follows the laws discovered for crystalloids its osmotic pressure would depend upon the number of molecules in solu- tion. By means of this weak but constant osmotic pressure of the indiffusible proteid it is possible to explain the fact that an isotonic or even a hypertonic solution of diffus- ible crystalloid may be completely absorbed by the blood from the peritoneal cavity.

Isotonic, Hypertonic, and Hypotonic Solutions. — In physiology the osmotic pressures exerted by various solutions are compared usually with that of the blood-serum. In this sense an isotonic or isosmotic solution is one having an osmotic pressure equal to that of serum, a hypertonic or hyperosmotic solution is one whose osmotic pressure exceeds that of serum, and a hypotonic or hyposmotic solution is one whose osmotic pressure is less than that of serum.

Diffusion, or Dialysis, of Soluble Constituents. — If two liquids of unequal concentration in a given constituent are separated by a membrane entirely permeable to the dissolved molecules of the substance, a greater number of these molecules will pass over from the more concentrated to the less concentrated side, and in time the composition will be the same on the two sides of the membrane. Diffusion of soluble constituents continually takes place, therefore, from the points of greater concentration to those ofless, and this may bap- pen quite independently of the direction of the osmotic stream of water. I f. for instance, a 0.9 per cent, solution of sodium chloride is injected into the peritoneal cavity, it will enter into diffusion relations with the blood in the blood-vessels; its concentration in sodium chloride being greater than that of the blood, the excess will tend to pass into the blood, while sodium carbonate, urea, sugar, and other soluble crystalloidal substances will pass from the blood into the salt solution in the peritoneal cavity. Through the action of this process of diffusion we can understand how certain constituents of the blood may pass

1 Journal of Physiology, L899, vol. 24, |>. .".IT.

70 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

to the tissues of various glands in amounts greater than could be explained if we sup- posed that the lymph of these tissues was derived solely by filtration from the blood- plasma. (See p. ~'l for an illustration.) Another important conception in this con- nection is the possibility that the capillary walls may be permeable in different degrees to the various soluble constituents of the blood, and furthermore the possibility that the permeability of the capillary walls may vary in different organs. With regard to the first possibility it has been shown by Roth ' that the blood-capillaries are more per- meable to the urea molecules than to sugar or NaCl. With the aid of these facts it is possible to explain in Large measure the transportation of material from the blood to the tissues, and vice versa. For example, to follow a line of reasoning used by Roth, we may suppose that the functional activity of the tissue-elements is attended by a con- sumption of material which in turn is made good by the dissolved molecules in the tissue-lymph. The concentration of the latter is thereby lowered, and in consequence a diffusion stream of these substance- is set up with the more concentrated blood. In this way, by diffusion, a constant supply of dissolved material is kept in motion from the blood to the tissue-elements. On the other hand, the functional activity of the tissue- elements is accompanied by a breaking down of the complex proteid molecule with the formation of simpler, more stable molecules of crystalloid character, such as the sul- phates, phosphates, and urea or some precursor of urea. As these bodies pass into the tissue-lymph they tend to increase its molecular concentration, and thus by the greater osmotic pressure which they exert serve to attract water from the blood to the lymph, forming one efficient factor in the production of lymph. On the other hand, as these substances accumulate in the lymph to a concentration greater than that possessed by the same substances in the blood, they will diffuse toward the blood. By this means the waste-products of activity are drawn off to the blood, from which in turn they are removed by the action of the excretory organs.

Diffusion of Proteids. — This simple explanation on purely physical grounds of the flow of material between the blood and the tissues can only be applied, however, at present to the diffusible crystalloids, such as the salts, urea, and sugar. The proteids of the blood, which are supposed to be so important for the nutrition of the tissues, are prac- tically indiffusible, so far as we know. It is difficult to explain their passage from the blood through the capillary walls into the lymph. Provisionally it may be assumed that this passage is due to filtration. The blood-plasma in the capillaries is under a slightly higher pressure than the lymph of the tissues, and this higher pressure tends t" Mpieeze the blood-constituents, including the proteid, through the capillary walls. Tin- explanation, however, cannot be said to be satisfactory, and in this respect the purely physical theory of lymph-formation waits upon a clearer knowledge of the nature of the nutritive proteids and their relations to the capillary walls.

LYMPH.

