1 Digitized by tlie Internet Arcliive in 2010 witli funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/textbookofphysio1878fost A TEXT BOOK OF PHYSIOLOGY, A TEXT BOOK OF PHYSIOLOGY BY M. FOSTER, M.A., M.D., F.RS., PK.ELECTOB IN PHYSIOLOGY AND FELLOW OF TRINITY COLLEGE, CAMBRIDGE. WITH ILLUSTRATIONS. SECOND EDITION, REVISED AND ENLARGED. Honbon : MACMILLAN AND CO. 1878 \_All Eights reserved.] gl? Camliritrge : PB.INTED BY C. J. CI.AY, M.A. AT THE UNIVEKSITY PRESS. PKEFACE TO THE SECOND EDITION. So short a time has passed since the appearance of the first edition that it has not seemed desirable to make any important changes. My previous decision not to introduce figures of instruments has been so generally disapproved, that I have waived my own judgment and inserted a number of illustrations, which I trust will be found to assist the reader. The areas of the cerebral convolutions, in spite of the difiiculties surrounding the true interpretation of the phenomena resulting from their stimulation, are of such interest, especially to the medical profession, that I have introduced illustrative figures for which I have to thank the kindness of Dr Ferrier. Otherwise my efibrts have been chiefly directed to removing inaccuracies and obscurities, in the hope of ren- dering the work more worthy of the favour with which it has been received. It will be observed that the largest changes and additions occur in the small print. F. p. b vi PREFACE. I have to thank Dr Pye- Smith and other friends as well as previously unknown correspondents for their valuable suggestions ; and I ana, as before, greatly indebted for the help given me by my former pupils, Mr Dew-Smith, Mr Langley, and Mr Lea. Trinity College, Cambridge, December, 1877. EEEATA. p. 70, 1. 6 from bottom, for Jcilogrammeters read grammeters. p. 184, 1. 11 from bottom, in the formula for dextrin for 0 read Og. p. 194, note 1, for Lehrb, i. 40 read Lehrh. p. 40. CONTENTS. • PAGE INTRODUCTOEY ........... 1 BOOK I. BLOOD. THE TISSUES OF MOVEMENT. THE VASCULAR MECHANISM. CHAPTER I. Blood, pp. 11 — 30. Sec. 1. The Chemical Composition of Blood • . . 12 Sec. 2. . The Coagulation of Blood ......... 14 Sec. 3. The History of the Corpuscles . . - 27 Sec. 4, The Quantity of Blood, and its distribution in the Body ... 30 CHAPTER II. The Contractile Tissues, pp. 32 — 84. Sec. 1. The Chemical Substances composing or present in iluscle ... 32 Sec. 2. The Phenomena of Muscle and Nerve 85 The Phenomena of a simple muscular contraction, p. 36. Tetanic contractions, p, 44. Changes in a nerve during the passage of a nervous impulse, p. 46. Changes in a muscle during contrac- tion, p. 52. The nature of the changes through which an electric current is able to generate a nervous impulse, Electrotonus, &c., p. 59. Circumstances affecting the amount and character of the contraction, p. 68. Sec. 3. Unstriated Muscular Tissue . . . i 82 Sec. 4. Cardiac Muscles 83 Sec. 5. Cilia _ . . 83 Sec. 6. Migrating Cells » » 84 CHAPTER III. The Fundamental Properties of JSTervous Tissues, pp. 85 — 95. Automatic actions, p. 88, Eeflex actions, p. 90. Inhibition, p. 93. viii CONTENTS. CHAPTEE IV. The Vascular Mechanism, pp. 96 — 179. PAGE I. The Physical Phenomena op the Circulation .... 96 Sec. 1. Main general facts of the Circulation ....... 97 The Capillary Circnlation, p. 97. The flow in the Arteries, p. 99. The flow in the Yeins, p. 106. Hydraulic principles of the Circula- tion, p. 107. Sec. 2. The Heart 113 The Phenomena of the Normal Beat, p. 113. The Mechanism of the Valves, p. 122. The sounds of the Heart, p. 126. The work done, p. 128. Variations in the Heart's Beat, p. 130. Sec. 3. The Pulse ............ 131 II. The Vital Phenomena of the Circulation .... 140 Sec. 4. Changes hi the Beat of the Heart 141 Nervous mechanism of the beat, p. 142. Inhibition of the beat, p. 144. The effects on the circulation of changes in the heart's beat, p. 151. Sec. 0. Changes in the calibre of the minute arteries. Vaso-motor actions . 154 Vaso-motor nerves, p. 155. Vaso-motor centre, p. 157. The effects of local vascular constriction or dilation, p. 170. Sec. 6. Changes in the Capillary Districts 171 Sec. 7. Changes in the Quantity of Blood 174 The Mutual Relations and the Co-ordination of the Vascular Factors . 176 BOOK II. THE TISSUES OF CHEMICAL ACTION WITH THEIR RESPECTIVE MECHANISMS. NUTRITION. CHAPTEE, I. The TisstTEs and Mechanisms of Digestion, pp. 183 — 252. Sec. 1. The Properties of the Digestive Juices 183 Saliva, p. 183. Gastric juice, p. 188. Bile, p. 195. Pancreatic juice, p. 198. Succus Entericus, p. 204. Sec. 2. The act of secretion in the case of the Digestive Juices and the Nervous Mechanisms which regulate it 205 Sec. 3. The Muscular Mechanisms of Digestion 224 Mastication, p. 225. Deglutition, p. 225. Peristaltic action of the small intestine, p. 227. Movements of the oesophagus, p. 230. Movements of the stomach, p. 232. Movements of the large in- testine, p. 233. Defffication, p. 233. Vomiting, p. 235. Sec. 4. The Changes which the Food undergoes in the Alimentary Canal . . 237 Sec. 5. Absorption of the Products of Digestion 244 CONTENTS. ix CHAPTEK II. The Tissues and Mechanisms of Eespiration, pp. 253 — 310. PAGE Sec. 1. The Mechanics of Pulmonary Respiration- 254 The Rhythm of Eespiration, p. 256. The Bespiratory Movements, p. 259. Sec. 2. Changes of the Air in Eespiration . . . . . . • • 264 Sec. 3. The Respiratory Changes in the Blood ....... 267 The relations of oxygen in the blood, p. 268. Haemoglobin; its properties and derivatives, p. 271. Colour of venous and arterial blood, p. 276. The relations of the carbonic acid in the blood, p. 280. The relations of the nitrogen in the blood, p. 281. Sec. 4. The Respiratory Changes in the Lungs 281 The entrance of oxygen, p. 281. The exit of carbonic acid, p. 282. See. 5. The Respiratory Changes in the Tissues 284 Sec. 6. The Nervous Mechanism of Respiration 288 Sec. 7. The Effects of Respiration on the Circulation . . . . . 295 Sec. 8. The Effects of Changes in the Air breathed . . . . . . 302 The effects of deficient air. Asphyxia. Phenomena of asphyxia, p. 302. The circulation in asphyxia, p. 304. The effects of an increased supply of air. Apncea, p. 306. The effects of changes in the com- position of the air breathed, p. 307. The effects of changes in the pressure of the air breathed, p. 308. Sec. 9. Modified Respiratory Movements 308 Sighing, Yawning, Hiccough, Sobbing, Coughing, Sneezing and Laughter, p. 309. CHAPTER III. Secretion by the Skin, pp. 311 — 316. The Nature and Amount of Perspiration . . . .■ . . . . 311 Cutaneous Respiration . , , . . . . . . . • . 313 The Secretion of Sioeat ........... 314 The Nervous Mechanism of Perspiration, p. 315. Absorption by the Skin 316 CHAPTER IV. Secretion by the Kidneys, pp. 317 — 329. Sec. 1. The Composition of Urine 317 Sec. 2. The Secretion of Urine . 320 The relation of the secretion of urine to arterial pressure, p. 321. Secretion by the renal epithelium, p. 324. Sec. 3. Micturition • • 327 X CONTENTS. CHAPTER V. The Metabolic Phenomexa of the Body, pp. 330 — 386. PAGE Sec. 1. Metabolic Tissues 330 The History of Glycogen, p. 330. The History of Fat. Adipose Tissue, p. 340. The Mammary Gland, p. 344. The Spleen, p. 346. Sec. 2. The History of Urea and its allies . . . . . . . . 348 Sec. 3. The Statistics of Nutrition 355 Composition of the animal Body, p. 355. The starving Body, p. 356. The Normal Diet, p. 357. Comparisons of Income and Outcome, p. 358. Nitrogenous Metabolism, p. 361. The effects of Fatty or Amyloid Food, p. 363. Sec. 4. The Energy of the Body 366 The income of energy, p. 366. The expenditure, p. 368. The sources of Muscular Energy, p. 368. The Sources and Distribution of Heat, p. 372. Sec. 5. The Influence of the Nervous System on Nutrition 381 Sec. 6. Dietetics 383 BOOK III. THE CENTRAL NERVOUS SYSTEM AND ITS INSTRUMENTS. CHAPTER T. Sensory Nerves, pp. 389 — 396. CHAPTER II. Sight, pp. 397—448. Sec. 1. Dioptric Mechanisms 397 The Formation of the Image, p. 397. Accommodation, p. 399. Movements of the Pupil, j). 405. Imperfections in the Dioptric apparatus, p. 410. Sec. 2. Visual Sensations ........... 413 Simple Sensations, j). 416. Colour Sensations, p. 420. Sec. 3. Visual Perceptions .......... 427 Modified Perceptions, p. 432. Sec. 4. Binocular Vision 436 Corresponding or identical points, p. 436. Movements of the eyeballs, p. 437. The Horopter, p. 442. Sec. 5. VisualJudyments 444 Sec. 6. The protective Mechanisms of the eye 417 CONTENTS. xi CHAPTER III. Hearing, Smell, and Taste, pp. 449 — 461. PAGE Sec. 1. Hearing 449 The acoustic apparatus, p. 449. Auditory Sensations, p. 452. Auditory Judgments, p. 457. Sec. 2. Smell * 458 Sec. 3. Taste 460 CHAPTER IV. Feeling and Touch, pp. 462 — 470. Sec. 1. General Sensibility and Tactile Perceptions . . . . . . 462 Sec. 2. Tactile Sensations . . . . , 463 Sensations of Pressure, p. 463. Sensations of Temperatm-e, p. 464. Sec. 3. Tactile Perceptions and Judgments . » 466 Sec. 4. The Muscular Sense . . . . , 468 CHAPTER Y. The Spinal Cord, pp. 471—488. Sec. 1. As a centre of Rejlex Action 471 In the Frog, p. 471. In the Mammal, p. 476. The time of Eeflex Actions, p. 478. Sec. 2. As a Centre or Group of Centres of Automatic Action .... 478 Sec. 3. As a Conductor of Afferent and Efferent Impulses 480 CHAPTER VI. The Brain, pp. 489—526. Sec. 1. On the Phenomena exhibited by an animal deprived of its Cerebral Hemispheres ........... 489 Sec. 2. The Mechanisms of Co-ordinated Movements 493 Forced Movements, p. 498. Sec. 3. The Functions of the Cerebral Convolutions 500 Sec. 4. The Functions of other parts of the Brain 509 Corpora striata and optic thalami, p. 510. Corpora quadrigemiua, p. 514. Cerebellum, p. 517. Pons Varolii and Crura Cerebri, p. 519. MeduUa oblongata, p. 520. Sec. 5. The Rapidity of Cerebral Operations 521 Sec. 6. The Cranial Nerves 523 xii CONTEXTS. CHAPTER VIT. Special IMuscular Mechanisms, pp. 527 — 538. PAOE Sec. 1. The Voice 527 Sec. 2. Speech 532 Vowels, p. 532. Consonants, p. 533. Sec. 3. Locomotor Mechanisms 536 BOOK IV. THE TISSUES AND MECHANISMS OF REPKODUCTION. CHAPTER I. Menstruation, pp. 542 — 544. CHAPTER II. Impregnation, pp. 545, 546. CHAPTER III. The Nutrition of the Embryo, pp. 547 — 552. CHAPTER lY. Parturition, pp. 553 — 555. CHAPTER V. The Phases of Life, pp. 556 — !iG(j. CHAPTER VI. Death, pp. 567, 568. APPENDIX. On the Chemical Basis of the Animal Body, pp. 571—626. INDEX, pp. 627—640. INTEODUCTORY. Among the simpler organisms known to Biologists, perhaps the most simple as well as the most common is that which has received the name of Amoeba. There are many varieties of Amoeba, and probably many of the forms which have been described are, in reality, merely amoebiform phases in the lives of certain animals or plants ; but they all possess the same general characters. Closely resembling the w^hite corpuscles of vertebrate blood, they are wholly or almost wholly composed of undifferentiated protoplasm, in the midst of which lies a nucleus, though this is sometimes absent. In many a distinction may be observed between a more solid external layer or ectosarc, and a more fluid granular interior or endosarc; but in others even this primary differentiation is wanting. By means of a continually occur- ring flux of its protoplasmic substance, the amoeba is enabled from moment to moment not only to change its form but also to shift its position. By flowing round the substances which it meets, it, in a "way, swallows them; and having digested and absorbed such parts as are suitable for food, ejects or rather flows away from the use- less remnants \ It thus lives, moves, eats, grows, and after a time dies, having been during its whole life hardly anything more than a minute lump of protoplasm. Hence to the Physiologist it is of the greatest interest, since in its life the problems of physiology are reduced to their simplest forms. Now the study of an amoeba, with the help of knowledge gained by the examination of more complex bodies, enables us to state that the undifferentiated protoplasm of which its body is so largely com- posed possesses certain fundamental vital properties. 1. It is contractile. There can be little doubt that the changes in the protoplasm of an amoeba which bring about its peculiar 'amoe- boid' movements, are identical in their fundamental nature with those which occurring in a muscle cause a contraction ; a muscular contraction is essentially a regular, an amoeboid movement an irre- gular flow of protoplasm. The body of the amoeba may therefore be said to be contractile. 1 Huxley and Martin, Elementary Biology, Lesson iii, F. P. 1 2 PROPERTIES OF PROTOPLASM. 2. It is irritable and automatic. When any disturbance, sucli as contact with a foreign body, is brought to bear on the amoeba at rest, movements result. These are not passive movements, the effects of the push or pull of the disturbing body and therefore proportionate to the force employed to cause them, but active manifestations of the contractility of the protoplasm; that is to say, the disturbing cause, or 'stimulus,' sets free a certain amount of energy previously latent in the protoplasm, and the energy set free takes on the form of movement. Any living matter which, when acted on by a stimulus, thus suffers an explosion of energy, is said to be 'irritable.' The irritability may, as in the amoeba, lead to movement; but in some cases no movement follows the application of the stimulus to irritable matter, the energy set free by the explosion taking on some other form (heat, &c.) than movement. Thus a substance may be irritable and yet not contractile, though contractility is the most common manifestation of irritability. The amoeba (except in its prolonged quiescent stage) is rarely at rest. It is almost continually in motion. The movements cannot always be referred to changes in surrounding circumstances acting as stimuli; in many cases the energy is set free in consequence of internal changes, and the movements which result are called spon- taneous or automatic^ movements. We may therefore speak of the j)rotoplasm of the amoeba as being irritable and automatic. 8. It is receptive and assimilative. Certain substances serving as food are received into the body of the amoeba, and being there in large measure dissolved, become part and parcel of the body of the amoeba, become in fact fresh protoplasm. 4. It is metabolic ^ and secretory. Fari jmssu with the recep- tion of new material, there is going on an ejection of old material, for the increase of the amoeba by the addition of food is not indefinite. In other words, the protoplasm is continually undergoing chemical change (metabolism), room being made for the new protoplasm by the breaking up of the old protoplasm into products which are cast out of the body and got rid of These products of metabolic action have in all probability subsidiary uses. Some of them, for instance, we have reason to think are of value for the purpose of dissolving and effecting other preliminary changes in the raw food mechanically introduced into the body of the amoeba; and hence are retained within the protoplasm for some little time. Such products are gene- rally spoken of as ' secretions.' Others which pass more rapidly away 1 This word has recently acquired a meaning almost exactly opposite to that which it originally bore, and an automatic action is now by many understood to mean nothing more than an action produced by some machinery or other. In this work I use it in the older sense, as denoting an action of a body, the causes of which appear to lie in the body itself. It seems preferable to 'spontaneous,' inasmuch as it does not necessarily carry with it the idea of irregularity, and bears no reference to a 'will.' 2 This term was introduced by Schwann (1839). Micros. Untersucli. p. 229. INTRODUCTORY. 3 are generally called 'excretions.' The distinction between the two is an unimportant and frequently accidental one. The energy expended in the movements of the amoeba is supplied by the chemical changes going on in the protoplasm, by the breaking up of bodies possessing much latent energy into bodies possessing less. Thus the metabolic changes which the food undergoes in passing through the protoplasm of the amoeba (as distinguished from the undigested stuff mechani- cally lodged for a while in the body) are of three classes: those pre- paratory to and culminating in the conversion of the food into protoplasm, those concerned in the discharge of energy, and those tending to economise the immediate products of the second class of changes by rendering them more or less useful for the first. 5. It is respiratory. Taken as a whole, the metabolic changes are pre-eminently processes of oxidation. One article of food, i.e. one substance taken into the body, viz. oxygen, stands apart from all the rest, and one product of metabolism peculiarly associated with oxidation, viz. carbonic acid, stands also somewhat apart from all the rest. Hence the assumption of oxygen and the excretion of carbonic acid, together with such of the metabolic processes as are more especially oxidative, are frequently spoken of together as constituting the respiratory processes. 6. It is reproductive. The individual amoeba represents a unit. This unit, after a longer or shorter life, having increased in size by the addition of new protoplasm in excess of that which it is con- tinually using up, may, by fission (or by other means) resolve itself into two (or more) parts, each of which is capable of living as a fresh unit or individual. Such are the fundamental vital qualities of the protoplasm of an amoeba; all the facts of the life of an amoeba are manifestations of these protoplasmic qualities in varied sequence and subordination. The higher animals, we learn from morphological studies, may be regarded as groups of amoebae peculiarly associated together. All the physiological phenomena of the higher animals are similarly the results of these fundamental qualities of protoplasm peculiarly asso- ciated together. The dominant principle of this association is the physiological division of labour corresponding to the morphological differentiation of structure. Were a larger or 'higher' animal to consist simply of a colony of undifferentiated amoebse, one animal differing from another merely in the number of units making up the mass of its body, without any differences between the individual units, progress of function would be an impossibility. The accumu- lation of units would be a hindrance to Avelfare rather than a help. Hence, in the evolution of living beings through past times, it has come about that in the higher animals (and plants) certain gToups of the constituent amoebiform units or cells have, in company with a change in structure, been set apart for the manifestation of certain 1—2 4 THE FUNDAMENTAL TISSUES. only of the fundamental properties of protoplasm, to the exclusion or at least to the complete subordination of the other properties. These groups of cells, thus distinguished from each other at once by the differentiation of structure and by the more or less marked exclusiveness of function, receive the name of 'tissues.' Thus the units of one class are characterized by the exaltation of the con- tractility of their protoplasm, their automatism, metabolism and reproduction being kept in marked abeyance. These units con- stitute the so-called muscular tissue. Of another tissue, viz. the nervous, the marked features are irritability and automatism, with an almost complete absence of contractility and a great restriction of the other qualities. In a third group of units, the activity of the protoplasm is largely confined to the chemical changes of secretion, contractility and automatism (as manifested by movement) being either absent or existing to a very slight degree. Such a secreting tissue, consisting of epithelium-cells, forms the basis of the mucous membrane of the alimentary canal. In the kidney, the substances secreted by the cells being of no further use, are at once ejected from the body. Hence the renal tissue may be spoken of as excretory. In the epithelium-cells of the lungs, the protoplasm plays an altogether subordinate part in the assumption of oxygen and the excretion of carbonic acid. Still we may perhaps be permitted to speak of the pulmonary epithelium as a respiratory tissue. In addition to these distinctly secretory or excretory tissues, there exist groups of cells specially reserved for the carrying on of chemical changes, the products of which are neither cast out of the body, nor collected in cavities for digestive or other uses. The work of these cells seems to be of an intermediate character ; they are en- gaged either in elaborating the material of food that it may be the more easily assimilated, or in preparing used up material for final excretion. They receive their material from the blood and return their products back to the blood. They may be called the metabo- lic tissues par excellence. Such are the fat-cells of adipose tissue, the hepatic cells (as far as the work of the liver other than the secre- tion of bile is concerned), and in general the blood. Each of the various units retains to a greater or less degree the power of reproducing itself, and the tissues generally are capable of regeneration in kind. But neither units nor tissues can reproduce other parts of the organism than themselves, much less the entire organism. For the reproduction of the complex individual, certain units are set apart in the form of ovary and testis. In these all the pro- perties of protoplasm are distinctly subordinated to the work of growth. Lastly, there are certain groups of units, certain tissues, which are of use to the body of which they form a part, not by reason of their manifesting any of the fundamental qualities of protoplasm, but on account of the physical and mechanical properties of certain substances which their protoplasm has been able by virtue of its metabolism to manufacture and to deposit. Such tissues are bone, INTRODUCTORY. 5 cartilage, connective tissue in large part, and the greater portion of the skin. We may therefore consider the complex body of a higher animal as a compound of so many tissues, each tissue correspond- ing to one of the fundamental qualities of protoplasm, to the develop- ment of which it is specially devoted by the division of labour. It must however be remembered that there is a distinct limit to the division of labour. In each and every tissue, in addition to its leading quality, there are more or less pronounced remnants of all the other protoplasmic qualities. Thus, though we may call one tissue par excellence metabolic, all the tissues are to a greater or less extent metabolic. The energy of each, whatever be its particular mode, has its source in the breaking up of the protoplasm. Chemical changes, including the assumption of oxygen and the production com- plete or partial of carbonic acid and therefore also entailing a cer- tain amount of secretion and excretion, must take place in each and every tissue. And so with all the other fundamental properties of protoplasm; even contractility, which for obvious mechanical reasons, is soonest reduced where not wanted, is present in many other tissues besides muscle. And it need hardly be said that each tissue retains the power of assimilation. However thoroughly the material of food be prepared by digestion and subsequent metabolic action, the last stages of its conversion into living protoplasm are effected directly and alone by the tissue of which it is about to form a part. Bearing this qualification in mind, we may draw up a physio- logical classification of the body into the following fundamental tissues: — • 1. The eminently contractile; the muscles. 2. „ „ irritable and automatic; the nervous system. 3. „ „ secretory, or excretory; digestive, urinary, and pulmonary &c., epithelium. 4. „ „ metabolic ; fat-cells, hepatic cells, lymphatic and ductless glands, &c. 5. „ „ reproductive ; ovary, testis. 6. The indifferent or mechanical; cartilage, bone, &c. All these separate tissues, with their individual characters, are however but parts of one body; and in order that they may be true members workiug harmoniously for the good of the whole, and not isolated masses each serving its own ends only, they need to be bound together by co-ordinating bonds. Some means of communica- tion must necessarily exist between them. In the mobile homo- geneous body of the amoeba, no special means of communication are required. Simple diffusion is sufficient to make the material gained by one part common to ■ the whole mass, and the native protoplasm is physiologically continuous, so that an explosion set up at any one point is immediately propagated throughout the 6 INTEGRATION. whole irritable substance. In tbe liigber animals, tlie several tissues are separated by distances far too great for the slow process of diffusion to serve as a sufficient means of communication, and their primary physiological continuity is broken by their being imbedded in masses of formed material, the product of the indifferent tissues, which being devoid of irritability, present an effectual barrier to the propagation of molecular explosions. It thus becomes necessary that in the increasing complexity of animal forms, the process of differen- tiation should be accompanied by a corresponding integration, that the isolated tissues should be made a whole by bonds uniting them together. These bonds moreover must be of two kinds. In the first place there must be a ready and rapid distribu- tion and interchange of material. The contractile tissues must be abundantly supplied with material best adapted by previous elabora- tion for direct assimilation, and the waste products arising from their activity must be at once carried away to the metabolic or excretory tissues. And so with all the other tissues. There must be a free and speedy intercourse of material between each and all. This is at once and most easily effected by the regular circulation of a common fluid, the blood, into which all the elaborated food is discharged, from which each tissue seeks what it needs, and to which each returns that for which it has no longer any use. Such a circulation of fluid, being in large measure a mechanical matter, needs a machinery, and calls forth an expenditure of energy. The machinery is supplied by a special construction of the primary tissues, and the energy is arranged for by the presence among these of contractile and irritable matter. Thus to the fundamental tissues there is added, in the higher animals, a vascular bond in the shape of a mechanism of circulation. In the second place, no less important than the interchange of material is the interchange of energy. In the amoeba the irritable surface is physiologically continuous with the more internal proto- plasm, while each and every part of the body has automatic powers. In the higher animal, portions only of the skin remain as eminently irritable or sensitive structures, while automatic actions are chiefly confined to a central mass of irritable or nervous matter. Both forms of irritable matter are separated by long tracts of indifferent material from those contractile tissues, through \\hich they chiefly manifest the changes going on in themselves. Hence the necessity for long strands of eminently irritable tissue to connect the skin and contractile tissues as well with each other as with the automatic centres. Similar strands are also needed, though perhaps less urgently, to connect the other tissues with these and with each other. To the vascular bond there must be added an irritable bond, along the strands of which impulses, set up by changes in one or another jDart, may travel in determinate courses for the regulation of the energy of distant spots. In other words, part of the irritable tissues must be specially arranged to form a coordinating nervous system. INTRODUCTORY. 7 Still further complications have yet to be considered. In the life of a minute homogeneous amoeba, possessing no special form or struc- ture, there is little scope for purely mechanical operations. As how- ever we trace out the gradual development of the more complex animal forms, we see coming forward into greater and greater pro- minence the arrangement of the tissues in definite ways to secure mechanical ends. Thus the entire body acquires particular shapes, and parts of the body are built up into mechanisms, the actions of which are to the advantage of the individual. Into the composi- tion of these mechanisms or ' organs ' the active fundamental tissues, as well as the passive or indifferent tissues, enter ; and the working of each mechanism, the function of each organ, is dependent partly on the mechanical conditions offered by the passive elements, partly on the activity of the active elements. The vascular mechanism, of which we have just spoken, is such a mechanism. Similarly the urgent necessity for the access of oxygen to all parts of the body, has given rise to a complicated respiratory mechanism ; and the needs of copious alimentation, to an alimentary or digestive me- chanism. Further, inasmuch as muscular movement is one of the chief ends, or the most important means to the chief ends of animal life, we find the animal body abounding in motor mechanisms, in which the prime mover is muscular contraction, while the machinery is sup- plied by complicated arrangements of muscles with such indifferent tissues as bone, cartilage, and tendon. In fact, the greater part of the animal body is a collection of muscular machines, some serving for locomotion, others for special manoeuvres of particular members and parts, others as an assistance to the senses, and yet others for the production of voice, and in man, of speech. Lastly, the simple automatism of the amoeba, with its simple responses to external stimuli, is replaced in the higher animals by an exceedingljr complex volition affected in multitudinous ways by influences from the world without ; and there is a correspondingly complex central nervous system. And here we meet with a new form of differentiation unknown elsewhere. While the contractility of the amoebal protoplasm differs at the most but slightly from the contractility of the vertebrate striated muscle, there is an enormous difference between the simple irritability of the amoeba and the com- plex action of the vertebrate nervous system. Excepting the nervous or irritable tissues, the fundamental tissues have in all animals exactly the same properties, being, it is true, more acute and perfect in one than in another, but remaining fundamentally the same. The elementary muscular fibre of a mammal is at most a mass of but slightly differentiated protoplasm, forming a whole physio- logically continuous, and in no way constituting a mechanism. Each fibre is a counterpart of all others ; and the muscle of one animal differs from that of another in such particulars only as are wholly subordinate. In the nervous tissues of the higher 8 CENTRAL NERVOUS MECHANISM. animals, on the contrary, we find properties unknown to those of the lower ones, and in proportion as we ascend the scale, we observe an increasing differentiation of the nervous system into unlike parts. Thus we have, what does not exist in any other tissue, a mechanism of nervous tissue itself, a central nervous mechanism of complex structure and complex function, the complexity of which is due not primarily to any mechanical arrangements of its parts, but to the further differentiation of that fundamental quality of irritability and spontaneity which belongs to all irritable tissues, and to all native protoplasm. In the following pages I propose to consider the facts of physio- logy very much according to the views which have been just sketched out. The fundamental properties of most of the elementary tissues will first be reviewed, and then the various special mechanisms. It will be found convenient to introduce early the account of the vascular mechanism, and of its nervous coordinating mechanism, while the mechanisms of respiration and alimentation will be best considered in connection with the respiratory and secretory tissues. The description of the purely motor mechanisms will be brief, and, save in a few instances, confined to a statement of general principles. The special functions of the central nervous system, including the senses, must of necessity be considered by themselves. The tissues and mechanism of reproduction naturally form the subject of the closing chapter. BOOK L BLOOD, THE TISSUES OF MOVEMENT. THE YASCULAR MECHANISM. CHAPTEE I. BLOOD. Blood is a tissue of whicli the corpuscles are the essential and active elements, -while the plasma is a liquid matrix. It may be compared to a cartilage, the firm matrix of which has become lique- fied, so that the cartilage-corpuscles are perfectly free to rnove about. Of the two kinds of corpuscles, the white, seeing that they alone exist in many invertebrata, must be regarded as the original and proper cellular elements. The red corpuscles are forms which have been specially modified for respiratory and other purposes. In re- garding, however, blood as a tissue, we find that it differs from the other tissues in possessing no one characteristic property. The pro- toplasm of the white corpuscles is native undifferentiated protoplasm, in no respect fitted for any special duty; as far as we know at present, the white corpuscles are in reality embryonic structures concerned chiefly in the production of other forms, such as red corpuscles and, it may be, under certain conditions, various elements of the other tissues. The red corpuscles have a definite respiratory function; but these form a part only of the blood. The largest portion of the blood, the whole mass of the plasma, is an unorganized fluid with no proper physiological (vital) properties of its own. Its function is to serve as the great medium of exchange between all the tissues of the body. It, together with lymph (whether in the lymph-canals or in the inter- stices of the tissues), may, as Bernard has suggested, be regarded as cm internal medium bearing the same relations to the constituent tissues that the external medium, the world, does to the whole individual. Just as the whole organism lives on the things around it, its air and its food, so the several tissues live on the complex fluid by which they are all bathed and which is to them their immediate air and food. Hence the composition and the characters of blood must be for ever varying in different parts of the body and at different times. The changes which blood is known to undergo in passing through the various tissues will best be dealt with when those tissues and organs are under consideration. At present it will be sufficient to treat of — 1st, the general chemical composition of Blood; 2nd, the phenomena of its coagulation; 3rd, the history of its corpuscles; 4th, the total quantity of blood in the body. 12 COMPOSITION OF SERUM. [Book i. Sec. 1. The Chemical Composition of Blood. Blood, within the living vessels, is a fluid; but when shed, or after the death of the vessels, becomes solid by the process known as coagulation. The average specific gravity of human blood is 1055, varying from 1045 — 1075 within the limits of health. It has an alkaline reaction, which in shed blood rapidly diminishes up to the onset of coagulation. Blood may, in general terms, be considered as consisting by weight of more than one-third and less than one-half of corpuscles, the rest being plasma, the corpuscles being supposed to retain the amount of water proper to them. Hoppe-Seyler gives, in 1000 pai-ts of the venous blood of the horse, Corpuscles, 326, Plasma, 674; C. Schmidt \ in human blood, Corpuscles, 513, Plasma, 487 ^ In coagulation, see Sec. 2, a substance called fibrin forms with the corpuscles the clot; and the plasma becomes, by the loss of the fibrin or fibrin-factors, converted into serum. The average quantity of fibrin in human blood is said to be "2 p. c, but the amount which can be obtained from a given quantity of plasma varies extremely ; the variation being due not only to circumstances affecting the blood, but also to the method employed. Since serum is nothing but blood-plasma deprived of its fibrin- factors, it will be best to consider the chemical composition of serum alone. Composition of serum. In 100 parts of serum there are in round numbers Water 90 parts Proteid Substances 8 to 9 „ Fat, Extractive, and Saline Matters 2 to 1 „ Of the Proteid^ substances the great mass consists of the so-called serum-albumin, but there are present also small quantities of fibrino- plastin or fibrinoplastic globulin, which may be precipitated by passing a stream of carbonic acid through diluted serum, and of alkali albu- minate or serum casein, which after removal of the globulin may be thrown down by dilute acetic acid, and which is totally devoid of fibrinoplastic powers. The fats, which are scanty, except after a meal or in certain patho- logical conditions, are the neutral fats, stearin, palmitin, and olein, with a certain quantity of their respective alkaline soaps. Lecithin and cholesterin occur in very small quantities only. Among the extrac- tives* present in serum may be put down all the nitrogenous and other substances which form the extractives of the body and of food, ^ Characteristic der Cholera, p. 3. 2 For the various methods of determination see Hoppe-Seyler, Hdb. Analyse, p. 327. ^ For detailed accounts of the characters of the several chemical substances men- tioned in this and succeeding chapters consult the Appendix under the appropriate headings. ■^ This word is used to denote soluble substances of varied origin and nature, occur- ring in small quantities, and therefore requiring to be ' extracted ' by special means. Chap, l] BLOOD. 13 such as urea, kreatin, sugar, lactic acid, &c. A very large number of these have been discovered in the blood under various circumstances, the consideration of which must be left for the present. The peculiar odour of blood-serum is probably due to the presence of volatile bodies of the fatty acid series. The faint yellow colour of serum is due to a special yellow pigment. The most characteristic and impor- tant chemical feature of the saline constitution of the serum is the preponderance of sodium salts over those of potassium. In this re- spect the serum offers a marked contrast to the corpuscles (see below). Less marked, but still striking, is the abundance of chlorides and the poverty of phosphates in the serum as compared with the corpuscles. The salts may in fact briefly be described as consisting chiefly of sodium chloride, with small quantities of sodium carbonate, sodium sulphate, sodium phosphate, calcium phosphate, and magnesium phos- phate. Composition of the red corpuscles. The corpuscles contain less water than the serum. In 100 parts of wet corpuscles there are of Water 5 6' 5 parts Solids 43'5 „ The solids are almost entirely organic matter, the inorganic salts in the corpuscles amounting to less than 1 p. c. Of the organic matter again by far the larger part consists of hasmoglobin. In 100 parts of the dried organic matter of the corpuscles of human blood, Jiidell^ found, as the mean of two observations, Hsemoglobin 90"54 Lecithin '54 Proteid Substances 8'67 Cholesterin '25. The composition and properties of haemoglobin will be considered in connection with respiration. Of the proteid substances which form the stroma of the non-nucleated red corpuscles this much may be said, that they belong to the globulin family. The amount of fibrinoplas- tic globulin, and the exact nature of the other members of the group present, must be considered as yet undetermined. As regards the in- organic constituents, the corpuscles are distinguished by the relative abundance of the salts of potassium and of phosphates. The distribution of inorganic salts in blood may be seen from the follow ■ ing analysis by C. Schmidt^ of the ash of plasma and corpuscles respectively In 1000 parts Corpuscles. In 1000 parts Plasma. Potassium chloride 3-679 Potassium chloride '359 „ sulphate •132 „ sulphate -281 „ phosphate 2-343 Sodium „ •633 Sodium phosphate '271 Calcium „ •094 Calcium ,, '298 Magnesium „ •060 Magnesium „ '218 Soda •341 Soda 1-532 Sodium chloride 6-546 7-282 8-505 Hoppe-Seyler, Vntersuch. in. 390. ^ Op. cit. 14 COAGULATION OF BLOOD. [Book i. It must be remembered tbat tlie arrangement of bases and acids in such an analysis is an artificial one, and moreover, that tlie asb does not repre- sent the inorganic salts present in a natural condition in the blood. Thus for instance, the phosphates in the ash are largely derived by oxidation from the phosphorus present in the lecithin, and the sulphates similarly from the sulphur of proteid substances. On the other hand, carbonic anhy- dride is absent from the above table, though carbonates undoubtedly exist in the serum. Free soda is put down as a constituent of the ash, because in the ash the bases preponderate over the acids (even when carbonic anhydride is reckoned with thein) ; this alone shews how little the salts of the ash correspond to those really present in the blood. Among the natural saline constituents of serum may be enumerated sodium chloride, calcic phosphate, which is enabled to exist in a state of solution in the alkaline blood by reason of its being combined in some way or other with the pro- teids, and sodium carbonate. Composition of tlie white corpuscles. If it be permitted to infer the composition of the white corpuscles from that of the pus- corpuscles which they so closely resemble, they would seem to consist of ^ — 1. Several proteid substances, viz. ordinary albumin, an albumin like that of muscle coagulating at 48°, an alkali albumin, a substance closely resembling myosin and yet differing from it, and a peculiar form of proteid material soluble with difficulty in hydrochloiic acid. The nuclei contain nuclein. See Appendix. 2. Lecithin, extractives, glycogen, and inorganic salts, there being in the ash a preponderance of potassium salts and of phosphates ; after the death of the corpuscle the glycogen appears to be converted into sugar. Both the corpuscles and the plasma (or serum) contain gases. These will be considered in connection with respiration. The main facts of interest then in the chemical composition of the blood are as follows. The red corpuscles consist chiefly of haemoglo- bin. The solids of serum consist chiefly of serum-albumin, the quan- tity of fibrin factors and of alkali albuminate being small. The serum or plasma contrasts with the corpuscles, inasmuch as the former contains chiefly chlorides and sodium salts while the latter are richer in phosphates and potassium salts. The extractives of the blood are remarkable rather for their number and variability than for their abundance, the most constant and important being perhaps urea, kreatin, sugar, and lactic acid. Sec. 2. The Coagulation of Blood. Blood, when shed from the blood-vessels of a living body, is perfectly fluid. In a short time it becomes viscid; it flows less readily from vessel to vessel. The viscidity increases rapidly until the whole mass of blood under observation becomes a complete jelly. The vessel into which it has been shed, can at this stage be inverted without a drop of the blood being spilt. The jelly is of the same 1 Miescher. Hoppe-Seyler, Vntersucliungen, iv. 441. Chap, i.] BLOOD. 15 bulk as the previously fluid blood, and if forcibly removed, presents a complete mould of the interior of the vessel. If the blood in this jelly stage be left untouched in a glass vessel, a few drops of an almost colourless fluid soon make their appearance on the surface of the jelly. Increasing in number, and running together, the drops after a while form a superficial layer of pale straw-coloured fluid. Later on, similar layers of the same fluid are seen at the sides and finally at the bottom of the jelly, which, shrunk to a smaller size and of firmer consistency, now forms a clot or crassamentum, floating in a perfectly fluid serum. The shrinking and condensation of the clot, and the corresponding increase of the serum, continue for some time. The upper surface of the clot is generally cupped. A portion of the clot examined under the microscope is seen to consist of a feltwork of fine granular fibrils, in the meshes of which are entangled the red and white corpuscles of the blood. In the serum nothing can be seen but a few stray corpuscles. In man, blood when shed becomes viscid in about two or three minutes, and enters the jelly-stage in about five or ten minutes. After the lapse of another few minutes the first drops of serum are seen, and coagulation is generally complete in from one to several hours. The times however will be found to vary according to the condition of the individual, the temperature of the air, and the size and form of the vessel into which the blood is shed. Among animals the rapidity of coagulation varies exceedingly in different species. The blood of the horse coagulates with remarkable slow- ness ; so slowly indeed that many of the red corpuscles (these are specifically heavier than the plasma) have time to sink before viscidity sets in. In consequence there appears on the surface of the blood an upper layer of colourless plasma, containing in its deeper portions many colourless corpuscles (which are lighter than the red). This layer clots like the other parts of the blood, forming the so-called ' buffy coat.' A similar buffy coat is sometimes seen in the blood of man, in inflammatory conditions of the body. This buffy coat makes its appearance in horse's blood even at the ordinary temperature of the air. If a portion of horse's blood be surrounded by a cooling mixture of ice and salt, and thus kept at about 0" C, coagulation may be almost indefinitely postponed. Under these circumstances a more complete descent of the corpuscles takes place, and a considerable quantity of colourless transparent plasma ■free from blood-corpuscles may be obtained. A portion of this plasma removed from the freezing mixture clots exactly as does the entire blood. It first becomes viscid and then forms a jelly, which subsequently separates into a colourless shrunken clot and serum. , This shews that the corpuscles are not an essential part of the clot. If a few cubic centimetres of the same plasma be diluted with 50 times its bulk of a "75 p.c. solution of sodium chloride^ coagulation is 1 A solution of sodium chloride of this strength will hereafter be spoken of as ^ normal saline solution.' 