LYMPH is a colorless liquid found in the lymph-vessels as well as in the extravascular spaces of the body. All the tissue-elements, in fact, may be regarded as being bathed in lymph. To understand its occurrence in the body one has only to hear in mind its method of origin from the blood. Throughout the entire body there is a rich supply of blood-vessels penetrating every tissue with the exception of the epidermis and some epidermal structures, as the nails and the hair. The plasma of the blood, by the action of physical or chemical processes, the details <d* which are not vet entirely understood, makes its way through the thin walls id' the capillaries, and is thus brought into immediate

1 Archiv fur Physiohgie, 1899, 8. 416.

LYMPH. 71

contact with the tissues, to which it brings the nourishment and oxygen of the blood and from which it removes the waste-products of metabolism. This extravascular lymph is collected into small capillary spaces that in turn open into definite lymphatic vessels. These vessels unite to larger and larger trunks, forming eventually one main trunk, the thoracic or left lymphatic duct, and a second smaller right lymphatic duct, which open into the blood- vessels, each on its own side, at the junction of the subclavian and internal jugular veins. While the supply of lymph in the lymph-vessels may be consid- ered as being derived ultimately entirely from the blood-plasma, it is well to bear in mind that at any given moment this supply may be altered by direct inter- change with the plasma on one side and the extravascular lymph permeating the tissue-elements on the other. The intravascular lymph may be augmented. for example, by a flow of water from the plasma into the lymph-spaces, or by a flow from the tissue-elements into the lymph-spaces that surround them. The lymph movement is from the tissues to the veins, and the flow is main- tained chiefly by the difference in pressure between the lymph at its origin in the tissues and in the large tymphatic vessels. The continual formation of lymph in the tissues leads to the development of a relatively high pressure in the lymph capillaries, and as a result of this the lymph is forced toward the point of lowest pressure — namely, the points of junction of the large lymph- ducts with the venous system. A fuller discussion of the factors concerned in the movement of lymph will be found in the section on Circulation. As would be inferred from its origin, the composition of lymph is essentially the same as that of blood-plasma. Lymph contains the three blood-proteids, the extractives (urea, fat, lecithin, cholesteriu, sugar), and inorganic salts. The salts are found in the same proportions as in the plasma; the proteids are less in amount, espe- cially the fibrinogen. Lymph coagulates, but does so more slowly and less firmly than the blood. Histologically, lymph consists of a colorless liquid con- taining a number of leucocytes, and after meals a number of minute fat-drop- lets; red blood-corpuscles occur only accidentally, and blood-plates, according to most accounts, are likewise normally absent.

Formation of Lymph. — The careful researches of Ludwig and his pupils were formerly believed to prove that the lymph is derived directly from the plasma of the blood mainly by filtration through the capillary walls. Emphasis was laid on the undoubted fact that the blood within the capillaries is under a pressure higher than that prevailing in the tissues outside, and it was Hip- posed that this excess of pressure is sufficient to squeeze the plasma of the blood through the very thin capillary walls. Various conditions that alter the pressure of the blood were shown to influence the amount of lymph formed in accordance with the demands of a theory of filtration. More- over, the composition of lymph as usually given seems to support such :i theory, inasmuch as the inorganic salts contained in it are in the same concen- tration, approximately, as in blood-plasma, while the proteids are in less con- centration, following the well-known law that in the filtration of colloids throueh animal membranes the filtrate is more dilute than the original solution.

72 AX AMERICAN TEXT-BOOK OE PHYSIOLOGY.

This simple and apparently satisfactory theory has been subjected to critical examination within recent years, and it has been shown that filtration alone does not suffice to explain the composition of the lymph under all circum- stances. At present two divergent views are held upon the subject. Accord- ing to some physiologists, all the facts known with regard to the composition of lymph may be satisfactorily explained if we suppose that this liquid is formed from blood-plasma by the combined action of the physical processes of filtration, diffusion, and osmosis. According to others, it is believed that, in addition to filtration and diffusion, it is necessary to assume an active secretory process on the part of the endothelial cells composing the capillary walls. A discussion upon these points is in progress in current physiological literature, and it is impossible to foresee definitely what the outcome will be, since a final conclusion can be reached only by repeated experimental investigations. The actual condition of our knowledge of the subject can be presented most easily by briefly stating some of the objections that have been raised by Heiden- hain1 to a pure filtration-and-diffusion theory, and indicating how these objec-