16 FIBRIN. [Book i. much retarded, and the various stages may be more easily watched. As the fluid is becoming viscid, fine fibrils of fibrin will be seen to be developed in it, especially at the sides of the containing vessel. As these fibrils multiply in number, the fluid becomes more and more of the consistence of a jelly, and at the same time somewhat opaque. Stirred or pulled about with a needle, the fibrils shrink up into a small opaque stringy mass; and a very considerable bulk of the jelly may by agitation be resolved into a minute fragment of shrunken fibrin floating in a quantity of what is really diluted serum. If a specimen of such diluted plasma be stirred from time to time, as soon as coagulation begins, with a needle or glass rod, the fibrin may be removed piecemeal as it forms, and the jelly-stage may be altogether done away with. When fresh blood which has not yet had time to coagulate is stirred or whipped with a bundle of rods (or anything presenting a large amount of rough surface), no jelly-like coagulation takes place, but the rods become covered with a mass of shrunken fibrin. Blood thus whipped until fibrin ceases to be deposited, is found to have entirely lost its power of coagulation. Putting all these facts together, it is very clear that the coagulation of blood is due to the appearance in the plasma of fine fibrils of fibrin. As long as these are scanty, the blood is simply viscid. When they become sufficiently numerous, they give the blood the firmness of a jelly. Soon after their forma- tion they begin to shrink ; and in their shrinking enclose in their meshes the corpuscles, but squeeze out the remaining fluid parts of the blood. Hence the appearance of the shrunken coloured clot and the colourless serum. Fibrin, whether obtained by whipping freshly-shed blood, or by washing a normal clot, or a clot obtained from colourless plasma, exhibits the same general characters. It is a proteid ; and gives the ordinary proteid reactions. It it insoluble in water and in dilute saline solutions ; and though it swells up in dilute hydrochloric acid, it is not thereby appreciably dissolved (see Appendix). Minor differences have been stated to exist in the characters of fibiin obtained, in various ways and from, various sources, ex gr. by whipping or by washing a blood-clot, from venous or from arterial blood. But these differences are unimportant. The characters are said to vary also in different animals. Coagulation then is due to the appearance in the blood-plasma of a substance, fibrin, which previously did not exist there as such. Such a substance must have antecedents, or an antecedent — what are they, or what is it ? If blood be received direct from the blood-vessels into one- third its bulk of a saturated solution of some neutral salt, such as magnesium sulphate, and the two gently but thoroughly mixed, coagulation, especially at a moderately low temperature, will be deferred for a very long time. If the mixture be allowed to stand, the corpuscles will sink, and a colourless plasma will be obtained similar to the plasma gained from horse's blood by cold, except that Chap, i.] BLOOD, 17 it contains an excess of the neutral salt .The presence of the neutra,l salt has acted in the same direction as cold : it has prevented the occurrence of coagulation. It has not destroyed the fibrin ; for if some of the plasma be diluted with ten or more times its bulk of water, it will coagulate speedily in quite a normal fashion, with the production of quite normal fibrin. If some of the colourless transparent plasma, obtained either by the action of neutral salts from any blood, or by the help of cold from horse's blood, be treated with some solid neutral salt, such as sodium chloride, to saturation, a white flakj?- somewhat sticky precipitate will make its appearance. If this precipitate be removed, the fluid is no longer coagulable (or very slightly so), even though the neutral salt present be removed by dialysis, or its influence lessened by dilation. With the removal of the substance precipitated, the plasma has lost its power of coagulating. If the precipitate itself, after being washed with a saturated solution of the neutral salt (in which it is insoluble) so as to get rid of all serum and other constituents of the plasma, be treated with a small quantity of water, it readily dissolves, and the solution rapidly filtered gives a clear colourless filtrate, which is at first perfectly fluid. Soon, however, the fluidity gives way to viscidity, and this in turn to a jelly condition, and finally the jelly shrinks into a clot floating in a clear fluid; in other words, the filtrate clots like plasma. Thus there is present in cooled plasma, and in plasma kept from clotting by the presence of neutral salts, a something, precipi table by saturation with neutral salts, a something which, since it is soluble in water, or in very dilute saline solutions, cannot be fibrin itself, but which in solution speedily gives rise to the appearance of fibrin. To this sub- stance its discoverer, Denis^ gave the name of plasmine. We are justified in saying that the coagulation of blood is due to the con- version of plasmine into fibrin. The question now arises. What is the exact nature of plasmine? Is it for instance a mixture of two or more substances which by their interaction produce fibrin? This view is suggested by the fact that plasmine cannot be kept in solution for any length of time without changing into fibrin, except when submitted to certain influences, such as cold. It is moreover supported by the following facts. The disease known as hydrocele is characterized by the presence in the tunica vaginalis (or serous sac of the testis) of an abnormal and often very considerable quantity of a clear, colourless, or faintly yellow fluid very similar to the serum of clotted blood. This secre- tion, when drawn from the living body without admixture of blood, will in the great majority of cases remain perfectly fluid, and enter into decomposition without having shewn any tendency whatever to clot. Ip. a few exceptional cases a coagulation, generally slight, but quite similar to that of colourless blood-plasma, may be observed. 1 Ann. d. Sci. Nat., (iv.) s. p. 25. F. P. 2 18 FIBRINOPLASTIN AND FIBRINOGEN. [Book i. If a small quantity of hydrocele fluid which, has been observed not to clot spontaneously be mixed with some serum or whipped blood, the mixture will after a longer or shorter time clot in a com- pletely normal manner. That is to say, two fluids neither of which apart clot spontaneously, will clot spontaneously when mixed together. In some cases no clot is formed; specimens of hydrocele fluid are occasionally met with in which coagulation cannot be thus produced. If serum be treated to saturation with solid sodium chloride, a flaky precipitate very similar in general appearance to plasmine will make its appearance. Like plasmine this precipitate is soluble in very dilute neutral saline solutions, and in consequence as thus pre- pared readily dissolves when treated with distilled water, since a certain amount of sodium chloride clings to it. Unlike plasmine, its filtered solution will not clot. If, however, some of the solution be added to hydrocele fluid, a clottiog takes place just the same as when serum itself is added. The rest of the serum from which this substance has been removed will not, after the removal by dialysis of the excess of salt, cause clotting in hydrocele fluid. Evidently it is the presence of this constituent, not coagulable of itself, which gives to serum its power of producing a coagulation in hydrocele fluid. The substance in question may also be prepared by diluting blood- serum with ten or twenty times its bulk of water and passing a brisk stream of carbonic acid through it. The mixture speedily becomes turbid, and if left to stand a copious white amorphous somewhat gi-anular precipitate settles down. The substance so thrown down belongs by its characters to the class of globulins (see Appendix). It is readily soluble in dilute neutral saline solutions, and its solutions in these cause coagulation of hydrocele fluid. It may also be thrown down by very cautiously adding dilute acetic acid to dilute serum. It has received the name of fibrinoplastiii or fihrinoplastic globulin or paraglobulm. If, on the other hand, hydrocele fluid, specimens of which have been observed to coagulate on the addition of serum or fibrinoplastin, be treated in the same way either with carbonic acid or with sodium chloride to saturation, a precipitate is obtained similar to, but more flaky and less granular in nature than, that produced in serum. When this precipitate, to which the name of fibrinogen has been given, dissolved in dilute neutral saline solution, is added to serum, the mixture coagulates spontaneously, while the hydrocele fluid from which the substance has been removed no longer causes coagulation in serum. Thus fibrinoplastin from serum causes coagulation of hydrocele fluid, and fibrinogen from hydrocele fluid causes coagula- tion of serum, though neither alone coagulate spontaneously. And serum deprived of its fibrinoplastin, and hydrocele fluid deprived of its fibrinogen, have lost all power of coagulating each other. It is worthy of remark tliat fibrinoplastin is more easy of extraction than fibrinogen, and that hydrocele fluid is much more readily and firmly coagulated by fibrinoplastin than is serum by fibrmogen. Chap, i.] BLOOD. 19 Lastly, if solid fibrinoplastin and fibrinogen, prepared by the sodium chloride method, be together dissolved in dilute saline solution, the fluid mixture will coagulate spontaneously with the production of quite normal fibrin. These facts seem to shew that plasmine is a mixture of fibrinogen and fibrinoplastin; indeed an artificial mixture of the two latter, obtained from serum and hydrocele fluid respectively, would be un- distinguishable from the former obtained from plasma. It must however be remembered that no one has yet succeeded in separating natural plasmine into fibrinogen and fibrinoplastin^. There are moreover facts which sliew that the above statements do not cover the whole ground; there is evidence of the existence of a third factor in the process. 1. If fibrinogen and fibrinoplastin be isolated by the carbonic acid method, their mixture in a sahne solution clots with great difiiculty or not at all ; prepared by the saturation method, they give a good firm clot. This suggests that something retained by the latter method is lost by the former methed. 2. Normal blood-plasma must naturally contain an excess of fibrino- plastin, since after coagulation the serum still contams a considerable quantity of that body. Yet even in blood-plasma, fibrinoplastiti, under certain circiimstances, will favour coagulation. If three parts of plasma be mixed with one part of a solution of magnesium sulphate (one of the salt to three and a half of water), the mixture diluted with eight parts of water will afford a dilute plasma, in which sj)ontaneous coagulation will either not occur at all or come on very slowly indeed. In this dilute plasma the fibrinoplastin is still in excess. Nevertheless the addition of a further quantity of fibrinoplastin, prepared by saturation with sodium chloride, will speedily cause coagulation. From this it may be inferred that in adding the fibrinoplastin thus prepared something else is added as well. 3. If blood-serum or defibrinated blood be poured into about twenty times its bulk of strong spirit and the mixture allowed to stand for some three weeks, or longer, the proteid matters including the fibrinoplastin become coagulated and almost wholly insoluble in water. Hence if the spuit be filtered ofi" from the copious precipitate, and the latter dried at a low temperature (below 40°) and extracted with distilled water, the aqueous extract contains no palpable amount of proteid material and gives but slight reactions with proteid tests. A small quantity of this aqueous extract of blood, however, though free from fibrinoplastin, will when added to the dilute plasma, spoken of above, bring about a rapid coagulation. 4. If the pericardial cavity of a large mammal (ox, horse, sheep) be laid open immediately after death, the fluid removed will coagulate spontane- ously and rapidly. The clot will on examination be found to consist of a 1 We owe the discovery of fibrinoplastin and fibrinogen to A. Schmidt, whose earher papers will be found in Eeichert and Du Bois-Eeymond's Archiv, 1861, p. 545, and 1862, p. 428. Schmidt's later results, which are discussed in the succeeding ijortions of this section, are contained in papers published in Pfliiger's ^j'cMu, vi. (1872) p. 413; si. (1875), pp. 291 and 515 ; sm. pp. 93 and 146. . 2 2 20 FIBRIM-FERMEFT. [Book i, rueshwork of normal fibrin in wliicli are entangled a multitude of white corpuscles. If the opening of the body be deferred to some twenty or more hours after death, the pericardial fluid will be found either not to coagulate at all or to coagulate very slowly and feebly. When, however, fibrinoplastin prepared by the saturation method is added to such a pericardial fluid a rapid and complete coagulation is gener- ally bi-ought about. But precisely tlie same coagulation may in many cases be brought about by the simple addition of the aqiieous extract just described. Most pericardial fluids in fact behave extremely like the dilute plasma spoken of above. Here then are indications of the existence of a substance which is neither fibrinogen nor fibrinoplastin, but which nevertheless ap])ears to be as necessary as either of the other two for the occuri-ence of coagulation. This third substance will not bring about coagulation with fibrinogen alone or with fibrinoplastin alone. It will not bring about coagulation in fluids such as ordinary hydrocele fluid, in which fibrinoplastin is apparently absent, nor in serum, in which fibrinogen is absent. It is efiicacious only in such cases where there are reasons for thinking that both fibrinoplastin and fibrinogen are present. But its most important feature is the following. In the cases in which coagulation is brought about by the addition of fibrinoplastin to fibrinogenous liquids, the quantity of fibrin produced bears, within certain limits, a proportion to the quantity of fibrinoplastin added ; whereas the addition of aqueous extract of blood only afiects the rajnclitT/ with which coagulation sets in, and not at all the quantity of fibrin produced. In other words, the aqueous extract does not contribute to the substance of the fibrin, but favours, or is essential to, the union of, the two fibrin factors. That is to say, the substance in the aqueous extract which thus afiects coagulation belongs to that class of substances which promote the union of other bodies, or cause changes in other bodies, without themselves entering into union or undei'going change. These substances we shall hereafter learn to speak of as "ferments;" and this particular substance has been called by its discoverer, A. Schmidt^, fibrin- ferment. Obviously the ferment is present in blood-plasma, in plasmine, and in fibrinoplastin as prepared by the saturation method, but is apparently in large measure lost when fibrinoplastin is prepared by the carbonic acid method. In conclusion then we may say, that coagulation is the result of the interaction of two bodies, fibrinoplastin and fibrinogen, brought about by the agency of a third body, fibrin-ferment. Where these three bodies are all present, as in blood-plasma, in plasmine, in pei-icardial fluid taken from the body immediately after death, spontaneous coagulation is witnessed : where the ferment is absent, but the other factors are present, as in many cases of pericardial fluid removed some time after death, coagi;lation will take place on the addition of ferment alone : where both ferment and fibri- noplastin are absent, as in many cases of hydrocele fluid, both these must be added before coagulation can come on. The exact nature of the pi-ocess by which the presence of all three factors leads to the formation of fibrin cannot be at present defined more closely than by the phrase ' interaction.' Beyond the broad fact that the quantity of fibrin formed is dependent on the quantity of fibrinoplastin ^ Op. cit. Ghap. I.] BLOOD. 21 and fibrinogen present, we have no knowledge of quantitative relations between the two constituents. That they do not unite simply together, as a base with an acid, seems to be clearly shewn by the fact, stated by Schmidt, that in artificial coagulations the quantity of fibrin formed is by weight always less than that of the fibrinoplastin used. Hammarsten' argues that the fibrinoplastin, or, as he would prefer still to call it, paraglo- bulin does not enter in any way into the fibrin, the latter being simply transformed fibrinogen. He explains the fibrinoplastic properties of para- globuliu as due to that substance obviating certain hindrances to the formation of the fibrin, for instance, preventing the solution by saline or other bodies of the fibrin while it is in M'hat may be called a nascent condition, i. e. in a stage intermediate between fibrinogen and fibrin. Ac- cording to him the quantity of fibrinoplastin present in a coagulating fluid, though of marked efiect on the quantity of fibrin produced, has no efiect on the total quantity of fibrinogen used up, i. e. transformed into fibrin or into something else. Still the conception of coagulation as a chemical process between certain factors renders easy of comprehension the influence of various conditions on the coagulation of blood. The quickening influence of heat, the retarding effect of cold, the favourable action of motion and of contact with surfaces, and hence the results of whipping and the influence exerted by the form and surface of vessels, become in- telligible. The greater the number of points, that is the larger and rougher the surface presented by the vessel into which blood is shed, the more quickly coagulation comes on, for contact with surfaces favours chemical union. So also the presence of spongy platinum, or of an inert powder like charcoal, quickens the coagulation of tardily clotting fluids, such as many cases of pericardial fluid. The action of neutral salts is still obscure. Schmidt has shewn that the presence of a neutral salt, such as sodium chloride, is essential to the process, coagulation not occurring even where all three factors are present, if no neutral salt accompany them ; thus bringing fibrin coagulation after all into the same category as the coagulation of albumin by heat : see Appendix. The presence of haemoglobin also, independently of the fibrino- plastin which may be present in the red corpuscles, appears to favour coagulation. Having thus arrived at an approximative knowledge of the nature of coagulation, we are in a better position for discussing the question. Why does blood remain fluid in the vessels of the living body and yet clot when shed ? The older views may be at once summarily dismissed. The clotting is not due to loss of temjierature, for cold retards coagu- lation, and the blood of cold-blooded animals behaves just like that of warm-blooded animals in clotting when shed. It is not due to loss of motion, for motion favours coagulation. It is not due to exposure to air, whereby either an increased access of oxygen or an escape of volatile matters is facilitated, for on the one hand the blood is fully exposed to the air in the lungs, and on the other shed blood i Pfljiger's Archiv, sit. (1877), 211. 22 INFLUENCE OF THE LIVING BLOOD-VESSELS. [Book i. clots when received, without any exposure to the atmosphere, in a closed tube over mercury. All the facts known to us point to the conclusion, that when blood is contained in healthy living blood-vessels, a certain relation or equilibrium exists between the blood and the containing vessels of such a nature that as long as this equilibrium is maintained the blood remains fluid, but that when this equilibrium is disturbed by events in the blood or in the blood-vessels or by removal of the blood, the blood undergoes changes which result in coagulation. The most salient facts in support of this conclusion are as follows. 1. After death, when all motion of the blood has ceased, the blood remains for a long time fluid. It is not till some time afterwards, at an epoch when post-mortem changes in the blood and in the blood- vessels have had time to develope themselves, that coagulation begins. Thus some hours after death the blood in the great veins may be found perfectly fluid. Yet such blood has not lost its power of coagu- lating ; it still clots when removed from the body, and clots too when received over mercury without exposure to air, shewing that the fluidity of the highly venous blood is not due to any excess of car- bonic acid or absence of oxygen. Eventually it does clot even within the vessels, but never so firmly and completely as when shed. It clots first in the larger vessels, remaining for a very long time, for many hours in fact, fluid in the smaller veins, where the same bulk of blood is exposed to the influence of, and reciprocally exerts an in- fluence on, a larger surface of the vascular walls than in the larger veins. Thus if the foot of a sheep be ligatured and amputated, the blood in the small veins will be found fluid and yet coagulable for many hours. 2. If the vessels of the heart of a turtle (or any other cold-blooded animal) be ligatured, and the heart be cut out and suspended so that it may continue to beat for as long a period as possible, the blood will remain fluid within the heart as long as the pulsations go on, i.e. for one or two days (and indeed for some time afterwards), though a por- tion taken away at any period of the experiment will clot very speedily \ 3. If the jugular vein of a large animal, such as an ox or horse, be ligatured when full of blood, and the ligatured portion excised, the blood in many cases remains perfectly fluid, along the greater part of the length of the piece, for twenty-four or even forty-eight hours. The piece so ligatured may be suspended in a framework and opened at the top so as to imitate a living test-tube, and yet the blood will often remain long fluid, though a portion removed at any time into another vessel will clot in a few minutes. If two such living test-tubes be prepared, the blood may be poured from one to the other without coagulation taking placed 1 Briicke, Brit, and For. 3Ied. Cliir. Bevino, xix. p. 183 (1857). 2 Lister, Proc. Roy. Soc, xn. p. 580 (1858). Chap, i.] BLOOD. 23 The above facts illustrate tlie absence of coagulation in intact or slightly altered living blood-vessels ; the following shew that co- agulation may take place even in the living vessels. 4. If a needle or piece of wire or thread be introduced into the living blood-vessel of an animal, either during life or immediately after death, the piece will be found encrusted with fibrin. 5. If in a living animal a blood-vessel be ligatured, the ligature being of such a kind as to injure the inner coat, coagulation takes place at the ligature and extends for some distance from it. Thus if the jugular vein of a rabbit be ligatured roughly in two places, clots will in a few hours be found in the ligatured portion, reaching upwards and downwards from each ligature, the middle portion being the least coagulated. Clots will also be found on the far side of each ligature. The clots will still appear if the ligature be removed im- mediately after being applied, provided that in the process the inner coat has been wounded. If the ligatures be applied in such a way as not to injure the inner coat, coagulation will not take place, though the blood may remain for many hours perfectly at rest between the ligatures. 6. When an artery is ligatured a conspicuous clot is formed on the cardiac side of the ligature. The clot is largest and firmest in the immediate neighbourhood of the ligature, gradually thinning away from thence and reaching usually as far as where a branch is given off. Between this branch and the ligature there is stasis ; the walls of the artery suffer from the want of renewal of blood, and thus favour the propagation of the coagulation. On the distal side of the ligature where the artery is much shrunken, the clot which is formed, though naturally small and inconspicuous, is similar. 7. Any injury of the inner coat of a blood-vessel causes a coagu- lation at the spot of injury. Any treatment of a blood-vessel tending to injure its normal condition causes local coagulation. 8. Disease involving the inner coat of a blood-vessel causes a coagulation at the part diseased. Thus inflammation of the lining membrane of the valves of the heart in endocarditis is frequently accompanied by the deposit of fibrin. In aneurism the inner coat is diseased, and layers of fibrin are commonly deposited. So also in fatty and calcareous degeneration without any aneurismal dilatation there is a tendency to the formation of clots. 9. Similar phenomena are seen in the case of serous fluids which coagulate spontaneously. If, as soon after death as the body is cold and the fat is solidified, the pericardium be carefully removed from a sheep by an incision round the base of the heart, the peri- cardial fluid may be kept in the pericardial bag as in a living cup for many hours without clotting, and yet a small portion removed with a 24 SOURCES OF TEE FIBRIN-FACTORS. [Book i. pipette clots at once, and a thread left hanging into the fluid soon becomes covered with fibrin. The only interpretation which embraces these facts is that so long as a certain normal relation between the lining surfaces of the blood- vessels and the blood is maintained, coagulation does not take place ; but when this relation is disturbed by the more or less gradual death of blood-vessels, or by their more sudden disease or injury, or by the presence of a foreign body, coagulation sets in. Two additional points may here be noticed. 1. Stagnation of blood favours coagulation wdthin the blood-vessels, apparently because the blood-vessels, like other tissues, demand a renewal of the blood on which they depend for the maintenance of their vital powers. 2. The influence of surface is seen even in the coagulation within the vessels. In cases of co- agulation from gradual death of the blood-vessels, as in the case of an excised jugular vein, the fibrin, when its deposition is sufficiently. slow, is seen to appear first at the sides, and from thence gradually, frequently in layers, to make its way to the centre. So in aneurism, the deposit of fibrin is frequently laminated. In cases where coagu- lation results from disease of the lining membrane, the rougher the interior, the more speedy and complete the clotting. So also a rough foreign body, presenting a large number of surfaces and points of attachment, more readily produces a clot when introduced into the living blood-vessels than a perfectly smooth one. Clear as it seems to be that some vital relation of blood to blood- vessel is the dominant condition affecting coagTilation, it is by no means easy to state distinctly what is the exact nature of that rela- tion. Some authors^ speak of the blood-vessels as exercising a re- straining influence on the natural tendency of the blood to coagulate. Others"'' regard the living blood-vessel (and indeed living matter in general) as being wholly inert towards the fibrin-factors. These they consider need the presence, the contact influence of some body, in order that they may act on each other to form fibrin ; thus contact with the sides of the vessel into which blood is shed, or with the surface of a foreign body introduced into a living vessel, is, according to them, the determining cause of coagulation. They suppose that living matter exercises no such contact influence. Befoi'e this point can be decided, further knowledge is needed concern- ing the exact condition of the fibrin-factors iia living blood within the Ijody. While the blood is flowing uncoagulated through the vessels are all the three fibrin-factors, fibrinoplastin, fibrinogen and ferment, already pre- sent in plasma % Or are they all, or is one or two absent, and if so is the appearance of them, or of one of them, in the plasma, the necessary invisible forerunner of coagulation ? Our scanty information on this point may be summarized as follows. 1. In all spontaneously coagnlable fluids white corpuscles are present, and the more abundant they are, the more pronounced is the coagulation, 1 Briicke, ojp. clt. " Lister, op. cit. Chap, i.] BLOOD. 25 Thus the spontaneously coagulating pericardial fluid is exceedingly rich in white corpuscles, and the clot formed seems under the microscope to be almost entirely composed of them, so completely do they hide the threads of fibrin. In the specimens of pericardial and of hydrocele fluid which do not coagulate spontaneously white corpuscles are absent, or at least scanty. 2. The deposition of flbrin round a thread if dipped into a coagulable fluid or drawn through a blood-vessel and left there, is preceded by an accumulation of white corpuscles. These cluster in greater numbers round the thread, and when the mass is examined under the microscope the cor- puscles seem to serve as starting points for the development of the threads of fibrin. 3. In the experiment of keeping blood fluid but coagulable in an excised jugular vein (of the horse), it is observed that when, as in course of time happens, the corpuscles have sunk to the bottom of the piece of vein, the upper layers of clear, corpuscle-free, plasma clot very feebly indeed when removed from the vein, whereas the lower layers rich in corpuscles clot most firmly. 4. When horse's blood is received from a blood-vessel into an ice-cold dilute solution of chloride of sodium, and the mixture kept just short of actually freezing, the whole mass of corpuscles sinks rapidly. It is then observed that the dilute plasma free from corpuscles clots feebly, whereas the lower layers of the same dilute plasma, containing all the corpuscles, gives an abundant coagulation. Plasma of horse's blood may be diluted with twelve times its bulk of distilled water and filtered, without coagulation setting in, provided that the whole operation is conducted at a temperature just short of freezing. The filtered diluted plasma, which is found to be exceedingly tree from white corpuscles, these being left on the filter, clots feebly ; the amount of fibrin it produces is less than half that obtainable from the same diluted plasma unfiltered'. These facts point very decidedly to the conclusion that the white cor- puscles have some share in bringing about coagulation ; they moreover suggest that one or more of the fibrin-factors have their source in the white corpuscles, and that coagulation is due to the passage of these elements from the body of the corpuscle into the plasma. The latter view is corroborated by the following facts. 5. In defibrinated blood or blood-serum a certain amount of fibrin- ferment is present. If however blood be treated with alcohol immediately on leaving the blood-vessels, very little ferment indeed is found to be present. The qviantity is found to increase from the moment of leaving the vessels to the onset of coagulation. The fibrin-ferment therefore is developed from some part of the blood. If horse's blood be kept at freezing tempe- rature, the formation of ferment is arrested. If after the corpuscles have sunk the undermost layers of the blood, containing almost exclusively red corpuscles, be removed, little or no ferment can be obtained from this ^^ortion, either when examined immediately, or after being allowed to clot at an ordinary temperature. In a portion taken from the upper layers (colourless plasma) of the same blood, while there is little or no ferment present before the coagulation of the specimen, there is abundance afterwards. If a ^ A. Schmidt, op. cit. 26 SOURCES OF TEE FIBRm-FACTORS [Book i. similar portion of the same colourless plasma be filtered in tlie cold, tlie fi^ltrate, which is nearly free from white corpuscles, is very poor in ferment both before and after the feeble and slow coagulation which the fluid undergoes ; the material on the filter, consisting almost entirely of white corpuscles, is very rich in ferment. These facts seem to shew that the fibrin-ferment which is present in blood-serum has its sovirce, not in the red but in the white corpuscles, and that the passage of the ferment from the white corpuscle into the ^^lasma is a precursor of coagulation, 6. The coagulation of filtered diluted plasma has been said to be both feeble and slow. The tardiness of the coagulation is due to the paucity of ferment ; the feebleness, i. e. the small quantity of fibrin produced, must be due to the scantiness of one or both of the fibrin-factors. On adding fibrino- plastin the quantity of fibrin produced is the same as that given by the same quantity of unfiltered plasma. The filtered plasma is therefore defi- cient in fibriuoplastiu. The material left on the filter is rich in fibrino- plastin. The inference which A. Schmidt draws from these facts, is that fibrinoplastin, like the fibrin-ferment, has its origin in the white corpiiscles, but that fibrinogen is a normal constituent of the plasma. 7. If a drop of horse's plasma kept from coagulating by cold be examined under the microscope, it will be found to contain a large number of white corpuscles mixed with which are corpuscles of an intermediate character between white and red, i. e. nxicleated cells whose protoplasm is loaded with coloured haemoglobin granules. As the drop is watched, a large number of the white corpuscles and all the intermediate forms are seen to break up into a granular detritus. This breaking up of the white cor- puscles is the precursor of coagulation, the threads of fibrin seeming to staii; from the remains of the corpuscles. Putting all these facts togethei', Schmidt concludes that when blood is shed, a number of white and intermediate coi-puscles fall to pieces, by which act a quantity of fibrin-ferment and of fibrinoplastin is discharged into the plasma. These meeting there with the already present fibrinogen give rise to fibrin, and coagulation results. In other mammals coagulation even at low temperatures is too rapid to permit of the changes in the corpuscles being watched as satisfactorily as in the horse, but even in these evidences of the existence of intermediate forms may be met ■svith. This view excludes the red corpuscles, as far as mammals are concerned, from any direct ' share in coagulation. Whether this ultimately prove to be correct or not, there are facts which shew that the nucleated red cor- puscles of other vertebrates, which it must be remembered are the homo- logiies of the intermediate forms, have a much clearer connection with the process. If the defibrinated blood of the frog or the bird be allowed to stand until the corpuscles have subsided, the latter, separated as much as possible from the serum, and treated with a considerable quantity of distilled water, yield a filtrate which coagulates spontaneously. That is to say, the water breaks up the red corpuscles and sets free a quantity of fibrin-factors which otherwise would have remained latent. The amount of fibrin thus obtained may be considerably greater than the quantity originally appearing in the blood. It is worthy of notice, that in this case the corpuscle is the source, not only of the fibrin-ferment and fibrinoplastin, but also of the fibrinogen. Chap, l] BLOOD. 27 Accepting this view as approximately correct, tlie coagulation of shed blood may be referred to tbe circumstance, that even the comparatively slight changes which must take place in the blood on its leaving the vessels are sufficient to entail the death, and so the breaking np, of a number of tbe delicate white corjjuscles. The formation of clots within the body is not so easy to explain. "VVe are driven in these cases to siippose that injured and diseased spots or foreign bodies first attract, and then, as it were by irritation, cause the death, of a certain number of corpuscles. But in any case, if this view be admitted, it must also be granted that tbe blood-vessels do in some manner or other exercise a restraining influence on the formation of fibrin. For many of these corpuscles must, in the natural course of events, die and break up in the blood-stream, without causing coagulation. Further, defibrinated blood contains both fibrin- ferment and fibrinoplastin ; it ought, therefore, when injected into the vessels which already in the natural blood contain fibrinogen, to occasion a rapid and speedy general coagulation. This it does not. The coagulations which occur after transfusion of defibrinated blood are partial and uncertain. "We might infer from this that the system has some power of rapidly either destroying ferment or changing the properties of fibrinoplastin. In support of this it has been stated, that a quantity of fibrin-ferment injected into the system may be detected in the blood immediately afterwards (and is present then without causing coagulation), but speedily disappears. The loss of spontaneous coagulability in pericardial fluid might be attx'ibuted to an escape by migration of the white corpuscles away fi'om the pericardial cavity, but this is inconsistent with the fact that in the majority of cases the ferment alone disappears while the fibrinoplastin remains. According to the facts given above, the white coi-puscles in escaping would caiTy away both ferment and fibrinoplastin, leaving the fibrinogen alone. Lastly, we should remember that all the above, even if correct, is only an approximative solution. The coagulation of muscle-plasma is a coagulation in which white corpuscles cannot serve as Dei ex machma ; moreover, as we shall see later on, the rigor mortis of the white corpuscle itself is a coagulation ; and for this its own subsequent disintegration cannot be regarded as an adequate cause. Sec. 3. The Histoey of the Corpuscles. In the living body red blood-corpuscles are continually being destroyed, and new ones as continually being produced. The proofs of this are, 1. The number of the red corpuscles in the blood at any given time (as determined by the examination of a drop of blood) varies much. After a very large reduction of the total number of red corpuscles, as by hsemorrhage or disease (anaemia), the normal pro- portion may be regained even within a very short time. 2. There are reasons for thinking that the urinary and bile- pigments are derivatives of hasmoglobin. If this be so, an immense number of corpuscles must be destroyed daily (and replaced by new ones) in order to give rise to the amount of iirinary and bile-pigment discharged daily from the body. 3., When the blood of one animal is injected into the vessels of 28 THE WHITE CORPUSCLES. [Book i. another {ex. gr. that of a bird into a mammal), the corpuscles of the first may for some time be recognised in blood taken from the second; but eventually they Avholly disappear. This of course is no strong evidence, since the destruction of foreign corpuscles might take place even though the proper ones had a permanent existence. Origin of the Med Corpuscles. In the embryo red corpuscles are produced, 1. From metamorphosis of certain mesoblastic cells in the vascular area. 2. By division of the corpuscles thus formed. 3. In a somewhat later stage, by the transformation of nucleated white corpiiscles, which probably arise in the liver and spleen, and pass thence into the blood. The cell-substance becomes impregnated with haemoglobin, and the nucleus breaks up and disappears. 4. By the direct transformation of the protoplasm of undifFerentiated connective-tissue corpviscles^, the red corpuscle appearing first as a minute speck in the protoplasmic cell-substance, and subsequently enlarging very much after the fashion of an oil-globule. In the adult, division of existing corpuscles is at least exceed- ingly rare, if it occurs at all. In the spleen-pulp small nucleated coloured corpuscles have been observed similar to those met with in the embryo ; transitional forms, shewing the presence of ha^moglobih in the cell-substance and degeneration of the nucleus, have been seen. In the wide capillaries of the red medulla of bones similar transi- tional forms have been observed, and they have also been noticed in circulating blood. Accordmg to Alex. Schmidt^, in living unchanged blood these forms are abundant; they break up and disappear, however, immediately that the blood is shed, unless special precautions (application of cold &c.) be used. From these several facts it is concluded that the red corpuscles take origin from colourless nucleated corpuscles similar to, if not identical with, the ordinary white corpuscles of the blood. In the case of animals with nucleated red corpuscles the change consists chiefly in a transformation of the native protoplasm of the white corpuscle into haemoglobin and stroma. In the case of animals with non-nucleated red corpuscles, most observers^ agree in the opinion that the nucleus of the white corpuscle breaks up and disappears, so that the red corjDuscle repre- sents only the modified cell-substance of its progenitor. "Wharton Jones, supported by Huxley, resting chiefly on the parallelism in size and form between the nuclei of the white corpuscles and the entire red corpuscles in different orders and families of mammals, concludes that the latter is in realitv the naked coloured nucleus of the former. Origin of the White Corpuscles. That the white corpuscles are continually being removed is evi- • 1 Schafer, Froc. Hoy. Soc, xxii. 213. ^ q^^ cit. 3 Kolliker, Neumann, Schmidt. Chap, l] BLOOD. 39 dent from the fact that they vary extremely in number at different times and under various circumstances. They are very largely increased by taking food. Thus during fasting they may be seen in a drop of blood to bear to the red the proportion of 1 in 800 or 1000. After a meal this proportion rises to 1 in 300 or 400. The fact that in the lymphatic glands, follicles and other adenoid struc- tures, corpiiscles, similar to if not identical with white blood-corpuscles, are to be seen of very varioiis sizes and with dividing nuclei, suggests that these organs are the birth-places of the white corpuscles. The lymph is continually pouring into the blood a crowd of white corpuscles, which for the most part make their appearance in the lymph-vessels after the latter have traversed the lymphatic gla,nds. And this view is further supported by the fact that in the disease Leuchsemia, where the white corpuscles ai-e so abundant as to number as much as 1 to 10 red, the spleen, the lymphatic glands, and other forms of adenoid tissue, are enlarged. (The phenomena are however capable of a converse interpretation, viz. that the white cor- puscles, failing to become converted into red corpuscles, are crowded into the lymphatic organs.) At the same time it is open for us to suppose that any proliferating tissue may give rise to new corpuscles; and Klein ^ states that he has seen them budded off from the reticulum of the spleen. The white corpuscles have also been observed to divide^. We may conclude therefore that the white corpuscles probably arise, chiefly by division, from the leucocytes of adenoid tissue, but that other sources may exist. Fate of the '\Mvite Corpuscles. As we have seen, it is extremely probable that a large number of the white corpuscles end by giving birth to red corpuscles. We know that in an inflamed area the white corpuscles migrate in large numbers into the extravascular elements of the tissues, and there are reasons for thinking that the new structures which make their appearance as the result of inflammation may arise in part at least from such migratory corpuscles. But the question to what extent this takes place, and how far the white corpuscles are concerned in tissue regeneration, is too unsettled and too long a matter to be discussed here. Fate of the Red Corpuscles. In the spleen we find, as Kolliker pointed out a long time ago, large protoplasmic cells in which are included a number of red cor- puscles: and these red corpuscles may be observed in various stages of apparent disintegration. It is probable therefore that the spleen is the grave of many of the red corpuscles. Since serum of fresh blood contains no dissolved haemoglobin, it is clear that the hsemo- globin of the broken-up corpuscles must speedily be transformed into some other body. Into what other body? In old blood-clots 1 .Q. J. Micros. Sci. xv. (1875) p. 370. ^ Hein, Hdb. Phjs. Lab. p. 8. 30 DISTRIBUTION OF BLOOD. [Book r. (as in those of cerebral haemorrhage) there are frequently found minute crystals of a body which has received the name Hcematoidin. There can be no doubt that the hsematoidin of these clots is a deri- vative from the hsemoglobin of the escaped blood. We know^ that haemoglobin contains a residue of hsematin. We know further that hgematin may lose its iron (which appears to be loosely attached), and yet remain a coloured body. So that there is no difficulty in the passage from the proteid-and-iron containing haemoglobin to the proteid-and-iron free haematoidin. But h^matoidin, not only in the form and appearance of its crystals, but also, as far as can be ascertained, by the analysis of the small quantities at disposal, in its chemical composition is identical with hiliruhin, the primary pigment of bile. Moreover, the injection of haemoglobin, or of dissolved red corpuscles, into the vessels of a living animal, gives rise to a large amount of bile-pigment in the urine, and at the same time increases enormously the relative quantity of hiliruhin in the bile. Thus though no one has yet succeeded in producing hiliruhin artificially from haemoglobin, facts point very strongly to the view that the red corpuscles are used up to supply bile-pigment. It must be added however that, according to Preyer^, the spectra of hasmatoidin and bilirubin are quite distinct, and that many observers have failed to obtain bile-pigment in the urine as the result of injection of a solution of hfemoglobin. Blood-clots frequently contain, besides or in place of heematoidin, a yellow substance named lutein, which is certainly distinct from bilirubin. Lutein is the substance which gives to corporea lutea their characteristic colour. Our knowledge of urinary pigments is so imperfect that little can be said as to their relation to haemoglobin. We cannot at present definitely trace the normal urinary pigment back to hsemoglobin, however probable such a source may seem ; but Jaffe finds in many urines, especially those of fever-patients, a body called urobilin, identical with hydro- hiliruhin obtained from bilirubin by reduction with sodium amalgam^ Sec. 4. The Quantity of Blood, and its distribution in THE Body. The total quantity of blood present in an animal body is esti- mated in the following way. As much blood as possible is allowed to escape from the vessels; this is measured directly. The vessels are then washed out with water or normal saline solution, and the washings carefully collected, mixed and measured. A known quantity of blood is diluted with water or normal saline solution until it possesses the same tint as a measured specimen of the washings. This gives the amount of blood (or rather of haemoglobin) in the measured specimen, from which the total quantity in the whole washings is calculated. Lastly, the whole body is carefully minced and washed free from blood. The washings are collected and filtered, 1 See Chapter on Changes of Blood in Eespiration. ^ Die Blut-Kry stall c. ^ CI'. Liebtrmaun, Pfliigor's Archiv. si. p. 181. Chap, i.] BLOOD. 31 and the amount of blood in them estimated as before by comparison with a specimen of diluted blood. The quantity of blood in the two washings, together with the escaped blood, gives the total quantit}^ of blood in the body. Estimated in this way, the total quantity of blood in the human body may be said to be about j^oth of the body-weight. There are several sources of error in the above method. One is that venous blood has less colourixig power than arterial blood. This has been met by Gscheidlen by poisonmg the animal with carbonic oxide, by which all the haemoglobin is reduced to one state, and therefore has throughout the same colouring power. The quantity of hsemoglobin in the muscular fibie itself is a source of error, but probably a very slight one. The difficulty of getting a clear infusion of the minced tissues is more serious. According to Ranke' the total blood in the body of a rabbit amounts to y^ of the body- weight, in a dog to -—5, in a cat to ^, in a frog to ■^, The blood^ is distributed as follows in round numbers: — About one-fourth in the heart, lungs, large arteries and veins, „ „ „ „ skeletal muscles, „ „ „ „ other organs. Since in the heart and great blood-vessels the blood is simply in transit, without undergoing any great changes (and in the lungs, as far as we know, the changes are limited to respiratory changes), it follows that the changes which take place in passing through the liver and skeletal muscles far exceed those which take place in the rest of the body. Ranke found the distribution to be as follows. In the Yiscera. Per cent, of Per cent, of Total Blood. Organ Weight. fLiving. 63-4 18-0 JDeadandElgid. 61-23 20-6 59-0 24-0 Rabbit. Doff. In the Carcase. Per cent, of Per cent, of Total Blood. Organ Weight. 36-6 2-7 38-77 2-7 41-0 3-4 In the various organs of the rabbit, Per cent, of Total Blood. Spleen . . . Brain and Cord Kidneys . Skin . . . Intestines . Bones &c. , Heart, Lungs, Great Blood-vessels Skeletal Muscles Liver , . .- •23 1-24 1-63 2-10 6-30 8-24 Per cent, of Organ Weight. 22-76 29-20 29-30 1 Blut-vertlieilung , 1S71. SHn .... 1-07 Bones . . 2-36 Al. Canal . . . 3-46 Muscles . 5-14 Brain and Cord 5-52 Kidney . . . 11-86 Spleen . . . 12-50 Liver . . . . 28-71 (Heart, Lungs, an d Great Vessels 63-11; . 2 Pianke, oi?, cit. CHAPTEK 11. THE CONTRACTILE TISSUES. The tissues of the body eminently endowed with contractility, the tissues whose primary reason of existence lies in their contractility, are the ordinary striated muscles, the cardiac muscles, the plain un^^ striated muscles, the ciliated cells, spermatozoa and the migrating cells. Of these the striated muscles, on account of the more complete de- velopment of their functions, are better studied first; the others, on account of their very simplicity, are in many respects less satisfac- torily understood. All the ordinary striated muscles are connected with nerves. We have no reason for thinking that their contractility is called into play, under normal conditions, otherwise than by the agency of nerves. Indeed a nerve-fibre may in part be regarded as a continuation of the muscular fibre with which it is connected by an end-plate. In Hydra the muscular fibre is but an eminently contractile process of an ectoderm cell, in Beroe the muscle-fibre thins out into a nerve- fibre which serves as a means of communication between the iso- lated contractile process, now an independent muscle-fibre, and the body of the ectoderm cell. Both nerve, and, as will be hereafter shewn, muscle are irritable; but the muscle only is contractile. A stimulus applied to a nerve sets up disturbances which are propa- gated on to the muscle; but it is only the muscle in which the dis- turbances manifest [themselves by a contraction. Neither striated muscle nor nerve-fibres distributed to muscles possess any distinct automatism. Spontaneous disturbances in either are at least rare if they occur at all. The two being thus so closely allied and in many points so similar, it will conduce to clearness and brevity if we treat them together. Sec. 1. The Chemical Substances composing or present in Muscle. In a muscle from the vessels of which the blood has been care- fully washed, by the injection of dilute saline solution, there will still be left a quantity of lymph surrounding the elementary fibres. The quantity however is under ordinary circumstariceS so small that it may be practically neglected. Chap, ii.] THE CONTRACTILE TISSUES. 33 If a dead muscle, from which all fat, tendon, fascia, and con- nective tissue have been as much as possible removed, and which has been freed from blood by the injection of saline solution, be minced and repeatedly washed with water, the washings will contain certain forms of albumin and certain extractive bodies, of which we shall speak directly. When the washing has been continued until the wash-water gives no proteid reaction, a large portion of muscle will still remain undissolved. If this be treated with a 10 p. c. solution of sodium chloride, a large portion of it will become imperfectly dis- solved into a viscid fluid which filters with difficulty. If the viscid filtrate be allowed to fall drop by drop into a large quantity of distilled water, a white flocculent matter will be precipitated. This flocculent precipitate is myosin. It is a proteid, giving the ordinary proteid reactions, and having the same general elementary composi- tion as other proteids. It is soluble in dilute saline solutions, espe- cially those of sodium chloride, and may be classed in the globulin family, though it is not so soluble as fibrinoplastic globulin. Dis- solved in saline solutions it readily coagulates when heated, is pre- cipitated and after long action coagulated by alcohol, and is pre- cipitated by an excess of the sodium chloride. By the action of dilute acids it is very readily converted into syntonin or acid-albumin, by the action of dilute alkalis into alkali-albumin. Speaking generally it may be said to be intermediate between fibrin and globulin. On keeping, and especially on drying, its solubility is much diminished. Of the substances which are left in muscle from which the myosin has thus been extracted by sodium chloride solution little is known. If washed muscle be treated directly with dilute hydro- chloric acid, the greater part of the material of the muscle passes at once into syntonin. The quantity of syntonin thus obtained may be taken as representing the quantity of myosin previously existing in the muscle. The portion insoluble in dilute hydrochloric acid con- sists partly of the substance of the sarcolemma, of the nuclei, and of the tissue between the bundles and partly of elements (? sarcous elements, muscle-rods) of the fibres themselves. If living' contractile frog's muscle, freed as before as much as possible from blood, be frozen \ and while frozen, minced, and rubbed up in a mortar with four times its weight of snow containing 1 p. c. of sodium chloride, a mixture is obtained which at a temperature below 0 C. is sufficiently fluid to be filtered, though with difficulty. The slightly opalescent filtrate, or muscle-plasTna as it is called, is at first quite fluid, but will, when exposed to the ordinary temperature become a solid jelly, and afterwards separate into a clot and serum. It will in fact coagulate like blood-plasma, with this difference, that the clot is not firm and fibrillar, but loose, granular and flocculent. ^ Since, as we sliall presently see, a miiscle may be frozen and thawed again -witliout losing any of its vital powers, we are at liberty to regard the frozen muscle as a still living muscle. F.P. 3 SV CONSTITUENTS OF MUSCLE. [Book i. During the coagulation the fluid, which before was neutral or slightly alkaline, becomes distinctly acid. The clot is myosin. It gives all the reactions of myosin obtained from dead muscle. The serum contains albumin and extractives. Besides ordinary serum-albumin coagulating at 75", Kuhne' (to whom ■we owe our knowledge of the above) found a peculiar form coagulating at 45", its appearance being probably connected with the salts present in the serum, (see Appendix) ; alkali-albumin is also present, as is probably also a small quantity of globulin. Such muscles as are red also contain a small quantity of hemoglobin, to which indeed their redness is due. Thus while dead muscle contains myosin, serum-albumin, and extractives with certain insoluble matters and certain gelatinous elements not referable to the muscle-substance itself, living muscle contains no myosin, but some substance or substances which bear somewhat the same relation to myosin that fibrinogen and fibrino- plastin do to fibrin, and which become myosin on the death of the muscle. Fats are present in considerable quantities, and the extractives are varied and numerous. The most important are kreatin, sarco- lactic or paralactic acid (a variety of lactic acid, differing from it chiefly in the solubility of its salts, and in the amount of water of crystallization contained in them), and sugar. To these may be added xanthin, hypoxanthin, (sarkin) inosit, (especially in the cardiac muscles), inosinic acid and traces of uric acid. Except in patho- logical conditions (and in the plagiostome fishes) urea is conspicuous by its absence. In living muscle glycogen is frequently present, and is at the death of the muscle transformed into sugar. Dextrin has also been found; and a special fermentable muscle-sugar has been described. It has been much debated whether kreatin or kreatinin, or both, are present in muscle; the evidence goes to shew that kreatin alone is present. ; The ashes of muscle, like those of the red corpuscles, are cha- racterized by the preponderance of potassium salts and of phosphates ; these form in fact nearly 80 p.c. of the whole ash. The general composition of human muscle is shewn in the follow- ing table of V. Bibra, Water ... 7445 Solids Myosin and other matters, elastic ele- ments, &c., insoluble in water ... 155'4 Soluble albumin ... ... ... 19'3 Gelatin 207 Extractives ... ... ... ... 371 Fats 230 255-5 Frotoplasma, Lieipzig, 1864. Chap, ii.] THE CONTRACTILE TISSUES. 35 Sec. 2. The Phenomena of Muscle and Nerve. If the trunk of a nerve be pinched, or subjected to sudden heat, or dipped in certain chemical substances, or acted upon by various galvanic currents, movements or contractions are seen in the muscles to which branches of the nerve are distributed. The substances qx agents which thus cause contractions are called ' stimuli.' The stimuli may be applied directly to the muscle. The muscle itself may be pinched, or subjected to galvanic currents, &c. ; in this case also contractions are produced. It might be supposed that the contractions so produced are in reality due to the fact that, although the stimulus is apparently applied directly to the muscle, it is, after all, the fine nerve-branches, so abundant in the muscle, which are actually stimulated. The following facts however go far to prove that the muscular fibres themselves are capable of being directly stimulated without the intervention of any nerves. When a frog (or other animal) is poisoned with' urari, the nerves may be sub- jected to the strongest stimuli without causing any contractions in the muscles to which they are distributed : yet even ordinary stimuli applied directly to the muscle readily cause contractions. If before introducing the urari into the system, a ligature be passed under- neath the sciatic nerve in one leg, for instance the right, and drawn tightly round the whole leg to the exclusion of the nerve, it is evident that the urari, when injected into the back of the animal, will gain access to the right sciatic nerve above the ligature, but not below, while it will have free access to the whole left sciatic. If, as soon as the urari has taken effect, the two sciatic nerves be stimulated, no movement of the left leg will be produced by stimu- lating the left sciatic, whereas strong contractions of the muscles of the right leg below the ligature will follow stimulation of the right sciatic, whether the nerve be stimulated above or below the ligature. Now since the upper parts of both sciatics are equally exposed to the action of the poison, it is clear that the failure of the left nerve to cause contraction is not attributable to any change having taken place in the upper portion of the nerve, else why should not the right, which has in its upper portion been equally exposed to the action of the poison, also fail ? Evidently the poison acts on some parts of the nerve lower down. If a single muscle be removed from the circulation (by ligaturing its blood-vessels), previous to the poisoning with urari, that muscle will contract when any part of the nerve going to it is stimulated, though no other muscle in the body will contract when its nerve is stimulated. Here the whole nerve right down to the muscle has been exposed to the action of the poison ; and yet it has lost none of its power over the muscle. On the other hand, if the muscle be allowed to remain in the body, and so be exposed to the action of the poison, but the nerve be cut out high up and gently removed from the body, except where it is 3—2 36 MUSCULAR IRRITABILITY. [Book i. attached to the muscle, so as to be taken away from the influence of the poison, stimulation of the nerve produces no contractions in the muscle, though stimuli applied directly to the muscle at once cause it to contract. From these facts it is clear that urari poisons the ends of the nerve within the muscle long before it affects the trunk, and it is exceedingly probable that it is the very extreme ends of the nerves (possibly the end plates, though we have no definite proof of this), which are affected. The phenomena of urari poisoning there- fore go far to prove that muscles are capable of being made to contract by stimuli applied directly to the muscular fibres them- selves ; and there are other facts which support this view. This question of 'independent tnuscular irritability'^ was once thought to be of importance. In old times, the swelling of a muscle during contraction ■was held to be caused by the animal spirits descending into it along the nerves ; and when the doctrine of 'spirits' was given up, it was still taught that the vital activity of the muscle was something bestowed upon it by the action of the nerve, and not properly belonging to itself. We owe to Haller the establishment of the truth, that the contraction of a mtiscle is a manifestation of the muscle's own energy, excited it may be by nervous action, but not caused by it. Haller spoke of the muscle as possessing a vis insita, while he called the nervous action, which excites contraction, the vis nervosa. He used the word irritability as almost synonymous with contractility, a meaning which is still adopted by many authors. In this work we have used it in the wider sense, first employed by Glisson, which includes other manifestations of energy than the change of form which constitutes a contraction. Since Haller^s time, the question whether muscles possess an independent irritability has shifted its ground ; it now means, not whether muscles are irritable or no,, but simply whether their irritability can be called into action in other ways than by the mediation of nerves. In addition to the urari argument just described, we may state that portions of muscular fibres, entirely destitute of nerves, such as the lower end of the sartorius of the frog, may be stimulated directly, with conti'actions as a result ; that the chemical substances which act as stimuli when applied directly to muscles, differ somewhat from those which act as stimuli to nerves, and lastly, that a portion of muscle-fibre quite free from nerves may be seen under the microsco]ie to contract. In the succeeding portions of this work abundant evidence will be aH'orded that the activity of contractile protoplasm is in no way essentially dependent on the presence of nervous elements. The Fhenomena of a simple Muscular Contraction. If the far end of the nerve of a muscle-nerve preparation (the gastrocnemius for instance of the frog with the attached sciatic nerve dissected out), Figs. 1 and 2, be laid on the electrodes of an induction- machine, the passage of a single induction-shock (either making or breaking) will produce no visible change in the nerve, but the muscle will give a short sharp contraction, i.e. will for an instant shorten itself, becoming thicker the while, and then return to its previous Chap, ii.] THE CONTRACTILE TISSUES. 37 38 MUSCULAR CONTRACTION. [Book i. Fig. 1. DiAGEAJt illustrating Apparatus arranged foe Experiments TnTH Muscle AND Nekve. A. The moist eliamber containing tlie muscle-nerve preparation. (Tlie muscle-nerve and electrode-holder are shewn on a larger scale in Fig. 2.) The muscle m, supported by the clamp cl, which firmly grasps the end of the femur /, is con- nected by means of the S hook s, and a thread with the lever I, placed below the moist chamber. The nerve n, with the portion of the spinal column n' still attached to it, is placed on the electrode-holder el, in contact with the wires x, y. The whole of the interior of the glass case gl is kept saturated with moisture, and the electrode-holder is so constructed that a piece of moistened blotting paper may be placed on it without coming into contact with the nerve. B. The revolving cylinder bearing the smoked paper on which the lever writes. A figm-e of the cylinder from a different point of view is shewn in Fig. 39. C. Du Bois-Eeymond's key arranged for short circuiting. The wires x and y of the electrode-holder are connected through binding screws in the floor of the moist chamber with the wires x', y , and these are secured in the key, one on either side. To the same key are attached the wires x", y" coming from the secondary coil s. c, of the induction-machine D. This secondaiy coil can be made to shde up and down over the primary coil pr. c, with which are connected the two wires x'" and y'". x'" is connected directly with one pole, for instance the copper pole c. p, of the battery JE. y'" is carried to a binding screw a of the Morse key F, and is continued as y^^ from another binding screw h of the key to the zinc pole z. p, of the battery. Supposing everything to be arranged, and the battery charged, on depressing the handle h a, of the Morse key F, a current will be made in the primary coil pr. c, passing from c. p, through x"' to pr. c, and thence through y'" to a, thence to b, and so through y^^ to z. p. On removing the finger from the handle of F, a spring thrusts up the handle, and primary circuit is in consequence immediately broken. At the instant that the primary current is either made or broken, an induced ciu-rent is for the instant developed in the secondary coil s. c. If the cross bar h in the Du Bois-Reymond's key be raised (as shewn in the thick line in the figure), the wires x", x', x, the nerve between the electrodes and the wires y, y', y" form the complete secondary circuit, and the nerve consequently experiences a making or breaking induction-shock whenever the primary current is made or broken. If the cross bar of the Du Bois-Eeymond key be shut down, as in the dotted line li' in the figure, the resistance of the cross bar is so slight compared with that of the nerve and of the wires going from the key to the nerve, that the whole secondary (induced) current passes from x" to y" (or from y" to x") along the cross bar, and none passes into the nerve. The nerve being thus short circuited, is not affected by any changes in the current. Fig. 2. The muscle-nerve preparation of Fig. 1, with the clamp, electrodes, and electrode-holder are here shewn on a larger scale. The letters as in Fig. 1. The form of electrode-holder figured is a convenient one for general purposes, but many other forms ai"e in uss. Chap, ii.] TEE CONTRAGTILE TISSUES. <39 condition. If one end of the muscle be attached to a lever, while the other is fixed, the lever will by its movement indicate the extent and duration of the shortening-. If the point of the lever be brought to bear on some rapidly travelling surface, on which it leaves a mark (being for this purpose armed with a pen and ink if the surface be plain paper, or with a bristle or needle if the surface be smoked glass or paper), so long as the muscle remains at rest the lever will describe an even line. When, however, a contraction takes place, as when a single induction-shock is sent through the nerve, some such curve as that shewn in Fig. 3 will be described, the lever rising with the Fig. 3, A Muscle-curve obtained by means of the Pendulum Myograph. (To be read from left to right.) a indicates the moment at which the induction-shock is sent into the nerve, h the commencement, c the maximum, and d the close of the contraction. The two smaller curves succeeding the larger one are due to oscillations of the lever. Below the muscle-curve is the curve drawn by a tuning fork making 180 double vibrations a second, each complete curve representing therefore -^^ of a second. It will be observed that the plate of the myograph was travelling more rapidly towards the close than at the beginning of the contraction, as shewn by the greater length of the vibration-curves. shortening of the muscle, and descending as the muscle returns to its natural length. This is known as the 'muscle-curve.' In order to make the 'muscle-curve' complete, it is necessary to mark on the recording surface the exact time at which the induction-shock is sent into the nerve, and also to note the speed at which the recording surface is travelling. These points are best effected by means of the pendulum myograph, Fig. 4. In this instrument a smoked glass plate, on which a lever wi-ites, swings with a pendulum. The pendukim with the glass plate attached being raised up, is suddenly let go. It swings of course to the opposite side, the glass plate travels through an arc of a circle, and, the lever being stationary, the point of the lever describes an arc on the glass plate. The rate at which the glass plate travels, i.e. the time it takes for the lever-point to describe a line of a given length on the glass plate may be calculated from the length of the pendulum, but it is simpler and easier to place a vibrating tuning- fork immediately under the point of the lever. If the vibrations of the tuning-fork are known, then the number of vibrations which are marked 40 PENDULUM MYOGRAPH. [Book i. Fig. 4. The Pendulum Myograph. The figure is diagrammatic, the essentials only of the instrument heing shewn. The smoked glass plate A swings on the "seconds" pendulum B by means of carefully Chap, ii.] THE CONTRACTILE TISSUES. 41 adjusted bearings at C. The contrivances by which the glass plate can be removed and replaced at pleasure are not shewn. A second glass plate so arranged that the first glass plate may be moved up and down without altering the smng of the pendulum is also omitted. Before commencing an experiment the pendulum is raised up (in the figure to the right), and is kept in that position by the tooth a catching on the spring-catch 5. On depressing the catch b the glass plate is set free, swings into the new position iudicated by the dotted lines, and is held in that position by the tooth a' catching on the catch V. In the course of its swing the tooth a' coming into contact with the projecting steel rod c, knocks it on one side into the position indi- cated by the dotted line c'. The rod c is in electric continuity with the wire x of the primary coil of an induction-machine. The screw d is in similarly electric continuity with the wire y of the same primary coil. The screw d and the rod c are armed with platinum at the points in which they are in contact, and both are insulated by means of the ebonite block e. As long as c and d are in contact the circuit of the primary coil to which x and y belong is closed. "When in its swing the tooth a' knocks c away from d, at that instant the circuit is broken, and a ' breaking ' shock is sent through the electrodes connected with the secondary coil of the machine, and so through the nerve. The lever I, the end only of which is shewn in the figure, is brought to bear on the glass plate, and when at rest describes a straight line, or more exactly an arc of a circle of large radius. The tuning-fork /, the ends only of the two limbs of which are shewn in the figure placed immediately below the lever, serves to mai'k the time. on the plate between any two points on the line described by the lever gives the time taken by the lever in passing from one point to the other. An easy arrangement permits the exact time at which the shock is seut through the nerve to be mai'ked on the line of the leA^er. To avoid too many markings on the plate the pendulum after describing an arc is caught by a spring catch on the opposite side. A complete muscle-curve, such as that shewn in Fig. 3, teaches us the following facts : 1. That althougli the passage of the induced current from electrode to electrode is practically instantaneous, its effect, measured from the entrance of the shock into the nerve to the return of the muscle to its natural length after the shortening, takes au appreciable time. In the figure, the whole contraction from a to c^ takes up the same time as eighteen double vibrations of the tuning-fork. Since each double vibration represents j^ of a second, the duration of the whole contraction figured was -^^ sec. 2. In the first portion of this period, from a to h, there is no visible change, no shortening of the muscle, no raising of the lever. 3. It is not until 6, that is to say after the lapse of -^ i.e. about ■^ sec, that the shortening begins. The shortening as shewn by the curve is at first slow, but soon becomes more rapid, and then slackens again until it reaches a maximum at c; the whole short- ening occupying about -^^ sec. 4. Arrived at the maximum of shortening, the muscle at once begins to relax, the lever descending at first slowly, then very rapidly, and at last more slowly again, until at d the muscle has regained its natural length; the whole retui'n from the maximum of contraction to the natural length occupying j^r-^, i. e. about -^^ sec. 42 VELOCITY OF A NERVOUS IMPULSE. [Book i. Thus a simple muscular contraction, a simple spasm as it is some- times called, produced by a momentary stimulus, such as an in- stantaneous induction-shock, consists of three main phases. 1. A phase antecedent to any visible alteration in the muscle. This phase, during which invisible preparatory changes are taking place in the nerve and muscle, is often called the 'latent period.' 2. A phase of shortening or contraction. 3. A phase of relaxation or return to the original length. In the case we are considering, the electrodes are supposed to be applied to the nerve at some distance from the muscle. Consequently the latent period of the curve comprises not only the preparatory ac- tions going on in the muscle itself, but also the changes necessary to conduct the immediate effect of the induction-shock from the part of the nerve between the electrodes, alonor a considerable length of nerve down to the muscle. It is obvious that these latter changes might be eliminated by placing the electrodes on the muscle itself or on the nerve close to the muscle. If this were done, the muscle and lever being exactly as before, and care were taken that the induction- shock entered into the nerve at the new spot, at the moment when the point of the lever had reached exactly the same point of the travelling surface as before, a curve like that shewn by the plain line in Fig. 5 would be gained. It resembles the first curve (indi- cated in the figure by a dotted line) in all points, except that the Fig. 5. Cukves illustrating the measurement of the Velocity op a Neevous Impulse. (Diagrammatic.) To be read from left to right. The same muscle-nerve preparation is stimulated (1) as far as possible from the muscle, (2) as near as possible to the muscle ; both contractions are registered by the pendulum myographion exactly in the same way. In (1) the stimulus enters the nerve at the time indicated by the line a, the con- traction, shewn by the dotted line, begins at 6'; the whole latent period therefore is indicated by the distance from a to b'. In (2) the stimulus enters the nerve at exactly the same time a ; the contraction, shewn by the unbroken line, begins at b ; the latent period therefore is indicated by the distance between a and h. The time taken up by the nervous impulse in passing along the length of nerve between 1 and 2 is therefore indicated by the distance between b and b', which may be measured by the tuning-fork curve below. N.B. No value is given in the figure for the vibrations of the tuning-fork, since the figure is diagrammatic, the distance be- tween the two curves, as compared with the length of either, having been purposely exaggerated for the sake of simplicity. Chap. II.] THE CONTRACTILE TISSUES. '43 latent period is shortened ; the contraction begins rather earlier. From this we learn two facts. 1. The greater part of the latent period is taken up by changes in the muscle itself, preparatory to the actual visible shortening, for the two latent periods do not differ much. Of course, even in the second case, the latent period includes the changes going on in the short piece of nerve still lying between the electrodes and the mus- cular fibres. To eliminate this with a view of determining the latent period in the muscle itself, the electrodes should be placed directly on the muscle poisoned with urari. If this were done, it would still be found that the latent period was chiefly taken up by changes in the muscular as distinguished from the nervous elements. 2. Such difference as does exist indicates the time taken up by the propagation, along the piece of nerve, of the changes set up at the far end of the nerve by the induction-shock. These changes we shall hereafter speak of, as constituting a nervous impulse; and the above experiment shews that it takes some appreciable time for a nervous impulse to travel along a nerve. In the figure the difference between the two latent periods, the distance between 6 and h', seems almost too small to measure accurately; but if a long piece of nerve be used for the experiment, and the recording surface be made to travel very fast, the difference between the duration of the latent period when the induction-shock is sent in at a point close to the muscle, and that when it is sent in at a point as far away as possible from the muscle, may be satisfactorily measured in fractions of a second. If the length of nerve between the two points be accurately measured, the rate at which a nervous impulse travels along the nerve to a muscle can be easily calculated. This has been found to be in the frog about 28, and in man about 33 metres per second. Thus when a momentary stimulus, such as a single induction- shock, is sent into a nerve connected with a muscle, the following events take place. 1. The creation at the spot stimulated of a nervous impulse, and the propagation of the impulse along the nerve to the muscle. The time taken up by this varies according to the length of the nerve. For the same length of nerve it is tolerably constant. 2. The setting up of certain molecular changes in the muscle, unaccompanied by any visible alteration in its form, constituting the latent period, and occupying on an average about y^o^h sec. The time taken up by the latent period varies somewhat according to circumstances. 3. The shortening of the muscle up to a maximum, occupying about jf^ sec. 4. The return of a muscle to its former length, occupying about 44 TETANUS. [Book i. j^Q sec. Both these last events vary much in duration according to circumstances \ Tetanic Contractions. If a single induction-shock be followed at a sufficiently short in- terval by a second shock of the same strength, the first simple con- traction or spasm will be followed by a second spasm, the two bearing some such relation to each other as that shewn by the curve in Fig. 6, where the interval between the two shocks was just long Fig. 6. Tbacing of a Double Muscle Curve. To be read from left to right. While the muscle was engaged in the first contraction (whose complete course, had nothing intervened, is indicated by the dotted line), a second induction-shock was thrown in, at such a time that the second contraction began just as the first was beginning to decline. The second curve is seen to start from the first as does the first from the base-line. enough to allow the first spasm to have passed its maximum before the latent period of the second was over. It will be observed that the second curve is almost in all respects like the first except that it starts, so to speak, from the first curve instead of from the base-line. The second nervous impulse has acted on the already contracted muscle, and made it contract again just as it would have done if there had been no first impulse and the muscle had been at rest. The two contractions are added together and the lever raised nearly double the height it would have been by either alone. A more or less similar result would occur if the second contraction began at any other phase of the first. The combined effect is, of course, greatest when the second contraction begins at the maximum of the first, being less both before and afterwards. If in the same way a third shock follows the second at a sufficiently short interval, a third curve is piled on the top of the second. The same with a fourth, and so on. When however repeated shocks are given it is found that the height of each contraction is rather less than the preceding one, and this diminution becomes more marked the greater the number of shocks. Hence after a certain number of shocks, the succeeding impulses do 1 The measurements hero stated are those ordinarily given. The curve described in the previous text happened to have a rather long latent period, and the lengthening to be of shorter instead of longer dui-ation than the shortening. Chap, il] THE CONTRACTILE TISSUES. 45 not cause any further shortening of the muscle, any further raising of the lever, but merely keep up the contraction already existing. The curve thus reaches a maximum which it maintains, subject to the depressing effects of exhaustion, as long as the shocks are repeated. When these cease to be given, the muscle returns, in the usual way, at first very rapidly, and then more slowiy, to its natural length. When the shocks do not succeed each other too rapidly, the indi- vidual contractions may readily be traced along the whole curve, as is seen in Fig. 7, where the primary current of the induction-machine Fig. 7. Muscle thrown into Tetanus, when the pmmaey current of an Induction- machine IS REPEATEDLY BROKEN AT INTERVALS OF SIXTEEN IN A SECOND. To be read from left to right. The upper line is that described by the muscle. The lower marks time, the intervals between the elevations indicating seconds. The intermediate line shews when the shocks were sent in, each mark on it corresponding to a shock. The lever, which describes a straight line before the shocks are allowed to fall into the nerve, rises almost vertically (the recording surface travelling in this ease slowly) as soon as the first shock enters the nerve at a. Having risen to a certain height, it begins to fall again, but in its fall is raised once more by the second shock, and that to a greater height than before. The third and succeeding shocks have similar effects, the muscle continuing to become shorter, though the shortening at each shock is less. After a while the increase in the total shortening of the muscle, though the individual con- tractions are still visible, almost ceases. At 6, the shocks cease to be sent into the nerve; the contractions almost immediately disappear, and the lever forthwith com- mences to descend. The muscle being lightly loaded, the descent is very gradual; the muscle had not regained its natural length when the tracing was stopped. was repeatedly broken at intervals of sixteen in a second. When the shocks succeed each other more rapidly, the individual contractions, visible at first,may become fused together and lost to view as the tetanus continues and the muscle becomes tired. When the shocks succeed each other still more rapidly (the second contraction beginning in the ascending portion of the first), it becomes difficult or impossible to trace out the single contractions. The curve then described by the lever is of the kind shewn in Fig. 8, where the primary current of an induction- machine was rapidly made and broken by the magnetic interruptor, 46 TETANUS. [Book i. Fig. 8. Tetanus peoduced with the obdinabt Magnetic Intereuptor op an Induc- tion-machine. (Recording surface travelling slowly.) To be read from left to right. The interrupted current being thrown in at a the lever rises rapidly, but at h the muscle reaches the maximum of contraction. This is continued till c, when the current is shut off and relaxation commences. Fig. 9. The lever, it will be observed, rises at a after the latent period (which is not marked), first rapidly, and then more slowly, in an appa- rently unbroken line to a maximum at about h, maintains the maxi- mum, subject to the effects of exhaustion, so long as the shocks con- tinue to be given, and when these cease to be given, as at c, gradually descends to the base-line. This condition of muscle, brought about by rapidly repeated shocks, this fusion of a number of simple spasms into an apparently smooth, continuous effort, is known as tetanus, or tetanic contraction. The above facts are most clearly shewn when induction-shocks, or at least galvanic currents in some form or other, are employed. They are seen, however, whatever be the form of stimulus employed. Thus in the case of mechanical stimuli, a single blow given to a nerve may cause a single spasm, repeated blows (if frequent enough) a tetanus. With chemical stimulation, as when a nerve is dipped in acid, it is impossible to secure a momentary application ; hence tetanus, generally irregular in cha- racter, is the normal result of this mode of stimulation. In the living body, the contractions of the striated muscles, brought about either by the will or by reflex action, are generally tetanic in character. Even very short sharp movements, such as a sudden jerk of the limbs, are in reality examples of tetanus of short duration. Such being the general visible characters of muscular contrac- tions, we may now attack the questions : What changes in a nerve constitute a nervous impulse ? What changes in a muscle constitute a muscular contraction ? Changes in a Nerve during the passage of a nervous impulse. These are of the same nature during the passage of either a single impulse leading to a simple muscular spasm, or repeated impulses leading to tetanus, the latter being merely an accumulation of the former. 1. There are no visible events. Chap, ii.] THE CONTRACTILE TISSUES. 47 Fig. 9. The Magnetic Inteeeuptoe. • The .figure is introduced to illustrate the action of this instrument as commonly used by physiologists. The two wires x and y from the battery are connected with the two brass pillars a and d by means of screws. Directly contact is thus made the current, indicated in the figure by the thick interrupted line, passes in the direction of the arrows, up the pillar a, along the steel spring h, as far as the screw c, the point of which, armed with platinum, is in contact with a small platinum plate on 6. The cijrrent passes from b through c and a conecting wire into the primary coil p. Upon its entering into the primary coil, an induced (making) current is for the instant developed in the secondary coil (not shewn in the figure). From the primary coil p the current passes, by a connecting wire, through the double spiral, m, and, did nothing happen, would con- tinue to pass from m by a connecting wire to the pillar d, and so by the wire y to the battery. The whole of this course is indicated by the thick interrupted line with its arrows. As the current however passes through the spirals m, the iron cores of these are made magnetic. They in consequence draw down the iron bar e, fixed at the end of the spring h, the flexibility of the spring allowing this. But when e is drawn down, the platinum plate on the upper surface of b is also drawn away from the screw c, and a similar platinum plate on the under surface of b is brought into contact with the platinum armed point of the screw /, the screws being so arranged that this takes place. In consequence of this change the current can no longer pass from h to c. On the contrary, it passes from b to f, and so down the pillar d, in the direction indicated by the thin interrupted line, and out to the battery by the wire y. Thus the current is "short-circuited" from the primary coil; and the instant that the current is thus cut off from the primary coil, an induced (breaking) current is for the moment developed in the secondary coU. But the current is cut off not only from the primary coil, but also from the spirals m ; in consequence their cores cease to be magnetized, the bar e ceases to be attracted by them, and the spring 5, by virtue of its elasticity, resumes its former position in contact with the screw c. This return of the spring however re-establishes the current in the primary coil, and in the spirals, and the spring is drawn down, to be released once more in the same manner as before. Thus as long as the current is passing along x, the contact of b is constantly alternating be- tween c and/, and the current is constantly passing into and being shut off from j9, the periods of alternation being determined by the periods of vibration of the spring b. With each passage of the current into, or withdrawal from the primary coil, an induced (making and, respectively, breaking) shock is developed in the secondary coil. 48 NMRVE CURRENTS. [Book i. 2. No chemical changes have been satisfactorily made out. 3. No change in temperature or in the general physical conditions of the nerve have been satisfactorily observed. 4. The only distinctly appreciable change is an electric one. Natural nerve-currents. If a piece of living nerve be placed on a pair of non-polarisable^ electrodes, connected with a sensitive gal- vanometer containing many convolutions, deflections of the galvano- meter-needle indicate the existence of currents which vary according^ to the position of the electrodes. The greatest deflection is observed when one electrode is placed at the mid-point or equator''' of the piece of nerve, and the other at either cut end ; and the deflection is of such a kind as to shew that positive currents are continually passing from the mid-point through the galvanometer to the cut end, that is to say, the cut end is negative relatively to the mid-point. The currents outside the nerve may be considered as completed by currents in the nerve from the cut end to the mid-point. Thus in the diagram Fig. 11, the arrows indicate the direction of the currents. If the one electrode be placed at the equator a b, the effect is the same at whichever 1 These (Fig. 10) consist essentially of a slip of thoroughly amalgamated zinc dip- ping into a saturated solution of zinc sulphate, which in turn is brought into connection Fig. 10. KoN-PoLAEiSABLE Electeodes. a, the glass tube ; z, the amalgamated zinc slips connected with their respective wires; z, s, the zinc sulphate solution; ch.c, the plug of china clay; c', the portion of the china-clay plug projecting from the end of the tube ; this can be moulded into any required form. with the nerve or muscle by means of a plug or bridge of china-clay moistened with dilute sodium chloride solution; it is important that the zinc should be thoroughly amalgamated. This form of electrodes gives rise to less polarisation than do simple platinum or copper electrodes. The clay affords a connection between the zinc and the tissue which neither acts on the tissue nor is acted on by the tissue. Contact of any tissue with copper or jDlatiniim is in itself sufficient to develope a current. 2 The transverse line containing all the mid-points, i.e. points midway between the two ends of the piece, is called the 'equator.' In the diagram, Fig. 11, the liue ab is the equator. Chap, ii.] THE CONTRACTILE TISSUES. 49 Fig. 11. Diagram illusteAting the elegtbic ctfEESitxs op neSte and muscle. Being purely diagrammatic, it may serve for a piece either of nerve or of muscle, except that the currents at the transverse section cannot be shewn in a nerve. The arrows shew the direction of the current through the galvanometer. ab the equator. The strongest currents are those shewn by the dark Iines> as from a, at equator, to x or to 1/ at the cut ends. The current from a to c is weaker than from a to y, though both, as shewn by the arrows, have the same direction. A current is shewn from e, which is near the equator, to / which is farther from the equator. The current (in muscle) from a point in the circumference to a point nearer the centre of the transverse section is shewn at gh. From a to & or frora X to %j, there is no current, as indicated by the dotted lines. of the two cut ends x ox y the other is placed. If, one electrode remainiag at the equator, the other be shifted from the cut end to a spot c nearer to the equator, the current continues to have the same direction, but is of less intensity in proportion to the nearness of the electrodes. If the two electrodes be placed at unequal distances e and /, one on either side of the equator, there will be a feeble current from the one nearer the equator to the one farther off, and the current will be the feebler, the more nearly they are equidistant from the equator. If they are quite equidistant, as for instance when one is placed on one cut end x, and the other on the other cut end y, there will be no current at all. These currents are spoken of as the natural nerve- currents. They are not transitory, they do not disappear immediately after they have manifested them- selves, but on the contrary continue for an indefinite period. They must therefore be maintained by changes taking place within the nerve. Hence they depend on the vital (nutritive) condition of the nerve. Du Bois-Reymond^ found tlie electromotive force of the sciatic nerve of a frog to amount to "022 Daniell, while that of the rabbit did not exceed '026 Daniell. Engelmann^ however obtained for the sciatic of the fros; a value of '046 Daniell. 1 Gesammelti Abhand. (1877) 11. 232. F. P. * Pfliiger'd Archiv, xv, (1877), p. 141. 4 50 NEGATIVE VARIATION. [Book i. Negative variation. When a nerve is stimulated, so that a nervous impulse passes along it, the natural nerve-current is dimin- ished ; it undergoes what is called a negative variation. This is not easily shewn in the case of a simple impulse, but is very evident when the repeated impulses of tetanus are generated. Thus if in a long piece of nerve, one electrode be placed at one cut end and the other at some distance from it, so as to give a well-marked deflection of the galvanometer, and the other end of the nerve be tetanized with the induction-machine working with a magnetic interrupter, the needle of the galvanometer which before the stimulation was de- flected, say to 60 or 70 divisions of the scale on one side of zero, will now swing back considerably towards or to zero or even to some distance on the other side of zero. A similar negative variation is observed wherever the electrodes be placed, and whatever point be stimulated. The effect is not due to any escape from the stimulating current on to the electrodes, for it ceases when the nerve is tied between the point stimulated and the electrodes, yet the ligature does not interfere with the physical conduction of a current along the nerve, though it puts an end to the propagation of vital changes. Moreover the same negative variation is seen whatever be the mode of stimulation. It is not confined especially to electrical stimula- tion, but occurs also when chemical or mechanical stimuli are used. The negative variation, like the natural current, is a vital phenomenon, and the intensity of both ebbs and flows with the changing vitality of the nerve. According to Bernstein' the deflection of the needle occurring during the negative variation may on very strong stimulation amount to two or three times the deflection, due to the natural current. When we come to study the changes which take place in a muscle during contraction we shall see that the nerve and muscle of a frog may be used instead of a galvanometer, by the method known as ' the rheoscopic frogV in which the natural current of one nerve, or the negative variation of that current, is used as stimulus to another nerve. And we shall learn from that experiment that when a nerve is tetanized, its natural current undergoes not a single, but a series of negative variations, each impulse in fact producing its own variation, so that repeated stimuli, corresponding in number to the variations, are thrown into the second nerve, and thus cause a tetanus in the attached muscle. This fact we cannot learn from the galvanometer, in which the needle from its inertia cannot follow rapidly enough the variations of the current, but gives one large swing which is the accumulation of the smaller swings due to the individual variations, just as the apparently continuous contraction of a tetanized muscle is the summation of a number of simple spasms. The main event then accompanying a nervous impulse of which 1 TJntersuch. u. d. Erregungsvorgang im Nerven- und Muskelsysteme. 1871. 2 See p. 53. Ghapil] the contractile TISSUES. 51 we are at present cognisant, is the negative variation of the natural nerve-current. Beyond the terminal effects of a muscular contrac- tion (in motor nerves and corresponding effects in sensory nerves), this is the one token we possess whereby we can judge of what is taking place in a nerve. By the help of an ingenious apparatiis Bernstein^ has been able to study the way in which the negative variation passes over any given spot in a nerve. Suppose a nerve is stimuhited with a single induction- shock at the point A ; and suppose the points B, £', of the nerve, at some distance from A, so chosen that they will give a natural nerve-current, are connected with a galvanometer. If the electrodes of E, B' are permanently connected with the galvanometer, a negative variation will be observed every time A is stimulated. But suppose that the points B, E, instead of being permanently connected with the galvanometer, are only brought into connection with it for an instant, and that at different small fractions of a second after A is stimulated; so that for instance on one occasion, the portion of nerve between E and B' is brought into momentary connection with the galvano- meter— is, as the telegraph engineers would say, 'tapped,' — at the very instant A is being stimulated ; and on another occasion, at an interval say of yijjSec. after A was stimulated, and so on; what should we expect to happen in reference to the nerve-current between B and E % This Bernstein investigated. Instead however of simply stimulating A once only on each occasion, he repeated the stimulation several times a second, bringing B, E' into momentary connection with the galvanometer at each stimulation. He thus had under his notice not the slight and probably hardly recog- nisable effect of a single stimulation, but the cumulative effect of several stimulations, the nerve being 'tapped' at exactly the same fraction of a second after the stimulation in each series of stimulations. By varying the interval in a number of series of stimulations, his apparatus consisting mainly of a revolving disc with moveable adjuncts, he was able to explore the condition of the natural current and the amount of negative variation at E, E during the whole interval between any two successive stimulations of A. He found that if B were tapped at the same instant that the shock passed through A, there was no negative variation at all of the natural current. When E was tapped a very small fraction of a second later a slight variation was observed, a little later still the variation was found to be greater, still later it had reached a maximum ; beyond this it began to decline, and so at last an interval was reached, at which the negative variation was again wholly absent. It had in fact in this last case passed over E, before E was tapped. These observations shew that the negative variation passes over any given spot of the nerve in the form of a wave, rising rapidly to a maximum and then more gradually declining again. Bernstein found that it travelled m the nerves of the frog at about the rate of 28 metres in a second, a rate identical, it will be noted, with that of the nervous impulse determined in quite other ways. He also found that the whole wave took -0007 sec. to pass over any given point m a nei've. Con- sequently the length of the wave was about 18 mm. Assuming, as we fairly may do, that the negative variation is a satisfac- tory sign of the whole set of changes which constitute a nervous impulse, 1 Op. cit. 4—2 52 MUSCLE CURRENTS. [Book i. we may say tliat a nervous impulse is a molecular disturbance propagated along the nerve in the form of a wave, of the length, and possessing the velocity, mentioned above. The Changes in a Muscle during contraction. Electrical changes. These deserve to be considered apart from the rest, because they alone are definitely known to occur in the latent period. A living muscle exhibits natural muscle-currents altogether similar to the natural nerve-currents but far more powerful. The diagram, Fig. 11, applies to muscle as well as to nerve. In a cylindrical or prismatic muscle with regularly disposed parallel fibres the equator is positive relatively to either end or to points between the end and the equator; and points on either side of the equator are positive or negative the one to the other, according to their distance from the equator. The muscle-currents are obtained not only from muscles still retaining their natural tendinous terminations, but also, and even in a more striking degree, from muscles the ends of which have been cut off, thus presenting terminal artificial trans- verse sections instead of the natural tendinous ones. In these, more- over, it is seen that the circumference of the transverse section is positive relatively to the centre, as shewn at ^ to ^ in Fig. 11. (In nerves this is not satisfactorily seen.) Thus, of all the points of a muscle the centre of either terminal transverse section and any point on the equator of the muscle are the most negative and positive relatively to each other. The currents are shewn not only with artificial transverse sections, but also with artificial longitudinal sections. In fact, in a mere piece of muscle the same distribution of currents may be witnessed. Du Bois-Reymond' finds the electromotive force of the natural current of a frog's muscle (gracilis or semimembranosus) to amount sometimes to •08 Daniell. That of the muscle of a rabbit never exceeded "OiO Daniell. It has been said that the currents in a muscle with artificial transverse sections are often more marked than those of an intact muscle. In fact, frequently when a muscle is removed with extreme care from the body, and the tendinous origins and insertions allowed to remain bathed in their natural lymph, the currents observed are very feeble indeed or even wholly absent. On dipping the tendon in acid or water however, strong currents are at once developed. To explain this Du Bois-Reymond supposes that the extreme end of the muscle is in the natural condition protected by a layer of positive elements whose action masks the natural current. lb is not until this parelectronomic layer, as he calls it, has been removed by the application of some reagent or by changes taking place in the muscle itself, that the natural current can manifest itself in its proper strength. Her- mann, on the other hand, regards tlie absence of currents as the natural condition of the muscle (or neive). He explains the current obtained with ^ Gesammelte Ahliandl. ii. 212. Chap, ii.] THE CONTRACTILE TISSUES. 53 the artificial transverse section as due to the exposed layer of muscular (or nervous) substance, as it dies or enters into rigor mortis, becoming negative relatively to the still living substance. Where natural currents are mani- fested in untouched muscles, the terminal portions of the fibres may be supposed to be dying in advance of the median portions. Under this view the negative variation during contraction (of which we shall speak directly) is of course to be regarded as an independent current generated by the molecules of the muscular substance becoming negative during the latent period, the negativity sweeping along the fibre in advance of the con- traction-wave, Engelmann' has brought forward a strong sujaport of Hermann's view, by shewing tbat in the heart, unstriated muscles, and nerves, the current jDroduced by a recently prepared artificial section sinks in the course of some hours almost to nil, but may be revived to its original strength by a fresh section slightly in advance of the old one. In the present state of our knowledge, there are many difficulties in the way of accepting either one view or the other, and a discussion of the subject sufficiently exhaustive to be of any value would be beyond the scope of this work. The reader who wishes to enter more fully into the matter is referred to the memoirs contained in Du Bois-Reymond, Gesammelte Abhandlungen, 1875 — 77, Hermann, Untersuch. zur Physiol, d. Musheln und Nerven, 1867 — 68, and numerous papers in Pfiiiger's Archiv. The currents are in part dependent on the form of the muscle or piece of muscle. Thus in a rhomb the blunt angles are positive towards the acute ones, and the natural currents are obscured by currents, the so-called currents of indinatioii, passing from the latter to the former. Hence the scheme of natural currents, illustrated by the diagram, Fig. 11, only holds good for regular muscles, the fibres of which are all parallel, ending in tolerably rectangular terminations. In an irregular muscle, such as the gastrocnemiu.s, for instance, in which the currents of inclination are very pronounced, the diagrammatic representation of the various currents gives a complicated figure wholly unlike. Fig. 11^^ DuriDg a contraction the natural muscle-current undergoes a negative variation. Not easily seen in a single spasm, this is exceed- ingly obvious during tetanus. If a pair of electrodes be placed on a muscle, one at the equator, and the other at or near the transverse section, and thus a considerable deflection of the galvanometer be gained, indicating a considerable natural current, the needle of the galvanometer will, when the muscle is tetanized by an interrupted current sent through its nerve (at a point too far from the muscle to allow an 3^ escape of the current into the electrodes connected with the galvanometer), swing back towards zero; it returns to its original deflection when the tetanizing current is shut off. This negative variation may not only be shewn by the galvano- meter, but it, as well as the natural current, may be used as a galvanic shock and so employed to stimulate a muscle, as in the experiment known as ' the rheoscopic frog.' For this purpose sensitive muscles and nerves in thoroughly good condition are required. Two muscle- 1 Pfiiiger's Archiv, xv. (1877), p. 116, p. 328. ^ Cf. Du Bois-Eeymoijd, op. cit. ii. G3. 54 EHEOSCOPIC FROG. [Book i. nerve preparations having been made and each placed on a glass plate for the sake of insulation, the nerve of the one is allowed to fall on the muscle of the other in such a way that one point of the nerve comes in contact with the equator of the muscle, and another point with one end of the muscle or with a point at some distance from the equator. At the moment the nerve is let fall and contact made, a current passes through the nerve ; this acts as a stimulus to the muscle connected with the nerve, and causes contraction in it. So the muscle A acts as a battery, the completion of the current of which by means of the nerve of B, serves as a stimulus, causing B to contract. If while the nerve of B is still in contact with the muscle of A, the nerve of the latter is tetanized with an interrupted current, not only is the muscle of A thrown into tetanus but also that of B ; the reason being as follows. At each spasm of which the tetanus of J. is made up, there is a negative variation of the muscle-current of A. Each negative variation in the muscle of A serves as a stimulus to the nerve of B, and is hence the cause of a spasm in the muscle of B; and the stimuli following each other rapidly as they must do being produced by tetanus of A, the spasms in B to which they give rise are also fused into a tetanus in B. B in fact contracts in harmony with A. This experiment shews that the negative variation accompanying the tetanus of a muscle, though it causes only a single movement of the galvanometer, is really made up of a series of negative variations, each single negative variation corresponding to the single spasms of which the tetanus is made up. Similar results are arrived at, though less readily, if the nerve of B, instead of being allowed to fall on the^muscle of J., is placed in contact with two points of the nerve of ^, so situate as to dev elope a current. When the nerve of B is let fall on the two points of the nerve oi A, so chosen that a nerve-current may be expected to pass between them, a single spasm, caused by the completion or making of the circuit of the nerve-current, may sometimes be observed in the muscle of B. When, the nerve of A is tetanized with an interrupted current, the muscle of B is thrown into tetanus ; in these cases it is the natural current (or its variation) of the nerve and not of the muscle, which acts as a stimulus. The negative variation falls entirely within the latent period. It is over and gone before the actual shortening commences. It is in fact a token of something like a nervous impulse passing over the muscular fibre as a forerunner of the events which lead to a change of form. Bernstein' has studied the history of this negative variation in muscle. He finds that it, like the negative variation in the nerve, travels in the form of a wave, with a velocity of about 3 metres. It is about -g-g-jj second in passing over any given point, and therefore has a wave-length of about 10 mm. Compared with the nerve- wave, therefore, it is much shorter 1 Op. cit. Chap, ii.] THE CONTRACTILE TISSUES. 55 and slower. These results were obtained by stimulating directly one end of a long muscle poisoned with urari in order to eliminate the nerves (see p. 35). The impulse then travelled away from the end stimulated along the whole length of the muscle. (When the muscle is stimulated through a nerve, the impulse starts from the end-plates, often situated in the middle of a fibre, and proceeds in both directions, up and down. Such a condition would be most unfavourable for studying the progress of the impulse.) We learn from this that there passes over the muscle, in the latent period before any change of form takes place, an .impulse-wave, not unlike a nervous impulse and yet distinctly differing from it. In its steep- ness and sluggishness the wave foreshadows the motor changes it is about to inaugurate. Contrary to the case of a nerve, Bernstein found that, in a muscle, when the natural current was obtained by help of an artificial transverse section, the deflection indicating the negative variation never exceeded the deflection of the natural current. The effect of the natural current mi2:ht be reduced to nil, but the needle was never carried, as it might be in a nerve, a long way the other side of zero. 2. Change of Form. At the close of the latent period the muscle shortens, that is, each fibre shortens, at first slowly, then more rapidly, and lastly more slowly again. The shortening (which in severe tetanus may amount to three-fifths of the length of the muscle) is accompanied by an almost exactly corresponding thicken- ing, so that there is hardly any actual change in bulk. If a muscle be placed horizontally, and a lever laid upon it, the thickening of the muscle will raise up the lever, and cause it to describe on a recording surface a curve exactly like that described by a lever attached to tlie end of the muscle. There appears to be a minute diminution of bulk not amounting to more than one thousandth. If a long muscle of parallel fibres, poisoned with urari, so as to eliminate the action of its nerves, be stimulated at one end, the contraction may be seen, almost with the naked eye, to start from the end stimulated, and to travel along the muscle. If two levers be made to rest on, or be suspended from two points of such a muscle placed horizontally, the points being at a known distance from each other and from the point stimulated, the progress of the contraction may be studied. It is found that the con- traction, like the preceding impulse, passes along the muscle in the form of the wave, with a velocity in the frog of about 3 or 4 (3-869) metises in a second ; its duration at any given point varies from '0533 to "0984, and hence it possesses a wave-length of from 198 — 380 mm. This statement is taken from Bernstein \ Hermann^ makes the rate about 3 metres. Aeby previously had given "8 — 1'2 metres per sec, and Engelmann l'17m. per sec. as the velocity. The slowness and the enormous length of this con- traction-wave place it in strong contrast with the impulse-wave. Seeing that the extreme limit of the length of a muscular fibre is about 3 to 4 cm., it is evident that in an ordinary contraction, even when the stimulation begins at one end, the whole fibre is not only in a state of contraction at the same 1 Op. cit. See also Du Bois-Keymond's ArcMv, 1875, 526. 2 PMger's Archiv, x. (1875), 48. 56 CHANGES DURIFG CONTRACTION. [Book i. time, but almost in tlie same phase of the contraction-wave. Still more is this the case when, as in ordinary stimulation through a nerve, the con- traction begins at or near the middle of a fibre in an end-plate, or at two jDoints (end-plates) of the same fibre at the same time. Nevertheless the length of the contraction- wave must vary within very wide limits. Thus in muscles examined under the microscope exceedingly short waves occupy- ing only a small portion of the length of a fibre are frequently witnessed. These however may be regarded as the abnormal results of exhaustion and commencing death, A ixmscle in the body, or one out of the "body when sufficiently loaded, returns after the contraction completely to its former length. Out of the body and unloaded, it generally falls somewhat short of this. The other changes in muscle are of a kind which cannot be restricted to any exact period of the whole event, and as a rule are much more distinctly recognised as the result of tetanus than of a single spasm. 3, Physical changes other than electricah During a contrac- tion the temperature of the muscle rises. This may be ascertained with a thermopile and galvanometer ; a delicate thermometer plunged into the midst of the muscles of the thigh of a frog, will also indicate a rise of temperature when these are tetanised. In a frog's muscle, the rise from a single contraction may, it is stated, reach '005° C; in tetanus it may amount to "IS" C. The extensibility of the muscle is increased. Living muscle at rest is very extensible, and its elasticity is very perfect, i.e. after extension it returns almost exactly to its natural length. When a muscle is extended by a series of weights increasing in magni- tude, the curve (obtained by making the weights abscissae and the exten- sions ordinates) is not a straight line, as is the case with dead elastic bodies, but a hyperbola. If a muscle at rest be loaded with a given weight, say 50 grammes, and its extension observed, and be then while unloaded thrown into tetanus, and the load applied during the tetanus, the extension in the second case will be distinctly greater than in the first, indicating a marked increase of extensibility during contraction. During tetanus a muscle gives out a sound, the muscular sound. This may be heard by applying the stethoscope to a muscle during contraction. It may be also heard by stopping the ears, and causing the masseter and temporal muscles to contract. When a muscle is thrown into tetanus by the will or by reflex action or by direct stimu- lation of the spinal cord, in fact, in any way through the action of the central nervous system, the same note is always heard, viz. one indicating 19"5 vibrations per second. The note actually heard is one indicating 39 (36 to 40) vibrations per sec. This is, however, an harmonic of the primary note of the whole sound. Chap, n.] THE CONTRACTILE TISSUES. 57 When a muscle is thrown into tetanus by interrupted shocks applied directly to the nerve or to the muscle, the note is the same as that of the interrupter determining the number of the shocks. This is naturally the case, since the note of the muscle-sound is determined by the rapidity of the spasms or vibrations which go to make up the tetanus, and these are determined by the rapidity with which the stimulus is repeated. 4. Chemical Changes. Acid is set free. A living muscle at rest is in reaction neutral, or, from some remains of lymph adhering to it, faintly alkaline. Tested by litmus paper it is frequently amphi- chroitic, i.e. it will turn blue litmus red and red litmus blue, — but the change from red to blue is more marked than that from blue to red. If a muscle thus found neutral or alkaline be tetanized vigorously, and its reaction then tested, it will be found to be most distinctly acid. The red colouration of the blue litmus thus obtained is per- manent, and cannot therefore be due to carbonic acid. It is probably due to sarcolactic acid\ Carbonic acid is set free in great excess. Blood in passing through a living muscle in the body, from being arterial becomes venous, i.e. the muscle takes up oxygen and gives out carbonic acid. This it does even when at rest ; during contraction the quantity of carbonic acid is increased largely. There is also an increase in the assumption of oxygen, but not at all in the ratio of the carbonic acid given out. To this point we shall return in speaking of respiration. If a muscle, ex. gr. a frog's muscle, removed from the body, be sus- pended in an atmosphere of known composition containing oxygen, a steady consumption of oxygen and a steady production of carbonic acid continues to take place for some time. When the muscle is tetanized, a very large increase in the production of carbonic acid is observed, but none or a very slight one only in the consumption of oxygen. A frog's muscle will continue to live for a while and to contract vigorously in an atmosphere perfectly free from oxygen. Now a muscle contains in itself no free or loosely combined oxygen such as would serve for its own oxidation. When a frog's muscle is subjected to the action of a mercurial air-pump, no oxygen can be extracted from it. In this respect muscle differs markedly from blood, which, as we shall see in dealing with respiration, gives up a very considerable quantity of oxygen to a vacuum. Hence when a muscle, itself containing no free or available oxygen, contracts in an atmo- sphere also free from oxygen, it is evident that during the contraction no direct oxidation takes place. Nevertheless the production of carbonic acid as the result of contraction goes on all the same. From this it is clear that the carbonic acid which is produced during contraction, cannot come from the direct oxidation of any carbon compounds. It probably has its source in the splitting up of some complex bodies, and the great parallelism which is found between 1 See p. 84 58 CHEMICAL RESULTS OF CON-TRACTION'. [Book i. the amoimt of carbonic acid and of sarcolactic acid formed suggests the idea that they have a common origin. The other chemical changes in muscle have not been clearly made out. Helmlioltz shewed long ago that by continued contraction the sub- stances in muscle which are soluble in water, i.e. the aqueous extractives, are dimmished, while those which are soluble in alcohol are increased. In other words, during contraction some substance or substances soluble in water are converted into another or other substances insoluble in water but soluble in alcohol. Ranke' concluded from his observations that the proteids are slightly diminished, and that sugar and fats are produced; but the data for these conclusions are, at present at all events, insufficient. It has been suggested that the glycogen naturally present in muscle is during contraction converted into sugar. The failure to obtain any satis- factory evidence of the production of nitrogenous crystalline bodies as the result of contraction is of interest; for though urea is conspicuous by its absence from muscle both during rest and after contraction, some observers have thought that the kreatin in muscle is increased by contraction: this has not been definitely proved. Putting all these facts together, the following may be taken as a brief approximate history of what takes place in a muscle and nerve when the latter is subjected to a single induction-shock. At the instant of the induced current passing through the nerve, changes occur, of whose nature we know nothing certain except that they occasion a negative variation of the natural nerve- current. These changes propagate themselves along the nerve in both direc- tioDS as a nervous impulse in the form of a wave, having a wave- length of about 18 mm., and a velocity (in frog's nerve) of about 28 m. per sec. Passing down the nerve-fibres to the muscle, flowing along the branching and narrowing tracts, the wave at last breaks on the end-plates of the fibres of the muscle. Here it is transmuted into a muscle-impulse, with a shorter steeper wave, and a markedly dimin- ished velocity (about 3 m. per sec). This muscle-impulse, of which we know hardly more than that it is marked by a negative variation in the muscle-current, travels from each end-plate in both directions to the end of the fibre. What there becomes of it we do not know, but it is immediately followed by the visible contraction-wave, travelling behind it at about the same rate, but with a vastly increased wave- length. The fibre, as the wave passes over it, swells and shortens, bringing its two ends together, its molecules during the change of form arranging themselves in such a way that the extensibility of the fibre is increased, while at the same time an explosive decomposition of material takes place, leading to a burst of carbonic and sarcolactic acids, and probably of other unknown things, with a considerable development of heat. 1 Tetanus, 1865. Chap, n.] TEE CONTRACTILE TISSUES. 59 The nature of the changes through which an electric current is able to generate a nervous impulse. Action of the Constant Current. There now comes before us the question, In what way is an induction-shock, single or repeated, thus able to generate a nervous impulse or impulses ? In an induc- tion-shock we have a galvanic current of short duration, possessing certain characters of its own. What happens when a constant gal- vanic current is sent into a nerve direct from the battery ? On examination the results, as far as muscular contraction is concerned, are found to vary considerably according to circumstances. Thus a contraction, a single spasm, may be witnessed when the current is made (thrown into the nerve), or when it is broken (taken away from the nerve), or at both events. Under certain conditions of the nerve and muscle a strong constant current may produce at making or breaking, not a simple spasm, but a prolonged and pronounced tetanus. This when it occurs is spoken of as the ' making tetanus ' or ' breaking tetanus.' These however are exceptional ; and as a general rule it may be stated, while the current is passing, provided that its intensity remains uniform, no contraction is produced. It requires either a sudden increase or a sudden decrease in the in- tensity (make and break being themselves a maximum increase and decrease), in order to generate a nervous impulse, and so to produce a contraction. Electrotonus. Nevertheless, even in the absence of all contrac- tions, the nerve, both between and beyond the electrodes, is, during the passage of the constant current, in a peculiar condition known as ' electrotonus,' The marked features of the electrotonic condition is that the nerve though apparently quiescent is changed in respect to its irritability ; and that in a different way in the neighbourhood of the two electrodes respectively. Suppose that on the nerve of a muscle-nerve preparation are placed two (non-polarisable) electrodes (Fig. 12, a, k) connected with a battery and arranged with a key so that a constant current can at pleasure be thrown into or shut off from the nerve. This constant current, whose effects we are about to study, may be called the ' polarizing current.' Let a be the positive electrode, or anode, and k the negative electrode or kathode, both placed at some distance from the muscle, and also with a certain interval between each other. At the point x let there be applied a pair of electrodes connected with an induction- machine. Let the muscle further be connected with a lever, so that its contractions can be recorded, and their amount measured. Before the polarizing current is thrown into the nerve, let a single induction- shock of known intensity (a weak one being chosen, or at least not one which would cause in the muscle a maximum contraction) be thrown in at x. A contraction of a certain amount will follow. That contraction may be taken as a measure of the irritability of the nerve 60 ELECTROTONUS. [Book i. A. II ^^ X B. a Fig, 12. Mtjscle-nekte Peeparations, -with the nerve exposed in ^ to a descending and in £ to an ascending constant current. In each a is the anode, k the kathode of the constant current, x reiDresents the spot where the induction-shocks used to test the irritability of the nerve are sent in. at the point x. Now let the polarizing current be thrown in, and let the direction of the current be a descending' one, with the kathode or negative pole nearest the muscle, as in Fig. 12 A. If while the current is passing, the same induction-shock as before be sent through X, the contraction which results will be found to be greater than on the former occasion. If the polarising current be shut off, and the point a; after a short interval again tested with the same induction-shock, the contraction will be no longer greater, but of the same amount, or perhaps not so great, as at first. During the pas- sage of the polarizing current, therefore, the irritability of the nerve at the point x has been temporarily increased, sinse the same shock applied to it causes a greater contraction in the muscle than in the absence of the current. But this is only true so long as the polar- izing current is a descending one, so long as the point x lies on the side of the kathode. On the other hand, if the polarizing current had been an ascending one, with the anode or positive pole nearest the muscle, as in Fig. 12 B, the irritability of the nerve at x would have been found to be diminished instead of increased by the polarizing current. That is to say, that when a constant current is applied ta a nerve, the irritability of the nerve between the polarizing electrodes and the muscle is increased when the kathode is nearest the muscle (and the polarizing current descending) and diminished when the anode is nearest the muscle (and the polarizing current ascending) during the passage of the current. The same result, mutatis mutandis, and with some qualifications to be referred to directly, would be gained if x were placed not between the muscle and the polarizing current, but on the far side of the latter. Hence it may be stated generally that during the passage Chap, ii.] THE CONTRACTILE TISSUES. 61 of a constant current through a nerve the irritability of the nerve is increased in the region of the kathode, and diminished in the region of the anode. The changes in the nerve which give rise to this increase of irritability in the region of the kathode are spoken of as hatelectrotonus, and the nerve is said to be in a katelectrotonic con- dition. Similarly the changes in the region of the anode are spoken of as anelectrotonus, and the nerve is said to be in an anelectrotonic condition. It is also often usual to speak of the katelectrotonic increase, and anelectrotonic decrease of irritability. This law remains true whatever be the mode adopted for deter- mining the irritability. The result holds good not only with a single induction-shock, but also with a tetanizing interrupted current, with chemical and with mechanical stimuli. The increase and decrease of irritability are most marked in the immediate neighbourhood of the electrodes, but spread for a considerable distance in either direc- tion in the extrapolar regions. The same modification is not confined to the extrapolar region, but exists also in the intrapolar region. In the intrapolar region there must be of course an indifferent point, where the katelectrotonic increase merges into the anelectrotonic decrease, and where therefore the irritability is unchanged. When the polarizing current is a weak one, this indifferent point is nearer the anode than the kathode, but as the polarizing current increases in intensity, draws nearer and nearer the kathode (see Fig. 13). Fig. 13. Diageam Illtjsteating the Vaeiatioxs of Ieeitabilitt during Electro- TONUS, WITH POLAEIZING CURRENTS OF INCREASING INTENSITY (frOm Pfliiger). The anode is supposed to be placed at A, tlae kathode at B ; AB is consequently the intrapolar district. In each of the three curves, the portion of the curve below the base line represents diminished irritability, that above, increased imtabiUty. y-^ represents the effect of a weak current ; the indifferent point rCj is near the anode A. in 1/2, a stronger current, the indifferent point a;^ is nearer the kathode B, the diminu- tion of mitabihty in anelectrotonus and the increase in katelectrotonus being greater than in y^ ; the effect also spreads for a greater distance along the extrapolar regions in both directions. In y.^ the same events are seen to be still more marked. The katelectrotonic increase and anelectrotonic decrease reach a maximum soon after the making of the polarizing current, and thenceforward gradually diminish. The two effects however are not quite parallel. The katelectrotonic increase is the first to be de- veloped; it rapidly rises to a maximum and somewhat rapidly 62 ELEGTROTONUS. [Book i. declines. The anelectrotonic decrease is not manifest at first ; when it does appear it increases slowly, and having reached a maximum diminishes slowly again. When the polarizing current is shut off there is a rebound at either pole ; a temporary increase of irritability in the anelectrotonic and a tem- porary decrease in the katelectrotonic regions. The amount of increase and decrease is dependent : (1) On the strength of the current, the stronger current up to a certain limit producing the greater effect. (2) On the irritability of the nerve, the more irritable, better conditioned nerve being the more affected by a current of the same intensity. The increase or decrease of irritability applies not only to the origination of impulses, but also to their propagation or conduction. At least anelectrotonus offers an obstacle to the passage of a nervous impulse. These variations of irritability at the kathode and anode respec- tively must be the result of molecular changes, brought about by the action of the constant current. We are not at present able to say what those molecular changes are, but we have evidence of physical phenomena accompanying and probably connected with the physio- logical phenomena just described. During the passage of a constant current through a nerve, variations in the electric currents of the nerve analogous in many respects to the variations of the irritability of the nerve may be witnessed. Thus if a constant current supplied by the battery P (Fig. 14) be applied to a piece of nerve by means of two non- polarisable electrodes p, p', the currents obtainable from various points of the nerve will be different during the passage of the polariz- ing current from those which were manifest before or after the current was applied ; and, moreover, the changes in the nerve-currents pro- duced by the polarizing current will not be the same in the neigh- bourhood of the anode (p) as those in the neighbourhood of the kathode (j)). Thus let G and II he two galvanometers so connected with the two ends of the nerve as to obtain good and clear evidence of the natural nerve-currents. Before the polarizing current is thrown into the nerve, the needle of ^will occupy a position indicating the passage of a current of a certain intensity from h to h' through the galvanometer (from the positive longitudinal surface to the negative cut end of the nerve), the circuit being completed by a current in the nerve from h' to h, i.e. the current will flow in the direction of the arrow. Similarly the needle of O will by its deflection indicate the existence of a current flowing from g to g' through the galvanometer, and from g' to g through the nerve, in the direction of the arrow. At the instant that the polarizing current is thrown into the nerve at pp, the currents at gg', hJi will suffer a negative variation corresponding to the nervous impulse, which, at the making of the polarizing current, passes in both directions along the nerve, and may Chap, ii.] THE CONTRACTILE TISSUES. 63 / llh k ■■mmm%mwm.mmm/ymmmm/mmk:'mM/^^^ ^ 9 s» — >